Latent TB and depressive symptoms in household contacts of persons with active TB.

BACKGROUND: Depression is common among persons with TB and is associated with poor clinical outcomes. However, little is known about the relationship between latent TB infection (LTBI) and depression. We assessed the association between LTBI and depressive symptoms among household contacts (HHCs) of patients receiving TB treatment.METHODS: We enrolled 1,009 HHCs of 307 patients receiving TB treatment in Lima, Peru, during 2016-2018. At enrollment, HHC LTBI status was assessed using the interferon-gamma release assay (IGRA). Depressive symptoms were assessed at baseline and 12 months later using the Patient Health Questionnaire-9 (PHQ-9) with a cut-off of ≥5. We used logistic regression to estimate the odds ratio (OR) for PHQ-9 ≥5, comparing HHCs with and without baseline LTBI.RESULTS: Among 921 HHCs, 374 (41.0%) had LTBI at baseline, and 69 (12.4%) of 567 HHCs had PHQ-9 ≥5. Compared to HHCs without LTBI at enrollment, those with LTBI had almost two times the odds of PHQ-9 ≥5 at follow-up after controlling for potential confounders (adjusted OR 1.93, 95% CI 1.09-3.39); this association was driven by greater severities of depressive symptoms.CONCLUSION: HHCs with LTBI had increased odds of depressive symptoms 1 year later. This population may benefit from mental health screening and interventions integrated into TB programs.

Tissue eosinophilia and computed tomography features in paediatric chronic rhinosinusitis with nasal polyps requiring revision surgery.

BACKGROUND: Endoscopic sinus surgery (ESS) is an effective and safe treatment modality for medically recalcitrant chronic rhinosinusitis (CRS) in the paediatric population, especially in older children or those with nasal polyposis (CRSwNP). We aimed to elucidate the inflammatory pattern and clinical characteristics of CRSwNP related to revision surgery after ESS in a paediatric population. METHODS: We retrospectively enrolled 146 patients with bilateral CRSwNP. Twenty-two patients had recurrent nasal polyps that required revision surgery. The clinical characteristics, computed tomography (CT) features, tissue eosinophil count, and immunoactivity of signature cytokines in the two groups were analysed. RESULTS: Tissue eosinophil infiltration and immunoreactivity of eosinophilic cationic protein and IL-5 in the sinus mucosa were higher in patients that required revision surgery. The revision surgery group was significantly younger and had positive aeroallergen test results, higher total Lund-Mackay scores, and ethmoid/maxillary sinus ratio on CT images than those without revision surgery. A nomogram was developed to predict the probability of the requirement of revision surgery according to the logistic regression analysis results. CONCLUSIONS: We developed a nomogram model using clinical characteristics, tissue eosinophilia, and CT features for the preoperative identification of patients vulnerable to revision surgery in paediatric CRSwNP. This could help clinicians predict the probability of recurrence and perform intensive postoperative adjunct therapy and follow-up.

Sleep impairment in patients with empty nose syndrome.

BACKGROUND: Empty nose syndrome (ENS) is characterized by paradoxical nasal obstruction that usually occurs after turbinate surgery. Patients with ENS may also experience significant psychiatric symptoms and sleep dysfunction, which negatively affect the quality of life of affected subjects. This study aimed to evaluate sleep impairment and sleepiness in patients with ENS. METHODS: Patients with ENS and control participants were recruited prospectively. The Sino-Nasal Outcome Test-25 (SNOT-25), Empty Nose Syndrome 6-item Questionnaire (ENS6Q), Epworth Sleepiness Scale (EpSS), and modified sleep quality index (MSQI) were used to evaluate the participants before and after nasal surgery. RESULTS: Forty-eight patients with ENS and forty-eight age- and sex-matched control subjects were enrolled. The SNOT-25, ENS6Q, EpSS, and MSQI scores in the ENS group were all significantly higher than those in the control group before and after surgery. After surgery, ENS patients all exhibited significant improvements in SNOT-25, ENS6Q, EpSS, and MSQI scores. Regression analysis revealed that SNOT-25 score was a significant predictor of EpSS and MSQI in preoperative evaluations. ENS patients experiencing daytime sleepiness suffered from significantly more "dryness of nose" and "suffocation" than those not experiencing daytime sleepiness. CONCLUSIONS: Patients with ENS experienced significantly impaired sleep quality and sleepiness. Nasal reconstruction surgery improved the sleep quality of ENS patients. The severity of sleep dysfunction is associated with the severity of ENS symptoms. Recognizing individuals with significant sleep impairment and sleepiness and providing appropriate management are critical issues for ENS patients.

