Nε-(carboxymethyl)lysine-receptor for advanced glycation end product axis is a key modulator of obesity-induced dysregulation of adipokine expression and insulin resistance.
Dysregulation of inflammatory adipokines by the adipose tissue plays an important role in obesity-associated insulin resistance. Pathways leading to this dysregulation remain largely unknown. We hypothesized that the receptor for advanced glycation end products (RAGE) and the ligand N(ε)-(carboxymethyl)lysine (CML) are increased in adipose tissue and, moreover, that activation of the CML-RAGE axis plays an important role in obesity-associated inflammation and insulin resistance. In this study, we observed a strong CML accumulation and increased expression of RAGE in adipose tissue in obesity. We confirmed in cultured human preadipocytes that adipogenesis is associated with increased levels of CML and RAGE. Moreover, CML induced a dysregulation of inflammatory adipokines in adipocytes via a RAGE-dependent pathway. To test the role of RAGE in obesity-associated inflammation further, we constructed an obese mouse model that is deficient for RAGE (ie, RAGE(-/-)/Leptr(Db-/-) mice). RAGE(-/-)/Leptr(Db-/-) mice displayed an improved inflammatory profile and glucose homeostasis when compared with RAGE(+/+)/Leptr(Db-/-) mice. In addition, CML was trapped in adipose tissue in RAGE(+/+)/Leptr(Db-/-) mice but not in RAGE(-/-)/Leptr(Db-/-). RAGE-mediated trapping in adipose tissue provides a mechanism underlying CML accumulation in adipose tissue and explaining decreased CML plasma levels in obese subjects. Decreased CML plasma levels in obese individuals were strongly associated with insulin resistance. RAGE-mediated CML accumulation in adipose tissue and the activation of the CML-RAGE axis are important mechanisms involved in the dysregulation of adipokines in obesity, thereby contributing to the development of obesity-associated insulin resistance.


Study on the Relationship Between Serum Iodine and Thyroid Dysfunctions: a Cross-Sectional Study.
The relationship between serum iodine (SIC) and thyroid dysfunctions in adults is poorly understood, and this study aimed to explore their relationship. A total of 1320 participants were included in the final analysis. We collected basic demographic information, blood, and spot urine samples to determine serological indices and iodine nutritional status. The median (IQR) of urinary iodine (UIC)/urinary creatinine (UCr), UIC, SIC were 138.1 (91.1, 207.6) μg/g, 155.8 (94.5, 211.1) μg/L, and 70.6 (59.8, 83.9) μg/L, respectively. The 90% reference ranges for UIC/UCr and SIC were 66.5-349.8 mg/g and 49.3-97.1 μg/L. SIC was positively correlated with UIC and UIC/UCr. The prevalence of overt hypothyroidism and subclinical hypothyroidism in female was significantly higher than that in male (P = 0.02, P = 0.002). In male, subjects above the upper reference value of SIC (97.1 μg/L) had a higher risk of subclinical hyperthyroidism (OR = 4.46, 95% CI: 1.29, 12.8) and overt hypothyroidism (OR = 5.59, 95% CI: 1.88, 6.42). In female, subjects below the lower reference value of SIC (49.3 μg/L) had a higher risk of overt hypothyroidism (OR = 2.18, 95% CI: 1.10, 4.06), TgAb positive (OR = 1.97, 95% CI: 1.15, 3.32) and TPOAb positive (OR = 2.48, 95% CI: 1.41, 4.26). In conclusion, serum iodine can be used as an indicator to evaluate iodine nutritional status and thyroid dysfunctions. Higher serum iodine concentration was associated with an increased risk of subclinical hyperthyroidism and overt hypothyroidism in men; lower serum iodine concentration was associated with an increased risk of overt hypothyroidism and positive TgAb and TPOAb in women.


A view on glaucoma--are we seeing it clearly?
Successful clinical management of glaucoma should not simply be about control of intraocular pressure, but must equate to correct decisions about intensifying treatment when patients are at risk of developing 'visual disability'. Yet little is known about what visual field defects, at different stages of glaucoma, specifically affect patients' abilities to perform everyday visual tasks. One way to do this is to measure patient performance in tasks in a lab setting. Another way is to ask patients themselves. The latter can be revealing and demystify views about how patients perceive the world. This short commentary highlights some of the current research in this area.


