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During biodiesel production process crude glycerol (a polyol) is obtained as a by-product. In this paper, an effort has been made for using it for pellet production from groundnut shell. Three types of pellets containing 20 wt%, 40 wt% and 60 wt% crude glycerol were prepared. Palletisation led to easy handling of biomass and also increases energy density. Furthermore, characterisation of prepared pellets was performed and subsequently, pyrolized. An increase of volatile matter from 72.45 wt% to 85.18 wt% in pellets was noted with addition of glycerol. Pyrolysis of glycerol containing pellets was carried out in batch (0.5kg) scale along with in-situ circulation of generated pyro-gas. Bio-oil yield increased from 30 wt% to 41 wt% in batch scale as glycerol content increased from 0 wt% to 60 wt%. Pyrolysis products were thoroughly characterised to understand the effects of crude glycerol addition. Calorific value of bio-char was increased from 20.89 MJ/kg to 23.67 MJ/kg as glycerol content increased. Calorific value of bio-oil was 32.66 MJ/kg. The pyro-gas produced was utilized to heat the pyrolysis reactor. Pyro-gas yield increased from 28 wt% to 32 wt% in batch scale as glycerol content increased. In-situ utilization of pyro-gas led to ~ 17% electricity saving.

Legacy turbojet engines suffer degradation in performance with usage. Degradations in engine components show different observable symptoms based on the control mode of the engine. Hence, to accurately model the engine and its degradations, a novel off-design modeling method that considers the control settings of the engine is presented. The improvement in degradation modeling due to the modified scheme is presented in detail. The mathematical model used in the degradation simulation is validated by comparing the model outputs to the engine mounted sensor measurements at various ratings in the engine test bed. The estimation component parameters used in the model through nonlinear gas path analysis and optimisation-based routines is also presented.

Unlike immunocompetent hosts, the duration of viral persistence after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be prolonged in immunosuppressed patients. Here, we present a case of viral persistence for over 19 weeks in a patient with a history of solid organ transplant and explore the clinical, virologic, and immunologic course. Our patient still demonstrated viral persistence at 138 days with low polymerase chain reaction cycle threshold values and evidence of continuing viral sequence evolution indicative of ongoing virus replication. These findings have important implications for infection prevention and control recommendations in immunosuppressed patients. Immune response, including neutralizing antibody titers, T cell activity, and cytokine levels, peaked around days 44-72 after diagnosis. Anti-S trimer antibodies were low at all time points, and T cell response was attenuated by day 119. As immune response waned and viral load increased, increased genetic diversity emerged, suggesting a mechanism for the development of viral variants.

We report severe acute respiratory syndrome coronavirus 2 in semen by using quantitative reverse transcription PCR during the late convalescent phase. Virus was associated with adequate humoral and cell-mediated responses, suggesting possible seeding of the immune-privileged testes. We provide longitudinal semen quality data for 6 other men, including 3 who had oligozoospermia.

OBJECTIVE: To investigate HIV- and age- related differences in hip bone structure in men and women. DESIGN: Cross sectional study of bone structure and HIV serostatus. METHODS: We used Quantitative Computed Tomography (QCT) data from the Multicenter AIDS Cohort Study (MACS) and Women’s Interagency HIV Study (WIHS) to examine cortical thickness (CT) and cortical (CBMD), trabecular TBMD), and integral (IBMD) bone mineral density across anatomic quadrants of the femoral neck in older adult men who have sex with men (MSM) and women with (PWH) and without (PWOH) HIV infection. The percent difference (%diff) in the means for CT and BMD overall and by quadrant between PWH and PWOH were estimated. RESULTS: Among 322 MSM (median age 60 years) with bone measures, distributions were similar between HIV serostatus groups with %diff in the quadrant means ranging from −7% to −1% for CT and from −1% to 4% for BMD, and overall lower hip cortical thickness than expected. In contrast, in 113 women (median age 51 years), PWH had lower CT, IBMD and TBMD consistently across all quadrants, with differences ranging from −10 to −20% for CT, −6 to −11% for IBMD and −3 to −6% for TBMD. Estimates reached statistical significance in superoanterior quadrant for CT and IBMD and inferoposterior for CT. CONCLUSION: Among women, PWH appear to have a thinner cortex and less dense integral bone compared to PWOH, particularly in the superior quadrants while MSM overall had a thinner than expected hip cortex.

