The effect of hypoxic ischemic encephalopathy towards multi-organ complications and its early outcome at a Malaysian district hospital.

INTRODUCTION: Hypoxic ischemic encephalopathy (HIE) is a clinically defined syndrome of disturbed neurologic function in the newborn with evidence of perinatal asphyxia. Stages of HIE are categorised into mild, moderate or severe based on the Sarnat classification. Neurological dysfunction constitutes a part of the wide spectrum of hypoxic ischemic insult as affected infants can have co-existing multi-organ dysfunction which further contributes to morbidities and mortality. This study aims to determine the relationship between the severity of HIE with multi-organ complications and early clinical outcomes. MATERIALS AND METHODS: All neonates who were admitted to the NICU at Hospital Sultan Abdul Halim between January 2018 to December 2022, who fulfilled the inclusion criteria were included. Demographic data, clinical course and investigation results were retrospectively obtained from the medical records. RESULTS: From a total of 90 infants (n = 90) who fulfilled our inclusion criteria, 31 (34%) were mild, 31 (34%) were moderate and 28 (31%) were severe HIE. The mean maternal age was 27 years. Common antenatal issues include diabetes mellitus (37.8%) and anaemia (22.2%). The Apgar scores at 1 and 5 minutes, initial resuscitation requiring intubation, chest compression and adrenaline were associated with higher severity of HIE (p < 0.05). Coagulation dysfunction was the most common complication (79.7%), followed by respiratory dysfunction (33.3%), cardiac dysfunction (28.9%), renal dysfunction (16.1%), haematological dysfunction (15.6%) and hepatic dysfunction (12%). Respiratory and haematological dysfunctions were significantly associated with higher mortality (p < 0.05). There was a significant longer hospital stay (p = 0.023), longer duration of ventilation (p < 0.001) and increase in frequency of seizures (p < 0.001) when comparing moderate and severe HIE patients to mild HIE patients. With increasing severity of HIE, there was also statistically significant higher mortality (p < 0.001). CONCLUSIONS: There is a significant relationship between multiorgan dysfunction, the severity of HIE and mortality. Early anticipation of multi-organ injury is crucial for optimal early management which would reduce the mortality and improve the neurological outcome of the patients.

Predicting short-term suicidal thoughts in adolescents using machine learning: developing decision tools to identify daily level risk after hospitalization.

BACKGROUND: Mobile technology offers unique opportunities for monitoring short-term suicide risk in daily life. In this study of suicidal adolescent inpatients, theoretically informed risk factors were assessed daily following discharge to predict near-term suicidal ideation and inform decision algorithms for identifying elevations in daily level risk, with implications for real-time suicide-focused interventions. METHODS: Adolescents (N = 78; 67.9% female) completed brief surveys texted daily for 4 weeks after discharge (n = 1621 observations). Using multi-level classification and regression trees (CARTSs) with repeated 5-fold cross-validation, we tested (a) a simple prediction model incorporating previous-day scores for each of 10 risk factors, and (b) a more complex model incorporating, for each of these factors, a time-varying person-specific mean over prior days together with deviation from that mean. Models also incorporated missingness and contextual (study week, day of the week) indicators. The outcome was the presence/absence of next-day suicidal ideation. RESULTS: The best-performing model (cross-validated AUC = 0.86) was a complex model that included ideation duration, hopelessness, burdensomeness, and self-efficacy to refrain from suicidal action. An equivalent model that excluded ideation duration had acceptable overall performance (cross-validated AUC = 0.78). Models incorporating only previous-day scores, with and without ideation duration (cross-validated AUC of 0.82 and 0.75, respectively), showed relatively weaker performance. CONCLUSIONS: Results suggest that specific combinations of dynamic risk factors assessed in adolescents' daily life have promising utility in predicting next-day suicidal thoughts. Findings represent an important step in the development of decision tools identifying short-term risk as well as guiding timely interventions sensitive to proximal elevations in suicide risk in daily life.

Development, validity and reproducibility of a whole grain food frequency questionnaire in Malaysian children.

