Care Bundle Approach to Minimizing Infection Rates after Neurosurgical Implants for Neuromodulation: A Single-Surgeon Experience.

INTRODUCTION: Implant-related infections carry a high morbidity. Infectious rates for neuromodulation implants range from 1% to 9% for deep brain stimulation (DBS), 0% to 10% for spinal cord stimulation (SCS) systems, and 3% to 15% for intrathecal (IT) pump systems. Meanwhile, studies of care bundles report infection rate reduction to 1.0% for SCS and 0.3% for cardiac implants. Herein, we evaluate the effectiveness of an infection prevention bundle (IPB) in minimizing infections after surgeries for neuromodulation implants. METHODS: An IPB focused on preoperative checklists, screening questionnaires, methicillin-resistant and methicillin-sensitive Staphylococcus aureus decolonization, weight-based antibiotic prophylaxis, strict draping and surgical techniques, and wound care education was implemented in our functional neurosurgery division in April 2015. We retrospectively reviewed all surgeries for implantation or replacement of SCS, DBS, and IT pump system components from March 2013 to October 2017. The patients were divided into pre-IPB and post-IPB groups. All procedures were performed by a single surgeon. Each surgical site was considered a unique surgical case. Infection rates were calculated for pre-IPB and post-IPB groups. RESULTS: A total of 688 patients underwent 1161 unique surgical procedures (222 DBS electrodes, 419 IPG, 203 SCS, 317 IT pumps) during the study period. There were 546 pre-IPB and 615 post-IPB surgical procedures. The pre-IPB infection rates were 0%, 1.3%, and 8.7% for SCS, DBS, and IT pumps, respectively. The post-IPB infection rates were 0%, 0.3%, and 1.8% for SCS, DBS, and IT pumps, respectively. CONCLUSIONS: Implementation of a standardized IPB approach reduced the number of infections for all neuromodulation implants studied. This approach can be adopted within any specialty to potentially decrease the incidence of implant-related infections.

Treatment of HCV infection by targeting microRNA.

BACKGROUND: The stability and propagation of hepatitis C virus (HCV) is dependent on a functional interaction between the HCV genome and liver-expressed microRNA-122 (miR-122). Miravirsen is a locked nucleic acid-modified DNA phosphorothioate antisense oligonucleotide that sequesters mature miR-122 in a highly stable heteroduplex, thereby inhibiting its function. METHODS: In this phase 2a study at seven international sites, we evaluated the safety and efficacy of miravirsen in 36 patients with chronic HCV genotype 1 infection. The patients were randomly assigned to receive five weekly subcutaneous injections of miravirsen at doses of 3 mg, 5 mg, or 7 mg per kilogram of body weight or placebo over a 29-day period. They were followed until 18 weeks after randomization. RESULTS: Miravirsen resulted in a dose-dependent reduction in HCV RNA levels that endured beyond the end of active therapy. In the miravirsen groups, the mean maximum reduction in HCV RNA level (log10 IU per milliliter) from baseline was 1.2 (P=0.01) for patients receiving 3 mg per kilogram, 2.9 (P=0.003) for those receiving 5 mg per kilogram, and 3.0 (P=0.002) for those receiving 7 mg per kilogram, as compared with a reduction of 0.4 in the placebo group. During 14 weeks of follow-up after treatment, HCV RNA was not detected in one patient in the 5-mg group and in four patients in the 7-mg group. We observed no dose-limiting adverse events and no escape mutations in the miR-122 binding sites of the HCV genome. CONCLUSIONS: The use of miravirsen in patients with chronic HCV genotype 1 infection showed prolonged dose-dependent reductions in HCV RNA levels without evidence of viral resistance. (Funded by Santaris Pharma; ClinicalTrials.gov number, NCT01200420.).

