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1.
PLoS One ; 19(4): e0293570, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38598477

RESUMO

TPO (Thyroid Peroxidase) is known to be one of the major genes involved in congenital hypothyroid patients with thyroid dyshormonogenesis. The present study aims to validate high-resolution melting (HRM) curve analysis as a substitute method for Sanger sequencing, focusing on the frequently observed non-synonymous mutations c.1117G>T, c.1193G>C, and c.2173A>C in the TPO gene in patients from Bangladesh. We enrolled 36 confirmed cases of congenital hypothyroid patients with dyshormonogenesis to establish the HRM method. Blood specimens were collected, and DNA was extracted followed by PCR and Sanger sequencing. Among the 36 specimens, 20 were pre-sequenced, and variants were characterized through Sanger sequencing. Following pre-sequencing, the 20 pre-sequenced specimens underwent real-time PCR-HRM curve analysis to determine the proper HRM condition for separating the three variations from the wild-type state into heterozygous and homozygous states. Furthermore, 16 unknown specimens were subjected to HRM analysis to validate the method. This method demonstrated a sensitivity and specificity of 100 percent in accurately discerning wild-type alleles from both homozygous and heterozygous states of c.1117G>T (23/36; 63.8%), c.1193G>C (30/36; 83.3%), and c.2173A>C (23/36; 63.8%) variants frequently encountered among 36 Bangladeshi patients. The HRM data was found to be similar to the sequencing result, thus confirming the validity of the HRM approach for TPO gene variant detection. In conclusion, HRM-based molecular technique targeting variants c.1117G>T, c.1193G>C, and c.2173A>C could be used as a high throughput, rapid, reliable, and cost-effective screening approach for the detection of all common mutations in TPO gene in Bangladeshi patients with dyshormonogenesis.


Assuntos
Hipotireoidismo Congênito , Humanos , Bangladesh , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/genética , Mutação , DNA , Reação em Cadeia da Polimerase em Tempo Real
2.
Gene ; 914: 148409, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38527673

RESUMO

BACKGROUND: Hexokinase, a key enzyme in glycolysis, has isoforms like HK-1, HK-2, HK-3, and Glucokinase. Unpublished exome sequencing data showed that two novel polymorphisms in HK-1 rs201626997 (G/T) and HK-3 rs143604141 (G/A) exist in the Bangladeshi population. We investigated the possible relationship of these SNPs with T2DM. MATERIALS AND METHODS: Peripheral blood samples from the study participants were used to isolate their genomic DNA. An allele-specific PCR was standardized that can discriminate between the wild-type and mutant-type alleles of HK-1 (rs201626997) and HK-3 (rs143604141) polymorphisms. The data was analyzed by SPSS for statistics. RESULTS: We performed allele-specific PCR for 249 diabetic patients and 195 control samples. For HK-1 (rs201626997), 24 (5.4%) have a mutant allele, and for HK-3 (rs143604141), 25 (5.6%) are mutant. There is no significant relationship between the individuals' disease condition and the HK-1 polymorphism (P value 0.537). But the GA genotype of the HK-3 rs143604141 pertains to an increased risk of diabetes (P value 0.039). HK-3 rs143604141 polymorphism has a moderate correlation (P value 0.078, OR, 3.11, 95% CI, 0.88-10.94) with a family diabetic history. Both polymorphisms showed no significant correlation with gender or BMI. However, hexokinase-1 polymorphism significantly related with diastolic blood pressure (P value 0.048). CONCLUSION: This study will help us to easily detect the polymorphisms of HK-1 (rs201626997) and HK-3 (rs143604141) in different populations of the world. Further studies with a greater number of participants and more physiological information are required to better understand the underlying genetic causes of T2DM susceptibility in Bangladesh.

