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Background and Purpose: Itch is associated with several pathologies and is a common drug‐induced side effect. Chloroquine (CQ) is reported to induce itch by activating the Mas‐related G protein‐coupled receptor MrgprA3 and subsequently TRPA1. In this study, we demonstrate that CQ employs at least two MrgprA3‐independent mechanisms to activate or sensitize TRPA1 and TRPV1. Experimental Approach: Patch clamp and calcium imaging were utilized to examine effects of CQ on TRPA1 and TRPV1 expressed in HEK 293T cells. Key Results: In calcium imaging, CQ induces a concentration‐dependent but MrgprA3‐independent activation of TRPA1 and TRPV1. Although CQ itself inhibits TRPA1 and TRPV1 in patch clamp recordings, co‐application of CQ and ultraviolet A (UVA) light evokes membrane currents through both channels. This effect is inhibited by the reducing agent dithiothreitol (DTT) and is reduced on mutants lacking cysteine residues accounting for reactive oxygen species (ROS) sensitivity. The combination of CQ and UVA light triggers an accumulation of intracellular ROS, removes fast inactivation of voltage‐gated sodium currents and activates TRPV2. On the other hand, CQ is a weak base and induces intracellular alkalosis. Intracellular alkalosis can activate TRPA1 and TRPV1, and CQ applied at alkaline pH values indeed activates both channels. Conclusion and Implications: Our data reveal novel pharmacological properties of CQ, allowing activation of TRPA1 and TRPV1 via photosensitization as well as intracellular alkalosis. These findings add more complexity to the commonly accepted dogma that CQ‐induced itch is specifically mediated by MrgprA3 coupling to TRPA1. [ABSTRACT FROM AUTHOR]

Objectives: This study examined the incidence rates and predictive utility of established prognostic factors for the progression to AIDS among people living with HIV under clinical care. Methods: We used data from two observational cohorts of people living with HIV in Germany between 1999 and 2018. The outcome measure was the first AIDS‐defining event that occurred during follow‐up. Incidence rates (IRs) per 1000 person‐years (PY) were calculated by years of follow‐up and calendar periods. We used Cox models in our prediction analyses, including CD4 count, viral load, and age at baseline to estimate the predictive performance. Additionally, we included transmission mode to examine its predictive utility. Results: A total of 23 299 people living with HIV were included in the analyses. Of these, 1832 developed a first AIDS event during follow‐up, constituting an overall rate of 14.6/1000 PY (95% confidence interval [CI] 13.9–15.2). IRs were highest in the first year of follow‐up (45.6/1000 PY, 95% CI 42.6–48.8) and then declined continuously. IRs were highest among people living with HIV who enrolled between 1999 and 2003 (36.1/1000 PY, 95% CI 32.6–40.0). A low CD4 count, high viral load, and older age at baseline increased the likelihood of progressing to AIDS. Adding transmission mode to the models did not improve the predictive performance. Conclusions: The rates of a first AIDS event among people living with HIV have continuously declined in Germany. Health outcomes depend on a person's CD4 count, viral load, and age but not on transmission mode. To further reduce the number of AIDS cases, the focus should be on groups more likely to present in progressed stages of their HIV infection. [ABSTRACT FROM AUTHOR]

Growing up with siblings may affect quality of life as well as hemodynamic parameters including blood pressure. Using weighted data from the nationwide and representative German KiGGs study, we assessed the relationship between only-child status, birth order, and arterial blood pressure in a cohort of 7311 adolescents aged between 11 and 17 years. Our data showed that only-children had the highest mean arterial blood pressure (87.3 ± 8.4 mmHg) as compared to first-born (86.3 ± 8.0), middle-born (86.4 ± 8.7), and youngest-born siblings (86.6 ± 8.2; p = 0.012). The two groups of only-children and first-borns differed significantly with respect to their age- and sex-specific, z-scored data for systolic (p = 0.047), diastolic (p = 0.012), and mean arterial blood pressure (p = 0.005). Linear regression models with blood pressure recordings as dependent variable adjusted to age, migration background, and age- and sex-specific z-scores of body-mass index confirmed that only-child status was an independent predictor of a higher diastolic blood pressure (p = 0.037). A similar result was observed for mean arterial blood pressure (p = 0.033), whereas systolic blood pressure was not associated with only-children status (p = 0.258). Conclusion: In summary, we found a significant and positive relationship between only-child status and blood pressure, with the highest recordings in only-children and the lowest in first-borns. Models adjusted for relevant clinical confounders demonstrated slightly higher blood pressure in only-children compared to first-borns, who are both in an alpha birth order. Although these blood pressure differences were statistically significant, they have limited, if any, clinical meaning in this age group. What is Known: • In children and adults, blood pressure is significantly higher in only-children compared to children with siblings. However, it is unclear whether there are also similar blood pressure differences in adolescents and between only-children and first-borns. What is New: • Among adolescents in the alpha birth order, growing up as an only-child is associated with significantly higher mean blood pressure than among first-borns living with younger siblings. [ABSTRACT FROM AUTHOR]

