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There is evidence for e-Health interventions for full-blown depression. Little is known regarding commonly untreated subthreshold depression in primary care. This randomized controlled multi-centre trial assessed reach and two-year-effects of a proactive e-Health intervention (ActiLife) for patients with subthreshold depression. Primary care and hospital patients were screened for subthreshold depression. Over 6 months, ActiLife participants received three individualized feedback letters and weekly messages promoting self-help strategies against depression, e.g., dealing with unhelpful thoughts or behavioural activation. The primary outcome depressive symptom severity (Patient Health Questionnaire;PHQ-8) and secondary outcomes were assessed 6, 12 and 24 months. Of those invited, n = 618(49.2 %) agreed to participate. Of them, 456 completed the baseline interview and were randomized to ActiLife (n = 227) or assessment only (n = 226). Generalised estimation equation analyses adjusting for site, setting and baseline depression revealed that depressive symptom severity declined over time, with no significant group differences at 6 (mean difference = 0.47 points; d = 0.12) and 24 months (mean difference = −0.05 points; d = −0.01). Potential adverse effects were observed at 12 months, with higher depressive symptom severity for ActiLife than control participants (mean difference = 1.33 points; d = 0.35). No significant differences in rates of reliable deterioration or reliable improvement of depressive symptoms were observed. ActiLife increased applied self-help strategies at 6 (mean difference = 0.32; d = 0.27) and 24 months (mean difference = 0.22; d = 0.19), but not at 12 months (mean difference = 0.18; d = 0.15). Self-report measures and lack of information on patients' mental health treatment. ActiLife yielded satisfactory reach and increased the use of self-help strategies. Data were inconclusive in terms of depressive symptom changes. • Active recruitment in primary care reaches many individuals with depression. • Individuals with a broad range of symptom severity could be involved in ActiLife. • ActiLife fostered self-help strategies in individuals with depressive symptoms. • There was no support for positive effects on depression symptom reduction. [ABSTRACT FROM AUTHOR]

As mental health systems move towards person-centred care, outcome measurement in clinical research and practice should track changes that matter to young people and their families. This study mapped the types of change described by three key stakeholder groups following psychotherapy for depression, and compared the salience of these outcomes with the frequency of their measurement in recent quantitative treatment effectiveness studies for adolescent depression. Using qualitative content analysis, this study identified and categorized outcomes across 102 semi-structured interviews that were conducted with depressed adolescents, their parents, and therapists, as part of a randomized superiority trial. Adolescents had been allocated to Cognitive-Behavioral Therapy, Short-Term Psychoanalytic Psychotherapy, or a Brief Psychosocial Intervention. The study mapped seven high-level outcome domains and 29 outcome categories. On average, participants discussed change in four domains and six outcome categories. The most frequently discussed outcome was an improvement in mood and affect (i.e., core depressive symptoms), but close to half of the participants also described changes in family functioning, coping and resilience, academic functioning, or social functioning. Coping had specific importance for adolescents, while parents and therapists showed particular interest in academic functioning. There was some variation in the outcomes discussed beyond these core themes, across stakeholder groups and treatment arms. Of the outcomes that were frequently discussed in stakeholder narratives, only symptomatic change has been commonly reported in recent treatment studies for adolescent depression. A shift towards considering multiple outcome domains and perspectives is needed to reflect stakeholder priorities and enable more nuanced insights into change processes. [ABSTRACT FROM AUTHOR]

Summary: Background: Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by urticarial exanthema, bone and joint alterations, fever and monoclonal gammopathy, which manifest mostly in the second half of life. It involves overactivation of the interleukin (IL)‐1 system, but the exact pathophysiological pathways remain largely unknown. Objectives: To identify and characterize the pathogenetic players in SchS. Methods: Blood parameters were quantified in patients with SchS compared with healthy controls and patients with psoriasis and hidradenitis suppurativa using enzyme‐linked immunosorbent assay (ELISA). CCL2 expression in cultured primary cells was analysed by quantitative reverse‐transcriptase polymerase chain reaction and ELISA. Results: CCL2, a chemoattractant for monocytic and further mononuclear immune cells, was found to be significantly elevated in patients with SchS. CCL2 levels showed a positive association with global disease activity, especially with bone pain, but not disease duration, gammopathy, neutrophilia or skin disease. In vitro stimulation assays demonstrated a strong CCL2 production capacity of mononuclear immune cells and fibroblasts, but not epithelial or endothelial cells. Among a range of inflammatory mediators, only IL‐1β (immune cells, fibroblasts) and tumour necrosis factor (TNF)‐α (fibroblasts) were important CCL2 inducers. TNF‐α, but not IL‐17, strengthened the CCL2‐inducing effect of IL‐1β in fibroblasts. Accordingly, CCL2 levels positively correlated with both TNF‐α and IL‐1β serum levels in patients with SchS. Therapeutic IL‐1β blockade decreased CCL2 blood levels in these patients as early as 1 week after the initiation of treatment. Conclusions: CCL2 may be an important component of the pathogenetic cascade leading to bone alterations, and a suitable marker of disease activity in patients with SchS. What's already known about this topic?Schnitzler syndrome (SchS) is a very rare acquired autoinflammatory disease, clinically characterized by urticarial exanthema, arthralgia and osteosclerosis, and episodes of fever.The pathogenesis involves overactivation of the interleukin‐1 system.The exact pathogenetic pathways are mostly unknown, and biomarkers are not available to assess the inflammatory activity in SchS. What does this study add? The chemokine CCL2 is a marker of SchS; its blood levels are significantly upregulated and linked to global disease activity and early therapy response in patients with SchS.While no clear relationship with patients' urticarial exanthema was detected, CCL2 may be involved in bone alterations in these patients.The cellular sources of CCL2 include mononuclear immune cells and fibroblasts.Interleukin‐1β and tumour necrosis factor‐α, blood levels of which correlate with CCL2 levels in patients with SchS, are important CCL2 inducers. What is the translational message? Quantifying CCL2 blood levels may allow the objective estimation of inflammatory disease activity and may help with the therapy decision in patients with SchS.CCL2 may be a key element of the pathogenetic cascades in SchS, especially those important for osteosclerosis. Linked Comment:Kambe and Nguyen. Br J Dermatol 2019; 180:706–707. Respond to this article Plain language summary available online [ABSTRACT FROM AUTHOR]

