Cough ability measurements and recurrent respiratory symptoms in individuals with Ataxia Telangiectasia

Objectives: Ataxia-Telangiectasia (A-T) individuals often present with respiratory muscle weakness, causing recurrent respiratory system infections, asthma-like symptoms, and chronic cough life-threatening events. The cough flow volume maneuver may reveal powerless airflow needed for efficient cough. The study aims to explore cough ability in relation to the flow/volume maneuver. Methods: Data collected retrospectively from clinical charts of 35 A-T patients (age 12.7?±?4.9 years) included forced expiratory and cough flow/volume maneuvers performed on the same day. Analysis compared among the maneuvers matching indices, numbers of cough-spikes, flow rate decay, and the reference data of similar ages. Adjusted to age, BMI, and number of hospitalizations prior to the tests, values were correlated with the cough indices. Results: Cough peak-flow (C-PF) was propagated within 90?±?20?ms compared with peak expiratory flow (PEF?>?200?ms). C-PF measured values were higher than expiratory peak-flow measured values (3.27?±?1.53?L/s versus 3.02?±?1.52?L/s, respectively, but C-PF (%predicted) values were significantly lower than expiratory peak-flow (%predicted) (46?±?15 versus 68?±?20 %predicted, respectively, p?<?0.002). The number of spikes/maneuver was low when compared with reference (2.0?±?0.8 versus 6–12 spikes) and cough vital-capacity was lower than expiratory vital capacity (0.95?±?0.43 versus 1.03?±?0.47; p?<?0.01). Inefficient C-PF was more prevalent in patients suffering from recurrent respiratory illness. The length of wheelchair confinement duration mostly influenced the C-VC level. Conclusions: The cough flow–volume curve can be applied as a method to follow cough ability in patients with A-T who showed a significantly reduced cough capacity. Further studies are needed to establish if the findings may aid decisions regarding cough assistance.     

Sexual Function and Quality of Life for Women with Mild‐to‐Moderate Stress Urinary Incontinence

Introduction: Sexual function is affected by stress urinary incontinence with or without pelvic organ prolapse. The aim of the study was to describe the sexual function of women with mild‐to‐moderate stress urinary incontinence, with or without pelvic organ prolapse (up to stage 2) and examine correlations with symptoms and quality of life. This investigation was part of a large, randomized, clinical trial of women with stress urinary incontinence who participated in an exercise intervention. Methods: Women included in the study suffered from stress urinary incontinence as measured by a pad test and were interested in an exercise intervention. All participants underwent assessment for prolapse staging. Instruments included: the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ‐12), Incontinence Quality of Life Questionnaire (I‐QOL), and a health and urinary leakage questionnaire. Results: One hundred and eighty‐seven ambulatory women, aged 20 to 65 years, had a mean sexual function score of 36.9 (standard deviation [SD] 5.9). No significant correlation was found between the sexual function scores and quantity of urinary leakage. A significant correlation existed between the sexual function and I‐QOL scores (P < .001). An additional finding was that women with urgency symptoms were older (P= .04) and had significantly lower sexual function scores (mean 35.7; SD 6.4) than those who did not report urgency (mean 38.7; SD 4.6; P < .001). Discussion: Women with mild‐to‐moderate stress urinary incontinence, without or with lower stages of pelvic organ prolapse, demonstrated good sexual function, which correlated with physical and psychosocial factors. Health professionals need to perform multifaceted intake assessments on women with urinary leakage to customize their health promotion regimen.     

The Involvement of Collagen Triple Helix Repeat Containing 1 in Muscular Dystrophies