Olfaction after endoscopic surgery for sellar and parasellar disease: an updated systematic review and meta-analysis.

BACKGROUND: Whether endoscopic surgery for sellar/parasellar disease causes significant deficits in olfactory function remains unclear. We aimed to systematically review the olfactory outcomes in such settings based on the evidence up to date. METHODS: PubMed, EMBASE, and CENTRAL were searched through February 1, 2021. Included studies were limited to endoscopic surgery for sellar/parasellar disease with follow-up olfactory function measured by standardized olfactory testing methods or subjective assessment. The primary outcome was the change in olfactory function after surgery assessed by standardized olfactory testing methods. The secondary outcome was the change in subjective olfactory function. Random-effects model was used in obtaining combine effects. Study quality was assessed using the Newcastleâ€"Ottawa scale. Sensitivity analysis was carried out using the leave-one-out approach, and publication bias was assessed using Egger's test. RESULTS: The results show no significant difference in olfaction assessed by standardized olfactory testing methods at 1-3 months post-surgery (880 patients in 16 studies) or at 6-12 months post-surgery (1320 patients in 16 studies) compared to pre-surgery, whereas a significantly lower subjective olfaction at 3 months was observed. In addition, the lack of significant change in olfaction as assessed by standardized olfactory testing methods was observed regardless of whether patients were treated with or without the nasoseptal flap (NSF) harvesting. Heterogeneity and publication bias were observed, whereas sensitivity analysis showed the meta-analysis results are robust. CONCLUSION: The findings of this updated systematic review and meta-analysis support the conclusion that endoscopic surgery for sellar and parasellar pathology may pose no greater risk of olfactory dysfunction. In addition, the current evidence does not support there is an increased risk of diminished olfaction among patients treated with NSF during surgery.

A radiomics method based on MR FS-T2WI sequence for diagnosing of autosomal dominant polycystic kidney disease progression.

OBJECTIVE: We aimed to construct/validate a radiomics method based on MR FS-T2WI sequence for the evaluation of kidney function in patients with autosomal dominant polycystic kidney disease (ADPKD). PATIENTS AND METHODS: The clinical data and MRI images of 114 patients with ADPKD were retrospectively analyzed. With a glomerular filtration rate of 60 mL/min per 1.73 m2 as the cutoff value, patients were divided into two groups, where there were 59 patients with GFR ≥60 mL/min per 1.73 m2 (including CKD1 and CKD2 phase) and 55 patients with GFR <60 mL/min per 1.73 m2 (including CKD3 phase and higher). All patients underwent the 3.0T MR scan of the kidney. Then, the kidney were delineated layer by layer based on the FS-T2WI sequence to obtain the volume of interest (VOI) for radiomics features extraction. The optimal radiomics features were selected by least absolute shrinkage and selection operator (LASSO). Three kinds of data modality including the pure clinical data, the pure image data and the clinical-image fused data were utilized to establish three types of models (clinical, image and with their combination) separately by five machine learning classifiers: k-nearest-neighbors (KNN), support vector machine (SVM), logistic regression (LR), random forests (RF) and multi-layer perception (MLP). Receiver operating characteristic (ROC) curve, areas under the curve (AUC), sensitivity, specificity and precision were employed to evaluate the model's effectiveness to diagnosis the glomerular filtration rate of patients with ADPKD based on different models. Besides, Delong test was applied to compare ROCs between models. RESULTS: 960 radiomics features were extracted from each VOIs, and clinical information included the gender and age of each patient. After feature selection, 23 and 21 features based on pure image data and clinical-image fused data were independently used to construct models for the kidney function evaluation. The clinical-image fused model (AUC=0.89) has better performance than the pure image model (p=0.046) and pure clinical model (p<0.001). Clinical-image fused model based on LR classifier showed the best diagnostic efficiency, with AUC=0.89, sensitivity=0.8867 and specificity=0.7959. CONCLUSIONS: The MR FS-T2WI radiomics analysis based on clinical-image fused model is instrumental in evaluating and predicting the kidney function of patients with polycystic kidney disease.

