Emotion regulation across psychiatric disorders.

OBJECTIVE: Difficulties with emotion regulation have been associated with multiple psychiatric conditions. In this study, we aimed to investigate emotional regulation difficulties in young adults who gamble at least occasionally (ie, an enriched sample), and diagnosed with a range of psychiatric disorders using the validated Difficulties in Emotion Regulation Scale (DERS). METHODS: A total of 543 non-treatment-seeking individuals who had engaged in gambling activities on at least 5 occasions within the previous year, aged 18-29 were recruited from general community settings. Diagnostic assessments included the Mini International Neuropsychiatric Inventory, Minnesota Impulsive Disorders Interview, attention-deficit/hyperactivity disorder World Health Organization Screening Tool Part A, and the Structured Clinical Interview for Gambling Disorder. Emotional dysregulation was evaluated using DERS. The profile of emotional dysregulation across disorders was characterized using Z-scores (those with the index disorder vs. those without the index disorder). RESULTS: Individuals with probable ADHD displayed the highest level of difficulties in emotional regulation, followed by intermittent explosive disorder, social phobia, and generalized anxiety disorder. In contrast, participants diagnosed with obsessive-compulsive disorder showed relatively lower levels of difficulties with emotional regulation. CONCLUSIONS: This study highlights the importance of recognizing emotional dysregulation as a trans-diagnostic phenomenon across psychiatric disorders. The results also reveal differing levels of emotional dysregulation across diagnoses, with potential implications for tailored treatment approaches. Despite limitations such as small sample sizes for certain disorders and limited age range, this study contributes to a broader understanding of emotional regulation's role in psychiatric conditions.

Sphingolipidomic profile and HDL subfractions in obese dyslipidemic type 2 diabetic patients.

PURPOSE: The aim of the study was to investigate changes in serum sphingolipid levels and high density lipoprotein (HDL) subtypes with relation to low-density lipoprotein cholesterol (LDL-C), non-HDL-C and triglyceride (TG) levels in type 2 diabetes mellitus (T2DM) patients. METHODS: Blood was obtained from 60 patients with T2DM. Levels of sphingosine-1-phosphate (S1P), C16-C24 sphingomyelins (SMs), C16-C24 ceramides (CERs), and C16 CER-1 P were determined by LC-MS/MS. Serum concentrations of cholesterol ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT) and apolipoprotein A-1 (apoA-I) were analyzed by enzyme-linked immunosorbent assay (ELISA). HDL subfraction analysis was performed by Disc polyacrylamide gel electrophoresis. RESULTS: C16 SM, C24 SM, C24-C16 CER and C16 CER-1 P levels were significantly increased in T2DM patients with LDL-C above 160 mg/dL, compared to those with LDL-C below 100 mg/dL. A significant correlation was observed between C24:C16 SM, C24:C16 CER ratios and LDL-C, non HDL-C levels. Higher serum levels of C24 SM, C24-C18 CER and C24:C16 SM ratio was seen in obese T2DM patients (BMI>30) compared to those with BMI 27-30. Patients with fasting TG levels below 150 mg/dL had significantly increased HDL-large and significantly decreased HDL-small fractions compared to those with fasting TG levels above 150 mg/dL. CONCLUSION: Obese dyslipidemic T2DM patients had increased levels of serum sphingomyelins, ceramides and HDL-small fractions. The ratio of serum C24:C16 SM, C24:C16 CER and long chain CER levels may be used as diagnostic and prognostic indicators of dyslipidemia in T2DM.

Temperament in trichotillomania and skin picking disorder.

