Relationship of chronic rhinosinusitis with Sjogren's syndrome, systemic lupus erythematosus, and ankylosing spondylitis.

BACKGROUND: Several studies have demonstrated the association between chronic rhinosinusitis (CRS) and autoimmune diseases. However, there are few long-term longitudinal studies on this relationship. Therefore, we investigated the association between CRS and the risk of a subgroup of autoimmune disease using a representative nationwide cohort sample. METHODOLOGY: We investigated the association between CRS and autoimmune diseases, including Sjogren's syndrome, systemic lupus erythematosus, and ankylosing spondylitis. A total of 15,130 CRS patients and 30,260 patients without CRS were enrolled after 1:2 propensity score matching. A Cox proportional hazards model was used to analyse the hazard ratio (HR) of CRS for autoimmune disease. RESULTS: The incidence of Sjogren's syndrome, systemic lupus erythematosus, and ankylosing spondylitis was 0.55, 0.10, and 0.48 per 1000 person-years, respectively. Among autoimmune diseases, the risk of Sjogren's syndrome in CRS patients was significantly increased to an adjusted HR (aHR) of 1.70, whereas we could not detect any significant risk of developing systemic lupus erythematosus or ankylosing spondylitis. In the subgroup analysis according to CRS phenotype, the adjusted HR of developing Sjogren's syndrome was greater in CRS patients without nasal polyps) than in CRS patients with nasal polyps. CONCLUSIONS: Our study suggests that CRS without nasal polyps is associated with an increased incidence of Sjogren's syndrome diagnosis compared to CRS without nasal polyps. Additionally, there was no association between CRS and systemic lupus erythematosus or ankylosing spondylitis, regardless of CRS phenotype.

Impact of antimicrobial stewardship interventions to improve antibiotic prescribing for hospital inpatients in Africa: a systematic review and meta-analysis.

Antimicrobial stewardship (AMS) interventions to improve antibiotic use are being implemented in Africa, but their impact is not fully known. The aim of this review was to estimate the effectiveness of interventions to improve antibiotic prescribing for hospital inpatients. Studies from PubMed, Embase, African Journals Online and Google Scholar were systematically searched from January 2010 to July 2022. Studies were included if they reported the impact of AMS interventions on outcomes of interest for hospital inpatients in Africa. Risk of bias was evaluated using the Cochrane Effective Practice and Organization of Care guidelines and the National Heart, Lung and Blood Institute tool. Findings were summarized in tables and meta-analyses were performed using random-effects models. A total of 28 studies were included, 89% being uncontrolled before and after studies. Most interventions employed were multi-faceted and found to be effective, evidenced by increased compliance, reduction in antibiotic utilization and cost, and slight reduction or no difference in mortality and length of hospital stay (LOS). Meta-analysis generated a relative risk of 0.82 [95% confidence interval (CI) 0.70-0.97] for mortality, and a standard mean difference of -0.30 (95% CI -0.41 to -0.19) for LOS. Generally, a decrease in resistance to most micro-organisms was observed. Despite an increase in the number of AMS studies conducted in Africa, the studies lack most of the quality design features for AMS studies. In conclusion, antimicrobial stewardship interventions are likely to be effective; however, efforts are still required to align the study design with the quality design features required for validity and to inform practice.

Acute carbon monoxide poisoning: MR imaging findings with clinical correlation.

PURPOSE: To assess the magnetic resonance imaging (MRI) findings, including diffusion-weighted imaging (DWI) in patients with acute carbon monoxide (CO) poisoning and correlate MRI findings with carboxyhemoglobin levels. MATERIALS AND METHODS: The MRI examinations and medical records of seven men with a mean age of 43±16.0years (SD) (range: 25-63 years) with acute CO poisoning were reviewed. MRI examinations were analyzed with respect to lesion location, imaging presentation on T1- and T2-weighted images, and diffusion characteristics on DWI and apparent diffusion coefficient (ADC) maps. We also evaluated clinical features and laboratory findings including the presenting symptoms and signs, carboxyhemoglobin level, and treatment. RESULTS: All seven patients presented with mental status change. The level of carboxyhemoglobin ranged between 8.3% and 34.8% (normal<1.5%). All seven patients (7/7, 100%) showed restricted diffusion of the lesions on ADC maps and bilateral involvement of globus pallidus. The mean ratios of ADC values was 0.63±0.15 (SD) (range: 0.46-0.92) on bilateral globi pallidi. Cerebral cortex, cerebral white matter, cerebellum, hippocampus, amygdala, splenium of corpus callosum, midbrain and insula were also involved. CONCLUSION: Bilateral globi pallidi with restricted diffusion may be a characteristic MRI feature in patients with acute CO poisoning. However, the relationship was not certain between the carboxyhemoglobin levels and the variety or severity of MRI findings.

