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1.
Int J Gen Med ; 17: 669-683, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435115

RESUMO

Introduction: Gastroesophageal reflux disease (GERD) and functional constipation (FC) are two common gastrointestinal disorders that affect many age groups in the community. A few studies were conducted to find the association between GERD and FC, but no study had been conducted in Saudi Arabia. Therefore, this study aims to find the overlap between GERD and FC and associated risk factors among the general population in the Eastern Province, Saudi Arabia. Methods: A cross-sectional study was conducted in the eastern province of Saudi Arabia between August and September 2022. GERDQ and Rome IV criteria were used to collect the data with participants' characteristics through an online questionnaire. Results: Out of 2007 respondents, 1481 filled the required criteria, among them 320 (21.6%) had GERD, and 1292 (87.2%) respondents had FC based on the listed criteria. Eighty percent of respondents with GERD had overlapping FC. Men were more likely than women to experience this significant relationship (53.1% versus 46.9%). Conclusion: There is a significant relationship between GERD and FC among the general population of the eastern province of Saudi Arabia. Consequently, this study could be used to improve the understanding of the overlapping between these gastrointestinal disorders and further new guidelines could be carried out to find the best treatment for these patients.

2.
PLoS One ; 18(11): e0290698, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37943868

RESUMO

The study highlights the potential characteristics of droughts under future climate change scenarios. For this purpose, the changes in Standardized Precipitation Evapotranspiration Index (SPEI) under the A1B, A2, and B1 climate change scenarios in Iran were assessed. The daily weather data of 30 synoptic stations from 1992 to 2010 were analyzed. The HadCM3 statistical model in the LARS-WG was used to predict the future weather conditions between 2011 and 2112, for three 34-year periods; 2011-2045, 2046-2079, and 2080-2112. In regard to the findings, the upward trend of the potential evapotranspiration in parallel with the downward trend of the precipitation in the next 102 years in three scenarios to the base timescale was transparent. The frequency of the SPEI in the base month indicated that 17.02% of the studied months faced the drought. Considering the scenarios of climate change for three 34-year periods (i.e., 2011-2045, 2046-2079, and 2080-2112) the average percentages of potential drought occurrences for all the stations in the next three periods will be 8.89, 16.58, and 27.27 respectively under the B1 scenario. While the predicted values under the A1B scenario are 7.63, 12.66, and 35.08%respectively. The relevant findings under the A2 scenario are 6.73, 10.16, 40.8%. As a consequence, water shortage would be more serious in the third period of study under all three scenarios. The percentage of drought occurrence in the future years under the A2, B1, and A1B will be 19.23%, 17.74%, and 18.84%, respectively which confirms the worst condition under the A2 scenario. For all stations, the number of months with moderate drought was substantially more than severe and extreme droughts. Considering the A2 scenario as a high emission scenario, the analysis of SPEI frequency illustrated that the proportion of dry periods in regions with humid and cool climate is more than hot and warm climates; however, the duration of dry periods in warmer climates is longer than colder climates. Moreover, the temporal distribution of precipitation and potential evapotranspiration indicated that in a large number of stations, there is a significant difference between them in the middle months of the year, which justifies the importance of prudent water management in warm months.


Assuntos
Mudança Climática , Secas , Irã (Geográfico) , Tempo (Meteorologia) , Modelos Estatísticos , Água
3.
Int J Surg Case Rep ; 113: 109062, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37980775

RESUMO

INTRODUCTION AND IMPORTANCE: Acral lentiginous melanoma (ALM), the least common subtype of cutaneous melanoma, poses challenges in early detection, resulting in low survival rates. Subungual melanoma (SUM), a rare form of ALM originating from the nail matrix, is less common on the hands than on the feet, accounting in the hands for only 0.3 % of all cutaneous melanomas. This makes the case of hand subungual melanoma that we are presenting very rare and significant. CASE PRESENTATION: A 64-year-old woman presented with an asymptomatic subungual lesion on her left fifth finger. The lesion, ranging in color from brown to black, did not cause bleeding and exhibited a clear nail plate rupture. An incisional biopsy confirmed the diagnosis of subungual melanoma. The patient underwent a proximal interphalangeal (PIP) joint amputation and remains in good health. Regular CT scans and clinical examination have shown no recurrence. CLINICAL DISCUSSION: Subungual melanoma, a rare subtype of acral lentiginous melanoma, comprises less than 1 % of all melanomas. While the Hallux and thumb are commonly affected, our case involved the little finger which is the rarest site of hand subungual melanoma. Occurrence ages are between 50 and 70. The Hutchinson sign, nail fold pigmentation, indicates poor prognosis in advanced stages, which was positive in our case. Recommended management is amputation at the level of the most distal unaffected joint. CONCLUSION: Our aim is to raise healthcare professionals' awareness of early recognition and management of subungual melanoma. Early detection and treatment reduce metastasis risk and improve survival rates.

