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1.
bioRxiv ; 2024 Feb 05.
Article En | MEDLINE | ID: mdl-38370821

Although genome-wide association studies (GWAS) have identified loci associated with alcohol consumption and alcohol use disorder (AUD), they do not identify which variants are functional. To approach this, we evaluated the impact of variants in 3' untranslated regions (3'-UTRs) of genes in loci associated with substance use and neurological disorders using a massively parallel reporter assay (MPRA) in neuroblastoma and microglia cells. Functionally impactful variants explained a higher proportion of heritability of alcohol traits than non-functional variants. We identified genes whose 3'UTR activities are associated with AUD and alcohol consumption by combining variant effects from MPRA with GWAS results. We examined their effects by evaluating gene expression after CRISPR inhibition of neuronal cells and stratifying brain tissue samples by MPRA-derived 3'-UTR activity. A pathway analysis of differentially expressed genes identified inflammation response pathways. These analyses suggest that variation in response to inflammation contributes to the propensity to increase alcohol consumption.

2.
Am J Case Rep ; 24: e941443, 2023 Dec 08.
Article En | MEDLINE | ID: mdl-38064410

BACKGROUND Non-ketotic hyperglycemic hemichorea-hemiballism (HCHB) is a rare complication of diabetes, which is mainly described in case reports. This condition occurs more commonly in older women and is known to be associated with T1 hyperintensity basal ganglia lesions on magnetic resonance imaging (MRI). The pathophysiology of non-ketotic hyperglycemic HCHB is not well defined, although a combination of regional metabolic failure and ischemia due to hyperglycemia is suspected to occur. Treatment entails tight blood glucose control, although antipsychotic medications such as risperidone may be helpful in refractory cases. CASE REPORT We describe a case of a middle-aged man with long-standing type 2 diabetes who experienced 3 weeks of progressive unilateral arm, leg, and face choreiform movements. Laboratory testing performed just prior to symptom onset was notable for a hemoglobin A1C of >15% and a serum blood glucose of 566 mg/dl. MRI revealed diffuse T1 hyperintensity in the left lentiform nucleus. Our patient's insulin regimen was adjusted, resulting in improvement in average serum glucose (A1C of 9.4%). However, his symptoms did not improve significantly. A trial of benzodiazepine was attempted, without success. When risperidone was started, the patient experienced resolution of symptoms. Recurrence of non-ketotic hyperglycemic HCHB while off risperidone has not occurred to date. CONCLUSIONS Non-ketotic hyperglycemic HCHB is a rare but important diagnosis to consider in patients with hyperglycemia and new-onset choreiform movements. Patients with long-standing type 2 diabetes may be affected, especially when glycemic control worsens. When tight blood glucose control does not resolve symptoms, a short course of antipsychotic agents may provide relief.


Chorea , Diabetes Mellitus, Type 2 , Dyskinesias , Hyperglycemia , Male , Middle Aged , Humans , Female , Aged , Chorea/drug therapy , Chorea/etiology , Chorea/diagnosis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Risperidone/therapeutic use , Glycated Hemoglobin , Dyskinesias/etiology , Dyskinesias/diagnosis , Hyperglycemia/complications
3.
Ann Med Surg (Lond) ; 85(7): 3646-3648, 2023 Jul.
Article En | MEDLINE | ID: mdl-37427199

Guillain-Barrè syndrome is a life threatening postinfectious disease causing acute paralytic neuropathy that rarely presents with asymmetrical limb weakness (1%) and unilateral facial nerve palsy (4.9%). Case Presentation: A 39-year-old male presented with pain and weakness in the right lower limb with right sided facial weakness. The cranial nerve examination revealed lower motor neuron type right facial palsy (Bell 's palsy). On rest neurological examination, he had decreased power in the right lower limb with an absent knee and ankle reflex on presentation. Later, the weakness was symmetrical in both lower limbs. Clinical Discussion: Cerebrospinal fluid analysis showed albuminocytologic dissociation with no cells and an elevated protein of 203.2 mg/dl. The nerve conduction study was abnormal in bilateral lower limbs suggesting severe demyelinating motor neuropathy. Intravenous Immunoglobulin was started with the dose of 25 gm (0.4 mg/kg) once daily for 5 days, that is, five doses. The patient started showing signs of recovery with the initial dose of immunoglobulin. Conclusion: The course of the disease usually recovers spontaneously and completely; however, plasma exchange and immunomodulatory therapy have shown improvement in patient with rapidly deteriorating symptoms.

