Irritation Score Research Articles

Physicochemical Characteristics, Stability, and Irritability of Nanostructured Lipid Carrier System Stabilized with Different Surfactant Ratios

Background: One of the vital variables affecting the stability and the characteristics of the Nanostructured Lipid Carrier (NLC) is the surfactant concentration. Using the two combinations of surfactants can cause higher stability and a better characteristic of NLC. Tween 80 and Span 20 are anionic surfactants whose combination has not been studied for use in NLC systems. Objective: Determine the effect of different surfactant ratios of Tween 80 and Span 20 on the physicochemical characteristics, stability, and irritability of NLC using the High Shear Homogenization (HSH) method. Methods: Four different surfactant ratios were used in the NLC formulation, in which the ratio of Tween 80:Span 20 were 5:5, 6:6, 7:7, and 8:8, respectively. In this NLC system, cetyl palmitate served as solid lipid, medium-chain triglyceride (CrodamolTM) as liquid lipid, Tween 80, and Span 20 as surfactant components. NLC was characterized for organoleptic, viscosity, pH, zeta potential, particle morphology, particle size, and polydispersity index (PDI), then evaluated for stability using the real-time and freeze-thaw method, and irritability effect. Results: The different ratios of Tween 80 and Span 20 had no significant effect on the particle size, PI, and irritation score of the NLC system. On the other hand, it influenced all formulas' pH value, viscosity, zeta potential, and stability. Conclusions: The different ratios of surfactant combination affect the characteristics and stability of the NLC system.

Buspirone, a 5-HT1A agonist attenuates social isolation-induced behavior deficits in rats: a comparative study with fluoxetine.

Social isolation is a potent stressor in both humans and animals that results in increased anger-like emotion, (anger in humans), aggression and suicidal ideation in humans [suicidal trait-related behavior in rats (STRB)]. The study's purpose was to compare the effects of buspirone (BUS) and fluoxetine (Flx) on social isolation-induced behavior deficits in rats. The male Wistar rats were randomized into six groups and caged individually for 14 days except for the non stress control (nSC) group. They were then divided into the following groups, stress control (SC), Flx (30), BUS (10), BUS (20) and BUS (40) and treated from day 14 to day 28. On the last day of treatment behavior parameters were recorded. Serum cortisol, blood pressure (BP) measurement, magnetic resonance imaging (MRI) of the rat's brain and brain-derived neurotrophic factor (BDNF) expression were performed. SC group showed a significant increase in anger-like emotion, aggression, irritability score, learned helplessness, increased cortisol level and reduced BDNF. These behavioral deficits were attenuated by BUS and Flx, Both were found to be equally beneficial in preventing anger-like emotions and aggression. Flx, which has been found to promote suicidal thoughts in people, did not reduce irritability in rats, showing that it did not affect it. BUS significantly improved all behavioral traits also reduced cortisol levels, significantly increased BDNF and normalized BP. Neuroimaging studies in SC brains showed a reduction in amygdala size compared to nSC, BUS treatment mitigated this reduction. Buspirone is effective in preventing social isolation induced behavioural-deficits.

Design of New Concept of Knitted Hernia Implant.

A knitted implant, unilaterally modified with plasma-assisted chemical-vapor deposition (PACVD), and with a nano-layer of fluorine derivative supplementation, for reducing the risk of complications related to adhesions, and the formation of a thick postoperative scar was prepared. The biological evaluation of designed or modified medical devices is the main aspect of preclinical research. If such studies use a medical device with prolonged contact with connective tissue (more than 30 days), biocompatibility studies require a safety assessment in terms of toxicity in vitro and in vivo, allergenicity, irritation, and cancerogenicity, reproductive and developmental toxicity. The ultimate aspect of biological evaluation is biofunctionality, and evaluation of the local tissue response after implantation, resulting in the determination of all aspects of local biocompatibility with the implemented synthetic material. The implantation of PACVD-modified materials in muscle allows us to estimate the local irritation effect on the connective tissue, determining the risk of scar formation, whereas implantation of the above-mentioned knitted fabric into the abdominal wall, assists with evaluating the risk of fistula formation—the main post-surgical complications. The research aimed to evaluate the local reaction of the soft tissues after the implantation of the knitted implants modified with PACVD of the fluoropolymer in the nanostuctural form. The local effect that occurred during the implantation of the designed implants was quantitatively and qualitatively evaluated when PACVD unmodified (reference), and modified medical devices were implanted in the abdominal cavity (intra-abdominal position) for 12 or into the muscles for 56 weeks. The comparative semi-quantitative histological assessment included the severity of inflammatory cells (multinucleated cells, lymphocytes, plasma cells, macrophages, giant cells) and the tissue response (necrosis, neovascularization, fibrosis, and fat infiltration) on a five-point scale. The knitted implants modified by PACVD did not indicate cumulative tissue response when they were implanted in the muscle and intra-abdominally with direct contact with the viscera. They reduced local tissue reaction (score −2.71 after 56 weeks of the implantation) and internal organ adhesion (irritation score −2.01 and adhesion susceptibility −0.3 after 12 weeks of the implantation) compared with the reference (unmodified by PACVD) knitted implant, which had an identical structure and was made of the same source.

