Thyroid autoimmunity and autoimmune thyroid disease in Malaysian girls with Turner syndrome: An understudied population.

AIMS: Knowledge on the spectrum of thyroid disorders amongst Turner syndrome (TS) patients in Southeast Asia is limited. This study aimed to evaluate the prevalence of thyroid autoimmunity, the spectrum of autoimmune thyroid disease and association with age and karyotype amongst Malaysian TS girls. METHODS: A cross-sectional study was conducted at 11 paediatric endocrine units in Malaysia. Blood samples for antithyroglobulin antibodies, antithyroid peroxidase antibodies and thyroid function test were obtained. In patients with pre-existing thyroid disease, information on clinical and biochemical thyroid status was obtained from medical records. RESULTS: Ninety-seven TS patients with a mean age of 13.4 ± 4.8 years were recruited. Thyroid autoimmunity was found in 43.8% of TS patients. Nineteen per cent of those with thyroid autoimmunity had autoimmune thyroid disease (Hashimoto thyroiditis in 7.3% and hyperthyroidism in 1% of total population). Patients with isochromosome X and patients with 45,X mosaicism or other X chromosomal abnormalities were more prone to have thyroid autoimmunity compared to those with 45,X karyotype (OR 5.09, 95% CI 1.54-16.88, P = 0.008 and OR 3.41, 95% CI 1.32-8.82, P = 0.01 respectively). The prevalence of thyroid autoimmunity increased with age (33.3% for age 0-9.9 years; 46.8% for age 10-19.9 years and 57.1% age for 20-29.9 years) with autoimmune thyroid disease detected in 14.3% during adulthood. CONCLUSION: Thyroid autoimmunity was significantly associated with the non 45,X karyotype group, particularly isochromosome X. Annual screening of thyroid function should be carried out upon diagnosis of TS until adulthood with more frequent monitoring recommended in the presence of thyroid autoimmunity.

SARS-CoV-2 viral RNA load dynamics in the nasopharynx of infected children.

It is important to understand the temporal trend of the paediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load to estimate the transmission potential of children in schools and communities. We determined the differences in SARS-CoV-2 viral load dynamics between nasopharyngeal samples of infected asymptomatic and symptomatic children. Serial cycle threshold values of SARS-CoV-2 from the nasopharynx of a cohort of infected children were collected for analysis. Among 17 infected children, 10 (58.8%) were symptomatic. Symptomatic children, when compared to asymptomatic children, had higher viral loads (mean cycle threshold on day 7 of illness 28.6 vs. 36.7, P = 0.02). Peak SARS-CoV-2 viral loads occurred around day 2 of illness in infected children. Although we were unable to directly demonstrate infectivity, the detection of significant amount of virus in the upper airway of asymptomatic children suggest that they have the potential to shed and transmit SARS-CoV-2. Our study highlights the importance of contact tracing and screening for SARS-CoV-2 in children with epidemiological risk factors regardless of their symptom status, in order to improve containment of the virus in the community, including educational settings.

A patient with massive cerebral arterial air embolism.

Cerebral air embolism is potentially a catastrophic event that occurs as a consequence of air entry into the vasculature. We report a mechanically ventilated 72-year-old woman who underwent multiple procedures during intensive care stay with few possible sources of emboli postulated. We also discuss regarding the preventive measures to minimise the risk of air embolism.

Disruption of the non-canonical Wnt gene PRICKLE2 leads to autism-like behaviors with evidence for hippocampal synaptic dysfunction.