One-Year Follow-up of the Changes in Renal Function After Liver Transplantation in Patients Without Chronic Kidney Disease.

BACKGROUND: Impaired renal function is a strong risk factor for morbidity and mortality after liver transplantation (LT). There is clearly a progressive deterioration in renal function after LT. The greatest loss of renal function occurs within the 1st year after LT. Several factors, including calcineurin inhibitors, are associated with decreased renal function. The aims of the present study were to identify changes in renal function before and after LT and to determine the risk factors related to decreased renal function after LT. METHODS: We reviewed medical records of 106 LT recipients without moderate to severe chronic kidney disease (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m(2)). We investigated eGFR changes from before to 1 year after LT with the use of propensity score matching. Statistical significance of differences between clinical parameters and 1-year eGFR changes was assessed with the use of univariate and multivariate analyses. RESULTS: Mean age was 49.5 ± 10.9 years, and 66% of the patients were male. Mean differences in 1-year eGFR and serum creatinine were -32.0 ± 29.2 mL/min/1.73 m(2) and 0.3 ± 0.3 mg/dL, respectively. Variables significantly associated with renal dysfunction 1 year after LT were old age, low pre-LT eGFR, low post-LT hemoglobin, and perioperative acute kidney injury. Multivariate analysis showed that pre-LT renal function was an independent risk factor for decreased renal function after LT. However, there was no significant correlation between 1-year eGFR change and serum tacrolimus level. CONCLUSIONS: Renal function significantly decreased the 1st year after LT, and baseline renal function was an independent risk factor for worsening renal function in LT recipients.

Ganciclovir and Foscarnet Therapy of Cytomegalovirus-Associated Meningoencephalitis in a Hemodialysis Patient With Liver Transplantation: Case Report.

Cytomegalovirus (CMV) infection in patients with liver transplantation (LT) remains a highly prevalent complication with a significant increase in morbidity and mortality. However, CMV-associated meningoencephalitis is rarely diagnosed, and treatment is very difficult. The aim of the present report is to review the experience of successful treatment with combined ganciclovir and foscarnet of CMV-associated meningoencephalitis refractory to ganciclovir alone in a hemodialysis (HD) patient after LT. A 54-year-old woman with end-stage renal disease on HD developed a seizure with loss of consciousness. She had received a liver transplant 4 months before. Blood CMV polymerase chain reaction was positive, and cerebrospinal fluid (CSF) analysis was compatible with viral meningitis. Brain magnetic resonance imaging (MRI) showed extensive dural thickening with enhancement and a round ring-like enhancement in the left centrum semiovale. She was diagnosed with CMV-associated meningoencephalitis. At that time, ganciclovir was started intravenously. After that, there were no improvements in mental state, CSF analysis, or brain MRI. Intravenous foscarnet at reduced dose was added to ganciclovir therapy. With combined ganciclovir and foscarnet, there was a slight improvement in her mental state and brain MRI.

Uremic Encephalopathy: MR Imaging Findings and Clinical Correlation.

