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1.
Mar Pollut Bull ; 203: 116439, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38718549

RESUMO

Saint Martin Island (SMI), the only coral island in Bangladesh, is located in the Bay of Bengal and has been identified as a marine protected area (MPA). Littering cigarette butts (CBs) waste in an ecologically sensitive environment can have numerous adverse effects. The purpose of this research is to investigate the abundance and density of CBs in SMI and to assess the pollution status using the Cigarette Butt Pollution Index (CBPI). This study is conducted based on the visual survey method in the three types of land use zones of SMI. During the peak season, the investigation was carried out from 9 a.m. to 5 p.m. in December 2023. A total of 4481 CBs item were counted, and the density ranged from 0.37 to 1.76 m-2 with an average value of 0.99 m-2 across 12 sampling campaigns. The highest density was observed at service zones, and the fishing zones had the lowest density. The calculated CBPI values revealed that 75 % of the sampling stations were in the "severe pollution" while 25 % were classified as "high pollution" status, underscoring the prevalence of hazardous CBs across most areas of SMI. To tackle these issues requires regulatory measures, public awareness initiatives, and community involvement. Effective waste management and eco-friendly product promotion can help reduce CBs pollution risks in marine protected islands.


Assuntos
Conservação dos Recursos Naturais , Monitoramento Ambiental , Ilhas , Bangladesh , Produtos do Tabaco
2.
Chem Commun (Camb) ; 59(74): 11093-11096, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37642496

RESUMO

Herein, we report on a series of homoleptic [GaL3] and heteroleptic organometallic [GaMe2L] complexes of inactive quinolone antibiotics; nalidixic acid, oxolinic acid and norfloxacin with their antibacterial activity (MIC 0.024-0.781 µM) towards four multi-drug resistant strains of Klebsiella pneumoniae through complexation to gallium.


Assuntos
Gálio , Klebsiella pneumoniae , Gálio/farmacologia , Antibacterianos/farmacologia , Norfloxacino
4.
Heliyon ; 9(6): e17368, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37441399

RESUMO

The central coast of Bangladesh is dynamic for its geographical location, hydrodynamic characteristics and residual flow. The research employed the Digital Shoreline Analysis System (DSAS), an ArcGIS extension tool, to conduct a historical trend analysis of shoreline. The study demonstrates that the central coast is eroding to the north and accreting to the south. The highest accretion value was found as 195.42 m/year, whereas the maximum value of erosion was estimated as -185.83 m/year, according to End Point Rate (EPR). The Linear Regression Rate (LRR) indicates that the average rate of erosion and accretion are -17.77 m/year and 17.88 m/year, respectively. Meanwhile, using Weighted Linear Regression (WLR), 0.48% of all transects demonstrated statistically significant erosion, while 0.43% showed statistically significant accretion. During the wet season, heavy river discharge leads to a low salt level in the ocean. Ocean currents hit central coast of Bangladesh from east to west, affecting the majority of the islands in the Meghna Estuary in the dry season. Changes in current directions can be seen during the wet seasons. Southern central coast areas are hit by south-east currents that split in two directions. The Sandwip Channel has a flow of 10,000 to 15,000 m³ s-1 northward. The Tetulia River, Shahbazpur Channel, and Hatia-Sandwip flow southward at rates ranging from 3000 to 17,000 m³ s-1, 14,000 to 60,000 m³ s-1, and 7000 to 39,000 m³ s-1, respectively. In the Meghna Estuary, the combined forces result in a counter-clockwise residual circulation, with the northward flow in the Sandwip channel and southbound flow in the Hatia and Shahbazpur channels. As a result of hydrodynamic, ocean currents, and residual flow, the Central Coast of Bangladesh is continually changing in appearance.

5.
Front Chem ; 11: 1151526, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37153532

RESUMO

Fluorescence probe is one of the most powerful tools for cellular imaging. Here, three phospholipid-mimicking fluorescent probes (FP1-FP3) comprising fluorescein and two lipophilic groups of saturated and/or unsaturated C18 fatty acids were synthesized, and their optical properties were investigated. Like in biological phospholipids, the fluorescein group acts as a hydrophilic polar headgroup and the lipid groups act as hydrophobic non-polar tail groups. Laser confocal microscope images illustrated that FP3, which contains both saturated and unsaturated lipid tails, showed great uptake into the canine adipose-derived mesenchymal stem cells.

