Inclusion of Trainee Stakeholders Is Necessary for Effective Change in Health-Service-Psychology Internship Training.

In a recent call to action, we described pressing issues in the health-service-psychology (HSP) internship from the perspective of interns. In our article, we sought to initiate a dialogue that would include trainees and bring about concrete changes. The commentaries on our article are a testament to the readiness of the field to engage in such a dialogue, and we applaud the actionable recommendations that they make. In our response to these commentaries, we seek to move the conversation further forward. We observe two themes that cut across these responses: the impetus to gather novel data on training (the "need to know") and the importance of taking action (the "need to act"). We emphasize that in new efforts to gather data and take policy-level action, the inclusion of trainee stakeholders (as well as others involved in and affected by HSP training) is a crucial ingredient for sustainable and equitable change.

Online rapid sampling microdialysis (rsMD) using enzyme-based electroanalysis for dynamic detection of ischaemia during free flap reconstructive surgery.

We describe an enzyme-based electroanalysis system for real-time analysis of a clinical microdialysis sampling stream during surgery. Free flap tissue transfer is used widely in reconstructive surgery after resection of tumours or in other situations such as following major trauma. However, there is a risk of flap failure, due to thrombosis in the flap pedicle, leading to tissue ischaemia. Conventional clinical assessment is particularly difficult in such 'buried' flaps where access to the tissue is limited. Rapid sampling microdialysis (rsMD) is an enzyme-based electrochemical detection method, which is particularly suited to monitoring metabolism. This online flow injection system analyses a dialysate flow stream from an implanted microdialysis probe every 30 s for levels of glucose and lactate. Here, we report its first use in the monitoring of free flap reconstructive surgery, from flap detachment to re-vascularisation and overnight in the intensive care unit. The on-set of ischaemia by both arterial clamping and failure of venous drainage was seen as an increase in lactate and decrease in glucose levels. Glucose levels returned to normal within 10 min of successful arterial anastomosis, whilst lactate took longer to clear. The use of the lactate/glucose ratio provides a clear predictor of ischaemia on-set and subsequent recovery, as it is insensitive to changes in blood flow such as those caused by topical vasodilators, like papaverine. The use of storage tubing to preserve the time course of dialysate, when technical difficulties arise, until offline analysis can occur, is also shown. The potential use of rsMD in free flap surgery and tissue monitoring is highly promising.

Systemic Challenges in Internship Training for Health-Service Psychology: A Call to Action From Trainee Stakeholders.

The challenges observed in health service psychology (HSP) training during COVID-19 revealed systemic and philosophical issues that preexisted the pandemic, but became more visible during the global health crisis. In a position paper written by 23 trainees across different sites and training specializations, the authors use lessons learned from COVID-19 as a touchstone for a call to action in HSP training. Historically, trainee voices have been conspicuously absent from literature about clinical training. We describe longstanding dilemmas in HSP training that were exacerbated by the pandemic and will continue to require resolution after the pandemic has subsided. The authors make recommendations for systems-level changes that would advance equity and sustainability in HSP training. This article advances the conversation about HSP training by including the perspective of trainees as essential stakeholders.

Inhibition of HERV-K (HML-2) in amyotrophic lateral sclerosis patients on antiretroviral therapy.

Reactivation of Human Endogenous Retrovirus K (HERV-K), subtype HML-2, has been associated with pathophysiology of amyotrophic lateral sclerosis (ALS). We aimed to assess the efficacy of antiretroviral therapy in inhibiting HML-2 in patients with ALS and a possible association between the change in HML-2 levels and clinical outcomes. We studied the effect of 24-weeks antiretroviral combination therapy with abacavir, lamivudine, and dolutegravir on HML-2 levels in 29 ALS patients. HML-2 levels decreased progressively over 24 weeks (P = 0.001) and rebounded within a week of stopping medications (P = 0.02). The majority of participants (82%), defined as "responders", experienced a decrease in HML-2 at week 24 of treatment compared to the pre-treatment levels. Differences in the evolution of some of the clinical outcomes could be seen between responders and non-responders: FVC decreased 23.69% (SE = 11.34) in non-responders and 12.71% (SE = 8.28) in responders. NPI score decreased 91.95% (SE = 6.32) in non-responders and 53.05% (SE = 10.06) in responders (P = 0.01). Thus, participants with a virological response to treatment showed a trend for slower progression of the illness. These findings further support the possible involvement of HML-2 in the clinical course of the disease.