Investigating the associations between irritability and hot and cool executive functioning in those with ADHD

BackgroundIrritability is especially pertinent to those with Attention Deficit Hyperactivity Disorder (ADHD) as it is highly prevalent and associated with a more severe clinical presentation and poorer longitudinal outcomes. Preliminary evidence suggests that top-down cognitive processes taking place in emotional contexts (i.e., hot executive functions) as opposed to those evoked in abstract scenarios (i.e., cool executive functions) may be relevant to the presentation of irritability in ADHD. This study explored the cognitive mechanisms underlying irritability in young people with ADHD, hypothesising that irritability would be associated with hot, but not cool, executive function impairments.MethodsOur sample included 219 individuals with ADHD. A composite irritability score was derived extracting items from a parent interview, with scores ranging from 0 to 5. Associations were investigated using linear regression analyses, between irritability and four hot tasks measuring sensitivity to risk, risk-taking behaviour following reward or punishment, acceptance of reward delay and reaction to unfair behaviour from others, and two cool tasks measuring set-shifting and motor inhibition.ResultsAs hypothesised, there were no significant associations between irritability and cool executive functions in those with ADHD; however, contrary to expectations, there was also no significant evidence that hot executive functions were associated with irritability.ConclusionsThese results, in a large well characterised sample and using a comprehensive task battery, suggest that the variation in irritability in those with ADHD may not be associated with differences in hot or cool executive function performance.

A Feasibility Study of the Usefulness of the TEMPS-A Scale in Assessing Affective Temperament in Athletes.

Background and objectives: Current studies show an important role of affective temperament in sport performance. The aim of this study was to assess the feasibility of the use of the TEMPS-A scale, by using it to examine five dimensions of affective temperament in three groups of athletes. We hypothesized that temperament may be a predisposing factor to the level of commitment and type of training. Materials and methods: The study group (N:71, 33 female) consisted of professional canoeists (N:25, aged 18–30), sports pilots (N:21, aged 19–57) and non-professionals regularly performing aerobic exercises (N:25, aged 23–33). The Affective Temperament of Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A) was used to evaluate affective temperament dimensions. Statistical analysis was performed using non-parametric tests. Results: The TEMPS_A scale shows good internal consistency; a hyperthymic temperament was associated with different factors compared to other temperament traits. The most prevalent trait in the study group was hyperthymic temperament. The study group scored higher on hyperthymic and lower on depressive and anxious temperaments when compared with the general population. Canoeists scored higher on cyclothymic temperament compared with non-professional athletes and on cyclothymic and irritable dimensions in comparison with pilots. Pilots obtained significantly lower scores on irritable and anxious temperaments than non-professional athletes. Females scored higher on both hyperthymic and irritable dimensions. No significant differences were found in respect of depressive, cyclothymic and anxious traits. Age was negatively correlated with cyclothymic and irritable temperament scores. Conclusions: TEMPS-A scale is a useful tool for assessing affective temperament in athletes. The results suggest that affective temperament may be a factor influencing physical activity engagement. Different types of activities may be connected with different temperament dimensions. Younger athletes present a higher tendency to mood lability and sensitivity to environmental factors. However, further research is needed, involving larger numbers of subjects.

Conjunctival Autograft versus Combined Amniotic Membrane and Mini-Simple Limbal Epithelial Transplant for Primary Pterygium Excision.

