Adjunct therapy with all-trans-retinoic acid improves therapeutic efficacy through immunomodulation while treating tuberculosis with antibiotics in a murine model.

Tuberculosis (TB) is the second leading infectious killer after COVID-19. Standard anti-tubercular drugs exhibit various limitations like toxicity, lengthy, and unresponsive to dormant and drug resistant organisms. Here, we report that all-trans-retinoic acid (ATRA) improves M.tb clearance in mice while treating with anti-tubercular drug isoniazid (INH). Interestingly, ATRA promoted activities of lysosomes, mitochondria, and production of various inflammatory mediators in macrophages. Furthermore, ATRA upregulated the expression of genes of lipid metabolic pathways in macrophages. Along this line, we registered that ATRA activated MEK/ERK pathway in macrophages in-vitro and MEK/ERK and p38 MAPK pathways in the mice. Finally, ATRA induced both Th1 and Th17 responses in lungs and spleens of M.tb-infected mice. Taken together, these data indicated that ATRA provides beneficial adjunct therapeutic value by modulating MEK/ERK and p38 MAPK pathways and thus warrants further testing for human use.

Smart Farming Revolution: Portable and Real-Time Soil Nitrogen and Phosphorus Monitoring for Sustainable Agriculture.

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.

Over Expression of Cancer Stem Cell Marker CD44 and Its Clinical Significance in Patients with Oral Squamous Cell Carcinoma.

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.

Cloud based evaluation of databases for stock market data.

About fifty years ago, the world's first fully automated system for trading securities was introduced by Instinet in the US. Since then the world of trading has been revolutionised by the introduction of electronic markets and automatic order execution. Nowadays, financial institutions exploit the associated flow of daily data using more and more advanced analytics to gain valuable insight on the markets and inform their investment decisions. In particular, time series of Open High Low Close prices and Volume data are of special interest as they allow identifying trading patterns useful for forecasting both stock prices and volumes. Traditionally, relational databases have been used to store this data; however, the ever-growing volume of this data, the adoption of the hybrid cloud model, and the availability of novel non-relational databases which claim to be more scalable and fault tolerant raise the question whether relational databases are still the most appropriate. In this study, we define a set of criteria to evaluate performance of a variety of databases on a hybrid cloud environment. There, we conduct experiments using standard and custom workloads. Results show that migration to a MongoDB database would be most beneficial in terms of cost, storage space, and throughput. In addition, organisations wishing to take advantage of autoscaling and the maintenance power of the cloud should opt for a cloud native solution.

Cinnamomum zeylanicum Extract and its Bioactive Component Cinnamaldehyde Show Anti-Tumor Effects via Inhibition of Multiple Cellular Pathways.

Cinnamomum zeylanicum is a tropical plant with traditional medicinal significance that possesses antimicrobial, antifungal, anti-parasitic, and anti-tumor properties. Here, we have elucidated the anti-tumor effects of Cinnamomum zeylanicum extract (CZE) and its bioactive compound cinnamaldehyde (CIN) on oral cancer and elucidated underlying molecular mechanisms. Anti-tumor activities of CZE and CIN were demonstrated by various in vitro experiments on oral cancer cells (SCC-4, SCC-9, SCC-25). The cell proliferation, growth, cell cycle arrest, apoptosis, and autophagy were analyzed by MTT, clonogenic assay, propidium iodide, annexin-V-PI, DAPI, and acridine orange staining, respectively. The binding affinity of CIN towards dihydrofolate reductase and p38-MAP kinase alpha was analyzed by molecular docking. Western blot assay was performed to assess the alteration in the expression of various proteins. CZE and CIN treatment significantly inhibited the growth and proliferation of oral cancer cells in a dose-dependent manner. These treatments further induced apoptosis, cell cycle arrest, and autophagy. CZE and CIN inhibited the invasion and cytoplasmic translocation of NF-κB in these cell lines. CIN showed a high affinity to MAP kinase P38 alpha and dihydrofolate reductase with binding affinities of -6.8 and -5.9 kcal/mol, respectively. The cancer cells showed a decreased expression of various PI3k-AKT-mTOR pathways related to VEGF, COX-2, Bcl-2, NF-κB, and proteins post-treatment.

