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Tuberculosis is the second leading infectious killer after coronavirus disease 2019 (COVID-19). Standard antitubercular drugs exhibit various limitations like toxicity, long treatment regimens, and lack of effect against dormant and drug-resistant organisms. Here, we report that all- trans -retinoic acid (ATRA) improves Mycobacterium tuberculosis clearance in mice during treatment with the antitubercular drug isoniazid. Interestingly, ATRA promoted activities of lysosomes and mitochondria, and production of various inflammatory mediators in macrophages. Furthermore, ATRA upregulated the expression of genes of lipid metabolism pathways in macrophages. We demonstrated that ATRA activated the MEK/ERK pathway in macrophages in vitro and MEK/ERK and p38 MAPK pathways in mice. Finally, ATRA induced both Th1 and Th17 responses in lungs and spleens of M. tuberculosis -infected mice. Together, these data indicate that ATRA provides beneficial adjunct therapeutic value by modulating MEK/ERK and p38 MAPK pathways and thus warrants further testing for human use. [ABSTRACT FROM AUTHOR]

Cancer stem cell marker CD44 is a cell-surface glycoprotein which is involved in various cellular functions such as cell–cell interactions, cell adhesion, haematopoiesis and tumour metastasis. The CD44 gene transcription is partly activated by beta-catenin and Wnt signalling pathway, the later pathway being linked to tumour development. However, the role of CD44 in oral squamous cell carcinoma (OSCC) is not well understood. We investigated the expression of CD44 in peripheral circulation, tumour tissues of oral cancer patients and oral squamous cell carcinoma cell lines by ELISA and quantitative (q)-RTPCR. Relative CD44s mRNA expression was significantly higher in peripheral circulation (p = 0.04), tumour tissues (p = 0.049) and in oral cancer cell lines (SCC4, SCC25 p = 0.02, SCC9 p = 0.03). Circulating CD44total protein levels were also significantly (p < 0.001) higher in OSCC patients that positively correlated with increasing tumour load and loco-regional spread of the tumour. The circulating tumour stem cell marker CD44 appears to be a potent indicator of tumour progression and may be useful for developing suitable therapeutics strategies for patients with oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is one of the most common (90%) types of oral carcinomas in the world. It is the 2nd most common and 3rd deadliest cancer in India. The lack of early detection marker is one of the major causes of worst prognosis. The vimentin belongs to intermediate filament family proteins which plays significant role in maintaining cellular integrity. Over-expression of vimentin has been widely reported in many epithelial cancers however the information regarding its prevalence in the oral cancers still needs further scientific intervention. The expression level of circulating vimentin protein in serum samples (n = 30) of oral submucous fibrosis (OSMF), OSCC patients and healthy controls were measured by performing ELISA. The serum level of vimentin was significantly higher in OSMF (p < 0.01) and OSCC (p < 0.003) patients as compared to healthy subjects. The circulating vimentin levels showed a gradual increase with increasing disease status (normal < OSMF < OSCC). Circulatory levels of vimentin may ba useful indicator of disease progression and as a suitable target for therapeutic intervention of oral submucous fibrosis and oral carcinoma. [ABSTRACT FROM AUTHOR]

The genetic diversity among 33 cluster bean genotypes was evaluated under rain fed conditions during kharif 2012. The genetic material exhibited wide range of genetic diversity for all the twelve characters investigated. All the genotypes were grouped into seven different clusters. Cluster I was the largest comprising 11 genotypes followed by cluster II consisting of 8 genotypes, cluster V (5), cluster VI (4), cluster IV (2), cluster VII (2), cluster III (1 ). The clustering pattern indicated that there was lot of diversity among the genotypes and there was no relationship between the genetic and geographical diversity of the genotypes, but the distribution of the genotypes was random and independent. The intra cluster distance was highest at cluster VI followed by cluster I and II over others. The higher magnitude of inter-cluster distance were observed between cluster IV and VI (7.644) followed by cluster IV and V (7.582); cluster II and IV (6.802); cluster IV and VII (6.682); cluster I and IV (6.569); cluster II and VII (6.052); cluster III and IV (5.861) and cluster II and V (5.834) indicating wider genetic diversity between the genotypes in these clusters. The uses of genotypes in hybridization from these clusters having most of the desirable characters are likely to produce more transgressive segregants. It is suggested that genotypes belonging to the clusters I, IV and VII having diversified growth habit may be crossed with genotypes belonging to cluster II as they may be expected to produce good segregants with high yield potential. [ABSTRACT FROM AUTHOR]

