Dear Editorrepair index”.A publication by Fahradi et al., (2017) describes the results of the study concerning micronucleus (MN) assay in buccal cells of smokers, a problem which was investigated by many scientists recently . But this problem is not solved, and MN induction in smokers is still questionable since both positive and negative results were reported in these studies . The authors studied along with MN also nuclear anomalies and presented the results of calculation of so-called “The main shortcoming of this publication (very serious one!) is that the authors scored only 500 cells per subject which were stained with Papanicolau stain (which is not DNA specific). I wonder why vast majority of scientists from some Asian counties (namely India) and Latin America (namely Brazil) ignore the validated and standardized buccal MN assay protocol . In this protocol is clearly stated that 2,000 buccal cells stained with DNA-specific stain should be scored to get reliable results . It is suggested in several publications that for the monitoring of genotoxic effects of carcinogens in exfoliated humans cells 3,000 - 10,000 cells per subject should be evaluated due to the lower baseline MN frequency . Recently, Ceppi et al., (2010) also calculated the minimum number of cells which should be evaluated to obtain reliable result in buccal MN assay and stated that it should be equal to 4,000.Crucial for buccal MN assay is staining because all epithelial cells have different types of keratohyalins. Cell injury (cytotoxicity) which can take place due to smoking (because of cell exposure to cytotoxic/genotoxic substances in tobacco smoke) can increase production of these proteins in cells (which appear in cells as bodies which do not contain DNA). When DNA non-specific stains are used, they visualize these bodies which can mimic MN. This phenomenon was for the first time showed by Casartelli et al., (1997) and Casartelli et al., (2000). Further, this phenomenon was confirmed in our study with different staining techniques in the buccal cells of smokers . In the buccal cell MN assay protocol and further guidelines, it is indicated that the presence of MN should be confirmed under fluorescent light because after this type of staining all bodies containing DNA fluorescent .Hence, the study by Fahradi et al., (2017) contains triple limitation  and therefore, the results obtained in the study are not reliable. Another serious problem of this publication is enormous high level of MN. Indeed, it is indicated in Tables 1 and 2 that MN levels in non-smokers are 27.3‰ (2.73%) and 37.0%, 47.4% and 29.0% in smokers. These numbers are extremely, unusually high! Indeed, MN in epithelial buccal cells are very rare events. In 1999, Fenech et al., (1999) stated that the average MN frequencies in exfoliated buccal cells of healthy subjects are between 1.0 and 3.0‰. Later, it was reported by Bonassi et al., (2011)  and Ceppi et al., (2010) (based on the data of 63 studies) that MN level in buccal cells of healthy unexposed persons are 0.74‰ (between 0.3 and 1.7%) and 1.10% (between 0.70 and 1.72%), respectively . In other words, in the study of Fahradi et al., (2017) the level of MN in non-exposed healthy subjects is much higher than in publications of other investigators. This level is between 24.9- and 36.9-fold higher compared with other data which is not possible, of course.differences were significant in smokers vs. nonsmokers for MN” . But careful examination of the data presented in Table 2 shows that difference between smokers with history of ≤10 years and non-smokers (from Table 1) is not significant . The authors wrote that “statistical analysis was performed using the t-test”. If so, the statistical significance of difference between mentioned data is t = [29.0 – 27.3 / √ (82 + 10.92)] = 1.7/13.5 = 0.12 which is far from critical value 1.96 to be significant at p < 0.05). It means that the difference between smokers with history of ≤10 years and non-smokers is not significant. In this case the authors should write that MN level increases significantly after 10 years of smoking, and duration smoking less than 10 years does not induce MN in buccal cells. The application of Student’s t test for statistical analysis of MN in buccal cells is not correct. Better to use non-parametric tests . At least, the authors ought to normalize the data by means of log or square root transformation and then apply t-test. The authors stated in the abstract and also in the text of the article that “karyorrhexis is a form of nuclear change in which nuclei are pyknotic or partially pyknotic”. This is completely wrong statement because they mixed up two types of nuclear anomalies, i.e. karyorrhexis and pyknosis . Fahradi et al., (2017) stated that “Marked by an Arrow”. But no one arrow is indicated. Also, the photos are of poor quality and it is not possible to see any anomaly in them. Instead of one cell there are several and it is absolutely not clear which cell the author mentioned. In all legends to Figures 1 – 3 in which different types of nuclear anomalies are presented, is written that anomalies are “The authors stated that there are several reports concerning MN induction in smokers and mentioned following papers: Kamboj et al., (2007); Stich et al., (1982); Majer et al., (2001) and Rosin et al., (1987). All these papers are not relevant in this regard. Indeed, the paper by Majer et al. is comprehensive review, research papers by Kamboj et al., (2007) describes MN score in patients with squamous cell carcinoma and leukoplakia and Stich et al., (1982) concerns betel quid chewers. I could not find the paper by Rosin et al., (1987) but in the abstract presented in PubMed is written that the paper concerns tobacco and betel quid users in the Philippines and snuff users in the Northwest Territories. Instead they could cite the paper which they mentioned in another regard, namely Stich and Rosin (1983) concerning MN assay in heavy smokers. repair index”, I am not sure about its usefulness. Indeed, this parameter is not indicated in the validated protocol. Instead of this index I suggest to the authors include into analysis scoring of basal cells. This parameter will show changes in the proliferation of buccal cells . I hesitate if it should be expressed as %. Indeed, RI of non-smokers (Table 1) is 1.51 + 1.29/ 2.73 + 0.9 = 0.77. So it is mistake to state that RI is expressed in %.As for “In summary, Fahradi et al., (2017) carried out research work with 60 subjects but made some mistakes which are unfortunately quite common in case of ignoring the validated and standardized protocol for buccal MN cytome assay . Consideration of all parameters suggested in the protocol will increase the reliability of the study and will give possibility to compare the results obtained in different laboratories.


