Pain and depression, two of the common symptoms among chronically ill older adults, have been found to be related in various populations; however, further knowledge is needed about their relationships and moderating factors among community-dwelling, chronically ill older adults, particularly in lower-income, rural areas with limited healthcare resources. Therefore, this study aimed to examine the association between pain level and depression among chronically ill older adults in rural areas. A total of 100 residents of a rural county in West Alabama, who are 55+ and have chronic illnesses and pain, were recruited from four community senior centers and were interviewed using a structured questionnaire. Pain levels were assessed by the Philadelphia Geriatric Center (PGC) Pain Scale, and depression by an abbreviated version of the Center for Epidemiologic Studies Depression Scale (CES-D). Bivariate correlation and multivariate analysis were conducted. The correlation between pain and depression was significantly positive . The results of the model indicated that pain scores and other control variables explained approximately 18 percent of the variance in depression. The multivariate analysis results confirmed that those who had higher pain scores were significantly likely to have increased depression scores . Education marginally significantly moderated the relationship between pain and depression (p = .059). The previously reported positive pain-depression relationship exists among chronically ill older adults in rural areas, calling for tailored interventions to reduce their pain and its impact on depression.


This study aimed to understand the movement behaviour and utilization distributions of Kori bustards in space and time in the Serengeti ecosystem. A total of 14 individuals were tracked with the aid of GPS  satellite transmitters, and their sexes were identified using DNA analysis. A species utilization distribution was estimated using the Brownian bridge movement model (hereafter dBBMM) in which the probability of being in an area is conditioned by starting and ending (GPS) relocations. Resource selections were analysed by comparing the GPS relocations with locations randomly placed within each individual’s region of utilization in a spatio-temporal approach. Vegetation information was derived from a Serengeti GIS vegetation map and Data Centre and was reclassified as Open grassland, Dense grassland, Shrubbed grassland, Treed grassland, Shrubland, and Woodland. The Shannon diversity index for vegetation was calculated based on the original vegetation classification. Used versus non-used habitats were contrasted using a generalized linear mixed-effects model with a binomial distribution. The results indicated that males were 21.5% more mobile than females, and movements were 6.3% more diffuse during the non-breeding period compared to the breeding period . Contrasting models indicated that males preferred more open grasslands during the non-breeding period and also preferred closed and shrubbed grassland during the breeding period. Females preferred more woody vegetation during the non-breeding season compared to the breeding season. The most parsimonious model indicated that females preferred to stay closer to rivers and diverse areas during the non-breeding period whereas males preferred areas that were farther from rivers and homogenous. Homogeneous areas were preferred during the breeding period, and heterogeneous areas were preferred during the non-breeding period. We conclude that the movement behaviours of Kori bustards changes with the season and habitat. Further research is needed to understand the factors driving the seasonal movement of Kori bustards in the Serengeti ecosystem. Habitat selection in animals helps maximize their fitness –4. HowevPeriods of reproduction may affect both the home range size and habitat selection. In birds, breeding pairs with chicks may have smaller home ranges because breeding birds require habitats with abundant food and safety for their young. Similarly, incubating females may have relatively small home ranges because their nests depend on incubation and protection . HoweverThe Kori bustard is the heaviest flying bird that is indigenous to the grasslands and lightly wooded savannahs of southern and east Africa ; howeverArdeotis kori struthiunculus is listed as near threatened by the IUCN and is included in Appendix II of the list of CITES species ). Whereas males preferred more open grasslands, females preferred to use more woody vegetation . Females preferred to stay closer to rivers, even more so during the non-breeding period . Females preferred more diverse areas contrary to males, who preferred more homogenous areas  in different seasons may be due to the tendencies of some individuals to have strong movements, while these tendencies may be absent in other individuals. According to , Kori bu [Tetrax tetrax) showed similar differences in habitat preferences between males and females [The spatial configuration of the habitats available within the Kori bustard minimum convex polygons and contrasting models based on AIC showed a species preference to woody vegetation, which is more heterogeneous and closer to rivers. The most parsimonious model explained the sexual differentiation in response to seasonal habitat/vegetation preferences wherein males preferred more open grasslands, and females preferred to use more woody vegetation. These preferences may reflect the species’ breeding system, where males and females require different microhabitats, as also observed in the Bengal florican alensis) . Males ralensis) , 47, 48. females , 49. TheArdeotis kori kori, female home ranges are confined by environmental conditions and the accessibility of resources [The most parsimonious model explaining the selection for distance to rivers indicated sexual differentiation in the seasonal responses to habitat preference . Femalesesources .Our study highlights how spatial use and habitat preferences shape the movements of Kori bustards in the Serengeti ecosystem. Overall, our results note the presence of distinct movement patterns related to breeding (December-June) and non-breeding (July-November) periods. We conclude that different movement patterns exist among individual Kori bustards during breeding and non-breeding periods, as females perform partial movements in their habitat of preference, whereas males migrate from one habitat to another. The Kori bustard habitat preferences in the Serengeti ecosystem are sex-specific and differ during different periods of the year, with males utilizing mostly shrubbed grassland and open grassland and females utilizing mostly woody vegetation with increasing habitat diversity. Finally, we recommend further studies on the factors that influence habitat preferences and differential movements of the Kori bustard in their ecosystem during different seasonal periods.S1 Fig6 km2) over Julian days from capture for six male (blue) and eight female (red) Kori bustards in the Serengeti Ecosystem during the breeding  and non-breeding period .Net-squared displacement (in 10(TIFF)Click here for additional data file.S1 Table(XLSX)Click here for additional data file.


This report describes the first case of extensive macular atrophy with pseudodrusen (EMAP) imaged with optical coherence tomography angiography (OCTA). A 58-year-old Caucasian man presented with decreased central vision in both eyes. Fundus examination showed large areas of macular atrophy centered on the fovea surrounded by diffuse reticular pseudodrusen. Spectral domain OCT (SDOCT) revealed outer retinal and choriocapillaris atrophy. OCTA demonstrated marked absence of choriocapillaris flow. Extensive macular atrophy with pseudodrusen is a rare clinical entity and a new extreme phenotype of macular degenerations that could shed more light on the role of pseudodrusen and choriocapillaris compromise in the pathogenesis of AMD. Extensive macular atrophy with pseudodrusen (EMAP) is a rare clinical entity that was first described by Hamel et al. in 18 patients with bilateral well-delineated chorioretinal atrophy extending to the temporal arcades without sparing the fovea and widespread pseudodrusen throughout the posterior pole and peripheral retina. Earlier onset, more rapid progression of atrophy, and severe visual loss were noted in contrast to age-related macular degeneration (AMD) .Optical coherence tomography angiography (OCTA) is a relatively new, fast, noninvasive imaging modality that analyzes high-speed OCT images, measures changing reflectance, and reconstructs high-resolution blood flow maps of the retina, allowing en face imaging of the retinal capillary plexuses and choroidal vasculature.The author describes the first case of EMAP imaged with optical coherence tomography angiography (OCTA).A 58-year-old Caucasian male presented with progressively decreasing central vision in both eyes over the past five years. He also complained of mild night blindness. There was no significant medical history and no family history of retinal disease. Best-corrected visual acuity was 20/60 in the right eye and 20/200 in the left eye with mild nuclear sclerotic cataracts. Fundoscopic examination revealed large areas of macular atrophy centered on the fovea surrounded by reticular pseudodrusen. Peripapillary atrophy was also present along with scattered areas of peripheral pavingstone degeneration OU Figures . There wExtensive macular atrophy with pseudodrusen (EMAP) is a retinal dystrophy that affects patients in their sixth decade and is defined by bilateral symmetric widespread macular atrophy centered on the fovea surrounded by diffuse macular and midperipheral pseudodrusen. Pavingstone lesions can also be found peripherally . An assoExtensive macular atrophy with pseudodrusen may be a new extreme phenotype of macular degenerations that could shed more light on the role of pseudodrusen and choriocapillaris compromise in the pathogenesis and progression of AMD. An association between pseudodrusen and decreased choroidal thickness has been documented  as has a


An abundance of research involving adults who care for family members with dementia has guided the creation of supportive programs/services. Much less is known about adolescents who are dementia caregivers. This descriptive secondary analysis utilized data collected during a qualitative examination into the psychological well-being of adolescent dementia caregivers. Eleven adolescent/adult dyads who provided dementia care for a family member completed surveys prior to the adolescents’ participation in focus groups. Five male and six female adolescents ages 12 to 17 and eleven female adults were asked similar questions about caregiving tasks, education resources, and demographic information. Using descriptive statistics, the results of the surveys provide a snapshot of caregiving among a group of adolescents living in northwest Ohio and highlight differences reported by the dyads. Adult accounts of adolescent preparatory education were incongruent with the adolescents’ and did not report their use of books or online caregiving resources. Conversely, three adults (27%), but no adolescents, identified hands-on and observational opportunities as education resources. Adults reported greater adolescent involvement in ten activities of daily living (71%), especially related to bathing, shopping, transportation, and managing medication and finances. Adolescents reported helping with tasks such as eating and laundry more often than adults. While the sample size was small, these findings suggest a need for triangulation when seeking knowledge about adolescent caregiving. These results may inform researchers wishing to investigate the role of adolescent caregivers, as well as guide supportive agencies who provide education materials to families caring for individuals with dementia.


