Ashish Datt Upadhyay

Identification of serum sirtuins as novel noninvasive protein markers for frailty.

Frailty has emerged as a major health issue among older patients. A consensus on definition and diagnosis is yet to be achieved. Various biochemical abnormalities have been reported in frailty. Activation of sirtuins, a conserved family of NAD‐dependent proteins, is one of the many mimics of calorie restriction which improves lifespan and health in experimental animals. In this cross‐sectional study, we assessed the circulating sirtuin levels in 119 (59.5%) nonfrail and 81 (40.5%) frail individuals, diagnosed by Frieds criteria. Serum SIRT1, SIRT2, and SIRT3 were estimated by surface plasmon resonance (SPR) and Western blot. Serum sirtuins level in mean+SD; SIRT1 (nonfrail –4.67 ± 0.48 ng/μL; frail – 3.72 ± 0.48 ng/μL; P < 0.0001), SIRT2 (nonfrail – 15.18 ± 2.94 ng/μL; frail – 14.19 ± 2.66 ng/μL; P = 0.016), and SIRT3 (nonfrail‐7.72 ± 1.84 ng/μL; frail – 6.12 ± 0.97 ng/μL; P < 0.0001) levels were significantly lower among frail patients compared with the nonfrail. In multivariable regression analysis, lower sirtuins level were significantly associated with frailty after adjusting age, gender, diabetes mellitus, hypertension, cognitive status (Mini Mental State Examination scores) and number of comorbidities. For detecting the optimum diagnostic cutoff value a ROC analysis was carried out. The area under curve for SIRT1 was 0.9037 (cutoff – 4.29 ng/μL; sensitivity – 81.48%; specificity – 79.83%) and SIRT3 was 0.7988 (cutoff – 6.61 ng/μL; sensitivity – 70.37%; specificity – 70.59%). This study shows that lower circulating SIRT1 and SIRT3 levels can be distinctive marker of frailty.

Corneal Changes in Childhood Glaucoma

OBJECTIVE To study the clinical features and topography of the cornea in eyes with childhood glaucoma. DESIGN Cross-sectional, observational study. PARTICIPANTS Fifty-eight eyes with childhood glaucoma and 28 eyes of age-matched controls. METHODS Clinical and topographic corneal changes were evaluated. MAIN OUTCOME MEASURES Corneal topographic changes were evaluated on Orbscan (Orbscan Topography System II; Bausch & Lomb, Salt Lake City, UT) in eyes with childhood glaucoma and those changes were compared with the control eyes. RESULTS Fifty-eight eyes with childhood glaucoma and 28 eyes of age-matched controls were evaluated. Thirty-six eyes (62.1%) were classified as having primary childhood glaucoma and 22 eyes (37.94%) as having childhood glaucoma with associated ocular anomalies. The corneas in 18 of 58 eyes (31.0%) with childhood glaucoma were clear, whereas 24.1% of eyes (14/58 eyes) had some corneal opacification. Haabs striae were noted in 44.8% of eyes (26/58 eyes) and were most frequently present between 3 and 5 mm from the optical axis. The mean posterior elevation recorded in eyes with childhood glaucoma controlled with medication or surgery was significantly higher than that in control eyes: 0.043 ± 0.027, 0.042 ± 0.017, and 0.018 ± 0.058 μm, respectively (P < 0.0001). The presence of Haabs striae was correlated significantly with a higher posterior elevation (P = 0.0396) and poor vision. The mean anterior elevation in eyes with childhood glaucoma (0.022 ± 0.015 μm) and in control eyes (0.015 ± 0.078 μm) was comparable (P = 0.08). Corneal astigmatism in eyes with childhood glaucoma was significantly higher and irregular compared with that in control eyes: 2.09 ± 1.40 versus 0.93 ± 0.60 diopter cylinder (P = 0.0001); the irregularity index was 2.8 (range, 1-18.1) and 2.3 (range, 0.6-2.3) at 3 mm (P = 0.0005) and 3.2 (range, 1.4-21.3) and 1.8 (range, 0.5-2.9) at 5 mm, respectively (P = 0.0003). Best-corrected visual acuity correlated significantly with cup-to-disc ratio, axial length, refractive error, astigmatism, and posterior corneal elevation. Multivariate analysis showed a significant correlation only with cup-to-disc ratio and axial length. CONCLUSIONS Childhood glaucoma causes a significant increase in posterior corneal elevation and irregular astigmatism, which contribute to visual disability in such eyes.

