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Background: Glide path establishment is a critical step in endodontic treatment, particularly in curved root canals, as it facilitates safe and effective canal shaping. The apically extruded debris during this process can cause postoperative complications, including pain and inflammation. Materials and Methods: In this in vitro study, 60 extracted human mandibular molars with curved mesial roots were selected and randomly divided into three groups (n = 20) based on the glide path establishment system used: Group A (manual stainless steel K-files), Group B (rotary PathFiles), and Group C (reciprocating R-Pilot files). Each root canal was instrumented following the manufacturer’s instructions for the respective system. The extruded debris was collected in preweighed Eppendorf tubes during the preparation and subsequently dried and weighed using an analytical balance with a precision of 0.0001 g. Results: The mean weight of apically extruded debris was significantly different among the groups (P < 0.05). Group A (manual K-files) had the highest mean debris extrusion (0.032 ± 0.005 g), followed by Group C (reciprocating R-Pilot files) with 0.021 ± 0.004 g. Group B (rotary PathFiles) exhibited the least amount of debris extrusion (0.015 ± 0.003 g). The differences between all groups were statistically significant (P < 0.05). Conclusion: The type of glide path establishment system significantly affects the amount of apically extruded debris in curved root canals. Rotary PathFiles produced the least debris, suggesting that they may be the most effective in minimizing postoperative complications associated with debris extrusion. Further clinical studies are needed to confirm these findings and to assess their relevance in vivo.

The authigenic 10Be/9Be dating method presents a valuable tool for reconstructing depositional chronologies in sedimentary environments, requiring only ubiquitous mud for sampling. Nevertheless, studies elucidating the variability of the 10Be/9Be record preserved in epicontinental successions are lacking, despite the essential nature of such knowledge for the application of authigenic 10Be/9Be in geochronology. In this study, we investigate the variability of measured natural 10Be/9Be ratios in sediment cores recovered from the Holocene Po River delta plain in Northern Italy, aiming to unveil the influence of changing sedimentary environments and provenance on the beryllium isotopic signature. We identified significant variations in the authigenic 10Be/9Be ratios across parasequences, which correlates with a provenance change from the Eastern Alps to the Po River. The observed variation would cause an age offset of ∼1 Myr if unrecognized in a dated succession. Our analysis revealed consistent ratios between the delta plain (primarily represented by swamp) and delta front consisting of proximal prodelta facies, suggesting a prevalent riverine signature in the proximal prodelta, likely maintained by hyperpycnal flow deposition. Statistical assessments based on random sampling and bootstrapping highlighted the importance of a sample size of n > 10. Furthermore, a standard deviation of the observed variability indicates a necessity of an additional 9% uncertainty in authigenic 10Be/9Be dating studies if the sample size is smaller. Overall, our findings emphasize that the normal regressive highstand settings of a deltaic system maintain relatively stable beryllium isotopic fluxes, which are favourable for the authigenic 10Be/9Be dating application, if provenance changes are known.

Renal vascular complications constitute a clinically significant cause of morbidity following renal transplantation. Transplant renal artery stenosis (TRAS) is a well-recognized complication accounting for ~75% of posttransplant vascular complications. Early recognition and prompt correction of TRAS can prevent adverse outcomes, including graft loss. This series is a summary of four renal transplant recipients who developed TRAS at varied time periods and with varied clinical presentations. A 23-year-old male who presented after 1½ months of renal transplantation with accelerated hypertension was diagnosed with TRAS and was treated successfully with percutaneous transluminal angioplasty with stenting. A 26-year-old male with acute allograft dysfunction after 1 month of transplantation without worsening hypertension was diagnosed with TRAS, which was treated successfully with angioplasty and stenting. A 49-year-old male who presented to the emergency with pulmonary edema secondary to accelerated hypertension (Pickering syndrome) after 2 months of transplantation was diagnosed to have TRAS, which was treated successfully with angioplasty with stenting. A 44-year-old male with an incidentally detected TRAS-like clinical picture secondary to kinking in the transplant renal artery in the immediate posttransplant period was successfully treated with re-exploration and repair. All the patients were screened with Doppler ultrasonogram and computed tomogram-angiography supported the diagnosis in three of the cases. None of the cases developed procedure-related complications including contrast-associated nephropathy. All the patients on follow-up after 6 months of the intervention are normotensive with normal renal function. A high index of suspicion is required in the early identification of TRAS, which is a reversible cause of hypertension and graft dysfunction. The risk of contrast-associated nephropathy cannot hinder or delay the diagnosis especially, in emerging transplant centers. The endovascular procedures used today for the treatment of TRAS are safe with high technical success rates.

