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A New Method of Designing High-Sensitivity Low-Dimensional Photodetectors.
professional counselor). When a peer counselor provided the message, loss framing reduced self-stigma toward seeking counseling to a greater degree than gain framing and, in turn, induced more favorable attitudes toward the behavior among people with a high severity of depressive symptomatology. Those findings provide theoretical insights into the masspersonal communication approach to health promotion and inform promising communication strategies to promote counseling-seeking behavior among people with depressive symptomatology.Editor's note After a distinguished career in academic medicine, including stints at the Children's Hospital of Philadelphia, INSERM and Genethon, Federico Mingozzi joined Spark Therapeutics 3 years ago as chief scientific officer. Mingozzi aims to build on the company's landmark success with Luxturna, the approved therapy for certain retinal diseases such as the type 2 version of Leber's congenital amaurosis. In this exclusive interview with Human Gene Therapy Executive Editor Kevin Davies, Mingozzi discusses his career highlights and surveys the hopes and challenges facing the human gene therapy community.Earworms refer to catchy tunes that run repeatedly through a person's mind. Empirical literature regarding earworms is scant; however, some researchers have conceptualized the phenomenon as an unwanted intrusion in the context of obsessive-compulsive disorder. The current study expands upon past research by characterizing the experience of earworms and examining associations of earworm-related distress and interference with theoretical constructs of interest, including obsessive beliefs and experiential avoidance. Two hundred forty participants completed an online survey regarding the experience of musical obsessions (e.g., duration, frequency, distress) and related theoretical constructs (e.g., experiential avoidance) of interest. Descriptive results regarding the frequency, duration, and associated distress and interference of earworms are presented. Furthermore, results reveal that experiential avoidance is a unique predictor of earworm-related distress and interference. Results suggest that interference and distress due to earworms may be related to attempts to suppress them. Study conclusions, limitations, and directions for future research are discussed.Studies investigating the impact of depressive symptoms on obsessive-compulsive disorder (OCD) treatment have yielded mixed findings. The purpose of the study is to extend previous research, which primarily used outpatient samples, to determine whether depression affects OCD treatment outcome among patients receiving intensive residential treatment. OCD patients receiving residential treatment based primarily on exposure and response prevention (ERP) provided data regarding symptoms of depression and OCD at admission and discharge. Patients reported large and significant reductions in OCD symptoms over the course of treatment. Change in OCD symptoms was not significantly affected by depressive symptoms, including patients with severe depressive symptoms. Change in depressive symptoms over the course of treatment was, however, robustly related to change in OCD symptoms, especially among patients who began treatment with severe symptoms of depression. These findings suggest that cognitive-behavior therapy delivered in a residential treatment setting drastically reduces OCD symptoms regardless of depressive symptoms.The aim of this study is to replicate the findings from previous research about the psychometric properties of the Mandarin Chinese version of the Obsessive-Compulsive Inventory-Revised (OCI-R), which assesses the presence of symptoms obsessive-compulsive disorder and the distress associated with those symptoms. The final clinical sample included 80 participants from multiple psychiatric outpatient clinics in China. Participants completed the following questionnaires the OCI-R, the Depression, Anxiety, and Stress Scale (DASS-21), the Yale-Brown Obsessive-Compulsive Scale-II (Y-BOCS-II), and the Clinical Global Impressions Scale, Severity (CGI-S). The Mandarin Chinese version of the OCI-R demonstrated good internal consistency for the total scale and each subscale. Good convergent and divergent validity was established. The Mandarin Chinese version of the OCI-R demonstrated good psychometric properties. Further research is needed to examine the factor structure of the Chinese version of the OCI-R and the extent to which it aligns with the original version.The authors investigated the effectiveness of acceptance and commitment therapy (ACT) for the treatment of death anxiety and obsessive-compulsive disorder (OCD) with eight adult women in Iran. The ACT protocol was conducted in weekly solo sessions with each participant for 8 weeks (45 minutes each). The results were analyzed by visual analysis method and improvement percentage. ACT resulted in a 60%-80% decrease in death anxiety and a 51%-60% decrease in obsessive-compulsive symptoms, thereby indicating promise for ACT as a treatment for OCD and death anxiety.
Anticalin proteins are engineered versions of lipocalins that constitute a novel class of clinical-stage biopharmaceuticals. The lipocalins exhibit a central β-barrel with eight antiparallel β-strands and an α-helix attached to its side. Four structurally variable loops at the open end of the β-barrel form a pronounced binding pocket, which can be reshaped to generate specificities toward diverse disease-relevant molecular targets.

This article reviews the current status of Anticalin engineering, from the basic principles to the development of Anticalins with high target affinity and specificity via combinatorial protein design and directed evolution, including examples of Anticalin-based drug candidates under preclinical and clinical development.

