Effect of Novel Laser Shoe Photobiomodulation on Neuropathic Pain and Plantar Pressure Profile in Type 2 Diabetes Mellitus with Peripheral Neuropathy.

BACKGROUND: Photobiomodulation (PBM) or Low-level laser is used to treat diabetic foot complications. The existing method of laser application to the foot did not cover the foot's entire area to improve the foot's microcirculation. Therefore, we have developed a cost-effective Special LASER Shoe device, focusing exclusively on the entire foot region to manage neuropathic pain and other symptoms in individuals with type 2 diabetes mellitus. OBJECTIVE: The main objective of the present study was to evaluate the effect of this newly developed special laser shoe PBM on neuropathic pain and plantar pressure profile in individuals with type 2 diabetes mellitus with neuropathy. METHODS: We included 60 participants with diabetic peripheral neuropathy of both genders and age more than 20 years. Participants were treated with PBM by a specially designed novel Laser Shoe. Outcomes were clinical variables like Vibration Perception Threshold (VPT), Visual Analogue Scale (VAS), Michigan neuropathy screening instrument A&B, Ankle-Brachial Index (ABI), and Static dynamic gait parameters. RESULTS: Participants were with an average age of 62, and the average duration of diabetes was 11 years. Analysis showed a significant difference in VPT, VAS, Michigan neuropathic screening inventory, and ankle-brachial index. (P < 0.05). CONCLUSION: We conclude that Novel laser shoe photobiomodulation using 'Laser Shoe' effectively reduces peripheral neuropathic pain. It is also effective in reducing average and maximum plantar pressure. Reduction in neuropathic pain and improvement in plantar pressure distribution can reduce further complications.

Clinical, laboratory profile and molecular characterization of Orientia tsutsugamushi among fatal scrub typhus patients from Karnataka, India.

BACKGROUND: Scrub typhus is a vector-borne infection caused by the obligate intracellular organism Orientia tsutsugamushi. In some cases, scrub typhus can result in severe complications, multiorgan failure and death. OBJECTIVE: To study the clinical and laboratory profiles of patients who succumbed to scrub typhus. METHODS: A prospective cohort study was conducted from August 2019 through April 2023 on scrub typhus patients admitted to our hospital. Clinical and laboratory parameters of all the patients were recorded, and blood samples were drawn. To confirm scrub typhus, a nested polymerase chain reaction (nPCR) was performed in collected samples. Viable amplicons were sequenced, and phylogenetic analyses were performed to identify infecting genotypes. RESULTS: A total of 261 patients were enrolled. Of these, nine (3.45%) patients succumbed at a median (Interquartile Range) duration of 5 (1.5, 10.5) days after admission. Sepsis with septic shock (9, 100%) and acute kidney injury (AKI) (6, 66%) were noted among the succumbed patients. All the succumbed patients (100%) required intensive care admission, inotropic and ventilatory support. While 5 (55%) patients required dialysis, two (22%) required blood transfusion. Three (33%) patient samples were co-positive for Leptospira IgM, and four (44%) patients had superinfection with Candida tropicalis, multi-drug-resistant (MDR) E. Coli sepsis, pan drug-resistant (PDR) Acinetobacter Baumanii, and Klebsiella pneumoniae. Phylogenetic analysis revealed Orientia tsutsugamushi Japanese Gilliam-variant (JG-v) like (50%), Karp-like (37.5%), and Japanese Gilliam (JG) like (12.5%) strains among succumbed patients. CONCLUSION: Delay in scrub typhus diagnosis can result in severe complications, septic shock, and multisystem organ failure, culminating in death.

Navigating the Solution to Drug Formulation Problems at Research and Development Stages by Amorphous Solid Dispersion Technology.

