Effects of antimicrobial photodynamic therapy with photodithazine® on methicillin-resistant Staphylococcus aureus (MRSA): Studies in biofilms and experimental model with Galleria mellonella.

Staphylococcus aureus infections are a severe health problem due to the high mortality rate. Conventional treatment of these infections is via the administration of antibiotics. However, its indiscriminate use can select resistant microorganisms. Thus, it is necessary to develop alternatives for antibiotic therapy. Antimicrobial Photodynamic Therapy (aPDT), a therapeutic method that associates a photosensitizer (PS), a light source with adequate wavelength to the PS, interacts with molecular oxygen generating reactive oxygen species responsible for cell inactivation, is a viable alternative. This work aimed to analyze, in vitro and in vivo, the action of aPDT with PS Photodithazine® (PDZ) on the methicillin-resistant S. aureus (MRSA) strain. In the in vitro method, the S. aureus biofilm was incubated with PDZ at 50 and 75 µg.mL-1 for 15 min, adopting the light dose of 25, 50, and 100 J/cm2. In addition, PS interaction, formation of reactive oxygen species (ROS), bacterial metabolism, adhesion, bacterial viability, and biofilm structure were evaluated by scanning electron microscopy. Subsequently, the strain was inoculated into models of Galleria mellonella, and the survival curve, health scale, blood cell analysis, and CFU/mL of S. aureus in the hemolymph were analyzed after aPDT. In the in vitro results, bacterial reduction was observed in the different PDZ concentrations, highlighting the parameters of 75 µg.mL-1 of PDZ and 100 J/cm2. As for in vivo results, aPDT increased survival and stimulated the immune system of G. mellonella infected by S. aureus. aPDT proved effective in both models, demonstrating its potential as an alternative therapy in treating MRSA bacterial infections.

Heat and shear stability of particle stabilised foams for application in gluten-free bread.

Bread forms an integral part of the daily diet in many cultures worldwide. At the same time, a significant number of people try to avoid wheat-based products for either health reasons or due to personal preferences. The absence of a protein network in gluten free bread affects its structure, taste, texture and shelf-life. This paper suggests a technological solution to this issue that uses a pre-foamed mass of gluten free raw materials which is mixed with the bread's ingredients, then kneaded and baked to form a high quality gluten free bread. To survive the high shear stresses during kneading and temperature increase during baking, the foam requires exceptional stability. This stability was achieved through particle stabilisation of the bubble interfaces. Both of the tested foams (with and without particles) exhibited thermal stability up to 80 °C. However, resistance to shear stresses was higher in the particle stabilised foams. Of all the tested particles, linseed press cake and banana powder led to the best results. In conclusion, particle stabilised foams seem very well suited to applications in gluten free baked goods. Further application potential is seen for vegan foamed desserts.

Fitness to fly for children and adolescents after Fontan palliation.

Introduction: At cruising altitude, the cabin pressure of passenger aircraft needs to be adjusted and, therefore, the oxygen content is equivalent to ambient air at 2,500 masl, causing mild desaturation and a rising pulmonary vascular resistance (PVR) in healthy subjects. For Fontan patients with passive pulmonary perfusion, a rising PVR can cause serious medical problems. The purpose of this fitness to fly investigation (FTF) is to assess the risk of air travel for children and adolescents after Fontan palliation. Methods: We investigated 21 Fontan patients [3-14y] in a normobaric hypoxic chamber at a simulated altitude of 2,500 m for 3 h. Oxygen saturation, heart rate, and regional tissue saturation in the forehead (NIRS) were measured continuously. Before entering the chamber, after 90 and 180 min in the hypoxic environment, blood gas analysis and echocardiography were performed. Results: Heart rate and blood pressure did not show significant intraindividual changes. Capillary oxygen saturation (SaO2) decreased significantly after 90 min by a mean of 5.6 ± 2.87% without further decline. Lactate, pH, base excess, and tissue saturation in the frontal brain did not reach any critical values. In the case of open fenestration between the tunnel and the atrium delta, P did not increase, indicating stable pulmonary artery pressure. Conclusion: All 21 children finished the investigation successfully without any adverse events, so flying short distance seems to be safe for most Fontan patients with good current health status. As the baseline oxygen saturation does not allow prediction of the maximum extent of desaturation and adaption to a hypoxic environment takes up to 180 min, the so-called hypoxic challenge test is not sufficient for these patients. Performing an FTF examination over a period of 180 min allows for risk assessment and provides safety to the patients and their families, as well as the airline companies.

