[Autoimmune enteropathy in adults : A rare and difficult but relevant differential diagnosis of chronic diarrhea]. / Die Autoimmunenteropathie beim Erwachsenen : Eine seltene und schwierige, aber relevante Differenzialdiagnose der chronischen Diarrhö.

Autoimmune enteropathy (AIE) was originally believed to be a pediatric disease until there were increasing numbers of adult cases reported over the last 20 years. AIE is an autoimmune disease that manifests as severe chronic diarrhea.The histological hallmark is villous atrophy. Histology alone is not sufficiently sensitive and consistent. Four different histological patterns are known. There are many differential diagnoses to be considered relating to both histology and symptoms.We present the case of a young woman with fatal AIE and homozygous germline-mutation of the CLEC7A gene. The course of disease is documented in multiple intestinal biopsies, which show a morphological change over time.Histology and symptoms often resemble celiac disease. In order to recognize this rare disease early in its course there is a need for a special awareness among attending physicians and pathologists.

Reconstruction of mining activities in the Western Alps during the past 2500 years from natural archives.

The geochemical analysis of natural archives can improve our knowledge of past mining activities and their environmental imprint. The sedimentary records from the Hasli-Aare floodplain (Bernese Alps) over the last 2500 years were analysed for metals. Evidence of past mining contamination was obtained from the XRF analyses of iron, copper, zinc and lead. These results were analytically and statistically processed to produce a metal content index. Positive metal anomalies indicate four major pulses of contamination coinciding with the end of the Iron Age, from the end of the Roman Period to the Early Medieval Period, the Late Medieval Period, and the Modern Period. These pulses show good agreement with local historical sources of mining in the Hasli-Aare catchment, dating back to the beginning of the 15th century. Furthermore, they are in phase with anthropogenic pollution trends inferred from glacier ice cores, lake sediments and peat bogs across the Western Alps, most notably during the Roman, Late Medieval and Modern Periods. However, close comparison between these records can show some differences, suggesting local variations in mining activities and/or a lag in metal transfer. The reconstructed periods of anthropogenic metal pollution are located in their political, economic and social contexts and compared with the climate periods of central Europe.

The association of cognitive distortions and the type of gambling in problematic and disordered gambling.

BACKGROUND: Previous studies have shown that particular types of gambling are related to the development of gambling-related problems. Further, gambling-related cognitive distortions contribute to the development of disordered gambling. The aim of the present study is to compare different gambling types with respect to cognitive distortions and the development of disordered gambling. METHODS: Based on a proactively screened sample of vocational school students (N = 6718), 309 students were selected to undergo an in-depth interview. We assessed the Gamblers-Belief-Questionnaire (GBQ) to measure gambling-related cognitive distortions and the Stinchfield questionnaire for assessing gambling-related problems. Associations between cognitive distortions, gambling-related symptoms, and types of gambling were analysed using logistic regression analyses. RESULTS: Higher scores on the GBQ subscale "belief in luck/perseverance" led to a significantly higher chance to be classified as a person with Gambling Disorder (Conditional Odds Ratio (COR) = 1.05, Confidence Interval (CI) = 1.02-1.08) as well as problematic gambling (COR = 1.04, CI = 1.01-1.06). Higher scores on the subscale "illusion of control" were also associated with problematic gambling (COR = 1.04, CI = 1.00-1.08). The multivariate analyses of the gambling types identified only sports betting as a predictor for problematic gambling (COR = 1.91, CI = 1.05-3.49). When controlling for cognitive distortions, sports betting was not significant anymore. With respect to disordered gambling, gambling on electronic gambling machines (EGMs) turned out to be a risk factor besides cognitive distortions (COR = 2.59, CI = 1.04-6.49). DISCUSSION: The present study confirmed the high relevance of cognitive distortions for problematic and disordered gambling especially for sports betting and gambling on EGMs. Preventive measures and psychotherapy should take these relationships into account.

The plasticity of dendritic cell responses to pathogens and their components.

Dendritic cells are involved in the initiation of both innate and adaptive immunity. To systematically explore how dendritic cells modulate the immune system in response to different pathogens, we used oligonucleotide microarrays to measure gene expression profiles of dendritic cells in response to Escherichia coli, Candida albicans, and influenza virus as well as to their molecular components. Both a shared core response and pathogen-specific programs of gene expression were observed upon exposure to each of these pathogens. These results reveal that dendritic cells sense diverse pathogens and elicit tailored pathogen-specific immune responses.