Combinatorial gene libraries together with powerful molecular selection techniques have enabled the expansion of the natural ligand specificities of lipocalins from small molecules to peptides and proteins. This biomolecular concept has been validated by strucbodies with promising and potentially superior features as next-generation biologics.In recent years, regulatory bodies have increasingly recognized the utility of real-world evidence (RWE) for supplementing and supporting clinical trial data in new drug applications. Nevertheless, the integration of RWE into established regulatory processes is complex and the generation of 'regulatory-grade' real-world data faces operational, methodological, data-related and policy-related challenges. In parallel with this evolving role for RWE, immuno-oncology therapies have emerged as leading cancer treatments and are expected to continue to play a central role in the future. In this article, we review the current literature on the use of RWE for regulatory submissions, with a focus on novel anticancer immunotherapies, and discuss the utility and current limitations of RWE in the context of drug development and regulatory approvals.Splenic injuries are mostly treated with nonoperative management (NOM) with observation to monitor for continued hemorrhage and holding early chemical DVT prophylaxis to reduce the risk of NOM failure. Eberle et al demonstrated chemoprophylaxis prior to 72 hours didn't increase failure rate of NOM. We chose to extrapolate this finding and compare outcomes in high-grade splenic injuries (HGSI) with chemoprophylaxis before and after 48 hours. From January 2013 to December 2017, 104 patients with HGSI received chemoprophylaxis with unfractionated heparin (UH) or low molecular weight heparin (LMWH) within 72 hours of diagnosis. Of these, 8 patients received chemoprophylaxis within 24 hours, 46 between 24 and 48 hours, and 50 patients between 48 and 72 hours. This population consisted of 70 males and 34 females, with an average age of 40.1 years. The average ISS was 23 and the majority (77%) were grade 3 injuries. We observed 6 failures of NOM 1 in the 24 groups or between the less then 48 hour and 48-72 hour groups. A linear regression analysis created a model describing the time to initiation of DVT prophylaxis using age, sex, splenic injury grade, and ISS; the failure rate decreased by 0.00002% for each hour prior to giving DVT prophylaxis, with a P value of .111. We conclude a noninferiority statement that DVT prophylaxis prior to 48 hours does not increase the risk of NOM failure.Glomerular filtration rate (GFR) is acutely increased following a high-protein meal or systemic infusion of amino acids. The mechanisms underlying this renal functional response remain to be fully elucidated. Nevertheless, they appear to culminate in preglomerular vasodilation. Inhibition of the tubuloglomerular feedback signal appears critical. However, nitric oxide, vasodilator prostaglandins, and glucagon also appear important. The increase in GFR during amino acid infusion reveals a "renal reserve," which can be utilized when the physiological demand for single nephron GFR increases. This has led to the concept that in subclinical renal disease, before basal GFR begins to reduce, renal functional reserve can be recruited in a manner that preserves renal function. The extension of this concept is that once a decline in basal GFR can be detected, renal disease is already well progressed. This concept likely applies both in the contexts of chronic kidney disease and acute kidney injury. Critically, its corollary is that deficits in renal functional reserve have the potential to provide early detection of renal dysfunction before basal GFR is reduced. Selleckchem AZD5069 There is growing evidence that the renal response to infusion of amino acids can be used to identify patients at risk of developing either chronic kidney disease or acute kidney injury and as a treatment target for acute kidney injury. However, large multicenter clinical trials are required to test these propositions. A renewed effort to understand the renal physiology underlying the response to amino acid infusion is also warranted.Antenatal glucocorticoids improve outcomes among premature infants but are associated with hyperglycemia, which can exacerbate hypoxic-ischemic injury. It is still unclear how antenatal glucocorticoids or hyperglycemia modulate fetal cardiovascular adaptations to severe asphyxia. In this study, preterm fetal sheep received either saline or 12 mg im maternal dexamethasone, followed 4 h later by complete umbilical cord occlusion (UCO) for 25 min. An additional cohort of fetuses received titrated glucose infusions followed 4 h later by UCO to control for the possibility that hyperglycemia contributed to the cardiovascular effects of dexamethasone. Fetuses were studied for 7 days after UCO. Maternal dexamethasone was associated with fetal hyperglycemia (P less then 0.001), increased arterial pressure (P less then 0.001), and reduced femoral (P less then 0.005) and carotid (P less then 0.05) vascular conductance before UCO. UCO was associated with bradycardia, femoral vasoconstriction, and transient hypertension. For the first 5 min of UCO, fetal blood pressure in the dexamethasone-asphyxia group was greater than saline-asphyxia (P less then 0.001). However, the relative increase in arterial pressure was not different from saline-asphyxia. Fetal heart rate and femoral vascular conductance fell to similar nadirs in both saline and dexamethasone-asphyxia groups. Dexamethasone did not affect the progressive decline in femoral vascular tone or arterial pressure during continuing UCO. By contrast, there were no effects of glucose infusions on the response to UCO. In summary, maternal dexamethasone but not fetal hyperglycemia increased fetal arterial pressure before and for the first 5 min of prolonged UCO but did not augment the cardiovascular adaptations to acute asphyxia.
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