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Abstract Background The optimal revascularization strategy in patients with left main coronary artery (LMCA) disease in the emergency setting is still controversial. Thus, we aimed to compare the outcomes of percutaneous coronary interventions (PCI) vs. coronary artery bypass grafting (CABG) in patients with and without emergent LMCA disease. Methods This retrospective cohort study included 2138 patients recruited from 14 centers between 2015 and 2019. We compared patients with emergent LMCA revascularization who underwent PCI (n = 264) to patients who underwent CABG (n = 196) and patients with non-emergent LMCA revascularization with PCI (n = 958) to those who underwent CABG (n = 720). The study outcomes were in-hospital and follow-up all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE). Results Emergency PCI patients were older and had a significantly higher prevalence of chronic kidney disease, lower ejection fraction, and higher EuroSCORE than CABG patients. CABG patients had significantly higher SYNTAX scores, multivessel disease, and ostial lesions. In patients presenting with arrest, PCI had significantly lower MACCE (P = 0.017) and in-hospital mortality (P = 0.016) than CABG. In non-emergent revascularization, PCI was associated with lower MACCE in patients with low (P = 0.015) and intermediate (P

Introduction: The evidence about the optimal revascularization strategy in patients with left main coronary artery (LMCA) disease and impaired renal function is limited. Thus, we aimed to compare the outcomes of LMCA disease revascularization (percutaneous coronary intervention [PCI] vs. coronary artery bypass grafting [CABG]) in patients with and without impaired renal function. Methods: This retrospective cohort study included 2,138 patients recruited from 14 centers between 2015 and 2,019. We compared patients with impaired renal function who had PCI (n= 316) to those who had CABG (n = 121) and compared patients with normal renal function who had PCI (n = 906) to those who had CABG (n = 795). The study outcomes were in-hospital and follow-up major adverse cardiovascular and cerebrovascular events (MACCE). Results: Multivariable logistic regression analysis showed that the risk of in-hospital MACCE was significantly higher in CABG compared to PCI in patients with impaired renal function (odds ratio [OR]: 8.13 [95% CI: 4.19–15.76], p < 0.001) and normal renal function (OR: 2.59 [95% CI: 1.79–3.73]; p < 0.001). There were no differences in follow-up MACCE between CABG and PCI in patients with impaired renal function (HR: 1.14 [95% CI: 0.71–1.81], p = 0.585) and normal renal function (HR: 1.12 [0.90–1.39], p = 0.312). Conclusions: PCI could have an advantage over CABG in revascularization of LMCA disease in patients with impaired renal function regarding in-hospital MACCE. The follow-up MACCE was comparable between PCI and CABG in patients with impaired and normal renal function.

BACKGROUND: Exposure to antiretrovirals at or early after HIV acquisition can suppress viral replication and blunt antibody (Ab) responses; a reduced HIV detectability could impact diagnosis and blood donation screening. METHODS: We used three antigen (Ag)/Ab assays and one nucleic acid test (NAT) to analyze samples collected in pre-exposure prophylaxis (PrEP) trials (iPrEx; Partners PrEP) before infection detection by Ab-only rapid diagnostic tests (RDTs), and in early antiretroviral treatment (ART) initiation studies (RV254; SIPP). RESULTS: Reactivity using NAT and Ag/Ab assays in samples collected up to 8 weeks prior to the first reactive RDT from 251 PrEP trials participants varied between 49-61% for active PrEP users and between 27-37% for placebo users. Among RV254 participants, reactivity in Ag/Ab assays was

In the study reported on here we looked at experiences of parental involvement in schools in Phoenix, KwaZulu-Natal. The objectives of the study were to determine how parents were involved in schools and what their experiences were. The study was guided by Epstein's Theory of Overlapping Spheres. A qualitative research approach within an interpretivist paradigm was followed. A multiple case design was used and the schools were drawn from privileged and underprivileged contexts in Phoenix. The methodology employed to generate data was the semi-structured interview, followed by an open-ended questionnaire completed by the participants. The sample of participants comprised 3 parents and 3 teachers from each of the 2 schools. Thematic analysis was used to analyse the data. The findings show that parents from both privileged and underprivileged communities were concerned about and employed a variety of strategies to get involved in their children's education, both academically and socially. Although parents from both schools participated in school events, the level of their participation differed, with the parents from the privileged schools being more involved than parents from the underprivileged school.