Intestinal Organoids as a Novel Complementary Model to Dissect Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBDs) include colitis ulcerosa and Crohn's disease, besides the rare microscopic colitis. Both diseases show a long-lasting, relapsing-remitting, or even chronic active course with tremendous impact on quality of life. IBDs frequently cause disability, surgical interventions, and high costs; as in other autoimmune diseases, their prevalent occurrence at an early phase of life raises the burden on health care systems. Unfortunately, our understanding of the pathogenesis is still incomplete and treatment therefore largely focuses on suppressing the resulting excessive inflammation. One obstacle for deciphering the causative processes is the scarcity of models that parallel the development of the disease, since intestinal inflammation is mostly induced artificially; moreover, the intestinal epithelium, which strongly contributes to IBD pathogenesis, is difficult to assess. Recently, the development of intestinal epithelial organoids has overcome many of those problems. Here, we give an overview on the current understanding of the pathogenesis of IBDs with reference to the limitations of previous well-established experimental models. We highlight the advantages and detriments of recent organoid-based experimental setups within the IBD field and suggest possible future applications.

Epigenetic Control of Gene Expression in Maize.

Epigenetic gene regulation is important for proper development and gene expression in eukaryotes. Maize has a large and complex genome that includes abundant repetitive sequences which are frequently silenced by epigenetic mechanisms, making it an ideal organism to study epigenetic gene regulation. Epigenetic modifications are chromosome-bound, heritable changes to the genome that do not affect the DNA sequence, and can include DNA methylation, histone modification, and RNA processing. Our appreciation and understanding of epigenetic regulation has grown with the field since its inception ∼65 years ago. Early examples of epigenetic regulation were often associated with transposable elements, starting with McClintock's early work in the 1950s. The observation of other intriguing phenotypes segregating in non-Mendelian ratios in the 1950s provided material for genetic screens that allowed for mechanistic studies of epigenetic regulation that have come to fruition within the past 20 years. The relationship between epigenetic mechanisms and genome organization has become clear with the application of new technologies to characterize maize epigenomes. Our understanding of epigenetic control of gene expression now encompasses the context of genes relative to DNA methylation, chromatin structure, and transposable element content.

Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase: Acceleration of fracture healing via inducible nitric oxide synthase.

OBJECTIVES: We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days. MATERIALS AND METHODS: Unilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression nail. Rats were treated daily either with vehicle, tadalafil or COMB-4. Biomechanical testing of the healed fracture was performed on day 42. The volume, mineral content and bone density of the callus were measured by quantitative CT on days 14 and 42. Expression of iNOS was measured by immunohistochemistry. RESULTS: When compared with the control group, the COMB-4 group exhibited 46% higher maximum strength (t-test, p = 0.029) and 92% higher stiffness (t-test, p = 0.023), but no significant changes were observed in the tadalafil group. At days 14 and 42, there was no significant difference between the three groups with respect to callus volume, mineral content and bone density. Expression of iNOS at day 14 was significantly higher in the COMB-4 group which, as expected, had returned to baseline levels at day 42. CONCLUSION: This study demonstrates an enhancement in fracture healing by an oral natural product known to augment iNOS expression.Cite this article: R. A. Rajfer, A. Kilic, A. S. Neviaser, L. M. Schulte, S. M. Hlaing, J. Landeros, M. G. Ferrini, E. Ebramzadeh, S-H. Park. Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase: Acceleration of fracture healing via inducible nitric oxide synthase. Bone Joint Res 2017:6:-97. DOI: 10.1302/2046-3758.62.BJR-2016-0164.R2.

Elevated interstitial fluid volume in rat soleus muscles by hindlimb unweighting.