BACKGROUND: Trichotillomania (TTM) and skin picking disorder (SPD) result in significant psychosocial burden. Despite this burden, however, risk factors related to the development of these disorders remain unclear. The present study assessed temperament in a well-characterized sample of adults with TTM or SPD. METHODS: A total of 202 adults age 18 to 65 were enrolled; 44 had TTM, 30 had SPD, and 128 served as controls. Participants completed the self-report Tridimensional Personality Questionnaire (TPQ) to examine the severity of TTM and SPD symptoms, quality of life, and temperament. Group differences were characterized and correlations with other measures were examined. RESULTS: Compared to controls, those with TTM or SPD scored significantly higher on harm avoidance and its subscales, with TTM associated with higher scores than SPD. Those with TTM or SPD scored significantly higher on only 1 measure of novelty seeking (extravagance). Higher TPQ harm avoidance correlated with worse hair pulling severity and worse quality of life. CONCLUSIONS: The temperament traits of participants with TTM or SPD differed in significant ways from controls; those with TTM or SPD generally demonstrated similar trait profiles. A dimensional approach to the personalities of those with TTM or SPD may offer insight and provide clues to treatment strategies.

Cognition in adults with borderline personality disorder.

OBJECTIVE: Borderline personality disorder (BPD) is a common and disabling mental health disorder and has detrimental effects on affected individuals across multiple domains. We aimed to investigate whether individuals with BPD differ from control subjects in terms of cognitive functions, and to see if there is a relationship between cognitive functions, impulsivity, and BPD symptom severity. METHODS: BPD individuals (n = 26; mean age = 26.7; 69.2% female) and controls (n = 58; mean age = 25.3; 51.7% female) were enrolled. Intra/Extra-Dimensional Set Shift (IED) and One Touch Stockings of Cambridge (OTS) tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used to assess cognitive functions. Barratt Impulsivity Scale-version 11 (BIS-11) was administered to measure impulsivity and both the Zanarini Scale for Borderline Personality Disorder self-report and the clinician-administered versions were used to assess BPD symptom severity. RESULTS: BPD group showed significantly impaired cognitive performance on the IED task versus controls, but there was not a significant difference in the OTS task. BPD symptom severity was positively correlated with trait (BIS-11) impulsivity and no correlation was found between BPD symptom severity and cognitive functions. CONCLUSIONS: This study suggests people with BPD experience impaired cognitive flexibility and heightened impulsivity. Only impulsivity appeared to be directly related to symptom severity, perhaps indicating that cognitive inflexibility could be a vulnerability marker. Future research should focus on a longitudinal approach to extend clinical and theoretical knowledge in this area.

Feasibility, acceptability and practicality of transcranial stimulation in obsessive compulsive symptoms (FEATSOCS): A randomised controlled crossover trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive form of neurostimulation with potential for development as a self-administered intervention. It has shown promise as a safe and effective treatment for obsessive compulsive disorder (OCD) in a small number of studies. The two most favourable stimulation targets appear to be the left orbitofrontal cortex (L-OFC) and the supplementary motor area (SMA). We report the first study to test these targets head-to-head within a randomised sham-controlled trial. Our aim was to inform the design of future clinical research studies, by focussing on the acceptability and safety of the intervention, feasibility of recruitment, adherence to and tolerability of tDCS, and the size of any treatment-effect. METHODS: FEATSOCS was a randomised, double-blind, sham-controlled, cross-over, multicentre study. Twenty adults with DSM-5-defined OCD were randomised to treatment, comprising three courses of clinic-based tDCS (SMA, L-OFC, Sham), randomly allocated and delivered in counterbalanced order. Each course comprised four 20-min 2 mA stimulations, delivered over two consecutive days, separated by a 'washout' period of at least four weeks. Assessments were carried out by raters who were blind to stimulation-type. Clinical outcomes were assessed before, during, and up to four weeks after stimulation. Patient representatives with lived experience of OCD were actively involved at all stages. RESULTS: Clinicians showed willingness to recruit participants and recruitment to target was achieved. Adherence to treatment and study interventions was generally good, with only two dropouts. There were no serious adverse events, and adverse effects which did occur were transient and mostly mild in intensity. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores were numerically improved from baseline to 24 h after the final stimulation across all intervention groups but tended to worsen thereafter. The greatest effect size was seen in the L-OFC arm, (Cohen's d = -0.5 [95% CI -1.2 to 0.2] versus Sham), suggesting this stimulation site should be pursued in further studies. Additional significant sham referenced improvements in secondary outcomes occurred in the L-OFC arm, and to a lesser extent with SMA stimulation. CONCLUSIONS: tDCS was acceptable, practicable to apply, well-tolerated and appears a promising potential treatment for OCD. The L-OFC represents the most promising target based on clinical changes, though the effects on OCD symptoms were not statistically significant compared to sham. SMA stimulation showed lesser signs of promise. Further investigation of tDCS in OCD is warranted, to determine the optimal stimulation protocol (current, frequency, duration), longer-term effectiveness and brain-based mechanisms of effect. If efficacy is substantiated, consideration of home-based approaches represents a rational next step. TRIAL REGISTRATION: ISRCTN17937049. https://doi.org/10.1186/ISRCTN17937049.