3.
bioRxiv ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38352351

RESUMO

Numerous studies have identified dopamine signaling in the hippocampus as necessary for certain types of learning and memory. Since dopamine in the striatum is strongly tied to rewards, dopamine in the hippocampus is thought to reinforce reward learning. Despite the critical influence of dopamine on hippocampal function, little is known about dopamine release in the hippocampus or the specific ways dopamine can influence hippocampal function. Based on the functional complexity of hippocampal circuitry, we hypothesized the existence of multiple dopamine signaling domains. Using optical dopamine sensors, two-photon imaging, and head-fixed behaviors, we identified two functionally and spatially distinct dopamine domains in the hippocampus. The "superficial" domain (cell somata and apical dendrites) showed reward-related dopamine transients early in Pavlovian conditioning but were replaced by "deep" domain transients (basal dendritic layer) with experience. These two domains also play distinct roles in a hippocampal-dependent, goal-directed virtual reality task where mice use exploratory licks to discover the location of a hidden reward zone. Here, positive dopamine ramps appeared in the superficial domain as mice approached the reward zone, similar to those seen in the striatum. At the same time, the deep domain showed strong reward-related transients. These results reveal small-scale, anatomically segregated, dopamine domains in the hippocampus. Furthermore dopamine domain activity had temporal-specificity for different phases of behavior. Finally, the subcellular scale of dopamine domains suggests specialized postsynaptic pathways for processing and integrating functionally distinct dopaminergic influences.

4.
Mar Pollut Bull ; 199: 115988, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38181469

RESUMO

This review paper exhibits the underexplored realm of heavy metal contamination and associated risks in sea cucumbers (SCs), which hold significant importance in traditional Asian marine diets and are globally harvested for the Asian market. The assessment focuses on heavy metals (HMs) presence in various SC species, revealing a global trend in HMs concentrations across anatomical parts: Fe > Zn > As > Cu > Hg > Pb > Mn > Cr > Ni > Cd. Specific species, such as Eupentacta fraudatrix, Holothuria mammata, Holothuria polii, Holothuria tubulosa, and Holothuria atra, exhibit heightened arsenic levels, while Stichopus herrmanni raises concerns with mercury levels, notably reaching 3.75 mg/kg in some instances, posing potential risks, particularly for children. The study sheds light on anthropogenic activities such as cultivation, fishing, and shipping, releasing HMs into marine ecosystems and thereby threatening ocean and coastal environments due to the accumulation and toxicity of these elements. In response to these findings, the paper suggests SCs as promising bioindicator species for assessing metal pollution in marine environments. It underscores the adverse effects of human actions on sediment composition and advocates for ongoing monitoring efforts both at sea and along coastlines.


Assuntos
Metais Pesados , Pepinos-do-Mar , Poluentes Químicos da Água , Animais , Criança , Humanos , Biomarcadores Ambientais , Ecossistema , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Metais Pesados/análise , Sedimentos Geológicos , Medição de Risco
5.
Photoacoustics ; 33: 100549, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37664559

RESUMO

Intraventricular (IVH) and periventricular (PVH) hemorrhages in preterm neonates are common because the periventricular blood vessels are still developing up to 36 weeks and are fragile. Currently, transfontanelle ultrasound (US) imaging is utilized for screening for IVH and PVH, largely through the anterior fontanelle. However for mild hemorrhages, inconclusive diagnoses are common, leading to failure to detect IVH/PVH or, when other clinical symptoms are present, use of second stage neuroimaging modalities requiring transport of vulnerable patients. Yet even mild IVH/PVH increases the risk of moderate-severe neurodevelopmental impairment. Here, we demonstrate the capability of transfontanelle photoacoustic imaging (TFPAI) to detect IVH and PVH in-vivo in a large animal model. TFPAI was able to detect IVH/PVH as small as 0.3 mL in volume in the brain (p < 0.05). By contrast, US was able to detect hemorrhages as small as 0.5 mL. These preliminary results suggest TFPAI could be translated into a portable bedside imaging probe for improved diagnosis of clinically relevant brain hemorrhages in neonates.

