Host immune response as well as virulence factors are key in disease susceptibility. There are no known association studies of HLA class I and II alleles with chikungunya (CHIKV) infection in Latin American population. We aim to identify Human Leukocyte Antigen (HLA) alleles present in patients with CHIKV infection when compared to healthy controls, as well as allele association with the clinical spectrum of the disease. A cross-sectional analysis nested in a community cohort was carried out. We included patients 18 years and older with serological confirmation of CHIKV infection. HLA typing of HLA-A, HLA-B and HLA-DRB1 alleles was performed. Two-by-two tables were used to establish associations between allele presence and clinical characteristics. Data from 65 patients with confirmed CHIKV infection were analyzed for HLA typing. CHIKV infection was associated with the presence of HLA-A*68, HLA-B*35, HLA-DRB*01, HLA-DRB1*04 and HLA-DRB1*13 alleles with statistical significance when compared to healthy subjects. A statistically significant relationship was found between the presence of rash in the face or the abdomen and the presence of HLA-DRB1*04. Our study demonstrated that in our cohort, HLA type I as well as type II alleles are associated with CHIKV infection, and specifically an HLA type II allele with dermatological symptoms. Further research is needed to set a path for future investigation on genes outside the HLA system to improve knowledge in the pathophysiology of CHIKV infection and its host-pathogen interaction.

Leishmaniasis is caused by protozoans of the Leishmania genus, which includes more than 20 species capable of infecting humans worldwide. In the Americas, the most widespread specie is L. braziliensis, present in 18 countries, including Bolivia. The taxonomic position of the L. braziliensis complex has been a subject of controversy, complicated further by the recent identification of a particular subpopulation named L. braziliensis atypical or outlier. The aim of this study was to carry out a systematic analysis of the L. braziliensis complex in Bolivia and to describe the associated clinical characteristics. Forty-one strains were analyzed by sequencing an amplified 1245 bp fragment of the hsp70 gene, which allowed its identification as: 24 (59%) L. braziliensis, 16 (39%) L. braziliensis outlier and one (2%) L. peruviana. In a dendrogram constructed, L. braziliensis and L. peruviana are grouped in the same cluster, whilst L. braziliensis outlier appears in a separate branch. Sequence alignment allowed the identification of five non-polymorphic nucleotide positions (288, 297, 642, 993 and 1213) that discriminate L. braziliensis and L. peruviana from L. braziliensis outlier. Moreover, nucleotide positions 51 and 561 enable L. peruviana to be discriminated from the other two taxa. A greater diversity, was observed in L . braziliensis outlier than in L. braziliensis- L. peruviana. The 41 strains came from 32 patients with tegumentary leishmaniasis, among which 22 patients (69%) presented cutaneous lesions (11 caused by L. braziliensis and 11 by L. braziliensis outlier) and ten patients (31%) mucocutaneous lesions (eight caused by L. braziliensis, one by L. braziliensis outlier and one by L. peruviana). Nine patients (28%) simultaneously provided two isolates, each from a separate lesion, and in each case the same genotype was identified in both. Treatment failure was observed in six patients infected with L. braziliensis and one patient with L. peruviana.

Extramedullary involvement of the endocardium is rare in multiple myeloma. Here we describe a case of multiple myeloma (plasma cell) with extramedullary plasmablastic transformation and endocardial involvement, which resulted in partial superior vena cava obstruction. We also conducted a literature review and summary analysis of space-occupying lesions in the heart in 12 patients with multiple myeloma (including the current case) in the last 10 years. Echocardiography is the preferred radiologic examination method for diagnosis and follow-up in multiple myeloma, and surgical resection is effective for alleviating symptoms.

Prevalence of primary coronary cameral fistula (CCF) is extremely rare, especially for CCF with the drainage site into the left ventricle. We describe a 45-year-old patient with chest tightness in whom a giant aneurysm associated with proximal right coronary artery (RCA), and the distal end of RCA terminated into the left ventricle through a fistula was discovered by echocardiography. Dual-source computer tomography revealed the CCF-related giant RCA aneurysm. The drainage site and coexistent abnormality could not be visualized well by coronary artery angiography because of the severely diluted contrast medium into the aneurysm. Finally, the patient received surgical treatment and is asymptomatic now.

