bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternariol alleviates breast carcinoma by inhibiting cellular proliferation correlated with increased apoptotic events in rats
Authors: Xin Jian , Shang Yitai
Published: December 2022

The breast cancer is most frequently diagnosed cancer in the women worldwide. Our study investigated the anticancer effect of alternariol, a secondary metabolite originated from endophytic fungi, against DMBA induced breast carcinoma on Wistar rats. The toxicity study investigated the LD50 and the subsequent doses of alternariol for the carcinogenic study. The breast cancer was developed in rats via induction of DMBA (5 mg/kg, i.v.) and the carcinogenic study was continued for 24 weeks. The induction of breast cancer and the chemotherapeutic effect of alternariol were assessed through histopathological analysis of rat mammary tissue, followed by immunohistochemical analysis, cell proliferation assay and apoptosis assay by TUNEL method. The result showed that alternariol therapy decreased the hyperplastic lesions of mammary tissue and restored the normal histopathological characteristics of breast tissue. Furthermore, alternariol treatment downregulated the expression of carcinogenic markers such as PI3K and Akt increased the expression of apoptotic markers including p53, caspase-3 and Bax. Alternariol therapy also decreased the cellular proliferation and enhanced the apoptotic events. In conclusion, the breast cancer progression was significantly reduced via induction of apoptotic events and inhibition of cell propagation which allowed constructing of suitable mechanism for alternariol mediated chemotherapeutic approach.
Hepatitis C virus: Its prevalence, risk factors and genotype distribution in Pakistan
Authors: Saleem Uzma , Aslam Nosheen , Siddique Rida , Iqbal Shabnoor , Manan Maria
Published: December 2022

Hepatitis C is a dangerous liver disease transmitted by Hepatitis C virus (HCV). HCV constitutes an important health issue in Pakistan. In Pakistani setting HCV is found frequently and is recognized as an alarming health problem. In this cross sectional study we reviewed published data regarding the seroprevalence of hepatitis C in general community, blood donors and pregnant females and risk factors linked with its occurrence in Pakistan. Data retrieved from163 studies published from 2001 to 2022 was utilized and weighted mean was calculated. Data of 1,875,232 individuals was collected and arranged into three groups, depending upon the population type such as (1) general population, (2) pregnant women, (3) blood donors. General population (765,426) and blood donors (973,260) formed the most of population. Mean Hepatitis C virus prevalence in general public and blood donors was 16.47% and 8.2% respectively. In pregnant females (136,546) the mean frequency was 9.3%. This study exhibits that the frequency of Hepatitis C in general population, pregnant females and blood donors groups was 11.32%. The data suggested that risks factors for transmitting HCV infection in Pakistan include unsterilized needle use, blood transfusions, shaving by barbers, lack of trained staff, needle stick injuries, injection drug users, household contacts/spousal transmission, unsterilized dental and surgical Instruments, improper disposal of hospital waste, poor infra-structure and others. The frequency of HCV infection is distressing in Pakistan. Health education and awareness programs are needed for decreasing Hepatitis C infection in Pakistan. The data necessitate the implementation of preventive and remedial approaches to decrease the disease load and mortality in Pakistan.
Mental health and neurodevelopment in children and adolescents with Turner syndrome
Authors: Wolstencroft Jeanne , Mandy William , Skuse David
Published: December 2022

Objectives:

Turner syndrome (TS) is a rare sex chromosome aneuploidy, with an incidence of four in 10,000 new-born girls. TS is often associated with impaired social communication skills, but the extent to which these are attributable to Autism Spectrum Disorders (ASD) is uncertain. We made standardized assessments of the mental health and associated neurodevelopmental disorders in children and adolescents with TS and report on the prevalence of concurrent conditions.

Methods:

Our sample comprised 127 girls with TS, 5–19 years of age. We obtained reports of their mental health from a combination of diagnostic interview (the Development and Wellbeing Assessment (DAWBA)), from the Strengths and Difficulties Questionnaire (SDQ) and from the Social Responsiveness Scale (SRS-2). Sources of information included parents, teachers and self-reports. The prevalence of mental health disorders in this sample was compared with age/sex matched national English data from typical controls.

Results:

Most individuals with TS (83%) had experienced significant social communication difficulties and nearly one in four (23%) met diagnostic criteria for ASD on the DAWBA. One-third (34%) had at least one mental health or neurodevelopmental condition, and those girls with an ASD were at a greater risk of a co-occurring emotional disorder and/or attention deficit hyperactivity disorder (ADHD).

Conclusion:

Children and adolescents with TS are substantially more likely to meet criteria for ASD than their typically developing peers. Our finding has clinical implications for appropriate behavioural management from preschool through to adolescence.
Prediction of gait independence using the Trunk Impairment Scale in patients with acute stroke
Authors: Ishiwatari Masahiro , Tani Mami , Isayama Reina , Honaga Kaoru , Hayakawa Masato , Takakura Tomokazu , Tanuma Akira , Kurosu Akihiro , Hatori Kozo , Wada Futoshi , Fujiwara Toshiyuki
Published: December 2022

Background:

Gait recovery is one of the primary goals of stroke rehabilitation. Gait independence is a key functional component of independent activities in daily living and social participation. Therefore, early prediction of gait independence is essential for stroke rehabilitation. Trunk function is important for recovery of gait, balance, and lower extremity function. The Trunk Impairment Scale (TIS) was developed to assess trunk impairment in patients with stroke.

