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1.
Cell Tissue Res ; 395(2): 199-210, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38087072

RESUMO

Spatial transcriptomics is a technique that provides insight into gene expression profiles in tissue sections while retaining structural information. We have employed this method to study the pathological conditions related to red and melanized focal changes in farmed Atlantic salmon (Salmo salar). Our findings support a model where similar molecular mechanisms are involved in both red and melanized filet discolorations and genes associated with several relevant pathways show distinct expression patterns in both sample types. Interestingly, there appears to be significant cellular heterogeneity in the foci investigated when looking at gene expression patterns. Some of the genes that show differential spatial expression are involved in cellular processes such as hypoxia and immune responses, providing new insight into the nature of muscle melanization in Atlantic salmon.


Assuntos
Doenças dos Peixes , Infecções por Reoviridae , Salmo salar , Animais , Infecções por Reoviridae/patologia , Salmo salar/genética , Músculo Esquelético/patologia , Perfilação da Expressão Gênica , Transcriptoma/genética , Doenças dos Peixes/patologia
2.
Haematologica ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38572568

RESUMO

Belantamab mafodotin (belantamab) is a first-in-class anti-BCMA antibody-drug conjugate approved for the treatment of triple-class refractory multiple myeloma. It provides a unique therapeutic option for patients ineligible for CAR-T and bispecific antibody therapy, and/or patients progressing on anti-CD38 treatment where CAR-T and bispecifics might be kept in reserve. Wider use of the drug can be challenged by its distinct ocular side effect profile, including corneal microcysts and keratopathy. While dose reduction has been the most effective way to reduce these toxicities, the underlying mechanism of this BCMA off-target effect remains to be characterized. In this study, we provide the first evidence for soluble BCMA (sBCMA) in lacrimal fluid and report on its correlation with tumor burden in myeloma patients. We confirm that corneal cells do not express BCMA, and show that sBCMA-belantamab complexes may rather be internalized by corneal epithelial cells through receptor-ligand independent pinocytosis. Using an hTcEpi corneal cell-line model, we show that the pinocytosis inhibitor EIPA significantly reduces belantamab-specific cell killing. As a proof of concept, we provide detailed patient profiles demonstrating that, after belantamab-induced cell killing, sBCMA is released into circulation, followed by a delayed increase of sBCMA in the tear fluid and subsequent onset of keratopathy. Based on the proposed mechanism, pinocytosis-induced keratopathy can be prevented by lowering the entry of sBCMA into the lacrimal fluid. Future therapeutic concepts may therefore consist of belantamab-free debulking therapy prior to belantamab consolidation and/or concomitant use of gamma-secretase inhibition as currently evaluated for belantamab and nirogacestat in ongoing studies.

3.
Scand J Gastroenterol ; : 1-5, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38885119

RESUMO

BACKGROUND: When commencing enteral feeding, patients and families will want to know the likelihood of returning to an oral diet. There is a paucity of data on the prognosis of patients with gastrostomies. We describe a large dataset of patients, which identifies factors influencing gastrostomy removal and assesses the likelihood of the patient having at home enteral nutrition. METHODS: Retrospective data was collected on patients from Sheffield Teaching Hospitals who had received a gastrostomy and had outpatient enteral feeding between January 2016 and December 2019. Demographic data, indication and outcomes were analysed. RESULTS: A total of 451 patients were assessed, median age: 67.7. 183/451(40.6%) gastrostomies were for head and neck cancer, 88/451 (19.5%) for stroke, 28/451 (6.2%) for Motor Neuron Disease, 32/451 (7.1%) for other neurodegenerative causes, 120/451 (26.6%) other. Of the 31.2% who had their gastrostomy removed within 3 years, head and neck cancer was the most common indication (58.3%) followed by stroke (10.2%), Motor Neuron Disease (7.1%) and other neurodegenerative diseases (3.1%). Gastrostomy removal was significantly influenced by age, place of residence, and having head and neck cancer (p < 0.05). There was the greatest likelihood of removal within the first year (24%). 70.5% had enteral feeding at home. CONCLUSION: This large cohort study demonstrates 31.2% of patients had their gastrostomy removed within 3 years. Head and neck cancer patients, younger age and residing at home can help positively predict removal. Most patients manage their feeding at home rather than a nursing home. This study provides new information on gastrostomy outcomes when counselling patients to provide realistic expectations.

