Perineal groove-a case report

The perineal groove is a rare congenital anomaly of the perineum. We present a case of this uncommon condition that had been misinterpreted as irritant dermatitis following treatment for diaper rash. To our knowledge this is the first report of this condition is the dermatology literature.     

Posterior vitreous wick syndrome: a potential cause of endophthalmitis following vitreo-retinal surgery

Endophthalmitis following pars-plana procedures such as a vitrectomy vitreo-retinal procedures has been infrequently reported in literature. The cited incidence is about 0.1% to 0.2%. In the 8 cases of endophthalmitis that have been reported in literature, the prognosis has been indicated as very poor due to a delay in diagnosis (1-3). Also, no possible source of an inoculum of the pathogenic organism reaching the vitreous cavity has been considered in these reports. We have encountered a few cases of endophthalmitis following vitreo-retinal surgeries at our tertiary eye care centre. Here again not being able to identify the possible source of infectious spread, we now report for the first time in literature, a new entity, the 'posterior vitreous wick syndrome'. This potential source of infectious spread, to the best of our knowledge, has not been considered earlier. We describe the patho-mechanism of the 'posterior vitreous wick syndrome' and also suggest methods of reducing its occurrence during vitreo-retinal procedures. This could also be the patho-mechanism of endophthalmitis following inadvertent loss of scleral integrity during extraocular surgeries like retinal detachment surgery and strabismus surgery (4,5).     

Evaluation of cytotoxic and anti-tumor activity of partially purified serine protease isolate from the Indian earthworm Pheretima posthuma

Objective

To isolate, partially purify and evaluate the cytotoxic and antitumor activity of a serine protease from the chosen Indian earthworm Pheretima posthuma.

Methods

Whole animal extract was prepared and purified its protein constituents by size and charge based chromatographic separation techniques using Sephadex G-50 and DEAE-Cellulose resin respectively. Average molecular weight of the protein isolate was determined and analyzed for its cytotoxic property against Vero cells in different dilutions (1: 20 and 1: 40) and anti-tumor activity by MTT assay (a colorimetric assay) using breast cancer cell line MCF-7, with tamoxifen as standard.

Results

One of the protein constituents after purification was characterized as serine protease by Caseinolytic plate diffusion assay. Average molecular weight of this purified isolate was determined, by SDS-PAGE analysis with standard protein ladder, as of 15 kDa. The performed tests suggested that the 15kDa fraction has potent cytotoxic activity and satisfactory antitumor activity as well in vitro.

Conclusions

Exact molecular mechanism of the cytotoxic and antitumor activities is yet to be explored and currently we are working on ultra-purification and biophysical characterization of this fraction. Further investigation into the mechanism(s) of cytotoxic and antitumor activities at molecular level would be useful in treatment of various classes of cancer and viral infections in future.     

Fluid as a critical biomarker in neovascular age-related macular degeneration management: literature review and consensus recommendations

Current guidelines on the management of patients with neovascular age-related macular degeneration (nAMD) lack clear recommendations on the interpretation of fluid as seen on optical coherence tomography (OCT) imaging and the incorporation of this information into an ongoing disease treatment strategy. Our objective was to review current guidelines and scientific evidence on the role of fluid as a biomarker in the management of nAMD, and develop a clinically oriented, practical algorithm for diagnosis and management based on a consensus of expert European retinal specialists. PubMed was searched for articles published since 2006 relating to the role of fluid in nAMD. A total of 654 publications were screened for relevance and 66 publications were included for review. Of these, 14 were treatment guidelines, consensus statements and systematic reviews or meta-analyses, in which OCT was consistently recommended as an important tool in the initial diagnosis and ongoing management of nAMD. However, few guidelines distinguished between types of fluid when providing recommendations. A total of 52 publications reported primary evidence from clinical trials, studies, and chart reviews. Observations from these were sometimes inconsistent, but trends were observed with regard to features reported as being predictive of visual outcomes. Based on these findings, diagnostic recommendations and a treatment algorithm based on a treat-and-extend (T&E) regimen were developed. These provide guidance on the diagnosis of nAMD as well as a simple treatment pathway based on the T&E regimen, with treatment decisions made according to the observations of fluid as a critical biomarker for disease activity.Subject terms: Drug therapy, Prognostic markers, Eye manifestations     

