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Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.06.531158v1?rss=1 Authors: Wendt, K., Memarian Sorkhabi, M., Stagg, C. J., Fleming, M. K., Denison, T., O'Shea, J. Abstract: Background: Intermittent theta-burst stimulation (iTBS) is a transcranial magnetic stimulation (TMS) protocol which can temporarily modulate the corticospinal excitability. Conventionally, TBS is only applied using biphasic pulses due to hardware limitations. However, monophasic pulses are hypothesised to more selectively recruit cortical neurons than biphasic pulses which may improve the effect of iTBS. A custom-made pulse-width modulation-based TMS device with improved energy recovery and pulse-shaping capabilities allows the generation of monophasic iTBS. Objective: To compare the effects of monophasic and biphasic iTBS on motor corticospinal excitability in healthy volunteers. Methods: Thirty volunteers participated in three separate sessions, where monophasic and biphasic iTBS were applied to the primary motor cortex (active condition) or the vertex (control condition) using a custom-made TMS device. Changes in corticospinal excitability were quantified using the peak-to-peak amplitude of motor evoked potentials (MEP) with single-pulse TMS collected at baseline and at 5 - 60 minutes after the application of TBS. Results: Both monophasic and biphasic active iTBS led to significant increases in MEP amplitude compared to baseline, with monophasic iTBS showing significantly larger effects (linear mixed effect model analysis: ({chi}2(1) = 8.48, p = 0.004)), even after subtracting the control condition from the active conditions ({chi}2(1) = 6.21, p = 0.013). Conclusions: This study demonstrates that the pulse shape affects the extent to which TBS can modulate corticospinal excitability. Monophasic intermittent TBS has the potential to increase the efficacy of clinical treatment protocols in the future. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Grapes could protect against sun damage, say dermatologists University of Alabama, February 3, 2021 Grapes may help protect against damage to the skin caused by the sun's ultraviolet radiation in healthy adults, according to a new study by researchers in the University of Alabama at Birmingham's Department of Dermatology. In research published in the Journal of the American Academy of Dermatology, a 74.8 percent increase in natural protection of the skin was shown when 19 healthy human subjects orally ingested a powder of freeze-dried grapes for 14 days. The study found that a group of natural compounds—polyphenols, found in grapes as well as other fruits and vegetables—can reduce acute UV radiation damage in healthy adults, which was previously demonstrated in mouse models. Additionally, it can decrease proteins in the body that promote inflammation. This is the first study showing that oral ingestion of table grapes has a photoprotective effect on the sunburn response in humans. "Study results indicate that oral consumption of grapes has systemic beneficial effects in healthy adults," said Allen Oak, M.D., a dermatologist in the UAB School of Medicine and a lead author of the study. "These benefits include inhibition of inflammation and repair of DNA damage."  In addition to consumption of the powder, the study also showed that the application of a topical extract made from a grape seed polyphenol, proanthocyanidin, can reduce sunburn cell formation. Furthermore, preliminary results suggest that grapes may help to prevent skin cancers as well, although more studies need to be conducted in this area before drawing conclusions. "Grape consumption may act as an 'edible sunscreen,'" Oak said. "This does not mean that grapes should be used in lieu of sunscreen, but they may offer additional protection which we are eager to continue learning more about. This research is exciting because our current findings provide building blocks for additional studies that may eventuate in an oral photoprotective product from a natural source."   Meta-analysis links higher magnesium levels with lower risk of premature mortality from all causes among kidney disease patients Vrije University (Netherlands), January 26, 2021 A systematic review and meta-analysis published on December 26, 2020 in Clinical Nutrition found an association between higher plasma or serum magnesium levels and a lower risk of cardiovascular mortality and events and all-cause mortality during follow-up among men and women with chronic kidney disease. Researchers at Vrije University in Amsterdam selected 33 studies that included 348,059 patients for the analysis. Subjects’ plasma or serum magnesium concentrations were obtained at the beginning of the studies and all-cause mortality, cardiovascular mortality and cardiovascular events, and/or other outcomes were documented during follow-up periods that varied from an average of 11.7 months to 278 months. Each 0.1 millimole per liter increase in magnesium was associated with a 15% lower risk of experiencing a cardiovascular event or dying from cardiovascular