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Malaria, caused by the protozoan parasites of the genus Plasmodium, is a major health problem in many countries of the world. Five parasite species namely, Plasmodium falciparum, P. vivax, P. malariae, P. ovale, and P. knowlesi, cause malaria in humans. Of these, P. falciparum and P. vivax are the most prevalent and account for the majority of the global malaria cases. In most areas of Africa, P. vivax infection is essentially absent because of the inherited lack of Duffy antigen receptor for chemokines on the surface of red blood cells that is involved in the parasite invasion of erythrocytes. Therefore, in Africa, most malaria infections are by P. falciparum and the highest burden of P. vivax infection is in Southeast Asia and South America. Plasmodium falciparum is the most virulent and as such, it is responsible for the majority of malarial mortality, particularly in Africa. Although, P. vivax infection has long been considered to be benign, recent studies have reported life-threatening consequences, including acute respiratory distress syndrome, cerebral malaria, multi-organ failure, dyserythropoiesis and anaemia. Despite exhibiting low parasite biomass in infected people due to parasite's specificity to infect only reticulocytes, P. vivax infection triggers higher inflammatory responses and exacerbated clinical symptoms than P. falciparum, such as fever and chills. Another characteristic feature of P. vivax infection, compared to P. falciparum infection, is persistence of the parasite as dormant liver-stage hypnozoites, causing recurrent episodes of malaria. This review article summarizes the published information on P. vivax epidemiology, drug resistance and pathophysiology.

Background A reduction in the frequency of agitation behaviors is a clinically meaningful outcome among patients with agitation associated with dementia due to Alzheimer’s disease. This post hoc analysis aimed to determine the percentage of patients treated with brexpiprazole who achieved sustained clinically meaningful response (CMR), over 12 and 24 weeks. Method Data for brexpiprazole 2 or 3 mg/day were obtained from two trials of patients with agitation associated with dementia due to Alzheimer’s disease: a 12‐week, randomized, double‐blind, placebo‐controlled trial (ClinicalTrials.gov identifier: NCT03548584) and a 12‐week, active‐treatment extension trial (NCT03594123). According to previous anchor‐ and distribution‐based analyses, a 20‐point reduction from baseline in Cohen‐Mansfield Agitation Inventory Total score represents a meaningful within‐patient change in this population. Hazard ratios (HRs) for non‐response and Kaplan–Meier curves for the cumulative proportions achieving CMR (a 20‐point score reduction) and sustained clinically meaningful response (SCMR; a 20‐point score reduction that was maintained to trial end) were calculated over (A) 12 weeks (data from the randomized trial for brexpiprazole versus placebo) and (B) 24 weeks (data from the randomized + extension trials for ‘prior brexpiprazole’ [i.e., received brexpiprazole in both trials] versus ‘prior placebo’ [i.e., received placebo in the randomized trial and brexpiprazole in the extension trial]). Result Over 12 weeks, the percentages of patients achieving CMR were 61.8% for brexpiprazole (n = 225) versus 44.8% for placebo (n = 116); HR = 0.64; p = 0.006. Corresponding percentages of patients achieving SCMR were 49.3% for brexpiprazole versus 32.8% for placebo; HR = 0.58; p = 0.004. Over 24 weeks, the percentages of patients achieving CMR were 81.8% for prior brexpiprazole (n = 159) versus 72.6% for prior placebo (n = 95); HR = 0.63; p = 0.011. Corresponding percentages of patients achieving SCMR were 75.5% for prior brexpiprazole versus 68.4% for prior placebo; HR = 0.59; p = 0.010 (Figure). Conclusion Among patients with agitation associated with dementia due to Alzheimer’s disease, a high percentage of patients on brexpiprazole 2 or 3 mg/day achieved sustained clinically meaningful response.

Yiwei Shen,1,* Cong He,1,* Yulin Wang,1 Yu Zhang,1 Zhengnan Liu,1 Xia Chen,1 Shun Wang,1,* Yan Bai2,* 1The Second Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China; 2Institute of Acupuncture and Moxibustion, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shun Wang, The Second Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China, Email hljwang@aliyun.com Yan Bai, Institute of Acupuncture and Moxibustion, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, People’s Republic of China, Email 1447003128@qq.comAbstract: Melatonin is a vital hormone that is important for antioxidant activity, neuroprotection, and biological rhythm control. Melatonin anomalies may have a high correlation with the onset and development of Parkinson’s disease, according to recent studies. A common neurodegenerative illness that severely lowers a patient’s quality of life, Parkinson’s disease is typified by non-motor symptoms and aberrant movement. A recent study found that abnormal melatonin levels may have a detrimental effect on patients’ motor function and cognitive ability, potentially exacerbating Parkinson’s disease symptoms. To completely comprehend the clinical symptoms linked to Parkinson’s disease and potential therapy options, further study is necessary to determine the exact role of melatonin in this condition. This article will investigate the relationship between melatonin and Parkinson’s disease, how it contributes to the illness’s progression, and the clinical symptoms that are linked with it in order to provide new perspectives and resources for more research and treatment strategies.Keywords: melatonin, Parkinson’s disease, mechanism, clinical manifestations, neuroprotection

After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as “coronavirus disease 2019” (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms.

