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1.
Cureus ; 16(5): e60119, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38864061

RESUMO

Coronary artery disease (CAD) is still a serious global health issue that has a substantial impact on death and illness rates. The goal of primary prevention strategies is to lower the risk of developing CAD. Nevertheless, current methods usually rely on simple risk assessment instruments that might overlook significant individual risk factors. This limitation highlights the need for innovative methods that can accurately assess cardiovascular risk and offer personalized preventive care. Recent advances in machine learning and artificial intelligence (AI) have opened up interesting new avenues for optimizing primary preventive efforts for CAD and improving risk prediction models. By leveraging large-scale databases and advanced computational techniques, AI has the potential to fundamentally alter how cardiovascular risk is evaluated and managed. This review looks at current randomized controlled studies and clinical trials that explore the application of AI and machine learning to improve primary preventive measures for CAD. The emphasis is on their ability to recognize and include a range of risk elements in sophisticated risk assessment models.

2.
J Endod ; 50(7): 976-981, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38522577

RESUMO

INTRODUCTION: The aim of this study was to investigate the feasibility of a real-time three-dimensional dynamic navigation system (3D-DNS) for post space preparation (PSP) in root canal-treated teeth and to compare the accuracy and efficiency of 3D-DNS to freehand (FH) for PSP. METHODS: Fifty-four maxillary molars were divided into two groups: 3D-DNS (n = 27) and FH group (n = 27). Cone beam computed tomography (CBCT) scans were taken preoperatively and postoperatively. The drilling path for the PSP was virtually planned in the preoperative CBCT scan in the X-guide software (X-Nav Technologies, Lansdale, PA). For the 3D-DNS group, the PSP drilling was conducted under dynamic navigation. The 3D deviations and angular deflections were calculated. The residual dentin thickness (RDT) was determined after PSP. The operation time and the total number of mishaps were recorded. Shapiro-Wilk, t-test or Mann-Whitney rank sum, weighted Cohen's kappa, and Fisher exact tests were used (P < .05). RESULTS: The PSP was completed in all samples (54/54). The 3D-DNS was more accurate than the FH, with significantly fewer 3D deviations and angular deflections (all, P < .05). The 3D-DNS required less operating time than the FH (P < .05). For the 3D-DNS, no teeth had RDT < 1 mm, whereas 6/27 in the FH showed RDT < 1 mm after the PSP. There was no difference in the total number of mishaps (P > .05). CONCLUSION: Within the limitations of this in vitro study, the 3D-DNS is feasible for PSP. The 3D-DNS improved the accuracy and efficiency of PSP. The dynamic navigation system can potentially become a safe and reliable technology for PSP.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Imageamento Tridimensional , Humanos , Imageamento Tridimensional/métodos , Técnicas In Vitro , Dente Molar/diagnóstico por imagem , Técnica para Retentor Intrarradicular , Preparo de Canal Radicular/métodos , Preparo de Canal Radicular/instrumentação , Estudos de Viabilidade , Tratamento do Canal Radicular/métodos
3.
Sci Total Environ ; 926: 171908, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38527533

RESUMO

The current study examined the level of Polychlorinated biphenyls (PCBs) in tumor and blood serum of female breast cancer patients and control individuals recruited from Punjab, Pakistan. Breast tumor and blood serum from 40 patients and only blood serum from ten control subjects were obtained and concentration of 32 PCB congeners was analyzed through Gas chromatography coupled with Mass spectrophotometry. Sociodemographic variables of the patients along with essential clinical and haematological parameters were taken as covariates. Tumor reflects the highest median (min-max) concentration (ng g-1 lw) of Æ©PCBs at 115.94 (0.05-17.75) followed by 16.53 (0.09-2.94) and 5.24 (0.01-0.59) in blood serum of cancer patients and control group respectively. Median concentrations (ng g-1 lw) of non-dioxine like Æ©PCBs were considerably higher at 83.04, 32.89 and 4.27 compared to 13.03 and 3.50 and 0.97 for dioxin like Æ©PCBs in tumor, serum of breast cancer patients and control subjects respectively. PCB-87 was most dominant congeners in tumor followed by PCB-170 and -82 whereas PCB-28 and -52 reflected greatest contribution in serum of breast cancer patients. Blood haemoglobin, potassium and chloride ions showed significant positive whereas body mass index reflect inverse relationship when regressed with Æ©PCBs in tumor. This pioneer study depicts elevated concentrations of PCBs in patients compared to control, reflecting potential positive association of PCBs with breast cancer which need further confirmation. We concluded that chronic exposure to PCBs might be associated with an increasing number of breast cancer incidences in developing countries like Pakistan, which should be further elucidated through detail in vitro and in vivo studies.


