Review of novel therapeutic medicines targeting androgen signaling in castration-resistant prostate cancer

Prostate cancer is the most common male malignant neoplasm.Androgens and the androgen receptor(AR)play a key role in the onset and progression of prostate cancer.The expression of the AR is still preserved in the majority of patients with castration-resistant prostate cancer(CRPC).CRPC is considered to be induced by the following mechanisms:(1)sustained AR activation by enhancing intracellular conversion of adrenal androgens to dehydrotestosterone via a de novo route;(2)AR hypersensitivity;(3)promiscuous activation of AR signaling;and(4)outlaw pathways.Recent advances in the treatment of CRPC include novel medicinestargeting AR signaling pathways.In addition,functional molecular studies have shown that some of the ARregulated genes and AR coregulators are prognostic markers and potential therapeutic targets for prostate cancer,particularly in the castration-resistant state.Therefore,identification of the AR signaling pathways responsible for establishment of CRPC is critical for developing new strategies for the treatment of CRPC.

Numerical Modeling and Computer Simulation of a Meander Line Antenna for Alzheimer’s Disease Treatment, a Feasibility Study

Alzheimer’s disease (AD) is a brain disorder that eventually causes memory loss and the ability to perform simple cognitive functions;research efforts within pharmaceuticals and other medical treatments have minimal impact on the disease. Our preliminary biological studies showed that Repeated Electromagnetic Field Stimulation (REFMS) applying an EM frequency of 64 MHz and a specific absorption rate (SAR) of 0.4 - 0.9 W/kg decrease the level of amyloid-β peptides (Aβ), which is the most likely etiology of AD. This study emphasizes uniform E/H field and SAR distribution with adequate penetration depth penetration through multiple human head layers driven with low input power for safety treatments. In this work, we performed numerical modeling and computer simulations of a portable Meander Line antenna (MLA) to achieve the required EMF parameters to treat AD. The MLA device features a low cost, small size, wide bandwidth, and the ability to integrate into a portable system. This study utilized a High-Frequency Simulation System (HFSS) in the design of the MLA with the desired characteristics suited for AD treatment in humans. The team designed a 24-turn antenna with a 60 cm length and 25 cm width and achieved the required resonant frequency of 64 MHz. Here we used two numerical human head phantoms to test the antenna, the MIDA and spherical head phantom with six and seven tissue layers, respectively. The antenna was fed from a 50-Watt input source to obtain the SAR of 0.6 W/kg requirement in the center of the simulated brain tissue layer. We found that the E/H field and SAR distribution produced was not homogeneous;there were areas of high SAR values close to the antenna transmitter, also areas of low SAR value far away from the antenna. This paper details the antenna parameters, the scattering parameters response, the efficiency response, and the E and H field distribution;we presented the computer simulation results and discussed future work for a practical model.

Safety of the long-term use of proton pump inhibitors

The proton pump inhibitors (PPIs) as a class are remarkably safe and effective for persons with peptic ulcer disorders. Serious adverse events are extremely rare for PPIs, with case reports of interstitial nephritis with omeprazole, hepatitis with omeprazole and lansoprazole, and disputed visual disturbances with pantoprazole and omeprazole. PPI use is associated with the development of fundic gland polyps (FGP); stopping PPIs is associated with regression of FGP. In the absence of Helicobacter pylori infection, the long-term use of PPIs has not been convincingly proven to cause or be associated with the progression of pre-existing chronic gastritis or gastric atrophy or intestinal metaplasia. Mild/modest hypergastrinemia is a physiological response to the reduction in gastric acid secretion due to any cause. The long-term use of PPIs has not been convincingly proven to cause enterochromaff in-like cell hyperplasia or carcinoid tumors. PPIs increase the risk of community acquired pneumonia, but not of hospital acquired (nosocomial) pneumonia. There is no data to support particular care in prescribing PPI therapy due to concerns about risk of hip fracture with the long-termuse of PPIs. Long-term use of PPIs does not lead to vitamin B12 def iciencies, except possibly in the elderly, or in persons with Zollinger-Ellison Syndrome who are on high doses of PPI for prolonged periods of time. There is no convincingly proven data that PPIs increase the risk of Clostridium difficile-associated diarrhea in persons in the community. The discontinuation of PPIs may result in rebound symptoms requiring further and even continuous PPI use for suppression of symptoms. As with all medications, the key is to use PPIs only when clearly indicated, and to reassess continued use so that long-term therapy is used judiciously. Thus, in summary, the PPIs are a safe class of medications to use longterm in persons in whom there is a clear need for the maintenance of extensive acid inhibition.

