Treatment Of Disorders Research Articles

Generalized 3D registration algorithm for enhancing retinal optical coherence tomography images.

Optical coherence tomography (OCT) has emerged as the standard of care for diagnosing and monitoring the treatment of various ocular disorders due to its noninvasive nature and in vivo volumetric acquisition capability. Despite its widespread applications in ophthalmology, motion artifacts remain a challenge in OCT imaging, adversely impacting image quality. While several multivolume registration algorithms have been developed to address this issue, they are often designed to cater to one specific OCT system or acquisition protocol. We aim to generate an OCT volume free of motion artifacts using a system-agnostic registration algorithm that is independent of system specifications or protocol. We developed a B-scan registration algorithm that removes motion and corrects for both translational eye movements and rotational angle differences between volumes. Tests were carried out on various datasets obtained from two different types of custom-built OCT systems and one commercially available system to determine the reliability of the proposed algorithm. Additionally, different system specifications were used, with variations in axial resolution, lateral resolution, signal-to-noise ratio, and real-time motion tracking. The accuracy of this method has further been evaluated through mean squared error (MSE) and multiscale structural similarity index measure (MS-SSIM). The results demonstrate improvements in the overall contrast of the images, facilitating detailed visualization of retinal vasculatures in both superficial and deep vasculature plexus. Finer features of the inner and outer retina, such as photoreceptors and other pathology-specific features, are discernible after multivolume registration and averaging. Quantitative analyses affirm that increasing the number of averaged registered volumes will decrease MSE and increase MS-SSIM as compared to the reference volume. The multivolume registered data obtained from this algorithm offers significantly improved visualization of the retinal microvascular network as well as retinal morphological features. Furthermore, we have validated that the versatility of our methodology extends beyond specific OCT modalities, thereby enhancing the clinical utility of OCT for the diagnosis and monitoring of ocular pathologies.

Safety and efficacy of inebilizumab for the treatment of neuromyelitis optica spectrum disorder: end-of-study results from the open-label period of the N-MOmentum trial

Inebilizumab, an anti-CD19 B-cell-depleting antibody, demonstrated safety and efficacy in neuromyelitis optica spectrum disorder in the randomised controlled period of the N-MOmentum trial. Here, end-of-study data, including the randomised controlled period and open-label extension period, are reported. In the double-blind, randomised, placebo-controlled, phase 2/3 N-MOmentum trial, adults aged 18 years and older with an neuromyelitis optica spectrum disorder diagnosis, Expanded Disability Status Scale score of 8·0 or less, and history of either at least one acute inflammatory attack requiring rescue therapy in the past year or two attacks requiring rescue therapy in the past 2 years, were recruited from 81 outpatient specialty clinics or hospitals in 24 countries. Eligible participants were randomly assigned (3:1), using a central interactive voice system or interactive web response system, and a permuted block randomisation scheme (block size of 4), to receive intravenous inebilizumab (300 mg) or identical placebo on days 1 and 15 of the randomised period, which lasted up to 197 days. Participants and all study staff were masked to treatment assignment. The primary endpoint of the randomised period of the trial was time to onset of adjudicated neuromyelitis optica spectrum disorder attack on or before day 197. Participants in the randomised controlled period who had an adjudicated attack, completed 197 days in the study, or were in the randomised controlled period when enrolment stopped, could voluntarily enter the open-label period. In the open-label period, participants either initiated inebilizumab if assigned placebo (receiving 300 mg on days 1 and 15 of the open-label period) or continued treatment if assigned inebilizumab (receiving 300 mg on day 1 and placebo on day 15, to maintain B-cell depletion and masking of the randomised controlled period). All participants subsequently received inebilizumab 300 mg every 6 months for a minimum of 2 years. The end-of-study analysis endpoints were time to adjudicated attack and annualised attack rate (assessed in all participants who received inebilizumab at any point during the randomised controlled period or open-label period [any inebilizumab population] and the aquaporin-4 [AQP4]-IgG seropositive subgroup [any inebilizumab-AQP4-IgG seropositive population]) and safety outcomes (in all participants who were exposed to inebilizumab, analysed as-treated). This study is registered with ClinicalTrials.gov, NCT02200770, and is now complete. Between Jan 6, 2015, and Sept 24, 2018, 467 individuals were screened, 231 were randomly assigned, and 230 received at least one dose of inebilizumab (n=174) or placebo (n=56). Between May 19, 2015, and Nov 8, 2018, 165 (95%) of 174 participants in the inebilizumab group and 51 (91%) of 56 in the placebo group entered the open-label period (mean age 42·9 years [SD 12·4], 197 [91%] of 216 were female, 19 [9%] were male, 115 [53%] were White, 45 [21%] were Asian, 19 [9%] were American Indian or Alaskan Native, and 19 [9%] were Black or African American). As of data cutoff for this end of study analysis (Dec 18, 2020; median exposure 1178 days [IQR 856-1538], total exposure of 730 person-years) 225 participants formed the any inebilizumab population, and 208 (92%) participants were AQP4-IgG seropositive. Overall, 63 adjudicated neuromyelitis optica spectrum disorder attacks occurred in 47 (21%) of 225 treated participants (60 attacks occurred in 44 [21%] of 208 in the AQP4-IgG seropositive subgroup); 40 (63%) of 63 attacks occurred in 34 (15%) of 225 treated participants during the first year of treatment. Of individuals who had an adjudicated attack while receiving inebilizumab, 36 (77%) of 47 were subsequently attack-free at the end of 4 years. Annualised attack rates decreased year-on-year, with end-of-study adjusted annualised attack rates being similar in the any inebilizumab-AQP4-IgG seropositive subgroup (0·097 [95% CI 0·070-0·14]) and any inebilizumab populations (0·092 [0·067-0·13]). Overall, 208 (92%) of 225 participants who received any inebilizumab had at least one treatment-emergent adverse event, the most frequent of which were urinary tract infection (59 [26%]), nasopharyngitis (47 [21%]), and arthralgia (39 [17%]). Infection rates did not increase over 4 years. Three (1%) of 225 participants in the any inebilizumab population died during the open-label period (one each due to a CNS event of unknown cause and pneumonia, respiratory insufficiency resulting from an neuromyelitis optica spectrum disorder attack and viral pneumonia related to COVID-19), all of which were deemed to be unrelated to treatment. Data from the end-of-study analysis of the N-MOmentum trial showed continued and sustained clinical benefits of long-term inebilizumab treatment in individuals with neuromyelitis optica spectrum disorder, which supports the role of inebilizumab as a CD19+ B-cell-depleting therapy in neuromyelitis optica spectrum disorder. MedImmune and Viela Bio/Horizon Therapeutics, now part of Amgen.