4.
Cryo Letters ; 44(3): 142-150, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37883167

RESUMO

BACKGROUND: Indian Wild Orange (Citrus indica Tanaka) is an endangered and endemic species from northeast India for which effective ex situ conservation strategies, including embryo cryopreservation, are urgently needed. MATERIALS AND METHODS: Desiccation tolerance and cryopreservation ability for embryonic axes of Citrus indica was determined using three techniques (air desiccation-freezing, PVS2 vitrification-freezing and encapsulation-dehydration-freezing). Success was assessed as survival and recovery in vitro. RESULTS: Successful cryopreservation of embryonic axes was achieved using all three methods, with the highest survival achieved when using air desiccation-freezing (90%) followed by encapsulation-dehydration (85%) and PVS2 vitrification cryopreservation (80%). Regeneration levels were lower than survival levels for all three proceedures. Post-cryo regeneration success was: encapsulation-dehydration (64%) > air desiccation-freezing (55%) > PVS2 vitrification (52%). CONCLUSION: Although there was relatively high post-cryopreservation recovery growth obtained using all the three techniques, the air desiccation-freezing technique is preferred, as it is a simple, practical and reproducible technique for the long-term cryobanking of this important wild species. Doi: 10.54680/fr23310110512.


Assuntos
Citrus , Criopreservação , Criopreservação/métodos , Desidratação , Sementes , Dessecação/métodos , Vitrificação
5.
J Foot Ankle Surg ; 62(5): 893-898, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37380121

RESUMO

Postoperative sagittal range of motion, in particular degree of dorsiflexion, is critical for satisfactory outcomes in total ankle arthroplasty (TAA). Although there is literature discussing techniques to treat a preoperative fixed equinus we are not aware of any papers presenting patient outcomes. We present patient-reported outcomes for our cohort of patients undergoing TAA with preoperative fixed equinus compared to plantigrade ankles. This is a single surgeon, cohort study of consecutive cases. Cases of primary TAA were identified from a local joint registry which prospectively records Foot and Ankle Outcome Scores (FAOS), Short Form-36 (SF-36), and patient satisfaction. Revision cases or those with inadequate data were excluded. Patients were classified as fixed equinus or neutral based on both preoperative weightbearing lateral radiographs and clinical records. Overall 259 cases were identified, 92 were excluded leaving 167 cases for analysis (mean follow-up 81.7 months), 147 were classified as neutral and 20 fixed equinus. The fixed equinus group were significantly younger (neutral 63.9 vs equinus 52.9, p < .001). Stiffness was the only FAOS domain that was detectibly different at baseline (neutral 36.6 vs equinus 25.6, p = .044). Final FAOS scores, change from baseline and patient satisfaction was the same in all domains for both groups. There was no difference in revision rates. With the numbers available we did not demonstrate a postoperative difference in outcomes for patients with preoperative fixed equinus.


Assuntos
Tornozelo , Artroplastia de Substituição do Tornozelo , Humanos , Tornozelo/cirurgia , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Estudos de Coortes , Artroplastia de Substituição do Tornozelo/efeitos adversos , Medidas de Resultados Relatados pelo Paciente , Estudos Retrospectivos , Resultado do Tratamento
6.
Mater Chem Phys ; 282: 125803, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35153357

RESUMO

The excellent strategy to mitigate the spread of the COVID-19 pandemic is to inhibit the transmission of the SARS-CoV-2. Since fomites are one of the vital routes of coronaviral transmission, disinfecting of fomites play a pivotal role in curbing its survival on the contaminated surfaces. Available commercial disinfectants cannot keep the contaminated surfaces sanitized all the time. Self-disinfecting ability of Ag-enriched TiO2 nanocoating due to its superb photocatalytic efficiency can effectively reduce infections caused by spread of pathogens at public places. Anatase Ag-TiO2 nanocoatings synthesized by sol-gel process at 0.5, 1.5, and 2.5% enriching concentrations were casted on glass substrates by spin-coating technique and subsequently annealed at 650 °C. The morphological shape, crystallographic structure, light absorbance, photo-luminosity, vibrational modes, and functional groups of Ag-TiO2 nanocoating on glass surface were studied by FE-SEM, GIXRD, UV-Visible, Photoluminescence, Raman, and FTIR spectroscopy. The developed anatase Ag-TiO2 nanocoatings manifested to improve photocatalytic disinfecting performance due to the achieved small crystallite size of 10.5-19.2 nm, diminished band gap energy of 2.56-2.60 eV, elevated surface area of 0.802-1.470 ×105 cm2/g, and enhanced light absorbance. Among the enriched specimens, 0.5% Ag-TiO2 nanocoatings predicted an overall exalted functionality compared to pristine one.