Hindlimb unweighting is a commonly used model to study skeletal muscle atrophy associated with disuse and exposure to microgravity. However, a discrepancy in findings between single fibers and whole muscle has been observed. In unweighted solei, specific tension deficits are greater in whole muscle than in single fibers. Also, metabolic enzyme activity when normalized per gram of mass is depressed in whole muscle but not in single fibers. These observations suggest that soleus muscle interstitial fluid volume may be elevated with atrophy caused by unweighting in rats. The purpose of this study was to determine if soleus muscle atrophy induced by unweighting is accompanied by alterations in muscle interstitial fluid volume and to calculate the effect of any such alterations on the muscle specific tension (N/cm2 muscle cross-sectional area). Nine female Wistar rats (200 g) were hindlimb unweighted (HU) by tail suspension. Soleus muscles were studied after 28 days and compared with those from five age-matched control (C) rats. Interstitial fluid volume ([3H]inulin space) and maximum tetanic tension (Po) were measured in vitro at 25 degrees C. Soleus muscles atrophied 58% because of unweighting (C = 147.8 +/- 2.3 mg; HU = 62.3 +/- 3.6 mg, P less than 0.001). Relative muscle interstitial fluid volume increased 107% in HU rats (35.5 +/- 2.8 microliters/100 mg wet mass) compared with the control value of 17.2 +/- 0.5 microliters/100 mg (P less than 0.001); however, absolute interstitial fluid volume (microliters) was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Age effects on myosin subunit and biochemical alterations with skeletal muscle hypertrophy.

The purpose of this study was to determine whether skeletal muscle mass, myofibrillar adenosinetriphosphatase activity, and the expression of myosin heavy (MHC) and light chain subunits are differentially affected in juvenile (4 wk) and young adult (12 wk) rats by a hypertrophic growth stimulus. Hypertrophy of the plantaris or soleus was studied 4 wk after ablation of either two [gastrocnemius (GTN) and soleus or plantaris] or one (GTN) synergistic muscle(s). There was no difference in the relative magnitude of hypertrophy because of age. Plantaris myofibrillar adenosinetriphosphatase activity was decreased 21 and 12% in juvenile and adult rats, respectively, as a result of ablation of both the GTN and soleus. Slow myosin light chain isoforms (1s and 2s) were expressed to a greater extent in hypertrophied plantaris muscles of both ages, but the increase in 1s was greater in juvenile rats. The relative expression of slow beta-MHC in hypertrophied plantaris muscles increased by 470 and 350%, whereas MHC IIb decreased by 70 and 33% in juvenile and adult rats, respectively. The relative expression of MHC IIa increased (56%) in the plantaris after ablation in juvenile rats only. These shifts in myosin subunit expression and the increases in mass were generally about one-half the magnitude when only the GTN was removed. There were no detectable myosin shifts in hypertrophied soleus muscles. Although the extent of muscle hypertrophy is similar, the shifts in myosin subunits were greater in juvenile than in young adult rats.

Regulation of skeletal muscle dihydropyridine receptor gene expression by biomechanical unloading.

Biomechanical unloading of the rat soleus by hindlimb unweighting is known to induce atrophy and a slow- to fast-twitch transition of skeletal muscle contractile properties, particularly in slow-twitch muscles such as the soleus. The purpose of this study was to determine whether the expression of the dihydropyridine (DHP) receptor gene is upregulated in unloaded slow-twitch soleus muscles. A rat DHP receptor cDNA was isolated by screening a random-primed cDNA lambda gt10 library from denervated rat skeletal muscle with oligonucleotide probes complementary to the coding region of the rabbit DHP receptor cDNA. Muscle mass and DHP receptor mRNA expression were assessed 1, 4, 7, 14, and 28 days after hindlimb unweighting in rats by tail suspension. Isometric twitch contraction times of soleus muscles were measured at 28 days of unweighting. Northern blot analysis showed that tissue distribution of DHP receptor mRNA was specific for skeletal muscle and expression was 200% greater in control fast-twitch extensor digitorum longus (EDL) than in control soleus muscles. A significant stimulation (80%) in receptor message of the soleus was induced as early as 24 h of unloading without changes in muscle mass. Unloading for 28 days induced marked atrophy (control = 133 +/- 3 vs. unweighted = 62.4 +/- 1.8 mg), and expression of the DHP receptor mRNA in the soleus was indistinguishable from levels normally expressed in EDL muscles. These changes in mRNA expression are in the same direction as the 37% reduction in time to peak tension and 28% decrease in half-relaxation time 28 days after unweighting. Our results suggest that muscle loading necessary for weight support modulates the expression of the DHP receptor gene in the soleus muscle.