Functional Neuroimaging Correlates of Placebo Response in Patients With Depressive or Anxiety Disorders: A Systematic Review.

BACKGROUND: The mechanisms underlying placebo effects of psychotropic drugs remain poorly understood. We carried out the first, to our knowledge, systematic review of functional neuroimaging correlates of placebo response in adults with anxiety/depressive disorders. METHODS: We systematically searched a large set of databases up to February 2021 based on a pre-registered protocol (PROSPERO CRD42019156911). We extracted neuroimaging data related to clinical improvement following placebo or related to placebo mechanisms. We did not perform a meta-analysis due to the small number of included studies and significant heterogeneity in study design and outcome measures. RESULTS: We found 12 relevant studies for depressive disorders and 4 for anxiety disorders. Activity in the ventral striatum, rostral anterior cingulate cortex and other default mode network regions, orbitofrontal cortex, and dorsolateral prefrontal cortex correlated with placebo antidepressant responses. Activity in regions of the default mode network, including posterior cingulate cortex, was associated with placebo anxiolysis. There was also evidence for possible involvement of the endogenous opioid, dopamine, and serotonin systems in placebo antidepressant and anxiolytic effects. CONCLUSIONS: Several brain regions and molecular systems may be involved in these placebo effects. Further adequately powered studies exploring causality and controlling for confounders are required.

Statistical predictors of psychosocial impairment in body-focused repetitive behaviors.

BACKGROUND: Skin picking disorder and trichotillomania, also characterized as body-focused repetitive behaviors (BFRBs), often lead to functional impairment. Some people with BFRBs, however, report little if any psychosocial dysfunction. There has been limited research as to which clinical aspects of BFRBs are associated with varying degrees of functional impairment. METHODS: Adults (n = 98), ages 18 to 65 with a current diagnosis of trichotillomania (n = 37), skin picking disorder (n = 32), trichotillomania plus skin picking disorder (n = 10), and controls (n = 19) were enrolled. Partial least squares regression (PLS) was used to identify variables associated with impairment on the Sheehan Disability Scale. RESULTS: PLS identified an optimal model accounting for 45.8% of variation in disability. Disability was significantly related to (in order of descending coefficient size): severity of picking, perceived stress, comorbid disorders (specifically, anxiety disorders / obsessive-compulsive disorder), trait impulsivity, family history of alcohol use disorder, atypical pulling/picking sites, and older age. CONCLUSIONS: At present mental disorders are viewed as unitary entities; however, the extent of impairment varies markedly across patients with BFRBs. These data suggest that whereas symptom nature/severity is important in determining impairment, so too are other variables commonly unmeasured in clinical practice. Outcomes for patients may thus be maximized by rigorously addressing comorbid disorders; as well as integrating components designed to enhance top-down control and stress management. Interestingly, focused picking and emotional pulling were linked to worse disability, hinting at some differences between the two types of BFRBs, in terms of determinants of impairment.

Clinical presentation of body-focused repetitive behaviors in minority ethnic groups.

