Category: Nevin Manimala

Environ Monit Assess. 2023 Jul 20;195(8):973. doi: 10.1007/s10661-023-11579-x.

ABSTRACT

Using an integrated analytical hierarchy process, remote sensing and geographic information system techniques, the current study aims to map and identify the potential groundwater zones of Kurukshetra District of Haryana, which is located in the Ghaggar and Upper Yamuna Basins in India. This is done in the context of a significant change in the use of groundwater pattern, with respect to its continuously increasing demand due to the growing population, expansion of area under irrigation and related economic factors. The amount and quality of groundwater are anticipated to be impacted by anthropogenic activities as well as natural factors such as geomorphology, soil type, lithology and rainfall variance owing to a changing climatic scenario. The potential index of groundwater for this study was calculated by using nine important factors, including geomorphology, rainfall, soil type, depth to groundwater level, lithology, land use land cover, normalized difference vegetation index, cumulative sand thickness and elevation. The integration of multiple thematic layers was accomplished using the overlay weighted method to generate a potential groundwater zonation map and the accuracy of the resulting map was validated against a groundwater resource potential map. Statistical measures demonstrate an 82% agreement between the two maps, indicating a high level of concurrence. Accordingly, three groundwater zones of good, average and bad potential have been identified in the study area. In the current study, a process that combines weighted ranking with spatial data transformation and harmonization has been developed to obtain information for accurate decision-making. The results accruing from this research have significant ramifications for creating regional sustainable groundwater management plans.

PMID:37470843 | DOI:10.1007/s10661-023-11579-x

Elife. 2023 Jul 20;12:RP85596. doi: 10.7554/eLife.85596.

ABSTRACT

The degradation of sperm-borne mitochondria after fertilization is a conserved event. This process known as post-fertilization sperm mitophagy, ensures exclusively maternal inheritance of the mitochondria-harbored mitochondrial DNA genome. This mitochondrial degradation is in part carried out by the ubiquitin-proteasome system. In mammals, ubiquitin-binding pro-autophagic receptors such as SQSTM1 and GABARAP have also been shown to contribute to sperm mitophagy. These systems work in concert to ensure the timely degradation of the sperm-borne mitochondria after fertilization. We hypothesize that other receptors, cofactors, and substrates are involved in post-fertilization mitophagy. Mass spectrometry was used in conjunction with a porcine cell-free system to identify other autophagic cofactors involved in post-fertilization sperm mitophagy. This porcine cell-free system is able to recapitulate early fertilization proteomic interactions. Altogether, 185 proteins were identified as statistically different between control and cell-free-treated spermatozoa. Six of these proteins were further investigated, including MVP, PSMG2, PSMA3, FUNDC2, SAMM50, and BAG5. These proteins were phenotyped using porcine in vitro fertilization, cell imaging, proteomics, and the porcine cell-free system. The present data confirms the involvement of known mitophagy determinants in the regulation of mitochondrial inheritance and provides a master list of candidate mitophagy co-factors to validate in the future hypothesis-driven studies.

PMID:37470242 | DOI:10.7554/eLife.85596

Hum Reprod. 2023 Jul 20:dead148. doi: 10.1093/humrep/dead148. Online ahead of print.

ABSTRACT

STUDY QUESTION: Can anti-Müllerian hormone (AMH) help predict how many oocytes will be retrieved following double stimulation (DuoStim)?

SUMMARY ANSWER: A simple clinical tool can use serum AMH values to predict ovarian response following DuoStim in IVF cycles.

WHAT IS ALREADY KNOWN: The knowledge that multiple follicular waves arise during a single ovarian cycle has led to the introduction of unconventional ovarian stimulation protocols. The DuoStim protocol involves two successive ovarian stimulations performed during a single ovarian cycle and has been proposed as an approach for patients with poor ovarian response and for medical fertility preservation. As AMH has been used as a marker of ovarian reserve and stimulation response, the current study aimed to investigate the diagnostic performance of AMH in predicting the number of retrieved oocytes following DuoStim.

STUDY DESIGN, SIZE, DURATION: This is a retrospective observational study involving 116 patients who received IVF treatment from January 2021 to September 2022.

PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at a private IVF centre. Only patients who had their AMH measured prior to treatment and had complete patient records regarding their clinical and IVF/ICSI cycle characteristics were included. The primary outcome was the correlation between AMH values and the number of oocytes retrieved following DuoStim. Parametric and non-parametric tests were used to compare baseline characteristics and outcomes. Spearman’s R was used to analyse correlations between variables, while the C statistic was used to calculate the diagnostic performance of AMH.

