A novel mutation in GCK gene: Beware of SGA child with diabetic mother.

MODY is a monogenic, autosomal dominant form of diabetes mellitus. MODY can be caused by mutations in several genes; glucokinase (GCK) accounts for 30-50% of the cases. The diagnosis can be suspected in early-onset diabetes with atypical features for type 1/type 2. Treatment is usually not recommended. A 5-year-old girl came to our attention for occasional episodes of hyperglycaemia. She was born at term, her birth weight was small for gestational age. At the beginning of her pregnancy, her mother was already on insulin therapy for impaired fasting glucose levels, detected before conception and confirmed in the first weeks of gestation. She was treated with insulin until the childbirth without further investigations. The patient was asymptomatic and in good clinical condition. Basal blood tests have shown a fasting plasma glucose of 125 mg/dl, an HbA1c of 6.5%. Antibodies against islet cells, anti-GAD and anti-ZNT8 antibodies were all negative. A 2-h oral glucose tolerance test was performed and underlined an impaired glucose tolerance. HLA haplotypes were screened, excluding susceptibility. GCK Sanger Sequencing identified a novel heterozygous variant. It is not described as a classical mutations. The analysis has been extended to the parents, finding out the same variant in her mother. To our knowledge this mutation has not been described previously; we believe that this variant is responsible for MODY2 due to FBG and Hb1Ac of all the affected members of family. We suggest high suspicion of an underlying GCK variant in SGA children with hyperglycaemia born to a diabetic mother.

Assessment of knowledge, attitude, and practice on livestock traceability among cattle farmers and cattle traders in peninsular Malaysia and its impact on disease control.

The ability to trace the movement of animals and their related products is key to success in animal disease control. To ensure that a traceability system is optimized, livestock farmers and traders must have good appreciation and understanding about animal tracing. The present study examined the traceability of cattle in Malaysia vis-à-vis the domains of knowledge, attitude, and practice among cattle farmers and traders. A total of 543 farmers and traders in Peninsular Malaysia were interviewed. The results revealed that over 60% of the respondents had satisfactory knowledge and attitude about cattle movement and traceability. A lower proportion of the respondents (49%) were involved in appropriate practice that facilitated traceability of cattle. We found that the type of husbandry system and stakeholders' participation in livestock management-specific short courses were positively associated with satisfactory knowledge, attitude, and practice. A structured education and training program should be formulated to improve these domains so that the benefit of traceability becomes clear, paving the way to a successful traceability program.

Detection of icaA, icaD, and bap genes and biofilm production in Staphylococcus aureus and non-aureus staphylococci isolated from subclinical and clinical bovine mastitis / Detecção dos genes icaA, icaD e bap e produção de biofilme por Staphylococcus aureus e estafilococos não-aureus isolados de mastite clínica e subclínica bovina

Algumas espécies de Staphylococcus causam infecções crônicas intramamárias e podem levar à formação de biofilme. No presente estudo, levantou-se a hipótese de que as espécies de Staphylococcus isolados da mastite bovina são capazes de formar biofilme in vitro associado à presença dos genes icaA, icaD ou bap. Um total de 200 isolados de Staphylococcus, sendo 100 Staphylococcus aureus de casos de mastite subclínica e 100 estafilococos não aureus (ENA) de casos de mastite subclínica e clínica, obtidos em duas fazendas leiteiras, no estado de São Paulo, foram avaliados quanto à capacidade de produzir biofilmes in vitro. A presença de icaA, icaD e bap foi confirmada por PCR, e a produção de biofilme em ágar vermelho congo (Congo Red Agar - CRA) e em teste de microplaca (Microtiter Plate - MtP) foi avaliada nos isolados de S. aureus e ENA. Os resultados mostraram a presença dos genes icaA, icaD e bap em S. aureus, mas não em ENA. A produção de biofilme pode estar associada à presença de outros fatores ou genes que estimulam a produção de biofilme in vitro. O ensaio de MtP serve como um modelo quantitativo para o estudo da aderência de espécies de estafilococos associados à mastite bovina.(AU)

Vision-Based Traffic Sign Detection and Recognition Systems: Current Trends and Challenges.

