Modified rankin scale is a reliable tool for the rapid assessment of stroke severity and predicting disability outcomes.

Background: 'Time is brain' goes the adage. Rapid and precise management of stroke is of the utmost essence. The modified National Institutes of Health Stroke Scale (mNIHSS) and the modified Rankin Scale (mRS) predict stroke severity and functional disability outcomes. However, the mRS can be administered more rapidly than the mNIHSS and therefore might be better to assess patient outcomes. Hence, the aim of this study was to assess the correlation of stroke severity on admission and functional disability outcomes on the day of discharge or on the 8th day of hospitalization. Materials and Methods: This was an observational, cross-sectional study with a sample size of 61 participants. The mNIHSS score was calculated on admission for patients with clinical features suggestive of stroke and mRS was calculated on the 8th day of hospitalization or on discharge. Evaluation of the association between continuous variables was done using Spearman's correlation analysis. Results: Correlation between mNIHSS and mRS was positive and statistically significant (rho = 0.866, 95% CI [0.751, 0.925]. For each point increase in the mNIHSS, the odds of having higher mRS scores are 153% more than the odds of having lower mRS scores (aOR = 2.534, 95% CI [1.904, 3.560]). Conclusion: Our study concluded that mRS can be reliably used to predict the functional outcomes for patients with stroke in circumstances where the mNIHSS may prove to be lengthy. Thus, where 'time is brain', the mRS can be used with a similar power to predict the outcome.

New thiazolyl-isoxazole derivatives as potential anti-infective agents: design, synthesis, in vitro and in silico antimicrobial efficacy.

Antimicrobial resistance threatens the efficacious prevention and treatment of infectious diseases caused by microorganisms. To combat microbial infections, the need for new drug candidates is essential. In this context, the design, synthesis, antimicrobial screening, and in silico study of a new series of 5-aryl-3-(2-arylthiazol-4-yl)isoxazole (9a-t) have been reported. The structure of new compounds was confirmed by spectrometric methods. Compounds 9a-t were evaluated for in vitro antitubercular and antimicrobial activity. Against M. tuberculosis H37Rv, fourteen compounds showed good to excellent antitubercular activity with MIC 2.01-9.80 µM. Compounds 9a, 9b, and 9r showed four-fold more activity than the reference drug isoniazid. Nine compounds, 9a, 9b, 9d, 9e, 9i, 9q, 9r, 9s, and 9t, showed good antibacterial activity against E. coli with MIC 7.8-15.62 µg/mL. Against A. niger, four compounds showed good activity with MIC 31.25 µg/mL. Against C. albicans, all twenty compounds reported excellent to good activity with MIC 7.8-31.25 µg/mL. Compounds 9c-e, 9g-j, and 9q-t showed comparable activity concerning the reference drug fluconazole. The compounds 9a-t were screened for cytotoxicity against 3t3l1 cell lines and found to be less or non-cytotoxic. The in silico study exposed that these compounds displayed high affinity towards the M. tuberculosis targets PanK, DprE1, DHFR, PknA, KasA, and Pks13, and C. albicans targets NMT, CYP51, and CS. The compound 9r was evaluated for structural dynamics and molecular dynamics simulations. The potent antitubercular and antimicrobial activity of 5-aryl-3-(2-arylthiazol-4-yl)isoxazole (9a-t) derivatives has recommended that these compounds could assist in treating microbial infections.Communicated by Ramaswamy H. Sarma.

Investigation of new 1,2,3-triazolyl-quinolinyl-propan-2-ol derivatives as potential antimicrobial agents: in vitro and in silico approach.