BACKGROUND: To date, there is no validated whole grain assessment tool for children in any Southeast Asian countries. Hence, there is a need for a valid tool to assess whole grain intake among Malaysian children. This study aimed to develop, validate and test the reproducibility of a food frequency questionnaire (FFQ) in estimating whole grain intake among Malaysian children. METHODS: A total of 392 children participated in the FFQ development and 112 children aged 9-12 years participated in the validation phase; with a subsample of 50 children participating in the reproducibility phase. Three-day diet record (3DR) as the reference method in validation phase. Spearman correlations, mean difference, Bland-Altman plot and cross-classification analyses were used to assess validity. The reproducibility was tested through a repeat administration of the FFQ, with 1 month time interval. Reproducibility analyses involved intra-class correlation coefficient (ICC), Cronbach's alpha and cross-classification analyses. RESULTS: The FFQ consisted of 156 whole grain food items from six food groups. Mean intake of whole grain in FFQ1 and 3DR were correlated well (r = 0.732), demonstrated good acceptance of the FFQ. Bland Altman plots showed relatively good agreement for both the dietary methods. Cross-classification of whole grain intake between the two methods showed that < 9.9% of children were grossly misclassified. Outcomes from ICC (0.989) and Cronbach's alpha (0.995) demonstrated excellent reliability. All the children were classified in the same or adjacent quartile of whole grain intake. CONCLUSIONS: Overall, the findings support the validity of the developed FFQ to appropriately estimate the whole grain intake in Malaysian children. This validated FFQ will be a valuable tool for future studies, to analyses the impact of whole grain consumption with disease relationship among Malaysian schoolchildren.

Whole-grain intake and its inverse relationships with fatty acids intake among multiethnic Malaysian schoolchildren.

INTRODUCTION: Little is known about the relationship of whole-grain intake with dietary fatty acids intake. The present study aimed to assess the whole-grain intake and its relationships with dietary fatty acids intake among multiethnic schoolchildren in Kuala Lumpur, Malaysia. METHODS: This cross-sectional study was conducted among 392 schoolchildren aged 9-11 years, cluster sampled from five randomly selected schools in Kuala Lumpur. Whole-grain and fatty acids intakes were assessed by 3-day, 24-h diet recalls. All whole-grain foods were considered irrespective of the amount of whole grain they contained. RESULTS: In total, 55.6% (n = 218) were whole-grain consumers. Mean (SD) daily intake of whole grain in the total sample was 5.13 (9.75) g day-1 . In the whole-grain consumer's only sample, mean (SD) intakes reached 9.23 (11.55) g day-1 . Significant inverse associations were found between whole-grain intake and saturated fatty acid (SAFA) intake (r = -0.357; P < 0.001), monosaturated fatty acid (MUFA) (r = -0.373; P < 0.001) and polyunsaturated fatty acid (PUFA) (r = -0.307; P < 0.001) intake. Furthermore, whole-grain intake was a significant predictor of SAFA (ß = -0.077; P = 0.004), MUFA (ß = -0.112; P = <0.001) and PUFA (ß = -0.202; P = <0.001) intakes, after controlling for sex, age and ethnicity. CONCLUSIONS: Whole-grain intake in Malaysia was well below recommendations. Schoolchildren who consumed higher whole grain tend to reduce fat intake; however, it would also reduce the SAFA, MUFA and PUFA intakes. Future collaboration may be conducted between industry, government and universities to promote unsaturated fatty acids-rich foods and whole-grain food, although not to promote processed whole-grain foods with a high sugar and salt content.

Multi-omics Analyses Reveal Synergistic Carbohydrate Metabolism in Streptococcus mutans-Candida albicans Mixed-Species Biofilms.