Background Accelerated epigenetic aging using DNA methylation (DNAm)-based biomarkers has been reported in people with human immunodeficiency virus (HIV, PWH), but limited data are available among African Americans (AA), women, and older PWH. Methods DNAm was measured using Illumina EPIC Arrays for 107 (69 PWH and 38 HIV-seronegative controls) AA adults ≥60 years in New York City. Six DNAm-based biomarkers of aging were estimated: (1) epigenetic age acceleration (EAA), (2) extrinsic epigenetic age acceleration (EEAA), (3) intrinsic epigenetic age acceleration (IEAA), (4) GrimAge, (5) PhenoAge, and (6) DNAm-estimated telomere length (DNAm-TL). The National Institutes of Health (NIH) Toolbox Cognition Battery (domains: executive function, attention, working memory, processing speed, and language) and Montreal Cognitive Assessment (MoCA) were administered. Participants were assessed for frailty by the Fried criteria. Results The PWH and control groups did not differ by sex, chronological age, or ethnicity. In total, 83% of PWH had a viral load Conclusions Evidence of epigenetic age acceleration was observed in AA older PWH using DNAm-based biomarkers of aging. There was no evidence of age acceleration independent of cell type National Institutes of Health composition (IEAA) associated with HIV, but this measure was associated with decreased cognitive function among PWH.

In this study, cotton stalk (CS) biochar was used as a sorbent for the removal of malachite green from wastewater. Batch sorption experiments revealed that dye removal increases along with rise in initial dye concentration, temperature of the sorption process, and sorbent weight. Dye removal was observed in the range of 35–40 mg/g for 100 mg/L initial dye concentration. Freundlich and Temkin isotherm models were used for modelling the sorption process. Furthermore, thermodynamic study indicated that the process is endothermic and that the spontaneity of sorption gradual rise with temperature. The changes in enthalpy and entropy were determined to be 57,697.25 J/mol and 177.768 J/mol, respectively. Pseudo-second-order kinetics was found to be suitable for the sorption process. Dynamic study revealed that film diffusion is the governing diffusion in the sorption process. Additionally, microwave-assisted heating was employed to regenerate the spent CS biochar, and a yield of 21–76% was obtained depending on the power of the microwave. It was observed that high-power regeneration distorts the pores; thereby, lowering the dye sorption capacity of the regenerated biochar.

The Omicron subvariant BA.2 accounts for a large majority of the SARS-CoV-2 infection worldwide today. However, its recent descendants BA.2.12.1 and BA.4/5 have surged dramatically to become dominant in the United States and South Africa, respectively. That these novel Omicron subvariants carry additional mutations in their spike proteins raises concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of our COVID-19 vaccines and therapeutic monoclonals. We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. On the other hand, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called Class 2 and Class 3 regions of the receptor-binding domain (RBD). The F486V mutation found in BA.4/5 facilitates escape from certain Class 1 and Class 2 antibodies to the RBD but compromises the spike affinity for the cellular receptor ACE2. The R493Q reversion mutation, however, restores receptor affinity and consequently the fitness of BA.4/5. Among therapeutic antibodies authorized for clinical use, only bebtelovimab (LY-COV1404) retains full potency against both BA.2.12.1 and BA.4/5. The Omicron lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies.

Background We previously reported lower bone mineral density (BMD) among premenopausal women with HIV (WWH) compared to women without HIV (HIV−). Rate of bone loss may be even greater for WWH during the menopausal transition. Methods Pre-, peri- and postmenopausal women in the Women\'s Interagency HIV Study (WIHS) underwent whole body DXA and central quantitative computed tomography to measure areal BMD (aBMD) and volumetric BMD (vBMD), respectively. Multivariable regression models with covariates associated with low aBMD (T score < −1.0) in univariate analyses (P≤.05) and known risk factors for low BMD assessed contributions of HIV and menopausal stage to the prediction of aBMD. Results Compared to HIV− women, in unadjusted analyses, WWH had 5–9% lower aBMD at the lumbar spine (P=.001), femoral neck (P=.04), total hip (P=.003) and the ultradistal radius (P=.004), and higher osteoporosis prevalence (T score Conclusions HIV infection and menopausal stage were independent predictors of lower BMD, and had an additive effect on lumbar spine and total hip BMD. Additional research is needed to better understand underlying mechanisms by which HIV impacts BMD as women age and transition through menopause, and develop strategies to mitigate osteoporosis and fracture risk in this growing population.

