Diagnostic Validation and Feasibility of a Non-invasive Haemoglobin Screening Device (EzeCheck) for 'Anaemia Mukt Bharat' in India.

Anaemia remains a major public health issue in India despite several efforts. It is crucial to introduce technology-based innovations for the mass screening and early diagnosis of anaemia. Traditional anaemia screening requires drawing blood and laboratory analysis and can be logistically expensive in resource-constrained settings. A non-invasive haemoglobin test for mass screening in such settings is vital which can quickly and efficiently screen large populations. This study validated the haemoglobin estimation between the invasive haematology analyzer and the non-invasive EzeCheck (EzeRx Health Tech Pvt. Ltd., Bhubaneswar, Odisha, India) in the community setting. We conducted a cross-sectional study among 416 urban slum members in Bhubaneswar, India. We used inter-rater reliability (kappa statistic) of haemoglobin estimation between the haematology analyzer and EzeCheck devices. The finding showed a moderate agreement between both devices (kappa=0.4221). Between both devices, 91.59% of the results were with +/-1.5 difference; 43.51%, no difference; 33.65%, less than one difference; and 14.42%, +/-1 to +/-1.5 difference of haemoglobin estimation. There was no significant difference in overall anaemia status estimates between the devices. Mass screening in schools and communities with non-invasive haemoglobin tests can help identify anaemic people for early diagnosis and bring patients for timely treatment, which can be used in remote areas to support 'Anaemia Mukt Bharat'.

Serosurveys to detect SARS-CoV-2 antibodies among high-risk groups in six urban cities of Odisha, India.

INTRODUCTION: Personnel involved in essential services or residing in high-risk areas during the COVID-19 pandemic are at increased risk of getting infected. We evaluated the proportion of personnel infected in several high-risk groups in Odisha using seroprevalence studies. METHODOLOGY: During July to November, 2020, individuals from multiple high-risk groups in 6 urban cities (Bhubaneswar, Berhampur, Cuttack, Malkangiri, Paralakhemundi, and Rourkela) in Odisha, India, were recruited to the study after obtaining written informed consent. Blood samples collected from the study participants were tested for IgG antibodies against COVID-19 in Roche Cobas e441 (Roche Diagnostics, Rotkreuz, Switzerland). Information on socio-demographic variables, association with a confirmed or suspected case, and other details were collected using an electronic data capture tool and analysed with a statistical software. RESULTS: The overall COVID-19 seroprevalence was 34.9% (95%CI 33.6-36.2) among the 5434 individuals. The seroprevalence varied from 21.8% (95% CI, 19.6-24.1) in Rourkela to 54.9% (95% CI, 51.5-58.2) in Bhubaneswar. Seropositivity was maximum among prisoners (47.7%), followed by municipality/ sanitation staff (43.5%), and other office going staff (40.8%). Multivariate logistic regression indicated that participants aged 18-29 years, 30-44 years, residents of slums and vending zone, municipality staff, prisoners, residents of urban cities Malkangiri, Cuttack, Paralakhemundi, Bhubaneswar and those with previous history of COVID-19 were independent co-relates of seropositivity. CONCLUSIONS: The risk of COVID-19 varied among the high-risk groups of Odisha. Periodic seroprevalence studies in future are essential to protect the high-risk personnel involved in frontline activities during the pandemic.

Hepatocellular carcinoma: Preclinical and clinical applications of nanotechnology with the potential role of carbohydrate receptors.

Hepatocellular carcinoma (HCC) is one of the most common types of liver cancer; accounts for 75-85% of cases. The treatment and management of HCC involve different sanative options like surgery, chemotherapy, immunotherapy, etc. Recently, various advancements have been introduced for the diagnosis and targeting of hepatic tumor cells. Among these, biomarkers are considered the primary source for the diagnosis and differentiation of tumor cells. With the advancement in the field of nanotechnology, different types of nanocarriers have been witnessed in tumor targeting. Nanocarriers such as nanoparticles, liposomes, polymeric micelles, nanofibers, etc. are readily prepared for effective tumor targeting with minimal side-effects. The emergence of various approaches tends to improve the effectiveness of these nanocarriers as demonstrated in ample clinical trials. This review focuses on the significant role of carbohydrates such as mannose, galactose, fructose, etc. in the development, diagnosis, and therapy of HCC. Hence, the current focus of this review is to acknowledge various perspectives regarding the occurrence, diagnosis, treatment, and management of HCC.