A framework to integrate EEG-correlated fMRI and intracerebral recordings.
EEG-correlated functional MRI (EEG-fMRI) has been used to indicate brain regions associated with interictal epileptiform discharges (IEDs). This technique enables the delineation of the complete epileptiform network, including multifocal and deeply situated cortical areas. Before EEG-fMRI can be used as an additional diagnostic tool in the preoperative work-up, its added value should be assessed in relation to intracranial EEG recorded from depth electrodes (SEEG) or from the cortex (ECoG), currently the clinical standard. In this study, we propose a framework for the analysis of the SEEG data to investigate in a quantitative way whether EEG-fMRI reflects the same cortical areas as identified by the IEDs present in SEEG recordings. For that purpose, the data of both modalities were analyzed with a general linear model at the same time scale and within the same spatial domain. The IEDs were used as predictors in the model, yielding for EEG-fMRI the brain voxels that were related to the IEDs and, similarly for SEEG, the electrodes that were involved. Finally, the results of the regression analysis were projected on the anatomical MRI of the patients. To explore the usefulness of this quantitative approach, a sample of five patients was studied who both underwent EEG-fMRI and SEEG recordings. For clinical validation, the results of the SEEG analysis were compared to the standard visual review of IEDs in SEEG and to the identified seizure onset zone, the resected area, and outcome of surgery. SEEG analysis revealed a spatial pattern for the most frequent and dominant IEDs present in the data of all patients. The electrodes with the highest correlation values were in good concordance with the electrodes that showed maximal amplitude during those events in the SEEG recordings. These results indicate that the analysis of SEEG data at the time scale of EEG-fMRI, using the same type of regression model, is a promising way to validate EEG-fMRI data. In fact, the BOLD areas with a positive hemodynamic response function were closely related to the spatial pattern of IEDs in the SEEG recordings in four of the five patients. The areas of significant BOLD that were not located in the vicinity of depth electrodes, were mainly characterized by negative hemodynamic responses. Furthermore, the area with a positive hemodynamic response function overlapped with the resected area in three patients, while it was located at the edge of the resection area for one. To conclude, the results of this study encourage the application of EEG-fMRI to guide the implantation of depth electrodes as prerequisite for successful epilepsy surgery.


Fabrication of magnetic covalent organic framework for effective and selective solid-phase extraction of propylparaben from food samples.
Efficient magnetic solid phase extraction using crystalline porous polymers can find important applications in food safety. Herein, the core-shell Fe3O4@COFs nanospheres were synthesized by one-pot method and characterized in detail. The porous COF shell with large surface area had fast and selective adsorption for propylparaben via π-π, hydrogen bonding and hydrophobic interactions. The extraction and desorption parameters were evaluated in detail. Under the optimized conditions, the extraction equilibrium was reached only in 5 min, the maximum adsorption capacity for propylparaben was 500 mg g-1 and the proposed Fe3O4@DhaTab-based-MSPE-HPLC-UV method afforded good linearity (4-20000 μg mL-1) with R2 (0.997), low limits of detection (0.55 μg L-1) and limits of quantification (1.5 μg L-1). Furthermore, the developed method was applied to determine propylparaben in soft drinks with the recoveries (97.0-98.3%) and relative standard deviations (0.61 to 3.75%). These results revealed the potential of Fe3O4@DhaTab as efficient adsorbents for parabens in food samples.


Incidence and profile of spinal tuberculosis in patients at the only public hospital admitting such patients in KwaZulu-Natal.
A retrospective chart review at the major provincial public hospital serving patients with spinal injuries/pathology. To determine the incidence of spinal tuberculosis (Tb) and establish the profile of these patients treated at King George V Hospital (KGV) in KwaZulu-Natal, South Africa. A total of 525 medical records for the period March 2005 to April 2006 were reviewed. Data from 104 files of Tb spine cases were categorized according to demographic details, medical conditions and length of stay in hospital. The South African mid-year 2006 census was used to calculate associations and risk rates for race, gender, adulthood, urbanization and employment and analyzed using the STATA version 9.0 statistical package. About 90% of the patients were African and 10% from other races. Females comprised 58% of the patients. The incidence of Tb spine is 1.02 per 100,000 and 3.13 per 100,000 for Africans and other races, respectively. The incidence rate is 1.17 per 100,000 females and 0.916 per 100,000 males. All the participants had a history of pulmonary Tb and 28% were human immunodeficiency virus positive. Thoracic spine was affected in 42% of the cases. About 32% presented with incomplete paraplegia. The average length of stay at this hospital for these patients was 41 days. About 20% of all patients seen for spinal conditions at KGV over the past year presented with Tb spine. A higher association between living in an urban area, adulthood (age 18+), being non-Black patients and the occurrence of spinal Tb was observed.