4.
Clin Lymphoma Myeloma Leuk ; 23(9): e260-e267, 2023 09.
Article En | MEDLINE | ID: mdl-37301630

BACKGROUND: Adolescent and Young Adults (AYAs) are an underserved, high-risk population. Identifying health care utilization patterns, and particularly acute care visits, is important as these are high-intensity, expensive services. We investigated whether differences exist in health care utilization between the AYA lymphoma population compared to their older adult counterparts. MATERIALS AND METHODS: Two correlated outcomes were used to measure health care utilization: 4 or more acute visits (emergency department or urgent care) and number of nonacute visits (office or telephone visits). We studied 442 patients with aggressive lymphoma patients 15 years or older at time of diagnosis managed at our cancer center within 2 years of their diagnosis. A multivariate generalized linear mixed model simultaneously estimated the effect of baseline predictors on 4 or more acute care visit with robust Poisson regression and nonacute visit counts with negative binomial regression allowing for a within-subject random effect. RESULTS: AYAs had increased risk of having ≥4 acute visits (RR = 1.96; P = .047) compared to their older counterparts. Obesity (RR = 2.04, P = .015) and living less than 50 miles from the cancer center (RR = 3.48, P = .015) were independently associated with higher risk of acute care usage. Acute care visits for psychiatric or substance use related reasons were significantly higher (P = .0001) among AYA (10/114, 8.8%) vs. non-AYA (3/328, 0.9%). CONCLUSION: Disease-targeted interventions to address high acute health care utilization is needed amongst AYAs. Additionally, early multidisciplinary involvement after cancer diagnosis particularly with psychiatric expertise amongst AYAs and palliative care involvement in both groups is needed.


Lymphoma , Neoplasms , Humans , Young Adult , Adolescent , Aged , Patient Acceptance of Health Care , Palliative Care , Healthcare Disparities
5.
Ann Med Surg (Lond) ; 85(4): 1030-1033, 2023 Apr.
Article En | MEDLINE | ID: mdl-37113826

Dengue infection may have various surgical complications. Splenic hematoma is a rare complication of dengue hemorrhagic fever and may be life-threatening. Case Presentation: A 54-year-old male, diagnosed with dengue infection detected at another hospital, presented on the 10th day of fever with left upper abdominal pain for 7 days without history of trauma. Urgent ultrasonography of the abdomen revealed findings suggestive of a splenic subcapsular hematoma, which was confirmed by computed tomography scan. The grade II splenic hematoma was being managed conservatively. Unfortunately, the patient developed hospital acquired pneumonia and died from septic shock. Clinical Discussion: Hemorrhagic manifestations are seen in the febrile and critical phase of dengue, but the spleen is infrequently involved. Splenic hematoma can lead to splenic rupture, which can be rapidly fatal. Specific treatment guidelines of such hematomas are needed in the context of dengue infection, as the treatment modality is controversial. Conclusion: Patients must be carefully evaluated for the complications and surgical manifestations of dengue as abdominal pain and hypotension from splenic hematoma may be misinterpreted as components of dengue hemorrhagic fever and dengue shock syndrome.

6.
Clin Case Rep ; 10(12): e6719, 2022 Dec.
Article En | MEDLINE | ID: mdl-36545553

Post-COVID syndrome, a cluster of symptoms that develops or persists even after the recovery from COVID-19 or viral clearance, can have multi-system manifestations. This entity should be considered in patients who recently tested positive for COVID-19 after ruling out other possible obvious causes. Its management should involve a multidisciplinary approach.