Background Cold contact urticaria ( CCU) is characterized by itchy wheal and flare responses due to the release of histamine and other pro-inflammatory mediators after exposure to cold. The treatment of choice is nonsedating antihistamines, dosages of which may be increased up to fourfold if standard doses are ineffective. Here, we assess the effects of a standard 20 mg dose and up-dosing to 40 and 80 mg of bilastine in reducing the symptoms of CCU and inflammatory mediator release following cold challenge. Methods Twenty patients with CCU were included in this randomized, crossover, double-blind, placebo-controlled 12-week study. They received placebo, 20, 40 or 80 mg of bilastine daily each for 7 days with 14-day washout periods. The primary readout was change in critical temperature thresholds ( CTT). Secondary readouts were changes in pruritus, levels of histamine IL-6, IL-8 and TNF-α collected by skin microdialysis and safety and tolerability of bilastine. Results Bilastine 20 mg was highly effective ( P < 0.0001) in reducing CTT. Up-dosing to 80 mg significantly ( P < 0.04) increased its effectiveness. At this dose, 19 of 20 (95%) patients responded to treatment, with 12 of 20 (60%) becoming symptom free. Only one patient was refractory to treatment. Microdialysis levels of histamine, IL-6 and IL-8 assessed 1-3 h after cold challenge were significantly ( P < 0.05) decreased following up-dosing with 80 mg bilastine. Bilastine treat-ment was well tolerated without evidence of increased sedation with dose escala-tion. Conclusions Bilastine was effective in reducing the symptoms of patients with CCU. Increased efficacy of bilastine with fourfold up-dosing was without sedation and supports urticaria treatment guidelines. [ABSTRACT FROM AUTHOR]

Reduction of flux through photorespiration has been viewed as a major way to improve crop carbon fixation and yield since the energy-consuming reactions associated with this pathway were discovered. This view has been supported by the biomasses increases observed in model species that expressed artificial bypass reactions to photorespiration. Here, we present an overview about the major current attempts to reduce photorespiratory losses in crop species and provide suggestions for future research priorities. [ABSTRACT FROM AUTHOR]

Urticarial skin reactions are one of the most frequent problems seen by allergists and clinical immunologists in daily practice. The most common reason for recurrent wheals is spontaneous urticaria. There are, however, several less common diseases that present with urticarial rash, such as urticarial vasculitis and autoinflammatory disorders. The latter include cryopyrin-associated periodic syndrome and Schnitzler's syndrome, both rare and disabling conditions mediated by increased interleukin-1 secretion. Apart from the urticarial rash, patients are suffering from a variety of systemic symptoms including recurrent fever attacks, arthralgia or arthritis and fatigue. Autoinflammatory diseases are often associated with a diagnostic delay of many years and do not respond to antihistamines and other treatments of urticaria. Also, the chronic inflammation may lead to long-term complications such as amyloidosis. It is therefore important not to miss these diseases when diagnosing and treating patients with chronic recurrent urticarial rash. Here, we present clinical clues and tips that can help to identify autoinflammatory disorders in patients presenting with chronic urticarial rash and discuss their clinical picture and management. [ABSTRACT FROM AUTHOR]

Background Schnitzler syndrome (SchS) is a rare disease with suspected autoinflammatory background that shares several clinical symptoms, including urticarial rash, fever episodes, arthralgia, and bone and muscle pain with cryopyrin-associated periodic syndromes ( CAPS). Cryopyrin-associated periodic syndromes respond to treatment with interleukin-1 antagonists, and single case reports of Schnitzler syndrome have shown improvement following treatment with the interleukin-1 blocker anakinra. This study evaluated the effects of the interleukin-1 antagonist rilonacept on the clinical signs and symptoms of SchS. Methods Eight patients with SchS were included in this prospective, single-center, open-label study. After a 3-week baseline, patients received a subcutaneous loading dose of rilonacept 320 mg followed by weekly subcutaneous doses of 160 mg for up to 1 year. Efficacy was determined by patient-based daily health assessment forms, physician's global assessment (PGA), and measurement of inflammatory markers including C-reactive protein ( CRP), serum amyloid A ( SAA), and S100 calcium-binding protein A12 (S100A12). Results Treatment with rilonacept resulted in a rapid clinical response as demonstrated by significant reductions in daily health assessment scores and PGA scores compared with baseline levels ( P < 0.05). These effects, which were accompanied by reductions in CRP and SAA, continued over the treatment duration. Rilonacept treatment was well tolerated. There were no treatment-related severe adverse events and no clinically significant changes in laboratory safety parameters. Conclusion Rilonacept was effective and well tolerated in patients with SchS and may represent a promising potential therapeutic option ( NCT01045772 [ Identifier]; Eudra CT #2006-004290-97). [ABSTRACT FROM AUTHOR]

Background:Previously, we reported a six-marker gene set, which allowed a molecular discrimination of benign and malignant thyroid tumours. Now, we evaluated these markers in fine-needle aspiration biopsies (FNAB) in a prospective, independent series of thyroid tumours with proven histological outcome.Methods:Quantitative RT-PCR was performed (ADM3, HGD1, LGALS3, PLAB, TFF3, TG) in the needle wash-out of 156 FNAB of follicular adenoma (FA), adenomatous nodules, follicular and papillary thyroid cancers (TC) and normal thyroid tissues (NT).Results:Significant expression differences were found for TFF3, HGD1, ADM3 and LGALS3 in FNAB of TC compared with benign thyroid nodules and NT. Using two-marker gene sets, a specific FNAB distinction of benign and malignant tumours was achieved with negative predictive values (NPV) up to 0.78 and positive predictive values (PPV) up to 0.84. Two FNAB marker gene combinations (ADM3/TFF3; ADM3/ACTB) allowed the distinction of FA and malignant follicular neoplasia with NPV up to 0.94 and PPV up to 0.86.Conclusion:We demonstrate that molecular FNAB diagnosis of benign and malignant thyroid tumours including follicular neoplasia is possible with recently identified marker gene combinations. We propose multi-centre FNAB studies on these markers to bring this promising diagnostic tool closer to clinical practice. [ABSTRACT FROM AUTHOR]

