Multi-planar transverse, U-type, and vertical sacral fractures occur from high energy trauma or as pathologic fractures and often have associated neurologic and extremity injuries. Modern treatment algorithms fall into two broad categories: 1) percutaneous posterior pelvic fixation  or 2) lumbopelvic fixation. Posterior pelvic screw fixation is minimally invasive but typically requires restricted weight bearing until fracture union. In many cases, lumbopelvic fixation allows for a closed reduction and provides stability to allow full weight bearing immediately after surgery; however, this fixation is often removed in a second surgery after fracture healing. Lumbopelvic fixation was originally described as an open procedure, minimally invasive lumbopelvic fixation is a recent variation and has shown promising results with less morbidity. We present a case series of unstable U-type sacral fractures treated with minimally invasive lumbopelvic fixation with staged hardware removal to illustrate the advantages and complications associated with this new technique. Ten patients with U-type sacral fractures underwent minimally invasive lumbopelvic fixation from 2016 to 2019. Six patients underwent scheduled hardware removal an average of 3.5 (range 1.9-5.5) months after index surgery. Two patients did not undergo hardware removal due to short life expectancy and diagnosis of pathologic fractures. One patient was lost to follow-up. One patient had failed fracture reduction and went on to sacral malunion that required a late sacral extension osteotomy to restore her ability to stand upright. Final disposition of all nine patients with follow-up was normal standing upright posture and normal ambulation without assistive device. There were no late displacements on postoperative upright radiographs. Complex sacral fractures are a challenging injury that can be treated with percutaneous posterior pelvic or lumbopelvic fixation. Lumbopelvic fixation offers the advantages of closed reduction to restore pelvic incidence and immediate weight bearing but has greater surgical morbidity than percutaneous posterior pelvic fixation and often requires hardware removal. The morbidity of lumbopelvic fixation may be reduced with minimally invasive techniques. Minimally invasive lumbopelvic fixation is a treatment option to be considered for complex sacral fractures. U-shaped sacral fractures are uncommon injuries that cause dissociation between the lower sacrum/pelvis from the upper sacrum/lumbar spine. These fracture patterns can be difficult to interpret on plain radiographs and early reports without the benefit of advanced imaging reflect the difficulty in understanding the fracture lines within the sacrum . Denis eU-type sacral fractures are zone three injuries that consist of many fracture lines but fundamentally only two main fracture fragments . The supThe two types of operative fixation for complex sacral fractures are posterior pelvic fixation  and lumbopelvic/triangular fixation. Fluoroscopy and navigation allow the placement of posterior pelvic fixation percutaneously . LumbopeIn this series, we review the outcomes and complications of 10 patients who underwent minimally invasive lumbopelvic fixation to treat unstable U-type sacral fractures. We highlight the advantages and disadvantages of lumbopelvic fixation for the treatment of these complex injuries.MethodsTen patients with unstable U-type or vertical sacral fractures were treated with minimally invasive lumbopelvic fixation and fracture reduction Figure -B. All pA lateral pelvis fluoroscopy image was checked to ensure that pelvic incidence had been restored. Fractures with excessive impaction or severe angulation can be difficult to reduce with this maneuver, however, every effort should be made to achieve a closed reduction since a sacral malunion requires a complex osteotomy for correction. Non-displaced fractures were instrumented in situ. Patients were mobilized immediately with no weight bearing restrictions. Radiographs were taken immediately post-op and at the 6-week post-op visit to assess maintained alignment Figure -B. HardwResultsTen patients underwent minimally invasive lumbopelvic fixation from 2016 to 2019. Eight patients had sacral fractures from high energy trauma, and two had pathologic sacral fractures from falls from standing height and did not undergo implant removal due to short life expectancy. One patient with polytrauma including complex neurologic injuries was lost to follow-up and did not have implant removal. Of the eight patients who had planned hardware removal, six underwent scheduled removal an average of 3.5 (range 1.9-5.5) months after index surgery. The hardware removals have been uncomplicated and performed as outpatient surgeries without extending the surgical incisions. One of the planned hardware removal patients was lost in follow-up. The one other planned hardware removal patient had a sacral malunion and required hardware revision and sacral osteotomy. All nine patients who have complete follow-up transitioned to full weight bearing immediately after surgery; final disposition of all patients was normal ambulation without assistive devices, restoration of upright posture, and a final fracture union with no late displacement. All patients with normal ability to ambulate had a restoration of their pelvic incidence to within two standard deviations of normal  allows in situ fixation of the fracture without a reduction maneuver, or may be performed in the prone position to exaggerate lordosis and achieve some fracture reduction. The disadvantages of percutaneous posterior pelvic fixation are the inability to directly manipulate the fracture fragments and insufficient stability for immediate weight bearing. Nork published his experience with a posterior pelvic fixation on 13 patients with unstable U-type sacral fractures where he used bracing and restricted each patient to a wheelchair after surgery for 8-12 weeks . PercutaOpen lumbopelvic fixation is associated with high rates of complications including infections, wound complications, dural tears, and pseudomeningocele that may be related to the soft tissue dissection needed to obtain adequate exposure . Our serTo reduce the sacral fracture and restore normal standing posture the surgeon must understand the relationship between the sacrum and the overall alignment of the spine. Dubousset described the state of balanced upright posture where the knees are fully extended, the hips are in a neutral position, and the pelvis with the rest of the spine are maintained upright within a narrow cone without active muscle contraction . If a maSpine surgeons now have a broader understanding of the concepts of sagittal balance and the “cone of economy” . PercutaThis series of patients illustrates the benefits and the complications of minimally invasive lumbopelvic fixation for complex sacral fractures. The advantages of lumbopelvic fixation include immediate full weight bearing. Lumbopelvic fixation can be used to maintain or to restore pelvic incidence. Our series is similar to previous reports that show minimally invasive lumbopelvic fixation for unstable sacral fracture is an option in treating these complex injuries. The minimally invasive technique is associated with lower wound complication rates compared to open lumbopelvic fixation and still allows for immediate full weight bearing -8. EveryWhen closed reduction and normal pelvic incidence was achieved, patients in this series had good clinical outcomes. When the pelvic incidence was not restored, as in our one patient, the clinical outcome was poor. If the surgeon carefully considers the restoration of pelvic incidence then minimally invasive closed reduction and lumbopelvic fixation is a viable treatment option for complex unstable sacral fractures.


Infrarenal abdominal aortic dissections (IAAD) are exceedingly rare, accounting for 1-4% of all aortic dissections. The evidence is scarce on how to best manage IAAD when they become symptomatic. Two main interventional approaches exist, open surgery and the endovascular approach. Conventional stent-graft systems make it difficult to treat nonaneurysmal aortic disease due to limb competition in a narrow distal aorta. Thus, we present a novel use of the Endologix Anatomical Fixation 2 (AFX2) Abdominal Aortic Aneurysm (AAA) endograft system for the treatment of four patients with IAAD. We also highlight an individual case study that was treated with an alternative endovascular approach and the complications that followed. This was to highlight and compare our successful experience with Endologix AFX2 AAA endograft system. There were multiple benefits for choosing this stent-graft; however the main advantage is its suitability in the narrow distal aorta. Our aim was to highlight an alternative endovascular approach for the successful treatment of a rare, challenging, and potentially fatal pathology. Infrarenal abdominal aortic dissections (IAAD) are exceedingly rare with most aortic dissections originating in the ascending thoracic aorta. Infrarenal abdominal aortic dissections (IAADs) account for 1% to 4% of all aortic dissections . They caWe report the clinical features and novel use of the Endologix AFX2 AAA endograft system for the treatment of four patients who presented to our institution with IAADs. Special emphasis is placed on the clinical presentation of this rare entity and the endovascular treatment and complications experienced within our institution.BH is a 59-year-old male presented after a high-speed motor vehicle accident. Screening Computed-Tomography (CT) imaging was carried out to exclude any injuries, revealing a L3 fracture and infrarenal aortic dissection. Dedicated CT angiography revealed a 7cm dissection in the infrarenal abdominal aorta extending into the proximal left common iliac artery (CIA) . The patA 73-year-old male presented with an incidental finding of an IAAD extending to the left CIA on CT angiography . Due to The case is a 56-year-old male who underwent a CT angiogram as a work-up for prostate surgery. There is an incidental finding of a 3.2cm infrarenal abdominal aortic aneurysm (AAA) with dissection extending distally involving both common iliac arteries . Due to The case is a 70-year-old female with an infrarenal aortic dissection and an associated AAA which showed progression at surveillance. CT angiography showed a minor eccentric saccular aneurysm measuring 23mm involving the right anterolateral aspect, extending over a 9mm intimal flap . Due to A 71-year-old female presented with a pulsatile mass in her left groin causing significant discomfort. CT angiography showed a dissection involving the infrarenal abdominal aorta extending from the level of the inferior mesenteric artery into an aneurysmal left common iliac artery (CIA) measuring 29mm x 27mm. The patient was treated with a 24mm x 56mm Zenith® Spiral-Z® AAA Iliac Leg Graft  and deployed into the infrarenal aorta. Kissing iliac stents were deployed to exclude both the dissection at its distal point and the left CIA aneurysm. At 12-month follow-up CT angiography demonstrated exclusion of both the dissection and the left CIA aneurysm. However, CT angiography at 48-month follow-up demonstrated a type 2 endoleak with filling of the false lumen of the dissection in the infrarenal aorta with associated mild aneurysmal dilatation . The patInfrarenal aortic dissections are rare. The increasing use of CT scanning for further investigation of undifferentiated abdominal pain has begun to reveal this condition more frequently . The mosThe most common risk factors for spontaneous infrarenal aortic dissection are hypertension, hyperlipidaemia, and atherosclerosis and these factors were observed across all six patients. A dissection left untreated may result in the formation of an aneurysm that could ultimately rupture or lead to progressive stenosis leading to distal arterial insufficiency.Nonpenetrating injuries of the abdominal aorta are rare, with only between 0.01% and 0.07% resulting in aortic dissection . AlthougTherapeutic options in the case of chronic IAADs include close observation with regular follow-up, prosthetic replacement of the involved aorta, or open surgery . ConservEndologix AFX2 AAA endograft system  differs from the other approved EVAR systems in several ways. It features the only unibody main body component, in contrast to the usual two- or three-component modular design. The device is deployed directly onto the aortic bifurcation, providing secure anatomic fixation, eliminating main body graft migration, and essentially relining the distal aorta and common iliac arteries. The base component is then complemented by an aortic extension cuff that is available in either an infrarenal or suprarenal option that provides seal through radial force and the ability of the compliant expanded polytetrafluoroethylene (ePTFE) graft material to accommodate irregularities in the aortic wall .The prevalence of a narrow distal aorta (< 20 mm) associated with AAA may be as high as 65%; this was noted amongst our cohort with an average diameter of 17.8mm (range = 9.4mm – 19.8mm). In these situations, relining the aortic bifurcation with the Endologix AFX2 AAA endograft sysytem is more appealing than trying to squeeze two limbs side-by-side within a narrow lumen. Relining the aorta provides the ability to more aggressively postdilate the bifurcation to ensure an adequate-flow lumen and lower limb occlusion rates .Finally, the main body device and aortic or iliac extensions are delivered through a single 17-Fr ID hydrophilic access sheath without the need for exchanges. The contralateral side is managed through a 7Fr sheath that is approved for standard percutaneous access and makes Endologix AFX2 AAA Endograft System the lowest profile system currently available . The sysAll patients treated with the Endologix AFX2 AAA endograft system had no complications perioperatively and had no evidence of endoleak on follow-up at 12 months. Our one patient treated with the Zenith® Spiral-Z® AAA Iliac Leg Graft  and kissing iliac covered stents which was deployed proximal to the origin of the dissection unfortunately developed a type 2 endoleak and persistent filling of the false lumen of the dissection with expansion of the luminal diameter. The reason for this treatment choice was that the Endologix AFX2 AAA endograft system was not available at our institution.Isolated infrarenal aortic dissections are a rare condition affecting both the young and elderly population. In those where aetiology is spontaneous, patients are often elderly with significant comorbidity. The use of the Endologix AFX2 AAA endograft System has been shown to be a safe and low-risk alternative to open aortic surgery in these populations.


