[Advances in clinical studies of chronic cough].

Chronic cough is a common complaint in respiratory specialist clinics, with a significant impact on cough-specific quality of life and psychophysiological health. The diagnosis, treatment and management of chronic cough remains a major challenge. We summarized a series of recent advances from clinical studies in the epidemiology, diagnosis and management of chronic cough over the past year.

Revision adenoidectomy in children: a meta-analysis.

BACKGROUND: To estimate the rate of revision surgery after previous adenoidectomy in children and to compare the rate of revision adenoidectomy in children with different conditions and by using different surgical techniques. METHODOLOGY: The study protocol was registered on PROSPERO (CRD42018107877). Two authors independently searched databases, specifically PubMed, MEDLINE, EMBASE, and the Cochrane Review database. The keywords used were "adenoids","adenoidectomy","reoperation","revision"and "regrowth". The revision rate was pooled using a random-effect model. Subgroup analyses were conducted for children based on different settings, countries, risks of bias, and surgical techniques. RESULTS: A total 16 studies with 95 727 children were analyzed (mean age: 4.69 (1.62) years; 60% boys; sample size: 5983 patients). Five studies had a low risk of bias, 10 studies had a moderate risk of bias, and one study had a high risk of bias. The rate of revision adenoidectomy was 1.9%. Ages at initial surgery and follow-up were not significantly associated with revision surgeries. The revision rate was not significantly different in children receiving surgeries in different settings (single center vs multicenter vs population-based, country (non-United States vs United States, and risk of bias. Moreover, surgical techniques, such as curettage, suction cautery, microdebridement, and coblation did not significantly affect revision rates in children who received adenoidectomy. CONCLUSIONS: Revision surgery was undertaken with a frequency of 1.9% in children who underwent adenoidectomy. A lack of strong evidence exists to correlate surgical techniques with revision rate in pediatric adenoidectomy.

Clinical and genetic features of patients with facial-sparing facioscapulohumeral muscular dystrophy.

BACKGROUND AND PURPOSE: Facial-sparing scapular myopathy (SHD) is the most common atypical form of facioscapulohumeral muscular dystrophy (FSHD), clinically defined as without apparent facial muscle weakness on neurological examination. The clinical profiles and genetic features of SHD are limited. METHODS: A cohort of 21 Chinese patients with SHD were confirmed by molecular genetic analysis based on pulsed-field gel electrophoresis. The clinical assessments and methylation analysis were noted. RESULTS: The patients had FSHD-related EcoRI fragments with 4qA haplotype ranging from 18 kb to 33 kb (mean 26.3 ± 4.6 kb). The mean onset age was 25.52 ± 8.3 years. Over half of the patients had scapular winging and asymmetry weakness consistent with FSHD, without facial symptoms during their visit. Their facial electromyogram results were almost normal or mild myogenic damage, as well as the myopathology and serum creatine kinase. A conflict was unexpectedly found in intergenerational DR1 methylation analysis. CONCLUSION: Facial-sparing scapular myopathy is characterized as mild myopathic symptoms and chronic progression of weakness. The diagnosis should be accurately confirmed through FSHD-sized fragment detection and 4qA/B variant determination. Although the next generations of SHD had more severe muscular symptoms, local hypomethylation within D4Z4 was not found as a modifier for clinical heterogeneity.

Polysomnographic findings after adenotonsillectomy for obstructive sleep apnoea in obese and non-obese children: a systematic review and meta-analysis.

