Adult hemiconvulsive hemiatrophy syndrome: a novel clinicoradiologic disorder in adults.

The association of focal motor seizures with cerebral hemiatrophy is a recognised rare paediatric syndrome known as 'hemiconvulsion, hemiatrophy and epilepsy' (HHE). To date, HHE has not been reported in adults. We present four adult patients with striking similarities to HHE, following alcohol withdrawal in chronic alcoholics. We document the imaging findings in the acute and subacute phases, discuss the underlying mechanisms and present a hypothesis regarding the pathophysiology.

Genomic, transcriptomic, and metabolomic analysis of Oldenlandia corymbosa reveals the biosynthesis and mode of action of anti-cancer metabolites.

Plants accumulate a vast array of secondary metabolites, which constitute a natural resource for pharmaceuticals. Oldenlandia corymbosa belongs to the Rubiaceae family, and has been used in traditional medicine to treat different diseases, including cancer. However, the active metabolites of the plant, their biosynthetic pathway and mode of action in cancer are unknown. To fill these gaps, we exposed this plant to eight different stress conditions and combined different omics data capturing gene expression, metabolic profiles, and anti-cancer activity. Our results show that O. corymbosa extracts are active against breast cancer cell lines and that ursolic acid is responsible for this activity. Moreover, we assembled a high-quality genome and uncovered two genes involved in the biosynthesis of ursolic acid. Finally, we also revealed that ursolic acid causes mitotic catastrophe in cancer cells and identified three high-confidence protein binding targets by Cellular Thermal Shift Assay (CETSA) and reverse docking. Altogether, these results constitute a valuable resource to further characterize the biosynthesis of active metabolites in the Oldenlandia group, while the mode of action of ursolic acid will allow us to further develop this valuable compound.

Osmotic demyelination syndrome: novel risk factors and proposed pathophysiology.

BACKGROUND: Osmotic demyelination syndrome (ODS) is non-inflammatory demyelination in response to an osmotic challenge. It can be pontine or extrapontine in presentation. AIMS: To retrospectively review cases involving ODS and define the spectrum of causes, risk factors, clinical and radiological presentations, and functional outcomes. RESULTS: The study utilised data from 15 patients with a mean age of 53.6 years. Malnutrition (9; 60%) and chronic alcoholism (10; 66.7%) were the most common associated disorders. Two (13.3%) patients had severe hyponatraemia (<120 mmol/L). The average highest single-day change was 5.1 mmol/L. Radiologically, 14 (93.3%) had pontine and 6 (40%) had extra-pontine lesions. Hypokalaemia (14; 93.3%) and hypophosphataemia (9; 60%) were commonly associated. Common clinical manifestations include altered consciousness/encephalopathy (9; 60%), dysphagia (4; 26.7%) and limb weakness (4; 26.7%). At 3 months, two (14.3%) had died and six (40%) were functionally independent (modified Rankin scale 0-2). CONCLUSION: We found that ODS occurred despite appropriate correction rates of hyponatraemia. Factors such as malnutrition, chronic alcoholism, hypokalaemia and hypophosphataemia are thought to play a role in its pathogenesis. Approximately half of the patients survived and became functionally independent.

Antecedent infections and vaccinations in chronic inflammatory demyelinating polyneuropathy: A European collaborative study.

INTRODUCTION/AIMS: Chronic inflammatory demyelinating polyneuropathy (CIDP) may be rarely preceded by infection. A causative link remains unproven, in contrast to Guillain-Barré syndrome (GBS), which is commonly postinfectious with well-demonstrated pathophysiological mechanisms of molecular mimicry following Campylobacter jejuni enteritis. Uncommonly, infections are reported before the onset of CIDP. In this study we aimed to determine the frequency and characteristics of CIDP occurring after antecedent infections or vaccinations in two large European cohorts. METHODS: We reviewed the records of 268 subjects with "definite" or "probable" CIDP from the Inflammatory Neuropathy Clinic, Birmingham, UK (129 subjects), and from the Serbian national CIDP database (139 subjects). RESULTS: Twenty-five of 268 (9.3%) subjects had a respiratory or gastrointestinal infection in the 6 weeks preceding CIDP onset, and 3 of 268 (1.1%) had received an influenza vaccination. CIDP disease onset occurred at a younger age (mean [standard deviation], 44.25 [17.36] years vs 54.05 [15.19] years; P < .005) and acute-onset CIDP was more common (42.9% vs 12.1%; odds ratio, 5.46; 95% confidence interval, 2.35-12.68; P < .001) in subjects with preceding infections or vaccinations. No differences in CIDP subtype, rates of cerebrospinal fluid protein level elevation, disability, or likelihood of treatment response, were observed. DISCUSSION: Antecedent infections or vaccinations may precede about 10% of cases of CIDP and are more common in younger subjects. Acute-onset CIDP is more frequent after antecedent events. These findings may suggest specific pathophysiological mechanisms in such cases.

