A novel opportunity to improve heart failure care: focusing on subcutaneous furosemide.

The prevalence of heart failure (HF) continues to rise in developed nations. Symptomatic congestion is the most common reason for patients to seek medical attention, and management often requires intravenous (IV) diuretic administration in the hospital setting. Typically, the number of admissions increases as the disease progresses, not only impacting patient survival and quality of life but also driving up healthcare expenditures. pH-neutral furosemide delivered subcutaneously using a proprietary, single-use infusor system (Furoscix) has a tremendous potential to transition in-hospital decongestive therapy to the outpatient setting or to the patient's home. This review is aimed at providing an overview of the pharmacodynamic and pharmacokinetic profile of the novel pH-neutral furosemide in addition to the most recent clinical trials demonstrating its benefit when used in the home setting. Given the newest data and approval by the Food and Drug Administration in the US, it has the potential to revolutionize the care of patients with decompensated HF. Undoubtedly, it will lead to improved quality of life as well as significantly reduced healthcare costs related to hospital admissions.

[Tuberculous pericarditis an infrequent extrapulmonary manifestation of TB]. / Pericarditis tuberculosa: una manifestación extrapulmonar infrecuente de TBC.

Extrapulmonary tuberculosis (TB) contributes to 15% of total cases, representing a great diagnostic and therapeutic challenge. Pericardial involvement is present in 1 to 2% of TB patients and is considered an unusual presentation form of TB. We report a 67-year-old male presenting with fever and progressive dyspnea. A chest CAT scan showed a bilateral pleural effusion and an extensive pericardial effusion. An echocardiogram showed signs of tamponade. Therefore, an emergency pericardiectomy was performed. The pathological report of pericardial tissue showed caseating necrosis and its Koch culture was positive. The patient was treated with anti-tuberculous drugs with a favorable evolution.

Severity of climacteric symptoms among Peruvian women from an urban coastal community and a rural Andean community.

INTRODUCTION: The aim of this study was to evaluate the severity of climacteric symptoms among two Peruvian communities, adjusted for sociodemographic and clinical variables in climacteric women. METHODS: A cross-sectional study was conducted on 90 subjects from two different communities (an urban coastal and a rural Andean district from Peru). The Menopause Rating Scale was used to assess climacteric symptoms. Prevalence ratios with 95% confidence interval (PR 95%CI) were estimated using generalized linear Poisson models with family robust standard errors. RESULTS: A higher probability of severe climacteric symptoms was found in women who were from the Andean community than those who were from the coastal one (PR 2.42, 95%CI 1.47-3.99; p=0.001), which remained in the adjusted model (RP 1.72, 95%CI 1.04-2.86; p=0.035). CONCLUSION: Understanding the variation of climacteric symptoms among geographically distinct communities could contribute to improving women's quality of life.

Metformin use is associated with a lower risk of osteoporosis in adult women independent of type 2 diabetes mellitus and obesity. REDLINC IX study.

Metformin may decrease cell senescence, including bone; hence we aimed at evaluating the association between metformin use and osteoporosis. This was a cross-sectional study carried out in 1259 Latin American adult women aged 40 or more who were not on anti-osteoporotic drugs, were on metformin and had a bone densitometry performed. Of the whole sample, 40.3% reported being on metformin (at least 1 year), 30.2% had type 2 diabetes mellitus and 22.6% had osteoporosis. Median (interquartile range) body mass index (BMI) for the whole cohort was 27.7 (4.6) kg/m2 and 30.2% had type 2 diabetes mellitus. Current use of hormone therapy, calcium, and vitamin D corresponded respectively to 10.7%, 47.7%, and 43.1% of all surveyed women. A logistic regression model was used to analyze the association of osteoporosis with various covariates incorporated into the model such as age (OR: 1.07, 95% CI: 1.05-1.09), BMI (OR: 0.92, 95% CI: 0.89-0.96) and metformin use (OR: 0.44, 95% CI: 0.32-0.59). Metformin use, regardless of the presence of type 2 diabetes or obesity, was associated with a lower risk of osteoporosis in adult women. We propose that one explanation for this observation could be the effect of the drug over cellular senescence.

Particle-based optical sensing of intracellular ions at the example of calcium - what are the experimental pitfalls?

