Respiratory Abnormalities Research Articles

Systematic review of drug therapy for chorea in NXK2-1-related disorders: Efficacy and safety evidence from case studies and series.

The NKX2-1-related disorders (NKX2-1-RD) is a rare disorder characterized by choreiform movements along with respiratory and endocrine abnormalities. The European Reference Network of Rare Neurological Disorders funded by the European Commission conducted a systematic review to assess drug treatment of chorea in NKX2-1-RD, aiming to provide clinical recommendations for its management. A systematic pairwise review using various databases, including MEDLINE, Embase, Cochrane, CINAHL, and PsycInfo, was conducted. The review included patients diagnosed with chorea and NKX2-1-RD genetic diagnosis, drug therapy as intervention, no comparator, and outcomes of chorea improvement and adverse events. The methodological quality of the studies was assessed, and the study protocol was registered in PROSPERO. Of the 1417 studies examined, 28 studies met the selection criteria, consisting of 68 patients. The studies reported 22 different treatments for chorea, including carbidopa/levodopa, tetrabenazine, clonazepam, methylphenidate, carbamazepine, topiramate, trihexyphenidyl, haloperidol, propranolol, risperidone, and valproate. No clinical improvements were observed with carbidopa/levodopa, tetrabenazine, or clonazepam, and various adverse effects were reported. However, most patients treated with methylphenidate experienced improvements in chorea and reported only a few negative effects. The quality of evidence was determined to be low. The management of chorea in individuals with NKX2-1-RD presents significant heterogeneity and lack of clarity. While the available evidence suggests that methylphenidate may be effective in improving chorea symptoms, the findings should be interpreted with caution due to the limitations of the studies reviewed. Nonetheless, more rigorous and comprehensive studies are necessary to provide sufficient evidence for clinical recommendations.

Abstract 060: Conditional Deletion Of Renin In The Mouse Brain Results In Cardiovascular And Respiratory Abnormalities In Response To Hypoxia Or Autonomic Blockade

Previously, we reported the existence of renin-expressing neurons in the nucleus ambiguus (NuAm), a major autonomic and respiratory center in the brainstem. Within the NuAm, renin is expressed in choline acetyltransferase (ChAT)-positive cardioinhibitory vagal neurons projecting to the cardiac ganglion. Based on this, we hypothesized that ablation of renin specifically in ChAT-positive neurons disrupts normal cardiorespiratory function. Cardiorespiratory function in control (WT) vs. mice lacking renin in cholinergic neurons (Ren-a ChAT-null ) was compared using an integrated radiotelemetry/whole-body plethysmography system. We measured parameters at baseline and upon acute respiratory or pharmacological challenge in males. Using in situ mRNA hybridization, we confirmed that Ren-a ChAT-null exhibit lower expression of renin in the NuAm compared to the WT (Ren-a ChAT-null : 0.7±0.3 vs. WT: 3.9±0.9 arbitrary units, p<0.05, n=4-5). At baseline, there were no major differences in cardiorespiratory function between groups. Therefore, mice were subjected to acute cardiorespiratory challenges. During acute hypoxia (12% O 2 for 10 minutes), Ren-a ChAT-null displayed lower hypoxic ventilatory response compared to WT (1.53±0.04 vs. 1.94±0.10 fold change compared to baseline, p<0.05, n=4). Additionally, Ren-a ChAT-null exhibited exacerbated tachycardia (640±19 vs. 564±11 bpm, p<0.05, n=3-4). Subsequently, when subjected to sympathetic blockade with propranolol (5 mg/kg, ip), Ren-a ChAT-null exhibited an exacerbated bradycardic and hypotensive effect compared to WT (14427±293 vs 15722±498 AUC bpm*min, p<0.05, n=7-9 and 3661±90 vs 3988±78 AUC mmHg*min, p<0.05, n=7-9, respectively). In response to parasympathetic blockade with methyl atropine (2 mg/kg, ip), Ren-a ChAT-null exhibited a lower systolic blood pressure elevation compared to WT (4001±112 vs. 4324±84 AUC mmHg*min, p<0.05; n=7-9). These data suggest that renin in cholinergic neurons exerts a functional physiological role and contributes to maintaining an appropriate cardiorespiratory response to acute stressors. Ongoing studies are currently underway to investigate 1) sex differences and 2) the phenotype of Ren-a ChAT-null mice in chronic conditions such as hypertension.

