A Fatal Case of Multidrug-Resistant Pleural Nocardiosis by Nocardia otitidiscaviarum in an Immunosuppressed Patient: A Case Report and Literature Review.

Nocardiosis is known as an opportunistic infection in immunocompromised hosts. We present to you a case of pleural nocardiosis in a 38-year-old male patient who was a chronic smoker and presented with a left-sided pleural effusion. He was a known case of thrombocytopenia due to immune thrombocytopenia (ITP) and was on steroid therapy. On admission, he was found to be positive for HIV. Pleural fluid was sent to microbiology, where acid-fast staining with 1% sulfuric acid (H2SO4)showed acid-fast branching filamentous rods and cultures grew Nocardia, which was resistant to ampicillin, ceftriaxone, imipenem, cotrimoxazole, erythromycin, tetracycline, and susceptible to amikacin, linezolid, and levofloxacin. The isolate was identified as Nocardia otitidiscaviarum using 16S rRNA gene sequencing. Culture from the chest wall drain grew Escherichia coli and Stenotrophomonas maltophilia. Subsequently, the patient developed sepsis, and paired blood cultures grew Candida guilliermondii. Unfortunately, the patient could not survive despite aggressive efforts and died after 40 days of admission.

A Multicenter Cohort Study From India of ABO-Incompatible Kidney Transplantation in Post-COVID-19 Patients.

BACKGROUND: There is a dearth of data regarding the consequences of ABO-incompatible kidney transplant (ABOiKTx) among post-COVID-19 candidates. METHODS: The study was designed as a retrospective, multicentric cohort study across 11 sites in India, from August 2020 to December 2021. The data for ABOiKTx conducted for post-COVID-19 candidates were investigated. The primary outcome of biopsy-proven acute rejection was compared with the ABO protocol implemented through Kaplan-Meier analysis. The secondary outcomes were graft loss, patient survival, and infections. RESULTS: A total of 38 ABOiKTx with candidates of median (interquartile range) age of 38.5 (31.25-47.5) years were performed. Nineteen cases had mild COVID-19 severity, while 9 cases (23.6%) had an oxygen requirement. Six (15.7%) donors also were post-COVID-19. The most common ABO incompatibility reported was A to O in 14 (36.8%) pairs followed by B to O in 10 (26.3%) pairs. The maximum isoagglutinin titer cutoff was 1:2048 and 1:64 for baseline and pretransplant levels, respectively. The median time from COVID-19 infection to surgery was 130 (63.2-183) days. Biopsy-proven acute rejection, graft loss, and mortality were 13.1%, 2.6%, and 2.6%, respectively. The Breslow-Wilcoxon's P value in Kaplan-Meier plots were 0.57 and 0.93 for thymoglobulin-based induction and high dose rituximab-based regimen, respectively. The incidence of reinfection was 2.6%. Two (5.2%) urinary tract infections were reported. No cytomegalovirus or BK polyomavirus infection was reported. The median serum creatinine at 1 year of follow-up was 1.1 (0.8-1.3) mg/dL. CONCLUSIONS: Our report implies that ABOiKTx in post-COVID-19 candidates can be successfully performed with no major deviation from standard ABO protocol.

One-Year Outcomes with Use of Anti-T-Lymphocyte Globulin in Patients Undergoing Kidney Transplantation: Results from a Prospective, Multicentric, Observational Study from India.