The combination of soluble tumor necrosis factor receptor type 1 and fibroblast growth factor 21 exhibits better prediction of renal outcomes in patients with type 2 diabetes mellitus.

PURPOSE: Numerous biomarkers of diabetic kidney disease (DKD) are associated with renal prognosis but head-to-head comparisons are lacking. This study aimed to examine the association of soluble tumor necrosis factor receptor type 1 (sTNFR1), fibroblast growth factor 21 (FGF-21), endocan, N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and renal outcomes of patients with or without clinical signs of DKD. METHODS: A total of 312 patients were enrolled in a prospective observational study that excluded individuals with estimated glomerular filtration rates (eGFR) < 30 mL/min/1.73 m2. Composite renal outcomes included either a > 30% decline in eGFR and worsening albuminuria or both from consecutive tests of blood/urine during a 3.5-year follow-up period. RESULTS: Higher sTNFR1 and FGF-21, rather than endocan and NT-pro-BNP, levels were associated with renal outcomes but the significance was lost after adjusting for confounders. However, sTNFR1 levels ≥ 9.79 pg/dL or FGF-21 levels ≥ 1.40 pg/dL were associated with renal outcomes after adjusting for the confounders (hazard ration [HR] 2.76, 95% confidence interval [CI] 1.36-5.60, p = 0.005 for sTNFR1 level; HR 1.95, 95% CI 1.03-3.69, p = 0.03 for FGF-21 level). The combination of both levels exhibited even better association with renal outcomes than did either one alone (adjusted HR 4.45, 95% CI 1.86-10.65, p = 0.001). The results were consistent among patients with preserved renal function and normoalbuminuria. CONCLUSION: Both sTNFR1 and FGF-21 levels were associated with renal outcomes of in patients with type 2 diabetes, and the combination of the abovementioned markers exhibits better predictability.

Reduction of postural nasal resistance following oropharyngeal surgery in patients with moderate-severe obstructive sleep apnea.

BACKGROUND: Patients with obstructive sleep apnea (OSA) have elevated nasopharyngeal resistances due to increased turbulent airflow. The study aims to investigate the effect of oropharyngeal surgery on nasal resistance in patients with various severity levels of OSA. METHODOLOGY: Patients with greater or equal to 5 events hourly on the apnea-hypopnea index (AHI) were enrolled. Patients with retropalatal obstruction underwent uvulopalatopharyngoplasty, while patients with concurrent retrolingual obstruction under- went uvulopalatopharyngoplasty (UPPP) plus tongue base suspension. Before surgery and after surgery, subjective outcomes were assessed using a visual analog scale (VAS), and objective outcomes were assessed using overnight polysomnography and rhinomanometry. The limitation of the study was that UPPP instead of expansion sphincter pharyngoplasty was performed in this study. RESULTS: Sixty-two patients were enrolled, while 30 patients were diagnosed as mild OSA (group Mild) and 32 patients were mo- derate-severe OSA (group MS). The preoperative VAS of nasal obstruction in recumbency during sleep was significantly reduced after surgery in group MS. However, no significant differences between preoperative and postoperative VAS were found in group Mild. The postoperative anterior and posterior total nasal resistances (TNR) in sitting and supine positions were not significantly different from those before surgery in group. In contrast, the postoperative posterior TNR in supine position was 0.292±0.301(Pa/ cm3/s), compared with 0.425±0.343(Pa/cm3/s) preoperatively. CONCLUSIONS: Oropharyngeal surgery improves nasal obstruction during sleep and lowers the supine TNR measured in poste- rior rhinomanometry in patients with moderate-severe OSA. Oropharyngeal surgery is a possible treatment for postural nasal obstruction in patients with moderate-severe OSA.

