Categorization of hotspots into three types - weak, moderate and strong to distinguish protein-protein versus protein-peptide interactions.

Protein-protein and protein-peptide interactions (PPI and PPepI) belong to a similar category of interactions, yet seemingly subtle differences exist among them. To characterize differences between protein-protein (PP) and protein-peptide (PPep) interactions, we have focussed on two important classes of residues-hotspot and anchor residues. Using implicit solvation-based free energy calculations, a very large-scale alanine scanning has been performed on benchmark datasets, consisting of over 5700 interface residues. The differences in the two categories are more pronounced, if the data were divided into three distinct types, namely - weak hotspots (having binding free energy loss upon Ala mutation, ΔΔG, ∼2-10 kcal/mol), moderate hotspots (ΔΔG, ∼10-20 kcal/mol) and strong hotspots (ΔΔG ≥ ∼20 kcal/mol). The analysis suggests that for PPI, weak hotspots are predominantly populated by polar and hydrophobic residues. The distribution shifts towards charged and polar residues for moderate hotspot and charged residues (principally Arg) are overwhelmingly present in the strong hotspot. On the other hand, in the PPepI dataset, the distribution shifts from predominantly hydrophobic and polar (in the weak type) to almost similar preference for polar, hydrophobic and charged residues (in moderate type) and finally the charged residue (Arg) and Trp are mostly occupied in the strong type. The preferred anchor residues in both categories are Arg, Tyr and Leu, possessing bulky side chain and which also strike a delicate balance between side chain flexibility and rigidity. The present knowledge should aid in effective design of biologics, by augmentation or disruption of PPIs with peptides or peptidomimetics.Communicated by Ramaswamy H. Sarma.

Quality of Life after Surviving a Spinal Cord Injury: An Observational Study in South India.

BACKGROUND: Spinal cord injury (SCI) and its negative impact on the quality of life (QOL) is a significant public health concern in India. People with SCI suffer from serious health, economic, and social consequences in their lives. Often, care for SCI survivors is left to their immediate family members in India. Appropriate planning is needed for prevention, rehabilitation, health, and psychological care for SCI in the country. PURPOSE: This study assessed the overall QOL of SCI survivors and their satisfaction levels with specific domains and their importance of QOL. MATERIALS AND METHODS: In this observational study, two instruments, Farrens and Power for QOL and Barthel Index for functional abilities, were administered to a convenience sample of participants drawn from Narayana Medical College, Nellore, in South India. RESULTS: Statistically, SCI survivors were found moderately and very satisfied with their QOL. Their perception about importance of health, functioning, social, and economic subscale also did not differ statistically.

Phenylbenzopyrone of Flavonoids as a Potential Scaffold to Prevent SARSCoV-2 Replication by Inhibiting its MPRO Main Protease.

BACKGROUND: In December 2019, an outbreak of a pneumonia-like illness, Corona virus disease 2019 (COVID-19), originating from Wuhan, China, was linked to novel coronavirus, now termed SARS-CoV-2. Unfortunately, no effective drugs or vaccines have been reported yet. The main protease (MPRO) remains the most validated pharmacological target for the design and discovery of inhibitors. OBJECTIVE: The purpose of the study was to find a prospective natural scaffold as an inhibitor for MPRO main protease in SARS-CoV-2 and compare it with repurposed antiviral drugs lopinavir and nelfinavir. METHODS: Natural compound libraries were screened for potential scaffold against MPRO main protease. Molecular dynamics simulation, MM-GBSA and principal component analyses of enzyme- ligand complexes were carried out with the top-ranking hits and compared with the repurposed antiviral drugs lopinavir and nelfinavir. RESULTS: The structure-based virtual screening indicated phenylbenzopyrone of flavonoids as one of the top-ranking scaffolds that have the potential to inhibit the main protease with the Oglycosidic form, performing better than the corresponding aglyconic form. Simulation studies indicated that glycosidic form of flavonoid is a more suitable inhibitor with compounds rutin, procyanidin B6, baicalin and galloylquercetin, demonstrating high affinity and stability, and rutin, emerging as one of the best candidate compounds. Interestingly, rutin was reported to have inhibitory activity against similar protease (3Cprotease of enterovirus A71) and implicated in lung fibrosis. CONCLUSION: The present study on flavonoids, possessing a potential scaffold for inhibiting main protease activity for all betacoronavirus is an attempt to provide new and safe drug leads within a reasonably short period.

SARS-CoV-2 in environmental perspective: Occurrence, persistence, surveillance, inactivation and challenges.

