STEPS - a patient centric and low-cost solution to ensure standards of TB care to patients reaching private sector in India.

BACKGROUND: More than half of the TB patients in India seek care from the private sector. Two decades of attempts by the National TB Program to improve collaboration between the public and private sectors have not worked except in a few innovative pilots. The System for TB Elimination in Private Sector (STEPS) evolved in 2019 as a solution to ensure standards of TB care to every patient reaching the private sector. We formally evaluated the STEPS to judge the success of the model in achieving its outcomes and to inform decisions about scaling up of the model to other parts of the country. METHODS: An evaluation team was constituted involving all relevant stakeholders. A logic framework for the STEPS model was developed. The evaluation focused on (i) processes - whether the activities are taking place as intended and (ii) proximal outcomes - improvements in quality of care and strengthening of TB surveillance system. We (i) visited 30 randomly selected STEPS centres for assessing infrastructure and process using a checklist, (ii) validated the patient data with management information system of National TB Elimination Program (NTEP) by telephonic interview of 57 TB patients (iii) analysed the quality of patient care indicators over 3 years from the management information system (iv) conducted in-depth interviews (IDI) with 33 beneficiaries and stakeholders to understand their satisfaction and perceived benefits of STEPS and (v) performed cost analysis for the intervention from the perspective of NTEP, private hospital and patients. RESULTS: Evaluation revealed that STEPS is an acceptable model to all stakeholders. IDIs revealed that all patients were satisfied about the services received. Data in management information system of NTEP were consistent with the hospital records and with the information provided by the patient. Quality of TB care indicators for patients diagnosed in private hospitals showed improvements over years as proportion of TB patients notified from private sector with a microbiological confirmation of diagnosis improved from 25% in 2018 to 38% in 2020 and the documented treatment success rate increased from 33% (2018 cohort) to 88% (2019 cohort). Total additional programmatic cost (deducting cost for patient entitlements) per additional patient with successful treatment outcome was estimated to be 67 USD. Total additional expense/business loss for implementing STEPS for the hospital diagnosing 100 TB patients in a year was estimated to be 573 USD while additional minimum returns for the hospital was estimated to be 1145 USD. CONCLUSION: Evaluation confirmed that STEPS is a low cost and patient-centric strategy. STEPS successfully addressed the gaps in the quality of care for patients seeking care in the private sector and ensured that services are aligned with the standards of TB care. STEPS could be scaled up to similar settings.

Nanomolar detection of biothiols via turn-ON fluorescent indicator displacement.

The thiol group is known to have a high affinity for gold nanoparticles and is capable of displacing other capping agents. We report a fluorescent indicator displacement technique for the detection of biothiols based on this principle. The displacement of BODIPY from the surface of gold nanoparticles served as a sensitive method for the detection of cysteine, homocysteine, and glutathione under a variety of conditions. It is noteworthy that the turn-ON fluorescence mechanism enabled the differentiation of normal cells from cancer cells because of the inherently higher concentrations of biothiols in the latter.

Crystal structure of (R)-6'-bromo-3,3-dimethyl-3',4'-di-hydro-2'H-spiro-[cyclo-hexane-1,3'-1,2,4-benzo-thia-diazine] 1',1'-dioxide.

In the title compound, C14H19BrN2O2S, the 1,2,4-thia-diazinane ring adopts an envelope conformation with the N atom (attached to the sulfonyl group) as the flap, while the cyclo-hexane ring adopts a chair conformation. The mean plane of the cyclo-hexane ring is almost normal to the benzene ring and the mean plane of the 1,2,4-thia-diazinane ring, making dihedral angles of 70.4 (2) and 71.43 (19)°, respectively. Furthermore, the dihedral angle between the benzene ring and the mean plane of the 1,2,4-thia-diazinane ring is 4.91 (18)°. The mol-ecular structure is stabilized by an intra-molecular C-H⋯O hydrogen bond, which encloses an S(6) ring motif. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds into chains along [10-1], forming a C(6) graph-set motif. These chains are inter-connected via C-H⋯π inter-actions, leading to chains along [-101], so finally forming sheets parallel to (010).

