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COVID-19 pandemic had a great impact on mental health, both in the general population and psychiatric patients. Little is known about the difference between these two populations in perceiving the pandemic as a traumatic event. The aim of the study was to compare psychiatric patients and healthy controls (HC) in terms of change over time of post-traumatic (PTSD) symptoms. Demographic and clinical variables were collected. Impact of Event Scale Revised (IES-R) scores were registered at T1 as lockdown period (March–April 2020) and T2 as restarting (May–June 2020). Descriptive analyses and linear regression models were performed. A total of 166 outpatients and 57 HC were recruited. Time (F = 15.76; p < 0.001) and diagnosis (F = 4.94; p < 0.001) had a significant effect on the change of IES-R scores, which resulted T1 > T2 (p < 0.001), except for subjects affected by Obsessive-Compulsive Disorder (OCD). Overall, IES-R scores were < in patients than in HC (p = 0.02), particularly in the schizophrenia (SKZ) subgroup (p < 0.001). IES-R scores of subjects with personality disorders (PDs) resulted to be > HC, although not statistically significant. The lockdown period was perceived as more traumatic than the reopening phase by both groups, with the exception of OCD patients, probably because of the clinical worsening associated with the urge of control against risks of contamination. Overall, HC reported more PTSD symptoms than psychiatric patients did, particularly SKZ ones. PD patients, in contrast, may be more vulnerable to PTSD symptoms probably as a result of poor coping skills. Together with OCD patients, subjects with PDs may need closer monitoring during the different phases of the pandemic. Trial Registration: ClinicalTrials.gov Identifier: NCT04694482 [ABSTRACT FROM AUTHOR]

Summary: A 9‐year‐old 390 kg games pony presented with acute onset of grade 5/5 (AAEP) right hindlimb (RH) lameness. During clinical examination, the source of lameness was localised to the tarsal region. Radiographic examination identified a closed, simple, nondisplaced, incomplete fracture of the calcaneal shaft. The pony was initially treated with box rest; however, despite an initial good response, the horse re‐presented with a grade 5/5 (AAEP) RH lameness, 2 weeks after initial presentation. The decision was made to treat the fracture using a tarsal sleeve cast extending from mid‐third of the tibia/crus to the level of distal metatarsus. The cast was replaced every 2 weeks and maintained for a total of 8 weeks. After cast removal, the horse was kept on strict box rest for 3 weeks. After discharge from the hospital, in‐hand walking exercise from the stable was commenced and gradually increased over a 4‐week period. The horse was then gradually reintroduced to small paddock turnout exercise for eight further weeks. The horse was able to return to full athletic function. Conservative treatment using a tarsal sleeve cast should be considered only in horses presenting an incomplete nondisplaced fracture of the calcaneal shaft. [ABSTRACT FROM AUTHOR]

Summary: Definitive diagnosis of a deep digital flexor tendon insertional lesion within the right fore foot was made by magnetic resonance imaging (MRI) examination and the lesion subsequently treated by injection with platelet‐rich plasma. MRI was used to guide positioning of the needle to achieve highly accurate injection. The volume injected was found to approximate the calculated lesion volume. On the basis of experience with this case, MRI‐guided injection of insertional deep digital flexor tendon lesions of the foot of horses under general anaesthesia is practicable. This technique is likely to be more accurate than the other techniques described (computed tomography, ultrasonography) and carries no risk of exposure to radiation (radiography). [ABSTRACT FROM AUTHOR]

Introduction/objective: Data on long-term treatment with Esketamine Nasal Spray (ESKNS) in real-world patients with treatment resistant depression (TRD) is scarce. The primary aim of the study is to evaluate the effectiveness and tolerability of ESK-NS treatment at 6 and 12-month follow-ups., Methods: This is part of an observational, retrospective, multicentric Italian study (REAL-ESK study). Subjects for the present study underwent psychiatric assessments after 6 and 12 months from the start of ESK-NS treatment. Repeated measures analysis of variance (ANOVA) was used to assess changes in continuous variables, such as scores on psychometric scales from baseline to follow-up time points., Results: Of 63 patients who maintained ESK-NS treatment for at least 6 months, 48 were responders or remitters (76.2%). Among 15 non-responders at 6 months, 4 significantly improved at 12-month follow-up. At least one side effect was reported by 71.8% of subjects with a 6-month follow-up assessment. An overall reduction of side effects was noticed as treatment progressed (42% of patients who continued the treatment reported side effects at 12 months). The most common side effects were sedation (31.7%) and dissociation (28.6%) during ESK-NS sessions. Only 2 patients discontinued ESK-NS for tolerability reasons., Conclusion: The results support the effectiveness and safety of esketamine in the mid and long-term treatment of TRD patients. The late clinical response of a subgroup of patients represents a novel finding. Data needs to be confirmed in larger samples and longer observation periods., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To describe the surgical technique for removal of hoof wall masses in horses under standing sedation (SS) and local anesthesia (LA), and to report complications and long-term outcome following surgery., Study Design: Observational retrospective study., Animals: Client-owned horses (n = 30)., Methods: Horses undergoing keratoma removal under SS and LA in a single equine hospital between August 2016 and July 2023 were included in the study. Signalment, affected foot, history of lameness and/or foot abscesses, degree of lameness on admission, imaging findings (radiography and magnetic resonance imaging [MRI] when available), location of the mass, surgical technique, remedial farriery, postoperative care, complications and outcome were recorded. Long-term follow-up information was obtained by telephone questionnaire., Results: A total of 30 horses met the inclusion criteria. Duration of lameness ranged from 1 to 289 days (mean 90 days). The degree of lameness varied from absent to grade 4/5 (AAEP) (mean grade 3/5). All horses underwent preoperative radiographic examination and 14/30 underwent MRI. All horses underwent partial hoof wall resection. The surgery was performed safely in all cases. Postoperative complications included marked lameness in the early postoperative period in 3/30 horses and exuberant granulation tissue formation in 2/30 horses. Long-term (>6 months) follow-up information was available for 28 horses, and 26/28 horses returned to previous levels of exercise. Recurrence was suspected in 1/30 horses., Conclusions: The complication rate was lower than previously reported for keratoma removal under general anesthesia (GA)., Clinical Significance: Removal of hoof wall masses under SS and LA can be considered as an alternative to removal under GA., (© 2024 American College of Veterinary Surgeons.)