Angiopep-2 Grafted PAMAM Dendrimers for the Targeted Delivery of Temozolomide: In Vitro and In Vivo Effects of PEGylation in the Management of Glioblastoma Multiforme.

The present study was aimed to synthesize, characterize, and evaluate the angiopep-2 grafted PAMAM dendrimers (Den, G 3.0 NH2) with and without PEGylation for the targeted and better delivery approach of temozolomide (TMZ) for the management of glioblastoma multiforme (GBM). Den-ANG and Den-PEG2-ANG conjugates were synthesized and characterized by 1H NMR spectroscopy. The PEGylated (TMZ@Den-PEG2-ANG) and non-PEGylated (TMZ@Den-ANG) drug loaded formulations were prepared and characterized for particle size, zeta potential, entrapment efficiency, and drug loading. An in vitro release study at physiological (pH 7.4) and acidic pH (pH 5.0) was performed. Preliminary toxicity studies were performed through hemolytic assay in human RBCs. MTT assay, cell uptake, and cell cycle analysis were performed to evaluate the in vitro efficacy against GBM cell lines (U87MG). Finally, the formulations were evaluated in vivo in a Sprague-Dawley rat model for pharmacokinetics and organ distribution analysis. The 1H NMR spectra confirmed the conjugation of angiopep-2 to both PAMAM and PEGylated PAMAM dendrimers, as the characteristic chemical shifts were observed in the range of 2.1 to 3.9 ppm. AFM results revealed that the surface of Den-ANG and Den-PEG2-ANG conjugates were rough. The particle size and zeta potential of TMZ@Den-ANG were observed to be 229.0 ± 17.8 nm and 9.06 ± 0.4 mV, respectively, whereas the same for TMZ@Den-PEG2-ANG were found to be 249.6 ± 12.9 nm and 10.9 ± 0.6 mV, respectively. The entrapment efficiency of TMZ@Den-ANG and TMZ@Den-PEG2-ANG were calculated to be 63.27 ± 5.1% and 71.48 ± 4.3%, respectively. Moreover, TMZ@Den-PEG2-ANG showed a better drug release profile with a controlled and sustained pattern at PBS pH 5.0 than at pH 7.4. The ex vivo hemolytic study revealed that TMZ@Den-PEG2-ANG was biocompatible in nature as it showed 2.78 ± 0.1% hemolysis compared to 4.12 ± 0.2% hemolysis displayed by TMZ@Den-ANG. The outcomes of the MTT assay inferred that TMZ@Den-PEG2-ANG possessed maximum cytotoxic effects against U87MG cells with IC50 values of 106.62 ± 11.43 µM (24 h) and 85.90 ± 9.12 µM (48 h). In the case of TMZ@Den-PEG2-ANG, the IC50 values were reduced by 2.23-fold (24 h) and 1.36-fold (48 h) in comparison to pure TMZ. The cytotoxicity findings were further confirmed by significantly higher cellular uptake of TMZ@Den-PEG2-ANG. Cell cycle analysis of the formulations suggested that the PEGylated formulation halts the cell cycle at G2/M phase with S-phase inhibition. In the in vivo studies, the half-life (t1/2) values of TMZ@Den-ANG and TMZ@Den-PEG2-ANG were enhanced by 2.22 and 2.76 times, respectively, than the pure TMZ. After 4 h of administration, the brain uptake values of TMZ@Den-ANG and TMZ@Den-PEG2-ANG were found to be 2.55 and 3.35 times, respectively, higher than that of pure TMZ. The outcomes of various in vitro and ex vivo experiments promoted the use of PEGylated nanocarriers for the management of GBM. Angiopep-2 grafted PEGylated PAMAM dendrimers can be potential and promising drug carriers for the targeted delivery of antiglioma drugs directly to the brain.