Candida albicans, a major opportunistic fungal pathogen, is frequently found together with Streptococcus mutans in dental biofilms associated with severe childhood caries (tooth decay), a prevalent pediatric oral disease. However, the impact of this cross-kingdom relationship on C. albicans remains largely uncharacterized. Here, we employed a novel quantitative proteomics approach in conjunction with transcriptomic profiling to unravel molecular pathways of C. albicans when cocultured with S. mutans in mixed biofilms. RNA sequencing and iTRAQ (isobaric tags for relative and absolute quantitation)-based quantitative proteomics revealed that C. albicans genes and proteins associated with carbohydrate metabolism were significantly enhanced, including sugar transport, aerobic respiration, pyruvate breakdown, and the glyoxylate cycle. Other C. albicans genes and proteins directly and indirectly related to cell morphogenesis and cell wall components such as mannan and glucan were also upregulated, indicating enhanced fungal activity in mixed-species biofilm. Further analyses revealed that S. mutans-derived exoenzyme glucosyltransferase B (GtfB), which binds to the fungal cell surface to promote coadhesion, can break down sucrose into glucose and fructose that can be readily metabolized by C. albicans, enhancing growth and acid production. Altogether, we identified key pathways used by C. albicans in the mixed biofilm, indicating an active fungal role in the sugar metabolism and environmental acidification (key virulence traits associated with caries onset) when interacting with S. mutans, and a new cross-feeding mechanism mediated by GtfB that enhances C. albicans carbohydrate utilization. In addition, we demonstrate that comprehensive transcriptomics and quantitative proteomics can be powerful tools to study microbial contributions which remain underexplored in cross-kingdom biofilms.

Large-area fabrication of microlens arrays by using self-pinning effects during the thermal reflow process.

Generally, the fabrication of curved structures such as microlens arrays has been regarded as an expensive and complicated process. Here, we propose a facile method to form a microlens array with controlled lens curvature by combining residue-free nanoimprint lithography (NIL) with V-shaped molds and the successive thermal reflow procedure of the printed polymeric structures. The V-shaped molds used in this study enable the bottom substrate to be exposed after the NIL process when the initial thickness is controlled. Then, we use the thermal reflow to realize hemi-cylindrical curved lenses by applying heat. The polymers are self-pinned on the exposed substrate, which is strong enough to fix the boundary to not dewet or be flattened in the broad temperature range of the reflow process, which is essential for a large-area fabrication. Furthermore, we demonstrate the modulation of the focal lengths of the lenses by controlling the initial polymer thickness coated on a substrate.

GReat-Child Trial™ based on social cognitive theory improved knowledge, attitudes and practices toward whole grains among Malaysian overweight and obese children.

BACKGROUND: Studies have reported that improvement of dietary habits through increased whole grain foods consumption at an early age has the potential to lead to betterment in lifelong health and wellness. The GReat-Child Trial™ was a 12-week quasi-experimental study with 6 months follow-up investigating a multi-component whole grain intervention, which consisted of behavioral, personal and environmental factors based on Social Cognitive Theory (SCT). This study aimed to evaluate the feasibility and acceptability of the GReat-Child Trial™, as well as to determine the changes in knowledge, attitudes and practices (KAP) of whole grains consumption among overweight/obese children. METHODS: Two schools in Kuala Lumpur with similar socio-demographic characteristics were assigned as intervention (IG) and control (CG), respectively. Inclusion criteria were healthy Malaysian overweight/obese children aged 9 to 11 years who had no serious co-morbidity. Children who reported consuming whole grain foods in their 3-day diet-recall during recruitment were excluded. A total of 63 children (31 IG; 32 CG) completed the intervention. KAP questionnaire was self-administered at baseline [T0] and post intervention (at 3rd [T1] and 9th month [T2]). The baseline differences between the IG and CG across socio-demographics and scores of KAP toward whole grains were determined using chi-square and t-test, respectively. ANCOVA was performed to determine the effect of the GReat-Child Trial™ on KAP towards whole grains at post-intervention and follow-up. Baseline variables were considered as covariates. RESULTS: The IG attained significantly higher scores in knowledge (mean difference = 4.23; 95% CI: 3.82, 4.64; p < 0.001), attitudes (mean difference = 7.39; 95% CI: 6.36, 8.42; p < 0.001) and practice (mean difference = 6.13; 95% CI: 4.49, 7.77; p < 0.001) of whole grain consumption compared to the CG, after adjusting for confounders. The IG reported significantly higher scores in knowledge (mean difference = 6.84; 95% CI: 6.53, 7.15; p < 0.001), attitudes (mean difference = 9.16; 95% CI: 8.08, 10.24; p < 0.001) and practice (mean difference = 8.03; 95% CI: 5.34, 10.73; p < 0.001) towards whole grains at T2 compared to T0. CONCLUSIONS: These findings indicate that this intervention made a positive impact on improving children's KAP on whole grains. We anticipate the GReat-Child Trial™ to be a program that could be incorporated into school interventions to improve whole grain consumption among Malaysian children for obesity prevention.

