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1.
Am J Epidemiol ; 193(4): 636-645, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-37968380

ABSTRACT

Extreme climate events are related to women's exposure to different forms of violence. We examined the relationship between droughts and physical, sexual, and emotional intimate partner violence (IPV) in India by using 2 different definitions of drought: precipitation-based drought and socioeconomic drought. We analyzed data from 2 rounds of a nationally representative survey, the National Family Health Survey, where married women were asked about their experiences of IPV in the previous year (2015-2016 and 2019-2021; n = 122,696). Precipitation-based drought was estimated using remote sensing data and geographic information system (GIS) mapping, while socioeconomic drought status was collected from government records. Logistic regression models showed precipitation-based drought to increase the risk of experiencing physical IPV and emotional IPV. Similar findings were observed for socioeconomic drought; women residing in areas classified as drought-impacted by the government were more likely to report physical IPV, sexual IPV, and emotional IPV. These findings support the growing body of evidence regarding the relationship between climate change and women's vulnerability, and highlight the need for gender responsive strategies for disaster management and preparedness.


Subject(s)
Droughts , Intimate Partner Violence , Humans , Female , Risk Factors , Violence , India/epidemiology , Sexual Partners/psychology , Prevalence
2.
Small ; : e2309428, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38529777

ABSTRACT

Bismuth sulfide (Bi2S3) exhibits a direct energy bandgap and an exceptional optical absorption capability over a broadband radiation, thus presents a novel class of 2D photodetector material. The field effect transistor (FET) photodetector device is fabricated from 2D Bi2S3. An anomalous variation in the transport characteristics of 2D Bi2S3 is observed with the variation in temperature. The electrical resistance reduces by 99.26% at 10 K compared to the response at 300 K. Defects due to the bismuth and sulfur vacancies play a critical role in the dramatic behavior, which is confirmed using photoluminescence, time-resolved photoluminescence, Hall measurements, and energy dispersive X-ray spectroscopy. The density functional theory calculations provide a significant insight into the thermodynamic properties of intrinsic defects in Bi2S3. Moreover, the effect of gate bias on responsivity additionally confirms its invariance at low temperature. The Bi2S3 based FET photodetector achieves ultrahigh responsivity in the order of ≈106 A W-1 and detectivity of ≈1014 Jones. Moreover, the external quantum efficiency of ≈107% is measured in a wide spectrum of optical illumination (532 to 1064 nm) with a noise-equivalent power of 3.5 × 10-18 W/√Hz at a bias of 0.2 V. The extraordinary performance of Bi2S3 photodetector outstands 2D photodetectors.

3.
Cytokine ; 173: 156435, 2024 01.
Article in English | MEDLINE | ID: mdl-37950929

ABSTRACT

The excessive production of IL-10, an anti-inflammatory cytokine, by Leishmania antigen-activated T cells is supposed to be a key player in the onset and progression of visceral leishmaniasis (VL). The IL-10-producing sources in VL remain unidentified and uncharacterized. In this study, we reveal that antigen-activated CD4+ T cells, i.e., CD44+CD4+ T cells expressing CD200R receptors, are the prime IL-10-producing phenotypes in Leishmania donovani infection-induced pathogenesis. These phenotypes are separate from CD25+Foxp3+CD4+ T regulatory cells, which are classical IL-10-producing phenotypes. In order to ascertain the role of CD200R and CD25 receptors in IL-10 overexpression-associated VL pathogenesis, we abrogated CD200R and CD25 receptor-mediated signaling in the infected mice. The splenic load of parasites and the size of the liver and spleen were significantly reduced in CD200-blocked mice as compared to CD25-blocked mice. Further, the CD200 blocking polarized CD4+ T cells to pro-inflammatory cytokines-producing phenotypes, as we observed a higher frequency of IFN-γ, TNF-α, and IL-12 positive cells as compared to controls including the CD25 blocking. Our findings suggest that in L. donovani infection-induced pathogenesis the expression of CD200R on antigen-activated T cells helps them to acquire IL-10-producing abilities as part of its one of the survival strategies. However, more studies would be warranted to better understand CD200R receptors role in VL pathogenesis and to develop the next generation of therapeutic and prophylactic control measures.


