However, FLX exposure did not alter anxiety, stress coping, and 5-HT1A receptor sensitivity. No differences were found in 5-HT1A receptor and clock genes Per1, Per2, Cry1, and Cry2 SCN gene expression. Conclusions Perinatal FLX exposure altered the response to a phase-shifting challenge in female rats, whether this may pose health risks remains to be investigated.Pexophagy is a peroxisome degradation process. The last two steps of penicillin biosynthesis in Penicillium rubens are carried out in peroxisomes. These organelles proliferate in large numbers during this process, so that after the penicillin secretion, their removal is essential as a regulatory mechanism. In this work, two pexophagy modes are described for the high-penicillin producing strain P. rubens P2-32-T, by transmission electron microscopy (TEM) on 24- and 48-h cultures (when maximum penicillin production is achieved). The obtained images show peroxisome phagocytosis by vacuoles in three different ways macropexophagy, micropexophagy, and a new proposed model unipexophagy.Venturia inaequalis is a notorious fungal pathogen and show classical gene for gene interaction with its apple host. Neutral markers provide clues about history, evolutionary potential, genetic diversity and population structure of V. inaequalis. The genetic diversity and population structure of fungus indicates that the pathogen is highly diverse with the capacity to breach the scab resistance genes. In the present study, we collected 108 V. inaequalis isolates from three apple cultivars differing in Rvi1 resistance gene. Based on the AMOVA, the variation was mostly distributed among the isolates, providing evidence of non-existence of subpopulation in orchards thus founder population is difficult to arise in Kashmir apple orchards. Pair wise genetic differentiation is less due to regular occurrence of gene flow between the populations residing on different orchard as infected material is transported without stringent quarantine measures. Based on principal coordinate analysis and clustering algorithm as implemented in STRUCTURE, we observed admixture between the two subpopulations, which is quite low, suggesting the existence of pre-zygotic and post-zygotic barriers to gene flow and we cannot rule out the existence of other structures shared by accessions belonging to different varieties. Due to the continuous increase in introduction and monoculture of apple varieties, mixed orchard with different host resistance specificities are more suitable for managing the apple scab in Kashmir valley.Selenium nanoparticles (SeNPs) are attractive nanomaterials for application in medical diagnosis, because their toxicities are lower than the elemental selenium which is a functional element and essential for human. In the current study, SeNPs synthesis capability of a novel soil originated indigenous Bacillus isolate was investigated. In this context, effects of processing conditions (SeO2 concentration, pH, temperature, and time), and yeast extract supplementation on the synthesis of SeNPs have been tested. In addition, nanoparticles were characterized and antioxidant capacity was determined. The cell-free supernatant of the bacterium, which was obtained after the cultivation of the isolate in nutrient broth at 33 °C for 24 h, was used for the synthesis. During the synthesis color change from light yellow to red-orange was an indication of the formation of SeNPs. Effect of SeO2 concentration was tested on the formation of nanoparticles and at concentrations higher than 10 mM, there was no formation of nanoparticles. The best production was achieved at 6.4 mM concentration, at pH 9 and 33 °C in 72 h. Field emission scanning electron microscopy (FESEM) images revealed that SeNPs were spherical in shape having the diameters between 31 and 335 nm, and the average diameter was determined to be 126 nm. Energy dispersive X-ray spectroscopy analysis confirmed the presence of elemental selenium. SeNPs possessed significant antioxidant activity that the scavenging capacity was up to 56.5 ± 5% (IC50 322.8 μg/mL).Spinal extradural arteriovenous fistulas (SEDAVFs) are a rare form of spinal arteriovenous fistulas, the etiology of which has not been completely elucidated. To our knowledge, this is the first reported case of SEDAVF that may have been caused by a spinal procedure. This report describes a 50-year-old female patient who presented with an SEDAVF at the L3/4 level that developed 3 years after a transforaminal epidural block due to disc extrusion, after which she underwent no other operation or trauma. From routine spine magnetic resonance imaging, disc sequestration was considered more likely than vascular malformation. However, on lumbar CT angiography (CTA) and three-dimensional volume rendering images (3D-VRI), the lesion showed good association with arteries of the aortic branches, allowing us to confirm the exact diagnosis of the lesion as SEDAVF. A limitation of 3D-VRI reconstruction is the difficulty in separate visualization of the vertebral body and blood vessels. On follow-up CTA, 3D dual-energy computed tomography (DECT) depicted smaller vascular structures and showed their anatomical relationships to the bone. While spinal angiography has been traditionally known as the gold standard for SEDAVF diagnosis, CTA with 3D-VRI, especially obtained by DECT, allows clinicians to make an accurate diagnosis and treatment plan that are difficult to judge by routine MRI.Objective To investigate the muscle activity patterns of the glenohumeral joint during internal rotation both with the arm at 0° and 90° of abduction using 2-deoxy-2-[18F] fluoro-D-glucose (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI). Materials and methods Six healthy male volunteers underwent PET examination after performing active glenohumeral internal rotation exercise using an elastic band both with the arm at 0° and 90° of abduction. As a control, PET scan under resting condition was also performed. The exercise was performed before and after 18 fluorodeoxyglucose injection. Each PET image was fused to the corresponding MRI to identify each muscle. The standardized uptake value (SUV) of each muscle was compared between the two arm positions. Results With the arm at 0° of abduction, the SUV increased significantly after exercise both in the middle and inferior 1/3 of the subscapularis, which