disease, and a 10% lower risk of dying from any cause during follow-up. “This review and meta-analysis demonstrate that plasma magnesium concentration is inversely associated with all-cause mortality and cardiovascular mortality and events in patients with CKD including those on dialysis,” Nicoline J. J. Leenders and colleagues wrote. “The inverse association between magnesium and all-cause mortality not only exists for normal compared to low magnesium, but also for magnesium above the reference range compared to normal magnesium.” The authors suggest the initiation of clinical trials to determine if plasma magnesium concentrations can be safely increased and to confirm the mineral’s effect on cardiovascular events and mortality and all-cause mortality. “In these trials, the intervention should ideally consist of an increase of dialysate magnesium in patients on dialysis, and dietary intervention or oral magnesium…in patients with CKD not on dialysis,” they recommended.     Bleeding gums may be a sign you need more vitamin C in your diet University of Washington, February 1, 2021 Current advice from the America Dental Association tells you that if your gums bleed, make sure you are brushing and flossing twice a day because it could be a sign of gingivitis, an early stage of periodontal disease. And that might be true. So if you are concerned, see your dentist. However, a new University of Washington study suggests you should also check your intake of vitamin C.  "When you see your gums bleed, the first thing you should think about is not, I should brush more. You should try to figure out why your gums are bleeding. And vitamin C deficiency is one possible reason," said the study's lead author Philippe Hujoel, a practicing dentist and professor of oral health sciences in the UW School of Dentistry. Hujoel's study, published Feb. 1 in Nutrition Reviews, analyzed published studies of 15 clinical trials in six countries, involving 1,140 predominantly healthy participants, and data from 8,210 U.S. residents surveyed in the Centers for Disease Control and Prevention's Health and Nutrition Examination Survey. The results showed that bleeding of the gums on gentle probing, or gingival bleeding tendency, and also bleeding in the eye, or retinal hemorrhaging, were associated with low vitamin C levels in the bloodstream. And, the researchers found that increasing daily intake of vitamin C in those people with low vitamin C plasma levels helped to reverse these bleeding issues. Of potential relevance, says Hujoel, who is also an adjunct professor of epidemiology in the UW School of Public Health, both a gum bleeding tendency and retinal bleeding could be a sign of general trouble in one's microvascular system, of a microvascular bleeding tendency in the brain, heart and kidneys. The study does not imply that successful reversing of an increased gingival bleeding tendency with vitamin C will prevent strokes or other serious health outcomes, Hujoel stresses. However, the results do suggest that vitamin C recommendations designed primarily to protect against scurvy -- a deadly disease caused by extremely low vitamin C levels -- are too low, and that such a low vitamin C intake can lead to a bleeding tendency, which should not be treated with dental floss. Consequently, Hujoel does recommend people attempt to keep an eye on their vitamin C intake through incorporation of non-processed foods such as kale, peppers or kiwis into your diet, and if you can't find palatable foods rich in vitamin C to consider a supplement of about 100 to 200 milligrams a day.  If someone is on a specialized diet, such as a paleo diet, it's important that they take a look at their vitamin C intake, Hujoel said. "Vitamin C-rich fruits such as kiwis or oranges are rich in sugar and thus typically eliminated from a low-carb diet."  This avoidance may lead to a vitamin C intake that is too low and is associated with an increased bleeding tendency. People who exclusively eat lean meats and avoid offal, the vitamin-rich organ meats, may be at a particularly high risk for a low vitamin C intake. The association between gum bleeding and vitamin C levels was recognized more than 30 years ago. In fact, two studies co-authored by former dean of the UW School of Dentistry Paul Robertson (published in 1986 and 1991) identified gum bleeding as a biological marker for vitamin C levels.  However, this connection somehow got lost in dental conversations around bleeding gums. "There was a time in the past when gingival bleeding was more generally considered to be a potential marker for a lack of vitamin C. But over time, that's been drowned out or marginalized by this overattention to treating the symptom of bleeding with brushing or flossing, rather than treating the cause," Hujoel said.  