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.

[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.

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.

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.

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.

Interruption of classic CD40L-CD40 signalling but not of the novel CD40L-Mac-1 interaction limits arterial neointima formation in mice.

The co-stimulatory immune molecule CD40L figures prominently in a variety of inflammatory conditions including arterial disease. Recently, we made the surprising finding that CD40L mediates atherogenesis independently of its classic receptor CD40 via a novel interaction with the leukocyte integrin Mac-1. Here, we hypothesised that selective blockade of the CD40L-Mac-1 interaction may also retard restenosis. We induced neointima formation in C57/BL6 mice by ligation of the left carotid artery. Mice were randomised to daily intraperitoneal injections of either cM7, a small peptide selectively inhibiting the CD40L-Mac-1 interaction, scM7, a scrambled control peptide, or saline for 28 days. Interestingly, cM7-treated mice developed neointima of similar size compared with mice receiving the control peptide or saline as assessed by computer-assisted analysis of histological cross sections. These data demonstrate that the CD40L-Mac-1 interaction is not required for the development of restenosis. In contrast, CD40-deficient mice subjected to carotid ligation in parallel, developed significantly reduced neointimal lesions compared with respective wild-type controls (2872 ± 843 µm² vs 35469 ± 11870 µm²). Flow cytometry in CD40-deficient mice revealed reduced formation of platelet-granulocyte and platelet-inflammatory monocyte- aggregates. In vitro, supernatants of CD40-deficient platelet-leukocyte aggregates attenuated proliferation and increased apoptosis of smooth muscle cells. Unlike in the setting of atherosclerosis, CD40L mediates neointima formation via its classic receptor CD40 rather than via its recently described novel interaction with Mac-1. Therefore, selective targeting of CD40L-Mac-1 binding does not appear to be a favorable strategy to fight restenosis.

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.

Articulatory changes with short-term deactivation of the cochlear implants of two prelingually deafened children.

OBJECTIVE: The purpose of this investigation was to determine how suddenly diminished auditory feedback affects articulatory behaviors for prelingually deafened children with cochlear implants (CIs). DESIGN: Two 6-yr-old children served as participants. Considering their level of hearing impairment, one child had above average speech perception and production skills while the other child had exceptionally good speech perception and production abilities. Baseline data were collected four times over the course of 2 days with the children wearing their CIs. For three additional days, data were collected while the children wore their CIs (ON condition) and then again after their CIs had been deactivated for 1 hr (OFF condition). Variables assessed included amount of jaw opening, F1, F2, nasal air flow, voice onset time (VOT), voicing duration, and the magnitude and duration of intraoral air pressure (Po). Findings were related to each other and to previously reported phonatory findings from the same two children (Higgins, McCleary, & Schulte, 1999) to determine whether changes in articulatory variables in the OFF condition were consistent with a direct effect of diminished auditory feedback or an indirect influence of suprasegmental parameters. RESULTS: Both children exhibited consistent and significant changes in articulatory parameters in the absence of auditory feedback. Such changes occurred more often for the child who had especially proficient speech perception and production skills. Some changes (i.e., reduced Po for [p] and reduced nasal air flow for [m]) appeared related to the influence of suprasegmental parameters, in particular, reduced subglottal air pressure. Other effects (i.e., increased F2 for [a] and reduced VOT for [p]) were suggestive of changes in the children's abilities to maintain appropriate articulatory placements and timing. Finally, a few changes (reduced jaw opening for [i] and increased Po duration for [p]) may have reflected compensatory strategies to maintain correct tongue placement and enhance temporal distinctions in the absence of auditory feedback. CONCLUSIONS: Based on the data of our two participants, it appears that some prelingually deafened children with CIs and good speech perception/production skills rely on auditory feedback to maintain articulatory precision. In the absence of auditory feedback, such children may demonstrate changes in articulatory placement and timing. In addition, data from one of our participants are consistent with the idea that some children may be aware that their articulatory control is compromised in the absence of auditory feedback and attempt to compensate by altering articulatory durations or the range of associated articulatory movements.

Altered phonatory physiology with short-term deactivation of children's cochlear implants.