Analysis of CD117-negative gastrointestinal stromal tumors

AIM: To identify the gastrointestinal stromal tumors(GISTs) that are negative for CD117 expression by immunohistochemistry and to characterize their malignant potential.METHODS: A total of 108 primary mesenchymal tumors of the gastrointestinal tract were screened to select CD117-negative tumors, from which KIT(exons 9, 11, 13, and 17)and PDGFRA (exons 10, 12, 14, and 18) were sequenced to identify GISTs. Tumor recurrence and distant metastasis were used as the criteria of malignancy.RESULTS: The result showed that approximately 25%(29/108) of the gastrointestinal mesenchymal tumors were negative for CD117 and approximately 6% (7/108)of the tumors were CD117-negative GISTs. All these CD117-negative tumors had a mutated KITand a wildtype PDGFRA. All CD117-negative GISTs with mutations at codons 557/558 of KIThad mitotic counts ＞10/50 high power field, and 75% (3/4) of them showed multiple recurrence or distant metastasis.CONCLUSION: CD1 17-negative KITmutated GISTs account for approximately 6% of the gastrointestinal mesenchymal tumors. Tumor recurrence or distant metastasis correlates to both theKITmutations at codons 557/558 and the mitotic counts, but not to the tumor size.

A plant-based diet for the prevention and treatment of type 2 diabetes

The prevalence of type 2 diabetes is rising worldwide, especially in older adults. Diet and lifestyle, particularly plant-based diets, are ef-fective tools for type 2 diabetes prevention and management. Plant-based diets are eating patterns that emphasize legumes, whole grains,vegetables, fruits, nuts, and seeds and discourage most or all animal products. Cohort studies strongly support the role of plant-based diets,and food and nutrient components of plant-based diets, in reducing the risk of type 2 diabetes. Evidence from observational and interven-tional studies demonstrates the benefits of plant-based diets in treating type 2 diabetes and reducing key diabetes-related macrovascular andmicrovascular complications. Optimal macronutrient ratios for preventing and treating type 2 diabetes are controversial; the focus should insteadbe on eating patterns and actual foods. However, the evidence does suggest that the type and source of carbohydrate （unrefined versus refined）,fats （monounsaturated and polyunsaturated versus saturated and trans）, and protein （plant versus animal） play a major role in the prevention andmanagement of type 2 diabetes. Multiple potential mechanisms underlie the benefits of a plant-based diet in ameliorating insulin resistance, in-cluding promotion of a healthy body weight, increases in fiber and phytonutrients, food-microbiome interactions, and decreases in saturated fat,advanced glycation endproducts, nitrosamines, and heme iron.

Influence of tacrolimus metabolism rate on renal function after solid organ transplantation

The calcineurin inhibitor(CNI) tacrolimus(TAC) is an integral part of the immunosuppressive regimen after solid organ transplantation. Although TAC is very effective in prevention of acute rejection episodes, its highly variable pharmacokinetic and narrow therapeutic window require frequent monitoring of drug levels and dose adjustments. TAC can cause CNI nephrotoxicity even at low blood trough levels(4-6 ng/m L). Thus, other factors besides the TAC trough level might contribute to CNI-related kidney injury. Unfortunately, TAC pharmacokinetic is determined by a whole bunch of parameters. However, for daily clinical routine a simple application strategy is needed. To address this problem, we and others have evaluated a simple calculation method in which the TAC blood trough concentration(C) is divided by the daily dose(D). Fast TAC metabolism(C/D ratio < 1.05) was identified as a potential risk factor for an inferior kidney function after transplantation. In this regard, we recently showed a strong association between fast TAC metabolism and CNI nephrotoxicity as well as BKV infection. Therefore, the TAC C/D ratio may assist transplant clinicians in a simple way to individualize the immunosuppressive regimen.