The automatic traffic sign detection and recognition (TSDR) system is very important research in the development of advanced driver assistance systems (ADAS). Investigations on vision-based TSDR have received substantial interest in the research community, which is mainly motivated by three factors, which are detection, tracking and classification. During the last decade, a substantial number of techniques have been reported for TSDR. This paper provides a comprehensive survey on traffic sign detection, tracking and classification. The details of algorithms, methods and their specifications on detection, tracking and classification are investigated and summarized in the tables along with the corresponding key references. A comparative study on each section has been provided to evaluate the TSDR data, performance metrics and their availability. Current issues and challenges of the existing technologies are illustrated with brief suggestions and a discussion on the progress of driver assistance system research in the future. This review will hopefully lead to increasing efforts towards the development of future vision-based TSDR system.

Genotyping of long term persistent Staphylococcus aureus in bovine subclinical mastitis.

Bovine mastitis affects dairy cattle worldwide and Staphylococcus aureus is one of the most common microorganisms involved in subclinical and chronic disease. Superantigens, such as enterotoxins contribute to S. aureus persistence and pathogenicity in this disease. Subclinical and chronic mastitis cases were diagnosed and S. aureus isolates from sub-clinical cases were investigated for carriage of virulence and antibiotic resistance genes that may contribute to long-term carriage and infection. Over a 12-month period, 116 S. aureus strains were recovered from 68 cows with subclinical mastitis. Classical enterotoxin genes (sea-see) were detected in 24.1% of isolates, and pvl and tsst-1 were identified in 3.4% and 46.6% the isolates, respectively. 18.1% that were persistent isolates were identified and characterized by pulsed field gel electrophoresis (PFGE), MLST, spa typing. Four isolates were methicillin-resistant S. aureus (MRSA) and belonged to SCCmec type I. Molecular typing showed that the agrI group was the most frequent, and a rare isolate was positive for both agrI and agrIII groups. Molecular characterization revealed the persistence of the spa type t10856 (ST133, clonal complex CC133, agr I), in a single animal for nine months and the persistence t605 (ST126, CC126) colonizing four animals for four months. These strains have been described recently in other herds in the same region, indicating their transmissibility and clonal expansion. We conclude that animals with subclinical mastitis are an important and somewhat overlooked reservoir for transmission within and between herds, and may carry virulence and antibiotic resistance genes contributing to persistent colonization, hinder the control of mastitis and may cause risks to the public health.

Ocorrência, patógenos e fatores de risco para mastite subclínica em cabras leiteiras / Occurrence, pathogens and risk factors for subclinical mastitis in dairy goats

Milk samples from 257 goats and 513 half udders of 10 dairy goat farms were analyzed by microbiological culture, to evaluate the sanitary management, and epidemiological questionnaire results. Multivariate analysis of risk factors for subclinical mastitis in goats, with the adjusted Odds Ratio for subclinical mastitis was performed. The prevalence of subclinical mastitis in goats by microbiological culture was 43.6%, and clinical mastitis was 5.84%. From 178 positive teats by microbiological culture, the most prevalent pathogens were coagulase-negative staphylococci - CNS (70%), S. aureus (13.5%), S. intermedius (7.9%), and Enterobacteriaceae (4%). The risk factors analysis revealed significant association between the disease and the flock size (OR= 3.33; P= 0.0268), and the farm was a confounding factor, being kept in the final statistical model. Despite the non-identification of all the factors associated with subclinical mastitis in herds and the existence of confounding factors that hinder statistical analyzes, the study of risk factors is important for the improvement of disease control and prevention programs in dairy goat, and it can be used as a tool in the reduction of environmental and contagious pathogens such as staphylococci that were the most identified pathogens causing caprine mastitis in the study.(AU)

Identification of subclinical mastitis caused by Mycoplasma spp. from screenings of bulk tanks / Identificação de mastite subclínica causada por Mycoplasma spp. de triagem de tanques de expansão