Objective:

To evaluate the predictive validity of the TIS for gait independence in patients with acute stroke.

Methods:

A total of 102 patients with acute stroke participated in this study. Every participant was assessed using the TIS, Stroke Impairment Assessment Set (SIAS), and Functional Independence Measure (FIM) within 48 h of stroke onset and at discharge. Gait independence was defined as FIM gait scores of 6 and 7. Multiple regression analysis was used to predict the FIM gait score, and multiple logistic regression analysis was used to predict gait independence. Cut-off values were determined using receiver operating characteristic (ROC) curves for variables considered significant in the multiple logistic regression analysis. In addition, the area under the curve (AUC), sensitivity, and specificity were calculated.

Results:

For the prediction of the FIM gait score at discharge, the TIS at admission showed a good-fitting adjusted coefficient of determination ( R2 = 0.672, p < 0.001). The TIS and age were selected as predictors of gait independence. The ROC curve had a TIS cut-off value of 12 points (sensitivity: 81.4%, specificity: 79.7%) and an AUC of 0.911. The cut-off value for age was 75 years (sensitivity: 74.6%, specificity: 65.1%), and the AUC was 0.709.

Conclusion:

The TIS is a useful early predictor of gait ability in patients with acute stroke.
Forecasting thermoacoustic instabilities in liquid propellant rocket engines using multimodal Bayesian deep learning
Authors: Sengupta Ushnish , Waxenegger-Wilfing Günther , Martin Jan , Hardi Justin , Juniper Matthew P.
Published: December 2022

We present a method that combines multiple sensory modalities in a rocket thrust chamber to predict impending thermoacoustic instabilities with uncertainties. This is accomplished by training an autoregressive Bayesian neural network model that forecasts the future amplitude of the dynamic pressure time series, using multiple sensor measurements (injector pressure/ temperature measurements, static chamber pressure, high-frequency dynamic pressure measurements, high-frequency OH* chemiluminescence measurements) and future flow rate control signals as input. The method is validated using experimental data from a representative cryogenic research thrust chamber. The Bayesian nature of our algorithms allows us to work with a dataset whose size is restricted by the expense of each experimental run, without making overconfident extrapolations. We find that the networks are able to accurately forecast the evolution of the pressure amplitude and anticipate instability events on unseen experimental runs 500 milliseconds in advance. We compare the predictive accuracy of multiple models using different combinations of sensor inputs. We find that the high-frequency dynamic pressure signal is particularly informative. We also use the technique of integrated gradients to interpret the influence of different sensor inputs on the model prediction. The negative log-likelihood of data points in the test dataset indicates that prediction uncertainties are well-characterized by our model and simulating a sensor failure event results in a dramatic increase in the epistemic component of the uncertainty, as would be expected when a Bayesian method encounters unfamiliar, out-of-distribution inputs.
Determinants of neonatal hypoglycemia among neonates admitted at Hiwot Fana Comprehensive Specialized University Hospital, Eastern Ethiopia: A retrospective cross-sectional study
Authors: Sertsu Addisu , Nigussie Kabtamu , Eyeberu Addis , Tibebu Abel , Negash Abraham , Getachew Tamirat , Debella Adera , Dheresa Merga
Published: December 2022

Objective:

The study aimed to assess the magnitude and determinants of neonatal hypoglycemia among neonates admitted to the Neonatal Intensive Care Unit at Hiwot Fana Specialized University Hospital, Eastern Ethiopia.

Methods:

An institutional-based cross-sectional study was conducted among 698 randomly selected neonates at Hiwot Fana Comprehensive Specialized Hospital from 1 January 2018 to 31 December 2020. By looking at the charts, data were gleaned from the medical records. Data were entered into Epi-Data version 3.1 and analysis was performed using SPSS version 22. Bivariable and multivariable logistic regression analyses were conducted to identify determinant factors of neonatal hypoglycemia. Association was described using an adjusted odds ratio along with a 95% CI. Finally, a p-value <0.05 in the adjusted analysis was considered to declare a statistically significant association.

Results:

Out of 698 neonates, 148 (21.2%; 95% CI: 18.3, 24.5) neonates had hypoglycemia. Preterm birth (AOR = 3.06; 95% CI: 1.02, 9.17), hypothermia (AOR = 2.65; 95% CI: 1.22, 5.75), neonatal sepsis (AOR = 2.61; 95% CI: 1.03, 6.59), diabetic mother (AOR = 2.34; 95% CI: 1.03, 5.33), and delay in initiation of breastfeeding for more than 1 h (AOR = 3.89; 95% CI: 1.17, 12.89) were identified as determinant factors of neonatal hypoglycemia.

Conclusion:

The magnitude of neonatal hypoglycemia was quite common among neonates. Neonatal hypoglycemia was found to be predicted by preterm birth, hypothermia, neonatal sepsis, maternal diabetes mellitus, and delay in starting nursing. We therefore strongly suggest health-care workers work in the postnatal unit to manage and control these and other determinant factors of hypoglycemia to prevent the occurrence of neonatal hypoglycemia.
Associations between smartphone keystroke dynamics and cognition in MS
Authors: Chen Michelle H , Leow Alex , Ross Mindy K , DeLuca John , Chiaravalloti Nancy , Costa Silvana L , Genova Helen M , Weber Erica , Hussain Faraz , Demos Alexander P
Published: December 2022

Objective

Examine the associations between smartphone keystroke dynamics and cognitive functioning among persons with multiple sclerosis (MS).