4.
Curr Radiopharm ; 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37877507

RESUMO

Crocetin is a kind of apocarotenoid carboxylic acid extracted from saffron (Crocus sativus L.), which is effective in upregulating tissue oxygenation. However, crocetin is difficult to solubilize. It was shown that the trans isomer of crocetin is effective in improving oxygen diffusivity, while its cis isomer appears not to be. Hence, the isolated trans isomer of crocetin or trans-sodium crocetinate (TSC) can be used instead of crocetin. It is shown that TSC can upregulate hypoxic tissue oxygenation and be effective in treating some hypoxia-related diseases. Moreover, experimental and clinical studies have reported no adverse effects following TSC treatment, even at high doses. The current study will discuss the potential role of TSC in hemorrhagic shock, ischemia, brain tumor radiotherapy, and others.

5.
Fundam Clin Pharmacol ; 37(6): 1092-1108, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37402635

RESUMO

BACKGROUND: Tamoxifen (TAM) is often recommended as a first-line treatment for estrogen receptor-positive breast cancer (BC). However, TAM resistance continues to be a medical challenge for BC with hormone receptor positivity. The function of macro-autophagy and autophagy has recently been identified to be altered in BC, which suggests a potential mechanism for TAM resistance. Autophagy is a cellular stress-induced response to preserve cellular homeostasis. Also, therapy-induced autophagy, which is typically cytoprotective and activated in tumor cells, could sometimes be non-protective, cytostatic, or cytotoxic depending on how it is regulated. OBJECTIVE: This review explored the literature on the connections between hormonal therapies and autophagy. We investigated how autophagy could develop drug resistance in BC cells. METHODS: Scopus, Science Direct, PubMed, and Google Scholar were used to search articles for this study. RESULTS: The results demonstrated that protein kinases such as pAMPK, BAX, and p-p70S6K could be a sign of autophagy in developing TAM resistance. According to the study's findings, autophagy plays an important role in BC patients' TAM resistance. CONCLUSION: Therefore, by overcoming endocrine resistance in estrogen receptor-positive breast tumors, autophagy inhibition may improve the therapeutic efficacy of TAM.


Assuntos
Neoplasias da Mama , Tamoxifeno , Humanos , Feminino , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Neoplasias da Mama/metabolismo , Receptores de Estrogênio/uso terapêutico , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Autofagia , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral
6.
EMBO Rep ; 23(12): e54978, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36321428

RESUMO

Mitochondrial Ca2+ ions are crucial regulators of bioenergetics and cell death pathways. Mitochondrial Ca2+ content and cytosolic Ca2+ homeostasis strictly depend on Ca2+ transporters. In recent decades, the major players responsible for mitochondrial Ca2+ uptake and release have been identified, except the mitochondrial Ca2+ /H+ exchanger (CHE). Originally identified as the mitochondrial K+ /H+ exchanger, LETM1 was also considered as a candidate for the mitochondrial CHE. Defining the mitochondrial interactome of LETM1, we identify TMBIM5/MICS1, the only mitochondrial member of the TMBIM family, and validate the physical interaction of TMBIM5 and LETM1. Cell-based and cell-free biochemical assays demonstrate the absence or greatly reduced Na+ -independent mitochondrial Ca2+ release in TMBIM5 knockout or pH-sensing site mutants, respectively, and pH-dependent Ca2+ transport by recombinant TMBIM5. Taken together, we demonstrate that TMBIM5, but not LETM1, is the long-sought mitochondrial CHE, involved in setting and regulating the mitochondrial proton gradient. This finding provides the final piece of the puzzle of mitochondrial Ca2+ transporters and opens the door to exploring its importance in health and disease, and to developing drugs modulating Ca2+ exchange.


