N-Terminal sequencing by mass spectrometry through specific fluorescamine labeling of α-amino groups before tryptic digestion.
We present a single-step procedure for the specific mass labeling of unblocked protein N termini. We show that the dye fluorescamine, which is commonly assumed to require mildly alkaline conditions for undergoing a nonspecific reaction with α- and ε-amino groups associated with amino acids, in fact shows a specific reaction only with α-amino groups present at protein N termini when mildly acidic conditions are used. We use this finding to label, identify, and sequence the trypsinolysis-derived N-terminal peptide of lysozyme, using only mass spectrometry, to illustrate how this method could be used with other proteins.


Community-based health care in Kibwezi, Kenya: 10 years in retrospect.
In response to the interest of the Kenya government in community-based health care, the Kibwezi Rural Health Scheme was developed by the African Medical and Research Foundation (AMREF) in a semi-arid district in eastern Kenya. Based on a community co-operative philosophy and focussing on health promotion and prevention, the scheme includes the following: a health centre with a 15-bed in-patient unit including four maternity beds, out-patient services, and a 15-bed nutrition rehabilitation unit; a cadre of volunteer community health workers, trained by AMREF, who form the backbone of the project; maternal child health/family planning and nutrition services including an applied nutrition programme, a water project; and a mobile health unit. Designed as a replicable model health programme, the intention was that services would be gradually taken over by the Ministry of Health of Kenya. Much has been learned in the development of the project which should be meaningful to others considering similar endeavours. One of the first lessons learned was that the time taken to sensitize the community to community-based health care is critical to the success of the project and may need to be as long as 1-2 years. Another was that gaining the support of the community for the community health workers (CHW) requires a considerable effort on the part of project staff, but seems to be the only viable solution to the remuneration and recognition of the CHW's work. It also became apparent that preventive and promotive health services should be integrated structurally and operationally with curative health services to provide the most benefits for the community served. Finally, although there are some differences of opinion, it is felt that with some refinements, the project could be replicated in other parts of Kenya.


[Molecular phylogeny and the time of divergence of minges (Chironomidae, Nematocera, Diptera) inferred from a partial nucleotide sequence of the cytochrome oxidase I gene (COI)].
This is the first study to infer the phylogenetic structure of minges of the subfamily Chironominae from the amino acid sequence of cytochrome oxidase I (COI). The subdivision of Chironominae into two tribes, Chironomini and Tanytarsini, has been confirmed. The segregation of the genera Pseudochironomus and Riethia into a separate tribe has not been confirmed. Stenochironomus gibbus forms a branch considerably deviating from the subfamily Chironominae. The genus Micropsectra is formed by a large polyphyletic cluster that also includes the genera Virgotanytharsus, Reotanytharsus, Kenopsectra, and Parapsectra. Tanytarsus is the basal genus of the tribe Tanytarsini. The times of divergence of the main taxa of Chironominae have been estimated. The calculated time of divergence of the genus Chironomus disproves the assumption that it is phylogenetically old.


Multimodal access to verbal name codes.
Congruent information conveyed over different sensory modalities often facilitates a variety of cognitive processes, including speech perception (Sumby & Pollack, 1954). Since auditory processing is substantially faster than visual processing, auditory-visual integration can occur over a surprisingly wide temporal window (Stein, 1998). We investigated the processing architecture mediating the integration of acoustic digit names with corresponding symbolic visual forms. The digits "1" or "2" were presented in auditory, visual, or bimodal format at several stimulus onset asynchronies (SOAs; 0, 75, 150, and 225 msec). The reaction times (RTs) for echoing unimodal auditory stimuli were approximately 100 msec faster than the RTs for naming their visual forms. Correspondingly, bimodal facilitation violated race model predictions, but only at SOA values greater than 75 msec. These results indicate that the acoustic and visual information are pooled prior to verbal response programming. However, full expression of this bimodal summation is dependent on the central coincidence of the visual and auditory inputs. These results are considered in the context of studies demonstrating multimodal activation of regions involved in speech production.


MrBayes 3: Bayesian phylogenetic inference under mixed models.
MrBayes 3 performs Bayesian phylogenetic analysis combining information from different data partitions or subsets evolving under different stochastic evolutionary models. This allows the user to analyze heterogeneous data sets consisting of different data types-e.g. morphological, nucleotide, and protein-and to explore a wide variety of structured models mixing partition-unique and shared parameters. The program employs MPI to parallelize Metropolis coupling on Macintosh or UNIX clusters.


Subsequent perinatal outcomes of pregnancy with two consecutive pregnancies with gestational diabetes mellitus: A population-based cohort study.
Gestational diabetes mellitus (GDM) is glucose intolerance diagnosed during pregnancy. We aimed to explore the different outcomes of women with two consecutive pregnancies with GDM. This study included 861 women with recurrent GDM who had two consecutive singleton deliveries at Fujian Maternity and Child Health Hospital between May 2012 and September 2020. Data on pregnancy complications and neonatal and delivery outcomes were collected and analyzed. Among those women with recurrent GDM, there was no difference in pregnancy complications in index pregnancy vs subsequent pregnancy. Our data revealed there was a significantly higher incidence of thyroid disease in the subsequent pregnancies than in the index pregnancy. (6% vs 10%, p = .003)In subsequent pregnancies, the birth weight was greater than that of the index pregnancy (3296.63 ± 16.85 vs 3348.99 ± 16.05, p = .025); and the incidence of large for gestational age (LGA) was higher than that of the index pregnancy (16.3% vs 20.6%, p = .021). More cesarean sections occurred in the subsequent pregnancy. (32.9% vs 6.6%, p = .039). Postpartum hemorrhage, premature birth, and placental abruption were not significantly different between the two pregnancies. The results suggest the effect of GDM on thyroid dysfunction may be persistent. Recurrent gestational diabetes results in a higher rate of cesarean delivery, incidence of LGA, and neonatal admission to the neonatal intensive care unit (NICU) in subsequent pregnancies. We need to pay attention to the postpartum thyroid function of pregnant women with GDM. Further studies are still needed on recurrent GDM to reduce this occurrence of admission to NICU.


Impact of chronic steroid use on outcomes of colorectal surgery.
Steroid use has been recognized as a factor which has various effects on multiple organs. We aim to investigate the association between chronic steroid use and postoperative complications after colorectal surgery. The National Surgical Quality Improvement Program database was used to examine the clinical data of patients undergoing colorectal resection during 2005 to 2013. Multivariate regression analysis was performed to investigate outcomes of patients with chronic steroid use. We sampled a total of 147,121 patients who underwent colorectal resection. Of these, 11,195 (7.6%) had a history of chronic steroid use. Patients who had chronic steroid use had a higher risk of preoperative sepsis (adjusted odds ratio [AOR]: 1.41, P < .01), hypoalbuminemia (AOR: 1.49, P < .01), bleeding disorders (AOR: 1.54, P < .01), and diabetes (AOR: 1.11, P = .01). Chronic steroid use was associated with a significant increase in the mortality and morbidity of patients (AOR: 1.56 and 1.25, respectively, P < .01). Patients with a chronic steroid use have a high risk of preoperative malnutrition, diabetes, bleeding disorders, and sepsis. A history of chronic steroid use was associated with a significant increase in the mortality and morbidity of patients.


[Effect of cold storage and freezing of bovine and porcine liver on activity and subcellular distribution of mitochondrial enzymes].
The subcellular distribution of the mitochondrial enzymes lipoamide dehydrogenase (LIPDH), citrate synthase (CS), and beta-hydroxyacyl-CoA-dehydrogenase (HADH) in bovine and porcine liver tissue was studied by measuring the enzyme activities in a phosphate buffer extract of tissue (total activity) and in liver press-juice (cell plasma). In slaughter-fresh liver most of the activity was located in the mitochondria. During storage of liver under refrigeration (+2 degrees C) for several days a large decrease in total LIPDH activity and a lesser decrease in HADH activity, but no change in CS activity were observed. There was no or only little release of the three enzymes into the cell plasma during storage; this indicates that storage of liver at +2 degrees C was not accompanied by a marked damage of mitochondria. Freezing (-20 degrees C) and thawing of bovine and porcine liver caused some losses of the total activity of HADH and particularly of LIPDH but not changes in CS activity. There was a considerable increase in the activities of LIPDH, CS, and HADH in the press juice after freezing and thawing of liver tissue. Apparently freezing of liver results in damage to the mitochondria and, therefore, in a partial release of the three enzymes from the inner membrane of the mitochondrion into the cell plasma. By storage of liver under refrigeration the mitochondria became more sensitive to freezing and thawing. Prolonged frozen-storage of liver resulted in an increased release of LIPDH, CS, and HADH into the cell plasma.


Energy content, storage substances, and construction and maintenance costs of Mediterranean deciduous leaves.
At monthly intervals water content, crude fibre, total and protein nitrogen, sugars, starch, total lipids, ash content and calorific total energy were measured throughout the lifespan of the leaves of the deciduous mediterranean shrubs Pistacia terebinthus L. and Cotinus coggygria Scop. From these data the construction costs and maintenance costs, as well as the construction costs of non-storage compounds and energy expenditure values were calculated. The latter values were also calculated for the evergreen stemmed shrub Ephedra distachya for reasons of comparison with an evergreen mediterranean species. The water status in the deciduous leaves is stable for a long time during the drought period until the beginning of senescence in August/September. In Cotinus an early and considerable increase of storage compounds is found, whilst in Pistacia terebinthus the accumulation is more uniform until August. The N-content is rather low compared with other deciduous leaves, the calorific energy is in the lower range of the values reported for similar species. The construction costs of the leaves of both deciduous species are significantly lower than those calculated by Williams et al. (1987) for two drought deciduous chaparral species but are in agreement with the data reported by other authors on deciduous leaves. Contrary to the findings of Williams et al. they are lower than those of evergreen species; this is also true when the construction cost of the non-storage compounds alone is considered. The values found for Ephedra are similar to the maintenance costs do not show a significant variation in the deciduous leaves. They are higher than those known for evergreen leaves but somewhat lower than the values calculated for deciduous chaparral leaves.


[Human genomic project and human genomic haplotype map project: opportunitiy, challenge and strategy in stomatology].
The human genomic project and the international HapMap project were designed to create a genome-wide database of patterns of human genetic variation, with the expectation that these patterns would be useful for genetic association studies of common diseases, thus lead to molecular diagnosis and personnel therapy. The article briefly reviewed the creation, target and achievement of those two projects. Furthermore, the authors have given four suggestions in facing to the opportunities and challenges brought by the two projects, including cultivation improvement of elites, cross binding of multi-subjects, strengthening construction of research base and initiation of natural key scientific project.