BACKGROUND: Body-focused repetitive behaviors (BFRBs), such as trichotillomania and skin picking disorder, are psychiatric disorders characterized by repetitive grooming that result in hair loss or excoriations. Questions remain as to whether there are racial/ethnic differences in the clinical presentation of BFRBs. METHODS: We recruited 539 adults with DSM-5 trichotillomania or skin picking disorder. Of these, 76 (14.1%) self-identified as Black, Asian, or Minority Ethnic (BAME), while 463 (85.9%) self-identified as white Caucasian (hereafter referred to as non-BAME). BAME and non-BAME participants were compared on demographics, symptom severity, comorbid conditions and psychosocial impairment. RESULTS: Groups did not differ in terms of age, sex, or education levels. BAME individuals reported significantly more time spent picking or hair pulling per day compared to non-BAME individuals, and were less likely to have received treatment for their BFRB symptoms. Some differences were also found with respect to where on the body people pull and pick from. DISCUSSION: In general, the clinical profiles of BFRBs appeared similar between those from BAME versus non-BAME backgrounds. However, differences were found in terms of treatments received and an aspect of symptom severity. The findings highlight the need to better understand the heterogeneity of BFRBs including potential health inequalities.

Early postoperative changes of sphingomyelins and ceramides after laparoscopic sleeve gastrectomy.

BACKGROUND: This study aimed to determine early postoperative changes of serum sphingomyelin (SM) and ceramide (CER) species following laparoscopic sleeve gastrectomy (LSG). METHODS: Twenty obese patients [mean body mass index (BMI) 45,64 ± 6,10 kg/m2] underwent LSG and normal weight control patients (mean BMI 31,51 ± 6,21 kg/m2) underwent laparoscopic cholecystectomy. Fasting blood samples were collected prior to surgery, at day 1 and day 30 after surgery. Circulating levels of C16-C24 SMs, C16-C24 CERs and sphingosine-1-phosphate (S1P) were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Serum activity of neutral sphingomyelinase (N-SMase) was assayed by standard kit methods, and ceramide-1-phosphate (C1P) levels were determined by enzyme-linked immunosorbent assay (ELISA). Lipid profile, routine biochemical and hormone parameters were assayed by standard kit methods. Insulin sensitivity was evaluated using homeostatic model assessment for insulin resistance (HOMA IR). RESULTS: A significant decrease was observed in serum levels of very-long-chain C24 SM, very-long-chain C22-C24 CERs, HOMA-IR, N-SMase and C1P in LSG patients after postoperation day 1 and day 30 compared to preoperation levels. At 30 days postsurgery, BMI was reduced by 11%, fasting triglycerides were significantly decreased, and insulin sensitivity was increased compared to presurgery values. A significant positive correlation was found between HOMA-IR and serum levels of C22-C24 CERs in LSG patients. CONCLUSION: We conclude that very long chain CERs may mediate improved insulin sensitivity after LSG.

Decreased eicosapentaenoic acid levels in acne vulgaris reveals the presence of a proinflammatory state.

This study aimed to determine circulating levels of polyunsaturated fatty acids (PUFAs), secretory phospholipase A2 (sPLA2), lipoprotein lipase (LPL) and measure circulating protein levels of angiopoietin-like protein 3 (ANGPTL3), ANGPTL4, cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in patients with acne vulgaris. Serum from 21 control subjects and 31 acne vulgaris patients were evaluated for levels of arachidonic acid (AA, C20:4n- 6), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3). PUFA levels were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Lipid profile, routine biochemical and hormone parameters were assayed by standard kit methods Serum EPA levels were significantly decreased while AA/EPA and DGLA/EPA ratio were significantly increased in acne vulgaris patients compared to controls. Serum levels of AA, DGLA and DHA showed no significant difference while activity of sPLA2 and LPL were significantly increased in acne vulgaris compared to controls. Results of this study reveal the presence of a proinflammatory state in acne vulgaris as shown by significantly decreased serum EPA levels and increased activity of sPLA2, AA/EPA and DGLA/EPA ratio. Increased LPL activity in the serum of acne vulgaris patients can be protective through its anti-dyslipidemic actions. This is the first study reporting altered EPA levels and increased sPLA2 activity in acne vulgaris and supports the use of omega-3 fatty acids as adjuvant treatment for acne patients.

