Nevin Manimala

Open Biol. 2023 Jan;13(1):220314. doi: 10.1098/rsob.220314. Epub 2023 Jan 18.

ABSTRACT

p38 kinases are key elements of the cellular stress response in animals. They mediate the cell response to a multitude of stress stimuli, from osmotic shock to inflammation and oncogenes. However, it is unknown how such diversity of function in stress evolved in this kinase subfamily. Here, we show that the p38 kinase was already present in a common ancestor of animals and fungi. Later, in animals, it diversified into three JNK kinases and four p38 kinases. Moreover, we identified a fifth p38 paralog in fishes and amphibians. Our analysis shows that each p38 paralog has specific amino acid substitutions around the hinge point, a region between the N-terminal and C-terminal protein domains. We showed that this region can be used to distinguish between individual paralogs and predict their specificity. Finally, we showed that the response to hyperosmotic stress in Capsaspora owczarzaki, a close unicellular relative of animals, follows a phosphorylation-dephosphorylation pattern typical of p38 kinases. At the same time, Capsaspora‘s cells upregulate the expression of GPD1 protein resembling an osmotic stress response in yeasts. Overall, our results show that the ancestral p38 stress pathway originated in the root of opisthokonts, most likely as a cell’s reaction to salinity change in the environment. In animals, the pathway became more complex and incorporated more stimuli and downstream targets due to the p38 sequence evolution in the docking and substrate binding sites around the hinge region. This study improves our understanding of p38 evolution and opens new perspectives for p38 research.

PMID:36651171 | DOI:10.1098/rsob.220314

Hepatology. 2023 Jan 19. doi: 10.1097/HEP.0000000000000286. Online ahead of print.

ABSTRACT

BACKGROUND AIMS: Nonalcoholic fatty liver disease (NAFLD) strongly associates with cardiovascular disease (CVD) risk factors; however, the association between NAFLD and incident CVD, CVD-related mortality, incident cancer, and all-cause mortality is unclear.

APPROACH RESULTS: We included 10,040 participants from the Framingham Heart Study, the Coronary Artery Risk Development in Young Adults (CARDIA) Study, and the Multi-Ethnic Study of Atherosclerosis (MESA) to assess the longitudinal association between liver fat (defined on computed tomography [CT]) and incident CVD, CVD-related mortality, incident cancer, and all-cause mortality. We performed multivariable-adjusted Cox regression models including age, sex, diabetes, systolic blood pressure, alcohol use, smoking, high-density lipoprotein, triglycerides, and body mass index (BMI) at baseline or time-varying covariates. The average age was 51.3±3.3 years and 50.6% were women. Hepatic steatosis was associated with all-cause mortality after 12.7 years of mean follow-up when adjusting for baseline CVD risk factors, including BMI [hazard ratio (HR) 1.21, 1.04-1.40]; however, results were attenuated when utilizing time-varying covariates. The association between hepatic steatosis and incident CVD was not statistically significant after we accounted for BMI in models considering baseline covariates or time-varying covariates. We observed no association between hepatic steatosis and CVD-related mortality or incident cancer.

CONCLUSIONS: In this large, multi-cohort study of participants with CT-defined hepatic steatosis, accounting for change in CVD risk factors over time attenuated associations between liver fat and overall mortality or incident CVD. Our work highlights the need to consider concurrent cardiometabolic disease when determining associations between NAFLD and CVD and mortality outcomes.

PMID:36651168 | DOI:10.1097/HEP.0000000000000286

Arch Esp Urol. 2022 Dec;75(10):867-872. doi: 10.56434/j.arch.esp.urol.20227510.126.

ABSTRACT

BACKGROUND: To investigate the influencing factors of health-related quality of life (HRQOL) in children and adolescents with congenital adrenal hyperplasia (CAH).

METHODS: Pediatric Quality of Life Inventory 4.0 (PedsQL4.0) and 8-item Morisky medication adherence scale (MMAS-8) were used to survey eighty-seven children and adolescents with CAH (5-18 years), as well as their parents. SPSS 26.0 software was utilized for statistical analysis.

RESULTS: The scores of social functions, school performance, social psychological function and total scores of CAH girls aged 13-18 years were lower than those of boys (p < 0.05). CAH children with older age, longer course of disease, older than 3 years old at first diagnosis, living in rural areas, lower education level of caregivers and lower family monthly income had lower scores. CAH patients with poor compliance and complications had significantly lower scores in each single domain, social psychological function, and total scores than those with good compliance and no complications (p < 0.05).