Assuntos
Neoplasias da Mama , Poluentes Ambientais , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Humanos , Feminino , Bifenilos Policlorados/análise , Neoplasias da Mama/epidemiologia , Soro/química , Paquistão/epidemiologia , Dibenzodioxinas Policloradas/análise , Poluentes Ambientais/análise
4.
J Endod ; 50(6): 844-851, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38369102

RESUMO

INTRODUCTION: This study evaluates the feasibility of an augmented reality (AR) head-mounted device (HMD) displaying a dynamic navigation system (DNS) in the surgical site for fiber postremoval in maxillary molars and compares it to the DNS technique. METHODS: Fifty maxillary first molars were divided into 2 groups: AR HMD + DNS (n = 25) and DNS (n = 25). The palatal canal was restored with RelyX fiber post (3M ESPE) luted with RelyX Unicem (3M ESPE). A core buildup was performed using Paracore (Coltene/Whaledent). Cone beam computed tomography (CBCT) scans were taken before and after postremoval. The drilling trajectory and depth were planned under X-guide software (X-Nav Technologies, Lansdale, PA). For the AR HMD + DNS group, the AR HMD (Microsoft HoloLens 2) displayed the DNS in the surgical site. The three dimensional (3D) deviations (Global coronal deviation [GCD] and global apical deviation [GAD]) and angular deflection (AD) were calculated. The number of mishaps and operating time were recorded. RESULTS: Fiber post was removed from all samples (50/50). The AR HMD + DNS was more accurate than DNS, showing significantly lower GCD and GAD deviations and AD (P < .05). No mishap was detected. The AR HMD + DNS was as efficient in time as DNS (P > .05). CONCLUSIONS: Within the limitations of this in vitro study, the AR HMD can safely display DNS in the surgical site for fiber post-removal in maxillary molars. AR HMD improved the DNS accuracy. Both AR HMD + DNS and DNS were time-efficient for fiber postremoval in maxillary molars.


Assuntos
Realidade Aumentada , Tomografia Computadorizada de Feixe Cônico , Maxila , Dente Molar , Humanos , Maxila/cirurgia , Cirurgia Assistida por Computador/métodos , Estudos de Viabilidade
5.
Am J Physiol Renal Physiol ; 326(1): F57-F68, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37916285

RESUMO

Tolvaptan, a vasopressin antagonist selective for the V2-subtype vasopressin receptor (V2R), is widely used in the treatment of hyponatremia and autosomal-dominant polycystic kidney disease (ADPKD). Its effects on signaling in collecting duct cells have not been fully characterized. Here, we perform RNA-seq in a collecting duct cell line (mpkCCD). The data show that tolvaptan inhibits the expression of mRNAs that were previously shown to be increased in response to vasopressin including aquaporin-2, but also reveals mRNA changes that were not readily predictable and suggest off-target actions of tolvaptan. One such action is activation of the MAPK kinase (ERK1/ERK2) pathway. Prior studies have shown that ERK1/ERK2 activation is essential in the regulation of a variety of cellular and physiological processes and can be associated with cell proliferation. In immunoblotting experiments, we demonstrated that ERK1/ERK2 phosphorylation in mpkCCD cells was significantly reduced by vasopressin, in contrast to the increases seen in non-collecting-duct cells overexpressing V2R in prior studies. We also found that tolvaptan has a strong effect to increase ERK1/ERK2 phosphorylation in the presence of vasopressin and that tolvaptan's effect to increase ERK1/ERK2 phosphorylation is absent in mpkCCD cells in which both protein kinase A (PKA)-catalytic subunits have been deleted. Thus, it appears that the tolvaptan effect to increase ERK activation is PKA-dependent and is not due to an off-target effect of tolvaptan. We conclude that in cells expressing V2R at endogenous levels: 1) vasopressin decreases ERK1/ERK2 activation; 2) in the presence of vasopressin, tolvaptan increases ERK1/ERK2 activation; and 3) these effects are PKA-dependent.NEW & NOTEWORTHY Vasopressin is a key hormone that regulates the function of the collecting duct of the kidney. ERK1 and ERK2 are enzymes that play key roles in physiological regulation in all cells. The authors used collecting duct cell cultures to investigate the effects of vasopressin and the vasopressin receptor antagonist tolvaptan on ERK1 and ERK2 phosphorylation and activation.


