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1.
Med Eng Phys ; 126: 104146, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38621847

RESUMEN

Low back pain (LBP) is a leading cause of disability, resulting in aberrant movement. This movement is difficult to measure accurately in clinical practice and gold standard methods, such as optoelectronic systems involve the use of expensive laboratory equipment. Inertial measurement units (IMU) offer an alternative method of quantifying movement that is accessible in most environments. However, there is no consensus around the validity and reliability of IMUs for quantifying lumbar spine movements compared with gold standard measures. The aim of this systematic review was to establish concurrent validity and repeated measures reliability of using IMUs for the measurement of lumbar spine movements in individuals with and without LBP. A systematic search of electronic databases, incorporating PRISMA guidelines was completed, limited to the English language. 503 studies were identified where 15 studies met the inclusion criteria. Overall, 305 individuals were included, and 109 of these individuals had LBP. Weighted synthesis of the results demonstrated root mean squared differences of <2.4° compared to the gold standard and intraclass correlations >0.84 for lumbar spine movements. IMUs offer clinicians and researchers valid and reliable measurement of motion in the lumbar spine, comparable to laboratory methods, such as optoelectronic motion capture for individuals with and without LBP.


Asunto(s)
Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/diagnóstico , Reproducibilidad de los Resultados , Rango del Movimiento Articular , Fenómenos Biomecánicos , Vértebras Lumbares , Movimiento
2.
Environ Sci Technol ; 58(15): 6693-6703, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38577981

RESUMEN

A major component of human skin oil is squalene, a highly unsaturated hydrocarbon that protects the skin from atmospheric oxidants. Skin oil, and thus squalene, is continuously replenished on the skin surface. Squalene is also quickly consumed through reactions with ozone and other oxidants. This study examined the extent of squalene depletion in the skin oils of the forearm of human volunteers after exposure to ozone in a climate chamber. Temperature, relative humidity (RH), skin coverage by clothing, and participants' age were varied in a controlled manner. Concentrations of squalene were determined in skin wipe samples collected before and after ozone exposure. Exposures to ozone resulted in statistically significant decreases in post-exposure squalene concentrations compared to pre-exposure squalene concentrations in the skin wipes when squalene concentrations were normalized by concentrations of co-occurring cholesterol but not by co-occurring pyroglutamic acid (PGA). The rate of squalene loss due to ozonolysis was lower than its replenishment on the skin surface. Within the ranges examined, temperature and RH did not significantly affect the difference between normalized squalene levels in post-samples versus pre-samples. Although not statistically significant, skin coverage and age of the volunteers (three young adults, three seniors, and three teenagers) did appear to impact squalene depletion on the skin surfaces.


Asunto(s)
Contaminación del Aire Interior , Ozono , Humanos , Adolescente , Escualeno/análisis , Ozono/análisis , Contaminación del Aire Interior/análisis , Piel/química , Oxidantes
3.
Hypertension ; 81(5): 1167-1177, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38497230

RESUMEN

BACKGROUND: The mTOR (mechanistic target of rapamycin) is an essential regulator of fundamental biological processes. mTOR forms 2 distinct complexes, mTORC1 (mTOR complex 1) when it binds with RAPTOR (Regulatory-associated Protein of mTOR) and mTORC2 (mTOR complex 2) when it associates with RICTOR (Rapamycin-insesitive companion of mTOR). Due to the previous link between the mTOR pathway, aldosterone, and blood pressure (BP), we anticipated that variants in the mTOR complex might be associated with salt-sensitive BP. METHODS: BP and other parameters were assessed after a one-week liberal Na+ (200 mmol/d) and a one-week restricted Na+ (10 mmol/d) diet in 608 White subjects from the Hypertensive Pathotype cohort, single-nucleotide variants in MTOR, RPTOR, and RICTOR genes were obtained for candidate genes analyses. RESULTS: The analysis revealed a significant association between a single nucleotide variants within the RPTOR gene and BP. Individuals carrying the RPTOR rs9901846 homozygous risk allele (AA) and heterozygous risk allele (GA) exhibited a 5 mm Hg increase in systolic BP on a liberal diet compared with nonrisk allele individuals (GG), but only in women. This single nucleotide variants effect was more pronounced on the restricted diet and present in both sexes, with AA carriers having a 9 mm Hg increase and GA carriers having a 5 mm Hg increase in systolic BP compared with GG. Interestingly, there were no significant associations between MTOR or RICTOR gene variants and BP. CONCLUSIONS: The RPTOR gene variation is associated with elevated BP in White participants, regardless of salt intake, specifically in females.


