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Infrared scattering-type near-field optical microscopy, IR s-SNOM, and its broadband variant, nano-FTIR, are pioneering, flagship techniques for their ability to provide molecular identification and material optical property information at a spatial resolution well below the far-field diffraction limit, typically less than 25 nm. While s-SNOM and nano-FTIR instrumentation and data analysis have been discussed previously, there is a lack of information regarding experimental parameters for the practitioner, especially in the context of previously developed frameworks. Like conventional FTIR spectroscopy, the critical component of a nano-FTIR instrument is an interferometer. However, unlike FTIR spectroscopy, the resulting interference patterns or interferograms are typically asymmetric. Here, we unambiguously describe the origins of asymmetric interferograms recorded with nano-FTIR instruments, give a detailed analysis of potential artifacts, and recommend optimal instrument settings as well as data analysis parameters.

Lacking biomarkers in psychiatry calls for a valid and reliable assessment of psychopathology across mental disorders that is easy to use, bridges research and clinical care, and that can capture clinician and patient perspectives. Herein we propose, a novel, brief, transdiagnostic tool to assess and visualize symptom severity in different psychiatric disorders. The Transdiagnostic Global Impression - Psychopathology scale (TGI-P) is based on the Clinical Global Impression - Severity scale (CGI-S), which was originally designed to measure global illness severity in one score. The TGI-P covers 10 transdiagnostic symptom domains and similar to the CGI-S, it is rated on a 7-point Likert-scale from 1 (normal) to 7 (extreme). These ten domains include positive symptoms, negative symptoms, manic symptoms, depressive symptoms, addiction symptoms, cognitive symptoms, anxiety symptoms, sleep symptoms, hostility symptoms, and self-harm symptoms. The results are visually presented, thus simplifying the monitoring of symptoms, and facilitating discussion with patients and caregivers. As part of the development process, the TGI-P was surveyed among 36 psychiatrists from 3 countries. Importantly, over 80 % of them was "very positive" or "positive" about the concept of the tool, and most of them (70 %) reported willingness to use it in their everyday practice. Further psychometric development and testing of the TGI-P is underway alongside future TGI scales covering adverse events, functioning and satisfaction., Competing Interests: Declaration of competing interest Zs.B.D., Á.B., Gy.N., and T.B. are employees of Gedeon Richter Plc. C.U.C has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Adock Ingram, Alkermes, Allergan, Angelini, Aristo, Biogen, Boehringer-Ingelheim, Bristol-Meyers Squibb, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Delpor, Denovo, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Jamjoom Pharma, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Maplight, Mylan, Neumora Therapeutics, Neurocrine, Neurelis, Newron, Noven, Novo Nordisk, Otsuka, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Sage, Saladax, Seqirus, SK Life Science, Sumitomo Pharma America, Sunovion, Sun Pharma, Supernus, Tabuk, Takeda, Teva, Tolmar, Vertex, Viatris and Xenon Pharmaceuticals. He provided expert testimony for Janssen, Lundbeck and Otsuka. He served on a Data Safety Monitoring Board for Compass Pathways, Denovo, Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Kuleon Biosciences, LB Pharma, Medlink, Mindpax, and Quantic. R.S.M. has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC)and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics,Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Neurawell,Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals,Viatris, AbbVie, and Atai Life Sciences. Dr. S. Roger McIntyre is a CEO of Braxia Scientific Corp., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objectives : Navigation systems are designed to enhance surgical precision, improving patient outcomes and reducing the risk of implant misplacement. In this study, we have evaluated a novel orthopedic surgical platform that utilizes CT imaging with AI-based algorithms to automate several critical aspects of total hip arthroplasty. It contains three modules-preoperative planning, navigation during surgery, and follow-up analysis. The primary objective of the current study was to evaluate the precision of the navigation tool in cup placement, i.e., whether the information displayed for navigation correctly reflected the actual position of the implant. Materials and Methods : Surgery outcomes of 15 inter-rater measurements on human cadavers and 18 surgeries on patients who underwent total hip replacement using the navigation tool were analyzed. Results : In the inter-rater assessment, the mean errors were -0.31 ± 1.42° for anteversion, 1.06 ± 1.73° for inclination, and -0.94 ± 1.76 mm for cup position depth. In patients' surgeries, the mean errors were -0.07 ± 2.72° for anteversion, -0.2 ± 0.86° for inclination, and 0.28 ± 0.78 mm for cup depth. Conclusions : The navigation tool offers intra-operative guidance on notable precision in cup placement, thereby effectively mitigating the risk of cup malpositioning outside the patient-specific safe zone.

