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Previous research on the perception of segmental features of languages has established a correlation between the phoneme inventory of a language and its speakers' perceptual abilities, as indexed by discrimination tasks and Mismatch Negativity (MMN). Building on this background, the current study elucidated the relationship between perceptual ability and tonal inventory by utilizing two tonal languages. Two groups of participants were included in the present experiment: Mandarin speakers and Hakka-Mandarin speakers. Onset latency analysis revealed a significant difference in the Mandarin syllable condition, with Hakka-Mandarin speakers demonstrating earlier MMN latency than Mandarin speakers. This suggests a more efficient auditory processing mechanism in Hakka-Mandarin speakers. Both groups, however, showed similar MMN latency in the Hakka syllable condition. The interaction between language background and syllable type indicates that other factors, such as syllable sonority, also influence MMN responses. These findings highlight the importance of considering multiple phonemic inventories and syllable characteristics in studies of tonal perception., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Hsu, Cheong and Huang.)

Background and Aims: The evolving mutants of SARS-CoV-2 have made the COVID-19 pandemic sustained for over 3 years. In 2022, BA.4 and BA.5 were the Omicron variants dominating the spread globally. Although COVID-19 was no longer a Public Health Emergency of International Concern (PHEIC) as announced by WHO, the SARS-CoV-2 variants remain a challenge to global healthcare under the circumstances of withdrawal and loosening of personal protective behavior in the post-quarantine era. This study aims to acknowledge the clinical characteristics caused by Omicron BA.4/BA.5 in COVID-19 naive people and analyze possible factors affecting disease severities., Methods: In this retrospective study, we report and analyze the clinical features of 1820 COVID-19 patients infected with the BA.4/BA.5 Omicron variants of SARS-CoV-2 during a local outbreak that occurred in Macao SAR, China, from June to July 2022., Results: A total of 83.5% of patients were symptomatic eventually. The most common symptoms were fever, cough, and sore throat. Hypertension, dyslipidemia, and diabetes mellitus were the leading comorbidities. There were significantly more elderly patients ( p  < 0.001), more patients with comorbidity ( p  < 0.001) and more patients without vaccination or not completing the series ( p  < 0.001) in the "Severe to Critical" group. All deceased patients were elderly with at least three comorbidities and were partial to totally dependent in their daily lives., Conclusion: Our data are consistent with a milder disease caused by BA.4/5 Omicron variants in the general population, while patients with old age and comorbidities have developed severe to critical diseases. Complete vaccination series and booster doses are effective strategies to reinforce protection against severe diseases and avoid mortality., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

The higher-order assembly of Bin-amphiphysin-Rvs (BAR) domain proteins, including the FCH-BAR (F-BAR) domain proteins, into lattice on the membrane is essential for the formation of subcellular structures. However, the regulation of their ordered assembly has not been elucidated. Here, we show that the higher ordered assembly of growth-arrested specific 7 (GAS7), an F-BAR domain protein, is regulated by the multivalent scaffold proteins of Wiskott-Aldrich syndrome protein (WASP)/neural WASP, that commonly binds to the BAR domain superfamily proteins, together with WISH, Nck, the activated small guanosine triphosphatase Cdc42, and a membrane-anchored phagocytic receptor. The assembly kinetics by fluorescence resonance energy transfer monitoring indicated that the GAS7 assembly on liposomes started within seconds and was further increased by the presence of these proteins. The regulated GAS7 assembly was abolished by Wiskott-Aldrich syndrome mutations both in vitro and in cellular phagocytosis. Therefore, Cdc42 and the scaffold proteins that commonly bind to the BAR domain superfamily proteins promoted GAS7 assembly.