BACKGROUND: Use of polysomnography (PSG) is the gold standard of diagnosis and measurement of treatment effectiveness for paediatric obstructive sleep apnoea (OSA). Although adenotonsillectomy (T&A) is effective in diminishing the apnoea-hypopnoea index (AHI), a meta-analysis of postoperative changes for all other PSG parameters and outcome comparisons between obese and non-obese children following T&A have never been conducted. OBJECTIVE OF REVIEW: To comprehensively review polysomnographic findings after surgery for obese and non-obese children with OSA. SEARCH STRATEGY: Study protocol was registered on PROSPERO (CRD42013004737). Two authors independently searched databases including PubMed, MEDLINE, EMBASE and Cochrane Review from January 1997 to July 2014. The keywords used included the following: sleep apnea, OSA, sleep apnea syndromes, tonsillectomy, adenoidectomy, infant, child, adolescent, and Humans. EVALUATION METHOD: A comprehensive systematic review and meta-analysis for literature for OSA children treated by T&A with polysomnography data. Random-effects model was applied to determine postoperative sleep parameter changes and the surgical success rate between obese and non-obese groups. The quality of studies was assessed using the Newcastle-Ottawa Scale. RESULTS: In total, 51 studies with 3413 subjects were enrolled. After surgery, sleep architecture was altered by a significant decrease in sleep stage 1, and an increase in slow-wave sleep and the rapid eye movement stage, and enhanced sleep efficiency. The mean difference between pre- and postoperative was a significant reduction of 12.4 event/h in AHI, along with a reduction of obstructive index, hypopnoea index, central index and arousal index. Mean and minimum oxygen saturation increased significantly after surgery. The overall success rate was 51% for postoperative AHI <1 (obese versus non-obese versus combined, 34% versus 49% versus 56%), and 81% for AHI <5 (obese versus non-obese versus combined, 61% versus 87% versus 84%). Meta-regression analyses demonstrate that postoperative AHI was positively correlated with AHI and body mass index z score before surgery. CONCLUSIONS: Meta-analysis of current literature shows T&A offers prominent improvement in a variety of sleep parameters. Improvements in non-obese children exceeded those for obese children. Postoperative residual OSA remained in roughly half of the children, especially those with severe disease and obesity, making additional treatment strategies and/or long-term follow-up highly desirable.

Randomized clinical trial of single-incision laparoscopic cholecystectomy versus minilaparoscopic cholecystectomy.

BACKGROUND: Transumbilical single-incision laparoscopic cholecystectomy (SILC) and minilaparoscopic cholecystectomy (MLC) are both increasingly being used to treat symptomatic gallstones. The present study compared SILC and MLC with respect to outcome in a prospective randomized trial. METHODS: Seventy patients with symptomatic cholelithiasis were randomized to SILC or MLC (35 in each group). The primary outcome measure was postoperative pain. Secondary outcomes were duration of operation, complications, postoperative analgesic requirements, length of hospital stay, cosmetic result, wound length and time to return to work. RESULTS: Surgical complications, postoperative pain scores, analgesic requirements and time to return to work were similar for both procedures. Statistically significant advantages of SILC were a shorter hospital stay, shorter total wound length and better cosmetic appearance. Duration of operation was significantly shorter for MLC. CONCLUSION: SILC is superior to MLC in terms of cosmetic outcome, but not in postoperative pain and requirement for analgesics.

Ultrastructure, steroidogenic potential, and energy metabolism of the Snell adrenocortical carcinoma 494. A comparison with normal adrenocortical tissue.

Electron microscope studies were carried out with the adrenocortical carcinoma 494 and normal adrenal cortex tissue. The mitochondria of the tumor cells showed marked differences when compared with mitochondria from fasciculata cells of the normal adrenal cortex. These differences were primarily related to mitochondrial number and crista structure. Corticosterone production in isolated tumor cells was extremely low and neither ACTH nor dibutyryl cyclic AMP had any stimulatory effect. Normal adrenal cells showed at least a tenfold increase under identical conditions. In the presence of corticosteroid precursors the amount of corticosterone produced by the tumor cells was much less than that produced by normal cells. The results indicate a reduced capacity for 11beta-hydroxylation in the tumor mitochondria and a possible reduced capacity for biosynthetic steps before the 11beta-hydroxylation reaction. Glycolysis in isolated tumor cells was also lower than in normal cells. Isolated tumor mitochondria oxidized succinate normally with a good degree of coupling with phosphorylation. However, unlike normal adrenal mitochondria, the tumor mitochondria showed little or no oxygen uptake with other Krebs cycle substrates. These data suggest that the tumor mitochondria may be lacking in the flavoprotein dehydrogenases responsible for the oxidation of NADH and NADPH, although other components of the respiratory chain may be intact.

