Diseases

Alzheimer’s disease (AD) is an age-dependent, progressive disorder affecting millions of people. Currently, the therapeutics for AD only treat the symptoms. Although they have been used to discover new products of interest for this disease, mammalian models used to investigate the molecular determinants of this disease are often prohibitively expensive, time-consuming and very complex. On the other hand, cell cultures lack the organism complexity involved in AD. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for the investigation of the pathophysiology of human AD. Numerous models of both Tau- and Aβ-induced toxicity, the two prime components observed to correlate with AD pathology and the ease of performing RNA interference for any gene in the C. elegans genome, allow for the identification of multiple therapeutic targets. The effects of many natural products in main AD hallmarks using these models suggest promising health-promoting effects. However, the way in which they exert such effects is not entirely clear. One of the reasons is that various possible therapeutic targets have not been evaluated in many studies. The present review aims to explore shared therapeutical targets and the potential of each of them for AD treatment or prevention. Full article

The aim of this article was to present a summary of the current resources available in the literature regarding the role of inflammation in anal cancer development. Anal cancer is relatively uncommon, accounting for about 2.7% of all reported gastrointestinal cancers in the United States. However, the importance of understanding the pathogenesis and risk factors for anal cancer has been recognized over the last several decades due to a noticed increase in incidence worldwide. Infections, autoimmune diseases, and inflammatory diseases of unknown etiology cause chronic inflammation that promotes tumorigenesis. The association between chronic inflammation and cancer development is widely accepted. It is based on different pathophysiological mechanisms that lead to cellular transformation and changes in immunological response, allowing tumor cells to avoid apoptosis and immune surveillance. However, there are still many molecular and cellular mechanisms that remain largely unexplored. Further studies on this topic could be of tremendous significance in elucidating anal cancer pathogenesis and developing immunotherapeutic approaches for its treatment. Full article

Objective: This study sought to assess the associations between occupation, serum concentrations of selected of Per- and Polyfluoroalkyl Substances (PFAS), and chronic physiological stress, as operationalized by Allostatic Load (AL), among adults aged ≥20 years. Methods: To explore the interactions of occupation with PFAS levels and AL, data from the National Health and Nutrition Examination Survey (NHANES) 2007–2014 were used. We performed Poisson regression modeling to evaluate AL’s relationships with PFAS concentrations and occupations on weighted data. Results: The results demonstrated that increased AL was positively associated with different occupation groups such as a) Public Administration and b) Arts, Entertainment, and Recreation (p-values 0.018 and 0.002, respectively), and with certain PFAS concentrations (Perfluorooctanoic acid, PFOA, p-value = 0.002). Finally, AL had a strong association with the interaction of some PFAS such as Perfluorobutane sulfonic acid (PFBS) and occupation (AL: PFBS: occupation, p-value < 0.0001), with different association measures existing across varying occupations. Conclusions: Occupation and PFOA seem to be associated with AL. This suggests the need of implementing further strategies to limit the exposure to stressors and PFAS in the work environment to promote longevity among the workforce in the U.S. Finally, policymakers must do more to clearly define standards and regulations in the work environment related to PFAS exposure. Full article

(1) Background: The production of anti-SARS-CoV-2 antibodies should help minimize the severity of COVID-19 disease. Our focus was to investigate and compare different vaccination schedules, monitoring circulating S-RBD Ab (antibodies anti—Spike protein—Receptor Binding Domain) levels after administering two doses in naïve patients. Likewise, vaccine-stimulated immunity in naïve and previously infected patients was compared. (2) Methods: We included 392 patients. Sera were evaluated by Elecsys anti-SARS-CoV-2 S. Statistical analyses were conducted by MedCalc and JASP. (3) Results: In COVID-19 patients, the median value of Ab levels was 154 BAU/mL, stable up to 9 months after the infection. From the data observed in vaccinated patients, higher median values were recorded in COVID-19/Pfizer BioNTech (18913 BAU/mL) than in other groups (Pfizer BioNTech: 1841; ChadOx1 961; heterologous vaccination: 2687) BAU/mL. (4) Conclusions: In conclusion, a single booster dose given to previously infected patients raised an antibody response much higher than two doses given to naïve individuals and heterologous vaccination generated a robust persistent antibody response at high levels, steady up to three months after administration. Full article