PurposeTo compare outcomes of conjunctival autograft (CAG) and combined amniotic membrane with mini-simple limbal epithelial transplant (mini-SLET) after primary pterygium excision.MethodsAll consenting adults with primary pterygium were included in this study. After pterygium excision, patients were randomized to receive either CAG or mini-SLET and both grafts were held in place with fibrin glue. The patients were followed-up at days 1, 3, 7, 14, and 30 and subsequently at the third, sixth, and ninth months. The recurrence rate was considered as the primary outcome measure whereas the operating time, postoperative symptoms, and surgical complications were considered the secondary outcome measures.ResultsThe study comprised of 264 eyes of 264 patients, of which 233 (88%) completed the nine months of follow-up. Of these, 118 (51%) received CAG and 115 (49%) received mini-SLET. The groups were comparable at baseline. Recurrence of pterygium was seen in two (1.6%) eyes in the CAG group and three (2.6%) eyes in the mini-SLET group (P = 0.68). Operative time for mini-SLET (20.33 1.28 min) was significantly higher than that for CAG (12.01 1.26 min) (P 0.001). Graft displacement was observed in one case in group II (P = 0.999). The Lim Bon Siong (foreign body sensation, lacrimation, pain, and irritation) score in the CAG group was statistically significant for all four symptoms at days 1 and 3; however, at day 7, foreign body sensation, pain, and irritation scores were significantly higher for the CAG group.ConclusionIn this study, the overall recurrence rate was very low and comparable between mini-SLET and the established technique of CAG after performing the primary pterygium excision. Despite a longer surgical time, mini-SLET appears to be a viable option for the management of primary pterygium.

Correlation between the International Prostate Symptom Score, Ultrasound Features and Maximum Flow Rate in Cameroonian Patients with Benign Prostatic Hypertrophy

Background: Benign prostatic hypertrophy is the non-malignant stromal and epithelial proliferation of the prostate gland, with or without associated anatomical enlargement of the gland and clinical symptoms. Symptomatic Benign prostatic hypertrophy may cause obstructive symptoms, irritative symptoms or both obstructive symptoms include a sensation of incomplete bladder emptying, straining to void, urinary hesitancy and weak stream while irritative symptoms include dysuria, nocturia, urinary frequency and urinary urgency. A quantitative measure of the severity of lower urinary tract symptoms due to benign prostatic hypertrophy can be obtained using the International Prostate Symptoms Score. Ultrasonography is useful for helping to determine bladder and prostate size in patients with urinary lower urinary tract symptoms. Uroflowmetry is a non-invasive test that assesses voiding function. It provides valuable data on the voided volume, time is taken to reach maximum flow rate and average flow rate. The goal of this study was to improve the follow up of patients with benign prostatic hypertrophy by providing simple, available, affordable and non-invasive that best predict bladder outlet obstruction and the quality of life in these patients. Method: This was a cross-sectional analytic study carried out over a period of five months from May 2020 to September 2020 at the Yaounde Gynaeco-Obstetric and Paediatric Hospital, which is a tertiary hospital in Cameroon. Were included in the study, adult males who presented with lower urinary tract symptoms and prostatic enlargement suggestive of benign prostatic hypertrophy taking into account clinical, uroflowmetry and ultrasound findings. Results: A study population of 103 participants was recruited. The mean age of patients was 63.17 ± 10.26 years. Concerning the International Prostate Symptoms Score, the mean total, voiding (obstructive) and storage (irritative) scores were 14.6 ± 6.2, 8.5 ± 4.1 and 6.05 ± 2.7 respectively. The mean maximum flow rate was 13.44 ± 3.88 mL/s. The mean prostate volume was 53.71 ± 16.46 ml. A majority of patients have an enlarged prostate 1.5 to 2 times (46 to 60 mL) the upper limit for normal value. The intravesical prostatic protrusion was present in eighty-three (80.58%) and absent in 20 (19.42%). Above a prostate volume of 60 mL, 91% to 100% of our patients had intravesical prostatic protrusion. There was strong evidence (p < 0.001) that a change from no intravesical prostatic protrusion to intravesical prostatic protrusion grade 1 increased the chances of having a low maximum flow rate with a crude odds ratio of 7.98. The adjusted odds ratio after multivariate analysis was 5.26 and this remained statistically significant (p = 0.03). Conclusion: the measure of intravesical prostatic protrusion is superior to the prostate volume in the assessment of maximum flow rate and thus the follow up of patients with benign prostatic hypertrophy. This measure which is non-invasive, easy to measure, easily accessible, and cost effective may be a useful tool in predicting voiding dysfunction and acute urinary retention.

Antihemorrhagic and Antimicrobial Property of Cotton Fabric Treated with Medicinal Herb Alfalfa

