Clinical Trials of Potential Cognitive-Enhancing Drugs in Schizophrenia: What Have We Learned So Far?

In light of the number of studies conducted to examine the treatment of cognitive impairment associated with schizophrenia (CIAS), we critically reviewed recent CIAS trials. Trials were identified through searches of the website “www.clinicaltrials.gov” using the terms “schizophrenia AND cognition,” “schizophrenia AND neurocognition,” “schizophrenia AND neurocognitive tests,” “schizophrenia AND MATRICS,” “schizophrenia AND MCCB,” “schizophrenia AND BACS,” “schizophrenia AND COGSTATE,” and “schizophrenia AND CANTAB” and “first-episode schizophrenia AND cognition.” The cutoff date was 20 April 2011. Included trials were conducted in people with schizophrenia, the effects on cognition were either a primary or secondary outcome, and the effect of a pharmacologically active substance was examined. Drug challenge, pharmacokinetic, pharmacodynamic, or prodrome of psychosis studies were excluded. We identified 118 trials, with 62% using an add-on parallel group design. The large majority of completed trials were underpowered to detect moderate effect sizes, had ≤8 weeks duration, and were performed in samples of participants with chronic stable schizophrenia. The ongoing add-on trials are longer, have larger sample sizes (with a number of them being adequately powered to detect moderate effect sizes), and are more likely to use a widely accepted standardized cognitive battery (eg, the MATRICS Consensus Cognitive Battery) and MATRICS guidelines. Ongoing studies performed in subjects with recent onset schizophrenia may help elucidate which subjects are most likely to show an effect in cognition. New insights into the demands of CIAS trial design and methodology may help increase the probability of identifying treatments with beneficial effect on cognitive impairment in schizophrenia.     

Rasmussen's Encephalitis with Concomitant Cortical Dysplasia: The Role of GluR3

Summary: The role of the glutamate receptor GluR3 in Rasmussen's encephalitis is actively under investigation. Autoimmune processes with this receptor as the target are currently theorized. We provide an additional case of pathologically proved Rasmussen's encephalitis (with concomitant cortical dysplasia) in the presence of antibodies against the GluR3 receptor.     

Point-of-Care and Label-Free Detection of Porcine Reproductive and Respiratory Syndrome and Swine Influenza Viruses Using a Microfluidic Device with Photonic Integrated Circuits

Swine viral diseases challenge the sector’s sustainability by affecting productivity and the health and welfare of the animals. The lack of antiviral drugs and/or effective vaccines renders early and reliable diagnosis the basis of viral disease management, underlining the importance of point-of-care (POC) diagnostics. A novel POC diagnostic device utilizing photonic integrated circuits (PICs), microfluidics, and information and communication technologies for the detection of porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza A (SIV) was validated using spiked and clinical oral fluid samples. Metrics including sensitivity, specificity, accuracy, precision, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated to assess the performance of the device. For PRRSV, the device achieved a sensitivity of 83.5%, specificity of 77.8%, and DOR values of 17.66, whereas the values for SIV were 81.8%, 82.2%, and 20.81, respectively. The POC device and PICs can be used for the detection of PRRSV and SIV in the field, paving the way for the introduction of novel technologies in the field of animal POC diagnostics to further optimize livestock biosecurity.     

Comparing Digital Therapeutic Intervention with an Intensive Obesity Management Program: Randomized Controlled Trial

In this study, we evaluated whether the digital program Vitadio achieves comparable results to those of an intensive in-person lifestyle intervention in obesity management. This is a 12-month prospective, randomized controlled trial. Obese patients with insulin resistance, prediabetes or type 2 diabetes were included. The intervention group (IG) used Vitadio. The control group (CG) received a series of in-person consultations. Body weight and various metabolic parameters were observed and analyzed with ANOVA. The trial is ongoing and the presented findings are preliminary. Among 100 participants (29% men; mean age, 43 years; mean BMI, 40.1 kg/m²), 78 completed 3-month follow-up, and 51 have completed the 6-month follow-up so far. Participants significantly (p < 0.01) reduced body weight at 3 months (IG: −5.9 ± 5.0%; CG: −4.2 ± 5.0%) and 6 months (IG: −6.6±6.1%; CG: −7.1 ± 7.1%), and the difference between groups was not significant. The IG achieved favorable change in body composition; significant improvement in TAG (−0.6 ± 0.9 mmol/l, p < 0.01), HDL (0.1 ± 0.1%, p < 0.05), HbA1c (−0.2 ± 0.5%, p < 0.05) and FG (−0.5 ± 1.5 mmol/l, p < 0.05); and a superior (p = 0.02) HOMA-IR reduction (−2.5 ± 5.2, p < 0.01). The digital intervention achieved comparable results to those of the intensive obesity management program. The results suggest that Vitadio is an effective tool for supporting patients in obesity management and diabetes prevention.     

