[Laryngomalacia in a follow-up of a child development cohort for antecedents of perinatal encephalopathy. Implications for nosologic conceptualization].
We conducted a retrospective analysis of 10 cases of congenital laryngeal stridor. Reports of laryngeal endoscopy and diagnosis define laryngomalacia as laryngeal flaccidity and stridor. Some authors postulate that in addition to immaturity of cartilage, there exist the possibility of laryngeal uncoordination and dyskinesia. They support this idea in cases of late presentation, neurological damage, and atypical cases related with functional state or anesthesia. Laryngeal endoscopies were carried out in 10 cases included in a cohort of subjects from a longitudinal follow-up diagnosed with neurologica damage of perinatal origin. One case was diagnosed with postoperative unilateral paralysis of vocal chord and another identified vascular ring. The eight remaining cases fulfilled laryngomalacia criteria of diagnosis, but because of their characteristics origin is not an anatomic alteration but a functional hypotonia. The need to carry out an integral study to describe co-morbidity is emphasized.


Flavonoid 6-hydroxylase from soybean (Glycine max L.), a novel plant P-450 monooxygenase.
Cytochrome P-450-dependent hydroxylases are typical enzymes for the modification of basic flavonoid skeletons. We show in this study that CYP71D9 cDNA, previously isolated from elicitor-induced soybean (Glycine max L.) cells, codes for a protein with a novel hydroxylase activity. When heterologously expressed in yeast, this protein bound various flavonoids with high affinity (1.6 to 52 microm) and showed typical type I absorption spectra. These flavonoids were hydroxylated at position 6 of both resorcinol- and phloroglucinol-based A-rings. Flavonoid 6-hydroxylase (CYP71D9) catalyzed the conversion of flavanones more efficiently than flavones. Isoflavones were hardly hydroxylated. As soybean produces isoflavonoid constituents possessing 6,7-dihydroxy substitution patterns on ring A, the biosynthetic relationship of flavonoid 6-hydroxylase to isoflavonoid biosynthesis was investigated. Recombinant 2-hydroxyisoflavanone synthase (CYP93C1v2) efficiently used 6,7,4'-trihydroxyflavanone as substrate. For its structural identification, the chemically labile reaction product was converted to 6,7,4'-trihydroxyisoflavone by acid treatment. The structures of the final reaction products for both enzymes were confirmed by NMR and mass spectrometry. Our results strongly support the conclusion that, in soybean, the 6-hydroxylation of the A-ring occurs before the 1,2-aryl migration of the flavonoid B-ring during isoflavanone formation. This is the first identification of a flavonoid 6-hydroxylase cDNA from any plant species.


Weight loss and incretin responsiveness improve glucose control independently after gastric bypass surgery.
The aim of the present study was to determine the mechanisms underlying Type 2 diabetes remission after gastric bypass (GBP) surgery by characterizing the short- and long-term changes in hormonal determinants of blood glucose. Eleven morbidly obese women with diabetes were studied before and 1, 6, and 12 months after GBP; eight non-diabetic morbidly obese women were used as controls. The incretin effect was measured as the difference in insulin levels in response to oral glucose and to an isoglycemic intravenous challenge. Outcome measures were glucose, insulin, C-peptide, proinsulin, amylin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) levels and the incretin effect on insulin secretion. The decrease in fasting glucose (r = 0.724) and insulin (r = 0.576) was associated with weight loss up to 12 months after GBP. In contrast, the blunted incretin effect (calculated at 22%) that improved at 1 month remained unchanged with further weight loss at 6 (52%) and 12 (52%) months. The blunted incretin (GLP-1 and GIP) levels, early phase insulin secretion, and other parameters of β-cell function (amylin, proinsulin/insulin) followed the same pattern, with rapid improvement at 1 month that remained unchanged at 1 year. The data suggest that weight loss and incretins may contribute independently to improved glucose levels in the first year after GBP surgery.


A Comparison of Radial and Linear Charts for Visualizing Daily Patterns.
Radial charts are generally considered less effective than linear charts. Perhaps the only exception is in visualizing periodical time-dependent data, which is believed to be naturally supported by the radial layout. It has been demonstrated that the drawbacks of radial charts outweigh the benefits of this natural mapping. Visualization of daily patterns, as a special case, has not been systematically evaluated using radial charts. In contrast to yearly or weekly recurrent trends, the analysis of daily patterns on a radial chart may benefit from our trained skill on reading radial clocks that are ubiquitous in our culture. In a crowd-sourced experiment with 92 non-expert users, we evaluated the accuracy, efficiency, and subjective ratings of radial and linear charts for visualizing daily traffic accident patterns. We systematically compared juxtaposed 12-hours variants and single 24-hours variants for both layouts in four low-level tasks and one high-level interpretation task. Our results show that over all tasks, the most elementary 24-hours linear bar chart is most accurate and efficient and is also preferred by the users. This provides strong evidence for the use of linear layouts - even for visualizing periodical daily patterns.


An adenovirus encoding proapoptotic Bax induces apoptosis and enhances the radiation effect in human ovarian cancer.
Overexpression of proapoptotic Bax favors death in cells resistant to ionizing radiation. We hypothesized that expression of Bax via adenoviral-mediated gene delivery could sensitize radiation-refractory cells to radiotherapy. An inducible Bax recombinant adenovirus (Ad/Bax) had been generated using the Cre/loxp system. Human ovarian cancer cell lines and primary, patient-derived cancer cells from ascites were irradiated and infected with the Ad/Bax and an expression-inducing vector, Ad/Cre. Cell death was evaluated by crystal violet staining, fluorescence-activated cell sorter analysis of Annexin V, and colony formation assay (cell lines only). To further characterize the mechanism of death, cell morphology was examined by nuclear staining with Hoechst 33258. Lastly, to evaluate the capacity of the combined treatment to inhibit tumor growth, mice were injected subcutaneously with ovarian cancer cells exposed to Bax, radiation therapy (RT), or both, and tumor size was measured periodically. Infection of the cancer cell lines and primary cells with both Ad/Bax and Ad/Cre significantly enhanced sensitivity to ionizing radiation, achieving high levels of cell killing in short-term assays. In addition, the combination of Bax and radiotherapy reduced the survival fraction of cell lines 2 logs in standard colony-forming assays. Investigation into the involved mechanism suggests that Bax-mediated radiosensitization occurs through both apoptosis and necrosis pathways. Further, mice subcutaneously injected with ovarian tumor cells previously treated with radiation, or with radiation and irrelevant viruses, consistently developed tumor nodules. In addition, approximately 80% of injections were followed by tumor formation after treatment with Ad/Bax and Ad/Cre alone. In contrast, tumor formation was completely inhibited after combined treatment with Ad/Bax and Ad/Cre and radiation. Augmentation of the effect of radiotherapy on human ovarian cancer cells and primary cancer cells from patients via a recombinant adenovirus encoding Bax is feasible.


Skin grafts as pharmacological agents: pre-wounding of the donor site.
Initially thought to act as tissue replacement, cultured epithelial allografts are now known to work by providing a potent stimulus for healing. In a similar fashion, we believe that traditional autografts may also provide a stimulus to help heal chronic wounds, thus acting as pharmacological agents for healing. We attempted to assess the possibility of augmenting the stimulatory properties of donor skin by initiating the healing process in the donor region prior to grafting. This was accomplished by pre-wounding the donor area 3 days prior to harvesting the donor skin. We compared these 'pre-wounded' grafts to those harvested immediately. Two patients underwent punch grafting for chronic leg ulceration. Half of the ulcer was grafted with donor skin harvested from an area that was pre-wounded and the other half from freshly harvested skin. We evaluated each for improvement of granulation tissue and degree of edge effect (migration of the previously dormant wound edges). All the grafts did well. There was marked improvement in granulation tissue in the ulcer bed after grafting, and the obvious presence of an edge effect. The edge effect was increased on the site where the pre-wounded grafts were placed. It may be possible to augment the growth stimulatory properties of donor skin. This may offer therapeutic options in patients with chronic wounds.


Laparoscopic Long Mesh Surgery with Augmented Round Ligaments: A Novel Uterine Preservation Procedure For Apical Pelvic Organ Prolapse.
We aim to assess the surgical outcomes of our novel hysteropexy procedure, laparoscopic long mesh surgery (LLMS) with augmented round ligaments. Twenty-five consecutive women with stage II or greater main uterine prolapse defined by the POP quantification staging system were referred for LLMS. Long mesh is a synthetic T-shaped mesh, with the body fixed at the uterine cervix and the two arms fixed along the bilateral round ligaments. The clinical evaluations performed before and 6 months after surgery included pelvic examinations, urodynamic studies, and questionnaires for urinary and sexual symptoms. After a follow-up time of 12 to 24 months, the anatomical reduction rate was 92% (23/25) for the apical compartment. The average operative time was 65.4 ± 28.8 minutes. No major complications were recognized during LLMS. The lower urinary tract symptoms and scores on the questionnaires improved significantly after the surgery, except urgency urinary incontinence and nocturia. Neither voiding nor storage dysfunction was observed after the operations. All of the domains and total Female Sexual Function Index (FSFI) scores of the 15 sexually active women did not differ significantly after LLMS. The results of our study suggest that LLMS is an effective, safe, and time-saving hysteropexy surgery for the treatment of apical prolapse.


Assessing age-related balance deterioration: Visual or mechanical tasks?
Mediolateral balance assessment (MELBA) comprises tracking of predictable and unpredictable targets moving at increasing frequencies, using centre-of-mass feedback. The mediolateral-balance-assessment was shown to be sensitive to subtle age-related balance deterioration. However, it has been suggested that performance during ground-level tasks can be more sensitive to balance deterioration. we developed a modified mediolateral-balance-assessment using tracking of surface translations with comparable waveforms (mechanical mediolateral-balance-assessment) to compare age sensitivity of the visual and mechanical mediolateral-balance-assessment, 15 older adults (68 SD 5 yr) and 12 young adults (30 SD 4 yr) performed both tasks. Phase-shift and gain between the CoM and either the visual target or the surface displacement for the visual and the mechanical mediolateral-balance-assessment, respectively, were calculated. To identify differences in tracking strategies between the visual and mechanical mediolateral-balance-assessment, phase-shift between trunk and leg angles was calculated. Overall, older adults performed worse than young across the predictable and unpredictable tracking and visual and mechanical tasks. Of all mediolateral-balance-assessment performance descriptors, a significant interaction between age and task (visual or mechanical) was only found for the mean phase-shift. Post-hoc comparisons revealed significant age differences in the visual but not in the mechanical mediolateral-balance-assessment. Significant differences in tracking strategies were found between visual and mechanical mediolateral-balance-assessment with a greater decoupling of trunk and legs during the mechanical than the visual mediolateral-balance-assessment. the visual mediolateral-balance-assessment was more sensitive to age-related balance deterioration than the mechanical mediolateral-balance-assessment, possibly because visual tracking elicits motor strategies that are more affected by ageing.