Background Tau PET tracers present distinct binding characteristics that might influence their trajectories and relationship with other biomarkers along the AD continuum. In a head‐to‐head study, we investigated the relationship between the emergence of PET tracers MK6240 and Flortaucipir, and plasma p‐tau217 abnormalities as a function of Aβ PET deposition. We further assessed the concordance between tau PET and plasma p‐tau217 positivity and its relationship with cognitive scores. Method We evaluated 352 individuals from the HEAD study (205 cognitively unimpaired and 147 cognitively impaired) with Aβ PET, MK6240 and Flortaucipir tau PET, and plasma p‐tau217 (ALZpath) and GFAP (Quanterix) measures. Tau PET Braak regions, plasma p‐tau217 trajectories were modeled as functions of Aβ burden (Centiloid scale) using the Lowess method. Biomarkers were z‐scored anchored on young individuals (n = 19, < 28 years old) as anchors. Tau PET (Braak 1 region) and plasma p‐tau217 were considered positive/abnormal when surpassing 2.5 z‐score. Result Among the tested markers, MK6240 was the earliest to show abnormality as a function of Centiloid, occurring at 22 Centiloids, followed by plasma p‐tau217 at 38 Centiloid and Flortaucipir at Centiloid 56 (Figure 1). Tau PET and plasma p‐tau217 positivity showed an overall high concordance (∼80% for both tracers; Figure 2). In MK6240 discordant cases, most individuals were MK6240+/p‐tau217‐ (13.8%), while 6.6% were MK6240‐/p‐tau217+ (Figure 2A). For Flortaucipir, 15% of discordant cases were Flortaucipir‐/p‐tau217+, while 4.8% were Flortaucipir+/p‐tau217‐ (Figure 2B). The discordant groups present higher Centiloid than the ptau217‐/Tau‐ group and overall decreased scores in cognitive tests, except for p‐tau217+/MK6240‐ group (Figure 3). Conclusion MK6240 becomes abnormal at lower levels of Aβ burden compared to plasma p‐tau217 and Flortaucipir. The relatively high prevalence of discordant tau PET positive or plasma p‐tau217 positive and suggests that some individuals may show tau PET positivity first, while others may exhibit plasma p‐tau217 positivity first. The distinct cognitive profiles of this groups suggest potential clinical relevance, warranting further investigation.

Background Interest in use of digital technology to advance AD/ADRD research has been growing exponentially over the last few years. This acceleration is fueled in part by growing awareness that both well used research methods as well as newer biomarker approaches are 1) inadequate for clinical symptom detection in the earliest stages of an insidious onset disease and 2) have resulted in inaccurate as well as biased data that is generating treatment and prevention solutions that are insufficiently relevant to some and potentially not relevant to many. Methods Sensors embedded in mobile devices such as smartphones and wearables deliver a high penetration, low‐cost solution for overcoming previous limitations of early detection sensitivity and limited representative reach. The advances in AD biomarker development has spilled over into the digital realm, leading to the misconception and misclassification of many digital measures as digital biomarkers. Results Re‐examination of what is and is not a digital biomarker today and rethinking what a digital biomarker could be tomorrow is warranted. The validation pathways for digital biomarkers are twofold: 1) the path of least resistance, which creates digital versions of what is currently already being done and 2) the path of greatest resistance, where the definition of such is still unknown, including to the FDA. Conclusion The impact of digital biomarkers today is still rather modest because research and clinical care remain relatively risk adverse. Re‐imagination not bounded by precedent will be needed to unleash the full potential of what digital biomarkers could and should be, which include well beyond what can be conceived of currently.

Lyme borreliosis is caused by certain genospecies of the Borrelia burgdorferi sensu lato complex, which are transmitted by hard ticks of the genus Ixodes. The most common clinical manifestation is erythema migrans, an expanding skin redness that usually develops at the site of a tick bite and eventually resolves even without antibiotic treatment. The infecting pathogens can spread to other tissues and organs, resulting in manifestations that can involve the nervous system, joints, heart and skin. Fatal outcome is extremely rare and is due to severe heart involvement; fetal involvement is not reliably ascertained. Laboratory support-mainly by serology-is essential for diagnosis, except in the case of typical erythema migrans. Treatment is usually with antibiotics for 2 to 4 weeks; most patients recover uneventfully. There is no convincing evidence for antibiotic treatment longer than 4 weeks and there is no reliable evidence for survival of borreliae in adequately treated patients. European Lyme borreliosis is a frequent disease with increasing incidence. However, numerous scientifically questionable ideas on its clinical presentation, diagnosis and treatment may confuse physicians and lay people. Since diagnosis of Lyme borreliosis should be based on appropriate clinical signs, solid knowledge of clinical manifestations is essential.

