Alzheimer's disease is the leading cause of dementia in the world. It affects 6 million people in the United States and 50 million people worldwide. Alzheimer's disease is characterized by the ...accumulation of amyloid-β plaques (Aβ), an increase in tau protein neurofibrillary tangles, and a loss of synapses. Since the 1990s, removing and reducing Aβ has been the focus of Alzheimer's treatment and prevention research. The accumulation of Aβ can lead to oxidative stress, inflammation, neurotoxicity, and eventually apoptosis. These insults impair signaling systems in the brain, potentially leading to memory loss and cognitive decline. Aniracetam is a safe, effective, cognitive-enhancing drug that improves memory in both human and animal studies. Aniracetam may prevent the production and accumulation of Aβ by increasing α-secretase activity through two distinct pathways: 1) increasing brain derived neurotrophic factor expression and 2) positively modulating metabotropic glutamate receptors. This is the first paper to propose an evidence-based model for aniracetam reducing the accumulation and production of Aβ.
Background Dermatologic surgeons will increasingly encounter patients on novel oral antiplatelet and anticoagulant medications. Objectives We conducted a complete overview of the pharmacokinetics, ...pharmacodynamics, and side effects of traditional and novel oral anticoagulant and antiplatelet therapies along with dietary supplements with anticoagulant or antiplatelet properties. Methods A PubMed search was completed for “aspirin,” “warfarin,” “clopidogrel,” “dabigatran,” “rivaroxaban,” “apixaban,” “prasugrel,” and “ticagrelor.” Review articles and publications emphasizing perioperative management of oral anticoagulant or antiplatelet medications were selected. An additional PubMed search was completed for “hemorrhage,” “bleeding,” and “thrombosis” in conjunction with “dermatology,” “dermatologic surgery,” and “cutaneous surgery.” Results Aspirin, clopidogrel, and warfarin have shortfalls in dosing, monitoring, and efficacy. Several trials show superior efficacy with dabigatran, rivaroxaban, and apixaban, with equal or reduced risk of bleeding compared with warfarin. Prasugrel and ticagrelor may be associated with an increased bleeding risk. Many over-the-counter medications also have anticoagulant properties with associated bleeding risks that cannot be overlooked. Limitations There are few publications evaluating the novel oral anticoagulants' effects on outpatient surgical procedures. Conclusion Novel anticoagulant and antiplatelet drugs are revolutionizing therapy for cardiovascular diseases. As these medications become more prevalent, dermatologists and dermatologic surgeons must be mindful of the bleeding risk that will apply in our everyday practices.
Introduction
Currently, the need for additional myofascial release (AMR) in addition to retromuscular dissection during open Rives–Stoppa hernia repair is determined intraoperatively based on the ...discretion of the surgeon. We developed a novel method to objectively predict the need for AMR preoperatively using computed tomography (CT)-measured rectus width to hernia width ratio (RDR).
Methods
A retrospective chart review of all patients who underwent open retro-muscular mesh repair of midline ventral hernia between August 1, 2007 and February 1, 2018, who had a preoperative CT scan within 1 year prior to their operation. The primary endpoint was the ability of the defect ratio to predict the need for AMR in pursuit of fascial closure. The secondary endpoint was the ability of Component Separation Index (CSI) to predict the need for AMR to obtain fascial closure.
Results
Of 342 patients, 208 repaired with rectus abdominis release alone (RM group), while 134 required AMR (RM + group). An RDR of > 1.34 on area under the curve analysis predicted the need for AMR with 77.6% accuracy. There was a linear decrease in the need for AMR with increasing RDR: RDR < 1 required AMR in 78.8% of cases, RDR 1.1–1.49 in 52%, RDR 1.5–1.99 in 32.1%, and RDR > 2 in just 10.8%. Similarly, CSI > 0.146 predicted the need for AMR with 76.3% accuracy on area under the curve analysis.
Conclusion
The RDR is a practical and reliable tool to predict the ability to close the defect during open Rives–Stoppa ventral hernia repair without AMR. An RDR of > 2 portends fascial closure with rectus abdominis myofascial release alone in 90% of cases.
There is a paucity of data providing direct comparison of outcomes, complications, and costs between general and local anesthesia in cutaneous surgery.
Analyze the literature from dermatologic and ...other specialties to compare outcomes, risks, and costs of general and local anesthesia.
