Levamisole-Induced Leukoencephalopathy in Russia: Analysis of 30 Cases

Aims: To raise medical specialists’ awareness regarding the severity of possible complications of levamisole administration and demonstrate the role of accurate medical history collection in differential diagnosis. Background: Levamisole, an anthelmintic drug with immunomodulatory effects, has long been used worldwide till early 2000s, when its association with demyelinating leukoencephalopathy was established. However, in the developing countries it is still widely used for prevention and treatment of helminthic invasion in humans. Actual prevalence of levamisole-induced multiple inflammatory leukoencephalopathy (LEV-induced MIL) in Russia remains unknown, and therefore, the study of its frequency and characteristics is indisputably important. Objectives: To determine the clinical features and MRI findings of levamisole-induced MIL in the Russian population and to analyse the frequency of diagnostic errors at the initial assessment. Methods: A single-center retrospective analysis of total 30 patients who were diagnosed with LEV-induced MIL and attended Research Center of Neurology was conducted. Inclusion criteria were 1) clinically: acute or subacute polysymptomatic onset of neurological disturbances, 2) MRI: multifocal demyelinating lesion with no evidence of dissemination in time, 3) anamnestic data: levamisole exposure from 2 to 8 weeks before symptoms onset as well as monophasic disease course (absence of relapses according to follow up assessments up to 3 years). Results: Clinically, presentation with constitutional symptoms, including headache, fever, fatigue and myalgia, focal motor disturbances and dysarthria prevailed in our cohort. On the brain MRI, multiple foci of demyelination with simultaneous gadolinium enhancement were observed. The link between neurological symptoms and levamisole intake has often been detected only during follow-up assessments. Patients were most often misdiagnosed with acute disseminated encephalomyelitis, stroke and multiple sclerosis. In most cases LEV-induced MIL was successfully treated with intravenous corticosteroids and/or plasma exchange (PLEX), however, residual neurologic symptoms preserved in some patients. Additionally, two detailed clinical cases of patients being initially misdiagnosed are presented in the article. Conclusion: The differential diagnosis remains difficult for suspected cases of LEV-induced MIL that could lead to delayed therapy initiation, and consequently incomplete recovery. Growing evidence suggests that a single administration of levamisole even in low doses might potentially lead to severe neurological deficit or death. Therefore, changes in medication management policies are required in order to prevent uncontrolled use of levamisole.

Seroprevalence of antibodies against SARS-Cov-2 in the high impacted sub-district in Jakarta, Indonesia

Background Understanding the actual prevalence of COVID-19 transmission in the community is vital for strategic responses to the pandemic. This study aims to estimate the actual infection of COVID-19 through a seroprevalence survey and to predict infection fatality rate (IFR) in Tanjung Priok, the hardest-hit sub-district by the COVID-19 in Jakarta, Indonesia. Methods We conducted a venous blood sampling (phlebotomy) to 3,196 individuals in Tanjung Priok between Nov 23, 2020, and Feb 19, 2021 to detect their antibodies against SARS-CoV-2. Using an enumerator-administered questionnaire, we collected data on the respondents’ demographic characteristics, COVID-19 test history, COVID-19 symptoms in the last 14 days, comorbidities, and protective behaviours during the last month. We employed descriptive analysis to estimate the seroprevalence and IFR. Findings The prevalence of Antibody against SARS-CoV-2 was 28.52% (95% CI 25.44–31.81%), with the result being higher in females than males (OR 1.20; 95% CI 1.02–1.42). By the end of the data collection (February 9, 2021), the cumulative cases of COVID-19 in Tanjung Priok were reported to be experienced by 9,861 people (2.4%). Those aged 45–65 were more likely to be seropositive than 15–19 years old (OR 1.42; 95% CI 1.05–1.92). Nearly one third (31%) of the subjects who developed at least one COVID-19 symptom in the last 14 days of the data collection were seropositive. The estimated IFR was 0.08% (95% CI 0.07–0.09), with a higher figure recorded in males (0.09; 95% CI 0.08–0.10) than females (0.07; 95% CI 0.06–0.08), and oldest age group (45–65) (0.21; 95% CI 0.18–0.23) than other younger groups. Conclusion An under-reporting issue was found between the estimated COVID-19 seroprevalence and the reported cumulative cases in Tanjung Priok. More efforts are required to amplify epidemiological surveillance by the provincial and local governments.

