MicroRNA-532-3p Modulates Colorectal Cancer Cell Proliferation and Invasion via Suppression of FOXM1.

Colorectal cancer (CRC) is a heterogeneous disease and classified into various subtypes, among which transcriptional alterations result in CRC progression, metastasis, and drug resistance. Forkhead-box M1 (FOXM1) is a proliferation-associated transcription factor which is overexpressed in CRC and the mechanisms of FOXM1 regulation have been under investigation. Previously, we showed that FOXM1 binds to promoters of certain microRNAs. Database mining led to several microRNAs that might interact with FOXM1 3'UTR. The interactions between shortlisted microRNAs and FOXM1 3'UTR were quantitated by a dual-luciferase reporter assay. MicroRNA-532-3p interacted with the 3'UTR of the FOXM1 mRNA transcript most efficiently. MicroRNA-532-3p was ectopically overexpressed in colorectal cancer (CRC) cell lines, leading to reduced transcript and protein levels of FOXM1 and cyclin B1, a direct transcriptional target of FOXM1. Further, a clonogenic assay was conducted in overexpressed miR-532-3p CRC cells that revealed a decline in the ability of cells to form colonies and a reduction in migratory and invading potential. These alterations were reinforced at molecular levels by the altered transcript and protein levels of the conventional EMT markers E-cadherin and vimentin. Overall, this study identifies the regulation of FOXM1 by microRNA-532-3p via its interaction with FOXM1 3'UTR, resulting in the suppression of proliferation, migration, and invasion, suggesting its role as a tumor suppressor in CRC.

Comparing coronary artery cross-sectional area among asymptomatic South Asian, White, and Black participants: the MASALA and CARDIA studies.

BACKGROUND: South Asian individuals have high risk of atherosclerotic cardiovascular disease (ASCVD). Some investigators suggest smaller coronary artery size may be partially responsible. METHODS: We compared the left anterior descending (LAD) artery cross-sectional area (CSA) (lumen and arterial wall) among South Asians in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study with White and Black participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, adjusting for BMI, height, and other ASCVD risk factors. We used thin-slice non-contrast cardiac computed tomography to measure LAD CSA. We used linear regression models to determine whether race/ethnicity was associated with LAD CSA after adjusting for demographic factors, BMI, height, coronary artery calcium (CAC), and traditional cardiovascular risk factors. RESULTS: Our sample included 3,353 participants: 513 self-identified as South Asian (44.4% women), 1286 as Black (59.6% women), and 1554 as White (53.5% women). After adjusting for age, BMI, height, there was no difference in LAD CSA between South Asian men and women compared to White men and women, respectively. After full adjustment for CVD risk factors, LAD CSA values were: South Asian women (19.9 mm2, 95% CI [18.8 - 20.9]) and men (22.3 mm2, 95% CI [21.4 - 23.2]; White women (20.0 mm2, 95% CI [19.4-20.5]) and men (23.6 mm2, 95% CI [23.0-24.2]); and Black women (21.6 mm2, 95% CI [21.0 - 22.2]) and men (26.0 mm2, 95% CI [25.3 - 26.7]). Height, BMI, hypertension, CAC, and age were positively associated with LAD CSA; current and former cigarette use were inversely associated. CONCLUSIONS: South Asian men and women have similar LAD CSA to White men and women, and smaller LAD CSA compared to Black men and women, respectively, after accounting for differences in body size. Future studies should determine whether LAD CSA is associated with future ASCVD events.

In silico, anti-inflammatory and acute toxicological evaluation of an indigenous medicinal plant Pterospermum rubiginosum using Sprague-Dawley rats.

