Health Care Innovation for Low-Resource Settings: The Value of Local Immersion and Partnership.

Health Care Innovation is the creation, development, and translation of new and better solutions to health care challenges. At its core, this endeavor does not require extending the frontiers of science or the creation of new fundamental technologies. Rather, it is primarily focused on the use of existing science and established technologies in the design of new solutions to problems in health care. Successfully innovating for low- and middle-income countries (LMICs) requires a needs and stakeholder-driven approach to enable development and adoption of available, accessible, and acceptable solutions tailored to the specific need and context of care.

A Retrospective Analysis of Clinico-Demographic and Genetic Characteristics and Treatment Outcomes in Isoniazid Mono-Resistant Tuberculosis Patients: A Single-Center Study.

INTRODUCTION: Treatment failure and relapse rates are more likely to occur when there is isoniazid (INH) resistance. So, we can no longer ignore the problem of isoniazid mono-resistance. It is pertinent to control the spread of primary INH resistance and prevent secondary resistance. AIM: This study aims to evaluate subjects' clinical, demographic, and genetic characteristics and explore their treatment outcomes. METHODS: All data of isoniazid mono-resistant tuberculosis (TB) patients, which were maintained in the electronic database of mandatory notifications (NIKSHAY Portal) between 2017 and 2022, were reviewed. A total of 54 patients were included after excluding five patients with ongoing treatment. RESULTS: Of 54 patients, 41 (75.9%) were cured, which was classified under favorable outcome, and the rest were classified under unfavorable outcome. Phenotypic, high-level mutation (katG) was found in 48 (88.9%) patients. Kaplan-Meier curves show that survival probabilities increase in weeks with regular intake of drugs. CONCLUSION: Our study found that those with younger ages and males were more affected. We found favorable outcomes in the majority of patients.

Digital lock-in amplifier for space rubidium atomic clock.

In many low-noise applications, extracting information from the extremely noisy signal is required. This task can be accomplished by a lock-in amplifier if the frequency of the signal is known before detection. Error signal output from the physics package of the rubidium atomic clock (RbAC) is one of those noisy signals. A lock-in amplifier extracts the desired information from such a signal as the frequency of the error signal is known beforehand. The Space Applications Centre of the Indian Space Research Organisation is developing the Indian Rubidium Atomic Frequency Standard (IRAFS) for Navigation with Indian Constellation. We have developed a digital lock-in amplifier with a very high-resolution frequency control voltage for IRAFS. This paper demonstrates the digital lock-in amplifier with a novel method of combining two 12-bit digital-to-analog converters (DACs) to get higher resolution 20-bit output for precise frequency control and tuning. This design technique allows a digital lock-in amplifier to be used for high-performance RbAC for space applications as precision DACs with higher resolution are not available in space-qualified versions.

Trends in overall survival and costs of multiple myeloma, 2000-2014.

Little real-world evidence is available to describe the recent trends in treatment costs and outcomes for patients with multiple myeloma (MM). Using the Truven Health MarketScan Research Databases linked with social security administration death records, this study found that the percentage of MM patients using novel therapy continuously increased from 8.7% in 2000 to 61.3% in 2014. Compared with MM patients diagnosed in earlier years, those diagnosed after 2010 had higher rates of novel therapy use and better survival outcomes; patients diagnosed in 2012 were 1.25 times more likely to survive 2 years than those diagnosed in 2006. MM patients showed improved survival over the study period, with the 2-year survival gap between MM patients and matched controls decreasing at a rate of 3% per year. Total costs among MM patients have increased in all healthcare services over the years; however, the relative contribution of drug costs has remained fairly stable since 2009 despite new novel therapies coming to market. Findings from this study corroborate clinical data, suggesting a paradigm shift in MM treatment over the past decade that is associated with substantial survival gains. Future studies should focus on the impact on specific novel agents on patients' outcomes.

Socio-demographic, Epidemiological and Environmental Determinants of Acute Gastroenteritis in Western India.