7.
J Nepal Health Res Counc ; 20(1): 234-240, 2022 Jun 02.
Article En | MEDLINE | ID: mdl-35945882

BACKGROUND: Mental health of pregnant individuals has been profoundly affected by the COVID-19 pandemic. Effective coping strategies are found to be associated with better psychological wellbeing during the COVID-19 pandemic. The objective of the present study is to assess psychological distress and coping among pregnant women during the COVID-19 pandemic. METHODS: A descriptive cross sectional study was conducted from May 2020 to July 2020 among 115 pregnant women attending obstetric unit of a tertiary care centre using convenience sampling technique. Ethical approval was obtained from the Institutional Review Committee of the Institute. Covid-19 Peritraumatic Distress Index and Brief COPE inventory was used to collect the data. Data entry was done in Microsoft Office Excel 2007 and analysed in SPSS version 16. RESULTS: Psychological distress was found in 2.6% of the participants. Psychological distress was significantly associated with occupation, fear of ANC visit, fear of visit to hospital for other health problems and fear of being alone or without help around delivery. Emotion focused coping was the most commonly used coping strategies among the pregnant women with the mean score of 21.37±3.130. Psychological distress and over all coping strategies had a positive correlation (<0.001). CONCLUSIONS: Psychological distress was found to be low among the pregnant women in this study. Fear of being without help and fear of contacting the virus during the visit to the hospital during the Covid-19 pandemic were the likely reasons of the psychological distress in the pregnant women.


COVID-19 , Psychological Distress , Adaptation, Psychological , COVID-19/epidemiology , Cross-Sectional Studies , Female , Humans , Nepal/epidemiology , Pandemics , Pregnancy , Pregnant Women/psychology , Stress, Psychological/epidemiology , Stress, Psychological/psychology
8.
BMJ Case Rep ; 15(7)2022 Jul 29.
Article En | MEDLINE | ID: mdl-35906040

Actinomyces naeslundii is rarely isolated in cases of actinomycosis. We present a case of thoracoabdominal actinomycosis caused by inadvertent enterotomy and gallstone spillage during a laparoscopic cholecystectomy. The actinomycosis initially presented as recurrent episodes of pneumonia, shortness of breath and unintentional weight loss. Initial CT imaging demonstrated pleural thickening along the right lung base as well as ill-defined consolidation in the right lower lobe. Repeat CT imaging showed progression of the mass-like region of consolidation with extrapulmonary spread to involve the abdomen, retroperitoneum and retrohepatic areas. Treatment involved intravenous antibiotics with concurrent abscess drainage followed by oral antibiotics.


Actinomycosis , Cholecystectomy, Laparoscopic , Gallstones , Lung Neoplasms , Actinomycosis/complications , Actinomycosis/diagnostic imaging , Anti-Bacterial Agents/therapeutic use , Cholecystectomy, Laparoscopic/adverse effects , Gallstones/complications , Humans , Lung , Lung Neoplasms/complications
9.
JNMA J Nepal Med Assoc ; 60(251): 621-624, 2022 Jul 01.
Article En | MEDLINE | ID: mdl-36705204

Introduction: The disastrous effect of COVID-19 pandemic on the mental health of vulnerable populations like pregnant women should not be neglected. The objective of the study was to find out the prevalence of anxiety among pregnant women attending the obstetrics unit of a tertiary care centre during the COVID-19 pandemic. Methods: A descriptive cross-sectional study was conducted from 16 May 2020 to 30 July 2020 among pregnant women attending obstetrics unit of a tertiary care centre. Ethical approval was obtained from the Institutional Review Committee (Reference number: 365/076/077-IRC). Convenience sampling method was used. Pregnancy-related anxiety questionnaires were used and semi-structured questionnaires were used for sociodemographic data. Point estimate and 95% Confidence Interval were calculated. Results: Out of 115 pregnant women, anxiety was found in 21 (18.26%) (11.20-25.32, 95% Confidence Interval). Conclusions: Anxiety among the pregnant women reported in this study was found to be lower than similar studies conducted in similar settings. Keywords: anxiety; COVID-19; pregnancy.


