Potential ultrasonic anatomical markers of obstructive sleep apnoea-hypopnoea syndrome.

AIM: To investigate the potential value of ultrasonography in evaluating the pathophysiology of obstructive sleep apnoea-hypopnoea syndrome (OSAHS) by assessing the correlation of critical ultrasonic anatomical characteristics of the oropharynx with the severity of OSAHS. MATERIALS AND METHODS: One hundred and seventy-one patients with suspected OSAHS underwent oropharyngeal sonographic examination and overnight polysomnography. Ultrasonic measurement was compared with the apnoea-hypopnoea index (AHI) and other parameters. An ordinal logistic regression model was used to identify potential ultrasonic anatomical markers for OSAHS. RESULTS: The AHI was significantly correlated with lingual height (r=0.40, p<0.01), maximal width of the tongue (r=0.35, p<0.01), and distance from the symphysis of the mandible to the hyoid bone (M-HB) (r=0.24, p<0.01). A positive relationship between Friedman tongue position (FTP) grades and lingual height (r=0.24, p<0.01), between FTP grades and maximal width of the tongue (r=0.23, p<0.01), and between FTP grades and width of tongue base (TB; r=0.17, p<0.05) was found. Multivariate models adjusted for sex, age, and body mass index (BMI) revealed that lingual height (95% confidence interval [CI]: 1.04-1.24; p=0.004) is independently associated with a higher risk for the severity of OSAHS. CONCLUSIONS: Ultrasonography may be a potential imaging method for providing additional useful information about the correlation between ultrasound findings and the severity of OSAHS. Lingual height could be considered an ultrasonic anatomical marker for determining the severity of OSAHS patients independent of age, sex, and BMI.

Vitiligo-like depigmentation in oncology patients treated with immunotherapies for nonmelanoma metastatic cancers.

Vitiligo-like depigmentation (VLD) is a characteristic cutaneous event described in patients with metastatic malignant melanoma receiving treatment with immune checkpoint inhibitors. We report the onset of VLD in three patients with other cancer types (cholangiocarcinoma, renal cell carcinoma and squamous cell carcinoma) following treatment with immunotherapy (combination pembrolizumab and nivolumab for the first, and pembrolizumab for the other two cancer types). Cases of VLD have not been reported previously in patients treated for any of these cancers, to our knowledge. Pembrolizumab and nivolumab are monoclonal antibodies targeting programmed cell death (PD)-1 receptors, while ipilimumab targets cytotoxic T-lymphocyte antigen-4. Our clinical finding challenges the current understanding of VLD as a malignant melanoma-specific immunotherapy-related adverse event.

The transmissibility estimation of influenza with early stage data of small-scale outbreaks in Changsha, China, 2005-2013.

Hundreds of small-scale influenza outbreaks in schools are reported in mainland China every year, leading to a heavy disease burden which seriously impacts the operation of affected schools. Knowing the transmissibility of each outbreak in the early stage has become a major concern for public health policy-makers and primary healthcare providers. In this study, we collected all the small-scale outbreaks in Changsha (a large city in south central China with ~7·04 million population) from January 2005 to December 2013. Four simple and popularly used models were employed to calculate the reproduction number (R) of these outbreaks. Given that the duration of a generation interval Tc = 2·7 and the standard deviation (s.d.) σ = 1·1, the mean R estimated by an epidemic model, normal distribution and delta distribution were 2·51 (s.d. = 0·73), 4·11 (s.d. = 2·20) and 5·88 (s.d. = 5·00), respectively. When Tc = 2·9 and σ = 1·4, the mean R estimated by the three models were 2·62 (s.d. = 0·78), 4·72 (s.d. = 2·82) and 6·86 (s.d. = 6·34), respectively. The mean R estimated by gamma distribution was 4·32 (s.d. = 2·47). We found that the values of R in small-scale outbreaks in schools were higher than in large-scale outbreaks in a neighbourhood, city or province. Normal distribution, delta distribution, and gamma distribution models seem to more easily overestimate the R of influenza outbreaks compared to the epidemic model.

Dynamic modelling of strategies for the control of acute haemorrhagic conjunctivitis outbreaks in schools in Changsha, China (2004-2015).