INTRODUCTION: Large-scale Indian data on the use of anti-T-lymphocyte globulin (ATLG) (Grafalon®) as induction therapy in kidney transplantation (KT) patients is lacking. The aim of this study was to determine the 1-year patient and graft survival outcomes with the use of ATLG as induction regimen in KT. METHODS: In a prospective, multicentric, observational study, adult patients who underwent ABO-compatible KT and had received ATLG as a part of induction were included in the study. The primary outcome measure was overall survival and death-censored graft survival at 12 months. The primary safety outcome was assessed by development of infectious complications and graft rejection. RESULTS: In total, 359 patients were included in this study. The mean age was 42.77 ± 12.30 years and 83% were male. The average ATLG dose per patient was 6.2 ± 2.2 mg/kg whereas average cumulative dose per patient was 389.6 ± 149.8 mg. The rate of graft dysfunction was 13.4% of patients and 6.7% had biopsy-proven acute rejection (BPAR). There were a total of 12 (3.3%) deaths and one graft loss. Overall survival and death-censored graft survival at 12 months were 96.65% and 99.44%, respectively. The rate of infections was 13.6% with urinary tract infections being most common. CONCLUSION: ATLG at an average dose of 6 mg/kg is an effective and safe induction regimen immunosuppressant for ABO-compatible KT with favourable impact on survival and graft function in Indian patients.

SARS-CoV-2 infection dynamics and genomic surveillance reveals early variant transmission in urban wastewater

Environmental surveillance (ES) of a pathogen is crucial for understanding the community load of disease. As an early warning system, ES for SARS-CoV-2 has complemented routine diagnostic surveillance by capturing near real-time virus circulation at a population level. In this longitudinal study in 28 sewershed sites in Bangalore city, we quantified SARS-CoV-2 RNA to track infection dynamics and provide evidence of change in the relative abundance of emerging variants. We describe an early warning system using the exponentially weighted moving average control chart and demonstrate how SARS-CoV-2 RNA concentrations in wastewater correlated with clinically diagnosed new COVID-19 cases, with the trends appearing 8-14 days earlier in wastewater than in clinical data. This was further corroborated by showing that the estimated number of infections is strongly correlated with SARS-CoV-2 RNA copies detected in the wastewater. Using a deconvolution matrix, we detected emerging variants of concern up to two months earlier in wastewater samples. In addition, we found a huge diversity in variants detected in wastewater compared to clinical samples. Our study highlights that quantifying viral titres, correlating it with a known number of cases in the area, and combined with genomic surveillance helps in tracking VOCs over time and space, enabling timely and making informed policy decisions.

Comparative evaluation of bond strength of resin cements with and without 10-methacryloyloxydecyl dihydrogen phosphate (mdp) to zirconia and effect of thermocycling on bond strength - An in vitro study.

Background: To compare bond strength of resin cements with and without 10-Methacryloyloxydecyl Dihydrogen Phosphate (MDP) to zirconia and evaluate effect of thermocycling on bond strength. Material and Methods: Standardised test specimens were fabricated as per ADA specification 131. Each Zirconia specimen was mounted in autopolymerzing acrylic resin material. The specimens were divided into 2 groups: Group 1 - specimens bonded with resin cement containing 10-MDP and Group II - specimens bonded with resin cement without 10-MDP. Forty samples of resin cement cylinders were prepared with dimensions of 6mm height and 4mm diameter in line with ADA specification 27 were cured onto the zirconia surface of 10mm x10mm x5mm using customised moulds. Specimens from each cement group were further divided into 2 subgroups: Subgroup A - Specimens that were not thermocycled and Subgroup B - Specimens that were thermocycled. Specimens were then subjected to tensile bond testing by using a Universal testing machine, the data were analysed using independent sample t test for bond strength and paired t test for effect of thermocycling. Statistical analysis used: Data was subjected to normalcy test (Shapiro-wilk test). Data showed normal distribution. Hence parametric test paired t test were applied. Results: Paired t test revealed that the thermocycling affected the bond strength to zirconia. The highest bond strength was achieved for the resin cement with 10-MDP before thermocycling, whereas the lowest bond strength values were recorded for resin cement without 10-MDP after thermocycling. Conclusions: Resin cement with 10-MDP showed superior bond strength to Zirconia than resin cement without 10-MDP. Adhesive failure was predominant at Zirconia and resin cement interface. Thermocycling had a significant effect on the bond strength of resin cements to zirconia, showing decreased bond strength. Key words:10-MDP, Tensile Strength, Zirconia.

Targeting Predialysis Glucose up to 180 mg/dl Reduces Glycemic Variability in End Stage Diabetic Nephropathy.