COVID-19 , Pandemics , Pregnancy , Female , Humans , Cross-Sectional Studies , Tertiary Care Centers , Pregnant Women , COVID-19/epidemiology , Anxiety/epidemiology
10.
JNMA J Nepal Med Assoc ; 59(236): 374-379, 2021 Apr 30.
Article En | MEDLINE | ID: mdl-34508530

INTRODUCTION: Understanding the attitude of caregivers towards suicide attempters could be useful in suicide prevention. The objective of this study was to study attitude towards suicide among caregivers of patients with suicide attempt admitted to a tertiary care hospital in Nepal. METHODS: A descriptive cross-sectional study was conducted with 52 caregivers of patients with suicide attempt who had been admitted to a tertiary care hospital of Nepal after obtaining ethical clearance from Institutional Review Committee (ref. IRC/0797/016). Data were collected through interviews using the Attitude towards Suicide Questionnaire and in-depth interviews conducted on five caregivers using the interview framework developed in the department for the purpose. Data and descriptive analysis were done using Statistical Package for the Social Sciences version 21. Point estimate at 95% Confidence Interval was calculated along with frequency and percentage for binary data. Content analysis was used for qualitative data. RESULTS: Majority of the caregivers 34 (65.4%) had unfavorable attitude towards suicide. Caregivers reported that mental and chronic physical illness, financial difficulty, working environment, and social factors such as undue pressure and failure to perform the task, difficulty maintaining the relationship, abuse, and neglect could be some of the possible causes of suicide. Caring and understanding attitude of family members, health professionals, and society towards the suicidal individuals providing appropriate training and education to the public would help in reducing the stigma and burden of suicidal patients. CONCLUSIONS: The overall attitude of the caregivers was unfavorable. Interventions targeted towards improving attitude towards suicide could be helpful in suicide prevention.


Caregivers , Suicide, Attempted , Cross-Sectional Studies , Hospitalization , Humans , Tertiary Care Centers
11.
J Nepal Health Res Counc ; 19(3): 481-486, 2021 Dec 10.
Article En | MEDLINE | ID: mdl-35140418

BACKGROUND: Family caregivers play a key role in preventing suicide attempts. The objective of this study was to study the caregiving stress of the patients admitted with suicide attempt at a tertiary care hospital in Nepal. METHODS: A mixed method study was conducted with 52 family caregivers of suicidal people who had been admitted at B. P. Koirala Institute of Health Sciences, Dharan with history of suicide attempt. Data were collected through interview using Kingston Caregiver Stress Scale and in-depth interview was conducted on five family caregivers using interview framework developed in the department for the purpose. RESULTS: The mean caregiving stress score was 29.84(SD=5.11), with the mean score of score 22.0 (±3.9) in caregiving issues, 4.3(±1.9) in family issues and 3.5(±0.9) in financial issues respectively. Majority (65.4%) of the caregiver had perceived stress scores above the mean score. Caregiver's stress was significantly associated with age (p= 0.023), marital status (p= 0.008) and patient's mode of attempt (p=0.035) with stress level being higher in those with older age, married and hanging as the mode of suicide attempt. In-depth interview showed that financial difficulties, emotional and physical problems, difficulty maintaining daily activities, and stigma related problem seem to significantly increase caregiver's stress. CONCLUSIONS: The study showed overall stress level of caregivers was high.


Caregivers , Suicide, Attempted , Aged , Hospitalization , Humans , Nepal , Stress, Psychological/epidemiology , Suicidal Ideation
12.
Mol Psychiatry ; 26(4): 1142-1151, 2021 04.
Article En | MEDLINE | ID: mdl-31477794

