Optimization of process variables for enhanced lactic acid production utilizing paneer whey as substrate in SMF

In the present study lactic acid production was enhanced by optimizing the three process variables viz; inoculum size, temperature and pH using three factor five level CCRD (central composite rotatable design) by Lactobacillus delbruckii under SMF (submerged fermentation process). Paneer (dairy by-product) whey was used as sole substrate for lactic acid production. Design Expert 8.0.2.0 software depicted that an optimum concentration of 8% (v/v) size of inoculum, 5.50 pH and 36.53C temperature gave lactic acid and biomass yield of 5.61 g/L and 4.27 g/L, respectively. Lactic acid production was scale up in 7.5 L bioreactor under optimized conditions and it gave lactic acid and biomass yield of 39.2±1.4 and 47.6±0.8 g/L, respectively. μg, YP/S, YP/X and productivity were found to be 0.14 h-1, 0.66 g/g, 0.7 g/g and 1.98 g/L. h, respectively. Leudking Piret equation deduced that lactic acid production was growth associated which varies from earlier reports. Lactic acid was characterized by FTIR (Fourier transform infrared spectroscopy) and HPLC (High performance liquid chromatography)

A validated RP-HPLC method for simultaneous determination of Metformin HCl and Vildagliptin in pharmaceutical formulation

A selective and sensitive reverse phase high performance liquid chromatographic (RP-HPLC) method has been developed for the separation and quantification of metformin HCl (MET) and vildagliptin (VILD) in tablet dosage form. The determination was carried out using phenomenax C18 column (4.6150 mm) as a stationary phase and mobile phase comprised of phosphate buffer (pH6.0): methanol (65:35v/v). The pH of phosphate buffer is adjusted to 6.0 by using orthophosphoric acid. The flow rate was maintained at 1.0ml/min and the eluent was monitored at 255nm.The retention time of MET and VILD were 1.503 min and 5.530 min respectively. The method was validated in terms of linearity, precision, accuracy, ruggedness, specificity and robustness. The method was linear over the range 50-150 g/ml for both MET (r = 0.999) and VILD (0.998). For precision studies; RSD for MET and VILD were 0.24 and 0.14 respectively. The percentage recoveries for both drugs from their tablets were 100.16 and 99.98 respectively. Inter-day; intra-day RSD for both drugs were found be 0.27 and 0.26, 0.13 and 0.29 respectively

In-hospital mortality rate and predictors of 30-day readmission in patients with iron deficiency anemia and diastolic heart failure : a cross-sectional study

Corresponding author: Karthik Gangu MD, Assistant Professor of Clinical Medicine, Department of Medicine, Division of Hospital Medicine, University of Kansas Medical CenterIntroduction: There is currently strong evidence of the adverse effects of anemia on the prognosis of heart failure with reduced ejection fraction. Unfortunately, the data on the effects of anemia on a large sample of patients with diastolic heart failure (DHF) is lacking. In this study, we aimed to evaluate the effect of iron deficiency anemia on DHF readmission rates and its corresponding causes and burdens on the healthcare system. Methods: We utilized 2018 Nationwide readmission data and included patients aged ≥18 years with ICD-10 CM code indicating acute or acute chronic diastolic heart failure and iron deficiency anemia was included in the study. The primary outcome is 30-day readmission rates. Secondary outcomes were mortality rates, common causes of readmission, and healthcare utilization. Independent predictors for readmission were identified using cox regression analysis. Results: The total number of admissions in our study was 795,777. The mean age was 74.4 years (SD=13.7), and 63.54% were females. The 30-day readmission rate in patients with diastolic heart failure and iron deficiency anemia was 18.32 % vs. 16.01% in patients without anemia. The mortality rate at index admission and readmission was 3.62 % (2601) and 5.82 % (737), respectively. The most common cause of readmission was hypertensive heart and kidney disease with heart failure (17.74%). The independent predictors of readmission were age [less than] 85 years, household income [less than] 59000$/per year, Medicare and Medicaid insurance, higher Elixhauser comorbidities score, longer Length of stay during the index admission, discharge to a nursing home, hospital located in a large metropolitan area. The financial burden on healthcare for all the readmission was$837 million for 2018. Conclusion: The 30-day readmission rate in patients with diastolic heart failure and iron deficiency anemia is 18.32% in the year 2018. The mortality rate increased from 3.62 % to 5.82 % with readmission. The financial burden for readmission during that year was $837 million. Future studies are warranted to treat iron deficiency anemia to prevent readmissions in diastolic heart failure.Karthik Gangu MD (Department of Medicine, Division of Hospital Medicine, University of Kansas Medical Center), Aniesh Bobba MBBS (Department of Medicine, Division of Hospital Medicine, John H Stroger Hospital of Cook County), Parth S.Patel MD (University of Missouri Kansas City School of Medicine), Sruthi Vellanki MD (Department of Medicine, Division of Hospital Medicine, Union Hospital), Anup Kumar Trikannad MD (Department of Medicine, Division of Hospital Medicine, Union Hospital), Sanket Basida MBBS (Department of Medicine, Pandit Deendayal Upadhyay Medical College), Sindhu Avula (Department of Cardiovascular Medicine, Division of Interventional Cardiology, University of Kansas Medical Center), Alok Tripathi (Department of Cardiovascular Medicine, Division of Interventional Cardiology, University of Kansas Medical Center)Includes bibliographical references