Objective: Even though the COVID-19 emergency has concluded, its consequences are still relevant. Recent evidence suggests that a significant proportion of individuals experience persistent symptoms long after the initial infection has resolved, classified as "Long COVID" condition. Fear of COVID-19 increases anxiety and stress levels in healthy individuals and exacerbates the symptoms of those with pre-existing psychiatric disorders; therefore understanding the impact of the pandemic on psychiatric disorders remains of utmost importance. The present study aimed at assessing the prevalence and predictive factors of fear of COVID-19 in a sample of patients with different psychiatric conditions., Method: A sample of 269 psychiatric patients were recruited from two different tertiary clinics in Italy and assessed with the Fear of COVID-19 Scale (FCV-19S). In order to compare patients with a significant fear of COVID-19 or without (Fear+ vs. Fear-) and to identify the main features in terms of clinical dimension, exploratory and predictive analysis were performed., Results: Female gender, age at illness onset, and insight levels emerged as positive predictors of FCV-19S. Conversely, current substance abuse emerged as a negative predictor of fear levels. Moreover, significantly lower FCV-19S scores were observed in patients with a diagnosis of schizophrenia spectrum disorders., Conclusions: Specific sociodemographic and clinical factors predicted higher levels of fear of COVID-19 in psychiatric patients. Further studies are warranted to determine the potential long-term consequences of the COVID-19 impact on mental health., Competing Interests: Competing interests: None., (© 2024 Giovanni Fioriti Editore s.r.l.)

Objective: To determine the influence of breed (cob [CB] and non-cob [NC]), obturator type and surgical experience on the number of attempts, time taken and iatrogenic damage (ID) created when entering the digital flexor tendon sheath (DFTS) tenoscopically., Study Design: Prospective experimental cadaveric study., Animals: A total of 104 cadaver limbs., Methods: An equal number of randomly selected CB and NC limbs were operated using a conical obturator (OB) or a switching stick (SS) by one boarded (BS) and one resident surgeon (RS). Skin measurements, number of attempts and time taken to enter the DFTS were recorded. The DFTS was endoscopically examined and then dissected to record ID and cumulative ID calculated., Results: Mean CB skin thickness (8.4 mm) was nearly twice that of NC limbs (4.5 mm) (p < .001). Mean DFTS entry took longer in CB limbs (133 s) compared to NC limbs (112 s) (p = .02). BS mean entry time in CB limbs was 115 s compared to 46 s in NC limbs (p < .001). Cumulative ID was greater in CB limbs (25 of 52 limbs with ID) compared to NC limbs (14 of 52 limbs with ID) (p = .04). No difference was noted between obturators. Surgical experience reduced attempts and time entering the DFTS., Conclusion: Surgeons take longer to enter DFTS in CB limbs and more cumulative ID is created, regardless of obturator type used., Clinical Significance: Skin thickness is a major determinant of time taken to enter the DFTS and increases the risk of ID. Awareness of the challenges in CB limbs is important., (© 2024 American College of Veterinary Surgeons.)

A newborn Thoroughbred filly presented with a large mass located on the ventro-rostral aspect of the mandible. The mass was surgically removed under general anaesthesia. Upon gross examination, the mass was well circumscribed with a heterogeneous lobulated appearance. The results of histopathology and immunohistochemistry were consistent with a diagnosis of congenital fetal rhabdomyoma. On follow-up at six months post-surgical excision, no abnormalities were noted on clinical examination., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Objective: To determine the outcome of tenoscopically guided palmar/plantar annular ligament (PAL) desmotomy to treat PAL constriction without concurrent intrathecal soft-tissue injury, notably of the digital flexor tendons and manica flexoria., Study Design: Retrospective multicenter cohort study., Animals: Sixty-five horses., Methods: Horses from four UK equine hospitals, with digital flexor tendon sheath (DFTS) tenosynovitis, which underwent tenoscopically guided PAL desmotomy for treatment of PAL constriction between 2017 and 2022 were included. All horses had lameness isolated to the DFTS/PAL, and PAL constriction was diagnosed tenoscopically when there was difficulty maneuvering the endoscope into or through the fetlock canal. Horses with tearing of the digital flexor tendons and/or manica flexoria, or any other intrathecal pathology, were excluded. Follow up was via structured telephone questionnaire., Results: Follow up (median 25 months) was available for 61 horses with cobs and ponies predominating. Forty-two returned to their previous level of work, or a higher level, postoperatively and 50 owners were satisfied with the outcome of surgery. Eleven horses returned to lower level exercise, and six were retired/euthanized as they did not regain soundness. Fifty-two horses achieved soundness (median 3 months postoperatively)., Conclusion: Tenoscopically guided PAL desmotomy for the treatment of PAL constriction in the absence of intrathecal soft tissue injury had a good prognosis for return to previous levels of exercise in a UK horse population., Clinical Significance: The prognosis for horses undergoing tenoscopically guided PAL desmotomy to treat PAL constriction in the absence of intrathecal injury is better than previously described. Cobs and ponies seem to be predisposed to PAL constriction in agreement with the previous literature., (© 2024 The Author(s). Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.)