The human G93A-superoxide dismutase-1 mutation, mitochondrial glutathione and apoptotic cell death.

Mutations in Cu/Zn superoxide dismutase are a cause of motor neuron death in about 20% of cases of familial amyotrophic lateral sclerosis (ALS). Although the molecular mechanism of which these mutations induce motor neuron cell death is to a large extent unknown, there is significant evidence that effects on mitochondrial function and development of oxidative stress make a major contribution to the selective death of motor neurons in this disease. In this overview article we review the current understanding of mutant SOD1-mediated motor neuron degeneration in ALS with focus on oxidative damage and mitochondrial dysfunction. We also present novel information on the role of mitochondrial glutathione for the survival of NSC-34 cells stably transfected with the human SOD1(G93A) mutation, putting forward the hypothesis that this antioxidant pool provides a potentially useful target for therapeutic intervention.

CD 271 (P75 neurotrophin receptor).

P75NTR (or CD271) is a member of the Tumor Necrosis Factor receptor (TNFR) super family of transmembrane proteins that share significant homology in their extracellular domains. Subsets of TNF receptors, including CD271, have a cytoplasmic death domain, although CD271 has unique intracellular structure and downstream signaling partners. CD271 is also differentiated from other members of the TNFR receptor family in that it binds pro and mature neurotrophins and affects the growth, differentiation and death of the nervous system. The ligands for CD271 are neurotrophins, which are Nerve Growth Factor (NGF), Brain-Derived Growth factor (BDNF), Neurotrophin 3 (NT3) and Neurotrophin 4/5 (NT4/5). Recent studies have provided evidence that CD271 also serves as a receptor for the pro-forms of these neurotrophins.

Platelet-derived growth factor, insulin-like growth factors, fibroblast growth factors and transforming growth factor beta do not account for the cell growth activity present in bovine milk.

Cation-exchange chromatography effectively concentrates the cell growth activity present in whey and we have used this process as a basis to characterise further the growth factors present in bovine milk. Under neutral conditions, total bioactivity in the growth factor-enriched cation-exchange fraction chromatographed with an apparent molecular mass of 80-100 kDa. In contrast, acid gel-filtration chromatography resolved two peaks of cell growth activity. A peak at 15-25 kDa contained the bulk of growth activity for Balb/c 3T3 fibroblasts while bio-activity for L6 myoblasts and skin fibroblasts eluted with a molecular mass of 6 kDa. A peak of inhibitory activity for Mv1Lu and MDCK cells also eluted at 15-25 kDa. Both IGF-I and IGF-II were purified from fractions that eluted at 6 kDa, although the IGF peptides alone did not account for the total bioactivity recovered. Platelet-derived growth factor (PDGF), identified by radioreceptor assay, eluted at a slightly higher molecular mass than the peak of growth activity for Balb/c 3T3 cells, and an anti-PDGF antibody was without effect on the growth of Balb/c 3T3 cells in response to the whey-derived factors. Further purification of the inhibitory activity for epithelial cells yielded a sequence for transforming growth factor beta (TGF-beta), and all inhibitory activity for Mv1Lu cells was immunoneutralised by an antibody against TGF-beta. In contrast, this antibody decreased the growth of Balb/c 3T3 fibroblasts in the whey-derived extract by only 10%. Finally, a cocktail of recombinant growth factors containing IGF-I, IGF-II, PDGF, TGF-beta and fibroblast growth factor 2 stimulated growth of Balb/c 3T3 cells to a level equivalent to only 51% of that observed in the milk-derived growth factor preparation. We conclude that: (i) cell growth activity recovered from bovine whey is present in acid-labile high molecular weight complexes; (ii) all cell growth inhibitory activity for epithelial cells can be accounted for by TGF-beta; (iii) IGF-I and IGF-II co-elute with the major peak of activity for L6 myoblasts and skin fibroblasts, although the IGF peptides alone do not explain the growth of these cells in the whey-derived extract; and (iv) neither PDGF nor TGF-beta account for the 15-25 kDa peak of Balb/c 3T3 growth activity. These data suggest the presence of additional mitogenic factors in bovine milk.

