Objective: To assess the incidence of serious complications and reoperations for recurrence after pelvic organ prolapse (POP) surgery and compare the three most common types of repair. Design: Prospective cohort study using a registry. Setting: 19 surgical centres in France. Population: 2309 women participated between 2017 and 2019. Methods: a multivariate analysis including an inverse probability of treatment weighting approach was used to obtain three comparable groups. Main outcome measures: Serious complications and subsequent reoperations for POP recurrence Results: Mean follow-up was 16.6 months. Surgeries included in the analysis were native tissue vaginal repair (N=504), transvaginal mesh placement (692), and laparoscopic sacropexy with mesh (1113). Serious complications occurred among 52 women (2.3%), and reoperation for recurrence was required for 32 (1.4%). At one year, the cumulative weighted incidence of serious complications was 1.8% for native tissue vaginal repair (95% confidence interval 0-3.9), 3.9% for transvaginal mesh (2.0-5.9), and 2.2% for sacropexy (1.1-2.6). Compared with the native tissue vaginal repair group, the risk of serious complications was higher in the transvaginal mesh group (weighted-HR 3.84, 2.43-6.08), and the sacropexy group (2.48, 1.45-4.23), while the risk of reoperation for prolapse recurrence was reduced in both groups (transvaginal mesh [0.22, 0.13-0.39] and sacropexy [0.29, 0.18-0.47]). Conclusions: Laparoscopic sacropexy with mesh appears to have a better risk profile (few serious complications and few reoperations for recurrence) than transvaginal mesh placement (more serious complications) and native tissue vaginal repair (more reoperations for recurrence). These results are useful for informing women and for shared decision making.

Background and Purpose: Traumatic brain injury (TBI) remains a leading cause of mortality and morbidity in young adults. The role of iron in potentiating neurodegeneration following TBI has gained recent interest since iron deposition has been detected in the injured brain in the weeks to months post-TBI, in both the preclinical and clinical setting. A failure in iron homeostasis can lead to oxidative stress, inflammation and excitotoxicity; and whether this is a cause or consequence of the long-term effects of TBI remains unknown. Experimental approach: We investigated the role of iron, and the effect of therapeutic intervention using a brain-permeable iron chelator, deferiprone, in a controlled cortical impact mouse model of TBI. An extensive assessment of cognitive, motor and anxiety/depressive outcome measures were examined, and neuropathological and biochemical changes, over a 3-month period post-TBI. Key Results: Lesion volume was significantly reduced at 3 months, which was preceded by a reduction in astrogliosis and a preservation of neurons in the injured brain at 2 weeks and/or 1-month post-TBI in mice receiving oral deferiprone. Deferiprone treatment showed significant improvements in neurological severity scores and locomotor/gait performance, and cognitive function, and attenuated anxiety-like symptoms post-TBI. Deferiprone reduced iron levels, oxidative stress and altered expression of neurotrophins in the injured brain over this period. Conclusion and Implications: Our findings support a detrimental role of iron in the injured brain and suggest that deferiprone (or similar iron chelators) may be promising therapeutic approaches to improve survival, functional outcomes and quality of life following TBI.

Immunodeficient patients are less prone to develop serious complications of COVID-19 and cytokine storm. However, they are more likely to develop opportunistic infections that can mimic the symptoms of the SARS-CoV-2. we presented a 27-year-old male case of SARS-CoV-2, who was complicated with Pneumocystis jirovecii pneumonia, following treatment with rituximab.

Tropical freshwater lakes are well-known for their high biodiversity, and the East African Great Lakes in particular are renowned for their endemic cichlid fish adaptive radiations. While comparative phylogenetic analyses of extant species flocks have revealed patterns and processes of their diversification, evolutionary trajectories within lineages, impacts of environmental drivers, or the scope and nature of now-extinct diversity remain largely unknown. Time-structured paleodata from geologically young fossil records, such as fossil counts and particularly ancient DNA data, would help fill this large knowledge gap. High ambient temperatures can be detrimental to the preservation of DNA, but refined methodology now allows data generation even from very poorly preserved samples. Here, we show for the first time that fish fossils from tropical lake sediments yield endogenous ancient DNA (aDNA). Despite generally low endogenous content and high sample drop-out, high-throughput sequencing and in some cases sequence capture allowed for taxonomic assignment to family or tribe level and phylogenetic placement of individuals. Even skeletal remains weighing less than 1 mg and up to 2700 years of age could be phylogenetically placed. We find that the relationship of degradation of aDNA with the thermal age of samples is similar to that described for terrestrial samples from cold environments adjusted for elevated temperatures. Success rates and aDNA preservation differed between the investigated lakes Chala, Kivu and Victoria, possibly caused by differences in water oxygenation at deposition. Our study demonstrates that sediments of tropical lakes preserve genetic information on rapidly diversifying taxa over time scales of millennia.

