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.

Evaluation of the ability of adhesives with antibacterial and remineralization functions to prevent secondary caries in vivo.

OBJECTIVE: The bonding interface of dental filling therapy is the weak point in resisting secondary caries. Adhesives containing nanoparticles of amorphous calcium phosphate (NACP) and dimethylaminohexadecyl methacrylate (DMAHDM) have been demonstrated in vitro to prevent bacteria from producing acid and to promote tooth remineralization. The present study aimed to evaluate the efficacy of adhesive with NACP and DMAHDM to prevent secondary caries in vivo. MATERIALS AND METHODS: Artificial cavities were created on the first molar on both sides of the maxillary in a rat model. One side was treated with adhesive containing NACP + DMAHDM, while on the other side, a commercial adhesive served as control. After 24 days of cariogenic feeding, the degree of secondary caries was evaluated by micro-CT and a modified Keyes scoring method. Quantitative real-time PCR (qPCR) and colony-forming unit (CFU) counts were used to evaluate the antibacterial efficacy of the materials. Biocompatibility was also investigated. RESULTS: In the rat model, the adhesive with NACP + DMAHDM showed excellent biocompatibility and effectively decreased the amount of bacteria. The experimental group demonstrated excellent remineralization effectiveness, with a lower modified Keyes score and mineral loss of 34.16 ± 2.13 vol% µm, compared with 77.44 ± 7.22 vol% µm in the control group, according to micro-CT (P < 0.05), showing excellent capacity to inhibit secondary caries. CONCLUSIONS: The NACP-DMAHDM-containing adhesive exhibited good performance in preventing secondary caries in vivo. CLINICAL RELEVANCE: Adhesives containing NACP and DMAHDM have great potential for use in clinical dentistry to prevent secondary caries by inhibiting bacterial growth and promoting remineralization.

Novel nanostructured resin infiltrant containing calcium phosphate nanoparticles to prevent enamel white spot lesions.

OBJECTIVES: The objective of this study was to develop a novel nanostructured resin infiltrant containing nanoparticles of amorphous calcium phosphate (NACP) to treat enamel white spot lesions (WSLs). Physical properties and the therapeutic effect of the new resin infiltrant were investigated for the first time. METHODS: NACP was incorporated into ICON (Icon caries infiltrant, DMG, Germany) with different mass fractions. Cytotoxicity, degree of conversion, surface hardness, calcium (Ca) and phosphorus (P) ions release concentrations were tested. After application to the demineralized enamel samples, the color changes were determined. Surface and cross-sectional hardness were measured, scanning electron microscopy (SEM) images were taken on the cross-section of samples to observe microstructure changes after 14-day pH cycling. RESULTS: Incorporating 10%-30% of NACP did not compromise the biocompatibility and physical properties of the resin infiltrant. ICON + 30% NACP group had long-lasting and high level of Ca and P ion release. After 14-day pH cycling, enamel surface hardness of ICON + 30% NACP group was 1.83 ± 0.21 GPa, significantly higher than the control group (1.32 ± 0.18 GPa) (p < 0.05). ICON + 30NACP group had the highest cross-sectional enamel hardness among all groups (p < 0.05), especially at 50 µm and 100 µm depth. SEM images showed that apparent enamel prism and inter-prism gaps in negative control were masked by mineral deposition in ICON + 30% NACP group. SIGNIFICANCE: The novel ICON+30% NACP infiltrant is promising to inhibit enamel WSLs, protect the enamel and increase its hardness.

Dentin remineralization in acidic solution without initial calcium phosphate ions via poly(amido amine) and calcium phosphate nanocomposites after fluid challenges.

