Alzheimer’s disease (AD), is a progressive neurodegenerative disease that affects behavior, thinking, learning, and memory in elderly individuals. AD occurs in two forms, early onset familial and late-onset sporadic; genetic mutations in PS1, PS2, and APP genes cause early onset familial AD, and a combination of lifestyle, environment and genetic factors causes the late-onset sporadic form of the disease. However, accelerated disease progression is noticed in patients with familial AD. Disease-causing pathological changes are synaptic damage, and mitochondrial structural and functional changes, in addition to increased production and accumulation of phosphorylated tau (p-tau), and amyloid beta (Aβ) in the affected brain regions in AD patients. Aβ is a peptide derived from amyloid precursor protein (APP) by proteolytic cleavage of beta and gamma secretases. APP is a glycoprotein that plays a significant role in maintaining neuronal homeostasis like signaling, neuronal development, and intracellular transport. Aβ is reported to have both protective and toxic effects in neurons. The purpose of our article is to summarize recent developments of Aβ and its association with synapses, mitochondria, microglia, astrocytes, and its interaction with p-tau. Our article also covers the therapeutic strategies that reduce Aβ toxicities in disease progression and discusses the reasons for the failures of Aβ therapeutics.

Evolving spectrum of diabetic nephropathy

Compared to female rape victims, the literature addressing male rape victims remains a growing area of interest for counselors and scholars. This article aims to review the growing literature on male sexual assault victims. Specifically, the review will examine the literature on male victims of sexual assault in nine sections: (a) an overview of male sexual assault, (b) male rape myths, (c) prevalence, (d) responses to male victimization, (e) populations and perpetrators of male victimization, (f) risk factors, (g) reporting, (h) the impact of sexual assault on men, (i) help-seeking, and (j) implications for counseling. Empirical studies, case reports, and books are included in the review.

The month of December 2019 became a critical part of the time of humanity when the first case of coronavirus disease 2019 (COVID-19) was reported in the Wuhan, Hubei Province in China. As of April 13th, 2020, there have been approximately 1.9 million cases and 199,000 deaths across the world, which were associated with COVID-19. The COVID-19 is the seventh coronavirus to be identified to infect humans. In the past, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome were the two coronaviruses that infected humans with a high fatality, particularly among the elderly. Fatalities due to COVID-19 are higher in patients older than 50 years of age or those with multimorbid conditions. The COVID-19 is mainly transmitted through respiratory droplets, with the most common symptoms being high fever, cough, myalgia, atypical symptoms included sputum production, headache, hemoptysis and diarrhea. However, the incubation period can range from 2 to 14 days without any symptoms. It is particularly true with gastrointestinal (GI) symptoms in which patients can still shed the virus even after pulmonary symptoms have resolved. Given the high percentage of COVID-19 patients that present with GI symptoms (e.g., nausea and diarrhea), screening patients for GI symptoms remain essential. Recently, cases of fecal–oral transmission of COVID-19 have been confirmed in the USA and China, indicating that the virus can replicate in both the respiratory and digestive tract. Moreover, the epidemiology, clinical characteristics, diagnostic procedures, treatments and prevention of the gastrointestinal manifestations of COVID-19 remain to be elucidated.

SLC13A5 is a Na⁺-coupled transporter for citrate that is expressed in the plasma membrane of specific cell types in the liver, testis, and brain. It is an electrogenic transporter with a Na⁺:citrate³⁻ stoichiometry of 4:1. In humans, the Michaelis constant for SLC13A5 to transport citrate is ~600 μM, which is physiologically relevant given that the normal concentration of citrate in plasma is in the range of 150–200 μM. Li⁺ stimulates the transport function of human SLC13A5 at concentrations that are in the therapeutic range in patients on lithium therapy. Human SLC13A5 differs from rodent Slc13a5 in two important aspects: the affinity of the human transporter for citrate is ~30-fold less than that of the rodent transporter, thus making human SLC13A5 a low-affinity/high-capacity transporter and the rodent Slc13a5 a high-affinity/low-capacity transporter. In the liver, SLC13A5 is expressed exclusively in the sinusoidal membrane of the hepatocytes, where it plays a role in the uptake of circulating citrate from the sinusoidal blood for metabolic use. In the testis, the transporter is expressed only in spermatozoa, which is also only in the mid piece where mitochondria are located; the likely function of the transporter in spermatozoa is to mediate the uptake of citrate present at high levels in the seminal fluid for subsequent metabolism in the sperm mitochondria to generate biological energy, thereby supporting sperm motility. In the brain, the transporter is expressed mostly in neurons. As astrocytes secrete citrate into extracellular medium, the potential function of SLC13A5 in neurons is to mediate the uptake of circulating citrate and astrocyte-released citrate for subsequent metabolism. Slc13a5-knockout mice have been generated; these mice do not have any overt phenotype but are resistant to experimentally induced metabolic syndrome. Recently however, loss-of-function mutations in human SLC13A5 have been found to cause severe epilepsy and encephalopathy early in life. Interestingly, there is no evidence of epilepsy or encephalopathy in Slc13a5-knockout mice, underlining the significant differences in clinical consequences of the loss of function of this transporter between humans and mice. The markedly different biochemical features of human SLC13A5 and mouse Slc13a5 likely contribute to these differences between humans and mice with regard to the metabolic consequences of the transporter deficiency. The exact molecular mechanisms by which the functional deficiency of the citrate transporter causes epilepsy and impairs neuronal development and function remain to be elucidated, but available literature implicate both dysfunction of GABA (γ-aminobutyrate) signaling and hyperfunction of NMDA (N-methyl-d-aspartate) receptor signaling. Plausible synaptic mechanisms linking loss-of-function mutations in SLC13A5 to epilepsy are discussed.

The earliest evidence from China suggested that COVID-19 patients are even more vulnerable to succumbing from complications in the presence of a multimorbid status, including metabolic syndrome. Due to ongoing metabolic abnormalities, non-alcoholic fatty liver disease (NAFLD) appears to be a potential risk factor for contracting SARS-CoV-2 infection and developing related complications. This is because of the interplay of chronically active inflammatory pathways in NAFLD- and COVID-19-associated acute cytokine storm. The risk of severe disease could also be attributed to compromised liver function as a result of NAFLD. We systematically reviewed current literature to ascertain the relationship between NAFLD and severe COVID-19, independent of obesity, which is considered the major factor risk factor for both NAFLD and COVID-19. We found that NAFLD is a predictor of severe COVID-19, even after adjusting for the presence of obesity (OR 2.358; 95% CI: 1.902–2.923, p < 0.001).