Context: Glycemic variability plays a major role in the development as well as the progression of cardiovascular disease in diabetes. Aims: We compared the mean plasma glucose and glycemic variability (GV) parameters on and off hemodialysis (HD) in patients with End-Stage Diabetic Nephropathy (ESDN) and End-Stage Renal Disease (ESRD). Settings and Design: Cross-sectional study. Methods and Material: We included 23 ESDN and 6 ESRD patients who underwent continuous glucose monitoring (CGM) (iPro2) for 6 days and a glucose-free dialysate for 4 hours thrice weekly. EasyGV software was used to calculate the variability parameters {mean glucose, Time in range (TIR), Time above and below range (TAR/TBR), CV (Coefficient of Variation) and MAGE}. Statistical Analysis Used: The quantitative data variables were expressed by using mean and SD. Unpaired t-test was used to compare the two groups. P value <0.05 was considered significant. Results: In the ESDN group, TIR was significantly lower whereas TAR and TBR were significantly higher on HD day. MAGE (101.88 ± 40.5 v/s 89.46 ± 30.0, P < 0.007) and CV (29.41% v/s 21.67%) were higher on HD day. Subjects with pre-HD glucose values ≥180 mg/dl (Group B, n = 24) had a rapid drop with a delayed higher rise in glucose values than those with pre-HD glucose values <180 mg/dl (Group A, n = 27). Ten patients had 13 episodes of hypoglycemia. The CGM parameters were not different in the ESRD group. Conclusions: Targeting a pre- HD glucose value <180 mg/dl could be a good strategy to prevent larger fluctuation during and post HD.

A Case of Hearing Impairment with Renal Dysfunction.

Hearing impairment in a patient with renal failure is an important clue towards etiologic diagnosis of kidney disease. Variety of hereditary diseases, developmental defects, and toxins involve these two organs. However, additional retinopathy is seen in quite a few diseases which include Alport's syndrome and Muckle-Wells syndrome (MWS). We are reporting a case of middle-aged woman with childhood-onset of hearing impairment who presented with renal failure and was diagnosed to have renal amyloidosis on kidney biopsy but without any light chain restriction. During evaluation for live donor kidney transplant, her brother was also found to have hearing impairment and retinopathy however with normal renal function and urinalysis. Genetic testing of both of them was done for panel of mutations related to hereditary amyloidosis which revealed NLRP3 mutation in both. This mutation is characteristic of MWS which can lead to secondary amyloidosis and renal failure.

Optimal secretion of thermostable Beta-glucosidase in Bacillus subtilis by signal peptide optimization.

Commercial applications of ß-glucosidase (BGL) demands its purity and availability on a large scale. In the present study, we aim to optimize the expression and secretion of a thermostable BGL from Pyrococcus furiosus (PfuBGL) in B. subtilis strain RIK1285. Initial studies with base strain BV002 harboring aprE signal peptide (aprESP) showed PfuBGL yield of 0.743 ± 0.19 pNP U/ml only. A library of 173 different homologous SPs from B. subtilis 168 genome was fused with target PfuBGL gene (PF0073) in pBE-S vector and extracellularly expressed in RIK1285 strain to identify optimal SP for PfuBGL secretion. High-throughput screening of the resulting SP library for BGL activity with a synthetic substrate followed by systematic scaling of the clones yielded a gene construct with CitHSP reporting a sixteen fold enhancement of PfuBGL secretion in comparison to base strain. Batch fermentation (7.5 L scale) PfuBGL yield of the BV003 strain with CitHSP-PF0073 fusion was observed to be 12.08 ± 0.21 pNP U/ml with specific activity of 35.52 ± 0.53 U/mg. Thus, the study represents report on the secretory expression of thermostable PfuBGL using B. subtilis as a host organism and demonstrating its high potential for industrial production of any protein/enzyme.

Is balloon-assisted maxillary sinus floor augmentation before dental implant safe and promising? A systematic review and meta-analysis.