Ágota Barabássy,1 Barbara Sebe,1 Károly Acsai,1 István Laszlovszky,1 Balázs Szatmári,1 Willie R Earley,2 György Németh1 1Medical Division, Gedeon Richter Plc, Budapest, Hungary; 2Clinical Development, AbbVie, Madison, NJ, USACorrespondence: Ágota BarabássyMedical Division, Gedeon Richter Plc, Gyömrői út 19– 21, Budapest, 1103, HungaryTel +36 1 505 7017Fax +36 1 261 5815Email barabassya@richter.huBackground: Long-term treatment with antipsychotic agents is indicated for patients with schizophrenia, but treatment is associated with adverse events (AEs) that contribute to medication discontinuation and nonadherence. Understanding drug safety profiles is critical to avoid unwanted side effects. Cariprazine is a potent dopamine D3/D2 receptor partial agonist that is approved for the treatment of adults with schizophrenia (EU, US) and acute manic/mixed and depressive episodes associated with bipolar I disorder (US).Methods: Post hoc analyses were conducted to characterize the safety profile of cariprazine within the recommended 1.5– 6 mg/d dose range for schizophrenia; data from 8 short- or long-term clinical trials were analyzed.Results: In the pooled cariprazine-treated safety population (n=2048), the rate of study completion was 52.8%, with withdrawal of consent, insufficient response, and AEs the most common reasons for premature discontinuation. The most commonly reported AEs (> 10%) in the overall cariprazine-treatment group were akathisia (14.6%), insomnia (14.0%), and headache (12.1%); most AEs were considered mild (71.0%) or moderate (26.5%). Most akathisia was mild/moderate (97.5%) and > 93% of patients remained on treatment; akathisia events were managed by rescue medications (56.3%) or dose reduction (18.3%). The metabolic profile of cariprazine was neutral in patients with short- and long-term exposure; mean weight gain was 1 kg for overall cariprazine, with an AE of weight increased reported for 5.1%. Other AEs of special interest that occurred at > 3% for overall cariprazine were extrapyramidal disorder (7.0%), sedation (3.7%), and somnolence (3.1%); prolactin elevation, cognition impairment, sexual dysfunction, suicidality, and QT prolongation occurred at ≤ 1%.Conclusion: Akathisia, the most common cariprazine-related AE, was mild/moderate and resulted in few study discontinuations; symptoms were well managed and most patients remained on treatment. Results of this analysis indicated that cariprazine in the recommended dose range was safe and generally well tolerated in patients with schizophrenia.Trial Registration: Studies registered with ClinicalTrials.gov (NCT00404573, NCT01104779, NCT00694707, NCT01104766, NCT01104792, NCT00839852, and NCT01412060) and EudraCT (2012– 005485-36).Keywords: cariprazine, atypical antipsychotic, schizophrenia, safety and tolerability, post hoc analysis

Galectin-13 (Gal-13) is predominantly produced by the syncytiotrophoblast, while laeverin is expressed on the outgrowing extravillous trophoblast, and both are thought to be biomarkers of preeclampsia. The aim of this study was to assess the correlation between concentrations of Gal-13 and laeverin measured in maternal serum and amniotic fluid at 16-22 weeks of gestation and the sonographic assessment of the fetoplacental measurements. Fetal biometric data and placental volume and perfusion indices were measured in 62 singleton pregnancies. Serum and amniotic levels of Gal-13 and laeverin levels were measured using a sandwich ELISA. Both amniotic fluid and serum Gal-13 levels expressed a negative correlation to the plasma laeverin level in mid-pregnancy. Serum laeverin level correlated positively with the gestational length at delivery (β = 0.39, p < 0.05), while the amniotic laeverin level correlated well with the abdominal circumference of the fetus (β = 0.44, p < 0.05). Furthermore, laeverin level in the amnion correlated positively with the estimated fetal weight (β = 0.48, p < 0.05) and with the placental volume (β = 0.32, p < 0.05). Logistic regression analyses revealed that a higher circulating Gal-13 level represents a slightly significant risk factor (OR: 1.01) for hypertension-related diseases during pregnancy. It is a novelty that laeverin can be detected in the amniotic fluid, and amnion laeverin concentration represents a potential biomarker of fetoplacental growth.