The InSight HP3 Penetrator (Mole) on Mars: Soil Properties Derived from the Penetration Attempts and Related Activities.

The NASA InSight Lander on Mars includes the Heat Flow and Physical Properties Package HP3 to measure the surface heat flow of the planet. The package uses temperature sensors that would have been brought to the target depth of 3-5 m by a small penetrator, nicknamed the mole. The mole requiring friction on its hull to balance remaining recoil from its hammer mechanism did not penetrate to the targeted depth. Instead, by precessing about a point midway along its hull, it carved a 7 cm deep and 5-6 cm wide pit and reached a depth of initially 31 cm. The root cause of the failure - as was determined through an extensive, almost two years long campaign - was a lack of friction in an unexpectedly thick cohesive duricrust. During the campaign - described in detail in this paper - the mole penetrated further aided by friction applied using the scoop at the end of the robotic Instrument Deployment Arm and by direct support by the latter. The mole tip finally reached a depth of about 37 cm, bringing the mole back-end 1-2 cm below the surface. It reversed its downward motion twice during attempts to provide friction through pressure on the regolith instead of directly with the scoop to the mole hull. The penetration record of the mole was used to infer mechanical soil parameters such as the penetration resistance of the duricrust of 0.3-0.7 MPa and a penetration resistance of a deeper layer ( > 30 cm depth) of 4.9 ± 0.4 MPa . Using the mole's thermal sensors, thermal conductivity and diffusivity were measured. Applying cone penetration theory, the resistance of the duricrust was used to estimate a cohesion of the latter of 2-15 kPa depending on the internal friction angle of the duricrust. Pushing the scoop with its blade into the surface and chopping off a piece of duricrust provided another estimate of the cohesion of 5.8 kPa. The hammerings of the mole were recorded by the seismometer SEIS and the signals were used to derive P-wave and S-wave velocities representative of the topmost tens of cm of the regolith. Together with the density provided by a thermal conductivity and diffusivity measurement using the mole's thermal sensors, the elastic moduli were calculated from the seismic velocities. Using empirical correlations from terrestrial soil studies between the shear modulus and cohesion, the previous cohesion estimates were found to be consistent with the elastic moduli. The combined data were used to derive a model of the regolith that has an about 20 cm thick duricrust underneath a 1 cm thick unconsolidated layer of sand mixed with dust and above another 10 cm of unconsolidated sand. Underneath the latter, a layer more resistant to penetration and possibly containing debris from a small impact crater is inferred. The thermal conductivity increases from 14 mW/m K to 34 mW/m K through the 1 cm sand/dust layer, keeps the latter value in the duricrust and the sand layer underneath and then increases to 64 mW/m K in the sand/gravel layer below. Supplementary Information: The online version contains supplementary material available at 10.1007/s11214-022-00941-z.

Facilitators and barriers to TB care during the COVID-19 pandemic.

BACKGROUND: Knowledge about factors influencing access and adherence to TB care, and on the impact of the COVID-19 pandemic on TB care in resource-restricted settings is scarce. We conducted this study in Atsimo-Andrefana, a rural region in southern Madagascar where TB prevalence, poverty and food insecurity rates are high. We aimed to determine facilitators and barriers to access to and provision of TB care in rural Madagascar during the COVID-19 pandemic. METHODS: We conducted qualitative focus group discussions (FGDs) and in-depth interviews (IDIs) with patients with TB, community health workers, facility-based health workers, public health officials and non-governmental organisation staff. We analysed interviews using thematic analysis. RESULTS: We conducted 11 FGDs and 23 IDIs. We identified three main barriers to access and adherence to TB care: 1) stigma, 2) indirect treatment costs, and 3) food insecurity. The facilitator perceived as most influential was high health worker motivation. The effects of the COVID-19 pandemic on TB care varied between stake-holders; some health workers described delays in TB diagnosis and increased workload. CONCLUSIONS: To improve access and adherence to TB care, both indirect treatment costs and stigma need to be reduced; undernourished patients with TB should receive food support.

