Hyaluronidase impacts exposures of long-acting injectable paliperidone palmitate in rodent models.

A significant challenge in the development of long-acting injectable drug formulations, especially for anti-infective agents, is delivering an efficacious dose within a tolerable injection volume. Co-administration of the extracellular matrix-degrading enzyme hyaluronidase can increase maximum tolerable injection volumes but is untested for this benefit with long-acting injectable formulations. One concern is that hyaluronidase could potentially alter the tissue response surrounding an injection depot, a response known to be important for drug release kinetics of long-acting injectable formulations.

Protective effect of Achyranthes aspera against compound 48/80, histamine and ovalbumin-induced allergic disorders in murine model.

Background: Achyranthes aspera L. (family Amaranthaceae) is a plant species valued in Ayurveda for the treatment of respiratory ailments. Scientific validation of its antiallergic potential was aimed.

The second wave of COVID-19 wreaked havoc: A look at clinical and laboratory parameters of survivors and non-survivors admitted to Intensive Care Unit, a single-centered retrospective study.

Background: The second wave of COVID-19 was disastrous and claimed many lives in India and abroad. The most challenging task was to provide the required treatment as per the patient's condition, within a limited span of time. The lack of prognostic predictors at the time of admission led to failure in prioritizing the patient's need for intensive care.

Teacher professional development for disability inclusion in low- and middle-income Asia-Pacific countries: An evidence and gap map.

Background: In the Asia-Pacific region, around one-third of the children who are out-of-school have a disability and given that teacher readiness and capability are key contributors for inclusive education, it is high time for a mapping of disability inclusive teacher professional development (TPD) interventions in this region.

Objectives: The key objective of this evidence and gap map (EGM) is to locate evidence on interventions for in-service TPD focussing on education for the inclusion of students with a disability in low- and middle-income countries (LMICs) in the Asia-Pacific region.

Search Methods: A broad range of bibliographic databases and repositories were searched electronically to identify the evidence published between January 2000 and December 2021.

Relation Between HbA1c and Lipid Profile Among Prediabetics, Diabetics, and Non-diabetics: A Hospital-Based Cross-Sectional Analysis.

Introduction: An unusually high blood glucose level is a hallmark of diabetes mellitus, with an imbalance between insulin levels and insulin sensitivity leading to an insulin functional deficit. Since it serves as both a risk indicator and a gauge of long-term glycemic control, the HbA1c concentration is a crucial component of standard diabetes treatment. The use of the HbA1c concentration in the diagnosis of diabetes is expanding as the test's accuracy increases.

Agricultural pesticide use and misuse: A study to assess the cognizance and practices among North Indian farmers.

Introduction: Farmers' cognizance regarding pesticide use and overuse is limited and their practices for handling of pesticides is unsatisfactory. However, their perception concerning risks and safety of pesticides play a very important role in safe spraying and indirectly protect them from adverse health hazards.

Objective: To assess the cognizance about use and risks of overuse of pesticides and evaluate practices for the storage, preparation, and disposal of pesticides.

The Novel Oxazolidinone TBI-223 Is Effective in Three Preclinical Mouse Models of Methicillin-Resistant Staphylococcus aureus Infection.

Staphylococcus aureus is an important cause of various infections in humans, including bacteremia, skin and soft tissue infections, and infections associated with implanted medical devices. The emergence of hospital- and community-acquired methicillin-resistant Staphylococcus aureus (MRSA) underscores the urgent and unmet need to develop novel, safe, and effective antibiotics against these multidrug-resistant clinical isolates. Oxazolidinone antibiotics such as linezolid have excellent oral bioavailability and provide coverage against MRSA infections.

Structure-Activity Relationship of Penem Antibiotic Side Chains Used against Mycobacteria Reveals Highly Active Compounds.

The rise of antibiotic-resistant and non-tuberculous mycobacterial infections has placed ever-increasing importance on discovering new antibiotics to treat these diseases. Recently, a new penem, , was discovered to have strong antimicrobial activity against and . Here, a penem library of C2 side-chain variants was synthesized, and their antimicrobial activities were evaluated against HRv and ATCC 19977.

