Challenges and Road Map towards Starting a New COVID Hospital.

Background and Aim: With advent of the Coronavirus Disease 2019 (covid-19) pandemic, need for a dedicated government hospital was felt. Following directions after a cabinet decision, a dedicated Covid hospital was made functional within a month in Central district of Delhi. This manuscript briefs the journey and challenges experienced during this mission. Method: As per decision of the state health ministry, bed allocation was planned along with provision for diagnosis, treatment and prevention of Covid -19. Various trainings were simultaneously conducted, licences were obtained and manpower and material were arranged starting with procurement to service provision and waste management. Result: Concerted efforts resulted in initiation of clinical and diagnostic services within one month of initiation of teamwork. Government supported in all the licencing requirements and material management. The hospital became functional during the first wave; and by the start of second wave, 20-bedded fully equipped Intensive Care Unit (ICU) was ready with pressure swing adsorber (PSA) oxygen generator in premises. Conclusion: A well-coordinated action in the right direction with administrative support can help in achieving difficult targets. Opening a new hospital amidst lockdown and resource constraints in an emergency situation was a rewarding achievement.

Initiation of Anti-Hypertensive Drugs and Outcomes in Patients with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: In patients with heart failure with reduced ejection fraction (HFrEF) and hypertension, systolic blood pressure is recommended to be maintained below 130 mmHg, although this has not been shown to be associated with improved outcomes. We examined the association between anti-hypertensive drug initiation and outcomes in patients with HFrEF. METHODS: In the Medicare-linked OPTIMIZE-HF, 7966 patients with HFrEF (ejection fraction ≤40%) without renal failure were not receiving anti-hypertensive drugs before hospitalization, of whom 692 received discharge prescriptions for those drugs (thiazides and calcium channel blockers). We assembled a propensity score-matched cohort of 687 pairs of patients initiated and not initiated on anti-hypertensive drugs, balanced on 38 baseline characteristics. Hazard ratios (HR) and 95% confidence intervals (CIs) for outcomes associated with anti-hypertensive drug initiation were estimated in the matched cohort. RESULTS: Matched patients (n = 1374) had a mean age of 74 years, 41% were female, 17% were African-American, 66% were discharged on renin-angiotensin system inhibitors and beta blockers, and 10% on aldosterone antagonists. During 6 (median 2.5) years of follow-up, 70% of the patients died and 53% had heart failure readmission. Anti-hypertensive drug initiation was not significantly associated with all-cause mortality (HR, 0.95; 95% CI, 0.83-1.07) or heart failure readmission (HR, 0.93; 95% CI, 0.80-1.07). Similar associations were observed during 30 days and 12 months of follow-up. CONCLUSIONS: Among hospitalized older patients with HFrEF receiving contemporary treatments for heart failure, initiation of an anti-hypertensive drug was not associated with a lower risk of all-cause mortality or hospital readmission.

Is waist circumference more strongly associated with metabolic risk factors than waist-to-height ratio in Asians?

OBJECTIVES: Differential distribution of fats can vary among ethnic groups and thus have varying effects on metabolic risk. Measuring metabolic risk of individuals using simple anthropometric measurements is essential to replace current invasive methods of obtaining blood samples. Waist-to-height ratio (WHtR) has been advocated as the best simple anthropometric measurement, but, because of the high visceral fat of Asians, there has been speculation as to the possibility of using only waist circumference (WC) to measure metabolic risk. The aim of this study was to compare the performance of WC and WHtR in terms of their association with measures of obesity and metabolic risk factors (e.g., homeostasis model assessment for insulin resistance, low-density lipoprotein, triacylglycerol, and ratio of triacylglycerol to high-density lipoprotein) and to obtain an optimal cutoff value for one anthropometric measurement. METHODS: The study was performed on healthy Asian Chinese (N = 527) men (n = 209) and women (n = 318) who participated in a cross-sectional study conducted at the Clinical Nutrition Research Centre located in Singapore. Association of WC and WHtR with metabolic risk factors was obtained using Spearman's rank correlation coefficient. Optimal cutoff value was obtained using receiver operating characteristic curve. RESULTS: WC and WHtR performed equally well in both sexes in terms of their strength of association between metabolic risk factors. Receiver operating characteristic curve analysis showed that 73.5 cm (in women) and 82.5 cm (in men) were the optimal WC cutoff values to identify insulin resistance. CONCLUSION: It is suggested that WC is a simpler anthropometric measurement that has strong association with an individual's metabolic risk level.

