Lack of STK11 gene expression in homozygous twins with Peutz-Jeghers syndrome

Clinical features of Peutz-Jeghers syndrome (PJS), an autosomal dominant disorder, include clusters of melanotic spots on the lips and limbs, polyposis of the gastrointestinal (GI) tract, and propensity to develop neoplasms of the GI tract, ovaries, testes, and other sites. We report twin sisters with PJS who were found to be homozygous, based on analyses of 9 DNA markers containing short tandem repeats (STR). Aberrant expression of a putative tumor suppressor gene, STK11, which encodes a serine threonine kinase, has been suggested as the etiologic factor in PJS. In both of the twin sisters with PJS, mRNA analyses by RT-PCR demonstrated a complete lack of STK11 gene expression. These results provide direct evidence that STK11 gene expression is abnormal in PJS. Detecting abnormal expression of the STK11 gene may serve as a molecular approach to the diagnosis of PJS and may facilitate genotype-phenotype correlations in PJS patients.     

Comparison of different PCR approaches for characterization of Burkholderia (Pseudomonas) cepacia isolates.

In this study, we evaluated three PCR methods for epidemiological typing of Burkholderia (Pseudomonas) cepacia--PCR-ribotyping, arbitrarily primed PCR (AP-PCR) and enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR)--and compared them with pulsed-field gel electrophoresis. The analysis was performed with 31 isolates of B. cepacia, comprising 23 epidemiologically unrelated isolates and 8 isolates collected from the same patient during two episodes of bacteremia. Pulsed-field gel electrophoresis, ERIC-PCR, and AP-PCR identified 23 distinct types among the 23 unrelated isolates, while PCR-ribotyping only identified 12 strain types, even after AluI digestion of the amplification products. Among the eight isolates collected from the same patient, all typing techniques revealed two clones of strains. The day-to-day reproducibilities of PCR-ribotyping and ERIC-PCR were good, while greater day-to-day variations were noted in the fingerprints obtained by AP-PCR. We conclude that all three PCR techniques are useful for rapid epidemiological typing of B. cepacia, but ERIC-PCR seems to be more reproducible and discriminative.     

Seroprevalence of hepatitis E virus infection among institutionalized psychiatric patients in Taiwan.

BACKGROUND: Hepatitis E virus infection (HEV) remains unclear in institutionalized psychiatric patients. OBJECTIVES: To investigate the prevalence and risk factors of HEV infection in a psychiatric institution in Taiwan. STUDY DESIGN: A total of 754 patients with psychiatric disorders were enrolled in the study. Clinical features, review of patient charts, and interviews with families were recorded for analysis. Antibody to HEV was tested using a commercial enzyme-linked immunosorbent assays. RESULTS: The prevalence of HEV infection in institutionalized patients was as high as 14.5%. Males had higher prevalence than females. It was also found prevalence increased significantly by age group. When compared with patients 30 years old or less, those in the 31-40 year old age group had an odds ratio of 4.89 [95% confidence interval (CI), 1.15-20.82], 41-50 years old of 6.30 (95% CI, 1.48-26.83), and 50 years or older of 6.20 (95% CI, 1.44-26.74). In multivariate logistic regression analysis, age and male gender were the independent risk factors. CONCLUSIONS: Institutionalized psychiatric patients had higher prevalence of HEV infection. In addition, there was an age-related increase in exposure to HEV with males that had a higher HEV seropositivity.     

Effect of accuracy constraint on joint coordination during pointing movements

Given the number of muscles and joints of the arm, more ways are available to produce an identical hand movement when pointing to a target than are strictly necessary. How the nervous system manages these abundant degrees of freedom was the focus of this study of pointing to targets of low and high indices of difficulty (ID). Two essential features of movement synergies were examined. The first reflects the preferred relations among the outputs of each movement element and was studied through principal component analysis. The second feature of synergy reflects the flexibility of those relationships evidenced by the use of multiple, goal-equivalent solutions to joint coordination. This second feature, which is the main focus of this report, was studied using the uncontrolled manifold approach. Motor abundance was defined operationally as the component of variance of joint combinations that left unchanged the value of important performance variables (goal-equivalent variability, GEV). This variance component was contrasted with the component of variance leading to a change in the value of these variables (non-goal-equivalent variability, NGEV). The difference between GEV and NGEV was evaluated with respect to the performance variables movement extent, movement direction, and path of the arm's center of mass. More than 90% of the variance of joint motions across the pointing trial were accounted for by one principal component, indicating a consistent temporal coupling among most joint motions in a single functional synergy. The flexible nature of this synergy was revealed by the variability analysis. All subjects had significantly higher GEV than NGEV for most of the movement path. Thus, variable patterns of joint coordination did not represent noise but the use of equivalent coordinative solutions related to stabilizing important performance variables. Higher GEV than NGEV was present regardless of the task's ID. One exception was at the time of peak velocity, leading to poorer control of movement extent than movement direction. Increasing the task's ID led to an overall reduction of joint configuraion variance, particularly GEV. These results support earlier work indicating that the use of goal-equivalent solutions to joint coordination is a common feature of the control of this and many other motor tasks. Functionally important performance variables appear to be controlled through flexible but task-specific coordination among the motor elements Electronic Publication     