Abstract IgA nephropathy is the most common primary glomerulonephritis worldwide and can progress to end-stage kidney disease (ESKD). The current “gold standard” for diagnosis is kidney biopsy, which is invasive and associated with morbidity. miRNAs are small, non-coding endogenous RNA that may serve as non-invasive biomarkers, and that are found in urinary exosomes. Thus far, there is a paucity of studies of the miRNA profile for the diagnosis of IgA nephropathy. Hence, we aimed to study the urinary exosomal miRNA signature of Indian patients with IgA nephropathy. Fifty biopsy-proven IgA nephropathy patients, 50 healthy controls and 25 patients with ESKD (IgA nephropathy) were recruited over 2 years (2020–2022). Urinary exosomes were isolated from which miRNA was extracted . Analysis of urinary exosomal miRNA was done using the digital multiplexed nCounter® human v3 miRNA Expression Assay which contains 799 unique miRNA barcodes. Candidate miRNAs were identified using Lasso regression and consensus clustering. The mean age of IgA nephropathy patients was 36.32 ± 3.067 years, mean creatinine was 2.26 ± 0.318 mg/dl and mean proteinuria was 2.69 ± 0.64 g/day. Compared to healthy controls, the majority (N = 150) of miRNAs were significantly downregulated. Five candidate miRNAs (hsa.miR.146b.3p, hsa.miR.599, hsa.miR.4532, hsa.miR.664b.5p and hsa.miR.221.5p) were able to differentiate between IgA nephropathy cases and controls (AUC > 0.90); the presence of all 5 was associated with 100% specificity and sensitivity for diagnosing IgA nephropathy cases. This study of Indian patients identified that there was a significant difference in the urinary exosomal miRNA profile between IgA nephropathy cases and healthy controls, suggesting that miRNAs may be valuable in the non-invasive diagnosis of IgA nephropathy.

BackgroundDiseases manifest differently according to gender in many medical specialties. However, sex differences in kidney diseases have not been well explored worldwide, especially in India. These differences could also be attributed to sociocultural factors. Although CKD is more prevalent in women worldwide, most men are initiated on kidney replacement therapy (KRT). This study aimed to examine sex disparities in patients on maintenance hemodialysis.Materials and methodsA cross-sectional observational study was conducted in two maintenance hemodialysis units at the Institute of Nephrourology, a tertiary care referral government center in Bengaluru, India. Demographic characteristics and laboratory parameters were also recorded.ResultsIn total, 374 adult patients (aged >18 years) were included in the study. Most patients (72.7%) were men. Mean age in men was 46.95 ± 12.65 years, and women was 46.63 ± 13.66 years. There was no significant difference in marital status and the availability of caretakers between the groups. Spouses were the predominant caretakers for both sexes (64% men and 51% women, P = 0.14). Sons cared more for patients with mother than fathers (19.6% vs 8.8%, P = 0.074). Diabetic nephropathy was the most common cause of ESKD in both groups (33.1% vs 31.3%, P = 0.92). Men had a significantly longer duration of HTN and received more HD sessions per week than women. Mean hemoglobin (9.9 ± 1.79 vs 9.46 ± 1.47 g%) and mean serum creatinine (7.76 ± 2.65 vs 6.41 ± 2.27 mg/dl) were higher in men compared to women (P