Audiogenic epileptic DBA/2 mice strain as a model of genetic reflex seizures and SUDEP.

Epilepsy is a chronic neurological disease characterized by abnormal brain activity, which results in repeated spontaneous seizures. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of seizure-related premature death, particularly in drug-resistant epilepsy patients. The etiology of SUDEP is a structural injury to the brain that is not fully understood, but it is frequently associated with poorly controlled and repeated generalized tonic-clonic seizures (GTCSs) that cause cardiorespiratory and autonomic dysfunctions, indicating the involvement of the brainstem. Both respiratory and cardiac abnormalities have been observed in SUDEP, but not much progress has been made in their prevention. Owing to the complexity of SUDEP, experimental animal models have been used to investigate cardiac and/or respiratory dysregulation due to or associated with epileptic seizures that may contribute to death in humans. Numerous rodent models, especially mouse models, have been developed to better understand epilepsy and SUDEP physiopathology. This review synthesizes the current knowledge about dilute brown agouti coat color (DBA/2) mice as a possible SUDEP model because respiratory arrest (RA) and sudden death induced by audiogenic generalized seizures (AGSs) have been observed in these animals. Respiratory/cardiac dysfunction, brainstem arousal system dysfunction, and alteration of the neurotransmitter systems, which are observed in human SUDEP, have also been observed in these mice. In particular, serotonin (5-HT) alteration and adenosine neurotransmission appear to contribute to not only the pathophysiological mechanisms of medication but also seizure-related respiratory dysfunctions in this animal model. These neurotransmitter systems could be the relevant targets for medication development for chronic epilepsy and SUDEP prevention. We reviewed data on AGSs in DBA/2 mice and the relevance of this model of generalized tonic-clonic epilepsy to human SUDEP. Furthermore, the advantages of using this strain prone to AGSs for the identification of possible new therapeutic targets and treatment options have also been assessed.

Preoperative small airway dysfunction is associated with skeletal muscle loss in early-stage non-small cell lung cancer

Postoperative skeletal muscle loss (SM loss) was reported to be associated with a poor prognosis in early-stage non-small cell lung cancer (NSCLC). Small airway dysfunction (SAD) is a common but neglected respiratory abnormality. Little information is known about the association between preoperative SAD and postoperative SM loss in early-stage NSCLC. Therefore, this study aimed to investigate the correlation between preoperative SAD and SM loss after surgery in early-stage NSCLC patients. There were 348 NSCLC patients with stages I-IIIA in this study from January 2017 to December 2020. All CT images were contrast-enhanced scans, and the skeletal muscle index (SMI) was measured using CT images. A 10.0% decrease in SMI over 12 months was determined as the cut-off value to define excessive SM loss. Logistic regression analyses were used to examine the relationship between SAD and SM loss. This study included 348 subjects who underwent pulmonary operation (159 males and 189 females; mean age: 57.5±8.8 years). 152 (43.7%) patients were identified as having SAD before surgery, and 179 patients (51.4%) were identified as having SM loss after 1 year. Moreover, a higher incidence of SAD was found in the SM loss group compared with that in the non-SM loss group (52.0% vs. 34.9%, p=0.001). The patients with SAD were older, had larger tumor size, and had lower albumin levels. Furthermore, there were significant correlations between the lung function parameters manifesting SAD and the percentage change in SMI (for the forced expiratory flow when 75% of forced vital capacity has been exhaled (FEF75%), Pearson r=-0.107, p=0.046; for FEF50%, r=-0.142, p=0.008; and for FEF25-75%, r=-0.124, p=0.021; respectively). However, no significant correlations were found between SMI and the lung function parameters reflecting proximal airway obstruction (p>0.05). Logistic regression analysis revealed that preoperative SAD (HR, 2.465; 95% CI, 1.256-4.838; p=0.009) was independent risk factor for postoperative SM loss in early-stage NSCLC. In addition, multivariable analysis revealed that SAD (HR, 1.816; 95% CI, 1.025-3.216, P=0.041) were associated with postoperative complications. Preoperative SAD is significantly associated with postoperative complications and SM loss in early NSCLC patients. Our results suggest that preoperative assessment of SAD may be useful for risk stratification of surgical candidates with potential for targeted interventions.