6.
BMJ Open ; 13(4): e068660, 2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-37045565

RESUMO

INTRODUCTION: Diarrhoea is one of the leading causes of under-5 childhood mortality and accounts for 8% of 5.4 million global under-5 deaths. In severely malnourished children, diarrhoea progresses to shock, where the risk of mortality is even higher. At icddr,b Dhaka Hospital, the fatality rate is as high as 69% in children with severe malnutrition and fluid refractory septic shock. To date, no study has evaluated systematically the effects of inotrope or vasopressor or blood transfusion in children with dehydrating diarrhoea (eg, in cholera) and severe acute malnutrition (SAM) or severe underweight who are in shock and unresponsive to WHO-recommended fluid therapy. To reduce the mortality of severely malnourished children presenting with diarrhoea and fluid refractory shock, we aim to compare the efficacy of blood transfusion, dopamine and epinephrine in fluid refractory shock in children who do not respond to WHO-recommended fluid resuscitation. METHODS AND ANALYSIS: In this randomised, three-arm, controlled, non-masked clinical trial in children 1-59 months old with SAM or severe underweight and fluid refractory shock, we will compare the efficacy of dopamine or epinephrine administration versus blood transfusion in children who failed to respond to WHO-recommended fluid resuscitation. The primary outcome variable is the case fatality rate. The effect of the intervention will be assessed by performing an intention-to-treat analysis. Recruitment and data collection began in July 2021 and are now ongoing. Results are expected by May 2023. ETHICS AND DISSEMINATION: This study has been approved by the icddr,b Institutional Review Board. We adhere to the 'Declaration of Helsinki' (2000), guidelines for Good Clinical Practice. Before enrolment, we collect signed informed consent from the parents or caregivers of the children. We will publish the results in a peer-reviewed journal and will arrange a dissemination seminar. TRIAL REGISTRATION NUMBER: NCT04750070.


Assuntos
Cólera , Desnutrição Aguda Grave , Humanos , Criança , Lactente , Pré-Escolar , Dopamina/uso terapêutico , Magreza , Resultado do Tratamento , Bangladesh , Epinefrina/uso terapêutico , Diarreia/complicações , Diarreia/terapia , Transfusão de Sangue , Desnutrição Aguda Grave/complicações , Desnutrição Aguda Grave/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Sensors (Basel) ; 22(23)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36501973

RESUMO

Smart cities can be complemented by fusing various components and incorporating recent emerging technologies. IoT communications are crucial to smart city operations, which are designed to support the concept of a "Smart City" by utilising the most cutting-edge communication technologies to enhance city administration and resident services. Smart cities have been outfitted with numerous IoT-based gadgets; the Internet of Things is a modular method to integrate various sensors with all ICT technologies. This paper provides an overview of smart cities' concepts, characteristics, and applications. We thoroughly investigate smart city applications, challenges, and possibilities with solutions in recent technological trends and perspectives, such as machine learning and blockchain. We discuss cloud and fog IoT ecosystems in the in capacity of IoT devices, architectures, and machine learning approaches. In addition we integrate security and privacy aspects, including blockchain applications, towards more trustworthy and resilient smart cities. We also highlight the concepts, characteristics, and applications of smart cities and provide a conceptual model of the smart city mega-events framework. Finally, we outline the impact of recent emerging technologies' implications on challenges, applications, and solutions for futuristic smart cities.


Assuntos
Blockchain , Ecossistema , Cidades , Comunicação , Tecnologia da Informação
8.
Curr Issues Mol Biol ; 44(10): 4977-4986, 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36286053

RESUMO

Fenbendazole (FZ) is a benzimidazole carbamate drug with broad-spectrum antiparasitic activity in humans and animals. The mechanism of action of FZ is associated with microtubular polymerization inhibition and glucose uptake blockade resulting in reduced glycogen stores and decreased ATP formation in the adult stages of susceptible parasites. A completely cured case of lung cancer became known globally and greatly influenced the cancer community in South Korea. Desperate Korean patients with cancer began self-administering FZ without their physician's knowledge, which interfered with the outcome of the cancer treatment planned by their oncologists. On the basis of presented evidence, this review provides valuable information from PubMed, Naver, Google Scholar, and Social Network Services (SNS) on the effects of FZ in a broad range of preclinical studies on cancer. In addition, we suggest investigating the self-administration of products, including supplements, herbs, or bioactive compounds, by patients to circumvent waiting for long and costly FZ clinical trials.