Genome-wide association studies (GWAS) of complex traits, such as alcohol use disorders (AUD), usually identify variants in non-coding regions and cannot by themselves distinguish whether the associated variants are functional or in linkage disequilibrium with the functional variants. Transcriptome studies can identify genes whose expression differs between alcoholics and controls. To test which variants associated with AUD may cause expression differences, we integrated data from deep RNA-seq and GWAS of four postmortem brain regions from 30 subjects with AUD and 30 controls to analyze allele-specific expression (ASE). We identified 88 genes with differential ASE in subjects with AUD compared to controls. Next, to test one potential mechanism contributing to the differential ASE, we analyzed single nucleotide polymorphisms (SNPs) in the 3' untranslated regions (3'UTR) of these genes. Of the 88 genes with differential ASE, 61 genes contained 437 SNPs in the 3'UTR with at least one heterozygote among the subjects studied. Using a modified PASSPORT-seq (parallel assessment of polymorphisms in miRNA target-sites by sequencing) assay, we identified 25 SNPs that affected RNA levels in a consistent manner in two neuroblastoma cell lines, SH-SY5Y and SK-N-BE(2). Many of these SNPs are in binding sites of miRNAs and RNA-binding proteins, indicating that these SNPs are likely causal variants of AUD-associated differential ASE. In sum, we demonstrate that a combination of computational and experimental approaches provides a powerful strategy to uncover functionally relevant variants associated with the risk for AUD.


Alcoholism , Genome-Wide Association Study , 3' Untranslated Regions/genetics , Alcoholism/genetics , Alleles , Genetic Predisposition to Disease/genetics , Humans , Polymorphism, Single Nucleotide/genetics
13.
Am J Nurs ; 120(12): 48-52, 2020 12.
Article En | MEDLINE | ID: mdl-33214374

PURPOSE: The aim of this quality improvement (QI) project was to increase the coprescription of naloxone kits at patient discharge as a harm reduction strategy to combat the opioid epidemic. An interdisciplinary team identified hospitalized medical patients who were at high risk for an opioid overdose or opioid-related adverse event. METHODS: Led by a physician champion, an interdisciplinary QI team composed of physicians (MDs and doctors of osteopathic medicine), advanced practice providers (NPs and physician assistants), RNs, care coordinators, social workers, and pharmacists developed and implemented a naloxone distribution program on one medical unit at an academic tertiary care center. The team developed and implemented criteria to identify high-risk patients, workflow for patient screening, staff and patient education programs, and processes for naloxone kit delivery to the patient's bedside. Data on naloxone kit distribution from the seven months prior to implementation (March 2018 to September 2018) and the seven months after implementation (October 2018 to April 2019) were evaluated and are reported descriptively. RESULTS: Two patients preimplementation and 64 patients postimplementation received a naloxone kit at discharge. In the postimplementation group, common reasons for identifying a patient as at high risk for an overdose or adverse event were a prescription for a pain medication at a daily dosage greater than or equal to 50 morphine milligram equivalents (50% of patients), concomitant opioid and benzodiazepine use (19%), history of substance use disorder (11%), and medication-assisted treatment (9%). Most patients in the postimplementation group (86%) received a naloxone kit at a personal cost of $1 or less. CONCLUSION: This unit-based pilot project was successful in identifying patients at high risk for an opioid overdose or opioid-related adverse event and in providing naloxone kits and education at hospital discharge.


Analgesics, Opioid/therapeutic use , Drug Overdose/prevention & control , Hospitals , Naloxone/therapeutic use , Narcotic Antagonists/therapeutic use , Patient Discharge , Quality Improvement , Analgesics, Opioid/adverse effects , Female , Harm Reduction , Humans , Male , Middle Aged , Opioid-Related Disorders/drug therapy , Patient Education as Topic , Pilot Projects , Retrospective Studies , Risk Factors
14.
Alcohol Clin Exp Res ; 44(12): 2494-2518, 2020 12.
Article En | MEDLINE | ID: mdl-33119910