Tuberculosis is a far-reaching, high-impact disease. It is among the top ten causes of death worldwide caused by a single infectious agent; 1.6 million tuberculosis-related deaths were reported in 2021 and it has been estimated that a third of the world’s population are carriers of the tuberculosis bacillus but do not develop active disease. Several authors have attributed this to hosts’ differential immune response in which cellular and humoral components are involved, along with cytokines and chemokines. Ascertaining the relationship between TB development’s clinical manifestations and an immune response should increase understanding of tuberculosis pathophysiological and immunological mechanisms and correlating such material with protection against Mycobacterium tuberculosis. Tuberculosis continues to be a major public health problem globally. Mortality rates have not decreased significantly; rather, they are increasing. This review has thus been aimed at deepening knowledge regarding tuberculosis by examining published material related to an immune response against Mycobacterium tuberculosis, mycobacterial evasion mechanisms regarding such response and the relationship between pulmonary and extrapulmonary clinical manifestations induced by this bacterium which are related to inflammation associated with tuberculosis dissemination through different routes.

Background To investigate the associations between courses of depression, the application of depression treatment, and the risk of incident dementia. Method In this prospective cohort study, 354,313 participants aged 50 to 70 years were recruited from the UK Biobank between 2006 and 2010, and were followed‐up until 2020, with a total of 4,212,929 person‐years. We initially studied the effect of depression on dementia incidence across four subgroups characterized by courses of depressive symptoms. Then, 46,820 participants with depression diagnose were further categorized into the treated and untreated groups. We compared the risks of dementia among different depression treatments groups in all participants that depressed as well as four courses of depressive symptoms by performing survival analyses. Result Depression was associated with a 51% higher risk of dementia, among which the increasing, chronically high and chronically low courses were associated with increased dementia risk while no association was found in the decreasing course. Compare to those who were depressed but untreated, receiving depression treatments corresponded to a hazard ratio of 0.7 (95% confidence interval = 0.62‐0.77). Among the three detrimental courses, treatments for increasing and chronically low symptoms of depression were associated with a 42% and 29% lower risk of dementia while the reduction effect for chronically high symptoms was insignificant. Conclusion The negative association between depression treatment and incident dementia was significant in the increasing and chronically low course, highlighting the necessity of timely interventional strategies before depression progress to a chronically severe state.

Background Mild Behavioral Impairment (MBI) is a construct that describes the emergence of sustainable and at least mildly impactful neuropsychiatric symptoms (NPS) after age 50. The Mild Behavioral Impairment Checklist (MBI‐C) is a provisional tool used to measure the NPS of MBI. However, who should provide the information for the assessment of the NPS remained unclear. Method We recruited 123 MBI participant‐informant dyads from a psychiatric outpatient clinic of a university medical center. The MBI‐C was administered to both the participant (MBI‐self) and informant (MBI‐I). Then, a researcher (psychologist) compared the two results, clarified the differences, and made the final assessment (MBI‐R). Result There were 49 with MBI only and 74 with MBI plus MCI. Among the 123 MBI subjects, the mean MBI‐C total score was 6.06 (SD 6.7), 5.27 (SD 7.67), and 6.34 (SD 6.4) for MBI‐S, MBI‐I, and MBI‐R. There was no significant difference among the three. However, for the motivation domain, the MBI‐S and MBI‐R scoring was significantly higher than the MBI‐I scoring (p < 0.001). For the affect domain, the MBI‐R scoring was significantly higher than the MBI‐I scoring (p = 0.019). For the social domain, the MBI‐I scoring was significantly higher than the MBI‐S scoring (p = 0.012). There were no significant differences among the 3 scorings for the impulse or psychosis domains. When we examined each item in the 5 domains, the general tendency was consistent with the findings mentioned above, except that there were 3 items in the impulse domain showing a significant difference among the 3 scorings (MBI‐I, MBI‐R > MBI‐S). Conclusion Our findings showed there might be differences among the 3 kinds of scorings for the 5 MBI domains. If the MBI‐R scoring was treated as the gold standard, it was close to the MBI‐S scoring but higher than the MBI‐I scoring for the motivation and affect domain. For the social domain, the MBI‐R scoring was close to the MBI‐I but higher than the MBI‐S.