Assuntos
Sistema de Sinalização das MAP Quinases , Receptores de Vasopressinas , Tolvaptan/farmacologia , Tolvaptan/metabolismo , Receptores de Vasopressinas/metabolismo , Fosforilação , Rim/metabolismo , Antagonistas dos Receptores de Hormônios Antidiuréticos/farmacologia , Antagonistas dos Receptores de Hormônios Antidiuréticos/metabolismo , Vasopressinas/farmacologia , Vasopressinas/metabolismo
6.
ACS Omega ; 8(38): 34458-34470, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37779929

RESUMO

Some new transition metal complexes were prepared by reacting metal(II) salts with Schiff base azines, which were prepared via condensation of 5-(diethylamino) salicylaldehyde and hydrazine with pyrrole-2-carbaldehyde. Their structures were confirmed based on CHN, UV-visible, FT-IR, and EPR measurements. The complexes were also assessed for their antibacterial, antioxidant, and anticancer properties. Some of these chemicals were said to be extraordinarily effective in this respect. The antibacterial activities of the complexes in vitro demonstrated their potential, although the [Cu(L)(bpy] complex was suggested to exhibit moderate activity against pathogens compared to all other in this series. The cytotoxic activity of the prepared analogues showed better cell viability compared with standard cisplatin. Moreover, there is a good agreement between the experimental and theoretical findings from docking and theoretical investigations done using DFT at the B3LYP level.

8.
Cancers (Basel) ; 15(18)2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37760488

RESUMO

Multiple myeloma (MM) induces dysfunctional bone marrow (BM) mesenchymal cells and neoangiogenesis. Pericytes and smooth muscle cells (SMCs) could detach from vessels and become cancer-associated fibroblasts. We found that the pericyte and SMC marker endothelin receptor type A (EDNRA) is overexpressed in whole MM bone biopsies; we sought to characterize its expression. EDNRA expression gradually increased with disease progression. High-risk MM patients had higher EDNRA expression than low-risk MM patients and EDNRA expression was highest in focal lesions. High EDNRA expression was associated with high expression of pericyte markers (e.g., RGS5, POSTN, and CD146) and the angiogenic marker FLT1. A single-cell analysis of unexpanded BM mesenchymal cells detected EDNRA expression in a subset of cells that coexpressed mesenchymal cell markers and had higher expression of proliferation genes. Immunohistochemistry revealed that the number of EDNRA+ cells in the interstitial BM increased as MM progressed; EDNRA+ cells were prevalent in areas near the MM focal growth. EDNRA+ cells were detached from CD34+ angiogenic cells and coexpressed RGS5 and periostin. Therefore, they likely originated from pericytes or SMCs. These findings identify a novel microenvironmental biomarker in MM and suggest that the presence of detached EDNRA+ cells indicates disrupted vasculature and increased angiogenesis.

