Seroprevalence of Toxocara at Tra Vinh University Hospital in Vietnam.

OBJECTIVE: The study aims to assess the seroprevalence of Toxocariasis and its associated risk factors among individuals attending the outpatient department at Tra Vinh University Hospital, Vietnam, in 2022. SUBJECTS AND METHODS: A cross-sectional survey was conducted among outpatients of Tra Vinh University Hospital. Toxocariasis diagnosis was based on the Enzyme-Linked Immunosorbent Assay (ELISA) performed at the hospital's laboratory department. We assessed the seroprevalence of Toxocariasis and evaluated associated risk factors, including demographics and certain behaviors. RESULTS: Of the 249 participants surveyed, 165 tested positive for Toxocariasis, yielding a seroprevalence of 66.3% (95% CI: 60.4-72.1). Multivariate analysis revealed that age groups up to 30 and 30-60 years had higher odds of Toxocariasis infection, with adjusted odds ratios (aOR) of 2.52 (95% CI: 1.04-6.11) and 3.21 (95% CI: 1.44-7.15) respectively. Additionally, individuals residing in rural areas and those in contact with dogs or cats had increased risks, with aORs of 2.21 (95% CI: 1.21-4.01) and 2.04 (95% CI: 1.10-3.79), respectively. Notably, hand washing before eating emerged as a protective factor against Toxocariasis, presenting an aOR of 0.38 (95% CI: 0.19-0.76). CONCLUSIONS: Our findings underscore a significant seroprevalence (66.3%) of Toxocara spp. among outpatients at Tra Vinh University Hospital. Proactive measures, including hand hygiene before meals and after pet interactions, are advocated. There is a pronounced need for community-level epidemiological surveillance for human Toxocariasis.

Transfer function approach to understanding periodic forcing of signal transduction networks.

Signal transduction networks are responsible for transferring biochemical signals from the extracellular to the intracellular environment. Understanding the dynamics of these networks helps understand their biological processes. Signals are often delivered in pulses and oscillations. Therefore, understanding the dynamics of these networks under pulsatile and periodic stimuli is useful. One tool to do this is the transfer function. This tutorial outlines the basic theory behind the transfer function approach and walks through some examples of simple signal transduction networks.

Influence of Irradiation on the Biology of the Brown Marmorated Stink Bug (Hemiptera: Pentatomidae).

Fifth-instar brown marmorated stink bug (Halyomorpha halys Stål) nymphs were treated by gamma-radiation 60Co at different doses of 8-64 Gy to investigate their irradiation biology and potential for the sterile insect technique (SIT). At adult emergence, males were mated with non-irradiated virgin females to assess the longevity of both sexes, female fecundity, and egg sterility. Biological parameters of their F1 progeny were investigated to determine whether negative effects from parental exposure to radiation were inherited. Results showed that irradiation significantly reduced the lifespan of male insects at doses above 20 Gy. Irradiated males did not affect the longevity and fecundity of their female partners, nor of their resulting adult progenies, but it did reduce the developmental duration of nymphs as well as weight gain of male F1 offspring. Egg hatch was significantly reduced at all tested doses and reached complete sterility at 64 Gy. Low hatch of eggs produced by F1 or F1 crossed adults indicated that negative effects from radiation were inherited by the subsequent generation. But F1 male offspring were not less fertile than their irradiated male parent, unlike what was observed in Lepidoptera. The results support the potential for the use of SIT for H. halys management by irradiating the fifth-instar male nymphs at doses from 16 Gy to 64 Gy.

Using online tools at the Bovine Genome Database to manually annotate genes in the new reference genome.