Precision agriculture is crucial for ensuring food security in a growing global population. Nutrients, their presence, concentration, and effectiveness, are key components in data-driven agriculture. Assessing macro and micro-nutrients, as well as factors such as water and pH, helps determine soil fertility, which is vital for supporting healthy plant growth and high crop yields. Insufficient soil nutrient assessment during continuous cropping can threaten long-term agricultural viability. Soil nutrients need to be measured and replenished after each harvest for optimal yield. However, existing soil testing procedures are expensive and time-consuming. The proposed research aims to assess soil nutrient levels, specifically nitrogen and phosphorus concentrations, to provide critical information and guidance on restoring optimal soil fertility. In this research, a novel chip-level colorimeter is fabricated to detect the N and P elements of soil onto a handheld colorimeter or spectrophotometer. Chemical reaction with soil solution generates color in the presence of nutrients, which are then quantitatively measured using sensors. The test samples are collected from various farmlands, and the results are validated with laboratory analysis of samples using spectrophotometers used in laboratories. ANOVA test has been performed in which F value > 1 in our study indicates statistically significant differences between the group means. The alternate hypothesis, which proposes the presence of significant differences between the groups, is supported by the data. The device created in this paper has crucial potential in terms of environmental and biological applications. [ABSTRACT FROM AUTHOR]

Directly Observed Treatment Short-course (DOTs), is an effective and widely recommended treatment for tuberculosis (TB). The antibiotics used in DOTs, are immunotoxic and impair effector T cells, increasing the risk of re-infections and reactivation. Multiple reports suggest that addition of immune-modulators along with antibiotics improves the effectiveness of TB treatment. Therefore, drugs with both antimicrobial and immunomodulatory properties are desirable. N1-(Adamantan-2-yl)-N2-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]ethane-1,2-diamine (SQ109) is an asymmetric diamine derivative of adamantane, that targets Mycobacterial membrane protein Large 3 (MmpL3). SQ109 dissipates the transmembrane electrochemical proton-gradient necessary for cell-wall biosynthesis and bacterial activity. Here, we examined the effects of SQ109 on host-immune responses using a murine TB model. Our results suggest the pro-inflammatory nature of SQ109, which instigates M1-macrophage polarization and induces protective pro-inflammatory cytokines through the p38-MAPK pathway. SQ109 also promotes Th1 and Th17-immune responses that inhibit the bacillary burden in a murine model of TB. These findings put forth SQ109 as a potential-adjunct to TB antibiotic therapy. The adamantine derivative SQ109 induces protective pro-inflammatory cytokines and promotes Th1 and Th17-immune responses that inhibit bacterial burden in a tuberculosis mouse model. [ABSTRACT FROM AUTHOR]

Background: Renal resistive index is a recognised and early indicator of type II diabetes mellitus-related cardiovascular risk as well as diabetic nephropathy. Aim: To determine the relationship between resistive index and estimated glomerular filtration rate of subjects with diabetic nephropathy and to determine the frequency of occurrence of high resistive index in subjects with diabetic nephropathy. Material and methods: The present cross sectional study entitled to study the correlation of renal resistive index and estimated glomerular filtration rate in diabetic nephropathy was conducted on 50 patients of type 2 diabetes mellitus with the diabetic nephropathy with reduced renal function (stage G1-G5), attending outdoor department or admitted in Medicine Department of Guru Nanak Dev Hospital, attached to Government Medical College, Amritsar. Results: Out of 50 patients, females comprise 22 (44%) and males 28 (56%). The mean egfr in patients with RI <0.7 was 28.5 and in patients with >0.7 was 20.1. The difference was significant (P< 0.05). The mean RI in patients with CKD stage 2 was 0.65, in patients with stage 3was 0.69, in patients with stage 4 was 0.74 and in patients with stage 5 was 0.78. A significant difference was observed (P< 0.05). Conclusion: Renal RI could be a useful complementary test for the evaluation of functional alterations in renal hemodynamics in the early stages of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Ipsilateral Hip and Femoral Shaft Fractures Treated With Intramedullary Nails" by M. Shantharam Shetty and colleagues.

Diagnostic programs and second opinion clinics have grown and evolved in the recent years to help patients with rare, puzzling, and complex conditions who often suffer prolonged diagnostic journeys, but there is a paucity of literature on the clinical characteristics of these patients and the efficacy of these diagnostic programs. This study aims to characterize the diagnostic journey, case features, and diagnostic outcomes of patients referred to a team-based second opinion clinic at Stanford. Retrospective chart review was performed for 237 patients evaluated for diagnostic second opinion in the Stanford Consultative Medicine Clinic over a 5 year period. Descriptive case features and diagnostic outcomes were assessed, and correlation between the two was analyzed. Sixty-three percent of our patients were women. 49% of patients had a potential precipitating event within about a month prior to the start of their illness, such as medication change, infection, or medical procedure. A single clear diagnosis was determined in 33% of cases, whereas the remaining cases were assessed to have multifactorial contributors/diagnoses (20%) or remained unclear despite extensive evaluation (47%). Shorter duration of illness, fewer prior specialties seen, and single chief symptom were associated with higher likelihood of achieving a single clear diagnosis. A single-site academic consultative service can offer additional diagnostic insights for about half of all patients evaluated for puzzling conditions. Better understanding of the clinical patterns and patient experiences gained from this study helps inform strategies to shorten their diagnostic odysseys. [ABSTRACT FROM AUTHOR]