A retrospective analysis of case comparison studies from other specialties comparing outcomes, risks, and/or costs in local versus general anesthesia was performed. A review of the literature from dermatology and other specialties was included.
A total of 51 studies were selected; 41 of them directly examined outcomes in procedures performed under local and general anesthesia, and none found a significant difference in outcomes. A total of 41 studies measured adverse effects. Of these, 15 studies (36.6%) report significantly better outcomes between the 2 techniques. Only 2 studies (4.9%) report significantly improved outcomes with use of general anesthesia; 15 of 36 studies (41.7%) report fewer adverse events in local anesthesia. Of the 13 studies that examined costs, all (100%) found significantly decreased costs with use of local anesthesia.
These data cannot be seamlessly applied to all cases of cutaneous surgery.
Local anesthesia techniques provide outcomes equal to or better than general anesthesia and with significantly lower costs.
The objective of this cross-sectional study was to estimate the prevalence of bovine respiratory disease (BRD) in California preweaned dairy calves and identify management practices that are ...associated with BRD. A convenience sample of 100 dairies in the 3 distinct dairy regions of California was surveyed. Regions evaluated were Northern California (NCA), northern San Joaquin Valley (NSJV), and greater Southern California (GSCA). A questionnaire on calf management practices and demographic information was administered via in-person interviews at each dairy and a random sample of preweaned calves was evaluated using the California BRD scoring system on the same day. Prevalence of BRD varied between the 3 dairy regions: 9.30% in NCA, 4.51% in NSJV, and 7.35% in GSCA. Breed was not associated with BRD prevalence at the statewide level, but differences in prevalence were observed between breeds across the regions with a higher prevalence in NCA for Jerseys and in GSCA for Holsteins, compared with NSJV. Prevalence of BRD was not different between organic and conventional dairies. Colostrum management practices, including heat treatment and feeding colostrum from multiparous cows, varied by region and were associated with lower BRD prevalence. Calves housed in group pens, a practice observed primarily in NCA, had a higher BRD prevalence than those in individual housing. Feeding salable milk was also more common in NCA and was associated with lower BRD prevalence. Ground and road surfaces adjacent to the calf raising area were also variable by region, and paved surfaces were associated with lower BRD prevalence. Management practices associated with BRD varied across the state and may be addressed to inform the adoption and implementation of potentially protective management decisions on California dairies and other regions with similar dairy systems.
Heat stress has the potential to adversely affect the physiology, passive immunity, and growth of preweaning dairy calves, increasing their risk of respiratory disease. The effect of heat stress on ...the risk for bovine respiratory disease (BRD) may be mediated in part through housing, ventilation, and management factors. As a result, differences may exist in meteorological measures recorded in the calf-rearing area (macroenvironment) and within a calf's enclosure (microenvironment). The objective of this prospective cohort study was to evaluate and compare the association between exposure to temperature and humidity measured at the macro- and microenvironment, and BRD in preweaning dairy calves; a secondary objective was to evaluate the correlation between the macro- and microenvironment. A cohort of 252 calves from 4 premises in central San Joaquin Valley, California (CA), was followed and evaluated for development of respiratory disease using the CA BRD scoring system for preweaning dairy calves, a standardized and validated scoring system. During this time, the meteorological conditions of the calf-rearing area and the within-hutch environment were measured and showed a significant correlation with regard to temperature and humidity. Mixed effects logistic regression and survival analysis were used to analyze the association between the exposures daily environmental measures of temperature, humidity, and temperature-humidity index (THI) and the outcome BRD, adjusted for dairy premises, calf age, sex, and breed. Results showed a significant positive association between daily maximum temperature and BRD in both the calf's macroenvironment odds ratio = 1.121 (95% confidence interval (CI) = 1.029–1.222) and microenvironment odds ratio = 1.203 (95% CI = 1.020–1.418). Estimated hazard rates also showed a significant positive association between BRD and daily maximum temperature in both the macroenvironment hazard ratio = 1.127 (95% CI = 1.053–1.206) and microenvironment hazard ratio = 1.119 (95% CI = 1.047–1.197). In contrast, we found no association between daily maximum humidity in a calf's microenvironment and BRD. Daily maximum THI within the hutch was significantly associated with only the rate of BRD cases hazard ratio = 1.070 (95% CI = 1.003–1,141) but not the odds of occurrence of BRD. Maximum THI is estimated using temperature and humidity, which in California's hot and dry summers may limit variability in THI, explaining its weaker significant association with risk of BRD (or lack of association with odds of BRD) compared with models for maximum temperature in this study. Calves exposed to high day temperatures and relatively low humidity may be experiencing heat stress that predisposes to BRD. Results of the current study suggest that heat abatement efforts should address heat stress at the microenvironment level to mitigate BRD in calves. Further research should investigate strategies to improve calf hutch systems, including hutch materials and design that may optimize ventilation, provide ample shade, spacing, cleanliness, and protection from heat.