Background: Peritoneal fluid lactate concentration is an important diagnostic tool in horses with abdominal pain. Information on peritoneal lactate concentrations is lacking following parturition in the mare., Objectives: To compare blood and peritoneal lactate concentrations in a population of mares within 36 h post-partum, report a normal reference range and identify any impact of retained foetal membranes (RFMs)., Methods: This is a retrospective study evaluating healthy mares from which blood and peritoneal samples had been obtained within 36 h of parturition. Exclusion criteria included signs of abdominal pain within this period. Data was interrogated for normality using a Shapiro-Wilk test. Wilcoxon signed-rank test and Bland-Altman analysis were used to compare blood and peritoneal lactate concentrations. Linear regression was used to compare age and breed data with peritoneal lactate concentrations. Significance was defined as p < 0.05., Results: Forty mares met the inclusion criteria. Mean age was 12.6 ± 4.1 years, and most mares were multiparous (65%). Peritoneal lactate ((1.2 (IQR = 0.9-1.6) mmol/L) was increased compared to blood lactate concentration (0.7 (IQR = 0-1.1)mmol/L; p < 0.001). Plasma total protein (TP) concentrations were 68 (IQR = 64-74) g/L and peritoneal protein concentrations 8 (IQR = 4-9.7) g/L. Six mares developed RFM. The median fold-increase in peritoneal lactate concentration compared to blood lactate concentration was 0.9 (IQR: 0.01-1.7; range: 0-2.5). The reference range for peritoneal fluid lactate concentration was 0-2.5 mmol/L., Conclusion: Peritoneal lactate concentrations in healthy post-partum mares remained within the normal reference range and were not influenced by RFM or parturition. Increased peritoneal lactate in this group warrants further investigation., (© 2024 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Schizophrenia is thought to reflect aberrant connectivity within cortico-cortical and reentrant thalamo-cortical loops, which physiologically integrate and coordinate the function of multiple cortical and subcortical structures. Despite extensive research, reliable biomarkers of such "dys-connectivity" remain to be identified at the onset of psychosis, and before exposure to antipsychotic drugs. Because slow waves travel across the brain during sleep, they represent an ideal paradigm to study pathological conditions affecting brain connectivity. Here, we provide proof-of-concept evidence for a novel approach to investigate slow wave traveling properties in First-Episode Psychosis (FEP) with high-density electroencephalography (EEG). Whole-night sleep recordings of 5 drug-naïve FEP and 5 age- and gender-matched healthy control subjects were obtained with a 256-channel EEG system. One patient was re-recorded after 6 months and 3 years of continuous clozapine treatment. Slow wave detection and traveling properties were obtained with an open-source toolbox. Slow wave density and slow wave traveled distance (measured as the line of longest displacement) were significantly lower in patients (p < 0.05). In the patient who was tested longitudinally during effective clozapine treatment, slow wave density normalized, while traveling distance only partially recovered. These preliminary findings suggest that slow wave traveling could be employed in larger samples to detect cortical "dys-connectivity" at psychosis onset., (© 2024. The Author(s).)