A quick and selective rhodamine based “smart probe” for “signal-on” optical detection of Cu²⁺ and Al³⁺ in water, cell imaging, computational studies and solid state analysis

A novel rhodamine hydrazone 1 has been synthesized by the condensation of rhodamine B hydrazide with allylsalicylaldehyde and has been fully characterized using various physicochemical techniques including single crystal XRD. Probe 1 can detect Cu2+ and Al3+ ions in aqueous media and displays a turn-on response in absorbance with a high degree of selectivity amongst other common interfering analytes. Al3+ ions lead to fluorescence enhancementby the opening of the spirolactum ring resulting in chelation enhanced fluorescence. DFT and TDDFT calculations support the experimental results. The 1-Al3+ ensemble acts as secondary sensor for pyrophosphate anion due to metal ion induced decomplexation resulting in a low detection limit. Probe 1 can be utilized for bio imaging and displays morphological transformations from crystalline to amorphous state with associated color changes due to mechanical switching. In the solid state, probe 1 displays distinct color changes with emission at different wavelengths in particular Al3+ and Hg2+result in a red shift of the CIE-diagram. While the band gap of probe 1can be tuned from 2.08 eV to 1.60 eV.Probe 1 meets many real-world-challenges in that it is prepared using simple synthetic methods, produces fast and distinct response towards multiple-ions, observed by the “naked eye” in solution and on a TLC plate, and can be exploited for binary data storage

Overexpression of Prothymosin Alpha Predicts Poor Disease Outcome in Head and Neck Cancer

In our recent study, tissue proteomic analysis of oral pre-malignant lesions (OPLs) and normal oral mucosa led to the identification of a panel of biomarkers, including prothymosin alpha (PTMA), to distinguish OPLs from histologically normal oral tissues. This study aimed to determine the clinical significance of PTMA overexpression in oral squamous cell hyperplasia, dysplasia and head and neck squamous cell carcinoma (HNSCC).Immunohistochemistry of PTMA protein was performed in HNSCCs (n = 100), squamous cell hyperplasia (n = 116), dysplasia (n = 50) and histologically normal oral tissues (n = 100). Statistical analysis was carried out to determine the association of PTMA overexpression with clinicopathological parameters and disease prognosis over 7 years for HNSCC patients.<0.001). Chi-square analysis showed significant association of nuclear PTMA with advanced tumor stages (III+IV). Kaplan Meier survival analysis indicated reduced disease free survival (DFS) in HNSCC patients (p<0.001; median survival 11 months). Notably, Cox-multivariate analysis revealed nuclear PTMA as an independent predictor of poor prognosis of HNSCC patients (p<0.001, Hazard's ratio, HR = 5.2, 95% CI = 2.3–11.8) in comparison with the histological grade, T-stage, nodal status and tumor stage.Nuclear PTMA may serve as prognostic marker in HNSCC to determine the subset of patients that are likely to show recurrence of the disease