9.
Leuk Res ; 133: 107355, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37499483

RESUMO

Bone marrow mesenchymal stem cells (MSCs) may have contrasting impacts on the progression of multiple myeloma (MM). Priming normal MSCs, by culturing them with MM cells, mimics the MSC-induced MM growth. We studied the contrasting effects of conditioned medium (CM) from unprimed or primed MSCs on growth of MM cells from newly diagnosed cases. We elucidated potential molecular pathways using global gene expression profiling and focused on the role of the mTOR2 component, RICTOR, as a novel mediator of dormancy in MM. Primed MSCs CM consistently increased proportions of proliferating cells and supported MM growth in 3-day (n = 20) and 10-day (n = 12) cultures, effects that were partially mediated through the IGF1 axis. In contrast, unprimed MSCs CM inhibited growth of MM cells in cases mainly from stages I/II MM. The genes most overexpressed in MM cells treated with primed MSCs CM were associated with cell cycle, DNA-damage repair, and proliferation; genes most overexpressed in MM cells treated with unprimed MSCs CM were associated with dormancy pathways including RICTOR (mTOR2 pathway), CXCR4, and BCL2. RICTOR protein level was induced by unprimed MSCs CM and was lower in KI67+ proliferating MM cells treated with primed MSCs CM. RICTOR was underexpressed in clinical relapse samples compared with baseline samples of the same patients. Inhibiting RICTOR expression in primary MM cells promoted their growth, and enforced expression of RICTOR in MM cell lines inhibited their growth. Our findings suggest that, after prolonged interactions with MM cells, bone marrow MSCs shift from MM-repressive to MM-permissive. AVAILABILITY OF DATA AND MATERIALS: Our institutional GEP data of MM cells from newly diagnosed patients used to show RICTOR expression have been deposited at Gene Expression Omnibus (GEO: GSE2658, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE2658).


Assuntos
Células-Tronco Mesenquimais , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Recidiva Local de Neoplasia/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fatores de Transcrição/metabolismo , Perfilação da Expressão Gênica , Proliferação de Células
10.
ACS Omega ; 8(23): 20389-20403, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37332804

RESUMO

In recent years, cheaply available cementitious materials (CMs) are increasingly finding useful applications in construction engineering. This manuscript focused on the development and fabrication of unsaturated polyester resin (UPR)/cementitious material composites to be potentially useful in a variety of construction applications. For this purpose, five types of powders from widely available fillers, i.e., black cement (BC), white cement (WC), plaster of Paris (POP), sand (S), and pit sand (PS), were used. Cement polymer composite (CPC) specimens were prepared by a conventional casting process with various filler contents of 10, 20, 30, and 40 wt %. Neat UPR and CPCs were investigated mechanically by testing their tensile, flexural, compressive, and impact properties. Electron microscopy analysis was used to analyze the relation between the microstructure and mechanical properties of CPCs. The assessment of water absorption was conducted. The highest tensile, flexural, compressive upper yield, and impact strength values were recorded for POP/UPR-10, WC/UPR-10, WC/UPR-40, and POP/UPR-20, respectively. The highest percentages of water absorption were found to be 6.202 and 5.07% for UPR/BC-10 and UPR/BC-20, while the lowest percentages were found to be 1.76 and 1.84% for UPR/S-10 and UPR/S-20, respectively. Based on the finding of this study, the properties of CPCs were found to depend on not only the filler content but also the distribution, particle size, and combination between the filler and the polymer.