Little is known of the influence of scanner field strength on quantitative diffusivity variables, especially kurtosis in healthy ovaries.To evaluate the influence of scanner field strength on quantitative diffusion variables in pelvic MRI of the ovaries.This prospective, single-centre study consisted of repeated 1.5-T and 3-T examinations in 30 female volunteers (mean age=27.9 years, age range=20.3–45.2 years) from July 2017 to September 2019. Multi b-value DWI 0, 50, 100, 800, 1500, 2000 s/mm2 was acquired over three timepoints during the menstrual cycle. Ovaries were segmented at b = 1500 s/mm2. Median apparent diffusion coefficient (ADC) and advanced kurtosis parameters Dapp and Kapp were calculated. Statistical analysis was performed with the variations of diffusivity variables being compared between 1.5-T and 3-T MRI using a Mann–Whitney rank-sum test.Median ADC and Dapp (µm²/ms) did not statistically differ. Median ADC were 1.509 (range=1.371–1.610), 1.619 (range=1.463–1.747), and 1.511 (range=1.423–1.639) at 1.5 T; 1.542 (range=1.428–1.682), 1.658 (range=1.510–1.806), and 1.572 (range=1.455–1.709) at 3 T (P = 0.14, 0.19, and 0.07), whereas median Dapp were 2.024 (range=1.913–2.152), 2.192 (range=2.010–2.327), and 2.045 (range=1.958–2.170) at 1.5 T; 2.013 (range=1.952–2.188), 2.179 (range=2.018–2.327), and 2.082 (range=1.959–2.194) at 3 T (P = 0.77, 0.99, and 0.34) for timepoints 1, 2, and 3, respectively. Statistical comparison of Kapp revealed significant differences for all timepoints: 0.629 (range=0.595–0.652), 0.604 (range=0.574–0.651), and 0.622 (range=0.581–0.664) at 1.5 T; 0.601 (range=0.563–0.626), 0.567 (range=0.526–0.633), and 0.599 (range=0.541–0.650) at 3 T (P < 0.001, 0.005, and 0.03).Diffusivity mapping in the ovaries provides similar absolute median diffusion values, but statistically significant differences in absolute kurtosis values between 1.5 T and 3 T. [ABSTRACT FROM AUTHOR]

Background: HIV infections which are diagnosed at advanced stages are associated with significantly poorer health outcomes. In Germany, the proportion of persons living with HIV who are diagnosed at later stages has remained continuously high. This study examined the impact of regional socioeconomic deprivation on the timing of HIV diagnosis. Methods: We used data from the national statutory notification of newly diagnosed HIV infections between 2011 and 2018 with further information on the timing of diagnosis determined by the BED-Capture-ELISA test (BED-CEIA) and diagnosing physicians. Data on regional socioeconomic deprivation were derived from the German Index of Socioeconomic Deprivation (GISD). Outcome measures were a non-recent infection based on the BED-CEIA result or an infection at the stage of AIDS. The effect of socioeconomic deprivation on the timing of diagnosis was analysed using multivariable Poisson regression models with cluster-robust error variance. Results: Overall, 67.5% (n = 10,810) of the persons were diagnosed with a non-recent infection and 15.2% (n = 2746) with AIDS. The proportions were higher among persons with heterosexual contact compared to men who have sex with men (MSM) (76.8% non-recent and 14.9% AIDS vs. 61.7% non-recent and 11.4% AIDS). MSM living in highly deprived regions in the countryside (< 100 k residents) were more likely to have a non-recent infection (aPR: 1.16, 95% CI: 1.05–1.28) as well as AIDS (aPR: 1.41, 95% CI: 1.08–1.85) at the time of diagnosis compared to MSM in less deprived regions in the countryside. No differences were observed among MSM from towns (100 k ≤ 1 million residents) or major cities (≥ 1 million residents), and no differences overall in the heterosexual transmission group. Conclusions: An effect of socioeconomic deprivation on the timing of HIV diagnosis was found only in MSM from countryside regions. We suggest that efforts in promoting HIV awareness and regular HIV testing are increased for heterosexual persons irrespective of socioeconomic background, and for MSM with a focus on those living in deprived regions in the countryside. [ABSTRACT FROM AUTHOR]

Background: HIV infections which are diagnosed at advanced stages are associated with significantly poorer health outcomes. In Germany, the proportion of persons living with HIV who are diagnosed at later stages has remained continuously high. This study examined the impact of regional socioeconomic deprivation on the timing of HIV diagnosis.Methods: We used data from the national statutory notification of newly diagnosed HIV infections between 2011 and 2018 with further information on the timing of diagnosis determined by the BED-Capture-ELISA test (BED-CEIA) and diagnosing physicians. Data on regional socioeconomic deprivation were derived from the German Index of Socioeconomic Deprivation (GISD). Outcome measures were a non-recent infection based on the BED-CEIA result or an infection at the stage of AIDS. The effect of socioeconomic deprivation on the timing of diagnosis was analysed using multivariable Poisson regression models with cluster-robust error variance.Results: Overall, 67.5% (n = 10,810) of the persons were diagnosed with a non-recent infection and 15.2% (n = 2746) with AIDS. The proportions were higher among persons with heterosexual contact compared to men who have sex with men (MSM) (76.8% non-recent and 14.9% AIDS vs. 61.7% non-recent and 11.4% AIDS). MSM living in highly deprived regions in the countryside (< 100 k residents) were more likely to have a non-recent infection (aPR: 1.16, 95% CI: 1.05-1.28) as well as AIDS (aPR: 1.41, 95% CI: 1.08-1.85) at the time of diagnosis compared to MSM in less deprived regions in the countryside. No differences were observed among MSM from towns (100 k ≤ 1 million residents) or major cities (≥ 1 million residents), and no differences overall in the heterosexual transmission group.Conclusions: An effect of socioeconomic deprivation on the timing of HIV diagnosis was found only in MSM from countryside regions. We suggest that efforts in promoting HIV awareness and regular HIV testing are increased for heterosexual persons irrespective of socioeconomic background, and for MSM with a focus on those living in deprived regions in the countryside. [ABSTRACT FROM AUTHOR]