A pilot study investigating early postoperative changes of plasma polyunsaturated fatty acids after laparoscopic sleeve gastrectomy.

BACKGROUND: This study aimed to determine early postoperative changes of plasma polyunsaturated fatty acids (PUFAs) following laparoscopic sleeve gastrectomy (LSG). METHODS: Ten obese patients (mean BMI: 51.10 ± 11.59 kg/m²) underwent LSG and eleven normal weight control patients (mean BMI: 24.37 ± 2.33 kg/m²) underwent laparoscopic abdominal surgery. Fasting blood samples were collected prior to surgery, at day 1 after surgery and after postoperation oral feeding. Plasma levels of arachidonic acid (AA, C20:4n6), dihomo-gamma-linolenic acid (DGLA, C20:3n6), eicosapentaenoic acid (EPA, C20:5n3) and docosahexaenoic acid (DHA, C22:6n3) were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Prostaglandin E2 (PGE2) was measured in serum samples by enzyme immunoassay. RESULTS: A significant decrease was observed in insulin and HOMA IR levels in sleeve gastrectomy patients after postoperation oral feeding compared to preoperation. Plasma AA levels and AA/EPA ratio were significantly increased in sleeve gastrectomy patients after postoperation oral feeding compared to postoperation day 1. Serum PGE2 levels and AA/DHA ratio was significantly higher in sleeve gastrectomy patients at preoperation, postoperation day 1 and after postoperation oral feeding when compared to control group patients. CONCLUSION: Increased peripheral insulin sensitivity associated with LSG may play a role in the significant increase of plasma AA levels in sleeve gastrectomy patients following postoperation oral feeding. The significant increase in PGE2 levels and AA/DHA ratio in sleeve gastrectomy group patients also confirms the presence of a proinflammatory state in obesity.

Re-assessing thermal response of schistosomiasis transmission risk: evidence for a higher thermal optimum than previously predicted.

The geographical range of schistosomiasis is affected by the ecology of schistosome parasites and their obligate host snails, including their response to temperature. Previous models predicted schistosomiasis' thermal optimum at 21.7 °C, which is not compatible with the temperature in sub-Saharan Africa (SSA) regions where schistosomiasis is hyperendemic. We performed an extensive literature search for empirical data on the effect of temperature on physiological and epidemiological parameters regulating the free-living stages of S. mansoni and S. haematobium and their obligate host snails, i.e., Biomphalaria spp. and Bulinus spp., respectively. We derived nonlinear thermal responses fitted on these data to parameterize a mechanistic, process-based model of schistosomiasis. We then re-cast the basic reproduction number and the prevalence of schistosome infection as functions of temperature. We found that the thermal optima for transmission of S. mansoni and S. haematobium range between 23.1-27.3 °C and 23.6-27.9 °C (95 % CI) respectively. We also found that the thermal optimum shifts toward higher temperatures as the human water contact rate increases with temperature. Our findings align with an extensive dataset of schistosomiasis prevalence in SSA. The refined nonlinear thermal-response model developed here suggests a more suitable current climate and a greater risk of increased transmission with future warming for more than half of the schistosomiasis suitable regions with mean annual temperature below the thermal optimum.

Re-assessing thermal response of schistosomiasis transmission risk: Evidence for a higher thermal optimum than previously predicted.