COVID-19 Clinical trials: quality matters more than quantity

Background The impact of lockdown measures can be widespread, affecting both clinical and psychosocial aspects of health. This study aims to assess changes in health services access, diabetes self-care, behavioral and psychological impact of COVID-19 and partial lockdown in Singapore. Methods We conducted a cross-sectional online survey amongst people with diabetes with the Diabetes Health Profile-18 (DHP-18). Hierarchical regression analyses were performed for each DHP-18 subscale (Psychological Distress, Disinhibited Eating and Barriers to Activity) as dependent variables in separate models. Results Among 301 respondents, 45.2% were women, majority were ethnic Chinese (67.1%), aged 40 to 49 years (24.2%), have Type 2 diabetes (68.4%) and on oral medications (42.2%). During the lockdown, nearly all respondents were able to obtain their medications, supplies (94%) and contact their doctors (97%) when needed. Respondents reported less physical activity (38%), checking of blood pressure (29%) and blood glucose (22%). Previous diagnosis of mental health conditions (β=11.44, p= 0.017), diabetes-related comorbidities (β= 3.98, p= 0.001) and Indian ethnicity (β= 7.73, p= 0.018) were significantly associated with higher psychological distress. Comorbidities were associated with higher disinhibited eating (β= 2.71, p= 0.007) while mental health condition was associated with greater barriers to activities (β= 9.63, p= 0.033). Conclusion Health services access were minimally affected but COVID-19 and lockdown had mixed impact on self-care and management behaviors. Greater clinical care and attention should be provided to people with diabetes with greater number of comorbidities and previous mental health disorders during the pandemic and lockdown.

Aim of the study: Subconjunctival hemorrage (SCH) is a frequent bleeding manifestation and a common cause of visits to the primary care. Trauma in young patients and vascular damage such as hypertension in the elderly are the most common causes of SCH and the prevalence of hematological diseases is less than 1%. We aimed to evaluate the prevalence of congenital or acquired bleeding disorders in patients with once or recurrent SCH. Methods used to conduct the study: It is a retrospective study and included fifty-two patients with SCH whose etiologic factor was not detected. Hemostatic tests were studied in 52 patients (25 male and 27 females). All patients included were evaluated for congenital or acquired bleeding disorder and SCH with once and those with 2 or more were compared for the laboratory results. Results of the study: Type I von Willebrand disease (vWD) was diagnosed in one patient with recurrent SCH and one patient with single SCH (3.8%). The prevalence of patients with type 1 vWD in the study was not statistically significant when compared with the frequency of vWD in the normal population. Fibrinogen level was found to be statistically higher in patients who had SCH once than those who had recurrent SCH. But fibrinogen level was in normal range in all patients. Conclusions drawn from the study and clinical implications: There was no increase in the incidence of congenital or acquired bleeding disorder in SCH compared to normal population. For this reason it was thought that there was no need for evaluation for bleeding disorders in spontaneous SCH.

Kawasaki Disease (KD) is a systemic vasculitis of small and medium arteries, preferably affecting coronary arteries. It is one of the most frequent causes of acquired heart disease in children. Despite being comprehensively studied, its etiopathogenesis is not totally explained. The surgical procedures usually become necessary during the late follow-up and may be coronary artery bypass grafting, cardiac defibrillator implantation with or without cardiac resynchronization therapy, or cardiac transplantation.

Competition between the sympatric harbour (Phoca vitulina) and grey seals (Halichoerus grypus) is thought to underlie some recent local declines of the former while the population of the latter remains stable or increases. A better understanding of the interactions between these two species is critical to elucidate current changes. This study aims at identifying and quantifying the niche overlap between harbour and grey seals at their Southern European limit range, in the baie de Somme (Eastern English Channel, France), in a context of exponential increase in the number of resident harbour seals and visiting grey seals. Isotopic niche overlap was quantified between both species using whisker δ13C and δ15N isotopic values, taking intra- and interindividual variability into account. Dietary overlap was quantified from scat contents using hierarchical clustering. A high degree of trophic niche overlap was identified between both species. The narrower isotopic niche of harbour seals was nested within that of grey seals (58.2% [CI95%: 22.7-100%] overlap). Six diet clusters were identified from scat content analysis. Two of them gathered most of harbour seals’ scats (85.5 % [80.3-90.2%]) and around half of grey seals’ ones (46.8% [35.1-58.4%]) that almost exclusively contained benthic flatfish. Consumption of this type of prey was identified here to be the root cause of trophic overlap. This highlighted the potential for competition between the two species at their Southern European limit range, linked to foraging on benthic flatfish, in coastal waters close to their haulout sites, especially during spring/summer. We suggest that (1) interspecific competition for prey could occur/increase in the future if the number of grey and harbour seals still increase and/or if flatfish supply decrease in this area, and (2) harbour seals would be disadvantaged in such a case if they do not adapt, as being specialised on flatfish at the colony scale.

