Tricuspid Annular Plane Systolic Excursion (TAPSE) in COPD Patients, A Systematic Review and Meta-Analysis.

Introduction: Tricuspid annular plane systolic excursion (TAPSE) is an echocardiographic parameter that serves as a prognostic indicator for severity of COPD clinical course. This study, consisting of a systematic review and meta-analysis, evaluates the current literature to elucidate the relationship between TAPSE measurement in COPD patients versus control subjects to discern baseline evidence of right heart strain. Methods: PubMedTM, ScopusTM, CINAHL, Web of Science, and Cochrane Review databases were searched from their beginning through November 1, 2023, for eligible studies. Outcomes included the difference of TAPSE measurement and right ventricular wall thickness between COPD patients and control patients. The Newcastle-Ottawa Scale was applied to assess risk of bias; Q-statistics and I2 values were used to assess for heterogeneity; and Egger's and Begg's test used to assess for publication bias. Results: The search yielded eleven studies reporting TAPSE values involving 1671 patients, 800 (47.9%) patients with COPD. The unadjusted mean TAPSE values for COPD patients was 18.9 mm (SD+/- 4), while the mean TAPSE value for control patients was 22.2 mm (SD+/- 0.8). The presence of COPD was significantly associated with decreased TAPSE values with the meta-analysis reporting the mean difference of TAPSE value between COPD and control patients was -3.0 (95% CI -4.3 to -1.7, P=0.001). Six studies reported the RV free wall thickness. The unadjusted mean RV free wall thickness for COPD patients was 4.9 mm (SD+/- 1.2), and control patients was 3.4 mm (SD+/- 0.7), respectively. Conclusions: This meta-analysis demonstrated statistically-significantly lower TAPSE values and thicker RV free wall among COPD patients versus control patients.

Tourists' Food Involvement, Place Attachment, and Destination Loyalty: The Moderating Role of Lifestyle.

Destination food has been increasingly appealing to tourists within adjacent markets. This trend has been widely recognised by destination marketers; however, scholars have paid limited attention to tourists' psychological and behavioural responses to destination food. Taking Shunde as the research site, using a questionnaire-based survey method equipped with the techniques of measurement modelling, path analysis, principal component analysis, and cluster analysis, this study explores how tourists' food involvement affects their place attachment and destination loyalty, as well as the differentiation of tourists with different lifestyles. The results show that food involvement significantly affects place attachment and destination loyalty. These relationships are differentiated by tourists' lifestyles. This study contributes to the psychological research of tourist behaviours and provides insights into destination marketing in the context of food tourism.

Development of a New Bead Movement-Based Computational Framework Shows that Bacterial Amyloid Curli Reduces Bead Mobility in Biofilms.

Biofilms exist in complex environments, including the intestinal tract, as a part of the gastrointestinal microbiota. The interaction of planktonic bacteria with biofilms can be influenced by material properties of the biofilm. During previous confocal studies, we observed that amyloid curli-containing Salmonella enterica serotype Typhimurium and Escherichia coli biofilms appeared rigid. In these studies, Enterococcus faecalis, which lacks curli-like protein, showed more fluid movement. To better characterize the material properties of the biofilms, a four-dimensional (4D) model was designed to track the movement of 1-µm glyoxylate beads in 10- to 20-µm-thick biofilms over approximately 20 min using laser-scanning confocal microscopy. Software was developed to analyze the bead trajectories, the amount of time they could be followed (trajectory life span), the velocity of movement, the surface area covered (bounding boxes), and cellular density around each bead. Bead movement was found to be predominantly Brownian motion. Curli-containing biofilms had very little bead movement throughout the low- and high-density regions of the biofilm compared to E. faecalis and isogenic curli mutants. Curli-containing biofilms tended to have more stable bead interactions (longer trajectory life spans) than biofilms lacking curli. In biofilms lacking curli, neither the velocity of bead movement nor the bounding box volume was strictly dependent on cell density, suggesting that other material properties of the biofilms were influencing the movement of the beads and flexibility of the material. Taken together, these studies present a 4D method to analyze bead movement over time in a 3D biofilm and suggest curli confers rigidity to the extracellular matrix of biofilms.IMPORTANCE Mathematical models are necessary to understand how the material composition of biofilms can influence their physical properties. Here, we developed a 4D computational toolchain for the analysis of bead trajectories, which laid the groundwork for establishing critical parameters for mathematical models of particle movement in biofilms. Using this open-source trajectory analyzer, we determined that the presence of bacterial amyloid curli changes the material properties of a biofilm, making the biofilm matrix rigid. This software is a powerful tool to analyze treatment- and environment-induced changes in biofilm structure and cell movement in biofilms. The open-source analyzer is fully adaptable and extendable in a modular fashion using VRL-Studio to further enhance and extend its functions.