The emergence of twisted metamaterials opens up an avenue for research in metamaterials. However, the current emphasis primarily lies in mechanics, rendering it intriguing to explore the application of compression-torsion coupling effect in optics. This present study introduces a thin-walled circular tube (TWCT) structure, characterized by a pronounced twisting angle of up to 59.5°, achieved only through a single-layer TWCT configuration. We demonstrate a significant compression-torsion coupling phenomenon, surpassing the findings of previous research endeavors. TWCT's deformation mechanism is harnessed in optical imaging through the integration of experimental, theoretical, and finite element approaches. The information stored in TWCT can be gradually projected through optical imaging when the elastic strain stimulates TWCT. These findings presented herein introduces a straightforward and valid approach to employ TWCT as a reliable mechanical switch for optical imaging, thereby showcasing its potential in the fields of cryptographic techniques, information storage, and transmission via optical imaging. [ABSTRACT FROM AUTHOR]

We aimed to investigate whether quantitative diffusivity variables of healthy ovaries vary during the menstrual cycle and to evaluate alterations in women using oral contraceptives (OC). This prospective study (S-339/2016) included 30 healthy female volunteers, with (n = 15) and without (n = 15) intake of OC between 07/2017 and 09/2019. Participants underwent 3T diffusion-weighted MRI (b-values 0–2000 s/mm2) three times during a menstrual cycle (T1 = day 1–5; T2 = day 7–12; T3 = day 19–24). Both ovaries were manually three-dimensionally segmented on b = 1500 s/mm2; apparent diffusion coefficient (ADC) calculation and kurtosis fitting (D app , K app) were performed. Differences in ADC , D app and K app between time points and groups were compared using repeated measures ANOVA and t -test after Shapiro-Wilk and Brown-Forsythe test for normality and equal variance. In women with a natural menstrual cycle, ADC and kurtosis variables showed significant changes in ovaries with the dominant follicle between T1 vs T2 and T1 vs T3, whilst no differences were observed between T2 vs T3: ADC ± SD for T1 1.524 ± 0.160, T2 1.737 ± 0.160, and T3 1.747 ± 0.241 μm2/ms (p = 0.01 T2 vs T1; p = 1.0 T2 vs T3, p = 0.003 T3 vs T1); D app ± SD for T1 2.018 ± 0.140, T2 2.272 ± 0.189, and T3 2.230 ± 0.256 μm2/ms (p = 0.003 T2 vs T1, p = 1.0 T2 vs T3, p = 0.02 T3 vs T1); K app ± SD for T1 0.614 ± 0.0339, T2 0.546 ± 0.0637, and T3 0.529 ± 0.0567 (p < 0.001 T2 vs T1, p = 0.86 T2 vs T3, p < 0.001 T3 vs T1). No significant differences were found in the contralateral ovaries or in females taking OC. Physiological cycle-dependent changes in quantitative diffusivity variables of ovaries should be considered especially when interpreting radiomics analyses in reproductive women. • Cyclic changes in diffusivity variables of healthy ovaries with dominant follicle. • No cyclic changes in diffusivity variables of ovaries without dominant follicle. • No cyclic changes in diffusivity variables of ovaries under oral contraceptives. [ABSTRACT FROM AUTHOR]

Changes in blood flow velocity play a crucial role during pathogenesis and progression of cardiovascular diseases. Imaging techniques capable of assessing flow velocities are clinically applied but are often not accurate, quantitative, and reliable enough to assess fine changes indicating the early onset of diseases and their conversion into a symptomatic stage. Magnetic particle imaging (MPI) promises to overcome these limitations. Existing MPI-based techniques perform velocity estimation on the reconstructed images, which restricts the measurable velocity range. Therefore, we developed a novel velocity quantification method by adapting the Doppler principle to MPI. Our method exploits the velocity-dependent frequency shift caused by a tracer motion-induced modulation of the emitted signal. The fundamental theory of our method is deduced and validated by simulations and measurements of moving phantoms. Overall, our method enables robust velocity quantification within milliseconds, with high accuracy, no radiation risk, no depth-dependency, and extended range compared to existing MPI-based velocity quantification techniques, highlighting the potential of our method as future medical application. [ABSTRACT FROM AUTHOR]

Changes in blood flow velocity play a crucial role during pathogenesis and progression of cardiovascular diseases. Imaging techniques capable of assessing flow velocities are clinically applied but are often not accurate, quantitative, and reliable enough to assess fine changes indicating the early onset of diseases and their conversion into a symptomatic stage. Magnetic particle imaging (MPI) promises to overcome these limitations. Existing MPI-based techniques perform velocity estimation on the reconstructed images, which restricts the measurable velocity range. Therefore, we developed a novel velocity quantification method by adapting the Doppler principle to MPI. Our method exploits the velocity-dependent frequency shift caused by a tracer motion-induced modulation of the emitted signal. The fundamental theory of our method is deduced and validated by simulations and measurements of moving phantoms. Overall, our method enables robust velocity quantification within milliseconds, with high accuracy, no radiation risk, no depth-dependency, and extended range compared to existing MPI-based velocity quantification techniques, highlighting the potential of our method as future medical application. [ABSTRACT FROM AUTHOR]