OBJECTIVES: A previous study showed that the combination of poly(amido amine) (PAMAM) and rechargeable composites with nanoparticles of amorphous calcium phosphate (NACP) induced dentin remineralization in an acidic solution with no initial calcium (Ca) and phosphate (P) ions, mimicking the oral condition of individuals with dry mouths. However, the frequent fluid challenge in the oral cavity may decrease the remineralization capacity. Therefore, the objective of the present study was to investigate the remineralization efficacy on dentin in an acid solution via PAMAM + NACP after fluid challenges for the first time. METHODS: The NACP nanocomposite was stored in a pH 4 solution for 77 days to exhaust its Ca and P ions and then recharged. Demineralized dentin samples were divided into four groups: (1) control dentin, (2) dentin coated with PAMAM, (3) dentin with recharged NACP composite, and (4) dentin with PAMAM + recharged NACP. PAMAM-coated dentin was shaken in phosphate-buffered saline for 77 days to desorb PAMAM from dentin. Samples were treated in pH 4 lactic acid with no initial Ca and P ions for 42 days. RESULTS: After 77 days of fluid challenge, PAMAM failed to prevent dentin demineralization in lactic acid. The recharged NACP nanocomposite raised the pH to above 6.5 and re-released more than 6.0 and 4.0 mmol/L Ca and P ions daily, respectively, which inhibited further demineralization. In contrast, the PAMAM + NACP combined method induced great dentin remineralization and restored the dentin microhardness to 0.54 ± 0.04 GPa, which approached that of sound dentin (P = 0.426, P > 0.05). CONCLUSIONS: The PAMAM + NACP combination achieved dentin remineralization in an acid solution with no initial Ca and P ions, even after severe fluid challenges. CLINICAL RELEVANCE: The novel PAMAM + NACP has a strong and sustained remineralization capability to inhibit secondary caries, even for individuals with dry mouths.

Remineralization effectiveness of adhesive containing amorphous calcium phosphate nanoparticles on artificial initial enamel caries in a biofilm-challenged environment.

OBJECTIVES: Dental caries is closely associated with acid-producing bacteria, and Streptococcus mutans is one of the primary etiological agents. Bacterial accumulation and dental demineralization lead to destruction of bonding interface, thus limiting the longevity of composite. The present study investigated remineralization effectiveness of adhesive containing nanoparticles of amorphous calcium phosphate (NACP) in a stimulated oral biofilm environment. METHODS: The enamel blocks were immersed in demineralization solution for 72 h to imitate artificial initial carious lesion and then subjected to a Streptococcus mutans biofilm for 24 h. All the samples then underwent 4-h demineralization in brain heart infusion broth with sucrose (BHIS) and 20-h remineralization in artificial saliva (AS) for 7 days. The daily pH of BHIS after 4-h incubation, lactic acid production, colony-forming unit (CFU) count, and content of calcium (Ca) and phosphate (P) in biofilm were evaluated. Meanwhile, the remineralization effectiveness of enamel was analyzed by X-ray diffraction (XRD), surface microhardness testing, transverse microradiography (TMR) and scanning electron microscopy (SEM). RESULTS: The NACP adhesive released abundant Ca and P, achieved acid neutralization, reduced lactic acid production, and lowered CFU count (P < 0.05). Enamel treated with NACP adhesive demonstrated the best remineralization effectiveness with remineralization value of 52.29 ± 4.79% according to TMR. Better microhardness recovery of cross sections and ample mineral deposits were also observed in NACP group. CONCLUSIONS: The NACP adhesive exhibited good performance in remineralizing initial enamel lesion with cariogenic biofilm. SIGNIFICANCE: The NACP adhesive is promising to be applied for the protection of bonding interface, prevention of secondary caries, and longevity prolonging of the restoration.

Possibility of long-termed prediction of NACPs and NADPs of COVID-19 in different countries and regions via tanh basic functions.

In this paper, we make long-termed prediction for numbers of accumulative confirmed patients (NACPs) and numbers of accumulative death patients (NADPs) of COVID-19 in different countries and regions by fitting method. We use hyperbolic tangent functions as basic functions for the fitting method. The results indicate that it is possible to make long-termed prediction for NACPs and NADPs of COVID-19 by using a small amount of data. And we can estimate the arrival times of the plateau phases of COVID-19 in some countries and regions. It shows that our method is simple (model-free) and very effective in long-termed prediction of NACPs and NADPs with small data.

Prediction of numbers of the accumulative confirmed patients (NACP) and the plateau phase of 2019-nCoV in China.