The geographical range of schistosomiasis is affected by the ecology of schistosome parasites and their obligate host snails, including their response to temperature. Previous models predicted schistosomiasis' thermal optimum at 21.7°C, which is not compatible with the temperature in sub-Saharan Africa (SSA) regions where schistosomiasis is hyperendemic. We performed an extensive literature search for empirical data on the effect of temperature on physiological and epidemiological parameters regulating the free-living stages of S. mansoni and S. haematobium and their obligate host snails, i.e., Biomphalaria spp. and Bulinus spp., respectively. We derived nonlinear thermal responses fitted on these data to parameterize a mechanistic, process-based model of schistosomiasis. We then re-cast the basic reproduction number and the prevalence of schistosome infection as functions of temperature. We found that the thermal optima for transmission of S. mansoni and S. haematobium range between 23.1-27.3°C and 23.6-27.9°C (95% CI) respectively. We also found that the thermal optimum shifts toward higher temperatures as the human water contact rate increases with temperature. Our findings align with an extensive dataset of schistosomiasis prevalence in SSA. The refined nonlinear thermal-response model developed here suggests a more suitable current climate and a greater risk of increased transmission with future warming for more than half of the schistosomiasis suitable regions with mean annual temperature below the thermal optimum.

Effect of insulin analog initiation therapy on LDL/HDL subfraction profile and HDL associated enzymes in type 2 diabetic patients.

BACKGROUND: Insulin treatment can lead to good glycemic control and result in improvement of lipid parameters in type 2 diabetic patients. This study was designed to evaluate the effect of insulin analog initiation therapy on low-density lipoprotein (LDL)/ high-density lipoprotein (HDL) sub-fractions and HDL associated enzymes in type 2 diabetic patients during early phase. METHODS: Twenty four type 2 diabetic patients with glycosylated hemoglobin (HbA1c) levels above 10% despite ongoing combination therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs (0.4 U/kg/day) plus metformin. Glycemic profiles were determined over 72 hours by continuous glucose monitoring system (CGMS) and blood samples were obtained from all patients at 24 and 72 hours. Plasma levels of cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-I) were determined by enzyme-linked immunosorbent assay (ELISA). Measurement of CETP and LCAT activity was performed via fluorometric analysis. Paraoxonase (PON1) enzyme activity was assessed from the rate of enzymatic hydrolysis of phenyl acetate to phenol formation. LDL and HDL subfraction analysis was done by continuous disc polyacrylamide gel electrophoresis. RESULTS: Mean blood glucose, total cholesterol (TC), triglyceride (TG) and very low-density lipoprotein cholesterol (VLDL-C) levels were significantly decreased while HDL-C levels were significantly increased after insulin treatment. Although LDL-C levels were not significantly different before and after insulin initiation therapy a significant increase in LDL-1 subgroup and a significant reduction in atherogenic LDL-3 and LDL-4 subgroups were observed. Insulin analog initiation therapy caused a significant increase in HDL-large, HDL- intermediate and a significant reduction in HDL-small subfractions. CETP protein level and activity was significantly increased while apoB levels were significantly decreased following insulin analog initiation therapy. No significant difference was found in LCAT mass, LCAT activity, apoA-I and PON-1 arylesterase levels following insulin initiation therapy. CONCLUSION: These findings indicate that insulin analog initiation therapy activates lipid metabolism via up-regulating CETP and shows anti-atherogenic effects by increasing HDL-large and decreasing LDL-3 and LDL-4 subfractions in a short time period.

LC-MS/MS analysis of plasma polyunsaturated fatty acids in type 2 diabetic patients after insulin analog initiation therapy.

BACKGROUND: Eicosanoids derived from omega-6 (n6) polyunsaturated fatty acids (PUFAs) have proinflammatory functions whereas eicosanoids derived from omega-3 (n3) PUFAs have anti-inflammatory properties. This study was designed to evaluate the effect of insulin analog initiation therapy on n6 and n3 PUFAs in type 2 diabetic patients during early phase. METHODS: Sixteen type 2 diabetic patients with glycosylated hemoglobin (HbA1c) levels above 10% despite ongoing combination therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs (0.4 U/kg/day) plus metformin. Blood samples were obtained from all patients at 24 and 72 hours. Plasma levels of arachidonic acid (AA, C20:4n6), dihomo-gamma-linolenic acid (DGLA, C20:3n6), eicosapentaenoic acid (EPA, C20:5n3) and docosahexaenoic acid (DHA, C22:6n3) were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Prostaglandin E2 (PGE2) was measured in serum samples by enzyme immunoassay. RESULTS: All measured PUFAs were significantly increased after treatment with insulin analogs plus metformin compared to before treatment levels. The mean AA/EPA ratio was significantly lower after treatment with insulin analogs plus metformin. A 22% decrease was observed in PGE2 levels after treatment with insulin analogs plus metformin compared to pretreatment levels (p > 0.05). CONCLUSION: The significant decrease in AA/EPA ratio indicates that insulin analog initiation therapy has anti-inflammatory properties by favoring the increase of n3 fatty acid EPA.

