Enduring Efficacy and Clinical Outcomes of Combined Palliative Chemotherapy With Gefitinib, Methotrexate, and Cyclophosphamide in Advanced Oral Cancer: A 3.5-Year Case Study of Carcinoma in the Buccal Mucosa and Hard Palate.

This case report outlines the diagnostic and treatment experience of a 50-year-old male diagnosed with moderately differentiated squamous cell carcinoma (SCC) in the right lower alveolus. It underscores the challenges of oral squamous cell carcinoma (OSCC) diagnosis and management, emphasizing the need for comprehensive multidisciplinary approaches. The patient's initial presentation with persistent mandibular pain highlighted the complexities of diagnosing oral and maxillofacial pathologies. A detailed clinical examination revealed unique ulceroproliferative growth, showcasing the importance of meticulous clinical assessment. Histopathological confirmation solidified the diagnosis. Treatment involved surgery, adjuvant radiotherapy, and concurrent chemotherapy. Post-chemotherapy, the patient responded positively, underlining treatment efficacy. Transitioning to oral chemotherapy demonstrated adaptability. Vigilant follow-up, exemplified by detecting non-healing ulcers and erosions, is crucial for early intervention. This case informs oral squamous cell carcinoma management. Integrated therapy's success underscores the value of combining surgery, chemotherapy, and radiotherapy. The patient's response to gefitinib, cyclophosphamide, and methotrexate suggests promise for targeted therapies. Patient-centered care, interdisciplinary collaboration, and adaptability are vital. This case report illustrates oral squamous cell carcinoma eradication through multidimensional treatment. The patient's journey highlights accurate diagnosis, adaptable therapy, and vigilant follow-up. It informs the field and fosters further research and innovation.

Efficacy of beetroot juice on reducing blood pressure in hypertensive adults with autosomal dominant polycystic kidney disease (BEET-PKD): study protocol for a double-blind, randomised, placebo-controlled trial.

BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD) impaired nitric oxide (NO) synthesis, in part, contributes to early-onset hypertension. Beetroot juice (BRJ) reduces blood pressure (BP) by increasing NO-mediated vasodilation. The aim of this double-blind, randomised, placebo-controlled study is to test the hypothesis that BRJ reduces systolic and diastolic clinic BP in hypertensive adults with ADPKD. METHODS: Participants with ADPKD and treated hypertension (n = 60) will be randomly allocated (1:1) to receive a daily dose of either nitrate-replete (400 mg nitrate/day) or nitrate-deplete BRJ for 4 weeks. The co-primary outcomes are change in mean systolic and diastolic clinic BP before and after 4 weeks of treatment with daily BRJ. Secondary outcomes are changes in daily home BP, urinary albumin to creatinine ratio, serum and salivary nitrate/nitrite levels and serum asymmetric dimethylarginine levels before and after 4 weeks of BRJ. DISCUSSION: The effect of BRJ in ADPKD has not been previously tested. BRJ is an accessible, natural dietary supplement that, if effective, will provide a novel adjunctive approach for treating hypertension in ADPKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT05401409. Retrospectively registered on 27th May 2022.

Enhancing specialty training in geropsychology competencies: An evaluation of a VA Geriatric Scholars Program advanced topics workshop.

There is a growing need for psychologists with specialized training in geriatric mental health competencies. The Geriatric Scholars Program for Psychologists (GSP-P) was created to address this shortage within a large integrated healthcare system. In 2019, GSP-P piloted an advanced workshop designed to enhance expertise in geriatric mental health competencies among graduates of its foundational competencies core course. The workshop included 3.5 days of expert-led seminars regarding the biopsychosocial needs of older adults with chronic medical illness and was followed by completion of an individualized learning plan. This paper describes the evaluation of the course using a mixed methods with data collected prior to the workshop, immediately post-workshop, and six months post-workshop. Results indicated enthusiasm for the workshop, significant improvements in four geropsychology domains on the Pikes Peak Geropsychology Knowledge and Skill Assessment Tool, and benefit from completion of the independent learning plans. Our findings demonstrate that continued enhancement of geropsychology competencies through advanced coursework is feasible and improves knowledge and skill, particularly when combined with individualized learning plans.

