To examine the role of AMP-activated protein kinase (AMPK) in muscle glucose transport, we generated muscle-specific transgenic mice (TG) carrying cDNAs of inactive ␣2 (␣2i TG) and ␣1 (␣1i TG) catalytic subunits. Extensor digitorum longus (EDL) muscles from wild type and TG mice were isolated and subjected to a series of in vitro incubation experiments. In ␣2i TG mice basal ␣2 activity was barely detectable, whereas basal ␣1 activity was only partially reduced. Known AMPK stimuli including 5-aminoimidazole-4-carboxamide-1-␤-4-ribofuranoside (AICAR), rotenone (a Complex I inhibitor), dinitrophenol (a mitochondrial uncoupler), muscle contraction, and sorbitol (producing hyperosmolar shock) did not increase AMPK ␣2 activity in ␣2i TG mice, whereas ␣1 activation was attenuated by only 30 -50%. Glucose transport was measured in vitro using isolated EDL muscles from ␣2i TG mice. AICAR-and rotenone-stimulated glucose transport was fully inhibited in ␣2i TG mice; however, the lack of AMPK ␣2 activity had no effect on contraction-or sorbitol-induced glucose transport. Similar to these observations in vitro, contraction-stimulated glucose transport, assessed in vivo by 2-deoxy-D-[ 3 H]glucose incorporation into EDL, tibialis anterior, and gastrocnemius muscles, was normal in ␣2i TG mice. Thus, AMPK ␣2 activation is essential for some, but not all, insulin-independent glucose transport. Muscle contraction-and hyperosmolarity-induced glucose transport may be regulated by a redundant mechanism in which AMPK ␣2 is one of multiple signaling pathways.Recent reports suggest that AMP-activated protein kinase (AMPK), 2 a member of a metabolite-sensing protein kinase family, controls blood glucose homeostasis by regulating glucose transport in skeletal muscle and glucose production in the liver (1, 2). In skeletal muscle activation of AMPK by pharmacological stimulation and transient expression of an AMPK-active mutant increases glucose transport (3-6). AMPK also seems to play a role in enhancing muscle (7) and whole body (8) insulin sensitivity and responsiveness for glucose transport. Because skeletal muscle accounts for ϳ80% of disposal of an oral glucose load (9, 10) and because type 2 diabetes is associated with reduced muscle glucose disposal (11), AMPK may be critical in the control of metabolic homeostasis and perhaps the development of type 2 diabetes (12, 13). Not surprisingly, AMPK is now considered a drug target for the treatment of type 2 diabetes (14).AMPK is a serine/threonine kinase consisting of a catalytic ␣ subunit and regulatory ␤ and ␥ subunits (15-17). Different isoforms have been reported for each subunit (␣1 and ␣2, ␤1 and ␤2, ␥1, ␥2, and ␥3) with tissue-specific distribution. In skeletal muscle, ␣2 (18, 19), ␤2 (20, 21), and ␥1 (18) or ␥3 (22) are the major isoforms expressed and form the majority of AMPK heterotrimer complexes. AMPK is activated in response to decreases in intracellular ATP and concomitant increases in AMP, increasing the AMP:ATP ratio (15-17).It has long been believed that there are two m...

Hepatitis C associated hypolipidemia has been demonstrated in studies from Europe and Africa. In 2 linked studies we evaluated the relationship between hepatitis C infection and treatment with lipid levels in an American cohort and determined the frequency of clinically significant post-treatment hyperlipidemia. A case-control analysis of patients with and without hepatitis C was performed. The Hepatitis C Group consisted of 179 infected patients. The Uninfected Control Group consisted of 180 age matched controls. Fasting cholesterol, low density lipoprotein (LDL), high density lipoprotein and triglycerides were compared. The second group was a retrospective cohort (Treated Hepatitis C Group) of 87 treated Hepatitis C patients with lipid data before and after therapy. In the case-control analysis, the Hepatitis C Group had significantly lower LDL and cholesterol than the Uninfected Control Group. In the retrospective cohort, patients in the Treated Hepatitis C Group who achieved viral clearance had increased LDL and cholesterol from baseline compared to patients without viral clearance. These results persisted when adjusted for age, sex and genotype. 13% of patients with viral clearance had increased LDL and 33% experienced increases in cholesterol to levels warranting lipid lowering therapy. Conclusion Hepatitis C is associated with decreased cholesterol and LDL levels. This hypolipidemia resolves with successful hepatitis C treatment but persists in non-responders. A significant portion of successfully treated patients experience LDL and cholesterol rebound to levels associated with increased coronary disease risk. Lipids should be carefully monitored in persons receiving antiviral therapy.