Clinical presentation and survival of retinoblastoma in Indian children

Objective To study the clinical presentation and survival among Indian children with retinoblastoma (RB) and to determine factors predictive of poor outcome. Methods A retrospective review of children newly diagnosed with RB at a tertiary referral centre was undertaken. Demographic and clinical characteristics and treatment outcomes were studied. Results A total of 600 patients (unilateral 67.6%, bilateral 32.4%) was studied. 61% was boys. The median age at presentation was 29 months (18 months vs 36 months in bilateral and unilateral cases, respectively, p<0.001). leukocoria was most common (83%), followed by proptosis (17%). Tumours were intraocular in 72.3% and extraocular in 27.7% cases. In the intraocular group, 78% were advanced Group D or E disease. Metastasis to the central nervous system was noted in 15.7% of extraocular cases. A statistically significant difference was seen between intraocular and extraocular groups in the median age (24 months vs 37.5 months, p<0.001) and median lag period (2.5 months vs 7 months, p<0.001). The Kaplan-Meier survival probability was 83%, 73% and 65% at 1 year, 2 years and 5 years, respectively. On univariate analysis, age >2 years (p=0.002), lag period >6 months (p=0.004) and extraocular stage (p<0.001) were associated with poor outcome. On multivariate analysis, extraocular invasion was predictive of low survival (HR 5.04, p<0.001). Conclusions Delayed presentation is a matter of concern. Improving awareness about the early signs and creating facilities for diagnosing and treating RB at the primary and secondary levels of healthcare are required to reduce mortality and morbidity, and lead to improved outcomes that are comparable with the developed nations.

Chromosomal aberrations, Yq microdeletion, and sperm DNA fragmentation in infertile men opting for assisted reproduction

Male infertility is a multi‐factorial disorder, and identification of its etiology in an individual is critical for treatment. Systematically elucidating the underlying genetic causes (chromosomal and Yq microdeletion) and factors, such as reactive oxygen species (ROS) levels and total antioxidant capacity (TAC), which contribute to sperm DNA damage, may help to reduce the number of men with idiopathic infertility and provide them with the most suitable therapeutics and counseling. This study was done to comprehensively investigate genetic and oxidative stress factors that might be the etiology of a large percentage of men with idiopathic infertility. One hundred twelve infertile men and 76 fertile controls were screened for chromosomal aberrations and Yq microdeletions. ROS, TAC, and sperm DNA damage were assessed in cytogenetically normal, non‐azoospermic men with intact Y chromosome (n = 93). ROS was assessed in neat and washed semen by chemiluminescence; seminal TAC with a commercially available kit; and sperm DNA damage by the comet assay. Two men had cytogenetic abnormalities and seven men harbored Yq microdeletions. ROS levels in neat and washed semen of infertile men were significantly higher (P < 0.01) than controls. Infertile men had significantly lower (P < 0.01) TAC levels (1.79 mM), whereas sperm DNA fragmentation in infertile men was significantly higher (P < 0.01) than controls. Genetic factors and oxidative stress cumulatively account for large number of idiopathic infertile cases. Unlike, genetic causes, which cannot be cured, timely identification and management of oxidative stress may help to reverse/reduce the effects on induced DNA damage, and improve the outcomes for infertile males. Mol. Reprod. Dev. 79: 637–650, 2012.

Genotype of the LMNA 1908C>T variant is associated with generalized obesity in Asian Indians in North India

Objective  To determine the frequency distribution of LMNA 1908C>T SNP and its association with generalized obesity, abdominal obesity and coexistent metabolic disorders in nondiabetic Asian Indians living in a metropolitan city of north India.

Evaluation of the Diagnostic Performance of Fibrin Monomer in Comparison to d-Dimer in Patients With Overt and Nonovert Disseminated Intravascular Coagulation.

Introduction: Disseminated intravascular coagulation (DIC) is a thrombohemorrhagic disorder characterized by hyperactivation of coagulation and secondary fibrinolysis. Aim: The primary aim of this prospective study was to evaluate and compare the diagnostic performance of fibrin monomer (FM) and d-dimer (DD) for the preemptive diagnosis of DIC in the early stages. Materials and Methods: The patients were categorized into 3 groups: overt DIC, nonovert DIC, and non-DIC based on the International Society of Thrombosis and Hemostasis scoring for overt DIC and the modified nonovert-DIC criteria. Coagulation tests were performed on freshly obtained plasma. Quantitative determination of FM and DD was done by immunoturbidimetric assay. Results: Median DD and FM levels in patients with overt DIC were significantly higher in comparison to the other 2 groups. Interestingly, unlike DD, the difference in FM levels was also found to be statistically significant between patients with nonovert DIC and non-DIC patients (P = .0001). At receiver–operator characteristic curve-generated cutoff values, FM had higher specificity and negative predictive value than DD for predicting onset of overt DIC. Multivariate analysis showed that only FM was as an independent predictive factor useful in differentiating patients with overt DIC from non-DIC patients (odds ratio [OR]: 43.3; confidence interval [CI] 4.61-406.68; P value = .001) as well as in distinguishing nonovert DIC from non-DIC patients (OR:18.3; CI 3.45-97.19; P value = .001). Conclusion: Fibrin monomer is a better indicator than DD in distinguishing patients with overt and nonovert DIC from non-DIC patients, raising the possibility for its diagnostic utility as a marker for impending overt DIC, aiding in early diagnosis and prompt therapeutic intervention.

Aspiration pneumonia related deaths in head and neck cancer patients: a retrospective analysis of risk factors from a tertiary care centre in North India.