BACKGROUND: Pterospermum rubiginosum has been traditionally used by the tribal inhabitants of Southern India for treating bone fractures and as a local anti-inflammatory agent; however, experimental evidence to support this traditional usage is lacking. The present study aimed to investigate the phytochemical characterization, in silico and in vitro anti-inflammatory evaluation, followed by in vivo toxicological screening of P. rubiginosum methanolic bark extract (PRME). RESULTS: The LCMS evaluation revealed the presence of 80 significant peaks; nearly 50 molecules were identified using the LCMS database. In silico analysis showed notable interactions with inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6). In vitro gene expression study supported the docking results with significant down-regulation of iNOS, IL-6, and IL-10. PRME was administered orally to the SD rats and was found to be non-toxic up to 1000 mg/kg body weight for 14 days. The antioxidant enzymes catalase and sodium dismutase exhibited an increased value in PRME-administered groups, possibly due to the diverse phytochemical combinations in bark extract. CONCLUSIONS: PRME administration significantly downregulated the gene expression of inflammatory markers, such as iNOS, IL-6, and IL-10. The molecular docking analysis of iNOS and IL-6 supports the in vitro study. In vivo toxicological study of PRME in SD rats was found to be non-toxic up to a concentration of 1000 mg/kg body weight for 14 days.

Gum acacia dietary fiber: Significance in immunomodulation, inflammatory diseases, and cancer.

Gum arabic/acacia (GA), derived from Acacia trees, is a versatile natural product offering a broad spectrum of applications. Its rich content of soluble dietary fibers, coupled with a low caloric profile, renders GA a valuable dietary component associated with numerous health benefits. Furthermore, its fermentation by gut microbiota yields short-chain fatty acids, renowned for their positive impact on health. Immunomodulation, a crucially regulated mechanism in the body, serves to fend off pathogenic infections by releasing pro-inflammatory cytokines. However, prolonged synthesis of these cytokines can lead to chronic inflammation, tissue damage, and potentially contribute to the development of autoimmune diseases and cancer. Hence, there is an urgent need to identify plant-based biomolecules that can effectively reduce inflammation and inhibit inflammation-induced complications or disorders. In this context, edible biomolecules like GA are gaining prominence for their noteworthy immunomodulatory properties. Therefore, in the present review we have explored the role of GA in immunomodulation, inflammation, and inflammation-associated metabolic diseases, and cancer.

Differential impact of COVID-19 on mental health and burnout.

BACKGROUND: There may be differential impact of the COVID-19 pandemic on mental health and burnout rates of healthcare professionals (HCPs) performing different roles. AIMS: To examine mental health and burnout rates, and possible drivers for any disparities between professional roles. METHODS: In this cohort study, online surveys were distributed to HCPs in July-September 2020 (baseline) and re-sent 4 months later (follow-up; December 2020) assessing for probable major depressive disorder (MDD), generalized anxiety disorder (GAD), insomnia, mental well-being and burnout (emotional exhaustion and depersonalization). Separate logistic regression models (at both phases) compared the risk of outcomes between roles: healthcare assistants (HCAs), nurses and midwives (nurses), allied health professionals (AHPs) and doctors (reference group). Separate linear regression models were also developed relating the change in scores to professional role. RESULTS: At baseline (n = 1537), nurses had a 1.9-fold and 2.5-fold increased risk of MDD and insomnia, respectively. AHPs had a 1.7-fold and 1.4-fold increased risk of MDD and emotional exhaustion, respectively. At follow-up (n = 736), the disproportionate risk between doctors and others worsened: nurses and HCAs were at 3.7-fold and 3.6-fold increased risk of insomnia, respectively. Nurses also had a significantly increased risk of MDD, GAD, poor mental well-being and burnout. Nurses also had significantly worsened anxiety, mental well-being and burnout scores over time, relative to doctors. CONCLUSIONS: Nurses and AHPs had excess risk of adverse mental health and burnout during the pandemic, and this difference worsened over time (in nurses especially). Our findings support adoption of targeted strategies accounting for different HCP roles.

