A Case Report of Case Report Pursuit by Medical Student

Medical students often seek case reports as vehicles for academic writing opportunities, conference presentation avenues, and residency/fellowship application highlights. Here we review a case where, due to unfortunate circumstances, a student made a unique diagnosis central to proper patient clinical care, wished to write up the case subsequently, but was ultimately excluded from the final work stemming from the patient case. We review the pitfalls that occurred in the process of pursuing publication of an interesting case, the educational value of pursuing case reports for students, the necessity for strong mentorship in this process, and general principles that medical students can follow regarding case report creation to avoid being burned

T-cadherin deficiency increases vascular vulnerability in T2DM through impaired NO bioactivity.

BACKGROUND: Endothelial dysfunction plays a critical role in the development of type 2 diabetes (T2DM). T-cadherin (T-cad) has gained recognition as a regulator of endothelial cell (EC) function. The present study examined whether T-cad deficiency increases vascular vulnerability in T2DM. METHODS: Vascular segments were isolated from WT or T-cad knockout mice. Endothelial function, total NO accumulation, and the expression of T-cad related proteins were determined. RESULTS: Ach and acidified NaNO2 induced similar vasorelaxation in WT groups. T-cad KO mice exhibited normal response to acidified NaNO2, but manifested markedly reduced response to Ach. NO accumulation was also decreased in T-cad KO group. T-cad expression was reduced in WT mice fed 8 weeks of high fat diet (HFD). Furthermore, exacerbated reduction of vasorelaxation was observed in T-cad KO mice fed 8 weeks of HFD. CONCLUSIONS: In the current study, we provide the first in vivo evidence that T-cadherin deficiency causes endothelial dysfunction in T2DM vascular segments, suggesting the involvement of T-cad deficiency in T2DM pathogenesis

Multifaceted Management of COVID in the Medical Student Population of Sidney Kimmel Medical College

COVID has created hardships in the lives of many persons. In a time of chaos, it was clear our institution needed an efficient workflow to track all students requiring quarantine, so that academic progress and student wellness would not be casualties. This presentation reviews that workflow in detail, for the purpose of sharing strengths of the process for the greater GSA/OSR network’s benefit.https://jdc.jefferson.edu/emposters/1002/thumbnail.jp

Systemic adiponectin malfunction as a risk factor for cardiovascular disease.

Adiponectin (Ad) is an abundant protein hormone regulatory of numerous metabolic processes. The 30 kDa protein originates from adipose tissue, with full-length and globular domain circulatory forms. A collagenous domain within Ad leads to spontaneous self-assemblage into various oligomeric isoforms, including trimers, hexamers, and high-molecular-weight multimers. Two membrane-spanning receptors for Ad have been identified, with differing concentration distribution in various body tissues. The major intracellular pathway activated by Ad includes phosphorylation of AMP-activated protein kinase, which is responsible for many of Ad\u27s metabolic regulatory, anti-inflammatory, vascular protective, and anti-ischemic properties. Additionally, several AMP-activated protein kinase-independent mechanisms responsible for Ad\u27s anti-inflammatory and anti-ischemic (resulting in cardioprotective) effects have also been discovered. Since its 1995 discovery, Ad has garnered considerable attention for its role in diabetic and cardiovascular pathology. Clinical observations have demonstrated the association of hypoadiponectinemia in patients with obesity, cardiovascular disease, and insulin resistance. In this review, we elaborate currently known information about Ad malfunction and deficiency pertaining to cardiovascular disease risk (including atherosclerosis, endothelial dysfunction, and cardiac injury), as well as review evidence supporting Ad resistance as a novel risk factor for cardiovascular injury, providing insight about the future of Ad research and the protein\u27s potential therapeutic benefits

Adiponectin protects against paraquat-induced lung injury by attenuating oxidative/nitrative stress.