The purpose of the present study is to present our experience and clinical results with surgical technique of discectomy and facet joint fusion. Our goal was to achieve pain free and stable back (segmental stability) after lumbar disc surgery and to assess the status of fusion and its relationship with clinical results. The proposed study is a prospective clinical study of low back pain/leg pain due to prolapse intervertebral disc treated with discectomy with facet joint fusion (using titanium screws) A case of symptomatic disc prolapse not improving on at least 6 weeks of conservative management. Clinical and radiological follow up was done up to average of five years. After laminectomy and disc removal. Denude the facet joint cartilage with help of fine curved curette and fine slivers of bone graft taken from spinous processes are impacted into facet joint space after distracting them with help of spreader. Titanium partially threaded cancellous screws with 2.7 mm drill bit without taping. Complete fusion across bilateral facets was achieved in 56.2% levels. Partial fusion was achieved in 34.3% levels. No fusion at all was seen in only 3 levels (9.3%). On applying chi square test between the 4 groups, chi square value came to be 44.92 with P value of <0.001. This implied that Post-op Oswestry score and clinical results have statistically significant association with status of fusion This study demonstrates that facet screw fixation has multiple advantages. The technique is not only easy to implement by placing a small screw through a facet joint without any excessive retraction of neural structures and any distraction of posterior elements thus preserving the segmental stability. It produces excellent clinical results that are comparable to other exhaustive surgical procedures and more bulky spinal instrumentation systems [ABSTRACT FROM AUTHOR]

Summary: Background: Although the proportion of ethnicities representing under‐represented minorities in medicine (URM) in the general population has significantly increased, URM enrolment in medical schools within the USA has remained stagnant in recent years. Methods: This study sought to examine the effect of an immersion in community medicine (ICM) programme on secondary school students’ desire to enter the field of medicine and serve their communities. The authors asked all 69 ICM alumni to complete a 14‐question survey consisting of six demographic, four programme and four career questions, rated on a Likert scale of 1 (completely disagree) to 5 (completely agree), coupled with optional free‐text questions. Data were analysed using GraphPad prism and nvivo software. Results: A total of 61 students responded, representing a response rate of 88.4 per cent, with a majority of respondents (73.7%) from URM backgrounds. An overwhelming majority of students agreed (with a Likert rating of 4 or 5) that the ICM programme increased their interest in becoming a physician (n = 56, 91.8%). Students reported shadowing patient–student–physician interactions to be the most useful (n = 60, 98.4%), and indicated that they felt that they would be more likely to lead to serving the local community as part of their future careers (n = 52, 85.3%). Of the students that were eligible to apply to medical school (n = 13), a majority (n = 11, 84.6%) have applied to medical school. URM enrolment in medical schools within the USA has remained stagnant in recent years Discussion: Use of a community medicine immersion programme may help encourage secondary students from URM backgrounds to gain the confidence to pursue a career in medicine and serve their communities. Further examination of these programmes may yield novel insights into recruiting URM students to medicine. [ABSTRACT FROM AUTHOR]

Introduction: Two aspects of the smile: the Smile Arc (SA) and Buccal Corridors (BC) have been the interest of the orthodontist in recent years. Aim: The present study was undertaken to evaluate the influence of the smile arc and buccal corridors on facial attractiveness as evaluated by orthodontists, general dentists and laymen. Materials and Methods: Two subjects (one male & one female) were selected from the regional population fulfilling the criteria of an ideal smile arc and ideal buccal corridors. Frontal smile view photographs of these subjects were taken and modified by using adobe photoshop 7.0 to create combination of three smile arc variance and three buccal corridors variations respectively which were shown to 25 orthodontists, 25 general dentists & 25 laymen, to rate the facial attractiveness of each image on a rating scale. Results: All the three groups (laypersons, dentists and orthodontists) showed significant difference in ratings, indicating that they had different perceptions on the facial attractiveness. Conclusion: Orthodontists were more precise in discerning the smile arc and buccal corridors compared to dentists and laypersons. [ABSTRACT FROM AUTHOR]

Unicondylar fractures of the lower end of the femur are uncommon injuries. We report a case of fracture of the anterior aspect of the lateral femoral condyle in coronal plane, which we termed as “Anterior Hoffa fracture”. With a different mechanism of injury, this type of fracture needs to be differentiated from osteochondral fractures of the distal end of the femur for proper management. After early debridement of the compound wound, we treated this case with open reduction and internal fixation. During the total follow-up period of 8 months, the patient had near normal joint range of motion with no joint instability. Open reduction and internal fixation with restoration of articular congruity is necessary for good functional outcome in this rare type of injury. [ABSTRACT FROM AUTHOR]