In silico, anti‑inflammatory and acute toxicological evaluation of an indigenous medicinal plant Pterospermum rubiginosum using Sprague‑Dawley rats / 한국실험동물학회지

Background@#Pterospermum rubiginosum has been traditionally used by the tribal inhabitants of Southern India for treating bone fractures and as a local anti-inflammatory agent; however, experimental evidence to support this traditional usage is lacking. The present study aimed to investigate the phytochemical characterization,In silico and in vitro anti-inflammatory evaluation, followed by in vivo toxicological screening of P. rubiginosum methanolic bark extract (PRME). @*Results@#The LCMS evaluation revealed the presence of 80 significant peaks; nearly 50 molecules were identified using the LCMS database. In silico analysis showed notable interactions with inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6). In vitro gene expression study supported the docking results with significant down-regulation of iNOS, IL-6, and IL-10. PRME was administered orally to the SD rats and was found to be non-toxic up to 1000 mg/kg body weight for 14 days. The antioxidant enzymes catalase and sodium dismutase exhibited an increased value in PRMEadministered groups, possibly due to the diverse phytochemical combinations in bark extract. @*Conclusions@#PRME administration significantly downregulated the gene expression of inflammatory markers, such as iNOS, IL-6, and IL-10. The molecular docking analysis of iNOS and IL-6 supports the in vitro study. In vivo toxicological study of PRME in SD rats was found to be non-toxic up to a concentration of 1000 mg/kg body weight for 14 days.

Low molecular weight carbohydrate patterns of mangrove macroalgae from different climatic niches under ocean acidification, warming and salinity variation.

Ocean acidification has increased due to the enhanced solubility of CO2 in seawater. Mangrove macroalgae in tropical and subtropical coastal regions can benefit from the higher availability of CO2 for photosynthesis and primary production. However, they can be negatively affected by the simultaneously occurring warming and increased salinity in estuaries. Thus, we analyzed the isolated effects of ocean acidification and the interactive effects of increased temperature and salinity on the low molecular weight carbohydrate (LMWC) contents of the mangrove red macroalgae Bostrychia montagnei and Bostrychia calliptera from Brazilian tropical and subtropical populations. Specimens from both climatic niches were tolerant to pH decreased by CO2 enrichment and enhanced their LMWC contents under increased availability of CO2. Specimens from both climatic niches also accumulated their dulcitol and sorbitol contents to cope with warming and salt stress. Nevertheless, temperature of 34 °C was lethal for tropical macroalgae, while 29 °C and 31 °C were lethal for subtropical B. calliptera under salinity of 35. Tropical and subtropical B. montagnei synthesized dulcitol (5-110 mmol kg-1 dry weight) and sorbitol (5-100 mmol kg-1 dry weight) as osmoregulatory, energy and thermal protection compounds, whereas tropical and subtropical B. calliptera synthesized mainly dulcitol (10-210 mmol kg-1 dry weight). Although digeneaside has an energy function in Bostrychia spp., it is not an osmolyte or thermal protection compound. Our data demonstrated that both tropical and subtropical Bostrychia spp. benefit from ocean acidification by CO2 enrichment, increasing their LMWC contents. However, warming and increased salinity in estuaries will be detrimental to them, even they producing protective metabolites. Multifactorial approaches are recommended to investigate whether negative effects of increased temperature and salinity nullify positive effects of ocean acidification on these Bostrychia species/populations.

Mitochondria-targeted biotin-conjugated BODIPYs for cancer imaging and therapy.

Two BODIPY-biotin conjugates KDP1 and KDP2 are designed and synthesized for targeted PDT applications. Both have good absorption with a high molar absorption coefficient and decent singlet oxygen generation quantum yields. The photosensitizers KDP1 and KDP2 were found to be localized in the mitochondria with excellent photocytotoxicity of up to 18.7 nM in MDA-MB-231 breast cancer cells. The cell death predominantly proceeded through the apoptosis pathway via ROS production.

Insights on the structural characteristics and molecular dynamic studies of methyl vanillin Schiff base bio-compounds.