Hujoel's literature review also determined that "retinal hemorrhaging and cerebral strokes are associated with increased gingival bleeding tendency, and that (vitamin C) supplementation reverses the retinal bleeding associated with low (vitamin C) plasma levels." So, missing the possible connection between gum bleeding and low levels of vitamin C has the potential to have serious health consequences. The study authors write: "A default prescription of oral hygiene and other periodontal interventions to 'treat' microvascular pathologies, even if partially effective in reversing gingival bleeding as suggested in this meta-analysis, is risky because it does not address any potential morbidity and mortality associated with the systemic microvascular-related pathologies."     Neonatal antibiotic use associated with reduced growth in boys Bar-Illan University (Israel), January 26, 2021 Exposure to antibiotics in the first days of life is thought to affect various physiological aspects of neonatal development. A new study, led by Bar-Ilan University's Azrieli Faculty of Medicine, reveals that antibiotic treatment within 14 days of birth is associated with reduced weight and height in boys - but not girls -- up to the age of six.  By contrast, the study showed significantly higher body mass index (BMI) in both boys and girls following antibiotic use after the neonatal period, and within the first six years of life.  The findings, published in the journal Nature Communications on January 26, 2021, may be the result of changes in the development of the gut microbiome. The impact of neonatal antibiotic exposure was investigated in a cohort of 12,422 children born between 2008-2010 at the Turku University Hospital in Turku, Finland. The babies had no genetic abnormalities or significant chronic disorders affecting growth and did not need long-term antibiotic treatment. Antibiotics had been administered within the first 14 days of life to 1,151 (9.3%) of the neonates in the study. The authors found that boys exposed to antibiotic treatment exhibited significantly lower weight as compared to non-exposed children throughout the first six years. They also exhibited significantly lower height and BMI between the ages of two and six. This observation was replicated in a German cohort. Further, antibiotic exposure during the first days of life was found to be associated with disturbances in the gut microbiome up until the age of two. Infants exposed to neonatal antibiotics exhibited significantly lower gut microbiome richness as compared to non-exposed infants at the age of one month. Interestingly, at the age of six months, the infants treated with antibiotics reached the bacterial richness level of a control group of infants, and at the ages of 12 and 24 months, the antibiotic-treated subjects gained significantly higher levels of bacterial richness as compared to the control subjects. In additional experiments led by PhD student Atara Uzan, the researchers demonstrated that germ-free male mice who were given the gut microbiome of antibiotic-exposed infants also displayed growth failure. These findings suggest a potential link between neonatal antibiotic exposure and impaired childhood growth, which may be a result of alterations caused by antibiotics in the composition of the gut microbiome.  "Antibiotics are vitally important and life-saving medications in newborn infants. Our results suggest that their use may also have unwanted long-term consequences which need to be considered," said Prof. Omry Koren, of the Azrieli Faculty of Medicine of Bar-Ilan University, who led the study together with Prof. Samuli Rautava, of the University of Turku and University of Helsinki.  Follow up research will aim to investigate other potential adverse outcomes related to neonatal antibiotic exposure.     Ten Days of Curcumin Supplementation Attenuates Subjective Soreness and Maintains Muscular Power Following Plyometric Exercise Ohio University, February 1, 2021   Curcumin has become a popular product used to decrease inflammation and enhance recovery from exercise. Purpose: To determine the effects of curcumin supplementation on delayed onset muscle soreness and muscle power following plyometric exercise. Methods: Participants (n = 22; five females, 17 males) consumed either curcumin (500 mg) or placebo twice daily for 10 days (6 days pre, day of and 3 days post exercise). Participants completed 5 x 20 drop jumps on day 7. Blood sampling and recovery tests were assessed at pre-supplementation, 24-hours and immediately pre-exercise, and immediately post-, 24, 48 and 72-hours post-exercise. Blood markers included serum creatine kinase (CK) and erythrocyte sedimentation rate (ESR), while soreness was measured during a squat and post vertical jump. Results: Both groups experienced muscle damage post-exercise with elevated CK (403 ± 390 ul; p 