Humic substances are breakdown products of decaying organic matter that co-extract with proteins from fossils. These substances are difficult to separate from proteins in solution and interfere with analyses of fossil proteomes. We introduce a method combining multiple recent advances in extraction protocols to both concentrate proteins from fossil specimens with high humic content and remove humics, producing clean samples easily analysed by mass spectrometry (MS). This method includes: (i) a non-demineralizing extraction buffer that eliminates protein loss during the demineralization step in routine methods; (ii) filter-aided sample preparation (FASP) of peptides, which concentrates and digests extracts in one filter, allowing the separation of large humics after digestion; (iii) centrifugal stage tipping, which further clarifies and concentrates samples in a uniform process performed simultaneously on multiple samples. We apply this method to a moa fossil (approx. 800–1000 years) dark with humic content, generating colourless samples and enabling the detection of more proteins with greater sequence coverage than previous MS analyses on this same specimen. This workflow allows analyses of low-abundance proteins in fossils containing humics and thus may widen the range of extinct organisms and regions of their proteomes we can explore with MS.


Lack of positive attitudes towards aging has shown to cause challenges within intergenerational networks in employment situations. These can include job satisfaction, intrinsic motivation to work, and ageism subjectivity as underlying determinants and consequences. The collaborative intervention pilot training program goals were two-fold: 1) To expose and understand ageism as a discriminatory action. 2) To create a more positive social dynamic network in a diverse workplace in regard to general expectations of ageism. Two team-based learning intervention programs were created in order to increase collaborative awareness of ageism and were presented to a medium size intergenerational department staff (N=64) as part of a professional development series on equity, diversity and inclusion. Through three multidimensional self-help training activities, learning was done individually, within similar age employee groups, and within intergenerational employee groups. Participants were able to discuss and express general understandings and expectations of aging and learning tools such as intergenerational reactivity and emotion regulation strategies were presented. Within survey responses at the completion of the trainings, key findings showed that respondents had a better understanding of ageism (76%) and felt better equipped to work within an employment team of diverse ages (71%). Additionally, the subject matter of this pilot training program resulted in re-conceptualized positive aging (61%). Future implications and goals for the program include interventions to further increase positive intergenerational understanding and workplace generational inclusiveness.


OBJECTIVES/SPECIFIC AIMS: The objectives of this study are to determine whether high-frequency ipsi-lesion or low-frequency contra-lesion ECS improves forelimb function following experimental stroke in aged animals with focal and large strokes. We also want to investigate whether ECS-induced improvements in motor function are related to an enhancement of neural structural plasticity (dendrites and synapses) and changes in growth promoting (BDNF) and growth inhibiting (NOGO-A) expression in the infarcted motor cortex in young and aged animals. METHODS/STUDY POPULATION: We will investigate whether excitatory ECS of the infarcted cortex or inhibition of the noninfarcted cortex combined with daily impaired-forelimb rehabilitative training (RT) results in greater motor functional recovery compared to RT alone. Immunohistochemical (IHC) analyses and unbiased stereological techniques will be performed to investigate changes in proteins associated with dendritic restructuring (MAP2), synaptic plasticity (PSD95 and synaptophysin), and alteration in the expression of BDNF and NOGO-A. RESULTS/ANTICIPATED RESULTS: We expect that inhibitory ECS of the noninfarcted motor cortex will improve behavioral outcomes in moderate to severe stroke animals compared with excitatory ECS or no stimulation  animals. We predict that the ECS condition that improves motor performance most significantly compared with RT alone will have a corresponding greater increase in remaining ipsi-infarct motor cortical dendritic and synaptic plasticity , and greater expression of BDNF. It is unknown, but also expected that better behavioral recovery will coincide with a greater reduction in NOGO-A in the injured motor cortex. DISCUSSION/SIGNIFICANCE OF IMPACT: These studies will aid in creating a model that will allow for a better understanding of the relationship between brain stimulation, severity of injury and, in future studies, aging. These studies will also help clarify previous conflicting brain stimulation results.


Aerobic training has been shown to be effective at improving cognitive and brain outcomes in older adults with mild subcortical ischemic vascular cognitive impairment (SIVCI). However, uncertainty remains regarding the underlying neurobiological mechanisms by which exercise elicits these improvements in cognition. Increased aberrant functional connectivity of the default mode network has been highlighted as a factor contributing to cognitive decline in older adults with cognitive impairment. Greater connectivity of the DMN at rest is associated with poorer performance on attention-demanding tasks, indicative of a lack of ability to deactivate the network on task. Our previous work on a randomized controlled trial of participants with mild SIVCI, demonstrated that 6-months of thrice weekly aerobic training led to improved global cognitive function, as measured by Alzheimer’s disease Assessment Scale-Cognitive subscale (ADAS-Cog), compared with a health education program. Thus, we conducted secondary analyses to investigate whether these changes in global cognitive function were associated with changes in resting state DMN connectivity. A subsample of 21 participants underwent a resting state functional magnetic resonance imaging (fMRI) scan before and after trial completion. Change in resting state DMN connectivity was found to significantly predict change in ADAS-Cog score  after controlling for age, intervention group, and baseline functional capacity = 3.507, p=.031). These findings suggest that functional connectivity of the DMN may underlie changes in global cognitive function. Furthermore, aerobic exercise is a promising intervention by which to elicit these changes in older adults with mild SIVCI.


The causes of chronic cough in children are mainly dependent on the setting and age of the child. Protracted bacterial bronchitis is a frequent cause of morbidity in childhood, and antibiotic treatment is beneficial. Prompt recognition and early treatment is important both to prevent inappropriate use of asthma medications and also progression to bronchiectasis, but the diagnosis should not be made uncritically, because chronic wet cough is not necessarily due to lower airway disease. Upper Airway Cough Syndrome (UACS) is considered by some to cause chronic cough in childhood. Underlying UACS are many common conditions, including allergic rhinitis, adenoiditis and rhinosinusitis. Diagnosis relies on a combination of clinical criteria that are relatively sensitive but non-specific. The role of nasal endoscopy in children with chronic cough and signs suggesting UACS is unclear. Nasal saline solution irrigation is commonly used in UACS, but most studies have methodological biases, and efficacy data are scanty. Randomized controlled trials are urgently required. However, if saline washes, rather than oral antibiotics, can effectively treat some children with wet cough associated with upper airway conditions, antibiotic resistance could potentially be reduced. There is a need to further study wet cough and not to assume it to be equivalent to lower airway infection in all children. All that coughs is not bronchitisCough is common in childhood . SpontanThis article aims to suggest a practical approach in children with wet cough and concomitant nasal symptoms through a vignette describing “a child” typical of those referred to outpatient services of two tertiary level Italian hospitals  by primary care pediatricians. The diagnostic work-up and the treatment options in this clinical setting are critically discussed.A preschool boy presented with a 3-weeks history of a troublesome cough that had developed after an acute respiratory infection (ARI). Cough was initially dry, but gradually became wet. A runny nose, nasal obstruction and snoring at night were other features. He had received a 10-days course of oral amoxicillin-clavulanate with minimal effect. The family history was unremarkable. The personal history revealed frequent episodes of ARI during winter since starting attending day care. There was no history of wheeze. Parents were concerned about the frequency of respiratory episodes and had wished for “some tests” over the previous year. Routine laboratory tests including full blood count, erythrocyte sedimentation rate and C-reactive protein, were normal. Pharyngeal swab was also normal. Skin prick testing revealed minor sensitization to house dust mites. Physical examination revealed only a moist cough. A “rattle” sound was audible over the chest. The ear/nose/throat (ENT) examination revealed yellowish mucus dripping down into the oropharynx, a cobblestone pharyngeal mucosa and swollen turbinates. Nasal endoscopy revealed mild adenoidal hypertrophy with no evidence of sinus involvement. A diagnosis of adenoiditis was made and a 7-days course of nasal douching with hypertonic solution was prescribed. At 2-weeks follow-up, his cough had completely disappeared and physical examination was unremarkable. He remained well with no antibiotic therapy until a new ARI recurred after 2 months.(PPB-micro) and new definitions were introduced  comprised a history of chronic wet cough, importantly a positive bronchoalveolar lavage (BAL) culture for a respiratory pathogen, and response to a 2-weeks course of oral amoxicillin-clavulanate . Since utroduced . PBB-cliPBB-clinical definition lacks specificity and inherently has limitations. First, many cases of PBB may be “prolonged acute cough” lasting 4–8 weeks, which most commonly follows a viral ARI and typically resolves without intervention  and quality (wet or productive) of cough, and excluding other causes of wet cough. The proposed rvention . Second,rvention . Differervention . In chilrvention . Interesrvention ; neverthrvention . Fourth,rvention . FinallyPBB-clinical definition may lead to substantial over-diagnosis and increased prescription of antibiotics if not meticulously verified. The evidence-base for benefits of antibiotic therapy in children with PBB mainly rely on a single randomized controlled study (RCT) involving children with chronic cough in Australia  , the optPost-nasal drip (PND) is the drainage of secretions from the nose or paranasal sinuses into the pharynx. The suspicion of PND rests on the patient recognizing that something is dripping down into the throat and/or is suffering from frequent throat clearing. The finding of mucoid secretions in the pharynx or a cobblestone aspect of pharyngeal mucosa is suggestive.The causal role of PND in chronic cough is a controversial issue both in adults  and in cThe reported incidence of UACS in children with chronic cough varies widely. Asilsoy et al.  used theThe ACCP guidelines for adults explicitly state that the treatment options for UACS-induced cough are somewhat dependent on the subcategory of disease that is present . AntihisNasal saline solution irrigation (NSSI) has recently gained popularity in selected settings . An ItalThe exact mechanism of action of NSSI is not known , but mechanical cleaning of the nasal mucosa, which leads to the removal of inflammatory mediators and temporary improvement of mucociliary clearance, may be important. This may favor to resolve inflammation/infection spontaneously or with drugs.Despite being used in daily practice, NSSI is only briefly mentioned in the guidelines for the treatment of RS , 39. SysAll children cough, but most of them are “expected”  or merely a normal part of common childhood respiratory infections. Isolated dry cough in a community setting in an otherwise well child is unlikely to betoken any serious underlying condition. On the other hand, children with chronic wet cough often pose a diagnostic and management dilemma to the physician. Children similar to the one described in the vignette are frequently seen in primary care.The clinical presentation of the case described does not fulfill the diagnostic criteria for PBB since the cough lasted only 3 weeks. Therefore, the prescription of antibiotics was inappropriate. Parents are often disturbed by cough and ask that “something is done.” In a prospective study in Australian children, a high proportion of parents thought antibiotics should be given for post-infectious cough (34%) or were unsure (24%); surprisingly, antibiotics were prescribed in 14% of episodes characterized by isolated dry cough with no fever . Post-inThe patient presented with a clinical history and physical signs consistent with UACS. There is no mention of nasal symptoms and/or signs in the recently extended list of cough pointers for the management of children with chronic wet cough . Some spIn the vignette, the diagnosis of adenoiditis was made by nasal endoscopy. The inflammatory involvement of adenoids is common in children, especially those attending day care , as uppeCough in the above child had not disappeared after antibiotic therapy but did a few days after treatment with NSSI; however, spontaneous resolution cannot be excluded. In a prospective study, most children with suspected UACS had cough which resolved after treatment with NSSI . Cough ibefore prescribing an antibiotic; and this includes making the diagnosis of “normal child” and reassuring the family. Unfortunately, available data demonstrate that is difficult not to give in to this temptation. Respiratory diseases are the most common reason for the prescription of antibiotics in primary care, but many of them are unnecessary , Amoroso Angelo (Pescara), Andreozzi Americo (Macerata), Basile Lucio (Pescara), Beghella Massimo (Ancona), Bellucci Nazareno (Todi), Bernacchi Stefania (Perugia), Bosco Fiorella (Pescara), Brachelente Linda (Perugia), Cappellucci Domenico (Pescara), Carnevale Maurizio (Pescara), Castiglione Giovanni Battista (Pescara), Chioccoloni Roberta (Marsciano), Coronati Valeria (Ancona), Della Vedova Giacomo (Spello), Di Filippo Antonella (Giulianova), Di Florio Rossana (Pescara), Di Giampietro Tiziana (Pescara), Di Girolamo Franca (San Benedetto del Tronto), Gabbanelli Gianna (Ancona), Gabriele Piera (Pescara), Gobbi Costantino (Macerata), Gonnellini Rita (Deruta), Guerrieri Arcangela (Ancona), Laguardia Luigi (Montesilvano), Liberati Marina (Ascoli Piceno), Martello Cecilia (Perugia), Merluzzi Angela (Città di Castello), Migliori Cesare (Ancona), Minucci Maria Giovanna (Foligno), Mora Marina (Ancona), Nuzzaci Roberto (Castelfidardo), Passali Maria Grazia (Pescara), Piermattei Loredana (Tolentino), Rossi Laura (Foligno), Ruggeri Anna Grazia (Matelica), Sardo Infirri Margherita (Spoleto), Solinas Lucia (Foligno), Truffarelli Francesca (Foligno).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.