Knowledge, attitudes and practices of schoolchildren toward whole grains and nutritional outcomes in Malaysia.

Whole grains play an important role in regulating body weight. However, interventions aimed to increase whole grains consumption have had limited impact on body mass index for age z-score (BAZ) due to insufficient understanding of knowledge, attitudes and practices (KAP) toward whole grains. This survey aimed to evaluate whole grains KAP among schoolchildren, as well as to investigate the associations of whole grains KAP with BAZ among the schoolchildren in Negeri Sembilan, Malaysia. This cross-sectional survey was conducted among 380 schoolchildren aged 9-11 years, cluster sampled from six randomly selected schools. Data were collected through a validated self-administered guided questionnaire. Body weight and height were measured. A majority of the schoolchildren had normal body weight (56.6%), moderate whole grains knowledge (42.6%), as well as neutral attitudes (66.1%) and poor practices (58.9%) toward whole grains consumption. Significant positive associations were found between knowledge and attitudes (r = 0.337; p < .01), attitudes and practices (r = 0.150; p < .01) and knowledge and practices (r = 0.190; p < .01). Further, whole grains consumption's practices was associated with BAZ after adjusting for sex, gender, race and area where children lived in (p < .001). Outcome of this present study implies that positive change in whole grain knowledge would help to inculcate positive attitudes and cultivate better practices toward whole grain consumption, which may be useful in lower BAZ among schoolchildren in Negeri Sembilan, Malaysia. This study reveals the importance of KAP toward whole grains among children to assist in identification of specific preventive childhood obesity actions.

Therapeutic Strategies Targeting Cariogenic Biofilm Microenvironment.

Cariogenic biofilms are highly structured microbial communities embedded in an extracellular matrix, a multifunctional scaffold that is essential for the existence of the biofilm lifestyle and full expression of virulence. The extracellular matrix provides the physical and biological properties that enhance biofilm adhesion and cohesion, as well as create a diffusion-modulating milieu, protecting the resident microbes and facilitating the formation of localized acidic pH niches. These biochemical properties pose significant challenges for the development of effective antibiofilm therapeutics to control dental caries. Conventional approaches focusing solely on antimicrobial activity or enhancing remineralization may not achieve maximal efficacy within the complex biofilm microenvironment. Recent approaches disrupting the biofilm microbial community and the microenvironment have emerged, including specific targeting of cariogenic pathogens, modulation of biofilm pH, and synergistic combination of bacterial killing and matrix degradation. Furthermore, new "smart" nanotechnologies that trigger drug release or activation in response to acidic pH are being developed that could enhance the efficacy of current and prospective chemical modalities. Therapeutic strategies that can locally disrupt the pathogenic niche by targeting the biofilm structure and its microenvironment to eliminate the embedded microorganism and facilitate the action of remineralizing agents may lead to enhanced and precise anticaries approaches.

New perspectives for Rashba spin-orbit coupling.

In 1984, Bychkov and Rashba introduced a simple form of spin-orbit coupling to explain the peculiarities of electron spin resonance in two-dimensional semiconductors. Over the past 30 years, Rashba spin-orbit coupling has inspired a vast number of predictions, discoveries and innovative concepts far beyond semiconductors. The past decade has been particularly creative, with the realizations of manipulating spin orientation by moving electrons in space, controlling electron trajectories using spin as a steering wheel, and the discovery of new topological classes of materials. This progress has reinvigorated the interest of physicists and materials scientists in the development of inversion asymmetric structures, ranging from layered graphene-like materials to cold atoms. This Review discusses relevant recent and ongoing realizations of Rashba physics in condensed matter.