CONCLUSIONS: Age, age at initial diagnosis, course of disease, complications, compliance, residence, education level of caregivers and family income were important factors affecting HRQOL of CAH children and adolescents, among which complications and compliance were independent key influencing factors.

PMID:36651098 | DOI:10.56434/j.arch.esp.urol.20227510.126

Arch Esp Urol. 2022 Dec;75(10):862-866. doi: 10.56434/j.arch.esp.urol.20227510.125.

ABSTRACT

OBJECTIVES: To evaluate the efficacy and cost effectiveness of two-stage percutaneous nephrolithotomy (PCNL) in complex renal calculus disease.

METHODS: The clinical data of 106 patients who underwent two-stage PCNL at the Second Affiliated Hospital of Kunming Medical University from January 2017 to May 2022 were analyzed. In order to select more accurate timing and strategies to reduce costs and surgery risk in two-stage PCNL patients, different parameters were measured-including the preoperative urinary tract infection, intraoperative bleeding, operative time, postoperative stone clearance and treatment costs. Patients were divided into group A and group B according to different timings of two-stage PCNL operation. Group A included patients who underwent two-stage PCNL during their period of hospitalization 5 to 9 days after the one-stage PCNL. Group B comprised patients who were re-hospitalized for two-stage PCNL 29 to 35 days after the one-stage PCNL.

RESULTS: There were statistically significant differences in the influence of stone diameter and operation time in intraoperative blood loss of PCNL in 106 patients (p < 0.001). Compared with one-stage PCNL, the intraoperative hemoglobin loss and hematocrit loss means of patients with two-stage PCNL were decreased, the stone diameter mean of was smaller, and the mean operative time was diminished (p < 0.001). There were no significant differences in the hemoglobin loss, hematocrit loss and stone clearance rate means between group A and group B (p > 0.05). The urinary tract infection rate in group A was lower than the one in group B, and the average treatment cost was lower than the one in group B (p = 0.006, p < 0.001, respectively).

CONCLUSIONS: Intraoperative bleeding in PCNL is influenced by stone diameter and operative time. Two-stage PCNL displays smaller calculi, shorter operation time and lower intraoperative blood loss than one-stage PCNL. Patients who had no surgical contraindication could undergo two-stage PCNL during the same hospitalization 5 to 9 days after one-stage PCNL to avoid rehospitalization. This approach could reduce the risk of urinary tract infection of indwelling nephrostomy tube and decrease the economic burden of patients.

PMID:36651097 | DOI:10.56434/j.arch.esp.urol.20227510.125

Arch Esp Urol. 2022 Dec;75(10):854-861. doi: 10.56434/j.arch.esp.urol.20227510.124.

ABSTRACT

BACKGROUND: Sexual function is an excellent marker of psychological, systemic, and specifically vascular performance. Endothelial dysfunction is the main determinant of coronavirus disease 2019 (COVID-19) symptoms. Considering the adverse effects of the COVID-19 pandemic on psychological and sexual functions, we hypothesized potential differences and underlying factors if there is any erectile function and premature ejaculation status of male patients with COVID-19 by comparing both with the control group.

METHODS: Hospitalized male patients diagnosed with COVID-19 pneumonia were evaluated. Male patients who applied to the Urology outpatient clinic were the control group. All participants completed the International Index of Erectile Function Form-15 (IIEF-15) and gave information regarding their premature ejaculation (PE) status if present. COVID-19 patients were called by phone to fill in the IIEF-15. Their PE status was questioned on the 45th and 90th days after discharge. The following parameters were in the data records: Age, comorbidity, length of hospital stay, treatment, oxygen saturation, pulmonary involvement, white blood cell (WBC), C-reactive protein (CRP), ferritin, fibrinogen, D-dimer, and sedimentation values.

RESULTS: The study had 253 participants, including 168 COVID-19 patients and 85 volunteers as the control group. The number of PE cases was less, whereas erectile dysfunction (ED) cases were more in the COVID-19 patient group in comparison to the control group in the pre-pandemic period (p = 0.00) (p = 0.00). In the post-pandemic period, PE developed in 13 more COVID-19 patients on the 45th and 90th days (p = 0.00). The IIEF-15 scores of COVID-19 patients decreased by 4-point in the short term and by 3-point in the long term (p = 0.002). Age and sedimentation were responsible for the difference in PE status. On the other hand, comorbidity, length of hospital stay, treatment type, WBC, D-dimer, ferritin, CRP levels, and pulmonary infiltration were responsible for the difference in ED.