12.
Curr Probl Cardiol ; 48(7): 101675, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36870550

RESUMO

With the emergence of the largest randomized control trial to date-the Stroke Protection With Sentinel During Transcatheter Aortic Valve Replacement (PROTECTED TAVR) study-we sought to conduct an updated meta-analyses to evaluate the utility of CEP devices on both clinical outcomes and neuroimaging parameters. Electronic databases were queried through November 2022 for clinical trials comparing the utility of Cerebral Embolic Protection (CEP) devices in Transcatheter Aortic Valve Replacement (TAVR) with non-CEP TAVR procedures. Meta-analyses were performed using the generic inverse variance technique, and a random-effects model, and results are presented as weighted mean differences (WMD) for continuous outcomes, and hazard ratios (HR) for dichotomous outcomes. Outcomes of interest included stroke, disabling stroke, nondisabling stroke, bleeding, mortality, vascular complications, new ischemic lesions, acute kidney injury (AKI), and total lesion volume. Thirteen studies (8 RCTs, 5 observational studies) consisting of 128,471 patients were included in the analysis. Results from our meta-analyses showed a significant reduction in stroke (OR: 0.84 [0.74-0.95]; P < 0.01; I2 = 0%), disabling stroke (OR: 0.37 [0.21-0.67]; P < 0.01; I2 = 0%) and bleeding events (OR: 0.91 [0.83-0.99]; P = 0.04; I2 = 0%) through CEP device use in TAVR. The use of CEP devices had no significant impact on nondisabling stroke (OR: 0.94 [0.65-1.37]; P < 0.01; I2 = 0%), mortality (OR: 0.78 [0.53-1.14]; P < 0.01; I2 = 17%), vascular complications (OR: 0.99 [0.63-1.57]; P < 0.01; I2 = 28%), AKI (OR: 0.78 [0.46-1.32]; P < 0.01; I2 = 0%), new ischemic lesions (MD: -1.72 [-4.01, 0.57]; P < 0.001; I2 = 95%) and total lesion volume (MD: -46.11 [-97.38, 5.16]; P < 0.001; I2 = 81%). The results suggest that CEP device use was associated with a lower risk of disabling stroke and bleeding events in patients undergoing TAVR.


Assuntos
Injúria Renal Aguda , Estenose da Valva Aórtica , Dispositivos de Proteção Embólica , Acidente Vascular Cerebral , Humanos , Resultado do Tratamento , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Valva Aórtica , Fatores de Risco
13.
Life Sci ; 296: 120444, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35245523

RESUMO

Peroxisome proliferator activated receptor alpha (PPAR-α) deletion has been shown to increase blood pressure (BP). We hypothesized that the BP increase in PPAR-α KO mice was mediated by increased expression and activity of basolateral Na+/K+ ATPase (NKA) pump. To address this hypothesis, we treated wild-type (WT) and PPAR-α knockout (KO) mice with a slow-pressor dose of angiotensin II (400 ng/kg·min) for 12 days by osmotic minipump. Radiotelemetry showed no significant differences in baseline mean arterial pressure (MAP) between WT and PPAR-α KO mice; however, by day 12 of infusion, MAP was significantly higher in PPAR-α KO mice (156 ± 16) compared to WT mice (138 ± 11 mmHg). NKA activity and protein expression (α1 subunit) were significantly higher in PPAR-α KO mice compared to WT mice. There was no significant difference in NKA mRNA levels. Angiotensin II further increased the expression and activity of the NKA in both genotypes along with the water channel, aquaporin 1 (Aqp1). In contrast, angiotensin II decreased the expression (64-97% reduction in band density) of sodium­hydrogen exchanger-3 (NHE3), NHE regulatory factor-1 (NHERF1, Slc9a3r1), sodium­potassium-2-chloride cotransporter (NKCC2), and epithelial sodium channel (ENaC) ß- and γ- subunits in the renal cortex of both WT and PPAR-α KO mice, with no difference between genotypes. The sodium-chloride cotransporter (NCC) was also decreased by angiotensin II, but significantly more in PPAR-α KO (59% WT versus 77% KO reduction from their respective vehicle-treated mice). Our results suggest that PPAR-α attenuates angiotensin II-mediated increased blood pressure potentially via reducing expression and activity of the NKA.


Assuntos
Angiotensina II/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Rim/metabolismo , PPAR alfa/genética , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Aquaporina 1/metabolismo , Pressão Sanguínea/fisiologia , Rim/efeitos dos fármacos , Masculino , Camundongos Endogâmicos , Camundongos Knockout , PPAR alfa/metabolismo , Fosfoproteínas/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , ATPase Trocadora de Sódio-Potássio/genética , Membro 1 da Família 12 de Carreador de Soluto/metabolismo
14.
Annu Rev Pharmacol Toxicol ; 62: 595-616, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34579536