As a city famous for tourism, the public healthcare system of Macau SAR has been under great pressure during the outbreak of the Coronavirus Disease 2019 (COVID-19). In this study, we report clinical and microbiological features of ten COVID-19 patients enrolled in the Centro Hospitalar Conde de São Januário (CHCSJ) between January 21 to February 16, 2020. Clinical samples from all patients including nasopharyngeal swab (NPS)/sputum, urine, and feces were collected for serial virus RNA testing by standard qRT-PCR assay. In total, seven were imported cases and three were local cases. The median duration from Macau arrival to admission in imported cases was 3 days. Four patients required oxygen therapy but none of them needed machinal ventilation. No fatal cases were noted. The most common symptoms were fever (80%) and diarrhea (80%). In the "Severe" group, there was significantly more elderly patients (p=0.045), higher lactate dehydrogenase levels (p=0.002), and elevated C-Reactive protein levels compared to the "Mild to Moderate" group (p<0.001). There were positive SARS-CoV-2 RNA signals in all patients' NPS and stool specimens but negative in all urine specimens. Based on our data on SARS-CoV-2 RNA shedding in stool and the possibility of a lag in viral detection in NPS specimens, the assessment of both fecal and respiratory specimen is recommended to enhance diagnostic sensitivity, and also to aid discharge decision before the role of viral RNA shedding in stool is clarified., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objectives: The inconsistent findings from genetic association studies may be related to the heterogeneity in different molecular subtypes of lung cancer. This study evaluated the predisposing single-nucleotide polymorphisms (SNPs) in epidermal growth factor receptor (EGFR) mutant and EGFR wild-type lung adenocarcinoma separately among never-smokers., Materials and Methods: This was a two-stage case-control study. Never-smokers with pathologically confirmed lung adenocarcinoma and healthy controls were recruited in Hong Kong and Macau. Genomic DNA was extracted and genotyped by MassARRAY. In the discovery stage, 51 SNPs were investigated at the SNP, gene and pathway level among 103 EGFR mutant and 78 EGFR wild-type lung adenocarcinoma cases compared with matched controls. In the validation stage, SNPs that were identified with significant lung cancer risk were replicated in a separate cohort of 84 lung adenocarcinoma cases and compared with 103 Chinese Han, Beijing and 105 Chinese Han, Southern public controls from the 1000 genome database., Results and Conclusion: The genetic association of IL-6 rs2069840 with EGFR mutant lung adenocarcinoma was ascertained. In the discovery stage, haplotype GGG in three SNPs (rs2069840, rs2069852, rs2066992) of IL-6, synergetic effects of IL-6 rs2069840 and environmental tobacco smoke in the workplace were found to be related to EGFR mutant lung adenocarcinoma. ERCC2 rs238406 showed a marginally significant association with EGFR mutant lung adenocarcinoma in the validation stage (P=0.096). ERCC2 rs50871 and ATM rs611646 showed significant association with EGFR wild-type lung adenocarcinoma in the discovery stage. In conclusion, IL-6 rs2069840 conferred susceptibility to EGFR mutant lung adenocarcinoma in a Hong Kong and Macau never-smoking Chinese population., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The presence of loss-of-heterozygosity (LOH) mutations in cancer cell genomes is commonly encountered. Moreover, the occurrences of LOHs in tumor suppressor genes play important roles in oncogenesis. However, because the causative mechanisms underlying LOH mutations in cancer cells yet remain to be elucidated, enquiry into the nature of these mechanisms based on a comprehensive examination of the characteristics of LOHs in multiple types of cancers has become a necessity., Methods: We performed next-generation sequencing on inter-Alu sequences of five different types of solid tumors and acute myeloid leukemias, employing the AluScan platform which entailed amplification of such sequences using multiple PCR primers based on the consensus sequences of Alu elements; as well as the whole genome sequences of a lung-to-liver metastatic cancer and a primary liver cancer. Paired-end sequencing reads were aligned to the reference human genome to identify major and minor alleles so that the partition of LOH products between homozygous-major vs. homozygous-minor alleles could be determined at single-base resolution. Strict filtering conditions were employed to avoid false positives. Measurements of LOH occurrences in copy number variation (CNV)-neutral regions were obtained through removal of CNV-associated LOHs., Results: We found: (a) average occurrence of copy-neutral LOHs amounting to 6.9% of heterologous loci in the various cancers; (b) the mainly interstitial nature of the LOHs; and (c) preference for formation of homozygous-major over homozygous-minor, and transitional over transversional, LOHs., Conclusions: The characteristics of the cancer LOHs, observed in both AluScan and whole genome sequencings, point to the formation of LOHs through repair of double-strand breaks by interhomolog recombination, or gene conversion, as the consequence of a defective DNA-damage response, leading to a unified mechanism for generating the mutations required for oncogenesis as well as the progression of cancer cells.