The specific mechanisms underlying paraquat (PQ)-induced lung injury remain unknown, which limits understanding of its cytotoxic potential. Although oxidative stress has been established as an important mechanism underlying PQ toxicity, multiple antioxidants have proven ineffective in attenuating the deleterious effects of PQ. Adiponectin, which shows anti-oxidative and antinitrative effects, may have the potential to reduce PQ-mediated injury. The present study determined the protective action of globular domain adiponectin (gAd) on PQ-induced lung injury, and attempted to elucidate the underlying mechanism or mechanisms of action. BALB/c mice were administered PQ, with and without 12 or 36 h of gAd pre-treatment. The pulmonary oxidative/nitrative status was assessed by measuring pulmonary O2(•-), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and 8-hydroxy-2-dydeoxy guanosine (8-OHdG) production, and blood 3-Nitrotyrosine (3-NT). At a dose of 20 mg/kg, PQ markedly increased O2(•-), SOD, MDA, NO and 8-OHdG production 3 h post-administration, but did not significantly increase 3-NT levels until 12 h. gAd inhibited these changes in a dose-dependent manner, via transient activation of MDA, followed by attenuation of MDA formation from 6 h onwards. Histological analysis demonstrated that gAd decreased interstitial edema and inflammatory cell infiltration. These results suggest that gAd protects against PQ-induced lung injury by mitigating oxidative/nitrative stress. Furthermore, gAd may be a potential therapeutic agent for PQ-induced lung injury, and further pharmacological studies are therefore warranted

Intermedin protects against myocardial ischemia-reperfusion injury in diabetic rats.

BACKGROUND: Diabetic patients, through incompletely understood mechanisms, endure exacerbated ischemic heart injury compared to non-diabetic patients. Intermedin (IMD) is a novel calcitonin gene-related peptide (CGRP) superfamily member with established cardiovascular protective effects. However, whether IMD protects against diabetic myocardial ischemia/reperfusion (MI/R) injury is unknown. METHODS: Diabetes was induced by streptozotocin in Sprague--Dawley rats. Animals were subjected to MI via left circumflex artery ligation for 30 minutes followed by 2 hours R. IMD was administered formally 10 minutes before R. Outcome measures included left ventricular function, oxidative stress, cellular death, infarct size, and inflammation. RESULTS: IMD levels were significantly decreased in diabetic rats compared to control animals. After MI/R, diabetic rats manifested elevated intermedin levels, both in plasma (64.95 +/- 4.84 pmol/L, p \u3c 0.05) and myocardial tissue (9.8 +/- 0.60 pmol/L, p \u3c 0.01) compared to pre-MI control values (43.62 +/- 3.47 pmol/L and 4.4 +/- 0.41). IMD administration to diabetic rats subjected to MI/R decreased oxidative stress product generation, apoptosis, infarct size, and inflammatory cytokine release (p \u3c 0.05 or p \u3c 0.01). CONCLUSIONS: By reducing oxidative stress, inflammation, and apoptosis, IMD may represent a promising novel therapeutic target mitigating diabetic ischemic heart injury

Cardiac Specific Overexpression of Mitochondrial Omi/HtrA2 Induces Myocardial Apoptosis and Cardiac Dysfunction.

Myocardial apoptosis is a significant problem underlying ischemic heart disease. We previously reported significantly elevated expression of cytoplasmic Omi/HtrA2, triggers cardiomyocytes apoptosis. However, whether increased Omi/HtrA2 within mitochondria itself influences myocardial survival in vivo is unknown. We aim to observe the effects of mitochondria-specific, not cytoplasmic, Omi/HtrA2 on myocardial apoptosis and cardiac function. Transgenic mice overexpressing cardiac-specific mitochondrial Omi/HtrA2 were generated and they had increased myocardial apoptosis, decreased systolic and diastolic function, and decreased left ventricular remodeling. Transiently or stably overexpression of mitochondria Omi/HtrA2 in H9C2 cells enhance apoptosis as evidenced by elevated caspase-3, -9 activity and TUNEL staining, which was completely blocked by Ucf-101, a specific Omi/HtrA2 inhibitor. Mechanistic studies revealed mitochondrial Omi/HtrA2 overexpression degraded the mitochondrial anti-apoptotic protein HAX-1, an effect attenuated by Ucf-101. Additionally, transfected cells overexpressing mitochondrial Omi/HtrA2 were more sensitive to hypoxia and reoxygenation (H/R) induced apoptosis. Cyclosporine A (CsA), a mitochondrial permeability transition inhibitor, blocked translocation of Omi/HtrA2 from mitochondrial to cytoplasm, and protected transfected cells incompletely against H/R-induced caspase-3 activation. We report in vitro and in vivo overexpression of mitochondrial Omi/HtrA2 induces cardiac apoptosis and dysfunction. Thus, strategies to directly inhibit Omi/HtrA2 or its cytosolic translocation from mitochondria may protect against heart injury

Sevoflurane Pre-conditioning Ameliorates Diabetic Myocardial Ischemia/Reperfusion Injury Via Differential Regulation of p38 and ERK.