Nivolumab-associated myositis myocarditis and myasthenia and anti-striated muscle antibodies.

An 82-year-old man was treated with neo-adjuvant nivolumab (programmed cell death protein 1 or PD-1 inhibitor) for local recurrence of melanoma developed myositis, myocarditis and a myasthenic-like syndrome with a fatal outcome. The occurrence of these three conditions may constitute a new immune checkpoint-induced syndrome. The relevance of the clinical features and the immunology is discussed. This case highlights the special role of anti-striated muscle antibodies as a predictor of mortality.

Checkpoint inhibitor myasthenia-like syndrome and myositis associated with extraocular muscle atrophy.

A patient with metastatic melanoma developed myasthenia-like syndrome and paraspinal myositis with subsequent extraocular muscle atrophy associated with immune checkpoint inhibitor treatment. MRI scan of the ocular muscles on admission was normal, however 3 months later revealed significant extraocular muscle atrophy.

Prevalence and risk factors of Toxoplasma infection - an update in Malaysian pregnant women.

Toxoplasma gondii is a protozoan parasite that is capable of causing a zoonotic disease, known as toxoplasmosis. Vertical transmission of T. gondii from the mother to the fetus, during pregnancy may cause severe complications to the developing fetus. This current study aimed to determine the seroprevalence and investigate the associated risk factors of Toxoplasma infection in pregnant women (n=219) visiting the antenatal clinic at UMMC. While the elevated level of anti-Toxoplasma IgG and IgM antibodies indicates the presence of infection, it fails to differentiate between a past and a recent infection. Thus, the study also demonstrates the usefulness of IgG avidity in validating the timing of infection. The serum samples were tested for the presence of anti-Toxoplasma IgG and IgM antibodies by ELISA test, and the seropositive samples for both anti-Toxoplasma IgG and IgM antibodies were further evaluated by IgG avidity. The results showed that the overall prevalence of T. gondii seropositivity was 34.7%. Of these, 30.6% (67/219) were positive for anti-Toxoplasma IgG antibody only, 2.3% (5/219) were positive for anti-Toxoplasma IgM only, and the remaining 1.8% (4/219) was positive for both anti-Toxoplasma IgG and IgM antibodies. All of the pregnant women who were positive for both anti-Toxoplasma IgG and IgM antibody were found to have past infection when evaluated by IgG avidity. In this study, Malay ethnicity and the number of existing previous children were significantly associated with T. gondii seropositivity (p<0.05). Based on these findings, information and education on the transmission and prevention of congenital toxoplasmosis are very crucial as a public health effort towards a healthier society.

Prevalence and risk factors of Toxoplasma infection – an update in Malaysian pregnant women

@#Toxoplasma gondii is a protozoan parasite that is capable of causing a zoonotic disease, known as toxoplasmosis. Vertical transmission of T. gondii from the mother to the fetus, during pregnancy may cause severe complications to the developing fetus. This current study aimed to determine the seroprevalence and investigate the associated risk factors of Toxoplasma infection in pregnant women (n=219) visiting the antenatal clinic at UMMC. While the elevated level of anti-Toxoplasma IgG and IgM antibodies indicates the presence of infection, it fails to differentiate between a past and a recent infection. Thus, the study also demonstrates the usefulness of IgG avidity in validating the timing of infection. The serum samples were tested for the presence of anti-Toxoplasma IgG and IgM antibodies by ELISA test, and the seropositive samples for both anti-Toxoplasma IgG and IgM antibodies were further evaluated by IgG avidity. The results showed that the overall prevalence of T. gondii seropositivity was 34.7%. Of these, 30.6% (67/219) were positive for anti-Toxoplasma IgG antibody only, 2.3% (5/219) were positive for anti-Toxoplasma IgM only, and the remaining 1.8% (4/219) was positive for both anti-Toxoplasma IgG and IgM antibodies. All of the pregnant women who were positive for both anti-Toxoplasma IgG and IgM antibody were found to have past infection when evaluated by IgG avidity. In this study, Malay ethnicity and the number of existing previous children were significantly associated with T. gondii seropositivity (p<0.05). Based on these findings, information and education on the transmission and prevention of congenital toxoplasmosis are very crucial as a public health effort towards a healthier society.