7.
Arch Pharm (Weinheim) ; 355(12): e2200360, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36029269

RESUMO

Bacterial resistance is spreading in an alarming manner, outpacing the rate of development of new antibacterial agents and surging the need for effective alternatives. Prenylated flavonoids are a promising class of natural antibiotics with reported activity against a wide range of resistant pathogens. Here, a large library of natural flavonoids (1718 structures) was virtually screened for potential candidates inhibiting the B-subunit of gyrase (Gyr-B). Twenty-eight candidates, predominated by prenylated flavonoids, appeared as promising hits. Six of them were selected for further in vitro antibacterial and Gyr-B enzyme inhibitory activities. Auriculasin is presented as the most potent antibacterial candidate, with a MIC ranging from 2 to 4 µg/ml against two clinically isolated multidrug-resistant Escherichia coli strains. Mechanistic antibacterial analysis revealed auriculasin inhibitory activity towards the Gyr-B enzyme on the micromolar scale (IC50 = 0.38 ± 0.15 µM). Gyr-B interaction was further detailed by conducting an isothermal titration calorimetric experiment, which revealed a competitive inhibition with a high affinity for the Gyr-B active site, achieved mostly through enthalpic interactions (ΔGbinding = -10.69 kcal/mol). Molecular modeling and physics-based simulations demonstrated the molecule's manner of fitting inside the Gyr-B active site, indicating a very potential nucleus for the future generation of more potent derivatives. To conclude, prenylated flavonoids are interesting antibacterial candidates with anti-Gyr-B mechanism of action that can be obtained from a plant-derived flavonoid.


Assuntos
Escherichia coli , Flavonoides , Flavonoides/farmacologia , Flavonoides/química , Relação Estrutura-Atividade , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana
8.
J Med Virol ; 93(5): 2815-2819, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33128396

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) is a Betacoronavirus that results in a severe fatal respiratory disease; however, it is also associated with mild inapparent infections. The western part of the Kingdom of Saudi Arabia (KSA) contains the holy places where millions of Muslims gathered from all over the world, all year round, with a high probability of mass disease transmission. The aim of this study was to estimate the prevalence of MERS-CoV among military personnel and their families during the period 2014-2019, in the western part of the KSA. A total of 35,203 sputum samples collected from patients with respiratory distress were screened for the presence of MERS-CoV using real-time reverse-transcription polymerase chain reaction in the examined patients. MERS-CoV infections were detected at a very low percentage in the examined patients. Only 42 of the examined subjects (0.12%) were found positive for MERS-CoV. Most infected cases (32/42) cases were detected in 2014, and the rest of the cases were reported in 2015-2019. The cases with fatal consequences (n = 20) were only detected in 2014. It was concluded that there is a very low prevalence of MERS-CoV infections among the military personnel and their families.


Assuntos
Infecções por Coronavirus/epidemiologia , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Militares , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Prevalência , Reação em Cadeia da Polimerase em Tempo Real/métodos , Síndrome do Desconforto Respiratório/epidemiologia , Arábia Saudita/epidemiologia
9.
Microb Pathog ; 147: 104405, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32707313