Crystal structure of rat intestinal alkaline phosphatase--role of crown domain in mammalian alkaline phosphatases.

Intestinal alkaline phosphatases (IAPs) are involved in the cleavage of phosphate prodrugs to liberate the drug for absorption in the intestine. To facilitate in vitro characterization of phosphate prodrugs, we have cloned, expressed, purified and characterized IAPs from rat and cynomolgus monkey (rIAP and cIAP respectively) which are important pre-clinical species for drug metabolism studies. The recombinant rat and monkey enzymes expressed in Sf9 insect cells (IAP-Ic) were found to be glycosylated and active. Expression of rat IAP in Escherichia coli (rIAP-Ec) led to ~200-fold loss of activity that was partially recovered by the addition of external Zn(2+) and Mg(2+) ions. Crystal structures of rIAP-Ec and rIAP-Ic were determined and they provide rationale for the discrepancy in enzyme activities. Rat IAP-Ic retains its activity in presence of both Zn(2+) and Mg(2+) whereas activity of most other alkaline phosphatases (APs) including the cIAP was strongly inhibited by excess Zn(2+). Based on our crystal structure, we hypothesized the residue Q317 in rIAP, present within 7 Å of the Mg(2+) at M3, to be important for this difference in activity. The Q317H rIAP and H317Q cIAP mutants showed reversal in effect of Zn(2+), corroborating the hypothesis. Further analysis of the two structures indicated a close linkage between glycosylation and crown domain stability. A triple mutant of rIAP, where all the three putative N-linked glycosylation sites were mutated showed thermal instability and reduced activity.

Preparation and characterization of Ni-doped TiO2 materials for photocurrent and photocatalytic applications.

Different amounts of Ni-doped TiO(2) (Ni = 0.1 to 10%) powders and thin films were prepared by following a conventional coprecipitation and sol-gel dip coating techniques, respectively, at 400 to 800°C, and were thoroughly characterized by means of XRD, FT-IR, FT-Raman, DRS, UV-visible, BET surface area, zeta potential, flat band potential, and photocurrent measurement techniques. Photocatalytic abilities of Ni-doped TiO(2) powders were evaluated by means of methylene blue (MB) degradation reaction under simulated solar light. Characterization results suggest that as a dopant, Ni stabilizes TiO(2) in the form of anatase phase, reduces its bandgap energy, and adjusts its flat band potentials such that this material can be employed for photoelectrochemical (PEC) oxidation of water reaction. The photocatalytic activity and photocurrent ability of TiO(2) have been enhanced by doping of Ni in TiO(2). The kinetic studies revealed that the MB degradation reaction follows the Langmuir-Hinshelwood first-order reaction relationship.

Clinico-radiological evaluation of juxta articular fractures and diaphyseal fractures of upper limb managed with locking compression plating.

BACKGROUND: Locking compression plate (LCP) fixation of juxta articular and diaphyseal fractures of upper limb is a new modality of operative management. METHODS: Twenty-five consecutive cases of juxta articular and diaphyseal fractures of upper limb were fixed with LCP and results were analyzed. RESULTS: All fractures healed in good anatomical position in 6-8 weeks with good functional outcome. CONCLUSION: LCP is a reliable fixation device for juxta articular and diaphyseal fractures of upper limb.

Indicator-based assessment of capacity development for disaster preparedness in the Indian context.