Autism spectrum disorders (ASDs) have been suggested to arise from abnormalities in the canonical and non-canonical Wnt signaling pathways. However, a direct connection between a human variant in a Wnt pathway gene and ASD-relevant brain pathology has not been established. Prickle2 (Pk2) is a post-synaptic non-canonical Wnt signaling protein shown to interact with post-synaptic density 95 (PSD-95). Here, we show that mice with disruption in Prickle2 display behavioral abnormalities including altered social interaction, learning abnormalities and behavioral inflexibility. Prickle2 disruption in mouse hippocampal neurons led to reductions in dendrite branching, synapse number and PSD size. Consistent with these findings, Prickle2 null neurons show decreased frequency and size of spontaneous miniature synaptic currents. These behavioral and physiological abnormalities in Prickle2 disrupted mice are consistent with ASD-like phenotypes present in other mouse models of ASDs. In 384 individuals with autism, we identified two with distinct, heterozygous, rare, non-synonymous PRICKLE2 variants (p.E8Q and p.V153I) that were shared by their affected siblings and inherited paternally. Unlike wild-type PRICKLE2, the PRICKLE2 variants found in ASD patients exhibit deficits in morphological and electrophysiological assays. These data suggest that these PRICKLE2 variants cause a critical loss of PRICKLE2 function. The data presented here provide new insight into the biological roles of Prickle2, its behavioral importance, and suggest disruptions in non-canonical Wnt genes such as PRICKLE2 may contribute to synaptic abnormalities underlying ASDs.

Differential patterns of allelic loss in estrogen receptor-positive infiltrating lobular and ductal breast cancer.

The two main histological types of infiltrating breast cancer, lobular (ILC) and the more common ductal (IDC) carcinoma are morphologically and clinically distinct. To assess the molecular alterations associated with these breast cancer subtypes, we conducted a whole-genome study of 166 archival estrogen receptor (ER)-positive tumors (89 IDC and 77 ILC) using the Affymetrix GeneChip(R) Mapping 10K Array to identify sites of loss of heterozygosity (LOH) that either distinguished, or were shared by, the two phenotypes. We found single nucleotide polymorphisms (SNPs) of high-frequency LOH (>50%) common to both ILC and IDC tumors predominately in 11q, 16q, and 17p. Overall, IDC had a slightly higher frequency of LOH events across the genome than ILC (fractional allelic loss = 0.186 and 0.156). By comparing the average frequency of LOH by chromosomal arm, we found IDC tumors with significantly (P < 0.05) higher frequency of LOH on 3p, 5q, 8p, 9p, 20p, and 20q than ILC tumors. We identified additional chromosomal arms differentiating the subtypes when tumors were stratified by tumor size, mitotic rate, or DNA content. Of 5,754 informative SNPs (>25% informativity), we identified 78 and 466 individual SNPs with a higher frequency of LOH (P < 0.05) in ILC and IDC tumors, respectively. Hierarchical clustering of these 544 SNPs grouped tumors into four major groups based on their patterns of LOH and retention of heterozygosity. LOH in chromosomal arms 8p and 5q was common in higher grade IDC tumors, whereas ILC and low-grade IDC grouped together by virtue of LOH in 16q.

Validity and reliability of the Moxy oxygen monitor during incremental cycling exercise.

INTRODUCTION: The Moxy is a novel, cutaneously placed muscle oxygen monitor which claims to measure local oxygen saturation (SmO2) and total haemoglobin (THb) using near-infrared spectroscopy. If shown to be reliable, its data storage and telemetric capability will be useful for assessing localised O2 usage during field-based exercise. This study investigated the reliability of the Moxy during cycling and assessed the correlations between its measurements, whole-body O2 consumption (VO2) and heart rate (HR). METHODS: Ten highly trained cyclists performed an incremental, step-wise cycling protocol on two occasions while wearing the Moxy. SmO2, THb, VO2 and HR were recorded in the final minute of each five-minute stage. Data were analysed using Spearman's Order-Rank Coefficient (SROC), Intraclass Correlation (ICC), and Coefficient of Variance (COV). Significance was set at p ≤ .05. RESULTS: SmO2 showed a 'strong' or 'very large' correlation between trials (SROC: r = 0.842-0.993, ICC: r = 0.773-0.992, p ≤ .01) and was moderately correlated with VO2 and HR (r = -0.71-0.73, p ≤ .01). SmO2 showed a moderate to high reliability at low intensities, but this decreased as relative exercise intensity increased. THb showed poor correlations between tests and with the other measured variables, but was highly reliable at all power outputs. CONCLUSIONS: The Moxy is a reliable device to measure SmO2 at low to moderate intensities, but at higher intensities, greater variation in measurements occurs, likely due to tissue ischaemia or increased movement artefacts due to more frequent muscular contractions. THb has low variation during exercise, and does not appear to be a valid indicator of muscle oxygenation.