RESUMO

The present study evaluated intracellular antibacterial efficacy of two short-chain cationic antimicrobial peptides (AMPs) namely, Cecropin A (1-7)-Melittin and lactoferricin (17-30) against three field strains of multi-drug resistant Salmonella Enteritidis. Initially, antimicrobial ability of both the AMPs was evaluated for their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against multi-drug resistant S. Enteritidis strains. Besides, the AMPs were evaluated for its in vitro stability (high-end temperatures, proteases, physiological concentrations of cationic salts and pH) and safety (haemolytic assay in sheep erythrocytes; cytotoxicity assay in murine macrophage RAW 264.7 cell line and human epithelioma HEp-2 cell line and beneficial gut lactobacilli). Later, a time-kill assay was performed to assess the intracellular antibacterial activity of Cecropin A (1-7)-Melittin and lactoferricin (17-30) against multi-drug resistant S. Enteritidis in RAW 264.7 and HEp-2 cells. The observed MBC values of Cecropin A (1-7)-Melittin and lactoferricin (17-30) against multi-drug resistant S. Enteritidis (128 µM; 256 µM) were generally twice or four-fold greater than the MIC values (64 µM). Further, both the AMPs were found variably stable after exposure at high-end temperatures (70 °C and 90 °C), protease treatment (trypsin, proteinase K, lysozyme), higher concentration of physiological salts (150 mM NaCl and 2 mM MgCl2) and hydrogen ion concentrations (pH 4.0 to 8.0). Both the AMPs were found non-haemolytic on sheep erythrocytes, revealed minimal cytotoxicity in RAW 264.7 and HEp-2 cells, and was tested safe against beneficial gut lactobacilli (L. acidophilus and L. rhamnosus). Intracellular bacteriostatic effect with both cationic AMPs against multi-drug resistant S. Enteritidis was evident in RAW 264.7 cells; however, in both the cell lines, the significant bactericidal effect was not observed (P > 0.05) with both cationic AMPs understudy against multi-drug resistant S. Enteritidis. Based on the results of the present study, both the cationic AMPs understudy may not be useful for the intracellular elimination of multi-drug resistant S. Enteritidis; hence, further studies such as conjugation of these AMPs with either cell-penetrating peptides (CPP) and/or nanoparticles (NPs) are warranted.


Assuntos
Antibacterianos , Anti-Infecciosos , Peptídeos Catiônicos Antimicrobianos , Meliteno , Preparações Farmacêuticas , Infecções por Salmonella , Animais , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Resistência a Múltiplos Medicamentos , Lactoferrina , Meliteno/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Fragmentos de Peptídeos , Infecções por Salmonella/tratamento farmacológico , Salmonella enteritidis , Ovinos
10.
Cryo Letters ; 41(5): 281-290, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33988666

RESUMO

BACKGROUND: Ichang Papeda (Citrus cavaleriei H.Lév. ex Cavalerie) is a wild and endangered species of NE India that requires urgent preservation of its genetic resources. OBJECTIVE: To characterize the storage physiology of the seeds and to cryopreserve the embryo and embryonic axis (EA). MATERIALS AND METHODS: The morphology and storage physiology of the seeds were determined, and the cryopreservation of embryos and EA attempted using various techniques (viz., air desiccation-freezing, vitrification and encapsulation-dehydration). RESULTS: Weighing up to 4 g, seeds of Citrus cavaleriei are the largest known in the genus. Based on estimates using the seed coat ratio - seed mass (SCR-SM) model there was a very high probability of seed desiccation intolerance, which was validated physiologically; seeds lost vigour on drying below 30% moisture content (MC) and no seeds germinating after drying to <12% MC. Embryos and EAs could be air dried to 25-30% MC and cryopreserved with c. 50% survival. In contrast, EA optimally exposed to PVS2 (20 min) or encapsulated, sucrose pretreated (0.5 M, 24 h) and dehydrated (6 h) had c. 40% survival after cryopreservation. CONCLUSION: Citrus cavaleriei produces large, recalcitrant seeds that can, nevertheless, be cryopreserved as embryos or isolated EA after air drying to c. 25-30% MC; encapsulation-dehydration and vitrification provide alternative options for the cryopreservation of EA.


Assuntos
Citrus , Criopreservação , Sementes , Citrus/classificação , Conservação dos Recursos Naturais , Dessecação , Espécies em Perigo de Extinção , Índia , Banco de Sementes
11.
J Assoc Physicians India ; 68(12): 21-27, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33247638