Fragmentation and exfoliation of 2-dimensional materials: a statistical approach.
The main advantage for applications of graphene and related 2D materials is that they can be produced on large scales by liquid phase exfoliation. The exfoliation process shall be considered as a particular fragmentation process, where the 2D character of the exfoliated objects will influence significantly fragmentation dynamics as compared to standard materials. Here, we used automatized image processing of Atomic Force Microscopy (AFM) data to measure, one by one, the exact shape and size of thousands of nanosheets obtained by exfoliation of an important 2D-material, boron nitride, and used different statistical functions to model the asymmetric distribution of nanosheet sizes typically obtained. Being the resolution of AFM much larger than the average sheet size, analysis could be performed directly at the nanoscale and at the single sheet level. We find that the size distribution of the sheets at a given time follows a log-normal distribution, indicating that the exfoliation process has a "typical" scale length that changes with time and that exfoliation proceeds through the formation of a distribution of random cracks that follow Poisson statistics. The validity of this model implies that the size distribution does not depend on the different preparation methods used, but is a common feature in the exfoliation of this material and thus probably for other 2D materials.


Prodromal Myocardial Infarction Fatigue: A Concept Analysis.
Patients' care-seeking behaviors are often based on the symptoms they experience. Prodromal myocardial infarction symptoms are those symptoms that occur prior to a myocardial infarction, and fatigue is common. However, the concept of prodromal myocardial infarction fatigue has not been explored from a multidimensional perspective using a concept analysis approach. The purpose of this concept analysis was to analyze this concept, using Walker and Avant's (2011) concept analysis methodology. A comprehensive literature search revealed 41 records for analysis. The structure and function of this concept was examined, and an operational definition of prodromal myocardial infarction fatigue was developed.


Perceptions of complementary and alternative medicine amongst medical students in Singapore--a survey.
In view of the current upsurge of interest in, practice of, and research into, complementary and alternative medicine (CAM) worldwide and locally, a survey was conducted to gauge the understanding, interest and knowledge of CAM amongst medical students in a local university. A total of 555 first to fifth year medical students completed a questionnaire (54% response rate) designed to assess their knowledge, beliefs and attitudes to CAM in general and 16 common CAM therapies. Acupuncture was the best known therapy, with 57% claiming to know at least something about it. No students claimed they knew a lot about chiropractic, osteopathy, Ayuverdic medicine, homeopathy and naturopathy, and many had not ever heard of these therapies. Knowledge of commonly held beliefs about the 16 CAM modalities was generally poor, even for modalities which students claimed to know most about. A significant number of students had knowledge about CAM that was erroneous. Lack of scientific support was considered to be the main barrier to implementation of CAM. Attitudes to CAM were positive, with 92% believing that CAM includes ideas and methods from which conventional medicine can benefit, 86% wishing to know more about CAM and 91% stating that CAM would play an important role in their future medical practice. As the public's use of various healing practices outside conventional medicine accelerates, ignorance about these practices by the country's future medical practitioners risks broadening the communication gap between the public and the profession that serves them. The majority of medical students recognise this risk and are keen to bridge this gap.


Lattice-site-specific spin dynamics in double perovskite Sr2CoOsO6.
Magnetic properties and spin dynamics have been studied for the structurally ordered double perovskite Sr2CoOsO6. Neutron diffraction, muon-spin relaxation, and ac-susceptibility measurements reveal two antiferromagnetic (AFM) phases on cooling from room temperature down to 2 K. In the first AFM phase, with transition temperature TN1=108 K, cobalt (3d7, S=3/2) and osmium (5d2, S=1) moments fluctuate dynamically, while their average effective moments undergo long-range order. In the second AFM phase below TN2=67 K, cobalt moments first become frozen and induce a noncollinear spin-canted AFM state, while dynamically fluctuating osmium moments are later frozen into a randomly canted state at T≈5 K. Ab initio calculations indicate that the effective exchange coupling between cobalt and osmium sites is rather weak, so that cobalt and osmium sublattices exhibit different ground states and spin dynamics, making Sr2CoOsO6 distinct from previously reported double-perovskite compounds.


Cyclophilin D and the mitochondrial permeability transition in kidney proximal tubules after hypoxic and ischemic injury.
Mitochondrial matrix cyclophilin D (CyPD) is known to promote development of the mitochondrial permeability transition (MPT). Kidney proximal tubule cells are especially prone to deleterious effects of mitochondrial damage because of their dependence on oxidative mitochondrial metabolism for ATP production. To clarify the role of CyPD and the MPT in proximal tubule injury during ischemia-reperfusion (I/R) and hypoxia-reoxygenation (H/R), we assessed freshly isolated tubules and in vivo injury in wild-type (WT) and Ppif(-/-) CyPD-null mice. Isolated mouse tubules developed a sustained, nonesterified fatty acid-mediated energetic deficit after H/R in vitro that could be substantially reversed by delipidated albumin and supplemental citric acid cycle substrates but was not modified by the absence of CyPD. Susceptibility of WT and Ppif(-/-) tubules to the MPT was increased by H/R but was less in normoxic and H/R Ppif(-/-) than WT tubules. Correction of the energetic deficit that developed during H/R strongly increased resistance to the MPT. Ppif(-/-) mice were resistant to I/R injury in vivo spanning a wide range of severity. The data clarify involvement of the MPT in oxygen deprivation-induced tubule cell injury by showing that the MPT does not contribute to the initial bioenergetic deficit produced by H/R but the deficit predisposes to subsequent development of the MPT, which contributes pathogenically to kidney I/R injury in vivo.


Conducting polymer PPy nanowire-based triboelectric nanogenerator and its application for self-powered electrochemical cathodic protection.
As a new type of energy harvesting device, the triboelectric nanogenerator (TENG) can convert almost all kinds of mechanical energy into electricity based on the coupling of triboelectrification and electrostatic induction. Here, a novel TENG is constructed with a conducting polymer polypyrrole nanowire (PPy NW) electrode, which is prepared by an electrochemical polymerization method with anodic aluminum oxide (AAO) as the template. The PPy NW-based TENG shows high output performance with a maximum short circuit current density of 23.4 mA m-2 and output voltage of 351 V, which can light 372 commercial red LEDs. Moreover, a self-powered anticorrosion system powered by the PPy NW-based TENG is designed, which can provide extra electrons to inject into the surface of the protected metals, forming effective impressed current cathodic protection by harvesting mechanical energy or wind energy. This smart device has potential applications for protecting metals from corrosion in daily life, industrial production and ocean exploration by harvesting the energies in the ambient environment.


Open Colectomies of Shorter Operative Time Do Not Result in Improved Outcomes Compared With Prolonged Laparoscopic Operations.
Laparoscopic colectomies are associated with reduced perioperative morbidity and mortality compared with open surgery. Nevertheless, many surgeons continue to utilize an open surgical approach due to the perceived benefits of shorter operative times. This study aims to compare the outcomes of laparoscopic versus open colectomies of equal or shorter operative duration. All patients undergoing elective laparoscopic or open colectomy in the American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP) were identified from the years 2005 through 2012. Patients were stratified first by operative procedure including partial colectomy, total colectomy, or low anterior resection. Each surgical group was then divided into 4 groups according to operative time: <90 minutes, ≥90 minutes and <3 hours, ≥3 hours and <6 hours, and ≥6 hours. In total, 30-day outcomes were compared between laparoscopic operations and open procedures of shorter or equivalent durations within each surgical group. Multivariate logistic regression was utilized to account for differences in patient demographics and comorbidities between the surgical groups. In total, 156,503 patients met inclusion criteria; 112,053 (71.6%) patients underwent a partial colectomy, 13,838 (8.8%) patients underwent a total colectomy, and 30,612 (19.6%) patients underwent a low anterior resection. A laparoscopic approach was used in 34% (37,789 patients) of the partial colectomies performed, 31% (4285 patients) of the total colectomies performed, and 45% (13,850 patients) of the low anterior resections performed. For all procedures, laparoscopic operations <6 hours were associated with superior outcomes compared with shorter open procedures. The benefit of laparoscopic operations was lost when operative time exceeded 6 hours. Laparoscopic colectomies are associated with improved outcomes compared with open operations that do not exceed an operative time of 6 hours. Given the potential to improve patient outcomes, consideration should be given to the laparoscopic approach for all colon surgeries expected to be completed in <6 hours.


Indications for hysteroscopy.
A description of current indications for hysteroscopy is presented, including a review of the literature. Emphasis is placed upon indications that are felt to be useful in the diagnosis and treatment of common gynecologic problems, including abnormal uterine bleeding, infertility, recurrent pregnancy wastage, and removal of intrauterine foreign bodies.


Body height and spinal pain in adolescence: a cohort study from the Danish National Birth Cohort.
To investigate how body height and trajectories of height from infancy through childhood and adolescence were associated with spinal pain in pre- and late adolescence. This prospective study included 43,765 individuals born into The Danish National Birth Cohort (DNBC) from 1996 to 2003. DNBC-data were linked with health and social data identified from Statistics Denmark registers. Spinal pain was self-reported in both the 11-year- and 18-year follow-up of DNBC and classified according to severity. Body height was measured from birth and onwards and further modelled as distinct developmental height trajectories by using latent growth curve modelling. Associations were estimated by using multinomial logistic regression models. Taller body height in childhood and adolescence was associated with approximately 20% increased likelihood of spinal pain in pre- and late adolescence among girls compared to their peers in the normal height group. For boys, taller body height was associated with spinal pain by late adolescence only. Spinal pain in pre-adolescence almost doubled the likelihood of spinal pain in late adolescence regardless of body height at age 18. Height trajectories confirmed the relationship for girls with the tall individuals being most likely to have spinal pain in both pre- and late adolescence. Tall body height during childhood and adolescence predisposes to spinal pain among girls in both pre-and late adolescence, and among boys in late adolescence. Body height is a contributing factor to the pathogenesis of spinal pain in adolescence; however, the mechanisms may be related to growth velocity, but for now uncertain.