Insights on Skin Quality and Clinical Practice Trends in Asia Pacific and a Practical Guide to Good Skin Quality from the Inside Out

ObjectiveWe sought to examine the current skin quality trends and gaps in clinical practice in the Asia Pacific region and develop a practical guide to improve skin quality.MethodsMedical practitioners from 11 countries in the Asia Pacific region completed an online survey on current trends in skin quality treatment. A panel of 12 leading experts convened for a virtual meeting to develop a practical guide for skin quality improvement.ResultsA total of 153 practitioners completed the survey. The four most common skin quality issues were uneven skin tone, skin surface unevenness, skin laxity, and sebaceous gland hyperactivity and enlarged pores. Most practitioners reported using a combination of treatment modalities for each skin quality issue. It was also observed that each treatment modality could be used to treat several skin quality issues. A multimodal approach targeting different interrelated issues across the tissue planes was recommended for balanced results. The panel developed a practical guide for the appropriate combinations and sequence of treatments, and created treatment protocols for specific skin quality outcome goals. The guide employed an “inside-out” approach, treating the deeper tissue planes prior to the superficial layers to achieve harmonious results.LimitationsFuture studies are needed to support the recommended treatment protocols for skin quality improvement.ConclusionThese findings provide valuable insights on current skin quality trends and gaps in clinical practice. The practical guide provides a framework for practitioners to customize their treatment plan according to each patient’s needs.     

Paraaortic sentinel lymph node detection in intermediate and high-risk endometrial cancer by transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR)

ObjectiveWe aimed to evaluate the accuracy of sentinel lymph node (SLN) mapping with transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) to detect lymph node (LN) metastases, in patients with intermediate and high-risk endometrial cancer (EC), focusing on its performance to detect paraaortic involvement.MethodsProspective study including women with preoperative intermediate or high-risk EC, according to ESMO-ESGO-ESTRO consensus, who underwent SLN mapping using the TUMIR approach. SLNs were preoperatively localized by planar and single photon emission computed tomography/computed tomography images, and intraoperatively by gamma-probe. Immediately after SLN excision, all women underwent systematic pelvic and paraaortic lymphadenectomy by laparoscopy.ResultsThe study included 102 patients. The intraoperative SLN detection rate was 79.4% (81/102). Pelvic and paraaortic drainage was observed in 92.6% (75/81) and 45.7% (37/81) women, respectively, being exclusively paraaortic in 7.4% (6/81). After systematic lymphadenectomy, LN metastases were identified in 19.6% (20/102) patients, with 45.0% (9/20) showing paraaortic involvement, which was exclusive in 15.0% (3/20). The overall sensitivity and negative predictive value (NPV) of SLNs by the TUMIR approach to detect lymphatic involvement were 87.5% and 97.0%, respectively; and 83.3% and 96.9%, for paraaortic metastases. After applying the MSKCC SLN mapping algorithm, the sensitivity and NPV were 93.8% and 98.5%, respectively.ConclusionThe TUMIR method provides valuable information of endometrial drainage in patients at higher risk of paraaortic LN involvement. The TUMIR approach showed a detection rate of paraaortic SLNs greater than 45% and a high sensitivity and NPV for paraaortic metastases in women with intermediate and high-risk EC.     

