From Dream to Reality: Conducting a Thorough Physical Exam With a Cell Phone

Background: The COVID-19 pandemic has prompted a surge in the utilization of telemedicine as physicians and patients attempt to protect themselves. The art of medicine is rooted in the ability to gather subjective and objective data from patients to make accurate diagnoses and recommendations. We must rely on creativity and innovation to gather this information in the new setting of telehealth in a manner with high consistency and reliability to maintain high-quality patient care. Case Presentation: After gathering a thorough history, we work with the patient’s guardian to systematically view the patient head to toe, perform cardiopulmonary auscultation, and assess exercise tolerance through a functional examination. This method of physical examination allows for teaching to be easily integrated as both attending physician and student are viewing and listening to the same thing at the same time. Just as importantly, this method of examination strengthens the doctor-patient relationship by creating a working partnership with parent and child to gather the information needed for a successful and reliable physical examination. The lack of training physicians have in performing a virtual physical examination is a concern. There is often a perceived barrier to what can be examined virtually, creating a potential disservice to the patient. Here, we present how mobile communication devices (i.e. cellular phones) can act as the sole peripheral device necessary to conduct a thorough history and physical examination as most of these devices now come equipped with a high-quality camera, microphone, and bright light allowing for a general head-to-toe visualization of the patient and auscultation. Conclusion: Technology will continually advance and become more accessible, but what is currently widely available for both the patient and clinician is the mobile communication device. Optimization of the use of technology that is currently available needs to be prioritized. We must also take advantage of the great opportunity we have been presented with to create unique partnerships between physician, guardian, and child that make them a part of their healthcare. These unique working relationships and the opportunity for improved medical teaching are drivers for high-quality healthcare

The PI3K pathway impacts stem gene expression in a set of glioblastoma cell lines

Background: The PI3K pathway controls diverse cellular processes including growth, survival, metabolism, and apoptosis. Nuclear FOXO factors were observed in cancers that harbor constitutively active PI3K pathway output and stem signatures. FOXO1 and FOXO3 were previously published to induce stem genes such as OCT4 in embryonic stem cells. Here, we investigated FOXO-driven stem gene expression in U87MG glioblastoma cells. Methods: PI3K-activated cancer cell lines were investigated for changes in gene expression, signal transduction, and clonogenicity under conditions with FOXO3 disruption or exogenous expression. The impact of PI3K pathway inhibition on stem gene expression was examined in a set of glioblastoma cell lines. Results: We found that CRISPR-Cas9-mediated FOXO3 disruption in U87MG cells caused decreased OCT4 and SOX2 gene expression, STAT3 phosphorylation on tyrosine 705 and clonogenicity. FOXO3 over expression led to increased OCT4 in numerous glioblastoma cancer cell lines. Strikingly, treatment of glioblastoma cells with NVP-BEZ235 (a dual inhibitor of PI3K and mTOR), which activates FOXO factors, led to robust increases OCT4 gene expression. Direct FOXO factor recruitment to the OCT4 promoter was detected by chromatin immunoprecipitation analyses using U87MG extracts. Discussion: We show for the first time that FOXO transcription factors promote stem gene expression glioblastoma cells. Treatment with PI3K inhibitor NVP-BEZ235 led to dramatic increases in stem genes in a set of glioblastoma cell lines. Conclusion: Given that, PI3K inhibitors are actively investigated as targeted cancer therapies, the FOXO-mediated induction of stem genes observed in this study highlights a potential hazard to PI3K inhibition. Understanding the molecular underpinnings of stem signatures in cancer will allow refinements to therapeutic strategies. Targeting FOXO factors to reduce stem cell characteristics in concert with PI3K inhibition may prove therapeutically efficacious

Translocation of the Na+/H+ exchanger 1 (NHE1) in cardiomyocyte responses to insulin and energy-status signalling