Differences in glottal opening pattern between Tokyo and Osaka dialect speakers: factors contributing to vowel devoicing.
In Japanese, high vowels /i/ and /u/ are often devoiced when they are preceded and followed by voiceless consonants. The phenomenon is called vowel devoicing. The frequency of its occurrence is high in dialects of eastern Japan including standard (Tokyo) Japanese and low in dialects of western Japan including Osaka dialect. It has been claimed that consonants, but not vowels, are pronounced more carefully in eastern dialects compared to western dialects, which results in higher frequency of vowel devoicing. This paper examines whether the glottal opening gesture of voiceless consonants differs between those Tokyo speakers who consistently show vowel devoicing and Osaka speakers who do not show vowel devoicing. The results indicated that the duration of glottal opening for /k/ in voiced CV syllables was significantly longer for Tokyo speakers than for Osaka speakers. For Tokyo speakers, duration and maximum size of the glottal opening in devoiced /kite/ are significantly larger than /k/ in voiced syllables. This difference cannot be explained by the simple addition of the glottal gestures of [k] and [t]. Furthermore, the difference in vowel length between /i/ and /e/ was related, at least in part, to the difference in the amount of the airflow passing through the vocal tract about the time the stop closure was released.


Identification of a Prognostic Immune Signature for Esophageal Squamous Cell Carcinoma to Predict Survival and Inflammatory Landscapes.
Immunotherapy has achieved success in the treatment of esophageal squamous cell carcinoma (ESCC). However, studies concerning immune phenotypes within the ESCC microenvironment and their relationship with prognostic outcomes are limited. We constructed and validated an individual immune-related risk signature for patients with ESCC. We collected 196 ESCC cases, including 119 samples from our previous public data (GSE53624) to use as a training set and an independent cohort with 77 quantitative real-time polymerase chain reaction (qRT-PCR) data, which we used for validation. Head and neck squamous cell carcinoma (HNSCC) and lung squamous cell carcinoma (LUSC) cohorts were also collected for validation. A least absolute shrinkage and selection operator (LASSO) model and a stepwise Cox proportional hazards regression model were used to construct the immune-specific signature. The potential mechanism and inflammatory landscapes of the signature were explored using bioinformatics and immunofluorescence assay methods. This signature predicted different prognoses in clinical subgroups and the independent cohort, as well as in patients with HNSCC and LUSC. Further exploration revealed that the signature was associated with specific inflammatory activities (activation of macrophages and T-cell signaling transduction). Additionally, high-risk patients exhibited distinctive immune checkpoints panel and higher regulatory T cell and fibroblast infiltration. This signature served as an independent prognostic factor in ESCC. This was the first applicable immune-related risk signature for ESCC. Our results furnished new hints of immune profiling of ESCC, which may provide some clues to further optimize associated cancer immunotherapies.


Galectin-3 protects keratinocytes from UVB-induced apoptosis by enhancing AKT activation and suppressing ERK activation.
Keratinocytes undergo apoptosis in a variety of physiological and pathological conditions. Galectin-3 is a member of a family of beta-galactoside-binding animal lectins expressed abundantly in keratinocytes and other epithelial cells. Here, we have studied the regulatory role of galectin-3 in keratinocyte apoptosis by using cells from gene-targeted galectin-3 null (gal3(-/-)) mice. We showed that galectin-3 mRNA was transiently upregulated in ultraviolet-B (UVB)-irradiated wild-type keratinocytes. We found that gal3(-/-) keratinocytes were significantly more sensitive to apoptosis induced by UVB as well as various other stimuli, both in vitro and in vivo, than wild-type cells. Moreover, we demonstrated that increased apoptosis in gal3(-/-) keratinocytes was attributable to higher extracellular signal-regulated kinase (ERK) activation and lower AKT activation after UVB irradiation. We conclude that endogenous galectin-3 is an anti-apoptotic molecule in keratinocytes functioning by suppressing ERK activation and enhancing AKT activation and may play a role in the development of apoptosis-related skin diseases.


Management issues in rheumatoid arthritis-associated interstitial lung disease.
Summarize recent evidence on the identification and management of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Clinical and subclinical interstitial lung disease (ILD) are frequent extra-articular manifestations of rheumatoid arthritis (RA). Better means of identifying and treating RA-ILD are needed to improve the prognosis, with a median survival of only 3-7 years after diagnosis. Several serum biomarkers are currently being evaluated for their ability to detect RA-ILD. Thorough evaluation and multidisciplinary discussion remains the gold standard for establishing the diagnosis of RA-ILD. Management is challenging with most RA disease-modifying antirheumatic drugs (DMARDs) linked to pneumonitis. Methotrexate is typically avoided in clinically significant ILD, although alternative therapies including leflunomide and biologic DMARDs also carry risks in RA-ILD. Antifibrotics appear to slow the progression of ILD, and a large phase II trial exclusively in RA-ILD is underway. In addition, smoking cessation, pulmonary rehabilitation, oxygen therapy, managing comorbidities, and lung transplantation evaluation are vital to improving patient outcomes in RA-ILD. With little high-quality evidence to guide the management of RA-ILD, multidisciplinary teams with expertise in RA-ILD are highly valuable for diagnosing and treating RA-ILD. Clinical and translational research in RA-ILD is needed to fill the many evidence gaps.


The Size of the Radial Tuberosity is Not Related to the Occurrence of Distal Biceps Tendon Ruptures: A Case-Control Study.
Hypertrophic changes at the radial tuberosity have traditionally been related to distal biceps tendon degeneration and rupture. From supination to pronation of the forearm, the space available for the distal biceps tendon between de lateral ulna and radial bicipital tuberosity (RBT) decreases by almost 50%. A hypertrophic change at the radial tuberosity further reduces this space with impingement of the distal biceps tendon as a result. The purpose of this study was to evaluate whether the size of the RBT plays a role in the pathophysiology of distal biceps tendon ruptures. Twenty-two consecutive patients with a surgically proven distal biceps tendon rupture were matched to controls, in a 1:1 ratio. The size of the RBT was expressed as a ratio of the maximum diameter of the radius at the RBT to the diameter of the diaphysis just distal to the RBT (RD ratio), measured on standard radiographs of the elbow. The RD ratio of patients and matched controls were compared. The mean RD ratio in control group was 1.25 and not significantly different from the mean 1.30 in the group of patients with a distal biceps tendon rupture. Each 0.1 point increase in RD ratio results in an estimated 60% increase of the rupture odds, which was not significant either. Based on the RD ratio on conventional radiographs of the elbow, there was no significant difference in RBT size between patients with a distal biceps tendon rupture and matched controls without biceps tendon pathology.


Modeling of Future COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Rates and Nonpharmaceutical Intervention Scenarios - United States, April-September 2021.
After a period of rapidly declining U.S. COVID-19 incidence during January-March 2021, increases occurred in several jurisdictions (1,2) despite the rapid rollout of a large-scale vaccination program. This increase coincided with the spread of more transmissible variants of SARS-CoV-2, the virus that causes COVID-19, including B.1.1.7 (1,3) and relaxation of COVID-19 prevention strategies such as those for businesses, large-scale gatherings, and educational activities. To provide long-term projections of potential trends in COVID-19 cases, hospitalizations, and deaths, COVID-19 Scenario Modeling Hub teams used a multiple-model approach comprising six models to assess the potential course of COVID-19 in the United States across four scenarios with different vaccination coverage rates and effectiveness estimates and strength and implementation of nonpharmaceutical interventions (NPIs) (public health policies, such as physical distancing and masking) over a 6-month period (April-September 2021) using data available through March 27, 2021 (4). Among the four scenarios, an accelerated decline in NPI adherence (which encapsulates NPI mandates and population behavior) was shown to undermine vaccination-related gains over the subsequent 2-3 months and, in combination with increased transmissibility of new variants, could lead to surges in cases, hospitalizations, and deaths. A sharp decline in cases was projected by July 2021, with a faster decline in the high-vaccination scenarios. High vaccination rates and compliance with public health prevention measures are essential to control the COVID-19 pandemic and to prevent surges in hospitalizations and deaths in the coming months.


A review of soft tissue calcifications.
The deposition of calcium and phosphorous salts in the soft tissues can be classified into three categories: metastatic calcification, dystrophic calcification, and calcinosis. Metastatic calcification occurs when the calcium-phosphorous levels are elevated. The calcifications involve normal tissues. Associated disease include hyperparathyroidism, neoplasms, milk-alkali syndrome, hypervitaminosis D, and tumoral calcinosis. Dystrophic calcification occurs in the presence of normal metabolism in damaged or devitalized tissues. Disorders included in this classification are: Ehlers-Danlos syndrome, pseudoxanthoma elasticum, arteriosclerosis obliterans, venous calcifications, crystal deposition disorders, and calcification resulting from neurologic disorders. Calcinosis is also found in persons with normal metabolism. It occurs most often in subcutaneous tissues, skin, and related connective tissues. Associated disorders include: calcinosis universalis, calcinosis circumscripta, scleroderma, dermatomyositis, and systemic lupus erythematosus.


[Polymerase chain reaction (PCR) and its possible applications in diagnosis of infection in ophthalmology].
The polymerase chain reaction (PCR) is a relatively new molecular biology-based technique that allows the specific identification of small amounts of DNA or RNA. This technique offers significant advantages compared to conventional microbiological tests, such as microscopy or culture. Increasing numbers of immunosuppressed patients with intraocular infections and, improvements in antibiotic therapy for specific organisms require a more accurate diagnosis. PCR is capable of providing such requirements. This technique is evolving rapidly and in cooperation with clinicians and molecular biologists a number of applications are being developed, which contribute to the growing demands on microbiological testings. This article describes the basics, indications and the limitations of the polymerase chain reaction.