9.
Cureus ; 14(6): e25804, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35836443

RESUMO

Compulsive sexual behavior (CSB) or sexual addiction is a term that generally indicates excessive and uncontrolled sexual behavior. This may lead to subjective distress, social and occupational impairment, or legal and financial consequences. Often, this condition is underreported and untreated. Until now there are no FDA-approved medications for sexual addiction or compulsive sexual behaviors. However, the therapeutic benefits of selective serotonin reuptake inhibitors (SSRIs) and naltrexone are known. This is a case of a 53-year-old male with a history of extensive alcohol use, alcohol withdrawal seizure, and delirium tremens. The patient was treated with naltrexone 50 mg/day for alcohol use disorder. The patient reported that his "sexual compulsion" also reduced after the medication and there was an improvement in both alcohol addiction and self-reported compulsive sexual behavior. This case report also includes a literature review of pharmacotherapy, especially naltrexone, for the treatment of sexual addiction/compulsive sexual behavior. The literature review has shown that patients' symptoms were improved in different doses without side effects, and based on this and our experience, it can be said that naltrexone is effective in the reduction and remission of the symptoms of CSB or sexual addiction.

10.
J Hum Reprod Sci ; 15(1): 27-33, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35494190

RESUMO

Background: Both visceral adiposity index (VAI) and lipid accumulation product (LAP) can be used to assess insulin resistance (IR) and metabolic syndrome (MetS) which are required for management of even lean polycystic ovary syndrome (PCOS) (body mass index [BMI] <23 kg/m2). Aim: This study was aimed to see the magnitude of associations of VAI and LAP with cardiometabolic risk factors including IR and MetS in lean PCOS. Study Setting and Design: This cross-sectional study was done amongst 62 newly detected lean PCOS patients and 58 age- and BMI-matched healthy controls. Materials and Methods: PCOS was diagnosed according to the Revised 2003 Rotterdam Consensus criteria. Along with relevant clinical data, fasting blood was taken to measure glucose, insulin and lipid profile by glucose oxidase, chemiluminescent microparticle immunoassay and by glycerol phosphate dehydrogenase-peroxidase method, respectively. IR was calculated by homeostasis model of IR (HOMA-IR). VAI and LAP were calculated from BMI, waist circumference, triglyceride and high-density lipoprotein cholesterol by using sex-specific formulae. Statistical Analysis Used: Linear and binary regression analyses and receiver operating characteristics curve (ROC) analyses were done as appropriate. Results: Only LAP had predictive associations with age, systolic and diastolic blood pressure and total and low-density lipoprotein cholesterol. Both VAI and LAP had predictive associations with history of subfertility and MetS. LAP had moderate discriminating index for IR with cut-off of HOMA-IR of 2.3. Both VAI and LAP had excellent discriminating index for MetS in lean PCOS patients. Conclusions: LAP had more associations with cardiometabolic risks than VAI and was a moderate discriminator of IR in lean PCOS.