Methods

Sixteen persons with MS with no self-reported upper extremity or typing difficulties and 10 healthy controls (HCs) completed six weeks of remote monitoring of their keystroke dynamics (i.e., how they typed on their smartphone keyboards). They also completed a comprehensive neuropsychological assessment and symptom ratings about fatigue, depression, and anxiety at baseline.

Results

A total of 1,335,787 keystrokes were collected, which were part of 30,968 typing sessions. The MS group typed slower ( P < .001) and more variably ( P = .032) than the HC group. Faster typing speed was associated with better performance on measures of processing speed ( P = .016), attention ( P = .022), and executive functioning (cognitive flexibility: P = .029; behavioral inhibition: P = .002; verbal fluency: P = .039), as well as less severe impact from fatigue ( P < .001) and less severe anxiety symptoms ( P = .007). Those with better cognitive functioning and less severe symptoms showed a stronger correlation between the use of backspace and autocorrection events ( P < .001).

Conclusion

Typing speed may be sensitive to cognitive functions subserved by the frontal–subcortical brain circuits. Individuals with better cognitive functioning and less severe symptoms may be better at monitoring their typing errors. Keystroke dynamics have the potential to be used as an unobtrusive remote monitoring method for real-life cognitive functioning among persons with MS, which may improve the detection of relapses, evaluate treatment efficacy, and track disability progression.
Stakeholders’ perceptions of equity in providing special education and inclusive education services in China: Zero rejection and multiple provision mechanisms
Authors: Alduais Ahmed , Deng Meng
Published: December 2022

A zero-rejection policy was adopted by the Chinese government to ensure that educational services are accessible to learners with a range of different needs. This included multiple provision mechanisms to ensure equal learning opportunities and a sense of belonging. This study highlights the existing gaps between males and females, basic and primary schools versus high and vocational schools, as well as urban and rural areas. Interviews with nine Chinese stakeholders provided insightful perspectives as attributions for such observed gaps. Several factors can explain the gender difference, including social (parents prefer to keep girls at home), biological (men are more vulnerable to disabilities), and demographic (males outnumber females). The disparity between rural and urban areas is caused by the movement of workers towards industrialized areas in search of work and thereby increasing the number of learners, requiring additional educational facilities. There are many rural areas that are scattered over a large distance which makes it difficult to open schools in all places. The enrolment is likely to be higher in primary and middle schools due to free compulsory education since parents tend to have difficulties managing tuition fees and living expenses for younger children attending high or vocational schools.
Molecular biomarkers predicting newly detected atrial fibrillation after ischaemic stroke or TIA: A systematic review
Authors: Ward Kirsty , Vail Andy , Cameron Alan , Katan Mira , Lip Gregory YH , Dawson Jesse , Smith Craig J , Kishore Amit K
Published: December 2022

Background:

Several molecular biomarkers are available that predict newly detected atrial fibrillation (NDAF). We aimed to identify such biomarkers that predict NDAF after an Ischaemic stroke (IS)/Transient Ischaemic Attack (TIA) and evaluate their performance.

Methods:

A systematic review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies of patients with IS, TIA, or both, who underwent ECG monitoring for ⩾24 h, which reported molecular biomarkers and frequency of NDAF after electronic searches of multiple databases were included.

Results:

Twenty-one studies (76% IS, 24% IS and TIA) involving 4640 patients were included. Twelve biomarkers were identified, with cardiac biomarkers evaluated in the majority (75%) of patients. Performance measures were inconsistently reported. Among cohorts selecting high-risk individuals (12 studies), the most studied biomarkers were N-Terminal-Pro Brain Natriuretic Peptide (NT-ProBNP, five studies; C-statistics reported by three studies, 0.69–0.88) and Brain Natriuretic Peptide (BNP, two studies; C-statistics reported in two studies, 0.68–0.77). Among unselected cohorts (nine studies), the most studied biomarker was BNP (six studies; C-statistics reported in five studies, 0.75–0.88). Only BNP was externally validated (two studies) but using different thresholds to categorise risk of NDAF.

Conclusion:

Cardiac biomarkers appear to have modest to good discrimination for predicting NDAF, although most analyses were limited by small, heterogeneous study populations. Their clinical utility should be explored further, and this review supports the need to assess the role of molecular biomarkers in large prospective studies with standardised selection criteria, definition of clinically significant NDAF and laboratory assays.
Knee Multiligament Reconstruction: ACL / PCL / MCL
Authors: Quinn Courtney , Ignozzi Anthony J. , Taleghani Eric , Miller Mark
Published: December 2022

Background:

Multiligament knee injury (MLKI) is a rare, complex injury that requires surgical intervention. However, there is a lack of consensus regarding optimal timing, staging, and graft choice for ligament reconstruction.

Indications:

Delayed, single-stage reconstruction offers the advantage of attaining improved preoperative range of motion and potential healing of extra-articular ligaments and may be necessary in the setting of multitrauma.