BACKGROUND Aspiration pneumonia is an important cause of death in head and neck cancer patients. This study therefore aimed to evaluate the risk factors associated with aspiration pneumonia in head and neck cancer patients. METHODS Hospital death records from 12 years (2000-2012) were reviewed to obtain the number of deaths. Treatment details and cause of death were analysed. Statistical analysis was performed to identify the risk factors for aspiration pneumonia. RESULTS The records revealed that aspiration pneumonia was the cause of death in 51 out of 85 patients. Primary tumour site (oropharynx and hypopharynx, odds ratio 3.3; 95 per cent confidence interval 1.17-9.4, p = 0.02) and advanced tumour stage (odds ratio 4.2, 95 per cent confidence interval 1.16-15.61, p = 0.02) had significant negative impacts on aspiration pneumonia related mortality. CONCLUSION Advanced pharyngeal cancer patients are at an increased risk of aspiration pneumonia related death. Investigations for the early detection of this condition are recommended in these high-risk patients.

Categories of foot at risk in patients of diabetes at a tertiary care center: Insights into need for foot care

Objective: Diabetic foot ulcers and amputations are preventable. Aim of this study was to determine the distribution of categories of foot at risk in patients with diabetes, attending a tertiary care hospital and factors that affect it. Materials and Methods: Detail history and examination including neurological and vascular assessment were performed in 100 patients with diabetes attending a Tertiary Care Hospital. Foot at risk was classified according to the task force of foot care interest Group of American Diabetes Association. Category of foot at risk was correlated with demographic and clinical features. Results: Fifty-two percent patients had foot at risk-category 1 and 2. Loss of protective sensation (LOPS) was present in 33% (category 1). Peripheral arterial disease (PAD) was present in 19% (category 2). Both LOPS and PAD were present in 10% patients. 95% had never received foot care advice by health professionals, let alone prescriptive footwear or vascular consultation. Conclusions: This study brings forth that foot at risk of ulcer is rampant in patients with diabetes. There are lacunae in diabetic foot care at all levels of care. With the increase in diabetes, cost effective steps are required to improve foot care among diabetes in India. Considering the demographic profile of patients in our study, growing number of patients with diabetes, lack of time and staff allocated for foot care in our setup, audiovisual aids seems a good option to spread foot care awareness among diabetes.

Prenatal music stimulation facilitates the postnatal functional development of the auditory as well as visual system in chicks (Gallus domesticus)

Rhythmic sound or music is known to improve cognition in animals and humans. We wanted to evaluate the effects of prenatal repetitive music stimulation on the remodelling of the auditory cortex and visual Wulst in chicks. Fertilized eggs (0 day) of white leghorn chicken (Gallus domesticus) during incubation were exposed either to music or no sound from embryonic day 10 until hatching. Auditory and visual perceptual learning and synaptic plasticity, as evident by synaptophysin and PSD-95 expression, were done at posthatch days (PH) 1, 2 and 3. The number of responders was significantly higher in the music stimulated group as compared to controls at PH1 in both auditory and visual preference tests. The stimulated chicks took significantly lesser time to enter and spent more time in the maternal area in both preference tests. A significantly higher expression of synaptophysin and PSD-95 was observed in the stimulated group in comparison to control at PH1-3 both in the auditory cortex and visual Wulst. A significant inter-hemispheric and gender-based difference in expression was also found in all groups. These results suggest facilitation of postnatal perceptual behaviour and synaptic plasticity in both auditory and visual systems following prenatal stimulation with complex rhythmic music.

Repetitive auditory stimulation at a critical prenatal period modulates the postnatal functional development of the auditory as well as visual system in chicks (Gallus domesticus)

The extrinsic sensory stimulation plays a crucial role in the formation and integration of sensory modalities during development. Postnatal behavior is thereby influenced by the type and timing of presentation of prenatal sensory stimuli. In this study, fertilized eggs of white Leghorn chickens during incubation were exposed to either species‐specific calls or no sound. To find the prenatal critical period when auditory stimulation can modulate visual system development, the former group was divided into three subgroups: in subgroup A (SGA), the stimulus was provided during embryonic day (E)10 to E16, in SGB E17‐ hatching, and in SGC E10‐hatching. The auditory and visual perceptual learning was recorded at posthatch day (PH) 1–3, whereas synaptic plasticity (evident from synaptophysin and PSD‐95 expression), was observed at E19, E20, and PH 1–3. An increased number of responders were observed in both auditory and visual preference tests at PH 1 following stimulation. Although a decrease in latency of entry and an increase in total time spent were observed in all stimulated groups, it was most significant in SGC in auditory preference and in SGB and SGC in visual preference test. The auditory cortex of SGC and visual Wulst of SGB and SGC revealed higher expression of synaptic proteins, compared to control and SGA. A significant inter‐hemispheric and gender‐based difference in expression was also found in all groups. These results indicate facilitation of postnatal behaviour and synaptogenesis in both auditory and visual systems following prenatal repetitive auditory stimulation, only when given during prenatal critical period of development.