The unprecedented global spread of the severe acute respiratory syndrome (SARS) caused by SARS-CoV-2 is depicting the distressing pandemic consequence on human health, economy as well as ecosystem services. So far novel coronavirus (CoV) outbreaks were associated with SARS-CoV-2 (2019), middle east respiratory syndrome coronavirus (MERS-CoV, 2012), and SARS-CoV-1 (2003) events. CoV relates to the enveloped family of Betacoronavirus (ßCoV) with positive-sense single-stranded RNA (+ssRNA). Knowing well the persistence, transmission, and spread of SARS-CoV-2 through proximity, the faecal-oral route is now emerging as a major environmental concern to community transmission. The replication and persistence of CoV in the gastrointestinal (GI) tract and shedding through stools is indicating a potential transmission route to the environment settings. Despite of the evidence, based on fewer reports on SARS-CoV-2 occurrence and persistence in wastewater/sewage/water, the transmission of the infective virus to the community is yet to be established. In this realm, this communication attempted to review the possible influx route of the enteric enveloped viral transmission in the environmental settings with reference to its occurrence, persistence, detection, and inactivation based on the published literature so far. The possibilities of airborne transmission through enteric virus-laden aerosols, environmental factors that may influence the viral transmission, and disinfection methods (conventional and emerging) as well as the inactivation mechanism with reference to the enveloped virus were reviewed. The need for wastewater epidemiology (WBE) studies for surveillance as well as for early warning signal was elaborated. This communication will provide a basis to understand the SARS-CoV-2 as well as other viruses in the context of the environmental engineering perspective to design effective strategies to counter the enteric virus transmission and also serves as a working paper for researchers, policy makers and regulators.

Endocrine disruptive estrogens role in electron transfer: bio-electrochemical remediation with microbial mediated electrogenesis.

Bioremediation of selected endocrine disrupting compounds (EDCs)/estrogens viz. estriol (E3) and ethynylestradiol (EE2) was evaluated in bio-electrochemical treatment (BET) system with simultaneous power generation. Estrogens supplementation along with wastewater documented enhanced electrogenic activity indicating their function in electron transfer between biocatalyst and anode as electron shuttler. EE2 addition showed more positive impact on the electrogenic activity compared to E3 supplementation. Higher estrogen concentration showed inhibitory effect on the BET performance. Poising potential during start up phase showed a marginal influence on the power output. The electrons generated during substrate degradation might have been utilized for the EDCs break down. Fuel cell behavior and anodic oxidation potential supported the observed electrogenic activity with the function of estrogens removal. Voltammetric profiles, dehydrogenase and phosphatase enzyme activities were also found to be in agreement with the power generation, electron discharge and estrogens removal.

Sorptive removal of endocrine-disruptive compound (estriol, E3) from aqueous phase by batch and column studies: kinetic and mechanistic evaluation.

Endocrine disruptive compounds (EDC) are a wide variety of chemicals which typically exert effects, either directly or indirectly, through receptor-mediated processes. They mimic endogenous hormones by influencing the activities of hormone activities even at nanogram concentrations and reported to disrupt the vital systems (e.g., the endocrine system) in aquatic organisms. The EDC are present in aquatic water bodies and sediments mainly due to the release of human and animal excreted waste. Estriol (E3) removal by adsorption process was investigated in this study to evaluate the potential of activated charcoal as adsorbent. Agitated non-flow batch sorption studies showed good E3 removal efficiency. Sorption kinetic data illustrated good fit with pseudo-first-order rate equation. Experimental data confirmed to linear Langmuir's isotherm model. Neutral pH condition showed comparatively good sorption of E3. Adsorption capacity showed a consistent increasing trend with increase in the operating temperature [DeltaH degrees , -9.189 kJ/mol); DeltaS degrees , 0.492 J/mol K) suggesting exothermic nature of E3 sorption process. Free energy (DeltaG degrees ) increased from 2.51 to 2.97 kJ/mol with increase in temperature from 0 to 50 degrees C. Further, E3 spiked distilled water, untreated domestic sewage and treated domestic sewage were studied in fixed bed column to assesses the potential of sorption process as tertiary unit operation in the ETP system. Total E3 concentration was determined quantitatively by employing direct competitive enzymatic-immuno assay (EIA) procedure.

Broad substrate Cytochrome P450 monooxygenase activity in the cells of Aspergillus terreus MTCC 6324.

Cytochrome P450 (CYP) monooxygenase activities with different category of substrates namely, alkanes, alkane derivatives, alcohols, aromatic compounds, organic solvents, and steroids were detected in the cells of Aspergillus terreus. High CYP specific activity was observed when methanol (5.6+/-0.017 U mg(-1)), acetone (7.76+/-0.02 U mg(-1)), dimethylsulphoxide (DMSO) (9.70+/-0.005 U mg(-1)), n-hexadecane (4.39+/-0.02 U mg(-1)), or n-octadecane (4.23+/-0.01 U mg(-1)) were used as substrates. Significant CYP specific activity was also detected when naphthalene (3.80+/-0.002 U mg(-1)) was used as substrate. The CYP catalysis of n-hexadecane had followed both terminal and sub terminal oxidations. The activity was localized in the cytosol of n-hexadecane grown cells, while, it was apparently distributed in light mitochondrial fraction and microsomal fraction of glucose grown cells. The substrate specificities of CYP present in all the locations were similar irrespective of the substrates used for the growth. Heme staining of the microsomal fraction containing CYP and other proteins in SDS-PAGE showed single heme protein band with corresponding molecular weight of 110 kDa.