BACKGROUND: Genome-wide association studies (GWAS) of alcohol dependence (AD) and related phenotypes have identified multiple loci, but the functional variants underlying the loci have in most cases not been identified. Noncoding variants can influence phenotype by affecting gene expression; for example, variants in the 3' untranslated regions (3'UTR) can affect gene expression posttranscriptionally. METHODS: We adapted a high-throughput assay known as PASSPORT-seq (parallel assessment of polymorphisms in miRNA target sites by sequencing) to identify among variants associated with AD and related phenotypes those that cause differential expression in neuronal cell lines. Based upon meta-analyses of alcohol-related traits in African American and European Americans in the Collaborative Study on the Genetics of Alcoholism, we tested 296 single nucleotide polymorphisms (SNPs with meta-analysis p values ≤ 0.001) that were located in 3'UTRs. RESULTS: We identified 60 SNPs that affected gene expression (false discovery rate [FDR] < 0.05) in SH-SY5Y cells and 92 that affected expression in SK-N-BE(2) cells. Among these, 30 SNPs altered RNA levels in the same direction in both cell lines. Many of these SNPs reside in the binding sites of miRNAs and RNA-binding proteins and are expression quantitative trait loci of genes including KIF6,FRMD4A,CADM2,ADD2,PLK2, and GAS7. CONCLUSION: The SNPs identified in the PASSPORT-seq assay are functional variants that might affect the risk for AD and related phenotypes. Our study provides insights into gene regulation in AD and demonstrates the value of PASSPORT-seq as a tool to screen genetic variants in GWAS loci for one potential mechanism of action.


Alcoholism/genetics , Polymorphism, Single Nucleotide/genetics , 3' Untranslated Regions/genetics , Cell Line , Gene Expression Regulation/genetics , Genetic Association Studies , High-Throughput Nucleotide Sequencing/methods , Humans
15.
J Epilepsy Res ; 10(1): 24-30, 2020 Jun.
Article En | MEDLINE | ID: mdl-32983952

BACKGROUND AND PURPOSE: Epilepsy is a chronic unpredictable debilitating condition. Epilepsy has great impacts not only on patients with epilepsies but also the persons around them. Burden among caregivers is understudied area. In view of the dearth of literature or studies focused on caregivers of children with epilepsy in Nepalese context, this study is expected to assess burden and its predictors among caregivers of children with epilepsy. METHODS: A total of 106 caregivers were interviewed using purposive sampling technique. The Zarit Burden Interview Scale short version was used to assess burden and Hospital Anxiety Depression Scale was used to assess anxiety and depression. Data were analysed using SPSS ver. 16.0. Chi-square test, multinomial logistic regression and linear regression analysis were done for analysis of inferential statistics to find out the predictors of burden. RESULTS: Majority of the caregivers (71.7%) were females and 64.2% of caregivers were mothers of children. Majority of responders (77.4%) were Hindus. Mild to moderate burden was found in 27.4% and high burden was found in 14.2% of the caregivers. Borderline anxiety, borderline depression, anxiety and depression were present in 7.5%, 8.5%, 6.6%, and 6.6% caregivers respectively. Burden was significantly higher in caregivers of epileptic children with poorly controlled seizure (p=0.003) and with co-morbidities (p=0.009). Similarly, burden score had significant positive correlation (p=0.001) with depression and significant negative correlation (p=0.005) with age of onset of epilepsy in children. CONCLUSIONS: Burden, anxiety and depression are common problems in caregivers of children with epilepsy. Poorly controlled seizure, presence of associated comorbidities, younger age of onset of seizure in children and presence of depression in caregivers are the important factors that predict burden among caregivers of children with epilepsy.

16.
JNMA J Nepal Med Assoc ; 58(224): 234-239, 2020 Apr 30.
Article En | MEDLINE | ID: mdl-32417860

INTRODUCTION: Mobile phones are becoming increasingly indispensable in daily life of the students which has resulted in mobile phone dependence. The objective of the study was to find the prevalence of mobile phone dependence among undergraduate students of a medical college of Eastern Nepal. METHODS: A descriptive cross-sectional study was conducted from October 2016 to March 2017 on a total of 390 undergraduate students aged between 17 and 25 years using stratified sampling technique. Students using mobile phones for more than one year was included in the study. Students were requested to complete a pretested self-administered questionnaire which comprised their socio-demographic characteristics, pattern of mobile phone usage and mobile phone addiction index developed by Leung. RESULTS: The prevalence of mobile phone dependence among the undergraduate students was found to be 85 (21.8%). Mobile phone dependence was found to be related with time spend on mobile; calls per day, money spend on recharge per month and years of ownership of mobile phone. There was no difference between males and females with regard to mobile phone dependence. CONCLUSIONS: The present study found that mobile phone dependence was common among the undergraduate medical students. These results suggest the need to develop educational programme to educate the students to use mobile phone meaningfully.