Felton Institute has been working to eliminate isolation and loneliness in San Francisco since its inception as a community social service agency 130 years ago. Felton offers culturally and linguistically appropriate programs and services that foster community and social connections among socially isolated, low income older adults, including those living with serious mental illness and those residing in local long-term care facilities. Examples include workforce programs for older adults; the foster grandparent program; and the senior companion program which includes friendly visiting, senior counseling, and peer escort services. This session will highlight lessons learned from these successful programs as well as how they have led to the development of new initiatives focused on conducting outreach, providing trauma-informed services, offering wellness classes, and organizing meaningful activities including a choir, intergenerational gardening, arts and dance classes, and cultural exchange opportunities to isolated older adults living in poverty in San Francisco’s Visitacion Valley.


Fundamental watershed-scale processes governing chemical flux to neighboring ecosystems are so poorly understood that effective strategies for mitigating chemical contamination cannot be formulated. Characterization of evapotranspiration, surface runoff, plant uptake, subsurface preferential flow, behavior of the chemicals in neighboring ecosystems, and an understanding of how crop management practices influence these processes are needed. Adequate characterization of subsurface flow has been especially difficult because conventional sampling methods are ineffective for measuring preferential flow of water and solutes. A sampling strategy based on ground-penetrating radar (GPR) mapping of subsurface structures coupled with near real-time soil moisture data, surface topography, remotely sensed imagery, and a geographic information system (GIS) appears to offer a means of accurately identifying subsurface preferential flow pathways. Four small adjacent watersheds draining into a riparian wetland and first-order stream at the USDA-ARS Beltsville Agricultural Research Center, Beltsville, MD are being studied with this protocol. The spatial location of some preferential flow pathways for chemicals exiting these agricultural watersheds to the neighboring ecosystems have been identified. Confirmation of the pathways is via examination of patterns in yield monitor data and remote sensing imagery.


Regulated hemostasis, inflammation and innate immunity entail extensive interactions between platelets and neutrophils. Under physiological conditions, vascular inflammation offers a template for the establishment of effective intravascular immunity, with platelets providing neutrophils with an array of signals that increase their activation threshold, thus limiting collateral damage to tissues and promoting termination of the inflammatory response. By contrast, persistent systemic inflammation as observed in immune-mediated diseases, such as systemic vasculitides, systemic sclerosis, systemic lupus erythematosus or rheumatoid arthritis is characterized by platelet and neutrophil reciprocal activation, which ultimately culminates in the generation of thrombo-inflammatory lesions, fostering vascular injury and organ damage. Here, we discuss recent evidence regarding the multifaceted aspects of platelet-neutrophil interactions from bone marrow precursors to shed microparticles. Moreover, we analyse shared and disease-specific events due to an aberrant deployment of these interactions in human diseases. To restore communications between the pillars of the immune-hemostatic continuum constitutes a fascinating challenge for the near future. The circulatory system provides functional integration to tissues throughout the body and constitutes a dynamic platform for tasks, such as immune patrolling and defense against threats –3. ConsiCellular membranes allow the segregation of selected information in compartments and modulate their subsequent effects on the environment by integrating multiple stimuli. Circulating membrane-endowed players in the immuno-hemostatic network encompass leukocytes, platelets and microparticles, with the endothelium as a fourth static counterpart , 13. PlaHemostasis and inflammation counterbalance the effect of injuring external stimuli. Selective regulation and polarization of these pathways enhance homeostatic responses at sites of tissue or vascular injury and minimize the detrimental effects to the host. Multiple mechanisms have developed, including variability in the lifespan of players involved in the immune-hemostatic balance and availability of soluble or membrane-bound moieties. Emission of membrane-endowed subcellular particles fine-tunes cellular activation and converts locally concentrated high-intensity responses into a sum of smaller but widespread and reciprocally independent biological events. Generation of extracellular vesicles enables the extension of the total membrane area interacting with the environment as well as of the range of potential cellular targets. In addition, segregation of information in multiple signaling quanta discloses the possibility of independent interactions with distinct cellular counterparts according to the differential needs of target tissues. Platelets are anucleate cell fragments released by megakaryocytes. After a multi-stage process of cytoplasm compartmentalisation and concentration of bioactive compounds into granules taking place over the course of days, platelets are released as elongated precursors (proplatelets), which undergo multiple iterative fission events to reach their final size. Preplatelets are round-shaped precursors constituting a reversible intermediate stage in the transition from proplatelets to platelets . Small vIncreased platelet demand and/or consumption during acute systemic inflammation warrants adaptation of megakaryocytes. Inflammatory cytokines, such as IL6 promote megakaryocyte increase in ploidy and prompt thrombocytopoiesis through increased liver synthesis of thrombopoietin as part of the acute phase response . PlateleControlled exocytosis or integration of bioactive compounds into platelet membrane is crucial for these tasks. Platelets are endowed with three classes of granules: alpha-granules; dense granules and few lysosomes. Some authors also described “T granules” equipped with Toll-like receptor 9 as a potential fourth platelet compartment –28. BesiNeutrophils constitute the most abundant leukocyte population in the blood and are in charge of the early innate effector response to noxious stimuli . NeutropPhagocytosis and digestion of invading pathogens constitutes the default-mode defensive task performed by neutrophils. However, frustrated microbial phagocytosis promotes the generation of extracellular traps (NETs) , i.e., tNeutrophils also account for tissue and vascular damage in immune-mediated diseases including inflammatory bowel diseases, systemic lupus erythematosus (SLE) rheumatoid arthritis (RA) and vasculitides either directly or through NET-induced facilitation of thrombosis , 74–76. Platelets interact productively with multiple cells types , althougVital neutrophil internalization (emperilopolesis) into megakaryocytes occurs in the bone marrow. Engulfed neutrophils provide megakaryocytes with activating stimuli (causing a rise in platelet production) and donate membrane segments causing enhanced phosphatidylserine expression by chimeric daughter platelets . It is tPlatelets and megakaryocytes communicate long-range with neutrophils through exocytosed mediators and microparticles with enhancing actions on neutrophil activation , 95. TheThe interaction between platelets and neutrophils impacts on multiple stereotyped pathological manifestations . A firstPatients with inflammatory diseases of the blood vessels , 131, coAberrant coagulation is detectable in immune mediated diseases , 119. AlThrombotic microangiopathy, consisting in diffuse deposition of thrombi along small vessels due to widespread endothelial activation with hemolysis and platelet consumption, might complicate SLE, SSc, antiphospholipid syndrome and other immune-mediated diseases –185. UndThe lung is a major inflammatory target . NeutropSystemic vasculitides encompass a very large set of immune-mediated diseases characterized by vascular injury and downstream organ ischemia as the core pathophysiological event . They caNeutrophils cause vascular damage in small-vessel vasculitis, possibly reflected by the accumulation of leukocyte cellular debris in peri-vasculitic lesions (leukocytoclasia). In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), neutrophil mediated vascular injury is part of a vicious circle linking exposure of myeloperoxidase (MPO) and/or proteinase-3 from granules to neutrophil surface or into the setting of NETs  to the dIn large vessel-vasculitides, activation of platelets may contribute to promote vascular remodeling through the release of signals, such as VEGF . Platelevasa vasorum and entailing aberrant platelet-neutrophil cross-talk.Little is known on platelet-leukocyte interactions in large vessel vasculitides, although relative depletion of neutrophil granule content has been reported in giant cell arteritis in association with platelet activation , 132. NoSLE is a multi-organ autoimmune disease with a wide spectrum of clinical manifestations and pathogenic mechanisms . FailureCardiovascular manifestations are frequent in patients with SLE and a cause of morbidity and mortality . AccelerEndothelial derived microparticles constitute the most abundant microparticle subset in patients with SLE and correlate with endothelial dysfunction and interferon-α signature , 232. HoMechanistically, platelet activation in SLE might depend on circulating immunocomplexes, which are abundant in SLE patients biological fluids and are recognized on platelet surface by FcγRIIA and Toll-like receptor 4,7 . PDμP thSSc is a systemic autoimmune disease, characterized by unrelenting inflammation with a wound repair response consisting in mesenchymal extracellular matrix deposition leading to fibrosis, and by microvascular dysfunction and aberrant neoangiogenesis , 238. PlActivated platelets in SSc contribute to impaired vascular tone  anRheumatoid arthritis is a relatively frequent autoimmune disease characterized by prominent involvement of the synovial joints. Although extra-skeletal manifestations are relatively less frequent compared to other immune-mediated diseases, patients with RA show an increased ischemic risk, pointing to the existence of a core pathophysiological event linking inflammatory manifestations to vascular dysfunction .Neutrophils undergoing NET generation might provide autoantigens in RA. Patients in fact frequently develop antibodies against citrullinated peptides (ACPA). Citrullination occurs thanks to the activity of deiminating enzymes, such as protein-arginine deiminase 4 (PAD4), abundantly expressed in neutrophils . CitrullPlatelets can be activated by collagen through the megakaryocyte lineage-specific glycoprotein VI and thus prompted to generate microparticles. Boilard and colleagues  showed tPlatelets and neutrophils are major determinants of the immune-hemostatic continuum and extensively interact based on cell-cell contact and/or exchange of soluble signals and microparticles to synergise in contrasting the noxious effects of endogenous or environmental stimuli toward vessel and tissue integrity and to promote physiological tissue renewal and homeostasis. These events, part of a set of simple, innate, but evolutionarily preserved stereotyped responses, are disproportionately active and self-sustained in patients with immune-mediated diseases, such as systemic vasculitides, SLE, SSc, RA and possibly allergic disorders and might account for the development of either some inflammatory manifestations and of cardiovascular complications. Patients with immune-mediated diseases consistently show signs of platelet (and/or PDμP) activation, possibly prompting either the formation of heterotypic aggregates with neutrophils (as in giant cell arteritis) or neutrophil activation toward enhanced survival and eventually NET generation . Diagnostic and therapeutic strategies currently employed in the setting of autoimmune diseases to prevent disease progression and the occurrence of secondary complications are generally not targeted on these pathogenic mechanisms, suggesting the existence of a largely unexplored window of opportunity to improve survival and quality of life for patients by dampening sustained neutrophil-platelet interactions.GR and NM collected the literature data, drafted, and revised the manuscript. AM revised the manuscript and provided critical analysis of intellectual content. All authors approved the final version of the manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work will appropriately be investigated and resolved.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.