E56 A 16-year diagnosis delay of a patient with Pigmented Villonodular Synovitis

Abstract Introduction Pigmented villonodular synovitis (PVNS), a subtype of tenosynovial giant cell tumours, is a rare non-cancerous proliferative synovial disorder usually affecting the knee in adults(1). The incidence rate is 1.8 patients per million people of the general population, with few reports amongst the paediatric population, hence it is frequently misdiagnosed(2). It has a slow onset of symptoms and has been noted to take ∼18 months to make a definitive diagnosis(3). Objective To describe a case of pigmented villonodular synovitis in a seventeen-year-old African female. Methods A retrospective chart review was done to ascertain the clinical presentation and management of the patient. Case description We present a case of a 17-year-old African female who presented with bilateral knee pain and swelling from 10 months of age. She had been on follow-up at a peripheral facility for 14 years, where she was being managed with methotrexate 12.5 mg weekly and folic acid 5 mg OD for Juvenile Idiopathic Arthritis with no marked improvement in her symptoms. In view of her poor response to therapy, the mother stopped her treatment 3 months prior to presentation in our facility. She initially had intermittent bilateral swelling of the small joints of the hand that were tender which eventually evolved to involve both knee joints. The pain was worse in the morning and was associated with the inability to ambulate and occasional night awakening. The systemic inquiry was otherwise unremarkable. She had an unremarkable birth history, and normal developmental milestones. She was however shorter than her peers and had not attained menarche. The patient had been admitted 8–10 times per year during the span of her illness for similar complaints and had undergone multiple knee joint fluid aspirations to relieve the swelling and several laboratory tests and radiological studies were done. On assessment, she was noted to be of fair general condition with gross asymmetric swelling of both knees and a surgical scar over the right knee with no limitation in the range of movement. There was minimal effusion of bilateral elbows and ankles, and the MCP, ICP and wrist joints weren’t affected. The patient had thoracic scoliosis, a grade 3/6 systolic murmur on the left lower sternal border, no radiation, and hepatomegaly 4 cm below the costal margin. She was prepubertal on sexual maturation rating. There was no central nervous system, abdominal, or respiratory abnormalities. A series of lab investigations to exclude the possibility of juvenile idiopathic arthritis were conducted. This panel included a complete blood count, which showed hypochromic, microcytic anaemia, c-reactive protein was raised at 61 mg/l but normal biochemistry and unremarkable autoantibody profile. Imaging done included a bilateral knee X-Ray followed by a bilateral knee MRI which showed large volume bilateral knee joint effusions associated with synovial-based masses causing extrinsic periarticular bony erosions and intra-articular synovial proliferation forming a villonodular appearance. The patient was referred to orthopaedic surgery and bilateral arthrotomy, drainage and synovectomy of both knees were done. She continues to be followed up in our paediatric rheumatology and orthopaedic clinic with good mobility and no other co-morbidities. She is currently undergoing work up for a delayed puberty. Conclusion Pigmented villonodular synovitis is a rare disease in the paediatric population. In the absence of awareness of its existence and expertise on how to diagnose it, patients may be misdiagnosed and mismanaged over a long duration of time as seen in the presented case.

Bagasse dust exposure and chronic respiratory symptoms among workers in the Metehara and Wonji sugar factories in Ethiopia: a longitudinal study design

BackgroundEthiopia’s sugar factories are growing by creating job opportunities for thousands of workers with varying educational, professional and socioeconomic backgrounds. These sugar factories are a source of several hazards that...

The complexities of investigating mitochondria dynamics in multiple sclerosis and mouse models of MS.