With the availability of a new highly contiguous Bos taurus reference genome assembly (ARS-UCD1.2), it is the opportune time to upgrade the bovine gene set by seeking input from researchers. Furthermore, advances in graphical genome annotation tools now make it possible for researchers to leverage sequence data generated with the latest technologies to collaboratively curate genes. For many years the Bovine Genome Database (BGD) has provided tools such as the Apollo genome annotation editor to support manual bovine gene curation. The goal of this paper is to explain the reasoning behind the decisions made in the manual gene curation process while providing examples using the existing BGD tools. We will describe the sources of gene annotation evidence provided at the BGD, including RNA-seq and Iso-Seq data. We will also explain how to interpret various data visualizations when curating gene models, and will demonstrate the value of manual gene annotation. The process described here can be applied to manual gene curation for other species with similar tools. With a better understanding of manual gene annotation, researchers will be encouraged to edit gene models and contribute to the enhancement of livestock gene sets.

Using fluorescence lifetime dequenching to estimate the average quinary stoichiometry of proteins in living cells.

Biological proteins are understood in terms of five structural levels-primary, secondary, tertiary, quaternary and quinary. The quinary structure is defined as the set of macromolecular interactions that are transient in vivo. This includes non-covalent protein-protein interactions occurring within the crowded intracellular environment. For much of twentieth century science, the canonical approach to studying biological proteins involved test tube environments. These uncrowded in vitro studies inadvertently failed to replicate and observe the quinary structures present within the original cells. Consequently, contemporary literature surrounding the fifth level of protein organisation is lacking. In particular, there is a lack of literature on the size of transient clusters within living cells. In an attempt to reconcile this gap in knowledge, we propose a quantitative method for estimating the average quinary stoichiometry in living cells. The method is based on lifetime self-quenching of fluorescently-labelled proteins in living cells. Close approach of two or more proteins in a quinary complex will result in self-quenching of the fluorescence lifetime from the fluorescent labels. Our method utilises the random mixing of proteins during cell division to mix fluorescently labelled with unlabelled proteins. Such mixing reduces the probability of adjacency between labelled proteins and, hence, decreases the probability of fluorescence lifetime quenching from labels. By monitoring fluorescence lifetime dequenching during multiple cell divisions, we can determine the average quinary structure in living proliferating cells. We demonstrate this method with a case study on cultured HeLa cells. The average quinary stoichiometry was found to be between five and six. That is, at any given point in time, there are five or six weakly interacting partners in the immediate neighbourhood of any given protein.

Characterization of PTEN mutations in brain cancer reveals that pten mono-ubiquitination promotes protein stability and nuclear localization.

PTEN is a PIP3 phosphatase that antagonizes oncogenic PI3-kinase signalling. Due to its critical role in suppressing the potent signalling pathway, it is one of the most mutated tumour suppressors, especially in brain tumours. It is generally thought that PTEN deficiencies predominantly result from either loss of expression or enzymatic activity. By analysing PTEN in malignant glioblastoma primary cells derived from 16 of our patients, we report mutations that block localization of PTEN at the plasma membrane and nucleus without affecting lipid phosphatase activity. Cellular and biochemical analyses as well as structural modelling revealed that two mutations disrupt intramolecular interaction of PTEN and open its conformation, enhancing polyubiquitination of PTEN and decreasing protein stability. Moreover, promoting mono-ubiquitination increases protein stability and nuclear localization of mutant PTEN. Thus, our findings provide a molecular mechanism for cancer-associated PTEN defects and may lead to a brain cancer treatment that targets PTEN mono-ubiquitination.

A new class of cancer-associated PTEN mutations defined by membrane translocation defects.

Phosphatase and tensin homolog (PTEN), which negatively regulates tumorigenic phosphatidylinositol (3,4,5)-trisphosphate (PIP3) signaling, is a commonly mutated tumor suppressor. The majority of cancer-associated PTEN mutations block its essential PIP3 phosphatase activity. However, there is a group of clinically identified PTEN mutations that maintain enzymatic activity, and it is unknown how these mutations contribute to tumor pathogenesis. Here, we show that these enzymatically competent PTEN mutants fail to translocate to the plasma membrane where PTEN converts PIP3 to PI(4,5)P2. Artificial membrane tethering of the PTEN mutants effectively restores tumor suppressor activity and represses excess PIP3 signaling in cells. Thus, our findings reveal a novel mechanism of tumorigenic PTEN deficiency.

