Work participation, social roles, and empowerment of Q-fever fatigue syndrome patients ≥10 years after infection.

OBJECTIVE: To determine work participation, social roles, and empowerment of QFS patients ≥10-year after infection. METHODS: QFS patients ≥10-year after acute infection, who were of working age, participated in a cross-sectional survey study. Work participation, fulfilment of social roles, and empowerment outcomes were studied for the total population, as well as for subgroups based on employment type and current work status. Associations between empowerment, work and social roles were examined. RESULTS: 291 participants were included. Of the 250 participants who had paid work before Q-fever, 80.4% stopped working or worked less hours due to QFS. For each social role, more than half of the participants (56.6-87.8%) spent less time on the role compared to before Q-fever. The median empowerment score was 41.0 (IQR: 37.0-44.0) out of 60. A higher empowerment score was significantly associated with lower odds of performing all social roles less due to QFS (OR = 0.871-0.933; p<0.001-0.026), except for parenting and informal care provision (p = 0.070-0.460). No associations were found between empowerment and current work status. CONCLUSION: Work participation and fulfilment of social roles is generally low in QFS patients. Many of the participants stopped working or are working less hours due to QFS, and most spent less time on social roles compared to before Q-fever. Minor variation was seen in total empowerment scores of participants; however, these slight differences were associated with the fulfilment of social roles, but not work participation. This new insight should be further explored in future studies.

Respiratory and sleep outcomes in children with SMA treated with nusinersen - real world experience.

It is unclear how improvements in peripheral motor function in children with spinal muscular atrophy (SMA), treated with nusinersen, translate into clinically significant respiratory/sleep outcomes. A retrospective chart review of SMA children at the Sydney Children's Hospital Network was undertaken looking at 2 years before and after receiving their first dose of nusinersen. Polysomnography (PSG), spirometry and clinical data were collected and analysed using paired and unpaired t-tests for PSG parameters and generalised estimating equations for longitudinal lung function data. Forty-eight children (10 Type 1, 23 Type 2, 15 Type 3) at mean age 6.98 yrs (SD 5.25) for nusinersen initiation were included. There was a statistically significant improvement in oxygen nadir during sleep in individuals post nusinersen (mean of 87.9% to 92.3% (95%CI 1.24 - 7.63, p = 0.01)). Based on clinical and PSG findings, 6/21 patients (5 Type 2, 1 Type 3) ceased nocturnal NIV post nusinersen. Non-significant improvements were demonstrated in mean slope for FVC% predicted, FVC Z-score and mean FVC% predicted. Within 2 years of commencing nusinersen, stabilisation of respiratory outcomes occurred. Whilst some of the SMA type 2/3 cohort ceased NIV, there were no statistically significant improvements lung function and most PSG parameters.

Prostate cancer in multi-ethnic Asian men: Real-world experience in the Malaysia Prostate Cancer (M-CaP) Study.

Prostate cancer is the third most common cancer in Malaysia with the lifetime risk of 1 in 117 men. Here, we initiated a longitudinal Malaysia Prostate Cancer (M-CaP) Study to investigate the clinical and tumour characteristics, treatment patterns as well as disease outcomes of multi-ethnic Asian men at real-world setting. The M-CaP database consisted of 1839 new patients with prostate cancer diagnosed between 2016 and 2018 from nine public urology referral centres across Malaysia. Basic demographic and clinical parameters, tumour characteristics, primary treatment, follow-up and vital status data were retrieved prospectively from the hospital-based patients' case notes or electronic medical records. Primary endpoints were overall survival (OS) and biochemical progression-free survival (bPFS). The median age at diagnosis of M-CaP patients was 70 years (interquartile range, IQR 65-75). Majority of patients were Chinese (831, 45.2%), followed by Malays (704, 38.3%), Indians (124, 6.7%) and other races (181, 9.8%). The median follow-up for all patients was 23.5 months (IQR 15.9-33.6). Although 58.1% presented with late-stage cancer, we observed ethnic and geographic disparities in late-stage prostate cancer diagnosis. Curative radiotherapy and primary androgen deprivation therapy were the most common treatment for stage III and stage IV diseases, respectively. The median OS and bPFS of stage IV patients were 40.1 months and 19.2 months (95% CI 17.6-20.8), respectively. Late stage at presentation remains a challenge in multi-ethnic Asian men. Early detection is imperative to improve treatment outcome and survival of patients with prostate cancer.