As shown by the current COVID-19 pandemic, emergency departments (ED) are the front line for hospital-andcommunity-based care during viral respiratory disease outbreaks. As such, EDs must be able to reorganize and reformat operations to meet the changing needs and staggering patient volume. This paper addresses ways to adapt departmental operations to better manage in times of elevated disease burden, specifically identifying areas of intervention to help limit crowding and spread. Using experience from past outbreaks and the current COVID-19 pandemic, we advise strategies to increase surge capacity and limit patient inflow. Triage should identify and geographically cohort symptomatic patients within a designated unit to limit exposure early in an outbreak. Screening and PPE guidelines for both patient and staff should be followed closely, as determined by hospital administration and the CDC. Equipment needs are also greatly affected in an outbreak; we emphasis portable radiographic equipment to limit transport, and an upstocking of certain medications, respiratory supplies, and PPE.

The heavy burden of disease attributable to rotavirus in Latin America suggests that vaccines currently being tested could have considerable impact in preventing hospitalizations, clinic visits, and deaths. The findings of the young age distribution of patients highlight the importance of early immunization for the success of a vaccine program. The data suggest that future surveillance for rotavirus diarrhea in Latin America should use a standardized surveillance protocol with an ELISA for detection. Data from surveillance studies will be critical to monitor the impact of the future introduction of vaccines.

Two recently commercialized enzyme-linked immunosorbent assay kits, the SRSV(II)-AD (Denka Seiken Co. Ltd., Tokyo, Japan) and IDEIA NLV (DakoCytomation Ltd., Ely, United Kingdom) kits, that detect human norovirus (HuNV) antigens in stool samples were evaluated to assess whether they could be used instead of reverse transcription-PCR (RT-PCR) for routine diagnosis. The sensitivities and specificities of the two kits were tested with a panel of 103 stool samples containing HuNVs of 4 and 10 genetic subgroups within genogroups I and II (GI and GII), respectively, and 39 stool samples containing other enteric viruses. The Denka kit had a high sensitivity (>70% for 10 of the 14 subgroups) but a specificity of only 69%, and the Dako kit had a low sensitivity (<30% for 6 GII subgroups) but a high specificity of 100%. Statistical analysis suggests that HuNVs of four subgroups (subgroups GII/2, GII/5, GII/6, and GII/n) are likely to elude detection by the Dako kit. The two kits also demonstrated differences in reactivities. While the Dako kit discriminated between the GI and GII antigens of HuNVs, the Denka kit cross-reacted with samples containing all GI and GII subgroups of HuNVs. Moreover, the Denka kit also reacted with samples containing human sapovirus (HuSV). We demonstrate that the cross-reactivity of the Denka kit is not due to specific reactions with HuNV and HuSV antigens. These results indicate that neither the Denka kit nor the Dako kit has all the performance characteristics required to replace the RT-PCR methods used to detect HuNVs.

Efforts to monitoring and managing hospital capacity depend on the ability to extract relevant time-stamped data from electronic medical records and other information technologies. However, the various characterizations of patient flow, cohort decisions, sub-processes, and the diverse stakeholders requiring data visibility create further overlying complexity. We use the Donabedian model to prioritize patient flow metrics and build an electronic dashboard for enabling communication. Ten metrics were identified as key indicators including outcome (length of stay, 30-day readmission, operating room exit delays, capacity-related diversions), process (timely inpatient unit discharge, emergency department disposition), and structural metrics (occupancy, discharge volume, boarding, bed assignation duration). Dashboard users provided real-life examples of how the tool is assisting capacity improvement efforts, and user traffic data revealed an uptrend in dashboard utilization from May to October 2017 (26 to 148 views per month, respectively). Our main contributions are twofold. The former being the results and methods for selecting key performance indicators for a unit, department, and across the entire hospital (i.e., separating signal from noise). The latter being an electronic dashboard deployed and used at The Johns Hopkins Hospital to visualize these ten metrics and communicate systematically to hospital stakeholders. Integration of diverse information technology may create further opportunities for improved hospital capacity.

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