Analyzing the effect of restrictions on the COVID-19 outbreak for some US states.

The ongoing pandemic disease COVID­19 has caused worldwide social and financial disruption. As many countries are engaged in designing vaccines, the harmful second and third waves of COVID­19 have already appeared in many countries. To investigate changes in transmission rates and the effect of social distancing in the USA, we formulate a system of ordinary differential equations using data of confirmed cases and deaths in these states: California, Texas, Florida, Georgia, Illinois, Louisiana, Michigan, and Missouri. Our models and their parameter estimations show social distancing can reduce the transmission of COVID­19 by 60% to 90%. Thus, obeying the movement restriction rules is crucial in reducing the magnitude of the outbreak waves. This study also estimates the percentage of people who were not social distancing ranges between 10% and 18% in these states. Our analysis shows the management restrictions taken by these states do not slow the disease progression enough to contain the outbreak.

The effect of changing COVID-19 restrictions on the transmission rate in a veterinary clinic.

With the declaration of the COVID-19 pandemic by the World Health Organization on March 11, 2020, the University of Tennessee College of Veterinary Medicine (UTCVM), like other institutions, restructured their services to reduce the potential spread of the COVID-19 virus while simultaneously providing critical and essential veterinary services. A mathematical model was developed to predict the change in the level of possible COVID-19 infections due to the increased number of potential contacts within the UTCVM hospital. A system of ordinary differential equations with different compartments for UTCVM individuals and the Knox county population was formulated to show the dynamics of transmission and the number of confirmed cases. Key transmission rates in the model were estimated using COVID-19 case data from the surrounding county and UTCVM personnel. Simulations from this model show the increasing number of COVID-19 cases among UTCVM personnel as the number of daily clients and the number of veterinary staff in the clinic are increased. We also investigate how changes within the Knox county community impact the UTCVM hospital. These scenarios show the importance of understanding the effects of re-opening scenarios in veterinary teaching hospitals.

Ruminations and their correlates in depressive episodes: Between-group comparison in patients with unipolar or bipolar depression and healthy controls.

BACKGROUND: Rumination is an important feature of affective disorders. Relationships between rumination, cognitive function, emotion regulation, and psychological resilience have been examined in unipolar depression; but few studies have determined whether unipolar and bipolar depressive episodes are distinguishable in terms of these variables. This study examined rumination in relation to clinical and cognitive variables in patients with unipolar depression or bipolar depression, and healthy controls. METHODS: In total, 150 participants (50 bipolar, 50 unipolar, 50 controls) were included. Assessments comprised the Ruminative Response Scale-Short Form, Positive Beliefs about Rumination Scale, Negative Beliefs about Rumination Scale, Brief Resilience Scale, Emotion Regulation Questionnaire, Stroop Test, and Trail Making Test A and B. RESULTS: The unipolar group had significantly higher scores in ruminative response and performed better in a neuropsychological test (Trail Making Test Part A) than the bipolar group. When duration of illness was controlled, no significant difference was found between depression groups in terms of rumination. There was a negative relationship between rumination and emotion regulation (cognitive reappraisal subscale), and rumination and psychological resilience in both patient groups, but no significant relationship was found in healthy controls. LIMITATIONS: Relatively small sample size: future studies in larger clinical samples would increase knowledge of rumination in both unipolar and bipolar depression. CONCLUSIONS: Patients experiencing unipolar or bipolar depressive episodes are potentially distinguishable in terms of ruminative response levels and cognitive functions. This differentiation may help in developing targeted interventions for unipolar and bipolar depression.

