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The objectives are to measure the early time-course of the flows of blood, red cells, and plasma in brain tissue destined to infarct following arterial occlusion. The flux of fluorescent red blood cells (fRBCs) through venules and the arteriovenous transit times (AVTT) of fluorescein-labeled plasma albumin were periodically monitored in anesthetized adult Wistar rats before and up to 60 min after permanent ligations of several small branches of the middle cerebral artery. Of note, fRBC is a function of venular erythrocyte flow and volume, whereas AVTT is a function of plasma flow and volume in visible arteriole–capillary–venule units. In another group of anesthetized rats, local cerebral blood flow (lCBF) was measured 1 h after permanent arterial occlusion by [14C]iodoantipyrine (IAP) autoradiography. With this model of focal ischemia, the lesion is highly reproducible and involves part of the whisker barrel cortex. Infarction of this area was observed in 12 of 13 rats. From 10 to 60 min after arterial occlusion, AVTT was nearly four times longer in the ischemic barrel cortex than at the same site before ligations, and fRBC flux was 25%. Neither parameter changed appreciably over this time. After 60 min of ischemia, lCBF on the ipsilateral barrel cortex was 18% of that on the contralateral side and 15% of the sham control value for the same area of the barrel cortex. Since whole blood flow in the ischemic barrel cortex was

Competing Interests: Declaration of Competing Interest None.

The hip capsule has been recognized as a vital structure in the stability and proper function of the hip. Preserving its integrity during arthroscopic surgery is one of the utmost important principles in hip preservation surgery. When capsular deficiency is present, capsular reconstruction may be indicated to restore stability and proper hip mechanics. In this technical note, we introduce a simple and reproducible shuttle method technique for hip capsular reconstruction using a dermal allograft., (© 2023 The Authors.)