OBJECTIVES: The purposes of this investigation were 1) to determine whether short-term auditory deprivation results in systematic phonatory changes for prelingually deafened children who use cochlear implants (CIs) and 2) to determine whether such changes are similar to those that have been reported for postlingually deafened adults. DESIGN: Participants were two 6-yr-old children with CIs. Both children had been prelingually deafened, had good to excellent speech production and speech perception skills, and had been using their CIs for 2.5 yr. A single-subject design was used. Intraoral air pressure (Po), phonatory air flow (Vl), electroglottograph (EGG) cycle width, fundamental frequency (F0), and intensity were measured during syllable production over two baseline days and three experimental days. Data were collected twice on each baseline day while the children wore their CIs, with a 1 hr break between data collection sessions. On experimental days, data were collected while the children wore their CIs (ON condition) and after their CIs had been removed for 1 hr (OFF condition). RESULTS: Both children demonstrated highly variable phonatory behaviors in baseline. The child with the more proficient speech production and perception skills showed consistent and significant reductions in Po, F0, and intensity in the OFF condition. These findings were dissimilar to those that occurred with repeated testing in the baseline condition and so were attributed to the sudden loss of auditory feedback. The other child showed a consistent and significant increase in mean Vl in the OFF condition. However, this child exhibited a similar finding with repeated testing in the baseline condition. Therefore, increased Vl in the OFF condition may have represented a practice effect. She also showed a small and consistent decrease in F0 in the OFF condition when F0 was derived from acoustic data, but this effect was not reliable in another data set when F0 was derived from the EGG signal. Our results with prelingually deafened children were inconsistent with reports of increased intensity and F0 in the absence of auditory feedback for postlingually deafened adults with CIs. CONCLUSIONS: Some prelingually deafened children who are successful CI users appear to use auditory feedback to self-monitor phonation. We suggest that the participant in our investigation who showed systematic phonatory changes in response to diminished auditory feedback was using auditory feedback primarily to stabilize her phonatory behaviors. She may not have had adequate experience with auditory feedback or adequate flexibility in her use of feedback mechanisms to implement the phonatory compensations that late-deafened adults use when auditory feedback suddenly is diminished. We further suggest that the phonatory changes that she exhibited during short-term auditory deprivation reflected disruption of her typical speaking strategies or apprehension about speaking when her ability to self-monitor auditorily was compromised.

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.

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.

Basic characteristics of click-evoked otoacoustic emissions in infants and children.

Since Kemp [J. Acoust. Soc. Am. 64, 1386-1391 (1978)] first described click-evoked otoacoustic emissions (COAEs), researchers have advocated their use as an excellent tool for diagnosing hearing loss in infants and children. However, there are few detailed reports of COAEs in this population, and those that do exist suggest that there are age-dependent differences. The purpose of the current study was to determine basic characteristics of COAEs in infants, toddlers, children, and young adults and to define any differences among age groups. An additional goal was to ensure that spontaneous otoacoustic emissions (SOAEs) did not confound any possible developmental effects. COAEs and SOAEs were measured from one ear of 223 normal-hearing subjects. COAE input/ output functions indicated that children aged less than one year have higher COAE levels than older children and adults. Children aged 1-5 yr had higher COAE levels than those aged 12-17 yr and adults. These differences were independent of level and SOAE status, but were dependent on frequency. The results of this study suggest that different clinical norms may be necessary for children aged less than 6 years.

Basic characteristics of distortion product otoacoustic emissions in infants and children.

Distortion-product otoacoustic emissions at the 2 f1-f2 frequency (DPOAEs) are being advocated as a clinical tool for diagnosis of peripheral auditory pathology. Because they can be measured quickly and noninvasively, they may be an excellent method for identifying hearing loss in infants and children. However, few studies have examined the characteristics of DPOAEs in infants and children or detailed if, and how, their responses differ from those of adults. The purpose of the current study was to determine basic characteristics of DPOAEs in infants, toddlers, children, and young adults and to define any differences among age groups. An additional goal was to ensure that the presence of spontaneous otoacoustic emissions (SOAEs) did not confound any developmental effect. DPOAE input/output (I/O) functions at seven f2 frequencies and SOAEs were measured from one ear of 196 subjects. Children aged less than 1 yr had significantly higher mean DPOAE levels than older children and adults, and children aged 1-3 yr had higher mean DPOAE levels than teens and adults. These differences were dependent on frequency but were independent of f2 level and SOAE status. At every f2 frequency, groups of individuals having SOAEs had higher mean DPOAE levels than those not having SOAEs.

