RESEARCH DESIGN AND METHODS -Eight healthy male volunteers were studied on 2 occasions in random order using a hyperinsulinemic (1.5 mU и kg Ϫ1 и min Ϫ1 ) glucose clamp technique. During control studies, euglycemia (5.01 ± 0.02 mmol/l) was maintained for 225 ± 3 min. On the other occasion, after a euglycemic baseline period, arterialized plasma glucose was allowed to fall rapidly to 2.65 ± 0.02 mmol/l, then maintained at this nadir for 90 min before euglycemia was rapidly restored.RESULTS -Cognitive function assessed by a battery of sensitive tests (4-choice reaction time, Stroop word, and color-word test) became impaired immediately at onset of hypoglycemia (P Ͻ 0.05 for all in the hypoglycemic study vs. those in the euglycemic study). Counterregulatory hormone responses (epinephrine, norepinephrine, glucagon, cortisol, and growth hormone) and symptomatic awareness of hypoglycemia (assessed by a questionnaire) were relatively delayed, being detected 20 min after the onset of hypoglycemia. There was no diminution (adaptation) of any responses, cognitive, humoral, or symptomatic, during sustained hypoglycemia. During recovery, the 4-choice reaction time continued to be abnormal even after resolution of symptomatic awareness (P = 0.025).CONCLUSIONS -During hypoglycemia, cognitive performance may become impaired before symptomatic awareness. During recovery from hypoglycemia, recovery of cognitive function lags behind the restoration of glucose levels and resolution of symptoms. Our findings have implications for the design of studies examining experimental hypoglycemia and need to be investigated in people with diabetes.

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Acute exercise may be an important intervention strategy to reduce the impact of cardiovascular hyper-reactivity on disease progression in males with familial risk of hypertension.

Background Molecular markers for antimalarial drug resistance can be used to rapidly monitor the emergence and spatial distribution of resistance to artemisinin-based combination therapies (ACTs). Little has been done to analyse molecular surveillance efforts or to assess surveillance coverage. This study aimed to develop an evidence map to characterise the spatial-temporal distribution and sampling methodologies of drug resistance surveillance in sub-Saharan Africa, specifically focusing on markers associated with ACT partner drugs.Methods By use of a systematic search, we identified studies that reported data on the following mutations associated with ACT partner drug resistance: pfmdr1 Asn86Tyr, Tyr184Phe, Asp1246Tyr, and copy number variation and pfcrt Lys76Thr, with sample collection occurring in sub-Saharan Africa between Jan 1, 2004, and Dec 31, 2018, corresponding to the uptake of ACTs. For each identified study, we extracted information on its sampling and laboratory methods, author and publication affiliations, years of sampling and of publication, geographic coordinates of the study sites, and prevalence of the partner drug resistance-associated markers. We used linear models to test whether urbanicity, population density, and endemicity were predictors of drug resistance survey sites and linear regressions to identify associations between the number of resistance surveys within a given country and the at-risk malaria population in 2010, the per-capita GDP in 2010, and the mean amount of funding directed to malaria and to determine trends in marker prevalence over time. For country case studies with three or more datapoints, we assessed global spatial autocorrelation using Moran's I. Findings Our search yielded 254 studies encompassing 492 year-specific and location-specific surveys from 35 malariaendemic countries, the most complete set of molecular partner drug surveillance data to date. We observed a median time lag of 3•1 years (95% CI 1•0-7•7) from final sample acquisition to publication. 22 (49%) of the 44 countries in the study region conducted, on average, one or fewer studies every 3 years. The locations of surveillance sites were positively associated with urbanicity (p<0•0001), and the abundance of country-level data was associated with reported donor funding in 2004-18 (p=0•0011) and local government funding in 2004-09 (p=0•014). Nearly all molecular markers displayed significant regional trends over time and global spatial autocorrelation in space. For selected countries with more widespread coverage of surveillance data, some markers also displayed spatial heterogeneity.Interpretation In most sub-Saharan countries, molecular data on antimalarial resistance might not be representative of the temporal and geographic heterogeneity of partner drug resistance, and likely do not represent the true spatially dependent distribution of partner drug resistance. Our results highlight several inefficiencies that can be improved upon to develop more accurate data landscapes, including the expansion of...