RGD-mimic polyamidoamine-montmorillonite composites with tunable stiffness as scaffolds for bone tissue-engineering applications.
This paper reports on the development of montmorillonite (MMT)-reinforced hydrogels, based on a peptidomimetic polyamidoamine carrying guanidine pendants (AGMA1), as substrates for the osteo-induction of osteoblast precursor cells. AGMA1 hydrogels of various degrees of crosslinking responded favourably to MMT reinforcement, giving rise to composite hydrogels with shear storage modulus G', when fully swollen in water, up to 200 kPa, i.e. 20 times higher than the virgin hydrogels and of the same order or higher than other hydrogel-based composites proposed for orthopaedic applications. This significant improvement was ascribed to the effective interpenetration between the polymer matrix and the inorganic filler. AGMA1-MMT hydrogels, when evaluated as scaffolds for the osteogenic differentiation of mouse calvaria-derived pre-osteoblastic MC3T3-E1 cells, proved able to support cell adhesion and proliferation and clearly induced differentiation towards the osteoblastic phenotype, as indicated by different markers. In addition, AGMA1-MMT hydrogels proved completely degradable in aqueous media at pH 7.4 and did not provide any evidence of cytotoxicity. The experimental evidence suggests that AGMA1-MMT composites definitely warrant potential as scaffolds for osteoblast culture and bone grafts. Copyright © 2016 John Wiley & Sons, Ltd.


Genetic lineage tracing identifies cardiac mesenchymal-to-adipose transition in an arrhythmogenic cardiomyopathy model.
Arrhythmogenic cardiomyopathy (ACM) is one of the most common inherited cardiomyopathies, characterized by progressive fibrofatty replacement in the myocardium. However, the cellular origin of cardiac adipocytes in ACM remains largely unknown. Unraveling the cellular source of cardiac adipocytes in ACM would elucidate the underlying pathological process and provide a potential target for therapy. Herein, we generated an ACM mouse model by inactivating desmosomal gene desmoplakin in cardiomyocytes; and examined the adipogenic fates of several cell types in the disease model. The results showed that SOX9+, PDGFRa+, and PDGFRb+ mesenchymal cells, but not cardiomyocytes or smooth muscle cells, contribute to the intramyocardial adipocytes in the ACM model. Mechanistically, Bmp4 was highly expressed in the ACM mouse heart and functionally promoted cardiac mesenchymal-to-adipose transition in vitro.


A Bridge Too Far? Real-World Practice Patterns of Early Glucocorticoid Use in the Canadian Early Arthritis Cohort.
To describe patterns of glucocorticoid use in a large real-world cohort with early rheumatoid arthritis (RA) and assess the impact on disease activity and treatment. Data are from adults with new RA (≤1 year) recruited to the Canadian Early Arthritis Cohort (CATCH) and are stratified on the basis of whether a person was prescribed oral glucocorticoids within 3 months of study entry. Disease activity was compared over 24 months. Mixed-effects logistic regression was used for adjusted odds ratios (aORs) of escalation to biologics separately for 12 and 24 months, with random effects terms to account for prescribing patterns clustering by study site. Among 1891 persons, 30% received oral steroids. Users were older, were less often employed, and had shorter disease duration and higher disease activity. Disease activity improved over time, with early glucocorticoid users starting at higher levels of disease activity. Participants with early oral glucocorticoids were more likely to be on a biologic at 12 months (aOR = 2.4; 95% confidence interval [CI], 1.5-3.7) and 24 months (aOR = 1.9; 95% CI, 1.3-3.0). Despite Canadian clinical practice guidelines to limit corticosteroid use to short-term or 'bridge' therapy, 30% of patients who used oral glucocorticoids still used them 2 years later. Early steroids were prescribed sparingly in CATCH and were often indicative of more active baseline disease as well as the need for progression to biologics.


Learned and handcrafted features for early-stage laryngeal SCC diagnosis.
Squamous cell carcinoma (SCC) is the most common and malignant laryngeal cancer. An early-stage diagnosis is of crucial importance to lower patient mortality and preserve both the laryngeal anatomy and vocal-fold function. However, this may be challenging as the initial larynx modifications, mainly concerning the mucosa vascular tree and the epithelium texture and color, are small and can pass unnoticed to the human eye. The primary goal of this paper was to investigate a learning-based approach to early-stage SCC diagnosis, and compare the use of (i) texture-based global descriptors, such as local binary patterns, and (ii) deep-learning-based descriptors. These features, extracted from endoscopic narrow-band images of the larynx, were classified with support vector machines as to discriminate healthy, precancerous, and early-stage SCC tissues. When tested on a benchmark dataset, a median classification recall of 98% was obtained with the best feature combination, outperforming the state of the art (recall = 95%). Despite further investigation is needed (e.g., testing on a larger dataset), the achieved results support the use of the developed methodology in the actual clinical practice to provide accurate early-stage SCC diagnosis. Graphical Abstract Workflow of the proposed solution. Patches of laryngeal tissue are pre-processed and feature extraction is performed. These features are used in the laryngeal tissue classification.


Telehealth for Treatment of Pediatric Dysphonia.
Vocal fold nodules are the most common etiology of chronic dysphonia in the pediatric population. Voice therapy is an effective first line of treatment, with increasing evidence supporting the use of telepractice in speech pathology. Despite this, there is limited data on its effectiveness in the pediatric population. The aim of this retrospective study was to investigate the feasibility and efficacy of telepractice in delivering voice therapy to children diagnosed with vocal fold nodules. A retrospective review was conducted of patients treated with virtual voice therapy from April 2020 to June 2021. Patients were included if diagnosed with vocal fold nodules, 2-18 years of age, and completed therapy in a virtual format. Data includes demographics, Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) scores and pediatric Voice Handicap Index (pVHI) scores. Twenty-three children were included, 17 (74%) male and six (26%) female (with an age range of 2.4-9.9 years at the start of therapy). Prior to treatment, the average CAPE-V Overall Severity score was 37.9 (SD 13.8); the average posttreatment score was 22.4 (SD 10.2). The average pVHI total score prior to treatment was 26.3 (SD 12.1), with an average posttreatment score of 20.2 (SD 11.7). Patients who underwent virtual voice therapy had improved posttreatment CAPE-V severity scores than those prior to treatment (average difference = -15.5 points; 95% CI: -8.3 to -22.7; P < 0.001). An increased number of therapy sessions was associated with both higher initial CAPE-V severity scores (r = 0.72; P < 0.01) and a greater decrease in posttreatment CAPE-V scores (r = -0.55; P < 0.01). Virtual voice therapy may be feasible and efficacious in treating dysphonic children diagnosed with vocal fold nodules. Significant improvements were found in perceptual CAPE-V scores in overall severity; positive changes were also seen in parental measures of quality of life. Delivery of voice therapy in a telehealth format may increase access of care and should be considered as a treatment option.


The Clinical Significance of Anastomotic Ulcers After Ileocolic Resection to Predict Postoperative Recurrence of Crohn's Disease.
The Rutgeerts score is used to predict postoperative recurrence in CD patients after ileocolic resection and is primarily based on endoscopic findings at the neoterminal ileum. However, the optimal assessment of anastomotic ulcers (AUs) remains subject to debate. We aimed to investigate the association between anastomotic ulcers (AUs) and endoscopic recurrence in postoperative Crohn's disease (CD) patients. This single-center retrospective study, conducted between 2000 and 2016, evaluated postoperative CD patients with endoscopic remission at the first ileocolonoscopy within 1 year after ileocolic resection and those who underwent subsequent ileocolonoscopic follow-up. The study outcome was the clinical significance of AUs in predicting endoscopic recurrence. Among 116 patients who were in endoscopic remission defined as the RS of i0 to i1 at the index postoperative ileocolonoscopy, 84.5% (98/116) underwent subsequent ileocolonoscopies. During the median 30.0 months (interquartile range, 21.3-53.3) of follow-up after the first ileocolonoscopy, 56.1% (55/98) of patients showed endoscopic recurrence. Furthermore, 65.8% (48/73) with AUs and 75.5% (40/53) with major AUs, defined as either an ulcer occupying ≥ 1/4 of the circumference, ≥ 3 ulcers confined to anastomotic ring, or any ulcers extending to the ileocolonic mucosa, showed endoscopic recurrence. On multivariable analysis, AUs (adjusted hazard ratio [aHR], 4.33; 95% confidence interval [CI], 1.87-10.0; P < 0.001) and major AUs (aHR, 3.64; 95% CI, 1.95-79; P < 0.001) were associated with endoscopic recurrence. AUs are associated with a significantly high risk of endoscopic recurrence in postoperative CD patients who are in endoscopic remission.


Macrolide-resistant Streptococcus pneumoniae clinical isolates that occur in Hokkaido prefecture, Japan.
We examined the macrolide susceptibility and the presence of macrolide-resistance genes in 780 Streptococcus pneumoniae strains that were isolated and collected at trunk hospitals and commercial clinical laboratories in Hokkaido prefecture, Japan, between 1999 and 2003. Of the 780 strains, 57.0% and 49.6% were found to bear the macrolide-resistance genes erm(B) and mef(A), respectively, while 87.9% had either or both of these genes. The mef(A)-positive strains were more frequently found in patients who were younger than 10 years (43.4%) compared to patients who were 10 years or older (30.3%), whereas the erm(B)-positive strains were similarly frequent in both groups (57.2% vs 54.9%). Strains that were extremely resistant to erythromycin (> or = 256 microg/ml) were frequently found in strains isolated at trunk hospitals but were rarely found in strains that had been collected at commercial clinical laboratories. In conclusion, the high frequency of emergence of macrolide resistance in S. pneumoniae strains was similar to reports from other areas of Japan and other east Asian countries. However, the distribution of resistant genes to macrolides and the distribution of the minimum inhibitory concentrations (MICs) differed depending on patients' ages and depending on whether the strains were isolated at trunk hospitals or commercial clinical laboratories.


Preparation and properties of trypsin and chymotrysin coupled covalently to poly (N-vinylpyrrolidone).
Water-soluble poly(N-vinylpyrrolidone) of molecular weight 10 000 was modified by hydrolysis of 5% of the gamma-lactam rings, and formation of the N-hydroxysuccinimidester. This activated polymer was bound covalently to trypsin (EC 18.104.22.168) and chymotrypsin (EC 22.214.171.124) to complexes of a molecular weight of about 150 000. The bound enzymes showed an increase in stability towards autolysis. Towards small molecular weight substrates the trypsin-poly (N-vinylpyrrolidone) conjugate showed an increase in specific activity of 1: 1.6, whereas the activity towards larger substrate was found to be only 20%. Chymotrypsin-poly(N-vinylpyrrolidone) showed decreased activity against small (50%) and large (7%) molecular weight substrates.