were significantly higher than that of the superior 1/3 of the subscapularis (P less then 0.05). The SUV of the inferior 1/3 of the subscapularis was significantly higher at 90° of abduction than at 0° of abduction and was significantly higher than that of the superior 1/3 at 90° of abduction (P less then 0.01). The SUV after exercise in the inferior infraspinatus and teres minor increased. Conclusions The middle and inferior parts of the subscapularis are the main shoulder internal rotators in 0° of abduction, whereas the inferior part of the subscapularis is the main internal rotator in 90° of abduction.We present a rare case of a 4-year-old girl suffering from a sclerotic lesion on the forehead as well as uveitis and epileptic seizures. The patient was diagnosed with linear scleroderma „en coup de sabre” (LSECDS). Faced with no gold standard for treatment of LSECDS with severe extracutaneous manifestations, the case was intensively discussed within an interdisciplinary team setting and successfully treated.Basal cell carcinoma is the most common type of cancer in Central Europe and has a high medical relevance. Due to its high tendency of recurrence, an important parameter in the planning of therapy is the risk of recurrence. After clinical and histological diagnosis, the majority of tumors are treated surgically, although radiation and topical procedures are also possible therapeutic alternatives in certain constellations. Hedgehog inhibitors, a completely new class of substances, have recently been approved for rare metastatic and locally advanced diseases, thus significantly expanding the range of treatments. This article provides an overview of the current guideline-based diagnosis and therapy of basal cell carcinomas in Germany.Background Percutaneous access to the renal pelvis still remains the most difficult step before nephrolitholapaxy (PCNL). New imaging techniques, such as 3D imaging and various navigation instruments such as electromagnetic, sonographic, CT-controlled and marker-based/iPAD try to simplify this step and reduce complications. Objectives In this review, various new techniques for puncturing the renal collecting system are presented and their advantages and disadvantages are evaluated. Materials and methods A systematic literature search was carried out in MEDLINE, whereby only puncture techniques that have already been evaluated in clinical studies were included. Results Five different navigation methods for puncturing the renal pelvis before PCNL were found. Conclusion Intraoperative navigation can be useful when puncturing the collecting system. The combination of ultrasound and fluoroscopy currently remains the gold standard. However, there is still a need for further, primarily clinical, prospective studies to determine which new imaging technology and navigation systems will prevail and thus facilitate the access route to the kidney, especially in the case of special anatomical conditions.Chamber-specific and temporally regulated perinatal cardiac growth and maturation is critical for functional adaptation of the heart and may be altered significantly in response to perinatal stress, such as systemic hypoxia (hypoxemia), leading to significant pathology, even mortality. Understanding transcriptome regulation of neonatal heart chambers in response to hypoxemia is necessary to develop chamber-specific therapies for infants with cyanotic congenital heart defects (CHDs). We sought to determine chamber-specific transcriptome programming during hypoxemic perinatal circulatory transition. We performed transcriptome-wide analysis on right ventricle (RV) and left ventricle (LV) of postnatal day 3 (P3) mouse hearts exposed to perinatal hypoxemia. Hypoxemia decreased baseline differences between RV and LV leading to significant attenuation of ventricular patterning (AVP), which involved several molecular pathways, including Wnt signaling suppression and cell cycle induction. Notably, robust changes in RVof cardiac chamber-specific maturation and adaptation to hemodynamic load and external environment. During hypoxemic perinatal transition, transcriptome reprogramming may affect chamber-specific growth and development, particularly in newborns with congenital heart defects (CHDs). Chamber-specific transcriptome changes during hypoxemic perinatal transition are yet to be fully elucidated. Systems-based analysis of hypoxemic neonatal hearts at postnatal day 3 reveals chamber-specific transcriptome signatures during hypoxemic perinatal transition, which involve attenuation of ventricular patterning (AVP) and repression of epithelial mesenchymal transition (EMT). Key regulatory circuits involved in hypoxemia response were identified including suppression of Wnt signaling, induction of cellular proliferation and dysregulation of TP53 network.Background Periprosthetic fractures of the knee joint are complex injuries and frequently represent a challenge for the surgeon. Objective The aim of this review is to present and discuss the current classification and treatment options for periprosthetic knee fractures. Material and methods A selective review of the existing literature on periprosthetic fractures around the knee was performed in PubMed. The various classifications and treatment regimens are discussed with respect to the advantages and disadvantages and from this knowledge a new algorithm was developed. Results The classifications of periprosthetic fractures have changed in recent years and have been replaced by a uniform fracture classification; however, not only the radiological evaluation of the fractures is crucial to determine the treatment regimen for periprosthetic fractures. A thorough evaluation of the inserted endoprosthesis should be carried out in order to be able to decide between the treatment options of osteosynthesis and revision arthroplasty. Treatment options are available for osteosynthesis and revision arthroplasty that enable a safe treatment of these complex injuries. Conclusion Periprosthetic fractures of the knee joint are complex injuries, requiring a thorough preoperative planning and an interdisciplinary treatment with trauma and endoprosthetic expertise.Acute kidney injury (AKI) has been reported in up to 25% of critically-ill patients with SARS-CoV-2 infection, especially in those with underlying comorbidities. AKI is associated with high mortality