Fluoroquinolone resistance in Haemophilus influenzae from nursing home residents in Taiwan: correlation of MICs and mutations in QRDRs.

AIMS: To study the association between number and positions of mutations with MICs of fluoroquinolone non-susceptible Haemophilus influenzae. METHODS AND RESULTS: More than 40% of 48 H. influenzae isolated from nursing home residents were not susceptible to fluoroquinolone. Amino acid changes in the quinolone resistance determining regions, and correlation with MICs and inhibition zone diameters were analysed. All isolates with reduced susceptibility to fluoroquinolones (MIC ≥0·125 µg ml-1 ) had at least one mutation in gyrA at position 84 and were resistant to nalidixic acid. Compared to isolates with reduced susceptibility, resistant isolates were associated with mutations in gyrA at positions 88 and 134, and in parC at position 88 (P < 0·001). Inhibition zone diameter for nalidixic acid disk ≥23 mm may detect susceptible isolates. CONCLUSIONS: Reduced susceptibility to fluoroquinolones was associated with mutations at position 84 in gyrA. A further increase in fluoroquinolone MIC was associated with mutations in gyrA at positions 88 and 134, and parC at position 88. SIGNIFICANCE AND IMPACT OF THE STUDY: Due to limited resistant H. influenzae strains, prior studies on association between positions of mutations and fluoroquinolone MICs were inconclusive. The comparison of mutations between isolates with susceptibility, reduced susceptibility and high resistance supported the importance of the present study.

Revisiting HERQL, the hernia-specific quality-of-life assessment instrument, to extend the clinical applicability for abdominal wall hernias.

PURPOSE: In the past we have developed and validated the hernia-specific quality of life assessment instrument, HERQL, for groin hernias. In current study we evaluated the conceptual structure and validated HERQL for abdominal wall hernias. METHODS: Subjective quality-of-life perceptions from abdominal wall hernia patients were assessed. Clinical responsiveness was evaluated comparing treatment naïve with follow-up hernia patients. Measurement invariance between groin and abdominal wall hernias was approached with structural equation modeling (SEM). Subgroup comparisons were conducted between primary ventral and incisional hernias, as well as the presence of co-morbidity, hernia incarceration, surgical complications, and recurrent abdominal wall hernias. RESULTS: A total of 775 HERQL assessments, including 167 from abdominal wall hernias, were successfully performed. Cronbach's alpha coefficients for the summative pain, worse symptoms for treatment-naïve patients, and improving summative pain scores across the pre-operative, immediately post-operative, and post-operative 3-month assessments indicating clinical responsiveness were observed and comparable between groin and abdominal wall hernias. Configural invariance was evidenced by that the same model held true for both types of hernias with multi-group SEM, while mean structure exploration showed that abdominal wall hernia patients reported less latent summative pain (- 0.535, p < 0.0001) but worse latent quality-of-life score (0.207, p < 0.0001). Patients with peri-operative complications suffered from worse pain during mild activities (2.7 versus 1.5, p = 0.01), and patients with recurrent hernias reported compromised global health/quality of life (2 versus 1.6, p = 0.001). CONCLUSIONS: The study successfully validated and extended the clinical applicability of HERQL across distinct types of hernias. Measurement invariance was ascertained and the same HERQL construct could be administered for both abdominal wall and groin hernias in Taiwan.

