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Abstract Magnetoencephalography (MEG) is a technology used in pediatric and adult epilepsy that records magnetic fields produced from electric currents in the brain. MEG can locate epileptogenic zone(s), lateralize language functions, localize sensorimotor cortex, and identify visually evoked fields. It is a powerful technology with key advantages in pediatrics. The majority of its limitations are resource driven. With advancing technology, MEG will become a more prominent and valuable tool used in pediatric epilepsy and epilepsy surgery in the future. We review MEG and provide illustrative cases to showcase its usage.

Abstract We aimed to investigate the effects of nitric oxide (NO) synthesis inhibition by NO synthase inhibitor N‐nitro‐L‐arginine‐methyl ester (L‐NAME) treatment on the sympathetic vasomotor nerve activity (SNA) on two sympathetic vasomotor nerves, the renal and splanchnic. NO plasma level and systemic oxidative stress were assessed. Hypertension was induced by L‐NAME (20 mg/kg per day, by gavage, for seven consecutive days) in male Wistar rats. At the end of the treatment, blood pressure, heart rate, arterial baroreflex sensitivity, renal SNA (rSNA), and splanchnic SNA (sSNA) were assessed in urethane anesthetized rats. L‐NAME‐treated rats presented increased blood pressure (152 ± 2 mmHg, n = 17) compared to the control group (101 ± 2 mmHg, n = 15). Both rSNA (147 ± 10, n = 15 vs. 114 ± 5 Spikes/s, n = 9) and sSNA (137 ± 13, n = 14 vs. 74 ± 13 spikes/s, n = 9) were significantly increased in the L‐NAME‐treated compared to the control group. A differential response on baroreflex sensitivity was found, with a significant reduction for rSNA but not for sSNA arterial baroreceptor sensitivity in L‐NAME‐treated rats. The adjusted regression model revealed that the reduction of systemic NO levels partially explains the variation in sSNA and blood pressure, but not rSNA. Taken together, our data show that hypertension induced by NO synthase blockade is characterized by increased SNA to the rSNA and sSNA. In addition, we found that the rats that had the greatest reduction in NO levels in plasma by L‐NAME were those that developed higher blood pressure levels. The reduction in the NO level partially explains the variations in sSNA but not in rSNA.

Abstract Objective The standard method of generating disorder‐specific disability scores has lay raters make rankings between pairs of disorders based on brief disorder vignettes. This method introduces bias due to differential rater knowledge of disorders and inability to disentangle the disability due to disorders from the disability due to comorbidities. Methods We propose an alternative, data‐driven, method of generating disorder‐specific disability scores that assesses disorders in a sample of individuals either from population medical registry data or population survey self‐reports and uses Generalized Random Forests (GRF) to predict global (rather than disorder‐specific) disability assessed by clinician ratings or by survey respondent self‐reports. This method also provides a principled basis for studying patterns and predictors of heterogeneity in disorder‐specific disability. We illustrate this method by analyzing data for 16 disorders assessed in the World Mental Health Surveys (n = 53,645). Results Adjustments for comorbidity decreased estimates of disorder‐specific disability substantially. Estimates were generally somewhat higher with GRF than conventional multivariable regression models. Heterogeneity was nonsignificant. Conclusions The results show clearly that the proposed approach is practical, and that adjustment is needed for comorbidities to obtain accurate estimates of disorder‐specific disability. Expansion to a wider range of disorders would likely find more evidence for heterogeneity.

Abstract Severe musculoskeletal diseases, such as those associated with congenital or traumatic events, that result in missing limbs may compromise the fitness and survival of free‐living felids. Here we report the space use of four amputee individuals from three felid species captured from 2017 to 2022 in Missouri (USA), Toledo and Badajoz (Spain), and Suitai Khairkhan Mountain (Mongolia). We describe home ranges and daily travel distances post‐release of free‐living felids that had either suffered a traumatic amputation or following a surgical amputation. We compared these data with those reported in the literature for felids without amputations. Forelimb or hindlimb amputation did not affect the hunting, mating, or territory patrolling behavior of any of the individuals. However, we recorded significant differences in the daily movement before and after the traumatic event of the Iberian lynx forelimb amputee. We attribute this difference to the physical impairment, although we consider other variables that may have played a role. Nevertheless, all animals appeared to cope well with their limb loss, showing home ranges and daily distances within those recorded for their sex and species. Unless amputee felids represent a threat to domestic livestock or humans, our data suggest these individuals may remain free‐living as they contribute to local population persistence and appear to maintain good general health and welfare.