Ganoderma boninense is known to be the causal agent of basal stem rot (BSR) disease in oil palm (Elaeis guineensis). This disease causes rotting in the roots, basal and upper stem of oil palm. Infection causes progressive destruction of the basal tissues at the oil palm trunk and internal dry rotting, particularly at the intersection between the bole and trunk. Molecular responses of oil palm during infection are not well study although this information is crucial to strategize effective measures to control or eliminate BSR. Here we report three sets of transcriptome data from samples of near-rot section of basal stem tissue of oil palm tree infected with G. boninense (IPIT), healthy section of basal stem tissue of the same G. boninense infected palm (IPHT) and the healthy section of basal stem tissue of the healthy palm (HPHT). The raw reads were deposited into NCBI database and can be accessed via BioProject accession number PRJNA530030.To date,  The data sets were named as IPHT , IPIT  and HPHT .22.1G. boninense fruiting body attached at the basal stem and the palm does not exhibit stress-related symptoms phenotypically. All collected basal stem tissues were immediately submerged in liquid nitrogen and kept at −80 °C freezer until further processing for RNA extraction.A pair of healthy and infected clonal mature palm was selected from Serting Hilir field research station, Negeri Sembilan, Malaysia owned by Felda Agricultural Services Sdn Bhd. Briefly, the bark was marked according to the health status. The healthy section (IPHT) and near-rot section (IPIT) of infected oil palm were collected from the cross section of the basal stem. The cross section of healthy tissue section of healthy oil palm tree (HPHT) was also collected. The healthy palm was determined by healthy oil palm phenotype with no 2.2et al., 2009 Total RNA of matured basal stem samples; IPHT, IPIT and HPHT were extracted using method from Saidi 2.3Messenger RNA isolation and cDNA synthesis were performed using TruSeq RNA Sample Preparation Kit  and SuperScript II Reverse Transcriptase  by following the manufacturers' protocol, respectively. The amount of synthesised cDNA was measured using Qubit 2.0 DNA Broad Range Assay . A minimum of 15 ng cDNA was fragmented using Covaris S220  to a targeted size of 200–300bp. The fragmented cDNA was then end repaired, ligated to Illumina TruSeq adapters, and PCR-enriched using TruSeq RNA Sample Preparation Kit  by following the manufacturer's protocol. The final sequencing libraries were quantified using KAPA kit  on Agilent Stratagene Mx-3005p quantitative PCR  and sizes were confirmed using Agilent BioAnalyzer High Sensitivity DNA Chip . The resulting libraries were sequenced using an Illumina flow cell and 209 cycles on the Illumina HiSeq 2000 platform .2.4E. guineensis genome Ganoderma boninense genome The quality of RNA-seq raw data was assessed using FastQC


In recent years, Medicare Advantage (MA) plan enrollment has increased, a trend that is expected to continue. Many skilled nursing facilities (SNFs) rely on MA managed care insurer referrals to maintain their census in a market with high competition for post-acute care patients. This study used semi-structured interviews to describe the relationship between MA plans and SNFs from the perspective of key decision-makers in SNFs. Twenty-three interviews were conducted with key stakeholders from 11 Denver Metropolitan area SNFs. A combined purposive-snowball sampling approach was used to identify and recruit select staff from the participating facilities. Interviews focused on the relationship between MA plans and SNFs, including mechanisms of control, power dynamics, and preferences for MA versus Fee-for-Service (FFS) Medicare patients. Key findings included: 1) challenges SNF staff had navigating MA plans’ case management processes, a key mechanism used by MA plans to influence the behavior of SNF decision-makers; 2) MA plans exercising power over beneficiaries’ length of stay, potentially leading to early discharge and heightened risk for rehospitalization; 3) SNF preference for admitting Medicare FFS over MA patients due to higher rates of Medicare FFS reimbursement and greater control over patient care. SNFs are increasingly reliant on MA plans for patient referrals and revenue. The themes suggest that this growing reliance may place SNFs at odds with MA plans on how best to manage overall patient care. It is therefore important that future research investigate how MA plans’ influence over care affects patient outcomes in SNFs and other post-acute settings.


Juglans nigra L.) is not practical and timber breeders have historically utilized only open-pollinated half-sib families. An alternate approach called “breeding without breeding,” consists of genotyping open-pollinated progeny using DNA markers to identify paternal parents and then constructing full-sib families. In 2014, we used 12 SSR markers to genotype 884 open-pollinated half-sib progeny harvested from two clonal orchards containing 206 trees, comprised of 52 elite timber selections. Seed was harvested in 2011 from each of two ramets of 23 clones, one upwind and one downwind, based on prevailing wind direction from the west—southwest. One orchard was isolated from wild black walnut and composed of forward selections while the other orchard was adjacent to a natural forest containing mature black walnut composed of backward selections. Isolation significantly increased within-orchard pollination (85%) of the progeny from the isolated orchard compared to 42% from the non-isolated orchard. Neither prevailing wind direction nor seed tree position in the orchard affected paternity patterns or wild pollen contamination. Genetic diversity indices revealed that progeny from both orchards were in Hardy–Weinberg equilibrium with very little inbreeding and no selfing. A significant level of inbreeding was present among the forward selected parents, but not the first generation (backward selected) parents. Some orchard clones failed to sire any progeny while other clones pollinated upwards of 20% of progeny.Artificial pollination of black walnut ( Juglans nigra L., is a valuable timber tree native to eastern North America that also provides mast and habitat for wildlife and watershed protection  d dFig 2E  progeny  and 5 of progeny . Three ograndis) .Unequal male reproductive success could lead to decreased genetic diversity and inbreeding which can lower survival and fecundity. Use of a mix of different pollen parents, or a “polymix,” , 51 to pPhenological markers such as the timing of bud-break, female and male bloom times and bloom duration vary yearly depending on local temperatures and winter chilling. We found that the period of pollen shed lasted 25 to 30 days over three consecutive years in LO. In Missouri, bud break among 21 black walnut cultivars over four years varied from 26 to 47 days . Among-yBloom phenology , in general, was a poor predictor of mating pairs in LO. Paternal clones that shed pollen during the intermediate bloom period pollinated more seedlings compared to early and late blooming clones. Early and late trees, which rarely mated with each other, were both receptive to intermediate pollen and highlighted the importance of having surfeit receptive parents throughout the flowering period. We also noted early and late flowering clones were more receptive to wild pollen than intermediate clones. Knowing such dynamics would help improve the timing of supplemental pollen application, for example, by focusing on the early and late bloom period rather than the intermediate period.This is the first large-scale examination of molecular genotyping used to identify open-pollinated black walnut timber family paternity. Open-pollinated half-sib breeding of black walnut can be improved utilizing DNA SSR markers to identify pollen parents. We found that isolation from other black walnut led to 85% within-orchard pollination in contrast to 42% within-orchard pollination from our non-isolated orchard. Now that we have genotyped LO and VO in their entirety, we can determine the male parent of selections in other progeny tests derived from these two orchards. New black walnut timber seed orchards should consider having at least 40 parents and be isolated from other walnuts to create a “polymix-like” open pollinated population.While VO had many more parents than LO, (37 versus 15 clones), VO parents showed a slight yet significant level of inbreeding while LO parents did not. The difference likely results from the fact that VO parents were forward selections from progeny harvested from a single grafted clone bank. In contrast, LO parents were primarily first generation backward selections. As  point ouSince most pollination occurred within 50 m, future orchards could be planted with single ramets of clones completely randomized to ensure all parents can cross pollinate. Given the practical difficulties of artificially pollinating black walnut in the field, and the expense and resources required to grow large grafted seed parents in a pollen-free greenhouse, “breeding without breeding” using DNA markers, is an excellent and effective method for advancing black walnut timber breeding.S1 Table(XLSX)Click here for additional data file.