Abstract In this work, medicinal plant alfalfa leaf extract was used as an antihemorrhagic, antimicrobial, and antifungal agent and applied to cotton fabrics. The medicinal herb alfalfa leaf was extracted using the ethanol and methanol solvents in the Soxhlet apparatus. The 50-µL, 100-µL, and 150-µL concentrations of extracted solution were tested against the positive and negative bacteria, namely Staphylococcus, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and the yeast fungi. The zone of inhibition was measured in each concentration. The 150-µL extract concentration in methanol extract showed good antibacterial activity against Staphylococcus and P. aeruginosa bacteria compared with the ethanol extract. The treated cotton fabrics were assessed for their antimicrobial property, and the zone of inhibition was found to be in the range of 13–15 mm. Then the antihemorrhagic property was assessed in both ethanol extract and methanol extract solution alone. The ethanol extracts showed a minimum time for clotting the blood, i.e., 2.2 min. The treated fabrics were assessed for the time taken to clot blood, and it was found that it took 1.2–1.4 min, which was improved when compared with the normal blood clotting time of 2–2.3 min. Biocompatibility Chorioallantoic membrane (CAM) preparation helps us to know the endpoints like hemorrhage, vascularlysis, coagulation, and irritation score of treated and untreated cotton fabric. The test is similar to the effects of the rabbit skin testing treatment, which shows the result of zero value for endpoints. The Medicago sativa herb exhibited good antimicrobial and antihemorrhagic properties for medicinal applications.

Analysis of concerns among patients operated for carpal tunnel syndrome

Introduction. Carpal tunnel release (CTR) is among the most commonly performed procedures within a hand, in a day surgery setting. Studies suggest that patient concerns and emotional state may influence CTR outcomes. Aim. To determine the frequency of preoperative concerns among patients operated for carpal tunnel syndrome (CTS) and their correlation with negative emotions, socio-demographic and clinical variables. Materials and methods. A total of 72 patients (81.9% women) scheduled for CTR were included in the study. Pain, anxiety, irritability, and depression were measured using the Visual Analogue Scale (VAS) on the day of surgery. Tailor-made questionnaires were used to explore patients’ concerns and to gather socio-demographic and clinical data. Statistical analysis was performed utilizing R language. α &lt; 0.05 was considered significant. Results. At least one concern was declared by the vast majority of patients (93.1%). Postoperative pain was the most prevalent concern, declared by 49.3% of participants. “Outcomes will not meet my expectations” was a concern for 43.3% of participants. Concern related to intraoperative complications was declared by 34.3% of participants. Patients scheduled for CTR had high mean VAS scores of anxiety and irritability and low score of depression. Anxiety reached the highest level among measured variables. Patients who declared postoperative pain had statistically significantly higher levels of pain, anxiety, irritability, and depression than patients without this concern. Concern that surgery outcomes will not meet patient’s expectations was declared statistically significantly more frequently by patients with any surgery in history. Conclusions. Preoperative concerns among patients operated for carpal tunnel syndrome are extremely prevalent. Those concerns are accompanied by a high level of negative emotions. Therefore assessment of emotional status, addressing particular concerns, and tailored preoperative intervention, all are of crucial importance. A meticulous approach to postoperative pain and patients’ expectations regarding outcomes seem to be essential. The mentioned strategy may positively influence patients’ comfort and surgery outcomes.

Self-Reported Complaints as Prognostic Markers for Outcome After Mild Traumatic Brain Injury in Elderly: A Machine Learning Approach.

Self-reported complaints are common after mild traumatic brain injury (mTBI). Particularly in the elderly with mTBI, the pre-injury status might play a relevant role in the recovery process. In most mTBI studies, however, pre-injury complaints are neither analyzed nor are the elderly included. Here, we aimed to identify which individual pre- and post-injury complaints are potential prognostic markers for incomplete recovery (IR) in elderly patients who sustained an mTBI. Since patients report many complaints across several domains that are strongly related, we used an interpretable machine learning (ML) approach to robustly deal with correlated predictors and boost classification performance. Pre- and post-injury levels of 20 individual complaints, as self-reported in the acute phase, were analyzed. We used data from two independent studies separately: UPFRONT study was used for training and validation and ReCONNECT study for independent testing. Functional outcome was assessed with the Glasgow Outcome Scale Extended (GOSE). We dichotomized functional outcome into complete recovery (CR; GOSE = 8) and IR (GOSE ≤ 7). In total 148 elderly with mTBI (median age: 67 years, interquartile range [IQR]: 9 years; UPFRONT: N = 115; ReCONNECT: N = 33) were included in this study. IR was observed in 74 (50%) patients. The classification model (IR vs. CR) achieved a good performance (the area under the receiver operating characteristic curve [ROC-AUC] = 0.80; 95% CI: 0.74–0.86) based on a subset of only 8 out of 40 pre- and post-injury complaints. We identified increased neck pain (p = 0.001) from pre- to post-injury as the strongest predictor of IR, followed by increased irritability (p = 0.011) and increased forgetfulness (p = 0.035) from pre- to post-injury. Our findings indicate that a subset of pre- and post-injury physical, emotional, and cognitive complaints has predictive value for determining long-term functional outcomes in elderly patients with mTBI. Particularly, post-injury neck pain, irritability, and forgetfulness scores were associated with IR and should be assessed early. The application of an ML approach holds promise for application in self-reported questionnaires to predict outcomes after mTBI.

