Age-dependent alteration in muscle regeneration: the critical role of tissue niche

Although adult skeletal muscle is composed of fully differentiated fibers, it retains the capacity to regenerate in response to injury and to modify its contractile and metabolic properties in response to changing demands. The major role in the growth, remodeling and regeneration is played by satellite cells, a quiescent population of myogenic precursor cells that reside between the basal lamina and plasmalemma and that are rapidly activated in response to appropriate stimuli. However, in pathologic conditions or during aging, the complete regenerative program can be precluded by fibrotic tissue formation and resulting in functional impairment of the skeletal muscle. Our study, along with other studies, demonstrated that although the regenerative program can also be impaired by the limited proliferative capacity of satellite cells, this limit is not reached during normal aging, and it is more likely that the restricted muscle repair program in aging is presumably due to missing signals that usually render the damaged muscle a permissive environment for regenerative activity.     

Academic Progression and Retention Policies of Colleges and Schools of Pharmacy

Objective. To describe academic progression and retention policies used by US colleges and schools of pharmacy.Methods. Student handbooks on the Web sites of 122 colleges and schools of pharmacy were reviewed between February 2012 and May 2012.Results. Data were available and obtained from 98 (80%) programs. Most used grade point average (GPA) as a criterion for progression, with 66% requiring a minimum GPA of 2.0. Cumulative GPA was the most frequently used criteria for probation. Most handbooks did not address remediation, but 38% noted that a failed course could only be retaken once. The most common criteria for dismissal were the cumulative number of times a student was on probation. The graduation requirements of most programs were a cumulative GPA of 2.0 and completion of the program within 6 years of enrollment. Conclusions. Colleges and schools of pharmacy use various criteria for academic progression and retention and frequently provide incomplete or inadequate information related to probation, progression, and dismissal. Information regarding remediation and academic performance during experiential learning is lacking. A clearinghouse containing institutional data related to progression and retention would assist programs in developing academic policies. The study also highlights the need for ACPE to ensure this information is provided to students.     

Psychosocial Correlates of Alexithymia in a Rural Adolescent Residential Population

This study used a multimethod approach to evaluate the relationship of alexithymia (as measured by the 20-item Toronto Alexithymia Scale and the 30-item Emotion Awareness Questionnaire), psychosocial development (assessed with the Measure of Psychosocial Development), and risk behavior (as measured by the Youth Comprehensive Risk Assessment) in 67 adolescents (85% from rural communities) in a rural residential treatment facility. Results revealed that both measures of alexithymia demonstrated good internal consistency and convergent validity. The EAQ-30 demonstrated stronger convergent validity over the TAS-20 with psychosocial measures of shame, inferiority, and role confusion and was more robust in differentiating risk behavior among males and females. Adolescent females scored higher on measures of alexithymia than males and demonstrated significantly more shame, diminished bodily awareness, and risk to self; whereas, males demonstrated significantly more risk to others. Overall, this study contributes to the current literature of alexithymia, provides further support for the validity of the alexithymia construct with adolescents, and sheds light on the importance of emotional awareness and expression in adolescent psychosocial development. Although exploratory, this study also increases clinical understanding of how risk behavior develops and manifests differently in male and female adolescents, specifically with regard to shame and diminished bodily awareness.     

Pro/con debate: Should PaCO2 be tightly controlled in all patients with acute brain injuries?

You are the attending intensivist in a neurointensive care unit caring for a woman five days post-rupture of a cerebral aneurysm (World Federation of Neurological Surgeons Grade 4 and Fisher Grade 3). She is intubated for airway protection and mild hypoxemia related to an aspiration event at the time of aneurysm rupture, but is breathing spontaneously on the ventilator. Your patient is spontaneously hyperventilating with high tidal volumes despite minimal support and has developed significant hypocapnia. She has not yet developed the acute respiratory distress syndrome. You debate whether to tightly control her partial pressure of arterial carbon dioxide, weighing the known risks of acute hypocapnia in other forms of brain injury against the potential loss of clinical neuromonitoring associated with deep sedation and neuromuscular blockade in this patient who is at high risk of delayed ischemia from vasospasm. You are also aware of the potential implications of tidal volume control if this patient were to develop the acute respiratory distress syndrome and the effect of permissive hypercapnia on her intracranial pressure. In this paper we provide a detailed and balanced examination of the issues pertaining to this clinical scenario, including suggestions for clinical management of ventilation, sedation and neuromonitoring. Until more definitive clinical trial evidence is available to guide practice, clinicians are forced to carefully weigh the potential benefits of tight carbon dioxide control against the potential risks in each individual patient based on the clinical issues at hand.     