Approximately 30-50% of people with serious mental illness have co-existing drug or alcohol problems (COSMHAD), associated with adverse health and social care outcomes. UK guidelines advocate both co-occurring needs being met within mental health services, but uncertainty remains about how to operationalise this to improve outcomes. Various unevaluated service configurations exist in the UK. A realist synthesis was done to identify, test, and refine programme theories of how context shapes the mechanisms through which UK service models for COSMHAD work, for whom, and in what circumstances. Structured and iterative realist searches of seven databases identified 5099 records. A two-stage screening process identified 132 papers. Three broad contextual factors shaped COSMHAD services across 11 programme theories: committed leadership, clear expectations regarding COSMHAD from mental health and substance use workforces, and clear care-coordination processes. These contextual factors led to increased staff empathy, confidence, legitimisation, and multidisciplinary ethos, which improved care coordination and increased the motivation of people with COSMHAD to work towards their goals. Our synthesis highlights that integrating COSMHAD care is complex, and both individual and cultural behavioural shifts in leadership, workforce, and service delivery are essential to ensure people with COSMHAD receive compassionate, trauma-informed care that meets their needs., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Previous research on the minimal clinically important difference (MCID) for depression and anxiety is based on population averages. The present study aimed to identify the MCID across the spectrum of baseline severity., Study Design and Settings: The present analysis used secondary data from 2 randomized controlled trials for depression (n = 1,122) to calibrate the Global Rating of Change with the PHQ-9 and GAD-7. The MCID was defined as a change in scores corresponding to a 50% probability of patients "feeling better", given their baseline severity, referred to as Effective Dose 50 (ED50)., Results: MCID estimates depended on baseline severity and ranged from no change for very mild up to 14 points (52%) on the PHQ-9 and up to 10 points (48%) on the GAD-7 for very high severity. The average MCID estimates were 3.7 points (23%) and 3.3 (28%) for the PHQ-9 and GAD-7 respectively., Conclusion: The ED50 method generates MCID estimates across the spectrum of baseline severity, offering greater precision but at the cost of greater complexity relative to population average estimates. This has important implications for evaluations of treatments and clinical practice where users can use these results to tailor the MCID to specific populations according to baseline severities., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Maintaining adequate muscle tissue oxygenation is of paramount importance during equine general anesthesia. The objectives of this study were to assess the feasibility, reliability and repeatability of near-infrared spectroscopy (NIRS) muscle oximetry using the Inspectra m650 in conscious healthy adult horses., Study Design: Prospective, observational study., Animals: A group of 30 healthy client-owned adult horses admitted to the equine hospital between July 2017 and July 2018., Methods: The probe of an Inspectra m650 NIRS tissue oximeter was placed on the hairless surface of five muscle sites (omotransversarius, triceps long head, extensor carpi ulnaris, vastus lateralis and lateral digital extensor) on the left side of the body of each standing, unsedated horse. Each site had muscle oxygenation (StO 2 ) recordings measured in triplicate and statistical modeling used to assess the reading reliability and repeatability within and between muscle sites., Results: The readings acquired at the vastus lateralis and extensor carpi ulnaris muscle sites had highly repeatable values [mean (90% confidence interval): StO 2 , 95% (93.8%, 96.5%) and 93% (91.6%, 93.9%), respectively; intraclass correlation coefficients, 0.92 and 0.80, respectively]. These two sites also had high reliability (represented by the percentage of successful readings; 70% and 86%, respectively)., Conclusions and Clinical Relevance: The use of NIRS muscle oxygenation technology is a clinically feasible means to assess tissue oxygenation in horses. The vastus lateralis and extensor carpi ulnaris muscle sites provided the most reliable and repeatable readings when using the Inspectra m650 machine in horses., (Copyright © 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objectives: Perineural invasion (PNI) has not yet gained universal acceptance as an independent predictor of adverse outcomes for prostate cancer treated with external beam radiotherapy (EBRT). We analyzed the prognostic influence of PNI for a large institutional cohort of prostate cancer patients who underwent EBRT with and without androgen deprivation therapy (ADT)., Material and Methods: We, retrospectively, reviewed prostate cancer patients treated with EBRT from 1993 to 2007 at our institution. The primary endpoint was biochemical failure-free survival (BFFS), with secondary endpoints of metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS). Univariate and multivariable Cox proportional hazards models were constructed for all survival endpoints. Hazard ratios for PNI were analyzed for the entire cohort and for subsets defined by NCCN risk level. Additionally, Kaplan-Meier survival curves were generated for all survival endpoints after stratification by PNI status, with significant differences computed using the log-rank test., Results: Of 888 men included for analysis, PNI was present on biopsy specimens in 187 (21.1%). PNI was associated with clinical stage, pretreatment PSA level, biopsy Gleason score, and use of ADT (all P<0.01). Men with PNI experienced significantly inferior 10-year BFFS (40.0% vs. 57.8%, P = 0.002), 10-year MFS (79.7% vs. 89.0%, P = 0.001), and 10-year PCSS (90.9% vs. 95.9%, P = 0.009), but not 10-year OS (67.5% vs. 77.5%, P = 0.07). On multivariate analysis, PNI was independently associated with inferior BFFS (P<0.001), but not MFS, PCSS, or OS. In subset analysis, PNI was associated with inferior BFFS (P = 0.04) for high-risk patients and with both inferior BFFS (P = 0.01) and PCSS (P = 0.05) for low-risk patients. Biochemical failure occurred in 33% of low-risk men with PNI who did not receive ADT compared to 8% for low-risk men with PNI treated with ADT (P = 0.01)., Conclusion: PNI was an independently significant predictor of adverse survival outcomes in this large institutional cohort, particularly for patients with NCCN low-risk disease. PNI should be carefully considered along with other standard prognostic factors when treating these patients with EBRT. Supplementing EBRT with ADT may be beneficial for select low-risk patients with PNI though independent validation with prospective studies is recommended., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To determine the short-term safety and biologic activity of radiation therapy (RT) for presumptive cardiac hemangiosarcoma in pet dogs., Animals: Six dogs with echocardiographic evidence of a right atrial/auricular mass, and hemorrhagic pericardial effusion, were enrolled in a prospective, single-arm clinical trial., Methods: A single fraction of 12 Gy was delivered using conformal external beam irradiation. Serum cardiac troponin I and plasma concentrations of vascular endothelial growth factor were quantified before, 4 and 24 h after RT. The frequency of required pericardiocenteses (quantified as the number of pericardiocenteses per week) before RT was compared to that after treatment. Overall survival time was determined., Results: No treatment-related complications were observed. Pericardiocentesis was performed an average of 0.91 times per week before RT, and an average of 0.21 times per week after RT; this difference was statistically significant (p=0.03, as compared using a Wilcoxon signed-rank test of paired data). Pre- and post-treatment plasma vascular endothelial growth factor concentrations were not significantly different at any time point; there was a statistically significant (p=0.04; Friedman's test for non-parametric repeated measures) increase in cardiac troponin concentrations 4 h after irradiation. Median overall survival time was 79 days., Conclusions: In this population of dogs, RT was delivered without complication, and appears to have reduced the frequency of periacardial tamponade that necessitated pericardiocentesis. Serum cardiac troponin levels are altered after RT. RT alone, or in combination with chemotherapy, may provide clinical benefit to dogs with presumptive diagnoses of cardiac hemangiosarcoma., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: To evaluate the clinical presentation, diagnosis, treatment, and outcomes of a group of dogs with sinoatrial node abnormalities., Animals: Ninety-three client-owned dogs at a referral institution., Materials and Methods: Medical records were reviewed for clinical history, diagnostic testing, and medical or permanent artificial pacemaker (PAP) treatment. Owners or veterinarians were contacted for long-term follow-up., Results: Sixty-one dogs were symptomatic for their bradyarrhythmia and were diagnosed with sick sinus syndrome (SSS). Thirty-two dogs were asymptomatic for their bradyarrhythmia and were diagnosed with sinus node dysfunction (SND). Miniature Schnauzers, West Highland White terriers, Cocker spaniels, and female dogs were overrepresented. Medical management with positive chronotropic drugs successfully controlled syncope long-term in 54% of SSS dogs, and acted as a bridge to PAP in 20%. Positive atropine response predicted medical treatment success. Forty-six percent of SSS dogs eventually underwent PAP implantation. Median survival time was approximately 18 months in SND and SSS dogs regardless of treatment strategy. Congestive heart failure (CHF) associated with progressive valvular heart disease occurred commonly in all groups, particularly in dogs with bradycardia-tachycardia syndrome., Conclusions: Sinus node dysfunction and SSS represent a spectrum of sinoatrial node disease, which for some dogs may also involve a component of autonomic dysfunction. Dogs with SND do not require treatment. Dogs with SSS often require treatment to reduce the frequency of syncope; medical management is often useful, particularly in atropine responsive dogs. Prognosis of SSS with treatment is good, though development of CHF does not appear to be mitigated by treatment., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The association between antihypertensive medications and survival in cancer patients remains unclear., Objectives: To explore the association between classes of antihypertensive drugs and survival in cancer patients., Methods: Provincial Cancer Registry data was linked with a Provincial Drug Program Information Network (DPIN) for patients with lung (n=4241), colorectal (n=3967), breast (n=4019) or prostate (n=3355) cancer between the years of 2004 and 2008. Cox regression analyses were used to compare survival of patients using beta blockers (BBs), angiotensin-converting enzyme inhibitors/receptor blockers (ACEi/ARB), calcium channel blockers (CCBs) or thiazide diuretics (TDs) to survival of patients who did not use any of these antihypertensive drugs. Survival of patients using only one class of antihypertensive drugs were compared to each other, with BBs as the reference class., Results: Compared to the antihypertensive drug non-user cohort, BBs had no effect on survival for any of the cancers. ACEi/ARBs use was weakly associated with increased deaths for breast cancer (HR: 1.22, 95% CI: 1.04-1.44) and lung cancer (HR: 1.11, 95% CI: 1.03-1.21) patients. Deaths were also increased with CCB use in patients with breast cancer (HR: 1.22, 95% CI: 1.02-1.47) and with TD use in lung cancer patients (HR: 1.1, 95% CI: 1.01-1.19). There was strong evidence (p-value <0.0001) of an increase in deaths with TD use for colorectal (HR: 1.28, 95% CI: 1.15-1.42), and prostate (HR 1.41, 1.2-1.65) cancer patients. When including only antihypertensive drug users prescribed one drug class, lung cancer patients receiving CCBs had improved survival compared to BBs (HR 0.79, 95% CI: 0.64-0.98)., Conclusions: Some classes of antihypertensive agents are associated with a decreased survival in certain cancers. The decrease could be due to more comorbidities in antihypertensive drug users. However, CCB use was associated with improved survival in lung cancer patients., (Copyright © 2013. Published by Elsevier Ltd.)