Exercise/therapy interventions). Six of the seven training studies were concerned with upper limb function , and one examined the effect of foot drop stimulator training. The six upper limb studies used a variety of training modalities including Wii-based upper limb therapy (two papers from one group), EMG-driven robotic devices with or without neuromuscular electrical stimulation (NMES) (three papers), and traditional physical/occupational therapy (one paper).The nineteen papers of the research topic Electromyography (EMG) Techniques for the Assessment and Rehabilitation of Motor Impairment Following Stroke highlight a variety of ways that EMG may be used to better understand and treat stroke-induced brain damage. Seven papers addressed the impact of weekly training on EMG properties and function post-stroke, and one paper examined the effect of a robotic exoskeleton on gait during a single training session (Mechanisms of motor impairment). These included one study that addressed coupling between the index finger and thumb, whereas another addressed upper limb synergies during reaching. One paper examined EMG co-contraction during gait, and one addressed gait EMG during obstacle crossing. One group examined reticulospinal pathways during elbow flexor activity using startling acoustic stimulation. Another studied masticatory muscle activity following brainstem stroke. Finally, one group addressed coupling between the electroencephalogram (EEG) and EMG signals during upper limb movements.Another seven papers were focused on using EMG to examine motor impairment after stroke ((Novel EMG processing techniques). These included new approaches to intramuscular EMG decomposition, coherence of motor unit firing patterns from surface EMG, clustering index analysis of surface EMG, and pattern recognition from high density surface EMG.Four studies used novel EMG processing techniques to study motor control and impairment post-stroke A number of studies examined the effects of an exercise/therapy program, or a single exercise session, on EMG and motor function. Some also addressed the associated cortical plasticity.Hesam-Shariati et al. examined changes in upper limb EMG activity resulting from the standardized 14-day Wii-based Movement Therapy program  in chronic stroke survivors. They found that training lead to different patterns of EMG changes that were related to the level of motor deficit. In their companion paper Hesam-Shariati et al. they quantified muscle synergies during therapy  based on EMG activity of the affected arm muscles using a non-negative matrix factorization algorithm. They were able to identify differences in the number of muscle synergies used by patients as a function of the level of motor deficit.Many addressed the effect of exercise/therapy on upper limb muscle activation properties. Lu et al. used forearm EMG signals to detect a stroke survivor's motion intent, and then used the EMG to drive a hand exoskeleton to assist with finger motion in real time. After 10-weeks of robot-assisted hand therapy, the patient showed improved grip strength and hand function. The results demonstrate the feasibility of robot-assisted training driven by myoelectric pattern recognition in chronic stroke survivors.Device-assisted interventions offer a way to study and train patients with more severe limb impairment. In a case study, Qian et al. evaluated the effects of 1 month (20 sessions) of EMG-driven NMES combined with robotic assistance, targeting the elbow, wrist, and fingers of subacute stroke survivors. EMG parameters, including the co-contraction index and the activation level of targeted muscles were used to monitor the muscle coordination patterns. They found that the NMES combined with robotic training could achieve higher motor outcomes at the distal joints and more effective reduction in muscle tone than traditional therapy.After a stroke, it is critically important to start rehabilitation early to take advantage of the highly plastic period of the neural system. In a pilot randomized control trial, Wilkins et al. found EMG-driven NMES task-specific arm/hand training (7 weeks) improved hand opening and functional use in chronic stroke survivors with moderate to severe motor impairments. Functional improvement was paralleled with functional reorganization in the ipsilesional primary sensorimotor cortex. The neural plastic reorganization after functional improvement was also seen with strengthened corticomuscular coupling. In a case study of a subacute stroke subject, Zheng et al. evaluated corticomuscular coupling between EEG and EMG (biceps) signals during elbow flexion before and after 1 month of regular physical and occupational therapy. Corticomuscular coherence was increased in the affected limb with functional improvement, but not in the non-affected limb. These results exemplify that stroke survivors with severe motor impairments may still have the potential to improve hand function if appropriate interventions are used to induce neural plasticity.Some investigators also addressed training-related cortical plasticity and corticomuscular coupling. Pilkar et al. used different EMG-based indices to quantify the effects of a foot drop stimulator on muscle activation during gait over a 6 month period of community walking. A wavelet-based time-frequency analysis approach was used to quantify activation changes of multiple ankle muscles in chronic stroke survivors. The findings suggest alterations in motor unit recruitment strategies after foot drop stimulator use. The outcomes establish the efficacy of a foot drop stimulator as a rehabilitation intervention that may promote motor recovery in addition to reducing foot drop.Androwis et al. used novel EMG analysis (Burst Duration Similarity Index) to quantify the intensity and timing of muscle activation during a single session of robotic gait therapy in acute stroke survivors. The authors showed that a robotic exoskeleton can reduce the soleus and rectus femoris muscle activity in the affected limb during stance phase, and can also improve the timing of muscle activation in the affected limb.Quantitative and continuous monitoring of muscle activation is necessary to adjust training protocols in a timely manner. Jones and Kamper studied the coupling of the index finger and thumb during close-open pinching motions in chronic stroke survivors. A Cable-Actuated Finger Exoskeleton was used to perturb joints of the index finger during pinching motions, while finger/thumb muscle surface EMG and finger kinematics were recorded. They found that involuntary finger-thumb coupling was present during the dynamic pinching task, with perturbation of the index finger impacting thumb activity. This finding reveals a potential mechanism to improve hand mobility following stroke. Li et al. analyzed motor synergies during arm reaching based on surface EMG recordings from multiple muscles and correlated with reaching kinematics. They were able to detect task-specific deficits in reaching movements after strokeSurface EMG together with other signals recorded peripherally or centrally provides a means to assess mechanisms of motor impairment. Ma et al. studied lower limb muscle activity during obstacle crossing using surface EMG in chronic stroke survivors. EMG activity of the leading limb during the swing phase was larger in all muscles in the stroke compared to the control group, and TA activity increased with obstacle height in both groups. Co-contraction between agonist-antagonist muscle pairs was larger in the stroke group in the leading/ trailing limb during certain phases. The authors suggested that the greater muscle activation during obstacle crossing following stroke may have a negative impact on balance.Banks et al. quantified surface EMG co-contraction of agonist-antagonist muscle pairs in three ways  and determined their association with gait impairment during treadmill walking. Co-contraction during the terminal stance phase was not different between healthy controls and the stroke subjects, regardless of the normalization method. Normalization also did not impact the ability to resolve group differences. Furthermore, the correlation between stance phase co-contraction and walking speed was modest. Pathological co-contraction may not be a primary factor contributing to impaired gait in most stroke survivors. The authors suggest other approaches that account for timing and amplitude components of the EMG  may better capture the relevant deficits.It remains unclear whether co-contraction of agonist-antagonist muscles is excessive and impacts gait significantly following stroke. In chronic stroke survivors, Gao et al. studied subacute stroke patients completing tasks such as hand gripping and elbow bending. Stroke subjects demonstrated greater strength in the bi-directional corticomuscular coupling between the EEG and EMG signals. Such changes suggest a compensational strategy after the brain lesion.The coupling strength between the EEG and EMG signals during motion is instructive in assessing motor function. in vivo even with the most advanced neuroimaging techniques. Startling acoustic stimulation is known to stimulate the reticulospinal pathways, thus allowing the opportunity to assess the role of brainstem motor system indirectly. Li et al. analyzed changes in EMG and force in response to startling acoustic stimulation during isometric elbow flexion in stroke survivors and healthy controls. They reported that the sound-induced force and EMG increase in stroke survivors was not significantly different from those in healthy controls. As such, there results suggest that the reticulospinal projections do not increase their contributions to muscle strength in stroke. Jian et al. analyzed surface EMG signals of bilateral masticatory muscles in stroke survivors after brainstem stroke using multiple EMG parameters. In addition to expected differences between muscles and sides, they did not observe the head position effect on muscle activation on both sides. These are valuable information as the results could advance the understanding whether head positions alter chewing and swallowing activities in stroke survivors.It is difficult to assess activities of brainstem nuclei Ren et al. developed a new intramuscular EMG decomposition technique to improve the accuracy of EMG decomposition with interference patterns. The technique was implemented by using six stages of analysis including feature extraction, clustering, refinement of the classification, and splitting of the superimposed MUAPs. A high accuracy of MUAP detection was reported in 8 subacute stroke survivors (88%) and 20 healthy control participants (94%).Examining motor unit discharge and recruitment patterns post-stroke can disclose valuable information pertaining to impaired spinal versus supraspinal motor control. EMG decomposition into constituent motor unit action potential (MUAP) trains, however, is challenging with severe superposition of multiple MUAPs. Dai et al. quantified the different types of connectivity in the spinal networks and changes in their relative contributions after a stroke. By comparing the coherence of motor unit firing pattern across different isometric contractions, they identified significant changes in coherence in three frequency bands: delta (1–4 Hz), alpha (8–12 Hz), and beta (15–30 Hz) in the paretic hand muscles. These changes reflect increased common synaptic inputs in the subcortical pathway and provide evidence on different origins of impaired muscle activation in stroke.Tang et al. applied clustering index analysis to examine surface EMG in the distal and proximal muscles of the upper limb from 12 stroke survivors. They observed abnormally high or low clustering index values in the paretic muscles compared to healthy controls. This finding may indicate that both neurogenic and myopathic changes may occur in paretic muscles.To further differentiate neurogenic and myopathic changes in the muscle, Wang et al. developed a novel pattern recognition technique for precise discrimination of 20 hand/upper limb functional movements in stroke survivors. Specifically, they applied wavelet packet to extract the neural control features and used the Fisher's class separability index and the sequential feedforward selection analyses to select appropriate channels in high density surface EMG. Such implementation can facilitate use of surface EMG control in stroke rehabilitation.Selection of appropriate features from surface EMG is essential for development of highly effective pattern recognition algorithms in the EMG-controlled devices. All authors made an equal contribution to the work, and approved it for publication.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.