Cell Phone , Internet Addiction Disorder/epidemiology , Students, Medical , Adolescent , Adult , Cell Phone/statistics & numerical data , Cross-Sectional Studies , Education, Medical, Undergraduate/statistics & numerical data , Female , Humans , Male , Nepal/epidemiology , Prevalence , Random Allocation , Schools, Medical/statistics & numerical data , Students, Medical/statistics & numerical data , Surveys and Questionnaires , Young Adult
17.
Alcohol ; 85: 119-126, 2020 06.
Article En | MEDLINE | ID: mdl-31923563

Cycles of heavy drinking and abstinence can lead to alcohol use disorder. We studied the effects of chronic intermittent ethanol exposure (CIE) over 3 weeks on neuroblastoma cells, using an ethanol concentration frequently attained in binge drinking (40 mM, 184 mg/dL). There were many changes in gene expression but most were small. CIE affected pathways instrumental in the development or plasticity of neurons, including axonal guidance, reelin signaling, and synaptogenesis. Genes involved in dopamine and serotonin signaling were also affected. Changes in transporters and receptors could dampen both NMDA and norepinephrine transmissions. Decreased expression of the GABA transporter SLC6A11 could increase GABA transmission and has been associated with a switch from sweet drinking to ethanol consumption in rats. Ethanol increased stress responses such as the unfolded protein response. TGF-ß and NFκB signaling were increased. Most of the genes involved in cholesterol biosynthesis were decreased in expression. Withdrawal for 24 h after CIE caused most of the CIE-induced expression changes to move back toward unexposed levels.


Cell Line/drug effects , Neuroblastoma , Transcriptome/drug effects , Alcoholism/metabolism , Ethanol/pharmacology , Humans , Neurons/drug effects , Receptors, N-Methyl-D-Aspartate/metabolism , Reelin Protein
18.
JNMA J Nepal Med Assoc ; 56(209): 522-526, 2018.
Article En | MEDLINE | ID: mdl-30058636

INTRODUCTION: The charm of mobile phone is more among young generation and the increasing use can lead to various harmful effects and may result in dependence. The objective of the study is to evaluate the pattern of mobile phone use among medical students. METHODS: A descriptive cross sectional study was conducted on a total of 229 medical students aged between 18 and 25 years who were using mobile phones for more than 1 year by using simple random sampling technique. Students were requested to complete a pre-tested self-administered questionnaire which comprised their socio-demographic characteristics and pattern of mobile phone usage. RESULTS: Among the total 229 students, all of them had their own smart phones. Major purpose of using mobile was for calling, listening music, taking photos/videos and internet use. Most of the students 97 (42.4%) have owned mobile phones since 4-6 years. The median time spent by the students on the mobile phone using different features of mobile phone was 3.5 hours. Majority of the students i.e. 157 (68.5%) use mobile phones at night. The median amount of money spent on recharge per month was 500. Age of student was significantly (P <0.05) associated with calls per day. There was no significant association of pattern of mobile phone use with other selected socio-demographic variables Conclusions: Students were found to use mobile phone excessively. The pattern of mobile phone usage among the students in this study may signal the evolution of mobile phone use from a habit to an addiction.