Ontogeny,growth and development of the small intestine:Understanding pediatric gastroenterology

Throughout our lifetime,the intestine changes.Some alterations in its form and function may be genetically determined,and some are the result of adaptation to diet,temperature,or stress.The critical period programming of the intestine can be modified,such as from subtle differences in the types and ratios of n3:m6 fatty acids in the diet of the pregnant mother,or in the diet of the weanlings.This early forced adaptation may persist in later life,such as the unwanted increased intestinal absorption of sugars,fatty acids and cholesterol.Thus,the ontogeny,early growth and development of the intestine is important for the adult gastroenterologist to appreciate,because of the potential for these early life events to affect the responsiveness of the intestine to physiological or pathological challenges in later life.

Imaging-based diagnosis of acute renal allograft rejection

Kidney transplantation is the best available treatment for patients with end stage renal disease. Despite the introduction of effective immunosuppressant drugs, episodes of acute allograft rejection still endanger graft survival. Since efficient treatment of acute rejection is available, rapid diagnosis of this reversible graft injury is essential. For diagnosis of rejection, invasive core needle biopsy of the graft is the "gold-standard". However, biopsy carries the risk of significant graft injury and is not immediately feasible in patients taking anticoagulants. Therefore, a non-invasive tool assessing the whole organ for specific and fast detection of acute allograft rejection is desirable. We herein review current imaging-based state of the art approaches for non-invasive diagnostics of acute renal transplant rejection. We especially focus on new positron emission tomography-based as well as targeted ultrasoundbased methods.

Survey of <i>C. difficile</i>-Specific Infection Control Policies in Local Long-Term Care Facilities

Introduction: The incidence and severity of Clostridium difficile infection (CDI) has been increasing and long-term care facility (LTCF) residents are at high risk given their age, co-morbidities, and high antibiotic exposure. Infection control policies are crucial for controlling CDI, but there are currently no regulatory guidelines in the United States. Therefore, we evaluated infection control policies in local LTCFs to define the CDI-specific policies and the administrative and staff understanding of CDI, so as to identify perceived barriers for compliance. Methods: IRB approval was sought and exemption granted, all 8 local LTCFs were asked to participate. Each facility was visited by study personnel who interviewed the administrative Infection Control Practitioner (ICP) and 3-4 Licensed Practical Nurses (LPNs) with distinct survey format. Infection control policies were then compared to the SHEA recommendations for CDI in LTCFs. Results: Of the eligible facilities, 75% (n = 6) participated. ICP (n = 6) and LPNs (n = 21) were interviewed. All facilities accept residents with active CDI and 2 had written CDI-specific infection control policies. All facilities had hand hygiene or glove use policies and 2 had policies for the use of sporicidal environmental cleaning. No facility restricted antibiotic use. Each facility has a policy to instruct their staff through in-services, either annually or upon new hire, but 33% (n = 7) LPNs reported no facility-based CDI training. While 80% (n = 17) of LPNs felt comfortable with the facility CDI policies, only 11 accurately restated it. ICPs felt the most relevant barrier to staff compliance was time constraints (n = 4, 67%), however, LPNs felt it was limited knowledge (n = 10, 48%) and poor communication (n = 2, 10%). Discussion and Conclusions: With the increasing incidence and severity of CDI in LCTF, few of the facilities surveyed had CDI-specific policies. Despite CDI-specific training, there is a perceived knowledge and communication gap for staff caring for residents with CDI.

Combined Effects of Blood Pressure and Aldosterone on Cardiac Left Ventricular Mass Index—Ethnic Differences between Kazakh, Uygur and Han Subjects

Previous Background: Hemodynamic factors, like blood pressure, have been established to be major determinants of cardiac left ventricular structure. However, several factors other than blood pressure to influence cardiac mass have been implicated. When we did medical survey, cardiac left ventricular mass index (LVMI) of one ethnic group that had higher blood pressure was found to be smaller than that of the other ethnic groups with a lower blood pressure. Such contradicted data from the present study were analyzed combining blood pressure, LVMI and chemical parameters obtained from blood and urine. Methods: In a medical survey conducted in Xinjiang, China, 279 people (65 - 70 years old) from three ethnic groups (Kazakh, Uygur and Han) from two separated regions provided blood and urine samples and underwent echocardiography and 24-h ambulatory blood pressure monitoring (ABPM). Results: Systolic and diastolic blood pressure obtained from ABPM and urinary sodium excretion values were significantly higher in Kazakh than that in Uygur and Han. However, LVMI in Kazakh was lower than that in other 2 groups. Plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were significantly lowest in Kazakh. The values of LVMI in all ethnic groups were positively related to both blood pressure and PAC. An inverse correlation was identified between PAC and urinary sodium excretion value. Conclusion: Although higher blood pressure in Kazakh subjects, their LVMI was lower than those of Uygur and Han, whose blood pressure was lower than that in Kazakh. These results suggest that blood pressure is not always a determinant for LVMI value. There is a possibility that relatively lower PAC resulted from higher sodium intake suppressed the rise in LVMI caused by higher blood pressure in Kazakh.