A new crystalline form of Schiff base, N-cyclohexyl-1-(3,4-dimethoxyphenyl)methanimine (CHADMB) was obtained from methanolic solution of cylohexylamine and (methylvanillin) 3,4dimethoxybenzaldehyde. Single crystal X-ray diffraction study reveals that the compound crystallized in monoclinic crystal system with P21/c space group having four molecules per unit cell (Z = 4). Hirshfeld surface (HS) analysis and 2D fingerprint plots reveals that weak non-covalent interactions are responsible for crystal packing. The UV-Vis spectroscopy study reveals that the optical band gap of the compound is 4.25 eV. The dielectric properties were studied as a function of frequency at room temperature and the results show that these properties can be exploited for optoelectronic applications. Thermal stability of the compound is revealed by thermogravimetric and differential thermogravimetric analysis. The in vitro antimicrobial activity against Gram negative (E. coli and P. aeruginosa and Gram positive (S. aureus ) bacterial strains and two fungal strains (C. albicans and A. niger) were studied by agar well diffusion method. It is found that the Schiff base is inhibiting the growth of the tested species to varying degrees. Molecular docking studies indicate that alkyl-pi and pi-pi weak interactions enhance the binding affinity of Schiff base-protein complexes. Molecular dynamics study reveals interaction of CHADMB complexed with bacterial protein, EC showed maximum stability which is in agreement with experimental result.Communicated by Ramaswamy H. Sarma.

New crystalline form of (N-cyclohexyl-1-(3,4-dimethoxyphenyl)methanimine Schiff base is synthesized.Synthesized compound is characterized by elemental analysis, SXRD, Raman, FT-IR, Mass, ¹H and ¹³C NMR spectroscopy.Band gap of the compound is calculated from absorption data.The dielectric properties of the compound are tested.Biological activity of the compound is tested against three bacterial and two fungal strains.Molecular docking and molecular dynamics studies were carried out to study the interaction of synthesized compound with various bacterial and fungal proteins.

Biocompatible Aza-BODIPY-Biotin Conjugates for Photodynamic Therapy of Cancer.

With an objective to develop efficient photosensitizers to cancerous tissues, we synthesized two novel biocompatible sensitizers based on aza-BODIPYs incorporated with heavy atoms and biotin moieties. The bioconjugates DPR2a and DPR2b exhibited a favorable absorption range (600-750 nm) with excellent triplet-state quantum yields (up to 79%) and singlet oxygen generation yields (up to 75%). In vitro photobiological investigations employing MDA-MB-231 breast cancer cell lines exhibited rapid cellular uptake, negligible dark toxicity, and high photocytotoxicity. The mechanism of cell death of these systems was predominantly due to the mitochondrial damage, leading to apoptosis mediated via the generation of singlet oxygen-triggered reactive oxygen species. The in vivo studies with the representative conjugate DPR2a employing female NOD/SCID mice models showed inhibition in tumor growth and significantly decreased tumor volume post photodynamic therapy (PDT) treatment. Our results validate that both DPR2a and DPR2b with iodine incorporation exhibit favorable and superior photophysical and photobiological aspects and demonstrate thereby their potential applications in imaging and PDT of cancer.

A Prospective Study of Recovery of Salivary Gland Function After Calculus Removal by Sialendoscopy.

Sialendoscopy is gaining popularity in treating obstructive sialolithiasis as a gland preserving procedure. The study aimed to determine if the salivary glands recovered apart from symptomatic improvement after interventional sialendoscopy for calculus removal. A prospective comparative study was conducted in a tertiary care center on 24 patients diagnosed with sialolithiasis. The eligibility criterion was patients who underwent calculus removal through interventional sialendoscopy. All patients underwent objective and subjective methods of assessments of function of the salivary glands with the help of salivary Technetium (Tc) 99 Scintigraphy, measurement of salivary flow rate, Chronic obstructive sialadenitis symptoms (COSS), and xerostomia index (XI) questionnaires. Assessments were done before the procedure and repeated after 3 months. Categorical variables were expressed using frequency and percentage. Numerical variables were represented using mean and standard deviation. To test the statistical significance of the difference in the mean of the four parameters Wilcoxen sign ranked test was used. According to our study improvement in functionality was noted in all of the subjective and objective parameters assessed namely Tc scintigraphy, salivary flow rate, COSS questionnaire, and XI questionnaire, with a statistically significant p value (< 0.001). Functionality of salivary gland showed improvement within 3 months of calculus removal through sialendoscopy. There was a marked improvement in the symptoms after sialendoscopy. This study demonstrates that removal of obstructing calculus results in rapid recovery of glandular function thereby emphasizing the need for salivary gland preservation. Level of evidence: Level III.