Assuntos
Antiporters , Prótons , Antiporters/genética
7.
Am J Hum Genet ; 109(9): 1692-1712, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36055214

RESUMO

Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) encodes an inner mitochondrial membrane protein with an osmoregulatory function controlling mitochondrial volume and ion homeostasis. The putative association of LETM1 with a human disease was initially suggested in Wolf-Hirschhorn syndrome, a disorder that results from de novo monoallelic deletion of chromosome 4p16.3, a region encompassing LETM1. Utilizing exome sequencing and international gene-matching efforts, we have identified 18 affected individuals from 11 unrelated families harboring ultra-rare bi-allelic missense and loss-of-function LETM1 variants and clinical presentations highly suggestive of mitochondrial disease. These manifested as a spectrum of predominantly infantile-onset (14/18, 78%) and variably progressive neurological, metabolic, and dysmorphic symptoms, plus multiple organ dysfunction associated with neurodegeneration. The common features included respiratory chain complex deficiencies (100%), global developmental delay (94%), optic atrophy (83%), sensorineural hearing loss (78%), and cerebellar ataxia (78%) followed by epilepsy (67%), spasticity (53%), and myopathy (50%). Other features included bilateral cataracts (42%), cardiomyopathy (36%), and diabetes (27%). To better understand the pathogenic mechanism of the identified LETM1 variants, we performed biochemical and morphological studies on mitochondrial K+/H+ exchange activity, proteins, and shape in proband-derived fibroblasts and muscles and in Saccharomyces cerevisiae, which is an important model organism for mitochondrial osmotic regulation. Our results demonstrate that bi-allelic LETM1 variants are associated with defective mitochondrial K+ efflux, swollen mitochondrial matrix structures, and loss of important mitochondrial oxidative phosphorylation protein components, thus highlighting the implication of perturbed mitochondrial osmoregulation caused by LETM1 variants in neurological and mitochondrial pathologies.


Assuntos
Proteínas de Ligação ao Cálcio , Doenças Mitocondriais , Proteínas de Ligação ao Cálcio/genética , Homeostase/genética , Humanos , Proteínas de Membrana/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Doenças Mitocondriais/genética , Doenças Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Sistema Nervoso/metabolismo , Saccharomyces cerevisiae/metabolismo
8.
Front Public Health ; 10: 914943, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35899168

RESUMO

Objectives: Preventing severe disease and acquiring population immunity to COVID-19 requires global immunization coverage through mass vaccination. While high-income countries are battling vaccine hesitancy, low-income and fragile nations are facing the double dilemma of vaccine hesitancy and lack of access to vaccines. There is inadequate information on any correlation between vaccine hesitancy and access to vaccines. Our study in a low-income nation aimed to fill this gap. Methods: In the backdrop of a severe shortage of COVID-19 vaccines in Yemen, a low-income fragile nation, we conducted a nation-wide cross-sectional survey among its healthcare workers (HCWs), between 6 July and 10 August 2021. We evaluated factors influencing agreement to accept a COVID-19 vaccine and any potential correlation between vaccine acceptance and lack of access to vaccines. Results: Overall, 61.7% (n = 975) of the 1,581 HCWs agreed to accept a COVID-19 vaccine. Only 45.4% of the participants agreed to have access to a COVID-19 vaccine, with no sex dependent variations. Although several determinants of vaccine acceptance were identified, including, having a systemic disease, following the updates about COVID-19 vaccines, complying with preventive guidelines, having greater anxiety about contracting COVID-19, previous infection with COVID-19, believing COVID-19 to be a severe disease, and lower concern about the side effects of COVID-19, the strongest was access to vaccines (OR: 3.18; 95% CI: 2.5-4.03; p-value: 0.001). Conclusion: The immediate and more dangerous threat in Yemen toward achieving population immunity is the severe shortage and lack of access to vaccines, rather than vaccine hesitancy, meaning, improving access to vaccines could lead to greater acceptance.