Mastitis caused by Mycoplasma spp., regardless of species, are considered highly contagious pathogens and, usually was not responsive to antimicrobial therapy. Five dairy herds, comprising 489 animals and 1,956 mammary glands, were used in this study. Milk samples were obtained from bulk tanks and subjected to polymerase chain reaction (PCR) for the identification of Mollicutes, Mycoplasma spp., and Mycoplasma bovis. Moreover, individual samples from cases of clinical and subclinical mastitis in quarters of the dairy herds' animals that yielded a positive PCR upon bulk tank analysis were subjected to molecular analysis. Only one bulk tank was positive for class Mollicutes by PCR. All positive samples classified as mastitis teats had their DNA extracted and tested by PCR for both class Mollicutes and M. bovis. Of these, two (2.08%) were positive for Mycoplasma genus, although none was positive for M. bovis. This result suggests that the PCR of bulk tanks is a viable tool in monitoring and preventing mastitis infections caused by Mycoplasma spp.(AU)

Mastites bovinas causadas por Mycoplasma spp., independentemente da espécie causadora, são consideradas de alta contagiosidade e geralmente não responsivas à terapia antimicrobiana. Cinco propriedades leiteiras foram utilizadas neste estudo, totalizando 489 animais e 1956 quartos mamários. As amostras de leite foram obtidas de tanques de expansão e submetidas à reação em cadeia da polimerase (PCR) para pesquisa de Mollicutes, Mycoplasma spp. e Mycoplasma bovis. Apenas um tanque de uma propriedade foi positivo na PCR para a classe Mollicutes. Amostras individuais de casos de mastite subclínica provenientes de propriedade com tanque positivo também foram submetidas à análise molecular; dessas, duas delas (2,08%) foram positivas para a classe Mollicutes e para o gênero Mycoplasma, entretanto nenhuma foi positiva para a espécie Mycoplasma bovis. Isso sugere que a PCR de tanques de expansão de propriedades leiteiras demonstra ser uma ferramenta viável no monitoramento e na prevenção de infecções por Mycoplasma spp.(AU)

Glucokinase mutations in pediatric patients with impaired fasting glucose.

AIMS: Our aim was to detect the frequency of glucokinase (GCK) gene mutations in a cohort of patients with impaired fasting glucose and to describe the clinical manifestations of identified variants. We also aimed at predicting the effect of the novel missense mutations by computational approach. METHODS: Overall 100 unrelated Italian families with impaired fasting glucose were enrolled and subdivided into two cohorts according to strict and to mild criteria for diagnosis of maturity-onset diabetes of the young (MODY). GCK gene sequencing was performed in all participants. RESULTS: Fifty-three Italian families with 44 different mutations affecting the GCK and co-segregating with the clinical phenotype of GCK/MODY were identified. All mutations were in heterozygous state. In Sample 1, GCK defects were found in 32/36 (88.9%) subjects selected with strict MODY diagnostic criteria, while in Sample 2 GCK defects were found in 21/64 (32.8%) subjects selected with mild MODY diagnostic criteria. CONCLUSIONS: Our study enlarged the wide spectrum of GCK defects by adding 9 novel variants. The application of strict recruitment criteria resulted in 88.9% incidence of GCK/MODY, which confirmed it as the commonest form of MODY in the Italian population. In order to avoid misdiagnosis of GCK/MODY, it could be useful to perform molecular screening even if one or more clinical parameters for the diagnosis of MODY are missing. Computational analysis is useful to understand the effect of GCK defect on protein functionality, especially when the novel identified variant is a missense mutation and/or parents' DNA is not available.

A review of schizophrenia research in malaysia.