'Sharpshooter' in Botanic Garden: the tale of a rare plant-insect interaction.

Here we report a unique plant-insect interaction between the leafhopper Aloka depressa (tribe Phlogisini) and the host liana, Diploclisia glaucescens, from a Botanic Garden located at the southern edge of Western Ghats in India. Field observations and SEM micrographs were employed to derive evidences on this rare plant-insect interaction. 20-Hydroxyecdysone (20E), insect moulting hormone, was detected and quantified in the host plant D. glaucescens using HPTLC-densitometry. 20E was isolated and characterized from D. glaucescens using column chromatography, 1H-, 13C-NMR and HR-MS. 20E was also detected in A. depressa excrement using HPTLC-densitometry. The leafhopper A. depressa is functioning as a 'sharpshooter' drawing nutrients from the host liana, D. glaucescens, and flinging the waste fluid as droplets through their tail ends. SEM micrographs of A. depressa revealed its external morphological features, characteristic of a sharpshooter. We quantified 20E (0.44-1.44%, dry wt.) in various parts of D. glaucescens. 20E (1.47%, dry wt.) was also detected in the excrement of A. depressa. This plant (D. glaucescens)-insect (A. depressa) association crucially is not damaging the host liana. Considering the diseases caused by sharpshooting leafhoppers in the Americas, this association and the survival of the host plant (D. glaucescens) is illustrating a unique plant-insect interaction.

Combatting emerging infectious diseases from Nipah to COVID-19 in Kerala, India.

BACKGROUND: The state of Kerala, India, has experienced several unprecedented events in the past few years. The current study was an attempt to explore perceptions of stakeholders on how the decentralised system helped during the Nipah virus (NiV) outbreaks and COVID-19 pandemic in Kerala. METHODS: This study used a qualitative descriptive approach built on the advocacy paradigm. The stakeholders who were involved in decision-making and the representatives of local self-government who had real-time experience and had handled the challenges were identified using purposive sampling. Seven key informant interviews (KIIs) and nine in-depth interviews (IDIs) were conducted. RESULTS: Findings indicate that decentralisation had enabled the state to effectively deal with the outbreaks and the pandemic. The survey revealed four major themes: decision-making, engagement level, people-centric action, and difficulties. Two to four categories have emerged for each theme. CONCLUSION: The study results highlight the importance of human resources and service delivery as balancing factors during public health emergencies in any developing nation with limited resources. Given that very few nations have the healthcare infrastructure and resources necessary to cater to the healthcare needs of the whole population, decentralisation should be reinforced.