Synthesis of some new indolo[2,3-c]isoquinolinyl pyrazoles, -1,3,4-oxadiazoles and their biological activities

A new series of novel compounds [10-substituted 6H, 7H-indolo[2,3-c]isoquinolin-5-one-6-yl]carbohydrazides (3a–c), 1-[10-substituted 6H, 7H-indolo[2,3-c]isoquinolin-5-one-6-yl]fomyl-, -3′,5′-dimethylpyrazoles (4a–c), -3′,5′-diphenylpyrazoles (5a–c), -3′-methylpyrazol-5′-ones (6a–c) and -1′,3′,4′-oxidiazole-2′-thiones (7a–c) linked to indoloisoquinoline at position-6 through formyl bridge was prepared. The structures of these newly synthesized compounds were confirmed by their spectral studies and elemental analysis. These compounds have been screened for their antimicrobial and antioxidant activities. Compounds 4a, 4b, 5a, 5b, 5c, 6b, 7a, and 7c exhibited the maximum zone of inhibition against A. niger, A. flavus, and A. fumigatus. Compounds 4a, 5a, 5c, 6b, 6c, 7a, and 7b showed good antibacterial activity. Compounds 4b, 4c, 5b, 5c, 6a, 6b, 7a, 7b, and 7c showed good radical scavenging activity compared with standards.     

3D-QSAR study of tyrosine and propanoic acid derivatives as PPARα/γ dual agonists using CoMSIA

The peroxisome proliferator-activated receptors (PPARs) have increasingly become attractive targets for developing novel therapeutics for Type 2 Diabetes. Three dimensional-quantitative structure–activity relationship approach has been applied to a series of α-substituted 3-phenylpropanoic acid and tyrosine derivatives, reported as PPARα/γ dual agonists. Comparative molecular similarity indices analysis has been employed in correlating pharmacological data available for single enantiomer at individual receptor subtype. Three models: PPARα, PPARγ and PPARdual-model, using sum of individual activities as dependent parameter, are developed with statistically significant r _cv ²  > 0.5 and r _ncv ²  > 0.9 and lower values of standard error of estimation. This information can be used to design and prediction of enantioselective novel PPAR agonists. Activities of two sets of designed new molecules have also been predicted using generated models.     

Variability in CYP2C9 allele frequency: A pilot study of its predicted impact on warfarin response among healthy South and North Indians

BackgroundWide variability exists in the frequency of pharmacogenetic markers for anticoagulant response in different populations. There is insufficient data on the prevalence of these variant genotypes in the Indian population. This study aims to determine the frequency of various genotype combinations of CYP2C9*2, *3 and VKORC1-1639G>A polymorphisms in the South and North Indians.MethodsGenotyping was carried out by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) technique in 209 North Indians (NI) and 82 South Indians (SI). Warfarin maintenance dose was predicted for all subjects based on FDA approved genotype-based dose estimates from revised COUMADIN medication guide. Fisher exact test and χ² test were applied to compare categorical data among the SI and NI groups.ResultsIn SI and NI, the allele frequency of CYP2C9*2 was 0.006 and 0.05 (significant variation; p < 0.001); of CYP2C9*3 was 0.09 and 0.11; and of VKORC1-1639A was 0.14 and 0.19 (not significant), respectively. The variation in the frequency of combined CYP2C9/ VKORC1 genotypes revealed plausible difference in warfarin response among SI and NI. Based on the FDA approved revised dosing guidelines, significantly higher percentage of NI were likely to require intermediate dose (3–4 mg/day; p = 0.015, RR = 2.16) and were also predicted to have an increased risk of bleeding episodes and over anticoagulation (p = 0.012, RR = 1.93).ConclusionsGenotype frequency of CYP2C9 and VKORC1 SNPs is variable among the two ethno-geographically distinct Indian populations. This could translate into diverse warfarin response among the Indian population.     

