Contiguous multiple cervicothoracic spinous process fractures in an adult: A case report

Fracture of isolated spinous processes at multiple levels is a rare injury. Herein, we present a 45-year-old male with cervical pain and swelling following a road traffic accident. Computerized tomography and magnetic resonance imaging revealed fractures of spinous process from C7 to D6 vertebra. The patient was managed with rest, analgesics and immobilization. At the 1-year follow-up, the patient is doing well without any neurological problem.     

Age estimation in children by measurement of open apices in teeth: a study in North Indian population

Age estimation is a prerequisite in forensic medicine, paediatric endocrinology and orthodontic treatment. Dental development has been proven to be suitable for age determination in children because of its lower variability. The aim of this study was to evaluate the applicability of using the open apex method proposed by Cameriere et al. for age estimation in Indian children. Digitalized panoramic radiographs were retrieved from the Department of Oral Medicine & Radiology of 558 Indian children (261 girls, 297 boys) with an age range from 5 to 15 years. The seven left permanent mandibular teeth were evaluated for length and open apices. Dental maturity was evaluated using measurements of the seven left permanent mandibular teeth (x_i = A_i/L_i, i = 1,...,7), the sum of the normalized open apices (s) and the number (N₀) of teeth with root development complete. Using a stepwise multiple regression model, a relationship between open apices, N₀ and age was evaluated. Statistical analysis revealed high accuracy with the morphological variables explaining 88.5% of the variations in estimated chronological age. This research suggests an open apex method could be successful for age estimation in Indian children and could be applied in legal issues pertaining to forensic medicine.     

PAHs and PM2.5 emissions and female breast cancer incidence in metro Atlanta and rural Georgia

Environmental chemical exposure could be an important etiologic factor for geographic differences in breast cancer incidence. In this study, we examined emissions of polycyclic aromatic hydrocarbons (PAHs) and PM_2.5 in relation to breast cancer incidence in metro Atlanta and rural Georgia by analyzing data from the Surveillance, Epidemiology, and End Results Program and the Environmental Protection Agency. The results showed that metro Atlanta had a significantly higher age-adjusted annual incidence rate of female breast cancer than rural Georgia (132.6 vs. 113.7 per 100,000) for 1992–2011. Emissions of both PAHs [adjusted β = 0.568 (95 % CI: 0.209, 0.927); p = 0.004] and PM_2.5 [adjusted β = 2.964 (95 % CI: 0.468, 5.459); p = 0.023] were significantly associated with breast cancer incidence in metro Atlanta area. This study suggests that ambient air pollution, especially PAHs and PM_2.5, could have a significant impact on the increased incidence of female breast cancer in urban areas.     

Preoperative Statin Therapy Decreases Risk of Postoperative Renal Insufficiency

Introduction: Although current guidelines recommend withholding statins in perioperative patients, little information is available on whether perioperative statin use increases risk for postoperative renal failure. Aims: We examined the relation between preoperative statin therapy and postoperative risk for renal insufficiency in patients undergoing cardiac surgery. Methods: Retrospective cohort review from the Texas Heart Institute research database was performed. Patients were divided into two groups: those who received preoperative statins and those who did not. Primary outcome was the development of postoperative renal insufficiency (requiring dialysis or not). Outcomes were assessed in the entire cohort and in subgroups undergoing isolated coronary artery bypass grafting (CABG), isolated valve surgery, or combined CABG and valve surgery. Results: Of 3001 patients, 56% received preoperative statins. In multivariate logistic regression analysis, preoperative statins were associated with significant reductions in risk for postoperative renal insufficiency in the entire cohort (odds ratio [OR]= 0.60, 95% confidence interval [CI] 0.38–0.95) and in patients undergoing isolated CABG (OR = 0.34, 95% CI 0.17–0.68). In patients undergoing isolated valve surgery (OR = 1.35, 95% CI 0.61–2.96) or combined CABG and valve surgery (OR = 1.39, 95% CI 0.48–3.99), preoperative statins were not associated with decreased incidence of postoperative renal insufficiency. Age >65 years, preoperative renal insufficiency, history of congestive heart failure, preoperative intra‐aortic balloon pump insertion, and total cardiopulmonary bypass time >80 min were also independent predictors associated with increased risk for postoperative renal insufficiency. Conclusions: Preoperative statin therapy was associated with decreased incidence of postoperative renal insufficiency in patients undergoing cardiac surgeries, particularly in patients undergoing isolated CABG.     