The data included in this article specify the characteristics of the Upper Miocene fill of the Turiec Basin and served for reconstruction of temporal evolution of depositional systems in this intermontane basin located within the Western Carpathians (Central Europe). The borehole lithological log data were used to describe the stratigraphy of the Turiec Basin in geological sections and were gained in the Geofond archive of the State Geological Institute of Dionýz Štúr. The sedimentological data were acquired by field research applying facies analysis to nine outcrop sites. The outcrops served for grain size analyzes performed by sieving and laser diffraction, for geochemical analyzes using ICP-ES, ICP-MS and XRF, and for mineralogical analyzes of whole rock and clay fraction by XRD. Moreover, the muddy layers on outcrops served for collection of 31 samples for the authigenic 10Be/9Be dating. The geochronological data are presented by using five different initial ratios for calculation, determined within the Turiec Basin at the Late Pleistocene alluvial fan and river terrace sites as well as at two Holocene muddy floodplain sites. Another initial ratio data are gained from an Upper Miocene lacustrine succession dated independently by magnetostratigraphy in previous research. Finally, a summary of previously published strontium isotope data from the Turiec Basin is included. The interpretations of the data are provided in Šujan et al., (2023) Palaeogeography, Palaeoclimatology, Palaeoecology 628, 111746.

Abstract Mycophenolate mofetil has an important role as immunosuppressive agent in solid organ transplant recipients. Exposure to the active mycophenolic acid (MPA) can be monitored using therapeutic drug monitoring. We present three cases in which MPA exposure severely decreased after oral antibiotic coadministration. By diminishing gut bacteria β‐glucuronidase activity, oral antibiotics can prevent deglucuronidation of the inactive MPA‐7‐O‐glucuronide metabolite to MPA and thereby possibly prevent its enterohepatic recirculation. This pharmacokinetic interaction could result in rejection, which makes it clinically relevant in solid organ transplant recipients, especially when therapeutic drug monitoring frequency is low. Routine screening for this interaction, preferably supported by clinical decision support systems, and pragmatic close monitoring of the MPA exposure in cases is advised.

Introduction: Tenofovir remains the cornerstone drug in various antiretroviral regimens and is commonly associated with renal failure in susceptible individuals with a renal biopsy suggestive of proximal tubular injury. Objectives: To investigate clinical, histopathological and outcome findings in tenofovir-induced nephrotoxicity patients. Patients and Methods: Between August 1, 2014, and March 31, 2017, an observational study was conducted in a government-run tertiary care facility in South India. All patients receiving a regimen based on tenofovir disoproxil fumarate (TDF) and testing positive for human immunodeficiency virus (HIV) were included. A renal biopsy was performed when needed. Results: A total of 27 cases were identified, with a mean age of 45.03± 12.95 years, while 19 (70%) of them were men. Mean creatinine and mean proteinuria among the participants were 5.78 ±2.71 mg/dL and 1643.96 ±1056.44 mg/dL, respectively, at the time of the renal biopsy. Interval between TDF treatments to kidney biopsies ranged between 7 to 52 weeks with mean (±SD) of 30.8±22 weeks. Phosphaturia and glycosuria were found in 10 (37.03%) and 8 (29.5%) patients respectively, all of whom had normoglycemia. In contrast to the remaining 13 instances, which all had moderate to severe diffuse inflammation, 14 patients exhibited toxic proximal tubular damage along with mild and localized interstitial inflammation. Hemodialysis was required by 10 individuals. A total of 22 patients were monitored after TDF was stopped, while 17 (77.27%) of them had fully recovered renal function at the end of monitoring period. Conclusion: This study demonstrates that TDF nephrotoxicity is a reversible form of toxic acute tubular necrosis with concurrent interstitial inflammation that affects the proximal tubules. As a result, it is crucial to carefully monitor renal parameters in these patients.

