a multicentre prevalence study

Objectives: The aim of this study was to measure the prevalence of skin diseases in aged nursing home residents and to explore possible associations with demographic and medical characteristics. Design: Descriptive multicentre prevalence study. Setting and participants: The study was conducted in a random sample of ten institutional long-term care facilities in the federal state of Berlin, Germany. In total, n=223 residents were included. Results: In total, 60 dermatological diseases were diagnosed. The most frequently diagnosed skin disease was xerosis cutis (99.1%, 95% CI 97.7% to 100.0%) followed by tinea ungium (62.3%, 95% CI 56.0% to 69.1%) and seborrheic keratosis (56.5%, 95% CI 50.2% to 63.0%). Only few bivariate associations have been detected between skin diseases and demographic and medical characteristics. Conclusion: Study results indicate that almost every resident living in residential care has at least one dermatological diagnosis. Dermatological findings range from highly prevalent xerosis and cutaneous infection up to skin cancer. Not all conditions require immediate dermatological treatment and can be managed by targeted skin care interventions. Caregivers need knowledge and diagnostic skills to make appropriate clinical decisions. It is unlikely that specialised dermatological care will be delivered widely in the growing long-term care sector. Trial registration number: This study is registered at https://clinicaltrials.gov/ct2/show/NCT02216526

Novel insights into PORCN mutations, associated phenotypes and pathophysiological aspects.

BACKGROUND: Goltz syndrome (GS) is a X-linked disorder defined by defects of mesodermal- and ectodermal-derived structures and caused by PORCN mutations. Features include striated skin-pigmentation, ocular and skeletal malformations and supernumerary or hypoplastic nipples. Generally, GS is associated with in utero lethality in males and most of the reported male patients show mosaicism (only three non-mosaic surviving males have been described so far). Also, precise descriptions of neurological deficits in GS are rare and less severe phenotypes might not only be caused by mosaicism but also by less pathogenic mutations suggesting the need of a molecular genetics and functional work-up of these rare variants. RESULTS: We report two cases: one girl suffering from typical skin and skeletal abnormalities, developmental delay, microcephaly, thin corpus callosum, periventricular gliosis and drug-resistant epilepsy caused by a PORCN nonsense-mutation (c.283C > T, p.Arg95Ter). Presence of these combined neurological features indicates that CNS-vulnerability might be a guiding symptom in the diagnosis of GS patients. The other patient is a boy with a supernumerary nipple and skeletal anomalies but also, developmental delay, microcephaly, cerebral atrophy with delayed myelination and drug-resistant epilepsy as predominant features. Skin abnormalities were not observed. Genotyping revealed a novel PORCN missense-mutation (c.847G > C, p.Asp283His) absent in the Genome Aggregation Database (gnomAD) but also identified in his asymptomatic mother. Given that non-random X-chromosome inactivation was excluded in the mother, fibroblasts of the index had been analyzed for PORCN protein-abundance and -distribution, vulnerability against additional ER-stress burden as well as for protein secretion revealing changes. CONCLUSIONS: Our combined findings may suggest incomplete penetrance for the p.Asp283His variant and provide novel insights into the molecular etiology of GS by adding impaired ER-function and altered protein secretion to the list of pathophysiological processes resulting in the clinical manifestation of GS

Novel insights into PORCN mutations, associated phenotypes and pathophysiological aspects.

BACKGROUND: Goltz syndrome (GS) is a X-linked disorder defined by defects of mesodermal- and ectodermal-derived structures and caused by PORCN mutations. Features include striated skin-pigmentation, ocular and skeletal malformations and supernumerary or hypoplastic nipples. Generally, GS is associated with in utero lethality in males and most of the reported male patients show mosaicism (only three non-mosaic surviving males have been described so far). Also, precise descriptions of neurological deficits in GS are rare and less severe phenotypes might not only be caused by mosaicism but also by less pathogenic mutations suggesting the need of a molecular genetics and functional work-up of these rare variants. RESULTS: We report two cases: one girl suffering from typical skin and skeletal abnormalities, developmental delay, microcephaly, thin corpus callosum, periventricular gliosis and drug-resistant epilepsy caused by a PORCN nonsense-mutation (c.283C > T, p.Arg95Ter). Presence of these combined neurological features indicates that CNS-vulnerability might be a guiding symptom in the diagnosis of GS patients. The other patient is a boy with a supernumerary nipple and skeletal anomalies but also, developmental delay, microcephaly, cerebral atrophy with delayed myelination and drug-resistant epilepsy as predominant features. Skin abnormalities were not observed. Genotyping revealed a novel PORCN missense-mutation (c.847G > C, p.Asp283His) absent in the Genome Aggregation Database (gnomAD) but also identified in his asymptomatic mother. Given that non-random X-chromosome inactivation was excluded in the mother, fibroblasts of the index had been analyzed for PORCN protein-abundance and -distribution, vulnerability against additional ER-stress burden as well as for protein secretion revealing changes. CONCLUSIONS: Our combined findings may suggest incomplete penetrance for the p.Asp283His variant and provide novel insights into the molecular etiology of GS by adding impaired ER-function and altered protein secretion to the list of pathophysiological processes resulting in the clinical manifestation of GS