Technique Description:

A hamstring graft was harvested and diagnostic arthroscopy performed. Three posterior portals were made for posterior cruciate ligament (PCL) reconstruction. Femoral and tibial pins were placed for both PCL and anterior cruciate ligament (ACL) tunnels, positions confirmed with fluoroscopy, and tunnels drilled over the pins. The Achilles allograft was shuttled through the femoral and tibial PCL tunnels in anterograde fashion and fixed with a metal interference screw on the femoral side. The hamstring autograft was passed through the ACL tunnels and suspended on the femoral side. Tibial fixation of both grafts was achieved with biocomposite interference. Medial collateral ligament reconstruction was performed through the medial incision from hamstring harvesting. The semitendinosis allograft was passed and fixed with screws and spiked washers. Fluoroscopy confirmed that screw trajectory did not interfere with the ACL or PCL tunnels.

Results:

Bagherifard et al reported a study of 41 consecutive patients with MLKI who underwent single-stage reconstruction with autograft and/or allograft. Mean postoperative Lysholm and International Knee Documentation Committee (IKDC) scores were 86.9 and 70, respectively, and only 7 patients experienced restricted range of motion. Billieres et al reported a study of 23 patients with MLKIs who underwent single-stage reconstruction with allograft only. Mean postoperative Lysholm and IKDC scores were 77.3 and 67.2, respectively, and 19 patients returned to sport. Goyal et al reported a study of 27 patients with MLKI who underwent single-stage reconstruction greater than 6 weeks after injury. At 2 years, there were significant improvements in Visual Analog Scale, IKDC, and Lysholm scores, and no patients had residual laxity of the knee joint.

Discussion/Conclusion:

Single-stage reconstruction of MLKIs is an effective intervention that has been supported in literature; however, further studies are necessary to determine optimal surgical timing and graft type. The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Short term effect of intermittent negative pressure ventilation in COPD patients with respiratory failure
Authors: Ambrosino N , Montagna T , Nava S , Negri A , Brega S , Fracchia C , Zocchi L , Rampulla C
Published: December 2022

Ten patients with stable chronic obstructive pulmonary disease (COPD) and hypercapnic respiratory failure were randomly submitted to intermittent negative pressure ventilation (INPV) 6 h per day for 5 consecutive days by either a cuirass or pneumo wrap ventilator. The effects were assessed by measurements of spirometry, blood gases, maximal inspiratory (MIP) and expiratory (MEP) pressures, 12 minutes walking distance test (12 mwd), sensation of dyspnoea by a visual analogue scale (VAS) and diaphragmatic electromyographic activity (Edi). Edi was recorded during INPV sessions in only 7 patients. The same measurements apart from Edi were also performed in 8 matched control patients randomly submitted to conventional physiotherapy. During INPV, Edi activity was reduced, at least temporarily down to 50% of baseline values. Comparison of baseline with post INPV values showed no changes in thoracic gas volume (TGV), forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC), arterial oxygen partial pressure (Pao2) and MEP; significant improvements were seen in MIP, vital capacity (VC), VAS, and 12 mwd only in patients submitted to INPV. A significant improvement in PaCO2 was observed in both groups of patients. We conclude that INPV may be effective in improving the functional reserve of the inspiratory muscles in selected COPD patients with hypercapnic respiratory failure and signs of inspiratory muscle dysfunction.
The pattern of resting breathing in patients with upper airway obstruction
Authors: Sanchis J , Diez-Betoret JL , Casan P , Milic-Emili J
Published: December 2022

The flow-time curve of resting breathing was recorded in 14 patients (aged 36 +/- 16 yrs) with mild to moderate symptoms of upper airway obstruction (UawO) and compared to that of 28 matched, healthy controls (HC) in order to characterize the breathing pattern of such patients. The inspiratory time over total time (TI/Ttot) was higher in the patients (0.42; SD 0.04) than in HC (0.37; SD 0.04) (p less than 0.001), and tidal volume (VT) over TI was lower in patients (0.37; SD 0.07 l.s-1) than in HC (0.43; SD 0.09 l.s-1) (p less than 0.01). Inspiratory and expiratory peak flows at rest were also lower in the patients (p less than 0.001). In these, the mean to peak flow ratio of inspiration (0.74; SD 0.07) was higher than in HC (0.66; SD 0.04) (p less than 0.0005). This indicates a more rectangular wave of inspiration in the patients. All of these changes may be due to the increased inspiratory load. However, since the patients were breathing at rest with VT and flows far below their values on the maximal flow volume loop, the changes can also be interpreted as adaptive rather than imposed by absolute mechanical limitations.
Choline magnesium trisalicylate in patients with aspirin-induced asthma
Authors: Szczeklik A , Nizankowska E , Dworski R
Published: December 2022

Treatment of inflammatory diseases of asthmatics can be a serious problem since some patients show intolerance to aspirin and other non-steroidal, anti-inflammatory drugs that are cyclooxygenase inhibitors. Salicylates were believed to be well tolerated, but recent reports have demonstrated that diflunisal and salicylsalicylic acid can precipitate asthma attacks in aspirin-intolerant patients. This study was designed to determine the tolerance of choline magnesium trisalicylate (CMT), a nonacetylated salicylate with potent analgesic and anti-inflammatory activity, in 23 asthmatics with aspirin hypersensitivity confirmed by oral challenge. The study consisted of three phases: 1) patients received increasing doses (50-1,500 mg) of CMT under a single-blind protocol; 2) patients received either a placebo or CMT challenge in a double-blind, randomized, cross-over design; 3) patients received CMT at daily 3,000 mg doses for 1 week. Throughout the study, pulmonary function tests, peak nasal inspiratory flow, and serum salicylate and thromboxane B2 (TXB2) levels were monitored. Results showed no airway obstruction, nasal congestion or rhinorrhea after CMT. There was no significant decrease in serum TXB2 levels, indicating the absence of cyclooxygenase inhibition with CMT. We conclude that choline magnesium trisalicylate is a safe drug for treatment of different anti-inflammatory disorders in asthmatics with aspirin hypersensitivity.
Pulmonary hypertension and fenfluramine
Authors: Pouwels HM , Smeets JL , Cheriex EC , Wouters EF
Published: December 2022