Capacity building and monitoring of response capacity are critical to disaster preparedness. Assessing disaster response capacity is a challenging task in India due to diverse geo-climatic conditions and exposure to different disasters. This paper addresses the absence of a methodological framework to measure multiple aspects of the disaster response capacity of districts in India through indicators. 26 indicators were identified under four factors namely; resources, communication and coordination, budget, and community engagement; anchored on a theoretical framework evolved through literature survey and key informant interviews. Each factor was modelled as a linear function of indicators based on data-sets maintained by district authorities. A Composite Index was constructed as a weighted aggregation of four factors using weightings elicited through Questionnaire Surveys among 151 expert respondents. Weightings were derived through an extension of Technique for Order Preference by Similarity to Ideal Solutions (TOPSIS) to balance the variability in perceptions of respondents. As disasters demand quick response, assessment of response capacity with a fewer number of indicators is desirable. Therefore, a reduced set of critical indicators sensitive to the Indian context were derived through model reduction applying probabilistic and statistical methods- l 2 norm-based sensitivity analysis and coefficient of variation method. Critical indicators are: number of rescue and health service personnel, NGOs, Self-Help-Groups; efficacy of existing SOPs; literacy; and budget options. Robustness of the Composite Index was checked in terms of sensitivity to weightings and model reduction. The critical indicators and the Composite Index would sensitize decision-makers on disaster response capacities across districts.

A case report on probable short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing following vairechanika nasya in Ménière's disease.

A 62 year old woman diagnosed with Ménière's disease, who underwent vairechanika nasya (VN) with shadbindu taila presented with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) like phenomena immediately after the procedure. Rescue measures of abhyanga (local oil massage) and nadi sweda (local fomentation) were administered. Within half an hour the symptoms considerably declined and after 1 hour got completely relieved. The exact symptom disclosure by the patient who herself was a doctor helped in detecting the classic pattern of 'saw tooth phenomena' giving leads into a rare manifestation of probable SUNCT. Naranjo scale yielded zero score and thus the probable causality of VN with shadbindu taila could not be established so as to cause probable SUNCT as an adverse drug reaction (ADR). This case study is not put up for reporting an ADR of VN with shadbindu taila; rather this illustrates an uncommon, yet imperative adverse event of probable SUNCT while undergoing nasya procedure probably due to judgment error while fixing the VN dose in a patient with Ménière's disease. Transparent reporting of such unusual events during panchakarma procedures is necessary so that clinicians can understand, evaluate and take appropriate initiatives to manage them.

Fine-Tuning Plasmon-Molecule Interactions in Gold-BODIPY Nanocomposites: The Role of Chemical Structure and Noncovalent Interactions.

Strong coupling between localized surface plasmons and molecular absorptions leads to remarkable changes in the photophysical properties of dye-loaded metal nanoparticles. Here, we report supramolecular nanocomposites consisting of BODIPY, tryptophan, and gold nanoparticles, and investigate the effect of structural variations on their photophysical properties. Our results indicate that the photostability and photosensitization properties of the nanocomposites depend on the chemical composition of the BODIPY molecules. The singlet oxygen quantum yield of the nanocomposites NC1 (BODIPY, B1 bearing a single methyl group) and NC3 (BODIPY, B3 with 5 methyl and 2 iodo groups) were 0.46 and 0.42, respectively, which were significantly higher compared to their individual components. Ultrafast spectroscopy studies revealed that the migration of photoexcited BODIPY electrons to the plasmonic photoexcitation allowed electron transfer into the singlet oxygen states, thereby leading to efficient generation of singlet oxygen.

A three-component supramolecular nanocomposite as a heavy-atom-free photosensitizer.

Design of photosensitizers capable of generating singlet oxygen is crucial for the success of photodynamic therapy, and biocompatible supramolecular systems are emerging in this area. We report a supramolecular nanocomposite consisting of BODIPY, tryptophan and gold nanoparticles. While the individual components in isolation were inactive, the nanocomposite was found to be photostable and exhibited efficient photosensitization properties.

Protein-protein interactions and nuclear trafficking of coat protein and betaC1 protein associated with Bhendi yellow vein mosaic disease.