Orthopedic sawblades. A case study.
Surgical stainless steel sawblades are frequently used with metal templates at implant surgery, hence there is a high potential for blade damage and suboptimal bone cuts. The authors appraised currently used operating room sawblades with a comparison of their cutting efficacy. There were numerous instances of damage to the cutting teeth surfaces. At a controlled cutting speed, such blades require significantly greater force than unused blades to cut cancellous and cortical samples of bovine bone. Microscopic assessment of cancellous bone specimens cut with damaged blades revealed torn, irregular, debris-filled surfaces. Blades should be inspected for damage after each use and discarded if their condition is in doubt.


Main features of hereditary cerebral amyloid angiopathies: A systematic review.
The term Cerebral Amyloid Angiopathy (CAA) refers to a group of neurovascular disorders characterized by amyloid deposition within the walls of leptomeningeal and cortical blood vessels of the brain, with specific predilection for arterioles, and (less often) capillaries and veins. Most CAA cases in the general population are sporadic in nature, and represent primarily an age-related condition affecting individuals in the fifth decade of life and beyond. Sporadic CAA is caused by deposition of amyloid-β (Aβ), originating from proteolytic cleavage of the Amyloid Precursor Protein (APP), within the walls of cerebral small caliber vessels. However, hereditary forms of CAA have also been described, generally presenting as rare familial disorder with monogenic (predominantly autosomal dominant) inheritance patterns. Hereditary CAA forms tend to affect younger individuals, and their course and clinical progression is more severe. Studies to date primarily focused on the vascular manifestations of sporadic and hereditary CAA, chiefly symptomatic lobar Intracerebral Hemorrhage (ICH). However, in the past decade sporadic CAA has also been consistently linked to progressive neurocognitive, neurobehavioral, and neuropsychiatric symptoms. This systematic review focuses on the genetics, pathogenesis, neuroimaging, neuropathology, and clinical manifestations of hereditary CAA with specific emphasis on previously overlooked cognitive, behavioral, and psychiatric symptoms.


Enhanced Recovery Care vs. Traditional Care in Laparoscopic Hepatectomy: A Systematic Review and Meta-Analysis.
Enhanced recovery care could alleviate surgical stress and accelerate the recovery rates of patients. Previous studies showed the benefits of enhanced recovery after surgery program in liver surgery, but the exact role in laparoscopic hepatectomy is still unclear. We aimed to perform a meta-analysis to evaluate the safety and efficacy of enhanced recovery after a surgery program in laparoscopic hepatectomy. The relative studies from a specific search of PUBMED, EMBASE, OVID, and Cochrane database from June 2008 to February 2022 were selected and included in this meta-analysis. The primary outcomes included length of hospital stay, duration to functional recovery, and overall postoperative complication rate. The secondary outcomes included operative time, intraoperative blood loss, cost of hospitalization, readmission rate, Grade I complication rate, and Grade II-V complication rate. A total of six studies with 643 patients [enhanced recovery care (n = 274) vs. traditional care (n = 369)] were eligible for analysis. These comprised three randomized controlled trials and three retrospective studies. Enhanced recovery care group was associated with decreased hospital stay [standard mean difference (SMD) = -0.56, 95% confidence interval (CI) = -0.83~-0.28, p < 0.0001], shorter duration to functional recovery (SMD = -1.14, 95% CI = -1.92~-0.37, p = 0.004), and lower cost of hospitalization Mean Difference (MD) = -1,539.62, 95% CI = -1992.85~-1086.39, p < 0.00001). Moreover, a lower overall postoperative complication rate was observed in enhanced recovery care group [Risk ratio (RR) = 0.64, 95% CI = 0.51~0.80, p < 0.0001] as well as lower Grade II-V complication rate (RR = 0.55, 95% CI = 0.38~0.80, p = 0.002), while there was no significant difference in intraoperative blood loss (MD = -65.75, 95% CI = -158.47~26.97, p = 0.16), operative time (MD = -5.44, 95% CI = -43.46~32.58, p = 0.78), intraoperative blood transfusion rate [Odds ratio (OR) = 0.71, 95% CI = 0.41~1.22, p = 0.22], and Grade I complication rate (RR = 0.73, 95% CI = 0.53~1.03, p = 0.07). Enhanced recovery care in laparoscopic hepatectomy should be recommended, because it is not only safe and effective, but also can accelerate the postoperative recovery and lighten the financial burden of patients.