Amomum subulatum Roxburg), is an ancient spice native to North-Eastern India and Southeast Asia, which belongs to the family Zingiberaceae under the order Scitaminae. Large cardamom is mostly affected by a viral disease termed Chirke caused by Large Cardamom Chirke Virus (LCCV). These disease has spread due to drastic changes in the ecosystem, inadequate rain in dry months and absence of good agricultural practices by the farmers resulting in aphid infestations. In the present study, using HiSeq™ 2000 RNA sequencing technology transcriptome sequencing was performed for both control (disease not expressed) and diseased large cardamom leaf tissues. RNA-seq generated 77260968 (7.72 GB) and 72239708 (7.22 GB) paired raw reads for large cardamom control and diseased samples respectively. The raw data were submitted to the NCBI SRA database under the accession numbers SRX2529373 and SRX2529372 and the assembled transcriptomes were submitted to TSA under the accession numbers GIAV01000000 and GIAW01000000 for the control and diseased samples respectively. The raw reads were quality trimmed and assembled de novo using TRINITY assembler which created 156822 (control) and 148953 (diseased) contigs with N50 values 2107 (control) and 2182 (diseased). The data were used to identify the significantly differentially expressed genes between control and diseased samples.Large cardamom ( The data files were deposited at NCBI SRA database under project accession no. PRJNA369131. Information generated from the raw data and that of assembly are provided in The dataset contains raw sequencing data obtained through transcriptome sequencing of leaf samples of large cardamom (22.1Amomum subulatum Roxburg). Large cardamom chirke virus (LCCV) was not expressed in one of the samples which served as the control whereas the disease was expressed in the other sample. Leaf tissues from both sets were collected followed by immediate freezing in liquid nitrogen.Transcriptome sequencing was carried out in leaf samples of large cardamom (2.2RNA extraction was done using a modified protocol of the RNeasy Plant Mini Kit (Qiagen) and CTAB method  RNA inte2.3De novo transcriptome assembly was performed using the Trinity [Raw reads were first quality checked using the FastQC  tool and Trinity  assemble Trinity  and the  Trinity  to produ Trinity .2.4https://www.ncbi.nlm.nih.gov/nuccore/?term=chirke) and found only 4 sequences for chirke . These were aligned to both infected and control sequences using BLAST+ [Virus genome sequences were fetched from NCBI (2.5A total of 156822 transcripts were generated from the control sample while 148953 were generated from the diseased. While converting the transcripts into peptides the control sample generated 76913 peptide sequences while the treatment generated 74060. The obtained peptides were clustered for non-redundancy which resulted in 30498 unique peptides being generated from control compared to the 29512 that were generated from the diseased .


She later developed local post-radiation retroperitoneal fibrosis with resulting ureteric stenosis. Serial oncological follow ups with Temporary glucose hypermetabolism in denervated muscle has been described in small patient groups. The exact mechanism of this hypermetabolism has not yet been elucidated. One proposed mechanism is the immunohistochemically proven increase of certain cellular membrane proteins  in response to denervation. Another theory links the rise in metabolism to widespread apoptosis – an energy-consuming process. Hypermetabolism due to denervation can be important in an oncological context, because unexpected FDG uptake increase in regional skeletal muscles might lead to false-positive diagnoses of cancer recurrence or metastases [


U test to compare obese Versus nonobese groups. RESULTS/ANTICIPATED RESULTS: Obese children have lower scores in measures of affect recognition than healthy weight children. They also showed higher median scores in both salivary and plasma IL-6 and TNF-α. DISCUSSION/SIGNIFICANCE OF IMPACT: Although no statistical differences were found among groups in either measurement, these preliminary data based on the initial recruitment suggest that children with higher body mass index may have difficulties in emotional processing. More data will be available after completing recruitment to determine if the association between obesity and affect recognition is significant and if it is mediated by inflammation.OBJECTIVES/SPECIFIC AIMS: Childhood obesity has become an issue of some concern worldwide. Some reviews and a recent study in adults have indicated that obesity-related inflammatory responses produce brain damage. However, studies exploring associations between inflammation and executive functions in children are overlooked. Therefore, the objective of this cross-sectional study is to determine whether difficulties in executive functions and emotional processing are associated with obesity and inflammation. METHODS/STUDY POPULATION: We have recruited 12 of a total of 60 children aged 6–8 years old. They have completed the NIH Toolbox Cognition Battery and the NEPSY II Affect Recognition tests. Samples of plasma and saliva were collected to quantify inflammatory biomarkers cytokines (IL-6 and TNF-α) assay by Luminex procedure. We performed descriptive analysis and Mann-Whitney


Giant retinal tear is usually challenging among retinal detachment with recurrent rate up to 45%. Here we presented a case of giant retinal tear being treated by microincision vitrectomy and retinal tacks fixation.A 53-year-old male presented to our hospital with blurred vision of his right eye for one week with floaters and obscured sensation over nasal visual field. Ocular examination showed a 120 degree giant tear with large inverted flap and retinal detachment of his right eye. The BCVA was only naming digit. Under the impression of giant retinal tear with retinal detachment, 23-gauge pars plana vitrectomy were performed using Constellation high speed vitrectomy system and Topcon non-contact wide angle viewing system. During surgery, the vitreous was removed and perfluorocarbon liquids (PFCL) was injected to help unfolding the large inverted retinal flap. Three retinal tacks were applied to help fixating the large inverted retinal flap. Then, fluid-gas exchange, endolaser photocoagulation and intraocular silicone oil tamponade were performed as well. Initial reattachment of his right retina was achieved and his best corrected visual acuity improved to 0.3 of his right eye postoperatively. There was no recurrent retinal detachment during follow up period of 19 months.Primary microincision vitrectomy using wide-angle viewing system with intraoperative perfluorocarbon liquids (PFCL) assistant, retinal tacks fixation and intraocular silicone oil tamponade appears to be safe and feasible for managing giant retinal tear with retinal detachment. Giant retinal tear (GRT) is usually challenging among retinal detachment with recurrent rate up to 45% . In ordeA 53-year-old male denied past medical and trauma history presented to our hospital with blurred vision of his right eye for one week with floaters and obscured sensation over nasal visual field. Ocular examination showed a 120 degree retinal tear (from 7 to 11 o’clock) with large inverted rigid flap and retinal detachment from 6 to 12 o’clock with macula-off in his right eye Fig. . The graPrevious studies had reported that primary success rate for GRT treated by 20-gauge PPV using PFCL assistant without scleral buckling can achieve over 90% . AnotherAlthough our report has limitation of small case number and relatively short follow-up period, our findings indicate that MIVS is a safe, effective and feasible method for managing GRT. In addition, in cases with large, inverted and rigid retinal flap, retinal tacks for stabilizing retinal flap might be inevitable to prevent retinal redetachment.


Percutaneous trans-splenic portal vein recanalization (PVR) has been reported for facilitation of transjugular intrahepatic portosystemic shunts (TIPS), however has not been applied to patients undergoing direct intrahepatic portosystemic shunt (DIPS). We report the utilization of trans-splenic-PVR with DIPS creation in a patient with chronic portal and hepatic vein occlusions undergoing liver transplantation evaluation.A 48-year-old male with decompensated alcoholic cirrhosis complicated by refractory ascites, hepatic encephalopathy, and variceal bleeding underwent CT that demonstrated chronic occlusion of the hepatic veins (HV), extrahepatic portal vein (PV), and superior mesenteric vein (SMV). Due to failed attempts at TIPS at outside institutions, interventional radiology was consulted for portal vein recanalization (PVR) with TIPS to treat the portal hypertension and ascites and also facilitate an end-to-end PV anastomosis at transplantation. After an initial hepatic venogram confirmed chronic HV occlusion, a DIPS with trans-splenic PVR was planned. The splenic vein was accessed under sonographic guidance using a micropuncture set and subsequently upsized to a 6 French sheath over a stiff guidewire. A splenic venogram via this access confirmed occlusion of the PV with drainage of the splenic vein (SV) through gastric varices. The thrombosed PV was then recanalized and angioplastied to restore PV flow via the transsplenic approach. A transjugular liver access kit with a modified 21-gauge needle was advanced into the IVC through the internal jugular vein (IJV) sheath and directed towards the target snare in PV. The needle was used to subsequently puncture the PV through the caudate lobe and facilitate placement of a wire into the SV. The initial portosystemic gradient (PSG) was 20 mmHg. The IJV sheath was advanced through the hepatic parenchymal tract into the main-PV and a stent-graft was placed across the main PV and into the IVC. A portal venogram demonstrated brisk blood flow through the DIPS, resolution of varices and a PSG of 8 mmHg. One month after the procedure, the patient had a significant reduction in ascites and MELD-NA score. Patient is currently listed and awaiting transplantation.In the setting of chronically occluded portal and hepatic veins, trans-splenic PVR DIPS may serve as an effective bridge to liver transplantation by facilitating an end to end portal vein anastomosis. The presence of hepatic vein (HV) occlusion poses challenges for patients with decompensated liver cirrhosis being considered for transjugular intrahepatic portosystemic shunts (TIPS). Such cases can be treated by recanalization of HVs with angioplasty and/or stenting prior to performing TIPS. Alternatively, direct intrahepatic portosystemic shunt (DIPS) creation from the IVC to portal vein can also be considered. DIPS has been shown in literature to have equivalent five-year survival rates and clinical outcomes to HV recanalization with TIPS in patients with Budd-Chiari syndrome . Prior studies have reported techniques for accessing the PV including fluoroscopic “gun sight”  interventional radiology was consulted for portal vein reconstruction in combination with TIPS to alleviate portal hypertension and ascites and to facilitate transplantation allowing direct portal- portal anastomosis. After a hepatic venogram confirmed chronic hepatic vein occlusion, a multidisciplinary discussion ensued during which time an attempt at DIPS with trans-splenic PVR was decided upon. The patient was scheduled for the procedure with interventional radiology under general anesthesia. Ultrasound guidance was used to allow two 10 French sheaths to be placed into the intra-hepatic IVC via the right internal jugular vein (IJV). A percutaneous trans-splenic access into the main splenic vein was subsequently obtained by puncturing a peripheral splenic venous branch with a micropuncture set  under sonographic guidance. The access was exchanged for a 6 Fr sheath over a stiff guidewire. A splenic venogram was performed, confirming chronic occlusion of the PV with primary drainage of the SV through gastric varices . After the PV was reconstructed, a snare was then placed into the main PV and used as a target for DIPS creation. A Roche-Uchida transjugular liver access kit with a modified 65-in. 21-gauge needle was advanced into the IVC through the sheath within the IJV and directed towards the PV. An intravascular echo probe was advanced into the IVC through the other IJV sheath and used for real time sonographic guidance of the needle puncture from the IVC to the snare in the reconstructed PV. The needle was then used to subsequently puncture the PV through the caudate lobe and facilitate placement of a wire into the SV , and distal superior mesenteric vein (SMV). ces Fig. . Next, tig. Fig. . After tTrans-splenic PVR has been described as an effective method for restoring patency to chronically thrombosed PVs in patients with decompensated liver failure awaiting liver transplant. (Thornburg et al.