Multiple sclerosis (MS) is a demyelinating, degenerating disorder of the central nervous system (CNS) that is accompanied by mitochondria energy production failure. A loss of myelin paired with a deficit in energy production can contribute to further neurodegeneration and disability in patients in MS. Mitochondria are essential organelles that produce adenosine triphosphate (ATP) via oxidative phosphorylation in all cells in the CNS, including neurons, oligodendrocytes, astrocytes, and immune cells. In the context of demyelinating diseases, mitochondria have been shown to alter their morphology and undergo an initial increase in metabolic demand. This is followed by mitochondrial respiratory chain deficiency and abnormalities in mitochondrial transport that contribute to progressive neurodegeneration and irreversible disability. The current methodologies to study mitochondria are limiting and are capable of providing only a partial snapshot of the true mitochondria activity at a particular timepoint during disease. Mitochondrial functional studies are mostly performed in cell culture or whole brain tissue, which prevents understanding of mitochondrial pathology in distinct cell types in vivo. A true understanding of cell-specific mitochondrial pathophysiology of MS in mouse models is required. Cell-specific mitochondria morphology, mitochondria motility, and ATP production studies in animal models of MS will help us understand the role of mitochondria in the normal and diseased CNS. In this review, we present currently used methods to investigate mitochondria function in MS mouse models and discuss the current advantages and caveats with using each technique. In addition, we present recently developed mitochondria transgenic mouse lines expressing Cre under the control of CNS specific promoters to relate mitochondria to disease in vivo.

Abnormal Respiratory Sound Identification Using Audio-Spectrogram Vision Transformer.

Respiratory disease, the third leading cause of deaths globally, is considered a high-priority ailment requiring significant research on identification and treatment. Stethoscope-recorded lung sounds and artificial intelligence-powered devices have been used to identify lung disorders and aid specialists in making accurate diagnoses. In this study, audio-spectrogram vision transformer (AS-ViT), a new approach for identifying abnormal respiration sounds, was developed. The sounds of the lungs are converted into visual representations called spectrograms using a technique called short-time Fourier transform (STFT). These images are then analyzed using a model called vision transformer to identify different types of respiratory sounds. The classification was carried out using the ICBHI 2017 database, which includes various types of lung sounds with different frequencies, noise levels, and backgrounds. The proposed AS-ViT method was evaluated using three metrics and achieved 79.1% and 59.8% for 60:40 split ratio and 86.4% and 69.3% for 80:20 split ratio in terms of unweighted average recall and overall scores respectively for respiratory sound detection, surpassing previous state-of-the-art results.

Does ABO Blood Type Implicate Susceptibility to Respiratory Abnormalities? A Controlled Cross-sectional Study among Indigenous University Students in Rivers State, Nigeria

Background: The blood typing is a genetically defined immune system characteristic that has a well-known role in transplantation and chemotherapy. However, it is unclear what role it could serve in diagnosing or predicting respiratory pathologies. The study aims at investigating the prevalence of respiratory disorder among ABO blood type. This study investigated the prevalence of respiratory disorder among ABO blood types.
 Methods: Using a quantitative survey research design, this cross-sectional study comprises of 102 young University students (64 females and 36 males) within the age of 17-28 years, extracted from different local Government Area in Rivers State. A semi-structured questionnaire was used to gather the social demograpgic characteristics of respondent’s. Anthropometric investigations and respiratory function test was done.
 Results: The prevalent blood types A, B, O, and AB was 19.6%, 16.7%, 56.9%, and 6.9% respectively. BMI showed that 2.9%, 39.2%, 38.2% and 19.6% was underweight, normal weight, overweight and obese respectively. Respiratory problems were distributed unevenly among blood types, with risk of obstructive pulmonary dysfunction having the highest frequency of occurrence.
 Conclusion: The susceptibility to respiratory abnormalities is not associated with any blood type, the risk of obstructive pulmonary disease is higher in blood type O, which is largely influenced by the predominancy.