CONTEXTE: Les connaissances sur les facteurs influençant l'accès et l'adhésion aux soins antituberculeux, ainsi que sur l'impact de la pandémie de COVID-19 sur les soins antituberculeux dans les milieux à ressources limitées sont rares. Nous avons mené cette étude à Atsimo-Andrefana, une région rurale du sud de Madagascar où la prévalence de la TB et les taux de pauvreté et d'insécurité alimentaire sont élevés. Nous avons cherché à déterminer les facilitateurs et les obstacles à l'accès et à la fourniture de soins antituberculeux dans les zones rurales de Madagascar pendant la pandémie de COVID-19. MÉTHODES: Nous avons mené des discussions qualitatives en groupe (FGD) et des entretiens approfondis (IDI) avec des patients atteints de tuberculose, des agents de santé communautaires, des agents de santé en établissement, des responsables de la santé publique et des membres d'organisations non gouvernementales. Nous avons analysé les entretiens en utilisant l'analyse thématique. RÉSULTATS: Nous avons mené 11 FGD et 23 IDI. Nous avons identifié trois principaux obstacles à l'accès et à l'observance des soins antituberculeux : 1) la stigmatisation, 2) les coûts indirects du traitement et 3) l'insécurité alimentaire. Le facilitateur perçu comme le plus influent était la forte motivation des agents de santé. Les effets de la pandémie de COVID-19 sur les soins antituberculeux varient selon les parties prenantes ; certains agents de santé ont décrit des retards dans le diagnostic de la TB et une augmentation de la charge de travail. CONCLUSIONS: Pour améliorer l'accès et l'adhésion aux soins antituberculeux, il faut réduire à la fois les coûts indirects du traitement et la stigmatisation ; les patients tuberculeux sousalimentés devraient recevoir une aide alimentaire.

A direct neural measure of variable precision representations in visual working memory.

Visual working memory (VWM) is an active representation enabling the manipulation of item information even in the absence of visual input. A common way to investigate VWM is to analyze the performance at later recall. This approach, however, leaves uncertainties about whether the variation of recall performance is attributable to item encoding and maintenance or to the testing of memorized information. Here, we record the contralateral delay activity (CDA), an established electrophysiological measure of item storage and maintenance, in human subjects performing a delayed orientation precision estimation task. This allows us to link the fluctuation of recall precision directly to the process of item encoding and maintenance. We show that for two sequentially encoded orientation items, the CDA amplitude reflects the precision of orientation recall of both items, with higher precision being associated with a larger amplitude. Furthermore, we show that the CDA amplitudes for the items vary independently from each other, suggesting that the precision of memory representations fluctuates independently.NEW & NOTEWORTHY The present work demonstrates for the first time that the contralateral delay activity (CDA), an online electrophysiological measure of the number of representations maintained in memory, is also a reliable measure of the precision of memory representations. Furthermore, we show that the CDA fluctuates independently for individual items held in memory, thereby providing unambiguous direct neurophysiological support for independently fluctuating memory representations.

[The diagnostic course : A new form of teaching in otorhinolaryngology education]. / Der Diagnostik-Parcours : Eine neue Lernform im Studierendenkurs der Hals-Nasen-Ohren-Heilkunde.

BACKGROUND: A lack of practical courses and increasing numbers of students generate a requirement for innovative teaching methods. We have established a diagnostic course representing the essence of our discipline of otorhinolaryngology. OBJECTIVE: The main aim of the diagnostic course is compact presentation of the functional diagnostic methods in an otorhinolaryngology department as well as the practical and varied organization of the training block. MATERIALS AND METHODS: The first day of the five-day training block includes a "mirror course", in which students learn how to perform an ENT mirror examination. After rotation in the wards, the outpatient department, and the operating rooms, the diagnostic course is completed on day 5, in which four different stations comprising practical ENT diagnostic exercises are passed through. RESULTS: The evaluation of the practical training block showed a significant improvement after introduction of the diagnostic course: in the 2019 summer semester, 38% of n = 105 had grade 1.4. Personal feedback and requests for clinical traineeships also underlined this positive assessment. CONCLUSION: The advantages of our diagnostic course are the opportunity to apply practical skills and the small group sizes (maximum five students). The discipline of otorhinolaryngology and its varied character could be optimally presented in this manner. Disadvantageous are the high personnel and logistic requirements, which should, however, be met during university teaching.