A new series of 1-((1-(4-substituted benzyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-(2-substituted quinolin-4-yl)propan-2-ol (9a-x) have been synthesized. The newly synthesized 1,2,3-triazolyl-quinolinyl-propan-2-ol (9a-x) derivatives were screened for in vitro antimicrobial activity against M. tuberculosis H37Rv, E. coli, P. mirabilis, B. subtilis, and S. albus. Most of the compounds showed good to moderate antibacterial activity and all derivatives have shown excellent to good antitubercular activity with MIC 0.8-12.5 µg/mL. To know the plausible mode of action for antibacterial activity the docking study against DNA gyrase from M. tuberculosis and S. aureus was investigated. The compounds have shown significant docking scores in the range of -9.532 to -7.087 and -9.543 to -6.621 Kcal/mol with the DNA gyrase enzyme of S. aureus (PDB ID: 2XCT) and M. tuberculosis (PDB ID: 5BS8), respectively. Against the S. aureus and M. tuberculosis H37Rv strains, the compound 9 l showed good activity with MIC values of 62.5 and 3.33 µM. It also showed significant docking scores in both targets with -8.291 and -8.885 Kcal/mol, respectively. Molecular dynamics was studied to investigate the structural and dynamics transitions at the atomistic level in S. aureus DNA gyrase (2XCT) and M. tuberculosis DNA gyrase (5BS8). The results revealed that the residues in the active binding pockets of the S. aureus and M. tuberculosis DNA gyrase proteins that interacted with compound 9 l remained relatively consistent throughout the MD simulations and thus, reflected the conformation stability of the respective complexes. Thus, the significant antimicrobial activity of derivatives 9a-x recommended that these compounds could assist in the development of lead compounds to treat for bacterial infections.Communicated by Ramaswamy H. Sarma.

Challenges in screening for sickle cell disease among newborns from the tribal region of Palghar, Maharashtra during the COVID-19 pandemic.

BACKGROUND OBJECTIVES: Despite several adversities imposed by the COVID-19 pandemic, it was crucial to sustain research having public health relevance such as investigations around sickle cell disease (SCD). Against this background, an ongoing ICMR-multicentric study for newborn screening of SCD in the tribal population at Model Rural Health Research Unit (MRHRU-Dahanu) in Palghar District, Maharashtra constituted the current study setting. This was a descriptive study wherein, certain measures were undertaken and strategies were developed in view of the challenges in newborn screening for SCD due to the COVID-19 pandemic during December 2019-September 2021 at Sub District Hospital, MRHRU-Dahanu. METHODS: During the onset of the pandemic, (December 2019-March 2020), the follow up was possible in 26.7 per cent (20/75) of the newborns. Subsequently, challenges such as travel restrictions, fear of COVID-19, shortage of staff were experienced with respect to enrolment and follow up visits. RESULTS: After implementing certain pragmatic strategies (ASHA involvement, usage of virtual platform and flexible visits), follow up rate increased to 47.5 per cent (66/139) between July 2020-April 2021 (post first lockdown) and to 66 per cent (65/98) during the second wave (May 2021-August 2021). INTERPRETATION CONCLUSIONS: The study emphasizes the importance of network building, use of virtual platform and engaging health workers in tribal settings. Such pragmatic approaches have the potential to pave a path for further implementation research involving specific interventions to improve health outcomes in tribal settings.

Study of the Urinary TGF-ß1 Profile in Diabetic Nephropathy: A Single-Center Experience From India.