2D-DIGE based urinary proteomics and functional enrichment studies to reveal novel Mycobacterium tuberculosis and human protein biomarker candidates for pulmonary tuberculosis.

In the absence of a sensitive and specific diagnostic modality capable of detecting all forms of tuberculosis (TB), proteomics may identify specific Mycobacterium tuberculosis (M.tb) proteins in urine, with a potential as biomarkers. To identify candidate biomarkers for TB, proteome profile of urine from pulmonary TB patients was compared with non-disease controls (NDC) and disease controls (DC, Streptococcus pneumonia infected patients) using a combination of two-dimensional difference gel electrophoresis (2D-DIGE) and liquid chromatography tandem mass spectrometry (LCMS/MS).

Assessment of knowledge and their practices regarding malaria among members of Village Health Sanitation Committee in rural Uttar Pradesh: A cross-sectional study.

Background: In 2019, the global number of malaria cases was estimated at 229 million. An estimated 409,000 deaths were attributed to malaria in 2019. Under-five children are the most susceptible to malaria, accounting for 67% (274,000) of all malaria deaths worldwide in 2019.

Enhanced Anti-Proliferative Effect of Carboplatin in Ovarian Cancer Cells Exploiting Chitosan-Poly (Lactic Glycolic Acid) Nanoparticles.

Objective: The present article aimed to enhance the therapeutic efficacy of carboplatin (CP) using the formulation of chitosan-poly (lactic glycolic acid) nanoparticles (CS-PLGA NPs).

Methods: Nanoparticles were synthesized by an ionic gelation method and were characterized for their morphology, particle size, and surface potential measurements by TEM and zeta sizer. This study was highlighted for the evaluation of drug entrapment, loading and in vitro drug release capabilities of the prepared nanoparticles by spectrophotometric analysis.

Efficacy of Long-Acting Bedaquiline Regimens in a Mouse Model of Tuberculosis Preventive Therapy.

Completion of preventive therapy is a major bottleneck in global tuberculosis control. Long-acting injectable drug formulations would shorten therapy administration and may thereby improve completion rates. Recently, a long-acting formulation of bedaquiline demonstrated antituberculosis activity for up to 12 weeks after injection in a validated mouse model of preventive therapy.

PROTOCOL: Teacher professional development for disability inclusion in low- and middle-income Asia-Pacific countries: An evidence and gap map.

According to prior research, teacher readiness and capability are key contributors for successful transition towards disability inclusive education, yet in-service teacher professional development for disability inclusion remains an under-researched area. The key objective of this evidence and gap map (EGM) is to locate evidence on interventions for disability inclusion focused teacher professional development (TPD) in low-to-middle-income-countries (LMICs) in the Asia-Pacific region. As such, it will illustrate different levels of evidence for TPD interventions as well as where there is no evidence (i.

Assessment of carbapenems in a mouse model of Mycobacterium tuberculosis infection.

We present further study of a subset of carbapenems, arising from a previously reported machine learning approach, with regard to their mouse pharmacokinetic profiling and subsequent study in a mouse model of sub-acute Mycobacterium tuberculosis infection. Pharmacokinetic metrics for such small molecules were compared to those for meropenem and biapenem, resulting in the selection of two carbapenems to be assessed for their ability to reduce M. tuberculosis bacterial loads in the lungs of infected mice.

Development of a penem antibiotic against Mycobacteroides abscessus.

β-lactams are the most widely used antibiotic class to treat bacterial infections in humans. Mycobacteroides abscessus is an emerging pulmonary pathogen resistant to most antibiotics, including penicillins and cephalosporins. With no current FDA-approved treatment and cure rates <50%, there is a pressing need for effective therapies.

-Trifluoromethylthiolated Sulfonimidamides and Sulfoximines: Anti-microbial, Anti-mycobacterial, and Cytotoxic Activity.

Herein we demonstrate the expanded utility of a recently described -trifluoromethylthiolation protocol to sulfonimidamide containing substances. The novel -trifluoromethylthio sulfonimidamide derivatives thus obtained were evaluated for antibacterial activity against (.) and and Gram + Ve (, ), and Gram - Ve (, ) bacteria.