CARRIAGE OF PSITTACOSIS CAUSATIVE AGENT IN PET BIRDS

The analysis of data on the actual prevalence of chla-mydiosisand thedamage to human health, poultry and livestock farming proves that the disease is a noteworthy problem for public health and farming. The spread of chla-mydia infection often leads to large scale damage to pet birds, as well as to humans, so its diagnosis and control measures are important. In Russia, in recent decade, the number of contaminated sites regarding ornithosis annually ranges from 30 to 53. The number of contaminated sites changes slightly but the number of sick birds noticeably changes from 131 to 2390 heads. According to the Veteri-nary Department, 9 contaminated sites were registered in the Altai Region from 2010 through 2020, i.e. 1-3 sites per year. The infectiousness of Clamydia psittaci is very high which leads to inapparent, chronic infection and long-term carriage, intense chlamydial release; that is an important epizootological prerequisite for a consistent continuous and latent infection in the animal population. Therefore, the main sources of the causative agent are sick birds and asymptomatic chlamydia carriers. Of the 145 examined individuals, inclusion bodies were found in 52, or 36%. In 2008, similar studies were carried out on 11 parrots; 6 birds were infected with the causative agent of psittacosis, or 54.5%. The autopsy of parrots revealed characteristic signs of psittacosis in 19 (82.6%) cases: pneumonia, exudate and fibrosis depositions in the air sacs, enlarged spleen and liver, in 5 cases -hemorrhages on the epicardium.

Optimal authoritative risk assessment score of Cancer-associated venous thromboembolism for hospitalized medical patients with lung Cancer

Background Cancer-associated venous thromboembolism (VTE) is common in patients with primary lung cancer. It has been understudied which authoritative risk assessment score of cancer-associated VTE is optimal for the assessment of VTE development in hospitalized medical patients with lung cancer. Methods Patients with lung cancer who had undergone computed tomography pulmonary angiography (CTPA), compression ultrasonography (CUS) of lower and upper extremities, and/or planar ventilation/perfusion (V/Q) scan to confirm the presence or absence of VTE during a medical hospitalization were retrospectively reviewed. Based on the actual prevalence of VTE among all patients, the possibility of VTE were reassessed with the Khorana score, the PROTECHT score, the CONKO score, the ONKOTEV score, the COMPASS-CAT score, and the CATS/MICA score, to compare their assessment accuracy for VTE development. Results A total of 1263 patients with lung cancer were incorporated into the final analysis. With respect to assessment efficiency for VTE occurrence, the scores with adjusted agreement from highest to lowest were the ONKOTEV score (78.6%), the PROTECHT score (73.4%), the CONKO score (72.1%), the COMPASS-CAT score (71.7%), the Khorana score (70.9%), and the CATS/MICA score (60.3%). The ONKOTEV score had the highest Youden index which was 0.68, followed by the PROTECHT score (0.58), the COMPASS-CAT score (0.56), the CONKO score (0.55), the Khorana score (0.53), and the CATS/MICA score (0.23). Conclusions Among the Khorana score, the PROTECHT score, the CONKO score, the ONKOTEV score, the COMPASS-CAT score, and the CATS/MICA score which are approved by authoritative guidelines, the ONKOTEV score is optimal for the assessment of VTE development in hospitalized medical patients with lung cancer.

Coagulation in Lymphatic System

The lymphatic system maintains homeostasis of the internal environment between the cells in tissues and the blood circulation. The coagulation state of lymph is determined by conditions of coagulation factors and lymphatic vessels. Internal obliteration, external compression or abnormally increased lymphatic pressure may predispose to localized lymphatic coagulation. In physiological conditions, an imbalance of antithrombin and thrombokinase reduces lymphatic thrombosis. However, the release of factor X by lymphatic endothelium injury may trigger coagulation casacade, causing blockage of lymphatic vessels and lymphedema. Heterogeneity of lymphatic vessels in various tissues may lead to distinct levels and patterns of coagulation in specific lymphatic vessels. The quantitative and qualitative measurement of clotting characteristic reveals longer time for clotting to occur in the lymph than in the blood. Cancer, infections, amyloidosis and lymph node dissection may trigger thrombosis in the lymphatic vessels. In contrast to venous or arterial thrombosis, lymphatic thrombosis has rarely been reported, and its actual prevalence is likely underestimated. In this review, we summarize the mechanisms of coagulation in lymphatic system, and discuss the lymphatic thrombosis-related diseases.