Amorphous Solid Dispersions (ASDs) have indeed revolutionized the pharmaceutical industry, particularly in drug solubility enhancement. The amorphous state of a drug, which is a highenergy metastable state, can lead to an increase in the apparent solubility of the drug. This is due to the absence of a long-range molecular order, which results in higher molecular mobility and free volume, and consequently, higher solubility. The success of ASD preparation depends on the selection of appropriate excipients, particularly polymers that play a crucial role in drug solubility and physical stability. However, ASDs face challenges due to their thermodynamic instability or tendency to recrystallize. Measuring the crystallinity of the active pharmaceutical ingredient (API) and drug solubility is a complex process that requires a thorough understanding of drug-polymer miscibility and molecular interactions. Therefore, it is important to monitor drug solids closely during preparation, storage, and application. Techniques such as solid-state nuclear magnetic resonance (ssNMR), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy, and dielectric spectroscopy have been successful in understanding the mechanism of drug crystallization. In addition, the continuous downstream processing of drug-loaded ASDs has introduced new automated methods for consistent ASD production. Advanced techniques such as hot melt extrusion, KinetiSol, electro spraying, and electrospinning have gained popularity. This review provides a comprehensive overview of Amorphous Solid Dispersions (ASDs) for oral drug delivery. It highlights the critical challenges faced during formulation, the impact of manufacturing variables, theoretical aspects of drug-polymer interaction, and factors related to drug-polymer miscibility. ASDs have been recognized as a promising strategy to improve the oral bioavailability of poorly water-soluble drugs. However, the successful development of an ASD-based drug product is not straightforward due to the complexity of the ASD systems. The formulation and process parameters can significantly influence the performance of the final product. Understanding the interactions between the drug and polymer in ASDs is crucial for predicting their stability and performance.

Lineage classification and antitubercular drug resistance surveillance of Mycobacterium tuberculosis by whole-genome sequencing in Southern India.

Whole-genome sequencing has created a revolution in tuberculosis management by providing a comprehensive picture of the various genetic polymorphisms with unprecedented accuracy. Studies mapping genomic heterogeneity in clinical isolates of Mycobacterium tuberculosis using a whole-genome sequencing approach from high tuberculosis burden countries are underrepresented. We report whole-genome sequencing results of 242 clinical isolates of culture-confirmed M. tuberculosis isolates from tuberculosis patients referred to a tertiary care hospital in Southern India. Phylogenetic analysis revealed that the isolates in our study belonged to five different lineages, with Indo-Oceanic (lineage 1, n = 122) and East-African Indian (lineage 3, n = 80) being the most prevalent. We report several mutations in genes conferring resistance to first and second line antitubercular drugs including the genes rpoB, katG, ahpC, inhA, fabG1, embB, pncA, rpsL, rrs, and gyrA. The majority of these mutations were identified in relatively high proportions in lineage 1. Our study highlights the utility of whole-genome sequencing as a potential supplemental tool to the existing genotypic and phenotypic methods, in providing expedited comprehensive surveillance of mutations that may be associated with antitubercular drug resistance as well as lineage characterization of M. tuberculosis isolates. Further larger-scale whole-genome datasets with linked minimum inhibition concentration testing are imperative for resolving the discrepancies between whole-genome sequencing and phenotypic drug sensitivity testing results and quantifying the level of the resistance associated with the mutations for optimization of antitubercular drug and precise dose selection in clinics. IMPORTANCE Studies mapping genetic heterogeneity of clinical isolates of M. tuberculosis for determining their strain lineage and drug resistance by whole-genome sequencing are limited in high tuberculosis burden settings. We carried out whole-genome sequencing of 242 M. tuberculosis isolates from drug-sensitive and drug-resistant tuberculosis patients, identified and collected as part of the TB Portals Program, to have a comprehensive insight into the genetic diversity of M. tuberculosis in Southern India. We report several genetic variations in M. tuberculosis that may confer resistance to antitubercular drugs. Further wide-scale efforts are required to fully characterize M. tuberculosis genetic diversity at a population level in high tuberculosis burden settings for providing precise tuberculosis treatment.

Effect of Multifactorial Balance Rehabilitation Program on Risk of Falls and Functional Fitness in Older Adults with Diabetic Peripheral Neuropathy.

BACKGROUND: Increasing age and the added disadvantage of diabetic peripheral neuropathy (DPN) put the individual at a higher risk of falls and reduced functional fitness. However, there is a dearth of literature on multifactorial balance intervention, especially targeting the needs of older adults with DPN. OBJECTIVE: The current study aimed to determine the effect of a multifactorial balance rehabilitation program on fall risk and functional fitness in older adults with DPN. METHODS: In this pre-post experimental study, 30 independently ambulating older adults (71.2 ± 4.70 years) with DPN, who were at risk of falling (timed up and go score ≥ 9.4 seconds), were recruited. Along with the standard care, all the participants received 12 weeks of the multifactorial balance rehabilitation program. RESULTS: Fall risk using the Fullerton Advanced Balance scale and functional fitness using the Senior Fitness Test were measured at baseline and after 12 weeks of the intervention. The intervention reduced the risk of falling score significantly (MD = 6.17, p < .001). All six parameters of functional fitness improved after 12 weeks of intervention. The improvement in lower limb strength (MD = 1.53 times), upper limb strength (MD = 2.48 times), endurance (MD = 16.07 seconds), lower limb flexibility (MD = 2.02 inches), upper limb flexibility (MD = 1.47 inches), and dynamic balance (MD = 1.53 seconds) was statistically significant at p < 0.05. CONCLUSION: This study provided encouraging evidence about the potential of multifactorial balance rehabilitation to reduce the risk of falling and improve functional fitness in older adults with DPN.