Determination of trace perchlorate concentrations by anion-selective membranes and total reflection X-ray fluorescence analysis.
In the present work a method for the determination of perchlorate trace levels by total reflection X-ray fluorescence (TXRF) is introduced. Perchlorate anions were concentrated on anion-selective membranes that had been prepared on the surface of TXRF quartz reflectors. Various complexation substances were used in the membranes. The reflectors were immersed in water solutions containing nanogram per milliliter (ppb) concentrations of perchlorate. After this step, the reflectors were taken out of the solution and they were analyzed by TXRF, using a copper X-ray tube and helium flow on the target (to lower the argon peak which is present in the air). The effects of various experimental parameters were examined, and the possibility of discrimination between chloride and perchlorate anions was shown. Minimum detection limits lower than 1 ng/mL and good linearity at the concentration range of 1-50 ng/mL were achieved. The method is applicable for the analysis of perchlorate in drinking water samples.


Designing a Fibular Flow-Through Flap with a Proximal Peroneal Perforator-Free Flap for Maxillary Reconstruction.
Reconstruction of a composite maxillary defect is frequently performed with a fibular osteocutaneous free flap to address both the bony and mucosal defect. If during the harvest of the fibula a distal skin perforator is not present due to vascular variations, reconstruction can potentially be done using the soleus muscle for filling of the palatal mucosal defect. An additional challenge arises when the accompanying skin paddle that has been harvested is not perfused, but the fibula remains viable. This case report describes salvage following loss of the skin paddle in an osteocutaneous fibular free flap by designing a fibular flow-through flap using a proximal peroneal perforator free flap. The use of this second free flap allows a skin paddle to be positioned on the distal fibular segment, provides a surgical backup, and limits the donor sites to the same extremity.


The use of vertical flow constructed wetlands for the treatment of hyper-eutrophic water bodies with dense cyanobacterial blooms.
Eutrophication often leads to the periodic proliferation of harmful cyanobacterial blooms (HCBs), which threaten the sustainability of freshwater ecosystems and lead to serious environmental, health and economic damage. Hence, it is vitally important to take effective measures to manage HCBs and associated problems. In this study, vertical flow constructed wetlands (CWs) were operated under different hydraulic loading rates (HLRs) to treat a hyper-eutrophic water body with HCBs. Six sampling ports (representing different layers) were evenly distributed along the water flow direction to study the purification processes of CWs. With HLRs ranging from 0.2 m/d to 0.8 m/d, total nitrogen (TN), total phosphorus (TP), COD, total suspended solid (TSS) and Chlorophyll a (Chl.a) were efficiently treated by CWs, and they were mainly removed at the second layer of CWs. The concentrations of two cyanobacterial metabolites (geosmin and β-cyclocitral) in the effluent were mostly below their odorous threshold concentrations. As the HLRs increased, the treatment efficiencies of the CWs decreased gradually. There was no removal of TP, Chl.a, geosmin, or β-cyclocitral at an HLR of 1.0 m/d. Under suitable HLRs, this type of CW could provide a promising way to control HCBs and associated odorous problems in hyper-eutrophic water bodies.


Case Report: Lack of Response to Givosiran in a Case of ALAD Porphyria.
Introduction: 5-Aminolevulinic acid dehydratase (ALAD) porphyria (ADP) is an autosomal recessive disease characterized by a profound deficiency in ALAD, the second enzyme in the heme biosynthetic pathway, and acute neurovisceral attacks with abdominal pain and peripheral neuropathy. Hemin infusions are often effective in treating and preventing such attacks. Givosiran was recently approved for prevention of attacks of acute hepatic porphyrias (AHPs), including ADP, but, to our knowledge, has not yet been applied in patients with this ultrarare disease. Case Description: We update the clinical course and report new treatment outcomes of a 32-year-old man with ADP managed for many years with weekly prophylactic hemin infusions. He has developed evidence of iron overload and was more recently found to have compensated cirrhosis. The patient was started on givosiran (Givlaari™, Alnylam), a small interfering RNA (siRNA) therapeutic that is effective in preventing frequently recurring attacks of acute intermittent porphyria (AIP), the most common type of AHP. Discussion: No adverse effects of givosiran on the liver were observed in this patient with cirrhosis during 6 months of treatment with givosiran. The patient has continued to have recurrent attacks, with transient decreases in ALA levels only as related to treatment of his attacks with hemin. Our experience limited to one patient with ADP suggests that givosiran may not be effective in this type of acute porphyria. Since ADP may have an erythropoietic component, treatment with hydroxyurea, which was beneficial in one previous case, is planned.


Select physical performance measures and driving outcomes in older adults.
Improving physical functioning may be a future intervention to keep older adults driving safely longer as it can help maintain both physical and cognitive health longer. This systematic review assesses the evidence on the association between three physical functioning measures: the Short Physical Performance Battery, the Timed Up-and-Go test, and the Rapid Pace Walk with driving outcomes in older adults. Older adult studies published between 1994 and 2015 that included the Short Physical Performance Battery, the Timed Up-and-Go test, or the Rapid Pace Walk as a measure of physical functioning and included a driving-related outcome were identified through a comprehensive search and reviewed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Thirteen studies involving 5,313 older adults met the inclusion criteria. Lower Short Physical Performance Battery scores were associated with reduced driving exposure and increased cessation in all three Short Physical Performance Battery studies. The Timed Up-and-Go test was not associated with the driving outcomes (cessation, ability, crashes, and citations) in either of the two Timed Up-and-Go studies. Poorer Rapid Pace Walk scores were associated with decreased driving ability in two studies and with reduced driving exposure in one study, but not associated with driving ability, crashes, citations, or cessation in the remaining five Rapid Pace Walk studies. The Timed Up-and-Go test measure appears not to be a useful measure of physical functioning for the driving outcomes included here. The Rapid Pace Walk may be useful in studies of driving ability and exposure. More driving studies should consider using the Short Physical Performance Battery to determine if it may be useful as a risk factor assessment for identifying individuals at risk of certain driving outcomes.


Effects of coenzyme Q and creatine supplementation on brain energy metabolism in rats exposed to chronic cerebral hypoperfusion.
It is known that oxidative stress and mitochondrial dysfunction both play an important role in animal models of brain ischemia. The present study was undertaken to test whether oral supplementation of coenzyme Q10 (ubiquinone) or creatine citrate could protect against brain ischemia-induced mitochondrial damage in the rats model. Brain ischemia was induced for 50 minutes with three-vessel occlusion (3-VO). Coenzyme Q10 was administered for 30 days before the ischemic event and coenzyme Q10 or creatine citrate for 30 days post-ischemia. Moreover, the concentrations of coenzyme Q10 and α-, γ- tocopherols as well as the formation of thiobarbituric acid reactive substances (TBARS) were measured in brain mitochondria and in plasma. Transient hypoperfusion revealed significant impairment in brain energy metabolism as detected by mitochondrial oxidative phosphorylation as well as decreased concentrations of brain and plasma endogenous antioxidants and increased formation of TBARS in plasma. When compared with the ischemic group, supplementation of coenzyme Q10 was ineffective as a preventive agent. However, the positive effect of therapeutic coenzyme Q10 supplementation was supported by the oxygen consumption values (p < 0.05) and ATP production (p < 0.05) in brain mitochondria, as well as by increased concentration of coenzyme Q9 (p < 0.05) and concentration of α-tocopherol (p < 0.05) in brain mitochondria and by increased concentration of α-tocopherol (p < 0.05) and γ-tocopherol in plasma. This suggests that coenzyme Q10 therapy involves resistance to oxidative stress and improved brain bioenergetics, when supplemented during reperfusion after ischemic brain injury.


Tube Exposure Repair.
All across the world, glaucomatologists are adopting broader use of glaucoma drainage implants even as a primary surgical modality. To avoid tube exposure, which may predispose the eye to endophthalmitis, the implanted tube must be covered by a patch graft. However, these patch grafts also carry a high rate of progressive thinning and erosion, which is believed to result from the lack of cellular infiltration from the surrounding host conjunctival stroma and poor integration of these patch grafts to the host tissue. An ideal patch graft should offer good tensile strength, be suitable for tectonic support, and have biological activities to promote cellular infiltration by the surrounding host conjunctival stroma, thus reducing progressive allogeneic patch graft thinning/erosion. This review talks about various materials and modalities used for an exposed tube repair. How to cite this article: Oana S, Vila J. Tube Exposure Repair. J Current Glau Prac 2012;6(3):139-142.


[Applicability of the Adnex score in predicting the malignancy of ovarian cysts].
Objective : Ovarian cancer screening is a difficult problem due to the anatomy of the ovaries. Only histology allows a definite diagnosis. Our objective was to study the contribution of the Adnex score in the histological characterization of adnexal images for adequate management. It was a retrospective, mono-center, descriptive and analytical. Sixty-five patients were included, those operated for an ovarian cyst and meeting the Adnex criteria: clinical, ultrasound and laboratory. The mean age of the patients was 38.6 years. They were nulliparous in 43% of cases, and only four had a history of operation on ovarian cyst. Abdominal pelvic pain was the most frequent reason for consultation in 48% of cases. An abdominopelvic mass was found on abdominal examination in 11% of cases. Pelvic ultrasound made it possible to objectify the presence of an ovarian mass in all cases, with an average size of 79.66 mm and a reassuring appearance in 66% of cases. The calculation of the Adnex score was done in all patients preoperatively, for a 10% cut-off, the model showed an 86% chance of benignity for tumors proven to be histologically benign. The main route of entry was laparoscopy, in 61% of cases. The treatment was in most cases conservative consisting essentially of a cystectomy. The Adnex score discriminated well between benign and malignant masses, allowing for a better diagnosis preoperatively. It thus deserves its applicability in the clinical setting.


Examination of candidate exonic variants for association to Alzheimer disease in the Amish.
Alzheimer disease (AD) is the most common cause of dementia. As with many complex diseases, the identified variants do not explain the total expected genetic risk that is based on heritability estimates for AD. Isolated founder populations, such as the Amish, are advantageous for genetic studies as they overcome heterogeneity limitations associated with complex population studies. We determined that Amish AD cases harbored a significantly higher burden of the known risk alleles compared to Amish cognitively normal controls, but a significantly lower burden when compared to cases from a dataset of unrelated individuals. Whole-exome sequencing of a selected subset of the overall study population was used as a screening tool to identify variants located in the regions of the genome that are most likely to contribute risk. By then genotyping the top candidate variants from the known AD genes and from linkage regions implicated previous studies in the full dataset, new associations could be confirmed. The most significant result (p = 0.0012) was for rs73938538, a synonymous variant in LAMA1 within the previously identified linkage peak on chromosome 18. However, this association is specific to the Amish and did not generalize when tested in a dataset of unrelated individuals. These results suggest that additional risk variation in the Amish remains to be identified and likely resides outside of the classical protein coding gene regions.