Nuclear S100A7 Is Associated with Poor Prognosis in Head and Neck Cancer

Tissue proteomic analysis of head and neck squamous cell carcinoma (HNSCC) and normal oral mucosa using iTRAQ (isobaric tag for relative and absolute quantitation) labeling and liquid chromatography-mass spectrometry, led to the identification of a panel of biomarkers including S100A7. In the multi-step process of head and neck tumorigenesis, the presence of dysplastic areas in the epithelium is proposed to be associated with a likely progression to cancer; however there are no established biomarkers to predict their potential of malignant transformation. This study aimed to determine the clinical significance of S100A7 overexpression in HNSCC.Immunohistochemical analysis of S100A7 expression in HNSCC (100 cases), oral lesions (166 cases) and 100 histologically normal tissues was carried out and correlated with clinicopathological parameters and disease prognosis over 7 years for HNSCC patients. Overexpression of S100A7 protein was significant in oral lesions (squamous cell hyperplasia/dysplasia) and sustained in HNSCC in comparison with oral normal mucosa (p(trend)<0.001). Significant increase in nuclear S100A7 was observed in HNSCC as compared to dysplastic lesions (p = 0.005) and associated with well differentiated squamous cell carcinoma (p = 0.031). Notably, nuclear accumulation of S100A7 also emerged as an independent predictor of reduced disease free survival (p = 0.006, Hazard ratio (HR = 7.6), 95% CI = 1.3-5.1) in multivariate analysis underscoring its relevance as a poor prognosticator of HNSCC patients.Our study demonstrated nuclear accumulation of S100A7 may serve as predictor of poor prognosis in HNSCC patients. Further, increased nuclear accumulation of S100A7 in HNSCC as compared to dysplastic lesions warrants a large-scale longitudinal study of patients with dysplasia to evaluate its potential as a determinant of increased risk of transformation of oral premalignant lesions

Assessing performance of the Healthcare Access and Quality Index, overall and by select age groups, for 204 countries and territories, 1990-2019: a systematic analysis from the Global Burden of Disease Study 2019

Background: Health-care needs change throughout the life course. It is thus crucial to assess whether health systems provide access to quality health care for all ages. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019), we measured the Healthcare Access and Quality (HAQ) Index overall and for select age groups in 204 locations from 1990 to 2019. Methods: We distinguished the overall HAQ Index (ages 0–74 years) from scores for select age groups: the young (ages 0–14 years), working (ages 15–64 years), and post-working (ages 65–74 years) groups. For GBD 2019, HAQ Index construction methods were updated to use the arithmetic mean of scaled mortality-to-incidence ratios (MIRs) and risk-standardised death rates (RSDRs) for 32 causes of death that should not occur in the presence of timely, quality health care. Across locations and years, MIRs and RSDRs were scaled from 0 (worst) to 100 (best) separately, putting the HAQ Index on a different relative scale for each age group. We estimated absolute convergence for each group on the basis of whether the HAQ Index grew faster in absolute terms between 1990 and 2019 in countries with lower 1990 HAQ Index scores than countries with higher 1990 HAQ Index scores and by Socio-demographic Index (SDI) quintile. SDI is a summary metric of overall development. Findings: Between 1990 and 2019, the HAQ Index increased overall (by 19·6 points, 95% uncertainty interval 17·9–21·3), as well as among the young (22·5, 19·9–24·7), working (17·2, 15·2–19·1), and post-working (15·1, 13·2–17·0) age groups. Large differences in HAQ Index scores were present across SDI levels in 2019, with the overall index ranging from 30·7 (28·6–33·0) on average in low-SDI countries to 83·4 (82·4–84·3) on average in high-SDI countries. Similarly large ranges between low-SDI and high-SDI countries, respectively, were estimated in the HAQ Index for the young (40·4–89·0), working (33·8–82·8), and post-working (30·4–79·1) groups. Absolute convergence in HAQ Index was estimated in the young group only. In contrast, divergence was estimated among the working and post-working groups, driven by slow progress in low-SDI countries. Interpretation: Although major gaps remain across levels of social and economic development, convergence in the young group is an encouraging sign of reduced disparities in health-care access and quality. However, divergence in the working and post-working groups indicates that health-care access and quality is lagging at lower levels of social and economic development. To meet the needs of ageing populations, health systems need to improve health-care access and quality for working-age adults and older populations while continuing to realise gains among the young. Funding: Bill & Melinda Gates Foundation

Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.publishedVersio

Vision, challenges and opportunities for a Plant Cell Atlas

With growing populations and pressing environmental problems, future economies will be increasingly plant-based. Now is the time to reimagine plant science as a critical component of fundamental science, agriculture, environmental stewardship, energy, technology and healthcare. This effort requires a conceptual and technological framework to identify and map all cell types, and to comprehensively annotate the localization and organization of molecules at cellular and tissue levels. This framework, called the Plant Cell Atlas (PCA), will be critical for understanding and engineering plant development, physiology and environmental responses. A workshop was convened to discuss the purpose and utility of such an initiative, resulting in a roadmap that acknowledges the current knowledge gaps and technical challenges, and underscores how the PCA initiative can help to overcome them.</jats:p