The humoral immune response is one of the central tenets of mammalian immunity. Delivered through the production of antibodies of multiple classes  and sub-classes  their activities are achieved through their inherent ability to bind with exquisite specificity to a given target antigen and then engage various immune effector functions to elicit the appropriate response. Chief amongst these are cellular immune effectors such as macrophages, NK cells, and neutrophils which are engaged through their expression of Fc receptors (FcR), binding the Fc portion of the immunoglobulins. Accordingly, different classes and isotypes of antibody engage a selection of different FcR. For example in the murine system there are receptors that are specific for IgG, IgM, IgE as well as receptors that are dually-specific for IgM and IgA with paralogues in human cells. A bewildering array of immune and non-immune cells express these various receptors in different combinations, leading to a highly complex system for regulating and evoking antibody responses. Various FcR evoke cellular activation (FcγRIIa and FcγRIIa), whereas others are inhibitory (FcγRIIb), with still others being capable of evoking intracellular transport and recycling of IgG (FcRn) to establish long serum half-lives. Clearly, careful regulation of expression, signaling and modulation is required for a healthy, well-functioning and balanced immune system. In this Research Topic, a series of articles are provided to reveal comprehensive insights on the role of these various FcR in health and disease, taking into account the wide spectrum of receptors and cells expressing them. Most importantly the insights presented in these articles pave the way for powerful immunotherapies and emerging principles about how FcR can be exploited for therapeutic purposes for various diseases, including infectious diseases, autoimmune diseases, and cancer.Kerntke et al. revisited the question of the number and expression pattern of FcγR on myeloid cells, Nagelkerke et al. dissected the genetic variation within the family, including duplications and deletions within the low affinity FcγR-locus. How the GPI-linked FcγRIIIb affects tumor cell killing by PMN through therapeutic monoclonal antibodies is furthermore tackled by Treffers et al. while Kang et al. describes a new re-engineered IgG molecule that selectively engages FcγRIIIa-V158 for enhanced therapeutic benefit through a single FcγR. Brandsma et al. also investigated the differential capacity of tumor killing through FcR that engage different antibody isotypes, specifically addressing the role of FcαR vs. FcγR. Parameters affecting the function of FcRn were also tackled. Finally, Kendrick et al. mathematically modeled FcRn kinetics and suggest a novel reduced-order model based on a new expression for the fractional catabolic rate that can be used to predict plasma IgG responses.In total, 6 original research articles were contributed on the various topics, spanning the genetics and function of the disparate FcγR. While Pyzik et al. and Nagelkerke et al. also contributes a comprehensive review of FcγRII-FcγRIII genetics. Anania et al. systematically discuss the structure-function relationship of FcγRII receptors, while the contribution of FcγRIIb in the development of autoimmune diseases in mouse models gets a comprehensive assessment by Verbeek et al.. Breedveld and van Egmond review pathologies and new opportunities resulting from targeting FcαR. In addition, Foss et al. extend the scope of this topic to the cytosolic FcR, TRIM21, while Liu et al. and Kubagawa et al. discuss the role of the IgM binding, FcμR in immunity. The role of FcR in infectious diseases and vaccine development is covered by Boudreau and Alter, discussing FcR and their role in the protection against influenza infection and future prospects to leverage FcR immune activity for the development of vaccines with Jenks et al. focusing on the subversion of immune responses by FcR encoded by Herpes simplex virus. The involvement of FcR in various inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and immune thrombocytopenia with a focus on antibody-mediated autoimmunity is covered by Mkaddem et al.. This includes the mechanism of FcR-receptor-mediated inflammation and how to potentially exploit this knowledge therapeutically. Katsinelos et al. focuses on the role of antibodies and receptors involved in neurodegeneration during Alzheimer's and Parkinson's disease, while Castro-Dopico and Clatworthy discuss the role of FcR in inflammatory diseases of the gut, namely inflammatory bowel diseases. Patel et al. discusses the multiple variables that are at play in the interface between target and effector cells through IgG-FcγR engagement, with a focus on the largely undescribed role for FcγR-glycosylation in mediating the underlying recognition events. FcR signaling is also specifically covered by Gomez et al. for FcεRI in Allergic disease, including seasonal rhinitis, atopic dermatitis, urticaria, anaphylaxis, and asthma, while Koenderman et al. reviews how the activation status of FcR can be affected by inside-out signaling. Finally, the importance of FcR in cancer and cancer therapies, in particular, the role of checkpoint inhibitors therein, is given comprehensive review by Chen et al. and special focus on FcγRIIb mediated antitumor immunity by Teige et al.This Research Topic also features 18 Review Articles spanning these disparate areas. FcRn is tackled by Overall, it is clear that the knowledge acquired from the articles contained within this special issue highlights the complexity of the FcR family and their importance in multiple aspects of health and disease. However, equally clear is the fact that this family of receptors, despite being investigated for over 4 decades, still harbors many secrets, reinforcing that we still lack a complete understanding of their complex regulation, interaction and impacts. As central to humoral immunity, modulating disease pathogenesis and acting as a key determinant of antibody therapeutics, it is also similarly evident that further research in this area is still warranted. We look forward to seeing what the intensive study of these receptors shows in the coming decade.All authors listed have made a substantial, direct and intellectual 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 objective of this study was to determine the prevalence of DRML and factors related to the lesions among denture wearers seen in a Nigerian teaching hospital.interviewer’s administered questionnaire was used to obtain information from consecutive patients that had used removable denture for at least six months and consented to participate. Data related to gender, age, types of denture and presence of denture induced oral lesions were obtained, entered into a computer and analyzed using IBM SPSS Version 20. Descriptive statistics were expressed as frequency and percentages. Fisher’s exact test was performed for discrete variables. A P-value less than 0.05 was regarded as statistically significant.a total of 104 respondents participated in the study and 14 had DRML giving a prevalence of 13.5%. The majority, 11 out of the 14 (78.57%) presented with mucosa ulceration, while 8 (57.14%) out of the 14 cases of DRML were caused by over extension of the denture flanges. There was no statistically significant relationship between daily removal of denture fore going to bed to sleep at night and DRML (p=0.776).the prevalence of denture related mucosal lesion was 13.3% and the major cause was over extension of denture flange. There is need to emphasize adherence to review appointments for early detection and correction of denture instability and over extension of denture flange to prevent DRML. Worldwide, the prevalence of edentulism is high and varies considerably between countries   while a et al. [et al. [et al. [et al. [et al. [et al. [et al. [The prevalence of denture induced oral lesions varies across different countries and ranges from 10.8% to 62% . A preva [et al.  reported [et al.  reported [et al.  revealed [et al. -13; Sadi [et al.  reported [et al.  48.2% an [et al. , epulisf [et al.  and papi [et al. . This ca [et al. . Coelho  [et al.  reportedThis was a cross-sectional study among removable denture wearers. A total of one hundred and four removable denture wearers were interviewed over a period of twelve months. Only patients that were willing to participate and had used the removable denture for at least six months were included in the study. After informed consent was obtained, data related to gender, age, type of denture, length of denture use, hygiene care, nocturnal denture wear, and presence of denture induced oral lesion were obtained using an interviewer´s administered questionnaire. The questionnaire was administered by one of the investigators. Confidentiality was ensured by not writing the name of the participants in the data form. Examination of each patient´s mouth was done on a dental chair by using a mouth mirror with gloved hand. Diagnosis of denture induced oral mucosa lesion was made based on the clinical appearance of the oral mucosa; denture stomatitis based on inflamed palatal mucosa, and ulceration was diagnosed based on presence of laceration or tearing on the oral mucosa in relation to denture. Patients with nodular mucosal swelling were referred to oral surgery clinic for excisional biopsy and the biopsies were sent to oral pathology laboratory for histological confirmation of mucosal hyperplasia. Also, the patients´ dentures were examined, and according to the quantity of plaque on the denture base, patients were divided into two groups by using Budtz-Jorgensen´s index   of the respondents were females and majority 48 (46.2%) were above 60 years . Table 2There was no statistically significant relationship between daily removal of denture before going to bed to sleep at night and DRML (p=0.776), types of denture and DRML (p=0.269) and presence of plaque on the denture and DRML (p=0.729) . Table 4et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [In this study 58.6% of denture wearers that participated were females and this is in agreement with a previous study by Arigbede et al. . The femet al. . The pre [et al.  but lowe [et al.  45.6% by [et al. , 20.5% p [et al. . The dif [et al. ,20,21 re [et al.  could beet al. [et al. [Candida albicans being reported as a major cause by previous studies [et al. [In this study, traumatic ulcer was the most common form of denture induce lesion 1178.6%), followed by mucosa hyperplasia 2 (14.3%). This is in contrast to previous studies ,21 that et al.  reported [et al.  reported [et al. . Our fin%, follow studies . The mos studies  as the m [et al.  stated tet al. [et al. [There is no significant relationship between not wearing the denture to bed at night and the development of DRML, although the group that sometimes remove their denture before bedtime had the highest (35.7%) incidence of DRMLs in this study. This is in contrast to the previous study that shows higher prevalence among those that wear denture to bed . The higet al.  reported [et al.  was thatThe prevalence of denture related mucosal lesion is 13.5% in this study and the major cause was over extension of denture flange. There is need to emphasize proper denture fabrication to prevent DRMLs and adherent to review appointments for early detection of denture instability and over extension of denture flange.Denture related mucosa lesion (DRML) has been studied and found to show varying prevalence across different countries;DRML was more common among complete denture wearer and in elderly;Denture stomatitis was found to be the most common form of DRML.The causes and factors related to the incidence of denture related mucosa lesion (DRML) was studied for the first time in Nigeria and we found that ulceration was the major cause of DRML especially among RPD wearers;There was a statistically significant relationship between forms of lesion and types of denture. Mucosa ulceration and epulisfissuratum occurred more commonly among removable partial denture and complete denture wearers respectively;There was no statistically significant relationship between the duration of use of denture and prevalence of DRML.


The choice of the type of stabilization device in the osteosynthesis of dorso-lumbar spine fractures remains a subject of controversy. The present study aims to evaluate the efficiency of short segment in patients suffering post-traumatic thoracolumbar fractures. This study was conducted in the Department of Orthopedic Surgery and Traumatology of the Habib Bourguiba University Hospital, Sfax, Tunisia. All our patients had a spinal osteosynthesis via the posterior approach with a short segment pedicle screw fixation. We established a record of the pre and post-operative data, the functional results in the post-operative stage during the follow-up period and in retrospect according to the Denis Pain Scale, as well as the Oswestry score. The correction was evaluated by determining the relative gain and loss at the last period of retrospect: vertebral kyphosis, regional kyphosis, Gardner Segment Kyphotic Deformity (GSKD), and computed tomography (CT) scan in retrospect to check the quality of the arthrodesis. The average Oswestry score was 14%. Twenty-nine patients had an Oswestry score ≤40%. The relative gain obtained postoperatively was 57.3% for vertebral kyphosis, 67.2% for regional kyphosis and 71.3% for Gardner kyphosis deformity; while the loss of correction at the last follow-up was 0.6° for vertebral kyphosis, 1.5° for regional kyphosis and 0.9° for GSKD. No cases of non-union were reported. The short segment fixation makes it possible to limit operating time, the abundance of bleeding and the aggression of the soft tissues. Over the last two decades, numerous technical advances in instrumentation and in the knowledge of spinal biomechanics have modified the surgical strategies for the synthesis of spinal-lumbar spine fractures . The choWe conducted a retrospective, descriptive study over an 8-year period involving 30 patients operated on for a thoracolumbar spine fracture at the Orthopedic Surgery and Trauma Department of the Habib Bourguiba University Hospital in Sfax, between July 2011 and July 2019. All patients were operated on by the same surgeon and with the same technique. All of our patients underwent a spinal osteosynthesis via the posterior short segment instrumentation, and a posterior and postero-lateral graft. In our study, we included patients with: age ≥15, complete preoperative, postoperative and retrospective radiological assessment with a minimum retrospect of 1 year. We established a record determining the clinical and radiological data of each patient. On the clinical level, we specified the general information about the patient and the circumstances of the accident. The record also included the characteristics of the fracture and its consequences on the spinal statics, the neurological status, the pre and post-operative data , and the postoperative. Retrospective clinical and anatomical results according to the Denis Pain Scale, the Oswestry score (ODI: Oswestry Disability Index), the Schöber Index and return to work were considered in the report. On the radiological level, we estimated the correction by determining the relative gain and losses at the last follow-up vertebral kyphosis (VK), regional kyphosis (RK) and Gardner Segment Kyphotic Deformity (GSKD). We also performed the study of sagittal balance through the sagittal heel in T9 and the sagittal vertical axis (SVA) measured on an x-ray of the entire spine standing front and in the profile made at the last retrospect. Scannographic analysis was performed to check the quality of the arthrodesis.Our population included 29 men and only 1 woman. Average age was 32.6 years with a standard deviation of 10.7. The trauma was due to falls from a high place in 50% of the cases  and to road accidents in 46.7% of the cases . AssociaThe mean operating time was 99.3 minutes with a standard deviation of 16.7 minutes. Pre- or postoperative transfusion was necessary in only one patient in our population. A laminectomy was performed in 8 cases (26.7%). The length of the hospital stay was 12.2 days on average and the delay in getting up postoperatively was of 2.9 days in average in non-neurological patients, with extremes ranging from 2 to 5 days. Four patients (13.3%) did not adhere to our rehabilitation protocol. The average decline in our series is 51.1 months with a standard deviation at 24 months. According to the Denis Pain Scale (DPS), 27 patients (90%) had a grade <3 and 3 patients (10%) had a grade ≥3 . The aveTwenty-six patients (86.7%) returned to work within 7.9 months and 4 patients (13.3%) stopped working permanently. The average Schöber index was 12.9/10 cm with a standard deviation of 0.6 cm. All patients initially presenting a partial neurological deficit improved by at least one grade according to the Frankel classification, 50% of which showed total neurological recovery. We also deplored a case of sepsis on early material. However, no case of non-union or implant failure was noted. Regarding the radiological results, the relative gain obtained postoperatively was 57.3% for VK, 67.2% for RK and 71.3% for GSKD  and the et al. [et al. [et al. [et al. [In congruity with the literature , the stuet al. , the abs [et al.  found th [et al.  found 36 [et al.  and that [et al. . Others  [et al. . The Loa [et al. .et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [According to the Magerl´s classification , type A et al. , this cl [et al.  question [et al. , the pre [et al.  thinks t [et al.  argues t [et al.  and Defi [et al.  used mon [et al.  (100 min [et al.  (101 minet al. [et al. [et al. [et al. [et al. [The comparison of bleeding abundance between the two types of segmental stabilization has been reported in several publications , 20, shoet al.  (12.4 da [et al.  (17 days [et al.  and Shin [et al.  noted go [et al.  with an  [et al.  and lack [et al. .et al. [et al. [et al. [et al. [El-Shehaby A et al.  reported [et al.  noted th [et al. . Compare [et al.  and less [et al. . As for Short segment fixation makes it possible to minimize the extent of the skin incision and to limit not only the operating time, the abundance of the bleeding and the damage of soft tissues , 30, butThoracolumbar fractures are common;Thoracolumbar fractures require osteosynthesis with a posterior and posterolateral graft;The choice of the type of stabilization remains a subject of controversy.The short segment minimizes the extent of the skin incision;The short segment limits the damage of soft tissues;Prescribing the short segment fixation makes it possible for consolidation and arthrodesis of thoracolumbar fractures without incurring a significant loss of correction or a high rate of instrumentation failure.The authors declare no competing interests.