rates in this setting, especially when renal replacement therapy is required. Several studies have highlighted changes in urinary sediment, including proteinuria and hematuria, and evidence of urinary SARS-CoV-2 excretion, suggesting the presence of a renal reservoir for the virus. The pathophysiology of COVID-19 associated AKI could be related to unspecific mechanisms but also to COVID-specific mechanisms such as direct cellular injury resulting from viral entry through the receptor (ACE2) which is highly expressed in the kidney, an imbalanced renin-angotensin-aldosteron system, pro-inflammatory cytokines elicited by the viral infection and thrombotic events. Non-specific mechanisms include haemodynamic alterations, right heart failure, high levels of PEEP in patients requiring mechanical ventilation, hypovolemia, administration of nephrotoxic drugs and nosocomial sepsis. To date, there is no specific treatment for COVID-19 induced AKI. A number of investigational agents are being explored for antiviral/immunomodulatory treatment of COVID-19 and their impact on AKI is still unknown. Indications, timing and modalities of renal replacement therapy currently rely on non-specific data focusing on patients with sepsis. Further studies focusing on AKI in COVID-19 patients are urgently warranted in order to predict the risk of AKI, to identify the exact mechanisms of renal injury and to suggest targeted interventions.A 57-year-old woman underwent esophagogastroduodenoscopy due to a continuous drop in hemoglobin levels reaching 7.4 g/dl after treatment with intravenous thrombolytic therapy 1 week earlier because of an ischemic insult. Numerous erosive lesions were found in the gastric corpus. Histological staining of a specimen from the gastric lesions revealed a poorly differentiated adenocarcinoma. Immunohistochemical examination confirmed the diagnosis of gastric metastasis from lung cancer based on positive staining for thyroid transcriptional factor‑1 (TTF-1) and cytokeratin 7 (CK7) as well as via negative staining for caudal-type homeobox‑2 (CDX-2). Chest computed tomography demonstrated a mediastinal mass, measuring 3.2 cm and involving the cervical and supraclavicular lymph nodes. A lymph node was subsequently extirpated. Immunohistochemical examination confirmed the diagnosis of lymph node metastasis from lung cancer by positive staining for TTF‑1 and CK7. Symptomatic gastric metastasis from lung cancer is an extremely rare clinical entity. Transesophageal echocardiography detected a mass measuring 1.6 cm at the mitral valve with pericardial effusion. On the basis of the echocardiographic findings, a malignant origin was suggested after exclusion of infectious endocarditis. We assumed that the multiple organ infarctions (spleen, kidney, and brain) and gastric hematogenous metastasis must have been caused by disseminated arterial tumor embolism from the intracardiac metastasis. The patient was treated palliatively and died.The original version of this article, published on 21 March 2019, unfortunately contains some typos in Figs. 2, 3, 4, and Supplemental Fig. 1. The corrected figures are given below.Objectives To identify and summarize the existing evidence on the efficacy, effectiveness and safety of biologic therapies used, either as indicated or off-label, in the treatment of FMF. Methods A systematic literature review was conducted using Embase®, MEDLINE®, MEDLINE®-In Process, and Cochrane databases to identify randomized/non-randomized controlled trials (RCTs/non-RCTs) and real-world observational studies of FMF published as full-text articles (2000-September 2017) or conference abstracts (2014-September 2017). Studies with data for ≥1 biologic were included. Studies with less then 5 patients were excluded. Results Of the 3342 retrieved records, 67 publications, yielding 38 unique studies, were included. All studies were published after the year 2010, and the majority (21) were full-text articles. Most studies (33/38) were prospective/retrospective observational; three were double-blind, placebo-controlled RCTs (one each of anakinra, canakinumab and rilonacept); and two were non-RCTs (both canakinumab). Anakinra (26), canakinumab (21) and etanercept (6) were the most frequently used biologics across studies, whereas use of adalimumab, tocilizumab, rilonacept and infliximab was limited (1-2 studies). The available evidence suggested benefits of anakinra and canakinumab in FMF. Conclusion Anti-IL-1 therapies (i.e. anakinra and canakinumab) appear to be effective and safe options in the treatment of overall FMF, including patients with colchicine resistance and FMF-related amyloidosis. There is a need for properly designed prospective or controlled studies to conclude the superiority of one anti-IL-1 therapy over another. Evidence on the use of TNF-α and IL-6 inhibitors is limited, and further research is suggested.Objective Cholangiocarcinoma (CCA) is a primary malignancy, which is often diagnosed as advanced and inoperable due to the lack of effective biomarkers and poor sensitivity of clinical diagnosis. Here, we aimed to identify the genomic profile of CCA and provided molecular evidence for further biomarker development. Methods The formalin-fixed paraffin-embedded and matching blood samples were sequenced by deep sequencing targeting 450 cancer genes and genomic alteration analysis was performed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was performed by Fisher’s exact test. Results The most commonly altered genes in this cohort were TP53 (41.27%, 26/63), KRAS (31.75%, 20/63), ARID1A and IDH1 (15.87%, 10/63, for both), SMAD4 (14.29%, 9/63), FGFR2 and BAP1 (12.70%, 8/63, for both), and CDKN2A (11.11%, 7/63). BAP1 mutations were significantly correlated with the CCA subtype. LRP2 mutations were significantly associated with the younger intrahepatic CCA (iCCA) patients, while BAP1 was associated with iCCA patients aged 55-65 years old. BAP1 and LRP2 mutations were associated with TMB. Conclusions Most Chinese CCA patients were 50-70 years old. BAP1 and LRP2 mutations were associated with the age of iCCA patients.Background Sex hormone-binding globulin (SHBG) is a circulating glycoprotein and a regulator of sex hormone levels, which has been shown to influence various traits and diseases. The molecular nature of SHBG makes it a feasible target for preventative or therapeutic