Abstract Clean river water is an essential and life-sustaining asset for all living organisms. The upper Ganga and Yamuna river system has shown signs of rejuvenation and tremendous improvement in the water quality following the nationwide lockdown due to the coronavirus pandemic. All the industrial and commercial activity was shut down, and there was negligible wastewater discharge from the industries. This article addresses the water quality assessment from the study area, which is based on the original data of physical parameters, major and trace elements, and stable isotopes (hydrogen and oxygen) systematics during the nationwide lockdown. The impact of the lockdown could be seen in terms of an increase in dissolved oxygen (DO). Water samples were collected from the Upper Ganga and Yamuna river basins (Alaknanda, Bhagirathi, and Tons rivers) during an eight-week lockdown in Uttarakhand, India. We discussed the signs of rejuvenation of riverine based on physical parameters, major ions, trace elements, isotopic ratios, and water pollution index (WPI). Results reveal that the water quality of the entire upper basins of the Ganga has significantly improved by 93%, reflecting the signs of self-rejuvenation of the rivers. Multivariate analysis suggests a negative factor loading for an anthropogenic element ( $${NO}_{3}^{-}$$ NO 3 - ), implying that they contribute little to the river water during the lockdown. Further, bicarbonate ( $${HCO}_{3}^{-}$$ HCO 3 - ) is a dominant element in both river basins. The geochemical facies are mainly characterized by the ( $${{Ca}^{2+} :{Mg}^{2+} : HCO}_{3}^{-}$$ Ca 2 + : Mg 2 + : H C O 3 - ) type of water, suggesting that silicate rock weathering dominates with little influence from carbonate weathering in the area. The positive factor loadings of some cations, like $${HCO}_{3}^{-}$$ HCO 3 - , $${Ca}^{2+}$$ Ca 2 + , and $${Mg}^{2+}$$ Mg 2 + reflect their strong association with the source of origin in the lockdown phases. Stable isotopic reveals that the glaciated region contributed the most to the river basin, as evidenced by the low d-excess in riverine water compared to anthropogenic contributions. Rivers can self-rejuvenate if issues of human influence and anthropogenic activities are adequately resolved and underline our responsibility for purifying the ecosystem. We observed that this improvement in the river water quality will take a shorter time, and quality will deteriorate again when commercial and industrial activity resumes.

In the present investigation, six genotypes of chickpea viz., PG0127, PG0126, CSG8962, ICCL87322, HC-1 and BG362 were used as parents for 6 × 6 diallel analysisexcluding reciprocals to estimate general and specific combining ability variances and effects. Genetic analysis revealed that both additive and non-additive genetic components of variation are important for inheritance of all the characters. However, the magnitude of non-additive (sca) variance was considerably higher than additive (gca) variance for all the characters except 100 seed weight representing the predominance of non additive gene action. The parents HC-1 and BG362 were found to be good general combiners for grain yield and most of its component characters and were one of the parents in most of the best specific cross combinations. The crosses HC-1 × BG362 and CSG8962 × HC-1 were the best cross combinations for yield and most of its components. In view of parallel role of both additive and non-additive genetic effects determining the inheritance of different characters, their simultaneous exploitation through adoption of biparental approach is suggested.

IntroductionAnimal models play a vital role in pharmaceutical research and development by supporting the planning and design of later clinical studies. To improve confidence and reliability of first in human dose estimates it is essential to assess the comparability of animal studies with the human situation. In the context of large molecules, it is particularly important to evaluate the cross-species-translatability of parameters related to neonatal fragment crystallizable receptor (FcRn) binding and target mediated drug disposition (TMDD), as they greatly influence distribution and disposition of proteins in the body of an organism.MethodsPlasma pharmacokinetic data of the therapeutic protein efalizumab were obtained from literature. Physiologically based pharmacokinetic (PBPK) models were built for three different species (rabbit, non-human primate (NHP), human). Target binding was included in the NHP and human models. The assumption of similar target turnover and target-binding in NHP and human was explored, to gain insights into how these parameters might be translated between species.ResultsEfalizumab PBPK models were successfully developed for three species and concentration-time-profiles could be described appropriately across different intravenously administered doses. The final NHP and human models feature a common set of parameters for target turnover and drug-target-complex internalization, as well as comparable target-binding parameters. Our analyses show that different parameter values for FcRn affinity are crucial to accurately describe the concentration-time profiles.DiscussionBased on the available data in rabbits, NHP and humans, parameters for FcRn affinity cannot be translated between species, but parameters related to target mediated drug disposition can be translated from NHP to human. The inclusion of additional pharmacokinetic (PK) data including different efalizumab doses would further support and confirm our findings on identifying TMDD and, thus, binding kinetics of efalizumab in NHPs. Furthermore, we suggest that information on target expression and internalization rates could make it possible to develop comprehensive human PBPK models with minimal animal testing. In this project, we compared the pharmacokinetics of a therapeutic protein in rabbit, NHP and human using an open PBPK modeling platform (Open Systems Pharmacology Suite, http://www.open-systems-pharmacology.org). Our findings could support similar translatory studies for first in human dose predictions in the future.