Asunto(s)
Presión Sanguínea , Hipertensión , Proteína Reguladora Asociada a mTOR , Cloruro de Sodio Dietético , Femenino , Humanos , Masculino , Proteínas Portadoras/genética , Hipertensión/genética , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 2 de la Rapamicina/metabolismo , Nucleótidos/metabolismo , Proteína Asociada al mTOR Insensible a la Rapamicina/metabolismo , Proteína Reguladora Asociada a mTOR/genética , Proteína Reguladora Asociada a mTOR/metabolismo , Sirolimus , Cloruro de Sodio Dietético/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Población Blanca
4.
Vet Sci ; 11(3)2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38535863

RESUMEN

Dogs with protein-losing enteropathy (PLE) caused by inflammatory enteritis, intestinal lymphangiectasia, or both, have a guarded prognosis, with death occurring as a result of the disease in approximately 50% of cases. Although dietary therapy alone is significantly associated with a positive outcome, there is limited ability to differentiate between food-responsive (FR) PLE and immunosuppressant-responsive (IR) PLE at diagnosis in dogs. Our objective was to determine if a transfer learning computational approach to image classification on duodenal biopsy specimens collected at diagnosis was able to differentiate FR-PLE from IR-PLE. This was a retrospective study using paraffin-embedded formalin-fixed duodenal biopsy specimens collected during upper gastrointestinal tract endoscopy as part of the diagnostic investigations from 17 client-owned dogs with PLE due to inflammatory enteritis at a referral teaching hospital that were subsequently classified based on treatment response into FR-PLE (n = 7) or IR-PLE (n = 10) after 4 months of follow-up. A machine-based algorithm was used on lower magnification and higher resolution images of endoscopic duodenal biopsy specimens. Using the pre-trained Convolutional Neural Network model with a 70/30 training/test ratio for images, the model was able to differentiate endoscopic duodenal biopsy images from dogs with FR-PLE and IR-PLE with an accuracy of 83.78%. Our study represents an important first step toward the use of machine learning in improving the decision-making process for clinicians with regard to the initial treatment of canine PLE.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38437868

RESUMEN

CONTEXT: Hypertension, a prevalent cardiovascular risk, often involves dysregulated aldosterone and its interaction with the mineralocorticoid receptor (MR). Experimental designs in animal models and human cohorts have demonstrated a sex and age dependency of aldosterone secretion that expands our pathophysiologic understanding. OBJECTIVE: This study explores the genetic variation of NR3C2, which encodes MR, in relation to aldosterone, considering age, sex, and race. METHODS: Incorporating 720 Caucasians and 145 Africans from the HyperPATH cohort, we investigated the impact of rs4835490, a single nucleotide risk allele variant, on aldosterone levels and vasculature. RESULTS: Notably, a significant association between rs4835490 and plasma aldosterone under liberal salt conditions emerged in individuals of European ancestry (P=0.0002). Homozygous carriers of the risk A allele exhibited elevated plasma aldosterone levels (AA=8.1±0.9 vs GG=4.9±0.5 ng/dl). Additionally, aldosterone activation through posture (P=0.025) and urinary excretion (P=0.0122) showed notable associations. Moreover, genetic interactions with race, sex, and age were observed. Caucasian females under 50 years displayed higher plasma aldosterone, urine aldosterone, and posture aldosterone with the AA genotype compared to females over 50 years, suggesting a potential connection with menopausal or estrogen influences. Interestingly, such age-dependent interactions were absent in the African cohort. CONCLUSIONS: our study highlights the significance of NR3C2 genetic variation and its interplay with age, sex, and race in aldosterone activation. The findings point towards an estrogen-modulating effect on MR activation, particularly in women underlining the role of aldosterone dysregulation in hypertension development. This insight advances our comprehension of hypertension's complexities and opens avenues for personalized interventions.