BACKGROUND AND PURPOSE: Uremic encephalopathy is a metabolic disorder in patients with renal failure. The purpose of this study was to describe the MR imaging findings of uremic encephalopathy. MATERIALS AND METHODS: This study retrospectively reviewed MR imaging findings in 10 patients with clinically proved uremic encephalopathy between May 2005 and December 2014. Parameters evaluated were lesion location and appearance; MR signal intensity of the lesions on T1WI, T2WI, and T2 fluid-attenuated inversion recovery images; the presence or absence of restricted diffusion on diffusion-weighted images and apparent diffusion coefficient maps; and the reversibility of documented signal-intensity abnormalities on follow-up MR imaging. RESULTS: MR imaging abnormalities accompanying marked elevation of serum creatinine (range, 4.3-11.7 mg/dL) were evident in the 10 patients. Nine patients had a history of chronic renal failure with expansile bilateral basal ganglia lesions, and 1 patient with acute renal failure had reversible largely cortical lesions. Two of 6 patients with available arterial blood gas results had metabolic acidosis. All basal ganglia lesions showed expansile high signal intensity (lentiform fork sign) on T2WI. Varied levels of restricted diffusion and a range of signal intensities on DWI were evident and were not correlated with serum Cr levels. All cortical lesions demonstrated high signal intensity on T2WI. Four patients with follow-up MR imaging after hemodialysis showed complete resolution of all lesions. CONCLUSIONS: The lentiform fork sign is reliable in the early diagnosis of uremic encephalopathy, regardless of the presence of metabolic acidosis. Cytotoxic edema and/or vasogenic edema on DWI/ADC maps may be associated with uremic encephalopathy.

Intervention versus Aggressive Medical Therapy for Cognition in Severe Asymptomatic Carotid Stenosis.

BACKGROUND AND PURPOSE: Asymptomatic carotid stenosis of ≥70% increases the incidence of microembolism and/or chronic hypoperfusion, which may consequently impair neurocognition and brain connections. We sought controlled evidence for any cognitive benefit of aggressive medical therapy and combined carotid revascularization. MATERIALS AND METHODS: Patients with asymptomatic, unilateral, ≧70% stenosis of the extracranial ICA chose either aggressive medical therapy alone or in combination with carotid artery stent placement in this nonrandomized controlled study. They were examined with a battery of neuropsychological tests, structural MR imaging, DTI, and resting-state fMRI before and 3 months after treatment. RESULTS: Forty patients were included with 15 in the medical group and 25 in the stent-placement group. Among them, 13 and 21 in the respective groups completed neuroimaging follow-up. The baseline characteristics and the changes in cognitive performance during 3 months showed no differences between treatment groups. Nevertheless, compared with the medical group, the stent-placement group showed subjective dizziness alleviation (P = .045) and a small increase in fractional anisotropy at the splenium of the corpus callosum and the posterior periventricular white matter ipsilateral to carotid artery stent placement. Moreover, only the stent-placement group showed interval improvement in immediate memory and visuospatial performance, which was accompanied by an increase of functional connectivity at the insular cortex of the dorsal attention network and the medial prefrontal cortex of the default mode network. CONCLUSIONS: Both aggressive medical therapy alone and combined carotid revascularization in ≧70% asymptomatic carotid stenosis similarly preserved cognition during 3-month follow-up, though the latter had the potential for dizziness alleviation and cognitive and connectivity enhancement.

Poor physical fitness is independently associated with mild cognitive impairment in elderly Koreans.

The purpose of this study was to investigate the association between physical fitness and mild cognitive impairment (MCI) in elderly Koreans. This was a cross-sectional study that involved 134 men and 299 women aged 65 to 88 years. Six senior fitness tests were used as independent variables: 30 s chair stand for lower body strength, arm curl for upper body strength, chair-sit-and-reach for lower body flexibility, back scratch for upper body flexibility, 8-ft up-and-go for agility/dynamic balance, and 2-min walk for aerobic endurance. Global cognitive function was assessed using the Korean version of the Mini-Mental State Examination (MMSE). Potential covariates such as age, education levels, blood lipids, and insulin resistance (IR) markers were also assessed. Compared to individuals without MMSE-based MCI, individuals with MMSE-based MCI had poor physical fitness based on the senior fitness test (SFT). There were significant positive trends observed for education level (p=0.001) and MMSE score (p<0.001) across incremental levels of physical fitness in this study population. Individuals with moderate (OR=0.341, p=0.006) and high (OR=0.271, p=0.007) physical fitness based on a composite score of the SFT measures were less likely to have MMSE-based MCI than individuals with low physical fitness (referent, OR=1). The strength of the association between moderate (OR=0.377, p=0.038) or high (OR=0.282, p=0.050) physical fitness and MMSE-based MCI was somewhat attenuated but remained statistically significant even after adjustment for the measured compounding factors. We found that poor physical fitness was independently associated with MMSE-based MCI in elderly Koreans.