Organotellurium and organoselenium compounds catalyze the oxidation of halide salts to hypohalous acids using H2O2. When sequestered into xerogel monoliths, the xerogel-chalcogenide combinations have demonstrated increased catalytic activity relative to the organochalcogen compound alone in solution for the oxidation of halide salts to hypohalous acids with H2O2. Diorganotellurides, diorganoselenides, and diorganodiselenides bearing triethoxysilane functionalities were sequestered into xerogel monoliths and their catalytic activity and longevity were investigated. The longevity of the catalyst-xerogel combinations was examined by isolating and recycling the catalyst-xerogel combination. It was found tellurium-containing catalyst 3 and selenium-containing catalyst 8 maintained their catalytic activity through three recycling trials and adding electron-donating substituents to catalyst 3 also increased the catalytic rate. The presence of organotellurium and organoselenium groups in the +4 oxidation state was determined by X-ray photoelectron spectroscopy.While H These catalysts will likely be based on telluride or seleninic acid functionality sequestered in xerogels tailored to direct the negatively charged halide ions to the active site.


Thirty-nine years old patient presented to the emergency department with left-sided chest pain for four months and 4kg weight loss through the same period. Physical examination showed bulging of the left scapula which is tender to touch and decreased breath sounds on the left side. Chest X-ray done in ED showed opaque left hemithorax with rib resections. A CT was done showing a heterogeneous mass shadow with a solid and cystic component associated with linear calcifications causing a near total collapse of the left lung with shifting of the mediastinum to the right side. Similar findings were seen on an MRI. A PET-CT scan showed hypermetabolic complex mass occupying most of the left hemithorax infiltrating the back muscles bulging to the subcutaneous fat with Irregular thick active gastric mucosa as well and intense large colon activity. A biopsy of the lesion and immunohistochemical studies were done and showed malignant diffuse spindle cell neoplasm positive for CD56, CD99, Bcl2 CKAE1/AE3, H. Caldesmon and EMA. The patient was started on IFOS/DOX chemotherapy regimen and completed three cycles uneventfully.


OBJECTIVES/SPECIFIC AIMS: Voiding postponement is common cause of LUT dysfunction in which children void infrequently with large volumes. This condition is modeled in mice that are subjected to social stress who show decreased voiding frequency and increased voided volumes along with increases in corticotropin-releasing hormone (CRH) expression in Barrington’s nucleus (BN) . Optogenetics is a technique to selectively stimulate cells or neurons of interest via light activated channel receptors . Here we examined the effects of optogenetic manipulation of CRH BN neurons on the in vivo voiding phenotype and urodynamics in awake mice. We hypothesized that stimulating these neurons at higher frequencies (10–50 Hz) would lead to CRH-dependent alterations in voiding phenotype . RESULTS/ANTICIPATED RESULTS: Fiberoptic stimulation (470 nm at 25 and 50 Hz) produced a significant rise in the intermicturition interval, bladder capacities and increased void volumes. This effect was especially pronounced in females in whom bladder capacity and intermicturition interval more than doubled at 50 Hz stimulation. Fluoroscopic images confirmed complete bladder emptying with each void. The increased bladder capacity at higher frequencies (25 and 50 Hz) was CRH-dependent as injection of a CRH antagonist (NBI 30775) blocked the optogenetic effect. Control non-double mice showed no effects from optogenetic stimulation. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results suggest that optogenetic stimulation of CRH-expressing neurons in BN at high frequency (25 and 50 Hz) inhibits micturition and recapitulates the voiding phenotype seen in socially stressed mice . Lower frequencies of optogenetic stimulation (2 and 10 Hz) had no effects on cystometry parameters or voiding phenotype. In addition, females had a greater response to optogenetic stimulation compared with males with larger bladder capacities and longer intermicturition intervals. The changes in voiding phenotype seen were CRH dependent as blockage of the CRH receptor prevented changes in cystometry parameters with optogenetic stimulation. Further elucidation of these and other neural subpopulations in BN are warranted to understand micturition and how it may be manipulated in disease states such as voiding postponement and acute urinary retention.


Virtually complete nitrification of the available ammonium in soil and nitrification activity in the forest floor are important factors predisposing forests in the San Bernardino Mountains of southern California to nitrogen (N) saturation. As a result, inorganic N in the soil solution is dominated by nitrate. High nitrification rates also generate elevated nitric oxide (NO) emissions from soil. High-base cation saturation of these soils means that soil calcium depletion or effects associated with soil acidification are not an immediate risk for forest health as has been postulated for mesic forests in the eastern U.S. Physiological disturbance  of ozone-sensitive ponderosa pine trees exposed to high N deposition and high ozone levels appear to be the greater threat to forest sustainability. However, N deposition appears to offset the aboveground growth depression effects of ozone exposure. High nitrification activity reported for many western ecosystems suggests that with chronic N inputs these systems are prone to N saturation and hydrologic and gaseous losses of N. High runoff during the winter wet season in California forests under a Mediterranean climate may further predispose these watersheds to high nitrate leachate losses. After 4 years of N fertilization at a severely N saturated site in the San Bernardino Mountains, bole growth unexpectedly increased. Reduced C allocation below- ground at this site, presumably in response to ozone or N or both pollutants, may enhance the bole growth response to added N.


In the final publication of “A micro X-ray computed tomography dataset of South African hermit crabs (Crustacea: Decapoda: Anomura: Paguroidea) containing scans of two rare specimens and three recently described species,” by Jannes Landschoff et al., many copyediting errors were erroneously published. These errors have been corrected throughout the article to improve clarity. No substantial revisions have been made to the paper's research.The Publisher regrets this error.


The recently published manuscript entitled “Epigenetically Altered T CellsContribute to Lupus Flares” summarizes recent advances in our understanding ofhow the environment alters the immune system to cause flares of systemic lupuserythematosus (SLE) in genetically predisposed people, and why it affects womenapproximately 9 times more often than men . SLEis The manuscript summarizes how in vitro studies on the epigenetic regulation ofgene expression in T lymphocytes can alter their function to cause lupus flares.Briefly, each nucleated cell in the human body contains approximately 3 meters of DNA,tightly packaged in the nucleus as chromatin, consisting of the DNA wrapped around acore of 8 histone proteins. The tightly packaged DNA is inaccessible to thetranscription factors, and the chromatin structure must be locally “openedup” to allow the relevant transcription factors to bind and allow mRNA synthesisto proceed. The cell promotes the condensation of DNA into a transcriptionallyrepressive configuration by methylating dC bases located in CpG pairs. This allows thebinding of methylcytosine binding proteins to the methylated regions, which then attractthe chromatin inactivation complex which promotes the condensation of the DNA into atightly packaged chromatin structure. However, the DNA methylation patterns must bereplicated accurately every time a cell divides, and it is at this point where DNAmethylation becomes sensitive to environmental influences. Inhibiting methylation of thenewly synthesized DNA strand allows expression of those genes previously suppressed byDNA methylation, and for which the cell expresses the necessary transcriptionfactors.+ T cells with thecovalent DNA methyltransferase inhibitor 5-azacytidine (5-azaC) converts antigenspecific CD4+ T cells into autoreactive cells which respond to self class IIMHC molecules on antigen presenting cells without added antigen, thus becomingautoreactive [+ murine T cells with 5-azacytidine (5-azaC) then injecting thetreated cells into syngeneic recipients. Mice receiving the treated, but not untreated Tcells developed lupus-like autoimmunity [+ T cells were found in lupuspatients, and the number of the epigenetically altered cells was directly proportionalto flare severity. In addition, the two drugs which cause drug-induced lupus mostfrequently, procainamide and hydralazine, were found to be DNA methylation inhibitors[+ T cells from patients with active lupus.Together the experiments indicate a mechanism by which environmental agents that causeinflammation can trigger lupus flares.Early studies demonstrated that treating CD4reactive . The pat


The subpleural arteriovenous shunts that are hallmarks of hepatopulmonary syndrome may cause stroke. A 76-year-old-woman was admitted for right hemiparesis. Her medical history included cirrhosis with portal hypertension known for 14 years. Her heart rhythm was regular, with a heart rate of 65 beats per minute. Brain MRI demonstrated an acute ischemic lesion in the left part of the pons. A brain cortical atrophic sequela was also seen in the right occipital lobe. Vascular arteriosclerosis and any cardiac cause of stroke were excluded by dedicated imaging. During the neurological revalidation, she developed a platypnea. SpO2 was <90%. Clinical examination demonstrated diffuse spider naevi predominantly on the abdominal wall. Chest CT angiography ruled out pulmonary embolism. MIP reconstructions in lung window showed dilated pulmonary vessels abutting the pleura on the non-dependent part of the right lung (Figure HPS is defined by a triad including liver disease regardless of type and severity, oxygenation impairment and intrapulmonary vascular dilatation resulting in right-to-left shunting . Contras


Dementia family caregivers are routinely enlisted as proxy assessors of care recipient quality of life (QOL). Proxy assessment is not ideal because proxy assessments differ systematically from self-assessments and the assessment process can elicit negative affect from family caregivers. Prompting adoption of the care recipient’s perspective can enhance assessment congruence and may improve the emotional experience for assessors. This study explored family caregivers’ cognitive and affective experiences during QOL proxy assessments made from both their own and care recipients’ perspectives. Thirty-six dementia family caregivers were recruited from senior service agencies. Subjects completed the Quality of Life-Alzheimer Disease (QOL-AD), Caregiver Version using standard instructions to assess QOL across thirteen domains of their care recipient’s life without specifying the perspective to be used. Subjects were next asked to repeat the QOL-AD with instructions to adopt the perspective of their care recipient, as they imagined it to be. Subjects were then interviewed about what they thought and felt during each proxy assessment experience. Content analysis indicated that spontaneous perspective shifts and response shifts frequently occurred. Most subjects (91.7%) reported changed thinking for one or more QOL-AD domains when they were prompted to switch perspectives. Over half (61.12%) reported changed affect when switching perspectives and 90.9% of those experiencing changed affect reported affective improvement. Little or no affective change was reported by 38.89%. Findings suggest awareness of perspective can enhance clinical interpretation of proxy assessed QOL and can inform clinical response to dementia family caregivers who experience negative emotions while proxy reporting QOL.


