Temperature impacts Atlantic salmon's (Salmo salar) immunological response to infectious salmon anemia virus (ISAv).

Ocean temperatures continue to rise annually due to the ever-growing consequences of global climate change. These temperature changes can have an impact on the immunological robustness of cultured fish, especially cold-water species such as Atlantic salmon. The salmon farming industry already loses hundreds of millions of dollars each year to infectious and non-infectious diseases. One particularly important and WOAH reportable disease is infectious salmon anemia caused by the orthomyxovirus ISAv. Considering the changing environment, it is necessary to find ways to mitigate the effect of diseases on the industry. For this study, 20 Atlantic salmon families were housed in each of 38 different tanks at the AVC, with half of the fish being kept at 10 °C and half being kept at 20 °C. Donor Atlantic salmon IP- injected with a highly virulent ISAv isolate (HPR4; TCID50 of 1 × 105/mL) were added to each tank as the source of co-habitation infection. Both temperatures were sampled at onset of mortality in co-habited fish and at resolution of mortality. Family background and temperature significantly impacted ISAv load, as assessed by qPCR, time to mortality and overall mortality. Mortality was more acute at 20 °C, but overall mortality was higher at 10 °C. Based on percent mortality calculated over the course of the study, different families demonstrated different levels of survival. The three families that demonstrated the highest percent mortality, and the three families with the lowest percent mortality were then assessed for their antiviral responses using relative gene expression. Genes significantly upregulated between the unexposed fish and ISAv exposed fish included mx1, il4/13a, il12rb2, and trim25, and these were further impacted by temperature. Understanding how ISAv resistance is impacted by temperature can help identify seasonal risks of ISAv outbreaks as well as ideal responses to be targeted through immunopotentiation.

Inequity Analysis in Faculty Recognition Awards at a School of Medicine.

As part of developmental networks, sponsors help provide recognition and visibility opportunities to their faculty protégés. Recognition awards given to the School of Medicine (SOM) faculty are an important mechanism for acknowledging what is valued in academic medicine. Beyond their impact on individual careers, awards help define the culture and climate of an organization. The literature suggests inequities in recognition awards for women and racial/ethnic underrepresented minority faculty. The study's purpose was to examine the characteristics of the awardees relative to the SOM faculty in a minority-serving institution in a minority-majority state. In this observational cross-sectional study, 47 SOM faculty were recognized between 2000-2023 as Regents' Lecturers (9), Regents' Professors (20), Community Engagement Awardees (5), and Gold-headed Cane Awardees (13). SOM sought nominations which a search committee competitively reviewed. Award recipients were characterized by their department, rank, academic track, degree, country of origin, sex, and race/ethnicity, and were compared to all SOM faculty. Male faculty were more likely than women faculty to receive an award (p=0.04). Faculty with tenure, Ph.D. degree, or Professor rank were more likely to receive an award than their counterparts (p<0.001, all analyses). Faculty in basic and diagnostic specialties were more likely to receive an award than medical or surgical specialties (p<0.001). Although rates of awards for racial/ethnic URM faculty were about half that of non-URM faculty, this difference did not reach statistical significance (p=0.14). In addition to demonstrating sex-related inequity in awards, recognized faculty are traditionally associated with the scholarship of discovery compared to other models of scholarship or clinical activity. Sponsors should promote women, physicians, and clinician educators for recognition awards to advance their academic careers. SOM leaders need to examine award criteria and processes to ensure recognition of the diversity of talents and achievements that are critical to the future of academic medicine.

Real-world treatment sequencing and survival in previously treated advanced renal cell carcinoma patients receiving nivolumab monotherapy: a UK retrospective cohort study.