BACKGROUND: Prior studies have measured accelerated aging in people with HIV (PWH) using a DNA methylation (DNAm)-based biomarker of aging, “epigenetic age”, but data are limited in African American (AA) young adults with perinatally-acquired HIV infection (PHIV). METHODS: We performed a cross-sectional study of AA young adults ages 20–35 years with PHIV (N=31) and seronegative controls (N=30) using DNAm measured in whole blood and cognitive function measured by the NIH Toolbox. Illumina EPIC Array was utilized to measure DNAm age, and accelerated aging markers including epigenetic age acceleration (EAA), as well as extrinsic (EEAA) and intrinsic (IEAA) epigenetic age acceleration. RESULTS: PHIV and controls did not differ by sex (45 vs. 43% male), chronological age (26.2 vs. 28.0 years), or ethnicity. Chronological age and DNAm age were correlated (r=0.56, p

Sawdust, cotton stalk and groundnut shell were used for removal of methylene blue from aqueous solution using batch sorption. Effect of initial dye concentration, temperature, and particle size of sorbents on methylene blue removal was investigated. Sorption capacity increases with rise in initial dye concentration and temperature. Impact of particle size on sorption of methylene blue was investigated and indicated that removal of dye increases with decrease in particle size of sorbents. Maximum sorption for sawdust, cotton stalks and groundnut shell were 9.22 mg g−1, 8.37 mg g−1 and 8.20 mg g−1 respectively; at 60 °C and 100 ppm initial dye concentration. Sorption isotherms were analyzed using fundamental Freundlich isotherm. Subsequently, sips isotherm model was employed for better fitting. Kinetic study shows that, biosorption process is pseudo-second-order in nature. During the course of this study, adsorption dynamics revealed that film diffusion was key step for biosorption. In addition, thermodynamics of sorption was studied; and it was found that Gibbs free energy (∆G°) decreases with increase in temperature. Sawdust was found to be best among all the sorbents. Therefore, column studies and breakthrough curve modelling were performed using sawdust. Furthermore, it was estimated that a scaled-up column using sawdust can treat 6672 L of wastewater in 24 h with 80% efficiency.

Asthma is a chronic inflammatory disease of the lungs prevalent in around 3% of the population, characterized by episodic wheezing, breathlessness and mucus production. On the other hand, COPD (chronic obstructive pulmonary disease) is a non-reversible condition seen mostly in smokers. Therapy is decided according to the severity of asthma, predominantly using topical administration rather than systemic. A variety of devices are used for this, including metered dose inhalers, spacers/chambers, dry powder inhalers and nebulizers in the emergency setting. The treatment consists of bronchodilators such as beta-2 agonists, muscarinic antagonists and phosphodiesterase inhibitors. Inflammation plays a major role and is treated with the help of corticosteroids, leukotriene antagonists, mast cell inhibitors, and anti IgE monoclonal antibodies.

Physical dependence and addiction differ in that addiction causes activation of certain dopaminergic pathways in the mesolimbic system. Addiction occurs when this reward circuit is stimulated by drugs which are absorbed rapidly into the body, cross blood–brain barrier and for which tolerance develops. Ethanol is a commonly abused drug and causes greater mortality than several chronic diseases combined. Ethanol is a CNS stimulant at initial doses, it causes depression at higher doses, death occurring by coma. Acute withdrawal or delirium tremens can be life threatening and is treated by benzodiazepines. Disulfiram, acamprosate, and naltrexone help sustain abstinence. Methanol toxicity results from accumulation of formic acid and is treated by inhibiting the enzyme aldehyde dehydrogenase. The most addictive agent, nicotine works by stimulating nicotinic cholinergic receptors. To prevent withdrawal, nicotine substitutes such as patches and gums are used. Vaping poses dangers of its own and its entry has been made illegal in India. Varenicline and bupropion help sustain abstinence. Cannabis has been made legal to consume in some countries, given its low chances of causing tolerance and withdrawal. Nabilone and dronabinol are used medically and act on CB1 receptors.