MAIN RESULTS AND THE ROLE OF CHANCE: AMH levels were significantly correlated with the total number of oocytes retrieved after the DuoStim (R 0.61; CI 0.44-0.70; P < 0.0001). The difference in the total number of oocytes retrieved between the first (median 4 oocytes, interquartile range (IQR) 2-6) and second (median 6 oocytes, IQR 3.2-8) stimulation was statistically significant (P < 0.0001). However, there was no significant difference in the number of mature oocytes that were retrieved (median of 3 and 4 in the first and second stimulations, respectively). After the first stimulation, 68% of patients had at least one blastocyst available, while after the second stimulation, 74% did (NS). Based on linear regression, each 0.25 ng/ml increase in basal AMH corresponds to one additional oocyte recovered at the end of both stimulations (R2: 0.32, P < 0.0001).

LIMITATIONS, REASONS FOR CAUTION: The results are limited owing to the observational nature of the study and the number of participants.

WIDER IMPLICATIONS OF THE FINDINGS: Counselling infertile couples regarding the intermediate outcome of IVF (i.e. number of retrieved oocytes) is one of the most demanding tasks that clinicians face. To our knowledge, this is the first study that provides an easy-to-use clinical tool that enables the quantitative prediction of ovarian response following DuoStim, based on serum AMH values.

STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. The authors declare no conflicts of interest.

TRIAL REGISTRATION NUMBER: N/A.

PMID:37470235 | DOI:10.1093/humrep/dead148

Eur J Public Health. 2023 Jul 20:ckad110. doi: 10.1093/eurpub/ckad110. Online ahead of print.

ABSTRACT

BACKGROUND: Intra-annual excess mortality is the most reliable measure of losses of lives due to short-term risk factors. The objectives of our study are (i) to estimate excess mortality across German states in the course of the coronavirus disease 2019 (COVID-19) pandemic years 2020 and 2021 and (ii) to identify possible regional-level determinants of spatial inequality in pandemic-related excess mortality.

METHODS: We use weekly mortality data series for the calculation of weekly death rates, standardized by age for each federal state of Germany. We estimate the expected level of mortality as state-specific mortality trends and excess mortality in 2020 and 2021. We explore ecological statistical relationships between excess mortality, COVID-19 morbidity, and selected regional socioeconomic indicators using fixed-effects regression models.

RESULTS: Our study shows that during the first pandemic year, there was South-to-North gradient in excess mortality in Germany, with excess mortality being higher in the South. Over the course of the second pandemic year 2021, this gradient changed to become an East-to-West gradient, with excess mortality being higher in the East. The results of the study show stronger effects of COVID-19 morbidity on excess mortality in East Germany. State-level indicators reflecting economic activity, employment, and capacity of intensive care units show significant correlations with excess mortality across the states.

CONCLUSIONS: The results show pronounced state-level differences in the magnitude of excess mortality during the COVID-19 pandemic in Germany. Economic activity, employment and capacity of intensive care units were the most important state-level characteristics associated with the observed spatial variations in excess mortality.

PMID:37470231 | DOI:10.1093/eurpub/ckad110

Hypertension. 2023 Jul 20. doi: 10.1161/HYPERTENSIONAHA.123.21217. Online ahead of print.

ABSTRACT

BACKGROUND: Although blood pressure (BP) increases throughout young adulthood for most individuals, the age-related slope is not uniform. This study aimed to assess associations of demographic, clinical, behavioral, psychosocial, and neighborhood characteristics with age-related BP slope among 4 race-sex groups who participated in the Coronary Artery Risk Development in Young Adults study.

METHODS: Individuals (n=3554) aged 18 to 30 years were included in this analysis if they had normal BP at baseline and ≥2 BP measurements during the years 1985/1986 to 2015/2016. Associations of exposure variables with systolic BP slope were assessed using multivariate linear models.

RESULTS: Over a mean follow-up of ~30 years, greater decade increases in systolic BP were estimated among Black than White participants (mean difference between Black females and White females: 3.0 mm Hg/decade; between Black males and White males: 4.7 mm Hg/decade). The exposure risk factors associated with greater increases in systolic BP throughout adulthood varied by race and sex. None of these factors were associated with increases in systolic BP in all race-sex groups. Parent history of high BP was associated with a steeper positive slope among Black females (effect size per decade: 1.1 [95% CI, 0.6-1.6]; P<0.01), Black males (0.6 [95% CI, 0.02-1.2]; P<0.05), and White females (0.6 [95% CI, 0.2-1.0]; P<0.01). Other risk factors were associated with greater age-related yearly increases in systolic BP among 1 or 2 of the 4 race-sex groups or were not statistically significant.

CONCLUSIONS: Culturally tailored BP reduction approach should be considered in conjunction with primordial prevention, to moderate increases in BP throughout adulthood.

PMID:37470199 | DOI:10.1161/HYPERTENSIONAHA.123.21217

Evolution. 2023 Jul 20:qpad133. doi: 10.1093/evolut/qpad133. Online ahead of print.