BACKGROUND: The CheckMate 025 trial established nivolumab monotherapy as one of the standards of care in previously treated advanced or metastatic renal cell carcinoma (aRCC). However, supporting real-world data is lacking. This study investigated characteristics, treatment sequences and clinical outcomes of patients who received nivolumab monotherapy for previously treated aRCC in the UK. METHODS: This was a retrospective cohort study of aRCC patients treated with nivolumab at second line or later (2L +) at 4 UK oncology centres. Eligible patients commenced nivolumab (index date) between 01 March 2016 and 30 June 2018 (index period). Study data were extracted from medical records using an electronic case report form. Data cut-off (end of follow-up) was 31 May 2019. RESULTS: In total, 151 patients were included with median follow-up of 15.2 months. Mean age was 66.9 years, male preponderance (72.2%), and mostly Eastern Cooperative Oncology Group performance status grade 0-1 (71.5%). Amongst 112 patients with a known International Metastatic RCC Database Consortium score, distribution between favourable, intermediate, and poor risk categories was 20.5%, 53.6%, and 25.9% respectively. The majority of patients (n = 109; 72.2%) received nivolumab at 2L, and these patients had a median overall survival (OS) of 23.0 months [95% confidence interval: 17.2, not reached]. All patients who received nivolumab at 2L had received TKIs at 1L. Amongst the 42 patients (27.8%) who received nivolumab in third line or later (3L +) the median OS was 12.4 months [95% CI: 8.8, 23.2]. The most common reasons for nivolumab discontinuation were disease progression (2L: 61.2%; 3L: 68.8%) and adverse events (2L: 34.7%; 3L: 28.1%). CONCLUSION: This study provides real-world evidence on the characteristics, treatment sequences, and outcomes of aRCC patients who received 2L + nivolumab monotherapy in the UK. Nivolumab-specific survival outcomes were similar to those achieved in the CheckMate 025 trial.

Low speech rate but high gesture rate during conversational interaction in people with Cornelia de Lange syndrome.

BACKGROUND: Cornelia de Lange syndrsome (CdLS) is a rare genetic syndrome with notable impaired expressive communication characterised by reduced spoken language. We examined gesture use to refine the description of expressive communication impairments in CdLS. METHODS: During conversations, we compared gesture use in people with CdLS to peers with Down syndrome (DS) matched for receptive language and adaptive ability, and typically developing (TD) individuals of similar chronological age. RESULTS: As anticipated the DS and CdLS groups used fewer words during conversation than TD peers (P < .001). However, the CdLS group used twice the number of gestures per 100 words compared with the DS and TD groups (P = .003). CONCLUSIONS: Individuals with CdLS have a significantly higher gesture rate than expected given their level of intellectual disability and chronological age. This result indicates the cause of reduced use of spoken language does not extend to all forms of expressive communication.

Chip fractures from the distal lateral trochlear ridge of the talus of a quarter horse gelding: a veterinary medicine clinical report.

An eighteen-month old quarter horse gelding was diagnosed with chip fractures from the distal lateral trochlear ridge of the talus. The horse presented with the symptom of persistent synovitis. The diagnosis was based on radiographic evidence. The horse was treated initially with arthroscopic surgery. He was given a non-steroidal anti-inflammatory agent, and a chondroprotective agent to prevent further damage to, and aid in the healing of, the damaged joint.

An open-label study of repeated use of diazepam rectal gel (Diastat) for episodes of acute breakthrough seizures and clusters: safety, efficacy, and tolerance. North American Diastat Group.

PURPOSE: To assess safety of diazepam rectal gel (DZPRG) for control of acute seizures in epilepsy patients and to evaluate tolerance with repeated use of DZPRG at intervals of > or =5 days. METHODS: Subjects were persons with epilepsy, age 2 years or older, with seizure clusters or prolonged seizures. Onset of a treatable episode was defined; caregivers were trained to administer DZPRG and to monitor respiration, seizures, and adverse effects (AEs). DZPRG was dispensed in a single-use, prefilled syringe; dosage was determined by age and weight. Maximal use was > or =5-day intervals, < or =5 times/month. After use, caregivers returned data booklets and syringe. Caregivers and physicians completed global ratings yearly. RESULTS: In 149 subjects treated, 77% of 1,578 administrations resulted in seizure freedom for the next 12 h. One hundred twenty-five received two or more treatments (two to 78; median, 8), 0.03-4.3/month (median, 0.4). To evaluate tolerance, subjects with two or more episodes were divided into low (two to seven episodes) and high use (eight to 78 episodes treated). There was no difference in proportion seizure free 12 h after the first administration versus last administration, for either infrequent or frequent administration. Sedation occurred in 17%, attributed to DZPRG in 9%. No respiratory depression was attributable to DZPRG. Three subjects withdrew because of AEs attributable to (agitation) or possibly attributable to DZPRG (chest pain, rash). Five subjects withdrew because of AEs unrelated to DZPRG. Caregiver and physician global ratings were highly positive at both 12 and 24 months. CONCLUSIONS: DZPRG is safe and effective in children and adults with epilepsy with breakthrough seizures. Neither tolerance nor significant medication-related AEs were seen with repeated DZPRG administration at intervals > or =5 days.