Efficacy and safety of CD34-selected and CD19-depleted autografting in multiple myeloma patients: a pilot study.
If multiple myeloma patients are to be cured after high-dose treatment supported by autologous stem cell transplantation, grafts must be purged of circulating myeloma cells. Myeloma cells are present in all grafts and have been identified as CD38(++)CD45(-) plasma cells, plasma blasts, and CD19(+) B cells. In an attempt to improve the purging strategy, we studied a two-step procedure consisting of CD34(+) enrichment followed by CD19 depletion. This article describes the evaluation of this sequential magnetic microbead selection after 18 procedures in 14 patients. The processed autografts contained a median CD34 purity of 81% (range 21-99%) and a recovery of 47% (range 15-82%). Flow cytometric analysis documented the expected reduction of CD34(-) B cells and plasma cells, in most cases to a level below the sensitivity of flow cytometry. Real-time reverse transcriptase polymerase chain reaction documented a CD19 mRNA relative reduction to 0.042 (range 0.01-0.21). Allele-specific oligonucleotide IgH primers were designed for five patients. All products were positive for clonal myeloma cells before processing, but only 1 of 5 was negative after the procedure. The clinical outcome after reinfusion of the processed autografts was evaluated by blood cell recovery and found to be within the range expected from engraftment of unmanipulated autografts. One patient who had delayed platelet recovery associated with cytomegalovirus infection recovered after anti-cytomegalovirus treatment. This pilot study documented engraftment after reinfusion of CD34-selected and CD19-depleted autografts. However, one patient suffered from unexpected prolonged thrombocytopenia. The efficacy of the procedure was evaluated and reduction of myeloma cells was indicated, with only one autograft free of clonal cells.


Corneal hysteresis in patients with dry eye.
To measure corneal hysteresis and intraocular pressure (IOP) in patients with dry eye and to compare with normal subjects. This cross-sectional study consists of 70 eyes of 40 patients with dry eye (group 1) and 75 eyes of 40 normal subjects (group 2). Eyes were diagnosed as dry eye or normal according to the clinical symptoms, biomicroscopical evaluation, and Schirmer test. Corneal hysteresis (CH), corneal resistance factor (CRF), and cornea-compensated intraocular pressure (IOPcc) were measured by the Ocular Response Analyser (ORA). Mean CH values were 10.56±0.25 mm Hg and 10.34±0.26 mm Hg, mean CRF values were 10.75±0.28 mm Hg and 10.70±0.28 mm Hg, mean CCT values were 542±3.20 μm and 543±3.89 μm in group 1 and group 2, respectively. There was no statistically significant difference between the groups for these three parameters. IOPcc values measured with ORA were 15.73±0.36 mm Hg in group 1 and 16.60±0.33 mm Hg in group 2, and there was no statistically significant difference between the two groups. Corneal biomechanical parameters such as CH and CRF are not influenced in dry eye. Also statistical difference was not found between the two groups according to CCT and IOPcc values.


Relationship between the dietary inflammatory index and kidney stone prevalence.
This study aimed to investigate the association between the dietary inflammatory index and lifetime kidney stone prevalence. We performed a cross-sectional study utilizing the 2013-2014 National Health and Nutrition Examination Survey data. Data were available on 2192 participants aged > 20 years with a complete kidney stone history and 24 h dietary intake interview. Weighted multivariable linear regression, subgroup analyses, and interaction terms were employed. Covariates including age, race, sex, energy and protein intake, total serum calcium, serum iron, PIR, phosphorus, serum/urine creatinine, HDL, glucose, diastolic and systolic pressure, education level, eGFR, BMI, albuminuria, diabetes, smoking status, and marital status were hierarchically adjusted in three different models. The average dietary inflammatory index for 2192 participants was - 0.11 ± 1.73, ranging from - 4.52 to 4.28. In the fully adjusted model, participants in the highest dietary inflammatory index tertile (the most proinflammatory) had 72% higher odds of the lifetime prevalence of kidney stones than those in tertile 1 (OR = 1.72, 95% CI: 1.03, 2.88, P = 0.0367). Subgroup analysis showed that the association between the dietary inflammatory index and kidney stone history was only statistically significant in the younger age (age ≥ 60), female, Mexican American groups, married people or people without diabetes, hypertension, low eGFR, and albuminuria. There is a positive association between the dietary inflammatory index and self-reported kidney stones in US adults, which indicates that dietary patterns could greatly impact kidney stone prevalence.


Off-pump coronary artery bypass with bivalirudin for patients with heparin-induced thrombocytopenia or antiplatelet factor four/heparin antibodies.
This study assessed the use of bivalirudin as an alternative anticoagulant in patients with heparin-induced thrombocytopenia-thrombotic syndrome (HIT/TS) or antiplatelet factor four-heparin (anti-PF4/H) antibodies undergoing off-pump coronary artery bypass (OPCAB). In a prospective, open-label, multicenter study, fifty-one patients with documented anti-PF4/H antibodies and (or) HIT/TS underwent OPCAB with bivalirudin anticoagulation (0.75 mg/kg i.v. bolus, 1.75 mg/kg/hour infusion). Procedural success (absence of death, Q-wave myocardial infarction, repeat revascularization, and stroke), bleeding, and transfusion at day seven/discharge, thirty days, and twelve weeks were assessed. Thirty-five patients (67%) were included with positive anti-PF4/H antibodies and no thrombocytopenia or thrombosis, eleven patients (22%) had thrombocytopenia, and five patients had clinical HIT/TS (10%). Procedural success at seven days/discharge was achieved in forty-seven patients (92%), while procedural success at thirty days and twelve weeks was 88%. There were no deaths. Chest tube output over the first twenty-four hours was 936 +/- 525 mL and twenty-five patients received a red blood cell transfusion during their hospitalization. Two patients required reexploration for persistent postoperative hemorrhage. Bivalirudin was an effective alternative anticoagulant for patients with HIT/TS or circulating anti-PF4/H antibodies undergoing OPCAB, with high rates of procedural success and an acceptable incidence of bleeding or transfusions.


A qualitative of stable symptomatology for patients with schizophrenia: do they have adequate post-discharge rehabilitative resources?
Many patients diagnosed with schizophrenia face obstacles to rehabilitation and discharge into the community, particularly with regard to the way resources are structured. Clarifying the difficulties will help health care providers address rehabilitation shortcomings. Semistructured in-depth interviews and participatory observations were conducted in various locations (family home, hospital ward, outpatient clinic, and on the street) with families, social workers, doctors, nursing staff, and patients with schizophrenia. These patients met the medical facility's hospital discharge standards and either had not been discharged or had been discharged within two weeks of meeting the discharge criteria. This study explores the complex and interdependent role of social differences in the rehabilitation of patients with schizophrenia after acute treatment. The study identified five topics related to structural difficulties in resources for the rehabilitation of patients diagnosed with schizophrenia: (1) the role of policy; (2) inadequate facilities and responsibilities; (3) rejecting communities; (4) difficult families; and (5) the threat of stigma. The rehabilitation of patients diagnosed with schizophrenia is a systemic problem. Systemic rehabilitation policies and integrated social support would be more conducive to the rehabilitation of patients. Perhaps cognitive remediation therapy or the Assertive Community Treatment (ACT) Model could benefit individuals with complex disorders.


Promotive Effect of Zinc Ions on the Vitality, Migration, and Osteogenic Differentiation of Human Dental Pulp Cells.
Zinc is an essential trace element for proper cellular function and bone formation. However, its exact role in the osteogenic differentiation of human dental pulp cells (hDPCs) has not been fully clarified before. Here, we speculated that zinc may be effective to regulate their growth and osteogenic differentiation properties. To test this hypothesis, different concentrations (1 × 10-5, 4 × 10-5, and 8 × 10-5 M) of zinc ions (Zn2+) were added to the basic growth culture medium and osteogenic inductive medium. Cell viability and migration were measured by cell counting kit-8 (CCK-8) and transwell migration assay in the basic growth culture medium, respectively. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the gene expression levels of selective osteogenic differentiation markers and zinc transporters. Alkaline phosphatase (ALP) activity analysis and alizarin red S staining were used to investigate the mineralization of hDPCs. Exposure of hDPCs to Zn2+ stimulated their viability and migration capacity in a dose- and time-dependent manner. RT-qPCR assay revealed elevated expression levels of osteogenic differentiation-related genes and zinc transporters genes in various degrees. ALP activity was also increased with elevated Zn2+ concentrations and extended culture periods, but enhanced matrix nodules formation were observed only in 4 × 10-5 and 8 × 10-5 M Zn2+ groups. These findings suggest that specific concentrations of Zn2+ could potentiate the vitality, migration, and osteogenic differentiation of hDPCs. We may combine optimum zinc element into pulp capping materials to improve their biological performance.


PPARγ alleviates peritoneal fibrosis progression along with promoting GLUT1 expression and suppressing peritoneal mesothelial cell proliferation.
Peritoneal fibrosis (PF) is commonly induced by bioincompatible dialysate exposure during peritoneal dialysis, but the underlying mechanisms remain elusive. This study aimed to investigate the roles of peroxisome proliferator-activated receptor gamma (PPARγ) in PF pathogenesis. Rat and cellular PF models were established by high glucose dialysate and lipopolysaccharide treatments. Serum creatinine, urea nitrogen, and glucose contents were detected by ELISA. Histological evaluation was done through H&E and Masson staining. GLUT1, PPARγ, and other protein expression were measured by qRT-PCR, western blotting, and IHC. PPARγ and GLUT1 subcellular distribution were detected using confocal microscopy. Cell proliferation was assessed by MTT and Edu staining. Serum creatinine, urea nitrogen and glucose, and PPARγ and GLUT1 expression in rat PF model were reduced by PPARγ agonists Rosiglitazone or 15d-PGJ2 and elevated by antagonist GW9662. Rosiglitazone or 15d-PGJ2 repressed and GW9662 aggravated peritoneal fibrosis in rat PF model. PPARγ and GLUT1 were mainly localized in nucleus and cytosols of peritoneal mesothelial cells, respectively, which were reduced in cellular PF model, enhanced by Rosiglitazone or 15d-PGJ2, and repressed by GW9662. TGF-β and a-SMA expression was elevated in cellular PF model, which was inhibited by Rosiglitazone or 15d-PGJ2 and promoted by GW9662. PPARγ silencing reduced GLUT1, elevated a-SMA and TGF-b expression, and promoted peritoneal mesothelial cell proliferation, which were oppositely changed by PPARγ overexpression. PPARγ inhibited high glucose-induced peritoneal fibrosis progression through elevating GLUT1 expression and repressing peritoneal mesothelial cell proliferation.