Coherent light sources emitting in the terahertz range are highly sought after for fundamental research and applications. Terahertz lasers rely on achieving population inversion. We demonstrate the generation of terahertz radiation using nitrogen-vacancy centers in a diamond single crystal. Population inversion is achieved through the Zeeman splitting of the S = 1 state in 15 tesla, resulting in a splitting of 0.42 terahertz, where the middle S z = 0 sublevel is selectively pumped by visible light. To detect the terahertz radiation, we use a phase-sensitive terahertz setup, optimized for electron spin resonance (ESR) measurements. We determine the spin-lattice relaxation time up to 15 tesla using the light-induced ESR measurement, which shows the dominance of phonon-mediated relaxation and the high efficacy of the population inversion. The terahertz radiation is tunable by the magnetic field, thus these findings may lead to the next generation of tunable coherent terahertz sources.

Background : Swept-source anterior segment optical coherence tomography (SS-AS-OCT) is a suitable examination for the vitreolenticular interface. Methods : In a prospective study using Anterion (Heidelberg Engineering, Heidelberg, Germany), 102 eyes of 102 patients were examined in pupil dilation, preoperatively and 6 times over 1-year follow-up. Preoperatively anterior hyaloid membrane (AHM) visibility was determined with Imaging App with high reliability. Postoperatively capsular bag-AHM distance was measured on six points by using Metrics App. Results : The AHM was visible in 18.6% preoperatively and postoperatively as well (Group 1), 49% of the preoperatively adherent AHMs became visible (Group 2A), 32.4% remained attached (Group 2B). Group 1: the average deepest point on the first day was 782.5 ± 324.1 microns, and it significantly differed from the later follow-up values. Group 2A: the average deepest value was 184.1 ± 220.1 microns, and there was no statistically significant difference between the postoperative visit values. The difference between the groups was statistically significant at every location and at each time point. Conclusions : AS-SS-OCT can be used to check BS both preoperatively (with limitations) and postoperatively.

Until the late 1800s, drug development was a chance finding based on observations and repeated trials and errors. Today, drug development must go through many iterations and tests to ensure it is safe, potent, and effective. This process is a long and costly endeavor, with many pitfalls and hurdles. The aim of the present review article is to explore what is needed for a molecule to move from the researcher bench to the patients' bedside, presented from an industry perspective through the development program of cariprazine. Cariprazine is a relatively novel antipsychotic medication, approved for the treatment of schizophrenia, bipolar mania, bipolar depression, and major depression as an add-on. It is a D3-preferring D3-D2 partial agonist with the highest binding to the D3 receptors compared to all other antipsychotics. Based on the example of cariprazine, there are several key factors that are needed for a molecule to move from the researcher bench to the patients' bedside, such as targeting an unmet medical need, having a novel mechanism of action, and a smart implementation of development plans.

Introduction: Trophoblast-derived angiogenic factors are considered to play an important role in the pathophysiology of various complications of pregnancy. Human Leukocyte Antigen-G (HLA-G) belongs to the non-classical human major histocompatibility complex (MHC-I) molecule and has membrane-bound and soluble forms. HLA-G is primarily expressed by extravillous cytotrophoblasts located in the placenta between the maternal and fetal compartments and plays a pivotal role in providing immune tolerance. The aim of this study was to establish a relationship between concentrations of soluble HLA-G (sHLA-G) in maternal serum and amniotic fluid at 16-22 weeks of gestation and the sonographic measurements of fetal and placental growth. Materials and methods: sHLA-G in serum and amniotic fluid, as well as fetal biometric data and placental volume and perfusion indices, were determined in 41 singleton pregnancies with no complications. The level of sHLA-G (U/mL) was tested with a sandwich enzyme-linked immunosorbent assay (ELISA) kit. Results: The sHLA-G levels were unchanged both in amniotic fluid and serum during mid-pregnancy. The sHLA-G level in serum correlated positively with amniotic sHLA-G level (β = 0.63, p < 0.01). Serum sHLA-G level was significantly correlated with abdominal measurements (β = 0.41, p < 0.05) and estimated fetal weight (β = 0.41, p < 0.05). Conversely, amniotic sHLA-G level and placental perfusion (VI: β = -0.34, p < 0.01 and VFI: β = -0.44, p < 0.01, respectively) were negatively correlated. A low amniotic sHLA-G level was significantly associated with nuchal translucency (r = -0.102, p < 0.05). Conclusions: sHLA-G assayed in amniotic fluid might be a potential indicator of placental function, whereas the sHLA-G level in serum can be a prognostic factor for feto-placental insufficiency.