Outbreaks of acute haemorrhagic conjunctivitis (AHC) - a rapidly progressing and highly contagious infection - often occur in schools during summer and autumn. We used dynamic modelling to evaluate the efficacy of interventions to control AHC outbreaks in schools. A susceptible-infected-recovered (SIR) model was built to simulate AHC outbreaks in Chinese schools, with isolation or school closure added into the model. We used outbreak data from the period 2004-2015 in our models to estimate the effective reproduction number and assess the efficacy of interventions. The median effective reproduction number (uncontrolled) of AHC outbreaks was 7·00 (range 1·77-25·87). The median effective reproduction number (controlled) of AHC outbreaks was 0·16 (range 0·00-2·28). Intervention efficacy is affected by the timing of isolation; earlier isolation is associated with a lower morbidity peak and smaller total attack rate (TAR). School closures were not effective; TARs were almost 100% and did not change even when different school closure durations were adopted. Isolation and school closure as a combined intervention strategy was used to simulate outbreak control, but the efficacy was the same as isolation alone. An isolation programme could be an effective primary intervention during AHC outbreaks in schools. However, school closure is not recommended.

Two-dimensional self-assembly of diacetylenic acid derivatives and their light-induced polymerization on HOPG surfaces.

The bottom-up fabrication of molecular nanodevices will require precise (photo)-control over self-assembled interfacial structures. Here, the self-assembly and photopolymerization behaviors of six diacetylenic acid derivatives on highly oriented pyrolytic graphite (HOPG) surfaces are studied by using scanning tunneling microscope (STM). The van der Waals interaction among alkyl chains is the predominant driving force for determining the varied assembly structure. Diacetylenic acid derivatives with the diacetylene moiety directly connected to the carboxyl group (2,4-heptadecadiynoic acid (C17H26O2), 2,4-nonadecadiynoic acid (C19H30O2) and 2,4-heneicosadiynoic acid (C21H34O2)) assemble to form surface monolayers with lamella-like structures where the alkyl chains interdigitate. Moreover, diacetylenic acid derivatives with the diacetylene group located in the middle of the side chains and far from the carboxyl group (10,12-tricosadiynoic acid (C23H38O2), 10,12-pentacosadiynoic acid (C25H42O2) and 10,12-heptacosadiynoic acid (C27H46O2)) tend to assemble into paralleled structures with the alkyl chains adopting a tail-to-tail assembly mode. This work thus elucidates in detail the structure-function relationships for photo-modifiable self-assembled interfacial nanostructures based on diacetylenic acid.

Inverse association between hepatic stellate cell apoptosis and fibrosis in chronic hepatitis C virus infection.

Perisinusoidal hepatic stellate cells (HSC) are the principal fibrogenic cells in the liver. In animal models, HSC apoptosis is the predominant clearance mechanism of activated HSC, although data evaluating whether the same processes occur in humans are limited. We conducted a cross-sectional study to evaluate the association between HSC apoptosis and fibrosis stage in subjects with chronic hepatitis C virus (HCV) infection (n = 44) and HCV-negative controls with normal liver histology (n = 9). We used immunohistochemical techniques to identify activated (alpha-smooth muscle actin+), proliferative (Ki-67+) and apoptotic (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP nick end-labelling+) HSC in liver biopsy specimens from all subjects. The same pathologist enumerated positive cells per high-power field (HPF, x 200) in 20 periportal/lobular areas. HSC apoptosis was decreased in HCV-positive subjects compared with controls (median 0.4, range 0.0-3.1 vs 1.1, 0.2-3.5 cells/HPF, P = 0.02). Among HCV-positive subjects, HSC apoptosis was decreased in those with moderate to advanced fibrosis (P = 0.04) compared with those with mild fibrosis. By multivariate analysis, HSC apoptosis decreased by an average of 0.14 cells/HPF (95% confidence interval 0.01-0.28 cells/HPF) per increase in fibrosis stage (P = 0.04). While the number of activated and proliferative HSC was significantly increased in HCV-infected subjects compared with that in uninfected controls, the numbers of these cells did not differ between HCV-infected subjects with mild vs moderate/advanced fibrosis. In conclusion, the number of apoptotic HSC was significantly decreased in HCV-infected subjects with advanced fibrosis. In chronic HCV infection, inhibition of HSC apoptosis may be one mechanism by which fibrosis progresses.