Long-term outcome of persons with diabetic and non-diabetic neuro-osteoarthropathy after foot correction using external fixation.

AIM: Diabetic neuro-osteoarthropathy (Charcot foot) is a serious form of diabetic foot syndrome, often leading to severe deformity of the foot and subsequently to ulcers and osteomyelitis. The aim of this retrospective study was to determine the success rate and long-term outcomes for a Charcot foot operation using external fixation in 115 individuals who underwent surgery between July 2008 and December 2012. METHODS: Some 115 consecutive persons, 78 (68%) men and 37 (32%) women, were enrolled in this study. The eligibility criterion for this retrospective study was reconstructive foot surgery using a Hoffmann II external fixator in diabetic and non-diabetic neuro-osteoarthropathy. The main examination parameters in the follow-up were walking ability, amputation and mortality. Average follow-up was 5.7 (± 3.2) years. RESULTS: Ninety-seven per cent of people were able to walk after the operation with bespoke shoes or an orthosis. At follow-up, 77% were able to walk and 51% were fully mobile even outside the home. Subsequent amputations were performed in 29 individuals (26%), with 17 (15%) minor and 12 (11%) major amputations. Forty-seven individuals died before follow-up, the majority (53%) from cardiovascular events. Average survival time post surgery was 4.5 (± 2.9) years. CONCLUSION: Reconstruction surgery using external fixation is a very useful method for maintaining walking ability in the case of conservatively non-treatable diabetic and non-diabetic neuro-osteoarthropathy. Individuals with severe Charcot foot disease had a low rate of major amputations. Osteomyelitis was the main reason for major amputations.

Scarlet fever outbreak in a primary and middle school in Germany: importance of case ascertainment and risk communication.

A cluster of 18 scarlet fever cases and large illness absenteeism (32%, 58/184) in a school prompted concern and further investigation. We conducted telephone interviews with parents to ascertain cases and better comprehend parents' views. We identified 19 cases, of which 13 reported scarlet fever diagnosis by a physician and only seven fulfilled the probable case definition. We concluded that the outbreak was far smaller than suspected and found that communication and reporting could be improved. Accurate information and communication is essential in an outbreak; the school's concern could have been alleviated sooner and response measures better targeted.

Replacing fishmeal with plant protein in Atlantic salmon (Salmo salar) diets by supplementation with fish protein hydrolysate.

The effects of feeding an 80% plant protein diet, with and without fish protein hydrolysate (FPH) supplementation, on the growth and gut health of Atlantic salmon were investigated. Fish were fed either (A) a control diet containing 35% fishmeal, (B) an 80% plant protein diet with 15% fishmeal, (C) an 80% plant protein diet with 5% fishmeal and 10% partly hydrolysed protein, or (D) an 80% plant protein diet with 5% fishmeal and 10% soluble protein hydrolysate. Fish on the 80% plant- 15% fishmeal diet were significantly smaller than fish in the other dietary groups. However, partly-hydrolysed protein supplementation allowed fish to grow as well as fish fed the control 35% fishmeal diet. Fish fed the FPH diets (diets C and D) had significantly higher levels of amino acids in their blood, including 48% and 27% more branched chain amino acids compared to fish on the 35% fishmeal diet, respectively. Plant protein significantly altered gut microbial composition, significantly decreasing α-diversity. Spirochaetes and the families Moritellaceae, Psychromonadaceae, Helicobacteraceae and Bacteroidaceae were all found at significantly lower abundances in the groups fed 80% plant protein diets compared to the control fishmeal diet.

Changes in incidence of severe hypoglycaemia in people with type 2 diabetes from 2006 to 2016: analysis based on health insurance data in Germany considering the anti-hyperglycaemic medication.