Diabetes mellitus (DM) significantly increases myocardial ischemia/reperfusion (MI/R) injury. During DM, cardioprotection induced by conventional pre-conditioning (PreCon) is decreased due to impaired AMP-activated protein kinase (AMPK) signaling. The current study investigated whether PreCon with inhaled anesthetic sevoflurane (SF-PreCon) remains cardioprotective during DM, and identified the involved mechanisms. Normal diet (ND) and high-fat diet (HFD)-induced DM mice were randomized into control and SF-PreCon (3 cycles of 15-minute period exposures to 2% sevoflurane) groups before MI/R. SF-PreCon markedly reduced MI/R injury in DM mice, as evidenced by improved cardiac function (increased LVEF and ±Dp/dt), decreased infarct size, and decreased apoptosis. To determine the relevant role of AMPK, the effect of SF-PreCon was determined in cardiac-specific AMPKα2 dominant negative expressing mice (AMPK-DN). SF-PreCon decreased MI/R injury in AMPK-DN mice. To explore the molecular mechanisms responsible for SF-PreCon mediated cardioprotection in DM mice, cell survival molecules were screened. Interestingly, in ND mice, SF-PreCon significantly reduced MI/R-induced activation of p38, a pro-death MAPK, without altering ERK and JNK. In DM and AMPK-DN mice, the inhibitory effect of SF-PreCon upon p38 activation was significantly blunted. However, SF-PreCon significantly increased phosphorylation of ERK1/2, a pro-survival MAPK in DM and AMPK-DN mice. We demonstrate that SF-PreCon protects the heart via AMPK-dependent inhibition of pro-death MAPK in ND mice. However, SF-PreCon exerts cardioprotective action via AMPK-independent activation of a pro-survival MAPK member in DM mice. SF-PreCon may be beneficial compared to conventional PreCon in diabetes or clinical scenarios in which AMPK signaling is impaired

Epigenetics in ovarian cancer: premise, properties, and perspectives.

Malignant ovarian tumors bear the highest mortality rate among all gynecological cancers. Both late tumor diagnosis and tolerance to available chemical therapy increase patient mortality. Therefore, it is both urgent and important to identify biomarkers facilitating early identification and novel agents preventing recurrence. Accumulating evidence demonstrates that epigenetic aberrations (particularly histone modifications) are crucial in tumor initiation and development. Histone acetylation and methylation are respectively regulated by acetyltransferases-deacetylases and methyltransferases-demethylases, both of which are implicated in ovarian cancer pathogenesis. In this review, we summarize the most recent discoveries pertaining to ovarian cancer development arising from the imbalance of histone acetylation and methylation, and provide insight into novel therapeutic interventions for the treatment of ovarian carcinoma

Implications of C1q/TNF-related protein superfamily in patients with coronary artery disease.

The C1q complement/TNF-related protein superfamily (CTRPs) displays differential effects on the regulation of metabolic homeostasis, governing cardiovascular function. However, whether and how they may serve as predictor/pro-diagnosis factors for assessing the risks of coronary artery disease (CAD) remains controversial. Therefore, we performed a clinical study to elaborate on the implication of CTRPs (CTRP1, CTRP5, CTRP7, and CTRP15) in CAD. CTRP1 were significantly increased, whereas CTRP7 and CTRP15 levels were decreased in CAD patients compared to the non-CAD group. Significant differences in CTRP1 levels were discovered between the single- and triple-vascular-vessel lesion groups. ROC analysis revealed that CTRP7 and CTRP15 may serve as CAD markers, while CTRP1 may serve as a marker for the single-vessel lesion of CAD. CTRP1 and CTRP5 can serve as markers for the triple-vessel lesion. CTRP1 may serve as an independent risk predictor for triple-vessel lesion, whereas CTRP15 alteration may serve for a single-vessel lesion of CAD. CTRP1 may serve as a novel superior biomarker for diagnosis of severity of vessel-lesion of CAD patients. CTRP7, CTRP15 may serve as more suitable biomarker for the diagnosis of CAD patients, whereas CTRP5 may serve as an independent predictor for CAD. These findings suggest CTRPs may be the superior predictive factors for the vascular lesion of CAD and represent novel therapeutic targets against CAD