Assuntos
COVID-19 , Vacinas , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos Transversais , Pessoal de Saúde , Humanos , Aceitação pelo Paciente de Cuidados de Saúde , Vacinação , Hesitação Vacinal
9.
Front Public Health ; 9: 794673, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35211453

RESUMO

Objectives: Even though several effective vaccines are available to combat the COVID-19 pandemic, wide disparities in vaccine distribution, and vaccine acceptance rates between high- and low-income countries appear to be major threats toward achieving population immunity. Our global descriptive study aims to inform policymakers on factors affecting COVID-19 vaccine acceptance among healthcare workers (HCWs) in 12 countries, based on income index. We also looked for possible predictors of vaccine acceptance among the study sample. Methods: A structured questionnaire prepared after consultation with experts in the field and guided by the "Report of the SAGE working group on vaccine hesitancy" was administered among 2,953 HCWs. Upon obtaining informed consent, apart from demographic information, we collected information on trust in vaccines and health authorities, and agreement to accept a COVID-19 vaccine. Results: Although 69% of the participants agreed to accept a vaccine, there was high heterogeneity in agreement between HCWs in low and lower-middle income countries (L-LMICs) and upper-middle- and high-income countries (UM-HICs), with acceptance rates of 62 and 75%, respectively. Potential predictors of vaccine acceptance included being male, 50 years of age or older, resident of an UM-HIC, updating self about COVID-19 vaccines, greater disease severity perception, greater anxiety of contracting COVID-19 and concern about side effects of vaccines. Conclusions: COVID-19 vaccine acceptance among HCWs in L-LMICs was considerably low as compared to those from UM-HICs. The lowest vaccine acceptance rates were among HCWs from the African continent. This underlines the need for the implementation of country-specific vaccine promotion strategies, with special focus on increasing vaccine supply in L-LMICs.


Assuntos
Vacinas contra COVID-19 , COVID-19 , COVID-19/prevenção & controle , Estudos Transversais , Pessoal de Saúde , Humanos , Masculino , Pandemias , SARS-CoV-2 , Inquéritos e Questionários
10.
Biomaterials ; 267: 120449, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33129188

RESUMO

The clinical success rate of islet transplantation, namely independence from insulin injections, is limited by factors that lead to graft failure, including inflammation, acute ischemia, acute phase response, and insufficient vascularization. The ischemia and insufficient vascularization both lead to high levels of oxidative stress, which are further aggravated by islet encapsulation, inflammation, and undesirable cell-biomaterial interactions. To identify biomaterials that would not further increase damaging oxidative stress levels and that are also suitable for manufacturing a beta cell encapsulation device, we studied five clinically approved polymers for their effect on oxidative stress and islet (alpha and beta cell) function. We found that 300 poly(ethylene oxide terephthalate) 55/poly(butylene terephthalate) 45 (PEOT/PBT300) was more resistant to breakage and more elastic than other biomaterials, which is important for its immunoprotective function. In addition, it did not induce oxidative stress or reduce viability in the MIN6 beta cell line, and even promoted protective endogenous antioxidant expression over 7 days. Importantly, PEOT/PBT300 is one of the biomaterials we studied that did not interfere with insulin secretion in human islets.


Assuntos
Células Secretoras de Insulina , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Materiais Biocompatíveis/metabolismo , Humanos , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Estresse Oxidativo
11.
MedEdPublish (2016) ; 9: 127, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-38073819

RESUMO

This article was migrated. The article was marked as recommended. In medical education, peer learning has a significant impact on deeper learning and considered an effective method of collaborative and deeper learning. This article highlights the adjustment of the final year medical students to the peer learning style during the COVID-19 pandemic. It explores the additional benefits of peer learning style and recommend key points that can help medical students to combat the current stressful situation. Adaptation to peer learning strategy may help to overcome this stressful situation and motivate each other to focus on studies. This approach can assist medical students to stay in touch with each other, collaborate, communicate, and boost each other morally. The peer learning style provides an opportunity for students to share thoughts and emotional reactions freely and friendly. This way can help to reduce stress and develop resilience. Students get rapid adaptation to technology-enhanced learning smoothly and effectively by helping each other to learn new skills. The feeling of staying connected with peers during the online sessions significantly augmented the ability to combat the crisis and augment social interactions.