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.11.292649v1?rss=1 Authors: Soustelle, L., Lamy, J., Le Troter, A., Hertanu, A., Guye, M., Ranjeva, J.-P., Varma, G., Alsop, D. C., Pelletier, J., Girard, O., Duhamel, G. Abstract: Purpose To propose an efficient retrospective image-based method for motion correction of multi-contrast acquisitions with a low number of available images (MC-MoCo) and evaluate its use in 3D inhomogeneous Magnetization Transfer (ihMT) experiments in the human brain. Methods A framework for motion correction, including image pre-processing enhancement and rigid registration to an iteratively improved target image, was developed. The proposed method was compared to Motion Correction with FMRIB's Linear Image Registration Tool (MCFLIRT) function in FSL over 13 subjects. Native (pre-correction) and residual (post-correction) motions were evaluated by means of markers positioned at well-defined anatomical regions over each image. Results Both motion correction strategies significantly reduced inter-image misalignment, and the MC-MoCo method yielded significantly better results than MCFLIRT. Conclusion MC-MoCo is a high-performance method for motion correction of multi-contrast volumes as in 3D ihMT imaging. Copy rights belong to original authors. Visit the link for more info

Objective: To investigate the effects of a predefined mini-trampoline therapy programme for increasing postural control, mobility and the ability to perform activities of daily living after stroke. Design: Randomized non-blinded controlled pilot study. Setting: Neurological rehabilitation hospital. Subjects: First-time stroke; age 18-80 years; independent standing ability for a minimum of 2 minutes. Intervention: Patients were randomized into two groups: the mini-trampoline group (n = 20) received 10 sessions of balance training using the mini-trampoline over three weeks. The patients of the control group (n =20) participated 10 times in a group balance training also over three weeks. Main measures: Postural control (Berg Balance Scale, BBS), mobility and gait endurance (timed up and go' test, TUG; 6-minute walk test, 6MWT) and the ability to perform activities of daily living (Barthel Index, BI). Measurements were undertaken prior to and after the intervention period. Results: Both groups were comparable before the study. The mini-trampoline group improved significantly more in the BBS (P = 0.003) compared to the control group. Mean or median differences of both groups showed improvements in the TUG 10.12 seconds/7.23 seconds, the 6MWT 135 m/75 m and the BI 20 points/13 points for the mini-trampoline and control group, respectively. These outcome measurements did not differ significantly between the two groups. Conclusion: A predefined mini-trampoline training programme resulted in significantly increased postural control in stroke patients compared to balance training in a group. Although not statistically significant, the mini-trampoline training group showed increased improvement in mobility and activities of daily living. These differences could have been statistically significant if we had investigated more patients (i.e. a total sample of 84 patients for the TUG, 98 patients for the 6MWT, and 186 patients for the BI).

Background: Conjugated linoleic acids (CLA) in general, and in particular the trans-10, cis-12 (t10, c12-CLA) isomer are potent modulators of milk fat synthesis in dairy cows. Studies in rodents, such as mice, have revealed that t10, c12-CLA is responsible for hepatic lipodystrophy and decreased adipose tissue with subsequent changes in the fatty acid distribution. The present study aimed to investigate the fatty acid distribution of lipids in several body tissues compared to their distribution in milk fat in early lactating cows in response to CLA treatment. Effects in mammary gland are further analyzed at gene expression level. Methods: Twenty-five Holstein heifers were fed a diet supplemented with (CLA groups) or without (CON groups) a rumen-protected CLA supplement that provided 6 g/d of c9, t11-and t10, c12-CLA. Five groups of randomly assigned cows were analyzed according to experimental design based on feeding and time of slaughter. Cows in the first group received no CLA supplement and were slaughtered one day postpartum (CON0). Milk samples were taken from the remaining cows in CON and CLA groups until slaughter at 42 (period 1) and 105 (period 2) days in milk (DIM). Immediately after slaughter, tissue samples from liver, retroperitoneal fat, mammary gland and M. longissimus (13th rib) were obtained and analyzed for fatty acid distribution. Relevant genes involved in lipid metabolism of the mammary gland were analyzed using a custom-made microarray platform. Results: Both supplemented CLA isomers increased significantly in milk fat. Furthermore, preformed fatty acids increased at the expense of de novo-synthesized fatty acids. Total and single trans-octadecenoic acids (e. g., t10-18:1 and t11-18:1) also significantly increased. Fatty acid distribution of the mammary gland showed similar changes to those in milk fat, due mainly to residual milk but without affecting gene expression. Liver fatty acids were not altered except for trans-octadecenoic acids, which were increased. Adipose tissue and M. longissimus were only marginally affected by CLA supplementation. Conclusions: Daily supplementation with CLA led to typical alterations usually observed in milk fat depression (reduction of de novo-synthesized fatty acids) but only marginally affected tissue lipids. Gene expression of the mammary gland was not influenced by CLA supplementation.