Background Diabetic nephropathy is one of the important causes of end-stage kidney disease (ESKD). Of the various cytokines playing a role in the pathogenesis of diabetic nephropathy, transforming growth factor beta-1 (TGF-ß1) is an important one. Its major role is to mediate extracellular matrix deposition. Increased renal expression of TGF-ß1 is found in diabetic nephropathy and its urinary excretion can serve as a useful marker of outcomes. Material and methods A prospective observational study was conducted, which included 10 cases of diabetic nephropathy in group A with age ≥ 18 years and a urinary protein creatinine ratio (UPCR) value of > 0.5 mg/mg and 10 healthy controls in group B. Patients with active urinary tract infection, chronic kidney disease (CKD) stage Vd patients on maintenance hemodialysis, and renal transplant recipients were excluded from the study. Urinary TGF-ß1 level estimation in a 24-hour urine sample, 24-hour urine protein, and other baseline laboratory investigations were done. Results In diabetic nephropathy cases (group A), the mean value of urinary TGF-ß1 levels was 88.33± 12.44 ng/24 hours. In the control group (group B), the mean value of urinary TGF-ß1 was 29.03 ± 3.23 ng/24 hours. Urinary TGF-ß1 levels were significantly elevated in group A as compared to group B (p<0.001). There was no significant correlation between urinary TGF-ß1 levels and estimated glomerular filtration rate (eGFR) (r=0.376, p= 0.285) as well as the urinary TGF-ß1 levels and 24-hour urine protein levels (p = 0.334, r = 0.341) in diabetic nephropathy cases. Glycosylated hemoglobin (HbA1c) levels didn't correlate with the urinary TGF-ß1 levels (r = -0.265, p = 0.46). Conclusion The urinary TGF-ß1 levels were significantly elevated in diabetic nephropathy patients as compared to healthy controls. There was no significant correlation between urinary TGF-ß1 levels and proteinuria, eGFR, or HbA1c levels in diabetic nephropathy patients.

Measured Glomerular Filtration Rate in Live Related Kidney Donors Three Months Post-Kidney Donation: A Single-Center Experience From Western India.

Background Glomerular filtration rate (GFR) estimation is pivotal in the evaluation of kidney donors. There are various methods available for assessing GFR, but there has been a lack of consensus on the measurement of GFR and the frequency of renal evaluation after kidney donation. Our study aims to analyze the measured GFR (m-GFR) before and three months after kidney donation and note the compensatory abilities of the remnant kidney in live related kidney donors. Methods This prospective observational study was conducted at the Department of Nephrology, Dr. D. Y. Patil Medical College, Hospital & Research Centre, Pune, from April 2021 to December 2022. The study included 30 donors from both genders aged between 23 and 73 years. The measured GFR was calculated using a technetium-99m diethylene triamine pentaacetic acid (Tc-99m DTPA) scan. We analyzed donor characteristics and various parameters that included demography, anthropometry, blood pressure, and serum creatinine and measured GFR (m-GFR) using a Tc-99m DTPA scan, which was compared before and three months after donor nephrectomy. Results Of the 30 donors, 25 (83.3%) were females and five (16.7%) were males. The mean age of donors was 49.23 ± 12.29 years. The mean body mass index (BMI) was noted to be 24.73 ± 5.58 kg/m2, whereas the mean body surface area (BSA) was 1.59 ± 0.12 m2. In terms of the measured GFR by DTPA scan, pre-donation and post-donation, the average GFR for our population was 103.83 ± 10.07 mL/minute/1.73 m2 and 60.47±6.57 mL/minute/1.73 m2, respectively. The mean measured GFR of remnant kidney increased by 9.21 ± 4.39 mL/minute/1.73 m2 in 28 donors, while two donors had a fall in the mean measured GFR by 6.8 ± 1.69 mL/minute/1.73 m2. Conclusions To safeguard donor health, accurate measurement of GFR at various timelines after kidney donation should be considered as there are various limitations associated with the use of serum creatinine-based GFR estimating equations for solitary kidneys. However, long-term studies are required to analyze the changes in GFR after nephrectomy and determine the adequacy of compensatory changes in the remnant kidney post-kidney donation.

Synthesis, biological screening and in silico studies of new N-phenyl-4-(1,3-diaryl-1H-pyrazol-4-yl)thiazol-2-amine derivatives as potential antifungal and antitubercular agents.