Purpose: Magnetic particle imaging (MPI) allows fast imaging of the spatial distribution of superparamagnetic iron‐oxide based nanoparticles (SPIONs). Recent research suggests that MPI furthermore promises in‐vivo access to environmental parameters of SPIONs as temperature or viscosity. Various medical applications as nanomedicine, stem cell‐based therapies or magnetic hyperthermia could benefit from in‐vivo multiparameter estimation by MPI. One possible approach to get access to functional parameters is particle excitation at multiple frequencies. To enable the investigation of the mentioned approach, a novel MPI device capable of multifrequency excitation is needed. Methods: MPI usually employs analog band‐stop filters to cancel the drive field feed‐through, which is magnitudes higher than the particle signal. To enable drive field frequency flexibility over a wide bandwidth, we propose a combined passive and active drive field feed‐through compensation approach. This cancellation technique further allows the direct detection of the SPIONs' signal at the fundamental excitation frequency. Results: A combined feed‐through suppression of up to −125 dB is reported, which allows to adjust the drive field frequency from 500 Hz to 20 kHz. Initial spectroscopic measurements and images are shown that demonstrate the concept of multifrequency excitation and prove the imaging capability of the presented scanner. A mean signal‐to‐noise ratio (SNR) enhancement by the factor of 1.7 was shown when the first harmonic is used for measurement‐based image reconstruction compared to when it is omitted. Conclusions: In this paper, the first one‐dimensional multifrequency magnetic particle imaging (mf‐MPI) that features adjustable excitation frequencies from 500 Hz to 20 kHz is presented. The device will be used to study the principle of multiparameter estimation by employing multifrequency excitation. [ABSTRACT FROM AUTHOR]

In industrial domains such as manufacturing control, a trend away from centralized planning and scheduling towards more flexible distributed agent-based approaches could be observed over recent years. To be of practical relevance, the local control mechanisms of the autonomous agents must be able to dependably adhere and dynamically adjust to complex numeric goal systems like business key performance indicators in an economically beneficial way. However, planning with numeric state variables and objectives still poses a challenging task within the field of artificial intelligence (AI). In this article, a new general-purpose AI planning approach is presented that operates in two stages and extends existing domain-independent modeling formalisms like PDDL with continuous (i.e., infinite-domain) numeric action parameters, which are currently still unsupported by state-of-the-art AI planners. In doing so, it enables the solution of mathematical optimization problems at the action level of the planning tasks, which are inherent to many real-world control problems. To deal with certain difficulties concerning reliable and fast detection of action applicability that arise when planning with real-valued action parameters, the implemented planner allows resorting to an adjustable “satisficing” strategy by means of partial execution and subsequent repair of infeasible plans over the course of time. The functioning of the system is evaluated in a multi-agent simulation of a shop floor control scenario with focus on the effects the possible problem cases and different degrees of satisficing have on attained plan quality and total planning time. As the results demonstrate the basic practicability of the approach for the given setting, this contribution constitutes an important step towards the effective and dependable integration of complex numeric goal systems and non-linear multi-criteria optimization tasks into autonomous agent-controlled industrial processes in a reusable, domain-independent way. [ABSTRACT FROM AUTHOR]

• The antipruritic natural coumarin induces calcium-influx mainly in mouse DRG neurons expressing TRPA1. • Osthole activates calcium-influx and inward currents in HEK 293 cells expressing human TRPA1. • Osthole is a non-electrophilic TRPA1-agonist targeting the motif S873/T874. The naturally occurring coumarin osthole has antipruritic properties, and recent reports suggest that this effect is due an inhibition or desensitization of the cation channels TRPV1 and TRPV3. Osthole was also suggested to activate TRPA1, an effect that should rather be pruritic than antipruritic. Here we characterized the effects of osthole on TRPA1 by means of ratiometric calcium imaging and patch clamp electrophysiology. In HEK 293 expressing human (h) TRPA1, osthole induced a concentration-dependent increase in intracellular calcium that was inhibited by the TRPA1-inhibitor A967079. In mouse dorsal root ganglion (DRG) cells, osthole induced a strong calcium-influx that was partly mediated by TRPA1. Osthole evoked fully reversible membrane currents in whole-cell as well as cell-free inside-out recordings on hTRPA1. Osthole failed to activate the mutant hTRPA1-S873V/T874L, a previously described binding site for the non-electrophilic TRPA1-agonists menthol and carvacrol. The combined application of osthole and carvacrol diminished channel activation, suggesting a competitive binding. Finally, osthole failed to activate TRPM8 and TRPV4 but induced a modest activation of hTRPV1 expressed in HEK 293 cells. We conclude that osthole is a potent non-electrophilic agonist of TRPA1. The relevance of this property for the antipruritic effects needs to be further explored. [ABSTRACT FROM AUTHOR]