Renal allograft aspergillus is a rare entity with a high mortality due to life-threatening complications. We report a case of renal aspergilloma causing obstructive uropathy after two months of transplantation in a 64 -year- old patient who was managed successfully with antifungal therapy without surgical intervention.

Fishbones migrated into surrounding tissues is relatively unusual. We present two cases of patients' migratory fish bones into the retropharyngeal space and hypopharynx. All fishbones were removed without complications. Early diagnosis of migratory fishbone and therapeutic management are essential for optimal patient survival.

Narcolepsy with cataplexy is an often underestimated disorder in both its primary and secondary forms. As with epilepsy, narcolepsy and cataplexy pose a high risk of injury to the patient. Yet, narcoleptics have historically received poorer care than epileptics with regard to non-pharmacological aids. This "White Paper" informs both professionals and patients about protective measures that are advisable.

Recent noteworthy advances in the development of high-performing microbial and mammalian strains have enabled the sustainable production of bio-economically valuable substances such as bio-compounds, biofuels, and biopharmaceuticals. However, to obtain an industrially viable mass-production scheme, much time and effort are required. The robust and rational design of fermentation processes requires analysis and optimization of different extracellular conditions and medium components, which have a massive effect on growth and productivity. In this regard, knowledge- and data-driven modeling methods have received much attention. Constraint-based modeling (CBM) is a knowledge-driven mathematical approach that has been widely used in fermentation analysis and optimization due to its capabilities of predicting the cellular phenotype from genotype through high-throughput means. On the other hand, machine learning (ML) is a data-driven statistical method that identifies the data patterns within sophisticated biological systems and processes, where there is inadequate knowledge to represent underlying mechanisms. Furthermore, ML models are becoming a viable complement to constraint-based models in a reciprocal manner when one is used as a pre-step of another. As a result, more predictable models are produced. This review highlights the applications of CBM and ML independently and the combination of these two approaches for analyzing and optimizing fermentation parameters.

Numerous studies have unsuccessfully tried to unravel the definitive host of the coccidian parasite Besnoitia besnoiti. Cattle infections by B. besnoiti cause a chronic and debilitating condition called bovine besnoitiosis that has emerged in Europe during the last two decades, mainly due to limitations in its control associated to the absence of vaccines and therapeutical tools. Although the exact transmission pathway of B. besnoiti is currently unknown, it is assumed that the parasite might have an indirect life cycle with a carnivore as definitive host. Current lack of studies in wildlife might underestimate the importance of free-living species in the epidemiology of B. besnoiti. Thus, the aim of the present study is to assess the presence of Besnoitia spp. in free-ranging mesocarnivores in Spain. DNA was searched by PCR on faeces collected from wild carnivores as a first approach to determine which species could be considered as potential definitive host candidates in further research. For this purpose, a total of 352 faecal samples from 12 free-living wild carnivore species belonging to the Canidae, Felidae, Herpestidae, Mustelidae, Procyonidae, and Viverridae families were collected in seven Spanish regions. PCR testing showed that Besnoitia spp. DNA was present in four faecal samples from red foxes collected in western Spain, an area with the greatest density of extensively reared cattle and associated to high incidence of bovine besnoitiosis in the country. To date, this is the first report of a Besnoitia besnoiti-like sequence (99.57% homology) from carnivore faeces in a worldwide context. Red foxes might contribute to the epidemiology of B. besnoiti, although further studies, mostly based on bioassay, would be needed to elucidate the accuracy and extent of these interesting findings.

Identifying the optimal treatment based on specific aetiology of each patient is the main promise of precision medicine. In order to realize this promise researches and physicians must first identify the underlying cause; over the last 10 years, advances in genetics have made this possible for several monogenic epilepsies. At present through next generation techniques we can reach the precise genetic aetiology in 30 to 50% of genetic epilepsies beginning in the paediatric age. While committed in such gene hunting, progresses in the study of experimental models of epilepsy have also provided a better understanding of the mechanisms underlying the condition. Such impressive advances is already being translated into improving care, management and treatment of some patients. Identification of a precise genetic etiology can already direct physicians to prescribe treatments correcting specific metabolic defects avoid antiseizure medicines that can aggravate the pathogenic defect or select the drug that counteract the functional disturbance caused by the gene mutation. Personalized, tailored treatments should not just focus on how to stop seizures but possibly preventing their onset and cure the disorder often consisting of epilepsy and its comorbidities including cognitive, motor and behavior deficiencies. This review discusses the therapeutic implications following a specific genetic diagnosis and the correlation between genetic findings, pathophysiological mechanism and tailored seizure treatment emphasizing the impact on current clinical practice.