Functional characterization of alcohol oxidases from Aspergillus terreus MTCC 6324.

Short chain alcohol oxidase (SCAO), long chain alcohol oxidase (LCAO), secondary alcohol oxidase (SAO), and aryl alcohol oxidase (AAO) activities were localized in the microsome of Aspergillus terreus during growth of the fungi on n-hexadecane. Zymogram analysis of the microsomes of n-hexadecane-grown cells in polyacrylamide gel electrophoresis showed distinct bands, H4, H3, H2, and H1, in a sequence of their molecular weight (Mr) from high to low. The Mr of the isozymes corresponding to the bands H4, H3, and H2 were close to each other and were higher than 272 kDa. While, the Mr of the isozyme H1 was found to be approximately 48 kDa. H1 gave activity only as SCAO. Although the substrates for other bands were varied, strong (S), medium (M), and weak (W) activity for the bands were as follows: H2: SAO (S), AAO (S), LCAO (M), SCAO (S); H3: LCAO (S), SCAO (S); H4: SCAO (S), LCAO (W), SAO (W). The pH and temperature optima of these isozymes were found to be 8.5+/-0.5 and 30+/-1 degrees C, respectively. The stability of the isozymes was drastically decreased beyond 30 degrees C. The SAO showed 33% enantiomeric excess for the R(-)2-octanol over S(+)2-octanol, which may be correlated with the lower Michaelis-Menten constant (K (M)) values of the enzyme for the R(-)2-octanol than the S(+)2-octanol. The fluorescence emission spectra of the chromatographically purified SCAO at 443 nm excitation were similar to that obtained with authentic flavin adenine dinucleotide.

Highly sensitive extractive spectrophotometric determination of palladium(II) in synthetic mixtures and hydrogenation catalysts using benzildithiosemicarbazone.

A simple and highly sensitive method was developed for the extractive-spectrophotometric determination of palladium with benzilidithiosemicarbazone. The metal ion formed a reddish brown complex with benzildithiosemicarbazone in a potassium chloride-hydrochloric acid buffer of pH 2.5, which was easily extractable into methyl isobutyl ketone. The 1:1 complex showed the maximum absorbance at 395 nm with a Beer's law range of 0.25-3.5 ppm. The molar absorptivity and Sandell's sensitivity were found to be 3.018 x 10(4) dm3 mol(-1) cm(-1) and 0.0035 microg cm(-2), respectively. The correlation coefficient of the Pd(II)-BDTSC complex was 0.998, which indicated an excellent linearity between the two variables. The repeatability of the method was checked by finding the relative standard deviation (RSD) (n = 10), which was 0.46%. The instability constant of the complex calculated from Edmond and Birnbaum's method was 2.41 x 10(-5), that of Asmus' method is 2.53 x 10(-5) at room temperature. The interfering effects of various cations and anions were studied. The proposed method was successfully applied to the determination of palladium(II) in synthetic mixtures and hydrogenation catalysts. The validity of the method was tested by comparing the results with those obtained using an atomic absorption spectrophotometer.

Policies and procedures in the management of AIDS

This document is comprised of Centre for Disease Control recommendations, guidelines from Health Department of the United Kingdom and other relevant organisations for prevention of transmission of HIV in health care settings

Jamaica's backyard nurseries

In Jamaica, tradition and economic necessity have required older women to play an important part in the life of the community by looking after small children whose mothers are out at work. (AU)

Public health training programs at the University of the West Indies

The Department of Preventive Medicine of the University of the West Indies was established in 1957 with the idea of improving undergraduate teaching facilities to enable medical students to study patients in their homes and social environment. The authors describe the two public health diploma programs available at the University and cite pertinent enrollment and geographic distribution statistics. Candidates for the Diploma in Public Health are registered medical practitioners who take a series of compulsory and elective subjects and have a period of supervised field training and research during the 12-month course. The Diploma in Community Health trains students in the health and diseases of man in his total environment. Students choose among three program options: the general program, specialization in health education, or specialization in health service administration. The general program is the most popular because it gives the student a rounded education suitable to the needs of small states. The 12-month diploma course features the interdisciplinary approach where students from various fields discuss important issues in community health. Comprehensive courses in these areas include health services administration, social sciences, environmental health, epidemiology and biostatistics, family health, communication science, and community mental health. The authors state that the candidate for the Diploma in Community Health is assessed on the basis of course and field work, a special project report, and a final written and oral examination. (SUMMARY)

Approaches to primary health care in the Commonwealth Caribbean

In this article the authors present a brief review of the health problems of the Commonwealth Caribbean and of the primary care activities being implemented to solve them. Special attention is given to programs which develop new categories of health workers and direct manpower toward learning a technology appropriate to the conditions in which they work. These programs enable the health worker and allied health personnel to adapt to their roles and functions accordingly and thus provide quality health within limited resources. The main programs are: development of new category of health workers such as the community health aide and the nurse practitioner; education and training of allied health personnel; and training of primary health care physicians. An account is also given of primary health care in Jamaica and in the smaller territories of the Caribbean.(Summary)