Development of bioflavonoid containing chemotherapeutic delivery systems for UV-damaged skin and kangri cancer

Abstract Background The lower abdomen and inner thighs are most likely to become affected by kangri cancer because those areas are exposed to continuous exposure to kangri. Objective In this article, formulation and characterization of a water-in-oil microemulsion of 5-fluorouracil with rutin (R-5FU) for better skin penetration and inhibition of kangri cancer (skin cancer surfactant) is discussed. Method To produce R-5-FU microemulsions, surfactant-cosurfactant was mixed with oil. Distilled water was added dropwise with the help of a burette by gentle stirring at a constant temperature. The surfactant and co-surfactant were mixed into three particular ratios 1:1, 2:1, and 3:1. Further characterizations were performed, such as visual inspection and thermodynamic stability including a stress test and centrifugation. In visual inspection included assessment of the colour, homogeneity, and odour of the formulation of FU microemulsion. Result All three microemulsions, labeled RME1, RME2, and RME3, are highly stable. An oval shape of surface morphology of 5-FU was noticed by using a TEM image. The viscosity of RME3 was found to be 17.25±0.22 pa-s. The average globule size was 100–300 nm for all three RME. The results of human cadaver skin permeability are almost of the same pattern, butRME3 indicates the best skin permeability with negligible side effects on the skin. Conclusion The quantity of 5-FU released from all formulations at 3-hr ranged from 95.57% to 83.67%. None of the three formulations resulted in skin irritation, with irritancy score of zero (IS=0). Observation revealed no lysis, hemorrhage, or coagulation after application.

Toxicological Profile of Biological Environment of Two Elastodontic Devices

Malocclusion and teething problems are common health problems globally, affecting people of all ages, especially children and adolescents. In addition to the pathophysiological complications associated with orthodontic problems, they also affect the well-being of the individual. Orthodontic appliances are frequently used, even from an early age, and their activity in different biological environments is very varied and incompletely described. Due to these considerations, the purpose of the study was to evaluate the toxicological profile of the biological environment (saliva at three pH values: 3, 7, and 10) of two elastodontic orthodontic appliances: Myobrace (MB) and LM TrainerTM 2 (LMD). In vitro techniques applied were conducted on human keratinocytes to evaluate cell viability (Alamar blue assay) and gene expression real-time reverse transcription–polymerase chain reaction (RT-PCR technique). In addition, it was assessed the irritating effect on the vascular plexus using as a biological model the chorioallantoic membrane of the hen’s egg by applying the hen’s egg-chorioallantoic membrane (HET-CAM) method. The obtained results showed a decrease in cell viability up to 82% in the case of LMD at pH = 3, a slight increase in mRNA expression for the anti-apoptotic marker (Bcl-2 and Bcl-xL), and a decrease in mRNA expression for the pro-apoptotic marker (Bad), and any type of toxic change at the capillary level (irritation score being below 0.9). Based on the data obtained, it can be stated that MB and LMD biological environments, at different pH values, present a safe toxicological profile.

Clinical features and prognosis of severe scorpion envenomation in children.

Scorpionism is endemic and represents a real public health problem in Morocco. The most dangerous arthropod in the central area is Androctonus mauretanicus (Am) scorpion. Its venom can be lethal, especially for children. This study aimed to determine a clinico-epidemiological profile of severe scorpion envenomation among children and identify risk factors for mortality. This retrospective cohort study included 606 children admitted for severe scorpion envenomation (SSE) from January 2010 to July 2015 in the Pediatric Intensive Care Unit (PICU) of Mohammed VI Teaching Hospital. The mean age of envenomed children was 6.3 ± 4.2 years. Seventy-four percent of them came from rural settings. Envenomation occurred mostly during the summer months and 78.4% of stings were nocturnal. The time between the sting and evaluation was greater than 2 h in 83% of cases. Bivariate analysis indicated that from 1 to 24 months of age (P = 0.001), hyperthermia (P = 0.022), episodes of diarrhea (P < 0.001), tachycardia (P < 0.001), abdominal distention (P < 0.001), skin marbling (P < 0.001), signs of respiratory distress (P < 0.001), irritability (P < 0.001), generalized seizures (P = 0.053), and Glasgow Coma Score (GCS) of 3 to 9 (P < 0.001) were significantly correlated with mortality. On multivariate analysis, diarrhea (P = 0.007), skin marbling (P = 0.006), and respiratory distress (P = 0.002), and GCS 3-9 (P = 0.007) were found to be independent risk factors for mortality in our patient population. Children are at high risk of developing serious complications, even death, from severe scorpion envenomation. Here we identified multiple factors that appear to increase the mortality risk in children after scorpion envenomation, including previously described central nervous system alterations.