Introduction: Intravenous ketamine (KET-IV) and intranasal esketamine (ESK-NS) are effective in the acute treatment of Treatment-Resistant Depression (TRD). Studies comparing KET-IV and ESK-NS concerning their action, safety, and tolerability are currently lacking., Materials and Methods: We combined patients' data from two unipolar TRD cohorts that received KET-IV (n = 171) at the Canadian Rapid Treatment Center of Excellence in Toronto, Canada, or ESK-NS (n = 140) at several TRD clinics in Italy. The Quick Inventory for Depression Symptomatology-Self-Report-16/QIDS-SR16 in the KET-IV group and Montgomery-Åsberg Depression Rating Scale/MADRS in the ESK-NS group measured depressive symptoms at baseline (T0) and after the acute treatment phase (T1) (i.e., four infusions of KET-IV and eight administrations of ESK-NS). As different scales were used, the primary outcome was to compare the improvement in depression severity in the two cohorts by measuring effect sizes, response and remission rates. Finally, we compare side effects and discontinuation rates., Results: At T1, KET-IV and ESK-NS significantly reduced depressive symptoms (respectively: QIDS-SR16 mean reduction = 5.65, p < 0.001; MADRS mean reduction = 11.41, p = 0.025). KET-IV showed larger effect sizes compared to ESK-NS (1.666 vs. 1.244). KET-IV had higher response rates (36 % vs. 25 %; p = 0.042) but not superior remission rates (13 % vs. 12 %; p = 0.845) than ESK-NS at T1. Despite more reported side effects, KET-IV did not cause more discontinuations for adverse events (4.6 % vs. 2.12 %; p = 0.228) than ESK-NS., Conclusion: KET-IV showed a higher short-term antidepressant effect, whereas ESK-NS exhibited lower side effects. Both were generally well tolerated. Future head-to-head studies should consider the long-term efficacy of these treatments., Competing Interests: Declaration of competing interest Dr. Taeho Greg Rhee was supported in part by the National Institute on Aging (NIA) (#R21AG070666; R21AG078972), National Institute of Mental Health (#R21MH117438), National Institute on Drug Abuse (#R21DA057540) and Institute for Collaboration on Health, Intervention, and Policy (InCHIP) of the University of Connecticut. Dr. Rhee serves as a review committee member for Patient-Centered Outcomes Research Institute (PCORI) and Substance Abuse and Mental Health Services Administration (SAMHSA) and has received honoraria payments from PCORI and SAMHSA. Dr. Rhee has also served as a stakeholder/consultant for PCORI and received consulting fees from PCORI. Dr. Rhee serves as an advisory committee member for International Alliance of Mental Health Research Funders (IAMHRF). Dr. Rhee is currently a co-Editor-in-Chief of Mental Health Science and has received honorarium payments annually from the publisher, John Wiley & Sons, Inc. Dr. Giorgio Di Lorenzo has been a speaker and/or a consultant for Angelini, FB-Health, Janssen-Cilag, Livanova, Lundbeck, Neuraxpharm, Otsuka, and Recordati. Dr. Raffaella Zanardi has been a consultant/speaker for Baldacci and Italfarmaco. Dr. Gianluca Rosso has been a speaker and/or consultant from Angelini, Janssen, Lundbeck, Otsuka, Viatris. Dr. Ileana Andriola was a speaker at Janssen sponsored conference. Dr. Bernardo Maria Dell'Osso has received lecture honoraria from Angelini, Lundbeck, Janssen, Pfizer, Neuraxpharm, Arcapharma, and Livanova. Dr. Rosenblat is the medical director of the Braxia Scientific Corp, which provides ketamine and esketamine treatment for depression; he has received research grant support from the American Psychiatric Association, the American Society of Psychopharmacology, the Canadian Cancer Society, the Canadian Psychiatric Association, the Joseph M. West Family Memorial Fund, the Timeposters Fellowship, the University Health Network Centre for Mental Health, and the University of Toronto and speaking, consultation, or research fees from Allergan, COMPASS, Janssen, Lundbeck, and Sunovion. Dr. Giovanni Martinotti has been a consultant and/or a speaker and/or has received research grants from Angelini, Doc Generici, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Servier, and Recordati. Dr. Roger McIntyre 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, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, Atai Life Sciences. Dr. Roger McIntyre is the CEO of Braxia Scientific Corp. The remaining authors declare that the research was conducted without any commercial or financial relationship that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: The pathophysiology of mental illnesses is not fully understood, leading to insufficient remission, frequent adverse drug reactions, and treatment resistance. Pharmacogenetic (PGx) testing, a personalized approach recently adopted also in psychiatry, can guide effective drug therapy and minimize side effects. The objective of this study was to determine the perspective of Slovak clinicians regarding the integration of PGx testing in psychiatric clinical practice., Methods: Questionnaires covering various aspects such as prior experience with PGx testing, self-perceived competence, perceived utility, potential risks and challenges were distributed directly to attendees at two psychiatric conferences held in Slovakia in 2023 and their responses were statistically analysed., Results: Out of 54 respondents, only 7.4% had previous experience with PGx in clinical practice. The most clinicians felt that they should possess the skills to apply PGx testing in psychiatric clinical practice and were enthusiastic about increasing their expertise. They found PGx useful in medication selection, adverse effect management, and treatment-resistant depression. The primary concerns centered around the lack of well-defined guidelines and the financial considerations linked to the testing., Conclusions: Considering the participants' interest in PGx and its integration into clinical practice, educational programmes based on recommendations, guidelines, and convincing evidence could be organized (Tab. 4, Ref. 30). Text in PDF www.elis.sk Keywords: pharmacogenetics, pharmacogenomics, psychiatry, personalized treatment, Slovakia, perspective.