The hypothalamic-pituitary-ovarian (HPO) axis is a tightly regulated system controlling female reproduction. HPO axis dysfunction leading to ovulation disorders can be classified into three categories defined by the World Health Organization (WHO). Group I ovulation disorders involve hypothalamic failure characterized as hypogonadotropic hypogonadism. Group II disorders display a eugonadal state commonly associated with a wide range of endocrinopathies. Finally, group III constitutes hypergonadotropic hypogonadism secondary to depleted ovarian function. Optimal evaluation and management of these disorders is based on a careful analysis tailored to each patient. This article reviews ovulation disorders based on pathophysiologic mechanisms, evaluation principles, and currently available management options. The hypothalamic-pituitary-ovarian (HPO) axis must be viewed as an entity that works in concert to allow for procreation by means of cyclic production of gonadotropic and steroid hormones. This cycle is tightly regulated to select a dominant follicle for ovulation, meanwhile priming the endometrium for implantation. The ovary plays a pivotal role in the production of steroid hormones necessary for follicular development and oocyte maturation. It contains a finite number of oocytes that a woman will have for the span of her reproductive life and influences the hormonal milieu required for oocyte maturation and fertilization. This complex regulation can be negatively impacted when pathologies occur within any juncture of the HPO axis.Ovulatory disorders are the leading cause of infertility classified into three categories according to the World Health Organization (WHO ). Group Here, we provide an overview of ovulation disorders categorized by pathophysiologic mechanism from recent literature, along with guidance on evaluation and currently available management options.Group I ovulation disorders, hypothalamic-pituitary failure (HPF) manifests as hypogonadotropic hypogonadism. Females with HPF typically present with delayed or impaired pubertal development, primary or secondary amenorrhea, and infertility. Idiopathic hypogonadotropic hypogonadism (IHH) due to a congenital absence of gonadotropic releasing hormone (GnRH) is the most common cause of HPF. IHH associated with anosmia is termed Kallmann syndrome, which results from failure of GnRH neuronal migration from the olfactory placode during embryonic development. This disorder has a multimodal genetic inheritance pattern and can be transmitted in an X- linked, autosomal dominant, autosomal recessive, or oligogenic fashion with variable penetrance. Several gene mutations in association with this disorder have been identified, most notably ANOS1 . The nasAcquired causes include panhypopituitarism, characterized by >50% deficiency of one or more tropic hormones secreted by the pituitary gland. Etiologies leading to panhypopituitarism involve tissue necrosis (secondary to acute ischemia or pituitary gland apoplexy), autoimmune or infectious hypophysitis and compression by pituitary adenomas or adjacent brain tumors. Postpartum hemorrhage and significant head trauma may temporarily or permanently impact hormone production from the anterior pituitary. Similarly, intracranial tumors may compress the anterior pituitary stalk disrupting axonal communication between the hypothalamus and pituitary gland. Craniopharyngioma, a benign brain tumor deriving from a Rathke’s pouch, is the most common brain tumor causing delayed puberty and primary amenorrhea. In addition to dysregulation of the HPO axis, bitemporal hemianopsia and chronic headaches may be observed if the optic nerve is compressed . AdditioLangerhans cell histiocytosis should be considered when more common causes of HPF are ruled out. This condition is marked by uncontrolled proliferation of dendritic cells associated with the monocyte-macrophage system . When LaA patient’s medical history can help delineate between the various etiologies, to tailor evaluation and management. Basic evaluation includes follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2). In some instances, further evaluation is advisable to exclude central hypothyroidism (low TSH), hypocortisolism (low ACTH) and low growth hormone, which are a hallmark of panhypopituitarism.Commonly, a head MRI is indicated to rule out morphologic pituitary anomalies or presence of a tumor . OverallGroup II, eugonadal ovulatory dysfunction, accounts for the majority of ovulation disorders and comprises a wide spectrum of disorders. Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive aged women with a prevalence of 6–10% . It is tExtremes of weight and body fat distribution, influences the regulation of ovulation. Obesity, particularly central type, interferes with endocrine and paracrine mechanisms involved in reproductive cycle regulation. Loss of normal GnRH pulsatility is commonly due to excessive aromatization of androgen precursors, DHEA and testosterone, to estrone in adipose tissue, decreased levels of sex hormone binding globulin (SHBG) and elevated production leptin by adipocytes . FurtherIn contrary, in underweight patients, GnRH pulsatility is affected by depletion of circulating leptin, excessive cortisol and neuropeptide Y production, in addition to elevated centrogenic opioid and endorphin secretion. Hyperprolactinemia is a common cause for ovulatory dysfunction. There are many known causes of hyperprolactinemia including anterior pituitary adenomas, prolactinomas, primary hypothyroidism with thyrotropin releasing hormone (TRH) stimulation of prolactin, renal failure with abnormal clearance of prolactin, and psychotropic medications altering dopamine release. Primary hypothyroidism hinders regulation of the HPO axis since excessive TRH secretion will interfere with GnRH pulsatility. Furthermore, abnormal thyroid function affects folliculogenesis and oocyte quality. Some studies have suggested thyroid stimulation hormone (TSH) > 2.5 μIU/mL may be enough to lead to disordered ovulation; however additional studies have presented conflicting data. The literature has demonstrated that during controlled ovarian hyperstimulation, TSH is noted to increase and if baseline TSH exceeds 3 μIU/mL, patients will experience clinical hypothyroidism ,17,18. AThe ultimate goal for anovulation caused by eugonadal hypothalamic-pituitary dysfunction is to correct the underlying etiology. The majority of endocrinopathy related infertility is reversible and can be managed medically. Patients who present with menstrual dyscrasias should undergo initial evaluation with AMH, TSH and total T4, and prolactin level. If clinical signs of hyperandrogenism are apparent, 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEA-S) and total testosterone should be measured to rule out presence of ovarian or adrenal androgen secreting tumors. It is important to consider that multiple endocrinopathies may co-exist and must be treated concurrently. Prior to medical management, preconceptual counseling and lifestyle optimization should be emphasized, particularly weight loss and exercise. Thyroid deficiency and hyperprolactinemia, when corrected often will lead to successful ovulation and pregnancy. Patients suffering with PCOS commonly require ovarian suppression with combined oral contraceptive pills (OCPs), unless conception is desired. Multiple non-contraceptive benefits exist with the use of OCPs in this setting including reversing hyperandrogenism with shrinkage of exaggerated ovarian stroma, regulation of menses and reducing the risk of ovarian and endometrial cancer . Those dGroup III ovulatory disorders is defined as ovarian insufficiency or failure with a hypergonadotrophic-hypogonadic profile that affects 5% of women with ovulatory dysfunction . Women pDespite a low incidence, the most common genetic form of POI remains Turner syndrome, 45 XO, with either complete or partial X chromosome deletions. These patients commonly present with primary amenorrhea due to accelerated oocyte depletion. The second most common cause of POI is chromosomal aberrations. Approximately 10–30% of cases appear to be familial, primarily exhibiting an x-linked inheritance pattern with varying penetrance ,24. SeveNOBOX) and factor in germline alpha (FIGLA) that are responsible for gonadal differentiation and folliculogenesis [Additional candidate genes have been proposed to be causative, however lack sufficient evidence. New headways illustrating causes for POI includes mutations in transcription factors such as nuclear receptor subfamily five group A member 1 (NR5A1), newborn ovary homeobox , type I and II, associated with endocrine gland and extra-glandular tissue destruction reported to cause POI. APS type I affects younger children, with 60% of girls affected experiencing primary amenorrhea and POI. Type II causes gonadal failure in 4% of affected individuals . AssociaCommon gynecologic disorders may also contribute to accelerated reproductive aging. Endometriosis affects 10% of reproductive aged women. In addition to structural pathologies, ovarian endometriosis may lead to ovarian destruction and consequently a hypoestrogenic state. A study performed by Cahill et al. described endometriosis related diminished LH levels in serum and follicular fluid impacting ovulation . InevitaA number of environmental toxins may lead to POI. Effects of cigarette smoking have been extensively investigated. Smoking is associated with accelerated follicular atresia, displayed by significant lower AMH and earlier onset of menopause . EnvironAs oncologic treatments continue to improve, and the number of cancer survivors continue to increase, so does the rate of iatrogenic ovarian insufficiency. Cancer therapy causes oocyte depletion in several ways, the most common being inhibiting growth and proliferation of cells that support oocytes. How chemotherapeutic drugs affect immature oocytes is still unclear, however commonly used toxins including alkylating agents, work by interlinking DNA causing breaks that damage the cell . AdditioPelvic and total body irradiation has significant ramifications on ovarian function. Radiation doses as low as 4–5 Gy results in permanent loss of ovarian function. Knowing these treatment modalities confer poor prognosis for post-therapy gonadal and uterine function, careful consideration can be made in planning for future fertility. The field of onco-fertility is ever growing, with fertility preservation becoming increasingly available. Both the quantity and quality of available oocytes significantly diminishes once a woman reaches 35 years of age with exponential decline until menopause. Ovarian insufficiency can be diagnosed by measuring AMH, estradiol, FSH levels and antral follicle count. Though spontaneous pregnancy is not impossible, it is certainly much more difficult to achieve without intervention. Patients faced with such a diagnosis should be provided reassurance and guidance to the alternate reproductive options currently available. Evaluation approach is dependent on medical history and physical examination. Reproductive aged women less than 35 years old with rapidly declining ovarian reserve warrant genetic and infectious disease testing. If genetic testing is abnormal, genetic counseling is prudent.Patients with Turner syndrome may present with lack of pubertal milestone or primary amenorrhea. Mosaic Turner syndrome patients may be aware of their diagnosis prior to complete follicular atresia and can salvage their fertility by means of oocyte and/or embryo cryopreservation. With newer vitrification techniques, oocyte cryopreservation has become a reliable and available method for fertility preservation . In factOnco-fertility patients also greatly benefit from oocyte or embryo preservation prior to gonadotoxic therapy. In recent years, random start ovarian hyperstimulation in preparation for egg retrieval allows physicians to shorten treatment duration to proceed with chemoradiotherapy . In a spIVF with donor oocytes currently remains the most successful treatment modality for women with POI or age related diminished ovarian reserve. Currently available options of fresh or frozen or known vs. unknown donors provides patients with more options. Furthermore, women may opt to have their young relatives, with abundant ovarian reserve, to donate oocytes to them . The use of mesenchymal stem cells (MSCs) has been emerging as a treatment option for patients with POI. Stem cell therapy has particularly been studied in the setting of iatrogenic ovarian destruction and shown great promise. Various sources of stem cells under investigation for this purpose include umbilical cord MSCs (UCMSCs), induced pluripotent adult stem cells (iPSCs), and embryonic stem cells. Mouse models with chemotherapy induced ovarian insufficiency undergoing subsequent treatment with UCMSCs have demonstrated improved ovarian function with recovery of sex steroid levels and decreased cumulus cell apoptosis ,46. The More novel therapeutic options are beginning to make strides for age related oocyte quality improvement. One suggested mechanism responsible for depleted ovarian reserve involves mitochondrial dysfunction . Though Those affected by POI have health implications if they remain in a chronic hypoestrogenic state including as cardiovascular risk, sexual function and bone health. Hormone replacement therapy (HRT) should be encouraged through use of estrogen therapy with cyclic progestin if a woman still has her uterus. Those who no longer have a uterus, estrogen replacement alone is recommended. HRT is important to reduce the risk of morbidity and mortality as it mimics normal ovarian function until the natural age of menopause . Dose tiIn summary, this review outlines an up to date classification of ovulatory disorders to serve as a guide for its evaluation and management. As ongoing research in etiology and pathogenesis emerges, novel treatment approaches continue to develop. Familiarity with ovulatory disorders will enable practitioners to provide high quality medical care and be a beacon of hope to a wide array of patients.