Adaptive radiation of fishes was long thought to be possible only in lacustrine environments. Recently, several studies have shown that also riverine and stream environments provide the ecological opportunity for adaptive radiation. In this study, we report on a riverine adaptive radiation of six ecomorphs of cyprinid hillstream fishes of the genus Garra in a river located in the Ethiopian Highlands in East Africa. Garra are predominantly highly specialized algae-scrapers with a wide distribution ranging from Southeastern Asia to Western Africa. However, adaptive phenotypic diversification in mouth type, sucking disc morphology, gut length and body shape have been found among these new species in a single Ethiopian river. Moreover, we found two novel phenotypes of Garra (‘thick-lipped’ and ‘predatory’) that were not described before in this species-rich genus (>160 species). Mitochondrial and genome-wide data suggest monophyletic, intra-basin evolution of Garra phenotypic diversity with signatures of gene flow from other local populations. Although sympatric ecomorphs are genetically distinct and can be considered to being young species as suggested by genome-wide SNP data, mtDNA was unable to identify any genetic structure suggesting a recent and rapid speciation event. Furthermore, we found evidence for a hybrid origin of the novel ‘thick-lipped’ phenotype, as being the result of the hybridization of two other sympatrically occurring species. Here we highlight how, driven by ecological opportunity, an ancestral trophically highly specialized lineage is likely to have rapidly adaptively radiated in a riverine environment, and that this radiation was promoted by the evolution of novel feeding strategies.

There is evidence that prey can perceive the risk of predation and alter their behaviour in response, resulting in changes in spatial distribution and potential fitness consequences. Previous approaches to mapping predation risk quantify predator space use to estimate potential predator-prey encounters, yet this approach does not account for successful predator attacks resulting in prey mortality. An exception is a prey kill-site, which reflects an encounter resulting in mortality, but obtaining these data can be expensive and requires time to accumulate adequate sample sizes. We illustrate an alternative approach using predator scat locations and their contents to quantify spatial predation risk for elk (Cervus canadensis) from multiple predators in Alberta, Canada. We combined predictions of scat-based resource selection functions for bears (Ursus arctos/U. americanus), cougars (Puma concolor), coyotes (Canis latrans), and wolves (C. lupus) based on scat-detection dog surveys with predictions for the probability that a predator-specific scat in a location contained elk. We evaluated our approach by comparing predictions to a predation risk model developed from elk kill sites and applied it to describing spatial patterns in predation risk that were consistent with changes in the distribution of elk over the past decade. We found a strong correlation between risk predicted by kill sites and risk predicted by our approach (r = 0.98, P < 0.001). There was a spatial pattern to predation risk, where elk that migrated east of their winter range were exposed to highest risk from cougars, non-migratory elk were exposed to high risk from wolves and bears, and risk to elk that migrated west of their winter range into protected areas was high only from bears. The patterns in predator risk were consistent with changes in the migratory tactics in this population. The scat-based approach we present permits broad-scale inferences on predation risk for prey.

Chagas cardiomyopathy is the most prevalent non-ischemic cardiomyopathy in Latin America, with high morbidity and mortality even today. Treatment of these patients is based on the use of medications for heart failure. This study evaluated a cohort of patients with Chagas heart disease who used sacubitril valsartan at a referral hospital for the disease in Brazil. After six months, there was a symptomatic improvement in these individuals assessed by the NYHA classification, with a 44.3% reduction in the absolute number of patients classified as III-IV in the period (p 0.035), but without changes in the parameters on the echocardiogram for reverse ventricular remodeling and still high mortality rate and hospitalization. These results emphasize the importance of studying the use of sacubitril valsartan in chagas heart disease to better describe its effectiveness taking into account the peculiarities of these individuals.