NeuroBox: Computational Mathematics in Multiscale Neuroscience.

The brain is a complex organ operating on multiple scales. From molecular events that inform electrical and biochemical cellular responses, the brain interconnects processes all the way up to the massive network size of billions of brain cells. This strongly coupled, nonlinear, system has been subject to research that has turned increasingly multidisciplinary. The seminal work of Hodgkin and Huxley in the 1950s made use of experimental data to derive a coherent physical model of electrical signaling in neurons, which can be solved using mathematical and computational methods, thus bringing together neuroscience, physics, mathematics, and computer science. Over the last decades numerous projects have been dedicated to modeling and simulation of specific parts of molecular dynamics, neuronal signaling, and neural network behavior. Simulators have been developed around a specific objective and scale, in order to cope with the underlying computational complexity. Often times a dimension reduction approach allows larger scale simulations, this however has the inherent drawback of losing insight into structure-function interplay at the cellular level. This paper gives an overview of the project NeuroBox that has the objective of integrating multiple brain scales and associated physical models into one unified framework. NeuroBox hosts geometry and anatomical reconstruction methods, such that detailed three-dimensional domains can be integrated into numerical simulations of models based on partial differential equations. The project further focusses on deriving numerical methods for handling complex computational domains, and to couple multiple spatial dimensions. The latter allows the user to specify in which parts of the biological problem high-dimensional representations are necessary and where low-dimensional approximations are acceptable. NeuroBox offers workflow user interfaces that are automatically generated with VRL-Studio and can be controlled by non-experts. The project further uses uG4 as the numerical backend, and therefore accesses highly advanced discretization methods as well as hierarchical and scalable numerical solvers for very large neurobiological problems.

Estimates of live birth prevalence of children with Down syndrome in the period 1991-2015 in the Netherlands.

BACKGROUND: In Western countries, increasing maternal age has led to more pregnancies with a child with Down syndrome (DS). However, prenatal screening programs, diagnostic testing and termination of pregnancy influence the actual DS live birth (LB) prevalence as well. The aim of this study is to examine these factors in the Netherlands for the period 1991-2015. In our study, we establish a baseline for DS LB prevalence before non-invasive prenatal testing will be made available to all pregnant women in the Netherlands in 2017. METHODS: Full nationwide data from the Dutch cytogenetic laboratories were used to evaluate the actual DS LB prevalence. In addition, nonselective DS prevalence, which is the DS LB prevalence that would be expected in absence of termination of pregnancies, was estimated on the basis of maternal age distribution in the general population. RESULTS: Because of an increase in maternal age, nonselective DS prevalence increased from around 15.6 [95% confidence interval (CI) 13.9-17.4] per 10 000 LBs in 1991 (311 children in total) to around 22.6 (95% CI 20.3-24.9) per 10 000 in 2015 (385), the increase levelling off in recent years. Actual LB prevalence rose from around 11.6 (95% CI 10.9-12.2) per 10 000 in 1991 (230 children) to an estimated peak of 15.9 (95% CI 15.6-16.2) per 10 000 in 2002 (322), gradually decreasing since to 11.1 (95% CI 10.8-11.5) per 10 000 in 2015 (190). Reduction of DS LBs resulting from elective terminations had been fairly constant between 1995 and 2002 at around 28% and rose afterwards from 35% in 2003 to around 50% in 2015. CONCLUSIONS: In spite of expansion of antenatal screening in the Netherlands in the 1990s and early 2000s, actual DS LB prevalence increased during this period. However, after 2002, this trend reversed, probably because of informing all pregnant women about prenatal testing since 2004 and the implementation of a national screening program in 2007.