Prevalence of type 5 familial hemophagocytic lymphohistiocytosis in Korea and novel mutations in STXBP2.

Familial hemophagocytic lymphohistiocytosis (F-HLH or FHL) is a potentially fatal immune dysregulation syndrome with a heterogeneous genetic background. Most recently, STXBP2 has been identified as the causative gene of type 5 FHL (FHL5) with a worldwide distribution. In this study, we investigated the prevalence of FHL5 in Korea. About 50 Korean pediatric patients with HLH who lacked pathogenic mutations in PRF1, UNC13D, or in STX11 from the previous series of 72 patients with HLH were analyzed for STXBP2 mutations by conventional sequencing analyses. As a result, we found one patient with two novel mutations of STXBP2: c.184A>G and c.577A>C. c.184A>G (p.Asn62Asp) was located within a highly conserved region of the STXBP2 protein and predicted to be deleterious. c.577A>C in exon 7 resulted in incomplete splicing mutation with exon 7 skipping concurrent with exon 7-retained transcript with p.Lys193Gln substitution. The frequency of FHL5 was ~1% (1/72) in Korean pediatric patients with HLH. This is the first study on FHL5 in Korea, and the data from a nationwide patient cohort provide another piece of genetic profiles of FHL.

Remission of proteinuria indicates good prognosis in patients with diffuse proliferative lupus nephritis.

Proteinuria is a well-known risk factor for the progression of renal dysfunction in chronic kidney disease; however, its importance for estimating the prognosis of lupus nephritis requires verification. Korean adult patients with renal biopsy-diagnosed diffuse proliferative lupus nephritis who had undergone three or more consecutive urine protein to creatinine ratio or urine dipstick tests within six months after renal biopsy were enrolled. The cumulative risks, predictors, and outcomes of proteinuric remission and flare were evaluated. This study included 26 men and 167 women with a mean age at renal biopsy of 31.2 ± 9.8 years. Eighty-two (42.5%) patients experienced proteinuric remission during the follow-up period. During a mean follow-up of 157.9 ± 69.5 months, among patients who achieved proteinuric remission, one died, one developed end-stage renal disease (ESRD), and two had composite outcomes; among patients without remission, nine died, 24 developed ESRD, and 30 had composite outcomes. Patients who achieved proteinuric remission had a 0.089-fold risk (95% CI: 0.011-0.736) of mortality, 0.110-fold risk (95% CI: 0.013-0.904) of incident ESRD, and 0.210-fold risk (95% CI: 0.048-0.920) of a composite outcome compared to patients without remission. Among the 82 patients who achieved proteinuric remission, 59 (72.0%) experienced at least one proteinuria flare; however, relapse did not correlate with the incidence of outcomes. In conclusion, proteinuric remission is an independent predictive prognostic marker of good renal survival and mortality, regardless of the interval from biopsy to remission, recurrence of proteinuria after remission, renal function status at remission, or hematuria remission.

Ethanol and/or radiofrequency ablation to treat venolymphatic malformations that manifest as a bulging mass in the head and neck.

AIM: To evaluate the efficacy of ultrasound (US)-guided ethanol ablation (EA) and radiofrequency ablation (RFA) for treating venolymphatic malformations (VLM) of the head and neck. MATERIALS AND METHODS: US-guided EA and/or RFA were performed on 17 patients with VLM of the head and neck. Computed tomography (CT) or magnetic resonance imaging (MRI) was used to locate the cranial nerves and salivary gland ducts that were close to targets, and these were avoided during the procedures. Treatment response was assessed using volume reduction and cosmetic grading scoring. RESULTS: Nine VLMs were located close to the functional structures: Stensen's duct (n=3), cranial nerve branch (n=3), or both (n=3). All patients demonstrated >50% volume reduction, except one patient with a microcystic lymphatic malformation that was abutting the facial nerve. Median cosmetic grading scores improved from 4 to 1 (p<0.001). CONCLUSION: US-guided EA and/or RFA are effective and safe treatment methods in patients with VLMs of the head and neck. Treatment selection of EA and/or RFA could be performed based on the composition of VLMs as assessed at CT and MRI.