Treatment-resistant depression (TRD) represents a severe clinical condition with high social and economic costs. Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD by EMA and FDA, but data about predictors of response are still lacking. Thus, a tool that can predict the individual patients' probability of response to ESK-NS is needed. This study investigates sociodemographic and clinical features predicting responses to ESK-NS in TRD patients using machine learning techniques. In a retrospective, multicentric, real-world study involving 149 TRD subjects, psychometric data (Montgomery-Asberg-Depression-Rating-Scale/MADRS, Brief-Psychiatric-Rating-Scale/BPRS, Hamilton-Anxiety-Rating-Scale/HAM-A, Hamilton-Depression-Rating-Scale/HAMD-17) were collected at baseline and at one month/T1 and three months/T2 post-treatment initiation. We trained three different random forest classifiers, able to predict responses to ESK-NS with accuracies of 68.53% at T1 and 66.26% at T2 and remission at T2 with 68.60% of accuracy. Features like severe anhedonia, anxious distress, mixed symptoms as well as bipolarity were found to positively predict response and remission. At the same time, benzodiazepine usage and depression severity were linked to delayed responses. Despite some limitations (i.e., retrospective study, lack of biomarkers, lack of a correct interrater-reliability across the different centers), these findings suggest the potential of machine learning in personalized intervention for TRD., Competing Interests: Declaration of Competing Interest The remaining authors declare that the research was conducted without any commercial or financial relationship that could be construed as a potential conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Obtaining a healthy wound environment that is conductive to healing in horses can be challenging. Negative-pressure wound therapy (NPWT) has been employed in humans to enhance wound healing for decades. The existing evidence for the effectiveness of NPWT remains uncertain in equine medicine. The aim of this review is to investigate NPWT applications and benefits in horses. A scoping review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines for scoping reviews on three databases (PubMed, Web of Science-Thompson Reuters, and Wiley Online Library). Twenty-four manuscripts were considered. After removing duplicates, 17 papers underwent abstract screening. Of these, 16 + 1 (cited by others) were evaluated for eligibility according to PICOs, including no case reports/retrospective studies, four original articles, and three reviews. Fifteen manuscripts met the inclusion criteria. The focus of the articles was wound management; they included three reports of wounds communicating with synovial structures. Traumatic wounds and surgical-site infections are indications for NPWT. NPWT presents several advantages and few complications making it an attractive alternative to conventional wound management. However, randomized controlled trials should be performed to quantify the benefits and establish precise protocols in horses.

Sirtuin 1 (SIRT1) is a sensor of cell energy availability, regulating metabolic homeostasis as well as leptin and ghrelin, and it could be considered as a potential plasmatic marker. The aim of this study was to assess whether circulating SIRT1 varies consistently with leptin, ghrelin, body mass index (BMI), and IgG reactive to hypothalamic antigens in anorexia nervosa (AN). Fifty-four subjects were evaluated: 32 with AN and 22 normal-weight control subjects. Serum levels of SIRT1, leptin, ghrelin, and IgG reactive to hypothalamic antigens were evaluated by ELISA. Results showed that serum SIRT1 is increased in patients with AN, and the amount is decreased in relation to the duration of the illness. SIRT1 concentration approaches the values obtained for the control group, although the difference is still statistically significant. A negative correlation between serum SIRT1 values and leptin or BMI values has been found. On the contrary, a positive correlation between SIRT1 and ghrelin or IgG specific for hypothalamic antigens is reported. These findings suggest that a peripheral evaluation of SIRT1 could be a possible clinical/biochemical parameter related to AN. In addition, we can assume that SIRT1 is related to autoantibody production and may correlate with the intensity/severity of AN. Thus, reducing the production of autoantibodies specific for hypothalamic cells could be a sign of improvement of the clinical condition.

Background: Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first-line therapeutic options, resulting in treatment-resistant bipolar depression (B-TRD). Esketamine, the S-enantiomer of ketamine, has recently been approved for treatment-resistant depression (TRD), but no data are available on its use in B-TRD., Objectives: To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B-TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B-TRD, focusing on the average risk of an affective switch., Methods: Thirty-five B-TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery-Asberg Depression Rating Scale/MADRS, Hamilton-depression scale/HAM-D, Hamilton-anxiety scale/HAM-A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up., Results: A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B-TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B-TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment-emergent affective switch., Conclusions: Our results supported the effectiveness and tolerability of esketamine in a real-world population of subjects with B-TRD. The low risk of manic switch in B-TRD patients confirmed the safety of this treatment., (© 2023 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Schizophrenia spectrum disorders (patients with a diagnosis of schizophrenia, schizotypal, and delusional disorders: F20-F29 according to International Classification of Diseases 10th revision (ICD-10)) are considered highly heritable heterogeneous psychiatric conditions. Their pathophysiology is multifactorial with involved dysregulated serotonergic neurotransmission and synaptic plasticity. The present study aimed to evaluate the association of SLC6A4 (5-HTTLPR), FTO (rs9939609), and BDNF (rs6265, rs962369) polymorphisms with schizophrenia spectrum disorders in Slovak patients. We analyzed the genotypes of 150 patients with schizophrenia, schizotypal, and delusional disorders and compared them with genotypes from 178 healthy volunteers. We have found a marginally protective effect of LS + SS genotypes of 5-HTTLPR variant of the serotonin transporter SLC6A4 gene against the development of schizophrenia spectrum disorders, but the result failed to remain significant after Bonferroni correction. Similarly, we have not proven any significant association between other selected genetic variants and schizophrenia and related disorders. Studies including a higher number of subjects are warranted to reliably confirm the presence or absence of the studied associations.

Astrocytes coordinate several homeostatic processes of the central nervous system and play essential roles for normal brain development and response to disease conditions. Protocols for the conversion of human induced pluripotent stem cells (hiPSCs) into mature astrocytes have opened to the generation of in vitro systems to explore astrocytes' functions in living human cell contexts and patient-specific settings. In this study, we present an optimized monolayer procedure to commit hiPSC-derived cortical progenitors into enriched populations of cortical astrocyte progenitor cells (CX APCs) that can be further amplified and efficiently differentiated into mature astrocytes. Our optimized system provides a valid tool to explore the role of these cells in neurodevelopmental and neuropsychiatric diseases, opening it up to applications in drug development and biomarkers discovery/validation.