Checkpoint inhibitor (CPI) therapy has only recently been introduced in the first-line treatment of advanced gastric cancer. However, later line monotherapy CPI efficacy in a subset of patients was presented about four years prior. Here, we present three cases of advanced gastric adenocarcinoma cancers treated with CPI in early lines years prior to the availability of randomized first line data. All three patients remain in remission without gastrectomy, with the median time from initial diagnosis of approximately 52 months. With long-term follow-up of more than four years, we present a proof of concept that, with early integration of CPI therapy, highly durable responses are possible even in the absence of surgery in patients with advanced gastric and gastroesophageal junction cancers. Full article

Gastroesophageal cancer is one of the most common cancers in the world, with a high rate of mortality. While there has been significant progress over the past decade, particularly with the addition of anti-HER2 therapies to platinum-based chemotherapy agents in the advanced setting, the prognosis remains poor and the treatment options for this disease entity remain limited. In this review, we discuss the current therapeutic landscape for HER2-positive gastroesphageal cancer and the seminal clinical trials that have shaped our approach to this disease entity. In addition, we highlight some of the challenges to the understanding and management of this disease, specifically discussing the breadth of molecular diversity and intratumoral heterogeneity of HER2 expression that impact the clinical efficacy and prognosis. Furthermore, we discuss the potential role of next-generation sequencing (NGS) and circulating-tumor DNA (ctDNA) as complementary tools to immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH) to guiding clinical decision making. Finally, we highlight promising clinical trials of new treatment regimens that will likely reshape the therapeutic approach to this disease entity. Full article

Introduction: Although 80% of symptomatic individuals with COVID-19 develop mild forms, it is the severe (15%) and critical (5%) forms that have the greatest impact in the hospital setting. Recognizing markers that can predict severe forms is essential, especially in high-altitude populations. Methods: We conducted a prospective cohort study at 3200 masl (meters above sea level) in a city in Peru to determine if MPV (mean platelet volume) level is a predictor of COVID-19 severity. Patients with mild/moderate disease were enrolled and followed for 21 days or until the development of severe disease (primary outcome). A bivariate analysis was used to identify variables associated with severe disease. A ROC analysis determined the best MPV (mean platelet count) cut-off to predict COVID-19 severity, and then, a multiple regression analysis was performed. Results: 64 patients were enrolled. The median age was 48.5 years (IQT 39–64.5) and the proportion of women was 51.6%, the most frequent symptoms were chest pain (73%), fever (71%), and dyspnea (67%). The median time to develop a severe form from the onset of symptoms was 11 days (IQT 10.5–13). The most common radiographic phase on CT scan (computed tomography) was progressive (60.38%). We observed that an MPV of more than 10.15 fL in the first week of disease predicted severity regardless of age and sex at high altitudes. Conclusions: MPV in the first week of the disease may predict severity in patients diagnosed with COVID-19 at high altitudes; however, we need prospective studies with a larger population and at a different altitude, levels to confirm these findings. Full article

Anorectal malignant melanoma is a rare culprit of malignancies in the anorectal region. With a presentation that mimics the vastly more common colorectal tumours, clinical misdiagnosis and diagnostic delays often occur, contributing to a dismal prognosis. The authors report a case of metastatic anorectal malignant melanoma presenting as seizures. Though our standard diagnostic pathway for suspected anorectal malignancies was followed, and despite the patient having computerized tomography (CT) of the head earlier, this presentation nonetheless led to a prolongation of time needed to reach histological diagnosis and delay in commencing definitive treatment. It also highlights the paucity of research into the pathophysiology and management of this infrequent but aggressive disease, and the need for raising awareness about this condition to the medical community so that it is considered as a plausible differential diagnosis from the outset and diagnostic pathways adjusted accordingly. Full article