Background: Clinical studies on intracoronary stem cell infusion in patients with acute myocardial infarction (AMI) have shown promising results for left ventricular ejection fraction (LVEF). However, preclinical studies have shown that intramyocardial cell injection is better than the intracoronary approach. Objective: To test safety and feasibility of intramyocardial cell injection and left ventricular electromechanical mapping (EMM) early after AMI. Design: On day 10.5 (5) (mean (SD)) after AMI and percutaneous coronary intervention with stent implantation (culprit lesion: 15 LAD, 3 circumflex and 2 right coronary arteries) 20 patients (mean (SD) 60.4 (11.4) years) received bone marrow derived mononuclear cells in the low-voltage area using EMM-guided percutaneous intramyocardial injection. EMM and coronary angiography were performed in 15 patients at 6-months' follow-up. Echocardiography, recording of laboratory data and clinical assessment (6-month and 12-month follow-up) were carried out in all 20 patients. Results: None of the patients showed periprocedural complications. Three patients received an implantable cardioverter-defibrillator for primary prevention of sudden cardiac death and 6 (30%) patients showed in-stent restenosis. One patient underwent bypass surgery owing to chronic stent occlusion after 6 months. 2.0 (0.6)x108 cells, including 1.0 (0.3)x106 CD45dim/CD34hi stem cells, were injected in each patient. EMM showed a mean (SD) improvement from a baseline unipolar voltage of 45.5 (14.3)% to 59.3 (19.8)% of normal voltage (p = 0.002) and reduction of the low-voltage area from 28.7 (12.1)% to 20.3 (13.5)%; (p = 0.016). During the 12-month follow-up, the left ventricular ejection fraction (LVEF) improved from 40.8 (6.9)% to 47.1 (10.6)%; (p = 0.037). Conclusion: Left ventricular EMM and percutaneous intramyocardial cell injection in patients with AMI was shown to be a safe procedure. It is associated with improved LVEF and electromechanical parameters after 12-months' follow-up. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effect of a low-moisture buffer block on ruminal pH and milk production in cows induced with subacute ruminal acidosis (SARA). Sixteen ruminally cannulated cows were randomly assigned to treatment (access to buffer blocks) or control (no buffer blocks). Ruminal pH was recorded each minute; dry matter intake (DMI), milk yield, and milk composition were measured daily. The experiment lasted 12 d and consisted of a 3-d pre-SARA period (without access to buffer blocks; d 1 to 3), after which 8 cows were given access to buffer blocks and 8 cows continued without access to buffer blocks. The next 4 d (d 4 to 7) were for evaluating the response to buffer blocks. On d 8, cows were restricted to 50% of previous DMI, and on d 9 SARA was induced (addition of 4 kg of wheat/barley pellet to pre-SARA total mixed ration (TMR). Cows were then monitored for a 3-d recovery period (d 10 to 12). The SARA challenge was successful in decreasing mean ruminal pH and time and area below pH 5.6. Intake of buffer blocks averaged 0.33 kg of DM/cow per day and was greatest on d 4 and d 8. Total DMI (TMR plus buffer block) and yields of milk and milk components were not affected by treatment. Although there was no overall effect of treatment on any of the ruminal pH variables measured, there were significant treatment by period interactions for several ruminal pH variables. Cows on the control treatment tended to experience a greater decrease in mean ruminal pH when induced with SARA than cows with access to buffer blocks (-0.55 vs. -0.20 pH units). Cows on the control treatment also experienced a greater increase in time (9.7 vs. 4.1 h/d) and area (249 vs. 83 min x pH units/d) below pH 5.6 compared with cows with access to buffer blocks. Ruminal volatile fatty acids, lactate, ethanol, and succinate concentrations during the SARA challenge did not differ between treatments. Eating behavior was not affected by treatment. Size of the first meal of the day was greater on the SARA challenge day than during the pre-SARA period (11.0 vs. 5.7 kg, as fed). Giving cows access to a buffer-containing molasses block may reduce the duration and the severity of a 1-d SARA challenge. [ABSTRACT FROM AUTHOR]

Abstract: Feeding diets high in grain and other highly fermentable carbohydrates to dairy cows increases milk production, but also increases the risk of subacute ruminal acidosis (SARA). SARA is defined as periods of moderately depressed ruminal pH, from about 5.5 to 5.0. SARA may be associated with laminitis and other health problems resulting in decreased production. Although ruminal pH varies considerably within a day, cows possess a highly developed system to maintain ruminal pH within a physiological range. However, if the acid production from fermentation is more than the system can buffer, ruminal pH compensation fails and ruminal pH may drop drastically. The risk of developing SARA can be reduced by adopting a feeding regime, which balances ruminal buffering with the production of volatile fatty acids from fermentation of carbohydrates. This can be achieved by providing adequate dietary fibre containing sufficient long particles. However, excessive amounts of long particles might lead to sorting and ultimately increase the risk of SARA. The level of fibre and long particles needed to maintain rumen health depends on the fibre source used. SARA is also dependent on the grain source fed and the degree of grain processing. Feeding highly fermentable grain increases the requirement for fibre. Feeding diet components separately appears to increase the risk for SARA compared to feeding a total mixed ration. Also, management practices that cause cows to eat fewer, larger, or irregular meals may be associated with increased incidence of SARA. Important management factors include feed access time, consistency of feeding schedule, and available bunk space. When dairy cows are fed for high production, good management practices are important even when dietary factors are optimal. [Copyright &y& Elsevier]

The article focuses on the modern approach in blood integration and plasma collections. There was a strict separation between whole blood donation and accumulation of plasma for industrial processing by apheresis. In Germany, most of the red cells gathered are donated at mobile settings. Blood products for clinical use are evaluated for special characteristics like blood group antigens.