SNX27 links DGKζ to the control of transcriptional and metabolic programs in T lymphocytes.

Sorting nexin 27 (SNX27) recycles PSD-95, Dlg1, ZO-1 (PDZ) domain-interacting membrane proteins and is essential to sustain adequate brain functions. Here we define a fundamental SNX27 function in T lymphocytes controlling antigen-induced transcriptional activation and metabolic reprogramming. SNX27 limits the activation of diacylglycerol (DAG)-based signals through its high affinity PDZ-interacting cargo DAG kinase ζ (DGKζ). SNX27 silencing in human T cells enhanced T cell receptor (TCR)-stimulated activator protein 1 (AP-1)- and nuclear factor κB (NF-κB)-mediated transcription. Transcription did not increase upon DGKζ silencing, suggesting that DGKζ function is dependent on SNX27. The enhanced transcriptional activation in SNX27-silenced cells contrasted with defective activation of the mammalian target of rapamycin (mTOR) pathway. The analysis of Snx27 -/- mice supported a role for SNX27 in the control of T cell growth. This study broadens our understanding of SNX27 as an integrator of lipid-based signals with the control of transcription and metabolic pathways.

Cortical expression of endothelin receptor subtypes A and B following middle cerebral artery occlusion in rats.

This work aimed to define the spatial expression of endothelin A (ET(A)) and B (ET(B)) receptors in the cerebral cortex after permanent middle cerebral artery occlusion (MCAO) and to identify the phenotype of cells expressing ET(A) and ET(B) receptors. Cortical expression of ET(A) and ET(B) receptors was determined at the mRNA level by semi-quantitative reverse transcription-polymerase chain reaction and at the protein level by immunofluorescence staining, 12, 24 and 72 h after MCAO. Cells expressing endothelin receptors were phenotyped by double labelling with antibodies, anti-protein gene product (PGP9.5) and anti-ED1, towards neurons and activated microglia/macrophages, respectively. Both ET(A) and ET(B) receptor mRNA expressions increased significantly in the ipsilateral cortex in a time-dependent manner after MCAO. Robust expression of ET(A) receptors was noted in most neurons of the ischemic core and in several neurons in laminae 3 and 4 of the peri-infarct region 24 and 72 h after MCAO. ET(B) receptor immunoreactivity was observed in activated microglia/macrophages, beginning 24 h after MCAO. These results provide the first evidence that the action of endothelin during ischemia may be mediated by neuronal ET(A) receptors and activated microglia/macrophage ET(B) receptors. This differential localization of ET(A) and ET(B) receptors suggests that endothelin is involved in some complex neuron-glial interactions in addition to its vascular modulatory activity during ischemia.

Predicting non-elective hospital readmissions: a multi-site study. Department of Veterans Affairs Cooperative Study Group on Primary Care and Readmissions.