Transforming growth factor beta in bovine milk: concentration, stability and molecular mass forms.

Transforming growth factor beta (TGF-beta) is one of the predominant growth factors present in milk. The concentration, molecular mass forms and stability of TGF-beta in bovine milk were investigated using a standard bioassay measuring the growth inhibition of a milk lung epithelial cell line. Most of the TGF-beta bioactivity in milk was found to be in a latent form, which was also retained in the whey fraction. After acid activation, the total TGF-beta concentration was 4.3 +/- 0.8 ng and 3.7 +/- 0.7 ng TGF-beta per ml of milk and cheese whey respectively. Cation-exchange chromatography at pH 6.5 was used to concentrate latent whey-derived TGF-beta, which could be activated by transient exposure to extremes of pH, urea or heat. Heparin did not significantly activate milk-derived TGF-beta. Neutral gel filtration of the cationic whey fraction revealed a major peak of latent TGF-beta with a molecular mass of 80 kDa and a smaller peak at 600 kDa. Transient acidification of the cationic whey fraction prior to neutral gel filtration, or gel filtration under acidic conditions, released low molecular mass TGF-beta from both high molecular mass peaks. Whey-derived TGF-beta was purified using a five-step chromatographic procedure. An N-terminal sequence was obtained for TGF-beta 2, which accounted for over 85% of the TGF-beta bioactivity in whey. All TGF-beta activity in whey could be neutralised by a monoclonal antibody directed against TGF-beta 1, -beta 2 and -beta 3. The results suggest that the majority of TGF-beta in bovine milk is present in a small latent complex.

Functional limitations and key indicators of well-being in children with disability.

OBJECTIVES: To compare measures of well-being in children with and without different types and severity of limitations. DESIGN: Nationally representative data for American children aged 5 to 17 years were drawn from the 1994 and 1995 National Health Interview Surveys on Disability (NHIS-D) (N = 41,300) and the Year 2000 Health Supplement to the 1994 NHIS-D (N = 9530). Family resources, safety, health status, and health access were measures of environment. The presence and severity of limitations were measured in the domains of mobility, self-care, communication, and learning. RESULTS: Children with functional limitations were more likely to live in families with limited resources and have greater exposure to secondhand smoke, less access to health care, and lower health status. Children with a limitation were not less likely to have a regular source of medical care, but they more often were delayed or prevented from getting necessary health care due to cost or insurance. CONCLUSIONS: Standard measures of child well-being were appropriate for children with functional limitations and showed their unfavorable situations. Children with functional limitations more often have unfavorable family resources, less healthy home environments, poorer health status, and less health service access than other children, making them more susceptible to developmental difficulties beyond those difficulties associated with the challenges of their specific functional limitations.

Surgical aspects of chronic post-thoracotomy pain.

Chronic post-thoracotomy pain is a continuous dysaesthetic burning and aching in the general area of the incision that persists at least 2 months after thoracotomy. It occurs in approximately 50% of patients after thoracotomy and is usually mild or moderate. However, in 5% the pain is severe and disabling. No one technique of thoracotomy has been shown to reduce the incidence of chronic postthoracotomy pain. The most likely cause is intercostal nerve damage, although the precise mechanism for this is not known. Future work needs to examine surgical technique in detail. Until then, patients need to be adequately warned of this sequela of thoracotomy.

Preliminary findings in the neurophysiological assessment of intercostal nerve injury during thoracotomy.