Colloidal particles with fluorescence read-out are commonly used as sensors for the quantitative determination of ions. Calcium, for example, is a biologically highly relevant ion in signaling, and thus knowledge of its spatio-temporal distribution inside cells would offer important experimental data. However, the use of particle-based intracellular sensors for ion detection is not straightforward. Important associated problems involve delivery and intracellular location of particle-based fluorophores, crosstalk of the fluorescence read-out with pH, and spectral overlap of the emission spectra of different fluorophores. These potential problems are outlined and discussed here with selected experimental examples. Potential solutions are discussed and form a guideline for particle-based intracellular imaging of ions.

Ventricular septal defect following mitral valve replacement.

Mitral valve surgery (MVS), with repair preferred to replacement, is a common procedure for the treatment of severe primary mitral regurgitation related to leaflet prolapse. Structural complications after MVS include left ventricular outflow obstruction, paravalvular leak and atrial septal defect. Intraoperative transoesophageal echocardiography and predischarge transthoracic echocardiography (TTE) specifically screen for these complications. Ventricular septal defect (VSD), a known complication after aortic valve surgery, is rarely reported after MVS. Recently, unsuccessful valvuloplasty prior to replacement was suggested as a risk factor. We present such a case and explore mechanisms with advanced cardiac imaging. In this case, the patient was found to have an elongated membranous septum that likely predisposed her to septal injury. Finally, we provide guidance on specific transoesophageal/transthoracic echocardiography views to avoid a missed diagnosis.

From Crisis to Connectivity: Exploring the Role of Information and Communication Technologies in Medical Education During the COVID-19 Pandemic.

INTRODUCTION: In a virtual setting at a private university in Lima, Peru, 277 medical students participated in a study in 2021 during the Coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE:  The aim was to investigate how information and communication technologies (ICTs) were utilized as educational aids in their field. RESULTS: The findings showed a high level of satisfaction with ICT resources, especially among female students (54%). However, challenges were present: 64% faced technical issues during virtual classes, while 60% saw information availability and internet access as major advantages. Despite connectivity problems affecting 83% of students, 55% believed ICTs supported collaborative learning. Interestingly, while 64% found ICT use distracting, 52% found it easy to use. CONCLUSION: ICTs played a significant role in medical education, introducing new methods and tools despite obstacles and providing a dynamic and adaptable e-learning environment.

Successful Surgical Excision of Retropharyngeal Plexiform Neurofibroma in a Non-neurofibromatosis Adult Male.

Plexiform neurofibromas are benign tumors that arise from neuronal cells and are commonly associated with neurofibromatosis type 1 (NF1) patients. However, the occurrence of plexiform neurofibromas in the pharyngeal region is extremely rare. In this particular case, we report the successful diagnosis of a retropharyngeal plexiform neurofibroma in an adult male patient without a history of neurofibromatosis. The diagnosis was made using magnetic resonance imaging (MRI) and confirmed by a biopsy. Following the diagnosis, the tumor was surgically excised, resulting in a successful removal of the neurofibroma.

Therapies for patients with coexisting heart failure with reduced ejection fraction and non-alcoholic fatty liver disease.

Heart failure with reduced ejection fraction (HFrEF) and nonalcoholic fatty liver disease (NAFLD) are two common comorbidities that share similar pathophysiological mechanisms. There is a growing interest in the potential of targeted therapies to improve outcomes in patients with coexisting HFrEF and NAFLD. This manuscript reviews current and potential therapies for patients with coexisting HFrEF and NAFLD. Pharmacological therapies, including angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, mineralocorticoids receptor antagonist, and sodium-glucose cotransporter-2 inhibitors, have been shown to reduce fibrosis and fat deposits in the liver. However, there are currently no data showing the beneficial effects of sacubitril/valsartan, ivabradine, hydralazine, isosorbide nitrates, digoxin, or beta blockers on NAFLD in patients with HFrEF. This study highlights the importance of considering HFrEF and NAFLD when developing treatment plans for patients with these comorbidities. Further research is needed in patients with coexisting HFrEF and NAFLD, with an emphasis on novel therapies and the importance of a multidisciplinary approach for managing these complex comorbidities.

Performance of Computed Tomographic Angiography-Based Aortic Valve Area for Assessment of Aortic Stenosis.