We aimed to assess the complications of minimally invasive balloon-assisted maxillary sinus floor augmentation, compared with the conventional sinus floor augmentation procedures done before placing a dental implant. A structured question was formulated and an electronic search was conducted in three databases (MEDLINE via PubMed, Google Scholar, and Scopus). A separate search of gray literature and a hand search for missing articles were also conducted. Apart from animal studies, in-vitro studies, and case reports, all other types of studies where maxillary sinus floor augmentation was done using a balloon were considered for review. Our review was registered in International Prospective Registration of Systematic Reviews (PROSPERO) under number CRD42018086770. Our search produced 73 articles. However, only eight articles were found eligible to be included in our review (seven case series and one case-control study). Quality check was done using Methodological Index for Non-Randomized Studies (MINORS). Results suggest that balloon-assisted augmentation is associated with low rates of membrane tears (9 out of 272 sinus augmentation attempts), and high follow-up bone gain levels (mean 212.91%, 95% confidence interval 158.07%-267.75%, I2 = 97.62%). Balloon-assisted augmentation seems to be safe. More clinical trials are needed to assess the advantages and disadvantages of balloon-assisted maxillary sinus floor augmentation compared with other procedures.

Photochemical hydrogen evolution from water by a 1D-network of octahedral Ni6L8 cages.

A self-assembled M6L8 type cage-connected 1D-coordination network of formula {[Ni6(MeSi(3py)3)8Cl9(H2O)2]Cl3·16H2O}∞ (1) was obtained from a 3-pyridyl substituted silane ligand MeSi(3py)3. This complex shows significantly high performance for the electrocatalytic and photocatalytic hydrogen evolution reaction (HER) in water. A maximum turnover number (TON) of 2824 has been observed for photocatalytic HER after 69 h.

Profiling of Germline Mutations in Major Hotspot Codons of TP53 Using PCR-RFLP.

Tumor suppressor protein, TP53 also known as the "guardian of the genome" plays a key role in preventing malignant transformation. Almost 50% of human tumors carry mutations in this gene; in the remaining tumors, the TP53 network is functionally inoperative. The majority of TP53 mutations are missense mutations and more than 90% of the missense mutations affect specific codons in the DNA-binding domain, called "hotspot codons." The present study was aimed at analyzing the germline mutation status of four hotspot codons in TP53 namely, codon 175, codon 245, codon 248 (within the DNA binding domain) and codon 72 (outside the DNA binding domain) in cancer cases encountered in a tertiary care hospital in South India by PCR-RFLP. The case-control study included 85-10 subjects respectively. The results of the study indicated that majority of the cancer cases did not harbor germline mutations in the four hot spot codons of TP53. The study further highlights the usefulness of PCR-RFLP as a simple and cost effective tool for checking gene mutations.

Occult Gallbladder Carcinoma Presenting as a Primary Ovarian Tumour: a Case Report and Review of Literature.

The ovary is a common site of metastasis from various organs. However, little is known about gallbladder carcinoma metastasising to the ovaries and presenting as a primary ovarian tumour. We report a case of a metastatic gallbladder carcinoma which mimicked a primary ovarian tumour in a 31-year-old woman who presented with menstrual symptoms and an ovarian mass without obvious signs and symptoms related to gallbladder carcinoma. Postoperatively histopathological examination diagnosed primary ovarian germ cell tumour for further chemotherapy. However, postoperative re-evaluation with radiology suggested the possibility of a primary gallbladder carcinoma. Exact diagnosis could only be made after repeat histopathological evaluation of the ovarian mass.

Design and evaluation of dental films of PEGylated rosin derivatives containing sparfloxacin for periodontitis.