Physiologically based pharmacokinetic (PBPK) modelling is an important tool to predict drug disposition in the body. Rabbits play a pivotal role as a highly valued small animal model, particularly in the field of ocular therapeutics, where they serve as a crucial link between preclinical research and clinical applications. In this context, we have developed PBPK models designed specifically for rabbits, with a focus on accurately predicting the pharmacokinetic profiles of protein therapeutics following intravenous administration. Our goal was to comprehend the influence of key physiological factors on systemic disposition of antibodies and their functional derivatives. For the development of the systemic PBPK models, rabbit physiological factors such as gene expression, body weight, neonatal fragment crystallizable receptor (FcRn) binding, target binding, target concentrations, and target turnover rate were meticulously considered. Additionally, key protein parameters, encompassing hydrodynamic radius, binding kinetic constants (KD, koff), internal degradation of the protein-target complex, and renal clearance, were represented in the models. Our final rabbit models demonstrated a robust correlation between predicted and observed serum concentration-time profiles after single intravenous administration in rabbits, covering IgG, Fab, F(ab)2, Fc, and Fc fusion proteins from various publications. These pharmacokinetic simulations offer a promising platform for translating preclinical findings to clinical settings. The presented rabbit intravenous PBPK models lay an important foundation for more specific applications of protein therapeutics in ocular drug development.

BackgroundPelvic fracture urethral injury (PFUI) occurs in up to 10% of pelvic fractures. There is mixed evidence supporting early endoscopic urethral realignment (EUR) over suprapubic tube (SPT) placement and delayed urethroplasty. Some studies show decreased urethral obstruction with EUR, while others show few differences. We hypothesized that EUR would reduce the rate of urethral obstruction after PFUI.MethodsTwenty-six US medical centers contributed patients following either an EUR or SPT protocol from 2015 to 2020. If retrograde cystoscopic catheter placement failed, patients were included and underwent either EUR or SPT placement based on their institution's assigned treatment arm. Endoscopic urethral realignment involved simultaneous antegrade/retrograde cystoscopy to place a catheter across the urethral injury. The primary endpoint was development of urethral obstruction. Fisher's exact test was used to analyze the relationship between PFUI management and development of urethral obstruction.ResultsThere were 106 patients with PFUI; 69 (65%) had complete urethral disruption and failure of catheter placement with retrograde cystoscopy. Of the 69 patients, there were 37 (54%) and 32 (46%) in the EUR and SPT arms, respectively. Mean age was 37.0 years (SD, 16.3 years) years, and mean follow-up was 463 days (SD, 280 days) from injury. In the EUR arm, 36 patients (97%) developed urethral obstruction compared with 30 patients (94%) in the SPT arm ( p = 0.471). Urethroplasty was performed in 31 (87%) and 29 patients (91%) in the EUR and SPT arms, respectively ( p = 0.784).ConclusionIn this prospective multi-institutional study of PFUI, EUR was not associated with a lower rate of urethral obstruction or need for urethroplasty when compared with SPT placement. Given the potential risk of EUR worsening injuries, clinicians should consider SPT placement as initial treatment for PFUI when simple retrograde cystoscopy is not successful in placement of a urethral catheter.Level of evidenceTherapeutic/Care Management; Level III.

Background: The hemodynamic advantages of maintaining AV synchrony through AV synchronous pacing are widely known as compared to single chamber pacing. DDD pacemaker implantation entails higher cost and is technically more challenging than the VDD pacemaker. Methods: Seventy one patients underwent VDD lead (Biotronik GmbH, St. Jude Medical and Medtronic Inc.) implantation at KEM hospital, Mumbai during a period of 3 years through subclavian, axillary and cephalic routes for degenerative, post-surgical or congenital high grade atrioventricular or complete heart block. They were followed up regularly for ventricular threshold and P wave amplitude of the floating atrial dipole. Results: Follow up data of almost 95% of patients is available for a period of 15.8 ± 6.7 months. P wave amplitude at implant was 2.1 ± 0.7mV and at follow up 1.1 ± 0.6mV with mean ventricular threshold of

ObjectiveTo determine patient outcomes across a range of pelvic fracture urethral injury (PFUI) severity. PFUI is a devastating consequence of a pelvic fracture. No study has stratified PFUI outcomes based on severity of the urethral distraction injury.MethodsAdult male patients with blunt-trauma-related PFUI were followed prospectively for a minimum of six months at 27 US medical centers from 2015-2020. Patients underwent retrograde cystourethroscopy and retrograde urethrography to determine injury severity and were categorized into three groups: (1) major urethral distraction, (2) minor urethral distraction, and (3) partial urethral injury. Major distraction vs minor distraction was determined by the ability to pass a cystoscope retrograde into the bladder. Simple statistics summarized differences between groups. Multi-variable analyses determined odds ratios for obstruction and urethroplasty controlling for urethral injury type, age, and Injury Severity Score.ResultsThere were 99 patients included, 72(72%) patients had major, 13(13%) had minor, and 14(14%) had partial urethral injuries. The rate of urethral obstruction differed in patients with major (95.8%), minor (84.6%), and partial injuries (50%) (P < 0.001). Urethroplasty was performed in 90% of major, 66.7% of minor, and 35.7% of partial injuries (P < 0.001).ConclusionIn PFUI, a spectrum of severity exists that influences outcomes. While major and minor distraction injuries are associated with a higher risk of developing urethral obstruction and need for urethroplasty, up to 50% of partial PFUI will result in obstruction, and as such need to be closely followed.