Protein profiling in unlocking the basis of varicocele-associated infertility

Varicocele is one of the major causes of male infertility and has a negative impact on spermatogenesis. The conventional semen analysis does not reveal the underlying subcellular mechanisms associated with defects in spermatozoa. Proteomics and bioinformatics analysis can be used to identify the molecular aetiologies associated with poor semen quality in varicocele patients. Mitochondrial dysfunction has been identified as the main factor affecting normal physiological functions of spermatozoa. This article discusses the proteomic studies of spermatozoa and seminal plasma in varicocele patients. Proteomics can identify potential spermatozoa and seminal plasma biomarkers in varicocele-mediated male infertility. In future, these protein biomarkers can be useful in the development of noninvasive diagnostic and therapeutic strategies for varicocele patients.     

Minority Race and Ethnicity is Associated With Higher Complication Rates After Revision Surgery for Failed Total Hip and Knee Joint Arthroplasty

BackgroundRacial and ethnic disparities in access to hip and knee total joint arthroplasty (TJA) and postoperative outcomes have wide-reaching implications for patients and the health care system. The aim of this study is to evaluate the effect of ethnicity on clinical outcomes and complications following revision hip and knee TJA.MethodsA single-institution, retrospective analysis of a consecutive series of 4424 revision hip and knee TJA patients was evaluated. Student’s t-test and chi-squared analysis were used to identify significant differences in patient demographics and clinical outcomes between Caucasians and various ethnic minorities, including African Americans, Hispanics, and Asians.ResultsWhen compared with white patients, African American patients demonstrated a significantly higher BMI (P = .04), ASA score (P = .04), length of hospital stay (P = .06), and postoperative infection rates (P = .04). Hispanics demonstrated a significantly higher BMI (P = .04), when compared with white patients, alongside a significantly higher risk for postoperative infection (P < .01). African American demonstrated a significantly higher ASA score (P = .02; P = .03), when compared with Hispanics and Asians, alongside a significantly increased length of stay (P = .01) and higher risk for postoperative infection (P = .02).ConclusionThe study findings demonstrate an underutilization of revision TJA by ethnic minority groups, suggesting that disparities in access to orthopedic surgery increase from primary to revision surgery despite higher failure rates of minority ethnic groups reported after primary TJA surgery. In addition, inferior postoperative outcomes were associated with African Americans and Hispanics, when compared to white patients, with African Americans demonstrating the highest risk of postoperative complications.     

Restarting LDLT During COVID-19: Early Results After Restructuring

IntroductionLiving-donor liver transplantation (LDLT) has been mostly suspended and deceased-donor living transplantation activity has been considerably reduced because of coronavirus disease 2019 (COVID-19). We modified our protocols and procedures in line with COVID-19 guidelines. Since the restructuring, we have performed 20 LDLTs. Our study reports the outcomes of these cases and demonstrates the feasibility of LDLT during this pandemic.Materials and MethodsThe changes were influenced by experiences and communications from across the globe. A month-long self-imposed moratorium was spent in restructuring the program and implementing new protocols. Twenty LDLTs were performed between April 18 and September 15 using the new protocols. Our experience includes 2 simultaneous liver-kidney transplants, 1 ABO-incompatible LDLT, and 1 pediatric case (age 11 months).ResultsNineteen patients recovered and 1 patient died. We maintained our postoperative immunosuppression protocol without many changes. Major complications were observed in 30% of recipients but none of the donors. One recipient was infected with COVID-19 during the postoperative period. A donor-recipient couple contracted COVID-19 after discharge from the hospital. All patients recovered from COVID-19 and liver enzymes were unaffected.ConclusionThis study represents a microcosm of experience in LDLT during the COVID-19 era. Outcomes of LDLT are not affected by COVID-19 per se, provided that we make necessary changes.     

Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection

BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.     

Demographic changes and their financial implications

The impressive rise in the number of elderly persons (65 years and over) will continue in the next two to three decades. Urinary incontinence is a common problem in the elderly, adversely affecting medical, social, and "quality of life" aspects. The cost of urinary incontinence is substantial and is expected to escalate enormously (e.g., by 160% from 1980 to 2040). An aggressive approach toward the diagnosis and management of urinary incontinence can result in an impressive reduction in health care costs and improvement in the quality of life.     

Intravitreal drug administration with depot devices

The administration of medications by depot devices is a rapidly developing technology in ocular therapeutics. Sustained delivery of ophthalmic medications is a novel approach to treating chronic ocular conditions where systemic therapy may be accompanied by unwanted side effects and where repeated intravitreal drug administration carries significant risks. Eye diseases particularly suitable to this form of treatment include proliferative vitreoretinopathy and chronic intraocular infections such as cytomegalovirus retinitis. Liposomes, which have been extensively investigated over the last two decades, have not found any acceptable clinical application. Nonerodible polymers such as the ethylvinyl acetate/polyvinyl alcohol cup are in advanced phase III trials. The current status of microsphere development in the treatment of posterior segment disease is examined in the review and studies investigating the potential uses of the osmotic minipump are mentioned.     

Splenic abscess following blunt abdominal trauma

A rare case of splenic abscess occurring after blunt abdominal trauma in a previously healthy boy is reported. The diagnosis was made by ultrasonography. The patient recovered after splenectomy and drainage of subphrenic and intraperitoneal pus.     

Persistent transgene product in retina, optic nerve and brain after intraocular injection of rAAV.

Recombinant adeno-associated virus (rAAV) is a promising vector for retinal application as it transduces photoreceptors and retinal pigment epithelium cells efficiently and in a stable fashion. Because rAAV also transduces retinal ganglion cells, we reasoned that ocular application of rAAV might result in delivery of transgenic protein to the CNS. Here we describe high levels of green fluorescent protein (GFP) persisting at least 6 months in optic nerves and brains of mice and dogs after intravitreal delivery of rAAV-GFP. There was no clinical or histological evidence of inflammatory response although a mild humoral Th-2 response to viral capsid proteins was detected. These findings have important implications with respect to therapeutic applications of rAAV.     

Knowledge and perceptions of residents regarding case management of acute diarrhea.

The knowledge and perceptions about case management of acute diarrhea were studied amongst 330 resident doctors working in Pediatric Departments of various Medical Colleges in the country. Our observations highlight the inadequacies in the medical curriculum and deficient clinical training in the management of acute diarrhea in the teaching institutions. Knowledge of signs of dehydration was correctly perceived by only 79.8% interns, 80.9% house physicians and 81.1% postgraduate students. It was appalling to observe that despite spending 1-3 years in pediatric wards, the knowledge and perceptions of postgraduate students had not significantly improved. On the contrary, the responses of postgraduate students were poorer as compared to interns in their perceptions of use of ORT in moderate dehydration (p less than 0.005) and in presence of vomiting (p less than 0.05). Adequate thrust on diarrhea and its management during undergraduate as well as during postgraduate teaching and proper training in diarrhea case management with "hands on training" needs to be viewed as a priority in the teaching institutions.