Background and objectiveWe characterized tumor prostate-specific membrane antigen (PSMA) levels as a reflection of cancer biology and treatment sensitivities for treatment-naïve prostate cancer.MethodsWe first correlated PSMA positron emission tomography (PET) maximum standardized uptake values (SUVmax) in primary prostate cancer with tumor FOLH1 (PSMA RNA abundance) to establish RNA as a proxy (n = 55). We then discovered and validated molecular pathways associated with PSMA RNA levels in two large primary tumor cohorts. We validated those associations in independent cohorts (18 total; 5684 tumor samples) to characterize the pathways and treatment responses associated with PSMA.Key findings and limitationsPSMA RNA abundance correlates moderately with SUVmax (ρ = 0.41). In independent cohorts, androgen receptor signaling is more active in tumors with high PSMA. Accordingly, patients with high PSMA tumors experienced longer cancer-specific survival when managed with androgen deprivation therapy for biochemical recurrence (adjusted hazard ratio [AHR] 0.54 [0.34-0.87]; n = 174). PSMA low tumors possess molecular markers of resistance to radiotherapy. Consistent with this, patients with high PSMA tumors experience longer time to recurrence following primary radiotherapy (AHR 0.50 [0.28-0.90]; n = 248). In the SAKK09/10 trial (n = 224), patients with high PSMA tumors who were managed with salvage radiotherapy experienced longer time to progression in the 64-Gy arm (restricted mean survival time [RMST] +7.60 [0.05-15.16]), but this effect was mitigated in the 70-Gy arm (RMST 3.52 [-3.30 to 10.33]). Limitations include using PSMA RNA as a surrogate for PET SUVmax.Conclusions and clinical implicationsPSMA levels in treatment-naïve prostate cancer differentiate tumor biology and treatment susceptibilities. These results warrant validation using PET metrics to substantiate management decisions based on imaging.

Background: Enterococcus faecalis is the most common and important microorganism found in infected root canals associated with persistent periapical periodontitis and failing endodontically treated tooth. Intracanal medicaments used after chemomechanical preparation of an infected root canal play a vital in eradication of this microorganism and pave the way for long-term success of endodontic therapy. Hence, the present in vitro study was conducted to assess the antimicrobial efficacy of calcium hydroxide (Ca(OH)2), triple antibiotic paste (metronidazole 400 mg + minocycline 100 mg + ciprofloxacin 500 mg), and 2% chlorhexidine (CHX) combined with 0.5% cetrimide on eradication of E. faecalis biofilm. Materials and Methods: Eighty dentin specimens were taken and infected extraorally with E. faecalis to induce microbial colonization. The specimens were then divided into four groups of twenty each based on medicaments used and further subdivided into two subgroups based on assessment of live cells done either immediately after the elimination of the medicament or after 24-h incubation in brain–heart infusion (BHI) medium: Group I specimens were treated with Ca(OH)2, Group II with triple antibiotic paste, Group III with 2% CHX combined with 0.5% cetrimide, and Group IV with saline (control) for 7 days at 37°C. Assessment of live cells was done using confocal microscope. Results: 2% CHX combined with 0.5% cetrimide (Group III) and triple antibiotic paste (Group II) showed a statistically significant result with high antimicrobial efficacy and lower percentage of live cells as compared to Ca(OH)2 (Group I). The mean percentage of live cells in Group I immediately after elimination of medicaments was 64.7%, in Group II was 1.52%, in Group III was 1.49%, and in Group IV was 83.4%. After 24 h of incubation in BHI medium, 2% CHX combined with 0.5% cetrimide (Group III) showed a statistically significant (p < 0.05) result of 1.27% mean live cells as compared to 84.2% in Ca(OH)2 (Group I), 1.82% in triple antibiotic paste (Group II), and 94.2% in saline (Group IV control). Conclusion: 2% CHX combined with 0.5% cetrimide exhibited maximum antimicrobial efficacy with least number of mean live cells followed by triple antibiotic paste as compared to Ca(OH)2. Based on these findings, 2% CHX combined with 0.5% cetrimide was most effective in eradicating E. faecalis from the extraorally infected dentine biofilm.