INTRODUCTION: An outbreak of acute gastroenteritis had occurred in Rajpara village of Bhavnagar district. The objective of this study was to find out the socio-demographic, epidemiological and environmental determinants of this outbreak. METHODS: A case-control study was conducted in Rajpara village among 238 cases of acute gastroenteritis and an equal number of controls in January 2015. Multiple logistic regression was used for identifying the variables independently predicting acute gastroenteritis. RESULTS: Upper socio-economic status, occupation requiring travel outside village, source of drinking water from well of 'new' Rajpara village, change in taste of water, use of chlorine tablets, travel outside village in last week, another family member affected with acute gastroenteritis, using common utensil for hand washing, hand washing before eating, ate food from outside in last week, having sanitary latrine at house, waste disposal in a common dump (instead of at house), waste accumulation around house and flies inside house were significantly associated with occurrence of acute gastroenteritis. On multiple logistic regression, change in taste of water (P<0.001), waste disposal in a common dump (P=0.012), another family member been affected (P<0.001), waste accumulation around house (P<0.001), higher socio-economic status (P=0.002) and eating outside food (P=0.011) made a significant contribution to prediction. CONCLUSIONS: Socio-demographic factors (higher socio-economic status), epidemiological correlates (change in taste of water, another family member been affected with acute gastroenteritis and eating outside food) and environmental determinants (waste disposal in a common dump and waste accumulation around house) significantly determines the occurrence of cases of acute gastroenteritis.

Recommendations for Vaccination Against Seasonal Influenza in Adult High Risk Groups: South Asian Recommendations.

Influenza is a global public health problem and concern especially in high risk people. Prevention plays a key role in avoiding complications of influenza related illnesses. Despite the existing prevalence of influenza, and documented importance of vaccination, the uptake of influenza vaccine is very poor. This document provide recommendations for influenza vaccination in high-risk individuals and help implement best practices in the South Asian region and improve coverage of influenza vaccination to achieve better outcomes in this population.

Effect of ventilation on cerebral oxygenation in patients undergoing surgery in the beach chair position: a randomized controlled trial.

BACKGROUND: Surgery in the beach chair position (BCP) may reduce cerebral blood flow and oxygenation, resulting in neurological injuries. The authors tested the hypothesis that a ventilation strategy designed to achieve end-tidal carbon dioxide (E'(CO2)) values of 40-42 mm Hg would increase cerebral oxygenation (Sct(O2)) during BCP shoulder surgery compared with a ventilation strategy designed to achieve E'(CO2) values of 30-32 mm Hg. METHODS: Seventy patients undergoing shoulder surgery in the BCP with general anaesthesia were enrolled in this randomized controlled trial. Mechanical ventilation was adjusted to maintain an E'(CO2) of 30-32 mm Hg in the control group and an E'(CO2) of 40-42 mm Hg in the study group. Cerebral oxygenation was monitored continuously in the operating theatre using near-infrared spectroscopy. Baseline haemodynamics and Sct(O2) were obtained before induction of anaesthesia, and these values were then measured and recorded continuously from induction of anaesthesia until tracheal extubation. The number of cerebral desaturation events (CDEs) (defined as a ≥20% reduction in Sct(O2) from baseline values) was recorded. RESULTS: No significant differences between the groups were observed in haemodynamic variables or phenylephrine interventions during the surgical procedure. Sct(O2) values were significantly higher in the study 40-42 group throughout the intraoperative period (P<0.01). In addition, the incidence of CDEs was lower in the study 40-42 group (8.8%) compared with the control 30-32 group (55.6%, P<0.0001). CONCLUSIONS: Cerebral oxygenation is significantly improved during BCP surgery when ventilation is adjusted to maintain E'(CO2) at 40-42 mm Hg compared with 30-32 mm Hg. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01546636.

Severe diarrhoea due to Cystoisospora belli in renal transplant patient on immunosuppressive drugs.

Cystoisospora belli, formerly known as Isospora belli, protozoal parasite endemic to many regions of the world including the Caribbean, Central and South America, Africa, and South-East Asia. It is frequently encountered in patients with acquired immunodeficiency syndrome (AIDS) and is considered to be an AIDS-defining illness. Chronic severe watery diarrhoea due to C. belli has also been reported in other immunodeficiency states. C. belli infection in immunosuppressed patients has rarely been described. We describe severe diarrhoea due to C. belli in a human immunodeficiency virus-negative renal transplant recipient on immunosuppressive drugs. Oocysts of C. belli were detected in direct smear preparation of the diarrheic stool sample of the patient. The patient responded to combination treatment with Bactrim-double-strength (trimethoprim-sulfamethoxazole) and Nitazoxanide.