6.
PLoS One ; 18(8): e0282553, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37561783

RESUMO

The disorder of thyroid gland development or thyroid dysgenesis accounts for 80-85% of congenital hypothyroidism (CH) cases. Mutations in the TSHR gene are mostly associated with thyroid dysgenesis, and prevent or disrupt normal development of the gland. There is limited data available on the genetic spectrum of congenital hypothyroid children in Bangladesh. Thus, an understanding of the molecular aetiology of thyroid dysgenesis is a prerequisite. The aim of the study was to investigate the effect of mutations in the TSHR gene on the small molecule thyrogenic drug-binding site of the protein. We identified two nonsynonymous mutations (p.Ser508Leu, p.Glu727Asp) in the exon 10 of the TSHR gene in 21 patients with dysgenesis by sequencing-based analysis. Later, the TSHR368-764 protein was modeled by the I-TASSER server for wild-type and mutant structures. The model proteins were targeted by thyrogenic drugs, MS437 and MS438 to perceive the effect of mutations. The damaging effect in drug-protein complexes of mutants was explored by molecular docking and molecular dynamics simulations. The binding affinity of wild-type protein was much higher than the mutant cases for both of the drug ligands (MS437 and MS438). Molecular dynamics simulates the dynamic behavior of wild-type and mutant complexes. MS437-TSHR368-764MT2 and MS438-TSHR368-764MT1 showed stable conformations in biological environments. Finally, Principle Component Analysis revealed structural and energy profile discrepancies. TSHR368-764MT1 exhibited much more variations than TSHR368-764WT and TSHR368-764MT2, emphasizing a more damaging pattern in TSHR368-764MT1. This genetic study might be helpful to explore the mutational impact on drug binding sites of TSHR protein which is important for future drug design and selection for the treatment of congenital hypothyroid children with dysgenesis.


Assuntos
Hipotireoidismo Congênito , Disgenesia da Tireoide , Criança , Humanos , Bangladesh , Hipotireoidismo Congênito/genética , Simulação de Acoplamento Molecular , Mutação , Receptores da Tireotropina/genética , Receptores da Tireotropina/metabolismo
7.
J Biophotonics ; 16(7): e202200313, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37052299

RESUMO

Brain hemorrhage, specifically intraventricular hemorrhage (IVH), is considered one of the primary and leading causes of cerebral anomalies in neonates. Several imaging modalities including the most popular, cranial ultrasound, are not capable of detecting early stage IVHs. Photoacoustic imaging (PAI) exhibited great potential for detecting cerebral hemorrhage in studies limited to small animal models, but these models are not comparable to neonatal brain morphology. However, hemorrhage detection in large animal models using PAI is rare due to the complexity and cost of inducing hemorrhage in vivo. Moreover, in vitro studies are unable to represent the physiology and environment of the hemorrhagic lesion. Here, we proposed a pseudo hemorrhage implementation method in the sheep brain that allows us to mimic different hemorrhagic lesions ex vivo without compromising the complexity of cerebral imaging. This approach enables a true evaluation of PAI performance for detecting hemorrhages and can be utilized as a reference to optimize the PAI system for in vivo imaging.


Assuntos
Encéfalo , Hemorragia Cerebral , Imagens de Fantasmas , Técnicas Fotoacústicas , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/patologia , Técnicas Fotoacústicas/métodos , Humanos , Recém-Nascido , Animais , Ovinos , Modelos Animais de Doenças
8.
New Microbes New Infect ; 52: 101104, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36915390