Exercise program combined with electrophysical modalities in subjects with knee osteoarthritis: A randomised, placebo-controlled clinical trial”. Gomes et al. concluded that the low-level laser therapy (LLLT) did not reduce knee osteoarthritis pain when applied as an adjunct to exercise therapy. We argue that Gomes et al. neglected relevant laser treatment recommendations in the conduct and reporting of the trial.We read with interest the article by Gomes et al. entitled: “Gomes et al. did not state the Joules per treatment spot applied. We calculated the Joules applied from other laser information in the report and found that it is too low of a dose according to the World Association for Laser Therapy (WALT) guidelines. Furthermore, we have published a meta-analysis of 22 placebo-controlled trials demonstrating a significant difference in pain-relieving effect between doses in adherence and non-adherence to the WALT guidelines. However, neither the WALT guidelines, nor our meta-analysis was mentioned by Gomes et al.Moreover, Gomes et al. did not state whether the output power of the laser device was measured, and this is concerning because in the city of São Paulo, where the trial was conducted, most laser devices have been found to deliver less of a dose than specified by the manufacturers.In summary, we found that the best available evidence regarding effective and ineffective LLLT dosing from systematic reviews was neglected in the conduct and reporting of the trial, and that the laser device may not have been calibrated. Exercise program combined with electrophysical modalities in subjects with knee osteoarthritis: A randomised, placebo-controlled clinical trial”. Gomes et al. concluded that the addition of low-level laser therapy (LLLT) “… did not increase the clinical benefit after 8 weeks of treatment (primary and secondary variables) when combined with an exercise protocol for knee osteoarthritis.” [We read with interest the article by Gomes et al. entitled: “hritis.” .We argue that the results of the trial were not interpreted in the light of what was already known in terms of LLLT dosing.2 was utilized in skin contact mode and that the energy density was 6 J/cm2 [2*0.1309 cm2 = 0.78 J).We are surprised that Gomes et al. did not state the Joules per treatment spot applied  since th 6 J/cm2 . This meIn the World Association for Laser Therapy (WALT) dose guidelines, irradiating the osteoarthritic knee with at least 1 J of 904 nm wavelength laser per treatment spot is recommended . Our res2 [2 is equivalent to J per treatment spot only in instances where the laser beam covers exactly 1 cm2, which it rarely does.The dose applied by Gomes et al. does not satisfy the WALT recommendations and our LLLT dose-response meta-analysis can explain the negative findings. However, neither the WALT recommendations , nor our2 . It is iGomes et al. did not state whether the output power of the laser device was measured. It is a major concern that in the greater São Paulo area of Brazil, where the study by Gomes et al. was conducted, 59 of 60 laser devices tested delivered less of a dose than specified by the manufacturers . We concIn summary, we found that the best available evidence regarding effective and ineffective LLLT dosing from other trials was neglected in the conclusion by Gomes et al. and that their laser device probably was not tested and most likely delivered an ineffective dose.


The development of DNA sequencing technology has provided an effective method for studying foodborne and phytopathogenic microorganisms on fruits and vegetables (F & V). DNA sequencing has successfully proceeded through three generations, including the tens of operating platforms. These advances have significantly promoted microbial whole‐genome sequencing (WGS) and DNA polymorphism research. Based on genomic and regional polymorphisms, genetic markers have been widely obtained. These molecular markers are used as targets for PCR or chip analyses to detect microbes at the genetic level. Furthermore, metagenomic analyses conducted by sequencing the hypervariable regions of ribosomal DNA (rDNA) have revealed comprehensive microbial communities in various studies on F & V. This review highlights the basic principles of three generations of DNA sequencing, and summarizes the WGS studies of and available DNA markers for major bacterial foodborne pathogens and phytopathogenic fungi found on F & V. In addition, rDNA sequencing‐based bacterial and fungal metagenomics are summarized under three topics. These findings deepen the understanding of DNA sequencing and its application in studies of foodborne and phytopathogenic microbes and shed light on strategies for the monitoring of F & V microbes and quality control. The principles of three generations DNA sequencing were depicted. Whole genome sequencing and DNA markers of foodborne and plant fungal pathogens were summarized. Bacterial and fungal metagenomics studies on fruits and vegetables were concluded. The amplicons of the DNA fragments are then sequenced in a system with four independent PCR arrays. In the four independent PCR assays, four chain‐terminating inhibitors  are added. In the PCR assays, the majority of DNA polymerase reactions are conducted by adding dNTPs. However, in several reactions, ddNTPs are added for polymerization, thus terminating chain extension. As a result, DNA amplicons with different lengths are obtained. An electrophoresis method is used to separate the terminated DNA amplicons. The continuous DNA sequence is obtained by docking the ends of the electrophoresis‐separated products.The initial DNA sequencing methodology was developed in the mid‐1970s. Sanger et al. established a method for determining DNA sequences via primed synthesis with DNA polymerase  was announced by Applied Biosystems Co. in 1987 , the single‐molecule real‐time (SMRT) approach and the Oxford Nanopore MinION sequencer . The representative E. albertii strain KF1 was the first to be sequenced and reported  serve as markers for specific VT‐producing E. coli  gene , salamae (II), arizonae (IIIa), diarizonae (IIIb), houtenae (IV) and indica  and flagellar (H) antigens . The genome of the representative S. enterica strain Typhi str. CT18 was the first to be reported . The sseL, spvC . Specifically, S. aureus is an important pathogen associated with toxin‐related food poisoning. As of recently, the genomes of approximately 10 630 S. aureus strains have been registered  genes of sea, seb, sec and see have been used to monitor toxic S. aureus in food , 113 strains of S. boydii (genome ID 496), 1338 strains of S. sonnei  have been registered  that encodes 2790 proteins. In PCR‐based detection assays, specific gene regions of ipaH, virA, ial and 16S rRNA have been used as targets for Shigella genus identification . The hip, 16S rRNA, rrs, cdaF, porA, Hyp, cjaA, ceuE, hipO, mapA, ceuA, askD, glyA, lpxA, ccoN, ORF‐C sequence, rpoB, oxidoreductase gene, cdtA and pepT genes are widely used for the PCR identification of C. jejuni  gene is considered to be a useful marker for distinguishing patulin‐producing and nonproducing Penicillium species , which differ between plant species , alternariol (AOH), alternariol monomethyl ether (AME), tentoxin (Ten) and altenuene (ALT). However, the genes responsible for Alternaria toxin biosynthesis have not yet been confirmed. To date, six strains of A. alternata have been registered  carrying HST genes. The genome characteristics of A. arborescens, A. brassicicola, A. solani and A. tenuissima are summarized in Table Alternaria species, such as high‐resolution melting (HRM) analyses, AFLP and SSR , Alt a1, AaSdhB, AaSdhC, AaSdhD, ITS and β‐tubulin have been used for Alternaria species identification . Genomic comparison revealed approximately 98% similarity between the six A. flavus species and 81% similarity between A. flavus and A. parasiticus species . As illustrated in previous reviews, the genes responsible for aflatoxin biosynthesis are integrated as a cluster that contains approximately 25 genes with a total length of 80 kb  regions in the Fusarium genus . A total of 15 strains of this pathogen have been sequenced (NCBI genome ID 13188). The representative F. fujikuroi strain IMI 58289 has been reported . The representative strain F. proliferatum ET1 has been reported  gene  rDNA (18S) gene  marker  region (Diguta et al., The et al., et al., et al., et al., et al., Metagenomic strategies are technological approaches that are increasingly being used to study the overall microbial community in complex biological samples (Cao Many studies have elucidated the bacterial and fungal communities on F & V by using 16S rDNA and ITS sequencing. For this review, we searched references mainly from the Web of Science, NCBI, ScienceDirect and CNKI platforms. A total of 64 original studies describing the microbiomes of various F & V were identified Table . Illuminet al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., Plant microbiomes are related to species/genotype specificity Fig. . Recentlet al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., The microbiomes of F & V are affected by differences in regional environments, farming practices and disease occurrences Fig. . Many enet al., et al., et al., Aspergillus, Botrytis, Mucor and Penicillium. The spinach phyllosphere was observed to present a decrease in bacterial diversity after 15 days of storage at 4°C or 10°C, which might be related to the inhibition of bacterial activity by the lower temperature (Lopez‐Velasco et al., et al., et al., et al., et al., The treatments applied to F & V during postharvest processing and storage affect microbial communities Fig. . RefrigeThe development of DNA sequencing technology has provided an effective method for microbial WGS and genetic analysis. In recent decades, DNA sequencing technologies have been successfully developed including approximately ten operational platforms. By performing DNA sequencing, microbial WGS is largely promoted. Genetic studies provide DNA markers for microbial identification at the genetic level. These markers are extensively used in PCR or chip‐based detection. On the basis of 16S rDNA and ITS sequencing, metagenomic approaches are now emerging technologies for analysing the entire microbial community in a complex F & V matrix. The microbiomes of F & V show huge differences between plant species/genotypes. In addition, the microbiomes of F & V are related to factors such as regional/environmental factors, farming practices and postharvest treatments. These studies shed light on ways to improve F & V cultivation, disease prevention and quality control.The authors declare no conflict of interest.