OBJECTIVE: In this study, PEGylated rosin derivatives (PRDs) namely D1 and D2 were synthesized and evaluated for their application to produce sustained-release antibacterial films containing sparfloxacin for periodontitis. SIGNIFICANCE: PRDs are biodegradable and biocompatible, and therefore sustained-release dental implant of PRD-sparfloxacin can provide an effectual treatment for periodontitis. METHODS: Films were produced by solvent casting technique and characterized for morphology, swelling-index, in vitro degradation and drug release kinetics. The impact of type of PRD, concentration of PRDs, and addition of plasticizer (dibutyl phthalate) on various film properties was evaluated. The films were also subjected to stability study at 30 °C and 40 °C for 90 days. RESULTS: Both D1 and D2 produced smooth and non-porous films with sparfloxacin. The D1 films, due to lower amount of polyethylene glycol 400 in D1, exhibited lower swelling-index, slower degradation, and slower drug release compared to D2 films. An increase in PRDs concentration decreased swelling-index, prolonged degradation time, and decreased drug release rate of films; addition of plasticizer showed the similar effect. At pH 7.6, D1 and D2 films showed complete degradation at the end of 58 and 51 days, respectively. At the end of 21 days, D1 and D2 films released 41.85% and 61.53% sparfloxacin, respectively. The drug release from D1 films followed Higuchi square-root kinetics, while D2 films released drug by the zero order kinetics. The stability conditions did not significantly alter PRDs-film properties. CONCLUSION: Results revealed that PRDs can be used successfully to produce sustained-release antibacterial films containing sparfloxacin for the treatment of periodontitis.

Light-driven Hydrogen Evolution from Water by a Tripodal Silane Based CoII6L18 Octahedral Cage.

The octahedral cage assembly [CoII6L18Cl6(H2O)6]Cl6 has been synthesized in a single-step reaction by using a polypyridyl-functionalized tripodal silane ligand. The electrochemical behavior of the cage in water exhibits the pH dependence of potential as well as catalytic current indicating the possible involvement of proton-coupled electron transfer in H2 evolution. Electrocatalytic hydrogen evolution from an aqueous buffered solution gave a turnover frequency of 16 h-1. Further, this cage assembly has been explored as a photocatalyst (blue light irradiation λ 469 nm) for the evolution of H2 from water in the presence of Ru(bpy)32+ as a photosensitizer and ascorbic acid as a sacrificial electron donor. This catalytic reaction is found to be pseudo first order with a turnover frequency of 20.50 h-1.

A ruthenium water oxidation catalyst containing a bipyridine glycoluril ligand.

A mononuclear ruthenium complex [Ru(tpy)(bpg)H2O]2+ bearing a bipyridine glycoluril where bpg = 4b,5,7,7a-tetrahydro-4b,7a-nepiminomethanoimino-6H-imidazo[4,5-f][1,10]phenanthro-line-6,13-dione acts as a robust water oxidation catalyst (WOC) at pH = 1 using Ce(iv) as a sacrificial oxidant. The turn over number (TON) for water oxidation is found to be ∼5 times higher than the parent complex [Ru(tpy)(bpy)H2O]2+ where tpy = 2,2':6',2''-terpyridine; bpy = 2,2'-bipyridine. The presence of intermolecular H-bonding groups and the electronic effect of the functionalized bipyridine ligand may play a significant role in water oxidation.

Diffuse large B-cell lymphoma in elderly: Experience from a tertiary care oncology center in South India.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most frequent non-Hodgkins lymphoma in the elderly. With the rising proportion of older persons in India, it is important to study current patterns and management of this disease, given that data in this regard are scarce in Indian settings. The aim of this study was to document the clinical features of DLBCL among elderly patients and their outcome over 7 years at a tertiary care oncology center. MATERIALS AND METHODS: This was a retrospective records review of 119 DLBCL cases between January 2007 and January 2015 aged 60 years and above done at Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India. Clinical staging was done according to Ann Arbor staging as modified by Cotswold's and International Prognostic Index (IPI) calculated. RESULTS: The mean age was 69.54 years (±5.44) with male: female ratio of 1.52:1. B symptoms were seen in 33% of patients. Thirty-six percent of the patients had stage II disease. The advanced stage was seen in 12% and bulky disease in 9.5%. Bone marrow was involved in 12%. The most common extranodal site was the head and neck region. The distribution according to the IPI was as follows: Low risk 38 (31.93%), low-intermediate risk 53 (44.54%), high-intermediate risk 20 (16.80%), and high risk 8 (6.72%). Among 119 patients, 98 (64.7%) received treatment with either combination of rituximab, cyclophosphamide, adriamycin, vincristine, epirubicin, and prednisolone. Overall response rate was 63.26% with a complete response rate of 38.77%. The overall survival ranged from 2 to 123 months with the median being 9.5 months. CONCLUSION: In elderly, DLBCL is common in seventh decade and most of them present in an early stage and low IPI. The incorporation of rituximab to anthracycline based chemotherapy shows a significant improvement in survival in elderly DLBCL.