Nutritional supplements are foods meant to be enriched in vitamins, minerals or amino acids. They can be unpurified plant extracts, where several constituents work in synergy. The 2016 FSSAI regulations classify food supplements into eight categories: health supplements such as vitamins, nutraceuticals such as ginseng, food for special dietary use such as that used in pregnancy, food for special medical purpose such as total diet replacement, specialty food containing plant or botanicals, probiotics, prebiotics, and novel foods prepared with novel engineering processes. These regulations specify the maximum allowable contents and a pre-approved list of botanicals, food additives, nutraceuticals, probiotics, and prebiotics. They are commonly indicated for treating urinary tract infections, constipation, anxiety, hypertriglyceridemia, arthritis, as immune-stimulants, anti-oxidants, to treat dementia and benign prostatic hypertrophy. Though commonly used over the counter, these agents are not free of concerns such as misguided efficacy and safety beliefs, drug interactions, and improper instructions for use.

Neurodegenerative disorders irreversibly and progressively affect specific parts of the CNS and include Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and Alzheimer’s disease. Parkinson’s disease which affects around 0.5% of the older adults selectively destroys dopaminergic neurons of the basal ganglia, causing tremors, rigidity, and bradykinesia. Therapy constitutes of levodopa, dopaminergic agonists, MAO/COMT inhibitors, and anti-cholinergics. In Alzheimer’s disease, there is deposition of beta-amyloid plaques in the temporal and hippocampal regions of the brain. This is accompanied by degradation of cholinergic neurons which explains the effectiveness of cholinesterase inhibitors like galantamine, donepezil, and rivastigmine. Amyotrophic lateral sclerosis is a degenerative disease of the motor neurons characterized by progressive weakness and spasticity. Riluzole is an agent which reduces excitotoxicity while baclofen and tizanidine treat spasticity.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, predominantly affecting the joints, skin, vessels, and the lungs. Non-steroidal analgesics such as ibuprofen and corticosteroids play a role in alleviating symptoms but should only be used as a bridge until disease modifying anti-rheumatic agents (DMARDs) start showing effect. A combination of DMARDs, such as methotrexate, hydroxychloroquine, sulfasalazine or leflunomide, is effective in inducing and maintaining remissions. Biologics can be used as single agents in inducing remission. They are classified as TNF-alpha inhibitors or non TNF-alpha inhibitors (inhibit CD-20 in B lymphocytes, JAK-STAT pathway, IL-6 and cytotoxic T-lymphocyte associated protein).

Congestive heart failure (CHF) is a systolic dysfunction of the heart in which the pumping efficiency or ejection fraction reduces and the body responses by compensatory mechanisms. Sympathetic activation and activating the RAAS help in the short run but are deleterious in the longer run and cause myocardial remodeling and apoptosis. Drugs which remove these stressors usually reduce mortality such as RAAS inhibitors, beta-blockers, mineralocorticoid antagonists and a combination of hydralazine and isosorbide dinitrate. Drugs which act to reduce congestion and other symptoms reduce preload (diuretics, nitrates) and afterload (RAAS inhibitors). Digoxin works uniquely by stimulating the heart but its use has come down because of its narrow therapeutic window and availability of better drugs. Newer agents include recombinant atrial natriuretic peptide and vasopeptidase inhibitors. Decompensated heart failure is treated by inotropic agents such as dopamine, dobutamine, and phosphodiesterase inhibitors.

Novel viral load monitoring strategies are needed to help individuals maintain an undetectable viral load (UVL). In 2018, U.S. MSM living with HIV with a past detectable VL received a dried blood spot (DBS) kit at baseline and 3-month follow-up and returned specimens to a research laboratory. Of 56 consenting participants, 91% returned specimens at baseline and 77% at 3-month follow-up; 74% who returned two specimens had UVL at both time points. At-home DBS collection and longitudinal VL monitoring is feasible among U.S. MSM with fluctuating viral load. This complementary approach to clinical care could improve viral suppression maintenance.Se necesitan nuevas estrategias para evaluar los niveles de la carga viral para ayudar a las personas viviendo con VIH a mantener una carga viral indetectable (CVI). En 2018, hombres viviendo con VIH, que reportaron sexo con hombres y una carga viral detectable, recibieron dos paquetes de materiales para colectar muestras de sangre seca después de completar una evaluación basal y después de tres meses de seguimiento. Participantes devolvieron las muestras de sangre seca a un laboratorio. De 56 participantes que dieron su consentimiento a participar en el estudio, el 91% devolvió una muestra de sangre seca al inicio del estudio y el 77% a los 3 meses de seguimiento. Además, el 74% que devolvió dos muestras de sangre seca tenían CVI en ambos puntos de tiempo. La colección de sangre seca en el hogar y el monitoreo longitudinal de la carga viral de VIH es factible entre los hombres viviendo con el VIH y que tienen sexo con hombres. Los resultados de este estudio pueden proporcionar un enfoque complementario a la atención clínica para mejorar la supresión viral del VIH.