Molecular dynamics simulations of unfolding and refolding of a β-hairpin fragment of protein G

We have studied the unfolding and refolding pathway of a beta-hairpin fragment of protein G by using molecular dynamics. Although this fragment is small, it possesses several of the qualities ascribed to small proteins: cooperatively formed beta-sheet secondary structure and a hydrophobic "core" of packed side chains. At high temperatures, we find that the beta-hairpin unfolds through a series of sudden, discrete conformational changes. These changes occur between states that are identified with the folded state, a pair of partially unfolded kinetic intermediates, and the unfolded state. To study refolding at low temperatures, we perform a series of short simulations starting from the transition states of the discrete transitions determined by the unfolding simulations.     

Spectro-electrochemical assessments of DNA/BSA interactions,cytotoxicity, radical scavenging and pharmacological implications of biosensitive and biologically active morpholine-based metal(ii) complexes: a combined experimental and computational investigation

Biosensitive and biologically active morpholine-based transition metal(ii) complexes (1–5) were constructed as [M^II(L) AcO]·nH₂O {where M = Cu (1) n = 1; Co (2), Mn (3), Ni (4), n = 4 and Zn (5) n = 2}, which were synthesized from 2-(-(2-morpholinoethylimino) methyl)-4-bromophenol ligand (HL) and structurally characterized by various analytical and spectroscopic techniques, which proposed a square planar and tetrahedral geometry around the central metal ion with lattice water molecules. The gel electrophoresis results revealed that complexes 1 and 5 had more potent DNA cleavage efficacy in the presence of an oxidizing agent (H₂O₂) as compared to the others. The observed DNA binding results for all the compounds as determined by spectro-electrochemical and hydrodynamic techniques were in the order 3.36 (1) > 3.06 (2) > 2.73 (4) > 2.61 (5) > 1.84 (3) > 1.00 (HL) × 10⁴ M⁻¹. The obtained bovine serum albumin (BSA) protein binding constant (K_b) results put forward the following order 2.38 (1) > 2.21 (2) > 2.18 (5) > 1.76 (4) > 1.40 (3) > 1.26 (HL) × 10⁴ M⁻¹. Also, the biothermodynamic parameters (, , ΔH° and ΔS°) and binding results divulged that all the complexes (1–5) could bind to DNA via intercalation in a spontaneous manner. Density functional theory calculations were employed to optimize the structure of ligand (HL) and its complexes (1–5) to gain insights into their electronic structures. Molecular docking analysis was carried out to identify the preferential binding modes of these complexes toward DNA and BSA protein. The theoretical observations of all cases were found to be very close to the experimental observations. Among the radical scavenging activity results for all the cases toward DPPH, hydroxyl radical, superoxide, nitric oxide and ferric reducing agents, complex (1) revealed a superior scavenging potency over the other compounds. In the screened antimicrobial reports against 10 different selected pathogenic species, although all the complexes (1–5) exhibited a greater significant inhibitory effect than the free ligand, complexes 4 and 5 achieved the best potency over standard drugs. The observed percentage of growth inhibition for all the compounds against the A549, HepG2, MCF-7 and NHDF cell lines suggested that complex 1 had enhanced growth-inhibitory potency over the other compounds and slightly affected normal cells as compared to the standard drug cisplatin, which may lead to its investigation as a promising anticancer agent in future research.

Morpholine-based metal(ii) complexes exhibited more significant biological activities than the free ligand. Among investigations towards DNA/BSA, the copper complex revealed excellent intercalating efficacy, which suggests it may have potential as a novel anticancer agent.     

Metabolic syndrome in urban Asian Indian adults--a population study using modified ATP III criteria