Quantifying midbrain serotonin transporter in depression: a preliminary study of diagnosis and naturalistic treatment outcome.

INTRODUCTION: Serotonin may play an important role in the pathology of major depressive disorder (MDD). However, the relationship between serotonin transporter (SERT) availability and the medical outcome of antidepressant treatment is uncertain. METHODS: In this naturalistic study, SERT availability (expressed as the specific uptake ratio, SUR) in the midbrain of 17 drug-free patients with MDD and 17 controls matched for age and gender was measured using SPECT with [(123)I]ADAM. The severity of MDD was measured by the Hamilton Depression Rating Scale before, and after 6 weeks of non-standardized antidepressant treatment. RESULTS: A total of 12 patients completed the study. The SUR of the patients with MDD was significantly lower than that of the healthy controls. The SUR of SERT was not found to have a linear relationship with the treatment outcome; however, supplemental analysis found a curvilinear relationship between treatment outcome and the SUR of SERT. DISCUSSION: The findings indicate that the SUR of SERT is lower in patients with MDD; however it did not predict treatment outcome in a linear fashion. Studies with larger sample sizes are required.

Correlation of plasma brain-derived neurotrophic factor and metabolic profiles in drug-naïve patients with bipolar II disorder after a twelve-week pharmacological intervention.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is thought to be involved in the pathophysiology of bipolar disorder (BD) and metabolic syndrome. We investigated the correlation between plasma BDNF with mood symptoms and metabolic indices in patients with BD-II over a 12-week pharmacological intervention. METHOD: Drug-naïve patients with BD-II (n=117) were recruited. Metabolic profiles [cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI)] and plasma BDNF wtrun "tblautotrun "tblsctrun "tbl_contere measured at baseline and 2, 8, and 12 weeks after beginning medication. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used. RESULTS: Seventy-six (65.0%) patients completed the intervention. Plasma BDNF levels were significantly associated with BMI (P=9.6E-5), low-density lipoprotein (P=0.034) and total (P=0.001) cholesterol, but not with the Hamilton Depression Rating Scale-17 and Young Mania Rating Scale scores over the 12-week treatment. CONCLUSION: We found initial evidence of a positive correlation between plasma BDNF levels and BMI, low-density lipoprotein and total cholesterol in drug-naïve patients with BD-II. The specific function of BDNF in regulating and maintaining peripheral metabolic health requires additional investigation.

The correlation between mid-brain serotonin transporter availability and intelligence quotient in healthy volunteers.

PURPOSE: This study was performed to investigate the association between the mid-brain serotonin transporter (SERT) availability and intelligence quotient (IQ). METHODS: One hundred and thirteen healthy participants, including 52 male and 61 female subjects, were recruited. We used SPECT with [(123)I]ADAM images to determine the SERT availability in the mid-brain, and measured the subjects' IQ using the WAIS-R. RESULTS: We found a significant positive correlation between the mid-brain SERT availability and the IQ of the participants. Even when controlling for age and sex, the significant association still existed. CONCLUSION: This result implied that the higher the SERT binding in the mid-brain, the better the IQ in healthy participants.

Effects of combination of rice straw with alfalfa pellet on milk productivity and chewing activity in lactating dairy cows.

An experiment was conducted to determine the effects of diets containing coarse-texture rice straw and small particle size alfalfa pellets as a part of total mixed ration (TMR) on milk productivity and chewing activity in lactating dairy cows. Sixteen multiparous Holstein dairy cows (670±21 kg body weight) in mid-lactation (194.1±13.6 days in milk) were randomly assigned to TMR containing 50% of timothy hay (TH) or TMR containing 20% of rice straw and 30% of alfalfa pellet mixture (RSAP). Geometric mean lengths of TH and RSAP were found to be 5.8 and 3.6, respectively. Dry matter intake, milk yield and milk composition were measured. Moreover, eating and ruminating times were recorded continuously using infrared digital camcorders. Milk yield and milk composition were not detected to have significant differences between TH and RSAP. Dry matter intake (DMI) did not significantly differ for cows fed with TH or RSAP. Although particle size of TH was larger than RSAP, eating, ruminating and total chewing time (min/d or min/kg of DMI) on TH and RSAP were similar. Taken together, our results suggest that using a proper amount of coarse-texture rice straw with high value nutritive alfalfa pellets may stimulate chewing activity in dairy cows without decreasing milk yield and composition even though the quantity of rice straw was 40% of TH.