RESUMO

BACKGROUND AND OBJECTIVES: A virtual registry study evaluating real world evidence on physicians' use of prophylactic regimens for protection against SARS-CoV-2. This paper summarizes the interim results. METHODS: Asymptomatic physicians at risk of acquiring SARS-CoV-2 responded to online questions at baseline and 7 weeks post-baseline. Baseline data included demographics, prophylaxis regimen (including "no prophylaxis") and start date. Participants who provided complete week-7 data (information on type of health facility [COVID/Non-COVID], number of presumed/confirmed cases exposed to, PPE use, SARS-CoV-2 testing and symptoms, regimen adherence and intercurrent illness) comprised the Completer population. Limited data (regimen adherence, SARS-CoV-2 testing) was collected for participants who failed to provide complete week7 data. Those providing limited/complete information comprised the Evaluable population. RESULTS: Of 369 enrolled participants, 182 (mean age 42±11.05 years) comprised the Evaluable population. They showed a male preponderance (67.6%). Practitioners from Maharashtra (59.9%) and specialties of Pediatrics, Internal Medicine, Anesthesiology and Critical Care (63.2%) accounted for the majority. ICMR's HCQ prophylaxis regimen was initiated by 125 (68.7%) participants with 31 (17%) initiating 'No prophylaxis'. The highest adherence was for the ICMRregimen (87.2%). In the Completer population comprising 150 participants, 87 were exposed to presumed (81) and/or confirmed cases (60). Most exposures to confirmed cases (49, 81.7%) were high-risk. PPE use was generally high (75-100%). Most participants (94.7%) did not report an AE. The proportions with an AE was similar with ICMR regimen (5.9%) and no prophylaxis (6.5%). INTERPRETATION AND CONCLUSIONS: Physicians in India preferred ICMR's HCQ regimen. The regimen appears to be safe and associated with a high level of adherence.


Assuntos
Infecções por Coronavirus , Pandemias , Médicos , Pneumonia Viral , Adulto , Betacoronavirus , COVID-19 , Teste para COVID-19 , Criança , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Humanos , Hidroxicloroquina , Índia/epidemiologia , Controle de Infecções , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , SARS-CoV-2 , Tratamento Farmacológico da COVID-19
12.
Georgian Med News ; (302): 123-126, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32672703

RESUMO

The great hopes of modern medicine for neuroprotective therapy have stimulated scientists around the world to actively search for new effective means of influencing the pathophysiological cascades of the development of neuronal damage. Aim. To evaluate the effect of the use of the adamantane derivative 1-adamantylethyloxa-3-morpholino-2-propanol hydrochloride (ademol) compared with amantadine sulfate and 0.9% NaCl solution on the activity dynamics of neuron-specific enolase in rats with acute traumatic brain injury (TBI) . The therapeutic effect of ademol in experimental traumatic brain injury was evaluated using a dose of 2 mg/kg (i/v) every 12 hours for 8 days. The pseudo-operated animals and the control group received a 0.9% NaCl solution at a dose of 2 ml/kg i/v, and the comparison group received amantadine sulfate at a dose of 5 mg/kg in the same mode. To determine the effectiveness of the studied drugs in brain injury, the level of neuron-specific enolase (NSE) was used. The course infusion in rats with TBI of solutions of ademol (2 mg/kg) and amantadine sulfate (5 mg/kg) during the 8 days of the TBI model, significantly reduced the increase in the NSE level in animals of the control pathology group by an average of 52.1 and 38.2%. Thus, the results obtained indicate that when using ademol at a dose of 2 mg/kg i/v and amantadine sulfate (5 mg/kg i/v), powerful neurocytoprotective properties appear against the background of a model head injury. Moreover, the neuroprotective effect of ademol manifested itself more clearly, since in terms of the ability to prevent the increase in NSE levels, it significantly dominated the reference drug by an average of 22.5%.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Animais , Benzotiadiazinas , Fosfopiruvato Hidratase
13.
Magn Reson Med ; 82(5): 1631-1645, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31183892

RESUMO

PURPOSE: To investigate the potential of continuous radiofrequency (RF) shifting (SWEEP) as a technique for creating densely sampled data while maintaining a stable signal state for dynamic imaging. METHODS: We present a method where a continuous stable state of magnetization is swept smoothly across the anatomy of interest, creating an efficient approach to dense multiple 2D slice imaging. This is achieved by introducing a linear frequency offset to successive RF pulses shifting the excited slice by a fraction of the slice thickness with each successive repeat times (TR). Simulations and in vivo imaging were performed to assess how this affects the measured signal. Free breathing, respiration resolved 4D volumes in fetal/placental imaging is explored as potential application of this method. RESULTS: The SWEEP method maintained a stable signal state over a full acquisition reducing artifacts from unstable magnetization. Simulations demonstrated that the effects of SWEEP on slice profiles was of the same order as that produced by physiological motion observed with conventional methods. Respiration resolved 4D data acquired with this method shows reduced respiration artifacts and resilience to non-rigid and non-cyclic motion. CONCLUSIONS: The SWEEP method is presented as a technique for improved acquisition efficiency of densely sampled short-TR 2D sequences. Using conventional slice excitation the number of RF pulses required to enter a true steady state is excessively high when using short-TR 2D acquisitions, SWEEP circumvents this limitation by creating a stable signal state that is preserved between slices.