Mechanism of human PTEN localization revealed by heterologous expression in Dictyostelium.

Phosphatase and tensin homolog (PTEN) is one of the most frequently mutated tumor suppressor genes in cancers. PTEN has a central role in phosphatidylinositol (3,4,5)-trisphosphate (PIP3) signaling and converts PIP3 to phosphatidylinositol (4,5)-bisphosphate at the plasma membrane. Despite its importance, the mechanism that mediates membrane localization of PTEN is poorly understood. Here, we generated a library that contains green fluorescent protein fused to randomly mutated human PTEN and expressed the library in Dictyostelium cells. Using live cell imaging, we identified mutations that enhance the association of PTEN with the plasma membrane. These mutations were located in four separate regions, including the phosphatase catalytic site, the calcium-binding region 3 (CBR3) loop, the Cα2 loop and the C-terminal tail phosphorylation site. The phosphatase catalytic site, the CBR3 loop and the Cα2 loop formed the membrane-binding regulatory interface and interacted with the inhibitory phosphorylated C-terminal tail. Furthermore, we showed that membrane recruitment of PTEN is required for PTEN function in cells. Thus, heterologous expression system in Dictyostelium cells provides mechanistic and functional insight into membrane localization of PTEN.

[Diagnosis of oesophageal reflux by PH, impedance, and bilirubin measurement: recommendations of the German Society of Neurogastroenterology and of the working group for neurogastroenterology of the German Society for Digestive and Metabolic Diseases]. / Ösophageale Refluxdiagnostik - pH-Metrie, Impedanzmessung, Bilirubin-Messung: Empfehlungen der Deutschen Gesellschaft für Neurogastroenterologie und Motilität und der Arbeitsgruppe Neurogastroenterologie der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten.

The current recommendations on indications, technical performance, and interpretation of diagnostic techniques for oesophageal reflux update the German recommandations about 24 hour pH measurement of 2003. The recommendations encompass conventional pH measurement, wireless pH measurement, pH and impedance measurements, and bilirubin measurement (duodenogastro-oesophageal reflux).

Mid-infrared prediction of lactoferrin content in bovine milk: potential indicator of mastitis.

Lactoferrin (LTF) is a milk glycoprotein favorably associated with the immune system of dairy cows. Somatic cell count is often used as an indicator of mastitis in dairy cows, but knowledge on the milk LTF content could aid in mastitis detection. An inexpensive, rapid and robust method to predict milk LTF is required. The aim of this study was to develop an equation to quantify the LTF content in bovine milk using mid-infrared (MIR) spectrometry. LTF was quantified by enzyme-linked immunosorbent assay (ELISA), and all milk samples were analyzed by MIR. After discarding samples with a coefficient of variation between 2 ELISA measurements of more than 5% and the spectral outliers, the calibration set consisted of 2499 samples from Belgium (n = 110), Ireland (n = 1658) and Scotland (n = 731). Six statistical methods were evaluated to develop the LTF equation. The best method yielded a cross-validation coefficient of determination for LTF of 0.71 and a cross-validation standard error of 50.55 mg/l of milk. An external validation was undertaken using an additional dataset containing 274 Walloon samples. The validation coefficient of determination was 0.60. To assess the usefulness of the MIR predicted LTF, four logistic regressions using somatic cell score (SCS) and MIR LTF were developed to predict the presence of mastitis. The dataset used to build the logistic regressions consisted of 275 mastitis records and 13 507 MIR data collected in 18 Walloon herds. The LTF and the interaction SCS × LTF effects were significant (P < 0.001 and P = 0.02, respectively). When only the predicted LTF was included in the model, the prediction of the presence of mastitis was not accurate despite a moderate correlation between SCS and LTF (r = 0.54). The specificity and the sensitivity of models were assessed using Walloon data (i.e. internal validation) and data collected from a research herd at the University of Wisconsin - Madison (i.e. 5886 Wisconsin MIR records related to 93 mastistis events - external validation). Model specificity was better when LTF was included in the regression along with SCS when compared with SCS alone. Correct classification of non-mastitis records was 95.44% and 92.05% from Wisconsin and Walloon data, respectively. The same conclusion was formulated from the Hosmer and Lemeshow test. In conclusion, this study confirms the possibility to quantify an LTF indicator from milk MIR spectra. It suggests the usefulness of this indicator associated to SCS to detect the presence of mastitis. Moreover, the knowledge of milk LTF could also improve the milk nutritional quality.