Stress-Related Behaviors in Companion Dogs Exposed to Common Household Noises, and Owners' Interpretations of Their Dogs' Behaviors

Sudden, loud noises are one of the most common triggers for fearful behaviors in dogs, and many companion dogs suffer from noise sensitivity. Existing research focuses on dramatic infrequent sounds (e.g., thunderstorms, fireworks). Anecdotally, and based on reports of undesirable behaviors in response to noises in the home, many common household noises may also be causing fear and anxiety in companion dogs. However, these responses have not yet been studied in home environments. We surveyed 386 dog owners about their dogs' responses to household sounds, and recorded dog behaviors and human reactions from 62 videos and compilations available on an online video sharing platform, featuring dogs reacting to common household noises. Numerous signs of canine fear and anxiety were reported by survey respondents and observed in the videos, in response to both daily, and irregular but “normal,” household noises. Responses were significantly stronger to sounds characterized as high frequency intermittent than to sounds characterized as low frequency continuous. Respondents appeared to underestimate their dogs' fearfulness, and the majority of humans in the videos responded to their dogs' behaviors with amusement; welfare concerns were rarely expressed. While these videos cannot be used to calculate actual prevalence of these issues, our data support that some owners are underestimating fearfulness in their dogs in response to household noises, and responding inappropriately to dogs' expressions of fear and anxiety. Better education is required for dog owners to accurately interpret canine body language, to both safeguard dogs' welfare and minimize development of anxiety-related behavior problems.

NOTCH2NLC-related disorders: the widening spectrum and genotype–phenotype correlation

GGC repeat expansion in the 5′ untranslated region of NOTCH2NLC is the most common causative factor in neuronal intranuclear inclusion disease (NIID) in Asians. Such expanded GGC repeats have been identified in patients with leukoencephalopathy, essential tremor (ET), multiple system atrophy, Parkinson’s disease (PD), amyotrophic lateral sclerosis and oculopharyngodistal myopathy (OPDM). Herein, we review the recently reported NOTCH2NLC-related disorders and potential disease-causing mechanisms. We found that visual abnormalities may be NOTCH2NLC-specific and should be investigated in other patients with NOTCH2NLC mutations. NOTCH2NLC GGC repeat expansion was rarely identified in patients of European ancestry, whereas the actual prevalence of the expansion in European patients may be potentially higher than reported, and the CGG repeats in LRP12/GIPC1 are suggested to be screened in European patients with NIID. The repeat size and interruptions in NOTCH2NLC GGC expansion confer pleiotropic effects on clinical phenotype, a pure and stable ET phenotype may be an early symptom of NIID, and GGC repeats in NOTCH2NLC possibly give rise to ET. An association may also exist between intermediate-length NOTCH2NLC GGC repeat expansion and patients affected by PD and ET. NOTCH2NLC-OPDM highly resembles NOTCH2NLC-NIID, the two disorders may be the variations of a single neurodegenerative disease, and there may be a disease-causing upper limit in size of GGC repeats in NOTCH2NLC, repeats over which may be non-pathogenic. The haploinsufficiency of NOTCH2NLC may not be primarily involved in NOTCH2NLC-related disorders and a toxic gain-of-function mechanism possibly drives the pathogenesis of neurodegeneration in patients with NOTCH2NLC-associated disorders.