[Infections and aging].
Elderly people are exposed to infectious risks in ways different from younger people. These risks relate to environment, transmission routes and vectors, microbial colonisation of body surfaces and quality of host defence. Admission to a nursing home or a hospital may easily lead to colonisation with (resistant) potentially pathogenic micro-organisms, while pre-existing morbidity, medication and functional disability impair the quality of host defence, to a greater degree than the process of aging. In general, infections have a great impact on the elderly patient. Not only are infections in the elderly often serious, but they often have a deleterious effect on comorbidity and functional ability. Infections in elderly people with serious comorbidity face the physician with the dilemma how far to go with diagnostic procedures and therapy.


Nuremberg lamentation: for the forgotten victims of medical science.
Fifty years after the Nuremberg medical trial there remain many unanswered questions about the role of the German medical profession during the Third Reich. Other than the question of human experimentation, important ethical challenges arising from medicine in Nazi Germany which have continuing relevance were not addressed at Nuremberg. The underlying moral question is that of the exercise of professional power and its impact on vulnerable people seeking medical care. Sensitisation to the obligations of professional power may be achieved by an annual commemoration and lament to the memory of the victims of medical abuse which would serve as a recurring reminder of the physician's vulnerability and fallibility.


Severe electrolyte disturbances after hyperthermic intraperitoneal chemotherapy: oxaliplatin versus mitomycin C.
Oxaliplatin (OX) is increasingly used for hyperthermic intraperitoneal chemotherapy (HIPC) for patients with peritoneal metastases. Our aim was to review electrolyte disturbances and complications after HIPC with oxaliplatin (OX) versus mitomycin C (MMC). We included patients enrolled in single-institution prospective clinical trials who underwent cytoreductive surgery and HIPC with MMC or OX. We reviewed patient demographics, pathology, perioperative course, HIPC administration, and postoperative electrolyte disturbances. Measured postoperative sodium values were corrected for systemic hyperglycemia using the formula: (measured Na(+)) × [(glucose - 100/100) × 1.6]. From January 2002 to April 2009 we performed 80 HIPC procedures. A total of 60 patients (75%) received MMC (dose range 12.5-50 mg/m(2)) carried in lactated ringers solution. There were 20 patients (25%) who received OX (dose range 300 × 400 mg/m(2)) carried in 5% dextrose solution. For patients receiving HIPC with OX, electrolyte disturbances were the most common complication. Compared with MMC, patients receiving OX had significant 24-h postoperative uncorrected hyponatremia (P < 0.001), corrected hyponatremia (P < 0.001), hyperglycemia (P < 0.001), and metabolic acidosis (P < 0.001). In the OX group, corrected (mean 130.5) and uncorrected (mean 127.4) sodium levels were significantly lower than preoperatively (mean 139.9, P < 0.001). The overall nonelectrolyte complication rate was 56.2%. (MMC n = 33, 55.0%; OX n = 12, 60%); the 30-day mortality rate was 0% in both groups. Compared with MMC, HIPC with OX was associated with significant but predictable electrolyte disturbances; however, these electrolyte disturbances were not associated with higher overall complication rates. Close monitoring with early correction is imperative to maximize perioperative care. Further studies are needed to provide mechanistic insight.


Imaging cyclic AMP changes in pancreatic islets of transgenic reporter mice.
Cyclic AMP (cAMP) and Ca(2+) are two ubiquitous second messengers in transduction pathways downstream of receptors for hormones, neurotransmitters and local signals. The availability of fluorescent Ca(2+) reporter dyes that are easily introduced into cells and tissues has facilitated analysis of the dynamics and spatial patterns for Ca(2+) signaling pathways. A similar dissection of the role of cAMP has lagged because indicator dyes do not exist. Genetically encoded reporters for cAMP are available but they must be introduced by transient transfection in cell culture, which limits their utility. We report here that we have produced a strain of transgenic mice in which an enhanced cAMP reporter is integrated in the genome and can be expressed in any targeted tissue and with tetracycline induction. We have expressed the cAMP reporter in beta-cells of pancreatic islets and conducted an analysis of intracellular cAMP levels in relation to glucose stimulation, Ca(2+) levels, and membrane depolarization. Pancreatic function in transgenic mice was normal. In induced transgenic islets, glucose evoked an increase in cAMP in beta-cells in a dose-dependent manner. The cAMP response is independent of (in fact, precedes) the Ca(2+) influx that results from glucose stimulation of islets. Glucose-evoked cAMP responses are synchronous in cells throughout the islet and occur in 2 phases suggestive of the time course of insulin secretion. Insofar as cAMP in islets is known to potentiate insulin secretion, the novel transgenic mouse model will for the first time permit detailed analyses of cAMP signals in beta-cells within islets, i.e. in their native physiological context. Reporter expression in other tissues (such as the heart) where cAMP plays a critical regulatory role, will permit novel biomedical approaches.


Dietary restriction causing iodine-deficient goitre.
Iodine-deficient goitre was common in some parts of the UK prior to the introduction of salt iodisation. Many contemporary salt preparations do not contain much iodine, and there are renewed concerns about the iodine status of the population. We present a boy with severe allergy who developed goitre and significant thyroid dysfunction in association with an iodine-deficient 'food-restricted' diet. The case highlights the importance of a comprehensive nutritional assessment in all children on multiple food restrictions.


Poly(methyl methacrylate) membranes with controlled porosity for advanced multi-step drug elution.
Most of the systems developed for controlled drug delivery applications depend on membrane technology and their preparation parameters. For some applications, a dense membrane structure used in controlled-release systems can excessively prolong drug release due to the low permeability of the coating to the drug or to the low solubility of the drug in water. In these cases, to increase the drug delivery rate, asymmetric membranes can be prepared by a phase-inversion technique, allowing a different drug delivery approach with respect to dense membranes. In this study, porous poly(methyl methacrylate) membranes with different vacuum degrees were prepared through the phase-inversion process. Ternary homogeneous solutions, obtained by mixing polymer, tetrahydrofuran (THF) and water in the desired amounts, were precipitated by the evaporation of a solvent (THF) and a non-solvent (water) at a controlled temperature and ventilation. Membrane morphology, investigated by scanning electron microscopy, showed it to have a diffuse porosity with a regular arrangement and geometry of pores on the top surface. The porosity degree of the membranes, mainly relying on the starting polymer concentration, was also investigated by the use of the software Image-Pro Plus, indicating the presence of a relationship between porosity and permeability characteristics. Membranes, containing folic acid as a model drug, were tested for their transport characteristics and drug delivery both in diffusive and in convective- diffusive conditions. Transport and release parameters, as well as permeability and effective diffusivity, were found to be dependent on the porosity and vacuum degree, which could be controlled by varying the preparation conditions. Furthermore, these membranes showed high hydraulic permeability and rapid drug release, suggesting their use for applications where an intensive therapy in the first few days is required, followed by a constant and slow release for a longer time (two-step drug delivery).


On the Nature of Evidence and 'Proving' Causality: Smoking and Lung Cancer vs. Sun Exposure, Vitamin D and Multiple Sclerosis.
If environmental exposures are shown to cause an adverse health outcome, reducing exposure should reduce the disease risk. Links between exposures and outcomes are typically based on 'associations' derived from observational studies, and causality may not be clear. Randomized controlled trials to 'prove' causality are often not feasible or ethical. Here the history of evidence that tobacco smoking causes lung cancer-from observational studies-is compared to that of low sun exposure and/or low vitamin D status as causal risk factors for the autoimmune disease, multiple sclerosis (MS). Evidence derives from in vitro and animal studies, as well as ecological, case-control and cohort studies, in order of increasing strength. For smoking and lung cancer, the associations are strong, consistent, and biologically plausible-the evidence is coherent or 'in harmony'. For low sun exposure/vitamin D as risk factors for MS, the evidence is weaker, with smaller effect sizes, but coherent across a range of sources of evidence, and biologically plausible. The association is less direct-smoking is directly toxic and carcinogenic to the lung, but sun exposure/vitamin D modulate the immune system, which in turn may reduce the risk of immune attack on self-proteins in the central nervous system. Opinion about whether there is sufficient evidence to conclude that low sun exposure/vitamin D increase the risk of multiple sclerosis, is divided. General public health advice to receive sufficient sun exposure to avoid vitamin D deficiency (<50 nmol/L) should also ensure any benefits for multiple sclerosis, but must be tempered against the risk of skin cancers.


LMNA variants cause cytoplasmic distribution of nuclear pore proteins in Drosophila and human muscle.
Mutations in the human LMNA gene, encoding A-type lamins, give rise to laminopathies, which include several types of muscular dystrophy. Here, heterozygous sequence variants in LMNA, which result in single amino-acid substitutions, were identified in patients exhibiting muscle weakness. To assess whether the substitutions altered lamin function, we performed in vivo analyses using a Drosophila model. Stocks were generated that expressed mutant forms of the Drosophila A-type lamin modeled after each variant. Larvae were used for motility assays and histochemical staining of the body-wall muscle. In parallel, immunohistochemical analyses were performed on human muscle biopsy samples from the patients. In control flies, muscle-specific expression of the wild-type A-type lamin had no apparent affect. In contrast, expression of the mutant A-type lamins caused dominant larval muscle defects and semi-lethality at the pupal stage. Histochemical staining of larval body wall muscle revealed that the mutant A-type lamin, B-type lamins, the Sad1p, UNC-84 domain protein Klaroid and nuclear pore complex proteins were mislocalized to the cytoplasm. In addition, cytoplasmic actin filaments were disorganized, suggesting links between the nuclear lamina and the cytoskeleton were disrupted. Muscle biopsies from the patients showed dystrophic histopathology and architectural abnormalities similar to the Drosophila larvae, including cytoplasmic distribution of nuclear envelope proteins. These data provide evidence that the Drosophila model can be used to assess the function of novel LMNA mutations and support the idea that loss of cellular compartmentalization of nuclear proteins contributes to muscle disease pathogenesis.