Review of upper and lower extremity musculoskeletal pain problems.
This article reviews common causes of upper and lower extremity pain problems, including bone pain, osteoarthritis, tendinopathy, and muscle pain problems. These common conditions affect many areas of the body; knowledge of their diagnosis and treatment guides the rehabilitation of many patients who have musculoskeletal complaints.


The Framework Convention on Tobacco Control (FCTC) and the adoption of domestic tobacco control policies: the Ecuadorian experience.
The present work concerns the adoption of domestic tobacco control legislation in Ecuador after ratification of the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC). Analysis of legislation, and data collection via interviews with key actors involved in the adoption and implementation of domestic legislation passed purportedly to implement the FCTC and research of the Ecuadorian Congressional Archives. While the FCTC helped raise awareness about tobacco's imminent and future threats to public health, paradoxically, it had the effect of further entrenching tobacco-friendly norms. Philip Morris, with 87% dominance over the Ecuadorian tobacco market, subtly harnessed the FCTC to protect its interests. This outcome was also influenced by poor governmental readiness and intervention, lack of legislative technical capabilities and weak civil society involvement. The Ecuadorian experience suggests that more support should be provided to health ministries, legislatures and local tobacco control organisations to offset the power of the tobacco industry as developing nations get ready to adopt domestic tobacco control legislation.


Corrigendum to "The novel putative methyltransferase METTL7A as one prognostic biomarker potentially associated with immune infiltration in human renal cancer".
[This corrects the article DOI: 10.1016/j.heliyon.2023.e15371.].


How to support the patient with chronic disease. A philosophical point of view.
The patient with chronic disease is influenced by the concept of disease and therapy, their scientific, social, psychological and cultural meaning. He depends on the specific relationship with the physician, his empathy and communication, manifests his individual attitude and behavior in coping with disease, expects understanding and assistance from the social surroundings and can gain essential help from literature, art and philosophy.


Antioxidants and muscle atrophy in colon cancer: beneficial or deleterious effects?
Cancer cachexia is a multifactorial syndrome characterized by an ongoing loss of body weight, mainly due to adipose tissue and skeletal muscle wasting. Muscle atrophy leads to a progressive functional impairment and contributes to a negative impact on patient's quality of life. Oxidative Stress (OS) seems to play a major role in muscle atrophy since OS markers are increased in plasma and muscles of cancer patients. Thus, supplementing patients with antioxidant may reduce OS and restore muscle mass and function. In this study, we assess the effects of antioxidant supplementation on muscle atrophy in a model of colon 26 tumor-bearing mice (C26-mice). Five-week old Balb/c mice receive a subcutaneous injection of PBS or C26 cancer cells with or without daily supplementation with Allopurinol or Oxynov (50mg/kg and 163mg/kg respectively). Blood and muscles are removed 20-22 days after injection. C26-mice develop cachexia, with a decrease in total body weight, muscular endurance and muscle fibers diameter. Furthermore, injection of C26 induces ubiquitination of muscles proteins, suggesting the enhancement of muscle proteolysis. Contrary to our expectations, supplementation with antioxidants (Allopurinol or Oxynov) doesn't prevent weight loss and muscle atrophy but induces premature death of mice. C26-mice exhibit systemic oxidative stress markers (i.e. carbonyl proteins and 4-HNE) and show an increase in phosphorylation levels of the redox-dependent kinase, JNK, in the atrophied muscles (i.e. gastrocnemius). Surprisingly, Allopurinol or Oxynov decrease the total antioxidant defenses in plasma but has no effect on C26-induced oxidative damages and JNK phosphorylation. Our results are in agreement with recent reports showing deleterious effects of antioxidants supplementation in lung and prostate cancer. However, such findings require further investigations.


Effects of age on elements of insulin-signaling pathway in central nervous system of rats.
Insulin resistance is known to play a pivotal role in type 2 diabetes. Senile individuals, besides being prone to insulin resistance and, consequently, to type 2 diabetes, manifest diseases of the central nervous system (CNS) that may be influenced by disturbances of insulin signaling in the brain, such as memory impairment, Parkinson disease, and Alzheimer disease. We investigated the expression and response to insulin of elements involved in the insulin-signaling pathway in the forebrain cortex and cerebellum of rats ages 1 d to 60 wk. The protein content of insulin receptors and SRC homology adaptor protein (SHC) did not change significantly along the time frame analyzed. However, insulin-induced tyrosine phosphorylation of the insulin receptor and SHC, and the association of SHC/growth factor receptor binding protein-2 (GRB2) decreased significantly from d 1 to wk 60 of life in both types of tissues. Moreover, the expression of SH protein tyrosine phosphatase-2 (SHP2), a tyrosine phosphatase involved in insulin signal transduction and regulation of the insulin signal, decreased significantly with age progression, in both the forebrain cortex and the cerebellum of rats. Thus, elements involved in the insulin-signaling pathway are regulated at the expression and/or functional level in the CNS, and this regulation may play a role in insulin resistance in the brain.


Tourniquet effects on muscle oxygen tension in dog limbs. Experiments with cooling and breathing intervals.
The effects of repeated tourniquet applications with breathing periods on muscle pO2 was studied in adult dogs. A tourniquet was applied to one hind limb. The tourniquet was repeatedly inflated for 1 h; four ischemic periods were separated by 20-min recirculation intervals. In other series the limb was cooled prior to tourniquet application, or the animal was treated with the proteinase inhibitor Trasylol. Following tourniquet deflation, the pO2 value in the gastrocnemius muscle initially increased, reaching a peak within 5 min. This initial increase became less apparent with repeated periods of ischemia as well as with prolongation of the ischemic period. The results indicate that cooling prior to tourniquet application represents a better technic than the use of breathing periods or Trasylol.


Adrenal cortical tumors in children.
A review of the literature reveals 230 cases of adrenal cortical tumors in children. We add an additional 7 cases. Signs, symptoms, laboratory studies, and treatment of this rare rate tumor are discussed.


The kinetic behaviour of radiolabelled IgG1 derived from different sources in adult sheep and neonatal lambs.
The turnover rate and pool volume of radiolabelled autologous IgG1 was similar to homologous IgG1 in adult sheep. In neonatal lambs there was no significant difference for either of these parameters between homologous serum IgG1 and maternal colostrum IgG1. However, the pool volume for IgG1 expanded by approx. 30% over the experimental period in the lambs. When the turnover rates were corrected for this increase they were found to be similar to those observed for IgG1 in adult animals.


Psychometric properties of the Patient Health Questionnaire-4 (PHQ-4) in 9230 adults across seven European countries: Findings from the ESTSS ADJUST study.
The four-item Patient Health Questionnaire-4 (PHQ-4) is a widely used screening measure for depression and anxiety. This study aimed to test factor structure and measurement invariance in an adult sample of the general population across seven European countries. A total sample of 9230 adults, 71.3 % female, Mage = 44.35 (SD = 14.11) from seven countries (Austria, Croatia, Georgia, Germany, Lithuania, Portugal, and Sweden) participated in the study. We applied confirmatory factor analysis (CFA) to examine the factor structure and measurement invariance testing to evaluate measurement equivalence across countries, gender, and age groups. The CFA yielded that a two-factor PHQ-4 model with separate depression and anxiety factors had the best fit. Partial scalar measurement invariance was established across different groups based on gender, age, and country. The PHQ-4 is a valid and reliable measure that can be applied to screen for depression and anxiety in the general population. The limitation of the study includes the sampling, which resulted in the sample structure with the majority of females, predominantly of high education and from urban communities.


Heart transplantation using bicaval anastomosis to concomitantly relieve superior vena caval obstruction in a pediatric patient with heart failure.
We describe a case of complex congenital heart disease treated using balloon septostomy, pulmonary artery banding. Blalock-Taussig shunt, and cardiac resynchronization therapy; however, heart failure developed. A bicaval anastomosis was used to relieve superior vena cava (SVC) obstruction despite possible anastomotic stenosis. The postoperative course was uneventful and the patient recovered rapidly. Thus, we recommend bicaval anastomosis using a longer donor SVC concomitantly performed during heart transplantation to relieve both heart failure and SVC obstruction in pediatric patients.


The epidemiology of muscle-strengthening exercise in Europe: A 28-country comparison including 280,605 adults.
Muscle-strengthening exercise (use of weight machines, free weights, push-ups, sit-ups), has multiple independent health benefits, and is a component of the Global physical activity guidelines. However, there is currently a lack of multi-country muscle-strengthening exercise prevalence studies. This study describes the prevalence and correlates of muscle-strengthening exercise across multiple European countries. Data were drawn from the European Health Interview Survey Wave 2 (2013-14), which included nationally representative samples (n = 3,774-24,016) from 28 European countries. Muscle-strengthening exercise was assessed using the European Health Interview Survey Physical Activity Questionnaire. Population-weighted proportions were calculated for (1) "insufficient" (0-1 days/week) or (2) "sufficient" muscle-strengthening exercise (≥2 days/week). Prevalence ratios were calculated using multivariate Poisson regression for those reporting sufficient muscle-strengthening by country and by sociodemographic/lifestyle characteristics (sex, age, education, income, self-rated health etc.). Data were available for 280,605 European adults aged ≥18 years. Overall, 17.3% (95% CI = 17.1%-17.5%) reported sufficient muscle-strengthening exercise (≥2 days/week). Muscle-strengthening exercise was geographically patterned with the lowest prevalence reported in South-eastern European countries (Romania, Malta and Cyprus: range: 0.7%-7.4%), and the highest prevalence in the Nordic countries (Iceland, Sweden, and Denmark: range: 34.1%-51.6%). Older age, insufficient aerobic activity, poorer self-rated health, lower income/education, being female, and being overweight/obese were significantly associated with lower likelihood of reporting sufficient muscle-strengthening exercise, independently of other characteristics. Most European adults do not report sufficient muscle-strengthening exercise, and prevalence estimates varied considerably across countries. Low participation in muscle-strengthening exercise is widespread across Europe, and warrants public health attention.