Changes in retinal blood flow after application of topical dipivefrine 0.1 %

Hintergrund: Viele der antiglaukomat?sen Medikamente beeinflussen den okul?ren Blutflu?. Die Blutflu?ver?nderungen in der vorderen Uvea sind in der Literatur beschrieben. über den Effekt von Antiglaukomatosa auf den Blutflu? des hinteren Augenpols wird in neuerer Zeit vermehrt berichtet. Wir pr?sentieren eine Placebo-kontrollierte Studie mit Blick auf den kurz- und mittelfristigen Einflu? von topisch appliziertem Dipivefrin 0,1 % auf den retinalen und papill?ren Blutflu?.     

Ovarielle Suppression in der adjuvanten Therapie des Mammakarzinoms: GnRH-Analoga, Ovarektomie oder Radiomenolyse - "Stein der Weisen" statt "Kammer des Schreckens"?

Hintergrund: Bei prämenopausalen Patientinnen mit rezeptorpositiven Mammakarzinomen stellt die ovarielle Suppression einen wichtigen Schritt in der adjuvanten Therapie dar. Neben der GnRH-Analoga kommen hierfür die Ovarektomie oder die Radiomenolyse infrage. Patienten und Methode: Die vorliegende Arbeit stellt die Vorteile der einzelnen Therapieoptionen den therapiebedingten Nebenwirkungen gegenüber und vergleicht die Methoden untereinander. Ergebnisse: Wegen der Reversibilität und der Patientenakzeptanz sollten GnRH-Analoga besonders bei jüngeren prämenopausalen Patientinnen angewendet werden. In der Differentialtherapie von Patientinnen, bei denen die Langzeitnebenwirkungen einer iatrogen induzierten Menopause weniger zu befürchten sind, kommen auch die anderen Verfahren in Betracht. Hierbei stehen Radiomenolyse und Ovarektomie gleichwertig nebeneinander. Schlussfolgerung: Die differentialtherapeutische Entscheidung zu einer der Methoden sollte individualisiert werden. Auch bei zunehmendem Gebrauch der GnRH-Analoga stellt die Radiomenolyse eine zeitgemäße und kostengünstige Therapiemodalität besonders bei peri- oder prämenopausalen Patientinnen über 45 Jahren dar. Background: Ovarian suppression in the adjuvant treatment of perimenopausal women with breast cancer is an important option. The therapeutic goal can be accomplished by administration of GnRH-analogues, ovarectomy or radiocastration. Patients and Methods: We describe the advantages and the therapy related side effects and compare the different treatment modalities with each other. Results: Because of its reversibility and patients' compliance GnRH-analogues seem to be advantageous especially in younger premenopausal women. When longer term side effects of artificially induced menopause are less important, therapeutic alternatives such as radiocastration or ovarectomy are effective without obvious superiority between these options. Conclusion: Even in the background of the increasing use of GnRH-analogues radiocastration remains still a therapeutic alternative because of its cost-effectiveness and feasibility. This accounts especially for peri- or premenopausal women above the age of 45.     

Adhesiveness of human uterine epithelial RL95-2 cells to trophoblast: rho protein regulation

Embryo implantation involves adhesion of trophoblast cells to the epithelial lining of the endometrium. Using an in-vitro model to simulate this initial interaction, we previously reported that attachment of human trophoblast-like JAR spheroids to human uterine epithelial RL95-2 cells provokes a Ca(2+) influx in RL95-2 cells depending on apically localized integrin receptors. Here, we demonstrate that adhesiveness of RL95-2 cells for JAR spheroids, measured by a centrifugal force-based adhesion assay, is dependent on Rho GTPases, most likely RhoA. Cellular expression and distribution of RhoA were studied by fluorescence confocal microscopy, focusing on the localization of RhoA and F-actin within the adhesion sites between JAR and RL95-2 cells. Contact areas contained high amounts of RhoA and F-actin fibres near the plasma membrane. To determine whether Rho GTPases may influence JAR cell binding, we treated RL95-2 cells with Clostridium difficile toxin A, which specifically inactivates Rho GTPases. Toxin A treatment changed the subcellular distribution of endogenous RhoA in RL95-2 cells and altered RhoA and F-actin colocalization. Adhesion of JAR spheroids to RL95-2 cells treated with toxin A was largely suppressed. These data indicate that Rho GTPases, most likely RhoA, play an important role in uterine epithelial RL95-2 cells for trophoblast binding, and suggest that RhoA may be involved in local signalling cascades during early embryo implantation in vivo.