Apolipoprotein E4 (APOE4) genotype is the strongest genetic risk factor for late-onset Alzheimer disease and confers a proinflammatory, neurotoxic phenotype to microglia. Here, we tested the hypothesis that bone marrow cell APOE genotype modulates pathological progression in experimental Alzheimer disease. We performed bone marrow transplants (BMT) from green fluorescent protein–expressing human APOE3/3 or APOE4/4 donor mice into lethally irradiated 5-month-old APPswe/PS1ΔE9 mice. Eight months later, APOE4/4 BMT–recipient APPswe/PS1ΔE9 mice had significantly impaired spatial working memory and increased detergent-soluble and plaque Aβ compared with APOE3/3 BMT–recipient APPswe/PS1ΔE9 mice. BMT-derived microglia engraftment was significantly reduced in APOE4/4 recipients, who also had correspondingly less cerebral apoE. Gene expression analysis in cerebral cortex of APOE3/3 BMT recipients showed reduced expression of tumor necrosis factor-α and macrophage migration inhibitory factor (both neurotoxic cytokines) and elevated immunomodulatory IL-10 expression in APOE3/3 recipients compared with those that received APOE4/4 bone marrow. This was not due to detectable APOE-specific differences in expression of microglial major histocompatibility complex class II, C-C chemokine receptor (CCR) type 1, CCR2, CX3C chemokine receptor 1 (CX3CR1), or C5a anaphylatoxin chemotactic receptor (C5aR). Together, these findings suggest that BMT-derived APOE3-expressing cells are superior to those that express APOE4 in their ability to mitigate the behavioral and neuropathological changes in experimental Alzheimer disease.Humans uniquely have three different apolipoprotein E (APOE) alleles (ɛ2, ɛ3, and ɛ4). APOE4 is the single greatest genetic risk factor for late-onset Alzheimer disease (AD), and there is a gene dosage effect.¹ However, genetic association does not inform function/pathogenesis. Multiple mechanisms have been postulated that predominantly focus on production, metabolism, or clearance of amyloid-β (Aβ) and that are variably supported by multiple observations, including: i) APOE genotype is strongly related to Aβ levels in brain and cerebrospinal fluid of AD patients^2,3; ii) modulation of apolipoprotein E (apoE) protein levels in brain results in alterations of Aβ burden^4,5; iii) Aβ degradation is at least partially apoE dependent^6,7; and iv) Aβ clearance is differentially modulated by apoE isoforms, with APOE4 mice exhibiting reduced central and peripheral Aβ clearance compared with APOE3 mice.^8–10 Aβ degradation and clearance is at least partially dependent on microglia, the innate immune effector cells of the brain. Microglia have migratory and phagocytic capacity, are increased in the vicinity of Aβ plaques, and phagocytose Aβ.^11–13 APOE genotype modulates central nervous system innate immune function in culture,¹⁴ including astrocyte and microglia elaboration of cytokines and chemokines,^15,16 microglia production of reactive oxygen species,¹⁷ microglia-mediated paracrine neurotoxicity,¹⁸ microglia migration,¹⁹ and other functions.²⁰ However, the specific contribution of microglial APOE genotype to AD pathophysiology in vivo is largely unknown.To address this critical question and to test a potential therapeutic application, we used the fact that bone marrow transplantation (BMT) results in the gradual replacement of endogenous (host) microglia (to the near exclusion of other cell types) with microglia derived from donor marrow, in both wild-type mice and transgenic mouse models of AD.^21–24 We used targeted-replacement (TR) APOE mice homozygous for either the APOE3 or APOE4 gene inserted into the mouse APOE regulatory elements^25,26 that coexpressed green fluorescent protein (GFP). We transplanted whole bone marrow (BM) isolated from TR APOE3/3;GFP or TR APOE4/4;GFP mice into lethally irradiated APPswe/PS1ΔE9 mice to determine the specific role of microglial APOE genotype in the pathological progression of AD.     

Development and validation of a delayed presenting clubfoot score to predict the response to Ponseti casting for children aged 2–10

The aim of the study was to develop a simple and reliable clinical scoring system for delayed presenting clubfeet and assess how this score predicts the response to Ponseti casting. We measured all elements of the Diméglio and the Pirani scoring systems. To determine which aspects were useful in assessing children with delayed presenting clubfeet, 4 assessors examined 42 feet (28 patients) between the ages of 2–10 years. Selected variables demonstrating good agreement were combined to make a novel score and were assessed prospectively on a separate consecutive cohort of children with clubfeet aged 2–10, comprising 100 clubfeet (64 patients). Inter-observer and intra-observer agreement was found to be greatest using the following clinically measured angles of the deformities. These were plantaris, adductus, varus, equinus of the ankle and rotation around the talar head in the frontal plane (PAVER). Measured angles of 1–20, 21–45 and?>?45 degrees scored 1, 2 and 3 points, respectively. The PAVER score was derived from both the sum of points derived from measured angles and a multiplier according to age. The sum of the points was multiplied with 1, 1.5 or 2 for ages 2–4, 5–7 and 8–10, respectively. This demonstrated a good association with the total number of casts to achieve a full correction (tau?=?0.71). A score greater than 18 out of 30 indicated a cast-resistant clubfoot. The score could be used clinically for prognosis and treatment, and for research purposes to compare the severity of clubfoot deformities.     