Diagnostic laparoscopy improves staging of pancreatic cancer deemed locally unresectable by computed tomography.

BACKGROUND: Computed tomography (CT) is insensitive to small metastatic deposits in patients with pancreatic cancer. This study aimed to evaluate additional staging information obtained by laparoscopy in the subset of patients with locally extending pancreatic cancer but no evidence of distant disease using computed tomography. METHODS: Between April 2000 and February 2004, 74 patients with locally unresectable pancreatic cancer and no evidence of metastasis detected by high-quality pancreas protocol computed tomography underwent outpatient staging laparoscopy and peritoneal lavage cytology. RESULTS: Occult tumor was found during staging laparoscopy in 25 of the 74 patients (34%). The results were positive for peritoneal lavage cytology in 27% (20/74), for liver lesions in 16% (12/74), and for peritoneal implants in 7% (5/74) of the patients. Body and tail tumors were twice as likely as pancreatic head tumors to have unsuspected metastasis (53% vs 28%). CONCLUSIONS: Even the best computed tomography scan is not adequate for accurate staging of locally extended pancreatic cancer because occult distant disease will be found in half of the patients with left-sided disease and one-fourth of those with right-sided pancreatic cancer.

Human immunodeficiency virus disease-related neutropenia and the risk of hospitalization for bacterial infection.

BACKGROUND: Neutropenia is common in patients with human immunodeficiency virus (HIV) disease. However, the degree of risk for serious bacterial infections associated with various levels of neutropenia in patients with HIV disease is not well defined. METHODS: A retrospective analysis of databases containing demographic information for patients attending the San Francisco General Hospital HIV outpatient clinic, test results reported by the hospital's clinical laboratory, and the San Francisco General Hospital inpatient International Classification of Diseases, Ninth Revision (ICD-9) hospital discharge diagnosis codes from October 1, 1992, through November 30, 1993. Risk window time periods were defined, encompassing dates that consecutive absolute neutrophil counts (ANCs) occurred in a single ANC stratum. One risk window at the lowest ANC stratum for each patient was analyzed for hospitalizations with ICD-9 codes indicating bacterial infections. A 5% random sample of medical records was reviewed for end point validation. RESULTS: Codes from ICD-9 had 98% and 96% positive and negative predictive values, respectively, for meeting National Institute of Allergy and Infectious Diseases Division of AIDS [acquired immunodeficiency syndrome] clinical trial end point definitions for bacterial infections. Among 2047 evaluable patients, a significant increase in the incidence of hospitalization for serious bacterial infections was observed for those in the ANC strata of 500 to 749 X 10(6)/L and below. The 95% confidence intervals for the incidence of hospitalization associated with each ANC stratum below 500 X 10(6)/L did not overlap with that for any stratum of 750 X 10(6)/L or higher (22-117 vs 0.4-19 patient hospitalizations per 10000 days at risk, respectively). A multivariate analysis revealed only the severity and duration of neutropenia and black race to be significant end point predictors. CONCLUSION: Among 2047 patients with HIV disease, significantly higher risks of hospitalization for bacterial infections were associated with ANCs lower than 750 X 10(6)/L, especially for ANCs lower than 500 X 10(6)/L.

Cardiovascular activity of aromatic guanidine compounds.

A series of aromatic guanidines and several 1-phenylbiguanides was prepared and tested for cardiovascular (CV) effects in anesthetized dogs measuring heart rate, blood pressure, carotid artery blood flow, and myocardial force changes. The predominant CV effect at minimally effective dose was vasoconstriction unassociated with cardiac stimulation. The structure-activity relationships of the compounds were discussed comparing their structural similarities to the beta-phenylethylamines. The most potent members of the series were phenylguanidines substituted in the 3 and 4 positions on the aromatic nucleus with hydroxy or chloro groups. Preliminary mechanism studies indicated that the 3,4-dihydroxyphenylguanidines act at least partially by a direct alpha-adrenergic mechanism

A role for maternal physiological state in preserving auditory cortical plasticity for salient infant calls.