Objectives: To assess the incidence, causes, risk factors and adverse outcomes of antepartum severe maternal morbidity (SMM) Design: Population-based case–control study Setting: 119 Maternity hospitals, 6 French regions Population: All women with antepartum SMM (cases, N=601), a randomly selected control sample of women who gave birth without SMM in the same hospitals during the same period (controls, N=3650) Methods: Uni- and multivariable logistic regression with multiple imputation Main outcomes measure: Antepartum SMM, defined as a morbid event occurring from 22 weeks of gestation and before the onset of labour Results: Antepartum SMM complicated 0.33% of pregnancies (95%CI, 0.30-0.36). Rates of prematurity, neonatal mortality, and transfer to the neonatal intensive care unit were 10 times higher for babies whose mothers had antepartum SMM than for the control mothers. Similarly, emergency caesarean and general anaesthesia were more frequent in women with antepartum SMM. Risk factors for antepartum SMM were maternal age >35 (aOR 1.55; 95% CI, 1.22-1.97), increased body mass index (aOR for 5kg/m2 increase, 1.24; 95% CI, 1.14-1.36), maternal birth in sub-Saharan Africa (aOR, 1.80; 95% CI, 1.29-2.53), pre-existing medical condition (aOR, 2.56; 95% CI, 1.99-3.30), nulliparity (aOR, 2.26; 95% CI, 1.83-2.80), previous pregnancy-related hypertensive disorders (aOR, 4.94; 95% CI, 3.36-7.26), multiple pregnancy (aOR, 5.79; 95% CI, 3.75-7.26), irregular prenatal care (aOR, 1.86; 95% CI, 1.27-2.72). Conclusion: Antepartum SMM is rare but associated with a massively higher incidence of adverse delivery and neonatal outcomes.

Post-inflammatory hyperpigmentation is the most benign cause of brownish discolorations of the skin. For this reason it has been little researched. In times of increasing treatments in the field of cosmetic medicine and simultaneous increased attention to the issue of skin cancer, a lack of knowledge may lead to over-treatment of post-inflammatory skin lesions.

As an essential micronutrient for many organisms, sodium plays an important role in ecological and evolutionary dynamics. Although plants mediate trophic fluxes of sodium, from substrates to higher trophic levels, we know relatively little about plants’ comparative growth and sodium accumulation responses to variation in substrate sodium. We carried out a systematic review to examine how plants respond to variation in substrate sodium concentrations. We compared growth and tissue-sodium responses among 107 populations (67 species in 20 plant families), broadly expanding beyond the agricultural and model taxa for which several generalizations previously have been made. We hypothesized a priori response models for each population’s growth and sodium accumulation responses as a function of increasing substrate NaCl. We used BIC to choose the best model. Additionally, using a phylogenetic signal analysis, we tested for phylogenetic patterning of growth and sodium accumulation responses across plant taxa. The influence of substrate sodium on growth differed across taxa, with most populations experiencing detrimental effects at high concentrations. Irrespective of growth response, tissue concentrations of sodium for most taxa increased as sodium concentrations in the substrate increased. We found no strong associations between growth and types of sodium accumulation responses across taxa. Our phylogenetic signal analyses found that evolutionary history helps predict the distribution of total plant growth responses across the phylogeny, but not sodium accumulation responses. Our study suggests that saltier plants in saltier soils may prove to be a broadly general pattern for sodium across plant taxa. Regardless of growth responses, sodium accumulation mostly followed an increasing trend and did not have any evident association with growth responses as substrate sodium levels increased. Finally, plant adaptations to substrate sodium vary with a degree of phylogenetic conservatism.

