This study evaluated the effects of dexamethasone (DXM) on contractile function of reperfused extensor digitalis longus (EDL) muscles following 3-hour ischemia and 24-hour reperfusion. The rats were divided into four groups: normal muscle, ischemia with saline treatment, ischemia/reperfusion with saline treatment, and ischemia/reperfusion with DXM treatment groups. DXM (0.6 mg kg −1 ) or saline (3.0 ml kg −1 ) was administered at 3 hours prior to ischemia. Results showed that although contractile force in all three treated groups was significantly lower than that of normal EDL, the average isometric tetanic contractile force in the DXMtreated group was significantly greater than that in the salinetreated ischemia and ischemia/reperfusion groups. A significant difference was also seen at the peak force and at 5 seconds of the fatigue trains, and with a longer fatigue halftime (FT 1/2 ) in the DXM-treated group than in the other two groups. Histologically, edema, inflammation and necrosis of muscle fiber were less severe in the DXM-treated group than in the saline-treated group. The results indicate that pretreatment with DXM appears to attenuate, but does not completely reverse, the contractile function deficit of ischemic skeletal muscle during the first 24 hours of reperfusion.

ImportanceGreater than 20% of cases and 0.4% of deaths from COVID-19 occur in children. Following demonstration of the safety and efficacy of the adjuvanted, recombinant spike protein vaccine NVX-CoV2373 in adults, the PREVENT-19 trial immediately expanded to adolescents.ObjectiveTo evaluate the safety, immunogenicity, and efficacy of NVX-CoV2373 in adolescents.Design, Setting, and ParticipantsThe NVX-CoV2373 vaccine was evaluated in adolescents aged 12 to 17 years in an expansion of PREVENT-19, a phase 3, randomized, observer-blinded, placebo-controlled multicenter clinical trial in the US. Participants were enrolled from April 26 to June 5, 2021, and the study is ongoing. A blinded crossover was implemented after 2 months of safety follow-up to offer active vaccine to all participants. Key exclusion criteria included known previous laboratory-confirmed SARS-CoV-2 infection or known immunosuppression. Of 2304 participants assessed for eligibility, 57 were excluded and 2247 were randomized.InterventionsParticipants were randomized 2:1 to 2 intramuscular injections of NVX-CoV2373 or placebo, 21 days apart.Main Outcomes and MeasuresSerologic noninferiority of neutralizing antibody responses compared with those in young adults (aged 18-25 years) in PREVENT-19, protective efficacy against laboratory-confirmed COVID-19, and assessment of reactogenicity and safety.ResultsAmong 2232 participants (1487 NVX-CoV2373 and 745 placebo recipients), the mean (SD) age was 13.8 (1.4) years, 1172 (52.5%) were male, 1660 (74.4%) were White individuals, and 359 (16.1%) had had a previous SARS-CoV-2 infection at baseline. After vaccination, the ratio of neutralizing antibody geometric mean titers in adolescents compared with those in young adults was 1.5 (95% CI, 1.3-1.7). Twenty mild COVID-19 cases occurred after a median of 64 (IQR, 57-69) days of follow-up, including 6 among NVX-CoV2373 recipients (incidence, 2.90 [95% CI, 1.31-6.46] cases per 100 person-years) and 14 among placebo recipients (incidence, 14.20 [95% CI, 8.42-23.93] cases per 100 person-years), yielding a vaccine efficacy of 79.5% (95% CI, 46.8%-92.1%). Vaccine efficacy for the Delta variant (the only viral variant identified by sequencing [n = 11]) was 82.0% (95% CI, 32.4%-95.2%). Reactogenicity was largely mild to moderate and transient, with a trend toward greater frequency after the second dose of NVX-CoV2373. Serious adverse events were rare and balanced between treatments. No adverse events led to study discontinuation.Conclusions and RelevanceThe findings of this randomized clinical trial indicate that NVX-CoV2373 is safe, immunogenic, and efficacious in preventing COVID-19, including the predominant Delta variant, in adolescents.Trial RegistrationClinicalTrials.gov Identifier: NCT04611802

It may be safe to proceed with aggressive rehabilitation after thermal microdebridement of the patellar tendon. However, the results in this cadaveric model should be interpreted with caution. Additional studies using an in vivo model will be required to completely assess the effects of thermal microdebridement on the biomechanical properties of human patellar tendons.

It is recommended that platelet-rich plasma for platelet aggregation testing be maintained at room temperature and be used between 2 and 4 hours after platelet donation.

This study evaluated the effects of dexamethasone (DXM) on contractile function of reperfused extensor digitalis longus (EDL) muscles following 3-hour ischemia and 24-hour reperfusion. The rats were divided into four groups: normal muscle, ischemia with saline treatment, ischemia/reperfusion with saline treatment, and ischemia/reperfusion with DXM treatment groups. DXM (0.6 mg kg[-1]) or saline (3.0 ml kg[-1]) was administered at 3 hours prior to ischemia. Results showed that although contractile force in all three treated groups was significantly lower than that of normal EDL, the average isometric tetanic contractile force in the DXM-treated group was significantly greater than that in the saline-treated ischemia and ischemia/reperfusion groups. A significant difference was also seen at the peak force and at 5 seconds of the fatigue trains, and with a longer fatigue half-time (FT1/2) in the DXM-treated group than in the other two groups. Histologically, edema, inflammation and necrosis of muscle fiber were less severe in the DXM-treated group than in the saline-treated group. The results indicate that pretreatment with DXM appears to attenuate, but does not completely reverse, the contractile function deficit of ischemic skeletal muscle during the first 24 hours of reperfusion.