Tracking the spread of pandemics and the evolution of the underlying pathogens are effective tools for managing deadly outbreaks. Forster et al.  use a meMJNs are not an appropriate representation of viral evolution. Although Forster et al.  state thAdditionally, MJNs are constructed using distance-based criteria, which is inappropriate for modeling the mutational process in viruses . In facthttps://www.fluxus-engineering.com/) merely links the “outgroup” sequence  to the most similar sequence of the already-produced “ingroup” network. Therefore, it neither roots the ingroup topology nor polarizes character transformations (The outgroup comparison by Forster et al.  is partirmations , 3.The authors’ misinterpretation of MJNs fosters misconceptions, inaccuracies, and misrepresentations of fundamental phylogenetic principles. Thus, unfortunately, Forster et al.’s study  misleads


Even if current guidelines suggest an early referral of young breast cancer (BC) patients to fertility preservation counselling, physicians still lack knowledge about the different available strategies. Hormonal stimulation to harvest mature oocytes is considered unsafe by many oncologists and experts in reproductive medicine, particularly in the setting of oestrogen receptor-positive BC. The aim of this mini-review is to provide an overview on the available data about this topic in order to clarify potential misunderstandings and to highlight the new trends in the oncofertility field with their pros and limitations. The European Society of Medical Oncology , the AmeControlled ovarian stimulation (COS) and subsequent oocyte/embryo freezing are the gold standard of fertility preservation (FP) in this setting –5. NonetAre these issues really clinically relevant?Several studies have showed no detrimental effects on BC recurrence or survival if CHT was delayed until 12 weeks after surgery, particularly in ER-positive, early stage BC patients . Nowadayet al [et al [et al [Up to now, there is no evidence that COS promotes BC growth . A systeet al  did not l [et al –22 devell [et al . Most ofl [et al . Subsequl [et al  confirmel [et al .et al [in vivo tumour response to adapt the subsequent adjuvant treatment [et al [p = 0.47). The relapse-free survival rate was not statistically significantly different between pre- and post-surgery groups (p = 0.44) [et al [p = 0.75), and the median time was 41.5 days versus 35.5 days (p = 0.50) in the 34 patients who underwent COS versus the 48 control patients, respectively. Thus, patients who underwent COS before NACT had a delay of approximately 1 week compared to control patients, which could hardly impact prognosis [More recently, Letourneau et al  comparedet al . Authorsreatment . Kim et t [et al  reported = 0.44) . Chien e) [et al  conducterognosis . Nonetherognosis .et al [A prospective multicentre study conducted by Marklund et al  comparedet al –27, 29.in vitro maturation—IVM) or using gonadotrophin-releasing hormone analogues (GnRHa) as medical gonadoprotection.Novel strategies have been developed to avoid hormonal stimulation in BC patients: harvesting ovarian tissue with subsequent cryopreservation, harvesting immature oocytes without COS (Over 130 live births have been reported after reimplantation of ovarian tissue , 30–41, et al [in vitro growth of human oocytes have been made, the pregnancy outcomes after IVM are still suboptimal, with lower implantation rates as compared with embryos obtained from mature oocytes [Grynberg et al  reported oocytes , 46.According to current guidelines, the ovarian suppression with GnRHa during CHT does not represent an option of FP but a strategy to reduce the detrimental impact of cytotoxic drugs on ovarian reserve  as data BRCA1/2-mutation carriers [To date, evidence on long-term reproductive outcomes after BC treatment is still scarce. A recent Swedish cohort study indicates that a successful pregnancy after BC is possible both in women who underwent FP and who did not . Noteworcarriers , 56.In conclusion, a timely COS for FP remains the first choice for young BC patients interested in FP, also if they have ER-positive tumours. Modified COS protocols with letrozole combined with gonadotrophins could increase safety and it should be recommended , 57, 58.The authors declare that they have no conflicts of interest.No funding was received for this specific research.All authors listed have contributed sufficiently to the writing and/or critical revision of the paper; they have approved the submitted final version.


To determine the functional outcomes, complications and revision rates following total knee arthroplasty (TKA) in patients with pigmented villonodular synovitis (PVNS).We conducted a systematic review of the literature. Five studies with a total of 552 TKAs were included for analysis. The methodological quality of the articles was evaluated using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) scale. Functional outcomes, complications and revision rates were assessed. The mean age was 61 years (range 33–94 years) and the mean follow-up period was 61.1 months (range 0.2–35 years).n = 32) of patients in our review. Symptomatic recurrence of PVNS, component loosening, tibial-component fracture, instability and periprosthetic infection were the main factors leading to the need for revision TKA.All the studies reported improvement in knee function following TKA. Post-operative stiffness was the most frequently reported complication, affecting 32.7% (The findings of this review support the use of TKA to alleviate the functional limitations and pain due to knee degeneration in patients with PVNS. The operating surgeon should be aware of the increased risk of post-operative stiffness, as well as a potentially higher risk of infection. Implant survival should also be considered inferior to the one expected for the general population undergoing TKA. Pigmented villonodular synovitis (PVNS) is a benign proliferative condition which affects the synovial tissue and is a subtype of tenosynovial giant-cell tumor . This raThe etiology of PVNS is still unclear, with some believing that the disease stems from chronic inflammation , 5, wherTreatment for PVNS aims at removing the pathological lesion(s) either through open or arthroscopic synovectomy . A meta-With the increasing number of TKAs performed each year, arthroplasty surgeons are likely to encounter cases of PVNS with established degenerative changes. Understanding the challenges associated with this group of patients is, hence, very important. Our initial intent was to perform a meta-analysis on TKA as a treatment modality for PVNS; however, due to both the disease’s rarity and the scarcity of available literature, we have, therefore, decided to perform a systematic review of the literature instead to determine the functional outcomes and complications of TKA in patients with PVNS of the knee.The literature search was conducted on Medline and EMBASE on 16 April 2020 by research librarians at two independent hospitals. Keywords used for the searches were “Pigmented Villonodular Synovitis” OR “Pigmented Villonodular Tenosynovitis” OR “Giant Cell Tumour of Tendon Sheath” AND “Arthroplasty, Replacement, Knee.” All relevant studies between 1946 and 2020 were identified in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) guidelines. All three authors then identified relevant studies by assessing the bibliographies of the included papers. The selected articles adhered to the PICO criteria for systematic reviews Population, Intervention, Comparison and Outcomes (PICO) criteria for systematic reviews.Our inclusion criteria for the study were as follows: (1) the studies selected should be about TKA as a treatment modality in PVNS, (2) the articles should be written in English, (3) the articles would report the functional outcomes post TKA and (4) the articles would report on complications post TKA.Our exclusion criteria were: (1) articles not reporting on the functional outcomes, (2) articles which included arthroscopic treatment of PVNS instead of TKA and (3) case reports which did not include the functional outcomes post TKA.After removal of duplicate articles, a full-text review of the selected studies was undertaken by two authors (YCT and KT).One reviewer (YCT) extracted data from the selected papers using a standardized data collection form. Information relating to the number of patients, their demographics, follow-up period, complications, revision rates, implant survival rates, recurrence and pre-operative and post-operative clinical and functional outcomes were compiled into a spreadsheet which was later checked by the second reviewer (JYT). There were no inconsistencies in the results.The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) scale was used to evaluate the articles . It was n = 10–48 patients, 11–48 TKAs) describing the outcome of TKA in patients with PVNS. Our largest study was by Casp et al. (n = 453 TKAs) [The four studies included were small to medium retrospective case series (53 TKAs)  and we d53 TKAs) , Casp et53 TKAs) , Lei et 53 TKAs)  and Su e53 TKAs)  scored a53 TKAs)  scored 9The results were summarized using descriptive statistics for continuous variables, frequencies and percentages for categorical variables. Microsoft Excel, 2016 version  was used for data analysis.The initial literature search identified 111 articles, of which 36 were duplicated articles. After screening the remaining 75 articles, a total of six studies satisfied the eligibility criteria. Two articles, Houdek et al.  and HamlThe studies included 552 TKAs; however, only 98 patients (99 TKAs) had reported functional outcomes. Among the 552 TKAs, 83 patients (84 TKAs) had D-PVNS and 15 had L-PVNS, while the remaining 453 patients from the study by Casp et al. were not characterized by the disease subtype . The meaThree studies reported a pre-operative and post-operative comparison of the KSS and demonstrated a mean improvement of 26.79 and 39.11 points post-operatively, in functional and clinical KSS respectively. Casp et al.  and Versp = 0.72). The study by Casp et al. [Both studies by Lei et al.  and Su ep et al.  and Versp et al.  did not n = 31 patients) compared to 4.69% (n = 85 patients) in the control group with osteoarthritis (odds ratio (OR) 1.48, p value = 0.023).Stiffness or decreased knee range was defined by authors Houdek et al.  as a fleIn total, there were a total of 16 infections (2.9%) in our patient population. Authors Casp et al.  utilized“Symptoms of disease recurrence” was defined by authors Houdek et al.  as recurp value = 0.92) in increased risk of revision at 2 years compared to the osteoarthritis (OA) group in the 2 years post-operative period. Authors Verspoor et al. [Revision was described as the removal of implants with or without replacement of the materials. Symptomatic recurrence of PVNS, component loosening, tibial-component fracture, instability and periprosthetic infection were the main factors leading to revision TKA . There wr et al.  reportedr et al.  reportedr et al. , 15.TKA has been shown to be a generally successful procedure in patients with PVNS and established degenerative changes and this is reflected in the improvement of post-operative functional and clinical KSS in the four studies included in this systematic review. The main complication of PVNS in our patient cohort appears to be stiffness and infection.A systematic review and meta-analysis of case series and national registry reports with more than 15 years of follow-up by Evans et al.  estimateAn interesting observation from the studies was that 33 patients (34 TKAs) were diagnosed with PVNS post-operatively, through histopathological samples taken during the arthroplasty procedure due to suspicious synovial changes. This was seen in 23 out of 28 patients (82.1%) in the Su et al. study  and 10 oo, range 50–115o) which co-related with their poor post-operative ROM; however, there appears to be no clear link between multiple interventions and increased stiffness post TKA in our patient population. Casp et al. [p value = 0.011).Stiffness was among the main complications post TKA in patient with PVNS. According to the UK National Joint Registry 16th Annual Report, the peak incidence for stiffness occurs between 1 and 3 years with 0.56 revisions performed per 1000 primary knee replacements (95% CI 0.53–0.60) with the trend for the development of stiffness decreasing after the 3-year mark . There wp et al.  evaluaten = 14) in the former versus 1.55% in the latter . Houdek et al. [There was a total of 16 infected joints in our patient population. Casp et al.  also comk et al.  reportedk et al.  administA total of seven patients were noted to have a recurrence of PVNS at a mean of 6 years (range 2–12 years) following the TKA. Both Houdek et al.  and VersPost-operative recurrence of PVNS can be identified with MRI, using metal artefact reduction sequence that optimizes the visualization of periprosthetic soft tissues. MRI can play an important role during post-operative surveillance as it is highly sensitive and non-invasive. Relevant findings are a mass or diffuse synovitis of low signal intensity, both of which warrant close follow-up .This systematic review has limitations. First, we have reported the pertinent complications, but recognize that there is a time-dependent bias, which, due to the relatively short follow-up, may lead to underrepresentation of their true incidence. Second, the available studies were characterized by having a low level of evidence as well as a lack of a complete uniformity in reporting outcomes. Additionally, the Casp et al.  study diThe findings of this review support the use of TKA to alleviate the functional limitations and pain due to knee degeneration in patients with PVNS. The operating surgeon should be aware of the increased risk of post-operative stiffness, as well as a potentially higher risk of infection. Implant survival should also be considered inferior to the one expected for the general population undergoing TKA.