Background: This study aimed at evaluating the use of hypnotics and other psychotropics for sleep disturbances in nursing home residents. Patients and methods: Data obtained from the Resident Assessment Instrument (2.0) were linked to health insurance medication claims data. This secondary analysis was based on data of 2109 residents captured in 37 nursing homes in 2008. Results: According to nurses' rating, 9.8 % of residents had difficulties in initiating or maintaining sleep on a daily or almost daily basis (6-7 days/week), a further 23.5 % on 1-5 days/week. In all, 16.7 % of the residents were treated with hypnotics (of which 3.9 % with benzodiazepines and 3.4 % with Z-drugs), and 47.4 % of the residents received antipsychotics. Prescribing of hypnotics (p < 0.001), antipsychotics (p < 0.001), and anxiolytics (p < 0.001) was significantly associated with sleep disturbances in residents, but not of antidepressants (p = 0.903). Conclusion: Although sleep disturbances were very common among the observed residents, traditional hypnotics were used only moderately. However, high prescription rates of antipsychotics must be evaluated critically. [ABSTRACT FROM AUTHOR]

The mobility of toxic metals and the transformation of organic pollutants in the environment are influenced and in many cases even controlled by iron minerals. Therefore knowing the factors influencing iron mineral formation and transformation by Fe(II)-oxidizing and Fe(III)-reducing bacteria is crucial for understanding the fate of contaminants and for the development of remediation technologies. In this study we followed mineral formation by the nitrate-reducing Fe(II)-oxidizing strain Acidovorax sp. BoFeN1 in the presence of the crystalline Fe(III) (oxyhydr)oxides goethite, magnetite and hematite added as potential nucleation sites. Mössbauer spectroscopy analysis of minerals precipitated by BoFeN1 in 57Fe(II)-spiked microbial growth medium showed that goethite was formed in the absence of mineral additions as well as in the presence of goethite or hematite. The presence of magnetite minerals during Fe(II) oxidation induced the formation of magnetite in addition to goethite, while the addition of humic substances along with magnetite also led to goethite but no magnetite. This study showed that mineral formation not only depends on the aqueous geochemical conditions but can also be affected by the presence of mineral nucleation sites that initiate precipitation of the same underlying mineral phases. [ABSTRACT FROM AUTHOR]

Abstract: Context: Sperm retrieval in combination with IVF/ICSI is the only medical procedure for an azoospermic man to father a child. Different techniques, especially testicular sperm extraction (TESE), have evolved over time and have dramatically improved the outlook for men with testicular azoospermia. However sperm retrieval rates are associated not only with the operation proposed but especially with a distinct pattern of prognostic factors that must be effectively managed for all these infertile patients for their best benefit. Objectives: To review the etiology, clinical work-up including operative techniques, and prognostic factors for testicular sperm retrieval in azoospermic men to maximin clinical benefit by these procedures. Evidence Acquisition: Data from basic and clinical studies with a defined, standardized approach pre- and postoperatively were analyzed. Evidence Synthesis: Different standardized surgical techniques can be offered to extract spermatozoa of azoospermic men from either the epididymis and/or the testis for ICSI. Sperm retrieval offers a treatment for both patients with testicular azoospermia and men with obstructive azoospermia in cases where microsurgical refertilization is not an option or has already failed. Among surgical techniques testicular sperm extraction (TESE) and microsurgical epididymial sperm aspiration (MESA) have become the most popular techniques. However, also percutaneous techniques are employed due their easy feasibility and low costs. By utilizing these techniques together with kryopreservation of extracted spermatozoa a single surgical intervention is able to provide spermatozoa for several ICSI attempts. Extensive surgical interventions in the testis of azoospermic patients have raised concerns about the potential influence on the endocrine compartment of the testis, particularly in patients with small testes and low levels of testosterone. Conclusions: Testicular sperm retrieval is a feasible and successful procedure. Testicular spermatozoa can be retrieved from the testis in up to 70% of patients, even in cases with testicular azoospermia and severe disorders of spermatogenesis. However, surgical damage of the testis might also compromise the interstitial compartment of the testis with testosterone deficiency as a consequence. Conclusively, endocrine follow-up can be considered mandatory. [Copyright &y& Elsevier]

BACKGROUND: Pre-, peri-, or postnatal childloss can have devastating consequences for bereaved families. This study explored the long-term sequelae of these experiences for the young adult siblings' psychological well-being and the perceived quality of parenting received during participants' first 16 years of life. METHODS: A bereaved group of young adult siblings was compared to a non-bereaved group on the Parent Bonding Instrument, the Rosenberg Self-esteem Scale and the Mental Health Index-5. RESULTS: The loss group reported their mothers, but not their fathers, to have been more protective/controlling than non-bereaved participants. No differences between the loss group and the comparison group were found for parental care, their own mental health or self-esteem. Those participants whose siblings died during the peri/post-natal period perceived their parents as more controlling than the miscarriage group as well as the non-bereaved group. Higher protection scores were evident among those born subsequent to the loss than those who were born before. Lower levels of protection were associated with better mental health across all groups. In the non-bereaved group lower levels of protection were associated with better self-esteem, but in the bereaved group a different even opposite pattern was shown. CONCLUSIONS: Young adults who lost a sibling when they themselves were under 5 recall their mothers as more protective/controlling than non-bereaved groups, although they do not report less care nor differ in mental health nor self-esteem. Higher levels of parental protection/control were found where the child was born subsequent to loss and for peri/post-natal loss rather than miscarriage. While high protection was associated with poorer mental health regardless of loss this may not be necessarily disadvantageous to the child's self-esteem. Differences with regard to parent gender were found. [ABSTRACT FROM AUTHOR]