Ahnak functions as a tumor suppressor via modulation of TGFß/Smad signaling pathway.

We provide detailed mechanisms of Ahnak-mediated potentiation of transforming growth factor ß (TGFß) signaling, which leads to a negative regulation of cell growth. We show that Smad3 interacts with Ahnak through MH2 domain and that Ahnak stimulates Smad3 localization into nucleus leading to potentiating TGFß-induced transcriptional activity of R-Smad. Moreover, overexpression of Ahnak resulted in growth retardation and cell cycle arrest through downregulation of c-Myc and cyclin D1/D2. We describe results from analyses of Ahnak(-/-) mouse model expressing middle T antigen in a mammary gland-specific manner (MMTV(Tg/+)Ahnak(-/-)), which showed significantly progressed hyperplasia of mammary glands compared with MMTV(Tg/+)Ahnak(+/+). Finally, we screened multiple human breast cancer tissues and showed that the expression of Ahnak in cancer tissues is lower than that in control tissues by 50%. Taken together, these data indicate that Ahnak mediates a negative regulation of cell growth and acts as novel tumor suppressor through potentiation of TGFß signaling.

Lower availability of midbrain serotonin transporter between healthy subjects with and without a family history of major depressive disorder - a preliminary two-ligand SPECT study.

PURPOSE: Serotonin transporter (SERT) and dopamine transporter (DAT) levels differ in patients with major depressive disorder (MDD) who are in a depressed state in comparison with healthy controls. In addition, a family history of depression is a potent risk factor for developing depression, and inherited vulnerability to serotonergic and dopaminergic dysfunction is suspected in this. The aim of this study was to examine the availabilities of midbrain SERT and striatal DAT in healthy subjects with and without a first-degree family history of MDD. METHODS: Eight healthy subjects with first-degree relatives with MDD and 16 sex- and age-matched healthy controls were recruited. The availabilities of SERT and DAT were approximated using SPECT, employing [¹²³I] 2-((2-((dimethylamino) methyl) phenyl)thio)-5-iodophenylamine (ADAM) and [(99m)Tc] TRODAT-1 as the ligands, respectively. There are missing data for one participant with a first-degree family history of MDD from the ADAM study, due to a lack of the radio-ligand at the time of experiment. RESULTS: SERT availability in the midbrain was significantly lower in subjects with a first-degree family history of MDD than in healthy subjects. However, DAT availability was no different between two groups. CONCLUSIONS: The results with regard to the midbrain SERT level suggest the heritability of MDD.

P300 waveform and dopamine transporter availability: a controlled EEG and SPECT study in medication-naive patients with schizophrenia and a meta-analysis.

BACKGROUND: Reduced P300 event-related potential (ERP) amplitude and latency prolongation have been reported in patients with schizophrenia compared to healthy controls. However, the influence of antipsychotics (and dopamine) on ERP measures are poorly understood and medication confounding remains a possibility. METHOD: We explored ERP differences between 36 drug-naive patients with schizophrenia and 138 healthy controls and examined whether P300 performance was related to dopamine transporter (DAT) availability, both without the confounding effects of medication. We also conducted a random effects meta-analysis of the available literature, synthesizing the results of three comparable published articles and our local study. RESULTS: No overall significant difference was found in mean P300 ERP between patients and controls in latency or in amplitude. There was a significant gender effect, with females showing greater P300 amplitude than males. A difference between patients and controls in P300 latency was evident with ageing, with latency increasing faster in patients. No effect of DAT availability on P300 latency or amplitude was detected. The meta-analysis computed the latency pooled standardized effect size (PSES; Cohen's d) of -0.13 and the amplitude PSES (Cohen's d) of 0.48, with patients showing a significant reduction in amplitude. CONCLUSIONS: Our findings suggest the P300 ERP is not altered in the early stages of schizophrenia before medication is introduced, and the DAT availability does not influence the P300 ERP amplitude or latency. P300 ERP amplitude reduction could be an indicator of the progression of illness and chronicity.

