Evolutionary divergence of facial muscle physiology between domestic dogs and wolves.

Domestic dogs (Canis familiaris) are descended from gray wolf (Canis lupus) populations that inhabited Western Europe and Siberia. The specific timing of dog domestication is debated, but archeological and genetic evidence suggest that it was a multi-phase process that began at least 15,000 years ago. There are many morphological differences between dogs and wolves, including marked divergence in facial muscle morphology, but we know little about the comparative physiology of these muscles. A better understanding of comparative facial muscle physiology between domestic dogs and gray wolves would improve our conceptual framework for the processual mechanisms in dog domestication. To address these issues, we assessed the myosin profiles (type I and type II) from the zygomaticus and orbicularis oris muscles of 6 domestic dogs and 4 gray wolves. Due to small sample sizes, statistical analyses were not done. Results reveal that sampled domestic dogs have almost 100% fast-twitch (type II) muscle fibers while gray wolves have less than 50%, meaning that dog faces can contract fast while wolf faces are able to sustain facial muscle contraction. Sample sizes are limited but the present study indicates that dog domestication is associated with not only a change in facial muscle morphology but a concomitant change in how these muscles function physiologically. Selective pressures in the development of communication between dogs and humans using facial expression may have influenced this evolutionary divergence, but the paedomorphic retention of barking in adult dogs may have also played a role.

Adrenocortical carcinoma: selective internal radiation therapy and liver metastases.

Selective internal radiation therapy (SIRT) is a novel intervention for both primary and metastatic malignant liver lesions. Adrenocortical carcinoma (ACC) is rare with limited treatment options; evidence for SIRT in ACC liver metastases consists of case reports only. Selective internal radiation therapy (SIRT) was employed to treat recurrent liver metastases in a 49-year-old gentleman with ACC, who previously underwent a left-sided hepatectomy. The patient opted for SIRT after reviewing the literature regarding mitotane chemotherapy and its toxicities. Selective internal radiation therapy (SIRT) provided several months of progression-free survival (PFS), with no toxicity and an excellent radiological response. The patient re-presented 12 years after the initial diagnosis with skeletal metastases and sadly died in September 2022. Substantial unmet need exists for effective treatments in ACC, with 75% of patients presenting with incurable disease. Developing widespread disease, SIRT offered 2 years' PFS in our patient; this was well tolerated with minimal residual liver impairment. Its use in ACC liver-limited disease warrants investigation. Significance statement: Adrenocortical carcinoma (ACC) is a rare and aggressive tumour with limited treatments. Once metastatic disease develops, existing standard-of-care treatments offer a dismal overall survival, alongside marked toxicities. Selective internal radiation therapy (SIRT) may represent a new intervention in the treatment paradigm for liver-limited, metastatic ACC. Here, we present the case of a patient treated with multiple rounds of SIRT for relapsed, liver-limited ACC, prolonging survival by several years. Recurrent SIRT led to maintained liver function and no toxicities. Little evidence outlines its use in ACC but further study is certainly warranted to ascertain the value of SIRT, considering the limited treatment landscape that currently exists.

Standard versus short stem cemented Exeter® when used for primary total hip arthroplasty: a survivorship analysis.