Prognostic utility of NT-proBNP greater than 70,000 pg/mL in patients with end stage renal disease

Natriuretic peptides are synthesized in ventricular myocytes and released into the circulation in response to increased myocardial wall stress, Causes of myocardial wall stress include pulmonary hypertension, ventricular dilatation, as well as heart failure with reduced or preserved left ventricular function.

Efficacy of MK615 for the treatment of patients with liver disorders

AIM： To investigate the hepatoprotective effect of MK615, a Japanese apricot extract, in an animal model, and its clinical therapeutic effect. METHODS： Wistar rats were administered physiologi- cal saline （4 mL/kg） or MK615 solution （4 mL/kg） for 7 d. On the sixth d, acute hepatic injury was induced by administering a single intraperitoneal injection （ip） of D-galactosamine hydrochloride （D-GaIN） （600 mg/kg）. Plasma levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined, and liver tissues were used for histopathological analy- sis. Fifty-eight patients with liver disorders [hepatitis C （n = 40）, non-alcoholic fatty liver disease （n = 15）, and autoimmune liver disease （n = 3）] were orally admin- istered commercially available Misatol ME-containing MK615 （13 g/d） daily for 12 wk. Blood and urine were sampled immediately before and 6 wk, 12 wk, and 16 wk after the start of intake to measure various bio- chemical parameters. The percentage change in ALT and AST levels after 12 wk from the pre-intake baseline served as a primary endpoint. RESULTS： D-GaIN effectively induced acute hepatic injury in the rats. At 48 h after the ip injection of D-GaIN, the plasma levels of ALT （475.6 ：t： 191.5 IU/L vs 225.3 ＋ 194.2 IU/L, P 〈 0.05） and AST （1253.9：1：223.4 IU/L vs 621.9 ＋ 478.2 IU/L, P 〈 0.05） in the MK615 group were significantly lower than the control group. Scattered single cell necrosis, loss of hepatocytes, and extensive inflammatory cell infiltration were observed in hepatic tissue samples collected from the control group. However, these findings were less pronounced in the group receiving MK615. At the end of the clinical study, serum ALT and AST levels were significantly de- creased compared with pre-intake baseline levels from 103.5 ：l： 58.8 IU/L to 71.8 ＋ 39.3 IU/L （P 〈 0.05） and from 93.5 ：E 55.6 IU/L to 65.5 ＋ 34.8 IU/L （P 〈 0.05）, respectively. A reduction of 〉~ 30% from the pre-study baseline ALT level was observed in 26 （45%） of the 58 patients, while 25 （43%） patients exhibited similar AST level reductions. The chronic hepatitis C group exhibit- ed significant ALT and AST level reductions from 93.4：1： 51.1 IU/L to 64.6 ＋ 35.1 IU/L （P 〈 0.05） and from 94.2 ＋ 55.5 IU/L to 67.2：1：35.6 IU/L （P 〈 0.05）, respective- ly. A reduction of 〉~ 30% from the pre-study baseline ALT level was observed in 20 （50%） of the 40 patients.ALT levels in both the combined ursodeoxycholic acid （UDCA） treatment and the UDCA uncombined groups were significantly lower after Misatol ME administration. MK615 protected hepatocytes from D-GaiN-induced cytotoxicity in rats. Misatol ME decreased elevated ALT and AST levels in patients with liver disorders. CONCLUSION： These results suggest that MK615 and Misatol ME are promising hepatoprotective agents for patients with liver disorders.