AIM: To investigate the incidence of severe hypoglycaemia over the past 10 years, taking into account changes in anti-hyperglycaemic therapy. METHODS: This retrospective population-based study used German health insurance data. All adults diagnosed with documented type 2 diabetes (extrapolated to the German population: 6.6 million in 2006; 7.9 million in 2011; 8.86 million in 2016) were screened for severe hypoglycaemia. Anti-hyperglycaemic agents were identified by Anatomical Therapeutic Chemical (ATC) code. RESULTS: The event rate for severe hypoglycaemia was 460 per 100 000 people in 2006, 490 per 100 000 in 2011 and 360 per 100 000 in 2016. The proportion of people with severe hypoglycaemia receiving sulfonylureas, as well as receiving combination therapy of metformin and sulfonylureas decreased from 2006 to 2016 (23.6% vs. 6.2%) Among those with severe hypoglycaemia in 2006, there were no prescriptions for dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists or sodium-glucose co-transporter 2 (SGLT2) agonists. The proportions of people with severe hypoglycaemia receiving DPP-4 inhibitors, GLP-1 receptor agonists or SGLT2 agonists in 2011 and 2016 were low. The proportion of people receiving human insulin also decreased (from 11.3% in 2006 to 10.3% in 2011 and 4.3% in 2016); the proportion of people receiving insulin analogues increased from 5.4% in 2006 to 11.5% in 2016. Therapy with mixed insulins was used by 19.7% of people with severe hypoglycaemia in 2006, by 14.0% in 2011 and by 7.3% in 2016. People undergoing therapy with insulin analogues have the highest risk of severe hypoglycaemia adjusted by age, gender, nephropathy diagnosis and year of survey [odds ratio (OR) 14.4, 95% confidence interval (95% CI) 13.5-15.5]. CONCLUSION: The incidence of severe hypoglycaemic events in Germany increased between 2006 and 2011, and decreased in 2016.

Medial prefrontal decoupling from the default mode network benefits memory.

In the last few years the involvement of the medial prefrontal cortex (mPFC) in memory processing has received increased attention. It has been shown to be centrally involved when we use prior knowledge (schemas) to improve learning of related material. With the mPFC also being one of the core hubs of the default mode network (DMN) and the DMN's role in memory retrieval, we decided to investigate whether the mPFC in a schema paradigm acts independent of the DMN. We tested this with data from a cross-sectional developmental study with a schema paradigm. During retrieval of schema items, the mPFC decoupled from the DMN with the degree of decoupling predicting memory performance. This finding suggests that a demand specific reconfiguration of the DMN supports schema memory. Additionally, we found that in the control condition, which relied on episodic memory, activity in the parahippocampal gyrus was positively related to memory performance. We interpret these results as a demand specific network reconfiguration of the DMN: a decoupling of the mPFC to support schema memory and a decoupling of the parahippocampal gyrus facilitating episodic memory.

IL-17C amplifies epithelial inflammation in human psoriasis and atopic eczema.

BACKGROUND: Key pathogenic events of psoriasis and atopic eczema (AE) are misguided immune reactions of the skin. IL-17C is an epithelial-derived cytokine, whose impact on skin inflammation is unclear. OBJECTIVE: We sought to characterize the role of IL-17C in human ISD. METHODS: IL-17C gene and protein expression was assessed by immunohistochemistry and transcriptome analysis. Primary human keratinocytes were stimulated and expression of cytokines chemokines was determined by qRT-PCR and luminex assay. Neutrophil migration towards supernatant of stimulated keratinocytes was assessed. IL-17C was depleted using a new IL-17C-specific antibody (MOR106) in murine models of psoriasis (IL-23 injection model) and AE (MC903 model) as well as in human skin biopsies of psoriasis and AE. Effects on cell influx (mouse models) and gene expression (human explant cultures) were determined. RESULTS: Expression of IL-17C mRNA and protein was elevated in various ISD. We demonstrate that IL-17C potentiates the expression of innate cytokines, antimicrobial peptides (IL-36G, S100A7 and HBD2) and chemokines (CXCL8, CXCL10, CCL5 and VEGF) and the autocrine induction of IL-17C in keratinocytes. Cell-free supernatant of keratinocytes stimulated with IL-17C was strongly chemotactic for neutrophils, thus demonstrating a critical role for IL-17C in immune cell recruitment. IL-17C depletion significantly reduced cell numbers of T cells, neutrophils and eosinophils in murine models of psoriasis and AE and led to a significant downregulation of inflammatory mediators in human skin biopsies of psoriasis and AE ex vivo. CONCLUSION: IL-17C amplifies epithelial inflammation in Th2 and Th17 dominated skin inflammation and represents a promising target for the treatment of ISD.