Advances in the Use of Electrospun Nanofibrous Polymeric Matrix for Dermal Healing at the Donor Site After the Split-Thickness Skin Graft Excision: A Prospective, Randomized, Controlled, Open-Label, Multicenter Study.

Dressings used to manage donor site wounds (DSWs) have up to 40% of patients experiencing complications that may cause suboptimal scarring. We evaluated the efficacy and safety of a portable electrospun nanofibrous matrix that provides contactless management of DSWs compared with standard dressing techniques. This study included adult patients who underwent an excised split-thickness skin graft (STSG) with a DSW area of 10 to 200 cm2. Patients were allocated into two groups; ie, the nanofiber group managed with a nanofibrous polymer-based matrix, and the control group managed using the standard of care such as Jelonet® or Biatain® Ibu dressing. Primary outcomes were postoperative dermal healing efficacy assessed by Draize scores. The time to complete re-epithelialization was also recorded. Secondary outcomes included postoperative adverse events, pain, and infections during the first 21 days and extended 12-month follow-up. The itching and scarring were recorded during the extended follow-up (months 1, 3, 6, 9, and 12) using Numerical-Analogue-Score and Vancouver scores, respectively. The nanofiber and control groups included 21 and 20 patients, respectively. The Draize dermal irritation scores were significantly lower in the nanofiber vs control group (Z = -2.509; P = .028) on the first postoperative day but became similar afterward (Z ≥ -1.62; P ≥ .198). In addition, the average time to re-epithelialization was similar in the nanofiber (17.9 ± 4.4 days) and control group (18.3 ± 4.5 days; Z = -0.299; P = .764), so were postoperative adverse events, pain, and infection incidence, itching and scarring. The safety and efficacy of electrospun nanofibrous matrix are similar to standard wound care allowing its use as an alternative donor site dressing following the STSG excision.

Novel insights into irritability: the relationship between subjective experience, age and mood.

The relationship between irritability as a subjective experience and the behavioural indicators typically used to measure the construct are not known. Its links to mood, and contextual relationships, vary with age and are yet to be thoroughly examined. First, to interrogate the relationship between the subjective experience of irritability and mood, and that with its behavioural indicators. Second, to determine how these relationships vary with age and over time. This study examined data from a previous clinical trial of adolescents and young adults (N = 82) with bipolar disorder, who received a psychological intervention over 18 months. Participants completed a battery of questionnaires, which included assessments of irritability. Analyses of covariance were conducted to examine the interaction between mood symptoms, subjective measures of irritability, behavioural measures of irritability and age over time. Subjective irritability scores differed significantly over time when controlling for manic, but not depressive, symptom scores. Further, subjective irritability significantly differed when controlling for behavioural measures of irritability (temper outbursts and argumentativeness). There were significant interactions between scores of depressive symptoms, temper outbursts and subjective irritability with age, wherein younger participants showed no correlation between depressive symptoms and temper outbursts. In addition, younger participants showed lower correlations between subjective irritability and both depressive and temper outburst scores, than older participants. Subjective irritability is linked to mood morbidity and behavioural outbursts, and these relationships are contingent on age. Our novel findings suggest that subjective irritability should be assessed in greater detail in patients with mood disorders.

Toxicity Outcomes After Low-Dose-Rate vs. High-Dose-Rate Brachytherapy Boost in Combination With External Beam Radiation for Intermediate and High-Risk Prostate Cancer