The chronology of third molar mineralization by digital orthopantomography.

The present study was designed to determine the chronology of third molar mineralization to establish Indian reference data and to observe the advantages of digital orthopantomography. Therefore, a cross-sectional study was undertaken by evaluating 167 digital orthopantomographs in order to assess the mineralization status of the mandibular third molar of Caucasian individuals (85 males and 82 females) between the age of 14 and 24. The evaluation was carried out using the 8-stage developmental scheme of Demirjian et al (1973). The range, mean age, standard deviation and Student t-test are presented for each stage of mineralization in all four quadrants. Statistically significant differences between males and females were not found for all four third molars. All the individuals in this study with mature third molar were at least 18 years of age. For medicolegal purposes, the likelihood of whether an Indian is older than 18 years or not was determined. The advantage of digital orthopantomography in the interpretation of the tooth mineralization over the traditional method was acknowledged.

Economic methods used in fabrication of tissue microarray: A pilot study.

BACKGROUND AND OBJECTIVE: Tissue microarray (TMA) is a method of harvesting small disks of tissue from a range of standard paraffin tissue blocks and placing them in an array on a recipient paraffin block such that hundreds of cases can be analyzed simultaneously by using only a few microliters of antibody in immunohistochemistry as a single experiment. The TMA construction done with the help of automated tissue arrayer or commercially available rubber molds are expensive. This study involved the fabrication of TMA using rubber-based additional silicone mold constructed in the department and comparison of this method with two other methods of fabricating TMA. MATERIALS AND METHODS: The TMA mold was fabricated using silicone material in the department. The recipient blocks were prepared. The tissue core prepared from donor blocks were inserted into the recipient blocks. The sections taken from this were compared with the TMA using double-sided adhesive tape technique and TMA by punching out holes in prefabricated dummy paraffin recipient block for insertion of tissue core. RESULTS: The TMA using a mold made of silicone showed more advantages than other two methods. CONCLUSION: Fabricating TMA mold using silicone in the department is inexpensive and yet efficient.

Recombinant Human Semenogelin-1 (Sg1) and Sg1 (1-159) form Detergent Stable Amyloid like Aggregates in vitro.

Senile seminal vesicle amyloidosis (SSVA) is associated with deposition of semenogelin-1 (Sg1) protein aggregates in seminal vesicles that may manifest as hematospermia. Sg1 is the predominant protein that entraps spermatozoa which are freed upon fragmentation of Sg1 by the protease prostate specific antigen (PSA), post semen release. Certain small peptide fragments of Sg1 have been reported to form amyloid aggregates in vitro that can enhance HIV infectivity to cell cultures. However, the amyloid deposits in the seminal vesicles are expected to be that of the full length Sg1, as PSA is encountered downstream. So far, amyloid forming ability of full length Sg1 has not been established in vitro. Here, we examined the amyloidogenicity of full length Sg1 and a large fragment Sg1 (1-159), using recombinant proteins and tested if Zinc has any effect on their aggregation. Levels of Zinc, which is essential for health of male reproductive system, gradually decline with age. We succeeded in forming amyloid-like aggregates of Sg1 full length and Sg1 (1-159) fragment showing detergent stability and found that presence of Zn2+ substantially inhibits their amyloid aggregation in vitro. Possibly, high Zn2+ found in seminal plasma of young individuals may have preventive role against aggregation of Sg1 in seminal vesicles.