An accurate diagnosis of the anatomy of the root canal system is a prerequisite for successful endodontic treatment. Morphological variations or additional roots/root canal should always be expected. These variations should be strongly considered before starting any endodontic treatment using various diagnostic aids for better outcome therapy. Nonsurgical endodontic re-treatment of a painful twin-rooted maxillary lateral incisor tooth of a 40-year-old female was carried out due to improper diagnosis of the extra root. The clinical examination and radiographic analysis confirmed the diagnosis of previously treated/necrotic pulp and symptomatic apical periodontitis. The patient remained asymptomatic at 6-month follow-up both clinically and radiographically. The case report emphasized on the need for clinicians to be extra careful while treating such teeth and use of cone-beam computed tomography for their diagnosis and management.

Background: Undergraduate students can provide valuable opinions and suggestions for modifying the educational program for the enhancement of learning. Therefore, the aim of this study was to explore the preparedness of undergraduate dental students with regard to practice endodontics in the rural and remote areas of India. Materials and Methods: The present cross-sectional questionnaire-based study was conducted among dental undergraduates (interns). The survey was conducted among the students of 3 private dental colleges. For the data collection, a close-ended questionnaire was designed to test the knowledge for performing endodontic therapy, root canal therapy (RCT), attitude, and behavior of performing these procedures in the rural set-ups. Unpaired t test and one way analysis of variance (ANOVA) was used to compare the significant difference based on demographics and Pearson's correlation was applied to find the associations among knowledge, attitude, and behavior of study participants. The level of significance was set at below 0.05. Results: A total of 79 students participated, out of which 22 respondents were males (27.8%), and 57 were females (72.15%). Overall mean knowledge scores for endodontics was 9.72 ± 2.19, and the scores of female students were slightly higher than males, whereas the attitude and behavior were better in males but there was no statistical significant difference between both the genders (P > 0.05). A statistically significant positive correlation was observed between attitude and behavior on practicing endodontics in rural settings among study subjects (P < 0.05). Conclusion: These findings highlights the necessity for taking initiatives to enhance the community-based dental education programs by various dental colleges for improving oral health care access for rural and isolated populations.

Introduction: Pre-exposure prophylaxis (PrEP) for HIV—using antiretroviral medication in non-infected individuals to prevent HIV—has immense potential to slow the spread of the virus. However, uptake has been insufficient, and stark racial disparities exist in both HIV acquisition and PrEP usage, making PrEP access a health equity issue. A promising venue to engage high-risk populations in PrEP care is the emergency department (ED); however, existing ED PrEP initiatives have been costly or have had limited success. We hypothesize that two strategies could overcome these barriers: prescribing PrEP during an ED visit and providing patients with an initial supply of PrEP medication in the ED. Here, we describe the results of a qualitative study exploring multidisciplinary emergency clinicians and HIV clinicians’ needs and views about the feasibility of such an initiative.Methods: We conducted 22 semi-structured interviews with multidisciplinary clinicians from an urban, safety-net medical center in the ED and the on-site HIV clinic that provides PrEP services.We performed thematic analysis to summarize challenges and potential solutions described by participants.Results: Participants’ responses fell into three thematic categories: operational challenges; patient-level considerations; and potential impacts. Operational challenges highlighted the difficulty of PrEP initiation in a busy ED and clinician support needs. Patient-level considerations included the complex psychosocial needs of ED patients who could benefit from PrEP. Finally, participants anticipated that an ED-based PrEP initiation program could positively impact both individual patients and public health.Conclusion: Interviews with emergency department and HIV clinic staff revealed important considerations and potential solutions for ED-initiated PrEP workflows. Clinicians in both specialties were enthusiastic about such an initiative, which could facilitate its success. This study lays the groundwork for the future design of an efficient and innovative workflow to leverage the ED as an essential entry point into HIV prevention services.