An Ancient Harappan Genome Lacks Ancestry from Steppe Pastoralists or Iranian Farmers.

We report an ancient genome from the Indus Valley Civilization (IVC). The individual we sequenced fits as a mixture of people related to ancient Iranians (the largest component) and Southeast Asian hunter-gatherers, a unique profile that matches ancient DNA from 11 genetic outliers from sites in Iran and Turkmenistan in cultural communication with the IVC. These individuals had little if any Steppe pastoralist-derived ancestry, showing that it was not ubiquitous in northwest South Asia during the IVC as it is today.

New β-Lactamase Inhibitors Nacubactam and Zidebactam Improve the Activity of β-Lactam Antibiotics against Mycobacterium abscessus Complex Clinical Isolates.

The new diazabicyclooctane-based β-lactamase inhibitors avibactam and relebactam improve the activity of β-lactam antibiotics against bacteria of the complex (MABC). Here, we evaluated the activities of two newer diazabicyclooctane-based β-lactamase inhibitors in clinical development, nacubactam and zidebactam, with β-lactams against clinical isolates of MABC. Both inhibitors lowered the MICs of their partner β-lactams, meropenem (8-fold) and cefepime (2-fold), respectively, and those of other β-lactams, similar to prior results with avibactam and relebactam.

Activity of New Tetracycline Analogs Omadacycline and Eravacycline against Drug-Resistant Clinical Isolates of .

Tigecycline is used in multidrug regimens for salvage therapy of infections but is often poorly tolerated and has no oral formulation. Here, we report similar activity of two newly approved tetracycline analogs, omadacycline and eravacycline, against 28 drug-resistant clinical isolates of complex. Since omadacycline and eravacycline appear to be better tolerated than tigecycline and since omadacycline is also formulated for oral dosing, these tetracycline analogs may represent new treatment options for infections.

Activity of a Long-Acting Injectable Bedaquiline Formulation in a Paucibacillary Mouse Model of Latent Tuberculosis Infection.

The potent antituberculosis activity and long half-life of bedaquiline make it an attractive candidate for use in long-acting/extended-release formulations for the treatment of latent tuberculosis infection (LTBI). Our objective was to evaluate a long-acting injectable (LAI) bedaquiline formulation in a validated paucibacillary mouse model of LTBI. Following immunization with rBCG30, BALB/c mice were challenged by aerosol infection with H37Rv.

Activity of the New β-Lactamase Inhibitors Relebactam and Vaborbactam in Combination with β-Lactams against Mycobacterium abscessus Complex Clinical Isolates.

Pulmonary disease due to infection with complex (MABC) is notoriously difficult to treat, in large part due to the intrinsic resistance of MABC strains to most antibiotics, including β-lactams. MABC organisms express a broad-spectrum β-lactamase that is resistant to traditional β-lactam-based β-lactamase inhibitors but inhibited by a newer non-β-lactam-based β-lactamase inhibitor, avibactam. Consequently, the susceptibility of MABC members to some β-lactams is increased in the presence of avibactam.

Antioxidant and Hepatoprotective Potential of and Extracts of and in Mice.

Background: In , five basic extraction procedures are mentioned in order of their decreasing potency. Swaras is considered as the most potent followed by, , , and .

Objective: Present study was carried out to investigate the antioxidant and hepatoprotective potential of swaras and hima extracts of and .

Substituted N-Phenyl-5-(2-(phenylamino)thiazol-4-yl)isoxazole-3-carboxamides Are Valuable Antitubercular Candidates that Evade Innate Efflux Machinery.

Tuberculosis remains one of the deadliest infectious diseases in the world, and the increased number of multidrug-resistant and extremely drug-resistant strains is a significant reason for concern. This makes the discovery of novel antitubercular agents a cogent priority. We have previously addressed this need by reporting a series of substituted 2-aminothiazoles capable to inhibit the growth of actively replicating, nonreplicating persistent, and resistant Mycobacterium tuberculosis strains.