RESUMO

Background: The use of silver is rapidly rising in wound care and silver-containing dressings are widely used along with other antibiotics, particularly ß-lactams. Consequently, concerns are being raised regarding the emergence of silver-resistance and cross-resistance to ß-lactams. Therefore, this study aimed to determine the phenotypic and genotypic profiles of silver-resistance and extended-spectrum ß-lactamases in isolates from chronic wounds. Methods: 317 wound swab specimens were collected from tertiary hospitals of Dhaka city and analysed for the microbial identification. The antibiotic resistance/susceptibility profiles were determined and phenotypes of silver resistant isolates were examined. The presence of silver-resistance (sil) genes (silE, silP, and silS) and extended-spectrum ß-lactamases (ESBL) (CTX-M-1, NDM-1, KPC, OXA-48, and VIM-1) were explored in isolated microorganisms. Results: A total of 501 strains were isolated with Staphylococcus aureus (24%) as the predominant organism. In 29% of the samples, polymicrobial infections were observed. A large proportion of Enterobacterales (59%) was resistant to carbapenems and a significantly high multiple antibiotic-resistance indexes (>0.2) were seen for 53% of organisms (P < 0.001). According to molecular analysis, the most prevalent types of ESBL and sil gene were CTX-M-1 (47%) and silE (42%), respectively. Furthermore, phenotypic silver-nitrate susceptibility testing showed significant minimum-inhibitory-concentration patterns between sil-negative and sil-positive isolates. We further observed co-occurrence of silver-resistance determinants and ESBLs (65%). Conclusions: Notably, this is the first-time detection of silver-resistance along with its co-detection with ESBLs in Bangladesh. This research highlights the need for selecting appropriate treatment strategies and developing new alternative therapies to minimize microbial infection in wounds.

9.
Life (Basel) ; 13(2)2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36836833

RESUMO

Male infertility is significantly influenced by the plasma-protein sex hormone-binding globulin (SHBG). Male infertility, erectile dysfunction, prostate cancer, and several other male reproductive system diseases are all caused by reduced testosterone bioavailability due to its binding to SHBG. In this study, we have identified 345 phytochemicals from 200 literature reviews that potentially inhibit severe acute respiratory syndrome coronavirus 2. Only a few studies have been done using the SARS-CoV-2 inhibitors to identify the SHBG inhibitor, which is thought to be the main protein responsible for male infertility. In virtual-screening and molecular-docking experiments, cryptomisrine, dorsilurin E, and isoiguesterin were identified as potential SHBG inhibitors with binding affinities of -9.2, -9.0, and -8.8 kcal/mol, respectively. They were also found to have higher binding affinities than the control drug anastrozole (-7.0 kcal/mol). In addition to favorable pharmacological properties, these top three phytochemicals showed no adverse effects in pharmacokinetic evaluations. Several molecular dynamics simulation profiles' root-mean-square deviation, radius of gyration, root-mean-square fluctuation, hydrogen bonds, and solvent-accessible surface area supported the top three protein-ligand complexes' better firmness and stability than the control drug throughout the 100 ns simulation period. These combinatorial drug-design approaches indicate that these three phytochemicals could be developed as potential drugs to treat male infertility.

10.
Sci Rep ; 12(1): 15394, 2022 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-36100615

RESUMO

The capability of photoacoustic (PA) imaging to measure oxygen saturation through a fontanelle has been demonstrated in large animals in-vivo. We called this method, transfontanelle photoacoustic imaging (TFPAI). A surgically induced 2.5 cm diameter cranial window was created in an adult sheep skull to model the human anterior fontanelle. The performance of the TFPAI has been evaluated by comparing the PA-based predicted results against the gold standard of blood gas analyzer measurements.


Assuntos
Técnicas Fotoacústicas , Adulto , Animais , Gasometria , Diagnóstico por Imagem , Humanos , Oxigênio , Técnicas Fotoacústicas/métodos , Ovinos
11.
Curr Biol ; 32(18): 3871-3885.e4, 2022 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-35907397