Posttraumatic dizziness and vertigo.

Traumatic brain injury is an increasingly common public health issue, with the mild variant most clinically relevant for this chapter. Common causes of mild traumatic brain injury (mTBI) include motor vehicle accidents, athletics, and military training/deployment. Despite a range of clinically available testing platforms, diagnosis of mTBI remains challenging. Symptoms are primarily neurosensory, and include dizziness, hearing problems, headaches, cognitive, and sleep disturbances. Dizziness is nearly universally present in all mTBI patients, and is the easiest symptom to objectify for diagnosis. Aside from a thorough history and physical exam, in the near future specialized vestibular function tests will be key to mTBI diagnosis. A battery of oculomotor (antisaccade, predictive saccade) and vestibular tasks (head impulse test) has been demonstrated to sensitively and specifically identify individuals with acute mTBI. Vestibular therapy and rehabilitation have shown improvements for mTBI patients in cognitive function, ability to return to activities of daily living, and ability to return to work. Dizziness, as a contributor to short- and long-term disability following mTBI, is ultimately crucial not only for diagnosis but also for treatment.

European non-invasive trisomy evaluation (EU-NITE) study: a multicenter prospective cohort study for non-invasive fetal trisomy 21 testing.

OBJECTIVE: To evaluate the performance of a directed non-invasive prenatal testing method of cell-free DNA analysis for fetal trisomy 21 (T21) by shipping the whole blood samples from Europe to a laboratory in the USA. METHODS: A European multicenter prospective, consecutive cohort study was performed enrolling pregnant women from Sweden and the Netherlands. Blood samples were drawn just prior to a planned of invasive diagnostic procedure in a population at increased risk for fetal T21 and then shipped to the USA without any blood processing. Chromosome-selective sequencing was carried out on chromosome 21 with reporting high risk or low risk of T21. Karyotyping or rapid aneuploidy detection was used as the clinical reference standard. RESULTS: Of the 520 eligible study subjects, a T21 test result was obtained in 504/520 (96.9%). Risk assessment was accurate in 503/504 subjects (99.8%). There was one false negative result for T21 (sensitivity 17/18, 94.4%, and specificity 100%). CONCLUSION: This is the first prospective European multicenter study showing that non-invasive prenatal testing using directed sequencing of cell-free DNA applied to blood samples shipped across the Atlantic Ocean, is highly accurate for assessing risk of fetal T21.

A 6Mb deletion in band 2q22 due to a complex chromosome rearrangement associated with severe psychomotor retardation, microcephaly and distinctive dysmorphic facial features.

High-resolution analyses of complex chromosome rearrangements (CCR) have demonstrated in individuals with abnormal phenotypes that not all seemingly balanced CCRs based on G-banding are completely balanced at breakpoint level. Here we report on an apparently balanced de novo CCR involving chromosomes 2, 3 and 5 present in a 6-month-old girl. She was referred for genetic evaluation because of severe psychomotor retardation, distinctive dysmorphic features and microcephaly. A 1Mb resolution array-CGH analysis of DNA from the patient revealed a deletion of about 6Mb for chromosome 2. FISH analysis showed that the deletion interval found in band 2q22 mapped at the translocation breakpoint, and that the ZFHX1B gene, which is known to be involved in the Mowat-Wilson syndrome, is located within the deletion interval. To our knowledge this is the first case of a complex chromosomal rearrangement associated with Mowat-Wilson syndrome. Our data illustrate the important role for high-resolution investigation of apparently balanced chromosome rearrangements in patients with unexplained psychomotor retardation and/or other clinical features, and should contribute to our understanding of the mechanisms involved in chromosome rearrangement.