Validation of the Italian version of the falls efficacy scale international (FES-I) and the short FES-I in community-dwelling older persons.

Fear of falling (FF) is a common problem in older persons. FF negatively affects the quality of life by generating anxiety, loss of confidence and of self-efficacy, and, ultimately, activity restriction and increased risk of falling. The FES-I and Short FES-I are two instruments developed to assess FF in older persons which have been already validated in some European countries. Our objectives are to develop the Italian version of FES-I and the Short FES-I and to validate them in older persons. The back translation protocol adopted by the ProFaNE group was used to translate both scales from English to Italian. Participants were 157 community-dwelling persons aged>65 years who underwent comprehensive geriatric assessment, including a structured interview concerning FF, and were administered the FES-I and the Short FES-I. Both scales were re-tested after 4 weeks in 151 persons. FES-I and Short FES-I had high internal validity and test-retest reliability. The Short FES-I is highly comparable with the FES-I. We conclude that the FES-I and the Short FES-I are excellent instruments to asses FF in Italian older subjects and they may be used in future research projects and clinical trials.

NRAGE, a p75NTR adaptor protein, is required for developmental apoptosis in vivo.

NRAGE (also known as Maged1, Dlxin) is a member of the MAGE gene family that may play a role in the neuronal apoptosis that is regulated by the p75 neurotrophin receptor (p75NTR). To test this hypothesis in vivo, we generated NRAGE knockout mice and found that NRAGE deletion caused a defect in developmental apoptosis of sympathetic neurons of the superior cervical ganglia, similar to that observed in p75NTR knockout mice. Primary sympathetic neurons derived from NRAGE knockout mice were resistant to apoptosis induced by brain-derived neurotrophic factor (BDNF), a pro-apoptotic p75NTR ligand, and NRAGE-deficient sympathetic neurons show attenuated BDNF-dependent JNK activation. Hair follicle catagen is an apoptosis-like process that is dependent on p75NTR signaling; we show that NRAGE and p75NTR show regulated co-expression in the hair follicle and that identical defects in hair follicle catagen are present in NRAGE and p75NTR knockout mice. Interestingly, NRAGE knockout mice have severe defects in motoneuron apoptosis that are not observed in p75NTR knockout animals, raising the possibility that NRAGE may facilitate apoptosis induced by receptors other than p75NTR. Together, these studies demonstrate that NRAGE plays an important role in apoptotic-signaling in vivo.

Molecular cytogenetic studies towards the full karyotype analysis of human blastocysts and cytotrophoblasts.