RESUMO

Systems biology can be defined as the study of a biological process in which all of the relevant components are investigated together in parallel to discover the mechanism. Although the approach is not new, it has come to the forefront as a result of genome sequencing projects completed in the first few years of the current century. It has elements of large-scale data acquisition (chiefly next-generation sequencing-based methods and protein mass spectrometry) and large-scale data analysis (big data integration and Bayesian modeling). Here we discuss these methodologies and show how they can be applied to understand the downstream effects of GPCR signaling, specifically looking at how the neurohypophyseal peptide hormone vasopressin, working through the V2 receptor and PKA activation, regulates the water channel aquaporin-2. The emerging picture provides a detailedframework for understanding the molecular mechanisms involved in water balance disorders, pointing the way to improved treatment of both polyuric disorders and water-retention disorders causing dilutional hyponatremia.


Assuntos
Receptores de Vasopressinas , Desequilíbrio Hidroeletrolítico , Aquaporina 2/metabolismo , Teorema de Bayes , Humanos , Receptores de Vasopressinas/genética , Receptores de Vasopressinas/metabolismo , Biologia de Sistemas
15.
Int Ophthalmol ; 42(4): 1085-1091, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34800234

RESUMO

PURPOSE: To determine the frequency and risk factors of narrow angles in pseudoexfoliation (PXF) patients. METHODS: A prospective case-control study was conducted during the period from March 2017 to December 2020. Adult patients (above 40 years) presenting with PXF were consecutively enrolled (study group). Cases were matched with individuals above 40 years presenting to a comprehensive ophthalmology clinic without evidence of PXF (control group). RESULTS: We enrolled 196 PXF patients and 98 controls. The occurrence of narrow angles was 25% in the PXF group and 5.1% in the control group (P = 0.0001). Compared to controls, PXF patients were older (72.6 ± 9.6 vs. 64.4 ± 8.5, P < 0.0001) and had a lower mean ACD (2.79 ± 0.4 vs. 3.05 ± 0.4, P < 0.0001). There was no difference in AL measurements between both groups (23.3 ± 1.4 vs. 23.7 ± 1.0, P = 0.0714). After stratification by age group and gender, the risk of narrow angles was higher in PXF patients above 70 years (OR, 4.15; 95% CI, 0.91-23.87; P, 0.044). There was no gender difference in the risk of developing narrow angles. CONCLUSION: Narrow angles are more frequently encountered in PXF patients compared to controls. Advanced age (> 70 years) is significantly associated with an increased likelihood of developing narrow angles.


Assuntos
Síndrome de Exfoliação , Adulto , Idoso , Estudos de Casos e Controles , Síndrome de Exfoliação/epidemiologia , Humanos , Pressão Intraocular , Fatores de Risco
16.
BMJ Open Respir Res ; 8(1)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34728475

RESUMO

BACKGROUND: WHO defines hypoxaemia, a low peripheral arterial oxyhaemoglobin saturation (SpO2), as <90%. Although hypoxaemia is an important risk factor for mortality of children with respiratory infections, the optimal SpO2 threshold for defining hypoxaemia is uncertain in low-income and middle-income countries (LMICs). We derived a SpO2 threshold for hypoxaemia from well children in Bangladesh residing at low altitude. METHODS: We prospectively enrolled well, children aged 3-35 months participating in a pneumococcal vaccine evaluation in Sylhet district, Bangladesh between June and August 2017. Trained health workers conducting community surveillance measured the SpO2 of children using a Masimo Rad-5 pulse oximeter with a wrap sensor. We used standard summary statistics to evaluate the SpO2 distribution, including whether the distribution differed by age or sex. We considered the 2.5th, 5th and 10th percentiles of SpO2 as possible lower thresholds for hypoxaemia. RESULTS: Our primary analytical sample included 1470 children (mean age 18.6±9.5 months). Median SpO2 was 98% (IQR 96%-99%), and the 2.5th, 5th and 10th percentile SpO2 was 91%, 92% and 94%. No child had a SpO2 <90%. Children 3-11 months had a lower median SpO2 (97%) than 12-23 months (98%) and 24-35 months (98%) (p=0.039). The SpO2 distribution did not differ by sex (p=0.959). CONCLUSION: A SpO2 threshold for hypoxaemia derived from the 2.5th, 5th or 10th percentile of well children is higher than <90%. If a higher threshold than <90% is adopted into LMIC care algorithms then decision-making using SpO2 must also consider the child's clinical status to minimise misclassification of well children as hypoxaemic. Younger children in lower altitude LMICs may require a different threshold for hypoxaemia than older children. Evaluating the mortality risk of sick children using higher SpO2 thresholds for hypoxaemia is a key next step.