MiR-26a is a Key Therapeutic Target with Enormous Potential in the Diagnosis and Prognosis of Human Disease.

MicroRNA-26a (miR-26a) belongs to small non-coding regulatory RNA molecules emerging as fundamental post-transcriptional regulators inhibiting gene expression that plays vital roles in various processes of human diseases such as depression, renal ischemia and reperfusion injury, liver injury and some refractory cancer. In this review, we expound on the results of studies about miR-26a with emphasis on its function in animal models or in vitro cell culture to simulate the most common human disease in the clinic. Furthermore, we also illustrate the underlying mechanisms of miR-26a in strengthening the antitumor activity of antineoplastic drugs. Importantly, dysregulation of miR-26a has been related to many chronic and malignant diseases, especially in neurological disorders in the brain such as depression and neurodegenerative diseases as well as cancers such as papillary thyroid carcinoma, hepatocellular carcinoma and so on. It follows that miR-26a has a strong possibility to be a potential therapeutic target for the treatment of neurological disorders and cancers. Although the research of miRNAs has made great progress in the last few decades, much is yet to be discovered, especially regarding their underlying mechanisms and roles in the complex diseases of humans. Consequently, miR-26a has been analyzed in chronic and malignant diseases, and we discuss the dysregulation of miR-26a and functional roles in the development and pathogenesis of these diseases, which is very helpful for understanding their mechanisms as new biomarkers for diagnosing and curing diseases in the near future.

A bZIP type transcription factor from Picrorhiza kurrooa modulates the expression of terpenoid biosynthesis genes in Nicotiana benthamiana