Fenfluramine is a widely prescribed anorectic drug as adjuvant therapy for obesity. Pulmonary vascular hypertension after use of fenfluramine is rarely reported. We present a patient with pulmonary hypertension and right heart failure after treatment with fenfluramine. Pulmonary hypertension resolved after withdrawal of the drug.
Enhanced reactivity to bradykinin, angiotensin I and the effect of captopril in the pulmonary vasculature of chronically hypoxic rats
Authors: Russell PC , Emery CJ , Cai YN , Barer GR , Howard P
Published: December 2022

We compared the reactivity of pulmonary vessels to bradykinin (BK) and angiotensin I (AI) in normal and chronically hypoxic rats; the latter have pulmonary hypertension and muscularized pulmonary arterioles. These peptides are respectively inactivated and activated by the angiotensin converting-enzyme (ACE) on pulmonary endothelium. Isolated lungs were perfused at a constant flow rate when changes in pulmonary artery pressure (Ppa) reflect changes in vascular resistance. Dose-response curves to BK (1 ng-10 micrograms) were derived during normoxia and pre-constriction by hypoxia; BK both decreased and increased vascular resistance, i.e. vasodilation and vasoconstriction. In normal rats only constriction was seen in normoxia, which reflected low basal vascular tone, whereas in chronically hypoxic rats there was only dilatation which reflected high basal vascular tone. In hypoxia in normal rats, low doses caused dilatation, high doses constriction; in chronically hypoxic rats there was again only dilatation which was larger than in controls. After the ACE-inhibitor captopril, constriction was exaggerated in control rats in both normoxia and hypoxia and took place in chronically hypoxic rats after high doses in both normoxia and hypoxia; oedema often followed. Dose-response curves to AI (1 ng-micrograms) in normoxia showed greatly enhanced pressor responses in chronically hypoxic compared with normal rats, probably attributable to increased sensitivity to angiotensin II (AII) rather than enhanced conversion of AI to AII. Captopril caused a proportionate reduction in responses in both groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of nonsteroidal anti-inflammatory drugs on the bronchial hyperresponsiveness of middle-aged male smokers
Authors: Lim TK , Turner NC , Watson A , Joyce H , Fuller RW , Pride NB
Published: December 2022

Bronchial hyperresponsiveness (BHR) in smokers is believed to be a consequence of airway wall inflammation. We have examined the effects of treatment with nonsteroidal anti-inflammatory drugs (NSAID) on BHR to inhaled histamine, measured as the provocative concentration reducing forced expiratory volume in one second (FEV1) by 20% (PC20), in middle-aged male cigarette smokers in two separate double-blind, placebo-controlled, cross-over trials. Baseline FEV1 in these smokers ranged from 41-117% predicted values. In the first study 15 men (mean age 58 yrs, FEV1 2.20 l) were examined before and one hour after a single dose of 1.2 g aspirin. There was no significant change in PC20 (geometric mean 1.88 mg.ml-1 pre-aspirin, 1.89 mg.ml-1 post-aspirin) or baseline FEV1 and we observed no tachyphylaxis to the effects of inhaled histamine at one hour after placebo. In the second study 10 men (mean age 60 yrs, FEV1 2.53 l) were examined before and after three days' treatment with the NSAID flurbiprofen 50 mg t.d.s. Baseline PC20 was higher in this group than in the first study. There was no relationship between the excretion of urinary thromboxane metabolites and the intensity of BHR under baseline conditions; flurbiprofen greatly reduced the urinary excretion of thromboxane metabolites, but baseline FEV1 was not altered. Analysis of change in PC20 was complicated by a difference in baseline PC20 before the two treatments, but treatment with flurbiprofen did not significantly attenuate BHR. The results suggest that thromboxane or other cyclo-oxygenase products of arachidonic acid metabolism do not play an important role in the short-term maintenance of BHR to histamine in middle-aged male cigarette smokers.
Azithromycin concentrations at the sites of pulmonary infection
Authors: Baldwin DR , Wise R , Andrews JM , Ashby JP , Honeybourne D
Published: December 2022

Azithromycin is a new macrolide antimicrobial. The distribution to the potential sites of pulmonary infection was assessed after the administration of a single 500 mg oral dose to 22 patients undergoing fibreoptic bronchoscopy. Concentrations of azithromycin in sputum, bronchial mucosa, eptihelial lining fluid (ELF) and alveolar macrophages (AM) were determined at intervals up to 96 h after dosing. The mean serum concentration was low at 12 h (0.13 micrograms.ml-1, SEM 0.05) but was still detectable at 96 h (0.01 micrograms.ml-1). In contrast, peak sputum ELF, bronchial mucosal and AM levels were found at 48 h. Bronchial mucosal concentrations were significantly greater than ELF concentrations, which were in turn greater than sputum concentrations. Mean peak AM concentrations were sixfold greater than bronchial mucosal concentrations (23 micrograms.ml-1, SEM 5.1 and 3.89 micrograms.ml-1, SEM 1.2, respectively). The high intracellular concentrations indicate that azithromycin is likely to be effective for sensitive intracellular pathogens and the favourable penetration into sputum, ELF and bronchial mucosa suggest that it should be useful in pneumonia and bronchial infections.
Carbamazepine and the lung
Authors: Barreiro B , Manresa F , Valldeperas J
Published: December 2022