Local animal health services in rural communities are mainly provided by village animal health workers (VAHW), although the participation and contribution of VAWHs to disease prevention is uncertain. To address this, a desktop review of national VAWH data between 2011 - 2020 also conducted in December 2020, supporting a detailed survey on the involvement of VAHWs in disease prevention programs conducted between February to March 2014. The survey used guided group discussion with VAHWs (n = 198) from the two Cambodian provinces of Kampong Cham and Pursat. This study identified that VAHWs generated less than 22% of their annual household incomes from animal health services. Less than one-third had vaccinated livestock against FMD, with none having vaccinated cattle every six months during the study period, and nearly half of the VAHWs having never vaccinated their own cattle against FMD. As no privately-provided FMD vaccination services occurred in these communities, with all vaccines delivered through the government-subsidised program, the findings confirmed that VAHWs only vaccinated animals against FMD when vaccines were made available by the Government. The desktop review found that the number of VAHWs in 2020 declined by more than 24% since 2017 and the proportion of female VAHWs was consistently low, with a mean of 8.26 (± 1.019). These findings confirm there are considerable weaknesses in the VAHW system in Cambodia, particularly in contributing to FMD control. Cambodian animal health authorities require more effective policies to strengthen the current VAHW system, improving: their services delivery; their retention as ‘active’; their development of more sustainable roles with lower ‘dropout’ rates; and the prolonged gender inequity. With the limited availability of government-subsidised FMD vaccination currently, extension programs that engage VAHWs and farmers in seeking privately funded and delivered FMD vaccination that incorporates appropriate multivalent FMD serotype vaccines of high quality, delivered in small dose vials from a robust cold chain, is suggested. This strategy would assist VAHWs to contribute to the provision of private livestock vaccination services that are likely essential for sustainable FMD prevention and control in Cambodia.

Abstract Objective To determine whether the introduction of a one-stop see and treat clinic offering early reflux ablation for Venous Leg Ulcer (VLU) patients in July 2016 has affected rates of unplanned inpatient admissions due to venous ulceration. Design Review of inpatient admission data and analysis of related costs. Materials The Hospital Inpatient Enquiry collects data from acute public hospitals in Ireland on admissions and discharges, coded by diagnosis and acuity. This was the primary source of all data relating to admissions and length of stay. Costs were calculated from data published by the Health Service Executive in Ireland on average costs per inpatient stay for given diagnosis codes. Methods Data were collected on admission rates, length of stay, overall bed day usage, and costs across a four-year period; the two years since the introduction of the rapid access clinic, and the two years immediately prior as a control. Results 218 patients admitted with VLUs accounted for a total of 2,529 inpatient bed-days, with 4.5(2-6) unplanned admissions, and a median hospital stay of 7(4-13) days per month. Median unplanned admissions per month decreased from 6(2.5-8.5) in the control period, to 3.5(2-5) after introduction of the clinic p=.040. Bed-day usage was significantly reduced from median 62.5(27-92.5), to 36.5(21-44) bed-days per month (p=.035), though length of stay remained unchanged (p=.57). Cost of unplanned inpatient admissions fell from median \euro33,336.25(\euro14,401.26-\euro49,337.65) per month to \euro19,468.37(\euro11,200.98-\euro22,401.96) (p=.03). Conclusions Admissions for inpatient management of VLUs have fallen after beginning aggressive endovenous treatment of venous reflux in a dedicated one-stop see-and-treat clinic for these patients. As a result, bed-day usage has also fallen, leading to cost savings.

Aims: To our knowledge, this is the first study investigating the impact of high visceral adiposity index on female sexual dysfunction (FSD). We aimed to show the impact of increased levels of visceral adiposity index (VAI) on FSD compared to body mass index (BMI) and waist circumference (WC). Methods: We included 158 participants in two groups: Group 1 (n=68 with normal sexual function) and Group 2 (n=90 with sexual dysfunction). Demographic, clinic data, presence of metabolic syndrome (MeTS) and comorbidities were recorded. The BMI, WC and the visceral adiposity index were calculated. Sexual function was assessed using the female sexual function index (FSFI). Results: The mean age and all the anthropometric variables were similar between the groups (p>0.05). Metabolic syndrome was associated with lower arousal and lubrication scores than those without metabolic syndrome (p=0.023). The higher VAI was associated with lower desire, lubrication and orgasm scores (p<0.05). Each integer increase of the VAI weakly predicted decrease of desire (p=0.015), arousal (p=0.015), lubrication (p=0.005) and satisfaction (p=0.046). Conclusion: The VAI was linked with lower scores in some female sexual function subdomains, but the correlation coefficient was low, indicating a weak association. Further studies with a higher number of participants are needed to conclude that the VAI may increase the risk of FSD, particularly in patients with metabolic syndrome.