Adequate vitamin D (VD) intake during pregnancy is needed for fetal development and maternal health maintenance. However, while there is no doubt regarding its importance, there is not a unified recommendation regarding adequate intake. The main aim of our study was to measure the VD serum level of studied women, together with its potential influencing factors: demographic (i.e., age, level of education, relationship status and type of residence), conception and pregnancy related factors. Results are based on secondary data analyses of a retrospective case-control study of 100 preterm and 200 term pregnancies, where case and control groups were analyzed together. Data collection was based on a self-administered questionnaire, health documentation, and maternal serum VD laboratory tests. VD intake was evaluated by diet and dietary supplement consumption. According to our results, 68.1% of women took some kind of prenatal vitamin, and only 25.9% of them knew about its VD content. Only 12.1% of included women reached the optimal, 75 nmol/L serum VD level. Higher maternal serum levels were associated with early pregnancy care visits ( p = 0.001), assisted reproductive therapy ( p = 0.028) and advice from gynecologists ( p = 0.049). A correlation was found between VD intake and serum levels ( p < 0.001). Despite the compulsory pregnancy counselling in Hungary, health consciousness, VD intake and serum levels remain below the recommendations. The role of healthcare professionals is crucial during pregnancy regarding micronutrients intake and the appropriate supplementation dose.

A growing body of work aims to explore the reasons behind startup failures. However, there is a need for integrative approaches organized around conceptual frameworks to avoid fragmented and perplexing knowledge about these reasons. To our knowledge, no previous research has systematically investigated the role of competency deficits in startup failures, a crucial element of these failures. In our study, we adapted Spencer's behavioral competence model specifically for startups to identify the competencies within startup teams that, according to their Chief Executive Officers, contributed to their downfall. Three coders meticulously analyzed 50 online accounts of startup failures using a modified Critical Incident Technique. This analysis revealed two prominent competency deficits as pivotal determinants of these startups' outcomes: information-seeking and customer service orientation. Additionally, deficits in technical expertise, analytical thinking, and flexibility emerged as significant factors contributing to these failures. The competency deficits identified in this study offer focal points for evaluating and enhancing startup teams, thereby helping to prevent failure., Competing Interests: AM was employed by TeamINSIGHT Labs Ltd. GN was employed by Corporate Values Kft. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Szathmári, Varga, Molnár, Németh, Szabó and Kiss.)

Background and Objectives : Increasing evidence points to the significant role of the angiogenic factor levels in screening for pregnancy outcome. To examine the potential relationship between concentrations of placental protein 13 (PP13) and soluble human leukocyte antigen-G (sHLA-G) in maternal serum and amniotic fluid at 16-23 weeks of gestation and the sonographic features of pregnancy as well as pregnancy outcome. Materials and Methods : PP13 and sHLA-G in serum and amniotic fluid, fetal biometrical data, and placental volume and perfusion indices were determined in 71 euploid, singleton pregnancies. Results : The serum sHLA-G level exhibits a negative correlation with the serum PP13 level (r = -0.186, p < 0.001) and a positive correlation with the sHLA-G level in amniotic fluid (r = 0.662, p < 0.001). A significant correlation was found between serum sHLA-G level and placental volume (r = 0.142, p < 0.05) and between amniotic sHLA-G level and placental perfusion (r = -0.450, p < 0.001). A low amniotic PP13 level significantly predicted the birth weight (r = -0.102, p < 0.05), the duration of pregnancy (r = -0.155, p < 0.05), and the fetal abdominal circumference (r = -0.098, p < 0.05). Conclusions : PP13 assayed in amniotic fluid might be a potential marker of fetal growth, and sHLA-G can be an adjunct modality reflecting placental sonographic parameters.

