Ferrer Adjustable Speaking Valve for Early Phonation in a Deconditioned Patient.

A patient with multiple comorbidities and an eight-year history of tracheostomy was being treated for tracheitis. At this point, she became incapable of using regular speaking valves, and multiple attempts to reintroduce the speaking valve failed. A Ferrer adjustable speaking valve (FASV) was designed with gradations of outflow closure, allowing air to go through the vocal cords for phonation. The FASV was offered to her through the compassionate use program at the FDA. At 20% initial closure, the patient was able to tolerate the valve and was advanced to 50% closure, at which point she could phonate partially. The use of the valve was terminated at the time of her transfer, 23 days after the initiation of use. This suggests the safety and possible efficacy of using an adjustable speaking valve earlier than regular valves, allowing patients to communicate earlier and further exercise their diaphragms.

Innate immune responses to SARS-CoV-2.

This chapter provides an overview of the innate immune response to SARS-CoV-2, focusing on the recognition, activation, and evasion strategies employed by the virus. The innate immune system plays a crucial role in the early defense against viral infections, and understanding its response to SARS-CoV-2 is essential for developing effective therapeutic approaches. The chapter begins by explaining the basics of the innate immune system, including its components and salient features. It discusses the various pattern recognition receptors involved in recognizing SARS-CoV-2, such as toll-like receptors, RIG-I-like receptors, NOD-like receptors, and other cytosolic sensors. The binding and entry of the virus into host cells and subsequent activation of innate immune cells, including neutrophils, monocytes, macrophages, dendritic cells, NK cells, and ILCs, are explored. Furthermore, the secretion of key cytokines and chemokines, including type I interferons, IL-6, IL-17, and TNF-alpha, is discussed as part of the innate immune response. The concept of PANoptosis, involving programmed cell death mechanisms, is introduced as a significant aspect of the response to SARS-CoV-2. The chapter also addresses the innate immune evasion strategies employed by SARS-CoV-2, which allow the virus to evade or subvert the host immune response, contributing to viral persistence. Understanding these strategies is crucial for developing targeted therapies against the virus.

A signature of five 7-methylguanosine-related genes is a prognostic marker for lung squamous cell carcinoma.

Background: N7-methylguanosine (m7G) is an important posttranscriptional modification affecting mRNA and tRNA functions and stability. The genes regulating the m7G process have been previously found involved in the carcinogenesis process. We aimed to analyze the role of m7G-related genes as potential prognostic markers for lung squamous cell carcinoma (LSCC). Methods: Twenty-nine m7G-related genes were selected for the analysis in the LSCC cohort of the Cancer Genome Atlas (TCGA). Univariate, multivariate, and Kaplan-Meier analyses were used to evaluate the predictive value of risk model developed with m7G signature for overall survival (OS).. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of differentially expressed genes (DEGs) were performed for high- and low-risk LSCC groups. Results: We identified 17 differentially expressed m7G methylation-related genes in LSCC versus normal tissues. The expression of five m7G-related genes (EIF3D, LSM1, NCBP2, NUDT10, and NUDT11) was identified as an independent prognostic marker for OS in LSCC patients. A risk model with these five m7G-related genes predicted 2-, and 3-year survival rates of 0.623 and 0.626, respectively. The risk score significantly correlated with OS: LSCC patients with a higher risk score had shorter OS (P<0.01) and it was associated with lower immune response (P<0.01). Conclusions: We developed a novel m7G-related gene signature that can be of great utility to predict the prognosis for patients with LSCC.

Effects of Ketogenic Diet on Reproductive Hormones in Women With Polycystic Ovary Syndrome.