A dearth of research investigates socio-environmental mechanisms of health disparities. Therefore, this paper tests the association between neighborhood characteristics and telomere length (TL), a biomarker of cellular age, and examines if this relationship differs by race and urban residence. Data from US-born, non-Hispanic Black and White midlife and older adults  in the 2008 Health and Retirement Study was analyzed to test the relationship between TL and perceived neighborhood safety, cleanliness, and social cohesion. Linear regression models stratified by race included interaction terms between neighborhood characteristics and urban residence. Negative perceptions of neighborhood characteristics were associated with shorter TL in Blacks, with urban-dwelling Blacks having shorter TL than Blacks in less urban areas. Findings suggest that negatively perceived neighborhoods may be more detrimental to TL for urban compared to rural Blacks. Future research should elucidate the biobehavioral consequences of socially disadvantaged urban neighborhoods on healthy aging among Black adults.


Ochotona curzoniae) populations distributed along an altitudinal gradient of the Tibetan Plateau. We predicted that high-altitude pika would be more docile and less active.Animals inhabiting high altitudes consistently show slow life-histories. The pace-of-life syndrome (POLS) hypothesis posits behavioural, physiological and/or morphological traits that mediate the trade-off between current and future reproduction or survival, which have coevolved along a slow-fast life history continuum. Previous studies have shown that the life histories of plateau pikas varied across altitude, high-altitude individuals showed slow pace of life which were characterized by few litters per year with small litter sizes. Thus, we hypothesized that pikas populations at higher altitudes would also express personalities characteristic associated with slow life history, such as high sociability, low activity or aggressiveness. We tested this hypothesis by comparing the activity and docility of three plateau pika (The behaviour of 556 pikas, from which 120 individuals were measured at least twice, was quantified. We observed that plateau pikas at high altitudes were less active and more docile than pika at lower altitudes. Activity and docility were significantly and negatively correlated in populations from high altitudes but not in populations from low altitudes.Our results support the POLS hypothesis, highlight the existence of personality variation among populations distributed along an altitudinal gradient and emphasise the importance of environmental selection on personality divergence. Species with wide ranges usually exhibit geographic variation in life history traits, such as growth and reproduction –3. GeogrJunco hyemalis) bred at high elevations showed delayed development of structures necessary for reproduction, reduced duration of reproductive period and fewer broods than low-elevation conspecifics ) and moderately  repeatable, respectively, indicating that variation in these two personality traits varies consistently among individuals over time.Activity and docility were highly  and ZK  populations but showed no correlation with docility in the GN  population.Three populations at different altitudes showed our predicted differences in activity and docility Table . ActivitWe investigated the phenotypic divergence of personality traits among plateau pika populations along an altitudinal gradient. Previous work on plateau pika populations indicates that the life-histories of high-altitude populations are slow. In support of the POLS hypothesis, we observed that higher-altitude populations also possessed personality traits that have been characterized as slow, i.e., less active and more docile, compared with the lower-altitude populations.The differences in activity and docility among plateau pika altitude-associated populations can be attributed to the differing life history strategies that have evolved in response to different climates and environments Table . Low-altOur findings indicate that differences in environmental conditions resulted in specific associations between behavioural traits of plateau pikas. These results indicate that behavioural syndromes could be adaptive, such that associations between behaviour may vary substantially in accordance with prevailing environmental conditions. Activity and docility were negatively associated in pikas from high- and medium-altitude sites. Correlations between these traits may corroborate the POLS hypothesis . In the We analysed behavioural differences among populations at the phenotypic level. As a result, we cannot rule out whether phenotypic differences reflect genetic differences or developmental plasticity . RegardlWe were unable to conclusively identify the precise divergences in the personality of pika populations distributed at higher altitudes, given that we focused on the traits of pika populations distributed within a limited altitude range. Nevertheless, our data reveal that the personality of pikas differs across altitudinal sites. Our study also provides valuable information regarding the effects of ecological conditions on the behavioural traits of animals at the population levels . AlthougPlateau pikas exhibit significant differences in activity and docility along the altitudinal gradient, supporting the POLS hypothesis. Future studies are needed to explore the mechanism and ecological consequences of personality divergences at large spatial-temporal scales and combine the animal personality with global climate changes.