A Guest Editorial in Archives of Toxicology by Schreiver and Luch  has poinFrom a consumer’s aspect, there is a notable increase in the incidence of “itchy tattoos” Kluger . From a Considerable progress has been made in tattoo pigment analysis. For identification of 36 specific organic pigments in tattoo inks, Schreiver et al.  describeA pivotal point of the toxicological discussion is the potential carcinogenicity of tattoo inks. At present, skin cancers on tattoos are considered so far as coincidental, except for keratoacanthomas on red tattoos Bauer et al.  report o(ii)TatS. This new and promising model emulates healed tattooed human skin. It underlines the advantages of 3D over traditional 2D cell culture systems. The methodological approach might be important for further research on the toxicology of tattooing, including used pigments and their destruction for tattoo removal.Hering et al.  establisThis issue of Archives of Toxicology presents two contributions to this topic.In the February issue of this journal Giulbudagian et al.  reviewedNevertheless, the assessment of risks remains a challenge, owing to knowledge gaps on biokinetics of highly complex inks and their degradation products. Giulbudagian et al.  point to


Matrix metalloproteinases (MMPs) are members of an enzyme family and, under normal physiological conditions, are critical for maintaining tissue allostasis. MMPs can catalyze the normal turnover of the extracellular matrix (ECM) and its activity is also regulated by a group of endogenous proteins called tissue inhibitors of metalloproteinases (TIMPs) or other proteins, such as Neutrophil Gelatinase-Associated Lipocalin (NGAL). An imbalance in the expression or activity of the aforementioned proteins can also have important consequences in several diseases, such as cancer, cardiovascular disease, peripheral vascular disease, inflammatory disease, and others. In recent years, MMPs have been found to have an important role in the field of precision medicine as they may serve as biomarkers that may predict an individual’s disease predisposition, state, or progression. MMPs are also thought to be a sensible target for molecular therapy ,2,3,4.This Special Issue includes ten papers: seven original articles and three review articles dealing with a broad range of diseases related to MMPs.The article by Santiago Ruiz et al  showed tThe study by Cione E et al.  evaluateThe paper by Rautava J et al.  deals wiThe article by Rodríguez-Sánchez E. et al.  exploresThe study by Heinzmann D et al.  exploredThe paper by Ferrigno A et al.  studied The article by O’Sullivan S. et al.  studied The study by Provenzano M. et al.  aimed toThe paper by Laronha H.  extensivThe article by Liu Z. et al.  reviewedThis Special Issue describes important findings related to MMPs function, and dysregulation in several areas, such as vascular, kidney, and respiratory systems and also highlights the most recent progress on the knowledge and the clinical and pharmacological applications related to the most relevant areas of healthcare.


Liver fibrosis and cirrhosis occur in the course of chronic HBV infection, with the increasing risk to develop hepatocellular carcinoma. In about 95% of adults’ acute hepatitis B virus infection is self-limited, whereas in 90% of young children HBV infection leads to chronic progression. It is likely that a fully developed immune system contributes to HBV clearance  has primed the determination of stealth or invisible virus. During the early HBV infection, transcriptome analysis failed to show a drastic change of hepatic gene expression, especially when compared to hepatitis C virus infection, which is associated with a strong IFN response (Wieland in vivo have revolutionized the field (Bissig et al.et al.et al.et al.et al.et al.Liver-chimeric mice, that have been developed to analyse HBV infection


We read with great interest the recent publication by Bankov et al. where they described the characteristics and functional activity of fibroblasts in Nodular Sclerosis (NS) Classical Hodgkin Lymphoma (cHL) . The autWe appreciate that the study of Bankov et al.  confirmeInt. J. Cancer ”, but in our manuscript published in . Cancer  in 2009 . Cancer . Moreove. Cancer  we repor”, but in. Cancer .In conclusion, we consider that there was a misinterpretation of our data since we have never claimed that IL-7R is up regulated in cHL fibroblasts or demonstrated that IL-7 secreted by HRS cells strongly induced the proliferation of cHL fibroblasts .


This unique diversity of photoinduced applications has spurred major research efforts on the rational design and development of photocatalytic materials with tailored structural, morphological, and optoelectronic properties in order to promote solar light harvesting and alleviate photogenerated electron-hole recombination and the concomitant low quantum efficiency. This book presents a collection of original research articles on advanced photocatalytic materials synthesized by novel fabrication approaches and/or appropriate modifications that improve their performance for target photocatalytic applications such as water  and air (NO Photocaatalysts .Research efforts have been accordingly focused on the design and fabrication of advanced photocatalytic materials relying on competent modification approaches such as coupling with plasmonic nanoparticles, surface engineering, and heterostructuring with other semiconducting and/or graphene-based nanomaterials, as well as tailoring the materials’ structure and morphology  in order to boost light harvesting and photon capture, charge separation, and mass transfer that play a pivotal role in photocatalytic environmental remediation and solar to chemical energy conversion applications ,5.2 photocatalysts, prepared by a one-pot hydrothermal method. The complete removal of MC-LR from aqueous solutions was achieved under visible light irradiation, related to the unique combination of visible light photogenerated electrons from anion-induced impurity states and interfacial charge transfer between the brookite and anatase phases.This Special Issue consists of 10 original full-length articles on advanced photocatalytic materials fabricated by innovative synthetic routes and judicious compositional modifications, with diverse applications ranging from the degradation of hazardous water and air pollutants to hydrogen evolution and photoelectrocatalytic hydrogen peroxide production. T. M. Khedr at al.  reported2 was utilized by M. Janus et al. [x decomposition without compromising, and even improving, cement’s mechanical properties. Laser pyrolysis was applied by K. Wang et al. [2 photonic crystals by graphene oxide (GO) nanocolloids and subsequent thermal reduction was reported by Diamantopoulou et al. [N-modified TiOs et al.  as an adg et al.  to synthu et al.  as a pro3 and Ag2S quantum dots with tunable photoelectrochemical response by the light incidence angle. Control over the shape and facet growth of TiO2 nanocrystals was demonstrated by Y. Du et al. [2 nanowires, grown on TiO2 nanotube arrays by electrochemical anodization, in combination with Au plasmonic nanoparticles were successfully applied by T.C.M.V. Do et al. [Fluorine-doped tin oxide (FTO) inverse opals crystal were also exploited by X. Ke et al.  as macrou et al.  by tunino et al.  for the 4 with annealing temperature, used as an alternative metal oxide photocatalyst beyond TiO2, leading to enhanced decomposition of methylene blue as a model dye pollutant under LED visible light.Plasmonic Ag nanomaterials were also incorporated in silver-copper oxide heterostructures by H. Suarez et al.  to promo2/FTO photoanodes, enabling broad visible light harvesting. These photoelectrodes combined with a Pt-free counter electrode, made of carbon cloth with deposited nanoparticulate carbon, were used for the assembly of a photoelectrochemical cell operating as a Photo Fuel Cell, i.e., without any external bias. These devices were demonstrated to photoelectrocatalytically produce substantial quantities of hydrogen peroxide with the Faradaic efficiency exceeding 100% in the presence of NaHCO3 carbonate electrolyte.The sensitization of mesoporous Titania films by nanoparticulate CdS and CdSe, in combination with ZnS passivation was used by T. S. Andrade et al.  for the All the published articles were thoroughly refereed through the standard single-blind peer-review process of Materials journal. As Guest Editor, I would like to acknowledge all of the authors for their excellent contributions and the reviewers for their valuable and prompt comments that greatly improved the quality of the papers. Finally, I would like to thank the staff members of Materials, in particular Ms. Floria Liu, Section Managing Editor, for her devoted efforts and kind assistance.