OBJECTIVE: Previous work has suggested that intercostal nerve injury is a major factor in the aetiology of chronic post-thoracotomy pain. The aim of this study was to establish if there was identifiable intercostal nerve injury during thoracotomy. METHODS: Intercostal nerves were stimulated and motor evoked potentials were recorded from intercostal muscles in 13 patients undergoing thoracotomy. Measurements were taken before and after entering the pleural space, after removal of the rib retractor and after intercostal space closure. RESULTS: Intercostal nerves functioned normally before and after entering the pleural space. After the rib retractor was removed, there was a total conduction block in the nerve immediately above the incision in every patient. In the nerves above this, six had a total block, one a partial block and three had normal conduction. There was a total conduction block in the nerve immediately below the incision in all but one patient. Of the nerves below this, four had a total block, two a partial block and three had normal conduction. In the cases of total conduction block, there was either a discrete block at the level of the distal end of the rib retractor or impairment throughout the whole nerve. Intercostal space closure did not injure any previously uninjured nerve. In a solitary patient where rib retraction was not employed, there was no impairment of the intercostal nerves throughout the operation. CONCLUSIONS: This study demonstrates for the first time that intercostal nerve injury occurs routinely due to rib retraction during thoracotomy. We believe that it may be an important step toward understanding the cause of post-thoracotomy neuralgia.

Pneumonectomy for non-small cell lung cancer: predictors of operative mortality and survival.

OBJECTIVE: The purpose of this study was to identify predictors of operative mortality and survival following pneumonectomy for non-small cell lung cancer (NSCLC). METHODS: All 206 patients having a pneumonectomy for NSCLC between 1991 and 1997 in our unit were prospectively studied. There were 162 males (79%) and 44 females (21%) with a mean age (+/- standard deviation) of 61+/-7.7 years (range 34-81 years). Squamous cell (75%) and adenocarcinoma (17.0%) were the predominant histological types. The possible impact of 29 parameters on operative mortality and survival was tested with univariate and multivariate analysis. The mean follow-up was 2.3+/-1.2 years, ranging between 0 and 6.8 years, and it was complete. RESULTS: Operative mortality was 6.8% (14 deaths). On multiple logistic regression older age (P=0.04) and the development post-operatively of bronchopleural fistula (BPF) (P=0.01) were independent predictors of operative mortality. The overall, Kaplan-Meier, 1-, 3- and 5-year survival (+/- standard error from the mean), inclusive of operative mortality, was 68+/-3.3, 42+/-4.1 and 35+/-4.5%. On Cox proportional hazards regression adenocarcinoma (P=0.006), the development of BPF (P=0.003), older age (P=0.03) and higher pathological stage (P=0.02) were independent adverse predictors of survival. CONCLUSION: Pneumonectomy for NSCLC carries a considerable, but acceptable, operative mortality and provides an important survival benefit. This study suggests that older age and BPF are major determinants of an unfavourable in-hospital outcome; older age, BPF, adenocarcinoma cell type and higher pathological stage significantly reduce the probability of a long-term survival.

Coexisting achalasia and paraoesophageal hiatal hernia.

Disorders of the oesophagus present a diagnostic and therapeutic challenge. The presenting symptoms of dysphagia, reflux, pain and vomiting are almost universal, irrespective of the underlying pathology. A combination of endoscopy, barium studies, pH studies and manometry are often required to determine the exact diagnosis and to plan the most effective treatment. Paraoesophageal hiatal hernia is an uncommon condition, present in 14% of all hiatal hernias, which requires urgent correction to prevent life-threatening complications. It is unusual for other oesophageal disorders to coexist. We present a case where achalasia and a paraoesophageal hiatal hernia probably coexisted.

Milk-derived growth factors as serum supplements for the growth of fibroblast and epithelial cells.

We have investigated the response of several epithelial and fibroblastic cells to a mitogenic extract of bovine milk. Cation exchange chromatography was used to produce a mitogen-rich fraction from an industrial whey source that, although comprising only 0.5% of total whey protein, contained the bulk of the growth factor activity. This fraction was a source of potent growth promoting activity for all mesodermal-derived cells tested, including human skin and embryonic lung fibroblasts, Balb/c 3T3 fibroblasts, and rat L6 myoblasts. Maximal growth of all these cell types exceeded that observed in 10% fetal bovine serum. Feline kidney and baby hamster fibroblasts and Chinese hamster ovary cells were less responsive, achieving a maximal growth response of 50-75% that observed in 10% fetal bovine serum. Maximal growth achieved in whey-extract-supplemented cultures of Balb/c 3T3 and human skin fibroblasts, and L6 myoblast cultures exceeded that seen in response to recombinant acidic or basic fibroblast growth factor, platelet-derived growth factor, insulin-like growth factor, or epidermal growth factor. Importantly, addition of low concentrations of fetal bovine serum to the whey-derived mitogenic fraction produced an additive response. However, concentrated milk-derived factors were found to be inhibitory to the growth of all epithelial lines tested, including rat intestinal epithelial cells, canine kidney epithelial cells, and mink lung cells. It is concluded that industrial whey extracted in this form constitutes an important source of potent growth-promoting agents for the supplementation of mesodermal-derived cell cultures.