OBJECTIVE: To determine clinical and patient-centered factors predicting non-elective hospital readmissions. DESIGN: Secondary analysis from a randomized clinical trial. CLINICAL SETTING: Nine VA medical centers. PARTICIPANTS: Patients discharged from the medical service with diabetes mellitus, congestive heart failure, and/or chronic obstructive pulmonary disease (COPD). MAIN OUTCOME MEASUREMENT: Non-elective readmission within 90 days. RESULTS: Of 1378 patients discharged, 23.3% were readmitted. After controlling for hospital and intervention status, risk of readmission was increased if the patient had more hospitalizations and emergency room visits in the prior 6 months, higher blood urea nitrogen, lower mental health function, a diagnosis of COPD, and increased satisfaction with access to emergency care assessed on the index hospitalization. CONCLUSIONS: Both clinical and patient-centered factors identifiable at discharge are related to non-elective readmission. These factors identify high-risk patients and provide guidance for future interventions. The relationship of patient satisfaction measures to readmission deserves further study.

Antibody to cloned HSV glycoproteins B and D plus adult human leukocytes protect neonatal mice from lethal HSV infection.

Antisera produced by HSV infection or following vaccination of guinea pigs with the cloned herpes simplex virus (HSV) glycoproteins gB and gD were compared for in vitro antibody-dependent cellular cytotoxicity (ADCC) activity and for in vivo protection. Antibody from guinea pigs was able to participate in ADCC with human mononuclear cells in vitro, anti-gBgD serum being equivalent to HSV convalescent sera. In vivo, each of the guinea pig sera was able to protect neonatal mice from a fatal HSV-1 infection when given with human mononuclear cells but not when given alone. The anti-gBgD serum was the most effective in vivo, protecting 15 of 17 (88%) neonatal mice when given at a 10(-4) dilution with human mononuclear cells and was the only guinea pig serum protective at a 10(-6) dilution (5 of 7 neonatal mice).

Validity of computer simulation of blood vessel imaging in angiography.

The computer-simulation technique for imaging of vessels in angiography is being recognized as a useful tool for the study of the effect of physical parameters on the vessel image. We have examined the validity of this technique by comparing the computed image distribution directly with experimental results. The imput x-ray pattern of a blood vessel phantom, the LSF of the focal spot, and the LSF of a screen-film system were measured. From the data obtained, the final image distributions of the phantom were computed and compared with the experimentally determined distributions. A high-precision device for the alignment and positioning of the vessel phantom was employed in the experiments. Results indicate that computer simulation can correctly predict the image distribution of the blood vessel phantom.

Investigation of basic imaging properties in digital radiography. 4. Effect of unsharp masking on the detectability of simple patterns.

The signal-to-noise ratios (SNRs) of simple radiologic patterns processed by the unsharp-masking technique were calculated on the basis of a statistical decision theory model that includes both the observer's visual transfer function and a noise component internal to his eye-brain system. For a variety of processing parameters, the contrast-detail diagrams predicted from this SNR agreed qualitatively with experimental results obtained in observer performance studies. Unsharp masking with a large mask and a large weighting factor improved the detection of square objects to a level comparable with that achieved by the overall contrast enhancement technique using a factor of 4. However, unsharp masking with a small mask and a large weighting factor can substantially degrade the detectability of these objects. The potential practical utility of the unsharp-masking technique is discussed.

Natural killer cell cytotoxicity and antibody-dependent cellular cytotoxicity to herpes simplex virus-infected cells in human pregnancy.

Natural killer cell (NKC) cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) represent the ability of human leukocyte effector cells to destroy target cells in the absence and presence of antibody, respectively. Since these immune systems play a pivotal role in the body's primary lines of defense against a variety of pathogens including herpes simplex virus (HSV), a study was undertaken to evaluate the influence of pregnancy on these systems. Eleven uncomplicated gravidas were followed serially through each trimester and compared to 11 nonpregnant female controls. Mononuclear cells were acquired by Ficoll-Hypaque centrifugation of heparinized blood. Chang liver cells infected with HSV-I were utilized as target cells in a 51Cr release assay. Mean NKC values in the pregnant patients were uniformly lower than in the controls. No similar decreases in ADCC activity were observed in a comparison between the two study populations. These data support previous observations suggesting that pregnancy represents a relatively immunocompromised state. Differences apparently exist between NKC and ADCC effector cell populations with regard to the influence of pregnancy. Although these physiologic alterations in immunoregulation may help support the fetoplacental allograph, detrimental conditions may exist regarding susceptibility to various pathogens such as HSV.