CONCLUSIONS: Based on our findings, we can say that we have enough evidence to suspect COVID-19 sequelae can affect male sexual health. After the pandemic, male patients with andrological problems should have enough time to feel more comfortable and their organic and psychogenic conditions should be optimized.

PMID:36651096 | DOI:10.56434/j.arch.esp.urol.20227510.124

Arch Esp Urol. 2022 Dec;75(10):819-830. doi: 10.56434/j.arch.esp.urol.20227510.120.

ABSTRACT

PURPOSE: Percutaneous nephrolithotomy (PCNL) requires perforating the kidney, which may damage part of the patient’s nephron. Further, compared with single-channel PCNL (S-PCNL), the safety of multi-channel PCNL (M-PCNL) and whether it affects the renal function of patients has been debated. The meta-analysis aimed to comprehensively evaluate the safety of M-PCNL.

METHODS: We carefully searched the Pubmed, Embass, and Web of Science databases for relevant research reported before October 30, 2021, and analyzed the included literature using the Stata software. Changes in the serum creatinine levels, split renal function and the incidence of postoperative complications were used to evaluate the safety of M-PCNL.

RESULTS: Overall, 11 articles were included in this meta-analysis. The results showed that there was no statistically significant difference between S-PCNL and M-PCNL in terms of changes in serum creatinine levels (pooled Mean Difference (MD) = -0.015, 95% CI: -0.047-0.018, I² = 0.0%, p = 0.92). Further, a sensitivity analysis showed that our conclusions were stable. With the p-values in both Egger’s and Begg’s tests being greater than 0.05, there was no significant publication bias in the included literature. A subgroup analysis based on patient ethnicity yielded consistent results. Our meta-analysis yielded similar results in terms of changes in split renal function (pooled MD = 0.008, 95% CI: -0.013-0.030, I² = 96%, p < 0.01). There was no significant difference in the incidence of postoperative renal perforation between M-PCNL and S-PCNL (pooled Odds Ratio (OR) = 1.686, 95% CI: 0.677-4.193, I² = 0.0%, p = 0.66). However, M-PCNL was found to cause more postoperative blood transfusion, postoperative infection, and pleural damage than S-PCNL (pooled OR = 3.104, 95% CI: 2.277-4.232, I² = 46%, p = 0.03, pooled OR = 1.862, 95% CI: 1.165-2.974, I² = 0%, p = 0.46, and pooled OR = 3.446, 95% CI: 1.168-10.171, I² = 0%, p = 1.00 respectively).

CONCLUSIONS: Compared with S-PCNL, M-PCNL showed no significant differences in terms of changes in serum creatinine levels in patients. However, M-PCNL showed a greater probability of resulting in postoperative blood transfusion, postoperative infection, and pleural damage.

PMID:36651092 | DOI:10.56434/j.arch.esp.urol.20227510.120

Proc Biol Sci. 2023 Jan 25;290(1991):20222204. doi: 10.1098/rspb.2022.2204. Epub 2023 Jan 18.

ABSTRACT

Helminth transmission and morbidity are dependent on the number of mature parasites within a host; however, observing adult worms is impossible for many natural infections. An outstanding challenge is therefore relating routine diagnostics, such as faecal egg counts, to the underlying worm burden. This relationship is complicated by density-dependent fecundity (egg output per worm reduces due to crowding at high burdens) and the skewed distribution of parasites (majority of helminths aggregated in a small fraction of hosts). We address these questions for the carcinogenic liver fluke Opisthorchis viverrini, which infects approximately 10 million people across Southeast Asia, by analysing five epidemiological surveys (n = 641) where adult flukes were recovered. Using a mechanistic model, we show that parasite fecundity varies between populations, with surveys from Thailand and Laos demonstrating distinct patterns of egg output and density-dependence. As the probability of observing faecal eggs increases with the number of mature parasites within a host, we quantify diagnostic sensitivity as a function of the worm burden and find that greater than 50% of cases are misdiagnosed as false negative in communities close to elimination. Finally, we demonstrate that the relationship between observed prevalence from routine diagnostics and true prevalence is nonlinear and strongly influenced by parasite aggregation.

PMID:36651047 | DOI:10.1098/rspb.2022.2204

Proc Biol Sci. 2023 Jan 25;290(1991):20221834. doi: 10.1098/rspb.2022.1834. Epub 2023 Jan 18.