Assuntos
Altitude , Saturação de Oxigênio , Adolescente , Bangladesh/epidemiologia , Criança , Pré-Escolar , Humanos , Hipóxia/diagnóstico , Hipóxia/epidemiologia , Lactente , Oximetria
17.
J Vis Exp ; (176)2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34723945

RESUMO

Cutaneous T-cell lymphomas (CTCL) are derived from the transformation and uncontrolled proliferation of mature skin-homing T cells, and mycosis fungoides (MF) and Sézary syndrome (SS) represent the most common subtypes. Despite a number of studies on characterizing gene expression, genetic alterations, and epigenetic abnormalities of CTCL, the molecular pathogenesis of MF/SS remains unclear. MF refers to the more common CTCL with a skin-predominance, and is usually limited to skin, whereas SS is an aggressive leukemic variant of CTCL with widespread skin involvement and is characterized by neoplastic distribution mainly involving blood, skin, and lymph node. Focusing on clinical practice, the identification of gene expression biomarkers has enormous potential to improve diagnosis and treatment of MF/SS. Indeed, recent transcriptomic studies have identified potential diagnostic biomarkers from differences in gene expression between normal and malignant T cells, which may improve our understanding of SS biology, and reveal potential therapeutic targets. This manuscript describes a detailed reproducible protocol for the isolation of peripheral blood mononuclear cells from fresh whole blood from patients diagnosed with SS, selection of CD4+ memory T cells (CD4+CD45RO+ T cells), chemical stimulation, and preparation of RNA suitable for transcriptomic profiling to discover novel prognostic molecular markers to gain additional insight in disease etiology. The stimulation using chemical agonist to activate nuclear regulation provides more specific assessment for pathways important in the dynamic transcription regulation and gene expression and eliminates confounding defects that may arise from upstream signaling defects arising from TCR antigen loss at the cell membrane. The data obtained from comparison of transcriptome of unstimulated to stimulated SS T cells unmasks functional regulatory gene expression defects not evident from analysis of quiescent unstimulated cells. Furthermore, the method outlined from this approach can be adapted for studying T cell gene expression defects in other T cell immune diseases.


Assuntos
Síndrome de Sézary , Neoplasias Cutâneas , Linfócitos T CD4-Positivos , Humanos , Leucócitos Mononucleares/patologia , Síndrome de Sézary/diagnóstico , Síndrome de Sézary/genética , Neoplasias Cutâneas/patologia , Transcriptoma
18.
Cureus ; 13(9): e18353, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34725605

RESUMO

OBJECTIVE: To measure the correlation between the ratio of oxygen saturation to fraction of inspired oxygen [SpO2/FiO2 (SF)] and the ratio of partial pressure of oxygen to fraction of inspired oxygen [PaO2/FiO2 (PF)] among children diagnosed with acute respiratory distress syndrome (ARDS). METHODOLOGY:  A cross-sectional study was conducted at the pediatric intensive care unit (PICU), National Institute of Child Health (NICH), Karachi, a tertiary care government hospital, from November 2020 to July 2021. One hundred twenty children (of either gender) having the age range of 2 months to 16 years, admitted to PICU with acute onset of respiratory distress, were included in the study. We measured SpO2, PaO2, FiO2 and calculated SF and PF ratios. SPSS (version 23) (Armonk, NY: IBM Corp) was used to analyze data, and the Spearmen's correlation test was applied to measure the relationship between SF and PF ratios. RESULTS: A total of 120 children were included, the mean age was 40.58±38.88 months and 67 (55.8%) were males. The mean FiO2 was 76.33%, the mean PaO2 and SpO2 were 100.35 mmHg and 94.37%, respectively. The mean PF ratio was 156.34, and the mean SF ratio was 156.45. There was a strong correlation between the SF ratio and the PF ratio (r=0.688; p=0.001). CONCLUSION: This study has shown that there is a strong correlation between the SF and PF ratios, and a statistically substantial agreement has been observed.