In the present study, I propose a novel fitting method to describe the outbreak of 2019-nCoV in China. The fitted data were selected carefully from the non-Hubei part and Hubei Province of China respectively. For the non-Hubei part, the time period of data collection corresponds from the beginning of the policy of isolation to present day. But for Hubei Province, the subjects of Wuhan City and Hubei Province were included from the time of admission to the Huoshenshan Hospital to present day in order to ensure that all or the majority of the confirmed and suspected patients were collected for diagnosis and treatment. The employed basic functions for fitting are the hyperbolic tangent functions tanh ( . ) since in these cases the 2019-nCoV is just an epidemic. Subsequently, the 2019-nCoV will initially expand rapidly and tend to disappear. Therefore, the numbers of the accumulative confirmed patients in different cities, provinces and geographical regions will initially increase rapidly and subsequently stabilize to a plateau phase. The selection of the basic functions for fitting is crucial. In the present study, I found that the hyperbolic tangent functions tanh ( . ) could satisfy the aforementioned properties. By this novel method, I can obtain two significant results. They base on the conditions that the rigorous isolation policy is executed continually. Initially, I can predict the numbers very accurately of the cumulative confirmed patients in different cities, provinces and parts in China, notably, in Wuhan City with the smallest relative error estimated to 0.021 % , in Hubei Province with the smallest relative error estimated to 0.012 % and in the non-Hubei part of China with the smallest relative error of -  0.195% in the short-term period of infection. In addition, perhaps I can predict the times when the plateau phases will occur respectively in different regions in the long-term period of infection. Generally for the non-Hubei part of China, the plateau phase of the outbreak of the 2019-nCoV will be expected this March or at the end of this February. In the non-Hubei region of China it is expected that the epidemic will cease on the 30th of March 2020 and following this date no new confirmed patient will be expected. The predictions of the time of Inflection Points and maximum NACP for some important regions may be also obtained. A specific plan for the prevention measures of the 2019-nCoV outbreak must be implemented. This will involve the present returning to work and resuming production in China. Based on the presented results, I suggest that the rigorous isolation policy by the government should be executed regularly during daily life and work duties. Moreover, as many as possible the confirmed and suspected cases should be collected to diagnose or treat.

Dentin remineralization via adhesive containing amorphous calcium phosphate nanoparticles in a biofilm-challenged environment.

OBJECTIVES: The remineralization of dentin at a bonded interface would help to strengthen the bonded interface and inhibit secondary caries, and would prolong the longevity of restoration. The aim of this study was to investigate the remineralization of demineralized human dentin in a dental biofilm environment via an adhesive containing nanoparticles of amorphous calcium phosphate (NACP). METHODS: Dentin demineralization was promoted by subjecting samples to a Streptococcus mutans acidic biofilm for 24 h. Samples were divided into a control group, a commercial fluoride-releasing adhesive group, and an NACP adhesive group. All samples were subjected to a remineralization protocol consisting of 4-h exposure per 24-h period in brain heart infusion broth plus 1% sucrose (BHIS) followed by immersion in artificial saliva for the remaining period. The pH of BHIS after 4-h immersion was measured every other day. After 10 days, the biofilm was assessed for colony-forming unit (CFU) count, lactic acid production, live/dead staining, and calcium and phosphate content. The mineral changes in the demineralized dentin samples were analyzed by transverse microradiography, hardness measurement, X-ray diffraction characterization, and scanning electron microscopy. RESULTS: The NACP adhesive achieved acid neutralization, decreased biofilm CFU count, decreased biofilm lactic acid production, and increased biofilm calcium and phosphate content (P < 0.05). The NACP adhesive group had higher remineralization value than the commercial fluoride-releasing adhesive group (P < 0.05). CONCLUSIONS: The NACP adhesive was effective in remineralizing dentin lesions in a biofilm model. Its ability to protect bond interface, inhibit secondary caries, and prolong the longevity of restoration is promising. CLINICAL SIGNIFICANCE: Using NACP-containing adhesives could be recommended because of the protective ability of its hybrid layer even under a biofilm-challenged environment.

Quality and effectiveness of counselling at antiretroviral therapy centres in India: capturing counsellor and beneficiary perspectives.