Tethering of monodisperse, chain-end-functionalized polymer from dilute solution to a solid surface shows three regimes of kinetics. This paper presents support for the hypothesis that the experimentally observed third regime is indeed the transition from mushroom to brush and that it occurs in a spatially nonuniform manner. Both time-step snapshots generated by a Monte Carlo simulation of the tethering process and atomic force microscopy images of actual surfaces during the process show that the third regime is characterized by nonuniform surface texture, while the surface texture is uniform prior to and after the third regime.

The objective of this paper was to study the incidence of 6 atypical pneumonia pathogens or atypical organisms in local patients admitted for acute exacerbation of chronic bronchitis. This is a prospective observational study. Over a period of 3 years (1995 to 1997), 90 patients admitted to a large general hospital in Singapore for acute exacerbation of chronic bronchitis were tested for the following infections: Legionella, Mycoplasma, Chlamydia, influenza A, influenza B and parainfluenza viruses, using paired serological examination. The antibiotic prescribing pattern by the attending physicians in these cases were also examined. Positive serologies were found in 31 patients (34%), of whom 26 patients (28%) had viral infections. The most common organism was influenza A with 18 positive serologies (20%). Five patients were tested positive for Legionella. There was no evidence of acute infections by Mycoplasma pneumoniae or chlamydia using serological tests.

Objective: The aims of this study were: (i) to document the presence and severity of obstructive sleep apnoea (OSA) in patients who complained of heavy snoring and other symptoms suggestive of the OSA syndrome; (ii) to examine the correlation between the clinical and polygraphic findings, and (iii) to document the efficacy and compliance of nasal continuous positive airway pressure (CPAP) among these Asian snorers with OSA., Methods: We analysed our clinical and nocturnal polysomnographic data between January 1986 and December 1995 for physician-referred patients who had complained of snoring and other symptoms suggestive of OSA., Results: A total of 277 diagnostic studies were performed of which 145 (52%) were positive to OSA. For studies performed in the last 2 years (n = 125), 72 of the 125 were positive for OSA. Anthropometric data was not discriminative between the OSA positive snorers and the OSA negative snorers. We found that hypertension and choking were the most significantly related to OSA, conferring a 7 and 4 times relative risk respectively. Nasal CPAP eliminated snoring, apnoeas and oxygen desaturations completely in almost all cases and there were only minor mask-related side effects., Conclusion: OSA may not be uncommon among Asian snorers. Of the major traits for OSA risk among our local population, a history of hypertension and reports of nocturnal choking were the most significantly related. We have also shown that nasal CPAP is safe and effective among our local snorers and should be considered a first-line treatment for OSA.

Background: Most published normal values for transdiaphragmatic pressure (Pdi) have been from Caucasian subjects and there is no universal agreement regarding the most appropriate manoeuvre for assessing Pdi., Aims: The aims of our study were to obtain normal values and to compare the different manoeuvres used to assess Pdi in normal young Singaporean adults., Methods: Twenty-four normal subjects (23 Chinese, one Indian) were studied by measuring Pdi during maximal sniffs from functional residual capacity (sniff Pdi), maximal inspiration to total lung capacity (Pdi TLC) and maximal static inspiratory efforts from residual volume (Pdi PImax)., Results: Mean values +/- SD for sniff Pdi, Pdi TLC and Pdi PImax were 101.8 +/- 31.7, 46.8 +/- 26.4 and 83.5 +/- 35.5 cm H2O respectively. Sniff Pdi was significantly higher than Pdi TLC (p < 0.001) and Pdi PImax (p = 0.005). Pdi PImax was significantly higher than Pdi TLC (p < 0.001). Males had significantly higher values for sniff Pdi (p = 0.026) and Pdi PImax (p = 0.022) than females. There was a significant correlation between the different methods of recording Pdi. Sniff Pdi had the highest values, least between- and within-subject variation and most consistent pattern of respiratory muscle recruitment with the lowest proportion of negative gastric pressure (Pg) values (p < 0.001)., Conclusions: Therefore, sniff Pdi may be better than Pdi TLC and Pdi PImax in assessing diaphragm function. Also, our subjects seemed to have lower sniff Pdi and Pdi PImax, and higher Pdi TLC compared with Caucasian subjects.