Management of cerebrospinal fluid (CSF) leak during minimally invasive lumbar tubular microdiscectomy poses challenges unique to the surgical approach. Primary repair can be limited via tubular retractor systems, and onlay graft and dural sealant are often the treatment of choice intraoperatively. Postoperative persistent CSF leak may lead to intracranial hypotension (IH) and positional headaches. Early epidural blood patch (EBP) efficacy in the treatment of spinal CSF leaks of both spontaneous and iatrogenic origin is well-established in numerous studies. However, there is no consensus on treatment of persistent IH symptoms for patients undergoing lumbar tubular microdiscectomy. We describe the clinical courses of two patients who were treated with early EBP for IH symptoms following CSF leak during tubular microdiscectomy. Both patients underwent intraoperative repair with onlay autologous tissue graft followed by dural sealant after discectomy was completed without evidence of pseudomeningocele, but they developed postoperative positional headaches and presumed IH. Both patients received an early EBP with an immediate and complete resolution of positional headaches sparing them reoperation and/or lumbar drainage. EBP should be considered as a first-line treatment to treat postoperative IH symptoms without pseudomeningocele after iatrogenic CSF leak during tubular microdiscectomy. Tubular microdiscectomy has become a widespread method of treating lumbar disc herniation due to its minimally invasive approach and favorable benefit and risk profile . A rare Case 1A 34-year-old female presented with intractable left leg radiculopathy. She reported moderate pain in her lower back with pain and numbness radiating down the left S1 distribution. She had no motor weakness or altered bowel or bladder function. Magnetic resonance imaging (MRI) demonstrated L5-S1 disc herniation compressing the S1 nerve root (Figure Case 2A 49-year-old male presented with intractable and progressive pain in the lower back and left leg. Additionally, he had weakness of left plantar flexion. MRI revealed a large disc herniation at L5-S1 with compression of the left S1 nerve root Figure . The patThe use of transmuscular tubular retractor systems represents a safe and efficacious surgical approach for the treatment of lumbar disc herniation ,2,7. CSFIn our cases, the CSF leaks were intraoperatively sealed with autologous tissue and a dural sealant. However, both patients reported significant spinal headaches postoperatively indicative of IH. Although the precise diagnosis of IH requires a brain or spinal MRI, orthostatic headache is a classical symptom of IH . If imagThere are several complications associated with an EBP. For instance, paresthesia, neck ache, facial nerve palsy, and lumbovertebral syndrome have been reported after the procedure ,12. AddiWe present our cases to outline a paradigm of using EBP as management for postoperative IH symptoms in patients with iatrogenic CSF leak associated with tubular lumbar microdiscectomy and without pseudomeningocele. EBP is a well-documented treatment for CSF leaks of both spontaneous and iatrogenic etiologies. In a study of 30 patients with spontaneous CSF leak, a complete cure was obtained in 77% of patients after application of EBP . In anotWe have demonstrated that the efficacy of EBP extends to the treatment of the postoperative sequelae of CSF leak associated with tubular microdiscectomy. In the absence of other complications such as pseudomeningocele, the application of EBP complements well the minimally invasive methodology of tubular spinal surgery, which may obviate the need for more aggressive treatments for CSF leak such as lumbar drain and exploratory reoperation. Patients may benefit from future studies examining the success rate of intraoperative EBP, which may enable patients to avoid re-exploration, and consequently an extended hospital stay and increased risk of infection.


A 14-year-old female patient was referred to our radiology department for evaluation of right hypoacousia. Unenhanced Computed Tomography (CT) of the temporal bones showed a 15 mm hypodense mass infiltrating the right cerebellopontine angle (CPA) and the internal auditory canal (IAC)  performed for better evaluation showed homogeneous high T1 signal of the lesion with signal drop on fat-saturated sequence, thus confirming the fatty composition of the mass  since CPA lipoma is considered a developmental disorder. Surgery should only be considered for symptomatic patients in whom conservative treatment has failed given that lipoma is a non-neoplasic slowly growing lesion closely related to nervous structures .


A wide range of neurosurgical implants, cranioplasty materials and catheters have been developed to treat a variety of intracranial disorders. Interpretation of postoperative imaging can be challenging and confounded by postoperative changes and implant-related complications. Review of recent literature suggested that there is a paucity of data on postoperative cranial implant-related complications.If not addressed appropriately in a timely manner, these complications may cause a delay in the patient’s treatment with subsequent prolongation of hospital stay. It is therefore paramount for clinicians and radiologists to be aware of the appearance of these implant-related complications on imaging during postoperative surveillance. Various neurosurgical implants and catheters have been developed to treat a variety of intracranial pathologies. Interpretation of postoperative imaging can be challenging due to postoperative changes and implant-related complications. Postoperative complications can be divided according to the period of occurrence: Immediate (<6 hours), early (between 6–72 hours) or late (>72 hours) following surgery . In thisA burr hole is created in the skull for evacuation of subdural hemorrhage or stereotactic tumor biopsy. After surgery, the burr hole can be repaired by applying patient’s autologous bone dust or titanium cover plates to prevent sinking of the overlying skin.Craniotomy is an operation for temporary removal of a bone flap to expose the underlying brain. Titanium CranioFix (Aesculap) plates are widely used to fix the bone flap to the cranium after craniotomy. Rarely, late complication may occur due to skin erosion overlying these plates. Patients with poorly vascularized or fragile skin are particularly vulnerable, risking infections such as meningitis and subdural empyema.Craniectomy is a similar surgical approach as craniotomy except that the skull flap is not replaced after surgery Figure . It is cThe material used for cranioplasty are either patient’s autologous bone flap, titanium mesh Figures  and 4, cThe most commonly used acrylic resin is methylmethacrylate (MMA), which is prefabricated and created with computer-aided 3D CT data of the skull defect. Acrylic cranioplasty may appear radiolucent on CT and contain gas bubbles formed during exothermic polymerization hence, it should not be mistaken for infection Figure  and 3B. Immediate postoperative complications following cranioplasties are intracranial hemorrhages and infections Figure . StaphylThese are among the most common cranial implanted materials. Immediate postoperative complications are hemorrhages along the shunt tracks Figures  and 6A pEarly complications are mechanical dysfunctions from shunt obstruction or disconnection leading to hydrocephalus. Dysfunctions of programmable shunt valves may necessitate adjustment of the valve threshold. Over-shunting of the cerebrospinal fluid (CSF) may result in slit-like ventricles and intracranial hypotension Figure . By adjuDBS is inserted to treat medically intractable Parkinson disease. The tips of DBS electrodes are ideally positioned in the subthalamic nuclei. The electrodes are subsequently tunneled under the skin to the chest to be connected to a battery powered internal pulse generator (IPG) in a subcutaneous pouch Figure . IntermeThe most common hardware-related complications are infections (5.12%), electrode breakage 0.94%), lead migration or misplacement (1.6%), and stricture formation (1.9%), fracture or failure of the lead or other parts of the implant , IPG malfunctions (1.1%), and skin erosions (0.5%) [3%, lead mEndovascular detachable coils have been widely used for treatment of intracranial aneurysms while liquid agents (include N-butyl cyanoacrylate and Onyx) are being used for treatment of arteriovenous malformations. Artifacts from these embolization materials and clips may pose some challenges during postoperative surveillance.Postoperative imaging can be challenging and confounded by postoperative changes and implant-related complications. Awareness of these complications are paramount to clinicians and radiologists during postoperative surveillance.


Fatty acid biosynthesis enzymes (Fab enzyme) are important targets for anti-malarial drug development. The present study describes thetoxicity screening of designed novel analogues which inhibit FabI enzyme regulation, a protein with multifunctional property. Newanalogues were prepared using ChemDraw Ultra 10 Software and converted into 3D PDB structure format for binding studies with FabI(PDB ID: 4IGE). Further Lipinski's rule of FIVE and ADMET profiling for toxicity prediction has been performed on the designedanalogues. The result shows that ISN-23 is potential analogue exhibiting inhibition at the active site of FabI enzyme with good bindingfeatures. Malaria is one of the most prominent tropical parasitic diseases Available drugs respond to three classes of compounds: (1) arylaminoalcohol compounds eg. quinine 2) antifolates dihydrofolatereductase inhibitors like pyrimethamine, and 3) Derivatives ofartemisinin. Artemisinin was first isolated in 1970 by Chinesescientists from Artemisia annua  antifola DerivatiThe anti-malarial effect of fatty acids has propelled towardsdeliberation in the past but the realization that fatty acidsthemselves might inhibit the fatty acid biosynthetic machinery ofthe parasite P. falciparum has only been presently examined to makestrategy towards combating of parasite. It is known that thatantimalarial property of n3 and n6 fatty acids which werepolyunsaturated in nature postulates the in-vitro invasion of intraerythrocytic forms of P. falciparum The structures of enzymes (FabI) involved in Plasmodium falciparumregulation was obtained from Protein Data Bank (PDB ID: 4IGE).Meta pocket 2.0 Finder was used for several separate procedures toperform active/ binding site prediction . To miniThe 2D-structure of Isoniazid and its 23 analogues were designedby using ACD lab software extension ChemDraw in MDL .molformat.The Lipinski rule of FIVE predicts the pharmacological, biologicaland ADME exercise of the particular compound and also predicting itspotentiality to an orally active drug in humans Using Pre ADMET online server Results show that Isoniazid drug inhibit the fabI enzyme regulationduring the erythrocytic phase of parasitic incubation. Hence, theactive site of FabI enzyme was predicted. Thus, different aminoacids residues of the enzymes were found out using meta-pocket2.0 Finder . The resVarious designed analogues or compounds are associated withknown anti-malarial drugs (isoniazid standard) by clocking FabIenzyme in the treatment of malaria caused by P. falciparum. Wedocument the predicted binding of 23 designed analogues with theFabI enzyme and show that ISN-23 analogue have the best bindingfeatures with FabI enzyme for further in vitro and in vivoconsideration.Authors declare no conflict of interest.