BACKGROUND: Ensuring the quality and effectiveness of counselling is imperative for enabling people living with HIV to cope with treatment adherence. Countrywide assessment of antiretroviral therapy (ART) centres was undertaken to assess the quality and effectiveness of counselling. The insights gained from the assessment are expected to build an improved understanding of the counselling aspect and contribute to informing decisions strengthening the counselling provided at ART centres. METHODS: Assessment of counselling at 357 ART centres entailed interviews with counsellors and beneficiaries using a structured questionnaire administered by trained technical experts. Two counsellors and five beneficiaries at each ART centre were interviewed to assess both the quality and effectiveness of counselling. Beneficiaries were selected from different risk groups to understand their varied concerns and experiences. RESULTS: During the assessment, 618 counsellors were interviewed (45% women); also, 1785 beneficiaries were interviewed, consisting of 892 (49.9%) men, 857 (48.1%) women and 36 (2.0%) transgender. Counsellors were found to be relatively well informed on topics pertaining to pre-ART, ART preparedness and positive healthy living, and the psychosocial support extended to patients. Counsellors surveyed were not aware of critical areas such as counselling of pregnant women (44.5%) , drug adherence (44.8%) and the use of information, education and communication material during counselling, and pill count. The majority of beneficiaries reported being informed on issues pertaining to retention; however, 30-40% of beneficiaries were not informed regarding the critical elements of adherence such as counselling on ART side effects (68.5%), pill count (62.8%) and information on access to social benefit schemes (25.7%). Factors such as client volume, the training of the counsellors and adequate space for counselling affected the quality of counselling. CONCLUSION: With concerted efforts in bridging the gaps in knowledge, infrastructure and information needs, India's national AIDS control programme (NACP) can enhance the counselling services at ART centres and improve the quality of services for patient retention.

Prediction of recurrence in solid nonfunctioning pituitary macroadenomas: additional benefits of diffusion-weighted MR imaging.

OBJECTIVE: A subset of benign, nonfunctioning pituitary macroadenomas (NFMAs) has been shown to undergo early progression/recurrence (P/R) during the first years after surgical resection. The aim of this study was to determine preoperative MR imaging features for the prediction of P/R in benign solid NFMAs, with emphasis on apparent diffusion coefficient (ADC) values. METHODS: We retrospectively investigated the preoperative MR imaging features for the prediction of P/R in benign solid NFMAs. Only the patients who had undergone preoperative MRI and postoperative MRI follow-ups for more than 1 year (at least every 6-12 months) were included. From November 2010 to December 2016, a total of 30 patients diagnosed with benign solid NFMAs were included (median follow-up time 45 months), and 19 (63.3%) patients had P/R (median time to P/R 24 months). RESULTS: Benign solid NFMAs with cavernous sinus invasion, failed chiasmatic decompression, large tumor height and tumor volume, high diffusion-weighted imaging (DWI) signal, and lower ADC values/ratios were significantly associated with P/R (p < 0.05). The cutoff points of ADC value and ADC ratio for prediction of P/R are 0.77 × 10-3 mm2/sec and 1.01, respectively, with area under the curve (AUC) values (0.9 and 0.91) (p < 0.01). In multivariate Cox proportional hazards analysis, low ADC value (< 0.77 × 10-3 mm2/sec) is a high-risk factor of P/R (p < 0.05) with a hazard ratio of 14.07. CONCLUSIONS: Benign solid NFMAs with low ADC values/ratios are at a significantly increased risk of P/R, and aggressive treatments accompanied by close follow-up with imaging studies should be considered.

Sensitivity and specificity of phospho-Ser129 α-synuclein monoclonal antibodies.

