Abstract Aim: To investigate the health care utilization and drug consumption of patients with fibromyalgia (FM). Materials and Methods: This is a cross-sectional study using the Clalit Health Care database. Clalit is the largest HMO in Israel, serving more than 4.4 million enrollees. We identified FM patients and age and sex-matched controls. Indicators of healthcare utilization and drug consumption were extracted and analyzed for both groups. Results: The study included 14,296 FM patients and 71,324 controls. The mean age was 56 years, with a female predominance of 92%. The mean number of visits across of all healthcare services (hospitalizations, emergency department visit, general practitioner clinic visits, rheumatology clinic visits and pain clinic visits) and the mean difference (MD) were significantly higher for FM patients compared to controls (MD 0.66, p<0.001; MD 0.23, p<0.001; MD 7.49, p<0.001; MD 0.31, p<0.001; MD 0.13, p<0.001), respectively. Drug use was significantly and consistently higher among FM patients compared to controls; NSAIDs (non-steroidal anti-inflammatory drugs) OR 2.56, P<0.001; Opioids OR 4.23, P<0.001; TCA (tricyclic antidepressants) OR 8.21, P<0.001; Gabapentinoids OR 6.31, P<0.001; SSRI (selective serotonin reuptake inhibitors) OR 2.07, P<0.001; SNRI (serotonin-norepinephrine reuptake inhibitor) OR 7.43, P<0.001. Conclusion: Healthcare utilization and drug use are substantially higher among patients with fibromyalgia compared to controls

Aldosterone binds to the mineralocorticoid receptor (MR), a transcription factor of the nuclear receptor family, present in the kidney and in various other non-epithelial cells including the heart and the vasculature (Cannavo et al., 2018). Indeed, extra-renal pathophysiological effects of this hormone have been characterized, extending its actions to the cardiovascular (CV) system (Messaoudi et al., 2012). A growing body of clinical and pre-clinical evidence suggests that MR activation plays an important pathophysiological role in CV remodeling by promoting cardiac hypertrophy, fibrosis, arterial stiffness, as well as in inflammation and oxidative stress (Bauersachs et al., 2015). The following review article outlines the role of MR in CV disease with a focus on myocardial remodeling and heart failure (HF) including clinical trials as well as cellular and animal studies.

Genetic monitoring using non-invasive samples provides a complement or alternative to traditional population monitoring methods. However, Next Generation Sequencing approaches to monitoring typically require high quality DNA and the use of non-invasive samples (e.g. scat) is often challenged by poor DNA quality and contamination by non-target species. One promising solution is a highly multiplexed sequencing approach called Genotyping-in-thousands by sequencing (GT-seq), which can enable cost-efficient genomics-based monitoring for populations based on non-invasively collected samples. Here, we develop and validate a GT-seq panel of 324 single nucleotide polymorphisms (SNPs) optimized for genotyping of polar bears based on DNA from non-invasively collected fecal samples. We demonstrate 1) successful GT-seq genotyping of DNA from a range of sample sources, including successful genotyping of 85.7% of non-invasively collected fecal samples determined to contain polar bear DNA, and 2) that we can reliably differentiate individuals, ascertain sex, assess relatedness, and resolve population structure of Canadian polar bear subpopulations based on a GT-seq panel of 324 SNPs. Our GT-seq data reveal similar spatial-genetic patterns as previous polar bear studies but at lesser cost per sample and using non-invasively collected samples, indicating the potential of this approach for population monitoring. This GT-seq panel provides the foundation for a non-invasive toolkit for polar bear monitoring and contribute to community-based programs – a framework which may serve as a model for wildlife management and contribute to conservation and policy for species worldwide.

Leptospirosis is a zoonotic neglected disease of worldwide public health concern. Leptospira species can infect a wide range of wild and domestic mammals and can lead to a spectrum of disease, including severe and fatal forms. Herein, we report for the first time a fatal Leptospira interrogans infection in a free-ranging nonhuman primate (NHP), a black-tufted marmoset. Icterus, pulmonary hemorrhage, interstitial nephritis and hepatocellular dissociation were the main findings raising the suspicion of leptospirosis. Diagnostic confirmation was based on specific immunohistochemical and PCR assays for Leptospira species. Immunolocalization of leptospiral antigens and identification of pathogenic species ( L. interrogans species) were important for better understanding the pathogenesis of disease. One Health related implications of free-ranging NHPs in anthropized areas and transmission dynamics of human and animal leptospirosis are discussed.