Data from experiments in which subacute ruminal acidosis (SARA) was induced in lactating dairy cows (days in milk = 154 ± 118) were evaluated to investigate the effectiveness of the induction protocol and its effect on production outcomes. For 13 cows in 3 trials, ruminal pH was measured continuously and recorded each minute; dry matter intake and milk yield were recorded daily. Milk composition data were obtained from 9 cows in 2 of these trials. The SARA induction protocol included 4 separate periods: 4 d of baseline [normal total mixed ration (TMR)], 1 d of 50% restricted feeding, 1 or 2 d of challenge feeding [addition of 3.5 or 4.6 kg of wheat-barley pellet (dry matter basis) to normal TMR], and 2 d of recovery measurements when feeding normal TMR. The SARA induction protocol lowered mean ruminal pH from 6.31 during the baseline period to 5.85 during the challenge period; pH remained below baseline level during the recovery period (6.16). Mean ruminal pH was highest (6.59) during the day of restricted feeding. Nadir ruminal pH decreased from baseline to challenge period (5.76 vs. 5.13). Hours below pH 5.6 increased from 1.10 to 8.26/d from baseline to challenge period and area below 5.6 (pH x min/d) increased from 15.0 to 190.3. Dry matter intake was not affected by SARA induction. Milk yield dropped from 35.2 kg/d during baseline to 31.7 k/d during the challenge period and did not return to baseline level during the recovery period (31.3 kg/d). No depression in milk fat percentage was observed when SARA was induced. Yield of fat was highest during the restricted feeding period (1.47 kg/ d) and was lower during the recovery period than during the baseline period (1.12 vs. 1.31 kg/d). The protocol successfully induced SARA (low ruminal pH without signs of acute ruminal acidosis) on the challenge day. Milk yield was substantially reduced and did not recover within 2 d after the challenge. [ABSTRACT FROM AUTHOR]

Studies the effects of forage particle size, forage source and grain fermentability on performance and ruminal pH in midlactation cows. Method of the study; Results and discussion; Conclusion.

Investigates the optimized control concepts used to minimize the number of additional tanks for the Wuppertal-Buchenhofen wastewater treatment plant in the catchment basin of the River Wupper in Germany. Description of the control concept for nitrification; Application spectrum of spectral absorption coefficient and SS measurement.

The solution conformation of the cyclic peptide J324 (cyclo[sup 0,6]-[Lys[sup 0],Glu[sup 6],D-Phe[sup 7]]BK), an antagonist targeted at the bradykinin (BK) B[sub 2] receptor, has been investigated using experimental and theoretical methods. In order to gain insight into the structural requirements essential for BK antagonism, we carried out molecular dynamics (MD) simulations using simulated annealing as the sampling protocol. Following a free MD simulation we performed simulations using nuclear Overhauser enhancement (NOE) distance constraints determined by NMR experiments. The low-energy structures obtained were compared with each other, grouped into families and analyzed with respect to the presence of secondary structural elements in their backbone. We also introduced new ways of plotting structural data for a more comprehensive analysis of large conformational sets. Finally, the relationship between characteristic backbone conformations and the spatial arrangement of specific pharmacophore centers was investigated. [ABSTRACT FROM AUTHOR]

Scattering from a one-dimensional random rough surface with Neumann boundary conditions is analyzed using a finite element formulation. Results are in excellent agreement with tapered-wave integral-equation solutions after averaging over realizations. Finite element advantages in CPU time, memory storage, and energy conservation tests are illustrated. [ABSTRACT FROM AUTHOR]

Investigates the rate of sucrose synthesis in cold-stored tubers. Measurement of the accumulation of sugars; Appearance of a form of sucrose phosphate synthase (SPS); Decrease of SPS expression that resulted in a reproducible but non-proportional decrease of soluble sugars in cold-stored tubers; Conclusion that SPS expression per se does not control sugar synthesis.

Background: The ongoing global SARS-CoV-2 pandemic has caused over 4.7 million infections greatly challenging healthcare workers (HCW) and medical institutions worldwide. The SARS-CoV-2 pandemic has shown to significantly impact mental and physical health of HCW. Thus, implementation of testing facilities supporting HCW are urgently needed.Methods: A low-threshold SARS-CoV-2 testing facility was introduced at the University Hospital Bonn, Germany, in March 2020. Irrespective of clinical symptoms employees were offered a voluntary and free SARS-CoV-2 test. Furthermore, employees returning from SARS-CoV-2 risk regions and employees after risk contact with SARS-CoV-2 infected patients or employees were tested for SARS-CoV-2 infection. Pharyngeal swabs were taken and reverse transcription polymerase chain reaction for detection of SARS-CoV-2 was performed, test results being available within 24 h. Profession, symptoms and reason for SARS-CoV-2 testing of employees were recorded.Results: Between 9th March and April 30, 2020, a total of 1510 employees were tested for SARS-CoV-2 infection. 1185 employees took advantage of the low-threshold testing facility. One percent (n = 11) were tested positive for SARS-CoV-2 infection, 18% being asymptomatic, 36% showing mild and 36% moderate/severe symptoms (missing 10%). Furthermore, of 56 employees returning from SARS-CoV-2 risk regions, 18% (10/56) were tested SARS-CoV-2 positive. After risk contact tracking by the hospital hygiene 6 patient-to-employee transmissions were identified in 163 employees with contact to 55 SARS-CoV-2 positive patients.Conclusion: In the absence of easily accessible public SARS-CoV-2 testing facilities low-threshold SARS-CoV-2 testing facilities in hospitals with rapid testing resources help to identify SARS-CoV-2 infected employees with absent or mild symptoms, thus stopping the spread of infection in vulnerable hospital environments. High levels of professional infection prevention training and implementation of specialized wards as well as a perfectly working hospital hygiene network identifying and tracking risk contacts are of great importance in a pandemic setting. [ABSTRACT FROM AUTHOR]

Background Platelet-activating factor ( PAF) causes wheal and flare responses which are abrogated by H1-antihistamines giving rise to the hypothesis that PAF-induced wheal development is secondary to histamine release from dermal mast cells. But is this hypothesis correct? Methods Wheal and flare responses were induced by intradermal injection of PAF, codeine and histamine in 14 healthy volunteers. Dermal histamine and PGD2 contractions were measured using microdialysis. Results PAF, unlike histamine and codeine, did not cause a statistically significant rise in mean histamine levels with ten persons showing negligible histamine release. Codeine caused a significant but variable histamine release, ranging from 29 to 282 ng/ml. Codeine, but not PAF or histamine, caused a small but statistically significant release of PGD2. Conclusion Wheal and flare reactions in human skin induced by PAF are not associated with histamine release and, therefore, appear to be independent of mast cell degranulation. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the cases of a 73-year-old woman and a 61-year-old woman with notalgia paraesthetica (NP) who both undergo treatment of the disease with an 8% capsaicin patch.