A new series of N-aryl-4-(1,3-diaryl-1H-pyrazol-4-yl)thiazol-2-amine, (8a-x) have been synthesized by a cyclo-condensation reaction of 2-bromo-1-(1,3-diphenyl-1H-pyrazol-4-yl)ethanone (6a-f) with N-aryl thiourea, (7a-d). The structure of newly synthesized N-aryl-4-(1,3-diaryl-1H-pyrazol-4-yl)thiazol-2-amine, (8a-x) derivatives was analyzed by 1H NMR, 13C NMR and Mass spectral analysis. The compounds 8a-x were screened for in vitro antimicrobial activity against Escherichia coli, Proteus mirabilis, Bacillus subtilis, Staphylococcus aureus, Candida albicans and Aspergillus niger. and antitubercular activity against M. tuberculosis H37Rv strain. Among the twenty-four pyrazolyl-thiazole derivatives, six compounds 8a, 8b, 8j, 8n, 8o and 8s showed good activity against S. aureus. Against A. niger, all synthesized derivatives showed good antifungal activity. Fifteen pyrazolyl-thiazole derivatives 8a, 8f, 8g, 8h, 8j, 8k, 8n, 8o, 8p, 8q, 8r, 8s, 8t, 8w and 8x showed good antitubercular activity with MIC 1.80-7.34 µM (0.8-3.12 µg/mL), these derivatives have showed more activity than the drugs isoniazid and ethambutol. The active compounds were further screened for cytotoxicity activity against the mouse embryonic fibroblast cells (3t3l1) cell lines at 12.5 and 25 µg/mL concentrations and found less or non-cytotoxicity. To know the plausible mode of action, the synthesized pyrazolyl-thiazole derivatives were studied for pharmacokinetics, toxicity profiles and binding interactions along with an in-depth analysis of structural dynamics and integrity using prolonged molecular dynamics (MD) simulation. The compounds have shown significant docking scores in the range of -7.98 to -5.52 and -9.44 to -7.2 kcal/mol with the M. tuberculosis enoyl reductase (M. tb. InhA) and C. albicans sterol 14-α demethylase (C. ab. CYP51), respectively. Thus, the significant antifungal and antitubercular activity of N-aryl-4-(1,3-diaryl-1H-pyrazol-4-yl)thiazol-2-amine, (8a-x) derivatives incited that, these scaffolds could assist in the development of lead compounds to treat fungal and antitubercular infections.

Synthesis of 2-(6-substituted quinolin-4-yl)-1-alkoxypropan-2-ol as potential antimycobacterial agents.

Resistance to antibiotic drugs has directed global health security to a life-threatening situation due to mycobacterial infections. In search of a new potent antimycobacterial, a series of (±) 2-(6-substituted quinolin-4-yl)-1-alkoxypropan-2-ol (8a-p) have been synthesized. The structures of the newly synthesized derivatives were characterized by spectrometric analysis. Derivatives 8a-p were evaluated for antitubercular activity against Mycobacterium tuberculosis H37Rv (ATCC 25177), antibacterial activity against Proteus mirabilis (NCIM2388), Escherichia coli (NCIM 2065), Bacillus subtilis (NCIM2063) Staphylococcus albus (NCIM 2178) and antifungal activity against Candida albicans (NCIM 3100), Aspergillus niger (ATCC 504). Thirteen 2-(6-substituted quinolin-4-yl)-1-alkoxypropan-2-ol (8a-m) derivatives reported moderate to good antitubercular activity against M. tuberculosis H37Rv with MIC 9.2-106.4 µM. Compounds 8a and 8h showed comparable activity with respect to the standard drug pyrazinamide. The active compounds screened for cytotoxicity activity against L929 mouse fibroblast cells showed no significant cytotoxic activity. Compounds 8c, 8d, 8e, 8g, 8k, and 8o displayed good activity against S. albus. Compounds 8c and 8n showed good activity against P. mirabilis and E. coli, respectively. The potential antimycobacterial activities imposed that the 2-(6-substituted quinolin-4-yl)-1-alkoxypropan-2-ol derivatives could lead to compounds that could treat tuberculosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-023-02741-3.