A feedback loop between dysbiotic gut microbiota, increased translocation of microbial products such as lipopolysaccharide, and inflammation has been hypothesized to cause immune system dysfunction in early HIV infection. However, despite evidence of a chronic inflammatory phenotype in patients on antiretroviral therapy (ART), the role of oral microbiota in systemic immune activation and the relationship between oral and gut bacterial and fungal diversity have not been explored. Our study suggests a crucial role for oral bacterial and fungal communities in long-term systemic immune activation in patients on ART, expanding the current paradigm focused on gut bacteria. Our results indicate that interventions targeting both inflammation and microbial diversity are needed to mitigate oral inflammation-related comorbidities, particularly in HIV-positive patients. More broadly, these findings can bolster general models of microbiome-mediated chronic systemic immune activation and aid the development of precise microbiota-targeted interventions to reverse chronic inflammation., Despite evidence of a chronic inflammatory phenotype in people living with HIV (PLWH) on antiretroviral therapy (ART), the role of oral microbiota in chronic immune activation has not been fully explored. We aimed to determine the relationship between oral and gut microbiome diversity and chronic systemic inflammation in ART-treated PLWH with prevalent severe periodontitis, an inflammatory condition commonly associated with HIV infection. We assessed bacterial and fungal communities at oral and gastrointestinal sites in a cohort (n = 52) of primarily postmenopausal women on ART using 16S rRNA and internal transcribed spacer (ITS) sequencing and measured cellular and soluble markers of inflammation and immune dysfunction. Linear mixed-effect regression and differential abundance analyses were used to associate clinical characteristics and immunological markers with bacterial and fungal diversity and community composition. Bacterial α-diversity in plaque, saliva, and gut was associated with different immunological markers, while mycobial diversity was not associated with soluble or cellular biomarkers of immune stimulation or T cell dysfunction. Furthermore, lipopolysaccharide-positive (LPS+) bacteria previously linked to inflammatory outcomes were enriched at oral sites in patients with severe periodontitis. Fungal α-diversity was reduced in plaque from teeth with higher clinical attachment loss, a marker of periodontitis, and in saliva and plaque from patients with a history of AIDS. Our results show that both bacterial and fungal oral microbiome communities likely play a role in chronic systemic immune activation in PLWH. Thus, interventions targeting both inflammation and the microbiome, particularly in the oral cavity, may be necessary to reduce chronic immune dysregulation in patients with HIV. IMPORTANCE A feedback loop between dysbiotic gut microbiota, increased translocation of microbial products such as lipopolysaccharide, and inflammation has been hypothesized to cause immune system dysfunction in early HIV infection. However, despite evidence of a chronic inflammatory phenotype in patients on antiretroviral therapy (ART), the role of oral microbiota in systemic immune activation and the relationship between oral and gut bacterial and fungal diversity have not been explored. Our study suggests a crucial role for oral bacterial and fungal communities in long-term systemic immune activation in patients on ART, expanding the current paradigm focused on gut bacteria. Our results indicate that interventions targeting both inflammation and microbial diversity are needed to mitigate oral inflammation-related comorbidities, particularly in HIV-positive patients. More broadly, these findings can bolster general models of microbiome-mediated chronic systemic immune activation and aid the development of precise microbiota-targeted interventions to reverse chronic inflammation.