ABSTRACT

Stereotypes are generalized beliefs about groups of people, which are used to make decisions and judgements about them. Although such heuristics can be useful when decisions must be made quickly, or when information is lacking, they can also serve as the basis for prejudice and discrimination. In this paper, we study the evolution of stereotypes through group reciprocity. We characterize the warmth of a stereotype as the willingness to cooperate with an individual based solely on the identity of the group they belong to. We show that when stereotype groups are large, such group reciprocity is less likely to evolve, and stereotypes tend to be negative. We also show that, even when stereotypes are broadly positive, individuals are often overly pessimistic about the willingness of those they stereotype to cooperate. We then show that the tendency for stereotyping itself to evolve is driven by the costs of cognition, so that more people are stereotyped with greater coarseness as costs increase. Finally we show that extrinsic ‘shocks’, in which the benefits of cooperation are suddenly reduced, can cause stereotype warmth and judgement bias to turn sharply negative, consistent with the view that economic and other crises are drivers of out-group animosity.

PMID:36651042 | DOI:10.1098/rspb.2022.1834

Sci Prog. 2023 Jan-Mar;106(1):368504221149798. doi: 10.1177/00368504221149798.

ABSTRACT

In numerous industrial procedures, the main concern of design engineers is ensuring adequate heat and mass transfer, such as in the heating and cooling practices of solar water heaters, geothermal systems, extrusion of metal, insulation of buildings, electronics, turbines, aerodynamics, electronics, paper manufacturing, and glass fiber production. The unsteady double-diffusive mixed convection flow of boundary layer nanofluids above a vertical region near stagnation point flow is developed and examined here. The Brownian motion and thermophoresis effects are incorporated by using Buongiorno’s model. In the thermal energy equations, diffusion of regular and cross types is also used. By the use of the local similarity method along with suitable similarity transformations, nonlinear unsteady partial differential equations are converted to nonlinear ordinary differential equations and are numerically solved by the Keller-Box method. The investigation expresses that these profiles of solute concentration and nanoparticle concentration, temperature, and velocity in their boundary layers, respectively, depending on several parameters. A graphic analysis of all these parameters’ possessions on nature’s boundary layers is depicted. The highest rate of heat transfer is obtained with negligible thermophoresis effect. Furthermore, it is perceived that an increase in Nc and Nt results in a reduction in the reduced Sherwood number of nanoparticles, whereas addition results in an increase in the Nb number. There is a reverse effect on the temperature field and layer thickness for heat generation. In the wake of the above-mentioned potential applications, the current study of fluid flow has been found to be very interesting and innovative in the analysis of the influence of Brownian motion and thermophoresis effects near stagnation point flow, which will further make revolutions in industrial fields. Moreover, Buongiorno’s model predicts the characteristics of double-diffusive fluids in enhancing heat transfers. This investigation has been established as a result of the numerous industrial applications mentioned above.

PMID:36651004 | DOI:10.1177/00368504221149798

CNS Neurosci Ther. 2023 Jan 17. doi: 10.1111/cns.14094. Online ahead of print.

ABSTRACT

MAIN PROBLEM: Inflammation plays an important role in the pathological progress associated with stroke. Serum uric acid (SUA) to lymphocyte ratio (ULR), a novel inflammatory biomarker, has been considered as a better risk stratification tool of adverse outcomes than SUA or lymphocyte alone. This study aimed to investigate whether ULR produced more predictive value for stroke and explore the potential mediators of the associations.

METHODS: This study enrolled 93,023 Chinese participants without stroke and myocardial infarction at baseline. Cox proportional hazard models were used to analyze the associations of ULR with stroke and subtypes. Mediation analyses were conducted to explore potential mediators of the associations.

RESULTS: During a median follow-up of 13.00 years, 6081 cases of incident stroke occurred, including 5048 cases of ischemic stroke (IS) and 900 cases of hemorrhagic stroke (HS). After adjustment for confounders, the Q4 group was associated with a higher risk of HS (HR, 1.25; 95% CI, 1.03-1.50), but not with total stroke (HR, 1.07; 95% CI, 1.03-1.13) or IS (HR, 1.04; 95% CI, 0.97-1.12). No significant associations were found between SUA or lymphocyte and any stroke. ULR outperformed SUA or lymphocytes alone in predicting stroke. Additionally, the significant association between ULR and HS was partially mediated by systolic blood pressure (20.32%), diastolic blood pressure (11.18%) and estimated glomerular filtration rate (9.19%).

CONCLUSIONS: ULR was significantly associated with the risk of HS, but not with IS. Systolic blood pressure, diastolic blood pressure and estimated glomerular filtration rate were potential mediators for the association.

PMID:36650955 | DOI:10.1111/cns.14094