interventions. A systematic study of its effects across the human phenome may uncover novel associations. Methods We used a Mendelian randomization phenome-wide association study (MR-pheWAS) approach to systematically appraise the potential functions of SHBG while reducing potential biases such as confounding and reverse causation common to the literature. We searched for potential causal effects of SHBG in UK Biobank (N = 334 977) and followed-up our top findings using two-sample MR analyses to evaluate whether estimates may be biased due to horizontal pleiotropy. Results Results of the MR-pheWAS across over 21 000 outcome phenotypes identified 12 phenotypes associated with genetically elevated SHBG after Bonferroni correction for multiple testing. Follow-up analysis using two-sample MR indicated the associations of increased natural log SHBG with higher impedance of the arms and whole body, lower pulse rate, lower bone density, higher odds of hip replacement, lower odds of high cholesterol or cholesterol medication use and higher odds of gallbladder removal. Conclusions Our systematic MR-pheWAS of SHBG, which was comprehensive to the range of phenotypes available in UK Biobank, suggested that higher circulating SHBG affects the body impedance, bone density and cholesterol levels, among others. These phenotypes should be prioritized in future studies aiming to investigate the biological effects of SHBG or develop targets for therapeutic intervention.Aims Brugada syndrome (BrS) is characterized by a unique electrocardiogram (ECG) pattern and life-threatening arrhythmias. However, the Type 1 Brugada ECG pattern is often transient, and a genetic cause is only identified in less then 25% of patients. We sought to identify an additional biomarker for this rare condition. As myocardial inflammation may be present in BrS, we evaluated whether myocardial autoantibodies can be detected in these patients. Methods and results For antibody (Ab) discovery, normal human ventricular myocardial proteins were solubilized and separated by isoelectric focusing (IEF) and molecular weight on two-dimensional (2D) gels and used to discover Abs by plating with sera from patients with BrS and control subjects. Target proteins were identified by mass spectrometry (MS). Brugada syndrome subjects were defined based on a consensus clinical scoring system. We assessed discovery and validation cohorts by 2D gels, western blots, and ELISA. We performed immunohistochemistry on myocardium from BrS subjects (vs. control). All (3/3) 2D gels exposed to sera from BrS patients demonstrated specific Abs to four proteins, confirmed by MS to be α-cardiac actin, α-skeletal actin, keratin, and connexin-43, vs. 0/8 control subjects. All (18/18) BrS subjects from our validation cohorts demonstrated the same Abs, confirmed by western blots, vs. 0/24 additional controls. ELISA optical densities for all Abs were elevated in all BrS subjects compared to controls. In myocardium obtained from BrS subjects, each protein, as well as SCN5A, demonstrated abnormal protein expression in aggregates. Conclusion A biomarker profile of autoantibodies against four cardiac proteins, namely α-cardiac actin, α-skeletal actin, keratin, and connexin-43, can be identified from sera of BrS patients and is highly sensitive and specific, irrespective of genetic cause for BrS. The four involved proteins, along with the SCN5A-encoded Nav1.5 alpha subunit are expressed abnormally in the myocardium of patients with BrS.We investigated the genetic origin of the phenotype of three children from two unrelated Italian families presenting with a previously-unrecognized, seemingly autosomal recessive disorder that included a severe form of spondylo-epiphyseal dysplasia, sensorineural hearing loss, intellectual disability, and Leber congenital amaurosis (SHILCA), as well as some brain anomalies that were visible at the MRI. Autozygome-based analysis showed that these children shared a 4.6 Mb region of homozygosity on chromosome 1, with an identical haplotype. Nonetheless, whole-exome sequencing failed to identify any shared rare coding variants, in this region or elsewhere. We then determined the transcriptome of patients’ fibroblasts by RNA sequencing, followed by additional whole-genome sequencing experiments. Gene expression analysis revealed a 4-fold downregulation of the gene NMNAT1, previously associated with Leber congenital amaurosis (LCA) and residing in the shared autozygous interval. Short- and long-read whole-genome sequencing highlighted a duplication involving 2 out of the 5 exons of NMNAT1 main isoform (NM_022787.3), leading to the production of aberrant mRNAs. No other pathogenic variants in NMNAT1 have been previously shown to cause non-syndromic LCA. However, no patient with null biallelic variants has ever been described, and murine Nmnat1 knockouts show embryonic lethality. We hypothesize that complete absence of NMNAT1 activity is not compatible with life. The rearrangement found in our cases, presumably causing a strong but not complete reduction of enzymatic activity, may therefore result in an intermediate syndromic phenotype, between non-syndromic LCA and lethality.Objectives We retrospectively investigated oncological outcomes after video-assisted thoracoscopic surgery (VATS) lobectomy with lobe-specific mediastinal lymph node dissection (MLND). Methods Between April 2008 and December 2016, a total of 660 patients underwent VATS lobectomy with lobe-specific MLND for clinical T1-3N0M0 non-small-cell lung cancer, of which 54 (8.2%) patients had pathological node-positive disease (18 N1 and 36 N2). We evaluated their oncological outcomes. Results The predominant histological type was adenocarcinoma (87%). Six (33%) patients in the pN1 and 11 (31%) patients in the pN2 received adjuvant chemotherapy. The median follow-up period was 51.6 months. Postoperative recurrence was observed in 5 (28%) pN1 and 22 (61%) pN2 patients. One (6%) pN1 and 12 (33%) pN2 patients experienced locoregional recurrence. None of the pN1 patient experienced local recurrence at the dissected zone, whereas 11 (31%) pN2 patients had lymph node recurrence, including four at the dissected area and three in the area omitted from dissection in the lobe-specific MLND. The 5-year overall survival rates were 88.1% in the pN1 patients and 80.0% in the pN2 patients; the 5-year recurrence-free