Minilaparotomy staging pelvic lymphadenectomy follow-up: a safe alternative to standard and laparoscopic pelvic lymphadenectomy.
Minilaparotomy pelvic lymphadenectomy (MINILAP), which utilizes a small 6-cm lower midline incision with the aid of standard retractors and instruments, was introduced in 1992 as an alternative to standard and laparoscopic pelvic lymphadenectomy. Since that time, MINILAP has been popularized by the urology community to become the procedure of choice for pelvic lymphadenectomy in patients who are at high risk for lymph-node prostate-cancer metastasis. A total of 24 patients who underwent MINILAP were followed prospectively for the assessment of perioperative morbidity. For the 15 patients who had MINILAP alone the length of hospitalization was < 1 day and the postoperative analgesic requirement was < 10 tablets of oral pain medication. All patients resumed their normal activity within 3-5 days. No acute or late complication was observed. Hence, MINILAP appears to be a safe alternative to either laparoscopic or standard pelvic lymphadenectomy.


Air Leak Management Program With Digital Drainage Reduces Length of Stay After Lobectomy.
Air leaks can impede recovery from lung resection. To help prevent and manage air leaks, we developed a comprehensive program that includes using precompression of lung staple lines, sealant, fissureless video-assisted thoracoscopic (VATS) lobectomy, a digital drainage system, and endobronchial valve placement for prolonged air leak. We assessed the effectiveness of this program on air leak duration, hospital length of stay (LOS), and chest tube duration in our high-risk veteran population. Using a prospectively maintained database, we retrospectively analyzed data from 226 patients who underwent lung resection for cancer by VATS lobectomy in a Veterans Affairs center. Patients were divided into two groups. Group A (n = 134; historical controls) underwent lobectomy from July 2009 through October 2013; group B (n = 92; intervention group) underwent lobectomy from November 2013 through July 2016 and received care per the comprehensive program. The median hospital LOS was significantly shorter in group B than in group A patients (5 days versus 6 days, respectively; p = 0.0001). Group B had a shorter median chest tube duration (2 days versus 3 days, p = 0.027). Prolonged air leak (more than 5 days) occurred in 5.4% of group B and 9.7% of group A patients (p = 0.24). Prolonged LOS (more than 14 days) was less frequent in group B (1.1%) than in group A (8.2%, p = 0.030). Multivariable analysis showed that predictors of decreased air leak duration, chest tube duration, and LOS included undergoing surgery in the later period (group B). Our comprehensive program was associated with reduced chest tube days and hospital LOS.


Energy-efficient distributed heterogeneous re-entrant hybrid flow shop scheduling problem with sequence dependent setup times considering factory eligibility constraints.
In the face of energy crisis, manufacturers pay more and more attention to energy-saving scheduling. In the paper, we consider the distributed heterogeneous re-entrant hybrid flow shop scheduling problem (DHRHFSP) with sequence dependent setup times (DHRHFSP-SDST) considering factory eligibility constraints under time of use (TOU) price, which means that each job can only be assigned to its available set of factories and all factories have different number of machines and processing capacity, and so on. To deal with DHRHFSP-SDST, a multi-objective Artificial Bee Colony Algorithm (MOABC) is proposed to optimize both the makespan and total energy consumption. For the MOABC, firstly, a hybrid initialization method is presented to initialize the population; then, due to the electricity price shows significant differences vary from periods under TOU price, the energy saving operator based on right-shift strategy is proposed to avoid processing jobs with the high electricity price without affecting the productivity; thirdly, based on the full consideration of distributed heterogeneous and factory eligibility, crossover and mutation operators, three neighborhood search operators and new food sources generation strategy are designed; lastly, extensive experiments demonstrate the effectiveness of the proposed algorithm on solving the DHRHFSP-SDST.