19.
Exp Clin Transplant ; 19(7): 651-658, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34325623

RESUMO

OBJECTIVES: COVID-19 has emerged as a global pandemic with significant impacts on health care systems. The present study was conducted to analyze the effects of the COVID-19 pandemic on nephrology and transplant services and clinical training at our center. MATERIALS AND METHODS: This observational study was conducted at the Institute of Kidney Disease and Research Centre (Ahmedabad, India). Our institute is one of the largest tertiary care centers of its kind in India with around 400 total inpatient beds for nephrology, urology, and transplant patients. In 2019, our center had annual outpatient and inpatient numbers of 132 181 and 7471, respectively, and conducted 412 renal transplant procedures. For this study, monthly data on number of outpatients, inpatients, and patients undergoing renal transplant, as well as various nonelective procedures, conducted in 2019 and 2020 were collected and analyzed. We investigated the impact of the COVID-19 pandemic on various non-COVID-19-related health care facilities and on clinical training and research activities at our institute. RESULTS: During the 2020 COVID-19 period, the number of outpatients and inpatients was greatly reduced compared with data from 2019. A similar decrease was seen in patients undergoing hemodialysis, renal transplant, and nonelective procedures at our center. The COVID-19 period also greatly affected clinical training of residents enrolled at our institute and research activities, as a result of focus on COVID-19 as a priority. CONCLUSIONS: The effects of reduced numbers of outpatients and inpatients on workflow, as well as reduced numbers of renal transplants and nonelective procedures on the health of our patients, are unknown. Hence, a strategic scheme is needed to develop new health care models that can help manage the COVID-19 pandemic at present and any further waves arising in the future.


Assuntos
COVID-19 , Atenção à Saúde , Nefropatias , Transplante de Rim/estatística & dados numéricos , Nefrologia/educação , COVID-19/epidemiologia , Humanos , Índia/epidemiologia , Nefropatias/terapia , Estudos Prospectivos
20.
Am J Physiol Cell Physiol ; 321(3): C507-C518, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34191628

RESUMO

The fluid in the 14 distinct segments of the renal tubule undergoes sequential transport processes that gradually convert the glomerular filtrate into the final urine. The solute carrier (SLC) family of proteins is responsible for much of the transport of ions and organic molecules along the renal tubule. In addition, some SLC family proteins mediate housekeeping functions by transporting substrates for metabolism. Here, we have developed a curated list of SLC family proteins. We used the list to produce resource webpages that map these proteins and their transcripts to specific segments along the renal tubule. The data were used to highlight some interesting features of expression along the renal tubule including sex-specific expression in the proximal tubule and the role of accessory proteins (ß-subunit proteins) that are thought to be important for polarized targeting in renal tubule epithelia. Also, as an example of application of the data resource, we describe the patterns of acid-base transporter expression along the renal tubule.


Assuntos
Nefropatias/genética , Glomérulos Renais/metabolismo , Medula Renal/metabolismo , Túbulos Renais/metabolismo , Organoides/metabolismo , Proteínas Carreadoras de Solutos/genética , Animais , Transporte Biológico , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Taxa de Filtração Glomerular , Humanos , Nefropatias/metabolismo , Nefropatias/patologia , Glomérulos Renais/patologia , Medula Renal/patologia , Túbulos Renais/patologia , Masculino , Camundongos , Anotação de Sequência Molecular , Organoides/patologia , Fatores Sexuais , Análise de Célula Única , Proteínas Carreadoras de Solutos/classificação , Proteínas Carreadoras de Solutos/metabolismo
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