Background A total of 40% of patients with severe aortic stenosis (AS) have low-gradient AS, raising uncertainty about AS severity. Aortic valve calcification, measured by computed tomography (CT), is guideline-endorsed to aid in such cases. The performance of different CT-derived aortic valve areas (AVAs) is less well studied. Methods and Results Consecutive adult patients with presumed moderate and severe AS based on echocardiography (AVA measured by continuity equation on echocardiography <1.5 cm2) who underwent cardiac CT were identified retrospectively. AVAs, measured by direct planimetry on CT (AVACT) and by a hybrid approach (AVA measured in a hybrid manner with echocardiography and CT [AVAHybrid]), were measured. Sex-specific aortic valve calcification thresholds (≥1200 Agatston units in women and ≥2000 Agatston units in men) were applied to adjudicate severe or nonsevere AS. A total of 215 patients (38.0% women; mean±SD age, 78±8 years) were included: normal flow, 59.5%; and low flow, 40.5%. Among the different thresholds for AVACT and AVAHybrid, diagnostic performance was the best for AVACT <1.2 cm2 (sensitivity, 85%; specificity, 26%; and accuracy, 72%), with no significant difference by flow status. The percentage of patients with correctly classified AS severity (correctly classified severe AS+correctly classified moderate AS) was as follows; AVA measured by continuity equation on echocardiography <1.0 cm2, 77%; AVACT <1.2 cm2, 73%; AVACT <1.0 cm2, 58%; AVAHybrid <1.2 cm2, 59%; and AVAHybrid <1.0 cm2, 45%. AVACT cut points of 1.52 cm2 for normal flow and 1.56 cm2 for low flow, provided 95% specificity for excluding severe AS. Conclusions CT-derived AVAs have poor discrimination for AS severity. Using an AVACT <1.2-cm2 threshold to define severe AS can produce significant error. Larger AVACT thresholds improve specificity.

Clinically Suspected Acute Myocarditis in the First Trimester of Twin Gestation: A Case Report.

Acute myocarditis (AM) in early pregnancy is a rare disease. Its clinical presentation varies from asymptomatic disease to cardiogenic shock and death. A 28-year-old woman, 12 weeks primigravida of a dichorionic and diamniotic pregnancy, was admitted for hyperemesis gravidarum, associated with a common cold-like condition. During hospitalization, she developed new-onset sinus tachycardia and dyspnea. An electrocardiogram revealed sinus tachycardia and diffuse ST-segment elevation. Laboratory tests showed elevated levels of troponin and pro-B-type natriuretic peptide. Pelvic obstetric ultrasound and chest X-ray were normal. Speckle-tracking echocardiography showed mild apical hypokinesia with preserved left ventricular ejection fraction. In view of these findings, AM was suspected, and cardiac magnetic resonance imaging was highly suggestive of AM. The patient had a favorable recovery without cardiovascular or obstetric complications.

Protein oriented ligation on nanoparticles exploiting O6-alkylguanine-DNA transferase (SNAP) genetically encoded fusion.

A bimodular genetic fusion comprising a delivery module (scFv) and a capture module (SNAP) is proposed as a novel strategy for the site-specific covalent conjugation of targeting peptides to nanoparticles. An scFv mutant selective for HER2 tumor antigen is chosen as the targeting ligand. SNAP-scFv is immobilized on magnetofluorescent nanoparticles and its targeting efficiency against HER2-positive cells is assessed by flow cytometry and immunofluorescence.

Integration of organic fluorophores in the surface of polymer-coated colloidal nanoparticles for sensing the local polarity of the environment.

Inorganic hydrophobically capped NPs such as quantum dots, superparamagnetic iron oxide, or gold nanoparticles can be modified to make them water-soluble by their embedding in an amphiphilic polymer shell. This polymer shell can be prefunctionalized by the integration of organic fluorophores, which allows the observation of the nanoparticles with fluorescence based techniques. The fluorophore could be either located more in the hydrophobic part of the inner polymer shell, or on the hydrophilic surface pointing towards solution. Herein we prepared gold nanoparticles decorated with the organic fluorophore FE, 4'-N,N-diethylamino-3-hydroxyflavone (FE), which possesses fluorescence sensitive to the polarity and hydrogen-bonding properties of the surrounding local environment. Based on the response of FE in the polymer shell to isopropanol, and CTAB compared to the response of free FE we conclude that the FE fluorophore is situated within the inner polymer shell. Nevertheless the fluorophore in the polymer shell can still sense polarity changes in solution.

Attenuation of endoplasmic reticulum stress using the chemical chaperone 4-phenylbutyric acid prevents cardiac fibrosis induced by isoproterenol.

