From nature's bounty to drug discovery: Leveraging phytochemicals and molecular approaches to combat multi-drug-resistant (MDR) tuberculosis.

A large number of people annually lose their lives to tuberculosis (TB), which is an age-old disease caused by the Mycobacterium tuberculosis. The global spread of TB is a concern for all regions. The south-east Asian region recorded 46% of all new TB cases in 2021, followed by the African and western Pacific regions with 23% and 18%, respectively. Researchers are always searching at natural substances for potential alternative therapeutics to tackle the worrisome growth in multi-drug-resistant (MDR) tuberculosis due to the high costs associated with developing new treatments and unfavourable side effects of currently used synthetic pharmaceuticals. Phytochemicals show promising results as a future health aid due to their multi-targeting ability on pathogen cells. In the search for new drug leads, the Ayurvedic and Siddha medical systems have made an extensive use of ethnomedicinal tools, including the use of plants like Amalaki (Emblica officinalis Gaertn.), Guduchi (Tinospora cordifolia willd.), Sariva (Hemidesmus indicus R.Br.), Kustha (Saussurea lappa Falc.), turmeric (Curcuma longa Mal.) and Green tea (Camellia sinensis Linn.). These sources are high in flavonoids, polyphenols, tannins and catechins, has been shown to reduce the risk of TB. In this overview, we look at how natural sources like plants, algae and mushrooms have helped researchers to find new drug leads, and how to back these natural sources through mapping the molecular approaches and other approaches has helped them to defeat MDR.

Development of Consensus Recommendations on the Management of Vitiligo and the Role of Decapeptide in Vitiligo by the Delphi Method.

Background: Treatment of vitiligo is still a challenge in dermatology. Literature is sparse on the definitive clinical role of basic fibroblast growth factor (bFGF) in vitiligo patients. Aims: We decided to generate a consensus in an attempt to answer some critical questions related to the management of vitiligo and the role of bFGF. Materials and Methods: A Delphi method among 21 experts across India was conducted. A consensus (agreement was 75% or greater) was taken on 27 statements on the prevalence, epidemiology, and treatment of vitiligo and the role of bFGF in the management of vitiligo. The consensus process was completed after two rounds. Results: Topical corticosteroid therapy is the first-line therapy for vitiligo; however, its adverse effects are widely known, especially in sensitive areas. Topical calcineurin inhibitors are preferred in stable vitiligo of the face, neck, genitals, or intertriginous regions as an alternative to topical corticosteroids. Topical bFGF is a relatively newer therapy with a promising role in stable vitiligo. bFGF is safe and effective in inducing repigmentation of vitiligo lesions. Combination therapy of bFGF with other topical therapies, phototherapy, and surgical procedures can be beneficial in patients of vitiligo. Conclusion: This consensus would complement the currently available literature on bFGF and help the practitioner to recognize the unmet need in the treatment of vitiligo.

A Real-World, Non-interventional Indian Study Evaluating Intensive Plant-Based Butter Moisturizing Cream in Psoriasis.

INTRODUCTION: Psoriasis is estimated to affect 0.44-2.8% of the Indian population. Moisturizers are a key adjuvant psoriasis treatment strategy, but data regarding their effectiveness, safety and compliance pattern in an Indian context are lacking. Hence, this real-world study on an intensive plant-based butter moisturizing cream (Venusia ® Max) was conducted among Indian patients with psoriasis. METHODS: This was an observational, patient-reported outcomes (PRO) study in patients with psoriasis aged 18-75 years who were prescribed the cream in routine clinical practice, as per clinician's discretion, over 4 weeks. The primary outcome measure was improvement from baseline in quality of life assessed using the Dermatology Quality of Life Index (DLQI) at 4 weeks of the study period. The secondary outcome measures were improvement in dryness using the Dry Skin/Ichthyosis Area and Severity Index (DASI) score at 4 weeks, safety and compliance. The DLQI and DASI scores were recorded by the clinicians at baseline and after 2 (optional) and 4 weeks of starting the cream. Safety was assessed throughout the study. RESULTS: The study included 400 patients from 9 outpatient dermatology centers across India. Of 400 patients, 384 completed the study. A significant reduction in both the mean DLQI score (66.7%; p < 0.001) and mean DASI score (84.6%; p < 0.001) was observed at week 4 after starting the cream vs. baseline in the overall population. Overall, the cream showed a good safety and compliance profile during the study period. There were no serious adverse events or deaths. CONCLUSIONS: The evidence from the PRO study suggests that use of the intensive plant-based butter moisturizing cream in a real-world scenario has a noticeable impact on improving the quality of life and reducing the skin dryness associated with psoriasis over 4 weeks. The moisturizing cream may serve as a valuable adjuvant treatment option for the management of psoriasis. TRIAL REGISTRATION NUMBER: CTRI/2017/03/008023. FUNDING: Dr. Reddy's Laboratories Ltd.