Mice that lack thrombospondin 2 display connective tissue abnormalities that are associated with disordered collagen fibrillogenesis, an increased vascular density, and a bleeding diathesis.

Thrombospondin (TSP) 2, and its close relative TSP1, are extracellular proteins whose functions are complex, poorly understood, and controversial. In an attempt to determine the function of TSP2, we disrupted the Thbs2 gene by homologous recombination in embryonic stem cells, and generated TSP2-null mice by blastocyst injection and appropriate breeding of mutant animals. Thbs2-/- mice were produced with the expected Mendelian frequency, appeared overtly normal, and were fertile. However, on closer examination, these mice displayed a wide variety of abnormalities. Collagen fiber patterns in skin were disordered, and abnormally large fibrils with irregular contours were observed by electron microscopy in both skin and tendon. As a functional correlate of these findings, the skin was fragile and had reduced tensile strength, and the tail was unusually flexible. Mutant skin fibroblasts were defective in attachment to a substratum. An increase in total density and in cortical thickness of long bones was documented by histology and quantitative computer tomography. Mutant mice also manifested an abnormal bleeding time, and histologic surveys of mouse tissues, stained with an antibody to von Willebrand factor, showed a significant increase in blood vessels. The basis for the unusual phenotype of the TSP2-null mouse could derive from the structural role that TSP2 might play in collagen fibrillogenesis in skin and tendon. However, it seems likely that some of the diverse manifestations of this genetic disorder result from the ability of TSP2 to modulate the cell surface properties of mesenchymal cells, and thus, to affect cell functions such as adhesion and migration.

Group A streptococcal infection caused by emm1 strains among children in southern Taiwan.

The aim of this study was to characterize the molecular epidemiology of invasive and non-invasive group A streptococcus (GAS) infections in children from 1997 through 2004 in southern Taiwan. A collection of 32 invasive and 150 non-invasive isolates were recruited for analysis. emm1 (34.4%) and emm12 (40.0%) predominated in the invasive and non-invasive isolates, respectively. The peak incidence of invasive GAS infection (IGASI) occurred between 2002 and 2003. emm4 and emm12 were the major types among clinical isolates before 2001, and was replaced by emm1 during 2002-2003. All emm1 isolates were clonal relatedness. The declined prevalence of erythromycin resistance occurred in the major shift of the endemic isolates to emm1 strains during 2002-2003 in the community.

Genomics of unrelated-donor hematopoietic cell transplantation.

Unrelated-donor hematopoietic cell transplantation is a proven curative modality for hematologic malignancies. The success of unrelated-donor transplantation has been achieved through a better understanding of the immunobiology of the HLA system and through more precise and comprehensive matching of donors and recipients. The extensive polymorphism of HLA genes confers important biological implications affecting engraftment, graft-versus-host disease and overall survival. Although more-complete HLA identity of the donor and recipient is associated with optimal transplant outcome, new information suggests that not every HLA disparity is functionally relevant. Future advances in unrelated-donor transplantation must include the identification of tolerable HLA mismatches, so that more patients may benefit from this therapeutic modality. Furthermore, the role of cytokine-gene polymorphisms and minor histocompatibility genes in transplant outcome requires investigation. Delineation of the function of these markers as transplantation determinants may provide alternative means for optimizing the results of hematopoietic cell transplantation.

Improved treatment results for childhood acute myeloid leukemia in Taiwan.

To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/- 9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.

Crystal growth of Dirac semimetal ZrSiS with high magnetoresistance and mobility.