Behavior, Addictive/epidemiology , Cell Phone Use/statistics & numerical data , Habits , Students, Medical , Cell Phone , Female , Humans , Male , Nepal/epidemiology , Students, Medical/psychology , Students, Medical/statistics & numerical data , Young Adult
19.
Trans R Soc Trop Med Hyg ; 112(2): 73-80, 2018 02 01.
Article En | MEDLINE | ID: mdl-29579308

Background: There is little information about the impact of anthelminthic treatment on clinical symptoms other than seizures in neurocysticercosis (NC). We investigated the effect of albendazole on non-seizure symptoms experienced by patients with NC. Methods: Data are from a randomized controlled trial comparing albendazole plus prednisone with placebo plus prednisone for treatment of NC among 173 patients with active or transitional NC cysts and new-onset symptoms. We performed negative binomial regression to examine the number of follow-up visits when a symptom was reported, logistic regression to examine the probability of experiencing the symptom and Cox proportional hazards models to examine the time to first reporting the symptom. Results: Eighty-five percent of patients reported at least one non-seizure symptom at baseline. Those treated with albendazole had significantly lower odds of memory loss and/or confusion during months 1-24 (odds ratio [OR] 0.42, p=0.037) and significantly increased odds of anxiety and/or depression during months 1-12 (OR 1.87, p=0.049). No treatment difference existed in experiencing symptoms in general or in experiencing headaches, limb weakness or gait disturbances, vomiting, nausea and/or stomach pain or visual disturbances over the follow-up period. Conclusions: While the prevalence of non-seizure symptoms was high, albendazole treatment was associated with only two significant differences in the non-seizure symptoms over follow-up. Further research is needed to identify strategies to reduce the long-term symptom burden in patients with NC.


Albendazole/administration & dosage , Anthelmintics/administration & dosage , Neurocysticercosis/drug therapy , Administration, Oral , Animals , Double-Blind Method , Drug Administration Schedule , Drug Therapy, Combination , Female , Gait Disorders, Neurologic/drug therapy , Gait Disorders, Neurologic/parasitology , Gastrointestinal Diseases/drug therapy , Gastrointestinal Diseases/parasitology , Headache Disorders/drug therapy , Headache Disorders/parasitology , Humans , Male , Muscle Weakness/drug therapy , Muscle Weakness/parasitology , Prednisone/administration & dosage , Taenia solium , Treatment Outcome
20.
Cell Cycle ; 17(1): 11-23, 2018.
Article En | MEDLINE | ID: mdl-28980861

Shugoshin is an evolutionarily conserved protein, which is involved in tension sensing on mitotic chromosomes, kinetochore biorientation, and protection of centromeric (CEN) cohesin for faithful chromosome segregation. Interaction of the C-terminus of Sgo1 with phosphorylated histone H2A regulates its association with CEN and pericentromeric (peri-CEN) chromatin, whereas mutations in histone H3 selectively compromise the association of Sgo1 with peri-CEN but not CEN chromatin. Given that histone H3 is absent from CEN and is replaced by a histone H3 variant CENP-ACse4, we investigated if CENP-ACse4 interacts with Sgo1 and promotes its association with the CEN chromatin. In this study, we found that Sgo1 interacts with CENP-ACse4 in vivo and in vitro. The N-terminus coiled-coil domain of Sgo1 without the C-terminus (sgo1-NT) is sufficient for its interaction with CENP-ACse4, association with CEN but not the peri-CEN, and this CEN association is cell cycle dependent with maximum enrichment in mitosis. In agreement with the role of CENP-ACse4 in CEN maintenance of Sgo1, depletion of CENP-ACse4 results in the loss of Sgo1 and sgo1-NT from the CEN chromatin. The N-terminus of Sgo1 is required for genome stability as a mutant lacking the N-terminus (sgo1-CT) exhibits increased chromosome missegregation when compared to a sgo1-NT mutant. In summary, our results define a novel role for the N-terminus of Sgo1 in CENP-ACse4 mediated recruitment of Sgo1 to CEN chromatin for faithful chromosome segregation.


Centromere/metabolism , Chromatin/metabolism , Chromosomal Proteins, Non-Histone/metabolism , DNA-Binding Proteins/metabolism , Nuclear Proteins/chemistry , Nuclear Proteins/metabolism , Saccharomyces cerevisiae Proteins/chemistry , Saccharomyces cerevisiae Proteins/metabolism , Saccharomycetales/metabolism , Cell Cycle , Chromosome Segregation , Protein Binding , Protein Domains , Two-Hybrid System Techniques
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