The 1, 2-ethylenediamine SQ109 protects against tuberculosis by promoting M1 macrophage polarization through the p38 MAPK pathway.

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.

Diagnostic journeys: characterization of patients and diagnostic outcomes from an academic second opinion clinic.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Training Internal Medicine Residents in Difficult Diagnosis: A Novel Diagnostic Second Opinion Clinic Experience.

Background: In primary care clinics, time constraints and lack of exposure to highly complex cases may limit the breadth and depth of learning for internal medicine residents. To address these issues, we piloted a novel experience for residents to evaluate patients with puzzling symptoms referred by another clinician. Objective: To increase internal medicine residents' exposure to patients with perplexing presentations and foster a team-based approach to solving diagnostically challenging cases. Methods: During the academic year 2020-2021, residents participating in their 2-week primary care "block" rotation were given protected time to evaluate 1-2 patients from the Stanford Consultative Medicine clinic, an internist-led diagnostic second opinion service, and present their patients at the case conference. We assessed the educational value of the program with resident surveys including 5-point Lickert scale and open-ended questions. Results: 21 residents participated in the pilot with a survey response rate of 66.6% (14/21). Both the educational value and overall quality of the experience were rated as 4.8 out of 5 (SD 0.4, range 4-5; 1:"very poor"; 5:"excellent"). Residents learned about new diagnostic tools as well as how to approach complex presentations and diagnostic dilemmas. Residents valued the increased time devoted to patient care, the team-based approach to tackling difficult cases, and the intellectual challenge of these cases. Barriers to implementation include patient case volume, time, and faculty engagement. Conclusions: Evaluation of diagnostically challenging cases in a structured format is a highly valuable experience that offers a framework to enhance outpatient training in internal medicine.

Circulating Vimentin Over-Expression in Patients with Oral Sub Mucosal Fibrosis and Oral Squamous Cell Carcinoma.

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.

Identification and validation of potent Mycobacterial proteasome inhibitor from Enamine library.

As a consequence of present status of tuberculosis (TB) it is the obligation to develop novel targets and potential drugs so that rate of drug resistant TB can be declined. Mycobacterium proteasome is considered to be significant target for the purpose of drug designing as it is responsible for resisting the effect of NO (nitric oxide) immune system defence mechanism against the bacterial cells. Small compounds library from Enamine database has already been tested using virtual screening and molecular docking studies. Further a reanalysis with two picked out significant compounds Z1020863610, Z106766984 was carried out using molecular dynamic simulation studies and in vitro validations (in vitro susceptibility assay, enzyme inhibition assay and MTT assay). In silico outcome that two inhibiters were interacting at the active site pocket of receptor with high stability, was found to be very consistent with in vitro results. So it was conferred that compounds (Z1020863610, Z106766984) are potential lead for future process of drug development (in vivo testing and clinical trials).Communicated by Ramaswamy H. Sarma.

Building Bridges Between Community Health Centers and Academic Medical Centers in a COVID-19 Pandemic.

The threat to the public health of the United States from the COVID-19 pandemic is causing rapid, unprecedented shifts in the health care landscape. Community health centers serve the patient populations most vulnerable to the disease yet often have inadequate resources to combat it. Academic medical centers do not always have the community connections needed for the most effective population health approaches. We describe how a bridge between a community health center partner (Roots Community Health Center) and a large academic medical center (Stanford Medicine) brought complementary strengths together to address the regional public health crisis. The 2 institutions began the crisis with an overlapping clinical and research faculty member (NKT). Building on that foundation, we worked in 3 areas. First, we partnered to reach underserved populations with the academic center's newly developed COVID test. Second, we developed and distributed evidence-based resources to these same communities via a large community health navigator team. Third, as telemedicine became the norm for medical consultation, the 2 institutions began to research how reducing the digital divide could help improve access to care. We continue to think about how best to create enduring partnerships forged through ongoing deeper relationships beyond the pandemic.

The COVID-19 Pandemic as an Opportunity for Operational Innovation at 2 Student-Run Free Clinics.