Abstract This study investigated the impact of changing abnormal home blood pressure monitoring (HBPM) cutoff from 135/85 to 130/80 mmHg on the prevalence of hypertension phenotypes, considering an abnormal office blood pressure cutoff of 140/90 mmHg. We evaluated 57 768 individuals (26 876 untreated and 30 892 treated with antihypertensive medications) from 719 Brazilian centers who performed HBPM. Changing the HBPM cutoff was associated with increases in masked (from 10% to 22%) and sustained (from 27% to 35%) hypertension, and decreases in white‐coat hypertension (from 16% to 7%) and normotension (from 47% to 36%) among untreated participants, and increases in masked (from 11% to 22%) and sustained (from 29% to 36%) uncontrolled hypertension, and decreases in white‐coat uncontrolled hypertension (from 15% to 8%) and controlled hypertension (from 45% to 34%) among treated participants. In conclusion, adoption of an abnormal HBPM cutoff of 130/80 mmHg markedly increased the prevalence of out‐of‐office hypertension and uncontrolled hypertension phenotypes.

Abstract Enteropathogenic Escherichia coli (EPEC) infection causes a histopathological lesion including recruitment of F‐actin beneath the attached bacteria and formation of actin‐rich pedestal‐like structures. Another important target of EPEC is the tight junction (TJ), and EspF induces displacement of TJ proteins and increased intestinal permeability. Previously, we determined that an EPEC strain lacking EspF did not cause TJ disruption; meanwhile, pedestals were located on the TJ and smaller than those induced by the wild‐type strain. Therefore, EspF could be playing an important role in both phenotypes. Here, using different cell models, we found that EspF was essential for pedestal maturation through ZO‐1 disassembly from TJ, leading to (a) ZO‐1 recruitment to the pedestal structure; no other main TJ proteins were required. Recruited ZO‐1 allowed the afadin recruitment. (b) Afadin recruitment caused an afadin–ZO‐1 transient interaction, like during TJ formation. (c) Afadin and ZO‐1 were segregated to the tip and the stem of pedestal, respectively, causing pedestal maturation. Initiation of these three discrete phases for pedestal maturation functionally and physically required EspF expression. Pedestal maturation process could help coordinate the epithelial actomyosin function by maintaining the actin‐rich column composing the pedestal structure and could be important in the dynamics of the pedestal movement on epithelial cells.

Introduction. The variability of the location of the parathyroid glands is directly related to the events that occur during embryonic development. The impact that an individual submits more than four parathyroid glands is close to 13%. However the presentation of a parathyroid adenoma in a supernumerary gland is an uncommon event. Case report. A 30-year-old man diagnosed with primary hyperparathyroidism with matching findings on ultrasonography and scintigraphy for parathyroid adenoma localization lower left regarding the thyroid gland. A cervicotomy explorer showed four orthotopic parathyroid glands. The biopsy of the inferior left gland was normal. No signs of adenoma were seen in the biopsy. Following mobilization of the ipsilateral thyroid lobe, fifth parathyroid gland was found increased significantly in size than proceeded to remove, confirming the diagnosis of adenoma. After the excision, the levels of serum calcium and parathyroid hormone were normalized. Conclusions. The presentation of a parathyroid adenoma in a supernumerary gland is a challenge for the surgeon. The high sensitivity having different imaging techniques has been a key to locate preoperatively the pathological parathyroid gland. Analytical or clinical persistence of primary hyperparathyroidism after parathyroid surgery can occur if the location of the adenoma is a supernumerary or ectopic gland location.