Correlates of vestibular evaluation results during the first year of life.

Prenatal and perinatal correlates of abnormal auditory brainstem responses in neonates have been studied extensively. In contrast, vestibular function during the first year of life has received sparse attention. Using a specially modified vestibular test battery, 65 infants (17 low-risk, 48 high-risk) were initially evaluated during their first 6 months of life. Results revealed normal vestibular function in 46 infants (13 low-risk, 33 high-risk) and abnormal findings at either 3 or 6 months in 19 infants (4 low-risk, 15 high-risk). Correlations between vestibular results and variables such as auditory brainstem response results, birth history, and postnatal course in the neonatal intensive care unit were analyzed statistically. While some differences were mildly significant, none were highly significant. The lack of significant correlation between abnormal auditory brainstem response and vestibular results is of particular interest.

Hearing research career development for deaf students.

One goal of the Americans with Disabilities Act is to enhance access to career opportunities for individuals with hearing loss. Hearing-impaired professionals are woefully underrepresented among the cadre of scientists currently involved in hearing and deafness research. Information was obtained by questionnaire from 190 consecutive attendees (13 through 17 years of age) at a summer program for gifted hearing-impaired adolescents regarding career goals, attitudes toward academic and extracurricular activities, educational placement, primary communication modality, and parental hearing status. A follow-up questionnaire completed by 80 of these youth, presently attending college, provided comparison data regarding type of college attended and academic major. Males were significantly more likely to select majors in mathematics and science-related disciplines. The percentage of college attendees majoring in the sciences was much lower than the percentage of high school students who aspired to a scientific career. Strategies for attracting qualified hearing-impaired students into science majors should include educational efforts directed at students, parents, and academic advisors.

Patterns of physical and sexual abuse of communicatively handicapped children.

Evidence suggests that handicapped children are at increased risk for abuse and neglect. Communicatively impaired youngsters are particularly vulnerable because of their limited ability to report the maltreatment. Of 482 abused handicapped children evaluated at Boys Town National Research Hospital, 212 had hearing impairment, 87 speech language disorders, 39 learning disorders, 43 behavioral-emotional disturbances, 74 mental retardation, 5 visual impairment, 3 cleft lip or palate, and 19 other disorders. The perpetrator was either a relative or a "trusted other" in 97.2% of sexual abuse cases. Handicapped males were much more likely to be victims of sexual abuse than nonhandicapped males in the general population. Children being educated in residential schools were more likely to be sexually abused than mainstreamed youngsters. These children may be at risk for abuse from a wide variety of potential perpetrators, including teachers, dormitory counselors, van drivers, clergy, classroom aides, older students, peer siblings, scout leaders, abused peers, baby-sitters, and custodians.

The effects of psychotherapy on behavior problems of sexually abused deaf children.

This study assessed the effectiveness of a broad based psychotherapeutic intervention with a sample of 72 children sexually abused at a residential school for the deaf. An untreated comparison group emerged when about half of their parents refused the offer for psychotherapy provided by the school. Treated and untreated children were randomly assigned to two assessment groups: those who participated in a pretreatment assessment and those who did not. Houseparents at the residential school used the Child Behavior Checklist (CBC) to rate the pretreatment assessment children before treatment and all 72 children one year after the implementation of psychotherapy. Children receiving therapy had significantly fewer behavior problems than children not receiving therapy. There was a differential response to therapy on the basis of sex. Boys receiving therapy had significantly lower scores on the following CBC scales than the no treatment group: Total, Internal, External, Somatic, Uncommunicative, Immature, Hostile, Delinquent, Aggressive, and Hyperactive. There were no differences on the Schizoid and Obsessive scales. Girls receiving therapy had significantly lower scores than the no treatment group on the following CBC scales: Total, External, Depressed, Aggressive, and Cruel. There were no differences on the Internal, Anxious, Schizoid, Immature, Somatic, and Delinquent scales.

Vowel-related differences in laryngeal articulatory and phonatory function.