Feasibility and acceptability of transcranial stimulation in obsessive-compulsive symptoms (FEATSOCS): study protocol for a randomised controlled trial of transcranial direct current stimulation (tDCS) in obsessive-compulsive disorder (OCD).

BACKGROUND: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder which often proves refractory to current treatment approaches. Transcranial direct current stimulation (tDCS), a noninvasive form of neurostimulation, with potential for development as a self-administered intervention, has shown potential as a safe and efficacious treatment for OCD in a small number of trials. The two most promising stimulation sites are located above the orbitofrontal cortex (OFC) and the supplementary motor area (SMA). METHODS: The aim of this feasibility study is to inform the development of a definitive trial, focussing on the acceptability, safety of the intervention, feasibility of recruitment, adherence and tolerability to tDCS and study assessments and the size of the treatment effect. To this end, we will deliver a double-blind, sham-controlled, crossover randomised multicentre study in 25 adults with OCD. Each participant will receive three courses of tDCS (SMA, OFC and sham), randomly allocated and given in counterbalanced order. Each course comprises four 20-min stimulations, delivered over two consecutive days, separated by at least 4 weeks' washout period. We will collect information about recruitment, study conduct and tDCS delivery. Blinded raters will assess clinical outcomes before, during and up to 4 weeks after stimulation using validated scales. We will include relevant objective neurocognitive tasks, testing cognitive flexibility, motor disinhibition, cooperation and habit learning. DISCUSSION: We will analyse the magnitude of the effect of the interventions on OCD symptoms alongside the standard deviation of the outcome measure, to estimate effect size and determine the optimal stimulation target. We will also measure the duration of the effect of stimulation, to provide information on spacing treatments efficiently. We will evaluate the usefulness and limitations of specific neurocognitive tests to determine a definitive test battery. Additionally, qualitative data will be collected from participants to better understand their experience of taking part in a tDCS intervention, as well as the impact on their overall quality of life. These clinical outcomes will enable the project team to further refine the methodology to ensure optimal efficiency in terms of both delivering and assessing the treatment in a full-scale trial. TRIAL REGISTRATION: ISRCTN17937049 . (date applied 08/07/2019). Recruitment (ongoing) began 23rd July 2019 and is anticipated to complete 30th April 2021.

Serum Sphingolipidomic Analysis in Acne Vulgaris Patients.

BACKGROUND: Limited data are available on serum levels of different sphingomyelin (SM) and ceramide (CER) species in acne vulgaris (AV). OBJECTIVES: This study aimed to identify circulating levels of neutral sphingomyelinase activity (N-SMase), ceramide-1-phosphate (C1P), sphingosine-1-phosphate (S1P), C16-C24 SMs and C16-C24 CERs in AV patients and controls. MATERIAL AND METHODS: Serum was collected from 30 AV patients and 20 age, gender-matched control subjects. Serum levels of C16-C24 SMs and C16-C24 CERs were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Serum activity of N-SMase was assayed by standard kit methods, C1P and S1P levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: A significant increase was observed in serum levels of C16 SM in patients with AV compared to controls. No significant difference was found in C18 and C24 SM levels between the two groups. Very-long-chain C24 CER was significantly decreased in AV patients compared to controls. Long chain C16-C20 CER levels showed no significant difference between AV patients and controls. A significant positive correlation was found between serum total cholesterol levels and all measured SMs and CERs in both the control and patient groups. Patients with AV had increased circulating levels of C16 SM, C1P and lower circulating levels of C24 CER compared to healthy controls, which may provide prognostic value for the disease. CONCLUSIONS: Future studies are needed to understand the role of altered sphingolipid levels in the pathophysiology of AV.