A 69 yr old man was admitted with a 10 day history of fever, arthromyalgia, dyspnoea, dry cough and pleuritic pain. Temperature was 38 degrees C; tachypnoea 36 rpm. Extensive crackles were audible over both upper lung fields. Chest X-ray showed bilateral alveolar infiltrates. Forced vital capacity was 49% of predicted, and carbon monoxide transfer coefficient was 32% of predicted value. The patient had been taking carbamazepine for one month because of a trigeminal neuralgia. After withdrawal of the drug he gradually recovered.
The relative contribution of bronchoalveolar macrophages and neutrophils to lucigenin- and luminol-amplified chemiluminescence
Authors: Ward C , Kelly CA , Stenton SC , Duddridge M , Hendrick DJ , Walters EH
Published: December 2022

The relationship between differential cell counts and latex-stimulated luminol and lucigenin-amplified chemiluminescence (CL) was investigated by mixing alveolar macrophages (AM) obtained at bronchoalveolar lavage (BAL) with allogeneic peripheral blood neutrophils (PMN) in varying proportions. In 5 non-asthmatic subjects, the mean luminol-amplified CL increased linearly from 2.1 (0.9 SEM) x 10(5) counts per second (cps) with less than 2% PMN, greater than 96% AM to 47.3 (11.1 SEM) x 10(5) cps with greater than 94% PMN, 0% AM (r = 0.996, p less than 0.001). The regression had a y-intercept indistinguishable from 0 cps, suggesting that luminol-amplified CL exclusively reflected PMN activity. Using the same technique, the mean lucigenin-amplified CL showed a fall from 35 (2.3 SEM) x 10(5) cps with a cell population of greater than 96% AM, less than 2% PMN to 20 (2.3 SEM) x 10(5) cps with 0% AM, greater than 94% PMN. Both PMN and AM appeared to contribute to lucigenin-amplified CL, with AM contributing approximately 1.7 times as much activity per cell as PMN. Lucigenin-amplified CL appeared to be an appropriate technique for measuring AM activity when the proportion of PMN in mixed cell populations was small. A linear relationship was found between percent PMN count and luminol-amplified CL measured in a mixed BAL cell population from asthmatic subjects (p less than 0.01) and non-asthmatic controls (p less than 0.01). The slope of this regression line was significantly greater for subjects with asthma than for control subjects (p less than 0.01), suggesting a uniform increase in PMN activity in cells obtained from asthmatic airways.
Bronchial epithelium in humans recently recovering from respiratory infections caused by influenza or mycoplasma
Authors: Soderberg M , Hellstrom S , Lundgren R , Bergh A
Published: December 2022

Sixty three bronchial mucosal biopsies were collected from 12 patients recovering from respiratory infections with influenza virus (n = 8) and Mycoplasma (n = 4). The bronchoscopy was performed within 1-6 wks from the onset of symptoms. Of the 63 biopsies prepared for light microscopy, 27 biopsies from the influenza patients and 10 from the Mycoplasia patients were further analysed at the light and electron microscope level. The epithelium and the underlying stroma was analysed morphometrically and the results were compared to those of 39 biopsies from 27 healthy subjects. A slightly raised bronchial reactivity was noted in two patients. In the influenza patients the epithelial height was greater compared to that of the healthy subjects and subepithelial lymphocytosis was noted. Areas with damaged epithelium, epithelium shedding, and occasionally a thickened basement membrane, considered typical for asthma, occurred in both infected groups, and in the biopsies of the healthy subjects.
Effect of positive expiratory pressure mask physiotherapy (PEP) versus forced expiration technique (FET/PD) on regional lung clearance in chronic bronchitics
Authors: van Hengstum M , Festen J , Beurskens C , Hankel M , Beekman F , Corstens F
Published: December 2022

On theoretical grounds it is assumed that positive expiratory pressure mask physiotherapy (PEP) as a means of promoting mucus clearance is especially effective in the more distal airways. In a randomized cross-over trial including a control measurement the effect of PEP and of the forced expiration technique combined with postural drainage (FET/PD) on regional lung clearance was evaluated in seven patients with chronic bronchitis and abundant sputum production (mean 32 g.day-1). PEP consisted of positive expiratory pressure mask breathing interspersed with breathing exercises, forced expiration manoeuvres (huffing) and, if necessary, coughing. FET consisted of breathing exercises, huffing and also, if necessary, coughing. FET was combined with PD. Following inhalation of a radio-aerosol regional lung clearance was estimated by means of gamma camera imaging. The results after PEP appeared to be not significantly different from control. The mean clearance in all three lung zones (peripheral, intermediate and inner) was largest after FET/PD as compared with PEP and control. Statistical significance (p less than 0.02) was reached only for clearance in the inner region. It is concluded that PEP has no demonstrable effect on regional lung clearance in these patients.
Occurrence of breathing disorders during CPAP administration in obstructive sleep apnoea syndrome
Authors: Marrone O , Stallone A , Salvaggio A , Milone F , Bellia V , Bonsignore G
Published: December 2022