High quality single crystal ZrSiS as a theoretically predicted Dirac semimetal has been grown successfully using a vapor phase transport method. The single crystals of tetragonal structure are easy to cleave into perfect square-shaped pieces due to the van der Waals bonding between the sulfur atoms of the quintuple layers. Physical property measurement results including resistivity, Hall coefficient (RH), and specific heat are reported. The transport and thermodynamic properties suggest a Fermi liquid behavior with two Fermi pockets at low temperatures. At T = 3 K and magnetic field of Hǁc up to 9 Tesla, large magneto-resistance up to 8500% and 7200% for Iǁ(100) and Iǁ(110) were found. Shubnikov de Haas (SdH) oscillations were identified from the resistivity data, revealing the existence of two Fermi pockets at the Fermi level via the fast Fourier transform (FFT) analysis. The Hall coefficient (RH) showed hole-dominated carriers with a high mobility of 3.05 × 104 cm2 V-1 s-1 at 3 K. ZrSiS has been confirmed to be a Dirac semimetal by the Dirac cone mapping near the X-point via angle resolved photoemission spectroscopy (ARPES) with a Dirac nodal line near the Fermi level identified using scanning tunneling spectroscopy (STS).

Heat shock protein 72 overexpression protects against hyperthermia, circulatory shock, and cerebral ischemia during heatstroke.

This study extends our earlier studies in rats by applying our heatstroke model to a new species. Additionally, transgenic mice are used to examine the role of heat shock protein (HSP) 72 in experimental heatstroke. Transgenic mice that were heterozygous for a porcine HSP70i gene ([+]HSP72), transgene-negative littermate controls ([-]HSP72), and normal Institute of Cancer Research strain mice (ICR) under pentobarbital sodium anesthesia were subjected to heat stress (40 degrees C) to induce heatstroke. In [-]HSP72 or ICR, the values for mean arterial pressure, the striatal blood flow, and the striatal PO2 after the onset of heatstroke were significantly lower than those in preheat controls. The core and brain temperatures, the extracellular concentrations of ischemic and injury markers in the striatum, and the striatal neuronal damage scores were significantly greater than those in the preheat controls. In [-]HSP72 or ICR, the body temperatures, cell ischemia content, and injury marker in the striatum were significantly higher, and the mean arterial pressure, striatal blood flow, and striatal PO2 concentration were significantly lower during heatstroke than in [+]HSP72. Accordingly, the latency and the survival times for [+]HSP72 significantly exceeded those of [-]HSP72 or ICR. These results demonstrate that the overexpression of HSP72 in multiple organs improves survival during heatstroke by reducing hyperthermia, circulatory shock, and cerebral ischemia and damage in mice.

Comparison of renal safety and efficacy of telbivudine, entecavir and tenofovir treatment in chronic hepatitis B patients: real world experience.

This study aims to assess the nephrotoxicity and efficacy of tenofovir disoproxil fumarate (tenofovir), telbivudine and entecavir. A retrospective study of 587 patients with chronic hepatitis B treated with tenofovir (n = 170), telbivudine (n = 184) and entecavir (n = 233) for at least 1 year. Renal function and efficacy were assessed. The estimated glomerular filtration rate (eGFR) decreased significantly in the tenofovir group after a mean of 17 months treatment (from 92.2 to 85.6 mL/min/1.73 m(2), p < 0.001), but increased in the telbivudine group after a mean of 32 months of treatment (from 86.1 to 95 mL/min/1.73 m(2), p < 0.001). There was no significant change in eGFR in the entecavir group after a mean of 44 months. By multivariate analysis, pre-existing renal insufficiency (p = 0.003), tenofovir (p = 0.007) and diuretic treatment (p = 0.001) were independent predictors for renal function deterioration. Cumulative virological breakthrough was 0% in tenofovir after 2 years, 3.4% in entecavir after 7 years and 22.9% in telbivudine after 5 years. Liver cirrhosis (p = 0.008) and virological breakthrough (p = 0.040) were independently associated with increased risk of hepatocellular carcinoma development. Tenofovir may lead to deterioration in renal function as assessed by serial eGFR measurements. Although telbivudine appeared to be associated with an improvement in eGFR, it was associated with high rates of virological breakthrough, which was an independent risk factor for HCC development. With low rates of virological breakthrough and preservation of renal function, entecavir could be the best choice among these three agents.