A rare case of Candida parapsilosis pneumonia in an immunocompetent patient

Introduction: The presence of fungus in an immunocompetent host is usually disregarded as a mere contaminant, as it can be a commensal organism of the skin, gastrointestinal, urogenital, and respiratory tract. Hence, its growth in cultures has to be interpreted within a clinical context. This case illustrates the challenges experienced when diagnosing Candida parapsilosis necrotizing pneumonia, and the importance for considering candida pneumonia as a differential diagnosis for an immunocompetent patient. After a thorough literature review, we would like to present the first case report of C. parapsilosis causing necrotizing pneumonia in an immunocompetent patient. Case Report: We present a case involving a middle-aged smoking male who presented with respiratory and metabolic abnormalities and was found to have necrotizing pneumonia. He was managed for severe sepsis with lactic acidosis, respiratory failure, and severe acute kidney injury (AKI), which improved with broad spectrum antibiotics and fluids. These conditions improved; however, his respiratory distress did not despite a prolonged course of antibiotics. This led to a workup for other causes of necrotizing pneumonia, after which cultures revealed the growth of C. parapsilosis. He was then started on antifungals and subsequently improved. Conclusion: Candida necrotizing pneumonia is a rare disease for an immune-competent individual; however, chronic lung damage in the setting of a smoking history may make individuals more susceptible. This case illustrates the challenges associated when dealing with such a case, and it is the team’s hope that publishing this case will add to awareness. Additionally, this can contribute to improved antibiotic stewardship and earlier diagnosis which will hopefully lead to a shorter hospital stay and improved morbidity and mortality.

Response to Singh et al. 2023: It is premature for a unified hypothesis of sudden unexpected death in epilepsy: A great amount of research is still needed to understand the multisystem cascade.

In response to the comments by Singh and colleagues about our recent paper proposing a unified hypothesis of SUDEP, we definitely agree that more research is needed. This research should include studies in other models, including Dravet mice, emphasized by Singh et al. However, we strongly believe the hypothesis is timely, because it is based on the continuing progress on SUDEP-related research on serotonin (5-HT) and adenosine as well as neuroanatomical findings.We propose testing of 5-HT enhancing drugs, neurotoxicity blocking drugs, such as N-methyl-D-aspartate (NMDA) antagonists and periaqueductal gray (PAG) electrical stimulation for SUDEP prevention. There are FDA-approved drugs that enhance the action of 5-HT, including fluoxetine and fenfluramine, which is approved for Dravet syndrome. NMDA antagonists, including memantine and ketamine, are also approved for other disorders. PAG electrical stimulation, which is proposed to activate a suffocation alarm, is also approved to treat other conditions and is known to enhance respiration. Experiments using these methods are currently being carried out in animal studies. If these approaches are validated in SUDEP models, treatments could be evaluated relatively quickly in patients with epilepsy (PWE) who exhibit a biomarker for high SUDEP risk, such as peri-ictal respiratory abnormalities. An example of such a study is the ongoing clinical trial of a selective serotonin reuptake inhibitor in PWE. Although, gene-based therapies may ultimately become treatments of choice to prevent SUDEP, as Singh et al suggested, one or more of the approaches we proposed could become temporizing treatments before gene-based therapies can be available. Establishing genetic treatments would require extensive time for each of the genetic abnormalities associated with SUDEP, and too many PWE are likely to die in the meantime.The temporizing treatments may help to reduce the incidence of SUDEP sooner, which is urgently needed.

Exposure to Dichlorvos pesticide alters the morphology of and lipid metabolism in the ventral prostate of rats.