Novel use of high-flow nasal cannula therapy in the management of pyriform aperture stenosis: case report.

BACKGROUND: Pyriform aperture stenosis is a rare form of congenital nasal obstruction; it poses a management dilemma for otolaryngologists and physicians alike. It can result in poor weight gain and potentially life-threatening airflow obstruction. The challenge lies in the difficulty to predict which patients will require invasive operative management versus conservative therapy alone. CASE REPORT: This case demonstrates the successful use of high-flow nasal cannula therapy in a young child with pyriform aperture stenosis.

[Multi locus sequence typing and antibiotic susceptibility of extended-spectrum beta-lactamases producing Enterobacteriaceae in rural residents in villages with pig-breeding farms in Shandong province].

Objective: To analyze the antimicrobial resistance and multilocus sequence typing (MLST) results of extended-spectrum ß-lactamase (ESBLs)-producing Escherichia coli in rural residents in villages with pig breeding farms in a county of Shandong province. Methods: Antimicrobial susceptibility testing was performed with agar dilution method by using 360 ESBLs-producing E. coli strains from fresh stool samples of rural residents in villages with pig breeding farms in a county of Shandong. PCR was conducted to amplify the CTX-M, TEM, SHV genes and capillary electrophoresis was used to screen positive strains in July, 2016. MLST was performed for molecular typing analysis, and eBURST v3.0 software was used for cluster analysis. Results: Among 360 strains of ESBLs-producing E. coli, the resistance rates to cefotaxime, tetracycline, trimethoprim-sulfamethoxazole and florfenicol were 100.0% (360/360), 82.2% (296/360), 81.1% (292/360) and 80.3% (289/360), respectively. The positive rate of CTX-M gene was 99.2% (357/360), in which the positive rate of CTX-M-9 was 35.6% (128/360) and the positive rate of CTX-M-1 was 24.4% (88/360). The positive rate of TEM gene was 26.9% (97/360). A total of 132 STs were identified through MLST. The predominant ST was ST10, accounting for 12.5% (45/360). Cluster analysis showed that CC10 was the most important clone group, including 39 ST clones, involving 148 strains (41.1%). Conclusions: The drug resistances of ESBLs-producing E. coli to cefotaxime, tetracycline, trimethoprim-sulfamethoxazole and flurfenicol are serious in this rural area. There is a small-scale clustering of CC10 and transmission mode from animals to humans might exist.

Organic nitrate chemistry and its implications for nitrogen budgets in an isoprene- and monoterpene-rich atmosphere: constraints from aircraft (SEAC4RS) and ground-based (SOAS) observations in the Southeast US.

Formation of organic nitrates (RONO2) during oxidation of biogenic volatile organic compounds (BVOCs: isoprene, monoterpenes) is a significant loss pathway for atmospheric nitrogen oxide radicals (NOx), but the chemistry of RONO2 formation and degradation remains uncertain. Here we implement a new BVOC oxidation mechanism (including updated isoprene chemistry, new monoterpene chemistry, and particle uptake of RONO2) in the GEOS-Chem global chemical transport model with ∼25 × 25 km2 resolution over North America. We evaluate the model using aircraft (SEAC4RS) and ground-based (SOAS) observations of NOx, BVOCs, and RONO2 from the Southeast US in summer 2013. The updated simulation successfully reproduces the concentrations of individual gas- and particle-phase RONO2 species measured during the campaigns. Gas-phase isoprene nitrates account for 25-50% of observed RONO2 in surface air, and we find that another 10% is contributed by gas-phase monoterpene nitrates. Observations in the free troposphere show an important contribution from long-lived nitrates derived from anthropogenic VOCs. During both campaigns, at least 10% of observed boundary layer RONO2 were in the particle phase. We find that aerosol uptake followed by hydrolysis to HNO3 accounts for 60% of simulated gas-phase RONO2 loss in the boundary layer. Other losses are 20% by photolysis to recycle NOx and 15% by dry deposition. RONO2 production accounts for 20% of the net regional NOx sink in the Southeast US in summer, limited by the spatial segregation between BVOC and NOx emissions. This segregation implies that RONO2 production will remain a minor sink for NOx in the Southeast US in the future even as NOx emissions continue to decline.