Gender dimensions of health-related challenges among urban poor during COVID-19 pandemic in low-and middle-income countries: a systematic review and gap analysis.

The COVID-19 pandemic has varying effects on men, women, and the transgender population. However, there is a paucity of systematic evidence on how gender and other social determinants of health during COVID-19 are affected in resource constraint urban settings. This review describes the gender dimensions of health-related challenges among the urban poor during COVID-19 in LMICs. We searched 11 scholarly online repositories including PubMed, Embase, Web of Science, CINAHL using the domain "slums," "COVID-19", "LMICs" and "gender identities." We used thematic framework analysis to synthesize qualitative data, and meta-analysis to determine the pooled prevalence. We registered in PROSPERO (CRD42020203783). We identified 6490 records, and 37 articles included. The studies reported stress among 74% women and 78% men, depression among 59% women and 62% men, and anxiety among 79% women and 63% men. Men had more stress than women during COVID-19; men are primarily responsible for household sustenance. Women had more anxiety than men, possibly because they are often the primary caregivers for children and the older population. While the severity varies according to gender identity, their vulnerability mostly related to their literacy and economy, highlighting the significance of including all social determinants in future primary studies. Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails.

Use of Portable Automated Auditory Brainstem Responses in Universal Neonatal Hearing Screening: A Mixed-Method Study in Odisha, India.

Hearing loss in children affects cognitive development, so early detection is crucial. It is because of the lack of portable technology that the majority of hearing problems go undetected. The authors conducted a mixed-method study in India to examine the concurrent validity and operational feasibility of portable automated brainstem response (P-AABR) and otoacoustic emissions (OAE) in universal neonatal hearing screening. They screened 198 children's ears using ABR and OAE devices. Additionally, 60 observations were recorded during the 'portable automated ABR' screening process. The hearing screening could be performed with P-AABR by any health care staff with basic skill-based training. However, the interpretation of the graphical wave required an audiologist. If the baby was quiet, the test could be performed in 20 min, including electrode implantation, impediment setting, earphone installation, and swipe counts. The P-AABR device can be used in the universal health coverage of hearing screening among infants in outreach areas due to its portability and minimal infrastructural requirements.

Impact of smokeless cooking fuel use on health status of women in a rural setting of eastern India.

The sustainable development goals (SDG 7.1) reinforce to ensure that everyone has access to affordable, safe and renewable energy. In India, women are typically responsible for cooking and are most vulnerable to household air contaminants. We conducted a descriptive cross-sectional comparative study in Odisha, India between exclusive LPG (liquefied petroleum gas) users and non-LPG users. A total of 900 women, 450 from each group, were randomly selected. The LPG-users had a better predictor of physical, psychological, social, and environmental wellbeing than non-LPG users. We found the ophthalmic disorders (adjusted odds ratio (AOR) 2.87, 95% CI 1.16-7.10, p = .023), asthma (AOR 2.05, 95% CI 1.15-3.65, p = .015), and ALRI (acute lower respiratory infections) (AOR 9.19, 95% CI 2.06-40.96, p < .004) were significantly higher in non-LPG users in comparison to LPG users. Access to smokeless cooking fuel will improve women's quality of life by eliminating the consumption of biofuel and thereby providing a healthier cooking environment.

A Systematic Review of Water, Sanitation, and Hygiene for Urban Poor in Low- and Middle-Income Countries during the COVID-19 Pandemic through a Gendered Lens.

Inadequate water, sanitation, and hygiene (WASH) among urban poor women is a major urban policy concern in low- and middle-income countries (LMICs). There was a paucity of systematic information on WASH among the urban poor during the pandemic. We reviewed the opportunities and challenges faced by the urban poor in LMICs during the COVID-19 pandemic. We used the PRISMA guidelines to conduct a comprehensive search of 11 databases, including MEDLINE, Embase, Web of Science, and CINAHL, between November 2019 and August 2021. We used thematic analysis to synthesize the qualitative data and meta-analyses to estimate the pooled prevalence. We screened 5008 records, conducted a full-text review of 153 studies, and included 38 studies. The pooled prevalence of shared water points was 0.71 (95% CI 0.37-0.97), non-adherence to hygiene practices was 0.15 (95% CI 0.08-0.24), non-adherence to face masks was 0.27 (95% CI 0.0-0.81), and access to shared community toilets was 0.59 (95% CI 0.11-1.00). Insufficient facilities caused crowding and long waiting times at shared facilities, making physical distancing challenging. Women reported difficulty in maintaining privacy for sanitation, as men were present due to the stay-at-home rule. Due to unaffordability, women reported using cloth instead of sanitary pads and scarves instead of masks.