Summary: An acute in vivo preparation of the microvasculature of the rabbit ear was used to evaluate the functional role of alpha, (al)-adrenoceptor subtypes in thermoregulatory microcirculation. The effect of al-adrenoceptor subtype blockade on phenylephrine-induced vasoconstriction was assessed with the alA, alB, and alD-adrenoceptor-selective antagonists 5-methyl-urapidil M ) . chloroethylclonidine (1 0-j M ) , and X-[2-[4(2-methoxyphenyl)-l-piperazinyl]ethyl]-8-azaspirol[4.S]decane-7,9-dione dihydrochloride (BMY7378) (10-6 M ) , respectively. The results demonstrated that pretreatment of the ear microvasculature with 5-methylurapidil or BMY7378 shifted the phenylephrine concentration-response curve rightward and significantly changed the log of the phenylephrine concentration, causing half-maximum stimulation (EC,,) in arterioles (p < 0.05). BMY7378 shifted the phenylephrinc concentration-response curve of the arteriovenous anastomoses about 100-fold rightward (p < 0.05). All three a,-adrenoceptor antagonists eliminated the vasoconstrictive effects of phenylephrine on venules. The results indicate that the ear microvasculature has a heterogenous distribution of ul-adrenoceptor subtypes. The alA and alD-adrenoceptor subtypes appear to have a greater influence on constrictive function in arterioles, whereas the alD-adrenoceptor is the dominant constrictor of arteriovenous anastomoses. In general, the al-adrenoceptor does not play a major vasoconstrictor role in venules. Chloroethylclonidine, an irreversible alB-adrenoceptor antagonist, induced contractile responses in the ear microvasculature, probably due to its a2-adrenoceptor agonist effects. This study extended our understanding of the adrenergic receptor control mechanisms of a cutaneous thermoregulatory end organ characterized by two parallel perfusion circuits providing nutritional and thermoregulatory functions.The microvasculature of the rabbit ear, like that of the human digit, consists of terminal arterioles, capillary loops, postcapillary venules, and arteriovenous anastomoses. The arteriovenous anastomoses allow blood to bypass the capillaries to flow directly into the deep venous plexus and are believed to be involved in thermoregulation (5). Skin blood vessels affect homeostasis of body temperature by dilating in response to heating and constricting in response to cooling. Changes in tonic sympathetic outflow are largely responsible for control of these vessels. The vasoconstrictor responses induced by exogenous norepinephrine, norepinephrine-like compounds, or sympathetic activation are mediated by alpha, (a1) and a,-adrenoceptors. Previous studies in our laboratory demonstrated that the resistance arterioles and arteriovenous anastomoses have different adrenoceptor control mechanisms (9,16): a,-adrenoceptors dominate arteriolar constriction, whereas the arteriovenous anastomoses are dually regulated by a, and a2-adrenoceptors (9,16). These findings provide a possible explanation of how blood flow in the ear is distributed between two parallel ...

An acute in vivo preparation of the microvasculature of the rabbit ear was used to evaluate the functional role of alpha1 (alpha1)-adrenoceptor subtypes in thermoregulatory microcirculation. The effect of alpha1-adrenoceptor subtype blockade on phenylephrine-induced vasoconstriction was assessed with the alpha1A, alpha1B, and alpha1D-adrenoceptor-selective antagonists 5-methyl-urapidil (10(-8) M), chloroethylclonidine (10(-5) M), and 8-[2-[4(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspirol[4.5]deca ne-7,9-dione dihydrochloride (BMY7378) (10(-6) M), respectively. The results demonstrated that pretreatment of the ear microvasculature with 5-methyl-urapidil or BMY7378 shifted the phenylephrine concentration-response curve rightward and significantly changed the log of the phenylephrine concentration, causing half-maximum stimulation (EC50) in arterioles (p < 0.05). BMY7378 shifted the phenylephrine concentration-response curve of the arteriovenous anastomoses about 100-fold rightward (p < 0.05). All three alpha1-adrenoceptor antagonists eliminated the vasoconstrictive effects of phenylephrine on venules. The results indicate that the ear microvasculature has a heterogenous distribution of alpha1-adrenoceptor subtypes. The alpha1A and alpha1D-adrenoceptor subtypes appear to have a greater influence on constrictive function in arterioles, whereas the alpha1D-adrenoceptor is the dominant constrictor of arteriovenous anastomoses. In general, the alpha1-adrenoceptor does not play a major vasoconstrictor role in venules. Chloroethylclonidine, an irreversible alpha1B-adrenoceptor antagonist, induced contractile responses in the ear microvasculature, probably due to its alpha2-adrenoceptor agonist effects. This study extended our understanding of the adrenergic receptor control mechanisms of a cutaneous thermoregulatory end organ characterized by two parallel perfusion circuits providing nutritional and thermoregulatory functions.

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