Airway fire during tracheostomy: prevention strategies for surgeons and anaesthetists.

Airway fires are an uncommon but real and devastating complication of tracheostomy. One such fire in a 31-year-old man is described. Surgical fires are discussed, and 15 reported cases of tracheostomy fire are reviewed. A tracheostomy protocol, adopted by our department and designed to avoid this life-threatening complication, is described. Surgeons and anaesthetists involved in tracheostomy must understand the fire hazard and how to avoid it.

Surgical treatment of para-oesophageal hiatal hernia.

The development of laparoscopic antireflux surgery has stimulated interest in laparoscopic para-oesophageal hiatal hernia repair. This review of our practice over 10 years using a standard transthoracic technique was undertaken to establish the safety and effectiveness of the open technique to allow comparison. Sixty patients with para-oesophageal hiatal hernia were operated on between 1989 and 1999. There were 38 women and 22 men with a median age of 69.5 years. There were 47 elective and 13 emergency presentations. Operation consisted of a left thoracotomy, hernia reduction and crural repair. An antireflux procedure was added in selected patients. There were no deaths among the elective cases and one among the emergency cases. Median follow-up time was 19 months. There was one recurrence (1.5%). Seven patients (12%) required a single oesophagoscopy and dilatation up to 2 years postoperatively but have been asymptomatic since. Two patients (3%) developed symptomatic reflux which has been well controlled on proton-pump inhibitors. Transthoracic para-oesophageal hernia repair can be safely performed with minimal recurrence.

A retrospective study: osteoporosis and hormone replacement therapy.

The purpose of this study was to determine if women who undergo hormone replacement therapy postmenopausally, will demonstrate less osteoporosis than women who do not undergo HRT. The osteoporosis subjects were 195 women who volunteered to participate in an NIH-sponsored double-blind clinical trial entitled Safety and Efficacy of Fluoride Therapy in Osteoporosis. A convenience sample of 78 controls was obtained by inviting women seeking regular medical attention to join an epidemiological investigation of osteoporosis. The data were analyzed using Chi-square and Student's t-ratio. The study concludes that future retrospective and prospective analyses appreciate the complexity of the problem in terms of individual risk for osteoporosis.

Selective transfection of microglia in the brain using an antibody-based non-viral vector.

There are currently few approaches to transiently manipulate the expression of specific proteins in microglia of the brain. An antibody directed against an extracellular epitope of scavenger receptor class B, type I (SR-BI) was found to be selectively taken up by these cells in the brain. Other antibodies tested were not internalised by microglia. A vector was produced by linking the SR-BI antibody to polyethyleneimine and binding a DNA plasmid encoding green fluorescent protein. Infusions of this vector into the hippocampus produced a widespread transfection of cells, more than 80% of which were immunoreactive for microglial/macrophage markers. Transfection was not detected in cells expressing markers for astrocytes or neurons. Reporter gene expression was most prominent near the infusion site but was seen in tissue up to 4mm away. DNA bound to polyethyleneimine alone or to a vector containing a different antibody did not produce transfection in the brain. Single injections of the vector containing the SR-BI antibody into the brain also resulted in transfection of microglia, albeit with lower efficiency. Vector modifications to promote lysis of endosomes or entry of DNA into the nucleus did not increase efficiency. The findings clearly demonstrate the capacity of the SR-BI antibody to selectively target brain microglia. This approach offers considerable potential to deliver DNA and other molecules capable of modifying the function of these cells in vivo.