Background: Secondary sclerosing cholangitis is a severe disease of the biliary tract. Over the last decade, several cases of sclerosing cholangitis in critically ill patients (SC-CIP) were reported. Reports in the literature so far are characterized by a wide variety of underlying causes of critical illness, thereby hindering a risk-factor analysis. We report on a homogenous cohort of critically ill patients with influenza A (H1N1) pneumonia and severe acute respiratory distress syndrome (ARDS), of whom a subgroup developed sclerosing cholangitis, allowing for probing of risk factors associated with SC-CIP. Methods: Twenty-one patients (5 female, 16 male, 46.3 +/- 10.8 years) with severe ARDS due to H1N1 pneumonia were retrospectively divided into two groups, characterized by the presence (n = 5) and absence of SC-CIP (n = 16). A large array of clinical data, laboratory parameters, and multi-detector computed tomography-derived measures were compared. Results: Both patient groups showed severe pulmonary impairment. Severity of disease on admission day and during the first 14 days of treatment showed no difference. The patients developing SC-CIP had a higher body mass index (BMI) (37.4 +/- 6.0 kg/m(2) vs. 29.3 +/- 6.8 kg/m(2); P = 0.029) and a higher volume of intraperitoneal fat (8273 +/- 3659 cm(3) vs. 5131 +/- 2268 cm(3); P = 0.033) and spent a longer cumulative period in the prone position during the first 14 days (165 +/- 117 h vs. 78 +/- 61 h; P = 0.038). Conclusion: Our results suggest that obesity, intraperitoneal fat volume, and a longer cumulative duration spent in the prone position may put patients with ARDS at risk of developing SC-CIP. These results lead us to propose that the prone position should be carefully deployed, particularly in abdominally obese patients, and that frequent checks be made for early hepatic dysfunction.

Objective: Transcranial repetitive magnetic stimulation (rMS) is widely used to modulate cortical function. Its potential peripheral use has not been as widely investigated. This study aimed to compare the effectiveness of two different conditioning peripheral rMS protocols in inducing excitability changes in the primary motor cortex in a group of healthy subjects. Methods: Transcranial magnetic stimulation (TMS) of the contralateral primary motor cortex was used to measure motor evoked potentials (MEP), motor recruitment curves (RC), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and the cortical silent period (CSP). These parameters were measured before (pre), immediately after (post) and 30 minutes after (post2) repetitive peripheral magnetic stimulation (rPMS) of the ulnar nerve in the area of the ulnar sulcus. Two different rPMS protocols were compared with control interventions (ipsilateral cortical stimulation). Protocol one was a high-frequency rPMS protocol (HFP: 35 series of stimulation each lasting 1.5 seconds with a frequency of 20 Hz). Protocol two was a low-frequency rPMS protocol (LFP: 15 series each lasting 10 seconds with a frequency of 3 Hz). The control interventions consisted of the same stimulation parameters as the rPMS protocols, but TMS was performed on the ipsilateral (right) primary motor cortex. The evoked MEP were recorded with surface electrodes above the right musculus abductor digiti 5. Results: Both test paradigms caused a significantly longer CSP (LFP: p = 0.015; HFP: p = 0.012) in the post2 measurement. rPMS in the HFP additionally increased CSP duration immediately after the intervention (p = 0.018). Increased MEP amplitudes (p = 0.05) and ICF amplitudes (p = 0.036) and a decrease in SICI (p = 0.008; p = 0.012) were observed only after rPMS in the LFP. The control interventions revealed no consistent significant changes after rPMS. Significance/Discussion: The nearly pain-free rPMS is capable of influencing motor cortical excitability most probably by afferent sensory input. It seems that the duration of the stimulation series is at least as important as the number of stimuli and the stimulation frequency. RPMS with a lower frequency but a longer stimulation series could therefore be a potential alternative to high frequency stimulation in rehabilitative strategies for brain injuries.