A quantitative in vitro study of fibroblast and endothelial cell migration in response to serum and wound fluid.
Chemoattractant activity for irradiated and nonirradiated rabbit skin fibroblast and bovine aortic arch endothelial cells was assayed in rabbit wound fluid and sera using a modification of the agarose well method originally described for polymorphonuclear leukocytes. Both serum and wound fluid contained chemoattractants for fibroblasts and endothelial cells. Fibroblast migration was decreased by 70 to 80% when the serum or wound fluid was heated to 56 degrees C for 30 min while endothelial cell migration was reduced by 50 to 60%. Platelet-poor plasma-derived serum had no directive effect on the migration of either cell type.


Production of interferon by human tumor cell lines.
Fourteen continuous human cell lines, including nine derived from tumors and five from non-neoplastic tissues, produced interferon in response to induction with bluetongue virus (BTV), Newcastle disease virus (NDV), and poly(I) . poly(C) complexed with DEAE-dextran. The seven best interferon-producing cell lines (one from a melanoma, five derived from carcinomas, and one SV40-virus-transformed kidney cell line) responded to at least one of the viral inducers with yields of interferon over 1000 units/ml. Because the HT-1376 bladder carcinoma cell line produced high yields of interferon in this survey, and is easily propagated, the optimal conditions for interferon production were investigated, using BTV as the inducer. Interferon yields in 59 inductions over a period of about two years consistently fell within a 6-fold range, and had a geometric mean titer of about 2700 reference units (RU)/ml, representing the production of about 3 RU/10(3) cells. This yield is comparable to mean titers of 1 to 10 RU/10(3) cells obtained by others with human leukocytes, foreskin cell strains, or the Namalva lymphoblastoid cell line. UV-inactivated BTV at a multiplicity corresponding to 10 PFU/cell was as effective an inducer in the HT-1376 cell line as the fully infectious virus at a multiplicity of 1 PFU/cell. The interferon produced by the HT-1376 epithelial cell line has characteristics similar to the interferon induced by poly(I) . poly(C) in human diploid fibroblasts. These studies clearly demonstrate that many different types of tumor-derived cells have the capacity to produce interferon, and that some equal or surpass the efficiency of diploid cells.


Comparison of Visibility and Risk of Neurovascular Tissue Injury Between Portals in Needle Arthroscopy of the Anterior Ankle Joint: A Cadaveric Study.
For needle arthroscopy with 0° viewing, the visible range of intra-articular structures and the difference between portals remain unknown, as do the risks for neurovascular tissue at each portal. To clarify the visibility and safety of needle arthroscopy. Descriptive laboratory study. Ten cadaveric ankle specimens were used. A needle arthroscope with a 1.9-mm diameter was inserted from 4 portals (anteromedial [AM], anterolateral [AL], medial midline [MM], and anterocentral [AC]). Visibility was assessed using a 15-point ankle arthroscopy checklist. In addition, the ankles were dissected to measure the distance between each portal and neurovascular tissues. The visibility of the ankle joint was compared between portals. The success rate of visibility in the deltoid ligament and the tip of the medial malleolus was 100% from the AM, MM, and AC portals and 10% from the AL portal, with significant differences between the portals (P < .01). The visibility success rates in the origin of the anterior talofibular ligament and the tip of the lateral malleolus were 20% for the AM portal, 90% for the MM and AC portals, and 100% for the AL portal, with significant differences between the portals (P < .01). All other points of the ankle joint were visualized from all the portals with a 100% success rate. The AC portal was in contact with the anterior neurovascular bundle in 4 of the 10 specimens. When needle arthroscopy was performed from the AM or AL portal, the site opposite to the portal in the ankle joint was difficult to visualize. Conversely, most points of the ankle joint could be visualized from the MM and AC portals. Care should be taken when creating an AC portal because of its proximity to the anterior neurovascular bundle. The present study provides information regarding which portal should be selected to perform needle arthroscopy in the ankle joint, which will be beneficial for management of ankle injuries.


Fully Ambulatory Laparoscopic Sleeve Gastrectomy: 328 Consecutive Patients in a Single Tertiary Bariatric Center.
Laparoscopic sleeve gastrectomy (LSG) is becoming one of the most popular bariatric procedures because of its short operative time, good resolution of comorbidities, excellent weight loss, and low complications rate. However, the safety of LSG as a day-surgery procedure has not yet been widely documented. A retrospective analysis of a prospectively collected bariatric database, in a single institution, between August 2012 and February 2015, yielded 980 patients who underwent LSG; 328 patients (33.5 %) responded to established criteria and were operated on a 1-day surgery basis (length of stay < 12 h). There were 258 (78 %) primary LSG and 70 revisional LSG (22 %) performed on 284 females and 44 males, with a mean age (±SD) of 38 ± 9 years. Mean (±SD) preoperative body mass index (BMI) was 45 ± 6 kg/m(2). Operative time was 68 ± 17 min (mean ± SD). There were no deaths. A total of 322 patients (98.2 %) were discharged home the day of surgery. There were 6 (1.8 %) unplanned overnight hospitalization, and 28 patients (8.5 %) were readmitted between days 1 and 30. Most patients (25/34, 73 %) were hospitalized for minor problems, such as pain, nausea, and/or vomiting. There were two cases of (0.6 %) gastric staple line leaks, three (0.9 %) of intra-abdominal hematomas, two (0.6 %) of pneumonia, one (0.3 %) of acute pancreatitis, and one (0.3 %) of urinary tract infection. All patients recovered well. LSG can be performed as an outpatient procedure in selected patients, with acceptable results in terms of retention, readmission, and complication rates.


[Surgical management of synovial cyst of the lumbar spine: retrospective study of 52 patients].
Lumbar synovial cysts are an uncommon cause of radiculopathy, low back pain and neurogenic claudication. We report a retrospective analysis of the clinical presentation, radiological studies, operative findings and outcome in 52 patients surgically treated for symptomatic lumbar synovial cysts. Retrospective data from 52 consecutive patients treated from January 1996 to February 2006 were analyzed. We studied the clinical symptoms, diagnostic methods and radiological findings in all patients, reviewed the types of conservative therapy applied, the surgical findings and techniques, as well as the immediate and long-term results. Surgical outcomes were evaluated according to the Friedberg scale. There were 35 women and 17 men with an average age of 63.2 years (range 36-84 years). The most common symptoms were radiculopathy (65,4%) and neurogenic multiroot claudication (34,6%). Forty-seven patients had back pain and 22 paresthesia. Preoperative neurological examination demonstrated motor weakness (5.7%), sensory loss (7.6%). The radiological work-up consisted in CT-scan and/or MRI for all patients. The correct preoperative diagnosis was established in 44 patients. A total of 56 cysts were found. Five patients had bilateral cysts. The L4-L5 level was affected in 66%. Total resection of the synovial cyst was possible for 46 patients. No fusion was performed as a first line procedure. However, subsequent fusion was necessary in one patient who developed delayed symptomatic spondylolisthesis. Mean follow up period was 14 months ranging from six to 24 months. Three recurrences occurred during the follow-up period. Functional outcome was excellent in 61.6%, good in 34.6% and poor in 3.8%. Surgery should be proposed when synovial cysts fail to respond to conservative therapy. Recurrence and surgical complication rates are low. The usefulness of systematic fusion procedure is questionable.


Daily oral supplementation of Hochu-Ekki-To prevents osteoclastic activation and bone loss in ovariectomized mice.
Bone remodeling is sophisticatedly regulated by two different cell types: bone-resorbing osteoclasts and bone-forming osteoblasts. Hochu-Ekki-To, a Japanese traditional herbal medicine, is commonly used for the treatment of chronic diseases or frailty after an illness; however, its effects on metabolic bone diseases such as osteoporosis are not well known. We herein report that daily oral Hochu-Ekki-To administration significantly inhibits osteoclast activation as well as the reduction in bone volume in ovariectomized mice. Our results suggest that supplementation with Hochu-Ekki-To might be beneficial for the prophylaxis and treatment of metabolic bone diseases associated with abnormal osteoclast activation.


The sensitive giant: the role of titin-based stretch sensing complexes in the heart.
Every heart beat is not equal. As physiological demands of the cardiovascular system change, cardiac myocytes modulate contractile parameters including the rate and force of contraction. Adaptive responses require the sensing of biomechanical signals involving the interface between the contractile cytoskeleton (myofibrils) and the sarcolemma at specialized cell-cell junctions (intercalated discs) and cell-substrate adhesion complexes (costameres). Recent studies have shed insight into how protein complexes within cardiac myocytes sense biomechanical signals, processes required for normal adaptive or pathological responses. This new evidence suggests that complexes associated with the giant, myofibrillar protein titin sense myocyte stretch. Here, we discuss evidence supporting titin being an ideal biomechanical sensor.


Incidence of hidradenitis suppurativa among tobacco smokers: a population-based retrospective analysis in the U.S.A.
The relationship between tobacco use and hidradenitis suppurativa (HS) is controversial. To determine the incidence of HS among tobacco smokers. Retrospective cohort analysis identifying incident HS cases among adult tobacco smokers and nonsmokers sampled from a demographically heterogeneous population-based sample of over 50 million unique patients across all census regions in the U.S.A. We identified 3 924 310 tobacco smokers, which included 7860 patients newly diagnosed with HS. Tobacco smokers diagnosed with HS were most commonly aged 18-39 years (3795 of 7860; 48·3%), women (5640 of 7860; 71·8%), white (5200 of 7860; 66·2%) and those with body mass index (BMI) ≥ 30 (5690 of 7860; 72·4%). Overall incidence of HS was 0·20% (7860 of 3 924 310) among tobacco smokers and 0·11% (8430 of 8 027 790) among nonsmokers (P < 0·001). Incidence was greatest among tobacco smokers who were aged 30-39 years (0·35%), women (0·28%), African Americans (0·46%) and those with BMI ≥ 30 (0·33%). The overall adjusted odds of developing HS was 1·90 (95% confidence interval 1·84-1·96) among tobacco smokers, compared with nonsmokers (P < 0·001). HS incidence among tobacco smokers remained increased within each demographic subgroup. Incidence of HS appears to be doubled among tobacco smokers. These findings may support evidence-based counselling efforts for the cessation of smoking in populations at risk for HS.