BackgroundPrehypertension is associated with higher cardiovascular risk, target organ damage, and incidence of hypertension. The Prevention of Hypertension in Patients with PreHypertension (PREVER‐Prevention) trial aimed to evaluate the efficacy and safety of a low‐dose diuretic for the prevention of hypertension and end‐organ damage. Methods and ResultsThis randomized, parallel, double‐blind, placebo‐controlled trial was conducted in 21 Brazilian academic medical centers. Participants with prehypertension who were aged 30 to 70 years and who did not reach optimal blood pressure after 3 months of lifestyle intervention were randomized to a chlorthalidone/amiloride combination pill or placebo and were evaluated every 3 months during 18 months of treatment. The primary outcome was incidence of hypertension. Development or worsening of microalbuminuria, new‐onset diabetes mellitus, and reduction of left ventricular mass were secondary outcomes. Participant characteristics were evenly distributed by trial arms. The incidence of hypertension was significantly lower in 372 study participants allocated to diuretics compared with 358 allocated to placebo (hazard ratio 0.56, 95% CI 0.38–0.82), resulting in a cumulative incidence of 11.7% in the diuretic arm versus 19.5% in the placebo arm (P=0.004). Adverse events; levels of blood glucose, glycosylated hemoglobin, creatinine, and microalbuminuria; and incidence of diabetes mellitus were no different between the 2 arms. Left ventricular mass assessed through Sokolow‐Lyon voltage and voltage‐duration product decreased to a greater extent in participants allocated to diuretic therapy compared with placebo (P=0.02). ConclusionsA combination of low‐dose chlorthalidone and amiloride effectively reduces the risk of incident hypertension and beneficially affects left ventricular mass in patients with prehypertension. Clinical Trial RegistrationURL: http://www.ClinicalTrials.gov, www.ensaiosclinicos.gov. Unique identifiers: NCT00970931, RBR‐74rr6s.

Melon ( L.) ranks among the highest-valued fruit crops worldwide. Some genomic tools are available for this crop, including a Sanger transcriptome. We report the generation of 689,054 high-quality expressed sequence tags (ESTs) from two 454 sequencing runs, using normalized and nonnormalized complementary DNA (cDNA) libraries prepared from four genotypes belonging to the two subspecies and the main commercial types. 454 ESTs were combined with the Sanger available ESTs and de novo assembled into 53,252 unigenes. Over 63% of the unigenes were functionally annotated with Gene Ontology (GO) terms and 21% had known orthologs of (L.) Heynh. Annotation distribution followed similar tendencies than that reported for , suggesting that the dataset represents a fairly complete melon transcriptome. Furthermore, we identified a set of 3298 unigenes with microsatellite motifs and 14,417 sequences with single nucleotide variants of which 11,655 single nucleotide polymorphism met criteria for use with high-throughput genotyping platforms, and 453 could be detected as cleaved amplified polymorphic sequence (CAPS). A set of markers were validated, 90% of them being polymorphic in a number of variable accessions. This transcriptome provides an invaluable new tool for biological research, more so when it includes transcripts not described previously. It is being used for genome annotation and has provided a large collection of markers that will allow speeding up the process of breeding new melon varieties.

We study the fixed point property (FPP) in the Banach space c0 with the equivalent norm ‖⋅‖D. The space c0 with this norm has the weak fixed point property. We prove that every infinite-dimensional subspace of (c0,‖⋅‖D) contains a complemented asymptotically isometric copy of c0, and thus does not have the FPP, but there exist nonempty closed convex and bounded subsets of (c0,‖⋅‖D) which are not ω-compact and do not contain asymptotically isometric c0—summing basis sequences. Then we define a family of sequences which are asymptotically isometric to different bases equivalent to the summing basis in the space (c0,‖⋅‖D), and we give some of its properties. We also prove that the dual space of (c0,‖⋅‖D) over the reals is the Bynum space l1∞ and that every infinite-dimensional subspace of l1∞ does not have the fixed point property.

COVID-19 serological tests complement the molecular diagnostics and can be used as important tool for serosurveillance and vaccine efficiency evaluation. The aim of this study was to develop and evaluate the diagnostic performance of an in-house ELISA for retrospective serosurveillance of SARS-CoV-2. Total IgG and IgM levels in sera of PCR positive SARS-CoV-2 patients ( n  = 50) from North Colombo Teaching Hospital were evaluated and compared with sera ( n  = 50) collected from prepandemic healthy individuals as controls. Patient sample collection was initiated before vaccination programme was widely started within the country. Seropositivity of 94.0% ( n  = 47/50) was observed for either IgG or IgM anti-SARS-CoV-2 antibodies against receptor binding domain of spike protein or nucleocapsid protein in confirmed cases while none of controls were seropositive. In contrast, the seropositivity of only 48.0% ( n  = 24/50) was demonstrated with commercial ELISA kits for detection of IgG or IgM. All samples detected seropositive by commercially available kits remained seropositive with either in-house IgM or IgG ELISA. Significant correlations ( p ≤ 0.001) were observed between Ab levels and day of sampling from the onset of illness. The overall sensitivity values of the in-house assays were 66.7%, 96.9%, and 100.0% for the first, second, and third week or longer after onset of symptoms for either in-house IgM or IgG ELISAs. Majority of the patients (>80.0%) were seropositive, regardless of age (<60 vs. >60 years), gender (male vs. female), or clinical severity (mild vs. moderate/severe). These data suggest that the developed in-house ELISAs can be applied to assess anti-SARS-CoV-2 antibody levels induced by either natural infections or vaccination., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Sisira L. Pathirana et al.)