Increasing evidence indicates that endoplasmic reticulum (ER) stress is involved in various diseases. In the human heart, ischemia/reperfusion has been correlated to ER stress, and several markers of the unfolded protein response (UPR) participate during cardiac remodeling and fibrosis. Here, we used isoproterenol (ISO) injection as a model for in vivo cardiac fibrosis. ISO induced significant cardiomyocyte loss and collagen deposition in the damaged areas of the endocardium. These responses were accompanied by an increase in the protein levels of the luminal ER chaperones BIP and PDI, as well as an increase in the UPR effector CHOP. The use of the chemical chaperone 4-phenylbutyric acid (4-PBA) prevented the activation of the UPR, the increase in luminal chaperones and also, leads to decreased collagen deposition, cardiomyocyte loss into the damaged zones. Our results suggest that cardiac damage and fibrosis induced in vivo by the beta-adrenergic agonist ISO are tightly related to ER stress signaling pathways, and that increasing the ER luminal folding capacity with exogenously administrated 4-PBA is a powerful strategy for preventing the development of cardiac fibrosis. Additionally, 4-PBA might prevent the loss of cardiomyocytes. Our data suggests that the attenuation of ER stress pathways with pharmacological compounds such as the chemical chaperone 4-PBA can prevent the development of cardiac fibrosis and adverse remodeling.

Double Trouble: A Unique Case of Hypercalcemia Caused by Two Underlying Etiologies.

Hypercalcemia has a variety of causes, with primary hyperparathyroidism and malignancies being the most frequently reported. We present the case of a patient presenting with chronic abdominal pain, constipation, and weight loss who was found to have hypercalcemia. The patient was initially diagnosed with colonic actinomycosis, but further investigations revealed an intra-abdominal diffuse large B-cell lymphoma (DLBCL). We suspect that the leading cause of hypercalcemia was the DLBCL, likely exacerbated by actinomycosis. Actinomycosis and DLBCL can have a similar presentation, so misdiagnosis or coexistence of both conditions should be suspected when a lack of response to one specific therapy is observed.

Physical Properties of Blood and their Relationship to Clinical Conditions.

It has been long known that blood health heavily influences optimal physiological function. Abnormalities affecting the physical properties of blood have been implicated in the pathogenesis of various disorders, although the exact mechanistic links between hemorheology and clinical disease manifestations remain poorly understood. Often overlooked in current medical practice, perhaps due to the promises offered in the molecular and genetic era, the physical properties of blood which remain a valuable and definitive indicator of circulatory health and disease. Bridging this gap, the current manuscript provides an introduction to hemorheology. It reviews the properties that dictate bulk and microcirculatory flow by systematically dissecting the biomechanics that determine the non-Newtonian behavior of blood. Specifically, the impact of hematocrit, the mechanical properties and tendency of red blood cells to aggregate, and various plasma factors on blood viscosity will be examined. Subsequently, the manner in which the physical properties of blood influence hemodynamics in health and disease is discussed. Special attention is given to disorders such as sickle cell disease, emphasizing the clinical impact of severely abnormal blood rheology. This review expands into concepts that are highly topical; the relation between mechanical stress and intracellular homeostasis is examined through a contemporary cell-signaling lens. Indeed, accumulating evidence demonstrates that nitric oxide is not only transported by erythrocytes, but is locally produced by mechanically-sensitive enzymes, which appears to have intracellular and potentially extracellular effects. Finally, given the importance of shear forces in the developing field of mechanical circulatory support, we review the role of blood rheology in temporary and durable mechanical circulatory support devices, an increasingly utilized method of life support. This review thus provides a comprehensive overview for interested trainees, scientists, and clinicians.

Low sexual function is associated with menopausal status in mid-aged women with human immunodeficiency virus infection.