Organophosphate pesticides are widely used in agriculture, leading to soil, water, and food contamination. Among these compounds is Dichlorvos [O,O-dimethyl O-(2,2-dichlorovinyl)phosphate, DDVP], which is listed as a highly toxic compound by the Environmental Protection Agency and World Health Organization. Exposure to DDVP can result in nervous, respiratory, hepatic, and reproductive abnormalities, in addition to endocrine disrupting, mutagenic, and carcinogenic effects. Little is known about the impacts of DDVP on the reprogramming of lipid metabolism, which is also associated with the development and progression of cancer, since the tumor cells need to recruit, capture, and use fatty acids to compose their building membranes. This study aimed to evaluate the influence of the pesticide DDVP on lipid metabolism in the prostate, after chemical induction by the carcinogen N-methyl-N-nitrosourea (MNU). For this, 32 Fischer rats aged 90days were randomly divided into four experimental groups: Control, DDVP, MNU, and MNU + DDVP. The MNU and MNU + DDVP groups underwent chemical induction with MNU (15mg/kg) and the DDVP and MNU + DDVP groups received a diet supplemented with DDVP (10mg/kg). Histopathological analyses of the rat ventral prostate showed 100% incidence of epithelial hyperplasia in the MNU and MNU + DDVP groups. This finding was accompanied by an increase of the epithelial compartment in the MNU + DDVP group. Immunolocalization of important proteins linked to lipid metabolism has been established. In the MNU + DDVP group, Western blotting analyses pointed out an increased expression of the protein LIMP II (Lysosomal Integral Membrane Protein-II), which is correlated with the capture and distribution of lipids in tumor cells. Together, these results indicate that the association of a low dose of DDVP with MNU was able to promote alterations in the morphology and lipid metabolism of the rat ventral prostate, which may be related to tumor progression in this organ.

Distinguishing Obstructive Sleep Apnea Using Electroencephalography Records

In this study, it was aimed to find out whether electroencephalographic (EEG) frequency bands can be used to distinguish people with obstructive sleep apnea (OSA) from those who do not have it. 11842 different cases taken from 121 patients suffering from OSA were combined with the case study of 30-person control group without sleep apnea. Apneas were highlighted at the respiration-record channels and EEG records which are concurrent with abnormal respiration cases were extracted from C4-A1 and C3-A2. Following that, they were examined with Fourier and Wavelet Transforms using a new software that was developed by us. The percentage values of Delta (0, 5-4 Hz), Theta (4-8 Hz), Alpha (8-13 Hz) and Beta (13-30 Hz) frequency bands were evaluated with the help of t-test and ROC Analysis to differentiate between apneas. The C3-A2 Beta (%) frequency level gave the highest distinguishing asset (AUC=0.662; p

Sleep and respiratory abnormalities in adults with developmental and epileptic encephalopathies using polysomnography and video-EEG monitoring.

This study evaluated sleep and respiratory abnormalities, and their relationship with seizures, in adults with developmental and epileptic encephalopathies (DEEs). We studied consecutive adults with DEEs undergoing inpatient video-EEG monitoring and concurrent polysomnography between December 2011 and July 2022. Thirteen patients with DEEs were included (median age: 31 years, range: 20-50; 69.2% female): Lennox-Gastaut syndrome (n = 6), Lennox-Gastaut syndrome-like phenotype (n = 2), Landau-Kleffner syndrome (n = 1), epilepsy with myoclonic-atonic seizures (n = 1), and unclassified DEEs (n = 3). Sleep architecture was often fragmented by epileptiform discharges and seizures resulting in arousals (median arousal index: 29.0 per h, range: 5.1-65.3). Moderate-to-severe obstructive sleep apnea (OSA) was observed in seven patients (53.8%). Three patients (23.1%) had tonic seizures that frequently occurred with central apnea; one met criteria for mild central sleep apnea. Of the patients with tonic seizures, two had other identifiable seizure manifestations, but in one patient, central apnea was commonly the only discernable seizure manifestation. Polysomnography during video-EEG is an effective diagnostic tool in detecting sleep and seizure-related respiratory abnormalities. Clinically significant OSA may increase the risk of comorbid cardiovascular disease and premature mortality. Treatment of epilepsy may improve sleep quality, and conversely, improved sleep, may decrease seizure burden.