Surface Engineered Dendrimers: A Potential Nanocarrier for the Effective Management of Glioblastoma Multiforme.

Gliomas are the most prevailing intracranial tumors, which account for approximately 36% of the primary brain tumors of glial cells. Glioblastoma multiforme (GBM) possesses a higher degree of malignancy among different gliomas. The blood-brain barrier (BBB) protects the brain against infections and toxic substances by preventing foreign molecules or unwanted cells from entering the brain parenchyma. Nano-carriers such as liposomes, nanoparticles, dendrimers, etc. boost the brain permeability of various anticancer drugs or other drugs. The favorable properties like small size, better solubility, and the modifiable surface of dendrimers have proven their broad applicability in the better management of GBM. However, in vitro and in vivo toxicities caused by dendrimers have been a significant concern. The presence of multiple functionalities on the surface of dendrimers enables the grafting of target ligand and/or therapeutic moieties. Surface engineering improves certain properties like targeting efficiency, pharmacokinetic profile, therapeutic effect, and toxicity reduction. This review will be focused on the role of different surface-modified dendrimers in the effective management of GBM.

Health-Related Challenges and Coping Strategies Among Women During Pandemics: A Systematic Review of Qualitative Studies.

Equality and empowerment for women are among the 17 Sustainable Development Goals (SDGs 5). Although women were confronted with more challenges in various ways during pandemics; however, there is hardly any systematic synthesis of evidence on women's health-related challenges during pandemics. We reviewed the health challenges faced by women during the pandemic. We searched MEDLINE, PsycINFO, and CINAHL following PRISMA guidelines. We identified 2,831 studies, of which we included 17. Reproductive health, psychosocial health, and gender-based violence emerged as significant challenges. Many studies reported challenges in provisions for routine services and increased anxiety, fear, and stress among women. The findings highlighted that pandemic have a significant impact on women's health. Women must have equal rights and opportunities without discrimination, which requires urgent action to enhance women's rights and to achieve SDGs. Women engagement/involvement in pandemic-related services needs to be explored, which will aid in developing strategies to alleviate vulnerabilities.

Serological survey for SARS-CoV-2 antibodies among tribal communities of Odisha post-second wave.

Background & objectives: Serial national level serosurveys in India have provided valuable information regarding the spread of COVID-19 pandemic in the general population, but the impact of the ongoing pandemic on the tribal population in India is not well understood. In this study, we evaluated the seroprevalence of COVID-19 antibodies in the tribal population of Odisha post-second wave (September 2021). Methods: A population-based, age-stratified, cross-sectional study design was adopted for the survey, carried out in seven tribal districts of Odisha from 30th August to 16th September 2021. A multistage random sampling method was used where serum samples were tested for antibodies against the SARS-CoV-2 nucleocapsid (N) protein in each district, and a weighted seroprevalence with 95 per cent confidence interval (CI) was estimated for each district. Results: A total of 2855 study participants were included from the seven tribal districts of Odisha in the final analysis. The overall weighted seroprevalence was 72.8 per cent (95% CI: 70.1-75.3). Serological prevalence was the highest among 18-44 yr (74.4%, 95% CI: 71.3-77.3) and from Sambalpur district [75.90% (66.90-83.10)]. Among participants, 41.93 per cent had received at least one dose of any COVID-19 vaccine. Kandhamal district had the highest number of fully immunized participants (24.78%), and in Sundergarh district, most of the study participants (58.1%) were unimmunized. Interpretation & conclusions: This study found high seroprevalence against SARS-CoV-2 in the tribal population of Odisha. The vaccination coverage is at par with the general population, and efforts to address some knowledge gaps may be needed to improve the coverage in the future.