Urodynamics in women from menopause to oldest age: what motive? What diagnosis?
To analyze age-associated changes as a motive for urodynamics and urodynamic diagnosis in community-dwelling menopausal women and to discuss the role of menopause and ageing. Four hundred and forty nine consecutive menopausal women referred for urodynamic evaluation of lower urinary tract (LUT) symptoms, met the inclusion criteria and were stratified into 3 age groups: 55-64 years (A), 65-74 years (B), and 75-93 years (C). Comprehensive assessment included previous medical history and clinical examination. Studied items were motive for urodynamics, results of uroflows (free flow and intubated flow) and cystometry, urethral pressure profilometry, and final urodynamic diagnosis. The main motive was incontinence (66.3%) with significant increase of mixed incontinence in group C (p = 0.028). Detrusor function significantly deteriorated in the oldest group, mainly in absence of neurological disease (overactivity p = 0.019; impaired contractility p = 0.028). In the entire population, underactivity predominated in group C (p = 0.0024). A progressive decrease of maximum urethral closure pressure occurred with ageing. In subjects with no detrusor overactivity there was a decrease with age of detrusor pressure at opening and at maximum flow, and of maximum flow while post void residual increased only in the C group. In our population of community-dwelling menopausal women, incontinence was the main motive for urodynamics increasing with ageing. A brisk change in LUT function of women older than 75 years underlined deterioration in bladder function with a high incidence of detrusor hyperactivity with or without impaired contractility while change in urethral function was progressive. Effect of ageing appears to be predominant compared to menopause.


An immuno-chemo-proteomics method for drug target deconvolution.
Chemical proteomics is an emerging technique for drug target deconvolution and profiling the toxicity of known drugs. With the use of this technique, the specificity of a small molecule inhibitor toward its potential targets can be characterized and information thus obtained can be used in optimizing lead compounds. Most commonly, small molecules are immobilized on solid supports and used as affinity chromatography resins to bind targets. However, it is difficult to evaluate the effect of immobilization on the affinity of the compounds to their targets. Here, we describe the development and application of a soluble probe where a small molecule was coupled with a peptide epitope which was used to affinity isolate binding proteins from cell lysate. The soluble probe allowed direct verification that the compound after coupling with peptide epitope retained its binding characteristics. The PKC-alpha inhibitor Bisindolylmaleimide-III was coupled with a peptide containing the FLAG epitope. Following incubation with cellular lysates, the compound and associated proteins were affinity isolated using anti-FLAG antibody beads. Using this approach, we identified the known Bisindolylmaleimide-III targets, PKC-alpha, GSK3-beta, CaMKII, adenosine kinase, CDK2, and quinine reductase type 2, as well as previously unidentified targets PKAC-alpha, prohibitin, VDAC and heme binding proteins. This method was directly compared to the solid-phase method (small molecule was immobilized to a solid support) providing an orthogonal strategy to aid in target deconvolution and help to eliminate false positives originating from nonspecific binding of the proteins to the matrix.


Effect of Dietary l-arabinose on the Intestinal Microbiota and Metabolism of Dietary Daidzein in Adult Mice.
This study examined the effects of L-arabinose on mouse intestinal microbiota and urinary isoflavonoids. Male mice were randomly divided into two groups: those fed a 0.05% daidzein-2.5% L-arabinose diet (AR group) and those fed a 0.05% daidzein control diet (CO group) for 28 days. The amounts of daidzein detected in urine were significantly lower in the AR group than in the CO group. The ratio of equol/daidzein was significantly higher in the AR group (p<0.01) than in the CO group. The composition of caecal flora differed between the AR and CO groups. The occupation ratios of Prevotella and Lactobacillales were significantly lower in the AR group. This study suggests that dietary L-arabinose has the potential to affect the metabolism of equol from daidzein by altering the metabolic activity of intestinal microbiota.


Long-term trends in hepatitis C prevalence, treatment uptake and liver-related events in the Swiss HIV Cohort Study.
Treatment for chronic hepatitis C virus (HCV) infections changed dramatically in the last decade. We assessed changes in the prevalence of replicating HCV infection, treatment uptake and liver-related morbidity and mortality in persons with HIV (PWH) and hepatitis C in the Swiss HIV cohort study. We included all cohort participants between 2002 and 2021. We assessed yearly prevalence of replicating HCV infection, overall and liver-related mortality, as well as the yearly incidence of liver-related events in persons with at least one documented positive HCV-RNA. Of 14 652 participants under follow-up, 2294 had at least one positive HCV-RNA measurement. Of those, 1316 (57%) ever received an HCV treatment. Treatment uptake increased from 8.1% in 2002 to a maximum of 32.6% in 2016. Overall, prevalence of replicating HCV infection declined from 16.5% in 2004 to 1.3% in 2021. HCV prevalence declined from 63.2% to 7.1% in persons who inject drugs, and from 4.1% to 0.6% in men who have sex with men. Among the 2294 persons with replicating HCV infection, overall mortality declined from a maximum of 3.3 per 100 patient-years (PY) to 1.1 per 100 PY, and incidence of liver-related events decreased from 1.4/100 PY to 0.2/100 PY. The introduction of DAA therapy was associated with a more than 10-fold reduction in prevalence of replicating HCV infection in PWH, approaching the estimates in the general population. Overall mortality and liver-related events declined substantially in persons living with HIV and hepatitis C.


Predictive Factors and Risk Model for Positive Circumferential Resection Margin Rate After Transanal Total Mesorectal Excision in 2653 Patients With Rectal Cancer.
The aim of this study was to determine the incidence of, and preoperative risk factors for, positive circumferential resection margin (CRM) after transanal total mesorectal excision (TaTME). TaTME has the potential to further reduce the rate of positive CRM for patients with low rectal cancer, thereby improving oncological outcome. A prospective registry-based study including all cases recorded on the international TaTME registry between July 2014 and January 2018 was performed. Endpoints were the incidence of, and predictive factors for, positive CRM. Univariate and multivariate logistic regressions were performed, and factors for positive CRM were then assessed by formulating a predictive model. In total, 2653 patients undergoing TaTME for rectal cancer were included. The incidence of positive CRM was 107 (4.0%). In multivariate logistic regression analysis, a positive CRM after TaTME was significantly associated with tumors located up to 1 cm from the anorectal junction, anterior tumors, cT4 tumors, extra-mural venous invasion (EMVI), and threatened or involved CRM on baseline MRI (odds ratios 2.09, 1.66, 1.93, 1.94, and 1.72, respectively). The predictive model showed adequate discrimination (area under the receiver-operating characteristic curve >0.70), and predicted a 28% risk of positive CRM if all risk factors were present. Five preoperative tumor-related characteristics had an adverse effect on CRM involvement after TaTME. The predicted risk of positive CRM after TaTME for a specific patient can be calculated preoperatively with the proposed model and may help guide patient selection for optimal treatment and enhance a tailored treatment approach to further optimize oncological outcomes.


Metabacillus sediminilitoris sp. nov., a marine bacterium isolated from a tidal sediment.
A Gram-stain-positive, endospore-forming, motile and rod-shaped bacterium, designated as strain DSL-17T, was isolated from a tidal sediment of the East China Sea and characterized phylogenetically and phenotypically. The strain could grow at 16-47 °C (optimum 37 °C), at pH 6.0-10.0 (optimum 6.0) and with 1-7% (w/v) NaCl (optimum 3 %). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain DSL-17T was related to members of the genus Metabacillus and shared the highest similarity with Metabacillus litoralis SW-211T (98.6 %), followed by Metabacillus halosaccharovorans E33T (97.9 %), Metabacillus crassostreae JSM 100118T (97.7 %), Metabacillus niabensis 4T19T (97.7 %) and Metabacillus malikii NCCP-662T (97.5 %). 16S rRNA gene sequence similarities between strain DSL-17T and other members of the genus Metabacillus were below 96.6 %. The sole respiratory quinone was MK-7. Strain DSL-17T had a cell-wall peptidoglycan based on meso-diaminopimelic acid. The polar lipids were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), three unidentified glycolipids and six unidentified lipids. The strain had iso-C15 : 0, anteiso-C15 : 0, iso-C14 : 0, C16 : 0 and iso-C16 : 0 as major fatty acids. The G+C content of the genomic DNA was 35.7 mol%. The combined genotypic and phenotypic data indicated that strain DSL-17T represents a novel species of the genus Metabacillus, for which the name Metabacillus sediminilitoris sp. nov. is proposed The type strain is DSL-17T (=MCCC 1K03777T=DSM 109843T).


Unconditional analyses can increase efficiency in assessing gene-environment interaction of the case-combined-control design.
A design combining both related and unrelated controls, named the case-combined-control design, was recently proposed to increase the power for detecting gene-environment (GxE) interaction. Under a conditional analytic approach, the case-combined-control design appeared to be more efficient and feasible than a classical case-control study for detecting interaction involving rare events. We now propose an unconditional analytic strategy to further increase the power for detecting gene-environment (GxE) interactions. This strategy allows the estimation of GxE interaction and exposure (E) main effects under certain assumptions (e.g. no correlation in E between siblings and the same exposure frequency in both control groups). Only the genetic (G) main effect cannot be estimated because it is biased. Using simulations, we show that unconditional logistic regression analysis is often more efficient than conditional analysis for detecting GxE interaction, particularly for a rare gene and strong effects. The unconditional analysis is also at least as efficient as the conditional analysis when the gene is common and the main and joint effects of E and G are small. Under the required assumptions, the unconditional analysis retains more information than does the conditional analysis for which only discordant case-control pairs are informative leading to more precise estimates of the odds ratios.