A developing finding from the novel coronavirus 2019 (COVID-19) pandemic is the burden of neuropsychiatric symptoms seen in COVID-19 survivors. While studies have shown clinically significant rates of depression, anxiety, insomnia, and trauma-related symptoms such as post-traumatic stress disorder (PTSD) after COVID-19, little is known about how these symptoms evolve over time. Here, we report findings from a cohort study of 52 participants recruited from the greater New York City area following acute COVID-19 infection. Participants completed the Patient Health Questionnaire-9 (PHQ-9) for depressive symptoms, the Generalized Anxiety Disorder-7 (GAD-7) for anxiety-related symptoms, the Insomnia Severity Scale (ISS) for sleep-related symptoms, and the PTSD Checklist-Civilian version (PCL-C) for trauma-related symptoms both at baseline and at long-term (24–60 weeks post-infection) follow-up. We found a high degree of correlation between psychiatric symptom scales within participants. More participants met established cutoffs for clinically significant insomnia and post-traumatic stress at follow-up compared to baseline. Symptom scales for depression, insomnia, and PTSD were increased at long-term follow-up, with only increased PCL-C scores surviving correction for multiple comparisons (Z ​= ​2.92, W ​= ​434, p ​= ​0.004). Our results present evidence from a small cohort that neuropsychiatric symptoms, particularly those related to PTSD, may worsen over time in COVID-19 survivors. Future studies should continue to investigate these questions in broader populations, while additionally exploring the potential biological and sociological mechanisms that may contribute to neuropsychiatric pathology after COVID-19 infection.

The commensal bacteria that are present in our body since infancy are known to play a role in metabolism, in health as well as disease. Diabetes is a growing epidemic, and a long-term solution that targets the disease at the molecular level is yet to be developed. In this article, we have reviewed the link between the body’s microbiota and disturbed glucose metabolism, as well as the reasons for bacterial dysbiosis and the mechanisms by which it causes inflammation. The link between dysbiosis and diabetes is convincing, particularly since probiotics have been shown to be of some benefit in normalising disturbed metabolism in diabetes patients. Probiotics have recently been found to have a wide application in diseases such as autoimmune, inflammatory, and allergic conditions. The efficacy of probiotics in diabetes has been proven by their ability to lower fasting glucose and insulin levels in a preclinical setting as well as in human trials. However, there is heterogeneity in these studies, including the species used, probiotic dosage, and the magnitude of efficacy. Based on the robust understanding of the benefits of probiotics in diabetes at the cellular level, in both animal studies and clinical trials, combined with their excellent tolerability, probiotics should be explored for their application in clinics.

We have previously reported that premenopausal women with idiopathic osteoporosis (IOP) have profound microarchitectural deficiencies and heterogeneous bone remodeling. Those with the lowest bone formation rate have higher baseline serum insulin-like growth factor-1 (IGF-1) levels and less robust response to teriparatide. Because IGF-1 stimulates bone formation and is critical for teriparatide action on osteoblasts, these findings suggest a state of IGF-1 resistance in some IOP women. To further investigate the hypothesis that osteoblast and IGF-1-related mechanisms mediate differential responsiveness to teriparatide in IOP, we studied circulating osteoblast progenitor (COP) cells and their IGF-1 receptor (IGF-1R) expression. In premenopausal women with IOP, peripheral blood mononuclear cells (PBMCs) were obtained at baseline (n = 25) and over 24 months of teriparatide treatment (n = 11). Flow cytometry was used to identify and quantify COPs (non-hematopoetic lineage cells expressing osteocalcin and RUNX2) and to quantify IGF-1R expression levels. At baseline, both the percent of PBMCs that were COPs (%COP) and COP cell-surface IGF-1R expression correlated directly with several histomorphometric indices of bone formation in tetracycline-labeled transiliac biopsies. In treated subjects, both %COP and IGF-1R expression increased promptly after teriparatide, returning toward baseline by 18 months. Although neither baseline %COP nor increase in %COP after 3 months predicted the bone mineral density (BMD) response to teriparatide, the percent increase in IGF-1R expression on COPs at 3 months correlated directly with the BMD response to teriparatide. Additionally, lower IGF-1R expression after teriparatide was associated with higher body fat, suggesting links between teriparatide resistance, body composition, and the GH/IGF-1 axis. In conclusion, these assays may be useful to characterize bone remodeling noninvasively and may serve to predict early response to teriparatide and possibly other bone formation-stimulating medications. These new tools may also have utility in the mechanistic investigation of teriparatide resistance in premenopausal IOP and perhaps in other populations. © 2017 American Society for Bone and Mineral Research.