Assuntos
Imageamento por Ressonância Magnética/métodos , Respiração , Artefatos , Mapeamento Encefálico/métodos , Simulação por Computador , Feminino , Humanos , Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Angiografia por Ressonância Magnética , Placenta/irrigação sanguínea , Placenta/diagnóstico por imagem , Gravidez
14.
Genet Med ; 21(4): 972-981, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30287923

RESUMO

PURPOSE: Following automated variant calling, manual review of aligned read sequences is required to identify a high-quality list of somatic variants. Despite widespread use in analyzing sequence data, methods to standardize manual review have not been described, resulting in high inter- and intralab variability. METHODS: This manual review standard operating procedure (SOP) consists of methods to annotate variants with four different calls and 19 tags. The calls indicate a reviewer's confidence in each variant and the tags indicate commonly observed sequencing patterns and artifacts that inform the manual review call. Four individuals were asked to classify variants prior to, and after, reading the SOP and accuracy was assessed by comparing reviewer calls with orthogonal validation sequencing. RESULTS: After reading the SOP, average accuracy in somatic variant identification increased by 16.7% (p value = 0.0298) and average interreviewer agreement increased by 12.7% (p value < 0.001). Manual review conducted after reading the SOP did not significantly increase reviewer time. CONCLUSION: This SOP supports and enhances manual somatic variant detection by improving reviewer accuracy while reducing the interreviewer variability for variant calling and annotation.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/normas , Mutação/genética , Neoplasias/genética , Software , Algoritmos , Humanos , Neoplasias/patologia , Polimorfismo de Nucleotídeo Único/genética , Alinhamento de Sequência
16.
J Biol Regul Homeost Agents ; 32(3): 705-709, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29921403

RESUMO

Pyrazinamide (PZA) is a key first-line antibiotic used for the short-course treatment of drug-sensitive and multidrug-resistant (MDR) isolates of tuberculosis. PZA exhibits potent action against semi-dormant bacilli in acidic environments. However, mutations that occur in target genes may cause technical difficulties in the diagnosis of PZA resistance during drug susceptibility testing. The objective of the current study is to identify mutations in pncAWT rpsA and rpsAWT panD genes among PZA-resistant isolates of Mycobacterium tuberculosis (MTB) circulating in the Pashtun dominant region, Khyber Pakhtunkhwa, Pakistan. We selected 18 PZA-resistant pncAWT strains from the Provincial Tuberculosis Reference Laboratory (PTRL) Khyber Pakhtunkhwa to investigate mutations in the coding region of rpsA and panD genes. The experiments were repeated for drug susceptibility testing using MGIT 960 automated system. In addition, eighteen PZA-resistant rpsA genes along with 5 susceptible strains and one H37Rv strain were sequenced. All 18 isolates were PZA-resistant. The majority of these isolates exhibited multidrug resistance (MDR) (13/18). We identified 14 non-synonymous and one synonymous mutation in the coding region of rpsA in 11 strains. All mutations were scattered throughout the gene and not reported previously. Further, we did not identify any mutation in 7 rpsAWT panD genes. Mutations in rpsA but not in panD occur in PZA-resistant pncAWT MTB isolates circulating in Khyber Pakhtunkhwa, Pakistan.


Assuntos
Amidoidrolases/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Mutação , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Humanos , Paquistão
18.
Niger J Clin Pract ; 21(11): 1495-1500, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30417850