Diabetes mellitus is a global health problem that affects 9.3% of the worldwide population and is associated with a series of comorbidities such as heart failure (HF) and chronic kidney disease (CKD). Diabetic patients, especially those with associated CKD, are more susceptible to present potassium disorders, in particular hyperkalemia due to kidney disease progression or use of renin-angiotensin-aldosterone blockers. Hyperkalemia is a potentially life-threatening condition that increases the risk of cardiac arrhythmia episodes and sudden death, making the management of potassium levels a challenge to reduce the mortality rate in this population. This review aims to briefly present the potassium physiology and discuss the main conditions that lead to hyperkalemia in diabetic individuals, the main signs, symptoms, and exams for the diagnosis of hyperkalemia, and the steps that should be followed to manage patients with this potentially life-threatening condition. Full article

Background: In Arizona Helicobacter pylori prevalence of infection among Navajo adults is about 62% and gastric cancer incidence rate is 3–4 times higher than that of the non-Hispanic White population. Aim: The aim of this study was to estimate the prevalence of specific H. pylori virulence factors (cagA and vacA) among Navajo patients undergoing and their association with gastric disease. Methods: Virulence genes, cagA and vacA, in H. pylori were investigated in gastric biopsies from 96 Navajo patients over age 18 who were undergoing esophagogastroduodenoscopy. Biopsies from the antrum and fundus were used for molecular characterization to determine cagA type and number of EPIYA motifs and presence of alleles in the signal (s) and medium (m) regions of the vacA gene. Results: H. pylori infection was found in 22.9% of the biopsy samples. The cagA gene amplified in 57.6% of samples and showed a predominant “Western cagA” type, with the EPIYA-ABC motif (45.4%), most prevalent. The vacA allele s1bm1 was the most prevalent (54.5%). Conclusions: H. pylori genotypes were predominantly cagA Western-type and ABC EPIYA motifs. The vacA s1bm1 genotype was the most prevalent and seemed to be associated with gastritis. American Indian/Alaska Native populations are at higher risk for gastric cancer. It is important to identify genotypes of H. pylori and virulence factors involved in the high prevalence of H. pylori and associated disease among the Navajo population. Full article

Rabies is a zoonotic disease caused by the rabies virus (RABV) that causes fatal encephalitis in mammals. Bats can transmit the disease to urban canines and felines, which rarely infect humans, establishing a secondary link. The last case of human rabies in Argentina was transmitted by a dog in 2008. We present the first case of human rabies originating from an insectivorous bat, Tadarida brasiliensis, transmitted by a feral cat in Buenos Aires province, Argentina. Full article

Aim: The impact of chronic kidney disease (CKD) on patient-related outcomes in patients with tricuspid regurgitation (TR) is well known. However, the impact of the progression of CKD in patients with TR and potentially modifiable risk factors of progressing CKD is unknown. Methods: 444 consecutive adult patients with TR and CKD stage 1–4 admitted in an inpatient setting between January 2010 and December 2017 were included. During a median follow-up of two years, eGFR and survival status were collected. Independent risk factors for CKD progression and all-cause mortality were determined. Patient survival statuses were grouped according to different combinations of the presence or absence of CKD progression and the TR grade. Results: Progression of CKD (OR 2.38 (95% confidence interval 1.30–4.35), p = 0.005), the grade of TR (OR 2.38 (1.41–4.00), p = 0.001) and mitral regurgitation (OR 1.72 (1.20–2.46), p = 0.003) were independent risk factors for all-cause mortality. Haemoglobin at admission (OR 0.80 (0.65–0.99), p = 0.043) and the presence of type 2 diabetes (OR 1.67 (1.02–2.73), p = 0.042) were independent risk factors for CKD progression. The combination of the status of CKD progression and the TR grade showed a stepwise pattern for all-cause mortality (p < 0.001). Patients with CKD progression and TR grade 1 had comparable all-cause mortality with patients without CKD progression but with TR grade 2 or 3. Even in patients with TR grade 1, the risk for all-cause mortality doubled if CKD progression occurred (OR 2.49 (95% CI 1.38–4.47), p = 0.002). Conclusion: CKD progression appears to be a risk factor for all-cause mortality in patients with TR. Anaemia and diabetes are potential modifiers of CKD progression. Full article