The purpose of this investigation was to study the interaction between the supralaryngeal and laryngeal components of the speech mechanism by examining vowel-related effects for a variety of vocal fold articulatory and phonatory measures. Secondary issues were to determine if vowel-related differences were influenced by the nature of the speaking task or gender. Between-vowel differences in estimated subglottal air pressure, peak oral air flow, mean phonatory air flow, air flow near the termination of the vowel, electroglottograph cycle width (EGGW), fundamental frequency, and voice onset time were examined for men and women during syllable repetitions and sentence productions. Significant vowel-related differences were found for all of the measures except mean phonatory air flow, and generally were not influenced by speaking task or gender. Vowel-related effects for estimated subglottal air pressure, peak oral air flow, fundamental frequency, and VOT were consistent with some earlier studies. New findings included vowel-related differences in EGGW and air flow near the termination of the vowel. We propose a model that includes the contribution of mechanical forces, reflexive neural activity, and learned neural activity to explain vowel-related effects. When vowel height is varied, changes in laryngeal cartilage positioning and vocal fold and vocal tract tension appear to influence laryngeal articulatory and phonatory function.

Phonatory air flow characteristics of adductor spasmodic dysphonia and muscle tension dysphonia.

The purpose of this study was to determine if phonatory air flow characteristics differed among women with adductor spasmodic dysphonia (AdSD), muscle tension dysphonia (MTD), and normal phonation. Phonatory air flow signals were gathered during [pa] syllable repetitions. Mean phonatory air flow, coefficients of variation, and the presence of large air flow perturbations (75 ml/s or more) were examined for the three groups of speakers. There was no significant difference in mean phonatory air flow across groups, and very large intersubject variation in mean phonatory air flow occurred for both the AdSD and MTD groups. Coefficients of variation were similar for the groups of women with MTD and normal phonation but were significantly larger for the group with AdSD. Air flow perturbations were common with AdSD and rare with MTD. Relatively large coefficients of variation and air flow perturbations of at least 75 ml/s did occur for some women with normal voices who were 70 years of age or older. It appears that intrasubject variability in phonatory air flow may aid in the differentiation of AdSD and MTD when used in conjunction with other elements of a thorough voice evaluation. However, the potential contribution of aging to increased intrasubject variability in phonatory air flow must be considered when interpreting findings.

Auditory brainstem responses elicited by 1000-Hz tone bursts in patients with sensorineural hearing loss.

Auditory brainstem responses were measured in response to 1000-Hz tone bursts from 115 patients with sensorineural hearing loss, presumably of cochlear origin. Mean wave V latencies and variability were comparable to those observed in normal hearing subjects for similar stimuli. The range of interaural differences in wave V latencies for 1000-Hz tone bursts were slightly greater than those observed for clicks, which may not be surprising, given the greater variability in wave V latencies for tonal stimulation, even in normal-hearing subjects. These differences, however, were not affected either by the magnitude or symmetry of hearing loss for frequencies at and above 1000 Hz. These data suggest that tone burst ABRs might be useful in otoneurologic evaluations, especially for patients with asymmetric hearing loss.

Developmental patterns of laryngeal and respiratory function for speech production.

Estimates of subglottal air pressure, laryngeal airflow, and laryngeal airway resistance from syllable repetitions of children and adults were used in describing developmental changes in these variables and in hypothesizing corresponding changes in respiratory function. A trend was found for pressure and resistance to decrease with increases in flow from preschool age through adulthood. These patterns could be explained by the smaller size of laryngeal airway structures and increased expiratory muscle forces during speech in the younger subjects. When the subglottal air pressures were combined with published data on air volume expired during speech and recoil pressures of the respiratory system, hypothetical functions were derived for respiratory muscle forces and the work of speech breathing. These functions predict (a) a developmental shift from the use of net expiratory muscle force in the speech of preschool children to the adult patterns of combined inspiratory and expiratory muscle forces, and (b) the expiratory work of speech breathing is greater in preschool children than in older children and adults.

[Arthrodesis of the carpometacarpal joint of the thumb for arthrosis deformans]. / Artrodese van het carpometacarpale gewricht van de duim wegens arthrosis deformans.

In a retrospective study we evaluated the results of arthrodesis of the carpometacarpal joints in 24 patients of whom three were operated on both sides. After one to 14 years 22 patients did not have any pain; only 2 patients complained of impaired function.