The onset of the COVID-19 pandemic and subsequent county shelter-in-place order forced the Cardinal Free Clinics (CFCs), Stanford University's 2 student-run free clinics, to close in March 2020. As student-run free clinics adhering to university-guided COVID policies, we have not been able to see patients in person since March of 2020. However, the closure of our in-person operations provided our student management team with an opportunity to innovate. In consultation with Stanford's Telehealth team and educators, we rapidly developed a telehealth clinic model for our patients. We adapted available telehealth guidelines to meet our patient care needs and educational objectives, which manifested in 3 key innovations: reconfigured clinic operations, an evidence-based social needs screen to more effectively assess and address social needs alongside medical needs, and a new telehealth training module for student volunteers. After 6 months of piloting our telehealth services, we believe that these changes have made our services and operations more robust and provided benefit to both our patients and volunteers. Despite an uncertain and evolving public health landscape, we are confident that these developments will strengthen the future operations of the CFCs.

Identifying Opportunities to Improve Intimate Partner Violence Screening in a Primary Care System.

BACKGROUND AND OBJECTIVES: Intimate partner violence (IPV) is a silent epidemic affecting one in three women. The US Preventive Services Task Force recommends routine IPV screening for women of childbearing age, but actual rates of screening in primary care settings are low. Our objectives were to determine how often IPV screening was being done in our system and whether screening initiated by medical assistants or physicians resulted in more screens. METHODS: We conducted a retrospective chart review to investigate IPV screening practices in five primary care clinics within a university-based network in Northern California. We reviewed 100 charts from each clinic for a total of 500 charts. Each chart was reviewed to determine if an IPV screen was documented, and if so, whether it was done by the medical assistant or the physician. RESULTS: The overall frequency of IPV screening was 22% (111/500). We found a wide variation in screening practices among the clinics. Screening initiated by medical assistants resulted in significantly more documented screens than screening delivered by physicians (74% vs 9%, P<0.001). CONCLUSIONS: IPV screening is an important, but underdelivered service. Using medical assistants to deliver IPV screening may be more effective than relying on physicians alone.

An Analysis of Lung Cancer Screening Beliefs and Practice Patterns for Community Providers Compared to Academic Providers.

Despite guidelines recommending annual low-dose computed tomography (LDCT) screening for lung cancer, uptake remains low due to the perceived complexity of initiating and maintaining a clinical program-problems that likely magnify in underserved populations. We conducted a survey of community providers at Federally Qualified Health Centers (FQHCs) in Santa Clara County, California, to evaluate provider-related factors that affect adherence. We then compared these findings to academic providers' (APs) LDCT screening knowledge, behaviors, and attitudes at an academic referral center in the same county. The 4 FQHCs enrolled care for 80 000 patients largely of minority descent and insured by Medi-Cal. Of the 75 FQHC providers (FQHCPs), 36 (48%) completed the survey. Of the 36 providers, 8 (22%) knew screening criteria. Fifteen (42%) FQHCPs discussed LDCT screening with patients. Compared to 36 APs, FQHCPs were more concerned about harms, false positives, discussion time, patient apathy, insurance coverage, and a lack of expertise for screening and follow-up. Yet, more FQHCPs thought screening was effective (27 [75%] of 36) compared to APs ( P = .0003). In conclusion, provider knowledge gaps are greater and barriers are different for community clinics caring for underserved populations compared to their academic counterparts, but practical and scalable solutions exist to enhance adoption.

Methemoglobinemia - The Cryptic Cause of Dyspnoea.

Methemoglobinemia is a life threatening condition that can be difficult to diagnose. It can be congenital or, more often an adverse drug effect. A good, detailed history taking and thorough knowledge of drugs and toxins is the secret to early diagnosis. We present two interesting cases of methemoglobinemia. First was phenol poisoning with G6PD deficiency leading to hemolysis and methemoglobinemia and second was phenol induced methemoglobinemia. Here we discuss the diagnosis and management of a patient with acquired methemoglobinemia.

Immersion medicine programme for secondary students.

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.

An Academic Achievement Calculator for Clinician-Educators in Primary Care.