Tinnitus in an active duty navy diver: A review of inner ear barotrauma, tinnitus, and its treatment.

This case elucidates subtle cues that must be appreciated by the examiner in diving related injuries, who may not have experience with barotrauma-mediated pathology. Inner-ear barotrauma (IEBT) does not mandate ostensible hearing loss or vertigo; tinnitus may be the sole manifestation. Symptoms may present hours or even days post-dive. A common misconception exists that there are no efficacious treatment options for IEBT short of surgery for an overt perilymphatic fistula. Treatment options are available including acute high dose steroid administration, as prescribed for acute noise-induced or idiopathic hearing loss, optimally administered within three weeks of the acute insult. Tinnitus does not necessarily constitute a chronic untreatable symptom, which the patient must learn "to live with".

Incidence of inpatient surgeries in children and young adults with childhood orthopaedic diagnoses.

The incidence of orthopaedic surgery for young people with childhood onset of orthopaedic disabilities is not well documented. This study tabulated that incidence in the past two decades in California. Trauma, tumors, and hand surgery were not included in the study. Common pediatric orthopaedic diagnoses by ICD-9 code requiring CPT orthopaedic surgical procedures were tabulated in three years: 1983, 1990, and 1999. The most common procedures in each of these years studied were, in order of incidence, scoliosis, congenital hip problems, slipped femoral capital epiphyses, and clubfeet. The incidence of surgery for scoliosis and slipped femoral capital epiphyses increased over the past two decades. These data should be helpful in planning for future inpatient services for orthopaedically handicapped children.

Medial condyle fractures of the humerus in children.

A retrospective study of 21 medial condylar fractures revealed that the complication rate for these rare fractures was 33%. Most of the minimally displaced fractures healed uneventfully with immobilization; however, one patient developed avascular necrosis of the trochlea, and one patient developed a nonunion. Operative treatment was performed if there was >2 mm of displacement at the fracture site. Two of three fracture-dislocations lost reduction in the early postoperative period, requiring revision with more stable fixation. Medial condylar fractures may be difficult to diagnose in younger children and should be considered when there is a history of trauma and medial-sided elbow pain. Oblique views, arthrography, or magnetic resonance imaging can be helpful in confirming the diagnosis. Management of this rare fracture must include adequate stabilization of the fracture and immobilization until there is radiographic evidence of healing.

Microdose gentamicin administration via the round window microcatheter: results in patients with Meniere's disease.

Transtympanic gentamicin is becoming increasingly popular in the treatment of Meniere's disease. In this report we examine our experience with the use of microdose gentamicin via the Round Window Microcatheter for the treatment of Meniere's disease. Thirty-six patients were treated with gentamicin administration via the Round Window Microcatheter between July 1997 and August 2000. The patients all underwent 10 days of continuous treatment with a total dose of 2.4-3.75 mg of gentamicin (10 mg/ml). All patients had extensive pre-, intra-, and post-therapy auditory and vestibular testing. In this group, vertigo was eliminated in 89% of the patients, and tinnitus and pressure were significantly reduced in over 60% of the patients. Only one patient suffered a significant hearing loss and, most importantly, in all but one patient vestibular function was improved or normalized after treatment. Round Window Microcatheter-administered microdose gentamicin is an exciting new treatment for Meniere's disease. Preliminary results indicate that vertigo can be controlled without a significant reduction in cochlear or vestibular function in most patients. These results suggest that this therapy may be acting at a non-hair cell site. Our results are compared to the published literature examining transtympanic injection. In addition, the underlying science supporting this type of treatment is examined.