This article, published in the journal Ultrasound in Obstetrics & Gynecology, presents the findings of a prospective case-control study on pregnancies complicated by gestational diabetes mellitus (GDM). The study aimed to identify the first detecting period of fetal myocardium hyperplasia in GDM. Ultrasound examinations were conducted on 84 pregnant women during the second and third trimesters, measuring fetal parameters such as estimated fetal weight, amniotic fluid quantity, and interventricular septum thickness. The results showed significant discrepancies in the interventricular septum measurements between the GDM group and the control group. The authors concluded that monitoring fetal myocardium parameters can be an effective screening method for perinatal outcomes in mothers with GDM. The study was supported by the 'Géza Hetényi' Grant and the Medical Faculty Research Fund at the University of Szeged. [Extracted from the article]

This article, titled "Identifying weak points of pelvic floor by sonoelastography in case of stress incontinence," discusses a study conducted at the Urogynecology Department of the Obstetrics and Gynecology Clinic at the University of Szeged. The study aimed to assess the condition of pelvic floor tissues in women with stress urinary incontinence (SUI) and map the weak points of the pelvic floor using ultrasound elastography. The researchers recruited 40 patients, half of whom had SUI, and used transvaginal ultrasound and sonoelastography to examine the mobility of the bladder neck and urethra and determine the elasticity of the paraurethral connective tissues. The results showed significant correlations between bladder neck-urethra mobility and changes in tissue elasticity, with age and BMI also playing a role. The researchers concluded that sonoelastography is a non-invasive method that can help assess tissue elasticity and contribute to the objective assessment and personalized treatment of incontinence. [Extracted from the article]

Achieving price efficiency via tenders, the sustainability of competition, and the prevention of shortages are hot topics in the debates about shaping the pharmaceutical markets. Single-winner tenders receive growing criticism for concentrating on achieving low prices at the expense of the long-term maintenance of a competitive pharmaceutical industry, the security of continuous supply, and disregarding the therapeutic needs of patient populations with specific conditions. This paper aims at drafting a concept to assist the design of multi-winner tenders for medicinal products with a focus on supply and sales guarantees, price efficiency, and equity in access. The concept shall be generally applicable to all kinds of medicinal products including generics, biosimilars, and on-patent products in the out- and in-patient sector. Principles for multi-winner tenders for medicinal products are set and a number of delimitations are made in order to get rid of factors that prevent clairvoyance amid the various pricing and reimbursement systems when designing a concept. The steps to plan and implement a multi-winner tendering procedure are drafted on the basis of the defined principles. The tender should consist of planning, bidding, preparation, sales, and evaluation phases. Pharmaceutical companies shall make bids with price and quantity pairs, which shall be ranked by prices and if applicable then taking into account other factors. The tenderer shall predefine market shares to the various places of the ranking. A double ceiling shall be applicable for the sales of the winners: their sales must not exceed their quantity offer and the predefined market share applicable to their place in the ranking. The implementation of the concept will require the careful adjustment of the tender conditions to the specificities of the pharmaceutical market concerned on the one hand and to the local pricing and reimbursement system on the other hand., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Németh, Mágó, Kaló, Lám, Balogh and Brodszky.)