The involvement of PI 3-K/Akt-dependent up-regulation of Mcl-1 in the prevention of apoptosis of Hep3B cells by interleukin-6.

Interleukin-6 (IL-6) is a pleitrophic cytokine that not only regulates growth and differentiation of many cell types, but also induces production of acute phase proteins (AAP) in hepatocytes. Our previous works have demonstrated that both PI 3-K/Akt and STAT3 pathways were concomitantly activated and cooperatively mediated the anti-apoptotic effect of IL-6. This investigation reports that IL-6 protected cells against apoptosis induced by a variety of agents including, TGF-beta, UV and retinoic acid (RA) in Hep3B cells, suggesting that IL-6 is a fundamental determinant of hepatic cell survival. Mcl-1, but not other Bcl-2 family members, was rapidly up-regulated by IL-6, with a peak (approximately 3-4-fold) appearing at 4 h. Transient transfection of cells with a mcl-1 antisense vector, resulting in a 50-60% reduction of the anti-apoptotic effect of IL-6, indicating that Mcl-1 is a downstream effector of IL-6. Which signaling pathway transduced by IL-6 responsible for the Mcl-1 up-regulation was further investigated. In Hep3B cells, the JAK/STAT3, ERK, and PI 3-K/Akt pathways were activated by IL-6 stimulation. Blocking JAK/STAT3 activation with a dominant-negative mutant STAT3F or a JAK inhibitor AG490 could not influence IL-6-mediated Mcl-1 up-regulation. Similarly, PD98059 treatment, a MEK specific inhibitor, also failed to inhibit Mcl-1 expression. However, the IL-6-induced Mcl-1 up-regulation was effectively attenuated in the presence of PI 3-K inhibitors, LY294002 and wortmannin. Expression of dominant-negative Akt, but not Etk, could abrogate the IL-6-induced increase of Mcl-1. In conclusion, our results suggest that the anti-apoptotic effect of IL-6 is mediated, at least in part, by Mcl-1 expression and that is mainly through the PI 3-K/ Akt-dependent pathway.

Alterations in physiologic functions and in brain monoamine content in streptozocin-diabetic rats.

In the present study, we used streptozocin (STZ) to induce diabetes in rats and observed alterations in several physiologic functions and in monoamine content of different brain regions. Rats with STZ diabetes displayed a thermoregulatory deficit in the cold. Both the body temperature and metabolic rate of the diabetic animals were reduced at ambient temperatures below 22 degrees C. These diabetic animals had a higher level of the spontaneous pain threshold, but displayed a reduced sensitivity of analgesic responses to morphine injection. In addition, these diabetic animals had a lower level of spontaneous motor activity, but displayed an increased sensitivity of locomotor stimulant responses to amphetamine administration. Biochemical examination revealed that the diabetic animals had a lower serotonin level in both the hypothalamus and the brainstem without changes in the serotonin levels of the corpus striatum. These diabetic animals also had a lower catecholamine level in the hypothalamus, but a higher catecholamine level in the corpus striatum. The alterations in brain monoamine content and in the above-mentioned physiologic parameters were reversed after insulin replacement therapy. The data suggest that alterations in various autonomic, somatosensory, and motor neural functions of untreated STZ-diabetic rats correlated with a reproducible pattern of monoamine content in various brain regions (a pattern that differed from that observed in healthy control rats), and that both the altered neural function and the altered brain monoamine pattern were reversed after insulin therapy.

Dopamine overload visualized in the basal ganglia of rabbit brain during heatstroke can be suppressed by hypothermia.