Context: Ketogenic diet has recently made a comeback as a part of lifestyle and dietary modifications in patients with polycystic ovary syndrome (PCOS). Despite studies suggesting its beneficial effects in reversing hormonal imbalance in women with PCOS, evidence has been patchy and derived from small populations under varying conditions. Objective: To pool evidence from clinical trials to study the effects of ketogenic diet on reproductive hormones (LH/FSH ratio, free testosterone, serum progesterone) and observe evidence of weight change. Methods: PubMed, ScienceDirect, Scopus, and Web of Science core collection were searched for clinical trials evaluating the effects of ketogenic diet in established PCOS women consistent with the Rotterdam classification. Single- or double-arm studies that included an outcome of interest were included. Two investigators worked independently to screen potential articles and a designated investigator extracted data on study characteristics and evaluated the outcomes. Data were pooled using a random-effects model. The quality of selected studies was assessed using the Cochrane Risk of Bias Tool. Results: Following ≥45 days of intervention with ketogenic diet among women with PCOS, significant improvement was observed in reproductive hormone levels, with reduced LH/FSH ratio (d -0.851; 95% CI -1.015, -0.686; P < .001), reduced serum free testosterone (d -0.223; 95% CI -0.328, -0.119; P  < .001), and an increased in serum sex hormone binding globulin (SHBG) (d 9.086; 95% CI 3.379, 14.792; P = .002). Significant weight loss was unanimously observed in all included studies (d -11.56; 95% CI -14.97, -8.15; P < .001). Conclusion: Short-term ketogenic diet potentially improved hormonal imbalances commonly associated with PCOS.

Noninvasive central hemodynamic monitoring in the primary care setting: improving prevention and management of cardiovascular diseases.

Background: Although cardiovascular disease (CVD) has markedly declined since the early 1960s due to medical advances and better management, this condition persists as the most critical and preventable cause of death in the US. For that reason, the identification and application of more sensitive, specific, validated, and noninvasive biomarkers of cardiovascular functioning in the primary care setting for the early identification of CVD risk at the subclinical level are warranted. Aim: The goal of the present review is twofold: first, to familiarize the primary care practitioner with noninvasive aortic hemodynamic parameters, including how these could be integrated into primary care services and patient management, and second, to propose a model for earlier detection of CVD based on the noninvasive hemodynamic parameters in the primary care setting. Relevance for Patients: Implementation of noninvasive hemodynamic monitoring in a primary care setting could help in the identification of heart disease risk at the early onset thus preventing the need for expensive treatment or death at later stages.

Biologically Potent Benzimidazole-Based-Substituted Benzaldehyde Derivatives as Potent Inhibitors for Alzheimer's Disease along with Molecular Docking Study.

Twenty-one analogs were synthesized based on benzimidazole, incorporating a substituted benzaldehyde moiety (1-21). These were then screened for their acetylcholinesterase and butyrylcholinesterase inhibition profiles. All the derivatives except 13, 14, and 20 showed various inhibitory potentials, ranging from IC50 values of 0.050 ± 0.001 µM to 25.30 ± 0.40 µM against acetylcholinesterase, and 0.080 ± 0.001 µM to 25.80 ± 0.40 µM against butyrylcholinesterase, when compared with the standard drug donepezil (0.016 ± 0.12 µM and 0.30 ± 0.010 µM, against acetylcholinesterase and butyrylcholinesterase, respectively). Compound 3 in both cases was found to be the most potent compound due to the presence of chloro groups at the 3 and 4 positions of the phenyl ring. A structure-activity relationship study was performed for all the analogs except 13, 14, and 20, further, molecular dynamics simulations were performed for the top two compounds as well as the reference compound in a complex with acetylcholinesterase and butyrylcholinesterase. The molecular dynamics simulation analysis revealed that compound 3 formed the most stable complex with both acetylcholinesterase and butyrylcholinesterase, followed by compound 10. As compared to the standard inhibitor donepezil both compounds revealed greater stabilities and higher binding affinities for both acetylcholinesterase and butyrylcholinesterase.

Introduction to Traditional Medicine and Their Role in Prevention and Treatment of Emerging and Re-Emerging Diseases.

Infectious diseases have been a threat to human health globally. The relentless efforts and research have enabled us to overcome most of the diseases through the use of antiviral and antibiotic agents discovered and employed. Unfortunately, the microorganisms have the capability to adapt and mutate over time and antibiotic and antiviral resistance ensues. There are many challenges in treating infections such as failure of the microorganisms to respond to the therapeutic agents, which has led to more chronic infections, complications, and preventable loss of life. Thus, a multidisciplinary approach and collaboration is warranted to create more potent, effective, and versatile therapies to prevent and eradicate the old and newly emerging diseases. In the recent past, natural medicine has proven its effectiveness against various illnesses. Most of the pharmaceutical agents currently used can trace their origin to the natural products in one way, shape, or form. The full potential of natural products is yet to be realized, as numerous natural resources have not been explored and analyzed. This merits continuous support in research and analysis of ancient treatment systems to explore their full potential and employ them as an alternative or principal therapy.