Type 2 Diabetes Mellitus (T2DM) is a complicated multifactorial illness involving hereditary and external environmental variables. The symptoms typically appear gradually over a number of years without realizing it. This viewpoint is further supported by the Ayurvedic constitution concept (Prakriti). Prakriti explains the biological variability that is observed in different individuals. This study was conducted a retrospective investigation to examine if there was a link between type 2 diabetes and an individual’s constitution based on anthropometric and biochemical characteristics. Physical and mental characteristics and anthropometric and biochemical markers were used to determine reported cases’ prevailing Dosha Prakriti (constitution). Based on biochemical and anthropometric data, significant differences in Prakriti were found between the case (T2DM patients) and control (person without diabetes) groups. The incidence of numerous secondary problems linked with T2DM patients was also evaluated according to their Prakriti types, which revealed a positive relationship. The three primary contributing parameters, such as waist-hip ratio, postprandial blood sugar, and serum creatinine, were correctly classified all person with or without diabetes subjects to 90.6% of the time, whereas the constitution-wise study classified person with diabetes and without diabetes individuals of Pitta and Kapha Prakriti to 94.3% and 90%, respectively. A discriminant function was created to predict a person with diabetes and without diabetes based on these three contributing factors. The primary contributing biochemical parameters discovered by Prakriti in the current study could be used as a biochemical disease diagnostic for predicting type 2 diabetes susceptibility. Full article

Inflammatory bowel diseases (IBD) are systemic conditions characterized by multiple intestinal and extra-intestinal manifestations related to the associated chronic inflammatory state. Among their diverse extra-intestinal complications, venous thromboembolism (VTE) remains one of the most under recognized causes of morbidity and mortality in these patients, highlighting the need for a better understanding of the underlying mechanism of hypercoagulability, in addition to the role of acquired and inherited risk factors that further increase the risk of thrombosis with its impact on patients’ outcomes. We hereby present a review of the data regarding thrombosis in the setting of IBD, elucidating the possible role for screening in this high-risk category of patients and specifically in areas where inherited thrombophilia is expected to be highly prevalent, reporting two patients with IBD, one who developed a cerebrovascular event and another one who had recurrent VTE events; nevertheless, both of them had inherited thrombophilic mutations. The identification of specific genetic abnormalities in those patients reintroduces the controversy related to the need to screen a specific category of patients with IBD for hereditary thrombophilia, especially in regions characterized by a higher prevalence of such thrombophilic alterations. Full article

New advancements in the medical community have rapidly occurred with the development of medical information across the globe during the COVID-19 pandemic. Several vaccine manufacturers were able to obtain clearance to administer vaccines in selected age groups and for those at high risk for COVID-19 complications. As vaccines became more readily available, there was a significant effort supported by scientific information to get people vaccinated to boost herd immunity. Acute demyelinating encephalomyelitis (ADEM) is a rare autoimmune disease, causing demyelination in the brain and spinal cord, presenting as monophasic, acute-onset, and rapidly progressive multifocal neurological deficits. A wide variety of precipitating factors can trigger ADEM, and it has long been known to be a rare adverse event following some types of vaccinations including rabies, diphtheria–tetanus–polio, smallpox, measles, mumps, rubella, pertussis, influenza, and hepatitis B vaccines. Recently, ADEM has also been associated with COVID-19 infection and (very rarely) with COVID-19 vaccination. We have a 56-year-old female who was not known to have any medical issues. She voluntarily received her first COVID-19 vaccination (AstraZeneca) ten days after immunization; she developed weakness of the lower limbs and slurred speech. She tested negative for COVID-19, and a brain MRI showed T2-weighted white-matter hyperintense lesions suggesting acute demyelinating encephalomyelitis. She was managed with pulse-dose steroids, which resulted in a marked improvement in her symptoms, and discharged in a stable condition. Physicians should be aware of this neurological disorder and the management options for better patient care and outcomes. Full article