The Na+/H+ exchanger NHE1 is a highly regulated membrane protein that is required for pH homoeostasis in cardiomyocytes. The activation of NHE1 leads to proton extrusion, which is essential for counteracting cellular acidity that occurs following increased metabolic activity or ischaemia. The activation of NHE1 intrinsic catalytic activity has been well characterized and established experimentally. However, we have examined in the present study whether a net translocation of NHE1 to the sarcolemma of cardiomyocytes may also be involved in the activation process. We have determined the distribution of NHE1 by means of immunofluorescence microscopy and cell-surface biotinylation. We have discovered changes in the distribution of NHE1 that occur when cardiomyocytes are stimulated with insulin that are PI3K (phosphoinositide 3-kinase)-dependent. Translocation of NHE1 also occurs when cardiomyocytes are challenged by hypoxia, or inhibition of mitochondrial oxidative metabolism or electrically induced contraction, but these responses occur through a PI3K-independent process. As the proposed additional level of control of NHE1 through translocation was unexpected, we have compared this process with the well-established translocation of the glucose transporter GLUT4. In immunofluorescence microscopy comparisons, the translocation of NHE1 and GLUT4 to the sarcolemma that occur in response to insulin appear to be very similar. However, in basal unstimulated cells the two proteins are mainly located, with the exception of some co-localization in the perinuclear region, in distinct subcellular compartments. We propose that the mechanisms of translocation of NHE1 and GLUT4 are linked such that they provide spatially and temporally co-ordinated responses to cardiac challenges that necessitate re-adjustments in glucose transport, glucose metabolism and cell pH

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines

Background: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. Methods: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, see Supplementary data) concluded the following: Results: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50–200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. Conclusions: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Glucosinolates in alugbati (Basella rubra)

Glucosinolates comprise a group of sulfur - containing glucoside which are known to exhibit biological activities with potential benefits to human health. In previous work it was found that the leaves of alugbati contain significantly high levels of glucosinolates, results that called for a more thorough investigation on these compounds in the plant. Four glucosinolates (GSL) were tentatively identified in alugbati. LC-MS analysis suggested the presence of sinigrin (allyl GSL), glucolepidiin (ethyl GSL), mercaptomethyl glucosinolate and a cinnamic glycoside glucocheirolin-6\u27 -O-sinapoyl-β-D-thioglucoside. This is the first report on these compounds in the Basselaceae. A compound present in the red - stemmed alugbati variety was not detected in the green - stemmed type; otherwise, both varieties exhibited similar glucosinolate profiles and individual glucosinolates were found in roughly the same proportions. Alugbati samples grown under different planting regimes were analyzed to determine the effects of traditional, organic and innovative farming practices on the glucosinolate content. Results showed that in general, the biosynthesis of specific glucosinolates was relatively unaffected by the planting conditions. The only notable differences observed were the levels of the major compound, which could be glucocheirolin-6\u27-sinapoyl-β-D-thioglucoside, which significantly decreased with the application of fertilizer and/or pesticide. The optimum hydrolysis procedure for alugbati glucosinolates was determined. The addition of exogenous myrosinase and the cofactor ascorbic acid increased the yield of hydrolysis products. The dichloromethane extracts of hydrolysates consisted of several metabolites which were identified by GC-MS analysis to be possible degradation compounds of the glucosinolate hydrolysis products such as those coming from sinigrin and the cinnamic glycoside. Other compounds that have been reported to possess health promoting and allelopathic properties were also identified in the DCM extracts

The genotoxic potential of alugbati leaf extracts on MCF-7 cells

To determine the genotoxicity of alugbati (Basella alba Linn. var. rubra) leaf extracts on breast adenocarcinoma, the Comet assay was employed on MCF-7 cells incubated with the following: lyophilized alugbati juice extracts reconstituted with 2 % DMSO (AJ) and in aqueous media (AJ2), and lyophilized alugbati hydrolysate (exogenous myrosinase (E.C. 3.2.3.1) assisted) re- dissolved with 2 % DMSO in culture media (AH). Untreated MCF-7 cells in 2 % DMSO served as the negative control. MANOVA and Post hoc Tukey\u27s HSD were employed to determine statistically significant differences among the samples. First, mutant cells in AJ and AH formed pronounced comet tails indicating that DNA damage had occurred significantly compared to that of the control. Post hoc comparisons between AJ and AH indicated that both samples exhibited comparable effects to MCF-7 cells. Due to the similarity of AJ to AH, it was presumed that hydrolysis occurred during the mechanical process of juice extraction. Second, AJ2 exhibited analogous results with the control; whereas, AJ was found to be statistically different. Aberrant cells incubated with the control and AJ2 trials exhibited relatively minimal genotoxicity as evidenced by intact nuclei. Overall, multiple comparisons illustrated that the most prominent DNA damage was observed by extracts AJ and AH in all parameters. The results of this study suggested that alugbati leaves subjected to enzyme-assisted hydrolysis or juice extractions prepared in DMSO caused considerable DNA damage in MCF-7 cells. © 2019 Jordan Journal of Biological Sciences