Lenticular oxygen toxicity.
To investigate the possible toxic effect of oxygen on lenses in an organ culture. Bovine lenses were exposed to four different combinations of ambient pressure and oxygen concentration in an organ culture throughout a 7-day period. Lens transparency, histology, enzymatic activities, and photomicrographs were compared in study and control groups. No differences were observed between study and control lenses in all measured parameters in a group subjected to a single exposure of 100% oxygen under increased (i.e., hyperbaric) ambient conditions and a group exposed repeatedly to high ambient pressure and normal oxygen partial pressure. Decreased lenticular transparency and enzymatic activities along with structural changes were observed in lenses exposed repeatedly to 100% oxygen concentration under both normal and increased ambient pressures. The observed changes were oxygen-load-dependent: the higher the oxygen partial pressure and the longer the time of exposure, the more severe the changes observed. Optical and structural changes in the lens occurred in a centripetal orientation: the greater the oxygen load, the more central the damage. High oxygen load has a toxic effect on bovine lenses in organ culture. These effects appear to be cumulative: the higher the oxygen partial pressure and the greater the number of exposures, the more severe the changes observed in the lenses. Changes marking toxicity follow the route of oxygen diffusion into the lens, from the periphery to the center. Cautious interpretation of the results may indicate a role of oxygen (and/or its derivatives) in human cataract formation.


Comparison of adhesion characteristics of common dairy sporeformers and their spores on unmodified and modified stainless steel contact surfaces.
The attachment of aerobic spore-forming bacteria and their spores to the surfaces of dairy processing equipment leads to biofilm formation. Although sporeformers may differ in the degree of attachment, various surface modifications are being studied in order to develop a surface that is least vulnerable to attachment. This study was conducted to compare the extent of adhesion of spores and vegetative cells of the thermotolerant sporeformer Bacillus licheniformis and the high-heat-resistant sporeformers Geobacillus stearothermophilus and Bacillus sporothermodurans on both native and modified stainless steel surfaces. We studied the effect of contact surface and cell surface properties (including surface energy, surface hydrophobicity, cell surface hydrophobicity, and zeta potential) on the adhesion tendency of both types of sporeformers and their spores. Attachment to native and modified (Ni-P-polytetrafluoroethylene, Ni-P-PTFE) stainless steel surfaces was determined by allowing interaction between the respective contact surface and vegetative cells or spores for 1 h at ambient temperature. The hydrophobicity of vegetative cells and spores of aerobic spore-forming bacteria was determined using the hexadecane assay, and zeta potential was determined using the Zeta sizer Nano series instrument (Malvern Panalytical, Malvern, UK). The results indicated a higher adhesion tendency of spores over vegetative cells for both thermotolerant and high-heat-resistant sporeformers. On comparing the sporeformers, B. sporothermodurans demonstrated the highest adhesion tendency followed by G. stearothermophilus; B. licheniformis exhibited minimal attachment on both surfaces. The tendency to adhere varied with cell surface properties, decreasing with lower cell surface hydrophobicity and higher cell surface charge. On the other hand, modifying contact surface properties for higher surface hydrophobicity and lower surface energy decreased attachment.


LINE-1 Cargo and Reverse Transcriptase Activity Profiles in Extracellular Vesicles from Lung Cancer Cells and Human Plasma.
Long Interspersed Element-1 (LINE-1) is an oncogenic human retrotransposon that 'copies and pastes' DNA into new locations via reverse transcription. Given that enzymatically active LINE-1 can be exported in extracellular vesicles (EVs), and that LINE-1 mRNA and its two encoded proteins, ORF1p and ORF2p, are required for retrotransposition, the present study examined LINE-1 EV loading patterns relative to reverse transcriptase (RT) activity in vivo and in vitro. Density gradient ultracentrifugation identified conserved patterns of LINE-1 mRNA and protein distribution in EVs, with RT activity readily detected in EV fractions containing both LINE-1 mRNA and protein. Unlike whole cell and tissue lysates, the ORF1p in EVs was detected as a dimer. EVs from ostensibly healthy plasma donors showed variable but consistent ORF1p profiles, with residual levels of LINE-1 mRNA measured in some but not all samples. EVs from cancer cell lines had elevated mean LINE-1 levels and 5-85 times greater RT activity than EVs from normal cells or healthy plasma. EV RT activity was associated with EV LINE-1 mRNA content and was highest in cell lines that also expressed an elevated expression of ORF1p and ORF2p. Given that LINE-1 activation is a hallmark of many cancer types, our findings suggest that an EV LINE-1 'liquid biopsy' may be developed to monitor LINE-1 activity during the course of malignant progression.


Systematic review: Glycomics as diagnostic markers for hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with one of the highest cancer-related mortality rates worldwide. Early diagnosis is crucial for improving the therapeutic options and reducing the disease-related mortality. To investigate serum N-glycomics as diagnostic markers for HCC. We performed a comprehensive search in PubMed, EMBASE, Web of Science and Scopus through August 17, 2023. Eligible studies assessed the potential use of serum N-glycomics as diagnostic biomarkers for HCC. Study selection, data extraction and quality assessment were performed by two independent reviewers. Of the 48 articles included, 11 evaluated the utility of N-glycomics for the diagnosis of HCC in whole serum while the remaining articles focused on specific protein glycoforms or protein levels. Of these specific proteins, haptoglobin, alpha-fetoprotein (AFP), kininogen (Kin), α-1-antitrypsin and Golgi protein 73 (GP73) were the most frequently studied. Increased levels of fucosylation and branching presented as the most prevalent post-translational modifications of glycoproteins in patients with HCC compared to controls. Notably, glycomics-based biomarkers may provide a clinical benefit for the diagnosis of early HCC, as several algorithms achieved AUCs between 0.92-0.97. However, these were based on single studies with limited sample sizes and should therefore be validated. Alterations in serum N-glycomics, characterised by increased levels of fucosylation and branching, have potential as diagnostic biomarkers for HCC. Optimisation of study design, patient selection and analysing techniques are needed before clinical implementation will be possible.


The development of sensorimotor influences in the audiovisual speech domain: some critical questions.
Speech researchers have long been interested in how auditory and visual speech signals are integrated, and the recent work has revived interest in the role of speech production with respect to this process. Here, we discuss these issues from a developmental perspective. Because speech perception abilities typically outstrip speech production abilities in infancy and childhood, it is unclear how speech-like movements could influence audiovisual speech perception in development. While work on this question is still in its preliminary stages, there is nevertheless increasing evidence that sensorimotor processes (defined here as any motor or proprioceptive process related to orofacial movements) affect developmental audiovisual speech processing. We suggest three areas on which to focus in future research: (i) the relation between audiovisual speech perception and sensorimotor processes at birth, (ii) the pathways through which sensorimotor processes interact with audiovisual speech processing in infancy, and (iii) developmental change in sensorimotor pathways as speech production emerges in childhood.


PROPOSAL OF A REVISIONAL SURGERY TO TREAT NON-INSULINOMA HYPERINSULINEMIC HYPOGLICEMIA POSTGASTRIC BYPASS.
Hyperinsulinemic hypoglicemia with severe neuroglycopenic symptoms has been identified as a late and rare complication in patients submitted to Roux-en-Y gastric bypass. However, the potential gravity of its manifestations requires effective treatment of this condition. The absence of treatment makes it necessary to develop more effective clinical or surgical methods. To present one surgical option to revisional surgery in the treatment of hyperinsulinemic hypoglicemia Methods : The procedure consists in reconstituting alimentary transit through the duodenum and proximal jejunum, while keeping the restrictive part of the gastric bypass. As an additional strategy to maintain weight loss, is realized gastric fundus resection, aiming to suppress ghrelin production more effectively. It was used in three patients with successful results in one year of follow-up. The procedure to reconstruct the food transit through the duodenum and proximal jejunum, keeping the restrictive component of gastric bypass in the treatment of hyperinsulinemic hypoglycemia showed good initial results and validated its application in other cases with this indication.


Using parent metaphors for learning about the neonatal care experience: An interpretive perspective.
This study focuses on how metaphors are used by parents who have had a premature baby to describe their neonatal care experience and how these can contribute to empathic learning of health professionals. In health, metaphors are commonly used to communicate and explain difficult topics. When patients tell their story, metaphor can be a means of expression from which we can learn about their experience of illness or hospitalisation. Limited research exits on how metaphor can improve our understanding of parent's emotional experience in neonatal care and subsequently inform education in this field. Employing narrative inquiry within an interpretive, constructivist paradigm, 20 narrative interviews with 23 parents of premature babies were analysed using a process of metaphor identification. Findings revealed common metaphors used to describe experience. Metaphor clusters used by parents in order of frequency were journeying, altered reality, darkness, breaking, connections, fighting, salvation and being on the edge. Parents widely used compelling and emotive metaphors to describe and express both difficult and challenging times as well as progression forward. Metaphors serve as a powerful way for health professionals to learn about the emotional experiences of parents and potentially enhance their empathic understanding.


Hypoxia increases the yield of photoreceptors differentiating from mouse embryonic stem cells and improves the modeling of retinogenesis in vitro.
Retinitis pigmentosa (RP), a genetically heterogeneous group of diseases together with age-related macular degeneration (AMD), are the leading causes of permanent blindness and are characterized by the progressive dysfunction and death of the light sensing photoreceptors of the retina. Due to the limited regeneration capacity of the mammalian retina, the scientific community has invested significantly in trying to obtain retinal progenitor cells from embryonic stem cells (ESC). These represent an unlimited source of retinal cells, but it has not yet been possible to achieve specific populations, such as photoreceptors, efficiently enough to allow them to be used safely in the future as cell therapy of RP or AMD. In this study, we generated a high yield of photoreceptors from directed differentiation of mouse ESC (mESC) by recapitulating crucial phases of retinal development. We present a new protocol of differentiation, involving hypoxia and taking into account extrinsic and intrinsic cues. These include niche-specific conditions as well as the manipulation of the signaling pathways involved in retinal development. Our results show that hypoxia promotes and improves the differentiation of mESC toward photoreceptors. Different populations of retinal cells are increased in number under the hypoxic conditions applied, such as Crx-positive cells, S-Opsin-positive cells, and double positive cells for Rhodopsin and Recoverin, as shown by immunofluorescence analysis. For the first time, this manuscript reports the high efficiency of differentiation in vivo and the expression of mature rod photoreceptor markers in a large number of differentiated cells, transplanted in the subretinal space of wild-type mice.


