Diseases, Volume 10, Issue 2 (June 2022) – 17 articles

Chronic kidney disease of unknown etiology was investigated for metal relations in an endemic area by a cross-sectional study with CKD stages G1, G2, G3a, G3b, G4, G5 (ESRD), and endemic and nonendemic controls (EC and NEC) as groups. Subjects with the medical diagnosis were classified into groups by eGFR (SCr, CKD-EPI) and UACR of the study. It determined 24 metals/metalloids in plasma (ICPMS) and metallothionein (MT) mRNA in blood (RT-PCR). MT1A at G3b and MT2A throughout G2–G5 showed increased transcription compared to NEC (ANOVA, p < 0.01). Both MT1A and MT2A remained metal-responsive as associations emerged between MT2A and human MT inducer Cr (in EC: r = 0.54, p < 0.05, n = 14), and between MT1A and MT2A (in EC pooled with G1–G5: r = 0.58, p < 0.001, n = 110). Human MT (hMT)-inducers, namely Zn, Cu, As, Pb, and Ni; Σ hMT-inducers; 14 more non-inducer metals; and Σ MT-binding metals remained higher (p < 0.05) in EC as compared to NEC. Declining eGFR or CKD progression increased the burden of Be, Mg, Al, V, Co, Ni, Rb, Cs, Ba, Mn, Zn, Sr, Σ hMT-inducers, and Σ MT-binding metals in plasma, suggesting an MT role in the disease. MT1A/2A mRNA followed UACR (PCA, Dendrogram: similarity, 57.7%). The study provides evidence that proteinuric chronic renal failure may increase plasma metal levels where blood MT2A could be a marker. Full article

Bone marrow, besides the known functions of hematopoiesis, is an active organ of the immune system, functioning as a sanctuary for several mature immune cells. Moreover, evidence suggests that hematopoietic stem cells (the bone marrow’s functional unit) are capable of directly sensing and responding to an array of exogenous stimuli. This chronic immune stimulation is harmful to normal hematopoietic stem cells, while essential for the propagation of myeloid diseases, which show a dysregulated immune microenvironment. The bone marrow microenvironment in myelodysplastic syndromes (MDS) is characterized by chronic inflammatory activity and immune dysfunction, that drive excessive cellular death and through immune evasion assist in cancer cell expansion. Acute myeloid leukemia (AML) is another example of immune response failure, with features that augment immune evasion and suppression. In this review, we will outline some of the functions of the bone marrow with immunological significance and describe the alterations in the immune landscape of MDS and AML that drive disease progression. Full article

Ensembles of Species Distribution Models (SDMs) represent the geographic ranges of pathogen vectors by combining alternative analytical approaches and merging information on vector occurrences with more extensive environmental data. Biased collection data impact SDMs, regardless of the target species, but no studies have compared the differences in the distributions predicted by the ensemble models when different sampling frameworks are used for the same species. We compared Ensemble SDMs for two important Ixodid tick vectors, Amblyomma americanum and Ixodes scapularis in mainland Florida, USA, when inputs were either convenience samples of ticks, or collections obtained using the standard protocols promulgated by the U.S. Centers for Disease Control and Prevention. The Ensemble SDMs for the convenience samples and standard surveys showed only a slight agreement (Kappa = 0.060, A. americanum; 0.053, I. scapularis). Convenience sample SDMs indicated A. americanum and I. scapularis should be absent from nearly one third (34.5% and 30.9%, respectively) of the state where standard surveys predicted the highest likelihood of occurrence. Ensemble models from standard surveys predicted 81.4% and 72.5% (A. americanum and I. scapularis) of convenience sample sites. Omission errors by standard survey SDMs of the convenience collections were associated almost exclusively with either adjacency to at least one SDM, or errors in geocoding algorithms that failed to correctly locate geographic locations of convenience samples. These errors emphasize commonly overlooked needs to explicitly evaluate and improve data quality for arthropod survey data that are applied to spatial models. Full article

Metabolic syndrome (MetS) is a cluster of symptoms that, when present, increase the risk for cardiovascular disease. There is a need for reliable screening tools that are ethnically sensitive. Two hundred and sixty-six college students were assessed anthropometrically. They had a fasting blood sample drawn, and blood pressure measured. They then completed a demographic questionnaire and The International Physical Activity Questionnaire (IPAQ). The prevalence of MetS was found to be 10.1% in males and 4.5% in females. Neck circumference (NC) was positively associated with BMI in males (r = 0.55, p < 0.001) and females (r = 0.53, p < 0.001) and was positively associated with hip circumference in both males (r = 0.47, p < 0.001) and females (r = 0.50, p < 0.001) and with waist circumference in males (r = 0.46, p < 0.001) and females (r = 0.49, p < 0.001.) An area under the curve (AUC) was calculated using receiver operating characteristics (ROC), and NC > 38 cm in males and NC> 36 cm in females were found to be appropriate cut-offs for diagnosing MetS. NC is a reliable and non-invasive screening tool that can be used to screen for MetS in males. NC could also serve as an anthropometric instrument to assess abdominal obesity and could be valuable for college students. Full article

Traumatic central nervous system injury is a leading cause of neurological injury worldwide. While initial neuroresuscitative efforts are focused on ameliorating the effects of primary injury through patient stabilization, secondary injury in neurotrauma is a potential cause of cell death, oxidative stress, and neuroinflammation. These secondary injuries lack defined therapy. The major causes of secondary injury in neurotrauma include endoplasmic reticular stress, mitochondrial dysfunction, and the buildup of reactive oxygen or nitrogenous species. Stress to the endoplasmic reticulum in neurotrauma results in the overactivation of the unfolded protein response with subsequent cell apoptosis. Mitochondrial dysfunction can lead to the release of caspases and the buildup of reactive oxygen species; several characteristics make the central nervous system particularly susceptible to oxidative damage. Together, endoplasmic reticulum, mitochondrial, and oxidative stress can have detrimental consequences, beginning moments and lasting days to months after the primary injury. Understanding these causative pathways has led to the proposal of various potential treatment options. Full article

Background: Pheochromocytoma is known for its instantaneous presentation, especially in the younger population. Hemodynamic instability may be the cause of severe complications and impede patients’ ability to undergo surgical treatment. These tumours are surgically difficult to treat due to the risk of catecholamine release during their manipulations, and when they are large, the tumour size represents an additional challenge. In our report, cardiogenic shock developed due to increases in systemic vascular resistance, and the lesion’s size induced surgeons to perform open surgery. Case presentation: A 46-year-old female patient was admitted to our intensive care unit with hypertension and later cardiogenic shock. Systolic dysfunction was noted, along with severely increased systemic vascular resistance. A CT scan showed a left-sided 8.5 cm adrenal mass, which was confirmed as pheochromocytoma using meta-iodobenzylguanidine scintigraphy. Anaesthesiologists and the surgical team planned an effective strategy of treatment. Given the lesion’s size and its apparent invasion of the neighbouring organs, open adrenalectomy (after prolonged hemodynamic stabilisation) was considered safer. The surgery was successful, and the patient remains free from disease two years after the initial event. Conclusions: Large pheochromocytoma can be safely and effectively treated with open surgery by experienced hands but only by seeking to reach hemodynamic stabilisation and minimising the release of catecholamine before and during surgery. Full article

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