Real-World, Non-Interventional, Observational Study of Hydroxyzine Hydrochloride in Chronic Pruritus: a Prospective, Non-Comparative Study.

INTRODUCTION: Although hydroxyzine is widely used for symptom relief in pruritus, its clinical safety and efficacy data in the Indian setting are scarce. We conducted a study to assess the effectiveness and tolerability of hydroxyzine in the management of Indian patients with chronic pruritus in a real-world setting. METHODS: This was a prospective, observational, patient-reported outcomes (PRO) study in patients with chronic pruritus due to dermatological causes treated with hydroxyzine as per the clinician's discretion for a period of up to 12 weeks. The primary outcome was improvement in quality of life from baseline, assessed using the 10-point Dermatology Quality of Life Index (DLQI) at week 12 of the study period. Secondary outcomes were improvement in the pruritus scores (5-D itch scale) at 12 weeks, improvements in the DLQI and 5-D itch scores at 2, 4 and 8 weeks and safety. RESULTS: The study included 400 patients (179 males, 221 females) from 7 dermatology centres across India. Of the 400 patients recruited, 391 patients completed at least 2 weeks of treatment. There was significant (p < 0.0001) improvement from baseline in the DLQI scores and 5-D itch scores at 2, 4, 8 and 12 weeks; 189/391 (48.34%) patients had symptom relief leading to early termination. Overall, the treatment was well tolerated with a total of 11 mild-to-moderate adverse events reported during the study, which included dizziness, constipation, drowsiness, dry mouth and sedation. All events resolved without any intervention. There were no serious adverse events. CONCLUSION: This real-world, observational, PRO study demonstrates that hydroxyzine significantly improves symptoms of pruritus and quality of life in patients with chronic pruritus due to dermatological causes over 12 weeks. Despite the sedating potential of the drug, hydroxyzine is well tolerated in real-world settings. TRIAL REGISTRATION: CTRI/2017/06/008847. FUNDING: Dr. Reddy's Laboratories.

Endovascular management of iatrogenic renal vascular injuries complicating percutaneous nephrolithotomy: Role of renal angiography and embolization; an analysis of 159 cases.

OBJECTIVE: To describe the use of renal angiography in the detection of renal vascular injuries following percutaneous nephrolithotomy and to assess the efficacy of endovascular management of these complications. MATERIALS AND METHODS: This was a retrospective review of 159 consecutive patients over a period of 12 years from 2005 to 2016 who presented with significant post nephrolithotomy hemorrhage and who were evaluated by renal angiography as a first-line diagnostic study, followed by embolization of identified renal vascular injuries in the same session. The parameters assessed for each patient included type of renal vascular injury identified, type of embolic material and therapeutic outcome. RESULTS: Renal vascular lesions identified in 119 patients were treated with embolization with complete resolution of hemorrhage, no further clinical deterioration and preservation of renal function. CONCLUSIONS: Renal vascular injury is a rare complication of percutaneous nephrolithotomy. Early renal angiography and selective embolization can play an integral diagnostic and therapeutic role.

Role of imprint/exfoliative cytology in ulcerated skin neoplasms.

Imprint cytology is a method of studying cells by taking an imprint from the cut surface of a wedge biopsy specimen or from the resected margins of a surgical specimen. It is rapid, simple and fairly accurate. Exfoliative cytology is an offshoot from the imprint cytology where in cells obtained from the surface of ulcers, either by scrape or brush, are analyzed for the presence of malignant cells. We undertook this study to see the role of imprint/exfoliative cytology in the diagnosis of ulcerated skin neoplasm and to check the adequacy of resected margins intra-operatively. This was a prospective investigative study conducted from September 2003 to July 2005. All patients presenting to surgical clinic with ulcerated skin and soft tissue tumours were included in the study. A wedge biopsy obtained from the ulcer and imprint smears were taken from the cut surface. Exfoliative cytology was analyzed from the surface smears. Wedge biopsy specimen was sent for histopathological (HPE) examination. The cytology and HPE were analyzed by a separate pathologist. Imprint cytology was also used to check the adequacy of resected margins in case of wide excision. This was compared with final HPE. Total of 107 patients was included in the present study and 474 imprint smears were done, with an average of 4.43 slides per lesion. Out of 59 wide excision samples, 132 imprint smears were prepared for assessing resected margins accounting for an average of 2.24 slides per each excised lesion. On combining imprint cytology with exfoliative cytology the overall sensitivity, specificity and positive predictive value were 90.38 %, 100 % and 90.38 % respectively. Only one out of 59 cases had a positive resected margin which was not picked by imprint cytology. Imprint cytology can be used for rapid and accurate diagnosis of various skin malignancies. It can also be used to check the adequacy of the resected margin intraoperatively.