Clinical, laboratory, and molecular epidemiology of Orientia tsutsugamushi infection from Southwestern India.

Scrub typhus is a vector borne disease which in a proportion of patients causes multiorgan involvement and death if untreated. Infecting genotype and virulence factors play a role in severity of infection and outcome. The current prospective cohort study was undertaken to elucidate the severity of illness in scrub typhus patients and to identify the circulating genotypes in Karnataka, India. A total of 214 patients of either gender from 9 districts of Karnataka and one patient each from Andhra Pradesh and Kerala, India were enrolled in the study. With a predefined severity criterion, 132 patients were segregated to the severe group. Multi organ involvement was seen in 59 (44.69%) patients. Phylogenetic analysis revealed JG-v like (48.97%), Karp-like (26.53%), JG-like (22.44%), and Kato-like (2.04%) strains in Karnataka. Patients infected with Orientia tsutsugamushi Karp-like strains had respiratory involvement (69.2%), cardiovascular involvement (46.2%) and thrombocytopenia (23.1%) and required higher hospital resource utilization.

Effect of physical form of the therapeutic diet on the behaviour of crossbred calves experimentally infected with foot-and-mouth disease virus.

The oral lesions associated with foot-and-mouth disease (FMD) negatively affect animal behavior, which can adversely impact animal production and welfare. Physical form of a therapeutic diet (TD) can improve the feed intake and wellbeing during the acute phase of FMD. Accordingly, we tested the effect of two physical forms of a previously developed TD on the behavior of calves experimentally infected with FMD virus (FMDV). Crossbred Holstein Friesian male calves of 10-12 months (n = 12) were experimentally infected with a virulent strain of FMDV and were offered a TD enriched with 19% CP and 2.9 Mcal ME/kg for 11 days post-FMDV infection. One group received the TD in mash form (TDM) while the other (n = 6/group) received it in cooked form (TDC). A group of four calves served as uninfected control and were fed TDM. The time spent by the calves on certain behaviours was recorded in a pre-set form from 06:00-18:00 h for 10 days from day 2-11 post-FMDV infection. The data was divided into two sessions. Session 1 (06:00-13:00 h) represented after the offering of TD, while session 2 (13:01-18:00 h) represented the data after offering green fodder. Based on exploratory data analysis, data recorded from day 2-7 post-FMDV infection was included in the final analysis. Linear mixed model was used by fitting treatment, day and their interaction as fixed effects while calf as random effect. Orthogonal contrast was applied by comparing the infected TDM with other two groups. The results revealed that the cooked form of TD improved the ingestion time, resting time, sleeping time and licking time from day 2-7 post-FMDV infection as compared with the infected TDM group. Ingestive behaviour was better in the infected TDC than that of TDM group (p < 0.01). The sleeping time was significantly high in the infected groups as compared to the uninfected TDM group (p < 0.01) till day 6 post-FMDV infection. Daily activities such as licking, standing and resting differed significantly between the infected TDM and TDC groups in session 1, but not in session 2. Urination and defecation did not differ significantly between the infected TDM and TDC groups. It was concluded that cooked form of TD remediated the effects of infection with FMDV as evidenced by improvement in the behaviour of the calves.

Determinants of Adherence to Antihypertensives Among Elderly: A Multifactorial Concern.

Purpose: The aim of the study was to assess the predictors of adherence among elderly on antihypertensives and to examine the difference in adherence among males and females. Patients and Methods: Cross-sectional survey design was adopted for the study. The data were collected from 800 patients of age 60 years and above using demographic proforma, clinical proforma and Morisky Medication Adherence Scale (MMAS-8) with due approval from the institutional ethical clearance committee and written informed consent from the participants. Results: The findings revealed no significant difference in the non-adherence rates among males and females. Number of medications was identified as the major predictor of adherence. Conclusion: Awareness of factors influencing medication adherence is crucial for health professionals to provide appropriate advice for patients to maintain quality health. The findings of the study highlight the importance of nurses' role towards imparting knowledge on hypertension and emphasizing on the importance of adherence to antihypertensives among elderly.

Effectiveness of Extended Infection Control Measures on Methicillin-Resistant Staphylococcus aureus Infection Among Orthopaedic Patients.