Chlorpheniramine, an Old Drug with New Potential Clinical Applications: A Comprehensive Review of the Literature.

Chlorpheniramine Maleate (CPM), also known as chlorphenamine, is a potent alkylamine first-generation H1 antihistamine that has been around since the 1950s. CPM is a widely popular drug commonly used to treat allergic conditions, given its antihistamine properties. Although mainly used in over-the-counter treatment for cough and colds, various studies discuss a wide range of CPM's clinical uses, such as treating asthma, plasma cell gingivitis, chronic urticaria, depression, among others. This antihistamine is usually taken orally; however, intravenous, intramuscular, and subcutaneous routes have been documented. Intranasal routes have recently been explored, especially due to its antiviral properties against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Accordingly, given CPM's extensive medical and safety profile, the present review explores this versatile drug's current and potential clinical applications. Although it is widely used mainly for treating common colds and aforementioned allergic conditions, it can be concluded that CPM can be considered to be used for other clinical indications. The repurposing of CPM for other clinical indications such as COVID-19 needs to be further explored through more extensive studies.

Association between hospitalizations for asthma exacerbation and weather conditions in Qingdao: an ecological study.

Background: The hospitalization for asthma exacerbation has varied with seasons, however, the underlying weather reasons have not been fully explored yet. This study is aimed to explore the effect of weather factors on increased number of hospitalization due to worsening of asthma symptoms. This will provide more information to the relevant authorities to allocate appropriate medical resources as per the weather conditions in Qingdao, China. Methods: All adult patients admitted for asthma exacerbation from 1 January, 2017 to 31 December, 2019 were enrolled from 13 main hospitals of Qingdao. The clinical data, including age, sex, smoking history, etc., were collected from the electronic medical record (EMR) systems. The hourly air quality of Qingdao from 2017-2019, including the air quality index (AQI), PM2.5 and PM10, was obtained from the China National Environmental Monitoring Centre. All these parameters during 2017-2019 were compared monthly. For meteorological data, the monthly horizontal wind at 850 hPa and vertical velocity at 500 hPa during 1960-2020 were obtained from National Center for Environmental Prediction (NCEP) and the National Center for Atmospheric Research (NCAR) global reanalysis dataset. The correlation analysis was applied to determine the association between asthma hospitalizations and the environmental factors, including atmospheric pressure, humidity, vertical visibility, and etc., monthly. Results: In all, 10,549 asthmatic inpatients (45.7% males, 54.3% females) were included in the study. The inpatients number for asthma exacerbation had a plateau lasting from March to June of 2019, accompanied with high PM2.5 and PM10, as well as bad air quality from January to March of 2019, potentially governed by the El Niño event in 2018. However, there was no significance correlation between the number of asthma hospitalizations and the average value of all environmental factors. Conclusions: The high rate of hospitalization for asthma exacerbation in Qingdao during the spring of 2019 was associated with the unfavorable weather conditions, which might be linked to the atmospheric circulation in East Asia.

Role of environmental toxicants in the development of hypertensive and cardiovascular diseases.

The incidence of hypertension with diabetes mellitus (DM) as a co-morbid condition is on the rise worldwide. In 2000, an estimated 972 million adults had hypertension, which is predicted to grow to 1.56 billion by 2025. Hypertension often leads to diabetes mellitus that strongly puts the patients at an increased risk of cardiovascular, kidney, and/or atherosclerotic diseases. Hypertension has been identified as a major risk factor for the development of diabetes; patients with hypertension are at two-to-three-fold higher risk of developing diabetes than patients with normal blood pressure (BP). Causes for the increase in hypertension and diabetes are not well understood, environmental factors (e.g., exposure to environmental toxicants like heavy metals, organic solvents, pesticides, alcohol, and urban lifestyle) have been postulated as one of the reasons contributing to hypertension and cardiovascular diseases (CVD). The mechanism of action(s) of these toxicants in developing hypertension and CVDs is not well defined. Research studies have linked hypertension with the chronic consumption of alcohol and exposure to metals like lead, mercury, and arsenic have also been linked to hypertension and CVD. Workers chronically exposed to styrene have a higher incidence of CVD. Recent studies have demonstrated that exposure to particulate matter (PM) in diesel exhaust and urban air contributes to increased CVD and mortality. In this review, we have imparted the role of environmental toxicants such as heavy metals, organic pollutants, PM, alcohol, and some drugs in hypertension and CVD along with possible mechanisms and limitations in extrapolating animal data to humans.