bZIP family of transcription factors are DNA-binding proteins which bind ACGT motifs in the upstream promoter region of genes. bZIP proteins play significant roles in regulation of plant growth, secondary metabolism, development, defense and response to various abiotic and biotic stresses. Up to now, there is no report on molecular and functional characterization of bZIP transcription factors in Picrorhiza kurrooa, a medicinally important endangered herb of north western Himalayan region. The species is widely used in several commercially available drug formulations like livomap, livocare and livplus for treatment of liver disorders. The medicinal properties of P. kurrooa are due to bioactive picrosides, synthesized by isoprenoid pathway. The promoters of regulatory genes viz., Pkdxs and Pkhmgr of picroside biosynthesis pathway have been reported to contain ACGT cis-acting elements (bzip motifs) at different locations. In this study, the functionality of ACGT motifs was confirmed by electrophoretic mobility shift assay (EMSA). Full length PkbZIP gene was cloned through RACE method. In silico analysis revealed PkbZIP contained a conserved signature bZIP domain (N-x7-R/K-x9-L-x6-L-x6-L). Transcriptional activation and subcellular localization assay confirmed nuclear localization of PkbZIP. EMSA with purified PkbZIP confirmed in vitro binding of PkbZIP to ACGT elements in Pkdxs and Pkhmgr promoters. The expression pattern of PkbZIP positively correlated with the picroside (active medicinal component of the plant) content in different tissues, at 15 °C and under light conditions. Transient overexpression in Nicotiana benthamiana suggested a role of PkbZIP in terpenoid biosynthesis. PkbZIP might prove as potential candidate gene to be used in genetic engineering program for enhancing the picroside content in P. kurrooa.

Capsules for the Diagnosis and Treatment of Gastrointestinal Motility Disorders- A Game Changer.

Over the last few decades, there have been remarkable strides in endoscopy and radiological imaging that have advanced gastroenterology. However, the management of neurogastroenterological disorders has lagged behind, in part handicapped by the use of catheter-based manometry that is both non-physiological and uncomfortable. The advent of capsule technology has been a game changer for both diagnostic and therapeutic applications. Here, we discuss several capsule devices that are available or under investigation. There are three technologies that are FDA approved. Wireless motility capsule measures pH and pressure and provides clinically impactful information regarding gastric, small intestine and colonic transit, without radiation that has been demonstrated to guide management of gastroparesis, dyspepsia and constipation. Wireless ambulatory pH monitoring capsule is currently the gold standard for assessing gastroesophageal acid reflux. In the therapeutics arena, an orally ingested vibrating capsule has been recently FDA approved for the treatment of chronic constipation, supported by a robust phase 3 clinical trial which showed significant improvement in constipation symptoms and quality of life. There are several capsules currently under investigation. Smart capsule bacterial detection system and Capscan® are capsules that can sample fluid in the small or large bowel and provide microbiome analysis for detection of small intestinal bacterial (SIBO) or fungal overgrowth (SIFO). Another investigational gas sensing capsule analyzing hydrogen, CO2, volatile fatty acids and capsule orientation, can measure regional gut transit time and luminal gas concentrations and assess gastroparesis, constipation or SIBO. Therapeutically, other vibrating capsules are in development. Innovations in capsule technology are poised to transform our ability to investigate gut function physiologically, and non-invasively deliver targeted treatment(s), thereby providing both accurate diagnostic information and luminally-directed, safe therapy.

The Effect of a Pilot Brief Educational Intervention on Preferences Regarding Treatments for Opioid Use Disorder

PurposeNegative perceptions around medications for opioid use disorder (MOUD) amongst the public could deter patients with opioid use disorder (OUD) from engaging with MOUD. Thus, we evaluated whether a brief intervention could improve preferences for MOUD in people who may or may not use opioids. MethodsWe employed a pre-post design to assess the effect of a brief educational intervention on preferences for methadone, buprenorphine, naltrexone, and non-medication treatment in an online sample of US adults stratified by race, who may or may not use opioids. Respondents ranked their preferences in OUD treatment before and after watching four one-minute educational videos about treatment options. Changes in treatment preferences were analyzed using Bhapkar’s test and post hoc McNemar’s tests. A binary logistic generalized estimating equation (GEE) assessed factors associated with preference between treatments. ResultsThe sample had 530 responses. 194 identified as White, 173 Black, 163 Latinx. Treatment preferences changed significantly towards MOUD (p<.001). This effect was driven by changes toward buprenorphine (OR=2.38; p<.001) and away from non-medication treatment (OR=0.20; p<.001). There was no significant difference in effect by race/ethnicity. People with lower opioid familiarity were significantly more likely to change their preferences towards MOUD following the intervention. ConclusionRespondent preferences for MOUD increased following the intervention suggesting that brief educational interventions can change treatment preferences towards MOUD. These findings offer insights into perceptions of OUD treatment in a racially stratified sample and serve as a foundation for future educational materials that target MOUD preferences in the general public.

A comprehensive review on pharmacognosy, phytochemistry and pharmacological activities of 8 potent species of southeast Asia.