Elucidating mechanisms underlying community assembly and biodiversity patterns is central to ecology and evolution. Genome size (GS, i.e. nuclear DNA content) determines species’ capacity to tolerate environmental stress or to exploit new environments and therefore potentially drive community assembly. However, its role in driving β-diversity (i.e., the site-to-site variability in species composition) remains unclear. We measured GS for 169 plant species and investigated their occurrences within plant communities across 52 sites spanning a 3200-km transect in the temperate grasslands of China. We found environmental factors showed larger effects on β-diversity of large-GS than that of small-GS species. Community weighted mean GS increased with mean annual precipitation, soil total nitrogen and phosphorus concentrations, but decreased with mean annual temperature, suggesting a negative selection against species with large GS in resources-limited or warmer climates. These findings highlight the roles for GS in driving community assembly and predicting species responses to climate change.

Conflicts of Interest: Marielle C. Young, Ian R. Roy, Ariel S. Frey-Vogel, and Kristina Dzara report no conflicts of interest. Michael Pistiner has served on advisory boards of kaléo, DBV Technologies, and Novartis, has received funding from kaléo, DBV Technologies, and the National Peanut Board, and is a co-founder of AllergyHome and of Allergy Certified Training.Financial Support: This project was completed without financial support.Keywords: food allergy, anaphylaxis, infant allergy, toddler allergy, pediatric residents, residency needs assessment, residency curriculum

Resource-use complementarity of producer species is often invoked to explain their generally positive diversity-productivity relationships. Additionally, multi-trophic interactions that link processes across trophic levels have received increasing attention as a possible key driver. Given that both are integral to natural ecosystems, their interactive effect should be evident but has remained hidden. We address this issue by analyzing diversity-productivity relationships in a simulation experiment of primary producer communities nested within complex food-webs, manipulating resource-use complementarity and multi-trophic animal richness. We show that both mechanisms' joint contribution to positive diversity-productivity relationships generally exceeds their individual effects, as both interactively create diverse communities of complementary producer species. Specifically, multi-trophic interactions in animal-rich ecosystems increase complementarity the most when resource-use complementarity is low. The interdependence of top-down and bottom-up forces in creating biodiversity-productivity relationships highlights the importance to adopt a more multi-trophic perspective on biodiversity-ecosystem functioning relationships.

In this paper, the global finite-time stabilization (FTS) of nonlinear systems with unknown functions (UFs) is studied. Firstly, in order to deal with UFs, a Lemma is proposed to avoid the Assumptions of UFs. Secondly, based on this Lemma, the control algorithm designed by using backstepping has no partial derivative of virtual controllers, so it avoids the “differential explosion” problem of backstepping. Thirdly, by using Lyapunov analysis method, backstepping and FTS method, a global FTS control algorithm of nonlinear systems with UFs is proposed. Finally, the feasibility of developed control approach is illustrated by the simulation results of a manipulator.

Background: Fibromyalgia syndrome (FMS) is a chronic syndrome primarily characterized by widespread musculoskeletal pain. Although its etiology is not fully understood, complex interactions between biological, genetic and psycho-sociological factors thought to be effective in the onset and maintenance of FMS. Psychological factors could be explained by social cognitive concepts, which include mentalizing other person’s intentions, beliefs, behaviors and attachment styles. Objectives: In this study we aimed to examine social cognitive and attachment profiles of FMS patients. Methods: The participants were recruited from Marmara University Pendik Training and Research Hospital. Sociodemographic data were questioned in both groups while FMS group was also administered Fibromyalgia Impact Questionnaire (FIQ) to determine disease severity. In order to evaluate social cognition profiles of the participants, Reading Mind in the Eyes Test (RMET), Empathy Quotient (EQ) and Experiences in Close Relationships-Revised were applied by the same researcher. Results: 41 women with FMS and 44 healthy women matched for education and age were involved in the study. There was no significant difference in sociodemographic parameters between FMS and control groups. FMS patients did not differ significantly from control subjects in means of RMET and EQ scores. Although no significant difference found between attachment anxiety, FMS patients were found to have more avoidant attachment style than control group. Conclusion: FMS patients may have no social cognition impairments, especially in lack of any psychiatric comorbidities. Moreover, these patients may suffer from avoidant type of insecure attachment and this attachment style may effect social support seeking behaviour of these patients.