RESUMO

The sleep-wakefulness cycle is regulated by complicated neural networks that include many different populations of neurons throughout the brain. Arginine vasopressin neurons in the paraventricular nucleus of the hypothalamus (PVHAVP) regulate various physiological events and behaviors, such as body-fluid homeostasis, blood pressure, stress response, social interaction, and feeding. Changes in arousal level often accompany these PVHAVP-mediated adaptive responses. However, the contribution of PVHAVP neurons to sleep-wakefulness regulation has remained unknown. Here, we report the involvement of PVHAVP neurons in arousal promotion. Optogenetic stimulation of PVHAVP neurons rapidly induced transitions to wakefulness from both NREM and REM sleep. This arousal effect was dependent on AVP expression in these neurons. Similarly, chemogenetic activation of PVHAVP neurons increased wakefulness and reduced NREM and REM sleep, whereas chemogenetic inhibition of these neurons significantly reduced wakefulness and increased NREM sleep. We observed dense projections of PVHAVP neurons in the lateral hypothalamus with potential connections to orexin/hypocretin (LHOrx) neurons. Optogenetic stimulation of PVHAVP neuronal fibers in the LH immediately induced wakefulness, whereas blocking orexin receptors attenuated the arousal effect of PVHAVP neuronal activation drastically. Monosynaptic rabies-virus tracing revealed that PVHAVP neurons receive inputs from multiple brain regions involved in sleep-wakefulness regulation, as well as those involved in stress response and energy metabolism. Moreover, PVHAVP neurons mediated the arousal induced by novelty stress and a melanocortin receptor agonist melanotan-II. Thus, our data suggested that PVHAVP neurons promote wakefulness via LHOrx neurons in the basal sleep-wakefulness and some stressful conditions.


Assuntos
Região Hipotalâmica Lateral , Vigília , Arginina Vasopressina/metabolismo , Região Hipotalâmica Lateral/fisiologia , Hipotálamo/metabolismo , Neurônios/fisiologia , Receptores de Orexina/metabolismo , Orexinas/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Receptores de Melanocortina/metabolismo , Sono/fisiologia , Vasopressinas/metabolismo , Vasopressinas/farmacologia , Vigília/fisiologia
12.
Mol Brain ; 15(1): 47, 2022 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-35606816

RESUMO

Self-grooming plays an essential role in hygiene maintenance, thermoregulation, and stress response. However, the neural populations involved in self-grooming remain largely unknown. The paraventricular hypothalamic nucleus (PVH) has been implicated in the regulation of self-grooming. Arginine vasopressin-producing neurons are among the major neuronal populations in the PVH (PVHAVP), which play important roles in water homeostasis, blood pressure regulation, feeding, and stress response. Here, we report the critical role of PVHAVP neurons in the induction of self-grooming. Optogenetic activation of PVHAVP neurons immediately induced self-grooming in freely moving mice. Chemogenetic activation of these neurons also increased time spent self-grooming. In contrast, their chemogenetic inhibition significantly reduced naturally occurring self-grooming, suggesting that PVHAVP-induced grooming has physiological relevance. Notably, optogenetic activation of PVHAVP neurons triggered self-grooming over other adaptive behaviors, such as voracious feeding induced by fasting and social interaction with female mice. Thus, our study proposes the novel role of PVHAVP neurons in regulating self-grooming behavior and, consequently, hygiene maintenance and stress response. Furthermore, uncontrolled activation of these neurons may be potentially relevant to diseases characterized by compulsive behaviors and impaired social interaction, such as autism, obsessive-compulsive disorder, and anorexia nervosa.


Assuntos
Arginina Vasopressina , Núcleo Hipotalâmico Paraventricular , Animais , Arginina Vasopressina/genética , Arginina Vasopressina/metabolismo , Feminino , Asseio Animal , Camundongos , Neurônios/metabolismo , Optogenética , Núcleo Hipotalâmico Paraventricular/metabolismo
13.
Biomed Opt Express ; 13(2): 676-693, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35284180

RESUMO

Transfontanelle ultrasound imaging (TFUI) is the conventional approach for diagnosing brain injury in neonates. Despite being the first stage imaging modality, TFUI lacks accuracy in determining the injury at an early stage due to degraded sensitivity and specificity. Therefore, a modality like photoacoustic imaging that combines the advantages of both acoustic and optical imaging can overcome the existing TFUI limitations. Even though a variety of transducers have been used in TFUI, it is essential to identify the transducer specification that is optimal for transfontanelle imaging using the photoacoustic technique. In this study, we evaluated the performance of 6 commercially available ultrasound transducer arrays to identify the optimal characteristics for transfontanelle photoacoustic imaging. We focused on commercially available linear and phased array transducer probes with center frequencies ranging from 2.5MHz to 8.5MHz which covers the entire spectrum of the transducer arrays used for brain imaging. The probes were tested on both in vitro and ex vivo brain tissue, and their performance in terms of transducer resolution, size, penetration depth, sensitivity, signal to noise ratio, signal amplification and reconstructed image quality were evaluated. The analysis of selected transducers in these areas allowed us to determine the optimal transducer for transfontanelle imaging, based on vasculature depth and blood density in tissue using ex vivo sheep brain. The outcome of this evaluation identified the two most suitable ultrasound transducer probes for transfontanelle photoacoustic imaging.