11.
Int J Mol Sci ; 23(8)2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35457127

RESUMO

Drug repositioning, the approach of discovering different uses for existing drugs, has gained enormous popularity in recent years in the anticancer drug discovery field due to the increasing demand for anticancer drugs. Additionally, the repurposing of veterinary antiparasitic drugs for the treatment of cancer is gaining traction, as supported by existing literature. A prominent example is the proposal to implement the use of veterinary antiparasitics such as benzimidazole carbamates and halogenated salicylanilides as novel anticancer drugs. These agents have revealed pronounced anti-tumor activities and gained special attention for "double repositioning", as they are repurposed for different species and diseases simultaneously, acting via different mechanisms depending on their target. As anticancer agents, these compounds employ several mechanisms, including the inhibition of oncogenic signal transduction pathways of mitochondrial respiration and the inhibition of cellular stress responses. In this review, we summarize and provide valuable information about the experimental, preclinical, and clinical trials of veterinary antiparasitic drugs available for the treatment of various cancers in humans. This review suggests the possibility of new treatment options that could improve the quality of life and outcomes for cancer patients in comparison to the currently used treatments.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antiparasitários/farmacologia , Antiparasitários/uso terapêutico , Reposicionamento de Medicamentos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/veterinária , Qualidade de Vida
12.
J Child Adolesc Psychopharmacol ; 32(1): 2-11, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35099269

RESUMO

Background: Schizophrenia at a young age deserves investigation because of the greater severity and burden of illness on individuals and health care than its adult onset. For this study, we included both childhood-onset schizophrenia and early-onset schizophrenia. We used the common term "childhood and adolescent-onset schizophrenia (CAOS)" for either type. This systematic review provides an overview of the clinical use, efficacy, and safety of clozapine treatment in managing CAOS. Methods: We conducted a systematic literature search in PubMed, Embase, and PsycINFO databases. We searched for randomized controlled trials (RCTs), open-label studies (OLSs), review articles, meta-analytic and observational studies. Our literature search resulted in 1242 search results. After the title, abstract, and full article review, 18 studies qualified (double-blind RCTs n = 4; OLS n = 4; observational studies n = 7; case reports n = 3). Results: Clozapine use in CAOS was generally well tolerated and not associated with any fatalities. Clozapine use in the short term (6 weeks) and long term (2-9 years) was superior in efficacy than other antipsychotics in CAOS management. Improvement in overall symptoms was maintained during long-term follow-up over the years in OLSs. Clozapine appeared to have a favorable clinical response and shorter hospital stays. Sedation and hypersalivation were commonly reported (90%), constipation was next in frequency (13%-50%). Neutropenia was seen in 6%-15% of cases and agranulocytosis (<0.1%). Although weight gain was common (up to 64%), followed by metabolic changes (8%-22%), treatment-onset diabetes was less frequent (<6%). Akathisia, tachycardia, and blood pressure changes were less commonly seen. Conclusions: Limited studies indicate that clozapine is a safe and efficacious option for CAOS management. We need large-scale and well-designed long-term RCTs for the use of clozapine in the management of CAOS.


Assuntos
Antipsicóticos , Clozapina , Esquizofrenia , Adolescente , Adulto , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/tratamento farmacológico , Aumento de Peso
13.
BMC Vet Res ; 18(1): 26, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996443

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) have favorable characteristics that render them a potent therapeutic tool. We tested the characteristics of MSCs after temporal storage in various carrier solutions, such as 0.9% saline (saline), 5% dextrose solution (DS), heparin in saline, and Hartmann's solution, all of which are approved by the U.S. Food and Drug Administration (FDA). Phosphate-buffered saline, which does not have FDA approval, was also used as a carrier solution. We aimed to examine the effects of these solutions on the viability and characteristics of MSCs to evaluate their suitability and efficacy for the storage of canine adipose-derived MSCs (cADMSCs). RESULTS: We stored the cADMSCs in the test carrier solutions in a time-dependent manner (1, 6, and 12 h) at 4 °C, and analyzed cell confluency, viability, proliferation, self-renewability, and chondrogenic differentiation. Cell confluency was significantly higher in 5% DS and lower in phosphate-buffered saline at 12 h compared to other solutions. cADMSCs stored in saline for 12 h showed the highest viability rate. However, at 12 h, the proliferation rate of cADMSCs was significantly higher after storage in 5% DS and significantly lower after storage in saline, compared to the other solutions. cADMSCs stored in heparin in saline showed superior chondrogenic capacities at 12 h compared to other carrier solutions. The expression levels of the stemness markers, Nanog and Sox2, as well as those of the MSC surface markers, CD90 and CD105, were also affected over time. CONCLUSION: Our results suggest that MSCs should be stored in saline, 5% DS, heparin in saline, or Hartmann's solution at 4 °C, all of which have FDA approval (preferable storage conditions: less than 6 h and no longer than 12 h), rather than storing them in phosphate-buffered saline to ensure high viability and efficacy.