Prostate cancer is frequently treated with radiotherapy. Unfortunately, aggressive radioresistant relapses can arise, and the molecular underpinnings of radioresistance are unknown. Modern clinical radiotherapy is evolving to deliver higher doses of radiation in fewer fractions (hypofractionation). We therefore analyzed genomic, transcriptomic, and proteomic data to characterize prostate cancer radioresistance in cells treated with both conventionally fractionated and hypofractionated radiotherapy. Independent of fractionation schedule, resistance to radiotherapy involved massive genomic instability and abrogation of DNA mismatch repair. Specific prostate cancer driver genes were modulated at the RNA and protein levels, with distinct protein subcellular responses to radiotherapy. Conventional fractionation led to a far more aggressive biomolecular response than hypofractionation. Testing preclinical candidates identified in cell lines, we revealed POLQ (DNA Polymerase Theta) as a radiosensitizer. POLQ-modulated radioresistance in model systems and was predictive of it in large patient cohorts. The molecular response to radiation is highly multimodal and sheds light on prostate cancer lethality.SignificanceRadiation is standard of care in prostate cancer. Yet, we have little understanding of its failure. We demonstrate a new paradigm that radioresistance is fractionation specific and identified POLQ as a radioresistance modulator.

Purpose: To compare the structural integrity and functional status of the donor corneas stored in Cornisol and Optisol-GS. Methods: Fifteen optical grade corneal donor buttons (6 pairs; 3 individual) obtained from Rotary Aravind International Eye Bank were used for the study. The left eye of the paired sample was preserved in Cornisol and the right in Optisol-GS. The three individual buttons were used for the baseline data. The corneas were assessed with slit lamp and specular microscope before and after storage time (7, 10, or 14 days). They were then immunostained for markers of structural integrity (ZO-1, Phalloidin) and functionality (Na+/K+ ATPase). The images were acquired using confocal microscope and analyzed using ImageJ software. Results: There was no difference in the clinical evaluation of the corneal layers between the two media. No marked variation was observed in the immunostaining data with reference to the storage period. Intact cellular integrity was identified in 91% (51%, 98%) [Median (min, max)] of cells in Cornisol and 94% (38%, 98%) cells in Optisol based on ZO-1 staining, comparable to the baseline data [87% (76%, 97%)]. Stress fibers were detected in 42.5% (1%, 88%) cells in Cornisol stored corneas and in 55% (11%, 94%) in Optisol when stained for actin cytoskeleton, which correlated with the presence of epithelial defect before storage and vacuolated endothelial cells after storage. No difference was observed between the two media based on the staining pattern for Na+/K+ ATPase. Conclusion: Cornisol and Optisol-GS are equivalent in maintaining the structural integrity and functionality of the donor corneas.

Recurrence of membranoproliferative glomerulonephritis (MPGN) is seen in 1965% cases of postrenal transplant resulting in graft loss in up to 35-50% of cases. A 31-year-old female, after 1% years on maintenance hemodialysis, underwent ABO compatible deceased donor kidney transplantation with basiliximab induction. During the immediate posttransplant period, the patient had delayed graft function, but achieved nadir creatinine of 0.9 mg/dL by 10 days. Nine months posttransplant, the patient developed fever, anasarca, and decrease in urine output with albuminuria 3+, active sediments in urine, serum creatinine 3.5 mg/dL, 24-h urine protein 7.5 g, and low C3. The patient underwent graft biopsy. Subsequently, the patient received pulse steroid for three days and five sessions of plasmapheresis. Renal biopsy report was suggestive of MPGN with focal crescents and acute tubular necrosis. Immunofluorescence showed Ig G3+, C3 3+, к 3+, and negative for λ or other immunoglobulins or complements. As her native kidney disease was immune-complex-mediated MPGN with no light chain restriction, paraffin tissue of the native kidney was reexamined for light chain restrictions by immunoperoxidase method, but did not show light chain restriction. The patient underwent extensive workup for paraproteinemias, but results were negative. Subsequently, she received four doses of bortezomib. The patient’s serum creatinine got reduced to 0.8 mg/dL and proteinuria reduced to 800 mg/day. Our case is unique as we were not able to demonstrate monoclonal deposits in native kidney sample although there was recurrence of MPGN with monoclonal light chain deposits post transplant. Our findings emphasize the need for thorough evaluation of paraproteinemias in patients with idiopathic MPGN even in the absence of light chain deposition in biopsy.