Dear Sir,On an eerily quiet, urban Dublin street lies an apartment block, it’s balconies chequered with identical Irish flags carrying a defiant yet simple, national slogan; ‘You’ll Never Beat the Irish’. It is the brilliance not only of the green–white–orange against the brutalist background that catches the eye but also the boldness, the sheer determination of the silent protest. It is a taunt to the insidious international public enemy that is COVID-19. It first barrelled through Ireland’s door in late February 2020. On March 12, 2020, our Taoiseach Leo Varadkar addressed the nation from Washington, DC, issuing guidance on a nationwide lockdown (Radio Teilifís Éireann, et al., et al. et al. et al. et al. During times of crisis, we as humans have a natural tendency to seek solace in collectivism and reassurance in joint protection from a threat or crisis (Baumeister & Leary, et al. et al. et al. While COVID-19 alone may not be the sole impetus for suicidality, the associated social disconnection, physical isolation and routine disruption may be a pernicious cocktail of risk factors (Ammerman In the words of Thomas Fuller, ‘if it were not for hope, the heart would break’ (Grayling,


In this issue of MJR there are interesting case reports, research protocols and reviews.1 reviewed the role of microRNAs (miRNAs) in the pathogenesis of osteoarthritis (OA) and their potential role as therapeutic targets in this disease. miRNAs are small, single-stranded non-coding RNAs that regulate gene expression at the post-transcriptional level.Panagopoulos et al.2 use a case of a woman with Adamantiades-Behcet disease (ABD), who subsequently developed monoclonal gammopathy of unknown significance (MGUS) to speculate on the mechanisms of development of MGUS and ABD. ABD shares features of auto-immune disease and autoinflammatory disease and the authors elaborate that an early event in B cells, such as IgH translocation, may make them sensitive to growth factors, such as interleukin(IL)-6 which is raised in ABD. Also, the CD56 marker, increased in ABD T cells, is also increased in MGUS plasma cells.Chikanza et al.7 will utilize stress perfusion cardiac magnetic resonance in asymptomatic patients with APS to detect myocardial ischemia.Patients with antiphopsholipid syndrome (APS) may develop angina and myocardial infarction. In a research protocol, Tektonidou et al.8 in a 5-year prospective protocol will study disease course, comorbidities, treatment efficacy and outcome in giant cell arteritis in Greece.Tsalapaki et al.9 in a research protocol will examine longitudinal relationships between sedentary behavior  while in a sitting, reclining or lying position, or light intensity physical activity(1.6-<3.0 METS) with health outcomes in rheumatoid arthritis.O’Brien et al.6 pointed out, this finding as well SSc may well be a consequence of silica exposure.Calcified chest lymph nodes in a patient with systemic sclerosis (SSc) is a rare finding in SSc. Yet, as Angelopoulou et al.5 reported on two patients with Sjogren’s syndrome (SjS) who developed polymyositis and inclusion body myositis and identified another 24 cases of SjS with inflammatory myopathies in the literature.Migkos et al.3 reported on a patient with ankylosing spondylitis who developed systemic sclerosis (SSc) and scleroderma renal crisis. The co-existence of ankylosing spondylitis and SSc is rare.Venetsanopoulou et al.4 described a patient with RA treated with steroids, methotrexate and adalimumab developed Orf disease, also known as ecthyma contagious; a rare self-limited disease caused by a DNA virus of the parapoxvirus group and transmitted to humans from goats and sheep.Patients on immunosuppressants are susceptible to various infections. In this issue, Kostopoulos et al


Ambio articles highlighted in this 50th Anniversary Issue have influenced the cultural narrative on environmental change, highlighting concepts such as “resilience,” “coupled human and natural systems”, and the “Anthropocene.” In this peer response, I argue that global change research is still paying insufficient attention to how to deliberately transform systems and cultures to avoid the risks that science itself has warned us about. In particular, global change research has failed to adequately integrate the subjective realm of meaning making into both understanding and action. Although this has been an implicit subtext in global change research, it is time to fully integrate research from the social sciences and environmental humanities.Research on global environmental change has transformed the way that we think about human-environment relationships and Earth system processes. The four  The Economist portrayed the Earth as a technical structure covered by riveted steel plates in dull blue colors. The accompanying story informed readers that “Humans have changed the way the world works. Now they have to change the way they think about it, too” (The Economist “Welcome to the Anthropocene.” The cover photo of the May 28, 2011 edition of The Economist cover story saw an impressive amount of research on global environmental change that has transformed the way that we think about human-environment relationships and Earth system processes. The concept of the Anthropocene has contributed to a new way of describing the significant role of humans in shaping the Earth’s geology and ecology. Yet climate change, biodiversity loss, poverty, inequality, and other global problems are even more serious concerns today, and the timeframe for taking actions to meet international commitments is shrinking, increasing the risk of reaching “tipping points” and experiencing catastrophic losses (IPCC how conscious transformations to sustainability can be realized.Yes and no. How we think about the way that the world works has changed dramatically over the past decades. The years leading up to ses IPCC . BusinesAmbio, it is clear that concepts such as “resilience,” “coupled human and natural systems,” and “the Anthropocene” represent important advances that have influenced both scientific and cultural narratives on environmental change. However, I would also argue that global change research is still paying insufficient attention to how to deliberately transform systems and cultures to avoid the risk of what Steffen et al. (In this peer reflection, I start by acknowledging the contributions of global change research to a dynamic, interconnected view of the world. With specific reference to four key articles published in n et al. , p. 14 dn et al. , p. 16 rThe importance of meaning making has long been an implicit subtext within global change research. In fact, the realm of human thought and ideas, also referred to as the “noosphere,” has historically had a close relationship with understandings of ecology and geology (see Samson and Pitt Ambio articles reviewed here include subtle yet significant references to the noosphere. For example, in “Resilience and Sustainable Development: Building Adaptive Capacity in a World of Transformations,” Folke et al. (The four e et al. , p. 437 e et al. , p. 438.In “Coupled Human and Natural Systems,” Liu et al.  emphasizAmbio, the article by Steffen et al. (terra incognita. The authors drew attention to some of the worst-case scenarios, noting that prior to the Anthropocene, humans “did not have the numbers, social and economic organization, or technologies needed to equal or dominate the great forces of Nature in magnitude or rate” (Steffen et al. th century, humans transformed the environment at a global scale, as evidenced by dramatic rises in atmospheric concentrations of greenhouse gas emissions. In describing The Great Acceleration that started in 1945, Steffen et al. (In the same issue of n et al.  on “The n et al.  noted thn et al. , p. 619.n et al. .Finally, the article by Steffen et al.  highlighAmbio articles identified the need for transformative change, and thus can be considered foundations for today’s rapidly-growing literature on transformations to sustainability. For example, Folke et al. (These four e et al. , p. 437 e et al.  concludee et al. , p. 644 e et al. , p. 753 e et al.  ranged fe et al. .The articles have certainly helped to steer global change research in a more integrated and action-oriented direction. For example, Folke et al.’s  focus onhow deliberate transformations to sustainability come about, particularly how transformations in perceptions, meaning making, and relationships with nature actually can and do shift, and how such changes play out in the political sphere. Importantly, in recent years there has been a dramatic increase in the number of research programs, projects, and articles on transformations to sustainability. Most of these are located within the social sciences and environmental humanities, and draw attention to the importance of integrating more complex understandings of social systems and more nuanced interpretations of human relationships with the natural world. In Urgency in the Anthropocene, Lynch and Veland (What these articles did not address was d Veland , p. 1 cod Veland . Indeed,d Veland .There are also many critical and emancipatory approaches in the social science that acknowledge the ways that social structures and institutions can limit or expand the potential for humans and non-human species to flourish in the Anthropocene Wright . For exaThe Economist, one cannot help but notice that the “world of transformations” described by Folke et al. (Returning to the “Welcome to the Anthropocene” article in e et al.  translate et al. , or more