A simplified baseband prefilter model with adaptive Kalman Filter for ultra-tight COMPASS/INS integration.

COMPASS is an indigenously developed Chinese global navigation satellite system and will share many features in common with GPS (Global Positioning System). Since the ultra-tight GPS/INS (Inertial Navigation System) integration shows its advantage over independent GPS receivers in many scenarios, the federated ultra-tight COMPASS/INS integration has been investigated in this paper, particularly, by proposing a simplified prefilter model. Compared with a traditional prefilter model, the state space of this simplified system contains only carrier phase, carrier frequency and carrier frequency rate tracking errors. A two-quadrant arctangent discriminator output is used as a measurement. Since the code tracking error related parameters were excluded from the state space of traditional prefilter models, the code/carrier divergence would destroy the carrier tracking process, and therefore an adaptive Kalman filter algorithm tuning process noise covariance matrix based on state correction sequence was incorporated to compensate for the divergence. The federated ultra-tight COMPASS/INS integration was implemented with a hardware COMPASS intermediate frequency (IF), and INS's accelerometers and gyroscopes signal sampling system. Field and simulation test results showed almost similar tracking and navigation performances for both the traditional prefilter model and the proposed system; however, the latter largely decreased the computational load.

GEDAS - Gene Expression Data Analysis Suite.

UNLABELLED: Currently available micro-array gene expression data analysis tools lack standardization at various levels. We developed GEDAS (gene expression data analysis suite) to bring various tools and techniques in one system. It also provides a number of other features such as a large collection of distance measures and pre-processing techniques. The software is an extension of Cluster 3.0 (developed based on Eisen Lab's Cluster and Tree View software). GEDAS allows the usage of different datasets with algorithms such as k-means, HC, SVD/PCA and SVM, in addition to Kohonen's SOM and LVQ. AVAILABILITY: http://gedas.bizhat.com/gedas.htm.

Exploring cellular activity of locked nucleic acid-modified triplex-forming oligonucleotides and defining its molecular basis.

Triplex-forming oligonucleotides (TFOs), as DNA-binding molecules that recognize specific sequences, offer unique potential for the understanding of processes occurring on DNA and associated functions. They are also powerful DNA recognition elements for the positioning of ubiquitous molecules acting on DNA, such as anticancer drugs. A prerequisite for further development of DNA code-reading molecules including TFOs is their ability to form a complex in a cellular context: their binding affinities must be comparable to those of DNA-associated proteins. To reach this goal, chemically modified TFOs must be developed. In this work, we present triplex-forming properties (kinetics and thermodynamics) and cellular activity of G-containing locked nucleic acid-modified TFOs (TFO/LNAs). In conditions simulating physiological ones, these TFO/LNAs strongly enhanced triplex stability compared with the non-modified TFO or with the pyrimidine TFO/LNA directed against the same oligopyrimidine.oligopurine sequence, mainly by decreasing the dissociation rate constant and conferring an entropic gain. We provide evidence of their biological activity by a triplex-based mechanism, in vitro and in a cellular context, under conditions in which the parent phosphodiester oligonucleotide did not exhibit any inhibitory effect.

Methicillin-resistant Staphylococcus aureus in community-acquired pyoderma.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial pathogen. It can also cause community-acquired infections. Indian reports about MRSA in community-acquired infections are rare. AIM: To evaluate the rate of MRSA in community-acquired pyoderma and the nasal colonisation with S. aureus in such patients. METHODS: Two hundred and fifty patients with community-acquired pyoderma, who attended outreach camps around Mangalore, south India between January 2000 and July 2001, were studied. Swabs collected from the skin lesions and anterior nares were inoculated onto blood agar and MacConkey's agar. Antimicrobial sensitivity testing was performed using Kirby-Bauer disk diffusion, agar dilution, and agar screen. RESULTS: Of 250 pyoderma cases, S. aureus was isolated from 202 (80.8%) patients. Twenty-two (10.9%) S. aureus isolates were methicillin resistant, 179 (88.6%) were resistant to penicillin, and 114 (56.4%) were resistant to erythromycin. S. aureus colonization in the anterior nares was observed in 136 (54.4%) cases, 11.8% of which were MRSA. Antibiograms of clinical isolates of S. aureus matched with nasal isolates in 99 (49%) cases. CONCLUSION: The emergence of MRSA in the community is a warning. A high nasal carriage rate may contribute to recurrent pyoderma. A correct antimicrobial policy and the avoidance of inappropriate antimicrobial usage are mandatory to reduce the spread of MRSA in the community.