Bhendi yellow vein mosaic disease (BYVMD) is caused by a complex consisting of a monopartite begomovirus BYVMV and a satellite DNA beta component. BYVMV represents a new member of the emerging group of monopartite begomoviruses requiring a satellite component for symptom induction. Here we report the results of the transient expression of green fluorescent protein (GFP) fused with the betaC1 and coat protein (CP) coding regions, in the epidermal cells of Nicotiana benthamiana. GFPCP was found to be targeted into the nucleus whereas GFPbetaC1 was localized towards the periphery of the cell. The sub-cellular localization of the betaC1 protein has been compared with that of the CP in yeast cells using a genetic system for detection of protein nuclear import and export. Expression of betaC1 ORF in transgenic N. benthamiana under the control of the Cauliflower mosaic virus 35S promoter produced severe developmental abnormalities in the plant, like distorted stem, leaves and stunting of the plant. We also present the results on the interaction of CP and betaC1 proteins using yeast two hybrid analysis, suggesting a collaborative role in the inter- and intracellular dynamics of BYVMD.

Combined modality treatment of cutaneous T cell lymphoma: results of a 6-year follow-up.

Thirty-nine patients with cutaneous T cell lymphoma (CTCL; including mycosis fungoides or the Sezary syndrome) with no previous treatment other than topical therapy or oral corticosteroids, received total skin electron beam irradiation (TSEB) and either sequential or simultaneous systemic chemotherapy. Median follow-up, measured from the time of initiation of therapy to the time of analysis, is in excess of 6 years and extends to 100+ months. Thirteen patients with stage I disease (limited to skin with no adenopathy) received 3,000 rad total skin electron beam irradiation followed by three 2-week courses of daily intravenous (IV) mechlorethamine. Twenty-six patients with advanced disease (stage II-IV) received 2,400 rad of TSEB and simultaneous chemotherapy with two alternating three-drug regimens: vinblastine, doxorubicin, and bleomycin (VAB) alternating with cyclophosphamide, methotrexate, and prednisone (CMP) administered over 54 weeks. The overall response rate was 92% with 16 of 39 patients (41%) achieving a histologically documented complete response (CR). Stage I patients had a significantly increased CR rate (77%) compared with stage II-IV (P less than .01). The overall 6-year survival was 92% for stage I patients and 26% for stage II-IV patients (23%) (P less than .001). Among ten completely responding stage I patients, six remain alive and disease-free in excess of 72 months. The median disease-free survival is 26 months for completely responding stage II-IV patients (P = .04), but none are continuous disease-free survivors after protocol treatment. We conclude that combined modality treatment can be safely administered and produces prolonged disease-free survival in some stage I patients, but not in more advanced stage patients.

Applicator for use of cesium-137 miniaturized tube sources in the treatment of uterine cervix cancer.

A modified afterloading Kumar Cervical Applicator with a 3 mm diameter central tandem permits insertion of the afterloading tandem into the uterus without need of manual cervical dilatation. While general anesthesia is required for insertion of standard cervical applicators, this is eliminated because the central tandem is no larger than a uterine sound, and the tandem may be painlessly inserted into the uterus while the patient is awake.

Continuous low dose rate brachytherapy with high activity iodine-125 seeds in the management of meningiomas.

The purpose of this study was to evaluate if meningiomas can be effectively treated with brachytherapy using permanent implantation of high activity I-125 seeds. Thirteen patients with intracranial meningiomas were treated by means of permanent stereotactic implantation of one or more high-activity I-125 seeds. The physical characteristics of I-125 enabled us to deliver a minimum tumor dose ranging from 100 Gy to 500 Gy at a low dose rate of 5 cGy to 25 cGy per hr. Indications for this procedure included recurrence after initial surgery or as primary modality of treatment in patients who were not candidates for surgery. All 13 patients are alive at a median follow-up of 25 months. Nine of 13 patients achieved complete resolution of the tumor and in the remaining four, more than 50% reduction in tumor volume was noted at the last follow-up. No late complications were observed. We conclude from this initial data that localized high dose irradiation delivered at a low dose rate using I-125 permanent implantation is an effective, safe, and simple method in the treatment of both recurrent and primary intracranial meningiomas.