AIMS: The aims were to compare the survival of the cemented standard (150 mm) with the short (DDH [35.5 mm offset or less], number 1 short stem [125 mm options of 37.5 mm, 44 mm, 50 mm offset] and revision [44/00/125]) Exeter® V40 femoral stems when used for primary total hip arthroplasty (THA). METHODS: Patients were retrospectively identified from an arthroplasty database. A total of 664 short stem Exeter® variants were identified, of which 229 were DDH stems, 208 number 1 stems and 227 revision stems were implanted between 2011 and 2020. A control group of 698 standard Exeter® stems used for THA was set up, and were followed up for a minimum of 10 years follow-up (implanted 2011). All-cause survival was assessed for THA and for the stem only. Adjusted analysis was undertaken for age, sex and ASA grade. RESULTS: The median survival time for the short stems varied according to design: DDH had a survival time of 6.7 years, number 1 stems 4.1 years, and revision stems 7.2 years. Subjects in the short stem group (n = 664) were significantly younger (mean difference 5.1, P < 0.001) and were more likely to be female (odds ratio 1.89, 95% CI 1.50 to 2.39, P < 0.001), compared to the standard group. There were no differences in THA (P = 0.26) or stem (P = 0.35) survival at 5 years (adjusted THA: 98.3% vs. 97.2%; stem 98.7% vs. 97.8%) or 10 years (adjusted THA 97.0% vs. 96.0 %; stem 96.7% vs. 96.2%) between standard and short stem groups, respectively. At 5 years no differences were found in THA (DDH: 96.7%, number 1 97.5%, revision 97.3%, standard 98.6%) or stem (DDH: 97.6%, number 1 99.0%, revision 97.3%, standard 98.2%) survival between/among the different short stems or when compared to the standard group. CONCLUSION: The Exeter® short stems offer equivocal survival when compared to the standard stem at 5- to 10-year follow-up, which does not seem to be influenced by the short stem design.

Traumatic Glenohumeral Dislocation in Pediatric Patients Is Associated With a High Risk of Recurrent Instability.

BACKGROUND: The natural history of traumatic glenohumeral dislocation is well-established in young adults, but it is less clear in pediatric patients. We aimed to determine the rate of recurrent instability and medium-term functional outcome following shoulder dislocation in patients aged 14 years or younger. METHODS: All patients aged 14 years or younger who sustained a glenohumeral dislocation from 2008 to 2019 presenting to our regional health-board were identified. Patients who had subluxations associated with generalized laxity were excluded. Data was collected regarding further dislocations, stabilization surgery, sporting activity and patient-reported outcomes using the Western Ontario Shoulder Instability (WOSI) Index and Quick Disabilities of the Arm, Shoulder, and Hand score. RESULTS: Forty-one patients with a radiologically confirmed traumatic glenohumeral dislocation were suitable for study inclusion [mean age at injury 12.3 y (range: 7.2 to 14.0 y), male sex 29 (70.7%), median 7.9 y follow-up]. The incidence rate of pediatric glenohumeral dislocation was 2.5 cases per 100,000 population (aged 0 to 14 y) per year. Recurrent dislocation occurred in 43.9% (n=18/41) at a median time of 14.7 months postinjury (range: 1 to 54 mo). Skeletal maturity was associated with significantly higher proportion of recurrent instability (immature 6/24 vs. mature 12/17, P=0.01). One in 5 patients required surgical intervention for recurrent instability [mean 8 (range: 1 to 14) dislocations before surgery]. Twenty-eight patients had completed outcome questionnaires. The median modified WOSI score was 87.1% [270 (interquartile range: 65 to 795)] and the median Quick Disabilities of the Arm, Shoulder, and Hand score was 3.4 (interquartile range: 0 to 9.7). Recurrent shoulder instability was significantly associated with poorer WOSI score (unstable 71.4% vs. stable 94.3%, 95% confidence interval of the difference 6.2-36.9, P=0.04). CONCLUSIONS: Traumatic glenohumeral dislocation in patients aged 14 years or younger occurs rarely but is not a benign event. One in 2 patients experienced recurrent dislocation and 1 in 5 ultimately underwent surgical stabilization. LEVEL OF EVIDENCE: Level IV.

Consent in forefoot surgery; What does it mean to the patient?