Research in schizophrenia has advanced tremendously. One hundred and seventy five articles related to Schizophrenia were found from a search through a database dedicated to indexing all original data relevant to medicine published in Malaysia between the years 2000-2013. This project aims to examine published research articles, in local and international journals in order to provide a glimpse of the research interest in Malaysia with regards to schizophrenia. Single case study, case series report, reviews and registry reports were not included in this review. Medication trial, unless it concerned a wider scope of psychopharmacology was also excluded from this review. A total of 105 articles were included in this review. Despite numerous genetics studies conducted and published, a definitive conclusion on the aetiology or mechanism underlying schizophrenia remains elusive. The National Mental Health - Schizophrenia Registry (NMHR) proved to be an important platform for many studies and publications. Studies stemmed from NMHR have provided significant insight into the baseline characteristic of patients with schizophrenia, pathway to care, and outcomes of the illness. International and regional collaborations have also encouraged important work involving stigma and discrimination in schizophrenia. Ministry of Health's hospitals (MOH) are the main research sites in the country with regards to schizophrenia research. Numbers of schizophrenia research are still low in relation to the number of universities and hospitals in the country. Some of the weaknesses include duplication of studies, over-emphasising clinical trials and ignoring basic clinical research, and the lack of publications in international and regional journals.

Analysis and optimization of spiral circular inductive coupling link for bio-implanted applications on air and within human tissue.

The use of wireless communication using inductive links to transfer data and power to implantable microsystems to stimulate and monitor nerves and muscles is increasing. This paper deals with the development of the theoretical analysis and optimization of an inductive link based on coupling and on spiral circular coil geometry. The coil dimensions offer 22 mm of mutual distance in air. However, at 6 mm of distance, the coils offer a power transmission efficiency of 80% in the optimum case and 73% in the worst case via low input impedance, whereas, transmission efficiency is 45% and 32%, respectively, via high input impedance. The simulations were performed in air and with two types of simulated human biological tissues such as dry and wet-skin using a depth of 6 mm. The performance results expound that the combined magnitude of the electric field components surrounding the external coil is approximately 98% of that in air, and for an internal coil, it is approximately 50%, respectively. It can be seen that the gain surrounding coils is almost constant and confirms the omnidirectional pattern associated with such loop antennas which reduces the effect of non-alignment between the two coils. The results also show that the specific absorption rate (SAR) and power loss within the tissue are lower than that of the standard level. Thus, the tissue will not be damaged anymore.

Energy harvesting for the implantable biomedical devices: issues and challenges.

The development of implanted devices is essential because of their direct effect on the lives and safety of humanity. This paper presents the current issues and challenges related to all methods used to harvest energy for implantable biomedical devices. The advantages, disadvantages, and future trends of each method are discussed. The concept of harvesting energy from environmental sources and human body motion for implantable devices has gained a new relevance. In this review, the harvesting kinetic, electromagnetic, thermal and infrared radiant energies are discussed. Current issues and challenges related to the typical applications of these methods for energy harvesting are illustrated. Suggestions and discussion of the progress of research on implantable devices are also provided. This review is expected to increase research efforts to develop the battery-less implantable devices with reduced over hole size, low power, high efficiency, high data rate, and improved reliability and feasibility. Based on current literature, we believe that the inductive coupling link is the suitable method to be used to power the battery-less devices. Therefore, in this study, the power efficiency of the inductive coupling method is validated by MATLAB based on suggested values. By further researching and improvements, in the future the implantable and portable medical devices are expected to be free of batteries.

Inductive coupling links for lowest misalignment effects in transcutaneous implanted devices.

Use of transcutaneous inductive links is a widely known method for the wireless powering of bio-implanted devices such as implanted microsystems. The design of the coil for inductive links is generally not optimal. In this study, inductive links were used on the basis of the small loop antenna theory to reduce the effects of lateral coil misalignments on the biological human tissue model at 13.56 MHz. The tissue, which measures 60 mm×70 mm×5 mm, separates the reader and the implanted coils. The aligned coils and the lateral misalignment coils were investigated in different parametric x-distance misalignments. The optimal coil layout was developed on the basis of the layout rules presented in previous studies. Results show that the gain around the coils, which were separated by wet and dry skin, was constant and confirmed the omnidirectional radiation pattern even though the lateral misalignment between coils was smaller or greater than the implanted coil radius. This misalignment can be <4 mm or >6 mm up to 8 mm. Moreover, coil misalignments and skin condition do not affect the efficient performance of the coil.