Subject(s)
Leishmania donovani , Leishmaniasis, Visceral , Animals , Mice , Interleukin-10/metabolism , Cytokines/metabolism , T-Lymphocytes, Regulatory , Phenotype
4.
Mol Pharm ; 21(2): 957-969, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38173336

ABSTRACT

One way to increase the slow dissolution rate and the associated low bioavailability of newly developed active pharmaceutical ingredients (APIs) is to dissolve the API in a polymer, leading to a so-called amorphous solid dispersion (ASD). However, APIs are often supersaturated in ASDs and thus tend to crystallize during storage. The kinetics of the crystallization process is determined by the amount of water the ASD absorbs during storage at relative humidity (RH), storage temperature, polymer type, and the drug load of the ASD. Here, the crystallization kinetics and shelf life of spray-dried ASDs were investigated for ASDs consisting of nifedipine (NIF) or celecoxib (CCX) as the APIs and of poly(vinylpyrrolidone-co-vinyl acetate) or hydroxypropyl methylcellulose acetate succinate as polymers. Samples were stored over 2 years at different RHs covering conditions above and below the glass transition of the wet ASDs. Crystallization kinetics and onset time of the crystallization were qualitatively studied by using powder X-ray diffraction and microscopic inspection and were quantitatively determined by using differential scanning calorimetry. It was found that the NIF ASDs crystallize much faster than CCX ASDs at the same drug load and at the same storage conditions due to both higher supersaturation and higher molecular mobility in the NIF ASDs. Experimental data on crystallization kinetics were correlated using the Johnson-Mehl-Avrami-Kolmogorov equation. A detailed thermodynamic and kinetic modeling will be performed in Part 2 of this paper series.


Subject(s)
Polymers , Water , Crystallization , Water/chemistry , Drug Stability , Solubility , Polymers/chemistry
5.
Mol Pharm ; 21(6): 2908-2921, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38743928

ABSTRACT

The physical stability of amorphous solid dispersions (ASDs) is a major topic in the formulation research of oral dosage forms. To minimize the effort of investigating the long-term stability using cost- and time-consuming experiments, we developed a thermodynamic and kinetic modeling framework to predict and understand the crystallization kinetics of ASDs during long-term storage below the glass transition. Since crystallization of the active phrarmaceutical ingredients (APIs) in ASDs largely depends on the amount of water absorbed by the ASDs, water-sorption kinetics and API-crystallization kinetics were considered simultaneously. The developed modeling approach allows prediction of the time evolution of viscosity, supersaturation, and crystallinity as a function of drug load, relative humidity, and temperature. It was applied and evaluated against two-year-lasting crystallization experiments of ASDs containing nifedipine and copovidone or HPMCAS measured in part I of this work. We could show that the proposed modeling approach is able to describe the interplay between water sorption and API crystallization and to predict long-term stabilities of ASDs just based on short-term measurements. Most importantly, it enables explaining and understanding the reasons for different and sometimes even unexpected crystallization behaviors of ASDs.


Subject(s)
Crystallization , Water , Crystallization/methods , Water/chemistry , Kinetics , Drug Stability , Nifedipine/chemistry , Vinyl Compounds/chemistry , Thermodynamics , Pyrrolidines/chemistry , Viscosity , Chemistry, Pharmaceutical/methods , Humidity , Temperature , Solubility , Methylcellulose/chemistry , Methylcellulose/analogs & derivatives
6.
Phys Chem Chem Phys ; 26(6): 5387-5398, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38270198

ABSTRACT

Here, we report a comparison study on the synthesis and characterization of perovskite SrSnO3 (SSO) and Sr2SnO4 (S2SO). Rietveld refinement studies were performed on both prepared samples and suggest that they crystallized in cubic (SSO) and tetragonal (S2SO) structures. Fourier-transform infrared (FTIR) and Raman spectroscopy studies supported the XRD observations. Improved dielectric parameters were observed for S2SO over SSO due to differences in dislocation density, larger crystallite size, and denser microstructure. The electrical conduction and relaxation processes followed the Arrhenius type in both samples through the migration of oxygen vacancies via the Sn-site and the transfer of electrons between the Sn sites in two different temperature regions. These processes in the samples occurred via correlated barrier hopping (CBH) in SSO and the non-overlapping of small-polaron tunnelling (NSPT) in S2SO. The conduction and relaxation processes had similar sources of charge carriers but differed in the concentration and mobility of charge carriers. The presented materials can be utilized for dielectric capacitors, sensors, and mixed ionic and electronic conductor-based electrodes in IT-SOFC applications.