survival rates were 63.9% in the pN1 patients and 34.8% in the pN2 patients. In pN2 patients, pathological T classification was a prognostic factor for overall survival (P less then 0.001) and recurrence-free survival (P = 0.034), and single-station N2 disease was also prognostic factor for overall survival (P = 0.023). Conclusions Recurrence at the omitted zone is an issue for this type of MLND. For pN1 patients, adequate MLND is an important factor for curative treatment. However, for pN2 patients, systemic treatment after recurrence may also contribute to survival.Allium leafminer, Phytomyza gymnostoma Loew, is the newest invasive pest of allium crops in North America. Larvae initially feed in the upper canopy before mining toward the base of the plant to pupate. Crop loss occurs when larvae destroy vascular tissue, facilitating infection by bacterial and fungal pathogens that cause rot. Contamination also occurs when larvae and pupae are present at harvest. In response to this invasion, efficacy of 14 insecticide active ingredients applied via foliar sprays, transplant treatments, and drip chemigation was evaluated for managing P. gymnostoma. Multiple field studies were conducted in onions, leeks, and scallions in Pennsylvania and New York, United States in 2018 and 2019. The highest and most consistent levels of P. gymnostoma control occurred using foliar applications of dinotefuran, cyantraniliprole and spinetoram (84-89% reduction in damage; 95% reduction in P. gymnostoma densities). Despite the success of dinotefuran and cyantraniliprole applied as foliar sprays, neither was effective in controlling P. gymnostoma when administered via drip chemigation. Other foliar-applied insecticides that significantly reduced densities of P. gymnostoma in one or two experiments included abamectin, acetamiprid, cyromazine, imidacloprid, lambda-cyhalothrin, methomyl, and spinosad. Active ingredients that never controlled P. gymnostoma included azadirachtin, kaolin clay, pyrethrin, and spirotetramat. Spinosad applied to bare-root and plug-tray transplants immediately before transplanting reduced P. gymnostoma damage in the field by >90%. Implications of using these insecticides and application strategies are discussed within the context of developing a sustainable IPM program.A study was carried out to determine Sarcophagidae diversity attracted to the different stages of decomposition of a Boa constrictor cadaver during late winter in the Yucatan Peninsula. As a result of this study, seven species of Sarcophagidae were documented, Oxysarcodexia conclausa (Walker, 1861) (Diptera Sarcophagidae), Peckia (Euboettcheria) volucris (Wulp, 1895) (Diptera Sarcophagidae), Blaesoxipha (Gigantotheca) plinthopyga (Wiedemann, 1830) (Diptera Sarcophagidae), Oxysarcodexia amorosa (Schiner, 1868) (Diptera Sarcophagidae), Ravinia derelicta (Walker, 1853) (Diptera Sarcophagidae), Ravinia effrenata (Walker, 1861) (Diptera Sarcophagidae), and Titanogrypa (Cucullomyia) placida (Aldrich, 1925) (Diptera Sarcophagidae), The last five species listed are the first documentation of their presence in the Yucatan Peninsula in Mexico. Sarcophagids were present throughout the decomposition process; however, the greatest abundance and diversity of this family were present during the advanced decay stage. This is the first work on flesh flies in the region and the first in the country that has focused on wildlife.Development of insecticide resistance often changes life history traits of insect pests, because metabolic detoxification of insecticides in insect bodies requires huge energetic reserves. The brown planthopper, Nilaparvata lugens (Stål), an important insect pest of rice crop in East and Southeast Asia, has developed strong resistance to imidacloprid from mid-2000s. The aim of this study was to examine the costs of life history traits and reveal changes in energy reserves with developing imidacloprid resistance. We compared the life history traits (survival time, fecundity, developmental time, and hatchability) and total lipid content between imidacloprid-resistant and imidacloprid-susceptible (control) brown planthopper strains. As compared to the control strains, adults’ survival time of the resistant females was shorter, and their fecundity was lower; the other life history traits did not differ significantly between the resistant and control strains. As the results, net reproductive rates (R0) were lower in the resistant strains than in the susceptible strains. However, the amount of stored lipids was larger in resistant females than control ones. Our findings demonstrated a physiological trade-off between the development of imidacloprid resistance and the reproductive traits of brown planthopper. The imidacloprid-resistant strains are likely to store lipids for metabolic detoxification rather than consume them for reproduction.Background It is unknown whether sarcopenia influences treatment outcome in patients with soft tissue sarcoma. Herein, we aimed to elucidate the impact of sarcopenia on sarcoma treatment. Methods A total of 163 soft tissue sarcoma patients were included. Skeletal muscle measures were calculated using computed tomography images. Skeletal muscle area (SMA) and density (SMD) at the L3 level were extracted, and SMA was normalized by height as skeletal muscle index (SMI). The skeletal muscle gauge (SMG) was calculated by multiplying SMD × SMI. The relationship of skeletal muscle measures and clinical factors to wound complications and prognosis was evaluated, and classification and regression tree (CART) analysis was used to develop classification models for risk groups of surgical wound complications. Results Thirty-three patients developed wound complications. In univariate analysis, age (P = 0.0022), tumour location of adductor compartment of the thigh (P = 0.0019), operating time (P = 0.010), blood loss (P = 0.030), SMD (P = 0.0004) and SMG (P = 0.0001) were significantly correlated with complications. In multivariate analysis, lower SMG was an independent risk factor (P = 0.031, OR = 3.27). CART analysis classified three risk groups of surgical wound complications by SMG, age, tumour location and operating time, and area under the receiver operating characteristic curve (AUROCC) was 0.75. SMG was not associated with prognosis in univariate analysis (P = 0.15). Conclusions The SMG does not affect overall