Automatic frequency controller for power amplifiers used in bio-implanted applications: issues and challenges.

With the development of communication technologies, the use of wireless systems in biomedical implanted devices has become very useful. Bio-implantable devices are electronic devices which are used for treatment and monitoring brain implants, pacemakers, cochlear implants, retinal implants and so on. The inductive coupling link is used to transmit power and data between the primary and secondary sides of the biomedical implanted system, in which efficient power amplifier is very much needed to ensure the best data transmission rates and low power losses. However, the efficiency of the implanted devices depends on the circuit design, controller, load variation, changes of radio frequency coil's mutual displacement and coupling coefficients. This paper provides a comprehensive survey on various power amplifier classes and their characteristics, efficiency and controller techniques that have been used in bio-implants. The automatic frequency controller used in biomedical implants such as gate drive switching control, closed loop power control, voltage controlled oscillator, capacitor control and microcontroller frequency control have been explained. Most of these techniques keep the resonance frequency stable in transcutaneous power transfer between the external coil and the coil implanted inside the body. Detailed information including carrier frequency, power efficiency, coils displacement, power consumption, supplied voltage and CMOS chip for the controllers techniques are investigated and summarized in the provided tables. From the rigorous review, it is observed that the existing automatic frequency controller technologies are more or less can capable of performing well in the implant devices; however, the systems are still not up to the mark. Accordingly, current challenges and problems of the typical automatic frequency controller techniques for power amplifiers are illustrated, with a brief suggestions and discussion section concerning the progress of implanted device research in the future. This review will hopefully lead to increasing efforts towards the development of low powered, highly efficient, high data rate and reliable automatic frequency controllers for implanted devices.

Risk factors for suicidal ideation, plans and attempts in Malaysia--results of an epidemiological survey.

OBJECTIVE: This is an epidemiological study to determine the prevalence of suicidal behavior and its association with generalised anxiety disorder (GAD) and major depressive disorder (MDD) in a nationally representative sample. METHOD: Suicidal ideation, plans and attempts were assessed in face-to-face interviews of respondents selected by a multistage probability sampling using items on suicidality from the WHO SUPRE-MISS questionnaire. The Mini International Neuropsychiatric Interview (MINI) was used to generate DSM-IV diagnoses of GAD and MDD. A total of 19309 subjects were studied. Multivariate regression analysis was conducted controlling for demographic characteristics such as age, gender and ethnicity. RESULTS: The prevalence estimates for suicide ideation, plans and attempts were 1.7% (95% CI: 1.4-1.9), 0.9% (CI: 0.7-1.1) and 0.5% (CI: 0.4-0.7) respectively. Younger people (16-24 years) had higher risk of suicidal behavior (OR: 2.6, CI: 1.08-6.2). Females (OR: 1.6, CI: 1.2-2.1) and Indians (OR: 3.3, CI: 2.2-4.9) also had higher risk. CONCLUSION: The prevalence of suicidal behavior in Malaysia is low, but it broadly corresponds to the pattern described in other countries. This national study confirms that Malaysians of Indian descent have much higher rates of suicidal behavior than other groups. The younger age group, females and the Indian ethnic group would need focused preventive efforts.

Suicide prevention program for at-risk groups: pointers from an epidemiological study.

OBJECTIVES: The aim of this paper is to identify at-risk groups for a focused suicide prevention program for Malaysia. METHODS: Data from 20,552 persons aged 16 years and above (males 45.9%), was obtained using stratified, random sampling in a national survey of psychiatric morbidity using locally validated General Health Questionnaire (GHQ-28) which included questions on suicidal ideation. RESULTS: The overall prevalence of suicidal ideation (SI) was 6.3%, CI 6.1-6.8 (n=1288). Logistic regression analysis was performed with age, ethnicity, gender, urban/rural residence, age group, marital status, household income, type of household, presence of chronic pain, social dysfunction, somatic, anxiety or depressive symptoms, obesity, and chronic medical illnesses as independent variables. Only Insomnia, Religion, Marital Status, Depression, Social Dysfunction and Anxiety were seen to be significant predictors. Prevalence of SI was significantly higher among Indians (11.0%, CI 9.5-12.5), especially those of the Hindu faith (12.2%, CI 10.5-14.0), Chinese (9.7%, CI 8.8-10.7) and those having depressive symptoms. CONCLUSION: In a developing country with competing priorities, prudent allocation of resources requires focusing suicide prevention efforts on treating depression in vulnerable groups.