Role of DRD2 and ALDH2 genes in bipolar II disorder with and without comorbid anxiety disorder.

The presence of comorbid anxiety disorders (AD) and bipolar II disorders (BP-II) compounds disability complicates treatment, worsens prognosis, and has been understudied. The genes involved in metabolizing dopamine and encoding dopamine receptors, such as aldehyde dehydrogenase 2 (ALDH2) and dopamine D2 receptor (DRD2) genes, may be important to the pathogenesis of BP-II comorbid with AD. We aimed to clarify ALDH2 and DRD2 genes for predisposition to BP-II comorbid with and without AD. The sample consisted of 335 subjects BP-II without AD, 127 subjects BP-II with AD and 348 healthy subjects as normal control. The genotypes of the ALDH2 and DRD2 Taq-IA polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. Logistic regression analysis showed a statistically significant association between DRD2 Taq-I A1/A2 genotype and BP-II with AD (OR=2.231, P=0.021). Moreover, a significant interaction of the DRD2 Taq-I A1/A1 and the ALDH2*1*1 genotypes in BP-II without AD was revealed (OR=5.623, P=0.001) compared with normal control. Our findings support the hypothesis that a unique genetic distinction between BP-II with and without AD, and suggest a novel association between DRD2 Taq-I A1/A2 genotype and BP-II with AD. Our study also provides further evidence that the ALDH2 and DRD2 genes interact in BP-II, particularly BP-II without AD.

Efficacy of the active middle-ear implant in patients with sensorineural hearing loss.

INTRODUCTION: This systematic review aims to advise on the effectiveness of the active middle-ear implant in patients with sensorineural hearing loss, compared with external hearing aids. METHODS: A systematic search of several electronic databases, including PubMed and Embase, was used to identify relevant studies for inclusion. RESULTS: Fourteen comparative studies were included. Nine studies reported on the primary outcome of functional gain: one found that the middle-ear implant was significantly better than external hearing aids (p < 0.001), while another found that external hearing aids were generally significantly better than middle-ear implants (p < 0.05). Six of the seven remaining studies found that middle-ear implants were better than external hearing aids, although generally no clinically significant difference (i.e. ≥ 10 dB) was seen. CONCLUSION: Generally, the active middle-ear implant appears to be as effective as the external hearing aid in improving hearing outcomes in patients with sensorineural hearing loss.

Peripheral blood gene expression signature differentiates children with autism from unaffected siblings.

Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders with high heritability, yet a majority of genetic contribution to pathophysiology is not known. Siblings of individuals with ASD are at increased risk for ASD and autistic traits, but the genetic contribution for simplex families is estimated to be less when compared to multiplex families. To explore the genomic (dis-) similarity between proband and unaffected sibling in simplex families, we used genome-wide gene expression profiles of blood from 20 proband-unaffected sibling pairs and 18 unrelated control individuals. The global gene expression profiles of unaffected siblings were more similar to those from probands as they shared genetic and environmental background. A total of 189 genes were significantly differentially expressed between proband-sib pairs (nominal p < 0.01) after controlling for age, sex, and family effects. Probands and siblings were distinguished into two groups by cluster analysis with these genes. Overall, unaffected siblings were equally distant from the centroid of probands and from that of unrelated controls with the differentially expressed genes. Interestingly, five of 20 siblings had gene expression profiles that were more similar to unrelated controls than to their matched probands. In summary, we found a set of genes that distinguished probands from the unaffected siblings, and a subgroup of unaffected siblings who were more similar to probands. The pathways that characterized probands compared to siblings using peripheral blood gene expression profiles were the up-regulation of ribosomal, spliceosomal, and mitochondrial pathways, and the down-regulation of neuroreceptor-ligand, immune response and calcium signaling pathways. Further integrative study with structural genetic variations such as de novo mutations, rare variants, and copy number variations would clarify whether these transcriptomic changes are structural or environmental in origin.