The glycaemic index and insulinaemic index of commercially available breakfast and snack foods in an Asian population.

A low-glycaemic-index (GI) breakfast has been shown to lower blood glucose levels throughout the day. A wide variety of breakfast foods are consumed, but their GI values are largely unknown, hence limiting consumers' ability to select healthier options. This study investigated the GI values of ten common breakfast (five Asian and five Western) foods in this region using a randomised, cross-over study design. Participants arrived after an overnight fast, and fasting blood sample was taken before participants consumed test foods. Next, blood samples were taken at fixed intervals for 180 min. Glycaemic and insulinaemic responses to test foods were calculated as incremental AUC over 120 min, which were subsequently reported as glycaemic and insulinaemic indices. In all, nineteen healthy men (nine Chinese and ten Indians) aged 24·7 (sem 0·4) years with a BMI of 21·7 (sem 0·4) kg/m2 completed the study. Asian breakfast foods were of medium (white bun filled with red bean paste=58 (sem 4); Chinese steamed white bun=58 (sem 3)) to high GI (rice idli=85 (sem 4); rice dosa=76 (sem 5); upma=71 (sem 6)), whereas Western breakfast foods were all of low GI (whole-grain biscuit=54 (sem 5); whole-grain biscuit filled with peanut butter=44 (sem 3); whole-grain oat muesli=55 (sem 4); whole-grain oat protein granola=51 (sem 4); whole-grain protein cereal=49 (sem 3)). The GI of test foods negatively correlated with protein (r s -0·366), fat (r s -0·268) and dietary fibre (r s -0·422) (all P<0·001). GI values from this study contribute to the worldwide GI database, and may assist healthcare professionals in recommending low-GI breakfast to assist in lower daily glycaemia among Asians who are susceptible to type 2 diabetes mellitus.

Effect of size and shape on toxicity of zinc oxide (ZnO) nanomaterials in human peripheral blood lymphocytes.

The multi-industrial applications of zinc oxide nanomaterials (ZnO NMs) lead to increasing exposure to humans. Though the ZnO nanoparticles (NPs) toxicity had been evaluated previously, toxicity of other forms of ZnO nanomaterials has not been evaluated. In this study, cytotoxicity and genotoxicity of four different types of ZnO NMs were evaluated using human peripheral blood lymphocytes (HPBL). In addition, the effect of anti-oxidants on ZnO NMs induced toxicity was also evaluated. Our results suggest that, size and shape of the nanomaterials have profound effects on their toxicity. The NPs and nanorods (NRs) possessed higher level of oxidative potential and ROS generation capacity than microparticles (MPs) and microrods (MRs). In contrast, MPs and MRs possessed higher level of lipid peroxidation capacity. The smaller NPs are more genotoxic while larger MPs and MRs were more cytotoxic in nature. Treatment with vitamin C or Quercetin significantly reduces the genotoxicity associated with ZnO NMs. The influence of size and shape in mediating NMs toxicity should be taken into account and the possible supplementation of anti-oxidants might mitigate the toxicity.

Key drivers of patient experience in ambulatory paediatric cardiology.

Patient experience is becoming a central focus of healthcare. A broad range of studies on how to increase patient satisfaction ratings exists; however, they lack the specificity to adequately guide physicians and hospitals on how to improve patient experience. The objective of this study was to define the aspects of patient experience within paediatric cardiologist practices that can serve as predictors of excellent patient satisfaction. From 1 January, 2013 to 28 February, 2015 (26 months), outpatients who visited paediatric cardiologists were asked to complete a 39-question patient satisfaction survey regarding their experience. Surveys were collected over a 26-month period by Press Ganey, an independent provider of patient satisfaction surveys. Participants were asked to rate their experience on a 1-5 Likert-scale: a score of 1 demonstrated a "poor" experience, whereas a score of 5 demonstrated a "very good" experience. This retrospective study of 2468 responses determined that cheerfulness of the practice (r=0.85, p<0.001), a cohesive staff (r=0.83, p<0.001), and a care provider explaining problems and conditions (r=0.81, p<0.001) were key aspects of a paediatric cardiologist's practice that can be used as predictors of overall patient satisfaction. Awareness of how doctors can personalise a patient's experience is vital to achieve greater patient satisfaction and, ultimately, better patient outcomes.