Genus Prunus comprising around 430 species is a vast important genus of family Rosaceae, subfamily amygdalaoidae. Among all 430 species, around 19 important species are commonly found in Indian sub-continent due to their broad nutritional and economic importance. Some most common species of genus Prunus are Prunus amygdalus, Prunus persica, Prunus armeniaca, Prunus avium, Prunus cerasus, Prunus cerasoides, Prunus domestica, Prunus mahaleb, etc. A newly introduced species of Prunus i.e Prunus sunhangii is recently discovered which is morphologically very similar to Prunus cerasoides. Plants of Prunus species are short to medium-sized deciduous trees mainly found in the northern hemisphere. In India and its subcontinent, it extends from the Himalayas to Sikkim, Meghalaya, Bhutan, Myanmar etc. Different Prunus species have been extensively studied for their morphological, microscopic, pharmacological and phytoconstituents characteristics. Total phenolic content of Prunus species explains the presence of phenols in high quantity and pharmacological activity due to phenols. Phytochemical screening of species of genus Prunus shows the presence of wide phytoconstituents which contributes in their pharmacological significance and reveals the therapeutic potential and traditional medicinal significance of this genus. Genus Prunus showed a potent antioxidant activity analyzed by 1,1-diphenyl-2-picryl-hydrazyl radical assay. Plant species belonging to the genus Prunus is widely used traditionally for the treatment of various disorders. Some specific Prunus species possess potent anticancer, anti-inflammatory, hypoglycemic etc. activity which makes the genus more interesting for further research and findings. This review is an attempt to summarize the comprehensive study of Prunus.

Biological Potential of a Bibenzyl Compound ‘Gigantol’ for the Treatment of Human Disorders: Pharmacological Activities and Analytical Aspects of an Active Phytochemical Isolated from Orchid

Background: Dendrobium chrysotoxum Lindl. is an important medicinal plant of the genus Dendrobium from the Orchidaceae family. Gigantol is one of the key bioactive phytochemicals found in Dendrobium plants. Gigantol is reported to have diverse pharmacological activities Aims: This narrative review explores the analytical aspects along with pharmacological activities of gigantol as reported in different scientific publications. Methods: To find appropriate information related to Dendrobium plants and gigantol, extensive data extraction was done using ScienceDirect, Google, PubMed, and Scopus databases, and diverse facts were collected, arranged and analyzed to know the therapeutic potential of gigantol. Analytical aspects of gigantol were also discussed in the present work. Results: Gigantol has a wide distribution in the Dendrobium officinale, Dendrobium chrysanthum, Dendrobium crystallinum, Dendrobium aphyllum, and Dendrobium devonianum. Available data indicates diverse pharmacological activities of gigantol. Preclinical studies have shown its effectiveness in the treatment of cataractogenesis, liver injury, leishmaniasis, nephrotoxicity, spasm, and skin disorders. Gigantol has been found to control hepatocellular cancer, lung cancer, breast cancer, bladder cancer, and cervical cancer. The neuroprotective, antinociceptive, anti-inflammatory, antioxidant, vasorelaxant, immune modulatory effect, antimalarial, and anti-herpetic properties of gigantol have also been observed. Applications of different analytical techniques for the isolation and characterization of gigantol were also discussed in detail. Conclusion: Gigantol has significant and diverse pharmacological activities that must be explored in clinical setup to develop therapeutic leads for different diseases and health conditions.

Anisomeles indica (L.) Kuntze leaf essential oil ameliorates LPS-induced inflammation in RAW 264.7 cells: An integrated approach of network pharmacology and experimental validation

Anisomeles indica (L.) Kuntze (Lamiaceae), commonly called catmint, is an essential oil-bearing herb used in traditional systems of medicine against rheumatism, convulsions, inflammatory skin disorders, and epilepsy. However, the efficacy and mechanism of action of its essential oil against inflammatory conditions remain elusive. The current study aims at the chemical characterization of the essential oil of A. indica leaves (AILEO) and understanding the mechanism of its anti-inflammatory effects by an integrated approach of network pharmacology and in vitro assays. GC–MS analysis of AILEO revealed a total of 30 constituents representing 94.19 % of the total oil. The majority of the chemical groups include diterpene hydrocarbons with abietatriene (58.13 %) and abietadiene (7.18 %) as the major constituents. Out of 30 compounds, 20 passed the ADME screening and were considered as active constituents. A total of 524 compound targets, 409 anti-inflammation targets, and 88 compound-disease intersecting targets were obtained. Multi-level network analysis revealed that the pharmacological mechanisms of alleviation of inflammation by AILEO are due to its interaction with five core inflammatory targets such as PI3K, AKT1, MEK1, ERK1, and RXRA involved in the PI3K-AKT signaling pathway. AILEO did not exhibit any cytotoxic effect on RAW 264.7 cells, but it significantly inhibited nitric oxide (NO) production and reduced the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in vitro assays. Further, AILEO enhanced the expression levels of endogenous antioxidant enzymes (CAT, SOD, GPx, and GSH) in comparison to the LPS-induced group. RT-qPCR analysis revealed that AILEO modulated the level of mRNA expression of all five core targets associated with the PI3K-AKT signaling pathway, which further supported the findings of network pharmacology. This study provides valuable insights into the intricate mechanisms by which AILEO exerts anti-inflammatory action indicating its pharmacological potential as a promising candidate for the treatment of disorders linked with inflammation.