A controlled pharmacokinetic evaluation of tizanidine and baclofen at steady state.

Clinical trials with tizanidine when administered alone have shown that 5-chloro-4-(2-imidazolin-2-ylamino)-2,1,3-benzothiodiazole (tizanidine) is safe and effective for spasticity control. However, given its mechanism of action and requirement for titration, clinical experience suggests that tizanidine is likely to be used in combination with other antispastic agents with different mechanisms of action, such as baclofen. The objective of this study was to examine the pharmacokinetics of both tizanidine and baclofen under steady-state conditions when administered alone or concomitantly. This was a randomized, three-period, multiple-dose, Latin Square design study consisting of tizanidine HCl, 4 mg t.i.d. for seven consecutive doses; baclofen, 10 mg t.i.d. for seven consecutive doses; and both regimens simultaneously for seven consecutive doses. Drug administration was performed every 8 h, three times daily. Fifteen normal men served as study subjects. A priori, a clinically significant difference was set as 30%. Concentrations of tizanidine and baclofen were nearly identical during the single and concomitant dosing periods. All of the calculated steady-state pharmacokinetic parameter changes for baclofen, tizanidine, and its major metabolites were within the 30% criterion. Small differences in renal clearance were observed when the two drugs were coadministered, but these changes are unlikely to be clinically important. Thus, it is unlikely that coadministration of tizanidine and baclofen during dose-titration of the former will result in a pharmacokinetic interaction.

Tizanidine treatment of spasticity: a meta-analysis of controlled, double-blind, comparative studies with baclofen and diazepam.

To conduct a meta-analysis of the antispastic efficacy and tolerability of tizanidine, we reviewed records of the European sponsor of tizanidine trials and selected double-blind, randomized studies of moderate duration in which oral tizanidine was compared with baclofen or diazepam. Studies were required to have individual patient data; three key outcome measures (Ashworth Rating Scale for muscle tone, a measure of muscle strength, and Global Tolerability to Treatment Rating); and patients with multiple sclerosis or cerebrovascular lesions. Ten trials involving 270 patients met these criteria. Seven studies used baclofen as the positive control; three used diazepam. As measured by Total and Lower Body Ashworth scores, tizanidine and similar spasticity-reducing effects to both baclofen and diazepam. Muscle strength was affected less by tizanidine than by either comparator, and investigators judged tizanidine to have greater tolerability. Within the limits of these comparisons, tizanidine, baclofen, and diazepam were equally effective in decreasing excessive muscle tone in patients with multiple sclerosis or cerebrovascular lesions. Muscle strength improved in all three treatment groups, but improvement was greatest with tizanidine.

The effects of sub-anaesthetic doses of ketamine on memory, cognitive performance and subjective experience in healthy volunteers.

The cognitive and subjective effects of sub-anaesthetic doses of ketamine on healthy volunteers were examined. Twelve healthy volunteers received 25 mg ketamine, 10 mg ketamine and saline placebo, i.m. in a double-blind, Latin square design. A cognitive, perceptual and self-report test battery was administered over 45 min. The order of tests was rotated to control for timing effects. Ketamine (25 mg) significantly affected verbal learning and memory, parallel visual search, some measures of psychomotor performance, measures of arousal, subjective mood ratings and visual perception. Measures of attention and frontal lobe functioning were relatively unaffected. Thus, low doses of ketamine had selective, dose-related effects on memory, perceptual and psychomotor functions. The disruption of memory and perceptual processes may help to explain the unique subjective state induced by ketamine.