Maintenance of acinar cell organization is critical to preventing Kras-induced acinar-ductal metaplasia.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers owing to a number of characteristics including difficulty in establishing early diagnosis and the absence of effective therapeutic regimens. A large number of genetic alterations have been ascribed to PDAC with mutations in the KRAS2 proto-oncogene thought to be an early event in the progression of disease. Recent lineage-tracing studies have shown that acinar cells expressing mutant Kras(G12D) are induced to transdifferentiate, generating duct-like cells through a process known as acinar-ductal metaplasia (ADM). ADM lesions then convert to precancerous pancreatic intraepithelial neoplasia (PanIN) that progresses to PDAC over time. Thus, understanding the earliest events involved in ADM/PanIN formation would provide much needed information on the molecular pathways that are instrumental in initiating this disease. As studying the transition of acinar cells to metaplastic ductal cells in vivo is complicated by analysis of the entire organ, an in vitro three dimensional (3D) culture system was used to model ADM outside the animal. Kras(G12D)-expressing acinar cells rapidly underwent ADM in 3D culture, forming ductal cysts that silenced acinar genes and activated duct genes, characteristics associated with in vivo ADM/PanIN lesions. Analysis of downstream KRAS signaling events established a critical importance for the Raf/MEK/ERK pathway in ADM induction. In addition, forced expression of the acinar-restricted transcription factor Mist1, which is critical to acinar cell organization, significantly attenuated Kras(G12D)-induced ADM/PanIN formation. These results suggest that maintaining MIST1 activity in Kras(G12D)-expressing acinar cells can partially mitigate the transformation activity of oncogenic KRAS. Future therapeutics that target both the MAPK pathway and Mist1 transcriptional networks may show promising efficacy in combating this deadly disease.

Propofol disrupts functional interactions between sensory and high-order processing of auditory verbal memory.

Current theories suggest that disrupting cortical information integration may account for the mechanism of general anesthesia in suppressing consciousness. Human cognitive operations take place in hierarchically structured neural organizations in the brain. The process of low-order neural representation of sensory stimuli becoming integrated in high-order cortices is also known as cognitive binding. Combining neuroimaging, cognitive neuroscience, and anesthetic manipulation, we examined how cognitive networks involved in auditory verbal memory are maintained in wakefulness, disrupted in propofol-induced deep sedation, and re-established in recovery. Inspired by the notion of cognitive binding, an functional magnetic resonance imaging-guided connectivity analysis was utilized to assess the integrity of functional interactions within and between different levels of the task-defined brain regions. Task-related responses persisted in the primary auditory cortex (PAC), but vanished in the inferior frontal gyrus (IFG) and premotor areas in deep sedation. For connectivity analysis, seed regions representing sensory and high-order processing of the memory task were identified in the PAC and IFG. Propofol disrupted connections from the PAC seed to the frontal regions and thalamus, but not the connections from the IFG seed to a set of widely distributed brain regions in the temporal, frontal, and parietal lobes (with exception of the PAC). These later regions have been implicated in mediating verbal comprehension and memory. These results suggest that propofol disrupts cognition by blocking the projection of sensory information to high-order processing networks and thus preventing information integration. Such findings contribute to our understanding of anesthetic mechanisms as related to information and integration in the brain.

Pigs expressing salivary phytase produce low-phosphorus manure.

To address the problem of manure-based environmental pollution in the pork industry, we have developed the phytase transgenic pig. The saliva of these pigs contains the enzyme phytase, which allows the pigs to digest the phosphorus in phytate, the most abundant source of phosphorus in the pig diet. Without this enzyme, phytate phosphorus passes undigested into manure to become the single most important manure pollutant of pork production. We show here that salivary phytase provides essentially complete digestion of dietary phytate phosphorus, relieves the requirement for inorganic phosphate supplements, and reduces fecal phosphorus output by up to 75%. These pigs offer a unique biological approach to the management of phosphorus nutrition and environmental pollution in the pork industry.

Cold weather injuries in an arctic environment.

The cases of eight Special Forces soldiers who sustained cold weather-related injuries while conducting winter training as part of Operation Arctic Saber in the Northwest Territories and Arctic Circle are reported. Environmentally related injuries can represent difficult diagnostic and treatment challenges in the field. Moreover, they may compromise the overall mission if they are not identified and treated early. Cold weather injuries can also result in long-term disfigurement and disability that may limit a soldier's future worldwide deployability. Mission requirements, equipment utilization, and environmental exposure place soldiers at particular risk for cold weather-related injuries in such austere settings. Nonetheless, with appropriate education and safety precautions, these potentially life-threatening risks can be greatly minimized.

Use of mental and health services by American Indian and Alaska Native elders.