Since the beginning of the 1990s, an increase in dissolved organic carbon (DOC) has been observed in rivers and lakes in various parts of Europe and North America. The processes responsible for the increased DOC concentrations are complex and not entirely understood. The aim of this review is to provide an overview of the recent debate about increases in the DOC concentrations in surface water and their possible drivers. [ABSTRACT FROM AUTHOR]

We report a case of a woman with a spontaneous dissection of the left main stem leading to a large aneurysm compressing the left coronary artery. The lesion was initially treated with a conventional multicellular stent. However, persistence of the aneurysm required that two polytetrafluoroethylene-covered stents be implanted. Follow-up angiographic and clinical results were excellent. [ABSTRACT FROM AUTHOR]

The article focuses on the pressure of standardized process of blood transfusion in Germany. Due to the decreasing numerous number of incapable donors of blood products, it costs pressures mainly in transfusion process. It is very expensive to gain a standardized procedure because it requires expensive devices like centrifuges and separators. One way of getting a high quality blood products is a bedside processing (BSP). BSP is the automated collection of blood products, with a high quality standardization and a high purity of the resulting product and a minimal number or no manual steps.

Linked Article: Krause et al. Br J Dermatol 2019; 180:859–868 [ABSTRACT FROM AUTHOR]

Summary: Schnitzler syndrome is a very rare chronic disease, which usually develops in the second half of life. It appears as skin rashes, muscle/skeletal pain and fever episodes. The trigger and molecular processes in the disease are not understood. However, drugs that inhibit the inflammatory molecule called interleukin‐1ß were found to relieve the disease. The authors of this German study wondered which further molecules are involved in Schnitzler syndrome. For this purpose, a range of molecules with inflammatory properties was quantified in the blood of the patients and, as a comparison, in healthy people and patients with other inflammatory diseases. Patients with Schnitzler syndrome were found to have strongly elevated levels of CCL2, a molecule known to attract inflammatory cells to affected tissues and to have a special role in bone alterations. CCL2 levels were particularly high in severely affected patients, especially those with intense bone pain. In the bone, CCL2 is known to be produced by certain bone‐modifying cells. Laboratory experiments revealed that CCL2 was also highly produced by immune cells and connective tissue cells (fibroblasts). Interleukin‐1ß as well as the inflammatory molecule TNF‐α triggered the production of CCL2 by these cells. When patients were treated with an interleukin‐1ß‐blocking drug, health improvement was paralleled by a drop of CCL2 levels. The authors concluded that in Schnitzler syndrome CCL2 is an important player in the inflammation process in bones and other body sites and may be used in the clinic as an indicator of disease severity. Linked Article: Krause et al. Br J Dermatol 2019; 180:859–868 [ABSTRACT FROM AUTHOR]

Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy in patients >50 years and characterized by both degenerative and autoimmune features. Rimmed vacuoles (RV) are a typical histological finding in sIBM. The aim of our study was to identify proteins that accumulate in RV by using a proteomic approach. Skeletal muscle samples of 18 sIBM patients were included in this study. RV samples and intraindividual control samples (CS; from muscle fibers without vacuolar changes) were collected from 10 μm H&E stained muscle sections by laser microdissection and analyzed by a highly sensitive mass spectrometry approach. A total of 3875 different proteins were identified and 215 of these showed a statistically significant accumulation in RV samples compared to CS. Proteins of the extracellular matrix and of the basal lamina, sarcolemmal proteins and intermediate filaments were the most abundant over-represented proteins in RV. In addition, we found an accumulation of proteins that play a role in protein degradation and of several chaperones including BiP and calreticulin, two proteins that are involved in unfolded protein response and SR stress, and components of a chaperone complex that was not described in the context of sIBM so far. Our proteomic approach also revealed an over-representation of proteins that play a role in inflammatory pathways, e.g. interferon-induced proteins and proteins involved in T-cell activation. In conclusion, our proteomic data provide essential new insights into the composition of rimmed vacuoles in sIBM. The application of a combined laser microdissection and mass spectrometry approach enabled the identification of more than 200 proteins that accumulate in RV areas. The results not only confirm previous findings but expand our knowledge about proteins and pathways that seem to be relevant in pathogenesis of sIBM. [ABSTRACT FROM AUTHOR]

Background: There is no consensus agreement on the optimal management strategy for ventral hernia in women of childbearing age. The theoretical increased risk of ventral hernia recurrence can impact management strategies. We conducted a systematic review of the literature to report the ventral hernia recurrence rate in women of childbearing age who underwent hernia repair prior to their pregnancy and propose a management algorithm.Methods: We systematically searched multiple databases including MEDLNE, PubMed, and the Cochrane Library sources from inception to August, 2017. Two reviewers independently identified 314 primary studies, assessed methodological quality, and extracted data. Quality of included studies was assessed by employing the Newcastle Ottawa quality assessment tool for cohort studies. A separate tool was utilized for assessing the methodological quality of case series. A meta-analysis of proportions was conducted of studies reporting incidence of recurrence using STATA, employing a random effects model, to calculate a pooled weighted incidence rate (with 95% confidence interval). Descriptive statistics were employed to report the findings of studies which did not report any ventral hernia recurrence.Results: Five retrospective studies were included in our review, enrolling a total of 14,638 female participants. Upon stratifying patients according to pregnancy status after primary hernia repair, 13,494 were found to be in the non-pregnant cohort whereas 1,144 were included in the pregnant cohort. Overall, 9% (95% CI 8-9%) of the non-pregnant patients experienced a recurrence whereas 12% (95% CI 10-15%) of patients that became pregnant subsequent to a ventral hernia repair experienced a recurrence. No major adverse events were recorded throughout the course of pregnancy.Conclusions: Ventral hernias in women of childbearing age have a pooled recurrence rate of 12%. Pregnancy may be considered a risk factor for ventral hernia recurrence. Female patients of childbearing age with asymptomatic or minimally symptomatic ventral hernias that do not pose a significant strain on the patients' quality of life could be provided with the option of watchful waiting, with appropriate education of risks while discussing management. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 48-year-old Caucasian woman who was successfully treated with anti-immunoglobulin E (IgE) therapy after developing severe urticaria factitia. It states that she was treated with nonsedating antihistamines after her skin produced massive pruritus and whealing but none of the treatments have resulted in sufficient symptom control. However, when the anti-IgE treatment was performed, complete protection from symptom development was achieved.