Declining stem cell function during aging leads to impaired tissue function and contributes to delayed tissue repair following damage. In adult skeletal muscle, loss of myofiber integrity caused by mechanical injuries or diseases are repaired by resident muscle stem cells (MuSCs), called satellite cells, which promptly exit from quiescence after disruption of muscle architecture to expand, differentiate and drive tissue regeneration. The fate of MuSCs fundamentally depends on the “niche”, their local environment, which is orchestrated by diverse cellular and acellular elements. Aging causes cell-extrinsic changes to the MuSC niche and dysregulates signaling pathways, which collectively alter the regenerative function of MuSCs . The lowFibro/adipogenic progenitors (FAPs) constitute a population of interstitial mesenchymal cells in skeletal muscle which are devoid of myogenic potential, but support muscle stem cell commitment and can differentiate to the adipogenic or fibrotic lineages  drives the perturbed support of aged FAPs to MuSCs. Genetic invalidation of WISP1 disrupts the communication between FAPs and MuSCs and leads to abnormal regeneration of skeletal muscle. Mechanistically, WISP-1 controls MuSC asymmetric expansion by activating Akt signaling. Importantly, this new paracrine mechanism can be targeted therapeutically by administering recombinant WISP-1 systemically. Altogether, our work reveals that loss of WISP1 from FAPs directly contributes to MuSC dysfunction in aged muscle and demonstrates that adipogenic progenitors are not just quiescent precursors waiting for pathological cues to elicit pathological conversions, but actually constitute bona fide elements of the stem cell niche, which regulate an active cross-talk with stem cells via paracrine signaling [The decline of MuSC function and muscle regenerative capacity during aging is under the control of a wide range of signals, out of which many arise from extrinsic cues coming from the local or systemic environment . In a reignaling .Along similar lines, a subpopulation of stromal progenitors in adipose tissue has recently been identified using single-cell RNA sequencing as a negative regulator of adipogenesis which represses the differentiation of adipocytes and keeps fat expansion in check . FAPs ar


OBJECTIVES/SPECIFIC AIMS: (i) Digitally quantify pathologically relevant glomerular microcompartmental structures in murine renal tissue histopathology images. (ii) Digitally model disease trajectory in a mouse model of diabetic nephropathy (DN). METHODS/STUDY POPULATION: We have developed a computational pipeline for glomerular structural compartmentalization based on Gabor filtering and multiresolution community detection (MCD). The MCD method employs improved, efficient optimization of a Potts model Hamiltonian, adopted from theoretical physics, modeling interacting electron spins. The method is parameter-free and capable of simultaneously selecting relevant structure at all biologically relevant scales. It can segment glomerular compartments from a large image containing hundreds of glomeruli in seconds for quantification—which is not possible manually. We will analyze the performance of our computational pipeline in healthy and streptozotocin induced DN mice using renal tissue images, and model the structural distributions of automatically quantified glomerular features as a function of DN progression. The performance of this structural-disease model will be compared with existing visual quantification methods used by pathologists in the clinic. RESULTS/ANTICIPATED RESULTS: Computational modeling will reveal digital biomarkers for early proteinuria in DN, able to predict disease trajectory with greater precision and accuracy than manual inspection alone. DISCUSSION/SIGNIFICANCE OF IMPACT: Automated detection of microscopic structural changes in renal tissue will eventually lead to objective, standardized diagnosis, reflecting cost savings for DN through discovery of digital biomarkers hidden within numerical structural distributions. This computational study will pave the path for the creation of new digital tools which provide clinicians invaluable quantitative information about expected patient disease trajectory, enabling earlier clinical predictions and development of early therapeutic interventions for kidney diseases.


Following presentation with abnormal liver function enzymes, confusion and fatigue, a 65-year-old male with alcoholic cirrhosis underwent spectral Doppler sonography that showed tardus parvus-like morphology in the main and left hepatic arteries, although peak systolic velocities and resistive indices remained normal. The patient’s continuing clinical symptoms prompted CT angiography, which demonstrated an unexpected, haemodynamically significant stenosis of the celiac artery. Although the stenosis was successfully stented and the hepatic arterial waveforms normalized, the transplanted liver had already undergone ischaemic necrosis, with resulting failure and the need for retransplantation. Recognition of abnormal waveforms, despite normal peak systolic velocities and resistive indices, with prompt definitive imaging evaluation of the arterial tree beyond just the main hepatic artery, may lead to the diagnosis of unexpected flow-limiting lesions in time to allow revascularization and thus prevent ischaemic transplant failure. CT angiography 2 days thereafter revealed not only a normal main hepatic artery and patent surgical arterial anastomosis, but also an unexpected, haemodynamically significant stenosis (exceeding 50% diameter2) at the origin of the celiac artery  should be pursued promptly when an abnormal hepatic arterial waveform is recognized in the setting of graft dysfunction.9 Some authors have noted that celiac artery compression by the arcuate ligament occurs in as many as 10% of patients undergoing liver transplantation.7 It is rarely symptomatic, owing to efficient arterial collateralization from the superior mesenteric and the gastroduodenal arteries; however, in patients without sufficient collateralization, symptomatic hepatic arterial insufficiency and/or thrombosis may result. Fortunately, the stenting procedure for our patient restored flow such that, for either possible cause, the patient’s retransplantation can proceed with adequate arterial inflow.It is essential to consider feeding vessels in addition to the main hepatic artery itself, such as the celiac artery, when searching for flow-limiting lesions. In the present case, the haemodynamically significant celiac stenosis undoubtedly developed after the patient’s original, successful transplant surgery. Because no calcifications were demonstrated at the site of the celiac stenosis by CT angiography, the differential diagnosis would include non-calcified atherosclerotic plaque as well as the median arcuate ligament syndrome.In summary, abnormal hepatic arterial waveforms following hepatic transplantation, even when other values such as RIs and peak systolic velocities are not abnormal, should elicit a prompt search for flow-limiting lesions using definitive imaging modalities such as CT angiography, with careful evaluation for lesions not only at the arterial anastomosis but also at other sites within the arterial tree supplying the transplanted liver.Abnormal hepatic arterial waveforms in hepatic transplant patients, despite normal peak systolic values and normal RIs, should elicit a search for flow-limiting arterial lesions.Definitive imaging, such as CT angiography, should be pursued promptly in the search for flow-limiting arterial lesions.Severe complications following liver transplantation may result from unexpected flow-limiting arterial lesions at sites other than the typical location at the donor/recipient anastomosis.Our institutional review board approved this study and waived informed consent in view of its retrospective nature. All procedures were conducted in compliance with the Health Insurance Portability and Accountability Act.


When patients develop destructive osteomyelitis, clinicians must always consider the possibility of SAPHO syndrome because even extremely destructive osteomyelitis can be cured by NSAIDs. YT: involved in manuscript drafting and clinical care of the patient. SY: involved in study conception and manuscript revision.