α-Synuclein (α-syn) is an abundant presynaptic protein that is the primary constituent of inclusions that define Lewy body diseases (LBDs). In these inclusions, α-syn is phosphorylated at the serine-129 residue. Antibodies directed to this phosphorylation site are used to measure inclusion abundance and stage disease progression in preclinical models as well as in postmortem tissues in LBDs. While it is critical to reliably identify inclusions, phospho-specific antibodies often cross-react with nonspecific antigens. Four commercially available monoclonal antibodies, two from rabbits (clones EP1536Y and MJF-R13) and two from mice (81a and pSyn#64), have been the most widely used in detecting pS129-α-syn inclusions. Here, we systematically evaluated these antibodies in brain sections and protein lysates from rats and mice. All antibodies detected pS129-α-syn inclusions in the brain that were induced by preformed α-syn fibrils in wild-type rats and mice. Antibody titrations revealed that clones EP1536Y and 81a comparably labeled inclusions in both the perikarya and neuronal processes in contrast to clones MJF-R13 and pSyn#64 that incompletely labeled inclusions at various antibody concentrations. Except for EP1536Y, the clones produced nonspecific diffuse neuropil labeling in α-syn knockout mice as well as mice and rats injected with monomeric α-syn, with some nonspecific staining titrating with pS129-α-syn inclusions. By immunoblot, all the clones cross-reacted with proteins other than α-syn, warranting caution in interpretations of specificity. Clone EP1536Y uniquely and robustly detected endogenous pS129-α-syn in highly soluble protein fractions from the mouse brain. In summary, EP1536Y had the highest sensitivity and specificity for detecting pS129-α-syn.

Long-term dentin remineralization by poly(amido amine) and rechargeable calcium phosphate nanocomposite after fluid challenges.

OBJECTIVE: Previous studies investigated short-term dentin remineralization; studies on long-term dentin remineralization after fluid challenges mimicking fluids in oral environment are lacking. The objective of this study was to develop a long-term remineralization method to via poly(amido amine) (PAMAM) and rechargeable composite containing nanoparticles of amorphous calcium phosphate (NACP) after fluid challenges for the first time. METHODS: NACP composite was immersed at pH 4 to exhaust its calcium (Ca) and phosphate (P) ions, and then recharged with Ca and P ions, to test the remineralization of the exhausted and recharged NACP composite. Dentin was acid-etched with 37% phosphoric acid. Four groups were prepared: (1) dentin control, (2) dentin with PAMAM, (3) dentin with the recharged NACP composite, and (4) dentin with PAMAM plus recharged NACP composite. PAMAM-coated dentin was immersed in phosphate-buffered saline with shaking for 72 days, because there is fluid flow in the mouth which could potentially detach the PAMAM from dentin. Specimens were treated with a cyclic artificial saliva/lactic acid regimen for 35 days. RESULTS: After 72days of immersion plus shaking, the PAMAM still successfully fulfilled its mineralization nucleation. The recharged NACP composite still provided acid-neutralization and ion re-release, which did not decrease with increasing the number of recharge cycles. The immersed-PAMAM plus NACP achieved complete dentin remineralization and restored the hardness to that of healthy dentin. SIGNIFIANCE: In conclusion, superior long-term remineralization of the PAMAM plus NACP method was demonstrated for the first time. The immersed-PAMAM plus recharged NACP completely remineralized the pre-demineralized dentin, even after prolonged fluid-challenge similar to that in oral environment. The novel PAMAM plus NACP composite method is promising to provide long-term tooth protection and caries inhibition.

α-Synuclein fibril-induced inclusion spread in rats and mice correlates with dopaminergic Neurodegeneration.

Proteinaceous inclusions in neurons, composed primarily of α-synuclein, define the pathology in several neurodegenerative disorders. Neurons can internalize α-synuclein fibrils that can seed new inclusions from endogenously expressed α-synuclein. The factors contributing to the spread of pathology and subsequent neurodegeneration are not fully understood, and different compositions and concentrations of fibrils have been used in different hosts. Here, we systematically vary the concentration and length of well-characterized α-synuclein fibrils and determine their relative ability to induce inclusions and neurodegeneration in different hosts (primary neurons, C57BL/6J and C3H/HeJ mice, and Sprague Dawley rats). Using dynamic-light scattering profiles and other measurements to determine fibril length and concentration, we find that femptomolar concentrations of fibrils are sufficient to induce robust inclusions in primary neurons. However, a narrow and non-linear dynamic range characterizes fibril-mediated inclusion induction in axons and the soma. In mice, the C3H/HeJ strain is more sensitive to fibril exposures than C57BL/6J counterparts, with more inclusions and dopaminergic neurodegeneration. In rats, injection of fibrils into the substantia nigra pars compacta (SNpc) results in similar inclusion spread and dopaminergic neurodegeneration as injection of the fibrils into the dorsal striatum, with prominent inclusion spread to the amygdala and several other brain areas. Inclusion spread, particularly from the SNpc to the striatum, positively correlates with dopaminergic neurodegeneration. These results define biophysical characteristics of α-synuclein fibrils that induce inclusions and neurodegeneration both in vitro and in vivo, and suggest that inclusion spread in the brain may be promoted by a loss of neurons.