RESUMO

CONTEXT: Various radiographic features have been associated with temporomandibular joint disorders (TMDs); however, these characteristics have not been compared among different racial groups. AIMS: To radiographically evaluate and compare craniofacial patterns and condylar findings suggestive of TMD among African, White, Chinese, Hispanic, and Indian racial groups. SETTINGS AND DESIGN: This multicenter retrospective study used data from three private orthodontic practices and a University Orthodontic Clinic. SUBJECTS AND METHODS: Panoramic and lateral cephalometric radiographs were collected from 250 subjects who were equally divided into five racial groups: Africans, Whites, Chinese, Hispanics, and Indians. All radiographs were initial records from patients seeking orthodontic treatment. Linear and angular cephalometric measurements were used to evaluate and compare cephalometric characteristics associated with TMD among groups. Panoramic radiographs were analyzed to compare the presence of condylar abnormalities and antegonial notching among groups. STATISTICAL ANALYSIS USED: One-way analysis of variance, followed by Tukey's test. RESULTS: African and Chinese groups had the smallest mean cranial base measurements, while the Indians had the largest. The mean Y-axis value was significantly larger in the Chinese group compared with the other groups. Increased mandibular plane angles were seen in the Chinese and African patients, compared with subjects from other groups. The mean percentage of condylar anomalies was higher in the Chinese subjects compared with all other groups. CONCLUSIONS: Chinese patients presented with more radiographic features suggestive of TMD, whereas the Indians showed the least, compared with subjects from the White, Black, and Hispanic racial groups.


Assuntos
Cefalometria/métodos , Etnicidade , Assimetria Facial/diagnóstico por imagem , Radiografia Panorâmica , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/etnologia , Adolescente , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Asiático/estatística & dados numéricos , Cefalometria/estatística & dados numéricos , Assimetria Facial/etnologia , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Indígenas Norte-Americanos/estatística & dados numéricos , Masculino , Radiografia , Estudos Retrospectivos , População Branca/estatística & dados numéricos
19.
J Postgrad Med ; 63(4): 268-270, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28272076

RESUMO

Sheehan's syndrome (SS) develops as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage and is characterized by various degrees of hypopituitarism. Although the occurrence of SS is now rare, it should still be considered in any woman with a history of peripartum hemorrhage who develops manifestations of pituitary hormone deficiency any time following the event. Appropriate hormone replacement therapy results in marked clinical improvement. We present an unusual case of SS in a young lady who continued to have normal menstruation after the index event, had two spontaneous pregnancies, and was diagnosed only 11 years later when she presented to us with acute heart failure.


Assuntos
Insuficiência Adrenal/etiologia , Síndrome da Sela Vazia/diagnóstico por imagem , Doenças Genéticas Inatas/etiologia , Glucocorticoides/uso terapêutico , Insuficiência Cardíaca/etiologia , Hipopituitarismo/diagnóstico , Transtornos da Lactação/etiologia , Prolactina/deficiência , Tiroxina/uso terapêutico , Adulto , Cardiomiopatia Dilatada/diagnóstico por imagem , Eletrocardiografia , Feminino , Humanos , Hipopituitarismo/complicações , Hipopituitarismo/tratamento farmacológico , Hipotireoidismo , Imageamento por Ressonância Magnética
20.
Klin Khir ; (2): 45-7, 2017.
Artigo em Ucraniano | MEDLINE | ID: mdl-30272941

RESUMO

There were studied the skin specimen from 40 dead persons, aged from 23 to 87 yrs, (52 ± 15.6) yrs at average, with the objective to investigate the biochemical properties and establishment of experimental deformation angles. Basing on the biomechanical tissues background of the anterior abdominal wall topographo-anatomic regions there were analyzed the results of treatment in the patients, оperated on for the anterior wall deformities and defects, concerning biomechanical possibilities of the flaps and classic methods of the tissues mobilization applied. There was established, that in borders of possible plastic deformity the tissues pressure distribution have persisted in normal range, and this have promoted the cicatricial tissue formation, which did not differ in characteristics from the adjacent connective tissues structures, what have had guaranteed the uncomplicated course of the wound process. Biomechanical properties of adiposo-cutaneous flaps must be taken into account while manipulating with them with the objective of obtaining an optimal distribution of pressure along the flaps and conditions for obtaining of the tissues adequate reaction on operative trauma, while performing interventions on the anterior abdominal wall for its defects and deformities, guaranteeing better esthetic result of treatment, reduction of postoperative morbidity and stationary stay.


Assuntos
Parede Abdominal/cirurgia , Abdominoplastia/métodos , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele/métodos , Retalhos Cirúrgicos/transplante , Parede Abdominal/anormalidades , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Fenômenos Biomecânicos , Cicatriz/patologia , Cicatriz/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Cicatrização/fisiologia
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