Title Page: MinicommentaryThis is a minicommentary on Reid et al. “How common are complications following polypropylene mesh, biological xenograft 3 and native tissue surgery for pelvic organ prolapse? A secondary analysis from the PROSPECT trial”.Title: Understanding Risk: a substitute for Information?Author : Swati Jha (MD, FRCOG)Consultant Gynaecologist and Honorary Senior Clinical Lecturer, Sheffield University. Subspecialist in UrogynaecologyInstitute : Department of Urogynaecology, Sheffield Teaching Hospitals NHS Foundation TrustAddress : Sheffield Teaching Hospitals, Level 4, Jessop Wing, Tree Root Walk, Sheffield. S10 [email protected] (0)114 2268568Fax : 0114 2268165

We are reporting a case of Guillain- Barré syndrome seven days after the first dose of Pfizer-BioNTech COVID-19 Vaccine. As this vaccine is still under investigation, reporting possible rare side effects is essential. In this case, the temporal relationship was suggestive of a vaccine-induced cause.

Title Page: Minicommentary

Mongolia and Eastern Siberia, Russia are border regions in Asia with high incidence of tuberculosis (TB). In this study, we aimed to investigate MDR -TB transborder transmission with a focus on endemic and epidemic Mycobacterium tuberculosis clones and drug resistance patterns. M. tuberculosis strains (291 from Mongolia and 754 from Russia) were collected within cross-sectional population-based surveys in 2010-2016. DNA was genotyped in 24 MIRU-VNTR loci and by PCR testing of the key SNP markers to discriminate within Beijing genotype. In total, 1045 isolates were divided into 435 MIRU-types that were assigned to Lineage 2 (Beijing isolates) and Lineage 4 (Ural, Haarlem, Latin-American-Mediterranean [LAM], S, and unclassified isolates). Beijing genotype was dominant in both countries, but most of Russian and all Mongolian Beijing strains belonged to different subtypes of the modern Beijing sublineage with only negligible overlap between the two countries. In particular, the Beijing types #342-32, #3819-32, #1773-32 (Asian African 2 group) were found only in Mongolia. LAM was the most common non-Beijing genotype (11.0% in Mongolia and 14.7% in Russia) and its isolates mostly belonged to LAM-RUS branch. MDR rate was higher in Russia compared to Mongolia among newly diagnosed patients: 29.4% versus 4.2% (p < 0.001) but similar and high in the retreatment subgroups (65.8% and 67.4%, respectively). In Russian collection, a higher MDR rate was observed in (i) Beijing compared to non-Beijing (47.5% versus 38.8%, p = 0.03), (ii) Beijing B0/W148 subtype compared to Beijing Central Asian/Russian subtype (64.5% versus 39.3%, p <0.001). In Mongolia, MDR rate was similar in Beijing (29.7%) and non-Beijing (27.5%) genotypes. In conclusion, population structures of the Beijing genotype in Mongolia and Russian borderline regions differ significantly including specific patterns of drug resistance. In contrast, largely overlapping LAM subtypes may correlate with historical endemic circulation of the LAM-RUS branch in Northern Eurasia.

This case report demonstrate concurrent of two rare complications of true silent inferior STEMI in the poorly controlled diabetic patient with de-novo heart failure, mimicking congenital VSD.This complication of myocardial infarction often have catastrophic manifestations and the presence of this complications of MI with smooth course is very scarce

This paper deals with an initial-boundary value problem of the planar compressible Hall-magnetohydrodynamic (for short, Hall-MHD) equations. For the fixed shear viscosity and Hall coefficients, it is shown that the strong solutions of Hall-MHD equations and corresponding MHD equations are global. As both the shear viscosity and the Hall coefficients tend to zero, the convergence rate for the solutions from Hall-MHD equations to MHD equations is given. The thickness of boundary layer is discussed by spatially weighted estimation and the characteristic of boundary layer is described by constructing a boundary layer function.