Background: The angiogenesis inhibitors TNP-470 and ovalicin potently suppress endothelial cell growth. Both drugs also specifically inhibit methionine aminopeptidase 2 (MetAP2) in vitro. Inhibition of MetAP2 and changes in initiator methionine removal in drug-treated endothelial cells have not been demonstrated, however., Results: Concentrations of TNP-470 sufficient to inactivate MetAP2 in intact endothelial cells were comparable to those that inhibited cell proliferation, suggesting that MetAP2 inhibition by TNP-470 underlies the ability of the drug to inhibit cell growth. Both drug-sensitive and drug-insensitive cell lines express MetAP1 and MetAP2, indicating that drug sensitivity in mammalian cells is not simply due to the absence of compensating MetAP activity. With a single exception, detectable protein N-myristoylation is unaffected in sensitive endothelial cells treated with TNP-470, so MetAP1 activity can generally compensate when MetAP2 is inactive. Analysis of total protein extracts from cells pulse-labeled with [(35)S]-methionine following TNP-470 treatment revealed changes in the migration of several newly synthesized proteins. Two of these proteins were identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and cyclophilin A. Purification and amino-terminal sequencing of GAPDH from TNP-470-treated cells revealed partial retention of its initiator methionine, indicating that methionine removal from some, but not all, proteins is affected by MetAP2 inactivation., Conclusions: Amino-terminal processing defects occur in cells treated with TNP-470, indicating that inhibition of MetAP2 by the drug occurs in intact cells. This work renders plausible a mechanism for growth inhibition by TNP-470 as a consequence of initiator methionine retention, leading to the inactivation of as yet unidentified proteins essential for endothelial cell growth.