The spectrum of breathing events during sleep in patients with obstructive sleep apnoea syndrome (OSAS) after the abolition of obstructive apnoeas has been extensively studied in tracheostomized patients, but has received much less attention in patients submitted to continuous positive airway pressure (CPAP). We analysed the breathing pattern during sleep in forty patients while CPAP was administered. A regular breathing pattern throughout the sleep study was observed in 15 patients. In the remaining 25 subjects, one or more of the following events was observed: central apnoeas, hypopnoeas, periodic breathing, prolonged oxyhaemoglobin desaturations. Central apnoeas during non-rapid eye movement (NREM) sleep appeared almost exclusively after arousals or wakefulness periods; their prevalence did not significantly differ between subjects who showed and who did not show similar events before CPAP. Central apnoeas in rapid eye movement (REM) sleep had a random occurrence. Hypopnoeas were found only in REM sleep, and, like central apnoeas, occurred randomly; in one patient they had a prolonged duration (up to 110 s). Periodic breathing was observed in only two subjects, one of whom had congestive heart failure: it was limited to NREM sleep and was not associated with arousals or shifts in sleep stage. Prolonged oxyhaemoglobin desaturations were found mainly in REM sleep; most subjects with such abnormalities had daytime blood gas alterations. In conclusion, abnormalities of the breathing pattern of patients with OSAS can be observed during CPAP and after tracheostomy, but periodic breathing is less common than is reported after tracheostomy, and is probably caused by different mechanisms.
Consequences of poor compliance in chronic respiratory diseases
Authors: Siafakas NM , Bouros D
Published: December 2022

In this short report, we reviewed the literature on the consequences of poor compliance in chronic respiratory diseases. Unquestionably, poor compliance is a very significant medical issue in the management of tuberculosis. Poor compliance could cause serious personal and public health problems and is probably the major obstacle to the elimination of tuberculosis. Similarly, important consequences have been attributed to poor compliance with prescribed treatment in bronchial asthma. Those consequences could vary from impairment of daily life to life threatening attacks and death. However, it is difficult to apply methods to produce solid evidence that such consequences are the result of poor compliance. In conclusion a greater number of well designed studies are needed to investigate the various consequences of poor compliance in chronic respiratory diseases; a major issue that undoubtedly affects the outcome of treatment.
Can measurement of peak expiratory flow enhance compliance in chronic asthma?
Authors: Gregg I
Published: December 2022

Almost all patients with chronic asthma will derive benefit from self-measurement of PEF. Unquestionably, this is of value for educating patients about their disease and treatment, leading in turn to improved compliance. It will be several years before it becomes clear what proportion of patients are willing to manage their asthma themselves and are sufficiently competent in the interpretation of their measurement of PEF to do so safely. It remains to be seen what effect greater use of PEF measurement by patients will have upon present levels of morbidity and mortality from asthma.
Influence of boundary conditions on acoustic emission propagation characteristics of Zelkova schneideriana
Authors: Zhao Yue , Li Ming , Fang Saiyin , Zhang Shaochun , Huang Changlin , Deng Tingting , Mao Feilong , Qin Gezhou , Zhu Daigen
Published: December 2022

To study the propagation characteristics of acoustic emission signals in Zelkova schneideriana under different boundary conditions, three types of boundary conditions were generated by applying aluminum plates and sound-absorbing cotton on the surface of Zelkova schneideriana specimens. Firstly, the sudden and continuous acoustic emission (AE) sources were simulated by PLB (pencil–lead break) tests and signal generator on the specimen surface, and the AE signals were collected by 5 sensors equally spaced on the surface of the specimen, and the sampling frequency was set to 500 kHz. Then, the detailed signals of different frequency bands were obtained by wavelet decomposition, and TDOA (the time difference of arrival) and correlation analysis method were used to calculate the time difference of longitudinal wave and surface transverse wave and the corresponding propagation velocity, respectively. Finally, the pulse trains with different energy levels generated by the signal generator were used as AE sources to study the attenuation law of AE signal energy with distance under different boundary conditions. The results show that the boundary changes can lead to a significant increase in the surface transverse wave velocity, and have no significant effect on the longitudinal wave velocity. At the same time, the energy attenuation of surface and longitudinal waves is faster after the aluminum plate and sound-absorbing cotton are affixed, and the distance of longitudinal waves attenuation to 90% is reduced from 186 to 139 mm, and the distance of surface transverse waves propagation is reduced from 312 to 226 mm.
MF-094 nanodelivery inhibits oral squamous cell carcinoma by targeting USP30
Authors: Zhang Xinyu , Han Yong , Liu Shuli , Guo Bing , Xu Shengming , He Yue , Liu Liu
Published: December 2022

Background

Oral squamous cell carcinoma (OSCC) is a common head and neck cancer, and the incidence of OSCC is increasing. As the mortality of OSCC keeps increasing, it is crucial to clarify its pathogenesis and develop new therapeutic strategies.

Methods

Confocal laser scanning microscopy was used to evaluate the uptake of nanoparticles (NPs). The potential functions of USP30 were evaluated by cell counting kit (CCK)-8, flow cytometry, biochemical assay, coimmunoprecipitation, qRT–PCR, and immunoblotting. The antitumor effect of NP-loaded USP30 inhibitor MF-094 was evaluated in vitro and in vivo.