Specular microscopy of hard contact lens wearers

Wide-field specular microscopy, slit-lamp examination, and pachometry were performed on 22 successful hard contact lens wearers and 22 controls matched for age, race, sex, and refractive error. A minimum of 600 cells per control and 1200 per contact lens wearer were manually digitized from the specular photomicrographs. Frequency distributions of cell areas were compared between the two groups using the parameters of mean, median, standard deviation, coefficient of variation, skewness and kurtosis. Slit-lamp examination was normal and there was no significant difference in corneal thickness between the patient group and the control group. Comparison of mean, median, and standard deviation also revealed no significant difference, but skewness (P less than .001), kurtosis (P less than .001) and coefficient of variation (P less than .004) were greater in the hard contact lens wear group. Hard contact lens wearing time correlated with increasing pleomorphism (P less than .05). Specular microscopy also revealed morphologic changes including deep stromal striae, intra- and extracellular "blackout" areas, and clustering of extremely small and large cells. The possible relationship between endothelial hypoxia and structural stromal changes are discussed.     

Adherence to COVID-19 Nutrition Guidelines Is Associated with Better Nutritional Management Behaviors of Hospitalized COVID-19 Patients

Good nutritional support is crucial for the immune system to fight against coronavirus disease 2019 (COVID-19). However, in the context of a pandemic with a highly transmissible coronavirus, implementation of nutrition practice may be difficult. A multicenter electronic survey involving 62 dieticians was conducted, in order to understand barriers associated with dieticians’ adherence to nutrition guidelines for hospitalized COVID-19 patients in Indonesia. 69% of dieticians felt under stress when performing nutrition care, and 90% took supplements to boost their own immunity against the coronavirus. The concerns related to clinical practice included a lack of clear guidelines (74%), a lack of access to medical records (55%), inadequate experience or knowledge (48%), and a lack of self-efficacy/confidence (29%) in performing nutritional care. Half (52%) of the dieticians had performed nutrition education/counseling, 47% had monitored a patient’s body weight, and 76% had monitored a patient’s dietary intake. An adjusted linear regression showed that guideline adherence independently predicted the dieticians’ nutrition care behaviors of nutrition counselling (ß: 0.24 (0.002, 0.08); p = 0.04), and monitoring of body weight (ß: 0.43 (0.04, 0.11); p = 0.001) and dietary intake (ß: 0.47(0.03, 0.10); p = 0.001) of COVID-19 patients. Overall, adherence to COVID-19 nutrition guidelines is associated with better nutritional management behaviors in hospitalized COVID-19 patients.     

In vivo imaging of neuroblastomas using GD2-targeting graphene quantum dots

BackgroundPatients with neuroblastoma, a common childhood malignancy, often have poor prognosis. It is mandatory to develop an accurate and efficient diagnostic tool for neuroblastomas, so that the treatment can be started early. Graphene quantum dot (GQD), a nanomaterial, can be used to carry proteins, genetic materials, or drugs. GD2, a disialoganglioside, is a surface antigen expressed on neuroblastoma. This study investigated the in vivo targeting and imaging of neuroblastomas using GD2-targeting GQDs.MethodsGQDs were synthesized and conjugated with anti-GD2 antibody (anti-GD2/GQDs). In vitro cytotoxicity of GQDs and anti-GD2/GQDs was studied in human neuroblastoma cells by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide)-based colorimetric assay. The tumor tracking and imaging of anti-GD2/GQDs in mice were investigated by in vivo imaging system (IVIS).ResultsTreatment with GQDs or anti-GD2/GQDs induced no or mild cytotoxicity in fibroblasts and neuroblastoma cells. After co-incubation, GQDs and anti-GD2/GQDs were located in the cytoplasm and nucleus of neuroblastoma cells, with GQDs showing a blue fluorescence and anti-GD2/GQDs an orange/red emission. The IVIS images demonstrated accumulation of the fluorescence of anti-GD2/GQDs in the subcutaneous tumors in mice 24 h after intravenous injection of anti-GD2/GQDs.ConclusionsAnti-GD2/GQDs may potentially be used for the targeting and imaging of neuroblastomas in vivo.     

Allosteric effects of mutations in the extracellular S5-P loop on the gating and ion permeation properties of the hERG potassium channel

The hERG channel has an unusually long (39 amino acids) extracellular loop between the transmembrane S5 segment and the pore region that may play a role in channel function. We explored this possibility by mutating two histidine residues in this region (H578 and H587, referred to as H1 and H2) to various residues and examined the resulting changes in channel function. Both positions could tolerate drastic changes in side-chain properties (proline, cysteine, glutamate and lysine), indicating that they are solvent exposed. None of the H1 mutations affected hERG channel function. On the other hand, although replacing H2 with glutamate had little or no effect on hERG properties, putting a proline or lysine at this position disrupted the C-type inactivation process and the pore's K selectivity. There was also a hyperpolarizing shift in the voltage dependence of activation. The phenotype of the H2C mutant was similar to that of H2P or H2K. However, dithiothreitol (DTT, a thiol-reducing agent) treatment converted the H2C phenotype to that of the wild-type channel. These observations suggest that the peptide backbone conformation around position 587 in the extracellular S5-P loop of hERG channel can affect the channel's gating and ion selectivity functions.