Correlation between kidney and peripheral nerve functions in Type 2 diabetes.

BACKGROUND: Although greater impairments in nerve functions parameters are most likely to occur with a lower kidney function, there is a paucity of information on the relationship between the kidney and peripheral nerve functions parameters in Type 2 diabetes. AIM: To address the impact of peripheral nerve functions in Type 2 diabetes patients in different stages of chronic kidney diseases (CKD). DESIGN: This prospective study enrolled 238 patients with Type 2 diabetes at a tertiary medical center. METHOD: We designed composite amplitude scores of nerve conductions (CAS) as a measure of severity of peripheral neuropathy (PN), and used estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) parameters to stage CKD in Type 2 diabetes patients. The intrapersonal mean, standard deviation and coefficient of variation of eGFR for 238 patients were obtained in the 3 years prior to the study. RESULTS: The patients who had lower eGFR and higher UACR were older, with longer diabetes duration, a greater percentage of retinopathy and PN and higher CAS. Multiple linear regression analysis revealed that diabetes duration and eGFR were independently associated with CAS, and a cut-off value of eGFR in the presence of PN was 65.3 ml/min/1.73 m2. CONCLUSION: We observed a close relationship between the severity of kidney and peripheral nerve function in patients with diabetes. If a patient's eGFR value is below 65.3 ml/min/1.73 m2 or the UACR value is above 98.6 mg/dl, caution is needed with the presence of PN even in diabetic patients who are asymptomatic.

What drives depression in empty nose syndrome? A Sinonasal Outcome Test-25 subdomain analysis.

BACKGROUND: Empty nose syndrome (ENS) is a debilitating disorder characterised by paradoxical nasal obstruction after excessive surgical excision of nasal tissues. ENS negatively impacts the quality of life (QOL) and psychological status of patients. This study aimed to determine the associations among disease-specific QOL impairments and the severity of anxiety and depression before and after surgery in ENS patients. METHODS: A total of 68 ENS patients were prospectively recruited and underwent submucosal Medpor implantation. QOL impairments and the severity of anxiety and depression were evaluated using the Sinonasal Outcome Test-25 (SNOT-25), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI) 1 day before and 6 months after surgery. RESULTS: The BDI-II and BAI scores were significantly associated with the total score and ear/facial symptoms, psychological dysfunction, sleep dysfunction, and empty nose symptoms domains of the SNOT-25. Surgery improved disease-specific and psychological symptoms. Post-operative changes in the BDI-II score were correlated with changes in the total score and sleep dysfunction and empty nose symptoms domains of the SNOT-25. A SNOT-25 total score of greater than 60, sleep dysfunction domain score of greater than 18, and empty nose symptoms domain score of greater than 14 were good predictors of moderate-to-severe depression. CONCLUSIONS: ENS symptoms are associated with psychological burden and could be good predictors of moderate-to-severe depression. Targeted symptom improvement could reduce the psychological burden.

The outcomes of statin therapy in patients with acute ischemic stroke in Taiwan: a nationwide epidemiologic study.