Background: Deqi is defined in relation to acupuncture needling as a sensory perception of varying character. In a recently published sham laser validation study, we found that subjects in the verum and the sham laser group experienced deqi sensations. Therefore, we aim to further analyze whether the perceptions reported in the two study arms were distinguishable and whether expectancy effects exhibited considerable impact on our results. Methods: A detailed re-analysis focusing on deqi sensations was performed from data collected in a previously published placebo-controlled, double-blind, clinical cross-over trial for a sham laser evaluation. Thirty-four healthy volunteers (28 +/- 10.7 years; 16 women, 18 men) received two laser acupuncture treatments at three acupuncture points LI4 (hegu), LU7 (lieque), and LR3 (taichong); once by verum laser and once using a sham device containing an inactive laser in randomized order. Outcome measures were frequency, intensity (evaluated by visual analogue scale; VAS), and quality of the subjects' sensations perceived during treatments (assessed with the "acupuncture sensation scale"). Results: Both, verum and the sham laser acupuncture result in similar deqi sensations with regard to frequency (p-value = 0.67), intensity (p-value = 0.71) and quality (p-values between 0.15 - 0.98). In both groups the most frequently used adjectives to describe these perceptions were "spreading"

Background: Our purpose was to compare the effect of triamcinolone and bevacizumab (Avastin) on the retinal thickness and functional outcome in patients with diabetic macular edema. Methods and Materials: A collective of 32 patients, who had been treated by a single 4.0-mg intravitreal triamcinolone injection (group 1), was matched to 32 patients ('matched pairs'), who had received 3 injections of 1.25 mg of bevacizumab within 3 months in 4-week intervals (group 2). The outcome variables were changes in best corrected visual acuity (VA) and central retinal thickness 3 months after therapy. Results: Both groups did not differ regarding preoperative VA and central retinal thickness measured by optical coherence tomography. The baseline mean VA was 0.72 +/- 0.39 logMAR in group 1 and 0.73 +/- 0.39 logMAR in group 2 (p = 0.709). The mean central retinal thickness measured by optical coherence tomography was 548 +/- 185 mu m in group 1 and 507 +/- 192 mu m in group 2. While the patients in group 1 experienced a slight increase in VA of on average 0.7 lines following a single triamcinolone injection to a mean of 0.64 +/- 0.40 logMAR (p = 0.066) after 3 months, the patients in group 2 showed almost no effect on VA with an average increase of 0.2 lines to a mean VA of 0.72 +/- 0.30 logMAR (p = 0.948) following 3 intravitreal injections of bevacizumab. Comparing the effect on VA between both groups no statistically significant difference (p = 0.115) was noted. Concerning decrease in central retinal thickness both therapies were highly effective (p < 0.001 each), again, without statistically significant difference between the groups (p < 0.128). Conclusion: Our data suggest that a single triamcinolone injection may be as effective as a 3 times repeated intravitreal administration of bevacizumab for the treatment of diabetic macular edema. Further prospective trials should be performed. Copyright (C) 2010 S. Karger AG, Basel

Introduction: A lack of studies on the effects of continuous blood pressure biofeedback led to the development of a screening and feedback software allowing for a `beat-to-beat' representation of arterial blood pressure. Through this method patients find that they can exert some control of their blood pressure. Patients and Methods: For evaluation purposes a pilot study was conducted with 84 hypertensive patients at the Klinik Hohenried, Germany. Two experimental groups which received the normal treatment program of the hospital and an additional 2 (20 patients) or 3-6 (22 patients) biofeedback sessions, respectively, were compared with one control group treated additionally with pseudo biofeedback (20 patients) and another control group (22 patients) which underwent the clinic program without biofeedback. Results: Both experimental groups yielded significantly more markedly blood pressure reductions (MAP) than the controls (p = 0.001), but patients who received 3-6 feedback sessions did not perform significantly better than patients who received only 2 sessions (p = 0.517). Conclusions: 2 sessions of feedback treatment can already have clinically relevant effects. This suggests a major influence of cognitive processes such as self-effectiveness and self-control.