Jensen's Inequality and the Impact of Short-Term Environmental Variability on Long-Term Population Growth Rates.

It is well established in theory that short-term environmental fluctuations could affect the long-term growth rates of wildlife populations, but this theory has rarely been tested and there remains little empirical evidence that the effect is actually important in practice. Here we develop models to quantify the effects of daily, seasonal, and yearly temperature fluctuations on the average population growth rates, and we apply them to long-term data on the endangered Black-faced Spoonbill (Platalea minor); an endothermic species whose population growth rates follow a concave relationship with temperature. We demonstrate for the first time that the current levels of temperature variability, particularly seasonal variability, are already large enough to substantially reduce long-term population growth rates. As the climate changes, our results highlight the importance of considering the ecological effects of climate variability and not just average conditions.

Physician behaviors surrounding the implementation of decision and communication AIDS in a breast cancer clinic: a qualitative analysis of staff intern perceptions.

The aim of this paper is to examine how physician behavior facilitated or impeded our implementation of decision and communication aids in a breast cancer clinic. Staff interns provided decision and communication aids to patients and wrote up case notes for each patient they served. We used grounded theory to code our staff interns' case notes. We then identified barriers and facilitators to our program's implementation from each category we generated in the coding. Facilitators included physicians reading patient questions and then bringing the staff interns to the consultation. Barriers included physicians forgetting to bring the staff interns to the appointments and discouraging interns from speaking during the consultation. Physicians vary in their cooperation with our program. Our next steps will be to inquire directly with physicians about how to adapt our program design. We will also seek to position the staff interns as mentees to increase physician commitment to our program.

Retroperitoneal lymph node dissection after chemotherapy in patients with elevated tumour markers: indications, histopathology and outcome.

OBJECTIVE: To evaluate the factors affecting outcome and the pathological findings in patients who had retroperitoneal lymph node dissection (pcRPLND) after chemotherapy with elevated tumour markers, as such patients have an unfavourable prognosis, with further salvage chemotherapy being the usual treatment of choice. PATIENTS AND METHODS: Information on the preoperative treatment, tumour markers, histopathology and outcome data of the patients who had pcRPLND were extracted from the hospital databases. Survival was analysed using the Kaplan-Meier method and multivariate analysis with Cox regression model. RESULTS: In all, 358 patients had pcRPLND between September 1992 and April 2006, by one surgeon. In 48 patients the tumour markers were elevated at the time of surgery, they were on a 'rising trend' in 26 (54%) and 'downward or stable' trend in 22 (46%). The overall incidence of active germ cell tumour, differentiated teratoma and necrosis in the resected specimens was 58%, 25% and 17%, respectively. The median follow-up was 51.5 months and the overall 5-year survival was 69%. The favourable prognostic factors assessed by univariate analysis were elevation of alpha-fetoprotein alone, complete resection of residual disease, histological finding of differentiated teratoma in the resected tissues and normalization of tumour markers after pcRPLND. By multivariate analysis the only statistically significant independent survival factor was the normalization of the tumour markers after pcRPLND. CONCLUSION: For selected patients with elevated tumour markers after chemotherapy, RPLND can offer a significant chance of cure with no need for further chemotherapy. The patients most likely to benefit are those with elevations of alpha-fetoprotein alone. In this group, pcRPLND can offer the prospect of long-term survival and should be considered in the management of selected patients.

Medical staff's knowledge of pulse oximetry: a prospective survey conducted in a tertiary children's hospital.

OBJECTIVES: To assess the knowledge of pulse oximetry of senior (SMO) and junior medical officers (JMO) in a tertiary paediatric hospital. METHODS: A 16-item multiple choice questionnaire was administered to SMO and JMO without prior notice or instruction in the area. The questions were completed voluntarily and anonymously, then proctored and collated by the principal investigator. RESULTS: The mean test scores for SMO and JMO were 70 +/- 15% and 65 +/- 13%, respectively (P = 0.06). A significant negative correlation was found between the test scores and the years of paediatric experience with the SMO. CONCLUSIONS: The results of the survey showed there is an insufficiency of knowledge and understanding among medical staff concerning the principles, clinical applications and limitations of pulse oximetry. More emphasis needs to be placed on teaching these principles to ensure quality care for patients.

nCPAP improves abnormal autonomic function in at-risk-for-SIDS infants with OSA.