Since suicide and suicidal behavior are considered highly heritable phenotypes, the identification of genetic markers that can predict suicide risk is a clinically important topic. Several genes studied for possible associations between genetic polymorphisms and suicidal behaviors had mostly inconsistent and contradictory findings. The aim of this case-control study was to evaluate the associations between completed suicide and polymorphisms in genes BDNF (rs6265, rs962369), SLC6A4 ( 5-HTTLPR ), and FTO (rs9939609) in relation to sex and BMI. We genotyped 119 completed suicide victims and 137 control subjects that were age, sex, and ethnicity matched. A significant association with completed suicide was found for BDNF rs962369. This variant could play a role in completed suicide, as individuals with the CC genotype were more often found among suicides than in control subjects. After sex stratification, the association remained significant only in males. A nominally significant association between the gene variant and BMI was observed for BDNF rs962369 under the overdominant model. Heterozygotes with the TC genotype showed a lower average BMI than homozygotes with TT or CC genotypes. FTO polymorphism (rs9939609) did not affect BMI in the group of Slovak suicide completers, but our findings follow an inverse association between BMI and completed suicide.

Generalized Anxiety Disorder (GAD) and Panic Disorder (PD) share underlying neurobiological mechanisms and several clinical features which, with medical comorbidities, may increase misdiagnosis and delay proper treatment. The aim of the study was to evaluate the association between clinical/socio-demographic markers and GAD/PD diagnosis. Outpatients (N = 290) with PD or GAD were identified in mental health services in Monza and Milan (Italy). Descriptive analyses and a binary logistic regression model were performed. Post-onset psychiatric ( p = 0.05) and medical ( p = 0.02) multiple co-morbidities were associated with GAD; treatment with selective serotonin reuptake inhibitors (SSRIs) was associated with PD, while GAD diagnosis was associated with treatment with atypical antipsychotics or GABAergic drugs ( p = 0.03), as well as psychodynamic psychotherapy ( p < 0.01). Discontinuation of the last pharmacological treatment was associated with GAD diagnosis rather than the PD one ( p = 0.02). GAD patients may have a worse prognosis than PD patients because of more frequent multiple co-morbidities, relapses and poorer treatment compliance. The different treatment approaches were consistent with the available literature, while the association between GAD and psychodynamic psychotherapy is an original finding of our study. Further studies on larger samples are necessary to better characterize clinical factors associated with GAD or PD.

Previous studies have shown, although not consistently, that first generation antipsychotics (FGA) are associated with a prevalence of extrapyramidal symptoms (EPS) higher than second generation antipsychotics (SGA). We assessed the prevalence and the incidence of antipsychotic-induced EPS in a large sample of community-dwelling Italian persons with schizophrenia before and after a 4-year naturalistic treatment, to shed light on their natural evolution and to identify possible predicting factors. EPS and psychopathology were assessed in 571 subjects with schizophrenia before (baseline) and after 4-year follow-up. Patients underwent treatment with SGA and/or FGA according to the referring clinicians' judgment. Relationships between EPS and psychopathology were assessed by network analysis, while a linear multiple regression investigated factors correlated to the presence of EPS at follow-up. EPS were significantly more frequent in the FGA- than in the SGA-treated group, and patients with EPS presented a more severe psychopathology. Parkinsonism was directly and positively connected with poor emotional expression at baseline and with poor emotional expression and disorganization at follow-up. Over the 4-year follow-up, emergent EPS were more frequent in FGA-treated patients, while relieved EPS occurred more frequently in SGA-treated persons. The presence of EPS at follow-up was significantly associated with EPS at baseline, illness duration, antipsychotic generation and the daily dose of antipsychotic medications. After a 4-year naturalistic treatment, EPS disappeared more frequently in SGA-treated patients, while they emerged more frequently in FGA-treated individuals. Therefore, although SGA did not eliminate the risk of EPS, these drugs seem to be associated to a more favorable EPS natural evolution., Competing Interests: Declaration of competing interest None., (Copyright © 2022. Published by Elsevier B.V.)

The advent of intra-nasal esketamine (ESK), one of the first so called fast-acting antidepressant , promises to revolutionize the management of treatment resistant depression (TRD). This NMDA receptor antagonist has proven to be rapidly effective in the short- and medium-term course of the illness, revealing its potential in targeting response in TRD. Although many TRD ESK responders are able to achieve remission, a considerable portion of them undergo a metamorphosis of their depression into different clinical presentations, characterized by instable responses and high recurrence rates that can be considered closer to the concept of Difficult to Treat Depression (DTD) than to TRD. The management of these DTD patients usually requires a further complex multidisciplinary approach and can benefit from the valuable contribution of new personalized medicine tools such as therapeutic drug monitoring and pharmacogenetics. Despite this, these patients usually come with long and complex previous treatments history and, often, advanced and sophisticated ongoing pharmacological schemes that can make the finding of new alternative options to face the current recurrences extremely challenging. In this paper, we describe two DTD patients-already receiving intranasal ESK but showing an instable course-who were clinically stabilized by the association with minocycline, a semisynthetic second-generation tetracycline with known and promising antidepressant properties.