7.
Environ Sci Technol ; 58(10): 4704-4715, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38326946

RESUMEN

Ozone reaction with human surfaces is an important source of ultrafine particles indoors. However, 1-20 nm particles generated from ozone-human chemistry, which mark the first step of particle formation and growth, remain understudied. Ventilation and indoor air movement could have important implications for these processes. Therefore, in a controlled-climate chamber, we measured ultrafine particles initiated from ozone-human chemistry and their dependence on the air change rate (ACR, 0.5, 1.5, and 3 h-1) and operation of mixing fans (on and off). Concurrently, we measured volatile organic compounds (VOCs) and explored the correlation between particles and gas-phase products. At 25-30 ppb ozone levels, humans generated 0.2-7.7 × 1012 of 1-3 nm, 0-7.2 × 1012 of 3-10 nm, and 0-1.3 × 1012 of 10-20 nm particles per person per hour depending on the ACR and mixing fan operation. Size-dependent particle growth and formation rates increased with higher ACR. The operation of mixing fans suppressed the particle formation and growth, owing to enhanced surface deposition of the newly formed particles and their precursors. Correlation analyses revealed complex interactions between the particles and VOCs initiated by ozone-human chemistry. The results imply that ventilation and indoor air movement may have a more significant influence on particle dynamics and fate relative to indoor chemistry.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire Interior , Ozono , Compuestos Orgánicos Volátiles , Humanos , Tamaño de la Partícula , Ozono/análisis , Ventilación/métodos , Material Particulado/análisis , Compuestos Orgánicos Volátiles/análisis , Contaminación del Aire Interior/análisis , Contaminantes Atmosféricos/análisis
8.
PLoS Negl Trop Dis ; 18(1): e0011926, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38285730

RESUMEN

The documentation of Plasmodium vivax malaria across Africa especially in regions where Duffy negatives are dominant suggests possibly alternative erythrocyte invasion mechanisms. While the transcriptomes of the Southeast Asian and South American P. vivax are well documented, the gene expression profile of P. vivax in Africa is unclear. In this study, we examined the expression of 4,404 gene transcripts belong to 12 functional groups and 43 erythrocyte binding gene candidates in Ethiopian isolates and compared them with the Cambodian and Brazilian P. vivax transcriptomes. Overall, there were 10-26% differences in the gene expression profile amongst geographical isolates, with the Ethiopian and Cambodian P. vivax being most similar. Majority of the gene transcripts involved in protein transportation, housekeeping, and host interaction were highly transcribed in the Ethiopian isolates. Members of the reticulocyte binding protein PvRBP2a and PvRBP3 expressed six-fold higher than Duffy binding protein PvDBP1 and 60-fold higher than PvEBP/DBP2 in the Ethiopian isolates. Other genes including PvMSP3.8, PvMSP3.9, PvTRAG2, PvTRAG14, and PvTRAG22 also showed relatively high expression. Differential expression patterns were observed among geographical isolates, e.g., PvDBP1 and PvEBP/DBP2 were highly expressed in the Cambodian but not the Brazilian and Ethiopian isolates, whereas PvRBP2a and PvRBP2b showed higher expression in the Ethiopian and Cambodian than the Brazilian isolates. Compared to Pvs25, gametocyte genes including PvAP2-G, PvGAP (female gametocytes), and Pvs47 (male gametocytes) were highly expressed across geographical samples.