Background. Pre-, peri-, or postnatal childloss can have devastating consequences for bereaved families. This study explored the long-term sequelae of these experiences for the young adult siblings' psychological well-being and the perceived quality of parenting received during participants' first 16 years of life. Methods. A bereaved group of young adult sibilings was compared to a non-bereaved group on the Parent Bonding Instrument, the Rosenberg Self-esteem Scale and the Mental Health Index-5. Results. The loss group reported their mothers, but not their fathers, to have been more protective/controlling than non-bereaved participants. No differences between the loss group and the comparison group were found for parental care, their own mental health or self-esteem. Those participants whose siblings died during the peri/post-natal period perceived their parents as more controlling than the miscarriage group as well as the non-bereaved group. Higher protection scores were evident among those born subsequent to the loss than those who were born before. Lower levels of protection were associated with better mental health across all groups. In the nonbereaved group lower levels of protection were associated with better self-esteem, but the bereaved group a different even opposite pattern was shown. Conclusions. Young adults who lost a sibling when they themselves were under 5 recall their mothers as more protective/controlling than non-bereaved groups, although they do not report less care nor differ in mental health nor self-esteem. Higher levels of parental protection/control were found where the child was born subsequent to loss and for peri/post-natal loss rather than miscarriage. While high protection was associated with poorer mental health regardless of loss this may not be necessarily disadvantageous to the child's self-esteem. Differences with regard to parent gender were found. [ABSTRACT FROM AUTHOR]

The study of bionic metamaterials with unique properties has gained increasing attention in recent years. This article introduces a double fish‐shaped metamaterial (DFSM) and investigates its elasticity and deformation behaviors. The Poisson's ratio of DFSM is derived from the energy principle and Mohr's theorem. The bending deformation behaviors of DFSM under given elastic strains are observed and tested by using the homemade experimental bench, which is further compared with finite element (FE) methods. The FE results show good agreement with experimental results. The bending vibration of DFSM under elastic tension is recorded and analyzed using a homemade prestrain bench in conjunction with a high‐speed camera. The present study proposes a straightforward and valid approach for incorporating the variable bending stiffness and the variable bending damping into DFSM. The revealed mechanical properties of DFSM in this article demonstrate its potential for engineering applications that require multistiffness and multidamping capabilities. [ABSTRACT FROM AUTHOR]

Transient receptor potential (TRP) ion channels are involved in the surveillance or regulation of the acid-base balance. Here, we demonstrate that weak carbonic acids, including acetic acid, lactic acid, and CO2 activate and sensitize TRPV2 through a mechanism requiring permeation through the cell membrane. TRPV2 channels in cell-free inside-out patches maintain weak acid-sensitivity, but protons applied on either side of the membrane do not induce channel activation or sensitization. The involvement of proton modulation sites for weak acid-sensitivity was supported by the identification of titratable extracellular (Glu495, Glu561) and intracellular (His521) residues on a cryo-EM structure of rat TRPV2 (rTRPV2) treated with acetic acid. Molecular dynamics simulations as well as patch clamp experiments on mutant rTRPV2 constructs confirmed that these residues are critical for weak acid-sensitivity. We also demonstrate that the pore residue Glu609 dictates an inhibition of weak acid-induced currents by extracellular calcium. Finally, TRPV2-expression in HEK293 cells is associated with an increased weak acid-induced cytotoxicity. Together, our data provide new insights into weak acids as endogenous modulators of TRPV2. Synopsis: The transient receptor potential vanilloid 2 (TRPV2) ion channel controls important physiological and pathophysiological processes, but its regulation by acid species remains unclear. Here, combined structure-function work uncovers activation of rat TRPV2 by endogenous weak acids and offers a detailed characterization of its membrane permeation-dependent acid sensitivity. Weak, but not strong acids activate and sensitize TRPV2. Membrane permeability of weak acids is required for TRPV2 activation. Positively charged S4-S5 linker residue His521 controls TRPV2 weak acid-sensitivity. Extracellular calcium inhibits weak acid-induced TRPV2 activation. Weak acetic acids are endogenous agonists of rat TRPV2 acting via permeation through the cell membrane. [ABSTRACT FROM AUTHOR]

Abstract: High temperature loads in cutting processes can cause high tool wear and damages in the subsurface zone of the workpiece. Especially, the interaction between different cutting parameters affects the thermal loads in the cutting zone. Hence, the knowledge of temperatures in cutting processes is an important factor, and it is the main focus of current investigations. Therefore, this paper deals with an in-process monitoring system for the resulting temperatures in a turning process. In contrast to the investigations performed hitherto, this research deals with a new tool sensor system for temperature measurement. This sensor system is realized by a PVD coating of a Nickel and a Nickel–Chromium layer on the rake face of cutting inserts. On the junction points of this layer system, three thermocouples are deposited. The development of the coating system and the resulting measurement is shown. Additionally, the results are discussed in comparison to thermal imaging system and conventional thermocouples. [Copyright &y& Elsevier]