Review of Oral Tablet

Abstract: Oral drug delivery is noninvasive, has a high rate of patient compliance, is easy to handle, and doesn't require any special sterile settings, it is the most popular method of administration. Nevertheless, a number of physical, biological, and pharmacological obstacles that certain medications must overcome in order to be absorbed into the systemic circulation reduce their therapeutic efficiency. The use of nanocarriers to deliver drugs orally has proven to be an effective solution to the aforementioned problems and is being explored as a potential replacement for oral medication administration. This chapter provides an overview of the latest developments in the use of nanocarriers for oral medication delivery in the treatment of different disorders. The chapter also describes how diverse nanocarrier designs and technologies improve therapeutic potential by overcoming physical, biological, and biochemical obstacles. it is easy to produce, has few sterility limitations, is less expensive, has flexible dosage form design, and has high patient compliance, oral drug delivery (ODD) is the most convenient and favored method of drug administration. However, low medication bioavailability—which is influenced by three crucial factors—is one of the difficulties associated with oral drug delivery. The other is solubility. Many mathematical models that predict the medication's rate of solubility and dissolution have been developed in order to achieve efficient drug absorption in vivo. Similarly, models that are noncellular and cellular determine permeability. Furthermore, the medication's behavior in the gastrointestinal tract (GIT) is influenced by physiological parameters, such as pH, microbial colonization, and enzymes, as well as intrinsic drug properties. A drug's dosage form is a method of getting it into a living organism. The medicine must be administered to the site of action at a rate and concentration that will maximize therapeutic benefit and minimize side effects in order to provide the intended result. Although the oral method is still commonly used, swallowing tablets and capsules can be a regular problem. As a result, numerous studies on cutting-edge drug delivery methods have been conducted. This review focuses on oral dispersible tablets, a novel approach to drug delivery systems that are currently more focused on formulation and set a new course that not only helped patients increase their level of therapy compliance.

A Review on Divine Tree Nyctanthes Arbor-Tristis Linn – A Treasure House of Therapeutic Components

Nyctanthes arbor-tristis Linn is a short ancient tree believed to be a divine tree in India. The tree bears beautiful white flowers known for its aura. It is extensively cultivated in tropical and subtropical regions across the world. Since time immemorial, crude extracts of each part of the tree is used as a classical medicine in treatment of organ disorders, fevers, infections, expectorant, allergies, gynaecological problems, and various other diseases. Nyctanthes arbor-tristis Linn possess phytochemicals such as Alkaloids, steroids, Glycosides, flavonoids, Terpenes, essential oils, proteins that exhibit pharmacological activities like anti-inflammatory, anti-cancer, anti-diabetic, hepato-protective, CNS depressant, anti-anaemic, antipyretic, sedative and many more. This review article has included all the possible details about the plant, its distribution phytochemical constituents, and pharmacological activities. Phytochemical studies and Nyctanthes arbor-tristis Linn’s pharmacological activities indicated it as a potential medicinal plant for various elements. However, more research is crucial to investigate the mode of action of the plant’s bioactive constituents and its therapeutic potential.