American Indian and Alaska Native elders are an important at-risk population in need of mental health services, yet little is known about the factors that influence Indian/Native elders to actually seek mental health services. This study uses the Anderson and Newman conceptual framework to identify need as well as enabling and predisposing factors for mental health service use in a national sample of reservation and urban American Indian and Alaska Native elders. Results indicate that self-perceived need is the strongest predictor of mental health service use for elders living on reservations. However, for Indian/Native elders in urban areas, degree of mental impairment is most likely to predict use of mental health services. For both groups of elders, enabling variables, such as total income, level of education and access to medical insurance, were the least important in influencing whether or not an elder elected to use mental health services.

Induction of peri-insulitis but not diabetes in islet transplants expressing a single foreign antigen. A multi-stage model of disease.

We have created a new transgenic model in which the human Epstein-Barr virus receptor, CR2 (CD21), has been expressed in pancreatic beta-cells. Mice derived from three transgenic founders bred into H-2b (C57BL/6) or H-2k (CBA) genetic backgrounds did not become spontaneously diabetic. After transplantation of CR2-expressing islets under the kidney capsule of genetically matched recipients, a histologic picture of peri-insulitis was found. However, animals did not manifest cellular invasion of the islets, destruction of the islets, or diabetes for at least 230 days. Significant numbers of both T and B lymphocytes were found in the cell population surrounding the islets. A pronounced serologic response to CR2 was also present and appeared to precede the onset of peri-insulitis. Thus, in this model, we have separated the process of diabetes induction into at least two phases. One is associated with peri-islet infiltration and an antibody response. However, at least one second signal is likely necessary for the process of islet destruction to follow.

Reasonable efforts for children with disabilities: the parents' perspective.

This article reports the results of a content analysis of focus group interviews of parents of children with developmental disabilities, emotional disorders, and technology-supported needs. Perspectives regarding special needs, crisis situations, and parent-professional relationships are discussed. Implications for policy and practice include targeting specific services, monitoring values of programs and staff, and minimizing system-induced crisis.

Digesta kinetics in sheep and cattle fed diets with different forage to concentrate ratios at high and low intakes.

Effect of maintenance and ad libitum intakes on digesta kinetics was studied with six ruminally fistulated cows and six ruminally fistulated wethers to validate the use of sheep as a model of cattle. Complete diets were made up of ratios of alfalfa:cracked corn and soybean meal of 80:20, 55:45, and 30:70. The rate of passage of Cr-mordanted alfalfa and soybean meal in the reticulorumen was negatively related to percentage of concentrate in the diet in both species at low intakes. Passage values of particulate and liquid markers were faster at high than at low intakes in both species for all diets. Rumen liquid volume increased with intake only in the cows on the low and intermediate concentrate diets. No substantial differences were found in particulate passage values between sheep and cattle. However, liquid passage rates from the rumen and the differentials between liquid and particulate dilution rates were higher in cows than in sheep for all diets at both intakes. These results together with those for digestibility data reported in a previous communication suggest that caution should be exercised when extrapolating results from one species to the other.

Response of cows to a reduction in dietary crude protein from 17% to 13% during early lactation.

Four treatments involving 48 multiparous cows (12 per group) were compared during wk 0 to 19 postpartum. Treatments involved decreasing dietary crude protein from 17% to 13% at the 5th, 10th, or 15th wk postpartum or leaving on the 17% diet throughout. Treatment means across periods for milk yields, solids-corrected-milk, dry matter intake, crude protein intake, and milk fatty acids of chain length less than or equal to palmitoleic acid, adjusted by covariance, in orders listed were 27.4, 28.0, 29.1, 29.5 kg; 23.2, 25.1 26.4, 26.8 kg; 19.0, 19.7, 20.4, 20.6 kg; 2.65, 2.98, 3.31, 3.44 kg; 59.83, 63.72, 62.74, 64.55%. There were linear increased as duration on 17% diet increased. The effect of decreasing dietary protein percent was greatest for the change at 5 wk postpartum. Milk fat, protein, and lactose percentages were not affected by treatment. Protein disappearance from nylon bags inserted in rumen fistulated steers was more rapid on 17% than 13% crude protein rations, but ration dry matter disappearance did not differ between rations.