Serum hCG-ß levels of postovulatory day 12 and 14 with the sequential application of hCG-ß fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle.

PURPOSE: To investigate hCG-ß level on postovulatory day (POD) 12 and its fold increase as predictors for pregnancy outcome after in vitro fertilization (IVF) cycles. METHODS: A retrospective cohort study was performed in total 1408 fresh and 598 frozen cycles between November 2008 and October 2011, which resulted in biochemical pregnancy, early pregnancy loss, or live birth of singleton pregnancy. The serum hCG-ß levels of POD 12 and 14 were compared among biochemical pregnancy, early pregnancy loss, and live birth groups. The cutoff values of POD 12 and 14 hCG-ß levels and the degree of hCG-ß increase from POD 12 to 14 were determined for each pregnancy outcome. RESULTS: POD 12 and 14 hCG-ß levels stratified based on pregnancy outcomes were significantly different among the biochemical pregnancy, early pregnancy loss, and live birth in both fresh and frozen cycles. Serum hCG-ß levels of POD 12 and 14 and the fold increase of hCG-ß levels from POD 12 to 14 significantly predict pregnancy outcomes after fresh and frozen cycles. Among these, the cutoff value of POD 14 hCG-ß had the highest sensitivity and positive predictive value (PPV). In fresh cycles, the cutoff values of POD 12 and 14 serum hCG-ß levels for clinical pregnancies were 30.2 mIU/mL (sensitivity 81.3 %, specificity 79.6 %, and PPV 92.3 %) and 70.5 mIU/mL (sensitivity 88.4 %, specificity 85.2 %, and PPV 94.7 %). In pregnancies with POD 12 serum hCG-ß levels ≥30.2 mIU/mL, the cutoff level of increase of hCG-ß for clinical pregnancy was 2.56 (sensitivity 73.6 %, specificity 72.4 %, and PPV 97.8 %). Sequential application of cutoff values such as POD 12 hCG-ß and fold increase of hCG-ß improved predictability of pregnancy outcome as compared with that of POD 12 hCG-ß alone. The cutoff values of POD 12 and 14 serum hCG-ß levels for live birth were 40.5 mIU/mL (sensitivity 75.2 %, specificity 72.6 %, PPV 78.9 %) and 104.5 mIU/mL (sensitivity 80.3 %, specificity 74.1 %, PPV 80.8 %). In the frozen cycles, the cutoff values of POD 12 and 14 serum hCG-ß level for clinical pregnancy were 31.5 IU/L (sensitivity 80.4 %, specificity 71.1 % and PPV 90 %) and 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %). In pregnancies with POD 12 serum hCG-ß level ≥31.5 mIU/mL, the cutoff value for fold increase of hCG-ß was 2.38 for clinical pregnancy (sensitivity 81.6 %, specificity 71.4 % and PPV 87.9 %). The cutoff values of POD 12 and 14 for live birth were 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %) and 101.6 mIU/mL (sensitivity 79.6 %, specificity 71.1 %, PPV 78.4 %). Sequential application of cutoff values for POD 12 hCG-ß level and fold increase of hCG-ß significantly increased PPV for live birth but not clinical pregnancy in frozen cycles. CONCLUSIONS: Early prediction of pregnancy outcome by using POD 12 and 14 cutoff levels and sequential application of cutoff value of fold increase could provide appropriate reference to health care providers to initiate earlier management of high-risk pregnancies and precise follow-up of abnormal pregnancies.

Noroviruses as a Cause of Diarrhea in Immunocompromised Pediatric Hematopoietic Stem Cell and Solid Organ Transplant Recipients.