7.
BMC Psychiatry ; 24(1): 330, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38689281

ABSTRACT

BACKGROUND: The study explored the levels and associated factors of undiagnosed depression among community-dwelling older Indian adults. It also identified the socio-demographic predictors of undiagnosed depression among the study population at national and state levels. METHODS: The study employed data from the Longitudinal Ageing Study in India wave-I, 2017-18. Based on the data on depression from interviewee's self-reporting and measurement on Composite International Diagnostic Interview- Short Form (CIDI-SF) and Centre for Epidemiological Studies- Depression scale (CES-D) scales, we estimated undiagnosed depression among older adults (age 60+). We estimated multivariable binary logistic regressions to examine the socio-demographic and health-related predictors of undiagnosed depression among older adults. FINDINGS: 8% (95% CI: 7.8-8.4) of the total older adults had undiagnosed depression on CIDI-SF scale and 5% (95% CI: 4.8-5.3) on the combined CIDI-SF and CES-D. Undiagnosed depression was higher among those who were widowed, worked in the past and currently not working, scheduled castes, higher educated and the richest. Lack of health insurance coverage, presence of any other physical or mental impairment, family history of Alzheimer's/Parkinson's disease/ psychotic disorder, lower self-rated health and poor life satisfaction were significant predictors of undiagnosed depression on both CIDI-SF and combined scales. CONCLUSION: To improve the health of older adults in India, targeted policy efforts integrating mental health screening, awareness campaigns and decentralization of mental healthcare to primary level is needed. Further research could explore the causal factors behind different levels of undiagnosed depression.


Subject(s)
Depression , Humans , India/epidemiology , Male , Female , Aged , Middle Aged , Longitudinal Studies , Depression/diagnosis , Depression/epidemiology , Aged, 80 and over , Psychiatric Status Rating Scales , Independent Living/statistics & numerical data , Depressive Disorder/diagnosis , Depressive Disorder/epidemiology , Socioeconomic Factors , Cost of Illness
8.
Rheumatol Int ; 44(5): 819-829, 2024 May.
Article in English | MEDLINE | ID: mdl-38082159

ABSTRACT

Antiphospholipid antibodies (APLA) are present in one-third of systemic lupus erythematosus (SLE) patients, and they are associated with both criteria and non-criteria manifestations. We studied the prevalence, clinical associations, and impact on mortality of APLA in SLE patients from India. Among the Indian SLE inception cohort (INSPIRE), patients who had data on all five routinely performed APLAs [lupus anticoagulant (LA), IgG and IgM anticardiolipin antibody (aCL) and anti-ß2-glycoprotein I(ß2GPI)] at enrolment were selected. Patients were divided into four categories based on the presence/absence of APLA associated manifestations and presence/absence of the APLA viz SLE-APS, SLE-APLA, SLE: events but no APLA, and SLE: no events, no APLA (reference group). 1035 SLE patients at least 1 APLA antibody was detected in 372 (35.9%). LA was present in 206 (19.9%), aCL in 126 (12.2%) and ß2-GPI in 178 (17.2%). There were 88 thrombotic events in 83 patients (8.0%); 73 (82.9%) being arterial; APLA positivity was present in 37 (44.6%) [AOR 1.70 (1.054, 2.76)]. SLE-APS patients were younger and had higher mortality [AOR 4.11 (1.51, 11.3)], neuropsychiatric and hematologic disease. SLE-APLA also had a higher mortality rate [AOR 2.94 (1.06, 8.22)] than the reference group. The mortality was highest in the subset of patients with thrombotic events in the presence of APLA [AOR 7.67 (1.25, 46.9)]. The mere presence of APLA also conferred higher mortality even in the absence of thrombotic events [AOR 3.51 (1.43, 8.63)]. Hematologic manifestations (36.1%) were the most common non-criteria-manifestation. One-third of SLE patients have APLA and its presence is associated with non-criteria hematologic manifestations, arterial thrombosis and higher mortality rate.


Subject(s)
Antiphospholipid Syndrome , Lupus Erythematosus, Systemic , Thrombosis , Humans , Antibodies, Antiphospholipid , Antibodies, Anticardiolipin , Lupus Erythematosus, Systemic/complications , Antiphospholipid Syndrome/complications , Lupus Coagulation Inhibitor
9.
Proc Natl Acad Sci U S A ; 118(5)2021 02 02.
Article in English | MEDLINE | ID: mdl-33495342