Purpose: The purpose of the study was to find the effectiveness of Extended Infection Control Measures (EICM) in reducing the rate of methicillin-resistant Staphylococcus aureus (MRSA) infection among orthopaedic surgery patients. Methods: The study adopted a quasi-experimental design and was conducted in the orthopaedic units of a tertiary care hospital. This study recruited 168 orthopaedic patients and 154 healthcare professionals (HCPs). EICM included hand hygiene, decolonizing the patients and HCPS, staff education, feedback of surveillance data, treatment of high-risk and MRSA-infected patients, having separate equipment for MRSA-infected patients, and appropriate cleaning of patient's unit. Results: The EICM effectively reduced MRSA infection from 21.2 to 6% (p < 0.001). It also resulted in improving the knowledge of HCPs in the prevention and management of MRSA infection (p < 0.001), and all colonized HCPs were successfully (100%) decolonized. Conclusion: EICM is a promising intervention to combat MRSA infection among orthopaedic wards. Hence, it can be executed in orthopaedic wards, thereby improving the treatment quality and reducing the infection-related consequences. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-022-00713-5.

Genome-scale protein interaction network construction and topology analysis of functional hypothetical proteins in Helicobacter pylori divulges novel therapeutic targets.

The emergence and spread of multi-drug resistance among Helicobacter pylori (H. pylori) strain raise more stakes for genetic research for discovering new drugs. The quantity of uncharacterized hypothetical proteins in the genome may provide an opportunity to explore their property and promulgation could act as a platform for designing the drugs, making them an intriguing genetic target. In this context, the present study aims to identify the key hypothetical proteins (HPs) and their biological regulatory processes in H. pylori. This investigation could provide a foundation to establish the molecular connectivity among the pathways using topological analysis of the protein interaction networks (PINs). The giant network derived from the extended network has 374 nodes connected via 925 edges. A total of 43 proteins with high betweenness centrality (BC), 54 proteins with a large degree, and 23 proteins with high BC and large degrees have been identified. HP 1479, HP 0056, HP 1481, HP 1021, HP 0043, HP 1019, gmd, flgA, HP 0472, HP 1486, HP 1478, and HP 1473 are categorized as hub nodes because they have a higher number of direct connections and are potentially more important in understanding HP's molecular interactions. The pathway enrichment analysis of the network clusters revealed significant involvement of HPs in pathways such as flagellar assembly, bacterial chemotaxis and lipopolysaccharide biosynthesis. This comprehensive computational study revealed HP's functional role and its druggability characteristics, which could be useful in the development of drugs to combat H. pylori infections.

Network topology analysis of essential genes interactome of Helicobacter pylori to explore novel therapeutic targets.

The Helicobacter pylori chronic colonization produces a wide range of gastric diseases in the gastric mucosa by abetting inflammation. Amidst coevolution and reorganization of its metabolism with humans, it has become difficult still imperative to understand and prevent its growth. This study focus to explore functional insights into identification of hub proteins/genes by aggregating the behavior of genes connected in a protein-protein interaction (PPI) network. We have constructed a PPI network of 123 essential genes along with 1213 interactions in H. pylori 26695. The degree and other centrality measures analysis assist in identifying the important hub nodes, which are top-ranked proteins. A total of nine proteins (recA, guaA, dnaK, rpsB, rplQ, rpmA, rpmC, rpmF, and rpsE) were obtained with high degree (k), betweenness centrality (BC) value. Gene ontology analysis reveals 8, 5 and 3 GO terms correspond to biological processes, cellular components and molecular function respectively. Gene complexes of hypothetical proteins (HPs) were related to aminoacyl-tRNA biosynthesis, biosynthesis of secondary metabolites, bacterial secretion system and protein export. The MCODE analysis revealed that protein from module M1, M3 and M6 include the proteins which have highest degree and BC values. It is noteworthy to mention that the bifunctional GMP synthase/glutamine amidotransferase protein (guaA), molecular chaperon (dnaK), recombinase A (recA) constitute as hub proteins. As a result, these genes are considered as network hub nodes that might be used as therapeutic targets. Our analysis affords a detailed understanding of the molecular process and pathways regulated by the essential genes in H. pylori 26695.

Short-term effect of foot-and-mouth disease (FMD) vaccination on the milk yield in the Deoni and crossbred cows.