Enhanced bare-bones particle swarm optimization based evolving deep neural networks

In this research, we propose a variant of the Bare-Bones Particle Swarm Optimization (BBPSO) algorithm for hyper-parameter selection and deep architecture generation for image, audio and video classification tasks. Since the search process of the original BBPSO model is guided by a single leader and the particles’ personal best experiences, there is a lack of interactions pertaining to the neighbouring elite solutions. To overcome this limitation, we propose a versatile search process for a modified BBPSO model that incorporates a number of effective components and operations. These include the neighbouring and global best signals, search actions with Cauchy/Levy scale factors, sub-dimension operations guided by the local and global elite solutions, and a Levy-driven local search mechanism. Moreover, root-finding algorithms are employed which use informative mathematical principles to estimate new root offspring for leader/particle enhancement. A reinforcement learning algorithm is subsequently used to identify the optimal sequential deployment of these numerical analysis methods to increase robustness. Several medical imaging data sets, i.e., ISIC 2017, PH2 and Dermofit skin lesion databases, the ALL-IDB2 microscopic blood image data set, the MURA musculoskeletal radiographic database, the CK + facial expression data set, as well as the Coswara respiratory audio data set and UCF101 video action data set, are employed for evaluation. The proposed BBPSO-optimized Convolutional Neural Network (CNN), bidirectional Long Short-Term Memory (BiLSTM) with attention mechanism, and CNN-BiLSTM models outperform those devised by other PSO and BBPSO variants, as well as state-of-the-art existing studies, significantly, for image, audio respiratory abnormality and realistic video action recognition.

Multimodal biofeedback for Parkinson’s disease motor and nonmotor symptoms

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor retardation, myotonia, quiescent tremor, and postural gait abnormality, as well as nonmotor symptoms such as anxiety and depression. Biofeedback improves motor and nonmotor functions of patients by regulating abnormal electroencephalogram (EEG), electrocardiogram (ECG), photoplethysmography (PPG), electromyography (EMG), respiration (RSP), or other physiological signals. Given that multimodal signals are closely related to PD states, the clinical effect of multimodal biofeedback on patients with PD is worth exploring. Twenty-one patients with PD in Beijing Rehabilitation Hospital were enrolled and divided into three groups: multimodal (EEG, ECG, PPG, and RSP feedback signal), EEG (EEG feedback signal), and sham (random feedback signal), and they received biofeedback training five times in two weeks. The combined clinical scale and multimodal signal analysis results revealed that the EEG group significantly improved motor symptoms and increased Berg balance scale scores by regulating β band activity; the multimodal group significantly improved nonmotor symptoms and reduced Hamilton rating scale for depression scores by improving θ band activity. Our preliminary results revealed that multimodal biofeedback can improve the clinical symptoms of PD, but the regulation effect on motor symptoms is weaker than that of EEG biofeedback.

Impact of admission viral load on respiratory outcomes in hospitalized SARS-CoV-2 infected patients with cancer and without cancer: A 2-, 4- and 6-months follow-up prospective study

BackgroundThis prospective follow-up study aimed to determine the temporal changes in respiratory outcomes over 6 months period in patients with and without cancer hospitalized for severe COVID-19 and to determine the associated risk factors based on admission viral load. MethodsAll adult patients hospitalized with a confirmed diagnosis of severe SARS-CoV-2 infection were investigated using rRT-PCR on nasopharyngeal swab specimens. Patients were divided into three arbitrary groups according to their cycle threshold (CT) values obtained at admission as high (CT<25.0), medium (CT between 25.0 and 30.0), and low (CT>30.0) viral load. Patients had pulmonary function tests, chest high-resolution computed tomography (HRCT), and a 6-minute walking time distance measured at each follow-up visit. ResultsThis follow-up study had a total of 112 participants, of which 75 were cancer-free and 37 had active cancer. Overall, 29.5% had a low viral load, compared to 48.2% who had a high viral load, and 22.3% had a medium viral load. For patients who did not have cancer, the mean age was 57.3 (SD 15.4) and for those who had cancer, it was 62.3 (SD 18.4). Most patients had overall better temporal changes in pulmonary function and tolerance, as well as exercise capacity, even though severe and chronic respiratory abnormalities persisted in a fraction of the patients. In patients without cancer who had a high viral load, we have seen a substantial reduction in diffusion capacity of the lungs for carbon monoxide (DLCO) predicted value with a median of 65 (IQR 63–70) while in patients with cancer, it was 60 (IQR 56–67) at 2 months. At 4 and 6 months, the predicted DLCO values for patients without cancer were 65 (IQR 61–70), whereas the predicted DLCO values for patients with active cancer were 62 (IQR 60–67) and 67 (59−73). Importantly, radiological abnormalities persisted in 22 (29%) non-cancer patients and 16 (43%) cancer patients. Multivariate regression analysis showed an increased odds ratio of impaired HRCT associated with a high viral load of 3.04 (95% CI:1.68–6.14; p < 0.001) for patients without cancer and 5.07 (95% CI: 4.04–10.8; p < 0.0001) for patients with cancer. The CT pneumonia score at hospitalization was 2.25 (95% CI:1.76–3.08; p = 0.041) and 2.85 (95% CI:1.89–5.14; p = 0.031) for non-cancer and cancer patients respectively. ConclusionsThe evidence of persistent pulmonary abnormalities and radiographic changes was found in both patient groups who had high viral load at hospital admission and suggesting that SARS-CoV-2 viral load might serve as a useful indicator to predict the development of respiratory complications in patients with COVID-19.