Background Bicuspid pulmonic valves are quite uncommon, being described in only 0.1% of donor hearts, while pulmonary artery aneurysms are even more rare, having been found in 8 out of 109,571 autopsies. This rarity makes it difficult to characterize the relationship between them. Materials & Methods We describe the case of a 66-year-old female who was found to have a bicuspid pulmonic valve and pulmonary artery aneurysm (5.1cm) on imaging by her cardiologist. Discussion & Conclusion This case raises the question of whether the association between bicuspid semilunar valve disease and vascular wall anomalies are more genetic or hemodynamic. Even on the aortic side, despite the robust association between bicuspid aortic valves and thoracic aortic aneurysms, the mechanism still remains unclear. In our patient there was no significant gradient across the bicuspid pulmonic valve, suggesting that hemodynamics are not the primum mobile of this association.

Dobhoff tubes, used for post-pyloric feedings, have a weighted metal end with a small diameter that enhances their flexibility to traverse the gastrointestinal tract. Unfortunately, the metal stylet can iatrogenically perforate surrounding structures in patients with diminished cough and gag (1); and extreme caution should be considered before its utilization.

Aim To describe the antiepileptic drug (AED) prescription pattern in pregnant women and women of childbearing age in the 2010-2019 period in the Lombardy region, Italy. Methods The Lombardy region administrative healthcare databases (2010-2019) were analysed. AEDs were classified as drugs belonging to the N03A subgroup of the Anatomical Therapeutic Chemical Classification System. Women 15-49 years old were considered as women of childbearing age, while exposure during pregnancy was estimated taking into account the 12 months before delivery (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM codes in the diagnosis record from 650 to 659). Results During 2019, 16,605 women of childbearing age (prevalence: 14.8‰) received at least one AED prescription. Pregabalin was the most widely used antiepileptic in women of childbearing age (22.3%), followed by valproic acid (20.0%). The prevalence of AED prescription in pregnant women was 3.8‰, and levetiracetam and lamotrigine (16.6%) were the most commonly prescribed drugs. The prevalence of AED prescription did not change from 2010 to 2019 in women of childbearing age or in pregnant women. Valproic acid was one of the most used AEDs in pregnancy until 2016, after which its prescription declined from 19% to 14% of AED users. Conclusions Despite the decrease in valproic acid prescription over time, this drug is still among the most used AEDs, in particular in women of childbearing age. Educational interventions for healthcare professionals and women are needed in order to reduce the risk of unplanned pregnancy.

Background and purpose. Venomous animals express numerous Kunitz-type peptides. The mambaquaretin-1 (MQ1) recently identified from the Dendroaspis angusticeps venom is the most selective antagonist of the arginine-vasopressin V2 receptor (V2R) and the unique Kunitz-type peptide active on a GPCR. We aimed to exploit other mamba venoms to enlarge the V2R-Kunitz peptide family and get insight into the MQ1 molecular mode of action. Experimental approach. We used a bio-guided screening assay to identify novel MQs and placed them phylogenetically. Several newly identified MQs were produced by solid phase peptide synthesis. They were characterized in vitro by binding and functional tests andin vivo by diuresis measurement in rats. Key results. Eight additional MQs were identified with nanomolar affinities for the V2R, all antagonists. MQs form a new subgroup in the Kunitz family, close to the V2R non-active dendrotoxins and to 2 V2R active cobra toxins. Sequence comparison between active and non-active V2R Kunitz peptides highlighted 5 specific V2R positions. Four of them are involved in V2R activity and belong to the 2 large MQ1 loops. We finally determined that 8 positions, part of these 2 loops, interact with the V2R. The variant MQ1-K39A showed specificity for the human versus the rat V2R . Conclusions and implications. A third function and mode of action is now associated with the Kunitz-peptides. The number of MQ1 residues involved in V2R binding is large and may explain its absolute selectivity. MQ1-K39A represents the first step in the improvement of the MQ1 design for medicinal perspective.