Rapid Assessment Zika Virus Knowledge Among Clinical Specialists in Singapore: A Cross-sectional Survey.

INTRODUCTION: We report the results of a rapid assessment of Zika virus awareness among key clinical specialties in Singapore. METHODS: Between June 6 and June 19, 2016 we conducted an online survey of doctors working in obstetrics and gynaecology, neonatology and paediatrics in Singapore. The survey included 15 multiple choice questions to measure respondents' knowledge of Zika virus in four domains covering clinical and public health. RESULTS: A total of 110 survey responses (15% response rate) were obtained, 82% of respondents worked in the public sector. Overall, the median respondent score was 9.4 (Max score=15), with substantial variation (range: 3.5 - 14.7). Microcephaly and Guillain-Barré syndrome were recognised as causal complications of Zika virus infection by 99% and 50% of respondents respectively.  Clinical features which could help differentiate Zika from Dengue were less well understood with 50% and 68% correctly identifying conjunctivitis and low grade fever respectively. Worryingly, 14% favoured non-steroidal anti-inflammatory drugs as part of treatment, without first excluding dengue as a diagnosis. Also, only 36% of respondents were aware of the current recommendation for preventing sexual transmission of Zika virus. Fewer than 50% were aware of the need for ophthalmological evaluation as part of congenital Zika virus infection. DISCUSSION: Our assessment demonstrates that there is good awareness of the clinical manifestation of Zika virus disease among key specialty doctors, but confusion with Dengue disease remains. It also highlights knowledge gaps in the prevention of sexually-transmitted Zika virus infection and the clinical management of congenital Zika virus infection in newborns. Our study identified strategic areas to improve communication to front-line doctors during public health response to the Zika epidemic.

Independent Mobility Achieved through a Wireless Brain-Machine Interface.

Individuals with tetraplegia lack independent mobility, making them highly dependent on others to move from one place to another. Here, we describe how two macaques were able to use a wireless integrated system to control a robotic platform, over which they were sitting, to achieve independent mobility using the neuronal activity in their motor cortices. The activity of populations of single neurons was recorded using multiple electrode arrays implanted in the arm region of primary motor cortex, and decoded to achieve brain control of the platform. We found that free-running brain control of the platform (which was not equipped with any machine intelligence) was fast and accurate, resembling the performance achieved using joystick control. The decoding algorithms can be trained in the absence of joystick movements, as would be required for use by tetraplegic individuals, demonstrating that the non-human primate model is a good pre-clinical model for developing such a cortically-controlled movement prosthetic. Interestingly, we found that the response properties of some neurons differed greatly depending on the mode of control (joystick or brain control), suggesting different roles for these neurons in encoding movement intention and movement execution. These results demonstrate that independent mobility can be achieved without first training on prescribed motor movements, opening the door for the implementation of this technology in persons with tetraplegia.

Tridimensional personalities and polymorphism of dopamine D2 receptor among heroin addicts.

BACKGROUND: Drug addiction is a multifactorial disorder. Researchers have posited that an individual's inherited behavioral propensity or temperament contributes to the disorder by shaping a personality strongly linked with the risk of drug abuse. Further, they hypothesize that the polymorphism of dopamine D2 receptor increases the susceptibility to and severity of addiction. We, therefore, investigated possible associations between dopamine D2 receptor (DRD2) and personality traits among intravenous heroin addicts. METHODS: We assessed 93 intravenous heroin addicts and controls using Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) and the Tridimensional Personality Questionnaire (TPQ). We confirmed drug-dependence status using a questionnaire based on DSM-IV criteria. We extracted DNA from the subjects' whole blood and genotyped it for DRD2 allelic variants. RESULTS: Genotype analysis showed a significantly higher frequency for the TaqIA polymorphism among the addicts (69.9%) compared to control subjects (42.6%; Fisher's exact χ(2), p < .05). We observed no significant differences for other variants between the addicts and controls. The addicts had higher scores for novelty seeking (NS) and harm avoidance (HA) personality traits but lower scores for reward dependence (RD) when compared to control subjects. LIMITATION: The environmental cues are different for the addicts, and the healthy university students we used as controls. We recommend that researchers employ a gene-environment interaction approach to study factors associated with addictive behaviors in future studies. CONCLUSION: Taq1A may be implicated for an increased vulnerability to addiction. Screening of this marker might be useful for identifying individuals at risk of addiction.

N-glycosylation of zona glycoproteins during meiotic maturation is involved in sperm-zona pellucida interactions of porcine oocytes.