ABSTRACT

miR-33 is an intronic microRNA within the gene encoding the SREBP2 transcription factor. Like its host gene, miR-33 has been shown to be an important regulator of lipid metabolism. Inhibition of miR-33 has been shown to promote cholesterol efflux in macrophages by targeting the cholesterol transporter ABCA1, thus reducing atherosclerotic plaque burden. Inhibition of miR-33 has also been shown to improve high-density lipoprotein (HDL) biogenesis in the liver and increase circulating HDL-C levels in both rodents and nonhuman primates. However, evaluating the extent to which these changes in HDL metabolism contribute to atherogenesis has been hindered by the obesity and metabolic dysfunction observed in whole-body miR-33-knockout mice. To determine the impact of hepatic miR-33 deficiency on obesity, metabolic function, and atherosclerosis, we have generated a conditional knockout mouse model that lacks miR-33 only in the liver. Characterization of this model demonstrates that loss of miR-33 in the liver does not lead to increased body weight or adiposity. Hepatic miR-33 deficiency actually improves regulation of glucose homeostasis and impedes the development of fibrosis and inflammation. We further demonstrate that hepatic miR-33 deficiency increases circulating HDL-C levels and reverse cholesterol transport capacity in mice fed a chow diet, but these changes are not sufficient to reduce atherosclerotic plaque size under hyperlipidemic conditions. By elucidating the role of miR-33 in the liver and the impact of hepatic miR-33 deficiency on obesity and atherosclerosis, this work will help inform ongoing efforts to develop novel targeted therapies against cardiometabolic diseases.


Subject(s)
Atherosclerosis/genetics , Atherosclerosis/physiopathology , Body Weight , Homeostasis , Liver/metabolism , Liver/physiopathology , MicroRNAs/metabolism , Animals , Atherosclerosis/blood , Biological Transport , Carbon Tetrachloride , Cholesterol/metabolism , Diet, High-Fat , Feeding Behavior , Gene Expression Regulation , Lipoproteins, HDL/blood , Mice , MicroRNAs/genetics , Obesity/genetics , Plaque, Atherosclerotic/genetics , Plaque, Atherosclerotic/physiopathology
10.
Proc Natl Acad Sci U S A ; 118(47)2021 11 23.
Article in English | MEDLINE | ID: mdl-34782454

ABSTRACT

Cholesterol biosynthetic intermediates, such as lanosterol and desmosterol, are emergent immune regulators of macrophages in response to inflammatory stimuli or lipid overloading, respectively. However, the participation of these sterols in regulating macrophage functions in the physiological context of atherosclerosis, an inflammatory disease driven by the accumulation of cholesterol-laden macrophages in the artery wall, has remained elusive. Here, we report that desmosterol, the most abundant cholesterol biosynthetic intermediate in human coronary artery lesions, plays an essential role during atherogenesis, serving as a key molecule integrating cholesterol homeostasis and immune responses in macrophages. Depletion of desmosterol in myeloid cells by overexpression of 3ß-hydroxysterol Δ24-reductase (DHCR24), the enzyme that catalyzes conversion of desmosterol to cholesterol, promotes the progression of atherosclerosis. Single-cell transcriptomics in isolated CD45+CD11b+ cells from atherosclerotic plaques demonstrate that depletion of desmosterol increases interferon responses and attenuates the expression of antiinflammatory macrophage markers. Lipidomic and transcriptomic analysis of in vivo macrophage foam cells demonstrate that desmosterol is a major endogenous liver X receptor (LXR) ligand involved in LXR/retinoid X receptor (RXR) activation and thus macrophage foam cell formation. Decreased desmosterol accumulation in mitochondria promotes macrophage mitochondrial reactive oxygen species production and NLR family pyrin domain containing 3 (NLRP3)-dependent inflammasome activation. Deficiency of NLRP3 or apoptosis-associated speck-like protein containing a CARD (ASC) rescues the increased inflammasome activity and atherogenesis observed in desmosterol-depleted macrophages. Altogether, these findings underscore the critical function of desmosterol in the atherosclerotic plaque to dampen inflammation by integrating with macrophage cholesterol metabolism and inflammatory activation and protecting from disease progression.