ABSTRACT

Since its emergence in late 2019, the SARS-CoV-2 virus has spread globally, causing the ongoing COVID-19 pandemic. In the fall of 2020, the Alpha variant (lineage B.1.1.7) was detected in England and spread rapidly, outcompeting the previous lineage. Yet, very little is known about the underlying modifications of the infection process that can explain this selective advantage. Here, we try to quantify how the Alpha variant differed from its predecessor on two phenotypic traits: the transmission rate and the duration of infectiousness. To this end, we analysed the joint epidemiological and evolutionary dynamics as a function of the Stringency Index, a measure of the amount of Non-Pharmaceutical Interventions. Assuming that these control measures reduce contact rates and transmission, we developed a two-step approach based on SEIR models and the analysis of a combination of epidemiological and evolutionary information. First, we quantify the link between the Stringency Index and the reduction in viral transmission. Secondly, based on a novel theoretical derivation of the selection gradient in an SEIR model, we infer the phenotype of the Alpha variant from its frequency changes. We show that its selective advantage is more likely to result from a higher transmission than from a longer infectious period. Our work illustrates how the analysis of the joint epidemiological and evolutionary dynamics of infectious diseases can help understand the phenotypic evolution driving pathogen adaptation.

PMID:37470192 | DOI:10.1093/evolut/qpad133

Soft Matter. 2023 Jul 20. doi: 10.1039/d3sm00835e. Online ahead of print.

ABSTRACT

Soft condensed matter structures often challenge us with complex many-body phenomena governed by collective modes spanning wide spatial and temporal domains. In order to successfully tackle such problems, mesoscopic coarse-grained (CG) statistical models are being developed, providing a dramatic reduction in computational complexity. CG models provide an intermediate step in the complex statistical framework of linking the thermodynamics of condensed phases with the properties of their constituent atoms and molecules. These allow us to offload part of the problem to the CG model itself and reformulate the remainder in terms of reduced CG phase space. However, such exchange of pawns to chess pieces, or ‘Hamiltonian renormalization’, is a radical step and the thermodynamics of the primary atomic and CG models could be quite distinct. Here, we present a comprehensive study of the phase diagram including binodal and interfacial properties of a dissipative particle dynamics (DPD) model, extended to include finite-range attraction to support the liquid-gas equilibrium. Despite the similarities with the atomic model potentials, its phase envelope is markedly different featuring several anomalies such as an unusually broad liquid range, change in concavity of the liquid coexistence branch with variation of the model parameters, volume contraction on fusion, temperature of maximum density in the liquid phase and negative thermal expansion in the solid phase. These results provide new insight into the connection between simple potential models and complex emergent condensed matter phenomena.

PMID:37470164 | DOI:10.1039/d3sm00835e

BJU Int. 2023 Jul 20. doi: 10.1111/bju.16134. Online ahead of print.

ABSTRACT

OBJECTIVES: to compare USC pentafecta and trifecta achievement comparing open radical cystectomy (ORC) vs robot-assisted RC (RARC) with totally intracorporeal UD (i-UD) from a randomised controlled trial (RCT) MATERIALS AND METHODS: Patients were eligible for randomization if they had a diagnostic TURBt with cT2-4, cN0, cM0, or recurrent HG NMIBC and no anesthesiologic contraindications to robotic surgery. Patients were enrolled with a covariate adaptive randomization process based on the following variables: BMI, ASA score, preoperative haemoglobin, planned UD, neoadjuvant chemotherapy and cT-stage. USC pentafecta was defined as the combination, 1-yr after surgery, of negative soft tissue surgical margins, ≥ 16 lymph node (LN) yield, absence of major (Clavien≥3) complications at 90 days, absence of UD-related long-term sequalae and absence of clinical recurrence. Trifecta was defined as the coexistence of daytime urinary continence, absence of major complications and recurrence-free status, all assessed at 1 year. Continuous and categorical variables were compared using Student t and Chi-Square tests, respectively. Univariable logistic regression analysis was performed to assess the role of USC pentafecta and trifecta achievement on HRQoL.

RESULTS: No statistically significant difference was observed in USC pentafecta and trifecta achievement between groups. Among secondary outcomes, univariable logistic regression analysis was performed and both 1yr USC Pentafecta and trifecta achievement were predictors of 2yrs unmodified global QoL.

CONCLUSIONS: This study supports equivalence of RARC-iUD and ORC with regard to surgical quality as described by USC pentafecta and trifecta. We described a significant impact of USC pentafecta and trifecta achievement on global health status/QoL, providing a strict correlation between objective evaluation of surgical outcomes and self-reported HRQoL.