Revisiting the AIDS Epidemic in Pakistan: Where We Stand and What We Must Aim For.

Human immunodeficiency virus type 1 (HIV-1) is the major cause of acquired immunodeficiency syndrome (AIDS) in humans, where the immune system totally succumbs to the virus. A large proportion of the AIDS infected belong to developing countries and AIDS prevalence is intensified by severe poverty, malnutrition, and famine; fatal illnesses with a scorn shortage of medical amenities complemented with the lack of education and development. Current Pakistani health system setting is in a dire need of improvement. Low literacy rates, high birth rates, and associated maternal mortality plus a lack of clean drinking water and appropriate sanitation system have a serious impact on general living conditions contributing to a relatively short lifespan. HIV is, therefore, becoming a growing health concern in Pakistan with a rapid rise in the reported cases. AIDS is most prevalent among injection drug users (IDUs), male/female sex workers, and unchecked deported migrant workforce. To combat this virus, the Pakistan Government has been working hard over the past few years with local bodies and international organizations in an effort to combat this menace. This review aims to discuss the risk factors for the rise of this epidemic in the country and the recommendations, efforts to be done to address this alarming issue.

Delivery of antiretroviral treatment services in India: estimated costs incurred under the National AIDS Control Programme

Competing domestic health priorities and shrinking financial support from external agencies necessitatesthat India’s National AIDS Control Programme (NACP) brings in cost efficiencies to sustain theprogramme. In addition, current plans to expand the criteria for eligibility for antiretroviral therapy(ART) in India will have significant financial implications in the near future. ART centres in India providecomprehensive services to people living with HIV (PLHIV): those fulfilling national eligibility criteriaand receiving ART and those on pre-ART care, i.e. not on ART. ART centres are financially supported(i) directly by the NACP; and (ii) indirectly by general health systems. This study was conducted todetermine (i) the cost incurred per patient per year of pre-ART and ART services at ART centres; and(ii) the proportion of this cost incurred by the NACP and by general health systems. The study usednational data from April 2013 to March 2014, on ART costs and non-ART costs (human resources,laboratory tests, training, prophylaxis and management of opportunistic infections, hospitalization,operational, and programme management). Data were extracted from procurement records andreports, statements of expenditure at national and state level, records and reports from ART centres,databases of the National AIDS Control Organisation, and reports on use of antiretroviral drugs. Theanalysis estimates the cost for ART services as US$ 133.89 (`8032) per patient per year, of which 66%(US$ 88.66, `5320) is for antiretroviral drugs and 34% (US$ 45.23, `2712) is for non-ART recurrentexpenditure, while the cost for pre-ART care is US$ 33.05 (`1983) per patient per year. The low costsincurred for patients in ART and pre-ART care services can be attributed mainly to the low costs ofgeneric drugs. However, further integration with general health systems may facilitate additional costsaving, such as in human resources.

Surface dose measurements and comparison of unflattened and flattened photon beams.

The purpose of this study was to evaluate the central axis dose in the build-up region and the surface dose of a 6 MV and 10 MV flattened photon beam (FB) and flattening filter free (FFF) therapeutic photon beam for different square field sizes (FSs) for a Varian Truebeam linear accelerator using parallel-plate ionization chamber and Gafchromic film. Knowledge of dosimetric characteristics in the build-up region and surface dose of the FFF is essential for clinical care. The dose measurements were also obtained empirically using two different commonly used dosimeters: a p-type photon semiconductor dosimeter and a cylindrical ionization chamber. Surface dose increased linearly with FS for both FB and FFF photon beams. The surface dose values of FFF were higher than the FB FSs. The measured surface dose clearly increases with increasing FS. The FFF beams have a modestly higher surface dose in the build-up region than the FB. The dependence of source to skin distance (SSD) is less significant in FFF beams when compared to the flattened beams at extended SSDs.