Effect of relative and overall amplitude on perception of voiceless stop consonants by listeners with normal and impaired hearing.

Previous studies of the /p/-/t/ contrast for normal-hearing listeners have shown that both manipulation of the amplitude of the burst relative to the vowel in the F4-F5 frequency region and overall presentation level can influence the perception of place of articulation [R. N. Ohde and K. N. Stevens, J. Acoust. Soc. Am. 74, 706-714 (1983); Gravel and Ohde, Asha 25, 101 (1983)], such that greater burst amplitude in the high frequencies and higher presentation levels result in more alveolar responses. The influence of relative amplitude and presentation level was tested for both normal-hearing (NH) and hearing-impaired (HI) listeners in the present study. Synthetic CV stimuli were used, and the amplitude of the burst relative to vowel-onset amplitude in the F4-F5 frequency region was manipulated across a 20-dB range. In addition, overall presentation level was varied across a 45-dB range. The findings revealed that the hearing-impaired listeners selected more alveolar responses than listeners with normal hearing when tested at equivalent SPLs. A group of five normal-hearing listeners were then presented the synthetic stimuli in a background of broadband noise at a level that produced thresholds at 4 kHz equivalent to the thresholds of five hearing-impaired listeners. Results from the noise-masked normal-hearing listeners did not consistently show more alveolar responses as presentation level of the stimuli was increased, thus failing to mimic the responses from the hearing-impaired listeners in quiet.

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.

Sarcoplasmic reticulum Ca2+ pump expression in denervated skeletal muscle.

This study was undertaken as one approach to better understand how contractile activity regulates excitation-contraction coupling phenotype in skeletal muscle. The effects of denervation on the expression of the sarcoplasmic reticulum (SR) Ca(2+)-adenosinetriphosphatase (ATPase), a key protein of the contraction-relaxation cycle, was analyzed in fast-twitch (FT) and slow-twitch (ST) skeletal muscle. Muscle mass, mRNA, and protein expression of specific isoforms of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) and contractile parameters related to muscle relaxation were measured in rat soleus and extensor digitorum longus (EDL) muscles at 1, 4, 7, 14, and 28 days after sciatic nerve transection. Wet muscle mass decreased to 35% of control by 28 days of denervation in both soleus and EDL muscles (P < 0.05). Northern and Western analyses showed decreases in mRNA and protein expression of the slow Ca2+ pump isoform (SERCA2a) in the denervated soleus muscle and in the fast Ca2+ pump isoform (SERCA1) in the denervated EDL muscle, particularly at later time points. There was no change in the expression of the alternate isoform in either muscle type. Prolongation of twitch contraction times, slowed rates of tension development, and leftward shifts in frequency-tension curves were consistent with the reduced Ca2+ pump density and suggested slowed Ca2+ handling in SR or denervated ST and FT muscles. The results are in marked contrast with those previously reported in non-weight-bearing muscle induced by biomechanical unloading.

[Satisfactory results of surgical reconstruction of rotator cuff ruptures, 1984-1990]. / Bevredigende resultaten van operatieve reconstructie van 'rotator cuff'-rupturen, 1984-1990.

OBJECTIVE: Evaluation of the middle-long term results of open surgical treatment of rotator cuff tears and identification of pre- and peroperative parameters with predictive value for the final result. DESIGN: Retrospective study (1984-1990). SETTING: Department of orthopaedics of the Sint Antonius Hospital, Nieuwegein, the Netherlands. METHOD: All patients were asked to cooperate on an extensive standard anamnesis and physical examination. Re-evaluation of the X-rays, arthrograms and operation reports took place. There were three stragglers. RESULTS: The follow-up concerned 41 shoulders in 40 patients (21 women, 19 men). The average age was 61 years (37-77). The average postoperative period was 5 years (2.5-9.2). The subjective final result was satisfactory in 80% as judged by persistent complaints and function of the operated shoulder. Young and active patients were less satisfied with the final result than older, female patients. More persistent complaints were seen in larger and longer existing cuff tears. CONCLUSIONS: Open surgical treatment of rotator cuff tears gave a satisfying result, as described in literature. Sex, age, level of activity and size of the tear appeared to be predictive parameters for the subjective final result.