The present study assesses the changes of dopamine levels in the basal ganglia (BG) of rabbit brain during heatstroke with or without hypothermia therapy. The dopamine levels were determined by using 6(F18) fluoro-L-dopa (FDOPA) positron emission tomography (PET) scan. Heatstroke was induced by exposing the anesthetized rabbits to a high blanket temperature (T(blanket)) of 45 degrees C. Hypothermia therapy was accomplished by decreasing T(blanket) from 45 to 16 degrees C. Regions-of-interest were carefully selected on the BG and cerebellum (C). The uptake ratio of FDOPA was defined as the mean counts per pixel from BG divided by the mean counts from C. BG/C ratios represent the dopamine levels of BG. The results showed that the values of mean arterial pressure (MAP) in heatstroke rabbits without hypothermia therapy were significantly lower than those in normothermic controls. However, BG/C FDOPA ratios were greater. Both the arterial hypotension and the increased BG/C FDOPA ratios observed during heatstroke were all reduced after hypothermia therapy. Our data demonstrate that the dopamine overload visualized in the BG of rabbit brain during heatstroke can be suppressed by hypothermia therapy.

Clinical and biological characteristics of acute promyelocytic leukemia in Taiwan: a high relapse rate in patients with high initial and peak white blood cell counts during all-trans retinoic acid treatment.

Acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA) and chemotherapy have been shown to have better outcome than those treated with conventional chemotherapy alone. However, the biological characteristics of leukemic cells and their clinical implications in patients treated with ATRA have not been well established. In this study, the biological and clinical features of 30 APL patients were reported. The risk factors for relapse and for occurrence of retinoic acid (RA) syndrome, which might cause morbidity or mortality of patients after ATRA treatment, were also analyzed. All patients showed 15;17 translocation by cytogenetic and/or gene analysis. Patients in this study had higher white blood cell (WBC) counts and a higher incidence of additional abnormalities than those from other areas. The ratio of long (L) form to short (S) form PML-RAR alpha fusion transcript was 1.8:1, a value lower than that of Latino patients but higher than that of Italians. Leukemic cells from four patients showed coexpression of T cell-associated antigen CD2 which was highly correlated with S form fusion transcript. Nine (36%) of the 25 patients treated with ATRA developed RA syndrome; all but one were successfully controlled by corticosteroid. Complete remission (CR) rate was 84%. Patients with high WBC counts tended to develop RA syndrome and had increased risk of relapse. Isochromosome for the long arm of the derivative chromosome 17, ider(17q), as an additional chromosomal abnormality was also associated with poor outcome in this study. In conclusion, APL in this study showed some different biological characteristics compared with those reported in other areas. High WBC count was a risk factor for relapse and development of RA syndrome after ATRA treatment. The prognostic implication of the presence of ider(17q) needs further clarification.

Transcultural issues.

Pharmacogenetics as a field of research is increasing the basis of knowledge on the use of psychotropics in different ethnic patient populations. This chapter summarizes current knowledge on the metabolism of anxiolytic agents with emphasis on pharmacogenetics and ethnic variations in drug responses.

Large single crystal growth, transport property, and spectroscopic characterizations of three-dimensional Dirac semimetal Cd3As2.

The three dimensional (3D) Dirac semimetal is a new quantum state of matter that has attracted much attention recently in physics and material science. Here, we report on the growth of large plate-like single crystals of Cd3As2 in two major orientations by a self-selecting vapor growth (SSVG) method, and the optimum growth conditions have been experimentally determined. The crystalline imperfections and electrical properties of the crystals were examined with transmission electron microscopy (TEM), scanning tunneling microscopy (STM), and transport property measurements. This SSVG method makes it possible to control the as-grown crystal compositions with excess Cd or As leading to mobilities near 5-10(5) cm(2)V(-1)s(-1). Zn-doping can effectively reduce the carrier density to reach the maximum residual resistivity ratio (RRRρ300K/ρ5K) of 7.6. A vacuum-cleaved single crystal has been investigated using angle-resolved photoemission spectroscopy (ARPES) to reveal a single Dirac cone near the center of the surface Brillouin zone with a binding energy of approximately 200 meV.