Risk of pancreatic adverse events associated with the use of glucagon-like peptide-1 receptor agonist and dipeptidyl peptidase-4 inhibitor drugs: A systematic review and metaanalysis of randomized trials

AIM: To systematically assess risk of pancreatic adverse events with glucagon-like peptide-1(GLP-1) receptor agonist and dipeptidyl peptidase-4(DPP-4) inhibitor drugs.METHODS: We searched Pub Med, Embase, CINAHL, Cochrane review of clinical trials, pharmaceutical company clinical trials register, United States Food and Drug Administration website, European Medicines Agency website and Clinical Trials.gov for randomized controlled trials from inception to October 2013. Randomized control trial studies were selected for inclusion if they reported on pancreatic complication events and/or changes in pancreatic enzyme levels(serum amylase and serum lipase) as adverse events or as serious adverse events for patients who were on GLP-1 receptor agonist and DPP-4 inhibitor drugs. Two independent reviewers extracted data directly. We performed Peto odds ratio(OR) fixed effect meta-analysis of pancreatic adverse events a, and assessed heterogeneity with the I^2 statistic.RESULTS: Sixty-eight randomized controlled trials were eligible. A total of 60720 patients were included in our analysis of the association of risk of pancreatic complication events with GLP-1 agents. A total of 89 pancreatic related adverse events occurred among the GLP-1 agents compared to 74 events among the controls. There was a statistically significant increased risk of elevation of pancreatic enzymes associated with GLP-1 agents compared with control(Peto OR = 3.15, 95%CI: 1.56-6.39, P = 0.001, I2 = 0%). There was no statistically significant difference in the risk of pancreatic adverse event associated with GLP-1 agent compared with controls(Peto OR = 1.00, 95%CI: 0.73-1.37, P = 1.00, I2 = 0%). There were a total of 71 pancreatitis events in patients on GLP-1 agents and 56 pancreatitis events occurred in the control patients. There were 36 reports of pancreatic cancer in these studies. Of these cases, 2 used linagliptin, 2 used alogliptin, 1 used vildagliptin, 7 used saxagliptin while 6 used sitagliptin. The remaining 18 cases occurred among controls.CONCLUSION: Although GLP-1 based agents are associated with pancreatic enzyme elevation, we were unable to confirm a significant risk of pancreatitis or pancreatic cancer.

Real-world cure rates for hepatitis C virus treatments that include simeprevir and/or sofosbuvir are comparable to clinical trial results

AIM To assess the real-world effectiveness and cost of simeprevir(SMV), and/or sofosbuvir(SOF)-based therapy for chronic hepatitis C virus(HCV) infection.METHODS The real-world performance of patients treated with SMV/SOF ± ribavirin(RBV), SOF/RBV, and SOF/RBV with pegylated-interferon(PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included. Rates of sustained virological response-the absence of a detectable serum HCV RNA 12 wk after the end of treatment [sustained virological response(SVR) 12]-were calculated on an intention-to-treat basis. Costs were calculated from the payer's perspective using Medicare/Medicaid fees and Redbook Wholesale Acquisition Costs. Patient-related factors associated with SVR12 were identified using multivariable logistic regression.RESULTS SVR 12 rates were as follows: 86%(95%CI: 80%-91%)among 178 patients on SMV/SOF ± RBV; 62%(95%CI: 55%-68%) among 234 patients on SOF/RBV; and 78%(95%CI: 68%-86%) among 96 patients on SOF/PEG/RBV. Mean costs-per-SVR 12 were $174442(standard deviation: ± $18588) for SMV/SOF ± RBV; $223003(± $77946) for SOF/RBV; and $126496(± $31052) for SOF/PEG/RBV. Among patients on SMV/SOF ± RBV, SVR12 was less likely in patients previously treated with a protease inhibitor [odds ratio(OR): 0.20, 95%CI: 0.06-0.56]. Higher bilirubin(OR: 0.47, 95%CI: 0.30-0.69) reduced the likelihood of SVR12 among patients on SOF/RBV, while FIB-4 score ≥ 3.25 reduced the likelihood of SVR 12(OR: 0.18, 95%CI: 0.05-0.59) among those on SOF/PEG/RBV. CONCLUSION SVR 12 rates for SMV and/or SOF-based regimens in a diverse real-world population are comparable to those in clinical trials. Treatment failure accounts for 27% of costs.