The addition of a brachytherapy boost to external beam radiation therapy (EBRT) reduces prostate cancer (PCa) recurrence compared with dose-escalated EBRT alone. However, combination therapy is associated with worse genitourinary (GU) toxicity compared with EBRT monotherapy. Whether brachytherapy boost technique, specifically low-dose-rate (LDR-BT) versus high-dose-rate (HDR-BT), impacts treatment-related toxicity is unclear and the subject of this analysis.This single institutional cohort study included 104 adult men with intermediate/high risk PCa treated with combination EBRT plus brachytherapy boost, with either LDR-BT or HDR-BT, between 2012 and 2018. Patient-reported outcomes (PRO) were assessed by the International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) surveys at 3-6-month intervals for up to three years following treatment, with higher scores indicating more severe toxicity. Provider-reported GU and gastrointestinal (GI) toxicities were assessed and graded per CTCAE V5.0 at each follow-up. Linear mixed models comparing PROs between LDR-BT versus HDR-BT were fitted. Stepwise multivariable analysis (MVA) was performed to account for age, gland size, androgen deprivation therapy (ADT) use, and alpha-blocker medication use. Incidence rates of grade 2+ GU/GI toxicity was compared using Chi-square test or Fisher's exact test.The median complete follow up time for LDR-BT and HDR-BT cohorts was 17 and 18.4 months, respectively. There was no difference in alpha-blocker use at baseline between groups (P = 0.16). Median prostate gland size was larger in the HDR-BT cohort compared with the LDR-BT cohort (39.99cc vs 26.58cc for HDR-BT vs LDR-BT, respectively; P < 0.001). The use of LDR-BT was associated with a greater change in IPSS (P = 0.003) and EPIC-CP urinary irritative score (P = 0.002) compared with HDR-BT, but effect size diminished over time (LDR-BT versus HDR-BT: baseline to 6-/24-month mean IPSS change, +6.4/+1.4 versus +2.7/-3.0, respectively; mean EPIC-CP irritative/obstructive change, +2.5/+0.1 versus +0.9/+0.1, respectively). These results remained significant on MVA. Incidence of post-treatment grade 2+ GU toxicity was significantly higher in the LDR-BT group (77.5% versus 42.9% for LDR-BT and HDR-BT, respectively; P < 0.001). There were no significant differences between LDR-BT and HDR-BT in EPIC-CP (total, urinary incontinence, bowel function, sexual, vitality) or provider-reported grade 2+ GI toxicity.In this single institution cohort, HDR-BT was associated with lower patient- and provider-reported GU toxicity compared with LDR-BT. However, differences in patient-reported toxicity diminished by 24 months post-treatment.

Strain-specific and outcome-specific efficacy of probiotics for the treatment of irritable bowel syndrome: A systematic review and meta-analysis.

BackgroundConsistent guidance for choosing an appropriate probiotic for the treatment of irritable bowel syndrome is lacking.MethodsLiterature databases searched included: PubMed, Google Scholar and NIH registry of clinical trials from inception to June 2021. Inclusion criteria: randomized controlled trials (RCTs) enrolling adult or pediatric IBS patients comparing probiotics against controls and ≥ 2 RCTs with common IBS outcome measures within each type of probiotic. Five common measures of IBS symptoms (changes in global Irritable Bowel Syndrome Severity Scoring System or IBS-SSS scores, frequency of global responders, changes in bloating or abdominal pain scores and frequency of abdominal pain relief) were used. This study was registered at Prospero (#CRD42018109169).FindingsWe screened 521 studies and included 42 randomized controlled trials (45 treatment arms, N = 3856). Four probiotics demonstrated significant reduction in abdominal pain relief: B. coagulans MTCC5260 (RR= 4.9, 95% C.I. 3.3, 7.3), L. plantarum 299v (RR= 4.6, 95% CI 1.9, 11.0), S. boulardii CNCM I-745 (RR= 1.5, 95% C.I. 1.1, 2.1) and S. cerevisiae CNCM I-3856 (RR= 1.3, 95% C.I. 1.04, 1.6). Mild-moderate adverse events were reported in 51% of the trials, none were more associated with the probiotic compared to controls.InterpretationAlthough the analysis of probiotic efficacy was limited by the diversity of IBS outcomes used in trials and lack of confirmatory trials for some strains, six single-strain probiotics and three different types of probiotic mixtures showed significant efficacy for at least one IBS outcome measure. These results might be relevant to clinical practice and policy.

LONGER-TERM TOLERABILITY AND EFFICACY OF ZYN002 CANNABIDIOL TRANSDERMAL GEL IN CHILDREN AND ADOLESCENTS WITH AUTISM SPECTRUM DISORDER: AN OPEN-LABEL PHASE 2 STUDY (BRIGHT [ZYN2-CL-030