OBJECTIVE: To assess the association between menopausal status and female sexual function among mid-aged women with human immunodeficiency virus (HIV) infection. METHODS: We carried out a cross-sectional study of 221 sexually active HIV-infected women ages 40 to 59 years, based on a secondary analysis of a three-hospital survey in Lima, Perú. We classified menopausal status according to Stages of Reproductive Aging Workshop criteria (STRAW+10); this exposure variable was categorized as binary (non-postmenopausal and postmenopausal) and-for exploratory analysis-as multinomial (pre-, peri-, and postmenopausal). We defined low sexual function (LSF) using the 6-item Female Sexual Function Index (total score ≤19). Socio-demographic and clinical variables were assessed, including age, used highly active antiretroviral therapy scheme, disease duration, depressive symptoms, and co-morbidities. We performed Poisson generalized linear models with a robust variance to estimate 95% confidence interval (CI), crude prevalence ratios (cPRs), and adjusted prevalence ratios (aPRs) by epidemiological and statistical approaches using nonparametric method of bias-corrected and accelerated bootstrap resampling with 1,000 repetitions. RESULTS: Studied women had a median age of 47.0 years (interquartile range: 7.5); 25.3% were premenopausal, 25.8% were perimenopausal, and 48.9% were postmenopausal. Also, 64.3% had LSF. The frequency of LSF was 53.6% in non-postmenopausal and 75.0% in postmenopausal women. Postmenopausal status was associated with LSF in both the crude (cPR = 1.39; 95% CI: 1.13-1.71) and the adjusted regression models (aPR = 1.38; 95% CI: 1.12-1.71). CONCLUSIONS: HIV-infected postmenopausal women have a higher prevalence of LSF than those non-postmenopausal ones, even when adjusting for multiple potential confounders.

Differential effects of nociceptin/orphanin FQ (NOP) receptor agonists in acute versus chronic pain: studies with bifunctional NOP/µ receptor agonists in the sciatic nerve ligation chronic pain model in mice.

1-(1-Cyclooctylpiperidin-4-yl)-indolin-2-one (SR14150) and 1-(1-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)piperidinl-4-yl)-indolin-2-one (SR16835) are moderately selective nociceptin/orphanin FQ (NOP) receptor agonists. In the [(35)S]guanosine 5'-O-(3-thiotriphosphate) assay in vitro, SR14150 is a partial agonist at both the NOP and µ-opioid receptors, whereas SR16835 is a full agonist at the NOP receptor and has low efficacy at µ receptors. These compounds were tested for antinociceptive and antiallodynic activity, using mice in chronic pain, subsequent to spinal nerve ligation (SNL) surgery. When administered subcutaneously to mice after SNL surgery, SR14150 but not SR16835 increased tail-flick latency, which was blocked by the opioid antagonist naloxone, but not by the NOP receptor antagonist (-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol (SB-612111). In contrast, both SR14150 and SR16835 had antiallodynic activity when mechanical allodynia was measured with von Frey monofilaments. This effect was completely blocked by SB-612111 but not by naloxone. On the other hand, morphine antinociception and antiallodynia were both blocked by naloxone and potentiated by SB-612111. These results indicate that, in mice, circuitry mediating antinociceptive activity in acute and chronic pain states is different. It is possible that during a chronic pain state, an up-regulated NOP system in the spinal cord leads to NOP receptor-mediated antiallodynia, which is blocked by NOP antagonists. However, supraspinal up-regulation could lead to an attenuation of morphine antinociception and antiallodynia, which can be alleviated by an NOP receptor antagonist. Thus, although neither NOP agonists nor antagonists are effective as analgesics in acute pain, they may have efficacy as analgesics, either alone or in combination with morphine, for treatment of chronic pain.

Light triggered detection of aminophenyl phosphate with a quantum dot based enzyme electrode.

An electrochemical sensor for p-aminophenyl phosphate (pAPP) is reported. It is based on the electrochemical conversion of 4-aminophenol (4AP) at a quantum dot (QD) modified electrode under illumination. Without illumination no electron transfer and thus no oxidation of 4AP can occur. pAPP as substrate is converted by the enzyme alkaline phosphatase (ALP) to generate 4AP as a product. The QDs are coupled via 1,4-benzenedithiol (BDT) linkage to the surface of a gold electrode and thus allow potential-controlled photocurrent generation. The photocurrent is modified by the enzyme reaction providing access to the substrate detection. In order to develop a photobioelectrochemical sensor the enzyme is immobilized on top of the photo-switchable layer of the QDs. Immobilization of ALP is required for the potential possibility of spatially resolved measurements. Geometries with immobilized ALP are compared versus having the ALP in solution. Data indicate that functional immobilization with layer-by-layer assembly is possible. Enzymatic activity of ALP and thus the photocurrent can be described by Michaelis- Menten kinetics. pAPP is detected as proof of principle investigation within the range of 25 µM-1 mM.