The objective was to determine whether N-glycosylation of zona pellucida (ZP) glycoproteins occurred during meiotic maturation of porcine oocytes, and whether this had a role in fertilization. In the first of three experiments, carbohydrate residues in the ZP of in vitro matured porcine oocytes were blocked with various lectins and the influence of such blocking on sperm-ZP interactions was studied. The second experiment used a lectin-binding assay to determine whether the number of GlcNAc residues in ZP was changed by N-glycosylation during in vitro maturation (IVM) of porcine oocytes. The last experiment determined the effects of tunicamycin, a specific N-glycosylation inhibitor, for various intervals during IVM, on sperm-ZP interactions in porcine oocytes. The primary findings were that: 1) N-glycosylation of GlcNAc residues in porcine ZP occurred during the first 24 h of IVM; and 2) such glycosylation was indispensible for sperm-ZP interactions, e.g., number of sperm bound to ZP, acrosome-reacted sperm, sperm penetration rate, and level of polyspermy (P < 0.05). However, blocking N-glycosylation by tunicamycin treatment during IVM did not adversely influence the progression of oocytes to meiotic metaphase II and male pronucleus formation, indicating that this glycosylation was involved only in the initial stages of fertilization. We inferred that the increase in terminal GlcNAc residues in ZP glycoprotein through new N-glycosylation during the first 24 h of meiotic maturation played a critical role in porcine ZP acquiring the capacity to accept sperm.

Health economic evaluation of outpatient management of fibromyalgia patients and the costs avoided by diagnosing fibromyalgia in France.

OBJECTIVES: To assess whether the decrease in medical resource use and cost after diagnosing fibromyalgia, observed in a large primary care population in the United Kingdom can be extrapolated to France. METHODS: A questionnaire was created based on medical resource use by 2,260 patients diagnosed with fibromyalgia between 01/01/1998 and 31/03/2003 in the General Practice Research Database in the UK. Sixty French experts (general practitioners, rheumatologists) assessed whether the data from that database are in line with their clinical practice and, if not, were asked to provide data reflecting their own experience. The evaluation period went from 4 years before to 4 years after diagnosis using 1-year cross-sections. Evaluated resources were drug use, diagnostics tests, general practitioners and specialist visits, and also paramedical or alternative treatments. Data regarding inpatient care and productivity loss were not collected. Medical resource use if no diagnosis had been established was estimated, so the impact of diagnosis could be evaluated. RESULTS: Whereas costs gradually increase before diagnosis, stagnation in costs occurs in the year after diagnosis, followed by a moderate decrease afterwards. The same trend was observed whether the panel consisted of general practitioners or rheumatologists. The savings made as a result of fibromyalgia diagnosis add up to 126 euros per patient per year for the health care payer. General practitioner visits, diagnostic tests and drug use represent respectively 57%, 23% and 12% of the savings. CONCLUSIONS: Also in France, early diagnosis of fibromyalgia leads to a decrease in resource use and health care costs.

Development of the Fibromyalgia Burden Assessment: measuring the multifaceted burden of fibromyalgia.

OBJECTIVES: To develop a questionnaire assessing the burden of fibromyalgia's impacts on patients' lives. METHODS: A literature review was conducted to identify impacts of fibromyalgia and their consequences on patients' lives. Exploratory interviews were performed with 15 fibromyalgia patients in France, Germany and Spain. Using patients' wording, items were generated simultaneously in French, German, Spanish, and UK English. Relevance and comprehension of the resulting questionnaire versions were tested with 21 additional fibromyalgia patients; questionnaires were revised accordingly. RESULTS: Three domains, Burden associated with the impacts of fibromyalgia, Symptoms and Influencing factors, were identified from the literature review. Following patient interviews, the burden domain was further divided based on the nature of the impact: Pain, Physical impact (including tiredness, sleep problems and other symptoms), Activities of Daily Living impact (including autonomy and coping), Social and Family Life impact, Work, Studies and Personal Finances impact, Psychological impact (including cognitive impact), and Relationship to Medicine and Disease. The resulting test versions of the questionnaire contained 79 items. Comprehension tests identified problematic items and cultural differences and suggested deletions or rewording. After revision and linguistic harmonization, the pilot version of the questionnaire contained 62 items divided into 7 sections, and was named Fibromyalgia Burden Assessment (FMBA©). CONCLUSIONS: The FMBA is a self-reported questionnaire allowing the assessment and a better understanding of the impacts of fibromyalgia and the burden associated with these on patients' daily lives. It is available in UK English, French, German and Spanish. Its scoring and validation remain to be undertaken.

Occurrence of Chlamydia trachomatis and Chlamydia pneumoniae in paediatric respiratory infections.