Traffic-Related Air Pollution (TRAP) in relation to respiratory symptoms and lung function of school-aged children in Kuala Lumpur

ABSTRACT Traffic-Related Air Pollution (TRAP) exposure has been connected to significant health impacts among children. A cross-sectional comparative study was conducted among school children in Malaysia to determine the relationship between their exposure to TRAP and respiratory health effects. Air monitoring was conducted in schools and residences, while the children’s routines were investigated using a diary of daily activities. Respondents’ background and respiratory symptoms were obtained from a validated questionnaire, while a spirometry test was performed to determine their lung function status. The distances between schools and residences from the had contributed to the higher concentration of air pollutants in this study, which had associations with the children’s respiratory symptoms and lung function status. PM2.5 was the main predictor influencing the respondents’ respiratory symptoms and lung function abnormalities. In conclusion, exposure of school children to a high TRAP level might increase their risk of getting respiratory symptoms and lung function reduction.

Respiratory system abnormalities in Prader-Willi syndrome: a literature review

Respiratory system abnormalities in Prader-Willi syndrome: a literature review

Catestatin Protects Against Diastolic Dysfunction by Attenuating Mitochondrial Reactive Oxygen Species Generation.

Background Catestatin has been reported as a pleiotropic cardioprotective peptide. Heart failure with preserved ejection fraction (HFpEF) was considered a heterogeneous syndrome with a complex cause. We sought to investigate the role of catestatin in HFpEF and diastolic dysfunction. METHODS AND RESULTS Administration of recombinant catestatin (1.5 mg/kg/d) improved diastolic dysfunction and left ventricular chamber stiffness in transverse aortic constriction mice with deoxycorticosterone acetate pellet implantation, as reflected by Doppler tissue imaging and pressure-volume loop catheter. Less cardiac hypertrophy and myocardial fibrosis was observed, and transcriptomic analysis revealed downregulation of mitochondrial electron transport chain components after catestatin treatment. Catestatin reversed mitochondrial structural and respiratory chain component abnormality, decreased mitochondrial proton leak, and reactive oxygen species generation in myocardium. Excessive oxidative stress induced by Ru360 abolished catestatin treatment effects on HFpEF-like cardiomyocytes in vitro, indicating the beneficial role of catestatin in HFpEF as a mitochondrial ETC modulator. The serum concentration of catestatin was tested among 81 patients with HFpEF and 76 non-heart failure controls. Compared with control subjects, serum catestatin concentration was higher in patients with HFpEF and positively correlated with E velocity to mitral annular e' velocity ratio, indicating a feedback compensation role of catestatin in HFpEF. Conclusions Catestatin protects against diastolic dysfunction in HFpEF through attenuating mitochondrial electron transport chain-derived reactive oxygen species generation. Serum catestatin concentration is elevated in patients with HFpEF, probably as a relatively insufficient but self-compensatory mechanism.