BACKGROUND: Acute stroke is the third leading cause of death in Taiwan. Although statin therapy is widely recommended for stroke prevention, little is known about the epidemiology of statin therapy after acute ischemic stroke (AIS) in Taiwan. To investigate the effects of statin therapy on recurrent stroke, intracranial hemorrhage (ICH), coronary artery disease (CAD), cost of hospitalization and mortality, we conducted a nationwide population-based epidemiologic study. METHODS: Cases of AIS were identified from the annual hospitalization discharge diagnoses of the National Health Insurance Research Database with the corresponding International Classification of Diseases, ninth revision codes from January 2001 to December 2010. We divided the AIS patients into three groups: non-statin, pre-stroke statin and post-stroke statin. RESULTS: A total of 422 671 patients with AIS (including 365 419 cases in the non-statin group, 22 716 cases in the pre-stroke statin group and 34 536 cases in the post-stroke statin group) were identified. When compared to the non-statin group, both statin groups had a lower recurrent stroke risk [pre-stroke statin: odds ratio (OR) = 0.84; 95% confidence interval (CI) = 0.82-0.87; P < 0.0001; post-stroke statin: OR = 0.89; 95% CI = 0.86-0.91; P < 0.0001], lower ICH risk (pre-statin: OR = 0.75; 95% CI = 0.69-0.82; P < 0.0001; post-stroke statin: OR = 0.75; 95% CI = 0.71-0.81; P < 0.0001), and a lower mortality rate (pre-stroke statin: OR = 0.56; 95% CI = 0.53-0.59; P < 0.0001; post-stroke statin: OR = 0.51; 95% CI = 0.48-0.53; P < 0.0001). In terms of CAD, only the post-statin group had a lower risk (OR = 0.81; 95% CI = 0.79-0.84; P < 0.0001) than the non-statin group. The post-statin group had the lowest 1-year medical costs after index discharge among the three groups. CONCLUSIONS: Statin therapy reduced the risks of recurrent stroke, CAD, ICH and the first year mortality in patients after AIS. Treatment with statin therapy after AIS is a cost-effective strategy in Taiwan.

Transplantation After Successful Downstaging by Multimodal Treatments of American Joint Committee on Cancer Stage IIIB Hepatocellular Carcinoma With Portal Vein Thrombi: A Case Report.

The effective treatment for hepatocellular carcinoma (HCC) with American Joint Committee on Cancer stage IIIB remains controversial and challenging because of the high recurrence rate after resection and low survival rate. The median survival of those with macroscopic portal vein tumor thrombus (PVTT) is short. We reported such a case which received liver transplantation (LT) after successful consecutive downstaging therapies. A 40-year-old man with alcohol related liver cirrhosis and repeated esophageal varices bleeding had HCC with tumor thrombi in right main portal vein and the second portal branch of segment VI (stage IIIB). The received percutaneous alcohol injection, radiofrequency ablation, 8 sessions of transcatheter hepatic arterial chemoembolization, radiotherapy, and target therapy with sorafenib. Computed tomography (CT) scan and magnetic resonance imaging after treatments showed no viable fragments in the tumor and revealed both the right main portal vein and V1 branch were patent. One month later, the patient received a deceased LT. The perioperative course was rather smooth. After discharge, the interval follow-up CT studies of the chest and liver and whole body bone scan showed no tumor recurrence or metastasis up to 20 months postoperation.

Exosomes derived from bone marrow mesenchymal stem cells improve osteoporosis through promoting osteoblast proliferation via MAPK pathway.

OBJECTIVE: Osteoporosis is the most common bone metabolic disease. Exosome exerts a crucial role in the development of multiple diseases. The aim of the study was to investigate the role of exosome derived from bone marrow mesenchymal stem cells (MSCs) in osteoporosis and its underlying mechanism. MATERIALS AND METHODS: MSCs were first isolated from rat bone marrow. After the surface antigen of MSCs was identified by flow cytometry, MSCs-derived exosomes (MSC-Exo) was extracted. The osteogenic and lipid differentiation abilities of BMSCs were determined by alizarin red staining and oil red staining, respectively. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the mRNA expressions of genes. Cell counting kit-8 (CCK-8) assay was used to detect the viability of hFOB 1.19 cells. Western blot was used to measure expressions of the specific surface markers in exosomes and the MAPK pathway-related proteins in hFOB 1.19 cells. Moreover, cell cycle of hFOB 1.19 was detected by flow cytometry. RESULTS: We observed a positive identification of surface antigens in MSCs, which presented good multidirectional differentiation ability. The isolated MSC-Exo exhibited typical morphology and particle size of exosomes, and the detection of specific surface labeled protein was positive under an electron microscope. After co-culture of MSC-Exo and osteoblast cell line hFOB 1.19, we found that MSC-Exo could promote the proliferation of hFOB 1.19 cells. Moreover, mRNA and protein expressions of GLUT3 in cells were increased, and the cell cycle was also promoted. The expressions of related proteins in the MAPK signaling pathway were found to be promoted. Rescue experiments demonstrated that MSC-Exo could promote the growth and cell cycle of hFOB 1.19, which were reversed by p-JNK knockdown. CONCLUSIONS: MSC-derived exosomes improve osteoporosis by promoting the proliferation of osteoblasts via MAPK pathway.