Photodynamic Therapy Is Effective Against Candida auris Biofilms.

Fungal infections are increasing in prevalence worldwide. The paucity of available antifungal drug classes, combined with the increased occurrence of multidrug resistance in fungi, has led to new clinical challenges in the treatment of fungal infections. Candida auris is a recently emerged multidrug resistant human fungal pathogen that has become a worldwide public health threat. C. auris clinical isolates are often resistant to one or more antifungal drug classes, and thus, there is a high unmet medical need for the development of new therapeutic strategies effective against C. auris. Additionally, C. auris possesses several virulence traits, including the ability to form biofilms, further contributing to its drug resistance, and complicating the treatment of C. auris infections. Here we assessed red, green, and blue visible lights alone and in combination with photosensitizing compounds for their efficacies against C. auris biofilms. We found that (1) blue light inhibited and disrupted C. auris biofilms on its own and that the addition of photosensitizing compounds improved its antibiofilm potential; (2) red light inhibited and disrupted C. auris biofilms, but only in combination with photosensitizing compounds; and (3) green light inhibited C. auris biofilms in combination with photosensitizing compounds, but had no effects on disrupting C. auris biofilms. Taken together, our findings suggest that photodynamic therapy could be an effective non-drug therapeutic strategy against multidrug resistant C. auris biofilm infections.

Alcohol induced NLRP3 inflammasome activation in the brain of rats is attenuated by ATRA supplementation.

Alcohol abuse affects several neurological pathways and causes significant alterations in the brain. Abstention from alcohol is an effective intervention against alcohol related diseases. But the recovery of the damaged cells to normal presents a major problem in those who have stopped alcohol consumption. Hence therapeutic interventions are needed. Our previous studies have shown that all trans retinoic acid (ATRA) is effective in reducing alcohol induced neuro toxicity. Chronic alcohol administration up-regulates and activates the NLRP3 inflammasome leading to caspase-1 activation and IL-1ß production causing neuroinflammation. Hence, we investigated whether ATRA has any impact on NLRP3 inflammasomes activation. Rats were divided into two groups and were maintained for 90 days as control and ethanol group (4 â€‹g/kg body weight). After 90 days, ethanol administration was stopped and animals in the control group were divided into control and control â€‹+ â€‹ATRA (100 â€‹µg/kg body weight per day) groups; those in the ethanol group as ethanol abstention and ATRA (100 â€‹µg/kg body weight per day) and maintained for 30 days. Administration of ATRA reduced reactive oxygen species and endotoxins which were elevated in alcoholic rats. There was also reduction in the expression of NLRP3 inflammasome and caspase 1. Our results suggested ATRA down regulated NLRP3 activation with concomitant decrease in the release of caspase -1 and production of IL1ß. However, all these parameters were higher in abstention in comparison with ATRA supplemented group. In short therapeutic intervention with ATRA regressed alcohol induced inflammasome activation better than abstention.

Calibration and characterization of intracellular Asante Potassium Green probes, APG-2 and APG-4.

The response of fluorescent ion probes to ions is affected by intracellular environment. To properly calibrate them, intracellular and extracellular concentrations of the measured ion must be made equal. In the first, computational, part of this work, we show, using the example of potassium, that the two requirements for ion equilibration are complete dissipation of membrane potential and high membrane permeability for both potassium and sodium. In the second part, we tested the ability of various ionophores to achieve potassium equilibration in Jurkat and U937 cells and found a combination of valinomycin, nigericin, gramicidin and ouabain to be the most effective. In the third part, we applied this protocol to two potassium probes, APG-4 and APG-2. APG-4 shows good sensitivity to potassium but its fluorescence is sensitive to cell volume. Because ionophores cause cell swelling, calibration buffers had to be supplemented with 50 mM sucrose to keep cell volume constant. With these precautions taken, the average potassium concentrations in U937 and Jurkat cells were measured at 132 mM and 118 mM, respectively. The other tested probe, APG-2, is nonselective for cations; this is, however, a potentially useful property because the sum [K+] + [Na+] determines the amount of intracellular water.