Following the identification of an index case of occupational asthma, we assessed the respiratory morbidity in 12 workers exposed to aliphatic polyamines in a chemical factory and in 60 unexposed workers in three other workplaces. Many amine workers reported symptoms of chronic cough (7/12), chronic phlegm (9/12), wheezing (4/12) and exertional breathlessness (3/12). These were significantly more frequent in exposed than in unexposed workers (P < 0.01). They also had significantly greater diurnal variation in peak expiratory flow rates (DV-PEFR) than the unexposed workers (P < 0.01). All four amine workers with wheezing reported onset of symptoms after employment at the factory, and all had DV-PEFR greater than 15%, compared to only one control worker (P < 0.01). A second case of occupational asthma was confirmed by bronchial challenge test. The study indicated a very high risk of asthma and chronic airways disease and a need for stringent measures to protect the health of industrial workers exposed to aliphatic amines in Singapore.

Cyanoacrylates are a rare cause of occupational asthma, there being only six cases reported previously. High humidity has been implicated to be protective in the pathogenesis of the asthma. This is a case report of occupational asthma due to cyanoacrylate glue after working three years in a factory manufacturing doors. Diagnosis was made by history, serial peak flow measurements on and off work and specific inhalation challenge which elicited a delayed bronchoconstrictive response. An unusual feature of this case was the positive reaction to cyanoacrylate despite the high ambient humidity in Singapore.

Previous work from our laboratory has indicated that mechanoreceptor feedback from the respiratory muscles may play an important role in arousal and apnea termination in obstructive sleep apnea (OSA). Other studies have pointed to a prominent role for chemoreceptor stimuli. We postulated that mechanoreceptor stimuli from the respiratory system are the primary determinant of apnea termination, and that chemoreceptor stimuli exert their effect indirectly through stimulation of ventilation and thus proprioceptive feedback. To test this, we measured the diaphragmatic tension-time index (TTdi) during obstructive sleep apneas in seven male subjects with severe untreated OSA. We compared the maximal TTdi values at end-apnea during administration of air, O2, and CO2. We reasoned that if mechanoreceptor stimuli mediate apnea termination, changing the degree of chemoreceptor stimulation during apneas should not alter the level of respiratory effort at end-apnea. O2 administration produced a significant increase in end-apneic arterial oxygen saturation (SaO2) and increased apnea duration. CO2 administration led to an increase in pre- and postapneic end-tidal carbon dioxide pressure (PETCO2), and tended to shorten apneas. However, the mean value for maximal end-apneic TTdi was 0.12 +/- 0.01 (SEM) during room air breathing and was unaltered by O2 (0.12 +/- 0.01) or CO2 (0.11 +/- 0.01) administration. The consistency of end-apneic TTdi values despite the varying chemical drive supports the hypothesis that apnea termination in OSA is mediated by mechanoreceptor feedback from the respiratory system, most likely from the respiratory muscles. The influence of chemoreceptor information may be mediated indirectly through an effect on ventilatory effort.

A 39-year-old man with no past or family history of asthma developed asthmatic symptoms five months after working as a burnisher in a hotel. He polished brass or silverware using "brasso" or "silvo" respectively. He noticed symptoms only when using "silvo". Specific bronchial provocation testing (BPT) to "brasso" was negative. Specific BPT to "silvo" produced a dual asthmatic reaction. Ammonia was present in both polishes. The ammonia-in-air levels during polishing was 8-15 ppm with "silvo" and less than 1 ppm with "brasso". A specific BPT to 12 ppm of ammonia produced an immediate asthmatic reaction. Our opinion is that he had occupational asthma from the ammonia liberated while polishing silverware with "silvo". Ammonia has been reported to cause asthma. However, there have been no previous reports of occupational asthma among burnishers doing silver polishing.

One of the newer occupational diseases in Singapore is occupational asthma. As on 31 December 1990 there were 35 confirmed cases of occupational asthma in the official statistics on occupational disease. We report in this paper our observations and experience based on these cases. The problem of under-reporting and the importance of early diagnosis are discussed.