Health system preparedness & community participation in Japanese encephalitis/acute encephalitis syndrome (JE/AES) prevention in a tribal district of Odisha, India.

BACKGROUND & OBJECTIVES: Japanese encephalitis/acute encephalitis syndrome (JE/AES) is one of the major zoonotic arbodiseases that has a significant effect on human and animal health. Though many studies have been published on the epidemiology and transmission mechanisms of JE/AES, but there is little evidence on health system preparedness, including community-based engagement. This study was undertaken to explore a multi-stakeholder perspective on health system preparedness for the prevention of JE/AES in a tribal district of Odisha, India. METHODS: This study was conducted at Malkangiri district of Odisha. A total of nine focus group discussions (FGDs) among women having under-five children, community volunteers, and community health workers (CHWs), and 20 in-depth-interviews (IDIs) among community leaders, healthcare providers, and programme managers were conducted. The FGDs and IDIs were digitally recorded, transcribed, translated and analysed using content analysis approach. RESULTS: Health system preparedness for the prevention of JE/AES was improved, including effective vector management, implementation of the surveillance system, and vaccination programme. The JE vaccine was introduced under Universal Immunization Programme in Odisha in 2016. Behavioural Change Communication activities were provided with the support of community volunteers on Village Health Nutrition and Sanitation Day (VHNSD) under Gaon Kalyan Samiti (GKS) platforms. The CHWs were actively involved in vector management and raising sanitation and hygiene awareness. INTERPRETATION & CONCLUSIONS: Community participation and coordination between different stakeholders have a significant impact on the successful implementation of the programme. It was suggested that there was a need for a sustainability approach to active participation, orientation and capacity building training among CHWs and community volunteers to successfully implement the programme.

Role of targeted immunotherapy for pancreatic ductal adenocarcinoma (PDAC) treatment: An overview.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid tumors with a high mortality rate and poor survival rate. Depending on the tumor stage, PDAC is either treated by resection surgery, chemotherapies, or radiotherapies. Various chemotherapeutic agents have been used to treat PDAC, alone or in combination. Despite the combinations, chemotherapy exhibits many side-effects leading to an increase in the toxicity profile amongst the PDAC patients. Additionally, these standard chemotherapeutic agents have only a modest impact on patient survival due to their limited efficacy. PDAC was previously considered as an immunologically silent malignancy, but recent findings have demonstrated that effective immune-mediated tumor cell death can be used for its treatment. PDAC is characterized by an immunosuppressive tumor microenvironment accompanied by the major expression of myeloid-derived suppressor cells (MDSC) and M2 tumor-associated macrophages. In contrast, the expression of CD8+ T cells is significantly low. Additionally, infiltration of mast cells in PDAC correlates with the poor prognosis. Immunotherapeutic agents target the immunity mediators and empower them to suppress the tumor and effectively treat PDAC. Different targets are studied and exploited to induce an antitumor immune response in PDAC patients. In recent times, site-specific delivery of immunotherapeutics also gained attention among researchers to effectively treat PDAC. In the present review, existing immunotherapies for PDAC treatment along with their limitations are addressed in detail. The review also includes the pathophysiology, traditional strategies and significance of targeted immunotherapies to combat PDAC effectively. Separately, the identification of ideal targets for the targeted therapy of PDAC is also reviewed exhaustively. Additionally, the review also addresses the applications of targeted immunotherapeutics like checkpoint inhibitors, adoptive T-cell therapy etc.

Diagnostic and therapeutic applications of smart nanocomposite dendrimers.

Dendrimers are three dimensional, multifunctional polymeric structures which are composed of a core and branches emanating from these structures, resembling a tree. Here, we review the key highlights of the dendrimers for diagnostic uses as MRI contrast agents, X-ray computed tomography and particularly for cancer treatment as an effective carrier for drug delivery and in boron capture therapy. We will discuss how dendrimers represent a new class of carriers that are able to deliver drugs effectively and in a sustained manner to the target tumor sites. Dendrimers are being utilized to a variety of cancer therapies to improve the safety and effectiveness of anticancer therapeutics. This review will also investigates the benefits utilizing dendrimers for cancer diagnosis and therapy.