14.
Talanta ; 240: 123202, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34998141

RESUMO

Nickel particles alone can oxidize hydrogen peroxide but confronts extreme stability problem which imparts a barrier to act as sensor. The porous Nafion bed on glassy carbon electrode (GCE) surface provides the sureness of incorporating of Ni particles which was further exploited as an electrochemical sensor for H2O2 detection through oxidative degradation process. The simple electrochemical incorporation of Ni particles along the pores of Nafion improves the stability of the sensor significantly. The oxidative pathway of hydrogen peroxide on GCE/Nafion/Ni was probed by analyzing mass transfer dependent linear sweep voltammograms both in static and rotating modes along with chronoamperometry. An electron transfer step determines the overall reaction rate with k°= 2.72 × 10-4 cm s-1, which is supported by the values of transfer coefficient (ß) in between (0.68-0.75). Sensing performance was evaluated by recording differential pulse voltammograms (DPVs) with the linear detection limit (LOD) of 1.8 µM and linear dynamic range (LDR) of 5-500 µM. Real samples from industrial sources were successfully quantified with excellent reproducibility mark GCE/Nafion/Ni electrode as an applicable sensor.


Assuntos
Carbono , Peróxido de Hidrogênio , Técnicas Eletroquímicas , Eletrodos , Polímeros de Fluorcarboneto , Reprodutibilidade dos Testes
15.
Diagnostics (Basel) ; 11(3)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800188

RESUMO

Microwave imaging (MI) is a consistent health monitoring technique that can play a vital role in diagnosing anomalies in the breast. The reliability of biomedical imaging diagnosis is substantially dependent on the imaging algorithm. Widely used delay and sum (DAS)-based diagnosis algorithms suffer from some significant drawbacks. The delay multiply and sum (DMAS) is an improved method and has benefits over DAS in terms of greater contrast and better resolution. However, the main drawback of DMAS is its excessive computational complexity. This paper presents a compressed sensing (CS) approach of iteratively corrected DMAS (CS-ICDMAS) beamforming that reduces the channel calculation and computation time while maintaining image quality. The array setup for acquiring data comprised 16 Vivaldi antennas with a bandwidth of 2.70-11.20 GHz. The power of all the channels was calculated and low power channels were eliminated based on the compression factor. The algorithm involves data-independent techniques that eliminate multiple reflections. This can generate results similar to the uncompressed variants in a significantly lower time which is essential for real-time applications. This paper also investigates the experimental data that prove the enhanced performance of the algorithm.