Subject(s)
Atherosclerosis/drug therapy , Desmosterol/pharmacology , Inflammasomes/metabolism , Inflammation/drug therapy , Macrophage Activation/drug effects , Animals , Atherosclerosis/metabolism , Atherosclerosis/pathology , Cholesterol/metabolism , Coronary Vessels , Foam Cells/metabolism , Humans , Inflammation/metabolism , Lipid Metabolism , Liver X Receptors/metabolism , Macrophages/metabolism , Male , Mice , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Oxidoreductases Acting on CH-CH Group Donors/genetics , Oxidoreductases Acting on CH-CH Group Donors/metabolism , Plaque, Atherosclerotic/metabolism , Sterols/metabolism
11.
Int J Urol ; 31(3): 252-257, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38124339

ABSTRACT

OBJECTIVES: Clinical T1 (cT1) renal mass treated surgically has a good prognosis, but there is an upstaging risk that potentially threatens oncological outcomes after partial nephrectomy (PN). We aim to analyze and study the incidence, predictors, perioperative morbidity, and oncological outcomes of pT3a upstaging. METHODOLOGY: A retrospective study of 313 patients who underwent PN for cT1 renal mass at a single center from a single tertiary referral center between 2000 and 2021 was done. Demographic, perioperative, pathological, and outcome variables were reviewed. We compared these parameters between upstaged and non-upstaged groups. Multivariate logistic regression analysis was used to study preoperative variables associated with upstaging. RESULTS: Nineteen patients were upstaged to pT3a. Making an incidence of 6.1%. Upstaged tumors were bigger (5.02 cm vs. 4.08 cm, p = 0.004), had higher clinical stage T1b (84.2 vs. 40.5%, p < 0.001), had more tumors which were central location (21 vs. 3.4%, p < 0.001), had more endophytic and mesophytic tumors (15.8 vs. 5.8% and 52.6 vs. 9.5%, p < 0.001), and had higher R.E.N.A.L Nephrometry score (8.05 vs. 6, p < 0.001). Upstaged tumors had more operative times (227 vs. 203 min, p = 0.01), more postoperative complications (68.4 vs. 13.1%, p < 0.001), more major complications of Clavien Dindo Grade 3 and above (15.8 vs. 4.4%, p < 0.001). Age (OR 1.035, p = 0.034), Radiological tumor dimension (OR 1.578, p = 0.003), Radiological or Clinical stage (T1b) (9.19, p = 0.008), Higher Nephrometry score (Intermediate and High) (OR 6.184, p = 0.004) were preoperative predictors of upstaging. Oncological outcomes were comparable. CONCLUSION: Tumor upstaging was uncommon with more perioperative morbidity. Higher age, larger tumor size, higher tumor stage, and higher nephrometry scores were preoperative predictors of upstaging.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/pathology , Retrospective Studies , Neoplasm Staging , Nephrectomy/adverse effects , Nephrectomy/methods
12.
Int Braz J Urol ; 50(4): 459-469, 2024.
Article in English | MEDLINE | ID: mdl-38743064

ABSTRACT

PURPOSE: To assess the incidence of the most common intra- and early postoperative complications following RIRS in a large series of patients with kidney stones. METHODS: We conducted a retrospective analysis of patients with kidney stones who underwent RIRS across 21 centers from January 2018 to August 2021, as part of the Global Multicenter Flexible Ureteroscopy Outcome (FLEXOR) Registry. RESULTS: Among 6669 patients undergoing RIRS, 4.5% experienced intraoperative pelvicalyceal system bleeding without necessitating blood transfusion. Only 0.1% of patients, required a blood transfusion. The second most frequent intraoperative complication was ureteric injury due to the ureteral access sheath requiring stenting (1.8% of patients). Postoperatively, the most prevalent early complications were fever/infections requiring antibiotics (6.3%), blood transfusions (5.5%), and sepsis necessitating intensive care unit admission (1.3%). In cases of ureteric injury, a notably higher percentage of patients exhibited multiple stones and stone(s) in the lower pole, and these cases were correlated with prolonged lasing and overall surgical time. Hematuria requiring a blood transfusion was associated with an increased prevalence of larger median maximum stone diameters, particularly among patients with stones exceeding 20 mm. Furthermore, these cases exhibited a significant prolongation in surgical time. Sepsis necessitating admission to the intensive care unit was more prevalent among the elderly, concomitant with a significantly larger median maximum stone diameter. CONCLUSIONS: Our analysis showed that RIRS has a good safety profile but bleeding requiring transfusions, ureteric injury, fever, and sepsis are still the most common complications despite advancements in technology.