T2 Relaxometry MRI Predicts Cerebral Palsy in Preterm Infants.

BACKGROUND AND PURPOSE: T2-relaxometry brain MR imaging enables objective measurement of brain maturation based on the water-macromolecule ratio in white matter, but the outcome correlation is not established in preterm infants. Our study aimed to predict neurodevelopment with T2-relaxation values of brain MR imaging among preterm infants. MATERIALS AND METHODS: From January 1, 2012, to May 31, 2015, preterm infants who underwent both T2-relaxometry brain MR imaging and neurodevelopmental follow-up were retrospectively reviewed. T2-relaxation values were measured over the periventricular white matter, including sections through the frontal horns, midbody of the lateral ventricles, and centrum semiovale. Periventricular T2 relaxometry in relation to corrected age was analyzed with restricted cubic spline regression. Prediction of cerebral palsy was examined with the receiver operating characteristic curve. RESULTS: Thirty-eight preterm infants were enrolled for analysis. Twenty patients (52.6%) had neurodevelopmental abnormalities, including 8 (21%) with developmental delay without cerebral palsy and 12 (31.6%) with cerebral palsy. The periventricular T2-relaxation values in relation to age were curvilinear in preterm infants with normal development, linear in those with developmental delay without cerebral palsy, and flat in those with cerebral palsy. When MR imaging was performed at >1 month corrected age, cerebral palsy could be predicted with T2 relaxometry of the periventricular white matter on sections through the midbody of the lateral ventricles (area under the receiver operating characteristic curve = 0.738; cutoff value of >217.4 with 63.6% sensitivity and 100.0% specificity). CONCLUSIONS: T2-relaxometry brain MR imaging could provide prognostic prediction of neurodevelopmental outcomes in premature infants. Age-dependent and area-selective interpretation in preterm brains should be emphasized.

Neuropsychiatric symptoms in Alzheimer's disease: associations with caregiver burden and treatment outcomes.

BACKGROUND: Caregivers play a major role in providing care for patients with Alzheimer's disease (AD) and are themselves at higher risk of health comorbidities. AIM: To address the impact of neuropsychiatric symptoms of patients in different stages of AD on their caregivers' burden. DESIGN: This prospective study enrolled 260 AD patients with clinical dementia rating (CDR) of 0.5, 1 and 2 at a tertiary medical center. METHODS: All patients were tested using the mini-mental state examination (MMSE), the cognitive abilities screening instrument (CASI), the neuropsychiatric inventory (NPI) and the CDR scale. Data regarding therapeutic outcomes of anti-Alzheimer's drugs were also collected. Caregivers were tested using NPI. RESULTS: The mean follow-up interval was 25.0 ± 12.2 months, and two patients died during follow-up. NPI-burden was positively correlated with NPI-sum ( r = 0.822, P < 0.001) but negatively correlated with years of education ( r = -0.140, P = 0.024), CASI score ( r = -0.259, P < 0.001) and MMSE score ( r = -0.262, P <0.001). Multiple linear regression analysis showed that only NPI-sum was independently associated with mean NPI-burden. Both higher mean CASI and MMSE scores had better therapeutic outcome of anti-Alzheimer's drugs ( P = 0.001 and P = 0.005, respectively). CONCLUSIONS: The severity of neuropsychiatric symptoms in patients with AD was positively associated with caregiver's stress, and patients with better cognitive functions, under treatment with anti-Alzheimer's drugs, had better therapeutic outcomes. To reduce the impact of neuropsychiatric symptoms, it is crucial to detect dementia in its early phases and provide early intervention with anti-Alzheimer's drugs, which might help decrease the caregiver burden, thereby improving their quality of life.