Novel 2-Aminobenzamides as Potential Orally Active Antithrombotic Agents

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Home continuous positive inotropic infusion as a bridge to cardiac transplantation in patients with end-stage heart failure.

BACKGROUND: The clinical use of positive inotropic therapy at home in patients awaiting cardiac transplantation has not been reported since United Network for Organ Sharing (UNOS) regulations were changed to allow home infusions in Status 1B patients. METHODS: We observed 21 consecutive patients with UNOS 1B status during positive inotropic therapy at home. We used hemodynamic monitoring at the initiation of therapy to optimize dosing. We selected for home therapy patients with stable clinical status and improved functional capacity during inotropic treatment. Implantable cardioverter defibrillators were placed in all but 1 patient before discharge. RESULTS: Initial positive inotropic therapy included dobutamine in 12 patients (mean dose, 4.5 mcg/kg/min; range, 2.5-7.5 mcg/kg/min), milrinone in 8 patients (mean dose, 0.44 mcg/kg/min; range, 0.375-0.55 mcg/kg/min), and dopamine at a dose of 3 mcg/kg/min in 1 patient. Patients had improved functional capacity (New York Heart Association Class 3.7 +/- 0.1 to 2.4 +/- 0.2, p < 0.01), improved renal function (serum creatinine, 1.5 +/- 0.1 to 1.3 +/- 0.1, p < 0.01), improved resting hemodynamics, and decreased number of hospitalizations during positive inotropic infusion therapy when compared with pre-treatment baseline. Implantable cardioverter defibrillator discharges were infrequent (0.19 per 100 patient days of follow-up). Actuarial survival to transplantation at 6 and 12 months was 84%. CONCLUSIONS: Continuous positive inotropic therapy at home was safe and was associated with decreased health care costs in selected patients awaiting cardiac transplantation.     

Exploring the Utility of Google Mobility Data During the COVID-19 Pandemic in India: Digital Epidemiological Analysis

BackgroundAssociation between human mobility and disease transmission has been established for COVID-19, but quantifying the levels of mobility over large geographical areas is difficult. Google has released Community Mobility Reports (CMRs) containing data about the movement of people, collated from mobile devices.ObjectiveThe aim of this study is to explore the use of CMRs to assess the role of mobility in spreading COVID-19 infection in India.MethodsIn this ecological study, we analyzed CMRs to determine human mobility between March and October 2020. The data were compared for the phases before the lockdown (between March 14 and 25, 2020), during lockdown (March 25-June 7, 2020), and after the lockdown (June 8-October 15, 2020) with the reference periods (ie, January 3-February 6, 2020). Another data set depicting the burden of COVID-19 as per various disease severity indicators was derived from a crowdsourced API. The relationship between the two data sets was investigated using the Kendall tau correlation to depict the correlation between mobility and disease severity.ResultsAt the national level, mobility decreased from –38% to –77% for all areas but residential (which showed an increase of 24.6%) during the lockdown compared to the reference period. At the beginning of the unlock phase, the state of Sikkim (minimum cases: 7) with a –60% reduction in mobility depicted more mobility compared to –82% in Maharashtra (maximum cases: 1.59 million). Residential mobility was negatively correlated (–0.05 to –0.91) with all other measures of mobility. The magnitude of the correlations for intramobility indicators was comparatively low for the lockdown phase (correlation ≥0.5 for 12 indicators) compared to the other phases (correlation ≥0.5 for 45 and 18 indicators in the prelockdown and unlock phases, respectively). A high correlation coefficient between epidemiological and mobility indicators was observed for the lockdown and unlock phases compared to the prelockdown phase.ConclusionsMobile-based open-source mobility data can be used to assess the effectiveness of social distancing in mitigating disease spread. CMR data depicted an association between mobility and disease severity, and we suggest using this technique to supplement future COVID-19 surveillance.