This study evaluated how sampling schedule influenced statistical interpretation of the dietary effects on ruminal pH in lactating cows. Data collected in two published Latin Square studies were utilized (JDS 85:1947: A, JDS 86:2433: B). Ruminal pH was continuously measured in each period for 5 d in A and 3 d in B using indwelling electrodes and averaged by hour such that each cow had 24 observations per day. Average treatment pH, calculated using the hour by treatment least square means within experiment, ranged 0.27 pH units for A and 0.50 pH units for B. In trial A equal portions of TMR were fed every 12 h, where in B 65% of the TMR was fed in the morning and 35% 12 h later. Effect of forage particle size (FPS), grain fermentability (GF) and their interaction were tested in both studies. In both studies an effect of GF was observed (P < 0.05). The effect of FPS was significant in A, but not in B. The GF by FPS interaction was not significant in either study. Data were re-analyzed using 3 abbreviated sampling schedules within day and for 1, 3 or 5 (only for A) consecutive days within period, utilizing rumen pH measured: 1) 8 h post am feeding, 2) every 4 h for 24 h, and 3) and every 2 h for 12 h after the am feeding. Data were analyzed as Latin Square designs utilizing the mixed procedure of SAS with repeated measures. Sampling schedules were compared by the capability to detect a treatment effect (P < 0.05). In study A, sampling for either 3 or 5 d utilizing either of the 3 sampling schedules produced similar results. When only 1 d was utilized in the analysis, sampling every 2 h over a 12 h period detected both treatment effects (P < 0.05). In study B, 3 d of multiple within day samples were required to detect a GF effect (P < 0.05). In contrast to the published analysis, sampling only once a day (1 or 3 d) or every 4 h for 3 d resulted in a GF by FPS interaction (P < 0.05). It is recommended to sample ruminal pH across multiple days and hours. It is important to consider post prandial pattern of ruminal pH when choosing the sampling schedule that will maximize the probability to detect a treatment effect. [ABSTRACT FROM AUTHOR]

In this essay, we discuss the under-representation of women in leadership positions in global health (GH) and the importance of mentorship to advance women's standing in the field. We then describe the mentorship model of GROW, Global Research forWomen. We describe the theoretical origins of the model and an adapted theory of change explaining how the GROW model for mentorship advances women's careers in GH. We present testimonials from a range of mentees who participated in a pilot of the GROW model since 2015. These mentees describe the capability-enhancing benefits of their mentorship experience with GROW. Thus, preliminary findings suggest that the GROWmentorship model is a promising strategy to build women's leadership in GH. We discuss supplemental strategies under consideration and next steps to assess the impact of GROW, providing the evidence to inform best practices for curricula elsewhere to build women's leadership in GH. [ABSTRACT FROM AUTHOR]

Summary: Background: Chronic spontaneous urticaria (CSU) is an inflammatory skin disorder characterized by recurrent weals, angio‐oedema or both. Recent studies have shown that the number of endothelial cells is increased in the skin of patients with CSU, but the underlying mechanisms and clinical implications of this are unclear. Aim: To evaluate whether mast cell (MC) or endothelial cell (EC) numbers correlate with CSU and whether they are relevant for disease duration, disease activity or the presence of clinical features. Methods: We determined the numbers of CD31+ ECs and MCs in nonlesional skin of 30 patients with CSU using quantitative histomorphometry, and assessed their correlation with each other and with clinical features such as disease duration, disease activity and occurrence of angio‐oedema. Results: The numbers of MCs and ECs were high in the nonlesional skin of patients with CSU, but did not correlate with each other. Neither MC number nor EC number correlated with disease duration or disease activity. Interestingly, patients with high numbers of cutaneous CD31+ ECs had higher rates of recurrent angio‐oedema and vice versa. Conclusions: Based on these findings, we speculate that vascular remodelling and MC hyperplasia in patients with CSU occurs independently and via different mechanisms. Targeting of the mechanisms that drive neoangiogenesis in CSU may result in novel therapeutic strategies for the management of patients with angio‐oedema. [ABSTRACT FROM AUTHOR]

FOXO transcription factors are key regulators of DNA damage repair, proliferation and apoptosis in thyrocytes. Thyroid malignancies show impaired FOXO function. In this study, we investigated the transcriptional regulation of FOXO isoforms in thyroid epithelial cells. mRNA expression of FOXO isoforms (FOXO1, 3 and 4) was determined in FRTL-5 cells stimulated with different growth factors and H2O2. Furthermore, the impact of PI3K/AKT signalling on FOXO transcription was investigated in PI3K p110α mutant FRTL-5 cells and regulatory dependence of FOXO transcription on FOXO was studied in FRTL-5 cells with hFOXO3 overexpression. Finally, mRNA expression levels of FOXO isoforms were determined in human epithelial thyroid tumours. Growth factor deprivation induced transcription of FOXO1, 3 and 4, whereas insulin stimulation decreased FOXO1 and FOXO4 transcription in FRTL-5 cells. Inhibition of the PI3K/AKT cascade amplified FOXO1 and FOXO4 expression. In contrast, 2O2 and TSH did not influence FOXO transcription in thyrocytes. Overexpression of PI3K p110α inhibited FOXO3 and induced FOXO4 transcription. In human thyroid tumours, FOXO1 and FOXO3 mRNA levels were significantly downregulated in papillary thyroid carcinoma when compared to normal tissues. In contrast, follicular thyroid carcinomas showed significant upregulation of FOXO4 mRNA. In this paper, we demonstrate an influence of PI3K signalling on FOXO transcription in thyrocytes. Moreover, we show that thyroid cancers exhibit alterations in FOXO transcription besides the previously reported alterations in posttranslational FOXO3 regulation. These findings may add to the concept of targeting the PI3K pathway in advanced thyroid cancers. [ABSTRACT FROM AUTHOR]

An abstract of the article "Electrophysiological effects after intramyocardial injection of mesenchymal vs. mononuclear bone marrow derived stem cells in the chronic ischaemic myocardium," by K. Krause and colleagues is presented.