Here we present a case of maternal-fetal hemorrhage characterized by intermittently reassuring fetal testing. Additional testing performed with ultrasound, including middle cerebral artery (MCA) doppler waveforms, confirmed fetal hemorrhage followed by emergent cesarean section. This report highlights the acute usage of MCA dopplers in obstetric decision making. The Newborn required transfusion but otherwise recovered well. MCA may be a useful tool for fetal assessment in Labor and Delivery units. Patient is a 32-year-old G1P0 at 33 weeks and 1 day gestation that was admitted to the hospital for further evaluation of decreased fetal movement for the two days. Pregnancy was uncomplicated prior to this admission. The patient was started on continuous fetal monitoring along with intravenous fluids. The patient was found to have alternating category II and III tracing . Given tFetal-maternal hemorrhage (FMH) is the presence of fetal blood cells in the maternal circulation prior to the time of delivery. Under normal circumstances, maternal and fetal circulations are kept separate from direct exchange by the placental membrane composed of syncytiotrophoblasts and cytotrophoblasts . GaseousMCA doppler ultrasonography is often used as a screening tool for chronic fetal anemia such as parvo B19 infection or twin anemia-polycythemia syndrome and is not routinely used on labor and delivery units . InpatieWhile fetal heart rate monitoring continues to be the initial assessment of fetal wellbeing, advanced supplemental ultrasonography may provide additional tools for clinical management of complex cases or extreme prematurity. In addition, a category III tracing is indicative of fetal acidemia. Ultrasonography offers a non-invasive method for assessing fetal well-being when compared to amniocentesis or cordocentesis . We unco


Accumulation of protein aggregates are a common pathology in many neurodegenerative disorders. This accumulation may be due to a function decline in the protein homeostasis network known to occur during the aging process. Small heat shock proteins are a class of molecular chaperones that assist in protein folding and ameliorates the degradation activity of the proteasome and autolysosome thereby decreasing disease-associated aggregates. Prior work in rodents and C. elegans has shown expression levels of the small heat shock protein 25 (HSP25) correlates with maximum lifespan potential. Increased levels of HSP25 extends lifespan in a transgenic C. elegans model. This lifespan extension is dependent on skn-1 with evidence suggesting an enrichment in several skn-1-related pathways, such as lysosomal genes. Concomitantly, proteasome activity declines while autolysosome activity increases. This observation might suggest a switch from proteasome degradation to autophagy as the main driver of protein degradation in C. elegans in this transgenic model. To investigate if a reduction of proteasome function and elevated lysosomal gene activation during aging and under proteotoxic stress are modulated by HSP25 we have crossed our HSP25-transgenic worm with an aggregating and non-aggregating tau worm model. This work will elucidate a possible mechanism that explains the change in the protein degradation response pathways potentially modulated by HSP25 during increased protein misfolding.


A 39-year-old male ex-smoker gave a history of exertional chest pain ever since he suffered a respiratory tract infection. Clinical examination, electrocardiogram and echocardiography were normal and he was referred for a cardiac CT scan to assess coronary artery calcification and patency. The scan demonstrated incidental fistulae between the right internal mammary artery and the right coronary artery, and the left internal mammary artery and the left anterior descending artery. A 39-year-old male ex-smoker gave a history of exertional chest pain ever since he suffered a respiratory tract infection. Similar symptoms after a previous chest infection a few years ago had cleared spontaneously. He was reviewed in the respiratory clinic and found to have no lung disease and then referred to cardiology. Clinical examination, electrocardiogram, echocardiography and chest radiograph  were norCT scan with volume-rendered and axial curved maximum intensity projection techniques elegantly demonstrated the fistulous communication (white and blue block arrows) between the right internal mammary artery (white chevron) and mid-right coronary artery (thin white arrow) and left internal mammary artery (thin blue chevron) and mid left anterior descending artery (thin blue arrow) . The patSupplementary Video A). Coronary angiography confirmed patent coronary arteries and the presence of the fistulae (Supplementary Videos B and C).A subsequent stress cardiac MR scan demonstrated normal cardiac function and no inducible perfusion defects  or pulmonary circulation (coronary arteriovenous fistula).The patient’s symptoms resolved spontaneously and it was felt that his fistulae were not of functional significance. He was reassured and discharged from regular review.Congenital coronary fistulae are rare and do not necessarily have functional significance. Common communications are to the cardiac chambers or pulmonary circulation.Fistulae involving the mammary arteries may be congenital or secondary to intervention.Informed consent to publish this case (including images and data) was obtained and is held on record.


The present study is to highlight the challenges in managing cervical spine injuries in toddlers (less than 4 years of age) without neurological deficit. Cases of unilateral cervical C4–C5 facet dislocation in toddlers are very rare.A 3-year-old girl suffered cervical spine injury after a motor vehicle collision with unilateral C4–C5 facet dislocation without neurological deficit. Magnetic resonance imaging (MRI) showed no spinal cord injury, Frankel grade E. Initial management was cervical spine protection. Definite treatment and complication were discussed with the patient’s parents before closed reduction maneuver with minerva cast was applied under sedation. The patient showed no complication after closed reduction and the cervical spine had aligned well in radiographs. The minerva cast was removed at 8 weeks, at which point neck muscle stretching rehabilitation program started. At one-year follow up, the child was asymptomatic, had full active cervical motion and good function. In radiographs, the cervical spine had normal alignment and was healed.Unilateral cervical facet dislocation in toddlers is very rare. Closed reduction maneuver and the minerva cast applied were optional in this case. The parents were highly satisfied with the effective treatment and outcome. Cervical spinal cord injury without radiographic abnormalities (SCIWORA) is more commonly seen in the pediatric age group than in adults. Incidences have been reported as 13–19% of spinal injuries in children . HoweverA 3-year-old girl suffered cervical spine injury after a motor vehicle collision while sitting in the car without wearing a seatbelt. ATLS protocol was performed on the patient at a local hospital and she was referred to the emergency department at author’s hospital within 12 h of the injury. The pediatric surgeon and our orthopedic team re-evaluated that the status of the patient showed head injury with alteration of consciousness, intubation, cervical spine protection with hard collar and first rib fracture without pneumohemothorax. The emergency radiographs x-ray and CT brain including cervical spine showed no intracerebral hemorrhage but the cervical spine suffered unilateral cervical C4–C5 facet dislocation. Radiographic features showed anterior dislocation of the affected vertebral body less than the vertebral body in anterior posterior diameter, discordant rotation above and below involved level, facet within intervertebral foramen on oblique view, widening of the disk space and “Bat wing sign” appearance of the overriding facet  which is a very rare condition. The most common causes of pediatric subaxial servical spine injury are motor vehicle accidents (50%) and sports-related activities (25%) [Knowledge of the anatomical characteristics of pediatric unilateral cervical facet dislocation is very important. Three studies , 9, 10 rIn our case, the purpose was to highlight the challenges in managing cervical spine injuries in toddlers without neurological deficit. The authors described the management of an acute pediatric unilateral facet dislocation by manual reduction and stabilization with minerva cast. The patient was asymptomatic, had full active cervical motion and good function. The cervical spine showed normal alignment and had healed in radiographs at one-year follow up. Unilateral cervical facet dislocation without neurological deficit in toddlers is very rare. The closed reduction maneuver and applied minerva cast is optional for treatment if successful manual reduction and stabilization with cervical orthosis has a good clinical outcome.


Phaseolus vulgaris L.). This study evaluated the genetic diversity and symbiotic nitrogen fixation of bacteria nodulating common bean in soils of Western Kenya. The genetic diversity was determined using 16S rRNA gene partial sequences while BNF was estimated in a greenhouse experiment. The sequences of the native isolates were closely affiliated with members from the genera Pantoea, Klebsiella, Rhizobium, Enterobacter and Bacillus. These results show that apart from rhizobia, there are non-rhizobial strains in the nodules of common bean. The symbiotic efficiency (SE) of native isolates varied and exhibited comparable or superior BNF compared to the local commercial inoculants (CIAT 899 and Strain 446). Isolates  recorded equal or significantly higher SE (p < 0.05) compared to N supplemented treatments. The results demonstrate the presence of genetic diversity of native bacteria nodulating bean that are effective in N fixation. These elite bacterial strains should be exploited as candidates for the development of Phaseolus vulgaris inoculants.Biological nitrogen fixation (BNF) in legumes plays a critical role in improving soil fertility. Despite this vital role, there is limited information on the genetic diversity and BNF of bacteria nodulating common bean ( Phaseolus vulgaris) is one of the most important legumes in the human diet and serves as a significant source of proteins  and KSM-011 [KP137106]) had >99% sequence identity with members of the genus Enterobacter while the other remaining two (MMUST-001 [KP027686] and MMUST-007 [KP137109]) had >99% sequence similarity with members of the genus Pantoea. The isolates that belonged to the three genera  formed one major cluster supported with a bootstrap value of 100% (Klebsiella variicola strain ALK036 (KC456523) and Klebsiella sp. N28 (KP410798). Isolates (KSM-001 and KSM-011) had a 100% sequence similarity with Enterobacter hormaechei strain D40 [KM019812]. Two isolates (MMUST-001 and MMUST-007) formed a sub-cluster with Pantoea dispersa [KM019887] supported with a bootstrap value of 96%  formed a single sub-cluster supported with a bootstrap value of 99% and this sub-cluster was affiliated with strains of Rhizobium tropici. Five isolates  formed a sub-cluster (Rhizobium cluster) supported with a bootstrap value of 100% and was affiliated to strains belonging to Rhizobium leguminosarum  formed a major cluster with several species belonging to the genus Bacillus. This was supported by a bootstrap value of 100%. These two isolates were affiliated with Bacillus aryabhattai [MF109128] and Bacillus megaterium [KY31279] with ≥99% sequence identity. The evolutionary relationship estimated using matrix pairwise genetic distances for the 16S rRNA partial gene sequences indicated that the isolates were closely related (Bacillus (KSM 007[KP027678]) and Pantoea (MMUST 001[KP027686]). Similar evolutionary distances were observed between isolates (KSM 007[KP027678]) and (KSM 001[KP027682]).The PCR amplification of 16S rRNA genes of 25 selected isolates produced a single band of approximately 1500 bp. The sequences were deposited in the Genebank and assigned accessions numbers . Compari of 100% . Isolatee of 96% . A total related . The lonp < 0.05) effective in N fixation compared to the reference strains (CIAT 899 and Strain 446). Similarly, CIAT 899 recorded signifcantly lower SE (p < 0.05) compared to all the isolates from Kisumu county  and Klebsiella sp. Gad1 (KJ940119) and have previously been isolated from soil and nodules, respectively. Nodulation is considered as a confirmatory test for bacteria nodulating legumes (BNL). Several authors have demonstrated that no bacterial isolate can be regarded as BNL until its identity has been confirmed through plant infection test on an appropriate host crop  and MMUST-002 [KP027689]) and were considered bean nodulating bacteria. The two isolates that failed to initiate nodulation were closely affiliated with ost crop , 48. Noto be BNL . Failureo be BNL . Our resa g58 KM0887 and Ko be BNL .P. vulgaris in soils of Western Kenyan soils. The differences in the SDW and N content of the plants inoculated with different strains of native bacteria indicate their variation in symbiotic N fixation. The varaition in N fixation among genera has been attributed to the differences in the chromosal or plasmid borne symbiotic genes [All the five genera of the native bacteria were able to nodulate and fix N with ic genes . For exaPhaseolus vulgaris.The results of this study have demonstrated that soils across different regions in Western Kenya harbour diverse indegenous symbiotic bacteria that initiate nodulation in common bean apart from the rhizobia. These native bacterial isolates exhibited comparable or superior symbiotc N fixation characteristics compared to the locally available commercial inoculants for P. vulgaris. These elite isolates should be subjected to further investigations under different environmental conditions to optimize their N fixing potentials.Notably, it was established that most of the symbiotic strains recovered are not known to commonly nodulate