survival but predicts surgical wound complications.In a recently published letter to the editor of this journal, the authors have called for the need to establish psychological support structures that cater to people’s mental health in this time of the coronavirus disease 2019 pandemic. To be more holistic, we extend this call to include people’s spiritual well-being as well. We highlight the initiatives of the Philippines’ religious sector. In particular, we report some of the interventions made by the Roman Catholic Church that have led to the social media hashtag, #ChurchInAction. These religious and spiritual interventions showcase the efforts of the Philippine Church and play an important role in providing assistance in time of public health crisis.Aims  Chronic volume-overload can impair systolic and diastolic myocardial properties. We tested the hypothesis that Intrinsic Cardiac Elastography may detect alterations in passive myocardial elasticity in patients with chronic severe mitral regurgitation (MR) and predict worsening left ventricular (LV) function after mitral valve repair (MVr). Methods and results  Comprehensive transthoracic echocardiography and cardiac elastography were performed in 80 patients with primary MR (prolapse and/or flail leaflets) of varying severity and compared with 40 normal subjects. In patients who underwent MVr (n = 51), elastography measurements were related to changes in left ventricular ejection fraction (LVEF) at short-term (3-4 days post-op) and mid-term (1 year) follow-up. Most patients were asymptomatic or mildly symptomatic and had preserved LVEF (>60%). Intrinsic velocity propagation (iVP) of myocardial stretch, a direct measure of myocardial stiffness, was higher in patients with severe MR median 2.0 [interquartile range (IQR) 1.5-2.2] m/s, range 1.1-3.4 m/s; n = 56 compared to normal subjects [median 1.7 (IQR 1.5-1.8) m/s; n = 40; P = 0.0005], but not in those with mild or moderate MR [median 1.7 (IQR 1.4-1.9) m/s; n = 24]. A higher iVP was associated with more severe LV volume-overload and LV and left atrial enlargement (P less then 0.05 for all). In patients undergoing MVr, a higher iVP independently predicted a larger drop in LVEF post-intervention (short-term, P = 0.001; 1 year, P = 0.007), incrementally to pre-operative LVEF (P less then 0.05). Conclusion  Non-invasive measurements of myocardial stiffness were able to predict functional deterioration after MVr for chronic primary MR. Further studies should investigate the mechanisms and practical utility of this novel measurement.Building vocabulary knowledge, especially breadth and depth of word meanings, is a crucial step in assisting students to read and comprehend print independently. A large body of research has documented the low reading achievement levels of a number of Deaf and hard-of-hearing (DHH) students. The goal of the present study was to examine the effects of a vocabulary intervention to teach 24 multiple-meaning words to fourth-grade DHH students in Saudi Arabia by utilizing a single-case experimental design (multiple probe design across participants). A total of 5 students with a profound hearing loss participated in the study. About 3 of 5 received the intervention, whereas two other students served as an additional control component and were administered the pretest and posttest only. The data showed that there was a significant improvement in the recognition and comprehension scores of students who received the intervention. In contrast, students who did not receive the intervention showed no significant improvement on the posttest.This research represents the first attempt to assess the spatial and temporal distribution based on micro-meso scales on two species with different host preference habits (anthropophilic vs zoophilic), in the major Leishmaniasis endemic area in Ecuador, tourist locations, and Biosphere reserve. Phlebotomine species, Lutzomyia trapidoi (Fairchild) and Lutzomyia reburra (Fairchild and Hertig), were analyzed by trap/habitat/month/locality/altitude, through the Poisson generalized regression model. Our data reveal a bimodal pattern for both species related with low precipitations and preference for forest habitat. Altitude, proximity to the forest, and the river were the variables that determine the hypervolume of the spatial distribution of relative abundance, where the overlap of these two species increases the risk of translocation and circulation of the etiological agent of leishmaniasis in sylvatic environments to rural-tourist-biosphere reserve areas and vice versa. The ecological characteristics of these two phlebotomines could explain the permanence of the major active and endemic focus of cutaneous leishmaniasis in the North-Western Ecuador a key aspect in tourism health-security in alternative tourism.Objectives To explore the relative contribution of cumulative physical workload, sociodemographic and lifestyle factors, as well as prior injury to hospitalization due to knee and hip OA. Methods We examined a nationally representative sample of persons aged 30-59 years, who participated in a comprehensive health examination (the Health 2000 Study). A total of 4642 participants were followed from mid-2000 to end-2015 for the first hospitalization due to knee or hip OA using the National Hospital Discharge Register. We examined the association of possible risk factors with the outcome using a competing risk regression model (death was treated as competing risk) and calculated population attributable fractions for statistically significant risk factors. Results Baseline age and BMI as well as injury were associated with the risk of first hospitalization due to knee and hip OA. Composite cumulative workload was associated with a dose-response pattern with hospitalizations due to knee OA and with hospitalizations due to hip OA at a younger age only. Altogether, prior injury, high BMI and intermediate to high composite cumulative workload accounted for 70% of hospitalizations due to knee OA. High BMI alone accounted for 61% and prior injury only for 6% of hospitalizations due to hip OA. Conclusion Our results suggest that overweight/obesity, prior injury and cumulative physical workload are the most important modifiable risk factors that need to be targeted in the prevention of knee OA leading to hospitalization. A substantial proportion of