In this research, an integrated pest management model using impulsive differential equations has been investigated for Jatropha curcas plantation to control its natural pests through relying on the release of infective pest individuals and spraying of chemical pesticides. Using Floquet’s theory and the small amplitude perturbation method, it is obtained that there exists an asymptotically stable susceptible pest eradication periodic solution when the release amount of infected pest is larger than the critical maximum value (or strength of chemical pesticide spraying is larger than some critical maximum value). Also, we have established the permanence of the system. After comparison, it is explored that integrated pest management is more effective than biological control or chemical control. Finally, verify the analytical results through numerical simulation.

The present paper studies a fractional-order SEIR epidemic model for the transmission dynamics of infectious diseases such as HIV and HBV that spreads in the host population. The total host population is considered bounded, and Holling type-II saturation incidence rate is involved as the infection term. Using the proposed SEIR epidemic model, the threshold quantity, namely basic reproduction number R0, is obtained that determines the status of the disease, whether it dies out or persists in the whole population. The model’s analysis shows that two equilibria exist, namely, disease-free equilibrium (DFE) and endemic equilibrium (EE). The global stability of the equilibria is determined using a Lyapunov functional approach. The disease status can be verified based on obtained threshold quantity R0. If R0 < 1, then DFE is globally stable, leading to eradicating the population’s disease. If R0 > 1, a unique EE exists, and that is globally stable under certain conditions in the feasible region. The Caputo type fractional derivative is taken as the fractional operator. The bifurcation and sensitivity analyses are also performed for the proposed model that determines the relative importance of the parameters into disease transmission. The numerical solution of the model is obtained by the generalized Adams- Bashforth-Moulton method. Finally, numerical simulations are performed to illustrate and verify the analytical results.

The time-fractional Gardner Burger (TFGB) equation is an efficient model for studying nonlinear fluctuations of different types of wave profiles, such as the gravity solitary waves in the ocean, ion-acoustic wave (IAW) in a plasma environment, etc. Here, to build an example of the existence of the classical Gardner Burger (GB) equation, a multi-component plasma environment is considered and a classical GB equation is derived by employing reductive perturbation technique (RPT) from the basic governing equation. Further, the classical GB equation is converted into the TFGB equation by applying Agrawal’s approach, where the Riesz fractional derivative is adopted on the time-fractional term. A new approach using the improved Bernoulli sub-equation function method (IBSEFM) is carried out to solve the TFGB equation. Finally, some $2D$ and $3D$ graphs are plotted through which the physical structures of the solution are explored and the effect of the Burgers term and fractional order of the equation are determined.

Objetives. To perform a description of the etiology of hospitalized children with community-acquired pneumonia (CAP) in Spain and analyze predictors related to etiology. Hypothesis. The different etiological groups of pediatric CAP are associated to different clinical, radiographic and analytical data. Design. Observational, multi-center, prospective study. Patient selection. Patients from 1 month to 17 years admitted because of CAP from April 2012 to May 2019. Methods. An extensive microbiological workup was done. Clinical, radiographic and analytical parameters were analyzed in order to differentiate viral, atypical bacteria (AB) and typical bacteria (TyB) pneumonia. Results. 495 children were enrolled. At least one likely causative pathogen was identified in 262 (52.9%). Pathogenic viruses in 155/262 (59.2%), AB in 84/262 (32.1%) and TyB in 40/262 (15.3%). Consolidation was found in 89/138 (64.5%) CAP attributed to virus only, in 74/84 (88.1%) of CAP attributed to AB and 40/40 (100%) of CAP attributed to TyB. Para-pneumonic pleural effusion (PPE) was found in 112/495 (22.6%) patients, 61/112 (54.5%) with a likely causative pathogen: virus 12/61 (19.7%), AB 23/61 (37.7%) and TyB 26/61 (42.6%). Viral etiology was significantly more frequent in younger patients and those with lower oxygen saturation, wheezing, no-consolidation and higher lymphocyte counts. Patients with AB were significantly more likely to have more days of fever at admission and a higher rate of use of antibiotics before admission. Conclusions. Viruses and AB are the main cause of pediatric CAP in Spain. Wheezing, younger age and no-consolidation on the X-ray support viral etiology. Viruses and AB can also cause PPE. The use of antibiotic in pediatric CAP can be restricted.