Comparative profile of tizanidine in the management of spasticity.

The therapeutic profile of a new antispastic drug cannot be defined solely on the basis of placebo-controlled studies. Its potential advantages must be evaluated in comparison with existing drugs. This review compares the efficacy and tolerability of tizanidine, a newer muscle relaxant, with that of baclofen and diazepam, the most widely used antispastic agents, for a variety of diagnoses and target symptoms associated with spasticity. More than 20 double-blind, comparative studies were conducted between 1977 and 1987. These included a total of 777 patients suffering from spasticity of various causes. The collected clinical data have been integrated into a combined analysis. Tizanidine emerges from this comparison as a valuable drug in the treatment of spasticity related to cerebral and spinal disorders.

Efficacy and side effects of methylphenidate for poststroke depression.

BACKGROUND: Depression after stroke impedes the rehabilitation process and causes additional suffering to patient and family. Few studies have systematically examined pharmacologic treatments of poststroke depression. In the present paper, the use of the stimulant methylphenidate is studied in a depressed, elderly stroke population. METHOD: Ten subjects (mean age = 73.2 years) meeting DSM-III-R criteria for major depression were followed-up during a 3-week efficacy and side effect trial involving methylphenidate. Subjects were selected from rehabilitation patients referred for psychiatric consultation. RESULTS: A total of 80% (8 of 10) of the subjects showed either a full or partial response as measured by Hamilton Rating Scale for Depression scores. The incidence of problematic side effects was low, and no subjects had to be discontinued from the study. CONCLUSION: Results of this methylphenidate trial for poststroke depression in elderly patients suggest that it is a safe and effective treatment for poststroke depression. Future studies are called for in which methylphenidate is compared with placebo controls and antidepressant medication.

Safety of estazolam. The United States clinical experience.

The safety profile of estazolam, a new triazolobenzodiazepine hypnotic medication, has been developed in 1,320 normal volunteers and patients with insomnia. No clinically significant effects of estazolam on vital signs or laboratory values were detected. Drug-specific adverse effects such as somnolence, dizziness, hypokinesia, and abnormal coordination occurred, but these are expected extensions of benzodiazepine pharmacologic activity. No consistent effects on psychomotor performance, including memory, were seen at the recommended hypnotic doses in insomniac subjects. These data, combined with the evidence for hypnotic activity, indicate that estazolam is a safe and effective treatment for insomnia.

Methylphenidate in treating poststroke depression.

The authors retrospectively studied the charts of 25 patients with poststroke depression who were treated with methylphenidate. The 13 patients (52%) who recovered completely from their depression did not differ significantly from the 12 nonresponders on demographic characteristics, location of cerebrovascular accident, and other variables. Mood usually improved within 48 hours; only 3 (12%) patients had side effects. Rapid response to treatment and lack of significant side effects indicate that methylphenidate may be a valuable treatment for poststroke depression.

Use of the dexamethasone suppression test with depressed and demented elderly.

Although some researchers have suggested that the dexamethasone suppression test (DST) may be useful in differentiating between major depression and dementia in the elderly, recent reports of abnormal DST results in nondepressed, demented elderly have questioned the validity of the test in this population. This study compared the frequency of abnormal DST results in three groups of elderly inpatients: depressed/not demented; demented/not depressed; and depressed and demented. Two geropsychiatrists independently evaluated 33 patients for symptoms of depression and/or dementia and then assigned each patient to one of the three groups. Subjects in the demented/not depressed group had a significantly larger proportion of abnormal DSTs (P less than .01), and the mean postdexamethasone, 4 PM blood cortisol level of the demented/not depressed group was significantly greater than the means of the other two groups (P less than .005). In this sample, the DST was more likely to identify dementia than depression. Until further investigations clarify the parameters of DST use in the elderly, the diagnosis of depression and dementia should continue to be determined by sensitive interpretation of clinical findings, history, and other diagnostic tests.