Chiral stationary phases (CSPs) with coated amylose tris(3,5-dimethylphenylcarbamate) (ADMPC) selector have long been recognized for their excellent chiral recognition ability in liquid chromatography. The conformational versatility behind this feature is the source of their known hysteretic behavior, which has been previously observed in polar organic (PO) mode eluents containing 2-propanol (IPA). Mixtures of IPA and acetonitrile (MeCN), a typical PO mode eluent system, have not been examined in this aspect yet, even though hysteresis is promising for finding unique unexplored enantioselectivities. Not only was the hysteresis detectable on ADMPC using mixtures of IPA and MeCN, but it was the typical behavior in a diverse set of test compounds. The difference in the retention time of the same analyte under conditions which only differed in the eluent history on the column can go up to 20-fold. The assumed hindered conformational changes of the selector were reflected in retention drift at certain eluent compositions. On the two sides of the transitions, distinct, useful states of the selector were detected. A series of IPA - MeCN compositions with defined pretreatment was selected and recommended as an extension of the preliminary, first choice method screening set that used only alcohols. The incorporation of a solvent possessing substantially different characteristics enhances the potential in practical applications, while keeping the technical simplicity. Stability and robustness of the additional states of the CSP were characterized. The examined columns of different brands shared the observed behavior. Kinetic stability of a column state is adequate for successful application. The evaluated states of ADMPC provide multiple enantiorecognition potential by using mixtures of IPA and MeCN also considering the pretreatment of the column. Unprecedented double and triple elution order reversals along the composition range supported the versatility of the available states. Our findings further enhance the usefulness of ADMPC-containing CSPs. We provide instructions for the application of the widespread chiral selector in common eluent mixtures to avoid pitfalls regarding reproducibility and robustness., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Schizophrenia is characterized by positive, negative, cognitive, and affective symptoms. Antipsychotic medications, which work by blocking the dopamine D 2 receptor, are the foundation of pharmacotherapy for schizophrenia to control positive symptoms. Cariprazine is a dopamine D 3 receptor-preferring D 3 /D 2 partial agonist antipsychotic that is approved for the treatment of schizophrenia (USA and European Union [EU]) and manic and depressive episodes associated with bipolar I disorder (USA). Partial agonist agents have a lower intrinsic activity at receptors than full agonists, so they act as either functional agonists or functional antagonists depending on the surrounding neurotransmitter environment. Beyond efficacy against positive symptoms, the unique D 3 -preferring partial agonist pharmacology of cariprazine suggests potential advantages against negative symptoms, and cognitive and functional impairment, which are challenging to treat. The efficacy and safety of cariprazine in adult patients with schizophrenia have been demonstrated in four short-term randomized, double-blind, placebo-controlled clinical trials, two long-term open-label studies, one relapse prevention study, and one prospective negative symptom study versus the active comparator risperidone. Additional post hoc investigations have supported efficacy across individual symptoms and domains in schizophrenia, as well as in diverse areas of interest including cognition, functioning, negative symptoms, hostility, and global well-being. This comprehensive review of cariprazine summarizes its pharmacologic profile, clinical trial evidence, and post hoc investigations. Collective evidence suggests that the pharmacology of cariprazine may offer broad-spectrum efficacy advantages for patients with schizophrenia, including effects against difficult-to-treat negative and cognitive symptoms, as well as functional improvements. Cariprazine was generally safe and well tolerated in patients with short- and long-term exposure and no new safety concerns were associated with longer-duration treatment.Trial registration ClinicalTrials.gov identifiers, NCT00404573, NCT00694707, NCT01104766, NCT01104779, NCT01412060, NCT00839852, NCT01104792., (© 2021. The Author(s).)