16.
Trop Med Int Health ; 26(7): 720-729, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33838068

RESUMO

OBJECTIVES: Characterisation of resistance phenotype and genotype is crucial to understanding the burden and transmission of antimicrobial resistance (AMR). This study aims to determine the spectrum of AMR and associated genes encoding aminoglycoside, macrolide and ß-lactam classes of antimicrobials in bacteria isolated from hospitalised patients in Bangladesh. METHODS: 430 bacterial isolates from patients with respiratory, intestinal, wound infections and typhoid fever, presenting to clinical care from 2015 to 2019, were examined. They included Escherichia coli (n = 85); Staphylococcus aureus (n = 84); Salmonella typhi (n = 82); Klebsiella pneumoniae (n = 42); Streptococcus pneumoniae (n = 36); coagulase-negative staphylococci (n = 28); Enterococcus faecalis (n = 27); Pseudomonas aeruginosa (n = 26); and Acinetobacter baumannii (n = 20). Reconfirmation of these clinical isolates and antimicrobial susceptibility tests was performed. PCR amplification using resistance gene-specific primers was done, and the amplified products were confirmed by Sanger sequencing. RESULTS: 53% of isolates were multidrug-resistant (MDR), including 97% of Escherichia coli. There was a year-wise gradual increase in MDR isolates from 2015 to 2018, and there was an almost twofold increase in the number of MDR strains isolated in 2019 (P = 0.00058). Among the 5 extended-spectrum ß-lactamases investigated, CTX-M-1 was the most prevalent (63%) followed by NDM-1 (22%); Escherichia coli was the major reservoir of these genes. The ermB (55%) and aac(6')-Ib (35%) genes were the most frequently detected macrolide and aminoglycoside resistance genes, respectively. CONCLUSION: MDR pathogens are highly prevalent in hospital settings of Bangladesh.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Farmacorresistência Bacteriana Múltipla/fisiologia , Genótipo , Fenótipo , Acinetobacter baumannii/isolamento & purificação , Bangladesh , Enterococcus faecalis/isolamento & purificação , Escherichia coli/isolamento & purificação , Humanos , Pacientes Internados , Klebsiella pneumoniae/isolamento & purificação , Pseudomonas aeruginosa/isolamento & purificação , Salmonella typhi/isolamento & purificação , Staphylococcus aureus/isolamento & purificação
17.
Mol Metab ; 49: 101202, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33676029

RESUMO

OBJECTIVE: Impaired circadian clocks can cause obesity, but their pathophysiological role in brown adipose tissue (BAT), a major tissue regulating energy metabolism, remains unclear. To address this issue, we investigated the effects of complete disruption of the BAT clock on thermogenesis and energy expenditure. METHODS: Mice with brown adipocyte-specific knockout of the core clock gene Bmal1 (BA-Bmal1 KO) were generated and analyzed. RESULTS: The BA-Bmal1 KO mice maintained normal core body temperatures by increasing shivering and locomotor activity despite the elevated expression of thermogenic uncoupling protein 1 in BAT. BA-Bmal1 KO disrupted 24 h rhythmicity of fatty acid utilization in BAT and mildly reduced both BAT thermogenesis and whole-body energy expenditure. The impact of BA-Bmal1 KO on the development of obesity became obvious when the mice were fed a high-fat diet. CONCLUSIONS: These results reveal the importance of the BAT clock for maintaining energy homeostasis and preventing obesity.


Assuntos
Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Adipócitos Marrons/metabolismo , Termogênese/genética , Termogênese/fisiologia , Tecido Adiposo Marrom/metabolismo , Animais , Peso Corporal , Ritmo Circadiano , Temperatura Baixa , Dieta Hiperlipídica , Metabolismo Energético , Ácidos Graxos , Homeostase , Masculino , Metaboloma , Camundongos , Camundongos Knockout , Obesidade/metabolismo , Proteína Desacopladora 1/metabolismo
18.
Proc Natl Acad Sci U S A ; 118(6)2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33526663

RESUMO

The suprachiasmatic nucleus (SCN), the central circadian pacemaker in mammals, is a network structure composed of multiple types of γ-aminobutyric acid (GABA)-ergic neurons and glial cells. However, the roles of GABA-mediated signaling in the SCN network remain controversial. Here, we report noticeable impairment of the circadian rhythm in mice with a specific deletion of the vesicular GABA transporter in arginine vasopressin (AVP)-producing neurons. These mice showed disturbed diurnal rhythms of GABAA receptor-mediated synaptic transmission in SCN neurons and marked lengthening of the activity time in circadian behavioral rhythms due to the extended interval between morning and evening locomotor activities. Synchrony of molecular circadian oscillations among SCN neurons did not significantly change, whereas the phase relationships between SCN molecular clocks and circadian morning/evening locomotor activities were altered significantly, as revealed by PER2::LUC imaging of SCN explants and in vivo recording of intracellular Ca2+ in SCN AVP neurons. In contrast, daily neuronal activity in SCN neurons in vivo clearly showed a bimodal pattern that correlated with dissociated morning/evening locomotor activities. Therefore, GABAergic transmission from AVP neurons regulates the timing of SCN neuronal firing to temporally restrict circadian behavior to appropriate time windows in SCN molecular clocks.