Transtympanic versus sustained-release administration of gentamicin: kinetics, morphology, and function.

OBJECTIVES/HYPOTHESIS: Transtympanic gentamicin therapy has become a popular treatment modality for Meniere's disease, but questions regarding the ideal dose of medicine, the best administration paradigm, and the safest treatment end-point remain unanswered. The goal of this study is to examine the inner ear kinetics of transtympanic gentamicin and compare this with the kinetics of sustained-release delivery in a basic science model. In addition, we plan to examine the relationship of these kinetics curves to the effect of the two treatment modalities on inner ear function and morphology. It is hoped that this analysis will help clinicians to better apply local medical therapy to the ear. STUDY DESIGN: The study is a basic science project designed to examine perilymph gentamicin concentrations, hearing results, and inner ear morphology in an animal model. METHODS: Gentamicin was applied to the right ear of chinchillas either through a transtympanic approach or in a sustained-release device. The left ear remained untreated as an internal control. At set time points the animals' hearing and balance function was studied and the perilymph was harvested, after which the animal was killed and preserved for histological evaluation. Kinetics curves were constructed for each of the two treatment paradigms and compared with histological and functional outcomes. RESULTS: The two groups yielded dramatically different kinetics curves. The transtympanic curve had a high peak level at 24 hours with rapid fall-off and almost total elimination by 48 hours, whereas the sustained-release curve was characterized by a long, flat plateau phase with a peak that was approximately one-third that of the transtympanic curve. In addition, the variability seen in perilymph concentrations was significantly higher in the transtympanic group than in the sustained-release group. Immunohistochemical analysis using antibodies against cleaved caspase-3 and cleaved caspase-7 demonstrated early damage in the spiral ganglion of both groups, before any obvious morphological change in the hair cells. The staining was significantly more dense in animals with transtympanic delivery. Cochlear and vestibular hair cell damage was seen at late time points in animals from both groups. Hearing loss (HL) progressed in an orderly fashion in the sustained-release group of animals, with no HL seen in the early time points and universal significant threshold shifts present by 72 hours. In the transtympanic group, the HL was more variable, with significant threshold shifts occurring as early as 4 hours after treatment, but with some animals demonstrating preserved hearing at the 72-hour time point. All animals demonstrated profound HL at the 6-day time point. CONCLUSIONS: There is a significant difference in the shape and variability of the perilymph kinetics curve when comparing sustained-release delivery to transtympanic delivery of gentamicin. High early peak levels of gentamicin seen with transtympanic therapy may have a profound effect on the spiral ganglion and produce early HL before obvious hair cell damage. Sustained delivery of gentamicin produces universal HL at 72 hours. The reliability of sustained-release delivery to the ear reduces functional and morphological variations between animals.

Targeted topical steroid therapy in sudden sensorineural hearing loss.

OBJECTIVE: To treat patients with sudden sensorineural hearing loss (SSNL) who failed oral prednisone therapy by using a round window membrane (RWM) microcatheter. This topical delivery strategy sought to improve effectiveness of steroid treatment to the inner ear by targeting drug delivery to the RWM. STUDY DESIGN: Nonrandomized prospective design. SETTING: Tertiary care facility. PATIENTS: Six patients with severe unilateral SSHL, five of whom were refractory to a course of oral steroid therapy treated within 6 weeks of SSHL and three additional patients treated more than 6 weeks after SSHL. INTERVENTION: Therapeutic use of RWM catheter. MAIN OUTCOME MEASURES: Pure-tone averages (PTAs) and word identification scores (WIS). RESULTS: Five of the six patients treated within 6 weeks of SSHL improved their WIS. Of the six, four returned to baseline hearing, one recovered hearing that could benefit by hearing amplification, and one regained moderate improvement in PTA but not WIS. CONCLUSION: Targeted topical steroid administration avoids the significant systemic side effects of oral steroids and may offer more effective dosing than simple transtympanic injection of medicine. Although these findings are preliminary, it is possible that after further study, targeted drug delivery may be a useful technique to consider in patients with severe to profound hearing loss that have failed all other management options.