N-([1,1'-biaryl]-4-yl)-1-naphthamide-based scaffolds synthesis, their cheminformatics analyses, and screening as bacterial biofilm inhibitor.

Naphthamides have pharmacological potential as they express strong activities against microorganisms. The commercially available naphthoyl chloride and 4-bromoaniline were condensed in dry dichloromethane (DCM) in the presence of Et3 N to form N-(4-bromophenyl)-1-naphthamide (86%) (3). Using a Pd(0) catalyzed Suzuki-Miyaura Cross-Coupling reaction of (3) and various boronic acids, a series of N-([1,1'-biaryl]-4-yl)-1-naphthamide derivatives (4a-h) were synthesized in moderate to good yields. The synthesized derivatives were evaluated for cytotoxicity haemolytic assay and biofilm inhibition activity through in silico and in vitro studies. Molecular docking, ADME (absorption, distribution, metabolism, and excretion), toxicity risk, and other cheminformatics predict synthesized molecules as biologically active moieties, further validated through in vitro studies in which compounds (4c) and (4f) showed significant haemolytic activity whereas (4e) exhibited an efficient biofilm inhibition activity against Gram-negative bacteria Escherichia coli and Gram-positive bacteria Bacillus subtilis. When forming biofilms, bacteria become resistant to various antimicrobial treatments. Currently, research is focused on the development of agents that inhibit biofilm formation, thus the present work is valuable for preventing future drug resistance.

The nephroprotective effects of Daucus carota and Eclipta prostrata against cisplatin-induced nephrotoxicity in rats.

The overuse of cisplatin (>50 mg/m2) is limited to nephrotoxicity, ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions. The objective of this study was to investigate the nephroprotective effects of Daucus carota and Eclipta prostrata extracts on cisplatin-induced nephrotoxicity in Wistar albino rats. The study involved male Wistar albino rats of 8 weeks weighing 220-270 g. A single injection of 5 mg/kg was injected into the rats for nephrotoxicity. Rats were divided into four groups based on dose conentrations. Blood and urine samples of rats were collected on the 0, 7th, 14th, and 21st days for nephrological analysis. The results showed that Cis + DC/Cis + EP (600 mg/kg) significantly (p < 0.001) increased the body weight and reduced the kidney weight of cisplatin-induced nephrotoxicity in rats (p < 0.001) as compared to Cis group. The results showed that 600 mg/kg administration of Cis + DC/Cis +EP successfully (p < 0.005) improved the urine and plasmin creatinine, Na, and K level compared to the Cis group. Histopathological results confirmed that Cis + EP/Cis + DC effectively improved the renal abnormalities. It is concluded that the co-administration of Cis + EP extract showed exceptional nephroprotective effects at a dose rate of 600 mg/kg.

Evolution of Complexity. Molecular Aspects of Preassembly.

An extension of neo-Darwinism, termed preassembly, states that genetic material required for many complex traits, such as echolocation, was present long before emergence of the traits. Assembly of genes and gene segments had occurred over protracted time-periods within large libraries of non-coding genes. Epigenetic factors ultimately promoted transfers from noncoding to coding genes, leading to abrupt formation of the trait via de novo genes. This preassembly model explains many observations that to this present day still puzzle biologists: formation of super-complexity in the absence of multiple fossil precursors, as with bat echolocation and flowering plants; major genetic and physical alterations occurring in just a few thousand years, as with housecat evolution; lack of precursors preceding lush periods of species expansion, as in the Cambrian explosion; and evolution of costly traits that exceed their need during evolutionary times, as with human intelligence. What follows in this paper is a mechanism that is not meant to supplant neo-Darwinism; instead, preassembly aims to supplement current ideas when complexity issues leave them struggling.

Scope of Artificial Intelligence in Gastrointestinal Oncology.