Background: With the current improvements in primary lung care, the long-term control of brain metastases becomes a clinical challenge. No established therapeutic approaches exist for cranial relapse after response to previous radiotherapy and systemic therapy. Tyrosine kinase inhibitors like erlotinib with its proven activity in non-small cell lung cancer may provide clinical benefits in such patients. Patients and Methods: Two case reports are presented illustrating the efficacy of erlotinib in patients with recurrent brain metastases and parallel thoracic progression. Results: Both patients showed lasting partial remissions in the brain and lung, and clinical symptom improvement. Conclusion: The observed survival times of above 18 and 15 months, respectively, since occurrence of cranial disease manifestation in line with the achieved progression-free survival times of 9 and 6 months by the erlotinib third-line therapy are remarkable. The use of targeted therapies after whole-brain irradiation should be investigated more systematically in prospective clinical trials.

Background: Folic acid plays a fundamental role in cell division and differentiation. Docosahexaenoic acid (DHA) has been associated with infantile neurological and cognitive development. Thus, optimal intrauterine development and growth requires adequate supply of these nutrients during pregnancy. Methods: Healthy pregnant women, aged 18-41 years, were recruited in Granada (Spain; n = 62), Munich (Germany; n = 97) and Pecs (Hungary; n = 152). We estimated dietary DHA and folate intake in weeks 20 (w20) and 30 of gestation (w30) using a food frequency questionnaire with specific focus on the dietary sources of folate and DHA. Results: Both w20 and w30 Spanish participants had significantly higher daily DHA intakes (155 +/- 13 and 161 +/- 9 mg/1,000 kcal) than the German (119 +/- 9 and 124 +/- 12 mg/1,000 kcal; p = 0.002) and Hungarian participants (122 +/- 8 and 125 +/- 10 mg/1,000 kcal; p = 0.005). Hungarian women had higher folate intakes in w20 and w30 (149 +/- 5 and 147 +/- 6 mu g/1,000 kcal) than Spanish (112 +/- 2 and 110 +/- 2 mu g/1,000 kcal; p < 0.001) and German participants (126 +/- 4 and 120 +/- 6 mu g/1,000 kcal; p < 0.001), respectively. Conclusion: Dietary DHA and folate intake of pregnant women differs significantly across the three European cohorts. Only 7% of the participants reached the recommended folate intake during pregnancy, whereas nearly 90% reached the DHA recommended intake of 200 mg per day. Copyright (C) 2008 S. Karger AG, Basel

Background: Children with congenital hearing impairment benefit from early detection and management of their hearing loss. These and related considerations led to the recommendation of universal newborn hearing screening. In 2001 the first phase of a national Newborn Hearing Screening Programme (NHSP) was implemented in England. Objective of this study was to assess costs and effectiveness for hospital and community-based newborn hearing screening systems in England based on data from this first phase with regard to the effects of alterations to parameter values. Methods: Design: Clinical effectiveness analysis using a Markov Model. Outcome measure: quality weighted detected child months (QCM). Results: Both hospital and community programmes yielded 794 QCM at the age of 6 months with total costs of 3,690,000 pound per 100,000 screened children in hospital and 3,340,000 pound in community. Simulated costs would be lower in hospital in 48% of the trials. Any statistically significant difference between hospital and community in prevalence, test sensitivity, test specificity and costs would result in significant differences in cost-effectiveness between hospital and community. Conclusion: This modelling exercise informs decision makers by a quantitative projection of available data and the explicit and transparent statements about assumptions and the degree of uncertainty. Further evaluation of the cost-effectiveness should focus on the potential differences in test parameters and prevalence in these two settings.