Polychlorinated biphenyl exposure and deiodinase activity in young infants.

BACKGROUND: Several studies have shown effects of polychlorinated biphenyls (PCBs) on serum thyroid hormone levels in pregnant woman and their infants, while other studies did not find such effects. How PCBs might affect thyroid hormone metabolism, is still unclear. Potential mechanisms are direct influence on the thyroid gland, binding to thyroid binding proteins, increased excretion or metabolism of thyroid hormones by deiodinases or sulfatases. It is also not well known whether the effect on thyroid hormone levels is caused by PCBs themselves, or by their hydroxylated metabolites (OH-PCBs). OBJECTIVE: To determine the effects of perinatal exposure to PCBs and OH-PCBs on thyroid hormone levels in cord blood and in serum of newborn infants. METHODS: In a Dutch cohort of 100 mother-infant pairs, exposed to background PCB levels, correlations were assessed between 10 PCBs and 6 OH-PCBs in maternal blood during pregnancy and serum thyroxine (T4), T4 sulfate (T4S), triiodothyronine (T3), reverse T3 (rT3), thyroid-stimulating hormone (TSH) and thyroxine-binding globulin (TBG) levels in cord blood and in serum of three- and 18-month-old infants. We corrected for age of the mother, gestational age, gender and type of feeding. RESULTS: After correction, prenatal levels of three of 10 measured PCBs showed a positive correlation with cord serum T3, and four PCBs showed a negative correlation with cord serum rT3. After correction, two PCBs and the sum of the 10 measured PCBs were positively correlated with the cord serum T3/rT3 ratio, an indicator of deiodinase 3 activity. No correlations were found between PCBs and T4, TSH and TBG in cord blood. 4-OH-PCB-107 was correlated with T4 at 3months and T4, T4S and T3 at 18months. CONCLUSION: Our results suggest that PCBs have a negative effect on deiodinase type 3 activity, as reflected by a positive correlation with the T3/rT3 ratio. We identified a potential mechanism by which PCBs may affect thyroid hormone metabolism during human development.

Comparative evaluation of two different remineralizing agents on the microhardness of bleached enamel surface: Results of an in vitro study.

CONTEXT: Various agents are studied for their remineralization potential. AIM: To evaluate the effect of GC Tooth Mousse and Toothmin Tooth Cream on microhardness of bleached enamel. SETTINGS AND DESIGN: In vitro- study. METHODS AND MATERIAL: Twenty freshly extracted anterior teeth were cut sagittally and impregnated in cold cure acrylic resin. Specimens were kept in artificial saliva to prevent from dehydration. After measuring baseline hardness, teeth were randomly divided into two groups. Everbrite In - Office Tooth whitening kit (Dentamerica) was used to demineralize the teeth following which hardness was measured again. Teeth in group one (n=10) and group two (n=10) were treated with GC tooth mousse (Recaldent) and Toothmin tooth cream (Abbott Healthcare Pvt.Ltd) daily for seven days and microhardness of enamel surface was measured. STATISTICAL ANALYSIS USED: Mean, SD, and percentage change in the microhardness were calculated. Student's paired t-test was used to evaluate the signifi cance of change from initial, after bleaching for 5 min and after 1-week remineralization Unpaired't' test was used to compare difference between groups. RESULTS: Microhardness significantly decreased in both groups after bleaching (% change group one: 3.24% group two: 3.26% in group; P<0.01 in both groups). Both products significantly increased mineralization after seven days of treatment (P<0.01). Remineralization was numerically better in Toothmin group (Abbott Healthcare Pvt.Ltd ) compared to GC Mousse(Recaldent) (% change 3.27% vs 6.34%). However, difference was not significant (P >0.05). CONCLUSION: Both GC Tooth Mousse (Recaldent) and Toothmin Tooth cream (Abbott Healthcare Pvt.Ltd) increase the microhardness of bleached enamel. Toothmin tooth cream is a better agent for increasing microhardness, although difference is not significant.

Prenatal exposure to polychlorinated biphenyls and their hydroxylated metabolites is associated with neurological functioning in 3-month-old infants.