Background: Angiogenesis, the formation of new blood vessels, is essential for tumor growth. The inhibition of angiogenesis is therefore emerging as a promising therapy for cancer. Two natural products, fumagillin and ovalicin, were discovered to be potent inhibitors of angiogenesis due to their inhibition of endothelial cell proliferation. An analog of fumagillin, AGM-1470, is currently undergoing clinical trials for the treatment of a variety of cancers. The underlying molecular mechanism of the inhibition of angiogenesis by these natural drugs has remained unknown., Results: Both AGM-1470 and ovalicin bind to a common bifunctional protein, identified by mass spectrometry as the type 2 methionine aminopeptidase (MetAP2). This protein also acts as an inhibitor of eukaryotic initiation factor 2alpha (elF-2alpha) phosphorylation. Both drugs potently inhibit the methionine aminopeptidase activity of MetAP2 without affecting its ability to block elF-2alpha phosphorylation. There are two types of methionine aminopeptidase found in eukaryotes, but only the type 2 enzyme is inhibited by the drugs. A series of analogs of fumagillin and ovalicin were synthesized and their potency for inhibition of endothelial cell proliferation and inhibition of methionine aminopeptidase activity was determined. A significant correlation was found between the two activities., Conclusions: The protein MetAP2 is a common molecular target for both AGM-1470 and ovalicin. This finding suggests that MetAP2 may play a critical role in the proliferation of endothelial cells and may serve as a promising target for the development of new anti-angiogenic drugs.

Culture and religion have a strong impact on clinical relationships, and attention to these issues has been shown to improve psychiatric care. Current issues in psychiatry and religion are explored, in order to demonstrate the clinical relevance of new findings in this area.

This paper examines all the cases of suicide and parasuicide (non-fatal self-destructive acts) which took place on the Caribbean island of Barbados between 1974 and 1978. There were two females and 18 males who committed suicide in that period, and 14 of them were below age 44. There were 250 individuals who had attempted suicide for the first time, with a male to female ratio of 1:2.33. Most of the parasuicides were young and female, and the phenomenon is increasing. Health care officials on the island would seem to be legitimately unconcerned about the low suicide rates. However, the increasing parasuicide numbers may require more organized psychiatric care to meet the needs of this subgroup of the island's population.

The authors describe the midweek evening service of an independent black church which employs prayer, testimony, and spirit possession. They compare this religious group experience to the theoretical model of the healing community and emphasize the concepts of "communitas" and "healing charisma." The authors suggest that the model of a healing community, as represented by this form of the black church service, represents culturally relevant and functional therapeutic assets for some black people.

The concept of the psychiatric unit as a social system, with staff members and patients working together to pursue a number of functions, is a departure from the disease model and the classic patient-doctor dyadic relationship. The organization of a psychiatric unit as a social system can facilitate an atmosphere that promotes a corrective emotional experience for patients and a positive emotional climate for the staff. The various ways in which social organization and environment can effect clinical change are described.