BACKGROUND AND OBJECTIVES: Academic medical centers need better ways to quantify the diverse academic contributions of primary care clinician-educators. We examined the feasibility and acceptability of an "academic achievement calculator" that quantifies academic activities using a point system. METHODS: A cohort of 16 clinician-educators at a single academic medical center volunteered to assess the calculator using a questionnaire. Key measures included time needed to complete the calculator, how well it reflected participants' academic activities, whether it increased their awareness of academic opportunities, whether they intend to pursue more academic work, and their overall satisfaction with the calculator. RESULTS: Most participants (69%) completed the calculator in less than 20 minutes. Three-quarters (75%) reported that the calculator reflected the breadth of their academic work either "very well" or "extremely well". The majority (81%) stated that it increased their awareness of opportunities for academic engagement, and that they intend to pursue more academic activities. Overall, three-quarters (75%) were "very satisfied" or "extremely satisfied" with the calculator. CONCLUSIONS: To our knowledge, this is the first report of a tool designed to quantify the diverse academic activities of primary care clinician-educators. In this pilot study, we found that the use of an academic achievement calculator may be feasible and acceptable. This tool, if paired with an annual bonus plan, could help incentivize and reward academic contributions among primary care clinician-educators, and assist department leaders with the promotion process.

Child maltreatment: Cross-sectional survey of general dentists.

BACKGROUND: Child abuse continues to be a social menace causing both physical and emotional trauma to benevolent children. Census has shown that nearly 50-75% of child abuse include trauma to mouth, face, and head. Thus, dental professionals are in a strategic position to identify physical and emotional manifestations of abuse. AIM: A cross-sectional survey was conducted to assess knowledge and attitude of dental professionals on the exigent issue of child abuse. METHODOLOGY: With prior consent, a 20-question survey including both multiple choice and dichotomous (yes/no) questions was mailed to 120 state-registered general dentists and the data collected were subjected to statistical analysis. STATISTICAL ANALYSIS: The overall response rate to the questionnaires was 97%. Lack of knowledge about dentist role in reporting child abuse accounted to 55% in the reasons for hesitancy to report. Pearson's Chi-square test did not show any significant difference between male and female regarding the reason for hesitancy to report and legal obligation of dentists. RESULTS: Although respondent dentists were aware of the diagnosis of child abuse, they were hesitant and unaware of the appropriate authority to report. CONCLUSION: Increased instruction in the areas of recognition and reporting of child abuse and neglect should be emphasized.

Patient and primary care provider attitudes and adherence towards lung cancer screening at an academic medical center.

Low dose CT (LDCT) for lung cancer screening is an evidence-based, guideline recommended, and Medicare approved test but uptake requires further study. We therefore conducted patient and provider surveys to elucidate factors associated with utilization. Patients referred for LDCT at an academic medical center were questioned about their attitudes, knowledge, and beliefs on lung cancer screening. Adherent patients were defined as those who met screening eligibility criteria and completed a LDCT. Referring primary care providers within this same medical system were surveyed in parallel about their practice patterns, attitudes, knowledge and beliefs about screening. Eighty patients responded (36%), 48 of whom were adherent. Among responders, non-Hispanic patients (p = 0.04) were more adherent. Adherent respondents believed that CT technology is accurate and early detection is useful, and they trusted their providers. A majority of non-adherent patients (79%) self-reported an intention to obtain a LDCT in the future. Of 36 of 87 (41%) responding providers, only 31% knew the correct lung cancer screening eligibility criteria, which led to a 37% inappropriate referral rate from 2013 to 2015. Yet, 75% had initiated lung cancer screening discussions, 64% thought screening was at least moderately effective, and 82% were interested in learning more of the 33 providers responding to these questions. Overall, patients were motivated and providers engaged to screen for lung cancer by LDCT. Non-adherent patient "procrastinators" were motivated to undergo screening in the future. Additional follow through on non-adherence may enhance screening uptake, and raising awareness for screening eligibility through provider education may reduce inappropriate referrals.

Influence of Smile Arc and Buccal Corridors on Facial Attractiveness: A Cross-sectional Study.

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.