The purpose of this study was to test the hypothesis that an intact cerebellar fastigial nucleus (CFN) is necessary for the hyperpnea of submaximal exercise. Bilateral stainless steel microtubules were implanted in the cerebellum inside (n = 12) or outside (n = 2) the CFN for injection (0.5 to 10 µl) of the neurotoxin ibotenic acid. All goats had difficulty maintaining normal posture and walking for up to one month after the implantation of the microtubules and again for hours or days after injecting the neurotoxin. As is typical for goats, prior to implantation of the microtubules the decrease in PaCO2 from rest during mild and moderate treadmill exercise was 2.0 ± 0.39 and 3.5 ± 0.45 mmHg, respectively. Implantation of the microtubules did not significantly change this exercise hyperventilation. However, neurotoxic lesioning with 10 µl ibotenic acid lesions significantly (P < 0.05) attenuated the decrease in PaCO2 by 1.3 and 2.8 mmHg at the first and second workload, respectively. The modest attenuation of the exercise hypocapnia at both workloads in CFN lesioned goats suggests that the CFN is part of the ventilatory control system that helps meet the gas exchange requirements of submaximal exercise. [ABSTRACT FROM AUTHOR]

Dialyzing mock cerebral spinal fluid (mCSF) equilibrated with 25% CO2 in the retrotrapezoid nucleus and the nucleus of the solitary tract of the awake rat increased inspiratory flow (VI) and tidal volume (VT) by 24 and 11%. In the awake goat, we found that dialyzing 25 and 80% CO2 at one site in the raphe increased VI and VT 8-10%, while dialyzing 50% in the rostral part of the cerebellar fastigial nucleus increased VI and VT 14-16%. The pre-Botzinger complex (PBC), a hypothesized respiratory rhythm generator, increased phrenic nerve activity after an acetazolamide-induced acidosis in the anesthetized cat. Thus, we tested the hypothesis that focal microdialysis (MD) of CO2/H+ in the PBC during wakfulness would stimulate breathing. Stainless steel microtubules were bilaterally implanted into the PBC of adult goats. Unilateral MD of mCSF equilibrated with 6.4% CO2 did not affect VI, VT or f. Unilateral MD of 25 or 50% CO2 did not affect VI or VT, but did significantly increase f by a maximum of 10% (P<0.05, n=12). Bilateral MD of 6.4 and 25% CO2 did not significantly affect VI, VT, or f. However, bilateral MD of 50% significantly increased f by a maximum of 8% (n<0.05, n=5), although VI and VT was unaffected. The findings that FA in the PBC of the awake goat affects only respiratory frequency lends support to the PBC's role in respiratory rhythm generation. Thus, our data suggests that the PBC may not only be instrinsically rhythmogenic, but chemosensitive as well. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 71-year old woman with systemic mastocytosis with history of smoking. It is noted that she was further diagnosed with tripe palms that are characterized clinically by thickened velvety palms with pronounced dermatoglyphics. The article mentions that Anaplastic lymphoma kinase (ALK) fusion oncogenes represent a novel molecular target in a small subset of non-small cell lung cancers (NSCLC).

A letter to the editor on benefit of doxycycline therapy in patients with chronic cold urticaria is presented.

Background Mastocytosis is frequently associated with mast cell-mediated symptoms which require relieving medication. While second generation antihistamines (sg AHs) are the first line therapeutic strategy to treat mast cell mediator-related symptoms, controlled clinical trials on how they improve quality of life have not been performed. Methods This randomized, double-blind, placebo-controlled, cross-over trial assessed rupatadine 20 mg daily in the treatment of mastocytosis symptoms in 30 adult patients. Symptoms were assessed by a visual analogue scale ( VAS) and symptom specific quality of life questionnaire ( Itchy Qo L). Results The mean Itchy Qo L total score and VAS symptom score were significantly improved in the rupatadine treatment phase compared with placebo. There were also significant reductions from placebo in the severity of itch, wheal and flare, flushing, tachycardia and headache but not gastrointestinal symptoms. Conclusions In this first comprehensive trial of a sg AH in mastocytosis, rupatadine 20 mg daily for 4 weeks significantly controlled symptoms and improved patients' quality of life. [ABSTRACT FROM AUTHOR]

Background Urticaria is a frequent reason for consultations. Recently, it has been demonstrated that the management of chronic spontaneous urticaria (csU) in the practice setting does not fully comply with published guidelines. In addition, it was shown that one of four csU patients is referred to specialized centres. Objective To analyse the management of urticaria patients in tertiary referral centres. Methods During a standardized expert-to-expert interview, 41 specialists from German tertiary care centres were asked for different aspects of urticaria patient care with a special focus on csU. Results On average, the participating centres saw 25 csU patients per month. All ran programmes for the identification of underlying causes with an average success rate of 45 ± 3% which is considerably higher as has been found in the practice setting. In those patients where an identification succeeds, infections, drugs, intolerance and autoreactivity were reported to be causes in 41%, 20%, 17% and 16%. In their symptomatic treatment the majority of centres (71%) followed the guidelines by using regular dosed non-sedating H1-antihistamines as first line and higher doses (61%) as second line option. In contrast to the practice setting, meaningful experience also existed for alternative therapies in antihistamine-resistant patients, such as dapsone, cyclosporin and omalizumab. The expenditure of time, laboratory costs and frequency of follow-up visits was reported to be above average in case of csU. Conclusion This study indicates that some urticaria patients, especially those with unknown causes or with an H1-antihistamine-resistant disease, may benefit from a referral to tertiary care centres. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective study aims to evaluate the feasibility, safety and complication rate of laparoscopic inguinal hernia repair for small babies weighing 3 kg or less.Methods: A retrospective analysis was performed on the surgical charts of 67 infants (47 boys and 20 girls) weighing 3 kg or less who underwent laparoscopic hernia repair in a 3-year period. A regular 5-mm scope was used for visualization, and 2 or 3-mm instruments were used for the closure of the inner inguinal ring using 3/0 non-absorbable suture. The median weight at surgery was 2,600 g (range 1,450-3,000 g). All except three were premature.Results: Of the 67 infants, 15 (22.3 %) presented with an irreducible hernia. In three cases of irreducible hernias, we also performed a transumbilical appendectomy at the end of the hernia repair. Minor problems related with anesthesia were noted in four cases. Hernia recurrence was observed in three patients (4.4 %). No cases of testicular atrophy occurred. In 10 boys, we observed 12 cases of high testes, only 4 testes requiring subsequent orchiopexy.Conclusions: Laparoscopic inguinal hernia repair for babies weighing 3 kg or less is feasible, safe and perhaps even less technically demanding than open inguinal herniotomy. [ABSTRACT FROM AUTHOR]