CHEMICAL CONSTITUENTS, TRADITIONAL USES AND PHARMACOLOGICAL PROPERTIES OF MADHUCA LONGIFOLIA: A REVIEW

Plant extracts and their derivatives are used by almost 80% of the world's population for the treatment of various infections and disorders. The current review was based on the chemical constituents, traditional uses and pharmacological properties of Madhuca longifolia. The Madhuca longifolia (Mahua) Symmachus indica is a huge deciduous tree native to Nepal, India, and Ceylon. It is also known as the Butter nut tree and is a member of the Sapotaceae family. The height of an M. longifolia tree can reach up to 70 feet. The fruiting period of the tree begins between the ages of 8 and 15, and can last up to 60 years. When ripe, the fruits have a greenish yellow colour and are oval in shape [4]. Sugars, vitamin A, ascorbic acid, thiamine, riboflavin, Ca, P, Fe, Mg, Cu, anthocyanins, betains, salts of malic and succinic acid, and many other vitamins and minerals can be found in flowers. It is the rich source of quercetin, 3-O-lrhamnosid, stigmasterol, n-hexacosanol, n-octacosanol, carotene, myricitin, erthrodiol, 3-caproxyolcan-12-en-28-ol, 3-galactoside and Xanthophylls. It was traditionally utilized in bronchitis, diabetes, rheumatism, haemorrhage, ulcer, tonsillitis, pharyngitis, and spongy gums etc. In conclusion, Madhuca longifolia is reported to be effective as antioxidant, analgesic, anti-pyretic, anti-inflammatory, immunosuppression, anti-ulcer, anti-hyperglycaemic, anti-neoplastic and anthelmintic.

The effect of education regarding treatment guidelines for schizophrenia and major depressive disorders on psychiatrists' hypnotic medication prescribing behavior: a multicenter study

BackgroundTo examine whether the "Effectiveness of Guideline for Dissemination and Education in psychiatric treatment (EGIUDE)" project affects the rate of prescriptions of hypnotic medication and the type of hypnotic medications prescribed among psychiatrists, for schizophrenia and major depressive disorder in Japan.MethodsThe EGUIDE project is a nationwide prospective study of evidence-based clinical guidelines for schizophrenia and major depressive disorder in Japan. From 2016 to 2021, clinical and prescribing data from patients discharged from hospitals participating in the EGUIDE project were used to examine hypnotic medication prescriptions The prescribing rate of hypnotics and the prescribing rate of each type of hypnotic (benzodiazepine receptor agonist, nonbenzodiazepine receptor agonist, melatonin receptor agonist, and orexin receptor antagonist) were compared among patients who had been prescribed medication by psychiatrists participating in the EGUIDE project and patients who had been prescribed medication by nonparticipating psychiatrists. Multivariate logistic regression analysis was performed to examine the effect of the EGUIDE project on the prescription of hypnotic medications.ResultsA total of 12,161 patients with schizophrenia and 6,167 patients with major depressive disorder were included. Psychiatrists participating in the EGUIDE project significantly reduced the rate of prescribing hypnotic medication and benzodiazepine receptor agonists for both schizophrenia (P < 0.001) and major depressive disorder (P < 0.001) patients.ConclusionThis is the first study to investigate the educational effects of guidelines for the treatment of psychiatric disorders on psychiatrists in terms of prescribing hypnotic medications to patients. The EGUIDE project may play an important role in reducing hypnotic medication prescription rates, particularly with respect to benzodiazepine receptor agonists. The results suggest that the EGUIDE project may result in improved therapeutic behavior.

Differences between criminal offender versus non-offender female patients with schizophrenia spectrum disorder: a retrospective cohort study.

The purpose of this study was to investigate the difference between offender female patients (OFS) and non-offender female patients (NOFS) with schizophrenia spectrum disorder (SSD).The patients in this study were admitted to the university psychiatry in Zurich Switzerland between 1982 and 2016. Demography, psychopathology, comorbidity, and treatment differences were analyzed using binary statistics to compare 31 OFS and 29 matching NOFS with SSD. The Fisher's exact test was used for categorical data variables in small size samples and the Mann-Whitney-U-Test for nonparametric test variables, adjusted with theBenjamini and Hochberg method.The results indicate that the NOFS were cognitively more impaired, they were more likely to have had antipsychotic drugs prescribed (NOFS; 100%, OFS: 71%, OR 1.41, 95% CI 1.13-1.77, p=0.022) and their medication compliance was higher (NOFS: 84.6%, OFS: 4.5%, OR 0.09, 95% CI 0.00-0.08, p=0.000). In contrast, the OFS had completed compulsory school less oftenand the were observed to be more often homeless and socially isolated (OFS: 72.4%, NOFS: 34.6%, OR 4.96, 95% CI 1.58-15.6, p=0.026), self-disorders (OFS: 51.6%, NOFS: 11.1%, OR 8.53, 95% CI 2.12-34.32, p=0.011), delusions (OFS: 96.8%, NOFS: 63%, OR 17.65, 95% CI 2.08-149.99, p=0.014) and substance use disorder (51.6%, OR 0.27, 95% CI 0.09-0.85, p=0.039). Clinicians treating female offender patients with SSD should focusmore on the treatment for substance use disorder, medication and early recognition of the illness for preventative purposes.