Ultrafast dynamics of hard tissue ablation using femtosecond-lasers.
Several studies on hard tissue laser ablation demonstrated that ultrafast lasers enable precise material removal without thermal side effects. Although the principle ablation mechanisms have been thoroughly investigated, there are still open questions regarding the influence of material properties on transient dynamics. In this investigation, we applied pump-probe microscopy to record ablation dynamics of biomaterials with different tensile strengths (dentin, chicken bone, gallstone and kidney stones) at delay times between 1 picosecond and 10 microseconds. Transient reflectivity changes, pressure and shock wave velocities and elastic constants were determined. The result revealed that absorption and excitation show the typical well-known transient behavior of dielectric materials. We observed for all samples a photomechanical laser ablation process, where ultrafast expansion of the excited volume generates pressure waves leading to fragmentation around the excited region. In addition, we identified tensile-strength-related differences in the size of ablated craters and ejected particles. The elastic constants derived were in agreement with literature values. In conclusion, pressure-wave-assisted material removal seems to be a general mechanism for hard tissue ablation with ultrafast lasers. This photomechanical process increases ablation efficiency and removes heated material, thus ultrafast laser ablation is of interest for clinical application where heating of the tissue must be avoided.


[Report of Mycobacterium avium-intracellulare associated with kidney mycobacteriosis].
Consecutive samples of urine from a patient presenting radiological images of multicystic kidneys were microbiologically analyzed searching the possible presence of acid-alcohol resistant bacilli. The patient had already undergone complementary tests, which evidenced a kidney failure. As a result, it was isolated a slow-growth non pigmented mycobacterial strain corresponding to group III of Runyon. It was classified as Mycobacterium avium-intracellulare, according to conventional and alternative bacteriological studies, such as the analysis of fractions of mycobacterial mycolic acids by thin layer chromatography technique.


Access to Enantiomerically Pure P-Chiral 1-Phosphanorbornane Silyl Ethers.
Sulfur-protected enantiopure P-chiral 1-phosphanorbornane silyl ethers 5a,b are obtained in high yields via the reaction of the hydroxy group of P-chiral 1-phosphanorbornane alcohol 4 with tert-butyldimethylsilyl chloride (TBDMSCl) and triphenylsilyl chloride (TPSCl). The corresponding optically pure silyl ethers 5a,b are purified via crystallization and fully structurally characterized. Desulfurization with excess Raney nickel gives access to bulky monodentate enantiopure phosphorus(III) 1-phosphanorbornane silyl ethers 6a,b which are subsequently applied as ligands in iridium-catalyzed asymmetric hydrogenation of a prochiral ketone and enamide. Better activity and selectivity were observed in the latter case.


On the Supervision of a Saturated SIR Epidemic Model with Four Joint Control Actions for a Drastic Reduction in the Infection and the Susceptibility through Time.
This paper presents and studies a new epidemic SIR (Susceptible-Infectious-Recovered) model with susceptible recruitment and eventual joint vaccination efforts for both newborn and susceptible individuals. Furthermore, saturation effects in the infection incidence terms are eventually assumed for both the infectious and the susceptible subpopulations. The vaccination action on newborn individuals is assumed to be applied to a fraction of them while that on the susceptible general population is of linear feedback type reinforced with impulsive vaccination actions (in practice, very strong and massive vaccination controls) at certain time points, based on information on the current levels of the susceptible subpopulation. Apart from the above vaccination controls, it is also assumed that the average of contagion contacts can be controlled via intervention measures, such as confinements or isolation measures, social distance rules, use of masks, mobility constraints, etc. The main objectives of the paper are the achievement of a strictly decreasing infection for all time periods and that of the susceptible individuals over the initial period if they exceed the disease-free equilibrium value. The monitoring mechanism is the combined activation of intervention measures to reduce the contagion contacts together with the impulsive vaccination to reduce susceptibility. The susceptibility and recovery levels of the disease-free equilibrium point are suitably prefixed by the design of the regular feedback vaccination on the susceptible subpopulation.


Safety and efficacy of catheter ablation of para-Hisian accessory pathway via a direct superior vena cava approach: A multicenter study.
Radiofrequency (RF) catheter ablation of para-Hisian accessory pathways (APs) can be challenging due to proximity to the conduction system. A total of 30 consecutive patients with para-Hisian AP were enrolled for ablation in three centers, 12 (40%) of whom had previously failed attempted ablation from the inferior vena cava (IVC) approach. Ablation was preferentially performed using a superior approach from the superior vena cava (SVC) in all patients. The para-Hisian AP was eliminated from the SVC approach in 28 of 30 (93.3%) patients. In the remaining two patients, additional ablation from IVC was required to successfully eliminate the AP. There were two patients experienced reversible complete atrial-ventricular block and PR prolongation during the first RF application. Long-term freedom from recurrent arrhythmia was achieved in 29 (96.7%) patients over a mean follow-up duration of 15.6 ± 4.6 months. Catheter ablation of para-Hisian AP from above using a direct SVC approach is both safe and effective, and should be considered especially in patients who have failed conventional ablation attempts from IVC approach.


Aspergillus fumigatus-specific antibodies in allergic bronchopulmonary aspergillosis and aspergilloma: evidence for a polyclonal antibody response.
Patients with the Aspergillus-induced diseases allergic bronchopulmonary aspergillosis (ABPA), aspergilloma (fungus ball), and Aspergillus skin test-positive asthma were differentiated immunologically by radioimmunoassay based on their total immunoglobulin E (IgE) and Aspergillus fumigatus-specific IgE levels. In this study, a new, highly sensitive biotin-avidin-linked immunosorbent assay was used to evaluate A. fumigatus-specific antibodies of all immunoglobulin classes. Studied populations included 13 patients with ABPA, 12 with aspergilloma, 9 with Aspergillus skin test-positive asthma, and 9 normal individuals without asthma. A. fumigatus-specific antibodies of all classes were elevated in patients with ABPA, variably elevated in those with aspergilloma, and lowest in the other two groups. This assay demonstrated significantly higher specific IgE antibody levels in the ABPA group over those of the other groups, even with 1:1,000 dilutions of the sera. This study demonstrated that ABPA is a disease characterized by a polyclonal antibody response to Aspergillus antigen and not just a response to IgE and IgG antibody classes. The measurement of other antibody classes, particularly IgD and IgA, could enhance the immunodiagnosis of ABPA. The biotin-avidin-linked immunosorbent assay was found to be a highly sensitive assay that can be a clinically useful alternative to radioimmunoassay in the measurement of A. fumigatus-specific antibodies.


Estradiol modulates translocator protein (TSPO) and steroid acute regulatory protein (StAR) via protein kinase A (PKA) signaling in hypothalamic astrocytes.
The ability of the central nervous system to synthesize steroid hormones has wide-ranging implications for physiology and pathology. Among the proposed roles of neurosteroids is the regulation of the LH surge. This involvement in the estrogen-positive feedback demonstrates the integration of peripheral steroids with neurosteroids. Within the female hypothalamus, estradiol from developing follicles stimulates progesterone synthesis in astrocytes, which activate neural circuits regulating gonadotropin (GnRH) neurons. Estradiol acts at membrane estrogen receptor-α to activate cellular signaling that results in the release of inositol trisphosphate-sensitive calcium stores that are sufficient to induce neuroprogesterone synthesis. The purpose of the present studies was to characterize the estradiol-induced signaling leading to activation of steroid acute regulatory protein (StAR) and transporter protein (TSPO), which mediate the rate-limiting step in steroidogenesis, ie, the transport of cholesterol into the mitochondrion. Treatment of primary cultures of adult female rat hypothalamic astrocytes with estradiol induced a cascade of phosphorylation that resulted in the activation of a calcium-dependent adenylyl cyclase, AC1, elevation of cAMP, and activation of both StAR and TSPO. Blocking protein kinase A activation with H-89 abrogated the estradiol-induced neuroprogesterone synthesis. Thus, together with previous results, these experiments completed the characterization of how estradiol action at the membrane leads to the augmentation of neuroprogesterone synthesis through increasing cAMP, activation of protein kinase A, and the phosphorylation of TSPO and StAR in hypothalamic astrocytes.


Proteomics reveal tissue-specific features of the cress (Lepidium sativum L.) endosperm cap proteome and its hormone-induced changes during seed germination.
Mature angiosperm seeds consist of an embryo surrounded by the endosperm and the testa. The endosperm cap that covers the radicle plays a regulatory role during germination and is a major target of abscisic acid-induced inhibition of germination. Cress (Lepidium sativum) is a close relative of the model plant Arabidopsis thaliana (Arabidopsis). Cress seeds offer the unique possibility of performing tissue-specific proteomics due to their larger size while benefiting the genomic tools available for Arabidopsis. This work provides the first description of endosperm cap proteomics during seed germination. An analysis of the proteome of the cress endosperm cap at key stages during germination and after radicle protrusion in the presence and absence of abscisic acid led to the identification of 144 proteins, which were clustered by the changes in their abundances and categorized by function. Proteins with a function in energy production, protein stability and stress response were overrepresented among the identified endosperm cap proteins. This strongly suggests that the cress endosperm cap is not a storage tissue as the cereal endosperm but a metabolically very active tissue regulating the rate of radicle protrusion.


Low-acuity emergency department use among patients in different primary care models in Hamilton and Ontario.
Jurisdictions such as Hamilton, Ontario, where most primary care practices participate in patient enrolment models with enhanced after-hours access, may demonstrate overall improved health equity outcomes. Non-urgent Emergency Department (ED) use has been suggested as an indicator of primary care access; however, the impact of primary care access on ED use is uncertain and likely varies by patient and contextual factors. This population-based, retrospective study investigated whether or not different primary care models were associated with different rates of non-urgent ED visits in Hamilton, a city with relatively high neighbourhood marginalization, compared to the rest of Ontario from 2014/2015 to 2017/2018. In Ontario, enrolment capitation-based practices had more non-urgent ED visits than non-enrolment fee-for-service practices. In Hamilton, where most of the city's family physicians are in enrolment capitation-based practices, differences between models were minimal. The influence of primary care reforms may differ depending on how they are distributed within regions.


[Hereditary microcephaly with autosomal dominant chorioretinal dysplasia (author's transl)].
Within the heterogeneous group of microcephalies, a syndrome can be defined characterized by microcephaly, mental retardation, and chorioretinal dysplasia, often also with microphtalmia and embryonic remnants such as persistance of the primitive vitreum. Although this condition is usually considered autosomal recessive, the authors report a family observation consistent with dominant transmission.