Successful treatment of plastic bronchitis with low fat diet and subsequent thoracic duct ligation in child with fontan physiology.

Plastic bronchitis is a rare condition characterized by the formation and expectoration of long, branching bronchial casts that develop in the tracheobronchial tree and cause airway obstruction. Plastic bronchitis has become increasingly recognized as a feared complication of the Fontan operation with a mortality of up to 50%. We report an 11 year old boy who developed severe plastic bronchitis following Fontan repair and the successful long-term control of cast formation utilizing a low-fat diet and subsequent thoracic duct ligation.

Adenovirus-mediated human paraoxonase1 gene transfer to provide protection against the toxicity of the organophosphorus pesticide toxicant diazoxon.

Human paraoxonase1 (hPON1) is a potential therapeutic against the toxicity of organophosphorus (OP) pesticides and chemical warfare nerve agents. We tested whether PON1 gene transfer using adenovirus provides protection against the toxicity of the OP diazoxon. Using an adenovirus construct containing hPON1 gene, we showed elevated levels of recombinant hPON1 in vitro in 293A cells and in vivo in mice. The recombinant enzyme was secreted by 293A cells into culture medium and into the systemic circulation of mice. Western blotting revealed that the virally expressed hPON1 had the expected molecular weight of 45 kDa. Recombinant hPON1 in mice was in complex with mouse high-density lipoprotein (HDL) and migrated more slowly than endogenous hPON1 in the human HDL complex. Mice injected with adenovirus expressed PON1 at 600-3480 U ml(-1) on day 5 post-treatment, which is 8-50-fold above endogenous. Six mice expressing hPON1 survived 2LD(50) doses of diazoxon. Four of the six mice survived a second dose of diazoxon (for a total of 4LD(50)) administered 24 h later. In contrast, none of the three mice in the control group survived one 2LD(50) dose. These results show that hPON1 in mice functions as a prophylactic and offers significant protection against lethal doses of diazoxon.

Iso-C/3-dimensional neuronavigation versus conventional fluoroscopy for minimally invasive pedicle screw placement in lumbar fusion.

BACKGROUND: Minimally invasive spinal surgery (MISS) has evolved over the past years due to the combination of microsurgery, minimal access strategies and neuronavigation. Percutaneous or mini-open pedicle screw placement is a challenge, especially for surgeons not experienced in the use of biplanar fluoroscopy or stereotactic imaging techniques. The aim of the study was to compare the precision of pedicle screw fixation for lumbar fusion procedures using Iso-C/stereotactic 3D neuronavigation (3D NAV) vs. standard AP/lateral fluoroscopy (2D NAV). METHODS: Our first 42 patients undergoing MISS for one- or 2-level lumbar or lumbosacral fusion procedures for degenerative lumbar pathology were included in this study. Either 3D NAV (n=29) or standard fluoroscopy (n=13) was used to aid screw placement. Demographics, operative time, blood loss, and screw placement accuracy were evaluated. Screw placement was evaluated postoperatively using lumbar CT scanning. Accuracy of 3D NAV was evaluated by comparing intraoperative planning screenshots to postoperative CT placement of screws. RESULTS: There were no significant differences between groups for mean age, gender or intraoperative blood loss. 90.9% of 3D NAV screws and 73.7% of fluoroscopy screws had no pedicle perforation (p=0.04). Intraoperative navigation screenshots accurately predicted pedicle screw placement in 90.9% of cases. There was a positive correlation between 3D NAV accuracy and better screw grade (rs 0.45, p=0.036). CONCLUSIONS: Utilization of 3D NAV for percutaneous or mini-open lumbar screw placement during the early learning curve for MISS was associated with higher screw accuracy. This study demonstrates that the use of 3D navigation can facilitate the learning curve for MISS.

Removal of 241Am from aqueous nitrate solutions by liquid surfactant membrane containing 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester as ion carrier.