Asunto(s)
Malaria Vivax , Plasmodium vivax , Masculino , Femenino , Humanos , Plasmodium vivax/genética , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Malaria Vivax/genética , Eritrocitos/metabolismo , Perfilación de la Expresión Génica , Transcriptoma , Antígenos de Protozoos/genética
9.
Environ Sci Technol ; 58(4): 1986-1997, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38237915

RESUMEN

Humans are the primary sources of CO2 and NH3 indoors. Their emission rates may be influenced by human physiological and psychological status. This study investigated the impact of physiological and psychological engagements on the human emissions of CO2 and NH3. In a climate chamber, we measured CO2 and NH3 emissions from participants performing physical activities (walking and running at metabolic rates of 2.5 and 5 met, respectively) and psychological stimuli (meditation and cognitive tasks). Participants' physiological responses were recorded, including the skin temperature, electrodermal activity (EDA), and heart rate, and then analyzed for their relationship with CO2 and NH3 emissions. The results showed that physiological engagement considerably elevated per-person CO2 emission rates from 19.6 (seated) to 46.9 (2.5 met) and 115.4 L/h (5 met) and NH3 emission rates from 2.7 to 5.1 and 8.3 mg/h, respectively. CO2 emissions reduced when participants stopped running, whereas NH3 emissions continued to increase owing to their distinct emission mechanisms. Psychological engagement did not significantly alter participants' emissions of CO2 and NH3. Regression analysis revealed that CO2 emissions were predominantly correlated with heart rate, whereas NH3 emissions were mainly associated with skin temperature and EDA. These findings contribute to a deeper understanding of human metabolic emissions of CO2 and NH3.


Asunto(s)
Amoníaco , Dióxido de Carbono , Humanos
10.
Biotechnol Biofuels Bioprod ; 17(1): 14, 2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38281959

RESUMEN

BACKGROUND: Recent engineering efforts have targeted the ethanologenic bacterium Zymomonas mobilis for isobutanol production. However, significant hurdles remain due this organism's vulnerability to isobutanol toxicity, adversely affecting its growth and productivity. The limited understanding of the physiological impacts of isobutanol on Z. mobilis constrains our ability to overcome these production barriers. RESULTS: We utilized a systems-level approach comprising LC-MS/MS-based lipidomics, metabolomics, and shotgun proteomics, to investigate how exposure to ethanol and isobutanol impact the lipid membrane composition and overall physiology of Z. mobilis. Our analysis revealed significant and distinct alterations in membrane phospholipid and fatty acid composition resulting from ethanol and isobutanol exposure. Notably, ethanol exposure increased membrane cyclopropane fatty acid content and expression of cyclopropane fatty acid (CFA) synthase. Surprisingly, isobutanol decreased cyclopropane fatty acid content despite robust upregulation of CFA synthase. Overexpression of the native Z. mobilis' CFA synthase increased cyclopropane fatty acid content in all phospholipid classes and was associated with a significant improvement in growth rates in the presence of added ethanol and isobutanol. Heterologous expression of CFA synthase from Clostridium acetobutylicum resulted in a near complete replacement of unsaturated fatty acids with cyclopropane fatty acids, affecting all lipid classes. However, this did not translate to improved growth rates under isobutanol exposure. Correlating with its greater susceptibility to isobutanol, Z. mobilis exhibited more pronounced alterations in its proteome, metabolome, and overall cell morphology-including cell swelling and formation of intracellular protein aggregates -when exposed to isobutanol compared to ethanol. Isobutanol triggered a broad stress response marked by the upregulation of heat shock proteins, efflux transporters, DNA repair systems, and the downregulation of cell motility proteins. Isobutanol also elicited widespread dysregulation of Z. mobilis' primary metabolism evidenced by increased levels of nucleotide degradation intermediates and the depletion of biosynthetic and glycolytic intermediates. CONCLUSIONS: This study provides a comprehensive, systems-level evaluation of the impact of ethanol and isobutanol exposure on the lipid membrane composition and overall physiology of Z. mobilis. These findings will guide engineering of Z. mobilis towards the creation of isobutanol-tolerant strains that can serve as robust platforms for the industrial production of isobutanol from lignocellulosic sugars.