Plasmodium falciparum infections carrying plasmepsin 2 duplications (associated with piperaquine resistance) in 7/65 recurrent infections within 2 months after DHA/PPQ treatment. These findings raise concerns about the long-term efficacy of DHA/PPQ treatment in Africa.Dihydroartemisinin/piperaquine (DHA/PPQ) is increasingly deployed as an antimalaria drug in Africa. We report the detection in Mali of  Plasmodium falciparum to develop drug resistance, many antimalarial programs have recently included dihydroartemisinin/piperaquine (DHA/PPQ) as a second-line antimalarial drug. This decision is sensible, considering the recent reports of substantially decreased artemether/lumefantrine cure rates in some regions, signaling a potential focus of lumefantrine resistance  coding for the food vacuole enzyme plasmepsin II, which is speculated to be a major piperaquine target.DHA/PPQ has shown near-perfect efficacy levels in clinical trials conducted in Africa; the combination also has been proposed as a tool for intermittent preventive approaches  with the CFX96 Real-Time System (Bio-Rad) detection system. We executed all procedures in triplicate. We determined copy number by using a SYBR-green–based quantitative PCR  in a protocol modified from the one previously described by Witkowski et al . In high-transmission areas, this long period of decreasing drug exposure is likely to progressively select less sensitive, potentially pfpm2 CNV–carrying parasites. Parallel studies conducted in these areas have not detected substantial altered parasite clearance dynamics or K13 mutations associated with artemisinin-derivative therapy (pfpm2 duplications are emerging despite the efficacy of dihydroartemisinin. Further studies are urgently needed to clarify the clinical implications of piperaquine resistance and to monitor occurrence in other areas of high malaria transmission in Africa.Our results clearly show that piperaquine resistance–associated


OBJECTIVES/SPECIFIC AIMS: Epidemiologic studies have found that the incidence of pancreatic cancer is greatest in countries that consume diets high in fat. The gastrointestinal peptide cholecystokinin (CCK) is released from the duodenum in response to dietary fat. CCK has also been shown to stimulate growth of pancreatic cancer through the CCK receptor that is over-expressed on pancreatic cancer cells. The aim of this investigation was to determine if dietary fat promotes growth of pancreatic cancer through the actions of CCK at its receptor. METHODS/STUDY POPULATION: The effects of dietary fat on growth of murine Panc02 pancreatic cancer xenografts were studied in 3 different systems with immune competent mice: (1) pharmacologic blockade with a CCK receptor antagonist, (2) genetic knockout of the CCK receptor by CRISPR, and (3) in genetically engineered mice lacking the CCK peptide (CCK-KO). After injection of 2×106 Panc02 cells subcutaneously, mice were fed either a high-fat diet or a control diet for 37–42 days. Tumor volumes and weights were measured and histology performed. RESULTS/ANTICIPATED RESULTS: Dietary fat significantly increased the size of pancreatic cancer xenografts and this effect was reversed by CCK receptor blockade. Receptor antagonist therapy also significantly reduced tumor-associated fibrosis and increased the influx of CD8+ lymphocytes in the micro-environment. Panc02 cancer cells lacking CCK receptors failed to respond exogenous administration of CCK in vitro and to dietary fat in vivo. Dietary fat did not stimulate Panc02 tumor growth in CCK-KO mice. DISCUSSION/SIGNIFICANCE OF IMPACT: The mechanism by which dietary fat stimulates growth of pancreatic cancer is by CCK and this effect is independent of obesity. This is a significant finding because of the potential beneficial effects of medications which can block the effects of CCK in populations at risk for pancreatic cancer consuming a high-fat diet.


Mitochondrial Thioredoxin Reductase (TrxR2) is a rate limiting enzyme in the mitochondrial thioredoxin system which serves as one of the major mitochondrial ROS scavenging pathways. Txnrd2 is also a repressor of the ASK-1 oxidative stress induced apoptotic pathway. Our group previously identified a correlation with the expression of this protein and long-lived species and its overexpression prolonged lifespan in Drosophila. We have generated a TrxR2 transgenic (T-tg) mouse which has ubiquitously heighted (two-fold) TrxR2 expression. We found that overexpression of TrxR2 leads to enhanced mitochondrial metabolism and increased resistance to mitochondrial oxidative damage in MEFs (data not shown). We also found that female T-tg mice showed a leaner trend and reduced food consumption, with improved glucose tolerance but no difference in insulin sensitivity. These mice showed a lower Oxygen consumption and CO2 production with lower energy expenditure in individual metabolic cages. We further tested their exercise capacity where T-tg mice had a similar performance to control mice. These results suggest that TrxR2 overexpression can lead to some beneficial metabolic changes that need to be further understood. .


Multinucleate Giant Cell (GC) reaction is a biological response that occurs secondary to infection, an implanted foreign body, tissue injury, or inflammation. In rare instances GC reactions have been reported following tissue ablation. Multinucleate GC reactions and tumefactive fat necrosis both have the ability to mimic cancer recurrence or metastasis and can appear as enhancing masses. We discuss a case of a surgically resected retroperitoneal perinephric mass thought to be recurrent renal cell carcinoma (RCC) that was pathologically confirmed as tumefactive fat necrosis with multinucleate GC reaction 2 years following percutaneous cryoablation of a small renal mass. Multinucleate Giant Cell (GC) reaction is typically a biological response to infection, tissue injury, or inflammation and can be noted following implantation of biomaterials or medical devices . The GC A 60-year-old male had incidentally discovered bilateral renal masses identified on computed tomography (CT) imaging. Robotic assisted partial nephrectomy of the right renal lesion was completed on a 4-centimeter Furman Grade 2, pT1a clear cell RCC with negative surgical margins. Due to the posterior location of the 2-centimeter mass on the left kidney , the patCryoablation is a favorable nephron-sparing treatment for certain renal lesions secondary to its ability to treat small, complex lesions in a minimally invasive fashion . Our repThe cellular disturbances that occur during cryoablative therapy can contribute to the development of a multinucleate GC reaction due to tissue damage, necrosis, and creation of cellular debris which stimulates an immune response . A GC reAlso notable in our case was the presence of abundant fat necrosis. A study by Lokken et al. found that necrotic fat and inflammatory nodules have the ability to mimic tumor seeding or recurrence following cryoablation with delayed presentation in 2.7% of cases [The histological appearance of our patient's radiographic abnormality following partial nephrectomy and perinephric fat excision is characterized by extensive tumefactive fat necrosis and multinucleate GC reaction at the site of previous ablative therapy . As seenGC reactions have been noted to be enhanced on both contrast-enhanced CT and MRI thereby mimicking cancer recurrence  Figure . VariousOur report describes the delayed presentation of tumefactive fat necrosis and multinucleate GC reaction following cryoablation of clear cell RCC. This case demonstrates the importance of considering every possibility when presented with a patient that develops new perinephric abnormalities following ablation. This knowledge, combined with thorough evaluation, may aid in avoiding unnecessary invasive treatments for suspicious but nonmalignant lesions following ablation treatments.


Following the publication of this article , the autBacillus group members than cultured phages. We speculate this pattern may reflect gene acquisition from host Firmicutes. Other authors have previously speculated that instances of strong homology observed between B. cereus phage MurNAc-LAA endolysins and host autolysins may reflect horizontal transfer between Bacillus phages and various B. cereus group hosts [30]. The molecular diversity of the BLP lysins and their homologs is exhibited primarily by the presence or absence of the C-terminal amidase_02C domain. Consistent with previous data on lysPBC4 [9] the N-terminal amidase_3 domain of the BLPs show greater conservation among their homologs than the C-terminal amidase_02C domain and linker re- gion that are absent in most phage endolysin homologs.”“Full-length sequences of the putative BLP endolysins display closer overall homology to