Stiff-person syndrome is a well-recognised disease in humans, whilst cases of stiff-horse syndrome (SHS) have been rarely reported in the veterinary medicine literature. SHS is a progressive immunomediated disorder of the central nervous system leading to a disturbance of gamma amino butyric acid transmission at the neuromuscular junction in which antibodies are produced against the enzyme glutamic acid decarboxylase. A 6 year-old Irish Sport Horse was presented for investigation of involuntary violent contraction of hindlimb and back muscles triggered by stress. The diagnosis of SHS was made after elevated anti-glutamic acid decarboxylase antibodies titres were detected in the horse's serum. Administration of oral corticosteroids (prednisolone 0.75 mg/kg bwt) resulted in resolution of the clinical signs. However, reoccurrence of clinical signs was observed after the dose of corticosteroids was reduced or the treatment discontinued. To the best of the authors' knowledge this is the first reported case of SHS in United Kingdom. Considering the potential implications on the horses' welfare, further investigation on SHS pathogenesis and treatment are warranted., (Copyright © 2022. Published by Elsevier Inc.)

SARS-CoV-2 infection causes a pulmonary disease (COVID-19) which spread worldwide generating fear, anxiety, depression in the general population as well as among subjects affected by mental disorders. Little is known about which different psychopathological changes the pandemic caused among individuals affected by different psychiatric disorders, which represents the aim of the present study. Specific psychometric scales were administered at three time points: T0 as outbreak of pandemic, T1 as lockdown period, T2 as reopening. Descriptive analyses and linear regression models were performed. A total of 166 outpatients were included. Overall, psychometric scores showed a significant worsening at T1 with a mild improvement at T2. Only psychopathology in schizophrenia (SKZ) patients and obsessive-compulsive (OC) symptoms did not significantly improve at T2. Subjects affected by personality disorders (PDs) resulted to be more compromised in terms of general psychopathology than depressed and anxiety/OC ones, and showed more severe anxiety symptoms than SKZ patients. In conclusion, subjects affected by PDs require specific clinical attention during COVID-19 pandemic. Moreover, the worsening of SKZ and OC symptoms should be strictly monitored by clinicians, as these aspects did not improve with the end of lockdown measures. Further studies on larger samples are needed to confirm our results. ClinicalTrials.gov Identifier: NCT04694482., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Treatment resistant depression (TRD) is associated with poor outcomes, but a consensus is lacking in the literature regarding which compound represents the best pharmacological augmentation strategy to antidepressants (AD). In the present review, we identify the available literature regarding the pharmacological augmentation to AD in TRD. Research in the main psychiatric databases was performed (PubMed, ISI Web of Knowledge, PsychInfo). Only original articles in English with the main topic being pharmacological augmentation in TRD and presenting a precise definition of TRD were included. Aripiprazole and lithium were the most investigated molecules, and aripiprazole presented the strongest evidence of efficacy. Moreover, olanzapine, quetiapine, cariprazine, risperidone, and ziprasidone showed positive results but to a lesser extent. Brexpiprazole and intranasal esketamine need further study in real-world practice. Intravenous ketamine presented an evincible AD effect in the short-term. The efficacy of adjunctive ADs, antiepileptic drugs, psychostimulants, pramipexole, ropinirole, acetyl-salicylic acid, metyrapone, reserpine, testosterone, T3/T4, naltrexone, SAMe, and zinc cannot be precisely estimated in light of the limited available data. Studies on lamotrigine and pindolol reported negative results. According to our results, aripiprazole and lithium may be considered by clinicians as potential effective augmentative strategies in TRD, although the data regarding lithium are somewhat controversial. Reliable conclusions about the other molecules cannot be drawn. Further controlled comparative studies, standardized in terms of design, doses, and duration of the augmentative treatments, are needed to formulate definitive conclusions.

Background: Major depressive disorder (MDD) patients not responding to two or more different antidepressant treatments are currently considered to suffer from treatment resistant depression (TRD). Recently, intranasal esketamine has been approved by both the American Food and Drug Administration and European Medicines Agency for TRD and, more recently, in moderate to severe episode of MDD, as acute short-term treatment for the rapid reduction of depressive symptoms, which, according to clinical judgement, constitute a psychiatric emergency. There is currently no indication for obsessive-compulsive disorder (OCD) although recently published studies have already shown a rapid and significant reduction of OCD-like symptoms following ketamine administration. The etiology of OCD has not yet been fully elucidated but there is a growing evidence that glutamate signaling dysfunction in the cortico-striatal-thalamo-cortical circuitry plays an essential role. This case report exemplifies possible clinical effects of esketamine on both depressive and OCD symptoms., Case Presentation: We present the case of a 39-year-old man suffering from TRD. During the first evaluation at our clinic, he also reported the presence of OCD spectrum symptoms, causing him to perform time-consuming mental rituals due to pathological doubts regarding the relationship with his wife as well as intrusive thoughts regarding his mental conditions. He underwent psychometric evaluations, therapeutic drug monitoring analysis, and pharmacogenomic tests. The overall results helped to explain patient's treatment-resistance. Moreover, we observed a significant reduction in both depressive and OCD symptoms after administration of esketamine., Conclusion: This case underlines the importance of pharmacogenomic tests in profiling TRD patients and confirms the possible use of esketamine in the treatment of comorbid OCD., (© 2021. The Author(s).)