A comparison of physical image quality indices and observer performance in the radiographic detection of nylon beads.

Although various models have been proposed in an attempt to predict the usefulness of a radiographic image in terms of its physical characteristics, no previous work has shown whether a single physical image quality index, such as a signal-to-noise ratio, can reliably predict the performance of a human observer over a broad range of image characteristics. We studied the relationship between physical and visual image quality for the task of detecting nylon beads in radiographs. Thirty-seven imaging cases with different combinations of physical image characteristics were considered; these included variations in object size and magnification, X-ray beam quality, screen-film system, screen-film contact, film density and illumination, and viewing distance. For each imaging case, visual image quality was quantified in terms of observer performance in a 2AFC visual detection experiment. Physical image quality indices were calculated according to eight different models of the detection process; these indices combined data regarding object size and attenuation, screen-film system MTF, film gradient, noise Wiener spectrum, and visual system response. The results of this work indicate that, for the conditions studied, human observer detection performance most closely resembles that of a sub-optimal statistical decision process.

Quality of life in cadaver and living-related renal transplant recipients in Kuala Lumpur hospital.

OBJECTIVE: To examine the quality of life in cadaver (CAD) and living-related (LRRT) renal transplant recipients. METHODS: A cross-sectional study was done on patients followed in renal transplant clinic from 1/4/03 to 1/7/03 using the SF-36 questionnaire. Inclusion criteria were age >16 years,minimum of 3 months' posttransplant, and informed consent. Exclusion criteria were current treatment for rejection or infection or any life-threatening conditions. Information on duration of transplant, duration of dialysis prior to transplant, number of co-morbidities, and sociodemodraphic data were collected. RESULTS: Sixty-four among 110 patients (58.1%) completed the SF36 questionnaire. The LRRT recipients were younger, had a longer duration of transplant, and had spent significantly less time on dialysis prior to transplant compared to CAD transplant patients. Overall, the physical composite and the mental composite scores were not significantly different between the two transplant groups. Age was negatively associated with the physical composite score (Spearman's rho -0.251, P < .05) and bodily pain (Spearman's rho -0.266, P < .05). Duration of dialysis prior to transplant was negatively correlated with social functioning (Spearman's rho -0.28, P < .05) and mental health (Spearman's rho -0.39, P < .005). In multiple regression analysis, age was a significant predictor of the SF36 physical composite score (P < .05). CONCLUSION: This study shows that the quality of life between LRRT and CAD recipients was not significantly different. Increased age was associated with poorer physical capacity.

Influence of naproxen therapy on natural killer cytotoxicity and antibody-dependent cellular cytotoxicity against cells infected with herpes simplex virus.

Natural killer cytotoxicity (NKC) and antibody-dependent cellular cytotoxicity (ADCC) represent one of the body's primary lines of defense against viral infections, including herpes simplex (HSV). This immune defense system is negatively influenced by prostaglandins. A project was undertaken to evaluate the influence of an antiprostaglandin agent in vivo on these cytotoxic effects against cells infected with HSV. Thirteen subjects without previous histories of clinical herpes simplex infection were studied during menses with and without naproxen therapy. A statistically significant augmentation (p = 0.05) of natural killer-cell function was identified in mononuclear cells during therapy. Subjects with baseline cytotoxicity of less than 45% demonstrated consistent elevations during naproxen therapy. No other significant differences could be found for mononuclear or polymorphonuclear cells with regard to NKC and ADCC. There appears to be a subset of patients who may benefit from immunologic augmentation with antiprostaglandin agents when experiencing herpes simplex virus infection.