The fate of allogeneic and xenogeneic neuronal tissue transplanted into the third ventricle of rodents

Neural grafts from day 17-19 fetal rats or mice survived well when transplanted into syngeneic, or immunodeficient hosts, thus demonstrating that there are no non-immunological barriers to cross-species transplantation of neuronal tissue in rats and mice. However, intraventricular grafts from rat to mouse, or vice versa, in immunocompetent animals were rejected in less than 30 days. By this time all graft tissue had been destroyed and scavenged, presumably by the macrophages seen infiltrating the grafts within 10 days of grafting. Rat allografts from major histocompatibility complex disparate donors disparate donors survived well as did grafts between rats differing only at minor histocompatibility loci. However, allografts from donors that differed from recipients at both major and minor histocompatibility complex loci had a variable survival time. When neural tissue was grafted into immunologically primed recipients, it was rejected as was similar tissue grafted beneath the kidney capsule of an allogeneic host. Concomitant grafting of allogeneic tissue under the kidney capsule and into the third ventricle was followed by rejection in both sites. A striking observation in these studies was the induction of Class I major histocompatibility complex antigens on grafted neuronal tissue. High levels of antigen expression were correlated with a vigorous host response and poor graft survival but lower levels were not indicative of impending graft destruction. Whilst the brain can be regarded as an immunologically privileged site, the privilege is not absolute and caution needs to be exercised in the interpretation of results from allogeneic or xenogeneic grafts.     

Lifestyle Modification Parallels to Sleeve Success

Background

The role of laparoscopic sleeve gastrectomy (LSG) has increased over the past 10 years. We present our results of patients who were 5 years out from surgery with regard to safety and long-term efficacy.

Methods

Retrospective analysis was carried out from prospectively collected data of patients who underwent LSG for morbid obesity. Bariatric Analysis and Reporting Outcome System (BAROS) and Food Tolerance Scores (FTS) were assessed. At 5 years, two lifestyle modification questions (regarding nutrition habits and physical fitness) were separately assessed.

Results

One hundred fourteen patients underwent LSG and were available for postoperative visits. Mean excess weight loss (EWL) was >65 % during the initial 3 years and declined to 45.3 % in 5 years. Of the patients, 71.92 % did not reach 50 % EWL at 60 months and were considered objective failures. BAROS and FTS scores were 7.15 and 4.32, and 23.5 and 22.5 at 30 and 60 months, respectively. Analyzing the 32 patients with EWL >50 % in the 5-year group, 26 (81.25 %) of them had scored ≥0.5 on the two lifestyle modification questions compared with 6 (18.75 %) that scored <0.5 (P?<?0.001).

Conclusion

LSG is an effective bariatric surgical procedure with significant long-term (5 year) weight loss, resolution of comorbid medical conditions and significant improvement in the quality of life. The basis for this success, which must be always emphasized preoperatively by the bariatric team, is knowledge and implementation of better nutritional habits and increasing physical fitness or, in other words, in significant lifestyle modification.     

The predictive value and the management of cycles with low initial estradiol levels

This study was undertaken to examine the predictive value of low estradiol (E2) after 5 days of human menopausal gonadotropin (hMG) stimulation response to therapy in that cycle. We further examined whether the outcome of such cycles can be improved by increasing the hMG dose. When 18 cycles in which day 8 E2 was less than or equal to 50 pg/mL were compared with 48 cycles with corresponding E2 levels of 51 to 150 pg/mL, the former showed a significantly worse response to subsequent hMG therapy. To determine the effect of an increase in hMG dose we studied 48 cycles with day 8 E2 of 51 to 150 pg/mL. In 32 cycles hMG dose was increased from three to a mean of five ampules a day, after 5 days of therapy. In 16 cycles it was kept constant at three ampules per day. Although a tendency towards lower fertilization rate was observed in the higher hMG groups, no significant differences were observed in the results between the two groups. We thus conclude that very low E2 levels after 5 days of gonadotropin therapy are predictive of low response in that cycle, and that in cycles with day 8 E2 of 51 to 150 pg/mL, increasing the dosage of hMG on day 8 and beyond does not alter the course of the cycle.