OBJECTIVES/GOALS: People living with HIV, despite antiretroviral therapy (ART), have increased burden of inflammatory and aging-related comorbidities such as periodontitis. Oral microbiota have been linked to periodontitis, but not in the context of HIV. We aim to compare relationships between the oral microbiome and periodontal disease in HIV+ vs healthy controls. METHODS/STUDY POPULATION: In an ongoing cohort study we have been recruiting pre- and post-menopausal women with HIV+ on ART for ≥6 months and HIV- controls matched by menopausal status (target n = 30 per arm; currently HIV+: n = 30 post- and 9 pre-M; HIV-: n = 15 post- and 6 pre-M). Patients age

Polymerase chain reaction or PCR is a method of multiplying DNA copies and was invented in 1983. This process depends on denaturation of DNA at high temperatures, annealing of primers to the DNA, and elongation and synthesis of new DNA strands by the heat-resistant Thermophilus aquaticus polymerase. It utilizes nucleotides and magnesium chloride as a cofactor. PCR can generate more than 30 billion copies of DNA in a couple of hours. Its advanced method, real-time PCR (RT-PCR), can quantify simultaneously while multiplying the DNA and is, hence, also known as quantitative PCR (qPCR). It uses fluorescence-emitting dyes such as SYBR green and TaqMan to quantify DNA multiplication. PCR is used in forensics to multiply DNA evidence, in diagnosing genetic diseases and mutations from body fluids like saliva and blood, and in genetic engineering.

Southern blotting, discovered in 1975 by E.M. Southern, represents a technique to detect a gene of interest in the DNA sample. The steps involved are isolation of DNA, its separation by electrophoresis, transfer to a suitable medium, hybridization to probes and visualization of the gene if it is present. Western blotting is the counterpart which is used to detect proteins. The difference lies in the visualization process. In Western blotting, this is made possible by primary and secondary antibodies, whereas in Southern blotting, a radiolabeled (fluorescent) probe or dye that binds to the DNA is used. Application of Western blotting includes identifying HIV antigens or Hepatitis B surface antigen in blood. Northern blotting is used to detect mRNA of interest, where after separation by electrophoresis, cDNA is used as a probe that binds to the RNA strand; the application includes finding alternate transcript size. The term ‘blotting’ in all the three techniques represents the transfer of material after separation to nitrocellulose paper by means of diffusion.

The burden of antimicrobial resistance (AMR) is on a consistent rise worldwide. Antibiotics still remain as the principal armamentarium in combating infectious diseases despite profound improvements in the field of infection control and vaccination technology. WHO also recommends national action plans for mitigating AMR and appropriate financial support to attain the same. Implementation of the “Global Action Plan on Antimicrobial Resistance (GAP-AMR)” is essential for the development and conservation of antibiotics for which the WHO along with the “Drugs for Neglected Diseases Initiative (DNDi)” is creating a “Global Antibiotic Research and Development Partnership”. The three parallel objectives of this independent product development partnership are antimicrobial and point-of-care diagnostics R&D, conservation, and access to existing antimicrobials. One of the ways to procrastinate, if not preclude, the time travel back to the “pre-antibiotic era” is to optimize the IP practices, thereby creating a congenial environment for all the stakeholders. Striving for a balance between strict antimicrobial patenting practices and broader access to innovative antimicrobials is an indispensable “trade-off” for the mere existence of antimicrobials. This chapter discourses about the connection between antimicrobial R&D and the pharma industry, the contribution of patents in antimicrobial discovery, the alternative antimicrobial patenting practices, and the Indian scenario.

Our genetic machinery is regulated extensively and is the reason why each organ has cells that express a unique set of genes, even though all cells in our body have the same chromosomes. Regulation starts at the epigenetic level, controlling the unwinding of chromosomes from histones by methylation and acetylation. Transcription of mRNA is immensely regulated by the promoter regions on the DNA. mRNA can also be regulated posttranscriptionally by miRNA and siRNA. Translation of proteins and their modification by ubiquitination after synthesis represents another level of regulation. The application of this science in the treatment of cancer is explained in this chapter along with the mechanisms by which drugs like vorinostat, romidepsin, miravirsen, steroids, and bortezomib act.