Background: Prophylactic and empirical antibiotic use is essential in cancer patients due to the underlying immune deficiencies. We examined the spectrum of causative bacteria and the appropriateness of empirical antibiotic prescription for three selected infections in cancer patients. Methodology . A descriptive cross-sectional study was conducted at the National Institute of Cancer (NIC), Sri Lanka, from June 2018 to February 2019. Bacterial isolates obtained from adult cancer patients with a diagnosis of lower respiratory tract infections (LRTI), skin and soft tissue infections (SSTI), or urinary tract infections (UTI) were included. Causative bacteria were identified and the antibiotic susceptibility was determined by standard microbiological methods. Empirical therapy was defined as appropriate if the isolated pathogen was susceptible in vitro to the given antibiotic., Results: A total of 155 bacterial isolates were included in the analysis. LRTI were the most prevalent infections (37.2%, 55/148) encountered during the study period. Majority (90.9%) of the isolated bacteria were ESKAPE pathogens. Klebsiella pneumoniae was the most frequent pathogen causing LRTI (42.4%, 25/59), whereas Escherichia coli (32%, 16/50) and Staphylococcus aureus (26.1%, 12/46) predominated in UTI and SSTI, respectively. Meropenem was the most prescribed empirical antibiotic for LRTI (29.1%, 16/55) and SSTI (26.6%, 11/43) while it was ceftazidime for UTI (36%, 18/50). Only 20.6% (32/155) of the isolated bacteria were susceptible to the empirical antibiotic prescribed while 48.4% (75/155) were resistant to them. The prescribed empirical antibiotic did not have the spectrum of activity for the isolated bacteria in 29% (45/155) of cases., Conclusion: High resistance rates were observed against the prescribed empirical antibiotics. National empirical antibiotic guidelines should be revised with updated data on causative organisms and their susceptibility patterns to ensure appropriate empirical antibiotic prescription., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Gayashan Chathuranga et al.)

Background: Fish oil (FO) supplementation as a source of omega 3 fatty acids is associated with beneficial effects on health. However, high unsaturated fatty acid content in the diet could result in increased lipid peroxidation and damage to proteins, lipids and DNA. We evaluated the effect of dietary FO supplementation on DNA damage in peripheral blood lymphocytes of dogs. Additionally, we determined the effect of FO supplementation on lipid peroxidation and lipid profile of these dogs., Methods: Healthy male dogs ( n  = 9) were randomly assigned to one of two diets during 90 days: control (CG, n  = 4), based on a commercial food, and FO (FOG, n  = 5), the same food supplemented with 1000 mg FO. Blood samples were collected on days -1, 30, 60 and 90. DNA damage was assessed with the comet assay, and the damage index was obtained. Malondialdehyde (MDA) levels were determined as an indicator of lipid peroxidation. Lipid profile determination included serum triglyceride, cholesterol, low-density lipoprotein and high-density lipoprotein levels (HDL)., Results: Damage index values (arbitrary units) were lower in FOG on day 30 (CG, 13.7 ± 2.5; FOG, 6.5 ± 2.5), 60 (CG, 14.7 ± 2.5; FOG, 3.5 ± 2.5) and 90 (CG, 15.5 ± 2.5; FOG, 3.0 ± 2.5) compared with CG (treatment × time interaction, p  < 0.01). Serum MDA and HDL concentrations were lower in FOG compared with CG on day 60 and 90 (treatment × time interaction, p  < 0.05)., Conclusion: These findings suggest that dietary FO supplementation did not induce DNA damage in peripheral blood lymphocytes of healthy dogs, but rather reduced it., Competing Interests: All authors declare that they have no conflict of interest., (© 2021 The Authors. Veterinary Record Open published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Background: Acute kidney injury (AKI) is one of most prevalent and serious complications of leptospirosis, a prevalent zoonotic disease in tropical countries. Prompt diagnosis of the leptospirosis-associated AKI is a challenge as there are no proper diagnostic tools that can identify patients in the early stage. Kidney injury molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1) are widely used novel AKI biomarkers that are studied in various disease conditions with AKI, but not in leptospirosis. Thus, this study is aimed at seeking the importance of KIM-1 and MCP-1 in determining the leptospirosis-associated AKI., Methods: Leptospirosis-suspected patients who were admitted to medical wards of two selected hospitals in the Western province of Sri Lanka were recruited. Leptospirosis was confirmed by three diagnostic tests: PCR, MAT, and culture, and the status of AKI was determined by Kidney Disease Improving Global Outcomes (KDIGO) criteria., Results: Of 170 leptospirosis-suspected patients, 79 were leptospirosis confirmed, and among them, 24.05% of patients were diagnosed to have AKI according to KDIGO criteria. Median serum KIM-1 ( p < 0.0001), urine KIM-1 (0.0053), serum MCP-1 (0.0080), and urine MCP-1 (0.0019) levels in those developing AKI were significantly higher than in patients not developing AKI. The biomarker levels associated with leptospirosis AKI had AUC-ROC of 0.8565, 0.7292, 0.7024, and 0.7282 for serum KIM-1, urine KIM-1, serum MCP-1, and urine MCP-1, respectively., Conclusion: This study revealed serum KIM-1 as a promising marker for leptospirosis-associated AKI among the tested biomarkers. Thus, further validation is recommended with a larger study group., Competing Interests: The authors declare that they have no conflicts of interests., (Copyright © 2021 Thilini Nisansala et al.)