Assuntos
Relógios Circadianos , Ritmo Circadiano , Neurônios/metabolismo , Núcleo Supraquiasmático/metabolismo , Vasopressinas/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Comportamento Animal , Cálcio/metabolismo , Relógios Circadianos/genética , Ritmo Circadiano/genética , Regulação da Expressão Gênica , Locomoção , Camundongos , Sinapses/fisiologia , Transmissão Sináptica/fisiologia , Fatores de Tempo , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/deficiência , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismo
19.
Int J Infect Dis ; 104: 482-490, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33460834

RESUMO

OBJECTIVES: To determine IgG immune responses and hepatitis E virus (HEV) viral load, and to explore the associations with pregnancy. METHODS: A total of 121 HEV-infected women (57 pregnant, 64 non-pregnant) were analysed. Quantitative reverse transcription PCR (RT-qPCR) was done for 78 HEV IgM-positive patients to determine viral load, and Sanger sequencing was performed for 62 HEV-RNA-positive patients to confirm genotyping. ELISA was conducted to determine HEV antibody and avidity indices. RESULTS: The HEV genotype was identified as variant 1. Significant negative correlations were observed between log HEV copy number and log hepatitis E virus IgG antibody index in the late acute phase of jaundice for both pregnant women (r = -0.7971, p = 0.0002) and non-pregnant women (r = -0.9117, p = 0.0002). Pregnant women had significantly higher serum log viral copy numbers and lower IgG antibody indices than non-pregnant women in the late acute phase of HEV-induced jaundice (p = 0.0196 and p = 0.0303, respectively). Moreover, pregnant women with acute HEV hepatitis had higher cross-reactive IgG antibodies compared to the non-pregnant women (p = 0.0017). Five patients with HEV hepatitis died, of whom four were pregnant. CONCLUSIONS: Pregnancy might be associated with higher viral loads and a lower IgG response in the HEV-induced late acute phase of jaundice.


Assuntos
Anticorpos Anti-Hepatite/sangue , Vírus da Hepatite E/genética , Hepatite E/imunologia , Imunoglobulina G/sangue , Carga Viral , Doença Aguda , Adolescente , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Genótipo , Hepatite E/virologia , Vírus da Hepatite E/imunologia , Humanos , Imunoglobulina M/sangue , Icterícia/virologia , Pessoa de Meia-Idade , Gravidez , Complicações Infecciosas na Gravidez/virologia , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
20.
Materials (Basel) ; 13(21)2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33147702

RESUMO

In this paper, a compact planar ultrawideband (UWB) antenna and an antenna array setup for microwave breast imaging are presented. The proposed antenna is constructed with a slotted semicircular-shaped patch and partial trapezoidal ground. It is compact in dimension: 0.30λ × 0.31λ × 0.011λ, where λ is the wavelength of the lowest operating frequency. For design purposes, several parameters are assumed and optimized to achieve better performance. The prototype is applied in the breast imaging scheme over the UWB frequency range 3.10-10.60 GHz. However, the antenna achieves an operating bandwidth of 8.70 GHz (2.30-11.00 GHz) for the reflection coefficient under-10 dB with decent impedance matching, 5.80 dBi of maximum gain with steady radiation pattern. The antenna provides a fidelity factor (FF) of 82% and 81% for face-to-face and side-by-side setups, respectively, which specifies the directionality and minor variation of the received pulses. The antenna is fabricated and measured to evaluate the antenna characteristics. A 16-antenna array-based configuration is considered to measure the backscattering signal of the breast phantom where one antenna acts as transmitter, and 15 of them receive the scattered signals. The data is taken in both the configuration of the phantom with and without the tumor inside. Later, the Iteratively Corrected Delay and Sum (IC-DAS) image reconstructed algorithm was used to identify the tumor in the breast phantom. Finally, the reconstructed images from the analysis and processing of the backscattering signal by the algorithm are illustrated to verify the imaging performance.

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