Niche theory predicts specialists will be more sensitive to environmental perturbation compared to generalists, a hypothesis receiving broad support in free-living species. Based on their niche breadth, parasites can also be classified as specialists and generalists, with specialists infecting only a few and generalists a diverse array of host species. Here, using avian haemosporidian parasites infecting wild bird populations inhabiting the Western Ghats, India as a model system, we elucidate how climate, habitat and human disturbance affects parasite prevalence both directly and indirectly via their effects on host diversity. Our data demonstrates that anthropogenic disturbance acts to reduce the prevalence of specialist parasite lineages, while increasing that of generalist lineages. Thus, as in free-living species, disturbance favors parasite communities dominated by generalist vs. specialist species. Because generalist parasites are more likely to cause emerging infectious diseases, such biotic homogenization of parasite communities could increase disease emergence risk in the Anthropocene

Physical disruption of gene flow among mountains is commonly viewed as an important process for the generation of hyperdiverse tropical mountain biotas. However, the role of in situ diversification within mountains has been seldom explored. Here we evaluate spatially fine-scale patterns of arthropod community assembly within a single mountain to understand the role of dispersal limitation and landscape features as drivers of tropical mountain diversity. We focus on a single tropical sky-island of the Transmexican Volcanic Belt, where we sampled whole-communities of arthropods for eight orders with a comparable design at a spatial scale ranging from 50 m to 20 km, using 840 pitfall traps and whole community metabarcoding. We explored multiple hierarchical levels, from individual haplotypes to lineages at 0.5, 1.5, 3, 5, 7.5% similarity thresholds, to evaluate patterns of richness, turnover and distance decay of similarity with isolation-by-distance and isolation-by-resistance approaches. Our results showed that distance and altitude influence distance decay of similarity at all hierarchical levels. This holds for arthropod groups of contrasting dispersal abilities, but with different strength depending on the spatial scale. Our results suggest long-term persistence of lineages within sky islands, combined with local-scale differentiation, may be an important driver of high arthropod biodiversity in tropical mountains.

Methaemoglobin results from the oxidation of ferrous to ferric iron in the centre of the haem moeity of haemoglobin. The production of dose-dependent methaemoglobinaemia by 8-aminoquinoline antimalarial drugs appears to be associated with, but is not directly linked to therapeutic efficacy against latent vivax and ovale malarias. Iatrogenic methaemoglobinaemia may be a useful pharmacodynamic measure in 8-aminoquinoline drug and dose optimization.

The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in December 2019, presumed from the city of Wuhan, Hubei province in China and the subsequent declaration of the disease as a pandemic by the World Health Organization (WHO) as COVID-19 in March 2020, had significant impact on health care systems globally. Each country responded to this disease in different ways but broadly by fortifying and prioritising health care provision as well as introducing social lockdown aiming to contain the infection and minimizing the risk of transmission. In the United Kingdom, a lockdown was introduced by the government on 23rd of March 2020 and all health care services were focussed to challenge the impact of COVID-19. To do so, the United Kingdom National Health Service had to undergo widespread service reconfigurations and the so-called “Nightingale Hospitals” were created de novo to bolster bed provision and industries were asked to direct efforts to the production of ventilators. A government led public health campaign was publicised under the slogan of: “Stay home, Protect the NHS (National Health Service), Save lives”. The approach had a significant impact on delivery of all surgical services but particularly cardiac surgery with its inherent critical care bed capacity. This paper describes the impact on provision for elective and emergency cardiac surgery in the United Kingdom, with a focus on Aorto-vascular disease. We describe our Aorto-vascular activity and outcomes during the period of UK lockdown and present a patient survey of attitudes to aortic surgery during COVID-19 pandemic.