Abstract: Abrupt, bilateral destruction of the pre-Bötzinger Complex (preBötC) leads to terminal apnea in unanesthetized goats and rats. In contrast, respiratory rhythm and pattern and arterial blood gases in goats during wakefulness and sleep are normal after incremental (over a month) destruction of >90% of the preBötC. Here, we tested the hypothesis that the difference in effects between abrupt and incremental destruction of the preBötC are a result of time-dependent plasticity, which manifests as anatomic changes at sites within the respiratory network. Accordingly, we report data from histological analyses comparing the brainstems of control goats, and goats that had undergone bilateral, incremental, ibotenic acid (IA)-induced preBötC lesioning. A major focus was on the parafacial respiratory group/retrotrapezoid nucleus (pFRG/RTN) and the pontine respiratory group (PRG), which are sites thought to contribute to respiratory rhythmogenesis. We also studied the facial (FN), rostral nucleus ambiguus (NA), medullary raphé (MRN), hypoglossal (HN), and the dorsal motor vagal (DMV) nuclei. Neuronal counts, count region area (mm2), and neuronal densities were calculated using computer-assisted analyses and/or manual microscopy to compare control and preBötC-lesioned animals. We found that within the ventral and lateral medulla 2mm rostral to the caudal pole of the FN (presumed pFRG/RTN), there were 25% and 65% more (P <0.001) neurons, respectively, in preBötC-lesioned compared to control goats. Lesioned goats also showed 14% and 13% more (P <0.001) neurons in the HN and medial parabrachialis nucleus, but 46%, 28%, 7%, and 17% fewer (P <0.001) neurons in the FN, NA, DMV, and Kölliker-Fuse nuclei, respectively. In the remaining sites analyzed, there were no differences between groups. We conclude that anatomic changes at multiple sites within the respiratory network may contribute to the time-dependent plasticity in breathing following incremental and near-complete destruction of the preBötC. [Copyright &y& Elsevier]

Introduction: We report the clinical, operative, and outcome results in 58 premature infants (with maximum weight of 5 000 g at time of surgery) undergoing laparoscopic herniorrhaphy. Patients and Methods: This study was designed as a prospective, non-randomized single center feasibility study. The inclusion criteria were: symptomatic inguinal hernia, gestational age up to 37 weeks and maximum weight of 5 000 g at the time of surgery. Out of 58 premature infants (42 boys and 16 girls), 24 had bilateral, 20 had right-sided and 14 had left-sided hernias. 14 (24.1%) infants were operated on for an irreducible hernia. Results: The median gestational age at birth was 33 weeks (range 23–37) and the median gestational age at operation was 41 weeks (range 33–52). The body weight at surgery ranged from 1 450 g to 5 000 g (median 3 900 g); 11 infants (19%) weighed less than 2 500 g. No intraoperative surgical complications occurred. Anesthesia complications were noted in 7 cases. At median follow-up of 25 months (range 6–51 months), there were 3 hernia recurrences in 2 infants (3.6%). In 5 boys, we observed high testes requiring subsequent orchiopexy. Regression analysis showed that the risk of undescended testes increased by 65.5% for every 1 kilo lower weight at surgery. Conclusion: Based on our early results, it seems that laparoscopic hernia repair in preterm infants and very low birth weight babies is a safe and feasible procedure and has some procedural benefits compared to the standard open technique. [ABSTRACT FROM AUTHOR]

Background Cold- and heat-induced urticaria are chronic physical urticaria conditions in which wheals, angioedema or both are evoked by skin exposure to cold and heat respectively. The diagnostic work up of both conditions should include skin provocation tests and accurate determination of critical temperature thresholds ( CTT) for producing symptoms in order to be able to predict the potential risk that each individual patient faces and how this may be ameliorated by therapy. Objective To develop and validate Temp Test ® 4, a simple and relatively inexpensive instrument for the accurate determination of CTT which may be used in clinical practice. Methods Temp Test ® 4 has a single 2 mm wide 350 mm U-shaped Peltier element generating a temperature gradient from 4 °C to 44 °C along its length. Using a clear plastic guide placed over the skin after provocation, CTT values may be determined with an accuracy of ±1 °C. Here, Temp Test ® 4 was compared with its much more expensive predecessor, Temp Test ® 3, in inducing wheals in 30 cold urticaria patients. Results Both Temp Test ® 4 and Temp Test ® 3 induced wheals in all 30 patients between 8 ° and 28 °C. There was a highly significant ( P < 0.0001) correlation between the instruments in the CTT values in individual patients. Conclusion The Temp Test ® 4 is a simple, easy to use, licensed, commercially available and affordable instrument for the determination of CTTs in both cold- and heat-induced urticaria. [ABSTRACT FROM AUTHOR]

Generates a model structure identification for wastewater treatment simulation based on computational fluid dynamics (CFD) using completely stirred tank reactor (CSTR) activated sludge compartments. Application of the method to the WWTP Wuppertal-Buchenhofen; Summary of the ideas of the algorithm starting with the results of the CFD stimulation.