CONTEXTE: L'État du Kérala, Inde, a connu plusieurs évènements sans précèdent au cours des dernières années. Cette étude a cherché à analyser l'opinion des parties prenantes quant à l'aide apportée par le système décentralisé pendant les épidémies de virus Nipah (NiV) et la pandémie de COVID-19 au Kérala. MÉTHODES: Cette étude a eu recours à une méthode descriptive qualitative construite à partir du paradigme de mobilisation. Les parties prenantes impliquées dans la prise de décisions et les représentants des administrations locales autonomes, forts de leur expérience en temps réel et de leur expérience de gestion des défis, ont été identifiés par échantillonnage dirigé. Sept entretiens avec des informateurs clés (KII) et neuf entretiens approfondis (IDI) ont été réalisés. RÉSULTATS: Les résultats indiquent que la décentralisation a permis à l'État de gérer les épidémies et la pandémie de manière efficace. L'enquête a mis en évidence quatre thèmes majeurs : prise de décisions, niveau d'engagement, action centrée sur les personnes et difficultés. Chaque thème a pu être divisé en deux à quatre catégories. CONCLUSION: Les résultats de l'étude soulignent l'importance des ressources humaines et de la fourniture de services en tant que facteurs d'équilibre en période d'urgence de santé publique dans tous les pays en développement dotés de ressources limitées. Puisque très peu de pays disposent des infrastructures de santé et des ressources nécessaires pour répondre aux besoins sanitaires de l'ensemble de la population, la décentralisation devrait être renforcée.

Local government stewardship for TB elimination in Kerala, India.

SETTING: The southern Indian state of Kerala has implemented 'Kerala Tuberculosis Elimination Mission' as 'People's Movement against TB' under the stewardship of local governments (LGs). The state has been certified by the Government of India for being on track to attain the UN Sustainable Development Goals related to TB elimination. OBJECTIVE: To document the role of LG stewardship in the successful implementation of the TB elimination activities in Kerala. DESIGN: 1) Key informant interviews with four state officials, 2) desk review of available documents, 3) in-depth interviews with seven LG leaders, three mid-level programme managers and three health department field staff. RESULTS: LG involvement led to the establishment of solutions based on local problems, enhanced outreach of services to the socially vulnerable individuals, improved treatment support to patients with TB, increased community ownership of TB elimination activities, reduced TB-related stigma and social determinants being addressed. Institutional mechanisms such as LG TB elimination task forces, formal guidance in planning interventions and appreciation of their performance in the form of awards were facilitators for LG involvement. CONCLUSION: LG stewardship can accelerate TB elimination. A good plan for engagement and institutional mechanisms are crucial for LG involvement.

CONTEXTE: L'État du Kérala, situé dans le sud de l'Inde, a mis en place la « Kerala Tuberculosis Elimination Mission ¼ dans le cadre du « People's Movement Against TB ¼, sous l'égide des gouvernements locaux (LG). Le gouvernement indien a certifié que le Kérala était sur la bonne voie pour atteindre les objectifs de développement durable des Nations unies en matière d'élimination de la TB. OBJECTIF: Documenter le rôle de l'intendance des LG dans la bonne mise en œuvre des activités d'élimination de la TB au Kérala. MÉTHODES: 1) Entretiens avec des informateurs clés (quatre responsables gouvernementaux), 2) analyse des documents disponibles, 3) entretiens approfondis avec sept responsables de LG, trois responsables de programme de niveau intermédiaire et trois membres du personnel de terrain du département de la santé. RÉSULTATS: L'implication des LG a permis d'établir des solutions au vu des problèmes locaux, d'améliorer l'accès aux services pour les personnes socialement vulnérables, d'améliorer le soutien au traitement des patients atteints de TB, de renforcer l'appropriation par la communauté des activités d'élimination de la TB, de réduire la stigmatisation liée à la TB et d'agir sur les déterminants sociaux. Les mécanismes institutionnels, tels que les groupes de travail pour l'élimination de la TB mis en place par les LG, les conseils officiels reçus pour planifier les interventions et l'appréciation des performances sous forme de récompenses ont facilité l'implication des LG. CONCLUSION: L'intendance des LG peut permettre d'accélérer l'élimination de la TB. Une bonne planification de l'engagement et des mécanismes institutionnels sont essentiels à l'implication des LG.

Role of decentralised governance in implementing the National AIDS Control Programme in Kerala.