11.
Adv Mater ; : e2310789, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38253339

RESUMEN

Conventional osteogenic platforms utilize active growth factors to repair bone defects that are extensive in size, but they can adversely affect patient health. Here, an unconventional osteogenic platform is reported that functions by promoting capture of inactive osteogenic growth factor molecules to the site of cell growth for subsequent integrin-mediated activation, using a recombinant fragment of latent transforming growth factor beta-binding protein-1 (rLTBP1). It is shown that rLTBP1 binds to the growth-factor- and integrin-binding domains of fibronectin on poly(ethyl acrylate) surfaces, which immobilizes rLTBP1 and promotes the binding of latency associated peptide (LAP), within which inactive transforming growth factor beta 1 (TGF-ß1) is bound. rLTBP1 facilitates the interaction of LAP with integrin ß1 and the subsequent mechanically driven release of TGF-ß1 to stimulate canonical TGF-ß1 signaling, activating osteogenic marker expression in vitro and complete regeneration of a critical-sized bone defect in vivo.

12.
Mov Disord ; 39(1): 141-151, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37964426

RESUMEN

BACKGROUND: The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP3 ) receptor type 1 (IP3 R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood. OBJECTIVES: We aimed to identify novel SCA29 and GLSP cases to define core phenotypes, describe the spectrum of missense variation across ITPR1, standardize the ITPR1 variant nomenclature, and investigate disease progression in relation to cerebellar atrophy. METHODS: Cases were identified using next-generation sequencing through the Deciphering Developmental Disorders study, the 100,000 Genomes project, and clinical collaborations. ITPR1 alternative splicing in the human cerebellum was investigated by quantitative polymerase chain reaction. RESULTS: We report the largest, multinational case series of 46 patients with 28 unique ITPR1 missense variants. Variants clustered in functional domains of the protein, especially in the N-terminal IP3 -binding domain, the carbonic anhydrase 8 (CA8)-binding region, and the C-terminal transmembrane channel domain. Variants outside these domains were of questionable clinical significance. Standardized transcript annotation, based on our ITPR1 transcript expression data, greatly facilitated analysis. Genotype-phenotype associations were highly variable. Importantly, while cerebellar atrophy was common, cerebellar volume loss did not correlate with symptom progression. CONCLUSIONS: This dataset represents the largest cohort of patients with ITPR1 missense variants, expanding the clinical spectrum of SCA29 and GLSP. Standardized transcript annotation is essential for future reporting. Our findings will aid in diagnostic interpretation in the clinic and guide selection of variants for preclinical studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Asunto(s)
Aniridia , Anhidrasas Carbónicas , Ataxia Cerebelosa , Discapacidad Intelectual , Trastornos del Movimiento , Degeneraciones Espinocerebelosas , Humanos , Ataxia Cerebelosa/genética , Mutación Missense/genética , Trastornos del Movimiento/complicaciones , Atrofia , Receptores de Inositol 1,4,5-Trifosfato/química , Receptores de Inositol 1,4,5-Trifosfato/genética , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Anhidrasas Carbónicas/genética , Anhidrasas Carbónicas/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética
14.
J Knee Surg ; 37(6): 452-459, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37714214

RESUMEN

The annual demand for knee arthroplasty has been steadily rising, particularly in younger patients. The primary objective of this systematic review was to determine the impact of knee arthroplasties on knee function and activity levels in young (≤55 years) patients. A PubMed search from inception (1977) to March 2022 to identify eligible studies produced 640 peer-reviewed studies for consideration. A total of 18 studies including 4,186 knee arthroplasties in 3,200 patients (mean patient age at the time of surgery: 47.4 years, range: 18-55 years) were ultimately included for analysis. Mean final follow-up (FFU) duration was 5.8 years (range: 2-25.1 years). Mean FFU improvement in Knee Society Clinical Score was 48.0 (1,625 knees, range: 20.9-69.0), Knee Society Function Score was 37.4 (1,284 knees, range: 20-65). Mean FFU for the Tegner and Lysholm activity scale was 2.8 (4 studies, 548 knees, range: 0.7-4.2); University of California Los Angeles Physical Activity Questionnaire score was 2.8 (3 studies, 387 knees, range: 1.2-5); lower extremity activity scale was 1.84 (529 knees). The available evidence suggest that young patients typically realize sustained improvements in knee function compared to preoperative levels; however, these improvements do not typically translate into a return to desired activity levels or quality of life, and this patient population should expect a higher and earlier risk for revision than their older counterparts. Further research, including robust registry data, is needed to establish evidence-based indications, expectations, and prognoses for outcomes after knee arthroplasty in young and active patients.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Osteoartritis de la Rodilla , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Calidad de Vida , Reoperación , Articulación de la Rodilla/cirugía , Rodilla/cirugía , Resultado del Tratamiento , Osteoartritis de la Rodilla/cirugía , Estudios Retrospectivos
15.
Sleep Health ; 10(1S): S144-S148, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37730474