12.
Pflugers Arch ; 471(6): 845-860, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30417250

RESUMO

Solute carrier family 41 member A1 (SLC41A1) has been suggested to mediate magnesium (Mg2+) transport by several in vitro studies. However, the physiological function of SLC41A1 remains to be elucidated. In this study, cellular Mg2+ transport assays combined with zebrafish slc41a1 knockdown experiments were performed to disclose SLC41A1 function and its physiological relevance. The gene slc41a1 is ubiquitously expressed in zebrafish tissues and is regulated by water and dietary Mg2+ availability. Knockdown of slc41a1 in zebrafish larvae grown in a Mg2+-free medium resulted in a unique phenotype characterized by a decrease in zebrafish Mg content. This decrease shows that SLC41A1 is required to maintain Mg2+ balance and its dysfunction results in renal Mg2+ wasting in zebrafish larvae. Importantly, the Mg content of the larvae is rescued when mouse SLC41A1 is expressed in slc41a1-knockdown zebrafish. Conversely, expression of mammalian SLC41A1-p.Asp262Ala, harboring a mutation in the ion-conducting SLC41A1 pore, did not reverse the renal Mg2+ wasting. 25Mg2+ transport assays in human embryonic kidney 293 (HEK293) cells overexpressing SLC41A1 demonstrated that SLC41A1 mediates cellular Mg2+ extrusion independently of sodium (Na+). In contrast, SLC41A1-p.Asp262Ala expressing HEK293 cells displayed similar Mg2+ extrusion activities than control (mock) cells. In polarized Madin-Darby canine kidney cells, SLC41A1 localized to the basolateral cell membrane. Our results demonstrate that SLC41A1 facilitates renal Mg2+ reabsorption in the zebrafish model. Furthermore, our data suggest that SLC41A1 mediates both Mg2+ uptake and extrusion.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Magnésio/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Proteínas de Transporte de Cátions/genética , Membrana Celular/metabolismo , Células HEK293 , Homeostase , Humanos , Larva/metabolismo , Camundongos , Peixe-Zebra , Proteínas de Peixe-Zebra/genética
13.
Am J Physiol Renal Physiol ; 315(3): F537-F546, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29767557

RESUMO

The PKD1 gene encodes polycystin-1 (PC1), a mechanosensor triggering intracellular responses upon urinary flow sensing in kidney tubular cells. Mutations in PKD1 lead to autosomal dominant polycystic kidney disease (ADPKD). The involvement of PC1 in renal electrolyte handling remains unknown since renal electrolyte physiology in ADPKD patients has only been characterized in cystic ADPKD. We thus studied the renal electrolyte handling in inducible kidney-specific Pkd1 knockout (iKsp- Pkd1-/-) mice manifesting a precystic phenotype. Serum and urinary electrolyte determinations indicated that iKsp- Pkd1-/- mice display reduced serum levels of magnesium (Mg2+), calcium (Ca2+), sodium (Na+), and phosphate (Pi) compared with control ( Pkd1+/+) mice and renal Mg2+, Ca2+, and Pi wasting. In agreement with these electrolyte disturbances, downregulation of key genes for electrolyte reabsorption in the thick ascending limb of Henle's loop (TA;, Cldn16, Kcnj1, and Slc12a1), distal convoluted tubule (DCT; Trpm6 and Slc12a3) and connecting tubule (CNT; Calb1, Slc8a1, and Atp2b4) was observed in kidneys of iKsp- Pkd1-/- mice compared with controls. Similarly, decreased renal gene expression of markers for TAL ( Umod) and DCT ( Pvalb) was observed in iKsp- Pkd1-/- mice. Conversely, mRNA expression levels in kidney of genes encoding solute and water transporters in the proximal tubule ( Abcg2 and Slc34a1) and collecting duct ( Aqp2, Scnn1a, and Scnn1b) remained comparable between control and iKsp- Pkd1-/- mice, although a water reabsorption defect was observed in iKsp- Pkd1-/- mice. In conclusion, our data indicate that PC1 is involved in renal Mg2+, Ca2+, and water handling and its dysfunction, resulting in a systemic electrolyte imbalance characterized by low serum electrolyte concentrations.