Anti-cancer treatments have never been so numerous and so efficient. As a result, the number of cancer survivors has been steadily increasing. At the same time, we are facing the challenge of a decade with increasing cancer incidence, which is expected to increase by 80% in middle and low-income countries and 40% in high-income countries from 2008 to 2030 . In 2008Immunotherapy, and especially different ways to boost patient immune systems to detect and fight cancer, has become an efficient way to treat cancer, showing great promise and potential against often otherwise non-curable cancers. In the review by Lichtenstern et al. , the autIt is known that solid tumors can often be difficult to treat with targeted therapeutic intervention strategies such as antibody–drug conjugates and immunotherapy. This is especially true for tumors with a low mutation burden, which are often not antigenic enough to be targeted by immunotherapy. In their review article, Khazamipour et al.  point ouCancer cell metabolism differs from that of normal cells. Tumors commonly activate metabolic pathways that upregulate nutrient synthesis and intake. Magaway et al.  discuss Extracellular signal-regulated kinases (Erks) encompass another kinase family that is often activated in cancers. Erks possess unique features that make them differ from other eukaryotic protein kinases. Unlike others, Erks do not autoactivate and they manifest no basal activity. They are activated as unique targets of the receptor tyrosine kinases (RTKs)–Ras–Raf–MEK signaling cascade, which controls numerous physiological processes and is mutated in most cancers. Smorodinsky-Atias et al.  discuss Multidrug resistance is a serious problem in cancer and targeting multidrug resistance by re-sensitizing resistant cancer cells is one of the big challenges in cancer biology. Among the key multidrug resistance mediating proteins are the ATP-binding cassette (ABC) transporters and the breast cancer resistance protein (BCRP). ABC transporters are plasma membrane-bound proteins that transport nutrients into cells and unwanted toxic metabolites out of cells. Cancer cells can utilize this function for transporting cancer drugs out of the cells. Several attempts to target ABC transporters to gain control in cancer have been reported, but thus far none of the inhibitors developed have been clinically approved. Ambjorner et al.  describe+ATPase (V-ATPase) that is located at lysosomal membranes, but can also be found at the plasma membranes of cancer cells that exhibit increased metabolic acid production, which makes them dependent on increased net acid extrusion. An acidic microenvironment favors cancer cell proliferation and survival and promotes their invasion. V-ATPase consists of at least 13 subunits, of which Flinck et al. [Another membrane bound protein family with important function in cancer is the vacuolar Hk et al.  has idenIn their review, Peulen et al.  discuss The vast majority of cancer deaths are caused by the primary tumor metastasizing into other organs. Invasion is a prerequisite for metastasis formation, and for this reason, the inhibition of invasion could efficiently prevent metastasis formation. For this, targeting the molecules regulating invasion could be useful. One of these is an oncogenic transcription factor, myeloid zinc finger 1 (MZF1), as reviewed by Brix et al. . P21 actNuclear protein localization protein 4 (NPL4) functions as an essential chaperone that regulates microtubule structures when a cell re-enters interphase. Majera et al.  provide high/CD24low) as well as aldehyde dehydrogenase (ALDH), among others, suggesting that additional factors can be targeted by sulconazole. NF-κB/IL-8 signaling is important for CSC formation and may be an important therapeutic target for treatment targeting breast cancer stem cells.Cancer stem cells (CSCs) are often responsible for therapeutic resistance. The study by Choi et al.  presentsThe formation of three-dimensional (3D) multicellular spheroids (MCS) in microgravity, mimicking tissue culture conditions, was used by Melnik et al.  as a metA study by Gruber et al.  on the o


Cryptosporidium parvum infection in calves. Included studies used multivariate analysis within cohort, cross-sectional or case-control designs, of risk factors among young calves, assessing C. parvum specifically. We tabulated data on characteristics and study quality and present narrative synthesis. Fourteen eligible studies were found; three of which were higher quality. The most consistent evidence suggested that risk of C. parvum infection increased when calves had more contact with other calves, were in larger herds or in organic production. Hard flooring reduced risk of infection and calves tended to have more cryptosporidiosis during warm and wet weather. While many other factors were not found to be associated with C. parvum infection, analyses were usually badly underpowered, due to clustering of management factors. Trials are needed to assess effects of manipulating calf contact, herd size, organic methods, hard flooring and temperature. Other factors need to be assessed in larger observational studies with improved disaggregation of potential risk factors.Cryptosporidiosis is common in young calves, causing diarrhoea, delayed growth, poor condition and excess mortality. No vaccine or cure exists, although symptomatic onset may be delayed with some chemoprophylactics. Other response and management strategies have focused on nutritional status, cleanliness and biosecurity. We undertook a systematic review of observational studies to identify risk or protective factors that could prevent The online version of this article (10.1007/s00436-020-06890-2) contains supplementary material, which is available to authorized users. Cryptosporidium parvum is a common protozoan parasite in cattle. It causes chronic diarrhoea (scour) leading to stunted growth, loss of yield and potentially death  are important contributors to total human deaths from diarrhoeal illness  under 4 months old. The vast majority of calves suffering from cryptosporidiosis are under 1 month old (Erbe Bos Taurus mixed with others) were considered individually, in case they provided sufficient cattle-specific information to be informative.Eligible studies had to address infection in bovine calves  molecular methods , (B) immunofluorescence microscopy or (C) contrast microscopy that detected oocysts that was concurrent with a large percentage of symptomatic animals (≥ 90% with diarrhoea).The outcome was Any concurrent observational design  was eligible. Studies were excluded if not available in a language known to the authors  or if the article could not be easily translated into English using Google Translate. Articles without abstracts or available full text were excluded.We searched these databases from inception to May/June 2019: Scopus, CAB International abstracts, MEDLINE (PubMed) and Embase. A limited grey literature search was undertaken of three government databases via websites in summer 2019: The UK Dept for Food and Rural Affairs, The US Dept. of Agriculture library (at Cornell University) and The European Commission, Agricultural and Rural Development section. Conference proceedings were not searched. Literature databases were chosen following recommendations about the most comprehensive bibliographic sources for veterinary science research  results. Grey literature search terms were Cryptosporidum, C. parvum, cryptosporidiosis).At least one of .After de-duplication, titles and abstracts were independently screened by two investigators (JB and CCH) against the inclusion criteria. Items were chosen for full text review or excluded. Selection disagreements were resolved by discussion or on the verdict of a third reviewer (PRH). Full texts were obtained where possible. Decisions about final inclusion or exclusion were made after full text review by one or more authors. Full-text review and data extraction were undertaken by LH, SM or JB and checked by each other.p ≤ 0.05 level of confidence were extracted and included in the results. After all such significant factors were identified and extracted, we checked back within the included studies to find instances where each factor had been assessed but found not to be a significant risk factor (to assess the consistency of importance of each factor and to reduce the risk of being influenced by random findings).Any risk or protective factors reported to be statistically significant at a Quality assessment was undertaken by LH or SM and checked by JB. Modified questions from the CASP checklist for cohort studies . Fourteen studies were eligible for inclusion and were data extracted and quality assessed. Characteristics of the included studies are found in Table Our search found 2522 possible relevant studies, see Fig. C. parvum was 6–78% of individual calves within studies, and studies assessed 1–119 herds and 63 to 2249 individual animals. As management interventions tend to differ by herd, rather than by animal, the studies were all limited in their ability to identify important risk factors.The calves were overwhelmingly part of dairy production . Studies were carried out in Europe (6 studies), North America (6 studies), New Zealand and Egypt (one study each). Prevalence of We found that three studies were the strongest methodologically: Trotz-Williams et al.  carried n = the number of studies that considered this potential risk factor): sex of animal (n = 1), cleanliness of actual animal (n = 1), breeding system (n = 1), dairy or beef farming (n = 1) and access to stream as water supply or not  when dams were in the maternity pen >3 weeks prior to birth, compared with when dams were only in the maternity pen for ≤2 days before birth. There is some higher quality but limited evidence that longer segregation of dams from the rest of the herd prior to birth is protective.Two studies assessed use of maternity pens, isolating dams from the herd in a period prior to giving birth. A moderate quality study , this increased risk of disease in Matoock et al.  OR 5.2, OR 0.96. No highC. parvum infection OR to 0.11 (95%CI 0.02–0.52) in Silverlås et al. . We further suspect some studies reported that calves had ‘colostrum’ when in reality calves had artificial colostrum. Some studies report universal or near-universal exposure status , so colostrum feeding could not be assessed as a risk factor. Colostrum that has been sterilized or stored loses antibody effectiveness , but the only higher quality study Silverlås et al. did not find that intake of unsterilised colostrum was protective.Silverlås et al. , Weber eC. parvum infection, but colostrum intake as a risk or protective factor has not been tested effectively.There is weak evidence that having colostrum could be protective against There is lack of consistent evidence that any specific feeding delivery system for colostrum (or milk) is riskier or protective than others.Two studies found that use of milk replacer  led to higher risk of oocyst shedding. Díaz et al.  reportedC. parvum with larger herd size. The odds ratios for larger herd sizes in the adjusted models ranged from 1.55 to 292 . All three of the highest quality studies considered herd size as a risk factor. Trotz-Williams et al.  on farms was considered by three studies as a risk factor for fresh C. parvum infection. Two studies found no support for increased risk, while Starkey et al. ; both studies found the risk to be higher in organic systems: Maddox-Hyttel et al.  found ORThis section deals with aspects of management not described elsewhere in this summary.C. parvum . A higher quality study  study . Weber et al. . There is some consistent evidence, including from a higher quality study , while Maddox-Hyttel et al.  was addressed by two studies .With regard to bedding, most studies considered hay under calf quarters although Silverlås et al.  assessedAmong the studies included in this review, Szonyi et al.  found thC. parvum shedding. The models in Brook et al. found that disease risk was much lower when bedding was deeper , compared with shallower bedding (0–5 cm). Brook et al. tested other depths. Six to 10 cm depth was also protective compared with 0–5 cm depth , while >15 cm depth was not protective compared with 0–5 cm depth . So the relationship between depth and disease risk was not linear and not consistent and only tested by two lower quality studies. Evidence about optimal bedding depth is limited and inconclusive.Brook et al.  and MaddSeparate from flooring management decisions, seven studies considered at least one aspect of how calf housing areas were cleaned.Díaz et al.  found thThe process of bedding removal involves walking and using equipment between animal groups and pens. In this process, personnel and equipment become fomites for spreading infection. A previous study found a similar effect  . Trotz-Williams et al. (C. parvum infection more likely.Two studies considered whether co-infection with other pathogens (known to cause bovine diarrhoea) could be linked to y et al.  concludes et al.  is the os et al.  is a higSome of the risk factor studies noted whether any animals were exposed to treatment that was meant to reduce illness, as reported below.Two studies mentioned that some calves were given halofuginone lactate (HfL). Díaz et al.  found thE. coli vaccine  as a risk factor. Díaz et al. , while the higher quality study, Trotz-Williams et al. . Trotz-Williams et al. (E. coli). First Defence was also found to increase incidence of cryptosporidiosis . The increased risk may be correlative; calves receiving the vaccine may have tended to be in herds that have more history of cryptosporidiosis. Evidence in favour of E. coli or similar vaccines was mixed and therefore inconclusive.Three studies assessed dams receiving an z et al.  found E.s et al. , found ts et al.  also assTrotz-Williams et al.  found thTwo higher quality studies . Trotz-Williams et al. . One higher quality study . Infection rates peaked in October in Urie et al. . Deep straw bedding is thought to increase cleanliness of the animals and keep them away from faeces. Additionally, conditions should be kept as dry as possible. Disinfection (buckets or pans) should be available to staff at entrances to calf sheds. Livestock management strategies related to welfare encompass keeping animals warm and hydrated with electrolytes if necessary. Nutrition measures address whether colostrum or colostrum substitutes better bolster immune systems and overall condition  was rarely reported. Even more difficult, it is likely that unobserved and/or unreported herd-specific factors affected the risks of a calf being ill or shedding oocysts. This missing information is a very important reason that future research needs to cluster observations by herd .A systematic review methodology for summarizing evidence is inherently conservative; this study design emphasizes only using demonstrable benefits or harms to inform policy and practice. This conservatism is meant to help prevent investment in futile measures but it cannot identify useful practices that have not been tested from types of evidence outside of the inclusion criteria. The strength of this systematic review is in highlighting how the body of evidence in risk factor studies on real animals needs to improve to make firm conclusions for better practices in herd management.The evidence base is generally insufficient to support any specific practice for controlling cryptosporidiosis in bovine calves. This is problematic because livestock managers cannot be sure which activities they should be doing to prevent this disease. Evidence-based practices are as important in veterinary science as in other biomedical sciences. Better quality and very specific evidence is needed about which modifiable risk factors should be prioritized in preventing cryptosporidiosis in calves.C. parvum infection increased when calves had more contact with other calves, were in larger herds or in organic production. Hard flooring reduced risk of infection, while calves tended to have more cryptosporidiosis during warm and wet weather. Co-infection with other pathogens was linked to being more likely to have a C. parvum-positive test in both studies that addressed this as a risk factor. All such factors should be formally tested in high-quality randomized controlled trials or case–control studies.No overwhelming evidence on risk or protective factors was found. The most consistent evidence was that risk of C. parvum infection. Funding for such large studies that carefully assess and report the full range of potential risk factors  are needed to enable the science to move forward and properly inform animal husbandry. Such studies need to use validated tools for assessment of risk factors, using pre-specified definitions, and high-quality methods of C. parvum detection in young calves.Many other risk factors were analysed but did not have consistent or conclusive effects. Being in individual or shared pens, being indoors or outdoors, whether the herd had history of cryptosporidiosis, breed, colostrum, time spent with dam after birth, type of flooring or bedding, whether calves were tied or free and use of nutritional supplements were not shown to consistently protect or increase risk of disease. However, most of these findings arose from relatively few studies: i.e. just two studies assessed each of organic production, nutritional supplements or being indoors/outdoors. Large high-quality studies across a large number of herds are needed that aim specifically to assess associations between rather than this range of management practices  and ESM 1(DOCX 14 kb)


Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to joint destruction. Various therapeutic agents have been showed to halt disease progression in clinical studies. In this special issue, we cover subjects from the periodontal condition of RA patients ,2 to theEriksson et al.  describeKöhler et al.  reviewedTaylor et al.  wrote thHirter et al.  reviewedIn two post-hoc analyses of the RA BEAM Study Fautrel et al.  and TaylIn summary, in this special issue the disease of RA and its therapy is described from different angles to provide a broad and profound insight into the disease.


The aim of this study is to compare the use of flutter valve drainage bag system as an alternative to conventional underwater seal drainage bottle in the management of non-massive malignant/paramalignant pleural effusion.Forty-one patients with non-massive malignant and paramalignant pleural effusions were randomized into two groups. Group A (21patients) had their chest tubes connected to an underwater seal drainage bottle, while group B (20 patients) had their chest tubes connected to a flutter bag drainage device. Data obtained was analyzed with SPSS statistical package (version 16.0).Breast cancer was the malignancy present at diagnosis in 24(58%) patients. Complication rates were similar, 9.5% in the underwater seal group and 10 % in the flutter bag drainage group. The mean duration to full mobilization was 35.0±20.0 hours in the flutter bag group and 52.7±18.5 hours in the underwater seal group, p-value 0.007. The mean length of hospital was 7.9±2.2 days in the flutter bag group and 9.8±2.7 days in the underwater seal group. This was statistically significant, p-value of 0.019. There was no difference in the effectiveness of drainage between both groups, complete lung re-expansion was observed in 16(80%) of the flutter bag group and 18(85.7%) of the underwater seal drainage group, p-value 0.70.The flutter valve drainage bag is an effective and safe alternative to the standard underwater seal drainage bottle in the management of non-massive malignant and paramalignant pleural effusion. The oneet al. . Vuorisa [et al.  showed t [et al. . Ogunley [et al. , also fo [et al.  in Lagoset al. [Malignant pleural effusion is confirmed by the presence of malignant cells in pleural fluid or tissue . In patiet al.  labels tet al. , 12. Malet al. , 9. Masset al. . Thus plth intercostal space mid axillary line and anchored to the skin with appropriate size non-absorbable suture.Patients with non-massive malignant or paramalignant pleural effusions admitted into the Lagos University Teaching Hospital (LUTH) from January 2014 to December 2014 were prospectively enrolled in the study. Approval was obtained from the Hospital's Health Research and Ethics Committee. Forty-one patients presenting with non-massive malignant and paramalignant pleural effusions were consecutively divided into two groups. Group A (21 patients) had their chest tubes connected to an underwater seal drainage bottle, while group B (20 patients) had their chest tubes connected to a flutter bag drainage device. All consenting adult patients (≥ 18years) with non-massive malignant and paramalignant pleural effusions were considered eligible for inclusion in the study. Individuals with effusions not due to or related to a malignancy, massive pleural effusion and complicated effusions  were excluded from the study. After obtaining informed consent, patients in both groups had a size 28F (French size) chest tube inserted aseptically under local anesthesia, via the 6Patients in Group A had their chest tubes connected to the standard underwater seal drainage system while Group B was connected to the flutter bag drainage system (Portex). All patients had administration of prophylactic antibiotics and adequate analgesia. A post insertion chest radiograph was obtained in all patients to confirm proper placement of chest tubes and daily drainage via chest tube was also noted. Drainage was discontinued and chest tubes were removed once daily output became ≤ 100ml/24hours for 2 consecutive days (in the presence of a patent tube) and chest radiograph showed re-expansion of the underlying lungs. Post chest tube removal radiographs were obtained and the patients were discharged home for follow up in clinic. Comparison was done between the two methods of chest drainage based on the selected parameters. Statistical analysis was conducted by using the SPSS 16.0 for Windows program . A P-value of < 0.05 using the Fishers exact test was considered significant.Of the 41 patients recruited for the study, there were 37 females (90.2%) and 4 males (9.8%) in the study population with a mean age of 50.3±14.3 years . Breast There was no significant difference in the mean duration of drainage between both groups, 6.5±2.6 days in the flutter bag group and 7.9±2.0 days in the underwater seal group, p-value 0.059 . Howeveret al. [et al. [et al. [et al. [The underwater seal drainage bottle has been the conventional reservoir for drainage of pleural effusion in most patients, however various studies including that of Graham et al.  and Vour [et al.  have dem [et al. . In this [et al. -9. There [et al.  and furt [et al. . The lac [et al.  Althoughet al. [et al. [The patients in the flutter valve drainage bag group had a shorter period of hospital stay when compared to the underwater seal group and this was statistically significant with a P value of 0.019. This contrasts with the works of Graham and Vourisalo, but it is in keeping with the findings of Kadkhodaei et al. . The dif [et al. , in theiet al. [et al. [et al. study, where the incidence of complication was 11(17%) in the flutter bag group vs 7(12%) for underwater seal. This similarity should be interpreted with caution, due to the larger sample size in the Graham et al. study compared to this study.Vega et al.  in their [et al.  is that Malignant and paramalignant pleural effusions occur more in females with breast cancer and majority of these patients are in the fourth and fifth decades of life. The flutter valve drainage bag is an effective and safe alternative to the standard underwater seal drainage bottle in the management of non-massive malignant and paramalignant pleural effusion. The flutter bag drainage system encourages earlier mobilization of patients when compared to the underwater seal drainage bottle and shortens the length of hospital stay. However, a multicentre study is needed to further validate the findings of this study.The flutter valve drainage bag can be used to manage patients with pneumothorax and persistent air leak;The Flutter valve drainage bag can be used as a postoperative chest drain.The use of the flutter valve bag can be extended to patients with non-massive malignant or paramalignant pleural effusion;This study also shows that the flutter valve drainage bag shortens in-hospital stay.The authors declare no competing interests.


Dear Editor,et al. [We read with interest the recent paper by Omar et al.  regardinThe results concluded that: (a) there was a difference between mean and postoperative IIEF scores in the anastomotic group at both the 3- and 6-month follow-up, but (b) no difference was noted in the substitution urethroplasty group; furthermore, when the mean change in IIEF score was compared in both groups over the study period no difference was noticed; and overall (c) the study demonstrated that any type of bulbar urethroplasty had no statistically significant impact on EF .The study again highlights one of the challenges facing urethral surgeons: measuring sexual function following urethroplasty . The IIEet al. [The authors reference a paper by Barbagli et al.  (using aet al. [The authors are to be commended for performing this study examining the impact of urethroplasty on EF specifically, but should acknowledge that the sample size is small and only a single questionnaire was used to assess EF. Urkmez et al.  in 2019 Ideally, successful outcome assessment following urethral surgery should objectively evaluate voiding and all sexual outcomes, in addition to quality-of-life improvements with a validated, reproducible questionnaire.et al. [Breyer et al.  have dev