AIMS: This study aimed to assess patient risk recall and find risk thresholds for patients undergoing elective forefoot procedures. METHODS: Patients were interviewed in the pre-assessment clinic (PAC) or on day of surgery (DOS); some in both settings. A standardised questionnaire was used for all interviews, regardless of setting. Patients were tested on which risks they recalled from their consent process, asked for thresholds for five pre-chosen risks and asked about a sham risk. RESULTS: Across all interviews, risk recall on DOS (2.34 risks/patient interview) was significantly lower (p=.05) than in PAC (2.95 risks/patient interview) - this was repeated when comparing results from patients interviewed in both settings only with PAC mean recall of 2.93 risks/patient interview and DOS mean recall of 2.57 risks/patient interview. The mean reported risk thresholds greatly exceeded NHS Lothian's observed complication rates for forefoot procedures. The five risks tested for thresholds produced the same order in each interview setting, suggesting a patient-perceived severity ranking. Patients answering the sham risk question incorrectly tended to recall fewer risks across all interviews. CONCLUSIONS: This study shows that patient risk recall is poor, as previous literature outlines, reinforcing that consent process improvements could be made. It also illustrates the value of PAC visits in patient education, as shown by higher levels of recall when compared to DOS.

Asymptomatic myocarditis during clozapine re-titration, in a patient who had previously been stable on clozapine for 10 years.

OBJECTIVE: We present a case of confirmed clozapine-induced myocarditis in a patient who was not naïve to the drug. METHOD: This patient, who had been stable on clozapine for 10 years, relapsed following self-cessation. Asymptomatic throughout inpatient re-titration, serum cardiac enzymes were nonetheless routinely taken. RESULTS: Occult myocarditis was only discovered due to an elevated Troponin I, and was confirmed by cardiac imaging. CONCLUSIONS: Once thought to be the preserve of initial exposure to the medication, clozapine-induced myocarditis can occur at any re-titration point if the immunological milieu permits. We therefore recommend routine monitoring of serum cardiac enzymes with all patients undergoing titration of clozapine, regardless of whether they have previously been stable on the drug.

The impact of insight in a first-episode mania with psychosis population on outcome at 18 months.

BACKGROUND: To explore whether poor initial insight during a first episode of mania with psychotic features was predictive of poor psychosocial and clinical outcomes at 18 months. METHODS: Secondary analysis was performed on data collected during an 8-week RCT comparing the efficacy of olanzapine versus chlorpromazine as an adjunct to lithium, and at 18-month follow-up. 74 participants were divided into three groups (no insight, partial insight, and full insight) according to the insight item from the Young Mania Rating Scale (YMRS). Differences between these three groups were examined at baseline and at 18 months on measures of symptoms (YMRS, HAMD-21, and CGI-S), and social and occupational functioning (SOFAS). Baseline differences between the three groups were determined using general linear models and chi-squared analyses. Group differences from baseline to 18-month follow-up were determined using repeated measures general linear models. RESULTS: At baseline there were significant differences between the three insight groups in terms of mania and functioning, but at 18 months all groups had improved significantly in terms of psychopathology, mania, depression and social and occupational functioning. There were no significant differences between the three groups at study completion with respect to these domains. LIMITATIONS: The study was limited by the lack of availability of a more detailed rating scale for insight, and it did not account for the duration of untreated psychosis (DUI). CONCLUSIONS: Poor initial insight during a first episode of mania with psychotic features does not predict poor clinical and psychosocial outcome at 18 months.

Effect of nucleotide substitutions in N-acetyltransferase-1 on N-acetylation (deactivation) and O-acetylation (activation) of arylamine carcinogens: implications for cancer predisposition.

Genetic polymorphism in N-acetyltransferase-1 (NAT1) is associated with increased risk of various cancers, but epidemiological investigations are compromised by poor understanding of the relationship between NAT1 genotype and phenotype. Human reference NAT1*4 and 12 known human NAT1 allelic variants possessing nucleotide polymorphisms in the NAT1 coding region were cloned and expressed in yeast (Schizosaccharomyces pombe). Large reductions in the N-acetylation of 4-aminobiphenyl and the O-acetylation of N-hydroxy-2-aminofluorene were observed for recombinant NAT1 allozymes encoded by NAT1*14B, NAT1*15, NAT1*17, NAT1*19, and NAT1*22. Each of these alleles exhibited substantially lower expression of NAT1 protein than the reference NAT1*4 and the other NAT1 alleles. These results show an important effect of the NAT1 genetic polymorphism on the N- and O-acetylation of arylamine carcinogens, suggesting modification of cancer susceptibility following exposures to arylamine carcinogens.