Subject(s)
Kidney Calculi , Postoperative Complications , Registries , Ureteroscopy , Humans , Ureteroscopy/adverse effects , Ureteroscopy/methods , Retrospective Studies , Female , Kidney Calculi/surgery , Male , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Middle Aged , Intraoperative Complications/epidemiology , Intraoperative Complications/etiology , Aged , Adult , Treatment Outcome
13.
Environ Geochem Health ; 46(5): 148, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38578547

ABSTRACT

A slight variation in ecological milieu of plants, like drought, heavy metal toxicity, abrupt changes in temperature, flood, and salt stress disturbs the usual homeostasis or metabolism in plants. Among these stresses, salinity stress is particularly detrimental to the plants, leading to toxic effects and reduce crop productivity. In a saline environment, the accumulation of sodium and chloride ions up to toxic levels significantly correlates with intracellular osmotic pressure, and can result in morphological, physiological, and molecular alterations in plants. Increased soil salinity triggers salt stress signals that activate various cellular-subcellular mechanisms in plants to enable their survival in saline conditions. Plants can adapt saline conditions by maintaining ion homeostasis, activating osmotic stress pathways, modulating phytohormone signaling, regulating cytoskeleton dynamics, and maintaining cell wall integrity. To address ionic toxicity, researchers from diverse disciplines have explored novel approaches to support plant growth and enhance their resilience. One such approach is the application of nanoparticles as a foliar spray or seed priming agents positively improve the crop quality and yield by activating germination enzymes, maintaining reactive oxygen species homeostasis, promoting synthesis of compatible solutes, stimulating antioxidant defense mechanisms, and facilitating the formation of aquaporins in seeds and root cells for efficient water absorption under various abiotic stresses. Thus, the assessment mainly targets to provide an outline of the impact of salinity stress on plant metabolism and the resistance strategies employed by plants. Additionally, the review also summarized recent research efforts exploring the innovative applications of zinc oxide nanoparticles for reducing salt stress at biochemical, physiological, and molecular levels.


Subject(s)
Zinc Oxide , Salt Stress , Stress, Physiological , Plant Growth Regulators/pharmacology , Antioxidants/metabolism , Salinity
14.
J Med Ultrasound ; 32(2): 143-147, 2024.
Article in English | MEDLINE | ID: mdl-38882630

ABSTRACT

Background: The brachiocephalic vein (BCV) is a feasible option for central venous access in the pediatric population and is rapidly developing as an alternative site for insertion of the central line in young children with faster insertion times, fewer attempts, and lower rates of complications. However, studies demonstrating the feasibility of BCV catheterization in adult patients are insufficient. The current study sought to assess the safety and effectiveness of ultrasound-guided supraclavicular right BCV cannulations in adults. Methods: A linear array Ultrasound (US) probe was used to obtain a longitudinal picture of the BCV beginning at the junction of the internal jugular vein and the subclavian vein in the supraclavicular region. Under US supervision, the needle was guided into the BCV using the in-plane approach. A prospective study was performed on 80 adult patients scheduled for elective and emergency operative procedures under general anesthesia requiring a central venous catheter (CVC). Success rates and complications that occurred during catheter insertion were analyzed. Results: CVC placement was successful in all adults. The procedure was successful at the first attempt in 74 cases (92.5%) and after 2 attempts in six patients (7.5%). The time to guide wire insertion was 31.26 s (19-58 s), and catheter insertion took 88.44 s (63-145 s). The mean length of catheter insertion was 10.46 cm. No complications were noted. Conclusion: Ultrasound-guided supraclavicular BCV catheterization offers a new and safe method for central venous line catheterization in adults. However, larger trials and meta-analyses are needed to confirm these findings and evaluate the safety of this technique.

15.
Proteins ; 2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37774104

ABSTRACT

Trimethylamine monooxygenase (Tmm, EC-1.14.13.148) belongs to the family of flavin-containing monooxygenases that oxidize trimethylamine into trimethylamine-N-oxide (TMAO). Conventional methods for assaying Tmm are accurate over a narrow range of substrate/product concentrations. Here we report a TMAO-specific enzymatic assay for Tmm using polyallylamine hydrochloride (PAHCl)-capped MnO2 nanoparticles (PAHCl@MnO2 ). We achieved TMAO specificity using iodoacetonitrile to remove interfering trimethylamine. The change in the concentration of TMAO is measured by observing the difference in the absorbance of 3,3',5,5'-tetramethylbenzidine (TMB) at 650 nm. The assay is tolerant to several interfering metal ions and other compounds. This method is more accessible and reliable than currently known methods. The limit of detection (LOD) and limit of quantitation (LOQ) are 1 µM and 10 µM, respectively, for direct TMAO measurement.