hospitalizations due to hip OA can be reduced by controlling excess body weight.Huntington’s disease and X-linked dystonia parkinsonism are two monogenic basal ganglia model diseases. Huntington’s disease is caused by a polyglutamine-encoding CAG repeat expansion in the Huntingtin (HTT) gene leading to several toxic interactions of both the expanded CAG-containing mRNA and the polyglutamine-containing protein, while X-linked dystonia parkinsonism is caused by a retrotransposon insertion in the TAF1 gene, which decreases expression of this core scaffold of the basal transcription factor complex TFIID. SRSF6 is an RNA-binding protein of the serine and arginine-rich (SR) protein family that interacts with expanded CAG mRNA and is sequestered into the characteristic polyglutamine-containing inclusion bodies of Huntington’s disease brains. Here we report decreased levels of the SRSF6 interactor and regulator SREK1-another SR protein involved in RNA processing-which includes TAF1 as one of its targets. This led us to hypothesize that Huntington’s disease and X-linked dystonia parkinsonism pathogeneses converge in TAF1 alteration. We show that diminishing SRSF6 through RNA interference in human neuroblastoma cells leads to a decrease in SREK1 levels, which, in turn, suffices to cause diminished TAF1 levels. We also observed decreased SREK1 and TAF1 levels in striatum of Huntington’s disease patients and transgenic model mice. We then generated mice with neuronal transgenic expression of SREK1 (TgSREK1 mice) that, interestingly, showed transcriptomic alterations complementary to those in Huntington’s disease mice. Most importantly, by combining Huntington’s disease and TgSREK1 mice we verify that SREK1 overexpression corrects TAF1 deficiency and attenuates striatal atrophy and motor phenotype of Huntington’s disease mice. Our results therefore demonstrate that altered RNA processing upon SREK1 dysregulation plays a key role in Huntington’s disease pathogenesis and pinpoint TAF1 as a likely general determinant of selective vulnerability of the striatum in multiple neurological disorders.The significance of pan-cancer categories has recently been recognized as widespread in cancer research. Pan-cancer categorizes a cancer based on its molecular pathology rather than an organ. The molecular similarities among multi-omics data found in different cancer types can play several roles in both biological processes and therapeutic developments. Therefore, an integrated analysis for various genomic data is frequently used to reveal novel genetic and molecular mechanisms. However, a variety of algorithms for multi-omics clustering have been proposed in different fields. The comparison of different computational clustering methods in pan-cancer analysis performance remains unclear. To increase the utilization of current integrative methods in pan-cancer analysis, we first provide an overview of five popular computational integrative tools similarity network fusion, integrative clustering of multiple genomic data types (iCluster), cancer integration via multi-kernel learning (CIMLR), perturbation clusteriate integrative tools according to different research tasks or aims in pan-cancer analysis.Many academics and researchers have responded to the COVID-19 pandemic by forming on-line national and international collaborative groups to rapidly investigate issues of prevention and treatment. This commentary describes the spontaneous formation of an international team of 115 researchers who summarized the literature on safe methods for decontaminating N95 filtering facepiece respirators in response to the supply crisis. The summary reports and fact sheets on the (www.n95decon.org) website have had more than 200 000 unique visits and the organization’s webinars have reached health care professionals from more than 50 countries. The team is extending its mission to cover other personal protective equipment. The success of these collaborations may alter how scientific questions are tackled in the future.Aim People experiencing homelessness are often excluded from treatment programs for alcohol use disorder (AUD). The goal of this study was to describe the impact of a multidisciplinary treatment program on alcohol consumption and social reintegration in individuals with AUD experiencing homelessness. Methods Thirty-one individuals with AUD experiencing homelessness were admitted to an inpatient unit for 5-6 days for clinical evaluation and to treat potential alcohol withdrawal syndrome. A group of volunteers, in collaboration with the Community of Sant’Egidio, provided social support aimed to reintegrate patients. After inpatient discharge, all patients were followed as outpatients. Alcohol intake (number drinks/day), craving and clinical evaluation were assessed at each outpatient visit. Biological markers of alcohol use were evaluated at enrollment (T0), at 6 months (T1) and 12 months (T2). Results Compared with T0, patients at T1 showed a significant reduction in alcohol consumption [10 (3-24) vs 2 (0-10); P = 0.015] and in γ-glutamyl-transpeptidase [187 (78-365) vs 98 (74-254); P = 0.0021]. The reduction in alcohol intake was more pronounced in patients with any housing condition [10 (3-20) vs 1 (0-8); P = 0.008]. Similarly, compared with T0, patients at T2 showed significant reduction in alcohol consumption [10 (3-24) vs 0 (0-15); P = 0.001], more pronounced in patients with any housing condition [10 (3-20) vs 0 (0-2); P = 0.006]. Moreover, at T2 patients showed a significant reduction in γ-glutamyl-transpeptidase [187 (78-365) vs 97 (74-189); P = 0.002] and in mean cell volume [100.2 (95-103.6) vs 98.3 (95-102); P = 0.042]. Conclusion Patients experiencing homelessness may benefit from a multidisciplinary treatment program for AUD. Strategies able to facilitate and support their social reintegration and housing can improve treatment outcomes.Aims  We aimed to analyse the time-serial change of cardiac function in light-chain (AL) cardiac amyloidosis patients undergoing active chemotherapy and its relationship with patient outcome. Methods and results  Seventy-two patients with AL cardiac amyloidosis undergoing active chemotherapy who had two or more echocardiographic examinations were identified from a prospective observational cohort (n = 34) and a retrospective cohort (n = 38). Echocardiographic parameters were obtained