Rescue missions for totally buried avalanche victims: conclusions from 12 years of experience

Abstract Hohlreider, Matthias, Stephanie Thaler, Walter Wuertl, Wolfgang Voelckel, Hanno Ulmer, Hermann Brugger, and Peter Mair. Rescue missions for totally buried avalanche victims: conclusions from 12 years of experience. High Alt. Med. Biol. 9:229-234, 2008.-The planning and execution of avalanche rescue missions to search for totally buried avalanche victims are mostly based on personal experience and preference, as evidence-based information from literature is almost completely missing. Hence, the aim of this study was to identify major factors determining the survival probability of totally buried victims during avalanche rescue missions carried out by organized rescue teams (Austrian Mountain Rescue Service, Tyrol). During the 12-year period studied, 109 totally buried persons (56 off-piste, 53 backcountry), were rescued or recovered; 18.3% survived to hospital discharge. Median depth of burial was 1.25 m; median duration of burial was 85 min. The majority (61.6%) of the rescue missions were conducted under considerably dangerous avalanche conditions. The probability of survival was highest when located visually and lowest for those located by avalanche transceiver; survival did not significantly differ between those found by rescue dogs and those located with avalanche probes. Multivariate analysis revealed short duration of burial and off-piste terrain to be the two independent predictors of survival. Whenever companion rescue fails, snow burial in an avalanche is associated with extraordinarily high mortality. Searching the avalanche debris with probe lines seems to be equally effective as compared to searching with rescue dogs. The potential hazard for rescuers during avalanche rescue missions comes mainly from self-triggered avalanches, hence thorough mission planning and critical risk-benefit assessment are of utmost importance for risk reduction.     

Melatonin and prostate cancer cell proliferation: interplay with castration,epidermal growth factor,and androgen sensitivity

BACKGROUND: Potential modulatory effects of melatonin on the proliferation of androgen-sensitive LNCaP and androgen-insensitive PC-3 and DU 145 prostate cancer cells were reported recently. In this study, we investigated the effects of combined melatonin and castration on LNCaP tumor growth in vivo, the interactions between melatonin and epidermal growth factor (EGF) on LNCaP cell proliferation, and melatonin actions on the proliferation of PC-3 and DU 145 cells. METHODS: Tumor development and growth in castrated nude mice inoculated with LNCaP cells or in intact animals inoculated with DU 145 cells, with or without daily melatonin treatment, were monitored by observation and caliper measurement. MT(1) receptor expression in native or transfected prostate cancer cell lines was examined by immunocytochemistry or 2-[(125)I]iodomelatonin binding. Cyclin D1 expression in LNCaP cells was assessed by Western blotting, and cell proliferation was measured by thymidine incorporation and/or cell count. RESULTS: Melatonin treatment was associated with further decreases in LNCaP tumor incidence and growth rate in castrated nude mice. Melatonin and 2-iodomelatonin (a melatonin receptor agonist) attenuated EGF-stimulated increases in LNCaP cell proliferation and cyclin D1 levels. Melatonin had no effect on the proliferation or growth of MT(1) receptor-expressing DU 145 cells, and of PC-3 cells in which MT(1) receptor protein was undetectable. The proliferation of transfected PC-3 cells expressing MT(1) receptor was unaffected by 2-iodomelatonin. CONCLUSION: Together with previous data, the present results indicate synergistic action of melatonin and castration in inhibiting the growth of androgen-sensitive LNCaP tumor. Androgen-sensitive prostate cancer cell proliferation may be modulated by opposite changes in cyclin D1 levels induced by activated MT(1) and EGF receptors. In androgen-insensitive prostate cancer cells, MT(1) receptor-mediated signal transduction may become defective not only through changes in membrane receptor protein expression and/or functions, but also by means of alterations in downstream postreceptor signaling events.     

First metatarsophalangeal arthrodesis: a clinical,pedobarographic and gait analysis study

This study investigated the results of first metatarsophalangeal (MTP) arthrodesis in terms of clinical outcome measures, plantar pressure distribution, and gait patterns. Ten feet in nine patients with severe hallux rigidus (HR) who underwent first MTP arthrodesis were studied. The preoperative evaluation included a subjective questionnaire, physical exam, AOFAS hallux score, radiographs and dynamic pedobarography (EMED). At follow-up (average 34 months) these were repeated, and gait analysis studies were obtained. Patients showed significant clinical improvement based on the subjective criteria. The mean AOFAS score improved from 38 preoperatively to 90 postoperatively. Postoperative EMED analysis showed restoration of the weightbearing function of the first ray, with greater maximum force carried by the distal hallux at toe-off. Kinematic and kinetic gait analysis from each patient's operative limb were compared to the unaffected contralateral limb and to age- and sex-matched healthy subjects. The kinematic data indicated a significantly shorter step length with some loss in ankle plantar flexion at toe-off on the fused side. The kinetic data indicated a reduction in both ankle torque and ankle power at push-off. Clinical results indicated effective pain relief and a high level of patient satisfaction, consistent with previous reports in patients with symptomatic Hallux Rigidus.     

Risk factors leading to midurethral sling revision: a multicenter case-control study

Introduction and hypothesis

To determine risk factors for sling revision after midurethral sling (MUS) placement.

Methods

This multicenter case-control study included patients who underwent MUS placement and subsequent revision secondary to voiding dysfunction from January 1999–2007 from nine Urogynecology centers across the USA. Direct logistic regression analysis was used to determine which diagnostic variables predicted sling revision.

Results

Of the patients, 197 met the study criteria. Patient demographics, urodynamic findings, and operative differences did not increase the risk for sling revision. Risk factors for sling revision did include: pre-existing voiding symptoms (OR 2.76, 95% CI 1.32–5.79; p?=?0.004) retropubic sling type (OR?=?2.28, 95% CI 1.08–4.78; p?=?0.04) and concurrent surgery (OR?=?4.88, 95% CI 2.16–11.05; p?<?0.001)

Conclusions

This study determined that pre-existing obstructive voiding symptoms, retropubic sling type, and concurrent surgery at the time of sling placement are risk factors for sling revision.