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.     

Restoration of myoelectrical propagation across a jejunal transection using microsurgical anastomosis

The aim of this study was to determine whether microsurgical anastomosis can restore propagation of jejunal pacesetter potentials (PPs) across a site of canine jejunal transection and preserve motility and transit in bowel distal to the transection. A complete jejunal transection with exact microsurgical anastomosis was performed in five dogs, while five dogs with intact jejunum and five dogs with complete transection and end-to-end conventional macrosurgical anastomosis were used as controls. Long-term recording electrodes and intraluminal, open-tipped pressure catheters were implanted in all dogs. The mean frequency of PPs decreased distal to the transection in both groups of transected dogs. However, aborad propagation of PPs across the anastomosis occurred episodically by 3 months in each dog that had a microsurgical anastomosis, but never occurred in any dog with a conventional macroanastomosis. Moreover, the motility and transit in bowel distal to the transection were unaltered in the dogs with a microsurgical anastomosis, whereas they decreased in the dogs with a macroanastomosis. The conclusion was that microsurgical anastomosis of transected canine jejunum restored episodic propagation of PPs across the anastomosis, and preserved motility and maintained transit in bowel distal to the anastomosis. The conventional macroanastomosis did none of these. Supported by the Mayo Foundation and the Nigrn Grant. Presented in part at the Thirty-Seventh Annual Meeting of The Society for Surgery of the Alimentary Tract, May 19–22, 1996, San Francisco, Calif.     

Comparative analysis of three genetic modifications designed to inhibit human serum‐mediated cytolysis

Hyperacute rejection (HAR) remains a critical immunologic hurdle in the development of xenogeneic organs for human transplantation. Strategies that simultaneously eliminate both natural antibody reactivity and complement activation on the xenogeneic cell surface may be the best approach to achieve clinical application of xenogeneic vascularized organ transplantation. We have developed multiple lines of genetically manipulated mice to evaluate the combination of different genetic approaches aimed at inhibiting antibody and complement-mediated cell lysis. We utilized transgenic mice expressing the human complement inhibitor, CD59, the human 1,2-fucosyltransferase (H-transferase, HT) and the α1,3-galactosyltransferase (α1,3-GT) knock-out mouse line (Gal KO). Our data show that expression of hCD59 in combination with HT expression or the null phenotype of α1,3-GT are equally effective at preventing human serum-mediated cytolysis. Interestingly, the triple combination affords no additional protective effect. Therefore, coexpression of HT and a complement inhibitor is the most immediate strategy to genetically engineer transgenic pigs to be used as xenogeneic donors.     

Outcomes and poor prognostic factors in endovascular thrombectomy for octo- and nonagenarians with large vessel occlusion: A real-world experience

Endovascular thrombectomy (EVT) is the preferred treatment for eligible patients with acute large vessel occlusions (LVOs). However, its role in very elderly patients remains uncertain. This study retrospectively analysed EVT outcomes, including successful reperfusion, change in National Institutes of Health Stroke Scale (NIHSS) score at 24 h after EVT, inpatient haemorrhagic transformation and favourable functional outcomes and mortality at 90 days after EVT in patients aged over 80 years. The primary outcome of the study was risk factors significantly associated with poorer functional outcomes at 90 days after EVT. The secondary outcomes were risk factors associated with higher NIHSS scores at 24 h after EVT and higher mortality rates at 90 days after EVT. Among the 73 octo- and nonagenarians, successful reperfusion was achieved in 86.3%, and up to 35.6% maintained functional independence at 90 days. Poorer outcomes were associated with internal carotid artery occlusion; risk factors such as hypertension, diabetes mellitus and atrial fibrillation; higher admission NIHSS score; longer time between symptom onset and successful reperfusion and unsuccessful reperfusion. EVT is both safe and effective in our elderly population, with over one-third of very elderly patients achieving satisfactory functional outcomes after EVT. Therefore, age alone should not be the sole criterion for excluding very elderly LVO patients from EVT. Instead, each patient should undergo individual assessment based on their premorbid condition, clinical presentation and LVO characteristics before making a treatment decision.     

Cerebral cortical oxygenation: a pilot study

BACKGROUND: Cerebral hypoxia (cerebral cortical oxygenation [Pbro2] < 20 mm Hg) monitored by direct measurement has been shown in animal and small clinical studies to be associated with poor outcome. We present our preliminary results observing Pbro2 in patients with traumatic brain injury (TBI). METHODS: A prospective observational cohort study was performed. Institutional review board approval was obtained. All patients with TBI who required measurement of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and Pbro2 because of a Glasgow Coma Scale score < 8 were enrolled. Data sets (ICP, CPP, Pbro2, positive end-expiratory pressure (PEEP), Pao2, and Paco2) were recorded during routine manipulation. Episodes of cerebral hypoxia were compared with episodes without. Results are displayed as mean +/- SEM; t test, chi2, and Fisher's exact test were used to answer questions of interest. RESULTS: One hundred eighty-one data sets were abstracted from 20 patients. Thirty-five episodes of regional cerebral hypoxia were identified in 14 patients. Compared with episodes of acceptable cerebral oxygenation, episodes of cerebral hypoxia were noted to be associated with a significantly lower mean Pao2 (144 +/- 14 vs. 165 +/- 8; p < 0.01) and higher mean PEEP (8.8 +/- 0.7 vs. 7.1 +/- 0.3; p < 0.01). Mean ICP and CPP measurements were similar between groups. In a univariate analysis, cerebral hypoxic episodes were associated with Pao2 < or = 100 mm Hg (p < 0.01) and PEEP > 5 cm H2O (p < 0.01), but not ICP > 20 mm Hg, CPP < or = 65 mm Hg, or Pac2 < or = 35 mm Hg. CONCLUSION: Cerebral oxymetry is confirmed safe in the patient with multiple injuries with TBI. Occult cerebral hypoxia is present in the traumatic brain injured patient despite normal traditional measurements of cerebral perfusion. Further research is necessary to determine whether management protocols aimed at the prevention of cerebral cortical hypoxia will affect outcome.