immediately prior to 1-3, 3-6, 6-12, and 12-24 months after the first chemotherapy. Study endpoint was a composite of death or heart transplantation (HT). During a median of 32 months (interquartile range 8-51) follow-up, 33 patients (45.8%) died and 4 patients (5.6%) underwent HT. Echocardiograms immediately prior to the first chemotherapy did not show differences between the patients with adverse events vs. those without. Significant increase in mitral E/e’ ratio and decline in left ventricular global longitudinal strain (LV-GLS) was observed, starting at 3-6 months after the first chemotherapy only in those who experienced adverse events on follow-up, which was also evident in those who responded to chemotherapy. Multivariate analysis demonstrated that B-natriuretic peptide >500 pg/mL and troponin I >0.15 ng/dL at initial diagnosis, hospitalization for heart failure, E/e’ >15, and LV-GLS less then 10% during follow-up were independent predictors of outcome. Conclusions  In AL cardiac amyloidosis patients undergoing active chemotherapy, the deterioration of LV function may occur, starting even at 3-6 months after the first chemotherapy. Serial echocardiography may help identify those who experience a clinical event in the near future despite active chemotherapy.Plague, caused by the flea-transmitted bacterial pathogen Yersinia pestis, is primarily a disease of wild rodents distributed in temperate and tropical zones worldwide. The ability of Y. pestis to develop a biofilm blockage that obstructs the flea foregut proventriculus facilitates its efficient transmission through regurgitation into the host bite site during flea blood sucking. While it is known that temperature influences transmission, it is not well-known if blockage dynamics are similarly in accord with temperature. Here, we determine the influence of the biologically relevant temperatures, 10 and 21°C, on blockage development in flea species, Xenopsylla cheopis (Rothschild) and Oropsylla montana (Baker), respectively, characterized by geographical distribution as cosmopolitan, tropical or endemic, temperate. We find that both species exhibit delayed development of blockage at 10°C. In Y. pestis infected X. cheopis, this is accompanied by significantly lower survival rates and slightly decreased blockage rates, even though these fleas maintain similar rates of persistent infection as at 21°C. Conversely, irrespective of infection status, O. montana withstand 21 and 10°C similarly well and show significant infection rate increases and slightly greater blocking rates at 10 versus 21°C, emphasizing that cooler temperatures are favorable for Y. pestis transmission from this species. These findings assert that temperature is a relevant parameter to consider in assessing flea transmission efficiency in distinct flea species residing in diverse geographical regions that host endemic plague foci. This is important to predict behavioral dynamics of plague regarding epizootic outbreaks and enzootic maintenance and improve timeous implementation of flea control programs.Background The mainstay of the treatment for desmoid-type fibromatoses has been shifting from surgery to drug treatment, making accurate prediction of the efficacy of drug treatment of extreme importance. On the other hand, desmoid-type fibromatoses arise everywhere in the body. The purpose of this systematic review was to address the clinical question of whether tumour location has an impact on the efficacy of drug treatment. Methods A literature search from January 1990 to August 2017 was conducted. Four reviewers independently assessed and screened the literature for eligibility and determined the final articles. They rated each report according to the Grading of Recommendations Development and Evaluation approach. Based on the quality of 'Body of Evidence’, our clinical guideline committee developed a recommendation for the clinical question. Results In total, 128 articles were extracted. After the screenings, 5 were chosen for the final evaluation. The drugs used in these articles were one each of toremifene, sorafenib, and methotrexate and vinblastine and of meloxicam. There were no randomized controlled trials, and two prospective and three retrospective case series were included. Therapeutic effects were observed slightly more markedly in extremity using meloxicam or methotrexate and vinblastine. In contrast, the efficacy of toremifene was slightly higher in non-extremity. However, the evidence level of all of the reports was judged to be low. Conclusions Considering the low evidence level, we concluded that the site-specific therapeutic effects of drugs could not be confirmed in desmoid-type fibromatoses.Background Second primary head and neck cancers after endoscopic resection of esophageal squamous cell carcinoma adversely affect patients’ outcomes and the quality of life; however, an adequate surveillance schedule remains unclear. Methods We analyzed 330 patients with early esophageal squamous cell carcinoma who underwent endoscopic resection and were registered in the multicenter cohort study to evaluate adequate surveillance for detection of second primary head and neck cancers. Gastrointestinal endoscopists examined the head and neck regions after 3-6 months of endoscopic resection for esophageal squamous cell carcinoma and subsequently every 6 months. An otolaryngologist also examined the head and neck regions at the time of endoscopic resection for esophageal squamous cell carcinoma and at 12 months intervals thereafter. Results During the median follow-up period of 49.4 months (1.3-81.2 months), 33 second primary head and neck cancers were newly detected in 20 patients (6%). The tumor site was as follows 22 lesions in the hypopharynx, eight lesions in the oropharynx, two lesions in larynx and one lesion in the oral cavity. The 2-year cumulative incidence rate of second primary head and neck cancers was 3.7%. Among them, 17 patients with 29 lesions were treated by transoral surgery. One patient with two synchronous lesions was treated by radiotherapy. Two lesions in two patients were not detected after biopsy. All patients were cured with preserved laryngeal function. Conclusions Surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months could detect second primary head and neck cancers at an early stage, thereby facilitating minimally invasive treatment.