Use of pocket pulse oximeters for detecting peripheral arterial disease in patients with diabetes mellitus

Recent Aims: New diagnostic methods are needed to detect peripheral arterial disease easier than using the ankle-brachial index measured by Doppler devices. We investigated whether the use of pocket pulse oximeters could meet sensitivity and specificity criteria as screening method to detect significant peripheral arterial perfusion deficits. Methods: We measured oxygen saturation (SaO2) at index fingers and great toes (on horizontal and elevated 30°) by a pocket pulse oximeter in 250 subjects with diabetes mellitus attending the outpatient clinic. A finger-to-toe SaO2 gradient greater than 2% was considered abnormal. Ankle-brachial index was measured by a hand held Doppler device. Peripheral arterial disease was defined as an ankle-brachial index less than 0.9. Results: A total of 1392 (93%) valid SaO2 readings were obtained. Twenty-seven (11%) patients were excluded due to not having measurable SaO2 finger-to-toe gradients. A total of 223 patients were analyzed. Peripheral arterial disease was detected in 47 (21%) patients. A finger-to-toe SaO2 gradient greater than 2% had sensitivity 42.6% (95% CI 30.0% - 55.3%), specificity 79.1% (95% CI 75.7% - 82.6%), positive predictive value 35.7% (95% CI 25.2% - 46.4%), negative predictive value 83.4% (95% CI 79.8 - 87.1), positive likelihood ratio 2.03 (95% CI 1.23 - 3.17) and negative likelihood ratio 0.73 (95% CI 0.54 - 0.93) to detect peripheral arterial disease. The area under the receiving operating characteristic curve was 0.69 (95% CI 0.62 - 0.77). Conclusion: Pocket pulse oximeters showed insufficient sensitivity as screening method for detecting peripheral arterial disease in patients with diabetes mellitus.

Endurance swimming and increased risk of atrial fibrillation

Dear editor, Diet and exercise have always been part of a healthy life- style. However, literature has identified an association between endurance exercise and atrial fibrillation with the implication that the incidence of atrial fibrillation increases in endurance athletes.1,2 To this point, researchers have grouped diverse activities （running, biking, etc.） of varying intensity in arriving at these conclusions,z＇ Proposed mechanisms for the associa- tion between prolonged physical activity and atrial fibrillation include left atrial remodeling, increased atrial ectopy, and increased vagal tone induced by endurance exercise.

Overuse and underuse of calcium and vitamin D in women with osteoporosis: A survey in a primary care setting

Introduction: Optimal calcium and vitamin D intake is important components of the treatment of osteoporosis. The national average calcium and vitamin D intake for women over age 50 is below the recommended levels for optimal bone health. The aim of this study was to assess whether deficiencies in calcium and vitamin D intake exist in women with osteoporosis in a general medicine practice, as well as evaluate whether physicians accurately document calcium and vitamin D supplementation in the health record. Methods: Using the Electronic Health Record (EHR), we identified all female patients age 50 and older with the diagnosis of osteoporosis who were seen at the study site clinic, an urban academic general medicine practice, between January 1st, 2010 and December 1st, 2010. Women were randomly selected to receive an invitation to participate in a telephone survey on osteoporosis treatment. Results: One hundred and sixteen women completed the telephone survey. The mean calcium intake was 1524 mg per day. Forty-nine percent of women surveyed reported taking less than 1200 mg/day of supplemental calcium. When considering reported calcium intake from diet, 33% percent consumed less than 1200 mg/day and 52% percent consumed more than 1500 mg/day. Twenty eight percent of patients were taking less than 800 IU/day of vitamin D;only four percent were taking more than 4000 IU/day. Agreement between patients’ self-reported intake of calcium, vitamin D and multivitamin supplements and physicians’ documentation of these supplements was 52% for calcium, 53% for vitamin D and 61% for multivitamin. Conclusion: Among women with osteoporosis getting regular care in a general medicine practice, approximately a third are getting less than the recommended daily amount of calcium and a quarter less than the recommended amount of vitamin D. In addition, a significant proportion of women are getting excessive daily amounts of calcium, which may also be a quality concern. Rates of agreement between self-reported calcium and vitamin D supplements and chart documentation of these supplements were low.