Scaling up of HIV-TB collaborative activities: Achievements and challenges in India.

India has been implementing HIV/TB collaborative activities since 2001 with rapid scale-up of infrastructure across the country during past decade in National AIDS Control Programme and Revised National TB Control Programme. India has shown over 50% reduction in new infections and around 35% reduction in AIDS-related deaths, thereby being one of the success stories globally. Substantial progress in the implementation of collaborative TB/HIV activities has occurred in India and it is marching towards target set out in the Global Plan to Stop TB and endorsed by the UN General Assembly to halve HIV associated TB deaths by 2015. While the successful approaches have led to impressive gains in HIV/TB control in India, there are emerging challenges including newer pockets with rising HIV trends in North India, increasing drug resistance, high mortality among co-infected patients, low HIV testing rates among TB patients in northern and eastern states in India, treatment delays and drop-outs, stigma and discrimination, etc. In spite of these difficulties, established HIV/TB coordination mechanisms at different levels, rapid scale-up of facilities with decentralisation of treatment services, regular joint supervision and monitoring, newer initiatives like use of rapid diagnostics for early diagnosis of TB among people living with HIV, TB notification, etc. have led to success in combating the threat of HIV/TB in India. This article highlights the steps taken by India, one of the largest HIV/TB programmes in world, in scaling up of the joint HIV-TB collaborative activities, the achievements so far and discusses the emerging challenges which could provide important lessons for other countries in scaling up their programmes.

Abrogation of α-synuclein-mediated dopaminergic neurodegeneration in LRRK2-deficient rats.

Missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene can cause late-onset Parkinson disease. Past studies have provided conflicting evidence for the protective effects of LRRK2 knockdown in models of Parkinson disease as well as other disorders. These discrepancies may be caused by uncertainty in the pathobiological mechanisms of LRRK2 action. Previously, we found that LRRK2 knockdown inhibited proinflammatory responses from cultured microglia cells. Here, we report LRRK2 knockout rats as resistant to dopaminergic neurodegeneration elicited by intracranial administration of LPS. Such resistance to dopaminergic neurodegeneration correlated with reduced proinflammatory myeloid cells recruited in the brain. Additionally, adeno-associated virus-mediated transduction of human α-synuclein also resulted in dopaminergic neurodegeneration in wild-type rats. In contrast, LRRK2 knockout animals had no significant loss of neurons and had reduced numbers of activated myeloid cells in the substantia nigra. Although LRRK2 expression in the wild-type rat midbrain remained undetected under nonpathological conditions, LRRK2 became highly expressed in inducible nitric oxide synthase (iNOS)-positive myeloid cells in the substantia nigra in response to α-synuclein overexpression or LPS exposures. Our data suggest that knocking down LRRK2 may protect from overt cell loss by inhibiting the recruitment of chronically activated proinflammatory myeloid cells. These results may provide value in the translation of LRRK2-targeting therapeutics to conditions where neuroinflammation may underlie aspects of neuronal dysfunction and degeneration.

Retention in pre-antiretroviral treatment care in a district of Karnataka, India: how well are we doing?

SETTING: Antiretroviral treatment (ART) Centre in Tumkur district of Karnataka State, India. There is no published information about pre-ART loss to follow-up from India. OBJECTIVE: To assess the proportion lost to follow-up (defined as not visiting the ART Centre within 1 year of registration) and associated socio-demographic and immunological variables. DESIGN: Retrospective cohort study involving a review of medical records of adult HIV-infected persons (aged ⩾15 years) registered in pre-ART care during January 2010-June 2012. RESULTS: Of 3238 patients registered, 2519 (78%) were eligible for ART, while 719 (22%) were not. Four of the latter were transferred out; the remaining 715 individuals were enrolled in pre-ART care, of whom 290 (41%) were lost to follow-up. Factors associated with loss to follow-up on multivariate analysis included age group ⩾45 years, low educational level, not being married, World Health Organization Stage III or IV and rural residence. CONCLUSION: About four in 10 individuals in pre-ART care were lost to follow-up within 1 year of registration. This needs urgent attention. Routine cohort analysis in the national programme should include those in pre-ART care to enable improved review, monitoring and supervision. Further qualitative research to ascertain reasons for loss to follow-up is required to design future interventions.