Gastrointestinal cancers are among the leading causes of death worldwide, with over 2.8 million deaths annually. Over the last few decades, advancements in artificial intelligence technologies have led to their application in medicine. The use of artificial intelligence in endoscopic procedures is a significant breakthrough in modern medicine. Currently, the diagnosis of various gastrointestinal cancer relies on the manual interpretation of radiographic images by radiologists and various endoscopic images by endoscopists. This can lead to diagnostic variabilities as it requires concentration and clinical experience in the field. Artificial intelligence using machine or deep learning algorithms can provide automatic and accurate image analysis and thus assist in diagnosis. In the field of gastroenterology, the application of artificial intelligence can be vast from diagnosis, predicting tumor histology, polyp characterization, metastatic potential, prognosis, and treatment response. It can also provide accurate prediction models to determine the need for intervention with computer-aided diagnosis. The number of research studies on artificial intelligence in gastrointestinal cancer has been increasing rapidly over the last decade due to immense interest in the field. This review aims to review the impact, limitations, and future potentials of artificial intelligence in screening, diagnosis, tumor staging, treatment modalities, and prediction models for the prognosis of various gastrointestinal cancers.

The Deleterious Effects of COVID-19 in the Peripartum Period: A Case Report.

While the Coronavirus Disease 2019 (COVID-19) pandemic continues to wreak havoc across the nation and the globe as one of the most significant global health crises of our time, recent attention has been turned to the effects of COVID-19 on pregnancy and the puerperium. Although most cases have been asymptomatic, for some patients, the disease may be accompanied by serious complications such as pneumonia, acute respiratory distress, multi organ failure, and death. Several case studies have noted that patients with co-morbidities are at a significant risk of these complications. In a recent systematic review and meta-analysis, authors conclude that cardiovascular disease was associated with increased composite poor outcome in patients with COVID-19. The following case report highlights the multi-system complications and severity of symptoms that can take place after childbirth in a patient with co-morbid obstetric and prenatal conditions and an initially asymptomatic COVID-19 infection.

Emerging Role of Fascin-1 in the Pathogenesis, Diagnosis, and Treatment of the Gastrointestinal Cancers.

Gastrointestinal (GI) cancers, including esophageal, gastric, colorectal, liver, and pancreatic cancers, remain as one of the leading causes of death worldwide, with a large proportion accounting for fatalities related to metastatic disease. Invasion of primary cancer occurs by the actin cytoskeleton remodeling, including the formation of the filopodia, stereocilia, and other finger-like membrane protrusions. The crucial step of actin remodeling in the malignant cells is mediated by the fascin protein family, with fascin-1 being the most active. Fascin-1 is an actin-binding protein that cross-links filamentous actin into tightly packed parallel bundles, giving rise to finger-like cell protrusions, thus equipping the cell with the machinery necessary for adhesion, motility, and invasion. Thus, fascin-1 has been noted to be a key component for determining patient diagnosis and treatment plan. Indeed, the overexpression of fascin-1 in GI tract cancers has been associated with a poor clinical prognosis and metastatic progression. Moreover, fascin-1 has received attention as a potential therapeutic target for metastatic GI tract cancers. In this review, we provide an up-to-date literature review of the role of fascin-1 in the initiation of GI tract cancers, metastatic progression, and patients' clinical outcomes.

Incidence, pattern and severity of abnormal liver blood tests among hospitalised patients with SARS-COV2 (COVID-19) in South Wales.

INTRODUCTION: SARS-CoV-2 (COVID-19) is a novel coronavirus that emerged in Wuhan, China in late 2019 and since become a global pandemic. As such, its clinical behaviour is a subject of much interest. Initial reports suggested a significant proportion of patients have abnormal liver blood tests. Gwent has experienced one of the highest incidences of COVID-19 infection in the UK, which itself has among the highest COVID-19 impacts worldwide. METHOD: We set out to report the incidence, clinical pattern and severity of liver blood test abnormalities in hospitalised patients with confirmed COVID-19 in our institution over a 3-week period. Data on clinical outcomes such as admission to intensive therapy unit (ITU), hospital discharge and mortality were recorded. RESULTS: 318 hospitalised COVID-19 positive had liver blood tests available for analysis. Ninety-seven patients (31%) had one or more abnormal liver blood tests and were abnormal admission in 64%. Liver tests were predominantly cholestatic (72%) in contrast to other studies to date. Male gender and abnormal liver blood tests were associated with ITU admission. CONCLUSIONS: Almost one-third of admissions with COVID-19 have abnormal LBTs which are typically mild and are associated with male gender. Importantly, we have identified that cholestatic patterns dominate but were not clearly associated with ITU admission or death.