We evaluated cardiovascular autonomic control and arousability during sleep in infants with obstructive sleep apnea (OSA) before and after 10 +/- 4 (mean +/- SD) days of treatment with nasal continuous positive airway pressure (nCPAP). Six OSA infants and 12 age-matched control infants were studied with polygraphic sleep studies at the age of 13 +/- 4 wk. During the study, 45 degrees head-up tilt tests were performed in slow-wave and rapid eye movement sleep. Blood pressure (BP) and heart rate (HR) were continuously monitored. All OSA infants had decreased initial BP and HR responses, followed by hypotension in two and hypertension in two. OSA infants displayed higher arousal thresholds in response to the tilt in rapid eye movement sleep (P < 0.005) and higher baseline HR (P < 0.05) than controls. nCPAP treatment normalized BP and HR responses as well as arousal thresholds to tilting and stabilized HR levels. OSA in infants may be linked with cardiovascular autonomic control disturbances and decreased arousability during sleep. These defects are improved by control of OSA with nCPAP.

P53 protein expression in transitional cell carcinoma of the bladder - experience of the University of Malaya Medical Centre.

OBJECTIVES: To study the incidence of p53 oncoprotein overexpression and its relationship to tumour grade, stage and clinical prognosis in a cohort of local Malaysian patients. METHODS: All cases of transitional cell carcinoma (TCC) of the bladder diagnosed and treated at the University of Malaya Medical Centre from January 1995 to December 2000 were retrieved from the hospital records. Sections from paraffin-embedded tissues were retrieved and stained for p53 oncoprotein using immunohistochemistry techniques. P53 oncoprotein results were analyzed in relation to tumour grade, stage and clinical prognosis. Fisher's exact test was used to evaluate the relationship between categorical variables and the Kaplan-Meier procedure was used to assess survival outcomes. The Cox regression model was used for multivariate analysis. RESULTS: A total of 64 cases were studied. The mean follow-up period was 23.7 months. The number of p53 positive cases was significantly higher in high-grade (G3) (p = 0.006) and muscle-invasive tumours ( summation operator T2, p = 0.035). The status of p53 expression had no significant association with recurrence-free (p = 0.594) or overall survival (p = 0.955). In multivariate analysis, a multiplicity of tumours at presentation (p = 0.004) and a history of cigarette smoking (p = 0.016) were independent predictors of recurrence. Tumour stage (p = 0.024) was the single independent predictor for poor overall survival. CONCLUSIONS: Overexpression of p53 is associated with TCC of higher grade and tumour stage. It had no significant impact on prognosis in this cohort of TCC cases.

Cardiovascular responses to three simple, provocative tests of autonomic activity in sleeping infants.

Whereas defective cardiovascular autonomic control has been implicated in the sudden infant death syndrome, relatively little is known about the normal development of autonomic control, due to the inability to measure blood pressure in infants noninvasively. We studied 12 normal infants [age: 13 +/- 2 (SD) wk] using a noninvasive method of continuous blood pressure recording and examined the cardiovascular responses to 45 degrees head-up tilting, a modified cold face test, and a loud noise. In head-up tilting, in both slow-wave sleep and rapid eye movement sleep, all infants displayed a rapid biphasic heart rate response (mean increase of 16% and mean decrease of 21%) and blood pressure response (mean increase of 16% and mean decrease of 16%), with a return to pretest values within 20 s. Both ice and noise caused a less pronounced biphasic response. In conclusion, at 3 mo, infants show the adult pattern of response to postural challenge. The short latency of the response suggests that neural inputs, apart from baroreceptors, are involved in the initial phase of the response.

Mucositis reduction by selective elimination of oral flora in irradiated cancers of the head and neck: a placebo-controlled double-blind randomized study.