The aim of the study was to examine the effectiveness and safety of cariprazine in routine psychiatric settings on schizophrenia patients with negative symptoms who have been treated with antipsychotics previously but without sufficient success. This was an open-label, flexible-dose, 16-week, observational study in Latvia. The primary outcome measure was an array of anamnesis-based clinical questions on schizophrenia symptoms rated on a seven-point scale. Other outcome measurements were the clinical global impression improvement (CGI-I) and severity (CGI-S) scales. Safety parameters included spontaneous reports of adverse events and specific assessments of extrapyramidal side-effects. A mixed model for repeated measures was fit to the data to evaluate the mean change from baseline for all visits. A total of 116 patients enrolled in the study (completion: 83%). Change from baseline to termination in symptom control was statistically significant (-7.3; P < 0.001), with the most improvement in negative symptoms (-6.3; P < 0.001). Over 70% of patients improved minimally or much based on the CGI-I scores at the final visit, and the CGI-S scores indicated an overall improvement in severity from moderately to mildly ill. 40% of patients experienced treatment-emergent adverse events. Over 70% of doctors were satisfied with the effectiveness and tolerability of cariprazine. Cariprazine significantly improved negative symptoms in schizophrenia patients., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives: Preterm birth as a complex phenomenon is influenced by numerous endogenic and exogenic factors, although its exact cause often remains obscure. According to epidemiological studies, maternal periodontal diseases, in addition to affecting general health, can also cause adverse pregnancy outcomes. Nonetheless, the existing results in the literature regarding this topic remain controversial. Consequently, our study aimed to determine the connection between poor maternal periodontal status and neonatal birth weight. Materials and Methods : A total of 111 primigravida-primiparous pregnant, healthy women underwent a periodontal examination in the second trimester of their pregnancies. Probing depth (PD) and bleeding on probing (BOP) were determined, and based on these diagnostic measurements, the patients were divided into three subgroups according to their dental status: healthy (H, n = 17), gingivitis (G, n = 67), and periodontitis (P, n = 27). Results: Considering that poor maternal oral status is an influencing factor for obstetrical outcomes, the presence of PD and BOP (characterized by the sulcus bleeding index, SBI) was evaluated. In the case of P, defined as PD ≥ 4 mm in at least one site and BOP ≥ 50% of the teeth, a significant correlation between BOP and a low neonatal birth weight at delivery ( p = 0.001) was found. An analysis of the relationship between SBI and gestational age (GA) at the time of the periodontal examination in the different dental status groups showed a significant correlation between these parameters in the G group ( p = 0.04). Conclusions: Our results suggest that a worse periodontal status during pregnancy may negatively affect obstetrical outcomes, especially the prematurity rate and newborn weight. Therefore, the importance of periodontal screening to prevent these complications is undeniable., Competing Interests: The authors declare no conflicts of interest.

Introduction: Placental perfusion can be evaluated using three-dimensional power-Doppler (3DPD) indices with sonobiopsy acquisition in a sphere or throughout the entire placenta., Objective: We aimed to explore the relation between these two measurement methods., Method: A prospective cohort study was conducted among normal pregnant women recruited at 11 to 40 gestational weeks. Placental vascularization was evaluated using the 3DPD indices (vascularization index [VI]; flow index [FI]; vascularization flow index [VFI]) with the application of the sphere ultrasound technique or scanned from the entire placenta., Results: A total of 150 women were recruited at a mean gestational age of 20.8 ± 7.22 weeks. We observed that scanned 3DPD indices using sphere technique decrease by gestational age between 11 and 40 weeks, whereas whole placental volume scanning yielded stable, non-decreasing indices during gestation. The indices were correlated to each other at least moderately, irrespectively of the method of scanning (r≥0.30)., Limitations: As gestation advances, less and less placentas can be visualized in one sweep for a whole view and at late period of gestation only a minority of placentas can be visualized as a whole., Conclusion: 3DPD indices acquired in a sphere of the placenta at umbilical cord insertion may reflect more to the decreasing vascularity of the exponentially growing placenta during gestation. Hence, sphere technique may have a greater screening opportunity in pathological pregnancies. Orv Hetil. 2023; 164(8): 300-307.

Background: The aim of the post hoc analysis was to better understand the efficacy and safety of cariprazine in patients with schizophrenia for less than 5 years (early stage) and for more than 15 years (late stage)., Methods: Data from three phase II/III randomized, double-blind, placebo-controlled trials with similar design in patients with acute exacerbation of schizophrenia were pooled and patients with early and late stage of schizophrenia were determined. A mixed-effects model for repeated measures approach was applied and least square (LS) mean changes from baseline to week 6 on the Positive and Negative Syndrome Scale (PANSS) total and factor scores were reported. Descriptive statistics were used for safety analyses including treatment emergent adverse events (TEAEs) and discontinuation rates., Results: Overall, 460 patients were identified as being in the early and 414 in the late stage of schizophrenia. The pooled analysis evaluating mean change from baseline to week 6 in the PANSS total score indicated statistically significant difference between cariprazine and placebo in favor of cariprazine in both the early (LS mean difference [LSMD] -7.5 P  < .001) and late stage (LSMD -6.7, P  < .01) subpopulation. Early stage patients experienced similar amount of TEAEs (CAR 67.3%, PBO 54.1%) as patients in the late stage (CAR 69.6%, PBO 65.6%)., Conclusion: In conclusion, cariprazine, a potent D 3 -D 2 partial agonist has been found to be safe and effective in the treatment of early and late stage schizophrenia.