RESUMEN

OBJECTIVES: This study assessed whether there was a time-of-day effect on nausea reports in participants during studies employing circadian protocols. METHODS: Visual-analog-scales of nausea ratings were recorded from 34 participants (18-70years; 18 women) during forced desynchrony studies, where meals were scheduled at different circadian phases. Subjective nausea reports from a further 81 participants (18-35years; 36 women) were recorded during constant routine studies, where they ate identical isocaloric hourly snacks for 36-40 hours. RESULTS: Feelings of nausea varied by circadian phase in the forced desynchrony studies, peaking during the biological night. Nausea during the constant routine was reported by 27% of participants, commencing 2.9 ± 5.2 hours after the midpoint of usual sleep timing, but was never reported to start in the evening (4-9 PM). CONCLUSIONS: Nausea occurred more often during the biological night and early morning hours. This timing is relevant to overnight and early morning shift workers and suggests that a strategy to counteract that is to pay careful attention to meal timing.

16.
J Back Musculoskelet Rehabil ; 37(2): 305-315, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37781790

RESUMEN

BACKGROUND: Despite wobble board use being common in physiotherapy the effect of certain factors, essential to clinical reasoning, have not been investigated. OBJECTIVE: To determine the effect of biological sex, anthropometrics, footwear and dual tasking (DT) on wobble board balance performance. METHODS: Eighty-six healthy participants (44 females) had their wobble board performance measured during double-leg-stance (DLS) with eyes open (DLSEO), closed (DLSEC) and single-leg-stance (SLS) tasks, with and without footwear and a DT added. Anthropometrics were also measured. RESULTS: Females outperformed males during most tasks, with some large effect sizes (ES). Performance was moderately related to weight and shoulder, waist and hip circumference. Overall, there were no differences between footwear and no footwear, except for males during SLS. DT made little difference, except during DLSEO and SLS, where single task was better than DT, though only females had a large ES. CONCLUSION: During wobble board tasks, biological sex differences were observed and a modest correlation between anthropometrics and performance noted. DT and footwear had minimal effect.


Asunto(s)
Equilibrio Postural , Humanos , Masculino , Adulto Joven , Femenino
17.
Hypertension ; 81(2): 330-339, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38018471

RESUMEN

BACKGROUND: Salt sensitivity of blood pressure (SSBP) is a substantial risk factor for cardiovascular morbidity and mortality. Striatin (STRN) is critical for estrogen and aldosterone nongenomic signaling. However, the role of biological sex on the SSBP phenotype associated with STRN gene variants remains unexplored. METHOD: Data from 1306 subjects participating in the Hypertensive Pathotype (HyperPATH) Consortium were used to identify STRN gene single-nucleotide variants associated with SSBP. Haploblock analysis revealed a novel diplotype in the upstream regulatory region of STRN (rs888083 and rs6744560), with 31% of subjects being homozygous for the risk diplotype. RESULTS: Individuals homozygous for the risk diplotype had significantly greater SSBP than nonrisk diplotypes (P<0.009). While a significant genotype/SSBP association was present in both sexes, their potential mechanisms differed. Women, but not men homozygous risk diplotypes, had significantly greater aldosterone levels than nonrisk diplotypes (5.8±0.4 versus 3.2±0.7 ng/dl; P=0.01; liberal Na+ diet, adjusted). Men, but not women, homozygous risk diplotypes, had significantly reduced renal plasma flow response to Angiotensin II than nonrisk diplotypes (delta 95.2±5.2 versus 122.9±10.2 mL/min per 1.73 m2; P=0.01; liberal Na+ diet, adjusted). The single-nucleotide variants composing the risk diplotype were associated with lower STRN mRNA expression in human tissues (in silico). CONCLUSION: In women, the primary driver of SSBP is increased aldosterone, while in men, it is reduced renal plasma flow responses. Thus, despite a common hypertensive phenotype (SSBP) in both sexes, the specific treatment approaches might differ to increase therapeutic gain and mitigate adverse effects. These genetic- and sex-based observational results require confirmation in a prospective clinical study.