Assuntos
Tecido Adiposo , Células-Tronco Mesenquimais , Tecido Adiposo/citologia , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Cães , Heparina/farmacologia , Células-Tronco Mesenquimais/citologia , Soluções para Preservação de Órgãos , Fosfatos , Lactato de Ringer
14.
Sex Reprod Health Matters ; 29(2): 1885790, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33625312

RESUMO

Child marriage is a globally recognised human rights violation that disproportionately affects girls, especially in developing countries. It has serious negative consequences on girls' physical, mental, sexual, and reproductive health and rights. Although well-pronounced laws against child marriage were enacted in Bangladesh, the practice remains a significant challenge. Lack of law enforcement and persistent social norms ultimately allow child marriage to persist around the country. Social norms have an impact on the prevalent attitudes toward child marriage. Therefore, this mixed-method study aimed to explore the legal knowledge, perception, and practice of child marriage in Bangladesh. This study was part of a broader evaluation of a UNICEF media programme. Adolescent boys and girls aged between 10 and 19 years and their parents were interviewed in three Bangladeshi districts. All the respondents were aware of the legal age of marriage and knew that child marriage is punishable by law. This study illuminated the reasons, including early marriage among boys, poverty, dowry, and sexual harassment. Communities and policymakers need to be engaged to trigger larger structural and cultural changes to remedy the harmful social norm and its practice.


Assuntos
Família , Casamento , Adolescente , Adulto , Bangladesh , Criança , Feminino , Humanos , Masculino , Comportamento Sexual , Normas Sociais , Adulto Jovem
15.
Vet Med Sci ; 7(3): 820-830, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33527778

RESUMO

Salmonellosis in poultry is an important disease that seriously impedes the development of the poultry industry. The increased resistance to antimicrobials against Salmonella has been a major public health concern worldwide. We conducted a study from January to June 2016 in and around the Rajshahi district of Bangladesh on the commercial chicken to isolate, identify and characterize poultry-specific Salmonella, to assess the potential risk factors and to determine the antimicrobial resistance pattern of the isolates. The overall prevalence of Salmonella enterica was 41% (49/120) [95% CI: 31.95%-50.17%] with 41.7% in broiler chicken (25/60) [95% CI: 29.06%-55.12%] and 40% in layer chicken (24/60, 40%) [95% CI: 27.56%-53.46%]. Samples collected from Rajshahi city (OR = 1.37, 95% CI: 0.50-3.73) and Puthia Upazila (OR = 1.51, 95% CI: 0.56-4.12) were more likely to be positive for Salmonella than Charghat Upazila. Salmonella detection was 1.3 times higher in chicken, providing loose feed than those provided ready feed. All the isolates fermented dextrose, maltose and mannitol with the production of acid and gas, but did not ferment sucrose and lactose. The isolates showed catalase, MR, citrate utilization test and TSI agar test positive, but indole and V-P tests negative. Salmonella isolates were sensitive to ciprofloxacin (90%), gentamycin (80%), amoxicillin (75%), streptomycin (70%), ampicillin (45%) and sulfamethoxazole-trimethoprim (45%), whereas highly resistant to penicillin (100%) and nalidixic acid (100%) followed by sulfamethoxazole-trimethoprim (55%), ampicillin (40%) and amoxicillin (25%). Salmonella enterica is endemic in commercial chicken production in Bangladesh with high prevalence. A considerable proportion of Salmonella isolates was found to be resistant to the majority of the common antimicrobial drugs. A good biosecurity system could be effective for the reduction of Salmonella. It is necessary to obtain universal commitments to establish prudent antibiotic use policies.