Higher risk for thyroid diseases in physicians than in the general population: a Taiwan nationwide population-based secondary analysis study.

BACKGROUND: Physicians have high work stress, responsibility for night shifts and chances of exposure to medical radiation, which may increase the risk for thyroid diseases. AIM: We conducted this study to assess the risk for thyroid diseases in physicians, which remain unclear. DESIGN: We used a secondary analysis of the Taiwan National Health Insurance Research Database for this study. METHODS: After excluding thyroid diseases occurring before 2006 and residents, physicians and general population were identified by matching with age and sex in 2009 in a 1:2 ratio. The risk for thyroid diseases was compared between the physicians and general population and among physicians by tracing their medical histories between 2006 and 2012. RESULTS: In total, 28,649 physicians and 57,298 general population were identified. Physicians had a higher risk for overall thyroid diseases than the general population [odds ratio (OR): 1.27; 95% confidence interval (CI): 1.10-1.47], including individual thyroid disease: thyroid cancer (OR: 1.89; 95% CI: 1.22-2.95), hypothyroidism (OR: 1.64; 95% CI: 1.23-2.18) and thyroiditis (OR: 1.48; 95% CI: 1.00-2.19). CONCLUSIONS: We showed that physicians had a significantly higher risk for thyroid diseases than the general population. This reminds us to pay more attention to thyroid diseases in physicians. Further studies about the underlying mechanisms are warranted.

A longitudinal study of the association between the GNB3 C825T polymorphism and metabolic disturbance in bipolar II patients treated with valproate.

This longitudinal study aimed to investigate the associations between the polymorphisms of guanine nucleotide-binding protein subunit ß-3 (GNB3) C825T and metabolic disturbance in bipolar II disorder (BP-II) patients being treated with valproate (VPA). A 100 BP-II patients received a 12-week course of VPA treatment, and their body weight and metabolic indices were measured. At baseline, the GNB3 C825T polymorphisms were associated with the triglyceride level (P=0.032) in BP-II patients. During the VPA treatment course, the polymorphisms were not only associated with body mass index (BMI) and waist circumference (P-values=0.009 and 0.001, respectively), but also with total cholesterol, triglyceride, low-density lipoprotein and leptin levels (P-values=0.004, 0.002, 0.031 and 0.015, respectively). Patients with the TT genotype had a lower BMI, smaller waist circumference, and lower levels of lipids and leptin than those with the CT or CC genotypes undergoing the VPA treatment course.

Integrated Drug Expression Analysis for leukemia: an integrated in silico and in vivo approach to drug discovery.

Screening for drug compounds that exhibit therapeutic properties in the treatment of various diseases remains a challenge even after considerable advancements in biomedical research. Here, we introduce an integrated platform that exploits gene expression compendia generated from drug-treated cell lines and primary tumor tissue to identify therapeutic candidates that can be used in the treatment of acute myeloid leukemia (AML). Our framework combines these data with patient survival information to identify potential candidates that presumably have a significant impact on AML patient survival. We use a drug regulatory score (DRS) to measure the similarity between drug-induced cell line and patient tumor gene expression profiles, and show that these computed scores are highly correlated with in vitro metrics of pharmacological activity. Furthermore, we conducted several in vivo validation experiments of our potential candidate drugs in AML mouse models to demonstrate the accuracy of our in silico predictions.