16.
J Cell Physiol ; 238(12): 2841-2854, 2023 12.
Article in English | MEDLINE | ID: mdl-37882235

ABSTRACT

Amyloid-ß (Aß) protein aggregation in the brain is a pathological hallmark of Alzheimer's disease (AD) however, the underlying molecular mechanisms regulating amyloid aggregation are not well understood. Here, we studied the propitious role of E3 ubiquitin ligase Pirh2 in Aß protein aggregation in view of its regulatory ligase activity in the ubiquitin-proteasome system employing both cellular and sporadic rodent models of AD. Pirh2 protein abundance was significantly increased during Streptozotocin (STZ) induced AD conditions, and transient silencing of Pirh2 significantly inhibited the Aß aggregation and modified the dendrite morphology along with the substantial decrease in choline level in the differentiated neurons. MALDI-TOF/TOF, coimmunoprecipitation, and UbcH7-linked in vitro ubiquitylation analysis confirmed the high interaction of Pirh2 with chaperone GRP78. Furthermore, Pirh2 silencing inhibits the STZ induced altered level of endoplasmic reticulum stress and intracellular Ca2+ levels in neuronal N2a cells. Pirh2 silencing also inhibited the AD conditions related to the altered protein abundance of HSP90 and its co-chaperones which may collectively involve in the reduced burden of amyloid aggregates in neuronal cells. Pirh2 silencing further stabilized the nuclear translocation of phospho-Nrf2 and inhibited the altered level of autophagy factors. Taken together, our data indicated that Pirh2 is critically involved in STZ induced AD pathogenesis through its interaction with ER-chaperone GRP78, improves the neuronal connectivity, affects the altered level of chaperones, co-chaperones, & autophagic markers, and collectively inhibits the Aß aggregation.


Subject(s)
Alzheimer Disease , Endoplasmic Reticulum Chaperone BiP , Signal Transduction , Alzheimer Disease/pathology , Amyloid , Amyloid beta-Peptides/metabolism , Glucose/metabolism , Molecular Chaperones/genetics , Molecular Chaperones/metabolism , Protein Aggregates , Male , Animals , Mice , Rats , Cell Line, Tumor , Rats, Sprague-Dawley , Endoplasmic Reticulum Stress
17.
J Am Chem Soc ; 145(1): 422-435, 2023 Jan 11.
Article in English | MEDLINE | ID: mdl-36537351

ABSTRACT

The development of an efficient photocatalyst for C2 product formation from CO2 is of urgent importance toward the deployment of solar-fuel production. Here, we report a template-free, cost-effective synthetic strategy to develop a carbazole-derived porous organic polymer (POP)-based composite catalyst. The composite catalyst is comprised of In2.77S4 and porous organic polymer (POP) and is held together by induced-polarity-driven electrostatic interaction. Utilizing the synergy of the catalytically active In centers and light-harvesting POPs, the catalyst showed 98.9% selectivity toward the generation of C2H4, with a formation rate of 67.65 µmol g-1 h-1. Two different oxidation states of the In2.77S4 spinel were exploited for the C-C coupling process, and this was investigated by X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS), and density functional theory (DFT) calculations. The role of POP was elucidated via several photophysical and photoelectrochemical studies. The electron transfer was mapped by several correlated approaches, which assisted in establishing the Z-scheme mechanism. Furthermore, the mechanism of C2H4 formation was extensively investigated using density functional theory (DFT) calculations from multiple possible pathways.

18.
J Urol ; 210(2): 323-330, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37126223

ABSTRACT

PURPOSE: We evaluated stone-free rate and complications after flexible ureteroscopy for renal stones, comparing thulium fiber laser and holmium:YAG laser with MOSES technology. MATERIALS AND METHODS: Data from adults who underwent flexible ureteroscopy in 20 centers worldwide were retrospectively reviewed (January 2018-August 2021). Patients with ureteral stones, concomitant bilateral procedures, and combined procedures were excluded. One-to-one propensity score matching for age, gender, and stone characteristics was performed. Stone-free rate was defined as absence of fragments >2 mm on imaging within 3 months after surgery. Multivariable logistic regression analysis was performed to evaluate independent predictors of being stone-free. RESULTS: Of 2,075 included patients, holmium:YAG laser with MOSES technology was used in 508 patients and thulium fiber laser in 1,567 patients. After matching, 284 patients from each group with comparable baseline characteristics were included. Pure dusting was applied in 6.0% of cases in holmium:YAG laser with MOSES technology compared with 26% in thulium fiber laser. There was a higher rate of basket extraction in holmium:YAG laser with MOSES technology (89% vs 43%, P < .001). Total operation time and lasing time were similar. Nine patients had sepsis in thulium fiber laser vs none in holmium:YAG laser with MOSES technology (P = .007). Higher stone-free rate was achieved in thulium fiber laser (85% vs 56%, P < .001). At multivariable analysis, the use of thulium fiber laser and ureteral access sheath ≥8F had significantly higher odds of being stone-free. Lasing time, multiple stones, stone diameter, and use of disposable scopes showed significantly lower odds of being stone-free. CONCLUSIONS: This real-world study favors the use of thulium fiber laser over holmium:YAG laser with MOSES technology in flexible ureteroscopy for renal stones by way of its higher single-stage stone-free rate.