Improved results of allogeneic bone marrow transplantation for advanced hematologic malignancy using busulfan, cyclophosphamide and etoposide as cytoreductive and immunosuppressive therapy.

Twenty-four patients between the ages of 8 and 48 years (median 27.5) with high-risk for relapse hematologic malignancy received a marrow transplant from an HLA and MLC compatible sibling donor after chemotherapy with busulfan, 4 mg/kg/day for 4 days by mouth, cyclophosphamide 60 mg/kg/day i.v. for 2 days, and etoposide 60 mg/kg i.v. over 4 h on the first day of cyclophosphamide treatment (BU/CY/VP). Toxicity consisted of mucositis, skin rash, and nausea and vomiting in all patients, transient fever thought to be due to etoposide administration in 16/24 (67%) patients, and clinical veno-occlusive disease (VOD) of the liver in 4/24 (17%). There were nine deaths from causes other than recurrent disease in the first 100 days after transplant and two deaths after day 100, a total transplant mortality of 11/24 (46%). Three patients relapsed, but 10/24 (40%) remain alive and disease free 26-182 weeks (median 60 weeks) from transplant. These results compare favorably with results in a group of 12 similar risk patients treated with total body irradiation (TBI) containing regimens during an overlapping time period. Six of the TBI patients have had persistent or recurrent disease and only two (17%) are currently alive and disease free. The probability of disease persistence or relapse is 67% in the TBI group and 20% in the BU/CY/VP group (p less than 0.02).

Complete response of granulosa cell tumor metastatic to liver after hepatic irradiation: a case report.

A case of granulosa cell tumor of the ovary with extensive metastases to the liver was treated by a course of fractionated hepatic irradiation consisting of 30.00 Gray delivered to the whole liver, followed by boost to gross disease for a total dose of 50.00 Gray given in six weeks. This was followed by complete tumor response with normal liver function tests, and computed tomography demonstrated a normal liver two years after radiotherapy. Liver metastases from granulosa cell tumor of the ovary are unusual, and little information has been published regarding management of this problem.

Transperineal percutaneous I-125 implant of prostate.

Although Iodine-125 seeds for interstitial radiation of prostatic cancer via the retropubic route is an established method of treatment, the retropubic implant technique has disadvantages: inadequate space for proper placement of the needles, possible bleeding from the prostatic venous plexus by the insertion of needles through these veins, and possible wound infection due to inadvertent puncturing of the bladder and/or rectum by the needles. A technique is described whereby Iodine-125 seeds for interstitial radiation are placed into the prostate through the perineum allowing more accurate placement of the seeds, assuring homogenous dose distribution, and decreasing the risk of bleeding and of bacterial contamination.

Permanent high-activity iodine-125 in the management of petroclival meningiomas: case reports.

Two cases of petroclival meningiomas are reported wherein the tumors were completely destroyed without surgical resection or external-beam irradiation by means of permanent stereotactic implantation of one or two high-activity iodine-125 seeds.

Local control of recurrent clival and sacral chordoma after interstitial irradiation with iodine-125: new techniques for treatment of recurrent or unresectable chordomas.

Using new 125I brachytherapy techniques, we were able to deliver safely a tumor volume dose of 16,000 rads to a previous irradiated, large, recurrent sacral chordoma by means of the intraoperative interstitial implantation of 229 low activity 125I seeds and 40,000 rads to a previously irradiated, small, recurrent clival chordoma by means of the transnasal needle implantation of two high activity 125I seeds. Iodine-125 brachytherapy was followed by regression of tumor, lessening of symptoms, and bony recalcification in both cases.

Reversal of visual impairment after interstitial irradiation of pituitary tumor.

Bilateral blindness secondary to a recurrent hemangiopericytoma of the pituitary fossa in a 22-year-old man was corrected by the transsphenoidal implantation of a single high activity iodine-125 seed.