Polychlorinated biphenyls (PCBs) are environmental chemicals which are potentially toxic to the developing brain. Their hydroxylated metabolites (OH-PCBs) are suggested to be even more toxic. Knowledge about the health effects of prenatal OH-PCB exposure is limited. We aimed to determine whether prenatal background exposure to PCBs and OH-PCBs is associated with neurological functioning in 3-month-old boys and girls. In a Dutch observational cohort study, we measured 10 PCBs and 6 OH-PCBs in maternal blood samples of 98 pregnant women. We assessed their infants neurologically with Touwen examination at 3 months and calculated an Optimality Score (OS, range 0-53, low-high optimality). We calculated correlation coefficients between compound levels and OS. Subsequently, we tested whether levels were associated with specific clusters and whether levels differed between infants with "normal" (dysfunction on ≤1 cluster) and "non-optimal" development (dysfunction on ≥2 clusters). The mean OS was 48 (range 44-52). Higher exposure to PCB-146 correlated significantly with higher OS (r = 0.209; p = 0.039). In boys, higher exposure to 4-OH-PCB-107 correlated with lower OS (r = -0.305; p = 0.030). Higher exposure to 9 PCBs and the sum of all PCBs was associated with better visuomotor and/or better sensorimotor function. Infants classified as "non-optimal" (n = 36) had significantly lower prenatal exposure to 6 PCBs and the sum of all PCBs (p < 0.05) compared with infants classified as "normal" (n = 62). In conclusion, higher prenatal exposure to Dutch background PCB levels is associated with better neurological functioning in 3-month-old infants. Prenatal exposure to 4-OH-PCB-107 is associated with less optimal neurological functioning in boys.

Characterization and genotoxicity evaluation of particulate matter collected from industrial atmosphere in Tamil Nadu state, India.

Ambient particulate matter (PM) collected in the vicinity of five industries (Cement, Chemical, Thermal power plant, Sponge-iron and Steel) in Tamil Nadu state, India was characterized for size distribution, metals and polycyclic aromatic hydrocarbons (PAHs) content. Genotoxicity of PM and organic matter (OM) extracted from PM was measured in human lung cancer cell-line, A549 and in human liver carcinoma cell-line, HepG2, respectively, using the comet assay. PM values varied from 57.0 µg/m(3) of air at Cement industry upstream to 561.0 µg/m(3) of air at Sponge iron industry downstream samples. Their metal content varied from 5.758 µg/m(3) of air at Chemical industry to 46.144 µg/m(3) of air at Sponge iron industry and PAH concentration varied from 0.5 ng/m(3) air in upstream Thermal power plant to 3302.4 ng/m(3) air in downstream Sponge iron industry samples. While all PM samples induced DNA strand breaks at higher dose levels, downstream samples of Steel and Sponge iron industries which contained relatively higher concentrations of PAHs and metals and exhibited higher levels of pro-oxidant activity as measured by DTT activity induced significantly higher levels of DNA damage in HepG2 and A549 cells. Pretreatment of A549 cells with vitamin C or quercetin significantly reduced PM induced DNA strand breaks.

Prenatal exposure to polychlorinated biphenyls and their hydroxylated metabolites is associated with motor development of three-month-old infants.

BACKGROUND: Polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants that are potentially toxic to the developing brain. Hydroxylated metabolites of PCBs (OH-PCBs) are suggested to be even more toxic. Little is known about their short-term effects on human health. OBJECTIVES: To determine whether prenatal background exposure to PCBs and OH-PCBs was associated with the motor development of three-month-old infants. METHODS: Ninety-seven mother-infant pairs participated in this Dutch, observational cohort study. We determined the concentrations of PCBs and OH-PCBs in cord blood samples. When the infants were three months old we evaluated their motor development by assessing the presence and performance of spontaneous movement patterns from video recordings. We calculated a Motor Optimality Score (MOS). The score could range from low (5) to high (28) optimality. We explored the correlations between PCB and OH-PCB levels and MOS. Subsequently, we tested whether the levels differed between infants with a low (<26) or high (≥26) MOS and whether the levels associated with detailed aspects of their motor repertoires. RESULTS: We found several associations between PCB and OH-PCB levels and MOS, including detailed aspects of the early motor development. High 4-OH-PCB-107 levels were associated with a low MOS (P=.013). High PCB-187 levels were associated with reduced midline arm and leg movements (P=.047 and P=.043, respectively). High 4'-OH-PCB-172 levels were associated with more manipulation (P=.033). CONCLUSIONS: Prenatal exposure to high background levels of most PCBs and 4-OH-PCB-107 seems to impair early motor development, whereas only 4'-OH-PCB-172 showed the opposite.