[Comparative analysis of incidence of main risk factors, behavior characteristics and work activity in ischemic heart disease with normolipemia and hyperlipoproteinemia type II and IV].
Examination was conducted of 180 healthy males 35 to 44 years of age, working as leading engineers, and of 174 patients with ischemic heart disease selected according to sex and occupation. A comparative analysis was made of the frequency of the main risk factors and some peculiarities of the labour activity and behaviour of patients with types II and IV hyperlipoproteinemia and those with normal lipid level. It is shown that a combination of known risk factors, behaviour peculiarities and conditions of labour activity is typical of patients with type IV hyperlipoproteinemia, which may promote the development of ischemic heart disease. Patients with normal blood lipid livel merit special attention. Additional factors contributing to the development of ischemic heart disease in these cases should be searched for.


Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib in Japanese patients with dyslipidemia.
This study evaluated the effects of anacetrapib (ANA) on lipids and safety when administered as monotherapy or in combination with atorvastatin (ATV) in Japanese patients with dyslipidemia. Patients (n = 407) were randomized equally to 1 of 10 groups: placebo, ATV 10 mg, ANA 10, 40, 100, or 300 mg once daily, and the same ANA doses in combination with ATV 10 mg. Patients were treated with study medication for 8 weeks and followed for an additional 8 weeks, during which ANA was switched to placebo. For the placebo and ANA monotherapy groups (10, 40, 100, and 300 mg), least squares mean percent changes from baseline at Week 8 for low-density lipoprotein cholesterol (LDL-C) calculated by the Friedewald equation were 3%, -12%, -27%, -32%, and -32%, respectively, and for high-density lipoprotein-cholesterol (HDL-C) were 1%, 56%, 116%, 134%, and 159%, respectively (p < 0.001 vs. placebo for all doses). All ANA doses co-administered with ATV 10 mg produced significantly greater LDL-C reductions and HDL-C increases compared with ATV 10 mg monotherapy. ANA was well tolerated, and dose-dependent relationships for adverse events were not observed across treatment groups. Changes from baseline in blood pressure and electrolytes were not significantly different between the active and control treatment groups. ANA, as monotherapy or co-administered with ATV, produced significant reductions in LDL-C and increases in HDL-C. ANA was generally well tolerated in Japanese patients with dyslipidemia.


Complications of vitreous surgery for diabetic retinopathy. I. Intraoperative complications.
One hundred seventy-nine eyes were analyzed to determine the incidence of intraoperative complications during vitrectomy for proliferative diabetic retinopathy. Inadvertent corneal epithelial defects occurred in 51 eyes (28%). The lens was removed in 42 (25%) of 170 phakic eyes. This was done through a pars plana approach. Accidental mechanical lens damage occurred in one eye, and mild pharmacologic lens damage occurred in two eyes. Some bleeding from fibrovascular tissue occurred in nearly every case, but this was controlled with diathermy except in seven eyes (4%) in which severe bleeding required premature termination of the operation. Latrogenic retinal tears occurred in 36 (20%) of the 179 eyes. Fifteen (34%) of the total of 44 retinal tears were anterior to the equator, and 11 (73%) of the 15 anterior tears were located posterior to the sclerotomy through which the vitrectomy probe was introduced. Twenty-nine (66%) of the 44 retinal tears were posterior to the equator, and 19 of the 29 occurred within 15 degrees radius of the fovea.


Serum-free culture of rat postnatal neurons derived from the dorsal motor nucleus of the vagus.
Previous studies on dorsal motor nucleus of the vagus (DMNV) neurons have mainly used in vivo animal models and in vitro brainstem slices. Primary culture of postnatal DMNV neurons in defined serum free medium has not been reported. We report a method for culture of postnatal rat DMNV neurons using serum free medium. Cultured DMNV neurons contain both Hu positive precursor cells and mature cells staining positively for microtubule associated protein 2 (MAP2) and choline acetyltransferase. Exposure of cultured DMNV neurons to glutamate (10(-7) to 10(-3)M) induced an increase in intracellular calcium concentration ([Ca(2+)](i)) in a dose-dependent manner, indicating the functional presence of glutamate receptors. Voltage-dependent calcium currents were present in cultured DMNV neurons. Active cell proliferation was demonstrated by BrdU incorporation. Upon removal of beta FGF, the percentage of MAP2 positive mature neurons was significantly increased from 36+/-3 to 73+/-3%. Our study demonstrates that postnatal rat DMNV neurons cultured in serum free medium retain morphological and physiological characteristics of DMNV neurons in situ.


Speech sounds learned by sleeping newborns.
It is not yet clear whether humans are able to learn while they are sleeping. Here we show that full-term human newborns can be taught to discriminate between similar vowel sounds when they are fast asleep. It is possible that such sleep training soon after birth could find application in clinical or educational situations.