Autism-Current Status and Challenges in Pakistan

Autism is a group of neuro-developmental disabilities. It has an early-onset and can be diagnosed up to 3 yearsof age. It is characterized by disturbances in child's socialization, communication and cognitive abilities, and anunusual repetitive and restricted behavior. The majority of subjects have comorbid conditions. Males are more1 affected than females.1 The prevalence of autism is increasing in the world that could be due to improvement in1 diagnostic procedures and awareness in public and its worldwide prevalence is around 1%.1In Pakistan, there is a lack of widespread awareness and understanding about autism. We do not have exactprevalence data on this disease in Pakistan. However, according to the Autism Society of Pakistan, there are2 probably 350,000 children with this disease in the country.2 But the actual prevalence is believed to be muchhigher. Many cases remain undiagnosed because of unawareness, lack of medical facilities and stigma that is3 attached to mental conditions in Pakistan. In Pakistan, the distribution of disabilities includes mentalretardation (MR), hearing impairment, visual impairment and physical disability. Autism is not considered as adisability in Pakistani society. Moreover, the term mental disability or cognition problem is considered as asocial stigma or disgrace. Therefore, many people do not disclose the condition to avoid stigma. Anotherimportant reason of undiagnosed cases is lack of medical facilities and untrained doctors that categories autism under intellectual disability that is another condition. Many people especially from rural areas opt traditional therapies or go to preachers for healing.

Detection of F1 hybrids from single-genome data reveals frequent hybridization in Hymenoptera and particularly ants

Hybridization occupies a central role in many fundamental evolutionary processes, such as speciation or adaptation. Yet, despite its pivotal importance in evolution, little is known about the actual prevalence and distribution of hybridization across the tree of life. Here we develop and implement a new statistical method enabling the detection of F1 hybrids from single-individual genome sequencing data. Using simulations and sequencing data from known hybrid systems, we first demonstrate the specificity of the method, and identify its statistical limits. Next, we showcase the method by applying it to available sequencing data from more than 1500 species of Arthropods, including Hymenoptera, Hemiptera, Coleoptera, Diptera and Archnida. Among these taxa, we find Hymenoptera, and especially ants, to display the highest number of candidate F1 hybrids, suggesting higher rates of recent hybridization in these groups. The prevalence of F1 hybrids was heterogeneously distributed across ants, with taxa including many candidates tending to harbor specific ecological and life history traits. This work shows how large-scale genomic comparative studies of recent hybridization can be implemented, uncovering the determinants of hybridization frequency across whole taxa.

Attitudes towards gender roles and prevalence of intimate partner violence perpetrated against pregnant and postnatal women: Differences between women immigrants from conflict-affected countries and women born in Australia

Background The aim was to compare, for the first time in a large systematic study, women born in conflict-affected countries who immigrated to Australia with women born in Australia for attitudes towards gender roles and men’s use of IPV and the actual prevalence of IPV. The study also examined if any associations remained across the two timepoints of pregnancy and postpartum. Methods Women were interviewed during their first visit to one of three Australian public hospital antenatal clinics and re-interviewed at home six months after giving birth. A total of 1111 women completed both interviews, 583 were born in conflict-affected countries and 528 born in Australia. Associations between attitudes towards gender roles and men’s use of IPV, socio-demographic characteristics and reported actual experiences of IPV were examined using bivariate and multiple logistic regression analyses. Results Attitudes toward inequitable gender roles including those that condone men’s use of IPV, and prevalence of IPV, were significantly higher (p<0.001) among women born in conflict-affected countries compared to Australia-born women. Women born in conflict-affected countries with the strongest held attitudes towards gender roles and men’s use of IPV had an adjusted odds ratio (aOR) of 3.18 for IPV at baseline (95% CI 1.85–5.47) and an aOR of 1.83 for IPV at follow-up (95% CI 1.11–3.01). Women born in Australia with the strongest held attitudes towards gender roles and IPV had an aOR of 7.12 for IPV at baseline (95% CI 2.12–23.92) and an aOR of 10.59 for IPV at follow-up (95% CI 2.21–50.75). Conclusions Our results underscore the need for IPV prevention strategies sensitively targeted to communities from conflict-affected countries, and for awareness among clinicians of gender role attitudes that may condone men’s use of IPV, and the associated risk of IPV. The study supports the need for culturally informed national strategies to promote gender equality and to challenge practices and attitudes that condone men’s violence in spousal relationships.