PMID:37470132 | DOI:10.1111/bju.16134

J Prosthodont. 2023 Jul 20. doi: 10.1111/jopr.13738. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this cross-sectional clinical study was to determine and compare alveolar ridge mucosa thickness at crestal, buccal, and lingual locations of the maxillary and mandibular arches in completely edentulous patients using a dedicated, ultrasonic gingival scanner.

MATERIALS AND METHODS: Thirty-eight completely edentulous subjects were included in the study. In each subject, soft tissue thickness was measured at 28 sites of the edentulous ridge by a single calibrated examiner. Intra-observer reliability was calculated with Intraclass Correlation Coefficients by measuring 10 subjects twice, after 1 week. Measurements (mm) were taken at the buccal, lingual, and crestal aspects of the ridge with a dedicated ultrasonic scanner. Repeated measures ANOVA and paired t-tests were used to compare the mean buccal, lingual, and crestal soft tissue thicknesses at each site. The Generalized Estimating Equations model was used to study the effects of age, gender, and race. Confidence level was set to 95%.

RESULTS: Mean tissue thickness ranged from 0.96 mm to 1.98 mm with a mean of 1.63 ± 0.25 mm. Intraclass Correlation Coefficients were >0.97. No significant differences between buccal, crestal, and lingual sites were noted for the mandibular arch as well as at 4 sites on the maxillary arch (maxillary right second molar, maxillary right canine, maxillary left first premolar, maxillary left second molar). However, significant differences in soft tissue thickness were noted for all remaining maxillary sites. Race was found to be positively correlated with tissue thickness, with black individuals showing a significantly greater thickness than whites at four sites (maxillary right first molar, maxillary left canine, mandibular right second premolar, mandibular right first molar). Age was found to be positively correlated with tissue thickness at 4 sites (maxillary left central incisor, maxillary left first molar, maxillary left second molar, mandibular left second premolar) and negatively correlated at 2 sites (mandibul0ar right canine, mandibular right second molar). Female gender was positively (maxillary left second premolar, maxillary left second molar) and negatively (mandibular right canine) correlated, respectively, with tissue thickness at 3 sites. When data for anterior and posterior sites was respectively pooled, tissue thickness was significantly less at anterior sextant lingual and crestal sites, while no difference was seen for buccal sites.

CONCLUSION: Statistically significant differences for alveolar ridge mucosa thickness were found at several sites in the maxilla and between anterior and posterior sextants for lingual and crestal sites in the maxillary and mandibular arches. Tissue thickness differences were also noted for race with black individuals showing greater tissue thickness at some sites. Age and gender did not show a clear effect on tissue thickness. Recorded differences in tissue thickness were however small and appear of uncertain clinical significance. This article is protected by copyright. All rights reserved.

PMID:37470112 | DOI:10.1111/jopr.13738

Eur J Heart Fail. 2023 Jul 20. doi: 10.1002/ejhf.2977. Online ahead of print.

ABSTRACT

AIMS: Mitiperstat (formerly AZD4831) is a novel selective myeloperoxidase inhibitor. Currently, no effective therapies target comorbidity-induced systemic inflammation, which may be a key mechanism underlying heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). Circulating neutrophils secrete myeloperoxidase, causing oxidative stress, microvascular endothelial dysfunction, interstitial fibrosis, cardiomyocyte remodelling and diastolic dysfunction. Mitiperstat may therefore improve function of the heart and other organs, and ameliorate heart failure symptoms and exercise intolerance. ENDEAVOR is a combined, seamless phase 2b-3 study of the efficacy and safety of mitiperstat in patients with HFpEF/HFmrEF.

METHODS: In phase 2b, approximately 660 patients with heart failure and ejection fraction >40% are being randomized 1:1:1 to mitiperstat 2.5 mg, 5 mg or placebo for 48 weeks. Eligible patients have baseline 6-min walk distance (6MWD) of 30-400 m with a < 50 m difference between screening and randomization and Kansas City Cardiomyopathy Questionnaire – total symptom score (KCCQ-TSS) ≤90 points at screening and randomization. The dual primary endpoints are change from baseline to week 16 in 6MWD and KCCQ-TSS. The sample size provides 85% power to detect placebo-adjusted improvements of 21 m in 6MWD and 6.0 points in KCCQ-TSS at overall two-sided alpha of 0.05. Safety is monitored throughout treatment, with a focus on maculopapular rash. In phase 3 of ENDEAVOR, approximately 820 patients will be randomized 1:1 to mitiperstat or placebo.

CONCLUSION: ENDEAVOR is the first phase 2b-3 study to evaluate whether myeloperoxidase inhibition can improve symptoms and exercise capacity in patients with HFpEF/HFmrEF. Clincaltrials.gov: NCT04986202 This article is protected by copyright. All rights reserved.

PMID:37470101 | DOI:10.1002/ejhf.2977