A liquid surfactant membrane (LSMs) containing 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester (H(2)A(2)) was tested for the extraction of americium(III) from aqueous nitrate solutions of different compositions. Span 80 a surface-active agent and 0.5M HNO(3) were used as emulsion stabilizer and internal phase respectively in the LSM system. Influence of some important experimental parameters such as pH of the exterior phase, ionic impurities in the exterior phase, concentration of H(2)A(2) and Span80 in liquid membrane phase on the LSM permeation process was systematically studied. The maximum efficiency of Am(III) extraction among group of experiments was 93+/-2% with modified permeability coefficient=1.21+/-0.02min(-1) and the corresponding concentration factor of Am(III) in the receiving phase was 10.5+/-0.2. Extraction of commonly associated fission product elements such as (137)Cs, (152,154)Eu, (90)Sr, (95)Zr, (144)Ce, (95)Nb and (103)Ru was also investigated from feed solution in the exterior phase adjusted at different pH. In a single batch of extraction, more than 90% removal and about 10 times concentration of Am(III) was obtained from uranium and plutonium depleted (process of Plutonium Uranium Recovery by Extraction) waste solution. A complete demulsification of metal loaded emulsion was obtained by chemical using 2-ethylhexanol and physical using freeze thaw method.

Neuronavigation in the minimally invasive presacral approach for lumbosacral fusion.

INTRODUCTION: Intraoperative 3D navigation (3D NAV) is gaining importance in spinal surgery, especially with the advancement of minimally invasive techniques in this field. We hypothesized that 3D NAV may be of benefit in the recently described minimally invasive presacral approach for L4-S1 fusion (AxiaLIF). METHODS: Five patients with refractory low back pain and L5-S1 degenerative disease underwent 3D NAV-assisted placement of a presacral L5-S1 screw. Additionally, a patient recently underwent a two-level AxiaLIF procedure (L4-S1) which was also performed with 3D NAV. Navigation was performed by acquiring intraoperative images via isocentric fluoroscopy and utilizing frameless stereotaxy. Accuracy of 3D NAV was confirmed by overlapping intraoperative images, navigation screenshots, and postoperative CT scans. Outcome was determined by pre- and postoperative VAS (back and leg pain) and ODI. RESULTS: Operative results were reviewed for all six patients and clinical outcomes were retrospectively reviewed for the five L5-S1 procedure patients. Postoperative imaging demonstrated accurate screw placement in comparison to intraoperative C-arm imaging and navigation imaging in all patients. No perioperative complications were encountered. In the five one-level patients, mean VAS (for back and leg pain) and ODI improved significantly at most recent follow-up. CONCLUSION: The minimally invasive presacral approach to L4-L5-S1 fusion can be performed safely and accurately with intraoperative 3D NAV. This is especially the case in two-level AxiaLIF procedures, where computer guidance can provide better planning possibilities for optimal screw trajectory.

Periodic sedimentation in a Stokesian fluid.

We study the sedimentation of two identical but nonspherical particles sedimenting in a Stokesian fluid. Experiments and numerical simulations reveal periodic orbits wherein the bodies mutually induce an in-phase rotational motion accompanied by periodic modulations of sedimentation speed and separation distance. We term these "tumbling orbits" and find that they appear over a broad range of body shapes.

Polyethylene glycosylation prolongs the circulatory stability of recombinant human butyrylcholinesterase.

Previous studies in rodents and non-human primates have demonstrated that pretreatment of animals with cholinesterases could provide significant protection against organophosphate (OP) nerve agent toxicity. Gene delivery/therapy is emerging as an approach to achieve high-level expression of proteins in vivo that are very similar to their native counterparts. Recently, adenoviral (Ad) vectors have proven to be excellent vehicles for delivering genes to cells in vitro and in vivo. In this study, we explored the use of the newly designed AdenoVATOR system for the expression of recombinant human butyrylcholinesterase (rHu BChE) in human embryonic kidney 293A (HEK-293A) cells. In these cells, rHu BChE was expressed as mostly tetrameric form by the simultaneous expression of proline-rich attachment domain. By optimizing the culture conditions, 1.5-2.0 U/ml of rHu BChE could be expressed in HEK-293A cells. Recombinant Hu BChE was purified to homogeneity by ammonium sulfate fractionation followed by affinity column chromatography using procainamide Sepharose and cobalt Sepharose gels. The enzymatic and physico-chemical properties of purified rHu BChE were similar to those of native serum-derived Hu BChE. To determine the suitability of this preparation for use as an antidote against highly toxic nerve agents, its pharmacokinetics were evaluated in mice. Recombinant Hu BChE exhibited a mean residence time of 18.3 h which was 2.5-fold shorter than that observed for native Hu BChE in mice. However, rHu BChE chemically modified with polyethyleneglycol (PEG) displayed a mean residence time of 36.2 h suggesting that PEG-modification can prolong the circulatory stability of rHu BChE. The efficacy of Ad-Hu BChE to induce the production of therapeutic levels of bioscavenger in vivo is under evaluation.