The objective of this cross-sectional study was to determine how management practices on California dairies may be associated with bovine respiratory disease (BRD) in preweaned calves. A convenience ...sample of 100 dairies throughout California, providing a study population of 4,636 calves, were visited between May 2014 and April 2016. During each farm visit, in-person interviews with the herd manager or calf caretaker were conducted to collect information about herd demographics, maternity pen, colostrum and calf management, herd vaccinations, and dust abatement. A random sample of preweaned calves was identified and evaluated for the presence of BRD using a standardized tool. A survey-adjusted generalized linear mixed model with a logit link function was fitted with calf as the unit of analysis and dairy as the random effect. Mean study herd size (±SE) was 1,718 (±189.9) cows. Survey-adjusted estimates of breed types in the sample were 81.6% (±0.6) Holstein, 13.1% (±0.4) Jersey, and 5.3% (±0.5) crossbred or other purebred breeds, and calf sex proportions were 73.8% (±1.0) female and 26.2% (±1.0) male. Overall survey-adjusted BRD prevalence in the study herds was 6.91% (±0.69). Housing factors positively associated with BRD were metal hutches compared with wood hutches odds ratio (OR) = 11.19; 95% confidence interval (CI) = 2.80–44.78, calf-to-calf contact in calves >75 d of age (OR = 9.95, 95% CI = 1.50–65.86), feeding Holstein calves <2.84 L of milk or replacer per day (OR = 7.16, 95% CI = 1.23–41.68), and lagoon water used for flushing manure under hutches compared with no flush (OR = 12.06, 95% CI = 1.93–75.47). Providing extra shade over hutches (OR = 0.08; 95% CI = 0.02–0.37), feeding calves at least 90% saleable milk (OR = 0.27, 95% CI = 0.13–0.54) or pasteurized milk (OR = 0.10; 95% CI = 0.03–0.36), and feeding >5.68 L of milk or replacer per day to Jersey calves (OR = 0.04; 95% CI = 0.01–0.28) were negatively associated with BRD. Our study identified management practices on California dairies with variability and that may contribute to differences in BRD prevalence, which will be incorporated into a risk-assessment tool to control and prevent BRD in preweaned dairy calves.
Introduction
Laparoscopic ventral hernia repair (LVHR) with intraperitoneal mesh placement is well established; however, the fate of patients requiring future abdominal operations is not well ...understood. This study identifies the characteristics of LVHR patients undergoing reoperation and the sequelae of reoperation.
Methods
A retrospective review of a prospectively maintained database at a hernia referral center identified patients who underwent LVHR between 2005 and 2014 and then underwent a subsequent abdominal operation. The outcomes of those reoperations were collected. Data are presented as a mean with ranges.
Results
A total of 733 patients underwent LVHR. The average age was 56.5 years, BMI 33.9 kg/m
2
, hernia size 115 cm
2
(range 1–660 cm
2
), and mesh size 411 cm
2
(range 17.7–1360 cm
2
). After a mean follow-up of 19.4 months, the overall hernia recurrence rate was 8.4 %. Subsequent abdominal operations were performed in 17 % (125 patients) at a mean 2.2 years. The most common indication for reoperation was recurrent hernia (33 patients, 26.4 %), followed by bowel obstruction (18 patients, 14.4 %), hepatopancreaticobiliary (17 patients, 13.6 %) and infected mesh removal (15 patients, 12 %), gynecologic (10 patients, 8 %), colorectal (8 patients, 6.4 %), bariatric (4 patients, 3 %), trauma (1 patient, 0.8 %), and other (19 patients, 15 %). The overall incidence of enterotomy or unplanned bowel resection (EBR) at reoperation was 4 %. This occurred exclusively in those reoperated for complete bowel obstruction, and the reason for EBR was mesh–bowel adhesions. No other indication for reoperation resulted in EBR. The incidence of secondary mesh infection after subsequent operation was 2.4 %.