The association between chronic inflammatory/infectious diseases of the male reproductive tract and the presence of antisperm antibodies (ASA) in semen is still controversial. We compared the results of the mixed agglutinin reaction (MAR) test and immunobead test for detecting ASA type IgG and IgA in 133 patients attending our special outpatient department for andrological infections and evaluated the differences in the detection rate of ASA. Patients were divided into three groups: a study group that included 79 patients with symptomatic nonacute inflammatory/infectious diseases of the seminal tract, a control group ( n = 44) and a third group of men with a history of successful vasectomy reversal ( n = 10). The two tests correlated in a statistically significant manner for the detection of IgG and IgA in all groups. The overall positive detection rate of clinical significant levels of IgG and IgA was 2.5% and 1.3% (respectively) in the patients with inflammation/infection of the seminal tract. No statistical significant difference in the detection rate of ASA levels between the inflammatory/infectious group and the controls was detected. The results of the MAR test and immunobead test have a statistical significant correlation and their results provide evidence that there is no association between inflammatory/infectious diseases of the male reproductive tract and the presence of ASA in semen. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE: Selective cyclo-oxygenase-2 (COX-2) inhibitors provide postoperative pain relief similar to conventional NSAIDs. However, many of these non-opioid analgesics are available only for oral administration, and are therefore ineffective in patients experiencing postoperative nausea or vomiting. The aim of this study was to compare the analgesic efficacy of the COX-2 inhibitor parecoxib with that of dipyrone (metamizole) administered intravenously for 48 hours after vaginal hysterectomy. METHODS: Fifty women undergoing vaginal hysterectomy under general anaesthesia were randomly assigned to two groups: the parecoxib group, who received intravenous parecoxib 40 mg intraoperatively and every 12 hours after surgery over a period of 48 hours, and the dipyrone group, who received intravenous dipyrone 2.5 g injected intraoperatively, followed by dipyrone 1 g every 6 hours after surgery over a period of 48 hours. Because of the double-blinded study protocol, patients in the parecoxib groups were required to receive placebo infusions 6, 18, 30 and 42 hours after the operation. Visual analogue scale (VAS [scale 0–10]) scores were recorded 0.5, 1, 2, 3, 4, 6, 9, 12, 15, 18, 24, 36 and 48 hours after surgery. To assess the cumulative opioid administration, all patients were fitted with an intravenous patient-controlled analgesia (PCA) device containing the opioid piritramide. An α value of 0.05 was considered statistically significant. RESULTS: VAS scores did not differ between groups with one exception: VAS scores were lower in the parecoxib group 12 hours after surgery than in the dipyrone group (1 and 2, respectively; p < 0.05). No significant differences in cumulative piritramide administration were measured between groups 1 hour or 24 hours after surgery (parecoxib 14.7 [+/- SD 4.4] and 30.6 [+/- 12.8] mg, respectively; dipyrone 11.8 [+/- 4.9] and 36.5 [+/- 10.7] mg, respectively). CONCLUSIONS: Parecoxib 40 mg twice daily provides postoperative pain relief equivalent to that of dipyrone 4 g daily during the first 48 hours in patients after hysterectomy. [ABSTRACT FROM AUTHOR]

Over 94 million domestic cats are susceptible to cancers and other common and rare diseases. Whole exome sequencing (WES) is a proven strategy to study these disease-causing variants. Presented is a 35.7 Mb exome capture design based on the annotated Felis_catus_9.0 genome assembly, covering 201,683 regions of the cat genome. Whole exome sequencing was conducted on 41 cats with known and unknown genetic diseases and traits, of which ten cats had matching whole genome sequence (WGS) data available, used to validate WES performance. At 80 × mean exome depth of coverage, 96.4% of on-target base coverage had a sequencing depth > 20-fold, while over 98% of single nucleotide variants (SNVs) identified by WGS were also identified by WES. Platform-specific SNVs were restricted to sex chromosomes and a small number of olfactory receptor genes. Within the 41 cats, we identified 31 previously known causal variants and discovered new gene candidate variants, including novel missense variance for polycystic kidney disease and atrichia in the Peterbald cat. These results show the utility of WES to identify novel gene candidate alleles for diseases and traits for the first time in a feline model. [ABSTRACT FROM AUTHOR]

Spatial distribution patterns of benthic organisms are the focus of various faunal marine studies. However, data on horizontal and bathymetric distribution of the deep-sea macrofauna are still scattered and incomplete, and conclusions are usually based on a low number of samples. Spatial distribution of benthic macrofauna was studied based on the material collected during the RV Polarstern expedition ARK-XXVII/2 in July 2012. Eleven stations along the latitudinal transect at the LTER (Long-Term Ecological Research) observatory HAUSGARTEN in the Fram Strait were taken at depths of about 2.3–2.7 km. Macrofauna was obtained using the box corer. A half core (0.125 m 2 ) was taken at each station and four subcores (0.03 m 2 ) were taken from each core and used for the quantitative analysis. The results suggest that a single, highly variable community with the dominance of polychaetes Galathowenia fragilis and Myriochele heeri inhabits the studied area. No latitudinal gradient in the community was revealed. The prevalence of a spatial variability in the community structure at a scale larger than the full sample per station (0.125 m 2 ) was detected. Several abundant taxa (e.g. the polychaetes Prionospio sp. and Galathowenia fragilis ) tend to form patches within a full sample. [ABSTRACT FROM AUTHOR]

Abstract: Increasing demands on the cutting process require a fundamental analysis concerning the design as well as the material selection for cutting insert and its wear protection. Apart from monitoring the wear and the cutting forces, the knowledge of the developed temperatures during cutting process is essential and necessary. In this work, an innovative technology was employed to measure in situ the temperature development during cutting process. The measurement was based on the Seebeck-effect. Coating adhesion was systematically analyzed and optimized by varying the pretreatment conditions. Furthermore, the design of masks was enhanced and finally turning experiments were carried out to scrutinize the efficiency of deposited temperature sensors in cutting tests. [Copyright &y& Elsevier]