Proteolytic cleavage of p70 ribosomal S6 kinase by caspase-3 during DNA damage-induced apoptosis.

p70 S6 kinase (p70S6K) plays an important role in protein translation and cell cycle progression. Increased levels of p70S6K have been associated with drug resistance. In this study, we have investigated the involvement of p70S6K in DNA damage-induced apoptosis. The DNA-damaging agent cisplatin caused a concentration-dependent decrease in the level of full-length p70S6K in small cell lung cancer H69 and non-small cell lung cancer A549 cells with a concomitant increase in the level of an approximately 45 kDa fragment. The proteolytic cleavage of p70S6K was inhibited by a broad specificity caspase inhibitor but not by the proteosome or calpain inhibitor. Cell-permeable peptide inhibitor and siRNA against caspase-3 inhibited cisplatin-induced proteolytic cleavage of p70S6K. In vitro-translated p70S6K was cleaved by human recombinant caspase-3. Cisplatin failed to induce cleavage of p70S6K in MCF-7 cells that lack functional caspase-3, but ectopic expression of caspase-3 in MCF-7 cells resulted in the cleavage of p70S6K. p70S6K was primarily cleaved at a noncanonical recognition site, Thr-Pro-Val-Asp, after Asp-393. Site-directed mutagenesis of Asp-393 to Ala resulted in protection against cisplatin-mediated apoptosis, whereas introduction of the N-terminal cleaved fragment resulted in potentiation of cisplatin-induced apoptosis. These results suggest that p70S6K is a novel substrate for caspase-3 and that the proteolytic cleavage of p70S6K is important for cisplatin-induced apoptosis.

Manipulation of PKC isozymes by RNA interference and inducible expression of PKC constructs.

Protein kinase C (PKC), a family of serine/threonine kinases, plays an important role in apoptosis. Several members of the PKC family act as substrates for caspases. In addition, PKCs can also regulate caspase activation and cell death by apoptosis. The cleavage of PKCs separates the regulatory domain from the catalytic domain. The full-length, the catalytic domain, and the regulatory domain of PKC family members may have distinct function in apoptosis. Delineating the role of protein kinase C (PKC) isozymes in apoptosis has been challenging because of the lack of selective inhibitors of PKC isozymes and difficulty in generating stable cell lines expressing pro-apoptotic PKC isozymes. In this chapter, we describe the use of RNA interference (siRNA) technology and tetracycline-inducible expression of PKC isozymes to study their function in apoptosis.

Involvement of proteolytic activation of PKCdelta in cisplatin-induced apoptosis in human small cell lung cancer H69 cells.

Proteolytic activation of protein kinase C delta (PKCdelta) has been associated with apoptosis induced by the DNA damaging agent cisplatin. In cells undergoing apoptosis, caspase-3 cleaves PKCdelta at the site DMQD downward arrowN to generate a 40-kDa catalytic fragment. We have previously shown that the PKC signal transduction pathway regulates sensitivity of human small cell lung cancer H69 cells to cisplatin. In the present study, we have investigated if proteolytic activation of PKCdelta is essential for cisplatin-induced apoptosis in H69 cells. The caspase cleavage-resistant mutant PKCdelta (DMQA) was generated by mutating the aspartate residue at the site of proteolysis DMQD downward arrowN to alanine (D330A), and the wild-type and mutant PKCdelta were introduced into H69 cells. Cisplatin induced a substantial increase in PKCdelta catalytic fragment in H69 cells overexpressing PKCdelta (H69/delta, and the level of PKCdelta catalytic fragment in H69 cells expressing DMQA mutant (H69/DMQA) was equivalent to that in H69 cells. However, the cleavage of poly(ADP-ribose) polymerase (PARP), another substrate for caspase-3, was similar in cells overexpressing wild-type PKCdelta and DMQA mutant PKCdelta. The ability of cisplatin to induce mitochondrial depolarization and cell death was also equivalent among the cell lines tested. These results suggest that the proteolytic fragment of PKCdelta does not play a critical role in the induction of apoptosis in H69 cells.