Assuntos
Antibacterianos/farmacologia , Galinhas , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana/veterinária , Salmonella/fisiologia , Animais , Bangladesh/epidemiologia , Feminino , Masculino , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/microbiologia , Prevalência , Salmonella/efeitos dos fármacos , Salmonelose Animal/epidemiologia , Salmonelose Animal/microbiologia
16.
Public Health Nutr ; 23(17): 3104-3113, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32799964

RESUMO

OBJECTIVE: To determine if a global mid-upper arm circumference (MUAC) cut-off can be established to classify underweight in adults (men and non-pregnant women). DESIGN: We conducted an individual participant data meta-analysis (IPDMA) to explore the sensitivity (SENS) and specificity (SPEC) of various MUAC cut-offs for identifying underweight among adults (defined as BMI < 18·5 kg/m2). Measures of diagnostic accuracy were determined every 0·5 cm across MUAC values from 19·0 to 26·5 cm. A bivariate random effects model was used to jointly estimate SENS and SPEC while accounting for heterogeneity between studies. Various subgroup analyses were performed. SETTING: Twenty datasets from Africa, South Asia, Southeast Asia, North America and South America were included. PARTICIPANTS: All eligible participants from the original datasets were included. RESULTS: The total sample size was 13 835. Mean age was 32·6 years and 65 % of participants were female. Mean MUAC was 25·7 cm, and 28 % of all participants had low BMI (<18·5 kg/m2). The area under the receiver operating characteristic curve for the pooled dataset was 0·91 (range across studies 0·61-0·98). Results showed that MUAC cut-offs in the range of ≤23·5 to ≤25·0 cm could serve as an appropriate screening indicator for underweight. CONCLUSIONS: MUAC is highly discriminatory in its ability to distinguish adults with BMI above and below 18·5 kg/m2. This IPDMA is the first step towards determining a global MUAC cut-off for adults. Validation studies are needed to determine whether the proposed MUAC cut-off of 24 cm is associated with poor functional outcomes.


Assuntos
Braço , Magreza , Adulto , África , Antropometria , Braço/anatomia & histologia , Ásia , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Masculino , América do Norte , América do Sul
17.
Bioessays ; 42(4): e1900232, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32053231

RESUMO

Transposable elements (TEs) are sequences currently or historically mobile, and are present across all eukaryotic genomes. A growing interest in understanding the regulation and function of TEs has revealed seemingly dichotomous roles for these elements in evolution, development, and disease. On the one hand, many gene regulatory networks owe their organization to the spread of cis-elements and DNA binding sites through TE mobilization during evolution. On the other hand, the uncontrolled activity of transposons can generate mutations and contribute to disease, including cancer, while their increased expression may also trigger immune pathways that result in inflammation or senescence. Interestingly, TEs have recently been found to have novel essential functions during mammalian development. Here, the function and regulation of TEs are discussed, with a focus on LINE1 in mammals. It is proposed that LINE1 is a beneficial endogenous dual regulator of gene expression and genomic diversity during mammalian development, and that both of these functions may be detrimental if deregulated in disease contexts.


Assuntos
Cromatina/genética , Elementos de DNA Transponíveis/genética , Expressão Gênica , Redes Reguladoras de Genes , Variação Genética , Mamíferos/crescimento & desenvolvimento , Mamíferos/genética , Animais , Sítios de Ligação , Desoxirribonuclease I/genética , Elementos Facilitadores Genéticos , Evolução Molecular , Humanos
18.
Mol Cell ; 74(3): 555-570.e7, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30956044

RESUMO

L1 retrotransposons are transposable elements and major contributors of genetic variation in humans. Where L1 integrates into the genome can directly impact human evolution and disease. Here, we experimentally induced L1 retrotransposition in cells and mapped integration sites at nucleotide resolution. At local scales, L1 integration is mostly restricted by genome sequence biases and the specificity of the L1 machinery. At regional scales, L1 shows a broad capacity for integration into all chromatin states, in contrast to other known mobile genetic elements. However, integration is influenced by the replication timing of target regions, suggesting a link to host DNA replication. The distribution of new L1 integrations differs from those of preexisting L1 copies, which are significantly reshaped by natural selection. Our findings reveal that the L1 machinery has evolved to efficiently target all genomic regions and underline a predominant role for post-integrative processes on the distribution of endogenous L1 elements.