[From premature ventricular complexes to sustained ventricular tachycardia : An overview of innovations in the 2022 ESC Guideline on the therapy of ventricular arrhythmias].
The recent 2022 European Society of Cardiology Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death are an update of the former 2015 European guidelines. With multiple tables, algorithms, and comprehensive integration of underlying study data, the new guideline is a user-oriented reference book for clinical practice that also covers special clinical situations such as cardiac arrhythmias in pregnancy or in the context of sports. Regarding the acute treatment of ventricular arrhythmias, cardioversion is now recommended in case of hemodynamically tolerated arrhythmias. Beyond that, the guideline places special emphasis on the management of the electrical storm. In long-term therapy, recommendations for drug therapy have been aligned with current heart failure guidelines. Catheter ablation of ventricular arrhythmias has gained importance not only for recurrent ventricular tachycardia under chronic amiodarone therapy and as an alternative to implantable cardioverter-defibrillators (ICDs) in selected patients with coronary artery disease, but especially for the treatment of idiopathic premature ventricular contractions and tachycardias. Risk stratification and criteria for primary preventive ICDs are still controversial topics, which are discussed in detail based on the specific disease entities.


The development and maintenance of human visceral pain hypersensitivity is dependent on the N-methyl-D-aspartate receptor.
Visceral hypersensitivity is a common feature of functional gastrointestinal disorders. One speculated mechanism is an activity-dependent increase in spinal cord neuronal excitability (central sensitization), which is dependent on activation of the N-methyl-D-aspartate (NMDA) receptor. Our aims were to determine whether the development and maintenance of human visceral hypersensitivity is NMDA receptor mediated. Healthy subjects were studied using a randomized, double-blind, placebo-controlled, crossover design. Pain thresholds to electrical stimulation were determined both in the proximal esophagus and in the foot (control) before and after a 30-minute distal esophageal infusion of 0.15 mol/L HCl acid. Ketamine (NMDA receptor antagonist) or saline (vehicle) was given intravenously either prior to or following acid infusion, and pain thresholds were measured for the following 120 minutes. Protocol 1: In 6 subjects, the effect of ketamine in the esophagus was assessed without acid infusion. Protocol 2: In 14 subjects, ketamine was given prior to esophageal acid. Protocol 3: In 12 subjects, ketamine was given after esophageal acid. Protocol 1: In the absence of esophageal acid, ketamine had no effect on either esophageal or foot pain thresholds (area-under-the-curve, [AUC] P = 0.36 esophagus, P = 0.34 foot, ANOVA) within 30 minutes of cessation of the infusion. Protocol 2: Acid-induced esophageal hypersensitivity was prevented by ketamine (AUC, P < 0.0001, ANOVA) without affecting foot pain thresholds (AUC, P = 0.06, ANOVA). Protocol 3: Ketamine delivered after acid reversed the induction of esophageal hypersensitivity induced by acid (AUC, P < 0.0001, ANOVA). The induction and maintenance of acid-induced esophageal hypersensitivity is prevented and reversed by ketamine. This finding strongly indicates that central sensitization is a mechanism of visceral hypersensitivity.


The fate and behavior of perfluorooctanoic acid (PFOA) in constructed wetlands: Insights into potential removal and transformation pathway.
Although constructed wetland (CW) technology is widely used to eliminate emerging organic pollutants, the removal pathway of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in CW system have not been fully understood yet. This study aims to deeply probe into the fate and behavior of perfluorooctanoic acid (PFOA) in CW system. Findings indicated that the removal efficiency of PFOA by CW system was 49.69-73.63 % with initial concentrations at 100-1000 μg/L. Substrate was the main "sink" of PFOA into the CWs (46.22-50.83 %), and the plant uptake (1.99-2.48 %) accounted for a small proportion. Transformation products in the effluent of CW systems included a series of short-chain perfluorinated carboxylic acids (PFCAs), hydrogen-containing perfluoroalkanes and other organic fluorides. Activated pathways of xenobiotics biodegradation suggested that enzyme-mediated biochemical reactions might be responsible for the PFOA transformation. The transformation pathway included enzymatic decarboxylation, hydroxylation, hydrolysis, dehydrogenation and dehalogenation, as well as non-enzymatic reactions. These discoveries provide new insights into the in-depth understanding environmental behavior of PFOA in ecosystem and lay the foundation for further ecological remediation.


Antibodies to skeletal muscle in myasthenia gravis. Part 1. Diagnostic value for the detection of thymoma.
The role of anti-muscle antibodies (AMA) in the diagnosis of thymoma in patients with myasthenia gravis (MG) is evaluated. We compared ELISA and Western blot assay for antibodies to citric acid muscle extract (a-CAE) with an immunofluorescence assay (IF). Sera from 234 selected MG patients and 123 controls were tested. There was no essential difference between ELISA and IF. Western blot was superior in young onset patients but less useful in patients with an onset beyond the age of 40 years. Unusually high post-test probabilities were found by our patient selection criteria which seem most realistic for clinical practice. Western blot revealed no differences in specificity of AMA in thymoma and non-thymoma patients irrespective of age at onset of disease.


Repair of UV-induced damage in wild-type and mutant strains of Schizophyllum commune.
The basidiomycete fungus Schizophyllum commune was found to have both photo-repair and dark-repair systems for UV-induced damage. Three UV-sensitive mutants were isolated and characterized for ability to repair UV-induced damage in light and dark, and for cross-sensitivity to caffeine and methyl methanesulfonate. Two of the mutants were damaged, to different extents, in their capacity for excision repair; one of these mutants was also probably damaged in post-replication repair. The third mutant was damaged only in post-replication repair.


Chest wall bone late recurrence of an endometrial adenocarcinoma.
Among gynecological malignancies, Endometrial cancer stands out as the most prevalent form of carcinoma. However, Adenocarcinoma is the most frequent histological type of Endometrial cancer. Endometrial metastases are generally confined to pelvis, and distant metastases are seen primarily in the lymph nodes, lungs, or liver. bone Endometrial metastases are detected from 2% to 6% at diagnosis. Bones metastasis are generally restricted to the pelvis, vertebrae, and femur. Other locations such as the peripheral skeletal, chest wall, cranium and bone recurrence later after initial treatment are very unusual. In cases of bone recurrence, adenocarcinoma is the most seen. CT and PET/CT scan are the most useful diagnostic modality for the detection of a bone metastasis. Here, we report a chest wall bone late recurrence of an endometrial adenocarcinoma.


Immunization with nanogram quantities of nitrocellulose-bound antigen, electroblotted from sodium dodecyl sulphate-polyacrylamide gels.
Intrasplenic immunization with antigen immobilized on nitrocellulose (NC) paper results in an immune response with nanogram amounts of antigen without the use of Freund's adjuvant. Comparing the sensitivity of the intrasplenic immunization with intraperitoneal or subcutaneous administration, we found that the intrasplenic method resulted in more positive animals with higher titres than did the other techniques with the smallest amount of antigen (70 ng of bovine serum albumin). With larger amounts of albumin the intraperitoneal method yielded the highest titres. No loss of antigenicity was observed when we immunized with equal amounts of protein separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotted and stained with either Coomassie brilliant blue R 250 or Amido black 10 B.


Sexually antagonistic selection during parental care is not generated by a testosterone-related intralocus sexual conflict-insights from full-sib comparisons.
The evolution of shared male and female traits can be hampered if selection favours sex-specific optima. However, such genomic conflicts can be resolved when independent male and female mechanisms evolve. The existence, extent and consequences of conflict and/or conflict resolution are currently debated. Endocrinological traits like plasma testosterone (T) are suitable test cases, given their important role in mediating correlated traits, plus their opposing sex-specific fitness effects. We compared full-sibling (brother/sister) captive canaries to test for (1) sexually antagonistic selection characterized by contrasting fitness patterns within pairs of relatives, (2) intersexual genetic correlation of plasma T (h(²) = 0.41 ± 0.31) and (3) intralocus sexual conflict over T levels featured by distinct sex-specific fitness optima. We found potential for sexually antagonistic selection, since high fledgling mass was reached by either brothers or sisters, but not by both. We report a positive intersexual correlation for T, as a requirement for intralocus sexual conflict. However, high levels of T were associated with increased female and decreased male fitness (fledgling mass), which contrasts our expectations and challenges the hypothesis of intralocus sexual conflict driven by T. We hypothesize that behavioural and physiological trade-offs differ between sexes when raising offspring, driving T levels towards a state of monomorphism.


Could blended payments broaden use of capitation?
If capitation is going to return as a viable health care mechanism, some changes will be needed. Here are suggestions for a blended payment approach that could do the trick.


Effects of ozone exposure at ambient air pollution episode levels on exercise performance.
Ozone is a principal component of photochemical air pollution endogenous to numerous metropolitan areas, which may induce irritant effects on the respiratory tract which impair pulmonary function, result in subjective symptoms of respiratory discomfort, including cough and shortness of breath, and can limit exercise performance. The effects of moderate ambient photochemical air pollution observed in a mobile laboratory have also been shown to be similar to those induced in laboratory chamber exposures to the same level of ozone alone. The metabolic demand of exercise increases minute ventilation (VE) and thus, the rate of ozone inhalation over that at rest. Potentially, exercise can also enhance the effects of ozone by: (a) reducing nasal passage absorption; (b) increasing the uniformity of ventilation throughout the lungs; and (c) replacing reacted ozone at a faster rate. However, results from 2-hour intermittent exercise and 1-hour continuous exercise exposures at the same total ventilation and ozone concentration have been shown to yield similar pulmonary function effects. It has been shown via significant variation in exercise intensity, and thus VE, that the simple product of ozone concentration, VE and exposure time (termed the ozone effective dose) predicts pulmonary function and exercise ventilatory pattern (induced rapid, shallow breathing) effects more precisely than ozone concentration alone. Better prediction of pulmonary function effects has been achieved via multiple regression analysis in which ozone concentration is given a greater weighting than VE and exposure time. Light intermittent exercise was first studied in 2-hour laboratory exposures to ozone at concentrations rarely seen in the ambient environment. In recent studies, heavy continuous exercise has been used in 1-hour exposures to ozone at levels routinely observed in photochemical episodes (less than or equal to 0.35 ppm). Statistically significant impairment of exercise performance has been observed at 0.18 ppm, a level reached for 1 hour, or more, on about 180 days per year in the Los Angeles basin. Responses of subpopulation groups, such as children, young adult females, older adults, and those with pre-existing pulmonary disease are not notably different from those of young adult males provided that the ozone effective dose is proportional to body size. Conversely, highly trained endurance athletes demonstrate significant responses at rather low ozone concentrations due to their ability to sustain very high VE over prolonged periods.(ABSTRACT TRUNCATED AT 400 WORDS)


Corpus luteum dysfunction: serum progesterone levels in diagnosis and assessment of therapy for recurrent and threatened abortion.
These studies were designed to show that properly timed measurements of serum progesterone (P) can be conveniently used in the diagnosis and treatment of patients with recurrent and threatened abortion. Luteal phase serum P levels between 2 and 10 ng/ml and serum P levels below 15 ng/ml in the first 10 weeks of gestation were considered diagnostic of corpus luteum (CL) dysfunction. Patients were treated with clomiphene, gonadotropins, and/or progesterone suppositories in order to correct serum P levels, thus elevating the serum P into the normal range. When treatment of patients with subnormal P levels resulted in normalization of serum P, successful pregnancies occurred. CL dysfunctions, either before or after conception, were found in eight of the nine patients with histories of recurrent spontaneous abortions. Correction of serum P was associated with successful pregnancy in these eight patients. Twelve patients with threatened abortion were also found to have subnormal serum P levels. Progesterone suppositories corrected the serum P levels in nine of the eleven patients treated, and none of these patients aborted. Serum P measurements provide a means for evaluation of CL function during early gestation. Management of patients with CL dysfunction can also be monitored with serial serum P measurements, provided that progesterone is the therapeutic agent rather than synthetic progestins.