Aims/hypothesis: To determine the prevalence of the Metabolic syndrome (MetS) using modified ATP III criteria in urban Asian Indian adults. Methods: 475 subjects (age 20–75 years) from a population data base were studied for the MetS using ATP III criteria but with a modified waist circumference (WC) appropriate for Indians. Presence of≥3 of the following; raised WC (Men≥90 cm, Women≥85 cm), triglycerides (TG) ≥1.7 mmol/l), HDL-Cholesterol (HDL-C)-<1.0 mmol/l for men, <1.3 mmol/l for women, fasting plasma glucose (FPG)≥6.1 mmol/l and blood pressure (BP)≥130/≥85 mm of Hg, or using BP medication, indicated the MetS. Insulin resistance (IR) was calculated using the Homeostasis Model Assessment (HOMA) equation. Factor analysis was used to identify clusters of correlated abnormalities. Results: MetS was present in 41.1%. WC was increased in 31.4%, TG in 45.6%, low HDL-C in 65.5%, hypertension in 55.4% and raised FPG 26.7%. MetS was present in 27.9% of subjects with FPG<6.1 mmol/l and its prevalence increased to >70% with higher FPG values. MetS was more common in women than in men (46.5 vs. 36.4%, χ²=4.6, P=0.03) and in older people. Four distinct clusters of abnormalities were identified with some gender variations. IR was more prevalent in MetS and was a component of two clusters but it was not a core component in factor analysis. Conclusions: MetS is common in Asian Indians. Its prevalence is age-related, and is more common in women. HOMA–IR or fasting plasma insulin was not a core component of the MetS.     

Immune checkpoint inhibitors in patients with solid tumors and poor performance status: A prospective data from the real-world settings

Immune checkpoint inhibitors (ICIs) are rapidly being incorporated as treatment option either alone or in combination with chemotherapy in most of the solid tumors. Since there is very limited data of ICI in patients with poor performance status (PS) from the real world settings, we performed a retrospective audit of patients who received ICI and report the analysis based on ECOG PS of these patients.This study is a retrospective audit of a prospectively collected database of patients receiving ICIs for advanced solid tumors in any line between August 2015 and November 2018 at Tata Memorial Hospital, Mumbai, India. All statistical calculations were performed using SPSS statistical software for windows version 20.0.A total of 155 patients who received ICIs during the specified period were evaluated for this study. Baseline ECOG PS 0–1 (n = 103, 66.4%) patients was associated with median OS 9.1 (95% CI [confidence interval], 4.4-NR) months when compared to ECOG 2–4 (n = 52, 33.5%) which had a median OS of 2.9 (95% CI; 1.8–5.5) months (HR, 1.7, 95% CI, 1.1–2.7, log rank P = .017). The disease control rate for the poor PS group was 34.6%. However, 27.3% patients (95% CI: 20.3–34.3) were still alive at 1 year. Median OS in patients with PS 2 was 3.7 months (95% CI: 0–11.6) as compared to 1.8 months (95% CI: 0.2–3.4) for those with PS 3–4 (HR-2.0; 95% CI: 1.0–3.9, P = .041). The tolerance to ICIs was good with no grade 3/4 toxicities in 44 (84.6%) patients.Immune checkpoint inhibitors are a safe and effective therapeutic option even in solid tumor patients with poor performance status.     

Differential nitros(yl)ation of blood and tissue constituents during glyceryl trinitrate biotransformation in vivo

Nitric oxide (NO)-derived products may modify tissue constituents, forming S- and N-nitroso adducts and metal nitrosyls implicated in NO signaling. Nitrovasodilator drugs have been in widespread use for more than a century, yet their biotransformation pathways to NO and their effects as NO donors across tissues remain ill defined. By using a metabonomics approach (termed "NObonomics") for detailing the global NO-related metabolism of the cornerstone nitrovasodilator, glyceryl trinitrate (GTN; 0.1-100 mg/kg), in the rat in vivo, we find that GTN biotransformation elicits extensive tissue nitros(yl)ation throughout all major organ systems. The corresponding reaction products remained detectable hours after administration, and vascular tissue was not a major nitros(yl)ation site. Extensive heart and liver modifications involved both S- and N-nitrosation, and RBC S-nitrosothiol formation emerged as a sensitive indicator of organic nitrate metabolism. The dynamics of GTN-derived oxidative NO metabolites in blood did not reflect the nitros(yl)ation patterns in the circulation or in tissues, casting doubt on the usefulness of plasma nitrite/nitrate as an index of NO/NO-donor biodynamics. Target-tissue NO metabolites varied in amount and type with GTN dose, suggesting a dose-sensitive shift in the prevailing routes of GTN biotransformation ("metabolic shunting") from thiol nitrosation to heme nitrosylation. We further demonstrate that GTN-induced nitros(yl)ation is modulated by a complex, tissue-selective interplay of enzyme-catalyzed pathways. These findings provide insight into the global in vivo metabolism of GTN at pharmacologically relevant doses and offer an additional experimental paradigm for the NObonomic analysis of NO-donor metabolism and signaling.