PURPOSE: The aim of the study was to test the hypothesis that aerobic Gram-negative bacteria (AGNB) play a crucial role in the pathogenesis of radiation-induced mucositis; consequently, selective elimination of these bacteria from the oral flora should result in a reduction of the mucositis. METHODS AND MATERIALS: Head-and-neck cancer patients, when scheduled for treatment by external beam radiation therapy (EBRT), were randomized for prophylactic treatment with an oral paste containing either a placebo or a combination of the antibiotics polymyxin E, tobramycin, and amphotericin B (PTA group). Weekly, the objective and subjective mucositis scores and microbiologic counts of the oral flora were noted. The primary study endpoint was the mucositis grade after 3 weeks of EBRT. RESULTS: Seventy-seven patients were evaluable. No statistically significant difference for the objective and subjective mucositis scores was observed between the two study arms (p = 0.33). The percentage of patients with positive cultures of AGNB was significantly reduced in the PTA group (p = 0.01). However, complete eradication of AGNB was not achieved. CONCLUSIONS: Selective elimination of AGNB of the oral flora did not result in a reduction of radiation-induced mucositis and therefore does not support the hypothesis that these bacteria play a crucial role in the pathogenesis of mucositis.

[Expression of adhesion molecules on CD34(+) hematopoietic precursor cells from normal human bone marrow, cord blood and mobilized blood].

OBJECTIVE: To investigate the expression of adhesion molecules on CD(34)(+) hematopoietic precursor cells from normal human bone marrow, cord blood and mobilized peripheral blood, and the mechanism of peripheral blood precursor cells mobilization. METHODS: CD(34)(+) hematopoietic cells were separated from bone marrow, cord blood and mobilized peripheral blood by CD(34) MultiSort Kit immunomagnetic bead system. The purity was examined by FACSort. The CD(34)(+) cells and post-short-term cultured CD(34)(+) cells were labeled in an indirect immuno-fluorescence procedure with adhesion molecules CD(11a), CD(18), CD(44), CD(49d), CD(54), CD(58) and CD(62L) monoclonal antibodies and assayed by FACSort. RESULTS: The expression of CD(11a), CD(18), CD(49d), CD(54), CD(58) and CD(62L) of mobilized peripheral blood CD(34)(+) cells was lower than that of bone marrow ones, especially for CD(49d) and CD(62L). Similar to mobilized peripheral blood CD(34)(+) cells, cord blood CD(34)(+) cells also showed a lower expression of CD(11a), CD(18), CD(44), CD(49d), CD(62L) than that of bone marrow ones, especially for CD(62L), but expression of CD(54) was higher than that of bone marrow and mobilized peripheral blood CD(34)(+) cells. CONCLUSION: The expressions of cell adhesion molecules on CD(34)(+) cells in normal bone marrow, cord blood and mobilized peripheral blood were quite different, the mechanism of peripheral blood precursors mobilization might be related to downregulation of cell adhesion molecule expression.

Is dipalmitoylphosphatidylcholine a substrate for convertase?

Convertase has homology with carboxylesterases, but its substrate(s) is not known. Accordingly, we determined whether dipalmitoylphosphatidylcholine (DPPC), the major phospholipid in surfactant, was a substrate for convertase. We measured [(3)H]choline release during cycling of the heavy subtype containing [(3)H]choline-labeled DPPC with convertase, phospholipases A(2), B, C, and D, liver esterase, and elastase. Cycling with liver esterase or peanut or cabbage phospholipase D produced the characteristic profile of heavy and light peaks observed on cycling with convertase. In contrast, phospholipases A(2), B, and C and yeast phospholipase D produced a broad band of radioactivity across the gradient without distinct peaks. [(3)H]choline was released when natural surfactant containing [(3)H]choline-labeled DPPC was cycled with yeast phospholipase D but not with convertase or peanut and cabbage phospholipases D. Similarly, yeast phospholipase D hydrolyzed [(3)H]choline from [(3)H]choline-labeled DPPC after incubation in vitro, whereas convertase, liver esterase, or peanut and cabbage phospholipases D did not. Thus convertase, liver esterase, and plant phospholipases D did not hydrolyze choline from DPPC either on cycling or during incubation with enzyme in vitro. In conclusion, conversion of heavy to light subtype of surfactant by convertase may require a phospholipase D type hydrolysis of phospholipids, but the substrate in this reaction is not DPPC.

Molecular cloning, characterization, and differential expression pattern of mouse lung surfactant convertase.