Esketamine (ESK) has been approved as a rapid-acting intranasal treatment for treatment-resistant depression (TRD). Although existing studies have investigated the efficacy of ESK in the 4-week induction phase, our knowledge about long-term ESK efficacy remains poor. The aim of this systematic review was to summarize the available data on long-term ESK efficacy for TRD. A systematic search was performed including articles in English, up to 31 March 2021. The search found 7 relevant studies, involving 1024 adult TRD patients. Continuing treatment with ESK after the 4-week induction phase may be associated with stable efficacy in relapse prevention among TRD patients. Conversely, the long-term antidepressant effectiveness upon discontinuation of ESK might be limited, although data from three studies had a moderate to high risk of bias. Overall, the results on the effectiveness of this compound in the long term are mixed. According to our findings, ESK treatment should be continued following the induction phase to reach a stable efficacy in relapse prevention, while the long-term antidepressant and anti-suicidal effects of ESK after discontinuation are inconsistent. Currently, the level of proof of ESK efficacy in long-term TRD treatment remains low and more RCTs with larger sample sizes and active comparators are needed.

Approximately 30% of Major Depressive Disorder (MDD) patients develop treatment-resistant depression (TRD). Among the different causes that make TRD so challenging in both clinical and research contexts, major roles are played by the inadequate understanding of MDD pathophysiology and the limitations of current pharmacological treatments. Nevertheless, the field of psychiatry is facing exciting times. Combined with recent advances in genome editing techniques, human induced pluripotent stem cell (hiPSC) technology is offering novel and unique opportunities in both disease modelling and drug discovery. This technology has allowed innovative disease-relevant patient-specific in vitro models to be set up for many psychiatric disorders. Such models hold great potential in enhancing our understanding of MDD pathophysiology and overcoming many of the well-known practical limitations inherent to animal and post-mortem models. Moreover, the field is approaching the advent of (es)ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, claimed as one of the first and exemplary agents with rapid (in hours) antidepressant effects, even in TRD patients. Although ketamine seems poised to transform the treatment of depression, its exact mechanisms of action are still unclear but greatly demanded, as the resulting knowledge may provide a model to understand the mechanisms behind rapid-acting antidepressants, which may lead to the discovery of novel compounds for the treatment of depression. After reviewing insights into ketamine's mechanisms of action (derived from preclinical animal studies) and depicting the current state of the art of hiPSC technology below, we will consider the implementation of an hiPSC technology-based TRD model for the study of ketamine's fast acting antidepressant mechanisms of action., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Objectives:  This article evaluates and compares the diffusion pattern of radiopaque contrast medium following perineural analgesia of the deep branch of the lateral plantar nerve performed using two different techniques: weight-bearing or flexed., Study Design:  This was an in vivo experimental study., Methods:  Eight horses were enrolled. Perineural injection of the right and left deep branch lateral plantar nerves was performed with a weight-bearing or flexed technique, using radiopaque contrast medium (iohexol). Radiographic evaluation was performed after 5 (T5), 15 (T15) and 30 (T30) minutes. The diffusion of contrast medium was assessed independently by two blinded readers who analysed the extension of the main contrast medium bulk and the maximum diffusion of contrast medium in both proximal and distal directions. The effect of time and technique employed on contrast medium diffusion was assessed using two-way analysis of variance for repeated measures ( p  ≤  0.05)., Results:  There was no significant difference in the diffusion of the contrast medium between the two techniques at T15. However, at T30 the weight-bearing technique resulted in a significantly increased diffusion in the proximal direction ( p  = 0.02). In one case, belonging to the weight-bearing group, contrast medium was identified within the tarsal sheath. There was no evidence of contrast medium in the tarsometatarsal joint of any horse, regardless of the technique used., Conclusions:  The two techniques resulted in a similar diffusion at T15. However, the use of a weight-bearing technique resulted in a significant increase in proximal contrast medium diffusion 30 minutes after injection., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

A 12-year-old Warmblood mare was presented with an acute onset left hindlimb lameness associated with generalised soft tissue swelling of the entire limb and medial saphenous vein (MSV) thrombophlebitis. A presumptive diagnosis of extremity compartment syndrome (ECS) was made. Due to the clinical deterioration, emergency fasciotomy of the crural fascia and biopsy was performed. Histological and immunohistochemical examination of the samples confirmed a diagnosis of leiomyosarcoma likely originating from the tunica media of the MSV. This report is the first to describe an unique combination of ECS and thrombophlebitis associated with a leiomyosarcoma in a horse., Competing Interests: The authors declare no conflicts of interest., (© 2020 The Korean Society of Veterinary Science.)

Epsins are part of the internalization machinery pivotal to control clathrin-mediated endocytosis. Here, we report that epsin family members are expressed in mouse embryonic stem cells (mESCs) and that epsin1/2 knockdown alters both mESC exits from pluripotency and their differentiation. Furthermore, we show that epsin1/2 knockdown compromises the correct polarization and division of mESC-derived neural progenitors and their conversion into expandable radial glia-like neural stem cells. Finally, we provide evidence that Notch signaling is impaired following epsin1/2 knockdown and that experimental restoration of Notch signaling rescues the epsin-mediated phenotypes. We conclude that epsins contribute to control mESC exit from pluripotency and allow their neural differentiation by appropriate modulation of Notch signaling.