Species data of littoral macroinvertebrate communities of alpine lakes along an elevational gradient (Hohe Tauern National Park, Austria) in July/August 2018

Alpine lakes support unique communities which may respond with great sensitivity to climate change. To understand the drivers of benthic macroinvertebrate community structure, samples were collected in the littoral of 28 lakes within Hohe Tauern National Park, Austria. Sampling took place from early July to early August 2018 between altitudes of 2,000 and 2,700 m a.s.l. The extent of habitat types in the lake littoral was estimated. Habitat types were classified into sediment (maximum grain size of 2 mm), small rocks (up to 20 cm x 15 cm x 5 cm), and large boulders/sheer rock faces. The extent of rocky habitats was calculated as the sum of areas covered by small rocks and boulders/sheer rock faces. A total area of 1 m² was sampled in each lake, using a hand net with a sharp frame (25 cm in width) and 500 µm mesh-size. Mixed samples were taken, covering each habitat type proportional to its extent in the lake (100% corresponding to 1 m²). For habitats covering up to 10% of the lake, a standardized area of 0.1 m² was sampled. In sediment, the uppermost 5 cm of the ground were scooped into the net by sweeping it swiftly through the sediment. When sampling large boulders or rock faces, a metal spatula was used to scrape macroinvertebrates off the surface and collect them in the net. Macroinvertebrates were brushed off small rocks using a toothbrush over water-filled trays. The dimensions of those small rocks were measured, and total surface area was calculated, assuming a suitable geometric form (ellipsoid or cuboid). Samples were presorted in the field and preserved in 4% formalin. After 3-4 weeks, all samples were rinsed in tap water and transferred to 70% ethanol for further storage. Identification was performed using a stereomicroscope (OLYMPUS SZX16, 11.2x-184x) to the lowest taxon possible

Littoral macroinvertebrate communities and environmental parameters of alpine lakes along an elevational gradient (Hohe Tauern National Park, Austria) in July/August 2018

Alpine lakes support unique communities which may respond with great sensitivity to climate change. To understand the drivers of benthic macroinvertebrate community structure, samples were collected in the littoral of 28 lakes within Hohe Tauern National Park, Austria. Sampling took place from early July to early August 2018 between altitudes of 2,000 and 2,700 m a.s.l. The extent of habitat types in the lake littoral was estimated. Habitat types were classified into sediment (maximum grain size of 2 mm), small rocks (up to 20 cm x 15 cm x 5 cm), and large boulders/sheer rock faces. The extent of rocky habitats was calculated as the sum of areas covered by small rocks and boulders/sheer rock faces. A total area of 1 m² was sampled in each lake, using a hand net with a sharp frame (25 cm in width) and 500 µm mesh-size. Mixed samples were taken, covering each habitat type proportional to its extent in the lake (100% corresponding to 1 m²). For habitats covering up to 10% of the lake, a standardized area of 0.1 m² was sampled. In sediment, the uppermost 5 cm of the ground were scooped into the net by sweeping it swiftly through the sediment. When sampling large boulders or rock faces, a metal spatula was used to scrape macroinvertebrates off the surface and collect them in the net. Macroinvertebrates were brushed off small rocks using a toothbrush over water-filled trays. The dimensions of those small rocks were measured, and total surface area was calculated, assuming a suitable geometric form (ellipsoid or cuboid). Samples were presorted in the field and preserved in 4% formalin. After 3-4 weeks, all samples were rinsed in tap water and transferred to 70% ethanol for further storage. Identification was performed using a stereomicroscope (OLYMPUS SZX16, 11.2x-184x) to the lowest taxon possible. Lake size was determined by aerial photograph in Google Earth Pro. To do so, the outlines of the lakes were traced, and the area of the polygon then calculated. Physical and chemical water parameters were measured with a multi-parameter sonde (EXO2 YSI) (for lakes 1-18 from a boat, otherwise from a rock or by wading into the lake): water temperature (°C), dissolved oxygen (% saturation), conductivity (µS/m), pH, nitrate (mg/l), turbidity (FNU), blue-green algae phycocyanin (µg/l) and chlorophyll-a (µg/l). Maximum depth (m) was measured with a sonar by rowing up to 10 transects across lakes. Maximum depth was not measured for lakes 19-28. Two data loggers had been planted per lake in lakes 1-18 in the previous year and were recovered in 2018. Data loggers measured water temperature at about half a meter depth in six-hour intervals over an entire year. Ice-free days were deduced from available logger data, assuming an ice-cover at water temperatures below 2 °C (daily maximum temperature). Additionally, zoo- and phytoplankton samples were taken from the first 18 lakes. Zooplankton was sampled with vertical tows from the hypolimnion to the surface in deeper lakes, and with oblique tows in shallow lakes using a 29 cm diameter net with a 30 µm mesh size. Samples were then fixed in sucrose-formalin and counted under an Olympus SZX16 stereomicroscope equipped with a 0.7 – 11.5 zoom objective. Phytoplankton samples from lakes 1-18 were taken with a 1.2 L water sampler from the middle of the epilimnion, and when one was present, also from the deep chlorophyll maximum. Samples were fixed with Lugol's iodine and counted in sampling chambers with a Nikon TE2000 inverted microscope using a 20x objective