Sociedade Portuguesa de CuidadosIntensivos summarizes the current evidence and gives six clinicalstatements and an algorithm aiming to provide a standardized prescribing policyfor the use of stress ulcer prophylaxis in the intensive care unit.Critically ill patients are at risk of developing stress ulcers in the upperdigestive tract. Agents that suppress gastric acid are commonly prescribed toreduce the incidence of clinically important stress ulcer-relatedgastrointestinal bleeding. However, the indiscriminate use of stress ulcerprophylaxis in all patients admitted to the intensive care unit is not warrantedand can have potential adverse clinical effects and cost implications. Thepresent guidelines from the  Systemic hemodynamic andlocal alterations result in gastric mucosal blood flow impairment with subsequentischemic mucosal injury. However, the crucial factor for the development ofulceration and gastric bleeding is the high gastric intraluminal acidity, which ispotentiated by fasting.(3) less than 50% ofpatients will have occult bleeding (defined as guaiac-positive gastric aspirate orguaiac-positive stool) and approximately 5%(5)will have overt bleeding . However, this does not necessarily translate into clinicallysignificant gastrointestinal bleeding ,(6) whose incidence seems to have decreased over theyears. In studies published before 1999, the incidence of clinically significantgastrointestinal bleeding was between 2% and 6% in patients not receivingprophylaxis.(6) However, in studies published since 2001, theincidence has been reported to range between 0.1% and 4% with or withoutprophylaxis,(7) which is related to better overall critical care,including the increased use of early enteral feeding. This, along with concernsrelated to the reported increasing frequency of infectious complications ,(9) has challenged thetraditional cornerstone of pharmacological prophylaxis with agents that suppressgastric acid for stress ulcer prophylaxis.(10)Endoscopically evident upper gastrointestinal lesions may be found in up to 90% ofcritically ill patients within 3 days of admission;Sociedade Portuguesa de Cuidados Intensivosaims to summarize current evidence and give clinical recommendations for the use ofstress ulcer prophylaxis in the intensive care unit (ICU) to provide a standardizedprescribing policy and avoid injudicious use.This guideline from the A multidisciplinary task force was assembled. The task force comprised physicians, nurses, pharmacistsand economists with special interest and expertise in stress ulcer prophylaxisand/or evidence-based medicine. All members of the task force declared that noconflict of interest influenced the development of the guidelines.(11) The availability of a Cochranereview(12) relevant to the clinical questions was confirmed bysearching the Cochrane Database of Systematic Reviews. A further complementaryliterature search of PubMed® was performed. Trial data identifiedby the search strategies were considered to represent the best-quality evidence. TheGrading of Recommendations Assessment, Development, and Evaluation (GRADE) systemprinciples(13) was used to assess the quality of evidence fromhigh to very low and to determine the strength of recommendations.Task force members participated in a discussion via e-mail, and six clinicalquestions were built for evidence evaluation. Each working member took charge of oneclinical question and built search queries in the PICO  format.(14) This was done according to the GRADE system andconsidered the following factors: evidence quality, certainty in the balance betweenadvantages and disadvantages, certainty or similarity in values and preferences, andresource implications. Arriving at a consensus required an average level ofagreement of ≥ 80%. When the agreement level was < 80%, furtherdiscussions and voting were conducted.Finally, the task force determined the direction (for or against) and strength(strong or weak) of the recommendations using a two-round (self-administeredquestionnaire with no meetings among the participants) simple Delphimethod.A strong recommendation was worded as "we recommend" and a weak recommendation as "wesuggest".Sociedade Portuguesa de Cuidados Intensivos in Oporto anddiscussed by the panel and audience members.The key recommendations were presented at the annual symposium of theWe recommend maintaining (or initiating) agents that suppressgastric acid  in patients with compellingindications for acid suppression. Strong recommendation, moderate qualityof evidence.Several clinical situations require gastric acid suppression , and indications should be respected, both in the ambulatory andhospital (including intensive care) settings.Patients with compelling indications include the following:Helicobacter pylori-negative ulcers; need tocontinue NSAID or failure to eradicate Helicobacterpylori; ulcers complicated at the outset; and giant(> 2cm), refractory or recurrentulcers].(15)- Known peptic ulcer disease in the healing phase and maintenancephase in selected circumstances  is comparingproton-pump inhibitors and histamine-2-receptor antagonists, and the results areexpected to provide more relevant data.(27)The efficacy of proton-pump inhibitors and histamine-2-receptor antagonists inpreventing stress-ulcer bleeding in critically ill patients has been compared inseveral randomized control trials and meta-analyses.(51) focused on the comparison betweenhistamine-2-receptor antagonists and proton pump inhibitors for the prophylaxisof stress ulcerrelated gastrointestinal bleeding. The results are contradictory,mainly due to the use of different clinical inputs, and there is no strongevidence regarding which is the most effective alternative. Data from the mostrecent meta-analysis of clinical trials indicate that proton pump inhibitorsshould be used. However, if one relies on a propensity score-matchedobservational cohort study, histamine-2-receptor antagonists are the preferredoption.(51) The only clear conclusion is that, as the costof prophylaxis is small when compared to the costs of complications, the mosteffective alternative will constitute a dominantalternative.(51)There are multiple pharmacoeconomic analyses(53) It is acknowledgedthat the published literature on this issue derives from heterogeneouspopulations of critically ill patients who may differ from the populations atrisk identified by the previous recommendation.Although the quality of evidence is suboptimal, proton-pump inhibitors have beenthe preferred regimen in intensive care units across Europe, the United Statesand Canada.(54) provided evidenceof an increase in pneumonia with proton-pump inhibitor use; however, this studywas related only to cardiac surgery patients, and confidence intervals werewide. Small randomized trials (55)) and a case-control study showed anincreased adjusted risk for Clostridium difficile infectionsduring treatment with proton-pump inhibitors, but this was more related to theduration of exposure.(56)Additionally, the expected adverse effects of proton-pump inhibitors are aconcern and must be taken into account. A cohort studyUltimately, the desirable consequences of stress ulcer prophylaxis withproton-pump inhibitors are expected to outweigh the undesirable consequencesamong the population at risk.We make no recommendation regarding specific proton-pump inhibitorregimens.The ideal drug regimen should be effective in reducing the risk of ulceration,with a low potential for adverse effects and drug interactions andpharmacokinetic characteristics that facilitate its use in patients with organdysfunction; it should also be cost-effective.a prioridefined subgroup analysis of at least one meta-analysis suggests that the routeof administration  and dosing (onceversus twice a day) do not affect theresults.(45)There is no direct comparison between different proton-pump inhibitor-basedregimens , and heterogeneity across studies (comparing proton-pump inhibitorsto other regimens) impairs the comparison of effects between the individualproton-pump inhibitor regimens tested to date. An e.g., vasopressor use, altered gastric emptying andmotility, feeding tube and nutrient interactions) may influence enteralabsorption in critically ill patients, and the intravenous route is generallypreferred.(57) This is disputed by a study showing that,despite a lower bioavailability, enteral lansoprazole suppressed acid inintensive care unit patients better than the intravenousformulation.(58) However, this has not been confirmed by furtherstudies, and lansoprazole requires a complex and labor-intensive galenicformulation for feeding tube administration.In relation to the route of administration, multiple factors(qd) may be a reasonable choice.(59) However, thedefinitive choice of the specific proton-pump inhibitor regimen should be basedon individual patient and medical values, experience, product labeling,cost-benefit analyses, anticipated risks of drug-drug interactions and adverseeffects.Due to its safety in (at least moderate) organ dysfunction, lower probability ofdrug-drug interactions, and available formulations, intravenous pantoprazoleThe most recent and comprehensive meta-analysis(61) found that therapywith agents that suppress gastric acid was associated with a significant risk ofClostridium difficile infections but that the risk waslower for histamine-2-receptor antagonists than with proton-pump inhibitors.Accumulating evidence suggests that the use of agents that suppress gastric acidmay increase the frequency of infectious complications.Clostridiumdifficile infections is still controversial because meta-analysisis weak in detecting a modest increase in these events.(62) Nevertheless, therisk of Clostridium difficile infections remains higher inpatients receiving proton-pump inhibitors compared with patients receivinghistamine-2-receptor antagonists.(8) Moreover, observationalstudies(64) have shown thatcontinued proton-pump inhibitor use during incident Clostridiumdifficile infections increases the risk of recurrence.In the critically ill population, the increased risk for Clostridium difficile infections, proton-pumpinhibitors should be avoided, and histamine-2-receptor antagonists should be thepreferred therapy when stress ulcer prophylaxis isindicated.(62)Based on available data and given the significant disease burden and mortalityassociated with We recommend stopping prophylaxis with agents that suppress gastricacid when risk factors are no longer present and the patient is receivingenteral nutrition. Strong recommendation, low quality ofevidence.(65) This is inagreement with studies that have concluded that 88.5% of stress ulcerprophylaxis in nonintensive care unit patients isinappropriate(66) and that a relatively restrictive stress ulcerprophylaxis program not only reduces inappropriate use without increasing therates of hospital-related gastrointestinal bleeding but also results in anestimated annualized cost savings of more than US$200.000.(67)Acid suppressants are inappropriately continued in a large proportion of patientsafter the resolution of risk factors and even after intensive care unit orhospital discharge, thus extending the potential risks and costs associated withstress ulcer prophylaxis beyond the intensive care unit.(26) there is some evidence to suggest that inpatients receiving enteral feeding, pharmacologic stress ulcer prophylaxis isnot beneficial, and combined interventions may even increase the risk of someinfectious complications. However, the evidence is still insufficient to justifywithholding stress ulcer prophylaxis from patients who are at high risk forgastrointestinal bleeding. It is sufficiently compelling to support thecessation of prophylaxis when risk factors are no longer present and the patientis receiving enteral nutrition.As previously described,(68) As one of the more common indications forstress ulcer prophylaxis is mechanical ventilation, extubation is crucial toidentify and possibly discontinue acid suppressiontherapy.(62)Patients should thus be evaluated daily during multidisciplinary care rounds forthe continued need for prophylaxis, and once the patient is receiving enteralnutrition and risk factors are no longer present, stress ulcer prophylaxisshould be discontinued. This strategy will reduce the overuse and unnecessarycontinuation of agents that suppress gastric acid upon discharge and in theoutpatient setting.Clostridiumdifficile infection, for which histamine-2-receptor antagonists arepreferred (Statement 5). Once the patient is receiving enteral nutrition andrisk factors are no longer present, stress ulcer prophylaxis should bediscontinued (Statement 6). The general algorithm for the prophylaxis of stress ulcer bleeding in theintensive care unit is presented in The authors suggest that the practices recommended in this guideline arecontinuously evaluated and monitored and that this guideline is updated as newevidence becomes available.


Housing coordination, a central component of the Money Follows the Person program, allows older adults and people with disabilities to experience greater independence and sense of well-being . This study was part of the 2017 Money Follows the Person (MFP) Process Evaluation involving 26 key informants (KIs) who completed telephone interviews sharing their experiences about program implementation. Of these, 13 KIs providing housing coordination services to the MFP transition team were asked about the housing coordination training they received and suggestions to improve the training. They were also asked about housing resources, how they develop their housing inventory, and recommendations for a “Housing Best Practices Report.” Interviews were audio-taped and transcribed. Data were analyzed using ATLAS.ti. Results demonstrate a need for more training and assistance to enable housing coordinators to expand their knowledge of housing alternatives, increase their awareness of housing policy/process changes, and further inform consumers about housing choices. Suggestions to improve housing coordination included offering more creative solutions during monthly housing coordination phone calls. Housing inventory challenges mentioned by KIs included time constraints, limited staff, administrative delays, and lack of affordable housing. Suggestions for housing inventory development focused on improving the management/maintenance of housing inventories. Best housing practices underscored the importance of communicating, teaming, building relationships with landlords and management companies, and standardizing housing policies and procedures. Overall recommendations included strengthening collaboration among housing coordinators to identify and implement best practices and improving housing inventory development to widen housing options for consumers.