Numerical chromosome aberrations in gametes typically lead to failed fertilization, spontaneous abortion or a chromosomally abnormal fetus. By means of preimplantation genetic diagnosis (PGD), we now can screen human embryos in vitro for aneuploidy before transferring the embryos to the uterus. PGD allows us to select unaffected embryos for transfer and increases the implantation rate in in vitro fertilization programs. Molecular cytogenetic analyses using multi-color fluorescence in situ hybridization (FISH) of blastomeres have become the major tool for preimplantation genetic screening of aneuploidy. However, current FISH technology can test for only a small number of chromosome abnormalities and hitherto failed to increase the pregnancy rates as expected. We are in the process of developing multi-color FISH-based technologies to score all 24 chromosomes in single cells within a three-day time limit, which we believe is vital to the clinical setting. Also, human placental cytotrophoblasts (CTBs) at the fetal-maternal interface acquire aneuploidies as they differentiate to an invasive phenotype. About 20-50% of invasive CTB cells from uncomplicated pregnancies were found to be aneuploid, suggesting that the acquisition of aneuploidy is an important component of normal placentation, perhaps limiting the proliferative and invasive potential of CTBs. Since most invasive CTBs are interphase cells and possess extreme heterogeneity, we applied multi-color FISH and repeated hybridizations to investigate the feasibility of a full karyotype analysis of individual CTBs. In summary, this study demonstrates the strength of Spectral Imaging analysis and repeated hybridizations, which provides a basis for full karyotype analysis of single interphase cells.

Relationship between bolus transit and LES-relaxation studied with concurrent impedance and manometry.

BACKGROUND/AIMS: Neuromuscular mechanisms regulating esophageal bolus transport are well studied. However, detailed data about the relationship between bolus transit and lower esophageal sphincter (LES)-relaxation during conventional motility testing are still lacking. METHODOLOGY: We performed systematic studies in 25 normal subjects, employing a catheter that integrates the two techniques impedancometry and manometry in a single instrument for simultaneous recording and analysis of the relationship between bolus transit and LES relaxation after swallowing saline or yogurt. RESULTS: 195 swallows were analyzed. LES relaxation occurred frequently later than UES relaxation. The mean latency between bolus entry into the esophagus and LES relaxation was 3.6 +0.2 sec. Two types of swallow-induced LES relaxation were observed: (a) LES relaxation preceding bolus transit (46 cases or 24%) and (b) LES relaxation occurring during bolus transit (149 cases or 76%). In the later case, during 114 (76%) cases of this deglutition, the position of the bolus was very close to the LES. CONCLUSIONS: During deglutition, LES relaxation seems to be modulated by bolus transit and occurs predominantly upon arrival of the bolus in the distal esophagus.

Impedance characteristics of esophageal motor function in achalasia.

Detailed data on patterns of esophageal bolus transport in patients with achalasia are still lacking. To study these we applied the novel technique of multichannel intraluminal impedance measurements. Ten patients with achalasia were studied using a 16 channel system. Liquid and semisolid boluses of 10 mL were applied with the patients in a supine position. Patterns of bolus transport were determined and analyzed as compared to results obtained from 20 healthy subjects. The healthy subjects featured a unique typical primary peristalsis pattern independent of bolus viscosity. In contrast, achalasia patients demonstrated different impedance characteristics, including: (i) significantly lower baseline esophageal impedance during the resting state as compared with healthy volunteers (999 omega +/- 108 versus 2749 omega +/- 113); (ii) failed bolus transport through the esophagus in all cases; (iii) impedance evidence of luminal content regurgitation in 35% of the swallows (iv) impedance evidence of pathological air movement within the proximal esophagus during deglutition in 38% of the swallows, so called air trapping. Thus, impedance characteristics of achalasia have been defined and can be attributed to known symptoms of achalasia. They can be used as basic findings for further classification of pathological bolus transports in other esophageal motility disorders.

[Clozapine and pregnancy]. / Clozapine et grossesse.