ZYN002 is a pharmaceutically manufactured transdermal cannabidiol gel. BRIGHT is a single-center, open-label phase 2 study that evaluated the tolerability and efficacy of ZYN002 in children and adolescents aged 3-17 years with autism spectrum disorder (ASD). Data through 14 weeks were previously presented. The objective is to present longer-term data through 38 weeks of treatment with open label ZYN002. Patients with Clinical Global Impression (CGI)–Severity scores ≥4 (moderate or greater) and Aberrant Behavior Checklist-Community (ABC-C) Irritability scores ≥18 were enrolled. Patients received ZYN002 250 or 500 mg/day on top of stable standard of care. Patients demonstrating ≥35% improvement in Irritability at week 14 were allowed to continue treatment. Safety assessments included adverse events (AEs), laboratory tests, and electrocardiograms (ECGs). Thirty-seven patients (mean age: 9.2 years) enrolled; 94% had moderate-to-severe symptoms; the mean baseline ABC-C Irritability score was 30.3. At week 14, significant improvements (p ≤ 0.0053) were observed for each ABC-C subscale, the Parent-Rated Anxiety Scale-ASD (PRAS-ASD) score, the Autism Parenting Stress Index (APSI) score and each Autism Impact Measure (AIM) domain in 28 who completed week 14. 57% of patients were improved (“much/very much improved”) based on CGI-Improvement (CGI-I). Eighteen patients demonstrated ≥35% improvement in Irritability and elected to continue. At week 38, improvements in the ABC-C subscale scores (50% to 61% across domains; p < 0.0001), the PRAS-ASD (42%; p < 0.0001), APSI (40%; p < 0.0001) and the AIM (19% to 36% across domains; p ≤ 0.0008) were maintained. Seventy-seven percent were improved on the CGI-I. Fifty-four percent of patients reported adverse events (AEs); mild (80%) or moderate (20%). Treatment-related AEs were reported in 19% of patients; most were mild and transient. One patient discontinued due to application site reaction. No serious or severe AEs or clinically significant changes in laboratory tests or ECGs were reported. BRIGHT provides initial evidence suggesting a positive risk-benefit profile for ZYN002 when added on top of stable standard of care in children and adolescents with ASD which was maintained over 38 weeks. Further studies are warranted.

Association between affective temperaments and severe coronary artery disease

BackgroundAffective temperaments are regarded as subclinical manifestations of major mood disorders and cumulating evidence suggest their role in cardiovascular (CV) pathology. We wished to analyze associations between affective temperaments and severe coronary artery disease (CAD), as assessed by coronary computed tomography angiography (CCTA). Methods225 consecutive patients referred to CCTA due to suspected CAD were included. Medical history and demographic parameters were recorded and all patients completed the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A). The severity and extent of CAD was evaluated by CCTA. Logistic regression analysis was used to identify predictors of severe CAD (≥70% luminal stenosis in ≥1 major coronary artery). ResultsAccording to multivariate logistic regression analysis, elevated hyperthymic affective temperament scores significantly decreased the odds of severe CAD (OR=0.92 CI: 0.84–1.00, p = 0.04), while independent positive associations were observed in case of dyslipidemia (OR=4.23 CI: 1.81–9.88, p = 0.001) and cyclothymic affective temperament scores (OR=1.12 CI: 1.02–1.23, p = 0.02). Furthermore, receiver operating curve (ROC) analysis was used to define ideal cutoff values. Hyperthymic temperament scores >11 (OR=0.41 CI: 0.19–0.90, p = 0.03), cyclothymic scores >7 (OR=3.23 CI: 1.35–7.76, p = 0.01) and irritable scores >6 (OR=2.79 CI: 1.17–6.69, p = 0.02) were also independently associated with severe CAD. LimitationsOur study was limited by the cross-sectional design and the self-report nature of the questionnaires. ConclusionsEvaluation of affective temperaments might help to identify patients with elevated risk for severe CAD and subsequent need for coronary intervention.

Covariance Between Parent and Child Symptoms Before and During the COVID-19 Pandemic.

ObjectiveCOVID-19 has had unprecedented effects on American families, including increases in depression, anxiety, and irritability for both parents and children. While parents and children influence each other’s psychological functioning during non-disaster times, this effect may be amplified during times of disaster. The current study investigated how COVID-19 influenced covariance of depressive symptoms and irritability in children and their parents.MethodsThree hundred and ninety-one parents and their 8- to 17-year-old children (Mage = 10.68 years old, 70% male, 86% White) from a large sample of children and parents, primarily from Southeastern Louisiana, completed self-report measures of depression and irritability approximately 6 weeks into the COVID-19 pandemic, as well as providing retrospective reports of their symptoms prior to the pandemic. Actor–partner interdependence models were used to measure the reciprocal effects of parent symptoms on children and vice versa, both before and during the pandemic.ResultsActor effects in both the depressive symptoms and irritability models suggested that pre-COVID-19 depressive symptoms and irritability were robust predictors of early-COVID-19 depressive symptoms and irritability for both parents and children. Partner effects were also detected in the irritability model, in that parental irritability prior to COVID-19 was associated with decreased child irritability during the pandemic. Both before and during the pandemic, associations between parent and child depressive symptoms and irritability scores were weaker in families evidencing greater dysfunction.ConclusionsResults suggest that COVID-19-related stress is associated with increases in both parent and child symptomatology, and that family relationships likely influence associations between these symptoms.