Influence of menstrual cycle variations on natural killer cytotoxicity and antibody-dependent cellular cytotoxicity to cells infected with herpes simplex virus.

Natural killer cytotoxicity (NKC) and antibody-dependent cellular cytotoxicity (ADCC) represent the ability of human leukocytes to destroy target cells. Those systems have been shown to influence herpes simplex virus (HSV) infections. Prostaglandins are known to inhibit these nonspecific immunologic defenses. Since prostaglandin production varies with the menstrual cycle, this study was undertaken to test for variations in cytotoxic activity against HSV-infected cells during the proliferative, secretory and menstrual phases in 13 normal volunteers. NKC and ADCC activity was not statistically different between the three menstrual phases when testing was done for both mononuclear and polymorphonuclear cells from donor sera. This study suggested that NKC and ADCC cannot be used to explain anecdotal experiences suggesting menstrual variations as a triggering mechanism for HSV recurrences.

Comparison of multiplex PCR and culture for detection of Legionellae in cooling tower water samples.

We compared multiplex polymerase chain reaction (PCR) and culture for detecting the presence of Legionella pneumophila and Legionella spp in cooling tower water samples. Multiplex PCR was performed after phenol extraction of DNA from the samples. The set of primers for the PCR assay involved the 5S rRNA (Legionella spp) and the mip (macrophage infectivity potentiator gene, specific for L. pneumophila) genes as target sequences for amplification. Both the sensitivity and the specificity of the PCR assay were 100% when the 5S rRNA gene was used as target sequence. Isolation of Legionellae from the samples was observed only with the PCR-positive samples. We propose that PCR be used as a screening test before attempting to culture Legionellae from cooling tower water samples.

Case reports of nocardiosis in patients with human immunodeficiency virus (HIV) infection.

INTRODUCTION: We present 4 local cases of nocardiosis in HIV-infected patients and discuss the diagnosis, clinical syndromes and therapy of nocardiosis. CLINICAL PICTURE: Two cases presented with pulmonary nocardiosis, one had a cervical lymph node abscess and one had disseminated nocardiosis with pulmonary, cerebral and soft tissue involvement. TREATMENT: Combination therapy is often employed. Sulphonamides or co-trimoxazole, amikacin, imipenen, minocycline and ceftriaxone are some of the drugs that could be used. OUTCOME: Outcome hinges on the early recognition and optimal treatment of this infection. CONCLUSIONS: Clinical presentations vary and diagnosis is difficult and frequently delayed. Nocardiosis should be suspected in patients who present with pulmonary lesions with soft tissue and/or cerebral abscesses.

Stroke disease management--a framework for comprehensive stroke care.

Disease management is an approach to patient care that coordinates medical resources for the patient across the entire healthcare delivery system throughout the lifetime of the patient with the disease. Stroke is suitable for disease management as it is a well-known disease with a high prevalence, high cost, variable practice pattern, poor clinical outcome, and managed by a non-integrated healthcare system. It has measurable and actionable outcomes, with available local expertise and support of the Ministry of Health. Developing the programme requires a multidisciplinary team, baseline data on target populations and healthcare services, identification of core components, collaboration with key stakeholders, development of evidence-based clinical practice guidelines and carepaths, institution of care coordinators, use of information technology and continuous quality improvement to produce an effective plan. Core components include public education, risk factor screening and management, primary care and specialist clinics, acute stroke units, inpatient and outpatient rehabilitation facilities, and supportive community services including medical, nursing, therapy, home help and support groups for patients and carers. The family physician plays a key role. Coordination of services is best done by a network of hospital and community-based care managers, and is enhanced by a coordinating call centre. Continuous quality improvement is required, with audit of processes and outcomes, facilitated by a disease registry. Pitfalls include inappropriate exclusion of deserving patients, misuse, loss of physician and patient independence, over-estimation of benefits, and care fragmentation. Collaboration and cooperative among all parties will help ensure a successful and sustainable programme.