Targeting bromodomain-containing protein 4 (BRD4) inhibits MYC expression in colorectal cancer cells.

The transcriptional regulator BRD4 has been shown to be important for the expression of several oncogenes including MYC. Inhibiting of BRD4 has broad antiproliferative activity in different cancer cell types. The small molecule JQ1 blocks the interaction of BRD4 with acetylated histones leading to transcriptional modulation. Depleting BRD4 via engineered bifunctional small molecules named PROTACs (proteolysis targeting chimeras) represents the next-generation approach to JQ1-mediated BRD4 inhibition. PROTACs trigger BRD4 for proteasomale degradation by recruiting E3 ligases. The aim of this study was therefore to validate the importance of BRD4 as a relevant target in colorectal cancer (CRC) cells and to compare the efficacy of BRD4 inhibition with BRD4 degradation on downregulating MYC expression. JQ1 induced a downregulation of both MYC mRNA and MYC protein associated with an antiproliferative phenotype in CRC cells. dBET1 and MZ1 induced degradation of BRD4 followed by a reduction in MYC expression and CRC cell proliferation. In SW480 cells, where dBET1 failed, we found significantly lower levels of the E3 ligase cereblon, which is essential for dBET1-induced BRD4 degradation. To gain mechanistic insight into the unresponsiveness to dBET1, we generated dBET1-resistant LS174t cells and found a strong downregulation of cereblon protein. These findings suggest that inhibition of BRD4 by JQ1 and degradation of BRD4 by dBET1 and MZ1 are powerful tools for reducing MYC expression and CRC cell proliferation. In addition, downregulation of cereblon may be an important mechanism for developing dBET1 resistance, which can be evaded by incubating dBET1-resistant cells with JQ1 or MZ1.

Efficacy of DiaLife, an education program for relatives of adult patients with diabetes - study protocol of a cluster randomized controlled trial.

BACKGROUND: The global prevalence of diabetes mellitus (DM) has been increasing over recent decades. In Germany, the prevalence for DM type 1 and type 2 in adults is estimated at about 7.7%. Hence, diabetes has to be classified as a serious public health concern. Being diagnosed with DM and facing possible sequelae might have a negative impact on patients' mental and physical well-being. However, diabetes not only affects patients themselves, but also their close relatives. To improve the quality of life for patients and relatives alike, the German Association of Diabetes Nurses and Education experts (VDBD) elaborated the first education program tailor-made for relatives of diabetes patients. This article describes the concept and design of the trial evaluating the efficacy of this education program called "DiaLife-Living Together with Diabetes". METHODS: This evaluation study is a cluster randomized controlled trial, in which the study centers will be randomly assigned either to the intervention group or the control group. Study centers will recruit relatives of and patients with DM type 1 and type 2. Members of the intervention group will participate in the education program DiaLife, whereas participants randomized in the control group will act as waiting-list controls. The study will assess the efficacy of DiaLife by comparing diabetes-related knowledge between the intervention and control groups as the primary outcome for participants. As the primary outcome in patients, the Hba1c value will be assessed. In addition, diabetes-related distress, family interaction, and other secondary endpoints will be considered as secondary outcomes. Long-term efficacy will be assessed 6 and 12 months after intervention. Hierarchical regression models will be used to analyze effects over time. DISCUSSION: While there is scientific evidence for the efficacy of education programs addressed to (diabetes) patients, there is a research gap with regard to intervention studies evaluating the efficacy of education programs designed for patients' relatives. The study results will provide information on the efficacy of the DiaLife education program. In addition, factors that might hinder a successful implementation of an education program for relatives will be identified. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00015157 . Registered on 24 August 2018.

[Drug treatment of Alzheimer's dementia : Status quo and perspectives]. / Pharmakologische Therapie der Alzheimer-Demenz : Aktueller Stand und Perspektiven.

Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system. AD is characterized by progressive impairments of memory as well as other cognitive functions and an increasing loss of autonomy in everyday life. This review article provides an overview of the current state-of-the-art (symptomatic) pharmacological treatment of Alzheimer's disease, specifics in the context of concomitant neuropsychiatric symptoms in multimorbid patients, and drugs currently under development that have a potentially causal (disease modifying) effect are also mentioned.