Establishing connectivity through microdissections of midbrain stimulation-related neural circuits.

Comprehensive understanding of the neural circuits involving the ventral tegmental area is essential for elucidating the anatomo-functional mechanisms governing human behaviour as well as the therapeutic and adverse effects of deep brain stimulation for neuropsychiatric diseases. While the ventral tegmental area has been successfully targeted with deep brain stimulation for different neuropsychiatric diseases, the axonal connectivity of the region has not been fully understood. Here using fiber micro-dissections in human cadaveric hemispheres, population-based high-definition fiber tractography, and previously reported deep brain stimulation hotspots, we find that the ventral tegmental area participates in an intricate network involving the serotonergic pontine nuclei, basal ganglia, limbic system, basal forebrain, and prefrontal cortex, which is implicated in the treatment of obsessive-compulsive disorder, major depressive disorder, Alzheimer's disease, cluster headaches, and aggressive behaviors.

The Ketogenic Diet as a Treatment for Mood Disorders

Abstract Purpose of Review The ketogenic diet is a low carbohydrate, moderate protein, and high fat diet which results in a metabolic state known as ketosis, in which fats are broken down into ketone bodies. The ketogenic diet is a 100-year-old evidence-based treatment for epilepsy and is gaining popularity as a treatment for various mental disorders, including mood disorders. Our objective is to explain the potential mechanisms through which ketogenic diets may improve the pathophysiology of mood disorders and provide a comprehensive review of recent clinical literature on the topic Recent Findings Mood disorders are associated with several proposed pathophysiological mechanisms, including mitochondrial dysfunction, oxidative stress, inflammation, and insulin resistance. The ketogenic diet shows promise in addressing these underlying pathophysiological mechanisms and emerging clinical data suggest that ketogenic diets may improve symptoms in people with mood disorders. Summary The ketogenic diet shows promise in the treatment of mood disorders. This metabolic intervention has the potential to directly target underlying disease mechanisms, potentially reduce the need for medications, and reduce common side effects and comorbidities, such as weight gain and insulin resistance.

Patient-related factors associated with patient retention and non-completion in psychosocial treatment of borderline personality disorder: A systematic review.

The potential efficacy of psychosocial interventions in the treatment of borderline personality disorder (BPD) is impacted by significant treatment non-completion (TNC), with meta-analytic studies reporting rates of attrition of between 25% and 28%. Increasing patient retention could facilitate outcomes and improve resource utilization, given limited healthcare services. A systematic search of PsycINFO, CINAHL, EMBASE, CENTRAL, and Web of Science Core Collection identified 33 articles that met the criteria for inclusion. Although substantial heterogeneity in terms of methodology and quality of analysis limited conclusions that could be drawn in the narrative review, a few consistent patterns of findings were elucidated, such as Cluster B personality disorder comorbidities and lower therapeutic alliance were associated with TNC. Interestingly, the severity of BPD symptoms was not a predictor of TNC. These findings are discussed in terms of their potential theoretical contribution to TNC. Clinically, there may be value in applying mindfulness and motivational interviewing strategies early on in treatment for individuals who present uncertainty about engaging in treatment. Further research to develop this empirical landscape includes focusing on high-powered replications, examining burgeoning lines of research, and investigating dynamic predictors of TNC.

Chiral Hydroxy Metabolite of Mebendazole: Analytical and Semi-Preparative High-Performance Liquid Chromatography Resolution and Chiroptical Properties

Mebendazole (MBZ) is a benzimidazole carbamate anthelmintic used worldwide for the treatment and prevention of parasitic disorders in animals and humans. A large number of in vivo and in vitro studies have demonstrated that MBZ also has anticancer activity in multiple types of cancers. After oral administration, the phenylketone moiety of MBZ is rapidly reduced to the hydroxyl group to form the chiral hydroxy metabolite (MBZ-OH). To the best of our knowledge, there is no information in the literature on the stereochemical course of transformation and the anthelmintic and antitumor activity of individual enantiomers of MBZ-OH. In the present study, we describe in detail the direct HPLC resolution of MBZ-OH on a 100 mm × 4.6 mm Chirapak IG-3 column packed with 3 μm silica particles containing amylose (3-chloro-5-methylphenylcarbamate) as a selector. At 25 °C and using pure methanol as the mobile phase, the enantioseparation and resolution factors were 2.38 and 6.13, respectively. These conditions were scaled up at a semi-preparative scale using a 250 mm × 10 mm Chiralpak IG column to isolate multi-milligram amounts of both enantiomeric forms of the chiral metabolite. The chiroptical properties of the collected enantiomers were determined and, through a theoretical study, were related to the more stable conformations of MBZ-OH. The first and second eluted enantiomers were dextrorotatory and levorotatory, respectively, in dimethylformamide solution. Finally, by recording the retention factors of the enantiomers as the water content in the water–acetonitrile mobile phases was progressively varied, U-shaped retention maps were generated, indicating a dual and competitive hydrophilic interaction liquid chromatography and reversed-phase liquid chromatography retention mechanism on the Chirapak IG-3 chiral stationary phase.