Assuntos
Água Corporal/metabolismo , Eletrólitos/metabolismo , Rim/metabolismo , Rim Policístico Autossômico Dominante/metabolismo , Canais de Cátion TRPP/deficiência , Equilíbrio Hidroeletrolítico , Animais , Cálcio/metabolismo , Modelos Animais de Doenças , Eletrólitos/sangue , Eletrólitos/urina , Regulação da Expressão Gênica , Absorção Intestinal , Rim/fisiopatologia , Magnésio/metabolismo , Masculino , Camundongos Knockout , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/fisiopatologia , Reabsorção Renal , Canais de Cátion TRPP/genética , Equilíbrio Hidroeletrolítico/genética
14.
Int J Appl Basic Med Res ; 8(1): 19-23, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29552530

RESUMO

BACKGROUND: Acinetobacter baumannii, is an emerging nosocomial multidrug resistance pathogen with the rapid spread of clones being reported in health-care settings and hospitals worldwide. Carbapenem resistance in this bacterium has been attributed to D OXA ß-lactamases with OXA-51-like ß-lactamase, being present in all A. baumannii isolate. The present study looks into the antibiotics susceptibility and molecular characterization of clinical A. baumannii isolates from Intensive Care Unit (ICU) samples in Al-Hofuf, South-eastern region of Saudi Arabia. MATERIALS AND METHODS: Eleven strains of ICU A. baumanni i isolates were used for the investigation. Bacteria isolation was by basic microbiological techniques. Organisms identification and antibiogram susceptibility testing was by the BioMerieux VITEK 2 compact automated system (BioMerieux, Marcy I'Etoile France), according to the manufacturers guidelines. Confirmation of A. baumannii was by the presence of the OX-51 gene, also, carbapenemase encoding resistant genesblaOXA-23, blaOXA-40, and blaOXA-51, were analyzed using multiplex PCR. The Student's t test was used to analyze the obtained data for between group comparisons with statistically significance level set at P < 0.05. RESULTS: Eight of the isolates were confirmed to be A. baumannii. Five of which were resistant to the carbapenems against which they had been tested. One isolate was resistant to tigecycline, whereas three tested intermediate to the drug. OXA-23 was detected in isolates 1, 4, 5, 6, and 7. CONCLUSION: It can, therefore, be concluded that the probable predominate carbapenems resistant genes in ICU isolates from the present investigation, are those associated with OXA-23.

15.
FASEB J ; 32(7): 3653-3668, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29452568

RESUMO

Renal tubular cells respond to mechanical stimuli generated by urinary flow to regulate the activity and transcript abundance of important genes for ion handling, cellular homeostasis, and proper renal development. The primary cilium, a mechanosensory organelle, is postulated to regulate this mRNA response. The aim of this study is to reveal the transcriptome changes of tubular epithelia in response to fluid flow and determine the role of primary cilia in this process. Inner-medullary collecting duct (CD) cells were subjected to either static or physiologically relevant fluid flow (∼0.6 dyn/cm2). RNA-sequencing analysis of ciliated cells subjected to fluid flow showed up-regulation of 1379 genes and down-regulation of 1294 genes compared with static control cells. Strikingly, only 54 of these genes were identified as gene candidates sensitive to primary cilia sensing of fluid flow, of which 16 were linked to ion or water transport pathways in the CD. Validation by quantitative real-time PCR revealed that only the expression of transferrin receptor, which is involved in iron transport; and tribbles pseudokinase 3, which is involved in insulin signaling, were unequivocally regulated by primary cilia sensing of fluid flow. This study shows that the involvement of primary cilia in ion transport in the collecting duct is exceptionally specific.-Mohammed, S. G., Arjona, F. J., Verschuren, E. H. J., Bakey, Z., Alkema, W., van Hijum, S., Schmidts, M., Bindels, R. J. M., Hoenderop, J. G. J. Primary cilia-regulated transcriptome in the renal collecting duct.


Assuntos
Cílios/metabolismo , Túbulos Renais Coletores/metabolismo , Transcriptoma , Animais , Linhagem Celular , Túbulos Renais Coletores/citologia , Camundongos , Microfluídica
16.
FASEB J ; 31(5): 1796-1806, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28100643