Synthesis, Characterization, and Antimicrobial Activity Screening of Some Novel 3-(2-(3-(Substituted benzyloxy)oxetan-3-yl)-3-fluorophenoxy)-8-fluoro-2-methylquinoline Derivatives as Potential Antimycobacterial Agents.

Microbial infections remain a grave threat to global health security due to increasing antibiotic resistance. The coronavirus pandemic has increased the risk of microbial infection. To combat these infections, the search for new therapeutic agents is in high demand. A series of new 3-(2-(3-(substituted benzyloxy)oxetan-3-yl)-3-fluorophenoxy)-8-fluoro-2-methylquinoline (9a-i) derivatives have been synthesized. The structure of synthesized compounds was analyzed by spectroscopic methods. The newly synthesized oxetanyl-quinoline derivatives were evaluated for in vitro antibacterial activity against Escherichia coli (NCIM 2574), Proteus mirabilis (NCIM 2388), Bacillus subtilis (NCIM 2063), Staphylococcus albus (NCIM 2178), and in vitro antifungal activity against Aspergillus niger (ATCC 504) and Candida albicans (NCIM 3100). Six oxetanyl-quinoline derivatives 9a, 9b, 9c, 9d, 9e, and 9h have shown good antibacterial activity against P. mirabilis with MIC 31.25-62.5 µM, 3-(((3-(2-fluoro-6-((8-fluoro-2-methylquinolin-3-yl)oxy)phenyl)oxetan-3-yl)oxy)methyl)benzonitrile (9f) reporting comparable activity against P. mirabilis with respect to the standard drug streptomycin. Compound 9a also showed good activity against B. subtilis with MIC 31.25 µM. The eight compounds 9a, 9b, 9d, 9e, 9f, 9g, 9h, and 9i have shown good antifungal activity against A. niger. The synthesized compounds were also screened for antimycobacterial activity against Mycobacterium tuberculosis H37Rv by MTT assay. Among the nine derivatives, compounds 9b, 9c, 9d, 9f, 9g, 9h, and 9i showed excellent antimycobacterial activity with MIC 3.41-12.23 µM, and two derivatives showed good activity with MIC 27.29-57.73 µM. All the derivatives were further evaluated for cytotoxicity against the Vero cell line and were found to be nontoxic. The in silico study of compounds 9a-i was performed against ATP synthase (PDB ID: 4V1F) and most of the compounds showed the stable and significant binding to ATP synthase, confirming their plausible mode of action as ATP synthase inhibitors. Thus, the significant antimycobacterial activity of 3-(2-(3-(substituted benzyloxy)oxetan-3-yl)-3-fluorophenoxy)-8-fluoro-2-methylquinoline derivatives has suggested that the oxatenyl-quinoline compounds could assist in the development of lead compounds to treat mycobacterial infections.

Synthesis of new thiazolyl-pyrazolyl-1,2,3-triazole derivatives as potential antimicrobial agents.

A series of 1-substituted benzyl-4-[1-phenyl-3-(4-methyl-2-aryl-1,3-thiazol-5-yl)-1H-pyrazol-4-yl]-1H-1,2,3-triazole derivatives (7a-y) have been synthesized by click reaction of 5-(4-ethynyl-1-phenyl-1H-pyrazol-3-yl)-4-methyl-2-aryl-1,3-thiazole (5a-e) with substituted benzyl azide. The starting compounds 5-(4-ethynyl-1-phenyl-1H-pyrazol-3-yl)-4-methyl-2-aryl-1,3-thiazole (5a-e) were synthesized from corresponding 3-(4-methyl-2-aryl-1,3-thiazol-5-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde (3a-e) by using Ohira-Bestmann reagent. All newly synthesized thiazolyl-pyrazolyl-1,2,3-triazole derivatives were screened for antibacterial activity against two Gram negative strains, Escherichia coli (NCIM 2574), Proteus mirabilis (NCIM 2388), a Gram positive strain Staphylococcus albus (NCIM 2178) and in vitro antifungal activity against Candida albicans (NCIM 3100), Aspergillus niger (ATCC 504) and Rhodotorula glutinis (NCIM 3168). Ten thiazolyl-pyrazolyl-1,2,3-triazole derivatives, 7b, 7g, 7i, 7j, 7k, 7l, 7m, 7n, 7p and 7v exhibited promising antifungal activity against A. niger with MIC 31.5 µg/mL. Compounds 7g, 7i, 7k, 7l and 7m were further evaluated for ergosterol inhibition assay against A. niger cells sample at 31.5 µg/mL concentration. The analysis of sterol inhibition assay revealed that ergosterol biosynthesis is decreased in the fungal samples treated with azole derivatives. Promising antifungal activity suggested that, these compounds could be further promoted for optimization and development which could have the potential to treat against fungal infection.