Ion transport modulators are most commonly used to treat various noncommunicable diseases including diabetes and hypertension. They are also known to bind to receptors on various immune cells, but the immunomodulatory properties of most ion transport modulators have not been fully elucidated. We assessed the effects of thirteen FDA-approved ion transport modulators, namely, ambroxol HCl, amiloride HCl, diazoxide, digoxin, furosemide, hydrochlorothiazide, metformin, omeprazole, pantoprazole, phenytoin, verapamil, drug X, and drug Y on superoxide production, nitric oxide production, and cytokine expression by THP-1-derived macrophages that had been stimulated with ethanol-inactivated Mycobacterium bovis BCG. Ambroxol HCl, diazoxide, digoxin, furosemide, hydrochlorothiazide, metformin, pantoprazole, phenytoin, verapamil, and drug Y had an inhibitory effect on nitric oxide production, while all the test drugs had an inhibitory effect on superoxide production. Amiloride HCl, diazoxide, digoxin, furosemide, phenytoin, verapamil, drug X, and drug Y enhanced the expression of IL-1 β and TNF- α . Unlike most immunomodulatory compounds currently in clinical use, most of the test drugs inhibited some inflammatory processes while promoting others. Ion pumps and ion channels could therefore serve as targets for more selective immunomodulatory agents which do not cause overt immunosuppression., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Steven C. Mitini-Nkhoma et al.)

Metastases to the pancreas and peripancreatic lymph nodes (PPLN) are unusual. Metastatic involvement of the PPLN without biliary obstruction, from a primary breast cancer has been published in only a single case in literature. We report the first metastatic breast cancer patient with PPLN deposit, presenting with obstructive jaundice., (© 2019 Wiley Periodicals, Inc.)

Gene mutations influencing melanocytes also impact on physiological and behavioural functions. In this study, we investigated their association with four different coat colours in the Pura Raza Español (PRE) horse using morphological traits and molecular datasets. Four different subpopulations were identified according to individual coat colour: grey, bay, chestnut and black. Coat colour significantly associated with morphological measurements. Observed and expected heterozygosity values were low in grey compared with the other three subpopulations, suggesting the presence of unique ancestral alleles probably arisen by genetic drift and selection mechanism effects. Nei's distance demonstrated a clear division among subpopulations, the grey being the most divergent group. Gene flow estimates were similar, showing the lowest values in grey. Divergence times among subpopulations assessed with the average square distance suggested that grey was the original PRE population which diverged from bay, chestnut and black. Our results also demonstrated a clear morphological differentiation according to coat colour. The close genetic structure of bay and chestnut PRE subpopulations and the clear differences in most morphological traits of grey and chestnut PRE mares would suggest the pleiotropic effect of genomic regions determining coat colour in horses. However, further analysis including genomic information would be necessary to elucidate the mechanisms involved., (© 2018 Japanese Society of Animal Science.)