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Articular cartilage and bony contact at the distal tibiofibular cartilage contact zone (TFCCZ) is variable. The appropriate placement of syndesmotic hardware would benefit from a more accurate characterization of the proximal extent of the TFCCZ allowing surgeons to place hardware that simultaneously improves biomechanical stability and decreases the risk of iatrogenic cartilage damage. In addition, Ilizarov wire fixation through the distal fibula and tibia can pass through the syndesmosis recess. Anatomically defining the proximal extent of this recess can help decrease the risk of inadvertent capsular penetration. This study anatomically defines the TFCCZ and syndesmosis recess establishing a safe and biomechanically advantageous distance from the plafond for orthopedic fixation. This study measured the height of the TFCCZ and the syndesmotic recess in 3158 anatomical and cadaveric specimens. A TFCCZ was present in 59% of the Robert J. Terry Anatomical Collection specimens. Maximal height of the TFCCZ averaged 5.7±1.7 mm (99% confidence interval [CI], 5.6-5.8 mm) for anatomical specimens and 5.6±1.6 mm (99% CI, 4.6-6.5 mm) for cadaveric dissections. The maximum TFCCZ height was 11.71 mm. Maximal height of the syndesmotic recess averaged 12.8±2.1 mm for anatomical specimens and 13.7±2.7 mm for cadaveric specimens. The "3 cm rule" appears to be appropriate for fine wire fixation accounting for capsular distension that can be associated with injuries but not applicable for syndesmotic fixation. There is a less than 0.1% chance of encountering the TFCCZ cartilage at 10.9 mm above the plafond and a less than 0.01% chance at 12 mm above the plafond. [Orthopedics. 2017; 40(2):e329-e333.].

Maintenance of airway stability is an essential part of critical care management of patients undergoing endovascular treatment for acute stroke. While some patients may undergo endovascular treatment utilizing conscious sedation alone, many patients require deeper sedation and emergent mechanical ventilation due to need to control patient movement, stabilize the airway, and facilitate patient comfort during prolonged procedures (average duration 1.9 hrs). Nine patients undergoing emergent intubation prior to endovascular treatment for acute stroke underwent observational study. Following completion of IRB-approved consent for study participation, patients received arterial line placement and vital signs were collected before, during, and after intubation and throughout endovascular treatment. Intubation was performed by experienced ED physicians using a variety of medications. An immediate and dramatic rise in mean arterial pressure (MAP) was associated with intubation (increased by 172% over baseline) followed by a decrease in the MAP (12% below baseline) in the ED prior to patient transfer to angiography. No consist trend was noted in PaCO2 levels drawn immediately after intubation but prior to initiation of mechanical ventilation. Average MAP in the angiogram suite during endovascular therapy was almost identical to pre-intubation baseline MAP (101% of baseline) despite utilization by interventionalists of a number of sedative medications. Transient decreases in the MAP to a nadir of 75 - 80 were seen during endovascular therapy in 3 patients; more significant drops did not occur. Mean duration of intubation, ICU stay, and total hospitalization was 3 days, 8 days, and 12 days respectively. In conclusion, real-world emergent intubation by ED physicians of acute stroke patients just prior to endovascular treatment is associated with significant fluctuations in MAP. Such fluctuations in either direction may further jeopardize tissue at risk. Recent reports from the national MERCI Registry Database indicate worse outcomes in intubated patients for unclear reasons; this could be due to fluctuations in MAP but might also be due to the effect of anesthesia itself. Assuming that these hemodynamic changes are causal in reducing clinical outcomes, ED intubation and angiographic sedation protocols should be designed to minimize fluctuations in MAP. Further investigations documenting improved MAP control utilizing standardized protocols are needed.

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