Microfluidic impedance cytometry is a powerful system to measure micro and nano-sized particles and is routinely used in point-of-care settings disease diagnostics and other biomedical applications. However, small objects near a sensor’s detection limit are plagued with relatively significant background noise and are difficult to identify for every case. While many data processing techniques can be utilized to reduce noise and improve signal quality, frequently they are still inadequate to push sensor detection limits. Here, we report the first demonstration of a novel signal averaging algorithm effective in noise reduction of microfluidic impedance cytometry data, improving enumeration accuracy and reducing detection limits. Our device uses a 22 μm tall microchannel and gold coplanar microelectrodes that generates an electric field, recording bipolar pulses from polystyrene microparticles flowing through the channel. In addition to outlining a modified moving signal averaging technique theoretically and with a model dataset, we also performed a compendium of characterization experiments including variations in flow rate, input voltage, and particle size. Multi-variate metrics from each experiment are compared including signal amplitude, pulse width, background noise, and signal-to-noise ratio (SNR). Incorporating our technique resulted in improved SNR and counting accuracy across all experiments conducted, and the limit of detection improved from 5 μm to 1 μm particles without modifying microchannel dimensions. Succeeding this, we envision implementing our modified moving average technique to develop next generation microfluidic impedance cytometry devices with an expanded dynamic range and improved enumeration accuracy. This can be exceedingly useful for many biomedical applications, such as infectious disease diagnostics where devices may enumerate larger-scale immune cells alongside sub-micron bacterium in the same sample.

This letter is a response to the commentary by Jonson & Do (Johnson and Do 2020) on our paper, entitled “A Vietnamese human genetic variation database” (Vinh et al. 2019). The commentators concerned about two issues: Firstly, the relation of Southeast Asian (SEA) and East Asian (EA) groups to African and European groups; Secondly, the history of migration and settlement in Southeast Asia. Our responses will clarify both concerns from the commentators.

Mittag-Leffler functions has many applications in various areas of Physical, biological ,applied, earth Sciences and Engineering. It is used in solving problems of fractional order differential, integral and difference equations. In this paper, we aim to define the m-parameter Mittag-Leffler function, which can be reduced to various already known extensions of Mittag-Leffler function. We then, discuss its various properties like recurrence relations, differentiation formula and integral representations. We also represent the new m-parameter Mittag-Leffler function in terms of some known special functions such as Generalized hypergeometric function, Mellin Barnes integral, Wright hypergeometric function and Fox H-function. We also discuss its various integral transforms like Euler-Beta, Whittaker, Laplace and Mellin transforms. Further, fractional differential and integral operators are considered to discuss few properties of m-parameter Mittag-Leffler function. Also, we use the m-parameter Mittag-Leffler function to define a generalization of Prabhakar integral and discuss its properties. Further, relation of m-parameter Mittag Leffler function with various other functions such as exponential, trigonometric, hypergeometric and algebraic functions is obtained and represented graphically using MATHEMATICA 12.

The field of optogenetics is rapidly growing in relevance and number of developed tools. Amongst other things, the optogenetic repertoire includes light-responsive ion channels and methods for gene regulation. This review will be confined to the optogenetic control of gene expression in mammalian cells as suitable models for clinical applications. Here optogenetic gene regulation might offer an excellent method for spatially and timely regulated gene and protein expression in cell therapeutic approaches. Well-known systems for gene regulation, such as the LOV-, CRY2/CIB-, PhyB/PIF-systems, as well as other, in mammalian cells not yet fully established systems will be described. Advantages and disadvantages with regard to clinical applications are outlined in detail. Among the many unanswered questions concerning the application of optogenetics, we discuss items such as the use of exogenous chromophores and their effects on the biology of the cells and methods for a gentle, but effective gene transfection method for optogenetic tools for in vivo applications.

The incidence of food allergy (FA) has continued to rise over the last several decades, posing significant burdens on health and quality of life. Significant strides into the advancement of FA diagnosis, prevention, and treatment have been made in recent years. In an effort to lower reliance on resource-intensive food challenges, the field has continued work toward the development of highly sensitive and specific assays capable of high-throughput analysis to assist in the diagnosis FA. In looking toward early infancy as a critical period in the development of allergy or acquisition of tolerance, evidence has increasingly suggested that early intervention via the early introduction of food allergens and maintenance of skin barrier function may decrease the risk of FA. As such, largescale investigations are underway evaluating infant feeding and the impact of emollient and steroid use in infants with dry skin for the prevention of allergy. On the other end of the spectrum, the past few years have been witness to an explosive increase in clinical trials of novel and innovative therapeutic strategies aimed at the treatment of FA in those whom the disease has already manifested. A milestone in the field, 2020 marked the approval of the first drug, oral peanut allergen, for the indication of peanut allergy. With a foundation of promising data supporting the safety and efficacy of single- and multi-allergen oral immunotherapy, current efforts have turned toward the use of probiotics, biologic agents, and modified allergens to optimize and improve upon existing paradigms. Through these advancements, the field hopes to gain footing in the ongoing battle against FA.