Modulation techniques for biomedical implanted devices and their challenges.

Implanted medical devices are very important electronic devices because of their usefulness in monitoring and diagnosis, safety and comfort for patients. Since 1950s, remarkable efforts have been undertaken for the development of bio-medical implanted and wireless telemetry bio-devices. Issues such as design of suitable modulation methods, use of power and monitoring devices, transfer energy from external to internal parts with high efficiency and high data rates and low power consumption all play an important role in the development of implantable devices. This paper provides a comprehensive survey on various modulation and demodulation techniques such as amplitude shift keying (ASK), frequency shift keying (FSK) and phase shift keying (PSK) of the existing wireless implanted devices. The details of specifications, including carrier frequency, CMOS size, data rate, power consumption and supply, chip area and application of the various modulation schemes of the implanted devices are investigated and summarized in the tables along with the corresponding key references. Current challenges and problems of the typical modulation applications of these technologies are illustrated with a brief suggestions and discussion for the progress of implanted device research in the future. It is observed that the prime requisites for the good quality of the implanted devices and their reliability are the energy transformation, data rate, CMOS size, power consumption and operation frequency. This review will hopefully lead to increasing efforts towards the development of low powered, high efficient, high data rate and reliable implanted devices.

A novel hepatocyte nuclear factor-1ß (MODY 5) gene mutation in a Romanian boy with pancreatic calcifications, renal and hepatic dysfunction.

We report a 12-years-old Romanian boy with a diagnosis of diabetes and renal insufficiency. Mutations in homeodomain-containing transcription factor hepatocyte nuclear factor (HNF-1ß) have been reported in association with maturity-onset diabetes of the young (MODY 5) and early maturity-onset diabetes, progressive non-diabetic renal dysfunction and bilateral renal cysts. We found a new heterozygous mutation in HFN-1ß located in the exon 3 (c.715 G>C; p.239R) associated to pancreatic calcifications. The importance of molecular diagnosis of MODY patients is reinforced and the need for a careful follow-up is stressed in order to monitor the progression of clinical manifestations and its correlation with the gene mutation.

Estimation of genetic risk for Type 1 diabetes mellitus in newborns on dried blood spot.

BACKGROUND: The main contribution to genetic susceptibility for Type 1 Diabetes Mellitus (T1DM) is conferred by the Human Leukocyte Antigens (HLA). AIM: We evaluated the feasibility of large scale screening on Dried Blood Spot (DBS) to estimate the genetic risk for T1DM in newborns. SUBJECTS AND METHODS: Peripheral blood DBS samples from 256 newborns, were genotyped for HLA DRB1 and DQB1 alleles identification by a commercially available assay based on a dissociation enhancer lanthanide fluorescence system available in many newborn screening laboratories. Results were compared with those obtained in two wide multicentric studies on cord blood (DIABFIN and PREVEFIN). RESULTS: Genotyping on DBS revealed 6 subjects at high risk for T1DM, 99 at moderate risk for T1DM and the remaining at low risk for T1DM. We found 100% concordance between both techniques for HLA-DQB1 and DRB1 determination, confirming the feasibility of large scale screening on DBS. CONCLUSIONS: DBSs represent a resource for future studies about new genetics markers. This assay for estimate the genetic risk of T1DM on DBS showed an excellent sensitivity, specificity and accuracy compared with conventional techniques. Moreover, this assay resulted less expensive, and it could be easily performed on material already collected for newborn screening programs.