Fluorescence in situ hybridization mapping of breakpoints in pleomorphic adenomas with 8q12-13 abnormalities identifies a subgroup of tumors without PLAG1 involvement.
Recently, we identified the PLAG1 gene as the target gene in pleomorphic adenomas with chromosome abnormalities involving 8q12. The majority of breakpoints were shown to reside within the 5' noncoding region of the gene. We now report three pleomorphic adenomas with breakpoints located distal to PLAG1 in band 8q13. These tumors had the following chromosome 8 abnormalities: ins(8;12)(q12-13;q14q15), t(8;12)(q13;q15), and t(6;8)(p21.3-22;q13). Fluorescence in situ hybridization mapping of the chromosome 8 breakpoints revealed a yeast artificial chromosome clone spanning the breakpoints in two tumors. In none of the cases was PLAG1 activated and/or disrupted. Three candidate genes, N8, HMGIC, and HMGIY, were analyzed for rearrangements and/or abnormal expression by using reverse transcriptase-polymerase chain reaction, rapid amplification of 3' cDNA ends, and Northern blot analyses.


Superior cervical ganglionectomy differentially modifies median eminence and anterior and mediobasal hypothalamic GABA content in male rats: effects of hyperprolactinemia.
This work was undertaken to analyze the changes in GABA concentrations in the anterior and mediobasal hypothalamus and in the median eminence after acute or chronic superior cervical ganglionectomy (SCGx), and whether high prolactin levels interfere with the effects of SCGx on GABA content. Acute but not chronic SCGx increased GABA content in all the areas studied, as compared to controls. The presence of a pituitary graft abolished the effects of acute SCGx in the median eminence and anterior hypothalamus, as compared to controls, but potentiated its effects in the mediobasal hypothalamus. Chronic SCGx increased GABA content in the mediobasal and anterior hypothalami, as compared to pituitary grafted controls. Acute SCGx decreased plasma prolactin and GH levels, but chronic surgery did not modify these hormone plasma levels. Acute SCGx increased plasma ACTH levels, whereas chronic SCGx did not modify them. Pituitary grafting increased circulating values of prolactin, ACTH and GH, as compared to controls. Acute SCGx did not modify plasma prolactin levels in grafted animals, although it increased plasma GH levels and decreased those of ACTH in this experimental group. Chronic SCGx further increased both plasma prolactin and GH levels, without modifying plasma ACTH levels. These results suggest that SCGx differentially modifies GABA content within the hypothalamus and median eminence. Induction of hyperprolactinemia in the neonatal age interferes with SCGx effects on both GABA content within the hypothalamus and median eminence and the secretory patterns of the pituitary hormones studied.


Bone loss during gonadotropin releasing hormone agonist treatment and use of nasal calcitonin.
Gonadotropin releasing hormone (GnRH) agonists have shown to be effective in the treatment of several sex-hormone-dependent conditions. However, their use could be limited by the bone loss they induce. To evaluate the use of nasal salmon calcitonin (sCT) in preventing this bone loss, 40 patients with endometriosis were treated for 6 months with triptoreline (3.75 mg monthly) and calcium (1 g daily), and randomized in three groups-placebo, sCT 100 IU daily and sCT 200 IU daily-in a prospective double-masked study. Dual-energy X-ray absorptiometry and biochemical parameters were used to evaluate the benefit of the treatment. At baseline, there were no statistically significant differences between the groups. After 6 months, estradiol and biochemical markers of bone metabolism were at postmenopausal levels, with no difference between the groups. There was no difference in bone loss in the three groups, at all sites. Mean lumbar bone loss was 4.01 +/- 2.59% (mean +/- SD) in this population. In this study dosages of 100 IU and 200 IU daily of nasal sCT were insufficient to prevent bone loss during GnRH agonist treatment.


Re-examination of the assay for plasma prostanoids by solid-phase extraction, and radioimmunoassay.
A method for the routine assay of plasma thromboxane and prostacyclin metabolites, thromboxane B2 and 6 keto-prostaglandin F1 alpha (employing solid phase extraction to remove the metabolites from interfering substances) and using commercially available antisera for their radioimmunoassay has been investigated. Modifications of previously published procedures have been explored, including the use of non-explosive solvents in the extraction procedure, and inclusion of a non-cross reacting internal standard, prostaglandin D2, to estimate recovery through the extraction procedures. Both the original and modified procedures can produce high blank values, which apparently result from the solid-phase extraction. These high backgrounds are constant for a given lot of solid phase extraction cartridges and can be corrected by subtraction. The modified method is linear with volume of plasma assayed to as little as one ml, and all cross-reacting material in normal human plasma was found to co-chromatograph with authentic standards on reverse-phase high performance liquid chromatography. Values for normal adult plasmas were found to be 0.44 +/- .15 pmol/ml 6 keto PGF1 alpha (mean +/- SD) and .103 +/- .07 for thromboxane B2. The method reported provides a convenient, reproducible way to assay these important plasma prostanoids.


Contact allergy to haptens in the Swedish baseline series: Results from the Swedish Patch Test Register (2010 to 2017).
Allergic contact dermatitis has considerable public health impact and causative haptens vary over time. To report the prevalence of contact allergy to allergens in the Swedish baseline series 2010 to 2017, as registered in the Swedish Patch Test Register. Results and demographic information for patients tested with the Swedish baseline series in 2010 to 2017 were analysed. Data for 21 663 individuals (females 69%) were included. Females had significantly more positive patch tests (54% vs 40%). The reaction prevalence rates were highest for nickel sulfate (20.7%), fragrance mix I (7.1%), Myroxylon pereirae (6.9%), potassium dichromate (6.9%), cobalt chloride (6.8%), methylchloroisothiazolinone/methylisothiazolinone (MCI/MI; 6.4%), MI (3.7%), colophonium (3.5%), fragrance mix II (3.2%), and formaldehyde (3.2%). Myroxylon pereirae reaction prevalence increased from 5% in 2010 to 9% in 2017 and that for methyldibromo glutaronitrile from 3.1% to 4.6%. MCI/MI and MI reactions decreased in prevalence after 2014. Nickel reaction prevalence decreased among females aged 10 to 19 years. Nickel remains the most common sensitizing agent, with reaction prevalence decreasing among females younger than 20 years. The changes in MCI/MI and MI reaction prevalence mirrored those in Europe. The register can reveal changes in contact allergy prevalence over time among patients patch tested in Sweden.


Stromal keratitis complicating anterior membrane dystrophy.
Recurrent erosion of the cornea has been well documented in patients with nontraumatic anterior membrane dystrophies of various types. We examined five patients who, in addition to an erosion, developed stromal keratitis. Three of these patients were subjected to a complete microbiologic workup, but the lesions were all sterile. The lesions healed with conservative treatment of patching and, in some cases, a soft contact lens. Stromal keratitis should be recognized as a complication of the non-traumatic recurrent erosion syndrome, which in turn is frequently associated with anterior membrane dystrophy. The finding of such anterior membrane changes in either eye will lead to the correct diagnosis and treatment of the affected eye.


Renal inflammatory myofibroblastic tumor: a rare tumor indistinguishable from renal cell carcinoma—report of two cases.
Renal inflammatory myofibroblastic tumor (IMT) is a rare soft-tissue tumor of controversial etiology with a potential for local recurrence after incomplete surgical resection. The radiological findings in renal IMT are not well described. We report two cases in adults with a renal mass treated with nephrectomy on suspicion of malignancy.


Determination of sulfur in coal using direct solid sampling and high-resolution continuum source molecular absorption spectrometry of the CS molecule in a graphite furnace.
An analytical method has been developed for the determination of sulfur in coal using direct solid sample analysis in a graphite tube furnace and high-resolution continuum source molecular absorption spectrometry (HR-CS GF MAS). The molecular absorbance of the carbon monosulfide molecule (CS), which is formed in the vaporization stage, has been measured using the rotational line at 258.033 nm. Several chemical modifiers were tested and Ru, applied as permanent modifier was chosen, because it exhibited the best performance. The optimum pyrolysis and vaporization temperatures were found to be 500 °C and 2200 °C, respectively. Aqueous standard solutions prepared from l-cysteine were used for calibration, as the linear regression obtained for this standard was not significantly different from that for a certified coal reference material (CRM) according to a Student t-test. The results obtained for sulfur in three coal CRM and six additional samples also showed no significant difference for the two calibration techniques according to the same statistical test. The sulfur concentration in the coal samples was found between 3.5 mg g(-1) and 33.7 mg g(-1) with a typical repeatability around 10%. The limit of detection for the direct analysis of solid coal samples was better than 0.1 μg S.


Predicting the transition from anxiety to depressive symptoms in early adolescence: Negative anxiety response style as a moderator of sequential comorbidity.
Anxiety often precedes depression. The anxiety response styles theory of comorbidity suggests anxious individuals with a tendency to ruminate or make hopeless attributions about anxiety symptoms (negative anxiety response styles [NARS]) are more vulnerable to subsequent depressive symptoms. However, this theory has never been tested in adolescence, when the anxiety-depression transition may frequently occur, or using an extended (one-year) follow-up period. 128 early adolescent girls (M=12.39 years) participated with caregivers in a one-year longitudinal study. At baseline and follow-up, participants completed diagnostic interviews and self-report measures assessing child NARS and brooding rumination. T1 NARS predicted longitudinal elevations in depressive symptoms and increased associations between T1 anxiety and T2 depressive symptoms. This study examines anxiety and depression comorbidity using a community sample. The sample is relatively low on sociodemographic diversity. Results support the anxiety response styles theory, with potential implications for early identification of anxious youth at risk for later development of comorbid depression.