SETTING: In alignment with the UN Sustainable Development Goals (SDGs), Kerala State in India aims to end the HIV/AIDS epidemic, using its strong background in local governance to implement the National AIDS Control Programme (NACP). OBJECTIVE: To examine the role of local governments in the implementation of NACP in tune with SDGs. DESIGN: We conducted a state-wide exploratory study using document reviews, key informant and in-depth interviews, which were analysed thematically. RESULTS: Four overarching themes that emerged were 1) preparation for programme implementation, 2) positive impact of local government involvement, 3) convergence with other organisations, and 4) barriers to implementation. Local government commitment to implementing the programme was evidenced by their adoption of the HIV/AIDS policy, facilitative interdepartmental coordination and local innovations. Interventions focused on improving awareness about the disease and treatment, and social, financial and rehabilitative support, which were extended even during the COVID-19 pandemic. Fund shortages and poor visibility of the beneficiaries due to preference for anonymity were challenges to achieving the expected outcomes. CONCLUSION: The NACP is ably supported by local governments in its designated domains of interventions, prevention, treatment, and care and support. The programme can achieve its target to end the AIDS epidemic by overcoming the stigma factor, which still prevents potential beneficiaries from accessing care.

CONTEXTE: En accord avec les Objectifs de développement durable (SDG) des Nations unies, l'État du Kérala en Inde a pour objectif de mettre fin à l'épidémie de VIH/SIDA en s'appuyant sur sa forte expérience de gouvernance locale en matière de mise en œuvre du Programme national de lutte contre le SIDA (NACP). OBJECTIF: Examiner le rôle des gouvernements locaux dans la mise en œuvre du NACP, en accord avec les SDG. MÉTHODES: Nous avons réalisé une étude exploratoire à l'échelle de l'État, par le biais d'analyses documentaires, d'entretiens avec des informateurs clés et d'entretiens approfondis, qui ont ensuite été analysés de manière thématique. RÉSULTATS: Quatre thèmes centraux ont été identifiés : 1) préparation de la mise en place du programme, 2) impact positif de l'implication des gouvernements locaux, 3) convergence avec d'autres organisations, et 4) obstacles à la mise en œuvre. L'engagement des gouvernements locaux à mettre en œuvre le programme se manifestait par l'adoption de la politique de lutte contre le VIH/SIDA, par une coordination interdépartementale facilitée et par des innovations locales. Les interventions portaient sur l'amélioration de la sensibilisation au VIH/SIDA et à son traitement, ainsi qu'aux systèmes de soutien social, financier et de réadaptation disponibles ; ces interventions ont même été maintenues pendant la pandémie de COVID-19. Le manque de financements et la mauvaise visibilité des bénéficiaires en raison d'une volonté d'anonymat représentaient autant d'obstacles empêchant d'atteindre les résultats escomptés. CONCLUSION: Les gouvernements locaux apportent leur soutien efficace au NACP dans les domaines d'intervention qui lui ont été assignés (prévention, traitement, soins et soutien). Le programme peut atteindre son objectif d'éradication de l'épidémie de SIDA s'il parvient à lutter contre la stigmatisation associée à la maladie, qui empêche encore d'éventuels bénéficiaires d'accéder aux soins.

A patient presenting with early syphilis and features of general paralysis of insane - An interesting case report in the 21st century!

A 66-year-old unemployed unmarried male with known men sex men activity since the age of 20 years presented with an erythematous well-defined ulcer on the lower lip and multiple discrete papulo-squamous lesions on the palms, soles, and scrotum. The patient was also in dysphoric mood with grandiose ideas with normal higher function. Knee and ankle jerk reflexes were absent and there was impaired tandem walking. Venereal Disease Research Laboratory (VDRL) and treponema pallidum hemagglutination assay were positive. Cerebrospinal fluid-VDRL was positive with grossly elevated proteins and glucose. HIV test was negative. Magnetic resonance imaging scan of the brain was normal. We made a diagnosis of neurosphilis - General paralysis of insane (GPI) with co-existing early syphilis. The patient was started on crystalline penicillin for 14 days after which there was significant improvement in behavior. We are reporting a rare case of GPI with early syphilis.