ERBB2 mutation frequency in lobular breast cancer with pleomorphic histology or high-risk characteristics by molecular expression profiling

HER2-positive breast cancer is defined by amplification or overexpression of the HER2/ERBB2 oncogene and accounts for about 15% of breast cancer cases. Somatic mutation of ERBB2 is an alternative mechanism, by which activation of HER2 signaling can occur. ERBB2 mutation has been associated with invasive lobular breast cancer (ILBC). This study investigates the frequency and phenotype of ILBC harboring mutated ERBB2. The ERBB2 mutation status was determined by next generation sequencing and/or pyrosequencing in n = 106 ILBCs, including n = 86 primary or locally recurrent tumors and n = 20 metastases from visceral organs, soft tissue, or skin. Immunohistochemical characteristics were determined using tissue microarrays. This series was enriched for ILBCs with pleomorphic histology and/or high-risk expression profiles (Oncotype DX, recurrence score RS > 25). Nearly all specimens were E-cadherin-negative (99%), estrogen receptor (ER)-positive (92%), and lacked ERBB2 overexpression (96%). ERBB2 mutations (p.V777L, p.L755S, p.S310F) were identified in 5/106 (5%) cases. ERBB2-mutated cases included 2/86 (2%) primary tumors and 3/20 (15%) metastases (P = 0.045). ERBB2-mutated cases were associated with loss of ER (2/7, 29%, P = 0.035) and histological grade 3 (4/34, 12%, P = 0.023), but not with solid growth (3/31, 10%, P = 0.148) or pleomorphic histology (2/27, 7%, P = 0.599). No ERBB2 mutation was detected in ILBCs with RS > 25 (0/22, 0%). In 10 patients with multiple matched specimens (n = 25), the ERBB2 mutational status was always concordant. In summary, a small subset of ILBCs harbors potentially actionable ERBB2 mutations. In ERBB2-mutated ILBCs, no association with pleomorphic histology was found

ERBB2 mutation is associated with sustained tumor cell proliferation after short-term preoperative endocrine therapy in early lobular breast cancer

Invasive lobular breast cancer (ILC) is a special breast cancer (BC) subtype and is mostly hormone receptor (HR)-positive and ERBB2 non-amplified. Endocrine therapy restrains tumor proliferation and is the mainstay of lobular BC treatment. Mutation of ERBB2 has been associated with recurrent ILC. However, it is unknown whether ERBB2 mutation impacts on the otherwise exquisite responsiveness of early ILC to endocrine therapy. We have recently profiled n = 622 HR-positive early BCs from the ADAPT trial for mutations in candidate genes involved in endocrine resistance, including ERBB2. All patients were treated with short-term preoperative endocrine therapy (pET, tamoxifen or aromatase inhibitors) before tumor resection. Tumor proliferation after endocrine therapy (post-pET Ki67 index) was determined prospectively by standardized central pathology assessment supported by computer-assisted image analysis. Sustained or suppressed proliferation were defined as post-pET Ki67 =10% or <10%. Here, we report a subgroup analysis pertaining to ILCs in this cohort. ILCs accounted for 179/622 (28.8%) cases. ILCs were enriched in mutations in CDH1 (124/179, 69.3%, P < 0.0001) and ERBB2 (14/179, 7.8%, P < 0.0001), but showed fewer mutations in TP53 (7/179, 3.9%, P = 0.0048) and GATA3 (11/179, 6.1%, P < 0.0001). Considering all BCs irrespective of subtypes, ERBB2 mutation was not associated with proliferation. In ILCs, however, ERBB2 mutations were 3.5-fold more common in cases with sustained post-pET proliferation compared to cases with suppressed post-pET proliferation (10/75, 13.3% versus 4/104, 3.8%, P = 0.0248). Moreover, ERBB2 mutation was associated with high Oncotype DX recurrence scores (P = 0.0087). In summary, our findings support that ERBB2 mutation influences endocrine responsiveness in early lobular BC