The role of the pulmonary autonomic nerves in the mediation of respiratory sensation is unclear. Pulmonary neurogenic mechanisms may contribute to dyspnea either directly or indirectly via an influence on the pattern of ventilation. Using human heart-lung transplantation as a model of pulmonary denervation, we studied the ventilatory response, respiratory drive (P0.1), and sensation of breathlessness (modified Borg scale) during maximal incremental bicycle exercise. The subjects were four female heart-lung transplant recipients 3 to 9 months post-transplant and 10 age-matched control subjects. The ventilatory response to increasing CO2 output (VCO2) was higher (p less than 0.001) in transplant recipients than in control subjects, such that ventilation at peak exercise was similar in the two groups despite a lower peak VCO2 in transplant recipients. The ratio of tidal volume to inspiratory capacity increased with increasing ventilation in a similar fashion in both groups. Although the respiratory rate increased more quickly in transplant recipients, it was similar at peak ventilation in the two groups. Ventilatory timing and duty cycle at half-peak and peak ventilation were similar in transplant recipients and control subjects. Dyspnea ratings were not different between the two groups at similar levels of ventilation. Dyspnea as a function of P0.1 was also similar in transplant and control groups. These results indicate that pulmonary neurogenic mechanisms play a role in determining the level, but not the pattern, of ventilation during exercise. Furthermore, these pathways do not appear to contribute significantly to the perception of breathlessness in normal humans.

Patients with sleep apnoea syndrome suffer considerable morbidity and an increased mortality. We reviewed the characteristics of 14 patients with sleep apnoea syndrome (11 males and 3 females) who were studied since 1986. All were less than or equal to 60 years of age with the majority in their 4th and 5th decade. Obesity was present in 8 patients (57%) and hypertension in 6 (43%). Overnight sleep studies showed that 11 patients had obstructive sleep apnoea, 2 had central and one had predominantly mixed sleep apnoea. Ten patients (71%) had some form of nose and/or throat pathology. Tonsillectomy seemed an effective therapeutic procedure in those with upper airway obstruction due to enlarged tonsils. Four out of 5 patients had significant symptomatic improvement post-tonsillectomy. Nasal continuous positive airway pressure was also effective in alleviating apnoeas and relieving symptoms in 4 other patients who had no obvious upper airway obstruction. A high proportion of our patients had obstructive sleep apnoea due to enlarged tonsils. Tonsillectomy offered a simple and effective therapy for such patients. Nasal continuous positive airway pressure was also effective in the treatment of obstructive sleep apnoea.

We studied the effect of maximal exercise on the prevalence of arrhythmias in 122 subjects with severe COPD. At rest, ten subjects had supraventricular arrhythmias while 13 had unifocal VPB greater than or equal to 6/min or ventricular bigeminy. At peak exercise, six subjects had supraventricular arrhythmias while 24 had VAs. Univariate and multivariate analysis with logistic regression did not show relationships between exercise-related cardiac arrhythmias and the severity of pulmonary disease, oxyhemoglobin desaturation or ECG evidence of chronic lung disease. Exercise-related arrhythmias were significantly associated with the presence of arrhythmias at rest and 87 percent of subjects who had no arrhythmias at rest did not have any during exercise. In patients with COPD, the development of potentially serious arrhythmias during exercise is uncommon without clinically apparent CAD or arrhythmias at rest. However, routine cardiac monitoring during exercise testing should not be abandoned in this population since VAs can occur despite their absence at rest.

Aeromonas, a genus of gram-negative bacteria normally found in water and soil, is well established as a pathogen in the animal kingdom. Often considered as a pathogen of low virulence, its role in human infections has recently been recognised. Aeromonas infections in humans range from cellulitis to septicaemia. Endocarditis is rare. We describe here a patient with a chronic liver disease with aeromonas bacteremia and endocarditis.

A prominent feature of the natural history of carcinoma of the lung is that it invariably metastasizes to other organs. The well-known sites include lymph nodes, liver, adrenals, bones and brain. Spread is mainly by lymphatic and haematogenous routes, or by direct extension. However, like many other primary malignancies, the spread of carcinoma of the lung to skeletal muscles is rare. This is despite its bulk and abundant blood supply. Why this is so is unknown. A search of the literature revealed only 3 published case reports of carcinoma of the lung spreading to skeletal muscles. In this paper, we report a case of squamous cell carcinoma of the lung with multiple metastases to skeletal muscles.