Toxoplasma gondii is a zoonotic intracellular parasite, able to infect any warm-blooded animal via ingestion of infective stages, either contained in tissue cysts or oocysts released into the environment. While immune responses during infection are well-studied, there is still limited knowledge about the very early infection events in the gut tissue after infection via the oral route. Here we briefly discuss differences in host-specific responses following infection with oocyst-derived sporozoites vs. tissue cyst-derived bradyzoites. A focus is given to innate intestinal defense mechanisms and early immune cell events that precede T. gondii's dissemination in the host. We propose stem cell-derived intestinal organoids as a model to study early events of natural host-pathogen interaction. These offer several advantages such as live cell imaging and transcriptomic profiling of the earliest invasion processes. We additionally highlight the necessity of an appropriate large animal model reflecting human infection more closely than conventional infection models, to study the roles of dendritic cells and macrophages during early infection. Toxoplasma gondii affects an estimated 25–30% of humans worldwide . Early in vivo situation and allow live cell imaging and transcriptomic profiling of the earliest invasion processes. Great advances in generation, cultivation and cell-type characterization of intestinal organoids (IOs) offer unique opportunities to observe these early events in different hosts with different T. gondii stages  and the savings on animal experiments once IOs have been established. They are also genetically tractable  are constantly renewed every 3–4 days . The vulnerability of T. gondii sporozoites  recognize the parasite through pattern recognition receptors on the cell surface, such as Toll-like receptors (TLRs), which activate secretion of pro-inflammatory cytokines that induce a subsequent Th1 response  DCs and MΦs directly phagocytose free, opsonized parasites upon crossing the epithelial barrier. (2) Both cell types also phagocytose infected apoptotic IECs  cells and CD8+ T cells to begin secreting IFN-γ, the primary mediator of resistance to T. gondii  and macrophages (MΦs). Once the intestinal barrier is overcome by T. gondii has evolved a means to subvert this host defense mechanism  .ED provided parts of The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Plasmodium falciparum gametocytes can be determined microscopically but recent transcriptomics studies paved the way for the development of molecular methods that allow sex-ratio assessments at much lower gametocyte densities. These sex-specific gametocyte diagnostics were recently used to examine gametocyte dynamics in controlled and natural infections as well as the impact of different antimalarial drugs. It is currently unclear to what extent sex-specific gametocyte diagnostics obviate the need for mosquito feeding assays to formally assess transmission potential. Here, we review recent and historic assessments of gametocyte sex ratio in relation to host and parasite characteristics, treatment, and transmission potential.A mosquito needs to ingest at least one male and one female gametocyte to become infected with malaria. The sex of  P. falciparum gametocyte sex-specific targets and provided new insights in gametocyte biology.Recent RNA sequencing studies have uncovered a number of in vitro experiments, molecular tools for assessing gametocyte sex ratio are now increasingly available for use in natural P. falciparum infections.After decades when gametocyte sex-ratio research was restricted to nonhuman malarias or Evidence that gametocyte sex ratio is influenced by total gametocyte density and antimalarial treatment, and improves predictions of transmission potential, highlight the relevance of understanding the gametocyte sex ratio during natural infections.P. falciparum gametocyte marker Pfs25 is expressed predominantly by female gametocytes and has non-negligible levels of background expression in asexual parasites necessitates a re-evaluation of existing gametocyte data.The finding that the most widely used  We present the merits and limitations of molecular tools for quantifying gametocyte sex ratio and review evidence for a sex-specific effect of antimalarial drugs on circulating gametocytes and the implications for malaria transmission potential.Here, we summarize historic and recent estimates of gametocyte P. falciparum, the sex ratio of circulating gametocytes is mostly female biased Pf77 (PF3D7_0621400) and Pfg377 (PF3D7_1250100), both enriched in female gametocytes Pfg27  Box 1AP2-G2 in P. bergheiPuf family of translational repressors in P. falciparumP. falciparum, respectively Molecular mechanisms underlying the differentiation switch towards becoming male or female gametocytes remain largely unknown. Candidate genes that may be associated with sex-specific differentiation include the Proteomic and transcriptomic data reflect this, showing upregulation of genes involved in nucleic acid metabolism, DNA replication, and axoneme formation. Female gametocytes, on the other hand, contain many proteins and transcripts intended for longer term sustainment of postfertilization stages, including genes involved in protein biosynthesis, degradation, transport, and metabolic activity. Another important female gametocyte-specific mechanism is translational repression in which stored transcripts support cellular processes immediately after fertilization, when transcription is absent for multiple hours P. berghei, results in full developmental arrest during ookinete formation, although fertilization is successful. The first indication that translational repression is also active in P. falciparum was obtained through deletion of Puf2, which resulted in altered expression of genes known to be translationally repressed, such as Pfs25 and Pfs28P. falciparum female gametocytes Male gametocytes are terminally differentiated forms with one last task ahead; producing motile microgametes upon activation. Alt-text: Box 1In natural infections of PF3D7_06200 and PfPF3D7_06200 and Pfet al. reported the first molecular assay for an indirect detection of gametocyte sexes based on in situ hybridization using a Pf77 RNA probe that targeted female gametocytes Pfs25 (PF3D7_1031000) transcript, which was considered highly specific for mature gametocytes, using qRT-PCR Pfs25) has recently been shown to be expressed predominantly by female gametocytes Plasmodium chabaudi using targets that were previously described in a proteomics study in Plasmodium bergheiCG1 or PSOP1: PCHAS_0620900) RNA, and male gametocytes by the male gametocyte-specific gene 1 . Schneider and colleagues P. falciparum through quantification of a combination of female-enriched (Pfs25) and male-enriched (Pfs230p) transcripts. The higher limit of detection for male  compared to female gametocytes  in this assay, and the typical female bias in natural infections, may affect the sensitivity of sex ratio determination at low gametocyte densities. Recently, additional male gametocyte-enriched transcripts  were identified that improved the detection limit of male gametocytes to the level comparable with female gametocytes P. falciparum-infected individuals. Whilst it remains plausible that (nearly) all infections produce gametocytes Box 2Mature male and female gametocytes can be distinguished on the basis of light microscopy on Giemsa-stained thin smears Pfs25 expression in asexual blood-stage parasites is not completely absent Pf13 and Pf230p) Suitable targets for gametocyte diagnostics require high and stable expression of the gene in the stage and sex of interest. In P. falciparumP. bergheiPfs25 shows lower expression in male gametocytes compared to females, ranging from 35-fold lower as detected by RNAseq PfMGET) and female (CCp4) targets was recently proposed as a more scalable and robust approach to molecular gametocyte sex ratio assessments.Differential Alt-text: Box 2Gametocyte detection has been improved in the last decade with the introduction and wider use of molecular detection tools. Baker P. falciparum, the sex ratio changed from female biased to equal sexes over 13 days Recently, molecular methods to accurately sex gametocytes have been used to assess the first appearance of mature male and female gametocytes after experimental infections. Gametocyte appearance is estimated to occur 10 days post blood-stage inoculum Plasmodium gallinaceum and rodent malaria Plasmodium vinckei further suggest that the sex ratio in Plasmodium infections varies substantially during the course of an infection proportion of male gametocytes in P. vinckei and increases overall gametocyte density in P. gallinaceumP. chabaudiData from the avian parasite f)/2, and f is Wright’s inbreeding coefficient P. chabaudi where genetic diversity was adjusted deliberately, sex ratio became more male-biased as the number of genotypes present increased Competition between parasites of different genotype can also affect sex ratio. Hamilton’s theory of ‘local mate competition’ (LMC) The effect of sex ratio on transmission success may depend on total gametocyte density P. vivax malaria also reported a shorter lifespan of male P. vivax gametocytes in vitro. Longitudinal studies are needed to understand the dynamics of male and female gametocyte densities during natural infections and their impact on transmissibility.Differences in the longevity of male and female gametocytes can also contribute to sex ratio differences. Two studies have also hinted towards a shorter circulation time of male gametocytes upon clearance of the asexual progenitors Plasmodium can indeed alter sex ratio in response to environmental cues, an essential outstanding question is what governs sex allocation. Candidate genes that may be associated with sex-specific regulation (other than or in addition to AP2-G) include MAPK1 (PF3D7_1431500) as potential regulator of female gametocytogenesis, and MAPK2 (PF3D7_1113900) as possible regulator of male gametocytogenesis P. falciparum infections and early commitment to the sexual stage (and plausibly gametocyte sex), any response to environmental triggers must involve significant ‘planning ahead' and cross-talk between potentially very low numbers of gametocytes or precursors. Even if environmental signals are as rapidly translated into elevated gametocyte conversion rates as recently shown for P. chabaudiP. falciparum to rapidly respond to environmental triggers is the bone marrow reservoir for gametocytes. It is conceivable that mature gametocytes may not all be immediately released upon completion of maturation but may be in part retained for release upon environmental stimuli.If -G transcripts Pfs16, PF14_0748) Plasmodium parasites or clones Our understanding of environmental factors that influence gametocyte sex ratio is incomplete. Moreover, some of the ‘known’ stimuli for overall investment in gametocyte production appear uncertain when assessed with current methodologies P. chabaudiP. falciparumP. falciparum parasites may respond to their proliferation state rather than directly to the presence of drugs. Drug pressure may thus lead to an initial increased investment in asexual proliferation  until survival is unlikely and a terminal investment in transmission occurs In vitro drug tests suggest that male gametocytes are more sensitive to a range of antimalarial drugs compared to female gametocytes, with impaired male gametocyte fitness (reduction in exflagellation) at drug concentrations that do not affect female gametocyte fitness (as measured by activation into gametes) Malaria parasites may alter their investment in asexual replication and transmission in response to drug pressure. Treatment with subcurative doses of antimalarial drugs has been shown to increase the rate of gametocytogenesis in the rodent malaria parasite mosquito feeding assays remain essential to predict transmission potential after treatment One important outstanding question is whether transmission potential is predictable after treatment based on gametocyte density and sex ratio, or whether P. falciparum to mosquitoes represents a developmental bottleneck in terms of parasite numbers; at the same time it is a very efficient process that may even increase in efficiency once transmission intensity declines Outstanding QuestionsWhat are the sensing mechanisms and stimuli that allow malaria parasites to adjust their sex ratio?Do male and female gametocytes differ in longevity or the duration of infectivity?What range of gametocyte sex ratio allows transmission under different conditions?Do different clones within the same infection vary in gametocyte sex ratio, and how does this affect their transmission?Do antimalarial drugs prevent transmission by means of gametocyte sterilization rather than gametocyte clearance?Can robust quantification of male and female gametocytes replace mosquito feeding assays?The transmission of


Formation of pancreatic pseudocyst is one of the well-known complication.While small pseudocyts are asymptomatic, large ones can become symptomatic and causeseveral complications including infection, rupture, bleeding, biliary complicationsand portal hypertension, Various interventions are available for the management of symptomatic pancreaticpseudocysts. Endoscopic ultrasound (EUS) guided cystogastrostomy is a choice fortreatment of large pseudocyts, witch bulge into gastric lumenFifty years old male was in reanimation clinic with the diagnosis of complicated andsevere acute pancreatitis due to gallstones for three months. His physicalexamination revealed a large sized mass extending from epigastric to left upperquadrant of abdomen. The contrast enhanced CT showed a cystic lesion with 150x100 mmdimensions in the tail and body of pancreas pushing the stomach . Thediagnostic upper gastrointestinal endoscopy revealed a bulge localized on largecurvature related to pancreatic pseudocyst. An endoscopic cystogastrostomy wasplanned. After detection of the area for cytogastrostomy in gastric lumen withstandard video-endoscope (Pentax EG 290 LK), it was marked by argon plasmacoagulation probe (30 watt); the gastric wall was opened step-by-step with the probe(60 watt) until pancreatic fluid drainage into stomach was seen. After aspiration ofpancreatic fluid (approximately 1500 ml), the gastric opening area enlarged by usingan ERCP sphincterotomy. Then a guide wire was inserted into the cyst with the C armfluoroscopy. Finally, 8.5 F pigtail plastic stent was placed into the cyst throughthe gastric lumen. The procedure was completed without any complication. ,,EUS guided cystogastrostomy is a safe method for management of pancreaticpseudocytsOur case has demonstrated that argon plasma coagulation without endoscopicultrasonography cytogastrostomy can be an option in handling large volume pancreaticpseudocyst during endoscopic cystogastrostomy.