An emerging body of evidence suggests that half of asthma in both children and adults is associated with chronic lung infection. The aim of the present study was to determine the frequency of viable Chlamydia pneumoniae (Cp) and C. trachomatis (Ct) in the respiratory tracts of paediatric patients with chronic respiratory diseases. Bronchoalveolar lavage fluid (BALF) samples obtained from 182 children undergoing bronchoscopy for clinical reasons were assayed using PCR analysis, in vitro tissue culture and immunofluorescence staining for the presence of Cp and Ct. Chlamydia-specific DNA was detected by PCR in 124 (68%) out of 182 patients; 79 were positive for Cp, 77 positive for Ct and 32 for both organisms; 75 patients had cultivable Chlamydia. Ct DNA prevalence decreased, whereas Cp positivity generally increased with age. A total of 59 out of 128 asthma patients and 16 out of 54 nonasthmatics were Chlamydia culture positive. When the patients were divided into inflammatory versus noninflammatory airway disease, there were 69 (46%) out of 150 and six (18%) out of 32 BALF samples with cultivable Chlamydia, respectively. Viable Chlamydia pneumoniae and Chlamydia trachomatis occur frequently in children with chronic respiratory diseases and may be more prevalent in asthma patients. To the current authors' knowledge, this is the first report of viable Chlamydia trachomatis in the lungs of children.

Anti-infiltration for fabrication of a suspended nanoparticle layer on porous close-packed colloidal arrays.

We develop a new method to fabricate suspended sheets of nanocrystals (NCs) on porous surfaces. The method relies on the resistance of an aqueous suspension droplet to infiltrate a porous network; hence, the method is named anti-infiltration. The process works by combining fluid dynamics of a liquid droplet during impact/absorption onto a porous surface with the convective self-assembly of NCs. The immobilization of the liquid droplet edge due to the self-assembly of NCs at the meniscus is harnessed to halt the lateral spreading of the droplet and, consequently, the capillary penetration of the liquid immediately after droplet impact. Further capillary penetration of the liquid is drastically reduced because of the competition between capillary forces and convective losses as well as the rapid occlusion of the pores as soon as a continuous NC film has formed upon evaporation of the suspension. This method holds promise for a wide variety of optoelectronic, sensing, and separation membrane applications. As an example, we demonstrate that these suspended NC layers are suitable candidates as planar defects embedded within a colloidal photonic crystal.

Health economic consequences related to the diagnosis of fibromyalgia syndrome.

OBJECTIVE: To evaluate the use and costs of medical resources before and after a diagnosis of fibromyalgia syndrome (FMS) in a large primary care population in the UK. METHODS: We applied an existing data set for medical resource use among patients with a coded diagnosis of FMS. The observed quantities of 157 types of medical resource use before and after the diagnosis of FMS were multiplied by unit costs in order to calculate the cost of care (general practitioner [GP] visits, drugs, referrals, and diagnostics) within the National Health Service, excluding hospital costs. Costs before diagnosis were used in a trend analysis to predict later costs, assuming the diagnosis had never been made, and these predicted costs were compared with the observed costs after diagnosis. RESULTS: Following a diagnosis of FMS, a decrease in costs as compared with the predicted trend was observed. In the 4 years after diagnosis, the average difference between the predicted and observed cost was pound66.21 per 6 months per patient. This suggests that making the diagnosis leads to savings and a decrease in resource use. The main effect was observed for tests and imaging ( pound24.02 per 6 months), followed by pharmaceuticals ( pound22.27), referrals ( pound15.56), and GP visits ( pound4.36). CONCLUSION: Failure to diagnose a true case of FMS has its own costs, largely in excess GP visits, investigations, and prescriptions.

Comparative cost-minimisation of oral and intravenous chemotherapy for first-line treatment of non-small cell lung cancer in the UK NHS system.

The National Institute for Health and Clinical Excellence recommends vinorelbine (VNB), paclitaxel, docetaxel, and gemcitabine in the treatment of non-small cell lung cancer. An economic model was prepared to determine the comparative cost of these agents, including the new oral formulation of VNB from a United Kingdom National Health System perspective. Clinical effectiveness was determined from published trials. Costs of drug acquisition, administration, toxicity management, and patient transportation costs were calculated from reference publications. A Markov model was used to estimate the cost per patient over 52 weeks. Intravenous VNB, gemcitabine, paclitaxel, and docetaxel incur annual follow-up costs of 3,746 pounds, 5,332 pounds, 5,977 pounds, and 6,766 pounds, respectively, while oral VNB with outpatient administration on d1, and self-administration at home on d8 every 21 days has a cost per patient per year of 2,888 pounds. Oral VNB allows further hospital resources savings.