Conclusion
In a large consecutive series of LVHR, the rate of abdominal reoperation was 17 %. Generally, these reoperations can be performed safely. A reoperation for bowel obstruction, however, may carry an increased risk of EBR as a direct result of mesh–bowel adhesions. Secondary mesh infection after reoperation, although rare, may also occur. Surgeons should discuss with their patients the potential long-term implications of having an intraperitoneal mesh and how it may impact future abdominal surgery.
Due to the increased morbidity and mortality of bovine respiratory disease (BRD) in dairy calves, as well as an increasing urgency for the judicious use of antimicrobials in farm animals, a ...comprehensive risk assessment tool for BRD in preweaned dairy calves has been designed based on a longitudinal and a cross-sectional study. As a multifactorial disease complex in which immune function stressors increase susceptibility to respiratory pathology, risk management programs for environmental and husbandry practices may be an effective approach for BRD control. Practices of known or suspected effect on BRD in preweaned calves have been explored in 2 large studies correlating management factors to BRD prevalence (BRD 100 study) and incidence (BRD 10K study) and forming the scores presented here. Priority was given to results from multivariable over univariable model estimates. However, when used, univariable model estimates were adjusted for confounders or stratified by effect modifiers if necessary. Regression coefficients were translated into scores, which are presented in a field-ready tool consisting of (1) a risk assessment questionnaire, which identifies the herd-specific risk factors and the risk scores associated with each; (2) the California BRD scoring system to estimate the BRD prevalence at the time of risk assessment for future comparison with the prevalence after interventions; and (3) the BRD control and prevention herd management plan, which can be used to plan and track the interventions identified. Scores for 100 dairies across California were used to benchmark a dairy's risk on a spectrum. With the help of the risk assessment tool, dairy producers, calf managers, and veterinarians may be able to adjust management factors that affect BRD risk on a farm and objectively monitor BRD prevalence before and after management interventions. As a result, the BRD risk assessment tool described here is the first comprehensive effort for herd-specific BRD control and prevention.
Compared with antibiotics for treating bacterial infections, there are a limited number of antifungal agents. This is due to several factors, including the difficulties of identifying suitable ...antifungals that target the fungal cell without damaging host cells, and the reduced rates of diagnosis of fungal infections compared with those caused by bacteria. The problem of treating fungal infections is exacerbated by an increasing incidence of antifungal resistance among human fungal pathogens. Three XF drugs (XF-73, XF-70, and DPD-207) have previously displayed innate bactericidal effects and a low propensity for microbial resistance, with XF-73 and XF-70 having a second, light-activated mechanism of action known as photodynamic therapy (PDT). In an effort to expand the repertoire of antifungal agents, this research assessed the
in vitro
activity of XF drugs via both mechanisms of action against six strains of the fungal pathogen
Candida albicans
in both planktonic and biofilm cultures. In addition, this research examined the effects of XF drug treatment on biofilms of
C. albicans
in a reconstituted human oral epithelium model. All
C
.
albicans
strains tested were susceptible to XF-73 and XF-70, with minimum inhibitory concentrations (MICs) between 0.25 µg/mL and 2 µg/mL; DPD-207 was less potent, with MICs between 4 µg/mL and 16 µg/mL, and light activation did not enhance these MICs. Complete biofilm eradication was not reported at the tested XF drug concentrations. However, live and dead staining of
C. albicans
cells in biofilms after XF drug treatment demonstrated that XF-73 and XF-70 were active against most
Candida
biofilms tested from 64 µg/mL; again, light activation did not enhance anti-biofilm activity.
Candida
biofilms were more resistant to DPD-207, with fungicidal effects occurring from 256 µg/mL. XF-73 and XF-70 reduced penetration of
C. albicans
biofilm into reconstituted human oral epithelium (RHOE) and resulted in less damage (as determined by reduced lactate dehydrogenase release) than untreated biofilms. Overall, the results highlight the potential of XF drugs as new drugs for the management of topical infections caused by
C. albicans
. Further studies are warranted on the development of XF drugs as antifungals, particularly for XF-73 and XF-70.
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