Subject(s)
Kidney Calculi , Lasers, Solid-State , Lithotripsy, Laser , Lithotripsy , Humans , Adult , Lithotripsy, Laser/adverse effects , Lithotripsy, Laser/methods , Thulium , Holmium , Lasers, Solid-State/therapeutic use , Ureteroscopy/methods , Retrospective Studies , Propensity Score , Kidney Calculi/surgery , Technology , Registries
19.
J Hum Genet ; 68(5): 355-358, 2023 May.
Article in English | MEDLINE | ID: mdl-36599958

ABSTRACT

Mutations in the PAX6 gene are generally associated with aniridia. We describe a family with Juvenile onset open angle glaucoma (JOAG), where one of the two children had JOAG and the other Juvenile ocular hypertension. Whole exome sequencing was performed for the parents and their two affected children where the proband and her sibling were detected to have a de novo PAX6 gene variant in the absence of aniridia. All previously described gene mutations for glaucoma were looked for in the family. The potential pathogenicity of the identified variants was assessed by determining their frequency in large public exome databases; as well as using the current ACMG guidelines. The same heterozygous variant at NM_000280.6:c.1124 C > A; p. Pro375Gln in the PAX6 gene was detected in the proband and her affected brother. The variant has been described in aniridia patients before and has been shown to cause a weaker DNA binding using functional studies. This report expands the phenotypic spectrum of the PAX6 gene to include Juvenile onset open angle glaucoma.


Subject(s)
Aniridia , Glaucoma, Open-Angle , Glaucoma , Humans , Male , Child , Female , Glaucoma, Open-Angle/genetics , PAX6 Transcription Factor/genetics , Homeodomain Proteins/genetics , Aniridia/genetics , Mutation , Glaucoma/genetics , Pedigree , Eye Proteins/genetics
20.
Mol Vis ; 29: 365-377, 2023.
Article in English | MEDLINE | ID: mdl-38577561

ABSTRACT

Purpose: To describe a novel association of TGFBI variants with congenital glaucoma in a family with GAPO (growth retardation, alopecia, pseudoanodontia, and progressive optic atrophy) syndrome, as well as among other unrelated cases of juvenile onset open-angle glaucoma (JOAG) and primary congenital glaucoma (PCG). Methods: This study of one family of GAPO with congenital glaucoma and three unrelated patients with JOAG analyzed a common link to glaucoma pathogenesis. Three girls with GAPO syndrome born to consanguineous parents in a multi-generation consanguineous family were identified. Two of the girls had congenital glaucoma in both eyes, while the elder sibling (a 10-year-old female) had features of GAPO syndrome without glaucoma. Results: A genetic evaluation using whole exome sequencing revealed a novel homozygous ANTXR1 mutation in all three affected siblings with GAPO. No other mutations were detected in the genes associated with glaucoma. A rare missense variant in the TGFBI gene was shared in the two siblings with congenital glaucoma and GAPO syndrome. We found three other unrelated patients with JOAG and one patient with primary congenital glaucoma with no known glaucoma causing gene mutations, but having four different missense variants in the TGFBI gene. One of these patients with JOAG had familial granular corneal dystrophy. Molecular dynamic simulations of TGFBI and 3-D structural models of three of its variants showed significant alterations that could influence TGFBI protein function. Conclusions: The possibility that variations in the TGFBI gene could have a possible role in the pathogenesis of congenital and juvenile onset open-angle glaucomas needs further evaluation.


Subject(s)
Alopecia , Anodontia , Extracellular Matrix Proteins , Glaucoma, Open-Angle , Glaucoma , Growth Disorders , Hydrophthalmos , Optic Atrophies, Hereditary , Transforming Growth Factor beta , Female , Humans , Child , Glaucoma, Open-Angle/genetics , Glaucoma/genetics , Glaucoma/congenital , Mutation/genetics , Pedigree , Microfilament Proteins/genetics , Receptors, Cell Surface/genetics
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