A novel taurocyamine kinase found in the protist Phytophthora infestans.
Phosphagen kinase (PK), which is typically in the form of creatine kinase (CK; EC 18.104.22.168) in vertebrates or arginine kinase (AK; EC 188.8.131.52) in invertebrates, plays a key role in ATP buffering systems of tissues and nerves that display high and variable rates of ATP turnover. The enzyme is also found with intermittent occurrence as AK in unicellular organisms, protist and bacteria species, suggesting an ancient origin of AK. Through a database search, we identified two novel PK genes, coding 40- and 80-kDa (contiguous dimer) enzymes in the protist Phytophthora infestans. Both enzymes showed strong activity for taurocyamine and, in addition, we detected taurocyamine in cell extracts of P. infestans. Thus, the enzyme was identified to be taurocyamine kinase (TK; EC 188.8.131.52). This was the first phosphagen kinase, other than AK, to be found in unicellular organisms. Their position on the phylogenetic tree indicates that P. infestans TKs evolved uniquely at an early stage of evolution. Occurrence of TK in protists suggests that PK enzymes show flexible substrate specificity.


Association Between Medicaid Expansion and the Use of Outpatient General Surgical Care Among US Adults in Multiple States.
The Affordable Care Act expanded access to Medicaid coverage in 2014 for individuals living in participating states. Whether expanded coverage was associated with increases in the use of outpatient surgical care, particularly among underserved populations, remains unknown. To evaluate the association between state participation in the Affordable Care Act Medicaid expansion reform and the use of outpatient surgical care. This case-control study used a quasi-experimental difference-in-differences design to compare the use of outpatient surgical care at the facility and state levels by patient demographic characteristics and payer categories (Medicaid, private insurance, and no insurance). Data from 2013 (before Medicaid expansion reform) and 2015 (after Medicaid expansion reform) were obtained from the State Ambulatory Surgery and Services Database of the Healthcare Cost and Utilization Project. The absolute and mean numbers of procedures performed at outpatient surgical centers in 2 states (Michigan and New York) that participated in Medicaid expansion (expansion states) were compared with those performed at outpatient surgical centers in 2 states (Florida and North Carolina) that did not participate in Medicaid expansion (nonexpansion states). The population-based sample included 207 176 patients aged 18 to 64 years who received 4 common outpatient procedures (laparoscopic cholecystectomy, breast lumpectomy, open inguinal hernia repair, and laparoscopic inguinal hernia repair). Data were analyzed from May 19 to August 25, 2019. State variation in the adoption of Medicaid expansion before and after expansion reform was implemented through the Affordable Care Act. Changes in the mean number of procedures performed at the facility level before and after Medicaid expansion reform in states with and without expanded Medicaid coverage. A total of 207 176 patients (106 395 women [51.35%] and 100 781 men [48.65%]; mean [SD] age, 45.7 [12.4] years) were included in the sample. Overall, 116 752 procedures were performed in Medicaid expansion states and 90 424 procedures in nonexpansion states. A 9.8% increase (95% CI, 0.4%-20.0%; P = .04) in cholecystectomies, a 26.1% increase (95% CI, 9.8%-44.7%; P = .001) in lumpectomies, and a 16.3% increase (95% CI, 2.9%-31.5%; P = .02) in laparoscopic inguinal hernia repairs were observed at the facility level in expansion states compared with nonexpansion states. Among patients with Medicaid coverage, the mean number of procedures performed in all 4 procedure categories increased between 60.5% (95% CI, 24.7%-106.6%; P < .001) and 79.2% (95% CI, 53.5%-109.2%; P < .001) at the facility level. The increases in the number of Medicaid patients who received treatment exceeded the reductions in the number of uninsured patients who received treatment with laparoscopic cholecystectomy, open inguinal hernia repair, and laparoscopic inguinal hernia repairs in expansion states compared with nonexpansion states. Black patients received more laparoscopic cholecystectomies, lumpectomies, and open inguinal hernia repairs in expansion states than in nonexpansion states. Study results suggest that Medicaid expansion was associated with increases in the use of outpatient surgical care in states that participated in Medicaid expansion. Most of this increase represented patients who were newly treated rather than patients who converted from no insurance to Medicaid coverage.


Evidence for a Pathogenic Role of CSMD1 in Childhood Apraxia of Speech.
Childhood apraxia of speech (CAS) is a pediatric motor speech disorder. The genetic etiology of this complex neurological condition is not yet well understood, although some genes have been linked to it. We describe the case of a boy with a severe and persistent motor speech disorder, consistent with CAS, and a coexisting language impairment.Whole exome sequencing in our case revealed a de novo and splicing mutation in the CSMD1 gene.


Electrophysiological association of spontaneous yawning and swallowing.
Yawning and swallowing are fundamental physiological processes that are present from fetal stages throughout life and that involve sequential motor activities in the oropharyngo-larynx making it likely that they may share neuroanatomical pathways. We postulate that yawning and swallowing are controlled by a distributed network of brainstem regions including the central pattern generator of swallowing, and therefore spontaneous swallowing is frequently associated with spontaneous yawning. In this study, we sought to test this hypothesis by evaluating the elementary features of yawning in the facial, masseter and submental muscles, together with laryngeal movement sensor and respiratory recordings for spontaneous swallowing. We investigated 15 healthy, normal control subjects, 10 patients with Parkinson's disease (PD) and 10 patients with brainstem stroke (BSS). Apart from four subjects with PD and two with BSS, who had dysphagia, none of the other study subjects were dysphagic by published criteria. Twenty-five subjects (10 control, 10 BSS, 5 PD) were evaluated by 1-h polygraphic recording, and 10 (5 control, 5 PD) underwent whole-night sleep recordings. One hundred thirty-two yawns were collected, 113 of which were associated with spontaneous swallows, a clear excess of what would be considered as coincidence. The yawns related with swallows could be classified into the following three categories. The characteristics or the duration of swallows and yawns were similar between controls and disease subjects, with the exception of increased duration of yawning in subjects with BSS. Our findings support the presence of common neuroanatomico-physiological pathways for spontaneous swallows and yawning.


Secreted peptides as regulators of neuron-glia and glia-glia interactions in the developing nervous system.
Secreted peptides of the nervous system help to regulate neuron-glia and glia-glia interactions during development. These regulatory factors, referred to as glia-promoting factors (GPFs), act on specific classes of glia and include oligodendroglia-stimulating peptides, interleukin-1 (IL-1), colony-stimulating factors (CSF), and fibroblast growth factor (FGF). The maturity of secretory and target cells determines, in part, the ability of a factor to influence glial proliferation, activation, or differentiation. During neural development, GPFs help to control such fundamentally important events as cell movement, neurite outgrowth, and myelination.


Erratum: Imaging Surveillance for Survivors of Breast Cancer: Correlation between Cancer Characteristics and Method of Detection.
[This corrects the article on p. 192 in vol. 20, PMID: 28690656.].


BLMM: Parallelised computing for big linear mixed models.
Within neuroimaging large-scale, shared datasets are becoming increasingly commonplace, challenging existing tools both in terms of overall scale and complexity of the study designs. As sample sizes grow, researchers are presented with new opportunities to detect and account for grouping factors and covariance structure present in large experimental designs. In particular, standard linear model methods cannot account for the covariance and grouping structures present in large datasets, and the existing linear mixed models (LMM) tools are neither scalable nor exploit the computational speed-ups afforded by vectorisation of computations over voxels. Further, nearly all existing tools for imaging (fixed or mixed effect) do not account for variability in the patterns of missing data near cortical boundaries and the edge of the brain, and instead omit any voxels with any missing data. Yet in the large-n setting, such a voxel-wise deletion missing data strategy leads to severe shrinkage of the final analysis mask. To counter these issues, we describe the "Big" Linear Mixed Models (BLMM) toolbox, an efficient Python package for large-scale fMRI LMM analyses. BLMM is designed for use on high performance computing clusters and utilizes a Fisher Scoring procedure made possible by derivations for the LMM Fisher information matrix and score vectors derived in our previous work, Maullin-Sapey and Nichols (2021).


Synergistical thermal modulation function of 2D Ti3C2 MXene composite nanosheets via interfacial structure modification.
MXene demonstrates high in-plane thermal transport merit as an emerging two-dimensional material, but its out-of-plane thermal transport did not fully explore. Here Ti3C2 MXene nanosheets with either GO or CNF fillers were fabricated by using the vacuum-assisted filtration method. It was found that the addition of GO and CNF enlarged the interlayer spacing of the MXene layers, bringing about the opportunity for changeable spatial configuration of fillers and the thermal regulation function. If the GO nanosheets were interspersed parallel to the MXene layers, strong interference of increasing oxygen-containing functional group suppresses the out-of-plane thermal transport, resulting in the thermal conductivity decreasing from 0.5 W/(m·K) to 0.31 W/(m·K) for 20 wt% GO addition. Moreover, CNFs formed out-of-plane protruding on the surface of MXene nanosheets, resulting in the thermal conductivity increasing to 0.81 W/(m·K) for 20 wt% CNF addition. This discovery navigates how to prepare MXene composites with customized thermal properties.


Metformin reduces pleural fibroelastosis by inhibition of extracellular matrix production induced by CD90-positive myofibroblasts.
Metformin, an AMP-activated protein kinase activator used to treat diabetes mellitus, has recently attracted attention as a promising anti-fibrotic agent. However, its anti-fibrotic effects on pleural fibroelastosis remain unknown. We induced mouse pleural fibroelastosis by intra-pleural coadministration of bleomycin and carbon and evaluated its validity as a preclinical model for human pleural fibrosis. We assessed the expression of the myofibroblast surface marker CD90 in the fibrotic pleura and the effects of metformin in vivo and in vitro. Finally, we evaluated the effects of metformin on human pleural mesothelial cells stimulated by transforming growth factor β1 (TGFβ1). The fibrotic pleura in mice had collagen and elastin fiber deposition similar to that seen in human fibrotic pleura. Moreover, CD90-positive myofibroblasts were detected in and successfully isolated from the fibrotic pleura. Metformin significantly suppressed the deposition of collagen and elastic fibers in the fibrotic pleura and decreased the expression of extracellular matrix (ECM)-related genes, including Col1a1, Col3a1, Fn1, and Eln, in pleural CD90-positive myofibroblasts. In human pleural mesothelial cells, metformin decreased TGFβ1-induced upregulation of ECM-related genes and SNAI1. Overall, metformin suppresses pleural fibroelastosis by inhibition of ECM production by pleural myofibroblasts, suggesting that this drug has therapeutic potential against human pleural fibrosis, including pleuroparenchymal fibroelastosis.