The squamous stratified epithelia contain a proliferative (harboring mitotic activity) and a differentiating compartment. Due to the potential of protein-carbohyd rate interactions to regulate cellular activities we introduced a mammalian lectin to cyto- and histochemical analysis. We answer the questions of whether and to what extent this new probe can pinpoint differentiation-dependent glycosylation changes in sections and in culture of keratinocytes. Material and Methods: Purification and labeling enabled monitoring of galectin-3 reactivity in frozen sections of human and pig epidermis and basal cell carcinomas as well as in culture of keratinocytes. The staining pattern of the lectin was correlated with the staining profile of other cell markers including desmosomal proteins, beta(1) integrin, and the proliferation marker Ki-67. The Dolichos biflorus agglutinin (DBA) sharing binding reactivity of galectin-3 to the A type histoblood group epitope was used for comparison. Results: Both lectins exhibit suprabasal binding. However, their profiles were not identical, substantiated by lack of coinhibition. Strong DBA reactivity was also observed in a limited number of basal layer cells, namely in cells without the expression of the proliferation marker Ki-67. Cultured mitotic epidermal cells have no reactivity for DBA. Presence of ligands for this plant lectin was connected with decreased positivity of nuclei for Ki-67 and the occurrence of ring-shaped nucleoli, micronucleoli or absence of nucleoli. Considering colocalization the pattern of galectin-3-binding sites coincided with the presence of desmosomal proteins such as desmoplakin-1 and desmoglein but not beta(1) integrin, a potential ligand. Interestingly, studied basal cell carcinomas expressed no binding sites for galectin-3, while a limited number of cells were DBA-reactive. Conclusion: The expression of galectin-3-binding sites and also DBA-reactive glycoligands correlates with an increased level of differentiation and/or cessation of proliferation in the examined squamous stratified epithelia. Further application of tissue lectins for characterizing ligand expression and its modulation is an important step to reveal functional relevance.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.11.021915v1?rss=1 Authors: Zhu, F., Wang, W., Ma, Q., Yang, Z., Ju, Y., Fan, Y., Guo, R., Wang, Q., Mu, X., Zhao, B., Gao, Y., He, X., Gao, F., Qian, L., Chen, C., Chen, Y., Gao, C., Ma, X.-c. Abstract: Objective: Gut microbiota dysbiosis and aberrant gut-brain functional modules including short-chain fatty acid (SCFA) production and long-lasting immune activation (IA) are presented in schizophrenia. Given the key roles of gut microbiota and SCFA in shaping immunity, we propose that dysbiosis-induced SCFA upregulation could contribute to IA and behavioral symptoms in schizophrenia. Design: Gut microbiota, SCFA, and IA biomarkers were compared between schizophrenic patients and healthy controls. The roles of SCFA in schizophrenia-related IA were analyzed in cultured peripheral blood mononuclear cells (PBMCs) and a mouse model of schizophrenia. The effects of SCFAs on schizophrenia-related phenotypes were analyzed in both human and mouse. Results: Both microbial-derived SCFA and SCFA-producing bacteria were elevated in the guts of schizophrenic patients, and this increased SCFA production in gut was associated with IA in schizophrenia. The microbiome signature underpinning schizophrenia-related IA includes increased diversity and increased SCFA-producing bacteria and inflammation-associated bacteria. The impact of SCFAs on immune responses of cultured PBMC depend on the diagnosis and IA status of donors. Small-molecule serum filtrates from immune-activated schizophrenic patients increased the inflammatory response of PBMCs from healthy volunteers, which can be enhanced and attenuated by SCFAs supplementation and inhibition of SCFA signaling, respectively. Chronically elevated SCFAs in adolescence induced neuroinflammation and schizophrenia-like behaviors in adult mice. Moreover, chronically elevated SCFAs in adult mice prenatally exposed to IA potentiated their expression of schizophrenia-like behaviors. Conclusion: microbiota-derived SCFAs are important mediators of dysregulated gut-brain axis and participant in pathogenesis via enhance IA in schizophrenia. Copy rights belong to original authors. Visit the link for more info