A growing interest in sensory system plasticity in the natural context of motherhood has created the need to investigate how intrinsic physiological state (e.g., hormonal, motivational, etc.) interacts with sensory experience to drive adaptive cortical plasticity for behaviorally relevant stimuli. Using a maternal mouse model of auditory cortical inhibitory plasticity for ultrasonic pup calls, we examined the role of pup care versus maternal physiological state in the long-term retention of this plasticity. Very recent experience caring for pups by Early Cocarers, which are virgins, produced stronger call-evoked lateral-band inhibition in auditory cortex. However, this plasticity was absent when measured post-weaning in Cocarers, even though it was present at the same time point in Mothers, whose pup experience occurred under a maternal physiological state. A two-alternative choice phonotaxis task revealed that the same animal groups (Early Cocarers and Mothers) demonstrating stronger lateral-band inhibition also preferred pup calls over a neutral sound, a correlation consistent with the hypothesis that this inhibitory mechanism may play a mnemonic role and is engaged to process sounds that are particularly salient. Our electrophysiological data hint at a possible mechanism through which the maternal physiological state may act to preserve the cortical plasticity: selectively suppressing detrimental spontaneous activity in neurons that are responsive to calls, an effect observed only in Mothers. Taken together, the maternal physiological state during the care of pups may help maintain the memory trace of behaviorally salient infant cues within core auditory cortex, potentially ensuring a more rapid induction of future maternal behavior.

Experience restores innate female preference for male ultrasonic vocalizations.

Mouse models are increasingly contributing to our understanding of the neural genetics of sensory processing and memory. For example, strain differences have helped elucidate basic mechanisms of age-related hearing loss and auditory fear conditioning. Assessing sensory differences arising in acoustic communication contexts is also important for understanding natural audition. While this topic has not been well studied, it is currently being addressed through auditory neuroethological studies in the CBA/CaJ strain, where insights will help lay a foundation for future neural genetic studies. Here, we focus on the responses of adult females to ultrasonic vocalizations of males. We tested a group of female mice in a place-preference paradigm before and after auditory and olfactory experience with a male. A control group was housed with other female cagemates between trials. All females showed an initial preference for male calls that rapidly decayed over the course of a trial. However, only females that had been pair-housed with a male during the inter-trial interval displayed a reinstated interest in male vocalizations, suggesting possible group differences in the assessment of the calls' behavioral relevance. These findings provide a timeframe during which auditory processing of male ultrasounds might be expected to show a difference depending on behavioral relevance, and also suggest an importance of social interactions in maintaining call recognition.

Arc/Arg3.1 mRNA expression reveals a subcellular trace of prior sound exposure in adult primary auditory cortex.

Acquiring the behavioral significance of sound has repeatedly been shown to correlate with long term changes in response properties of neurons in the adult primary auditory cortex. However, the molecular and cellular basis for such changes is still poorly understood. To address this, we have begun examining the auditory cortical expression of an activity-dependent effector immediate early gene (IEG) with documented roles in synaptic plasticity and memory consolidation in the hippocampus: Arc/Arg3.1. For initial characterization, we applied a repeated 10 min (24 h separation) sound exposure paradigm to determine the strength and consistency of sound-evoked Arc/Arg3.1 mRNA expression in the absence of explicit behavioral contingencies for the sound. We used 3D surface reconstruction methods in conjunction with fluorescent in situ hybridization (FISH) to assess the layer-specific subcellular compartmental expression of Arc/Arg3.1 mRNA. We unexpectedly found that both the intranuclear and cytoplasmic patterns of expression depended on the prior history of sound stimulation. Specifically, the percentage of neurons with expression only in the cytoplasm increased for repeated versus singular sound exposure, while intranuclear expression decreased. In contrast, the total cellular expression did not differ, consistent with prior IEG studies of primary auditory cortex. Our results were specific for cortical layers 3-6, as there was virtually no sound driven Arc/Arg3.1 mRNA in layers 1-2 immediately after stimulation. Our results are consistent with the kinetics and/or detectability of cortical subcellular Arc/Arg3.1 mRNA expression being altered by the initial exposure to the sound, suggesting exposure-induced modifications in the cytoplasmic Arc/Arg3.1 mRNA pool.