Asunto(s)
Aldosterona , Hipertensión , Femenino , Humanos , Masculino , Presión Sanguínea/genética , Nucleótidos , Estudios Prospectivos , Sodio , Cloruro de Sodio Dietético
18.
Diabetes Care ; 47(3): 393-400, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38151474

RESUMEN

OBJECTIVE: This multicenter prospective cohort study compared pancreas volume as assessed by MRI, metabolic scores derived from oral glucose tolerance testing (OGTT), and a combination of pancreas volume and metabolic scores for predicting progression to stage 3 type 1 diabetes (T1D) in individuals with multiple diabetes-related autoantibodies. RESEARCH DESIGN AND METHODS: Pancreas MRI was performed in 65 multiple autoantibody-positive participants enrolled in the Type 1 Diabetes TrialNet Pathway to Prevention study. Prediction of progression to stage 3 T1D was assessed using pancreas volume index (PVI), OGTT-derived Index60 score and Diabetes Prevention Trial-Type 1 Risk Score (DPTRS), and a combination of PVI and DPTRS. RESULTS: PVI, Index60, and DPTRS were all significantly different at study entry in 11 individuals who subsequently experienced progression to stage 3 T1D compared with 54 participants who did not experience progression (P < 0.005). PVI did not correlate with metabolic testing across individual study participants. PVI declined longitudinally in the 11 individuals diagnosed with stage 3 T1D, whereas Index60 and DPTRS increased. The area under the receiver operating characteristic curve for predicting progression to stage 3 from measurements at study entry was 0.76 for PVI, 0.79 for Index60, 0.79 for DPTRS, and 0.91 for PVI plus DPTRS. CONCLUSIONS: These findings suggest that measures of pancreas volume and metabolism reflect distinct components of risk for developing stage 3 type 1 diabetes and that a combination of these measures may provide superior prediction than either alone.


Asunto(s)
Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/diagnóstico , Estudios Prospectivos , Páncreas/diagnóstico por imagen , Páncreas/metabolismo , Factores de Riesgo , Autoanticuerpos , Imagen por Resonancia Magnética
20.
Viruses ; 15(12)2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-38140568

RESUMEN

The 2022 global Mpox outbreak swiftly introduced unforeseen diversity in the monkeypox virus (MPXV) population, resulting in numerous Clade IIb sublineages. This propagation of new MPXV mutations warrants the thorough re-investigation of previously recommended or validated primers designed to target MPXV genomes. In this study, we explored 18 PCR primer sets and examined their binding specificity against 5210 MPXV genomes, representing all the established MPXV lineages. Our results indicated that only five primer sets resulted in almost all perfect matches against the targeted MPXV lineages, and the remaining primer sets all contained 1-2 mismatches against almost all the MPXV lineages. We further investigated the mismatched primer-genome pairs and discovered that some of the primers overlapped with poorly sequenced and assembled regions of the MPXV genomes, which are consistent across multiple lineages. However, we identified 173 99% genome-wide conserved regions across all 5210 MPXV genomes, representing 30 lineages/clades with at least 80% lineage-specific consensus for future primer development and primer binding evaluation. This exercise is crucial to ensure that the current detection schemes are robust and serve as a framework for primer evaluation in clinical testing development for other infectious diseases.


Asunto(s)
Bioensayo , Monkeypox virus , Humanos , Consenso , Brotes de Enfermedades , Monkeypox virus/genética , Reacción en Cadena de la Polimerasa
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