This article reviews the relations between clozapine and pregnancy. Six case reports are identified in the literature of pregnant patients who received clozapine. Novartis at Basle, Switzerland, through its pharmacovigilance and epidemiology, service, has data on nearly 200 cases summarized in this article. We also describe the case of a patient with paranoid schizophrenia who was hospitalized 10 times between the age of 22 to 32. She received clozapine when she was 29 years old and, with a daily dosage of 350 mg, she became asymptomatic. At the age of 33 and 37, she became pregnant and continued clozapine during her 2 pregnancies. During her first pregnancy, she received insulin due to gestational diabetes associated with a body weight mass (BWM) of 30.4 (N = 20 to 25). During her second pregnancy, the BWM was 23.7 and she did not develop diabetes. She delivered at term 2 daughters who are at the time of this report 5 and 3 years old. The two girls are doing well and have no developmental delay. Psychotic symptoms exacerbation: the plasma concentration of clozapine diminishes during pregnancy due to a higher hepatic metabolism and distribution volume. Monitoring plasma concentration of clozapine can help to adjust its dosage. In case of psychotic symptoms exacerbation, the following can be recommended: 1) Increase the clozapine dosage; 2) Add a classic antipsychotic like perphenazine, trifluoperazine or haloperidol. Diabetes: obesity, glucose intolerance or a family history of diabetes are risk factors to develop gestational diabetes. The follow-up of patients, who take an atypical antipsychotic, should include constant monitoring of the blood glucose or Hb1A and lipid dosages. Complications at labor: Clozapine increases the secretion of oxytocine and the contraction of the uterine muscle. But, no studies can explain how clozapine affects the labor exactly. Some case studies report use of forceps, vacuum or cesarean. CONVULSIONS: Stoner (1997) described neonatal convulsions 8 days after birth. The mother was receiving 350 mg of clozapine, but also lorazepam and haloperidol during her pregnancy. The newborn withdrawal of lorazepam can increase the risk of convulsions and also haloperidol can diminish the convulsion threshold. Floppy infant syndrome: in the case described by Dimichele (1996), the mother received a daily dosage of 300 mg of clozapine and 2.5 mg of lorazepam 3 to 5 times a day. This can explain hypotonia. Stoner (1997) reports a second case where a mother, who received 600 mg of clozapine during pregnancy, gave birth to a child who had no convulsions neither hypotonia. DEVELOPMENT: The cases described concerning studies of children until age 2 to 3 years by Stoner (1997) and Dickson (1998) and until 6 years old by Barnas (1994), do not mention any developmental problem, similar to the two daughters of our patient. The pharmacovigilance service of Novarits reports 6% of malformations. But these reports must be considered with caution since they represent only the pregnancies reported spontaneously to the pharmaceutical company. This is only a portion of all pregnancies associated with clozapine. CONCLUSION: No specific risks for the mother and children can be attributed to the use of clozapine during pregnancy. However, the plasma concentration of clozapine is higher in the fetus compared to the mother (Barnas, 1994); therefore, a minimal dosage should be used. Since clozapine is present in the maternal milk, breast feeding should be avoided. The advantages to use clozapine during pregnancy must exceed the risks. It is justified to continue the use of this medication even if data on classic antipsychotics (e.g.: haloperidol) are more extensive. Because the risk of psychotic exacerbation is higher, the substitution of clozapine is not recommended. The psychosocial support and the obstetrical follow-up must be intensive too. An institutional pharmacovigilance service should complement the one provided by the industry. Also, further case-control and cohort studies are essential to better estimate the long-term risks.

[Retroperitoneal giant angiomyolipoma diagnosed post-partum with lymph node involvement]. / Postpartal diagnostiziertes retroperitoneales Riesenangiomyolipom mit Lymphknotenbefall.

HISTORY AND PRESENTING COMPLAINT: A 30-year-old primipara after a normal pregnancy had delivered a 3340 g child. After an uneventful post-partum period she had noticed her abdomen failing to reduce in size. INVESTIGATIONS, DIAGNOSIS AND TREATMENT: The abdominal sonography discovered a large retroperitoneal tumor. CT and MRI showed a giant tumor which originated from the right kidney. Suspecting the diagnosis of renal liposarcoma the kidney and tumor were excised with removal of enlarged precaval and preaortal lymph nodes. Gross inspection revealed a ca. 3,2 kg myxoid tumor, measuring 27 x 19 x 10 cm. The histological examination of the surgical preparation revealed a retroperitoneal angiomyolipoma. CONCLUSION: This is the first case of a giant retroperitoneal angiomyolipoma with lymph node involvement diagnosed post partum.