We recently reported the purification and partial amino acid sequence of "surfactant convertase," a 72-kDa glycoprotein involved in the extracellular metabolism of lung surfactant (S. Krishnasamy, N. J. Gross, A. L. Teng, R. M. Schultz, and R. Dhand. Biochem. Biophys. Res. Commun. 235: 180-184, 1997). We report here the isolation of a cDNA clone encoding putative convertase from a mouse lung cDNA library. The cDNA spans a 1,836-bp sequence, with an open reading frame encoding 536 amino acid residues in the mature protein and an 18-amino acid signal peptide at the NH2 terminus. The deduced amino acid sequence matches the four partial amino acid sequences (68 residues) that were previously obtained from the purified protein. The deduced amino acid sequence contains an 18-amino acid residue signal peptide, a serine active site consensus sequence, a histidine consensus sequence, five potential N-linked glycosylation sites, and a COOH-terminal secretory-type sequence His-Thr-Glu-His-Lys. Primer-extension analysis revealed that transcription starts 29 nucleotides upstream from the start codon. Northern blot analysis of RNA isolated from various mouse organs showed that convertase is expressed in lung, kidney, and liver as a 1,800-nucleotide-long transcript. The nucleotide and amino acid sequences of putative convertase are 98% homologous with mouse liver carboxylesterase. It thus may be the first member of the carboxylesterase family (EC 3.1.1.1) to be expressed in lung parenchyma and the first with a known physiological function.

Protein-lipid interactions and enzyme requirements for light subtype generation on cycling reconstituted surfactant.

Surfactant convertase is required for conversion of heavy density (H) natural surfactant to light density (L) subtype during cycling in vitro, a technique that reproduces surfactant metabolism. To study mechanisms of H to L conversion, we prepared liposomes of dipalmitoylphosphatidylcholine (DPPC) and phosphatidylglycerol (PG), or the phospholipids (PL) in combination with either surfactant protein A (SP-A), surfactant protein B (SP-B), or both SP-A and SP-B. Phospholipids alone showed time-dependent conversion from heavy to light subtype on cycling in the absence of convertase, which was decreased by adding SP-B, but not SP-A, to phospholipids (p < 0.01 for PL+SP-B, or PL+SP-A+SP-B vs. PL, or PL+SP-A). The ultrastructure, surface activity, buoyant density, and L subtype generation on cycling PL+SP-A+SP-B with partially purified convertase or with phospholipase D were similar to those of natural TM. In conclusion, a reconstituted surfactant mimics the behavior of natural surfactant on cycling, and reveals that interaction of SP-B with phospholipids decreases L subtype generation. In addition, esterase/ phospholipase D activity is required for conversion of heavy to light subtype on cycling.

Lung "surfactant convertase" is a member of the carboxylesterase family.

The extracellular conversion of lung surfactant from tubular myelin to the small vesicular form has previously been shown to require a serine-active enzyme called "surfactant convertase." In the present study, a 72kD serine-active enzyme previously identified in mouse lung alveolar lavage and having convertase activity was partially sequenced. Sixty-eight residues obtained from amino acid sequencing of this protein show that it is a new member of the mouse carboxylesterase family (EC 3.1.1.1). The 72kD lung protein also has esterase activity. A commercial esterase of the same family was able to reproduce surfactant convertase bioactivity in vitro, unlike several serine proteinases previously tested. We conclude that surfactant convertase is a carboxylesterase which mediates a biochemical step in the extracellular metabolism of surfactant.

Nasal mask continuous positive airway pressure in the treatment of chronic nocturnal cough in a young child.

The objective of this case report was to define the effects of nasal mask continuous positive airway pressure (CPAP) on the respiratory and sleep characteristics of a 3 year-old boy with a 2 year history of snoring and 1 year history of chronic nocturnal cough. The method employed was all-night polysomnography before and during treatment with CPAP after the identification of partial upper airway obstruction in association with cough. The results indicated that the child had evidence of mild upper airways obstruction on initial all-night sleep study. Nasal mask CPAP was instituted. On a subsequent sleep study 4 weeks later, this was documented to prevent the upper airway obstruction at a pressure of 5.2 cm of water. In addition, nasal mask CPAP markedly reduced the nocturnal coughing, the total number of coughs decreasing from 92 to one. The rate of cough per h of study (cough disturbance index) decreased from 9.8-0.1. Sleep efficiency (total sleep time as a percentage of study duration) improved on CPAP from 87 to 99%. This study suggests that chronic nocturnal cough can result from upper airway obstruction in sleep in children and is an important initial observation.