Synthesis and antimycobacterial screening of new thiazolyl-oxazole derivatives.

In the present study a series of 4-methyl-2-aryl-5-(2-aryl/benzyl thiazol-4-yl) oxazole (4a-v) have been synthesized and evaluated for their preliminary antitubercular, antimicrobial and cytotoxicity activity. Among all the synthesized compounds, 4v reported comparable activity against dormant M. tuberculosis H37Ra and M. bovis BCG strains with respect to standard drug rifampicin. The active compounds from the antitubercular study were further tested for anti-proliferative activity against HeLa, A549 and PANC-1 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antibacterial activities with MIC range of 2.1-26.8 µg/mL. High potency, lower cytotoxicity and promising antimycobacterial activity suggested that these compounds could serve as good leads for further optimisation and development.

Synthesis and biological screening of 2'-aryl/benzyl-2-aryl-4-methyl-4',5-bithiazolyls as possible anti-tubercular and antimicrobial agents.

A series of 2'-aryl/benzyl-2-aryl-4-methyl-4',5-bithiazolyl derivatives, 25-64 were synthesized and evaluated for inhibitory activity against Mycobacterium smegmatis MC(2) 155 strain and antimicrobial activities against four pathogenic bacteria Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Proteus vulgaris. Among them, compounds 40, 49, 50, and 54 exhibited moderate to good inhibition on the growth of the bacteria Mycobacterium smegmatis at the concentration of 30 µM. Compounds 26, 40, 44, 54 and 56 exhibited moderate to good antibacterial activity. Compound 5-(2'-(4-fluorobenzyl)thiazol-4'-yl)-2-(4-fluorophenyl)-4-methyl-thiazole (54) exhibited both antitubercular as well as antimicrobial activity against all tested strains.

Modeling and experimental studies on intermittent starch feeding and citrate addition in simultaneous saccharification and fermentation of starch to flavor compounds.

Simultaneous saccharification and fermentation (SSF) is a combined process of saccharification of a renewable bioresource and fermentation process to produce products, such as lactic acid and ethanol. Recently, SSF has been extensively used to convert various sources of cellulose and starch into fermentative products. Here, we present a study on production of buttery flavors, namely diacetyl and acetoin, by growing Lactobacillus rhamnosus on a starch medium containing the enzyme glucoamylase. We further develop a structured kinetics for the SSF process, which includes enzyme and growth kinetics. The model was used to simulate the effect of pH and temperature on the SSF process so as to obtain optimum operating conditions. The model was experimentally verified by conducting SSF using an initial starch concentration of 100 g/L. The study demonstrated that the developed kinetic was able to suggest strategies for improved productivities. The developed model was able to accurately predict the enhanced productivity of flavors in a three stage process with intermittent addition of starch. Experimental and simulations demonstrated that citrate addition can also lead to enhanced productivity of flavors. The developed optimal model for SSF was able to capture the dynamics of SSF in batch mode as well as in a three stage process. The structured kinetics was also able to quantify the effect of multiple substrates present in the medium. The study demonstrated that structured kinetic models can be used in the future for design and optimization of SSF as a batch or a fed-batch process.