Case reports describe significant norovirus gastroenteritis morbidity in immunocompromised patients. We evaluated norovirus pathogenesis in prospectively enrolled solid organ (SOT) and hematopoietic stem cell transplant (HSCT) patients with diarrhea who presented to Texas Children's Hospital and submitted stool for enteric testing. Noroviruses were detected by real-time reverse transcription polymerase chain reaction. Clinical outcomes of norovirus diarrhea and non-norovirus diarrhea patients, matched by transplanted organ type, were compared. Norovirus infection was identified in 25 (22%) of 116 patients, more frequently than other enteropathogens. Fifty percent of norovirus patients experienced diarrhea lasting ≥14 days, with median duration of 12.5 days (range 1-324 days); 29% developed diarrhea recurrence. Fifty-five percent of norovirus patients were hospitalized for diarrhea, with 27% requiring intensive care unit (ICU) admission. One HSCT recipient developed pneumatosis intestinalis. Three HSCT patients expired ≤6 months of norovirus diarrhea onset. Compared to non-norovirus diarrhea patients, norovirus patients experienced significantly more frequent ICU admission (27% vs. 0%, p = 0.02), greater serum creatinine rise (median 0.3 vs. 0.2 mg/dL, p = 0.01), and more weight loss (median 1.6 vs. 0.6 kg, p < 0.01). Noroviruses are an important cause of diarrhea in pediatric transplant patients and are associated with significant clinical complications.

Presence of macronodules in thoracic sarcoidosis: prevalence and computed tomographic findings.

AIM: To assess the prevalence and radiological findings of macronodules in patients with thoracic sarcoidosis. MATERIALS AND METHODS: Data was collected regarding 226 patients with pathologically proven thoracic sarcoidosis. Among them, macronodules defined as well-defined nodules greater than 5 mm were found in 58 patients. The macronodules were evaluated by their number, size, margin, shape, lobar location, distance from the pleura, and temporal change. Patients were classified into two groups, patients with macronodules (n = 58) and without macronodules (n = 168). The level of serum angiotensin-converting enzyme (ACE), systemic involvement, and the maximum standardized uptake value (maxSUV) on (18)F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in both groups were then compared. RESULTS: A total of 216 macronodules were identified in 58 patients. The mean number of macronodules per patient was 3.3, and the mean size was 6.3 mm. Most of the macronodules were located in lower lobes (63.4%) and showed round-to-ovoid (95.8%) shape. The mean distance from the pleura was 5 mm. In 76% of the 63 nodules that were followed using CT scanning, any interval changes in size was also accompanied by the same change in mediastinal lymphadenopathy. On comparison of the two groups, the presence of lymphadenopathy, parenchymal involvement, and the maxSUV of thoracic lymphadenopathy were shown to be statistically different. CONCLUSION: Well-defined macronodules greater than 5 mm were not uncommonly seen in patients with thoracic sarcoidosis. The macronodules are usually located in the lower lobes near the pleura, and the interval changes in mediastinal lymphadenopathy may be associated with similar changes in the size of nodules.

Quality of functional haematopoietic stem/progenitor cells from cryopreserved human umbilical cord blood.

BACKGROUND AND OBJECTIVES: Transplantation of cryopreserved umbilical cord blood (UCB) can be used to treat a multitude of haematologic and immunological diseases. In this study, we examined the quality of UCB cryopreserved for 2 (group I), 4 (group II) and 6 (group III) years. METHODS: The following parameters and procedures were used to test individual units of cryopreserved UCB: the number of total nucleated cells (TNC), cell viability, CFU-GM assay, T-cell activation in vitro and haematopoietic stem cell engraftment in NOD/SCID mice in vivo. RESULTS: The TNC recovery rates for groups I, II and III were 106·2 ± 6·17%, 96·69 ± 6·39% and 100·38 ± 5·27%, respectively, and the mean percentages of viable cells after thawing were 86·88%, 86·38% and 87·43%. When TNC were plated at 5 × 10(3), the number of CFU-GM was 13·6 (group I), 13·8 (group II), 14·2 (group III) and 14·7 (fresh UCB). We confirmed that the huCD4(+) and huCD8(+) T cells within cryopreserved UCB are functionally responsive by assessment of activated huCD25(+) cells. Moreover, the percentage of huCD45(+) cells in the bone marrow was 4·32 ± 1·29% (group I), 4·48 ± 1·11% (group II), 4·40% ± 1·12% (group III) and 4·50% ± 0·66% (fresh UCB), and that in the peripheral blood was 14·69 ± 3·08% (group I), 15·24 ± 4·05% (group II), 15·74 ± 3·43% (group III) and 17·48 ± 3·74% (fresh UCB) in NOD/SCID mice infused with isolated huCD34(+) cells. CONCLUSION: These results indicated that cryopreserved UCB units efficiently retrieve in functionally competent form and are suitable for transplantation.