RESUMO

In kidney, transcellular transport of Ca2+ is mediated by transient receptor potential vanilloid 5 and Na+-Ca2+ exchanger 1 proteins in distal convoluted and connecting tubules (DCTs and CNTs, respectively). It is not yet understood how DCT/CNT cells can adapt to differences in tubular flow rate and, consequently, Ca2+ load. This study aims to elucidate the molecular mechanisms by which DCT/CNT cells sense fluid dynamics to control transepithelial Ca2+ reabsorption and whether their primary cilia play an active role in this process. Mouse primary DCT/CNT cultures were subjected to a physiologic fluid shear stress (FSS) of 0.12 dyn/cm2 Transient receptor potential vanilloid 5 and Na+-Ca2+ exchanger 1 mRNA levels were significantly increased upon FSS exposure compared with static controls. Functional studies with 45Ca2+ demonstrated a significant stimulation of transepithelial Ca2+ transport under FSS compared with static conditions. Primary cilia removal decreased Ca2+ transport in both static and FSS conditions, a finding that correlated with decreased expression of genes involved in transepithelial Ca2+ transport; however, FSS-induced stimulation of Ca2+ transport was still observed. These results indicate that nephron DCT and CNT segments translate FSS into a physiologic response that implicates an increased Ca2+ reabsorption. Moreover, primary cilia influence transepithelial Ca2+ transport in DCTs/CNTs, yet this process is not distinctly coupled to FSS sensing by these organelles.-Mohammed, S. G., Arjona, F. J., Latta, F., Bindels, R. J. M., Roepman, R., Hoenderop, J. G. J. Fluid shear stress increases transepithelial transport of Ca2+ in ciliated distal convoluted and connecting tubule cells.


Assuntos
Cálcio/metabolismo , Resistência ao Cisalhamento/fisiologia , Animais , Transporte de Íons/fisiologia , Rim/metabolismo , Camundongos , Sódio/metabolismo , Trocador de Sódio e Cálcio/metabolismo , Estresse Fisiológico , Canais de Cátion TRPV/metabolismo
17.
Avian Pathol ; 44(5): 333-41, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26023824

RESUMO

Vaccination is the main tool implemented in Egypt since 2007 to control H5N1 avian influenza. The present study aimed at comparing the effectiveness of three avian influenza vaccination regimes in commercial broiler chickens carrying high levels of maternally derived antibodies (MDAs). Day-old chicks were divided into four experimental groups. Group I received only the rHVT-H5 vaccine (recombinant turkey herpesvirus (HVT) which carries a H5 clade 2.2 insert) administered at D1. Group II received only the KV-H5 (an oil emulsion killed vaccine prepared from reassortant HPAI virus (A/duck/Anhui/1/06)) vaccine (inactivated reverse genetic H5N1 clade 2.3.4 virus) administered at D8. Group III received rHVT-H5 and KV-H5 as prime/boost. Group IV served as unvaccinated control. Weekly serological monitoring was conducted using the haemagglutination inhibition test. Two challenge experiments were conducted at D28 and D35 using HPAI H5N1 clade 2.2.1 virus. Birds were monitored daily 14 days post-challenge for morbidity and mortality, and oropharyngeal swabs were collected for virological monitoring. Initially, day-old chicks had high mean MDA titres (9 + 0.9 log2). The MDA half-life was >7 and <7 days, respectively, for unvaccinated and vaccinated birds. Group III showed the highest post-vaccination humoral immune response and seroconversion rate. The highest protection rate against morbidity (80-90%) and mortality (90-90%) was obtained in Group III after challenge at D28 and D35, respectively, as compared to Group I (70-70%) and (80-90%) and Group II (0-0%) and (30-30%). Groups I and III had lower number of shedder birds. The vaccination regime with prime/boost conferred the highest and earliest protection, and can hence be recommended for the broiler production sector in endemic and high HPAI H5N1 challenge areas.


Assuntos
Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Aviária/prevenção & controle , Doenças das Aves Domésticas/prevenção & controle , Vacinação , Animais , Galinhas , Egito , Testes de Inibição da Hemaglutinação , Vacinas contra Influenza/imunologia , Influenza Aviária/epidemiologia , Influenza Aviária/imunologia , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia
18.
Open Access Maced J Med Sci ; 3(2): 250-5, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-27275230