All trans retinoic acid modulates TNF-α and CYP2E1 pathways and enhances regression of ethanol-induced fibrosis markers in hepatocytes and HSCs in abstaining rodent model.

Context: Our previous studies showed that all trans retinoic acid (ATRA) ameliorates alcohol-induced toxicity. Hence, we evaluated the efficacy of ATRA and abstention in the regression of alcohol-induced hepatotoxicity. Materials and methods: After ethanol administration to rats for 90 days, the regression of alcohol-induced toxicity was studied by supplementing ATRA at a dose of 100 µg/kg body weight for 30 days. It was also compared with animals in abstention. Results and discussion: Ethanol administration enhanced oxidative stress, activated HSCs and increased collagen deposition. All these alterations were reversed to a certain extent by ATRA supplementation. Conclusions: ATRA had better efficacy than just abstention in reducing ethanol-induced toxicity. The mechanism might be downregulation of CYP2E1, leading to reduced oxidative stress in the hepatocytes and thus impeding NFκB activation, cytokine production, activation of HSC and resulting in the reduction of inflammation and remodelling of fibrosis by modulating MMP and TIMP.

All Trans Retinoic Acid Attenuates Markers of Neuroinflammation in Rat Brain by Modulation of SIRT1 and NFκB.

Alcohol abuse affects several neurological pathways and causes significant alterations in the brain. Abstention from alcohol causes only a marginal decrease in oxidative stress and neuro inflammation. Our previous studies had shown that an active metabolite of vitamin A, all trans retinoic acid (ATRA), ameliorates alcohol induced toxicity. Hence in the present study we investigated whether ATRA regressed alcohol induced neuroinflammation. We focused on the role of silent mating type information regulation 2 homolog 1(SIRT1) and nuclear factor kappa-B (NFκB). Animals were administered with ethanol at a daily dose of (4 g/kg body weight) for 90 days. On the 91st day ethanol administration was stopped and animals were divided into ethanol abstention (A) and ATRA supplementation group (ATRA + A) (100 µg/kg body weight) and maintained for 30 days. Ethanol exposure increased markers of oxidative stress, inflammation and the activities of alcohol and acetaldehyde dehydrogenases and reduced the expression of SIRT1 in the whole brain.The ethanol induced altered expressions of NFκB and SIRT1 were modulated by supplementation of ATRA. Abstention also reduced toxicity, but to a lower extent in comparison with supplementation of ATRA. Our results seemed to suggest that ATRA regressed the mediators of ethanol induced neuroinflammation by reducing oxidative stress and by regulating the expression of NFκB and SIRT1. The ameliorative potential of ATRA was much higher than abstention.

Characterization of cAMP/PKA/CREB signaling cascade in the bonnet monkey corpus luteum: expressions of inhibin-alpha and StAR during different functional status.

Luteinizing hormone mediates its nuclear action primarily by activating cAMP/Protein kinase A (PKA) pathway leading to phosphorylation of cAMP response element binding (CREB) family of transcription factors. Earlier studies have documented altered cAMP responsiveness of luteal cells during maturation, and in the rhesus monkey, extinction of CREB expression following luteinization and ovulation. In the course of studies aimed at characterizing LH-cAMP signaling pathway, we serendipitously discovered that CREB is after all present in the monkey corpus luteum (CL). The present experiments were carried out to examine the PKA activity, CREB expression and RT-PCR expression of inhibin-alpha (Inh-alpha) subunit and steroidogenic acute regulatory protein (StAR) in CL obtained from a variety of model systems. PKA activity in the CL was maintained throughout the luteal phase. Messenger RNA expression by RT-PCR and Northern analyses and protein levels employing antibodies specific to total- and phospho-forms demonstrated presence of CREB in the CL. Additionally, immuno-histo/cytochemical analyses, Electrophoretic mobility shift assays and chromatin immunoprecipitation assays for Inh-alpha and StAR genes further confirmed the presence of CREB in the CL. The present study, contrary to an earlier report, demonstrates the presence of CREB (both transcript and protein) in the monkey CL. Also, analysis of expression of Inh-alpha and StAR genes (considered to be cAMP responsive), during different functional status of CL suggests that LH regulates their expression perhaps by cAMP/PKA/CREB pathway.