Reversal of diminished inhibitory sensory gating in cocaine addicts by a nicotinic cholinergic mechanism.

Cocaine addiction, as with other stimulant abuse, produces psychotic symptoms. Although often moderate to mild in severity, these symptoms are, nevertheless, associated with poorer over-all outcome. Recent studies suggest diminished nicotinic cholinergic neurotransmission as a mechanism of a physiological deficit found in schizophrenia, failure of auditory sensory inhibition. Diminished inhibitory sensory gating also occurs in cocaine addicts, probably because of their increased catecholaminergic neurotransmission, which blocks the inhibition. In the present study, 11 cocaine addicts in the first week of detoxification were recorded electrophysiologically, after which the effects of 6 mg of nicotine gum, were assessed in a double-blind placebo-controlled crossover design. The test was repeated 10 days later. Treatment with nicotine, but not placebo, briefly reversed the inhibitory abnormality on both test days. Although nicotine itself may not be a desirable therapeutic agent, because desensitization of nicotinic receptors limits the time course of its effect, the study identifies a previously unexploited therapeutic target for new drug development for the neuropsychiatric sequelae of cocaine addiction.

Growth factor treatment enhances vestibular hair cell renewal and results in improved vestibular function.

The vestibules of adult guinea pigs were lesioned with gentamicin and then treated with perilymphatic infusion of either of two growth factor mixtures (i.e., GF I or GF II). GF I contained transforming growth factor alpha (TGFalpha), insulin-like growth factor type one (IGF-1), and retinoic acid (RA), whereas GF II contained those three factors and brain-derived neurotrophic factor. Treatment with GF I significantly enhanced vestibular hair cell renewal in ototoxin-damaged utricles and the maturation of stereociliary bundle morphology. The addition of brain-derived neurotrophic factor to the GF II infusion mixture resulted in the return of type 1 vestibular hair cells in ototoxin-damaged cristae, and improved vestibular function. These results suggest that growth factor therapy may be an effective treatment for balance disorders that are the result of hair cell dysfunction and/or loss.

Use of the round window microcatheter in the treatment of Meniere's disease.

OBJECTIVES/HYPOTHESIS: Transtympanic gentamicin is an increasingly popular treatment for Meniere's disease. The present report examines the 2-year follow-up of our first 27 patients with Meniere's disease treated with the use of microdose gentamicin through the Round Window Microcatheter. We applied the 1995 American Academy of Otolaryngology-Head and Neck Surgery criteria to this patient group to analyze the results of treatment. STUDY DESIGN: This study is an evaluation of consecutive patients with predetermined data collection on each patient. METHODS: Patients with confirmed Meniere's disease underwent placement of the Round Window Microcatheter, which was filled with 10 mg/mL gentamicin, after placement into the round window niche was confirmed. Ten milligrams per milliliter of gentamicin was injected into the catheter by hand on two occasions after device placement in the first several patients. The remaining patients had continuous infusion of 10 mg/mL gentamicin at 1microL/h for the next 10 days. The catheter was removed 10 days after placement. All patients underwent an extensive set of hearing and vestibular tests on several occasions before, during, and after treatment. RESULTS: In the patients in the study, vertigo was eliminated in 92.6%, with 3.7% of patients (1/27) demonstrating a mild permanent threshold shift in hearing. Tinnitus and pressure were significantly reduced in more than 65% of patients. Only one patient demonstrated a reduction of vestibular function after treatment. CONCLUSIONS: Results of this study on this group of patients indicate that vertigo can be controlled in the long term using microdose gentamicin without a significant reduction in cochlear or vestibular function in most of the patients in our series. Our results are compared with the published literature examining transtympanic injection. In addition, the underlying science supporting this type of treatment is examined.