Discovery of ITI-333, a Novel Orally Bioavailable Molecule Targeting Multiple Receptors for the Treatment of Pain and Other Disorders.

Development of more efficacious medications with improved safety profiles to manage and treat multiple forms of pain is a critical element of healthcare. To this end, we have designed and synthesized a novel class of tetracyclic pyridopyrroloquinoxalinone derivatives with analgesic properties. The receptor binding profiles and analgesic properties of these tetracyclic compounds were studied. Systematic optimizations of this novel scaffold culminated in the discovery of the clinical candidate, (6bR,10aS)-8-[3-(4-fluorophenoxy)propyl]-6b,7,8,9,10,10a-hexahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxalin-2(3H)-one (compound 5, ITI-333), which exhibited potent binding affinity to serotonin 5-HT2A (Ki = 8.3 nM) and μ-opioid receptors (MOR, Ki = 11 nM) and moderate affinity to adrenergic α1A (Ki = 28 nM) and dopamine D1 (Ki = 50 nM) receptors. ITI-333 acts as a 5-HT2A receptor antagonist, a MOR partial agonist, and an adrenergic α1A receptor antagonist. ITI-333 exhibited dose-dependent analgesic effects in rodent models of acute pain. Currently, this investigational new drug is in phase I clinical development.

Efficacy and tolerability of chitin-glucan combined with simethicone (GASTRAP® DIRECT) in irritable bowel syndrome: A prospective, open-label, multicenter study

BACKGROUND Irritable bowel syndrome (IBS), defined according to the Rome IV diagnostic criteria, is a chronic functional gastrointestinal disorder characterized by recurrent abdominal pain related to altered bowel habits. First-line recommended treatments are limited to combining drugs targeting predominant symptoms, particularly pain (antispasmodics), constipation (laxatives), and diarrhea (loperamide), yielding only a limited therapeutic gain. GASTRAP® DIRECT is a class IIa medical formulation composed of a combination of chitin-glucan and simethicone indicated for the symptomatic treatment of gas-related gastrointestinal disorders by combining different mechanisms of action. AIM To evaluate the efficacy, tolerability, and safety of 4-week GASTRAP® DIRECT treatment in patients with IBS. METHODS In this prospective, multicenter, open-label trial, 120 patients with IBS received three sticks of GASTRAP® DIRECT (1.5 g/d of chitin-glucan and 0.75 mg/d of simethicone) per day for 4 weeks. The primary endpoint was the responder rate, defined as the number of patients whose abdominal pain score decreased by ≥ 30% from baseline to week (W) 4. The analysis was performed using the per-protocol set. Cardinal symptoms, impact of global symptoms on daily life, change in stool consistency, and improvement in defecatory disorders were evaluated. RESULTS Overall, 100 patients were evaluated. At W4, 67% (95%CI: 57-75) showed improvement in abdominal pain (score: 5.8 ± 2.4 vs 2.9 ± 2.0, P &lt; 0.0001). Similar improvements were observed for bloating [8.0 ± 1.7 vs 4.7 ± 2.9, P &lt; 0.0001; 60% (95%CI: 50-70) responders], abdominal distension [7.2 ± 2.1 vs 4.4 ± 3.1, P &lt; 0.0001; 53% (95%CI: 43-63) responders], and impact of global symptoms on daily life [7.1 ± 2.0 vs 4.6 ± 2.9, P &lt; 0.0001; 54% (95%CI: 44-64) responders]. Stool consistency improved in most patients (90% and 57% for patients with liquid and hard stools, respectively). Overall, 42% of patients with defecatory disorders reported very much/considerable improvements by W2. No severe adverse event occurred, and tolerability was rated “good” or “very good” by 93% of patients. CONCLUSION GASTRAP® DIRECT is safe and well tolerated, alleviating IBS symptoms rapidly in 2 weeks. This open-label study suggests that the combination of chitin-glucan and simethicone could be beneficial in patients with IBS.