Biannual vaccination of the cattle with inactivated foot-and-mouth disease (FMD) vaccine is the control strategy in endemic countries. Reduction in the milk yield is one of the main reasons for poor compliance of the cattle owners to FMD vaccination. As it can adversely affect the herd immunity, the present study aimed to quantify the losses in the milk yield post-FMD vaccination. Retrospective data on the milk yield (kg) recordings, days in milk, parity, and age at vaccination of the Deoni and crossbred cows were collected from 10 days before (-10) to 10 days after (+10) FMD vaccination (dpv). Days in milk were categorized into three stages of lactation for Deoni and crossbred cows. Age (month) was categorized into four classes. Least squares means of the milk yield were generated after adjusting for year, age, parity, and stage of lactation. Based on exploratory data analysis, the corrected milk yield records from -2 to +2 dpv for 5 years comprising 614 data points on Deoni cows (n=54) and 488 data points on crossbred cows (n=55) were used for the final analysis. Because of the correlated errors on the corrected milk yield, linear mixed model ANOVA was done by fitting dpv as fixed effect and cow as random effect, and the results revealed the effect of dpv was non-significant (P>0.05) in either breed. With respect to dpv 0, a marginal reduction of 90 g in the corrected milk yield in the Deoni cow was recorded on dpv 1, while the reduction was about 360 g on dpv 0 as compared dpv -1 in the crossbred cow. It was concluded that FMD vaccination caused a transient non-significant reduction in the milk yield in the Deoni and crossbred cows.

Impact of multimodal interventions on medication nonadherence among elderly hypertensives: a randomized controlled study.

Purpose: The study was conducted to investigate the effects of multimodal interventions on medication nonadherence, quality of life (QoL), hypertension (HTN), self-efficacy, and clinical outcome in terms of blood pressure (BP) among elderly people with HTN. Methods: An experimental design using a randomized controlled trial was adopted (N=80+80). The experimental group received multimodal interventions and the control group received routine care. Both groups were followed up at baseline and at 3 and 6 months. The data collection tools of demographic and clinical proforma, structured knowledge questionnaire on HTN (r=0.84), Revised Medication Adherence Self-Efficacy Scale (r=0.94), Morisky Medication Adherence Scale (r=0.83), World Health Organization Quality of Life-BREF scale (r=0.87), and digital BP apparatus were used. Necessary administrative permission was obtained for the study. Results: The study results proved that nurse-led multimodal interventions led to an improvement in medication adherence [F(1.75,214.30)=774.18, p<0.001], knowledge on HTN [F(2,244)=43.83, p<0.001], and self-efficacy [F(1,122)=3.99, p=0.04] of elderly people on antihypertensives over a period of 6 months. Overall QoL did not exhibit any statistically significant improvement, and no statistically significant reductions in the systolic BP (SBP) and diastolic BP (DBP) scores were obtained (p>0.05) in the experimental group over a period of 6 months. However, the clinical significance of multimodal interventions for improvements in medication adherence, QoL, knowledge on HTN, and self-efficacy was more favorable compared with the reduction in SBP and DBP scores. Conclusion: Nurses play a crucial role in improving medication adherence among elderly people with HTN. Trial details: Ethical clearance was obtained (IEC no. KH IEC 253/2012) from the Institutional Ethical Committee of Manipal University, Manipal, and the study was conducted in accordance with the Declaration of Helsinki. The study is registered under Clinical Trials Registry of India (CTRI/2017/04/008405). Informed consent was obtained from participants, and the confidentiality of information was assured.

Photobiomodulation therapy in neuroischaemic diabetic foot ulcers: a novel method of limb salvage.

OBJECTIVE: Low-level laser therapy (also known as photobiomodulation therapy, PBMT) promotes accelerated healing of diabetic foot ulcers (DFUs), thereby preventing the risk of future complications and amputation. The aim of this study was to determine the effect of PBMT, with structured, graded mobilisation and foot care, on DFU healing dynamics. METHOD: Patients diagnosed with type 2 diabetes, diabetic peripheral neuropathy and presenting with a chronic neuroischaemic DFU, were treated with PBMT using scanning and non-contact probe methods. The DFU was clinically observed and the area measured every seven days until complete healing. Neuropathic parameters were also measured. The PBMT was administered until complete closure of the DFU and patients also undertook a programme of graded mobilisation. RESULTS: A total of 17 participants were recruited, with a mean age of 69±8 years, and a mean duration of diabetes of 13±5 years. Mean complete closure time was 26±11days. In addition, a mean reduction of the semi-quantitative vibration pressure threshold from 49±2 volts to 20±4 volts was observed in all participants. CONCLUSION: PBMT can be effectively used as a treatment mode for neuroischaemic DFUs in patients with type 2 diabetes. Graded mobilisation with focused foot care could improve the function of people living with type 2 diabetes with a chronic DFU.