Numerical Analysis and Design of an EMF Birdcage Wearable Device for the Treatment of Alzheimer’s Disease: A Feasibility Study

In this study, we performed a numerical analysis of a novel EMF Birdcage wearable device for the treatment of Alzheimer’s disease (AD). We designed the new device to generate and radiate a frequency of 64 MHz and a specific absorption rate (SAR) of 0.6 W/kg to a simulated human brain tissue. We determined these parameters from our experimental studies on primary human brain cultures at the Indiana University School of Medicine (IUSM). We found that this frequency and SAR decreased the toxic Aβ levels in the cell cultures. The frequency of 64 MHZ has good skin depth penetration, which will easily pass through the various head layers, including hair, skin, fat, dura, the cerebrospinal (CSF), and grey matter, and reach deeply into the brain tissues. The SAR of 0.6 W/kg was achieved with lower power input and energy, decreasing the probability of thermal injury. Therefore, these parameters enhance the safety of these potential treatments. This Birdcage device emulates a small-scale MRI machine, producing the same 64 MHz frequency at much lower operating input power. In this work, we utilized a high-frequency simulation system (HFSS/EMPro) software to produce the birdcage structure for the required EMF parameters. The 64 MHz radiating frequency produced the scattering S11 parameter of −15 dbs. We obtained a SAR of 0.6 W/kg when an input power of 100 W was applied. The coil dimensions were found to be near 15 cm in height and 22 cm in diameter, which fits in wearable systems. We found that the distribution of the electric field and SAR radiate homogeneously over the simulated human head with good penetration into the brain, which proves to be an appropriate potential therapeutic strategy for Alzheimer’s disease.

Towards automated calculation of evidence-based clinical scores

AIM To determine clinical scores important for automated calculation in the inpatient setting.METHODS A modified Delphi methodology was used to create consensus of important clinical scores for inpatient practice. A list of 176 externally validated clinical scores were identified from freely available internet-based services frequently used by clinicians. Scores were categorized based on pertinent specialty and a customized survey was created for each clinician specialty group. Clinicians were asked to rank each score based on importance of automated calculation to their clinical practice in three categories-"not important", "nice to have", or "very important". Surveys were solicited via specialty-group listserv over a 3-mo interval. Respondents must have been practicing physicians with more than 20% clinical time spent in the inpatient setting. Within each specialty, consensus was established for any clinical score with greater than 70% of responses in a single category and a minimum of 10 responses. Logistic regression was performed to determine predictors of automation importance.RESULTS Seventy-nine divided by one hundred and forty-four(54.9%) surveys were completed and 72/144(50%) surveys were completed by eligible respondents. Only the critical care and internal medicine specialties surpassed the 10-respondent threshold(14 respondents each). For internists, 2/110(1.8%) of scores were "very important" and 73/110(66.4%) were "nice to have". For intensivists, no scores were "very important" and 26/76(34.2%) were "nice to have". Only the number of medical history(OR = 2.34; 95%CI: 1.26-4.67; P < 0.05) and vital sign(OR = 1.88; 95%CI: 1.03-3.68; P < 0.05) variables for clinical scores used by internists was predictive of desire for automation. CONCLUSION Few clinical scores were deemed "very important" for automated calculation. Future efforts towards score calculator automation should focus on technically feasible "nice to have" scores.

Therapeutics of Stem Cell Treatment in Anti-Aging and Rejuvenation

Aging populations are increasing the incidence of age-related diseases, resulting in problems at the individual and socioeconomic level. The need for effective strategies in regenerative medicine for the elderly is more important than ever. Previous studies have shown that the number and function of stem cells decline with age, thereby undermining endogenous repair processes. It has also been suggested that the aging-induced deterioration of stem cell function may play a key role in the pathophysiology of various aging-related diseases. Recent advances in our understanding of tissue regeneration and the development of methods aimed at inducing and differentiating pluripotent stem cells for cell replacement therapy which provides exciting opportunities for the treatment of degenerative diseases, such as those related to senility. In this review article, we examine several mechanisms that are believed to contribute to the aging-related dysfunction of stem cells associated with diseases of the immune system, cardiac tissue, neuronal system, articular cartilage, and skeletal muscle. We also discuss factors that affect the therapeutic potential of adult stem/progenitor cells as well as current trends in the treatment of these conditions using regenerative medicine.