Results

In this study, increased USP30 expression was found in OSCC specimens and cell lines through qRT–PCR and immunoblotting. CCK-8, flow cytometry, and biochemical assay revealed that the deubiquitylated catalytic activity of USP30 contributed to cell viability and glutamine consumption of OSCC. Subsequently, USP30 inhibitor MF-094 was loaded in ZIF-8-PDA and PEGTK to fabricate ZIF-8-PDA-PEGTK nanoparticles, which exhibited excellent inhibition of cell viability and glutamine consumption of OSCC, both in vitro and in vivo.

Conclusion

The results indicated the clinical significance of USP30 and showed that nanocomposites provide a targeted drug delivery system for treating OSCC.
Comprehensive analysis of pre-mRNA alternative splicing regulated by m6A methylation in pig oxidative and glycolytic skeletal muscles
Authors: Tan Baohua , Zeng Jiekang , Meng Fanming , Wang Shanshan , Xiao Liyao , Zhao Xinming , Hong Linjun , Zheng Enqin , Wu Zhenfang , Li Zicong , Gu Ting
Published: December 2022

Background

Different types of skeletal myofibers exhibit distinct physiological and metabolic properties that are associated with meat quality traits in livestock. Alternative splicing (AS) of pre-mRNA can generate multiple transcripts from an individual gene by differential selection of splice sites. N6-methyladenosine (m6A) is the most abundant modification in mRNAs, but its regulation for AS in different muscles remains unknown. 

Results

We characterized AS events and m6A methylation pattern in pig oxidative and glycolytic muscles. A tota1 of 1294 differential AS events were identified, and differentially spliced genes were significantly enriched in processes related to different phenotypes between oxidative and glycolytic muscles. We constructed the regulatory network between splicing factors and corresponding differential AS events and identified NOVA1 and KHDRBS2 as key splicing factors. AS event was enriched in m6A-modified genes, and the methylation level was positively correlated with the number of AS events in genes. The dynamic change in m6A enrichment was associated with 115 differentially skipping exon (SE-DAS) events within 92 genes involving in various processes, including muscle contraction and myofibril assembly. We obtained 23.4% SE-DAS events (27/115) regulated by METTL3-meditaed m6A and experimentally validated the aberrant splicing of ZNF280D, PHE4DIP, and NEB. The inhibition of m6A methyltransferase METTL3 could induce the conversion of oxidative fiber to glycolytic fiber in PSCs.

Conclusion

Our study suggested that m6A modification could contribute to significant difference in phenotypes between oxidative and glycolytic muscles by mediating the regulation of AS. These findings would provide novel insights into mechanisms underlying muscle fiber conversion.
Evaluation of (sdLDLc*HCYc)/HDLc ratio in clinical auxiliary diagnosis of primary cerebral infarction
Authors: Luo Chunhua , Luo Yucheng , Ma Qin , Chen Chunyan , Xian Sheng , Gong Feng , Zhao Wu , Zeng Jingjing , Luo Jun
Published: December 2022

Background

Timely detection of cerebral infarction is of vital importance in planning intervention effect of rapid rehabilitation. The clinical auxiliary diagnosis value of single biomarker, including small dense low-density lipoprotein concentration (sdLDLc), homocysteine concentration (HCYc) and high-density lipoprotein cholesterol concentration (HDLc) for cerebral infarction has been confirmed by many studies. Whether the use of three biomarkers in combination by calculating (sdLDLc*HCYc)/HDLc ratio could improve the diagnosis ability for primary cerebral infarction remains to be unclear. In the present study, we conducted a cross-sectional study to evaluate the value of (sdLDLc*HCYc)/HDLc ratio in clinical auxiliary diagnosis of primary cerebral infarction.

Methods

A total of 583 participants, including 299 healthy participants as control group and 284 participants diagnosed with first cerebral infarction as experiment group, were included in this respective study. The serum sdLDLc, HDLc and HCYc were measured by peroxidase method, enzyme‐linked immunosorbent assay and an enzymatic method, respectively.

Results

The average concentration of sdLDL and HCY (0.69 ± 0.29 mmol/L and 18.14 ± 6.62 μmol/L) in experiment group was significantly higher than those in the control group (0.55 ± 0.22 mmol/L and 10.77 ± 2.67 μmol/L, P < 0.05). However, the average concentration of HDL (1.47 ± 0.25 mmol/L) in the control group was higher than that in the experiment group (1.33 ± 0.28 mmol/L, P < 0.05). Spearman correlation coefficient showed the three indicators are independent of each other. The positive predictive value of (sdLDLc*HCYc)/HDLc ratio (61.27%, 95% CI: 55.31–66.92) is higher than that in single biomarker (sdLDLc: 6.69 95% CI: 4.19–10.42, HCYc: 38.38%, 95% CI: 32.75–44.33, HDLc: 3.87%, 95% CI: 2.05–7.02). Receiver-operating characteristic curve (ROC) analysis illustrated that predictive power of (sdLDLc*HCYc)/HDLc was higher than single biomarker, including sdLDLc, HCYc and HDLc, in primary cerebral infarction.

Conclusions

Therefore, (sdLDLc*HCYc)/HDLc ratio might be a better new indicator in clinical auxiliary diagnosis of primary cerebral infarction, which could be contributed to predicting cerebral infarction occurrence and provide a scientific basis for early prevention.