Assuntos
Elementos de DNA Transponíveis/genética , Genoma Humano/genética , Elementos Nucleotídeos Longos e Dispersos/genética , Retroelementos/genética , Mapeamento Cromossômico , Replicação do DNA/genética , Genômica , Células HeLa , Humanos
19.
Brain Stimul ; 12(1): 54-61, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30316742

RESUMO

BACKGROUND: Transcranial direct-current stimulation (tDCS), a non-invasive neurostimulation treatment, has been reported in a number of sham-controlled studies to show significant improvements in treatment-resistant auditory hallucinations in schizophrenia patients, primarily in ambulatory and higher-functioning patients, but little is known of the effects of tDCS on hospitalized, low-functioning inpatients. OBJECTIVE/HYPOTHESIS: The purpose of this study was to examine the efficacy and safety of tDCS for auditory hallucinations in hospitalized ultra-treatment-resistant schizophrenia (TRS) and to evaluate the effects of tDCS on cognitive functions. We hypothesized that treatment non-response reported in previous tDCS studies may have been due to the insufficient duration of direct-current stimulation. METHODS: Inpatient participants with DSM-V schizophrenia, long-standing treatment-resistance, and auditory verbal hallucinations (AVH) participated in this 4-week sham-controlled, randomized trial. Assessments included the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) at baseline and endpoint (at the end of Week 4), and the Auditory Hallucinations Rating Scale (AHRS) administered at baseline, endpoint, and weekly throughout the study. Participants were randomized to receive active vs. sham tDCS treatments twice daily for 4 weeks. RESULTS: Twenty-eight participants were enrolled (tDCS, n = 15; control, n = 13) and 21 participants completed all 4 weeks of the trial. Results showed a significant reduction for the auditory hallucination total score (p ≤ 0.05). We found a 21.9% decrease in AHRS Total Score for the tDCS group and a 12.6% decrease in AHRS Total Score for the control group. Significant reductions in frequency, number of voices over time, length of auditory hallucinations, and overall psychopathology were also observed for the tDCS group. When assessing cognitive functioning, only Working Memory showed improvement for the tDCS group. CONCLUSION: Although there was only a small improvement noted in auditory hallucination scores for the tDCS group, this improvement was meaningful when compared to no standard treatment of the control group. While this makes the interpretation of clinical significance debatable, it does confirm that tDCS combined with pharmacological intervention can provide clinical gains over pharmacological intervention alone. Therefore, tDCS treatment appears to be effective not only for ambulatory, higher-functioning patients, but also for patients with ultra-treatment-resistant schizophrenia.


Assuntos
Alucinações/terapia , Esquizofrenia/terapia , Estimulação Transcraniana por Corrente Contínua/efeitos adversos , Adulto , Cognição , Método Duplo-Cego , Feminino , Humanos , Masculino , Memória de Curto Prazo , Pessoa de Meia-Idade , Estimulação Transcraniana por Corrente Contínua/métodos
20.
Stem Cells Int ; 2018: 8329174, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30123294

RESUMO

Stem cell therapy has prompted the expansion of veterinary medicine both experimentally and clinically, with the potential to contribute to contemporary treatment strategies for various diseases and conditions for which limited or no therapeutic options are presently available. Although the application of various types of stem cells, such as bone marrow-derived mesenchymal stem cells (BM-MSCs), adipose tissue-derived mesenchymal stem cells (AT-MSCs), and umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs), has promising potential to improve the health of different species, it is crucial that the benefits and drawbacks are completely evaluated before use. Umbilical cord blood (UCB) is a rich source of stem cells; nonetheless, isolation of mesenchymal stem cells (MSCs) from UCB presents technical challenges. Although MSCs have been isolated from UCB of diverse species such as human, equine, sheep, goat, and canine, there are inherent limitations of using UCB from these species for the expansion of MSCs. In this review, we investigated canine UCB (cUCB) and compared it with UCB from other species by reviewing recent articles published from February 2003 to June 2017 to gain an understanding of the limitations of cUCB in the acquisition of MSCs and to determine other suitable sources for the isolation of MSCs from canine. Our review indicates that cUCB is not an ideal source of MSCs because of insufficient volume and ethical issues. However, canine reproductive organs discarded during neutering may help broaden our understanding of effective isolation of MSCs. We recommend exploring canine reproductive and adipose tissue rather than UCB to fulfill the current need in veterinary medicine for the well-designed and ethically approved source of MSCs.

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