Contexte : Centre de traitement antirétroviral (ART) du district de Tumkur dans l'état de Karnataka, Inde. Il n'y a pas de document publié sur les perdus de vue avant le traitement ART en Inde.Objectif : Evaluer la proportion de perdus de vue (définis comme l'absence de visite au centre d'ART dans l'année suivant l'enregistrement) et les variables sociodémographiques et immunologiques qui y sont associées.Schéma : Etude rétrospective de cohorte impliquant une revue des dossiers médicaux des patients adultes infectés par le VIH (âge ⩾15 ans) enregistrés en soins pré-ART entre janvier 2010 et juin 2012.Résultats : Sur 3238 patients enregistrés, 2519 (78%) étaient éligibles pour le traitement ART tandis que 719 (22%) ne l'étaient pas. Quatre de ces derniers ont été transférés. Parmi les 715 individus enrôlés en soin pré-ART, 290 (41%) ont été perdus de vue. Les facteurs associés avec le fait d'être perdus de vue en analyse multivariée incluaient la tranche d'âge ⩾45 ans, un niveau d'instruction faible, le célibat, le stade 3 ou 4 de l'OMS et la résidence en milieu rural.Conclusion : Près de quatre individus sur 10 en soins pre-ART ont été perdus de vue dans l'année suivant leur enregistrement. Ceci requiert une attention urgente. L'analyse de cohorte en routine du programme national devrait inclure les patients en soins pré-ART afin d'améliorer la revue des cas, leur suivi et leur supervision. Une recherche qualitative ultérieure afin de cerner les raisons des pertes de vue est nécessaire pour concevoir les interventions futures.

Marco de referencia: El centro de tratamiento antirretrovírico (ART) en el distrito de Tumkur del estado de Karnataka en la India. Hasta el momento no existen publicaciones sobre la pérdida de vista de los pacientes seropositivos durante el seguimiento antes de comenzar el ART en la India.Objetivo: Se buscó definir la proporción de pacientes perdidos de vista durante el seguimiento (definidos como los pacientes que no habían acudido al centro de ART hasta un año después de haberse registrado) y evaluar las variables socioeconómicas e inmunitarias que se asociaban con esta situación.Método: Se llevó a cabo un estudio retrospectivo de cohortes a partir del examen de las historias clínicas de los adultos (⩾15 años de edad) infectados por el virus de la inmunodeficiencia humana (VIH), que se inscribieron a la atención clínica previa al ART de enero del 2010 a junio del 2012.Resultados: De los 3238 pacientes registrados, 2519 cumplían con los requisitos para iniciar el ART (78%) y 719 de ellos no eran aptos (22%); cuatro pacientes de este último grupo se remitieron a otro centro. De las 715 personas restantes, inscritas en la atención previa al ART, 290 se perdieron de vista durante el seguimiento (41%). El análisis multifactorial puso en evidencia que los factores asociados con la pérdida de vista de los pacientes fueron el grupo de edad de ⩾45 años, una baja escolaridad, el hecho de ser solteros, el estado 3 o 4 de la enfermedad según la clasificación de la Organización Mundial de la Salud y la residencia en zona rural.Conclusión: Cerca de cuatro de cada diez pacientes inscritos en la atención clínica previa al ART se perdieron de vista durante el seguimiento en el primer año después de haberse registrado. Esta situación exige una atención urgente. Es importante que los análisis sistemáticos de cohortes del programa nacional incluyan a las personas infectadas que reciben atención antes de comenzar el ART, a fin de mejorar la evaluación, el seguimiento y la supervisión de los pacientes. Es preciso fomentar la realización de nuevas investigaciones cualitativas que determinen las razones de la pérdida de vista durante el seguimiento y contribuyan a la planificación de las intervenciones futuras.