Course of colonization by multidrug-resistant organisms after allogeneic hematopoietic cell transplantation.

Multidrug-resistant organisms (MDRO) have been developing as an emerging problem in allogeneic hematopoietic cell transplantation (HCT). Since no data are available on the course of MDRO colonization after HCT, we investigated in this retrospective, single-center study, persistence and clearance of MDRO after HCT. From June 2010 to December 2015, 121 consecutive HCT patients were included. Patients received a MDRO screening before conditioning as well as surveillance cultures after HCT. In MDRO-colonized patients, surveillance specimens were taken until MDRO were no longer detectable. Thirty-three patients (27%) were found to be colonized by at least one MDRO at any time point until day 100 post HCT. Day 100 (2-year) non-relapse mortality (NRM) and overall survival (OS) of MDRO-colonized (MDRO+) versus non-colonized (MDRO-) patients were essentially the same. NRM is 15% (21%) versus 15% (24%). Two-year OS is 60 versus 55% for MDRO+ versus MDRO- patients. Out of the 33 MDRO+ patients, 21 cleared the MDRO. Median time to non-detectability of MDRO was 6 months. In 12 patients, the MDRO persisted. There was a significant (p < 0.0001) survival difference between patients who cleared the MDRO versus those with MDRO persistence (2-year OS 80 vs 40%). Except for the length of antibiotic therapy as a potential risk factor for MDRO persistence after HCT, no other conventional factors could be identified. (a) colonization by MDRO per se had no negative impact on the outcome, (b) MDRO can be cleared by the majority of patients after allogeneic HCT, and (c) to increase the probability to clear MDRO, the use of antibiotics in MDRO+ patients should be reviewed critically.

2D:4D and spatial abilities: From rats to humans.

Variance in spatial abilities are thought to be determined by in utero levels of testosterone and oestrogen, measurable in adults by the length ratio of the 2nd and 4th digit (2D:4D). We confirmed the relationship between 2D:4D and spatial performance using rats in two different tasks (paired-associate task and watermaze) and replicated this in humans. We further clarified anatomical and functional brain correlates of the association between 2D:4D and spatial performance in humans.

Increase in the incidence of severe hypoglycaemia in people with Type 2 diabetes in spite of new drugs: analysis based on health insurance data from Germany.

AIM: To evaluate the use of new anti-hyperglycaemic agents that offer effective glycaemic control while reducing risk of hypoglycaemia, by analysing the incidence rates of severe hypoglycaemia in 2006 vs 2011 in relation to the medication. METHODS: This cross-sectional, population-based study used German health insurance data. All adults diagnosed with Type 2 diabetes mellitus (extrapolated to the German population: 6.35 million in 2006 and 7.52 million in 2011) were screened for severe hypoglycaemia. Anti-hyperglycaemic agents were identified by their Anatomical Therapeutic Chemical code, and defined daily doses of each medication were calculated. RESULTS: The severe hypoglycaemic event rate was 460 per 100,000 people/year in 2006 and 490 per 100,000 people/year in 2011. In 2006 and 2011, 10.9% and 7.3%, respectively, of all people with severe hypoglycaemia were on sulfonylureas, while 12.7% and 9.3%, respectively, were on a combination therapy of metformin and sulfonylureas. Among those with severe hypoglycaemia, there were no prescriptions of dipeptidyl peptidase-4 inhibitors or glucagon-like peptide-1 receptor agonists in 2006, but in 2011, 1.55% and 0.17%, of those with severe hypoglycaemia were receiving the respective treatments. In 2006 vs 2011, human insulin was prescribed for 11.3% vs 10.3% of people with severe hypoglycaemia, while insulin analogues were prescribed for 5.4% vs 8.1%, and mixed human insulins for 19.7% vs 14.0% of patients with severe hypoglycaemia. People receiving insulin analogue therapy had a higher risk of severe hypoglycaemia than those receiving metformin, after adjusting for age, gender, nephropathy diagnosis and year of survey (odds ratio 14.6; CI 13.3-15.9). CONCLUSION: The incidence of severe hypoglycaemic events in Germany increased between 2006 and 2011, despite increased use of newer anti-hyperglycaemic agents and decreased use of insulins.