The impact of drug-resistant cytomegalovirus in pediatric allogeneic hematopoietic cell transplant recipients: a prospective monitoring of UL97 and UL54 gene mutations.

BACKGROUND: Cytomegalovirus (CMV) infection is a major cause of morbidity in allogeneic hematopoietic cell transplant (alloHCT) recipients. Little is known about the epidemiology of antiviral resistance in the pediatric population. We performed the prospective study to assess the impact of drug-resistant CMV infections in pediatric alloHCT recipients. METHODS: Pediatric alloHCT recipients who developed CMV infection were consecutively enrolled from May 2009 to April 2012. CMV polymerase chain reaction amplification and sequencing analysis for UL97 and UL54 genes were performed at enrollment and during follow-up. RESULTS: In total, 208 sequence data from viruses in 49 recipients were eligible for the final analysis. Resistant CMV infection caused by UL97 and UL54 mutations occurred in 4.1% (2/49) and 2.0% (1/49), respectively. Known UL97 mutations, M460V and C592G, were observed in each of 2 patients. One patient with the M460V UL97 mutation had an additional T700A UL54 mutation. Drug-resistant CMV attributable mortality was 2.0% (1/49). One or more known sequence variants (drug-sensitive) were observed in all 49 patients. Thirty-one (63.3%) and 28 patients (60.9%) already had known UL97 and UL54 sequence variants before antiviral therapy, respectively. CONCLUSION: This study provides comprehensive information on the epidemiology of both UL97 and UL54 variants and mutations in alloHCT recipients.

Clinical and histopathological study of Charcot-Marie-Tooth neuropathy with a novel S90W mutation in BSCL2.

The objective of the study was to investigate the disease-causing mutation in an autosomal dominant Charcot-Marie-Tooth disease type 2 family and examine the clinical and histopathological evaluation. We enrolled a family of Korean origin with axonal Charcot-Marie-Tooth disease neuropathy (FC305; 13 males, six females) and applied genome-wide linkage analysis. Whole exome sequencing was performed for two patients. In addition, sural nerve biopsies were obtained from two patients. Through whole exome sequencing, we identified an average of 20,336 coding variants from two patients. We also found evidence of linkage mapped to chromosome 11p11-11q13.3 (LOD score of 3.6). Among these variants in the linkage region, we detected a novel p.S90W mutation in the Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene, after filtering 31 Korean control exomes. Our p.S90W patients had frequent sensory disturbances, pyramidal tract signs, and predominant right thenar muscle atrophy in comparison with reported p.S90L patients. The phenotypic spectra were wide and demonstrated intrafamilial variability. Two patients with different clinical features underwent sural nerve biopsies; the myelinated fiber densities were increased slightly in both patients, which differed from two previous case reports of BSCL2 mutations (p.S90L and p.N88S). This report expands the variability of the clinical spectrum associated with the BSCL2 gene and describes the first family with the p.S90W mutation.

Effect of neovestitol-vestitol containing Brazilian red propolis on accumulation of biofilm in vitro and development of dental caries in vivo.

The present study examined the influences of the neovestitol-vestitol (NV) containing fraction isolated from Brazilian red propolis on the development of biofilm and expression of virulence factors by Streptococcus mutans using saliva-coated surfaces of hydroxyapatite. In addition, NV was tested in a rodent model of dental caries to assess its potential effectiveness in vivo. Topical applications of NV (800 µg ml(-1)) significantly impaired the accumulation of biofilms of S. mutans by largely disrupting the synthesis of glucosyltransferase-derived exopolysaccharides and the expression of genes associated with the adaptive stress response, such as copYAZ and sloA. Of even greater impact, NV was as effective as fluoride (positive control) in reducing the development of carious lesions in vivo. NV is a promising natural anti-biofilm agent that targets essential virulence traits in S. mutans, which are associated with the formation of cariogenic biofilm and the subsequent onset of dental caries disease.