RESUMO

BACKGROUND: IDH1 (isocitrate dehydrogenase 1) mutation might be encounter in the low grade glioma and directs the progression of the tumor to a higher grade. OBJECTIVE: To assess the frequency of IDH1 mutations in gliomas and to correlate the IDH1 positivity with the type and grade of tumors, the age and sex of the patients. MATERIAL AND METHODS: A retro- and prospective case series study. One hundred and nine cases of intracranial gliomas were collected between 2008 and 2014 from Mosul Private Laboratories and Al-Jamboree Teaching Hospitals in Mosul. IDH1 mutations were assessed immunohistochemically using anti-IDH1 R132H mouse monoclonal antibody. RESULTS: IDH1 mutation was perceived in 34.86% of gliomas. In adult gliomas, the secondary glioblastoma and the low-grade astrocytoma had the greatest values of IDH1 positivity (88.88% and 62.5% respectively), followed by oligoastrocytoma/oligodendroglioma (50.0%), and anaplastic astrocytoma (47.36%). The primary glioblastomsa showed 17.64% IDH1 positivity. Males and females expressed the IDH1 equally. While, there was no role of IDH1 in pediatric gliomas. CONCLUSION: IDH1 mutation is commonly present in adult gliomas particularly in low-grade gliomas, and secondary glioblastoma, with equal sex distribution, but it has no role in pediatric gliomas.

19.
J Infect Dev Ctries ; 8(10): 1328-33, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25313611

RESUMO

INTRODUCTION: The current status of percutaneous injury and mucous exposures (PMEs) of hospital workers and factors associated with the injuries have not been studied in Iraq. This study aimed to evaluate the epidemiology of PMEs with blood or body fluids that leads serious risks for healthcare workers (HCWs). METHODOLOGY: An analytic, cross-sectional survey study was conducted among HCWs in Erbil city center, Iraq. The study was performed at sevenhospitals, and 177 participants were included. The dependent variable was the occurrence of PMEs in the last year, and the independent variables were age, sex, occupation of HCWs, working site, and work duration. RESULTS: A total of 177 HCW participants included 57 nurses/midwives (32.2%), 59 doctors (33.3%), 27 laboratory workers (15.3%), and 34 paramedics/multipurpose workers (19.2%) from seven hospitals. The study concluded that 67.8% of the participants reported at least one occupational PME in the last year. In all, 13.3/person/year PME incidents were reported for nurses, 9.74/person/year for paramedics/multipurpose workers, 6.71/person/year for doctors, and 3.37/person/year laboratory workers. The mean number of PME incidents was 8.91/person/year. HCWs showed 85.0% compliance with wearing mask in risky situations. The most dangerous action for occupational exposure was blood taking (39.0%). In the univariate analysis, none of the investigated variables were found to be significantly related to PME. CONCLUSIONS: Occupational injuries and exposures in Iraqi HCWs are extremely common; awareness about protection is not sufficient. Nurses were found to be the highest risk group among HCWs. Preventive actions should be taken to avoid infection.


Assuntos
Líquidos Corporais , Pessoal de Saúde , Exposição Ocupacional/estatística & dados numéricos , Adolescente , Adulto , Atitude do Pessoal de Saúde , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Incidência , Iraque , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
20.
Perm J ; 17(2): 41-3, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23704842

RESUMO

INTRODUCTION: Pain medication use is enormous in those looking for relief of chronic back pain. The impact of long-term analgesia use might serve as a marker for prolonged hospitalization due to undertreating postoperative pain, which could ultimately result in higher health care costs. METHODS: We studied preoperative pain intensity and chronicity and the amount of postoperative analgesia as a marker of length of stay (LOS) in patients undergoing spinal fusion. The charts of patients undergoing cervical or lumbar spinal fusion were reviewed, and data on their intensity of pain at admission and length of pain was documented, as was the amount of morphine used. RESULTS: Regression analysis revealed statistical significance only between LOS and surgical site (neck or lumbar spine). It showed no significance between LOS as the dependent variable and preoperative pain parameter, postoperative morphine per kilogram, sex, or age as predictors. CONCLUSION: Postoperative pain management continues to be a challenge because of the need to balance satisfactory analgesia in patients with the fear of adverse effects due to overdosing. This challenge is even greater in patients with long-term narcotic use. Anecdotally, patients undergoing spinal fusion show an inverse relationship between LOS and amount of use of postoperative pain medication. A more extensive scientific review of current postoperative pain control protocols is warranted in patients undergoing spinal fusion.


Assuntos
Dor nas Costas/tratamento farmacológico , Dor Crônica/tratamento farmacológico , Tempo de Internação/estatística & dados numéricos , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico , Fusão Vertebral , Idoso , Analgésicos Opioides/administração & dosagem , Dor nas Costas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Cuidados Pós-Operatórios , Período Pré-Operatório , Análise de Regressão
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