Upregulation of galanin binding sites and GalR1 mRNA levels in the mouse locus coeruleus following chronic morphine treatments and precipitated morphine withdrawal.

The neuropeptide galanin and its receptors are expressed in the locus coeruleus (LC), a brain area associated with drug dependence and withdrawal. Although galanin peptide mRNA levels do not change during withdrawal, it is not known whether galanin receptor levels are regulated following opiate withdrawal. This study demonstrates that galanin binding in the LC is upregulated by chronic-intermittent morphine administration or by precipitated withdrawal, but not by acute morphine treatment, suggesting that increased activity in the LC may be able to regulate galanin binding sites. Moreover, the increase in galanin binding sites seems to be caused by increased transcription or stabilization of the galanin receptor 1 (GalR1) gene, because there is a dramatic increase in mRNA levels following withdrawal in the LC. It is, therefore, possible that the increase in GalR1 could be an adaptive mechanism that leads to regulation of cAMP levels and possibly firing rate of LC neurons.

Centrally administered galanin blocks morphine place preference in the mouse.

Galanin is a neuropeptide with appetitive, antinociceptive and neuroendocrine functions. Galanin and galanin binding sites are present in brain areas that mediate reinforcement, such as nucleus accumbens and ventral tegmental area, as well as locus coeruleus, an area known to be involved in development of drug dependence and withdrawal. This localization, coupled with the observation that there is a strong interaction between morphine and galanin in spinal cord, made it of interest to study whether galanin might have effects on morphine reinforcement. Using the place preference paradigm we found that galanin (1 microg i.c.v.) alone does not possess reinforcing or aversive properties but attenuates the preference conditioned by peripheral administration of morphine (5 mg/kg s.c.). Quantitative receptor autoradiography showed that morphine treatment that could condition a place preference decreased galanin binding in the nucleus accumbens and increased galanin binding in the locus coeruleus. In contrast, acute naltrexone administration increased galanin binding in the nucleus accumbens, suggesting that levels of galanin binding are tonically regulated by opioid receptors in that area. Contrary to what is seen in the spinal cord, these results indicate that galanin and morphine have an antagonistic interaction in the brain that results in attenuation of morphine reinforcement by activation of the galaninergic system.

Solid-phase sequence scanning for drug resistance detection in tuberculosis.

DNA chip arrays hold considerable promise for diagnostic sequencing of polymerase chain reaction (PCR) products. To date, however, arrays have been relatively expensive, complex to use and difficult to interpret, preventing their adaptation to the clinical lab. A moderate density array method has been developed that enables efficient, easy-to-interpret and robust solid-phase PCR product sequencing. Here, the results of Mycobacterium tuberculosis rifampin resistance mutation detection by primer-extension-based sequence scanning of the rpo B gene of M. tuberculosis are presented. Rifampin resistant clinical isolates were identified in as little as 1 h post PCR amplification with visual results detection.

Nested genetic bit analysis (N-GBA) for mutation detection in the p53 tumor suppressor gene.

There is a growing and significant demand for reliable, simple and sensitive methods for repeated scanning of a given gene or gene fragment for detection and characterization of mutations. Solid-phase sequencing by single base primer extension of nested GBATM primers on miniaturized DNA arrays can be used to effectively scan targeted sequences for missense, insertion and deletion mutations. This paper describes the use of N-GBA arrays designed to scan the sequence of a 33 base region of exon 8 of the p53 gene (codons 272-282) encompassing a hot spot for mutations associated with the development of cancer. Synthetic DNA templates containing various missense, insertion and deletion mutations, as well as DNA prepared from pancreatic and biliary tumor cells, were genotyped using the exon 8 arrays.