Abstract: Analyses of energy consumption in manufacturing processes have shown that most of the energy is needed for the production of material such as aluminum or steel and not for further manufacturing steps like forming or cutting. To reduce energy consumption and also a reduction of CO2 emissions in manufacturing processes, a reduction of the amount of primary material, made from first melting after mining, as well as secondary material, made from melting of recycled scrap material, is needed. In this work, the re-use of aluminum AA-6060 scrap based on milling and turning chips, by direct hot extrusion is presented. To prevent further use of primary aluminum or melting of the chips the process aims at using compacted chips as billet material. The production of the chips as well as the compaction of billets, the extrusion process and the properties of the final profile is presented. In addition to the use of chips based on one alloy the mixture and extrusion of aluminum and SiC particles is presented. The investigations have shown that using billets made of AA-6060 chips can lead to similar mechanical and microstructural properties as using of conventional cast aluminum billets. Investigations on an additional cutting or drilling of the extruded profiles have shown even improved properties due to a reduced chip length. [Copyright &y& Elsevier]

There is a consensus on the diagnostic management of bacterial prostatitis (acute and chronic). In chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) the diagnostic approach remains unclear, because inflammatory and noninflammatory CP/CPPS might be one entity with varying findings over time. The WHO definition of male accessory gland infection does not differentiate between prostatitis, epididymitis, and other inflammatory alterations of the urethral compartment. The definition therefore cannot be further accepted as a rational tool for the diagnosis of prostatitis and related diseases in urological andrology. Therapy in infectious prostatitis is standardised and antibiotics are the primary agents. Andrological implications are well defined, side-effects are minimal. CP/CPPS therapy has the goal to reduce pelvic pain. However, treatment regimens are not as standardised. Andrological side-effects are well defined and mainly due to the functional background of these agents. [ABSTRACT FROM AUTHOR]

This study aimed to develop and validate a brain injury outcome measure with sufficient discriminatory power for use in a post-acute rehabilitation setting. A 56-item questionnaire - the Post- acute Rehabilitation Measure (PARM) - covering disability and participation restriction was validated against the Functional Independence Measure and Functional Assessment Measure (RM+FAM) using both carers and the rehabilitation team as respondents. Participants were 67 patients with acquired brain injury from 12 post-acute rehabilitation facilities. PARM showed a lower mean score than FIM+FAM on all sections except emotions. Correlations between sections of PARM and FIM+FAM ranged 0.63-0.89. Test-retest reliability ranged 0.84-a 97. Inter-rater reliability (carer vs team) was more variable. PARM is therefore a reliable and valid measure for post-acute outpatient rehabilitation that has the advantage of being completed by either the carer or the team. It shows fewer ceiling effects than FIM+FAM in this population. [ABSTRACT FROM AUTHOR]

Background: During conventional cardiac surgery ischemia and reperfusion may cause excessive production of reactive oxygen species leading to tissue damage including early arrhythmias. We therefore assessed the kinetics of markers of radical stress including oxidized and reduced glutathione (GSSG/GSH), oxidized proteins (PCG) and malondialdehyde (MDA), and tested the hypothesis that different steroid treatments inhibit these markers and early reperfusion-associated supraventricular and ventricular extrasystolic beats.Methods: In a randomized, controlled, blinded, prospective trial 36 patients received a preoperative infusion of methylprednisolone (MP, 15 mg kg-1, n = 12), tirilazad mesylate (TM, 10 mg kg-1, n = 12) or placebo (PL, NaCl, n = 12). Coronary sinus and arterial blood was drawn at baseline and 2, 5, 15, 30, 60 and 240 min after aortic declamping. Holter-ECG analysis was used to identify arrhythmias.Results: Cardiac GSSG release occurred very early (< 15 min) and was not significantly attenuated by either drug treatment. Cardiac PCG production showed biphasic increases, lasted > 4 h and was significantly reduced only by TM. Cardiac MDA release was short (< 30 min) and significantly reduced by MP and TM. Neither treatment had a significant influence on the early occurrence of ventricular or supraventricular arrhythmias. The number of patients needing cardioversions or defibrillations also were not different.Conclusions: The results indicate that cardiac production of reactive oxygen species occurs after reperfusion in humans and is not inhibited by steroid treatment. Steroid treatment effectively reduces lipid peroxidation during cardiac surgery but has no influence on arrhythmias. [ABSTRACT FROM AUTHOR]

The incidence and severity of cognitive deficits after surgery for aneurysmal subarachnoid haemorrhage and their relationship to aneurysm site remains controversial. The aim of this study was to investigate the pattern of regional cerebral blood flow which exists in patients one year post-surgery and to identify whether different patterns exist which may be related to the type of cognitive deficit or the location of the aneurysm. 62 patients underwent cognitive assessment and HMPAO SPECT imaging at a mean time of 12 months following surgery. Results were compared to those from healthy control subjects (n = 55 for neuropsychological testing; n = 14 for SPECT imaging). In the patient group, significant stable cognitive deficits occurred in all cognitive domains but no cognitive measure differentiated aneurysm site. On SPECT images, statistical parametric mapping identified a large common area of subcortical hypoperfusion in the patient group as a whole. The findings of this study suggest a possible link between reduced subcortical function and the extent and severity of cognitive deficits. [ABSTRACT FROM AUTHOR]