Introduction: Periodontitis is the most prevalent inflammatory disease worldwide. Its inflammatory levels spread systemically, which can be associated with chronic kidney disease. Biomarkers have the potential to diagnose and correlate periodontitis and chronic kidney disease, helping to monitor systemic inflammation. Thereby, this study aimed to analyze the association between chronic kidney disease and periodontitis by conducting a biomarker analysis on blood and saliva. Material and methods: An electronic search through PubMed/MEDLINE, EMBASE, and Web of Science databases was conducted to identify clinical studies published in the last ten years, with no language restrictions. Twelve articles met all the inclusion criteria, two randomized controlled trials, one cohort study, and nine observational studies. Results: The studies included a total of 117 patients for saliva biomarkers, with a mean age of approximately 57 years old, and 56.68% of the subjects were female. After analyzing all the included studies, it was possible to verify the following biomarkers assessed: CRP, WBC, fibrinogen, IL-4 and -6, cardiac troponin T, NOx, ADMA, albumin, osteocalcin, cystatin C, PGLYRP1, cholesterol, HDL, LDL, triglycerides, and hemoglobin. Conclusion: A direct cause–effect association between periodontitis and CKD could not be established. However, it was possible to conclude that there was a correlating effect present, through the analyzed biomarkers. Full article

Primary malignancies of the lung, skin (melanoma), and breast have higher propensity for metastatic spread to the brain. Advances in molecular tumour profiling have aided the development of targeted therapies, stereotactic radiotherapy, and immunotherapy, which have led to some improvement in patient outcomes; however, the overall prognosis remains poor. Continued research to identify new prognostic and predictive biomarkers is necessary to further impact patient outcomes, as this will enable better risk stratification at the point of primary cancer diagnosis, earlier detection of metastatic deposits (for example, through surveillance), and more effective systemic treatments. Brain metastases exhibit considerable inter- and intratumoural heterogeneity—apart from distinct histology, treatment history and other clinical factors, the metastatic brain tumour microenvironment is incredibly variable both in terms of subclonal diversity and cellular composition. This review discusses emerging biomarkers; specifically, the biological context and potential clinical utility of tumour tissue biomarkers, circulating tumour cells, extracellular vesicles, and circulating tumour DNA. Full article

Background: Hearing impairment (HI) is a major problem in Ghana; however, the few attempts at shedding light on its causes appear to overlook the adverse effects of some medications—a gap that this study sought to fill. Aminoglycoside therapy for tuberculosis (TB) treatment is one of these medications. Aim: The aim of this study was to establish the potential of aminoglycoside as a cause of hearing impairment among patients on anti-TB treatment. Method: This was a case–control study, involving patients receiving treatment for TB with aminoglycoside at the chest clinic of the Tema General Hospital and a control group of age- and gender-matched healthy volunteers. A structured questionnaire was administered to obtain the demographic data and case history of the participants. The hearing sensitivity of the participants was assessed using conventional pure tone audiometry and transient evoked otoacoustic emission tests. Results: A hearing loss prevalence of 20% (12/60) was found among patients receiving treatment for TB, with the intensity of impairment ranging from mild to severe. Hearing thresholds of patients receiving anti-TB medications were significantly elevated (p < 0.05) in comparison to the thresholds of the control group, especially at the high frequencies. Conclusion: This study shows that aminoglycoside therapy for tuberculosis may contribute to hearing impairment among tuberculosis patients in Ghana. Audiological management of these patients should therefore be an essential part of their therapeutic treatment plan. Full article