In vitro and in vivo evaluation of cyclosporine-graphene oxide laden hydrogel contact lenses.
Drug-eluting contact lens can substitute the multiple eye drop therapy. However, loading hydrophobic drug like cyclosporine in the contact lens is very challenging, due to low drug uptake (via soaking method); and alteration in the swelling and optical properties which restricts its clinical application. To address the above issues, graphene oxide (GO, large surface area with oxygen containing functional groups) was incorporated in the contact lenses during fabrication. These GO-laden contact lenses (SM-GO-Cys) as well as blank contact lenses (SM-Cys) were soaked in the solution of cyclosporine. Alternatively, cyclosporine-laden contact lenses (DL-Cys-20) and cyclosporine-GO-laden contact lenses (DL-Cys-20-GO) were fabricated by adding drug and drug-GO (at various level of GO) during fabrication, respectively. Contact angle and swelling data showed increase in water holding capacity of GO laden contact lenses. Optical property was significantly improved due to molecular dispersion of drug on the surface of GO sheets. The drug uptake and in vitro release profile was improved with GO-laden contact lenses by soaking method (SM-GO-Cys-400n) due to hydrophobic interactions between GO and drug. Adding cyclosporine-GO (DL-Cys-20-GO-800n) during fabrication significantly improved drug release kinetics with higher drug leaching (during extraction and sterilization) due to increased swelling, improved dissolution and molecular dispersion of drug on GO sheets. Ocular irritation and histopathological studies demonstrated the safety of GO-contact lens. The in vivo drug release studies in the rabbit eye showed significant improvement in mean residence time (MRT) and area under the curve (AUC) using DL-Cys-20-GO-800n contact lens compared to eye drop solution with reduction in protein adherence value. The study demonstrated that the incorporation of GO into the contact lens can control the release of cyclosporine as well as improved the lens swelling and transmittance properties.


Microbial transformations of steroids--IV. 6,7-Dehydrogenation; a new class of fungal steroid transformation product.
Microbial steroid dehydrogenation is quite common. The reaction seems to occur mainly in bacteria and usually results in hydrogen abstraction from positions C(1)-C(2) and/or C(4)-C(5) with occasional aromatisation of ring A. We have screened large numbers of fungal cultures for their ability to monohydroxylate steroids at unusual sites and in the course of our investigations we have identified seven fungal strains capable of dehydrogenating ring B of progesterone and androstenedione at positions C(6)-C(7). Microbiological dehydrogenation at this site seems not to have been reported previously. The structures of the metabolites isolated from progesterone, and the producing fungi, are: 6-dehydroprogesterone (Botryodiplodia theobromae), 11 alpha-hydroxy-6-dehydroprogesterone (Botryosphaerica obtusa, Mucor racemosus and Nigrospora sphaerica), 12 alpha-, 15 beta- and 16 alpha-hydroxy-6-dehydroprogesterones (B. obtusa) and 14 alpha-hydroxy-6-dehydroprogesterone (Apiocrea chrysosperma) [1]. From androstenedione we isolated 6-dehydroandrostenedione (Absidia coerulea and Curvularia lunata) and 6-dehydrotestosterone (C. lunata).


Outcomes of elbow fracture-dislocations treated with and without an Internal Joint Stabilizer of the Elbow (IJS-E): A retrospective cohort study.
The internal joint stabilizer of the elbow (IJS-E) adds to techniques for maintaining reduction of elbow fracture-dislocations while allowing early motion. Literature on this device is limited to small case series. Retrospective comparison of function, motion and complications in patients who sustained elbow fracture-dislocations reconstructed with (30 patients) and without (34 patients) an IJS-E by a single surgeon. The minimum follow up was 10 weeks. The mean follow up was 16 ± 17 months. The mean final flexion arc did not differ between the two groups, however patients without an IJS achieved greater pronation. There were no differences in mean Mayo Elbow Performance, Quick-DASH and pain scores. Five patients (17%) underwent IJS-E removal. The rates of capsular releases for stiffness after 12 weeks and recurrent instability were similar. The use of an IJS-E to supplement traditional repair of elbow fracture-dislocations does not appear to affect final function or motion, and appears to be effective in reducing the risk of recurrent instability in a group of patients deemed high risk. However, its use is weighed against a 17% rate of removal at early follow up and possibly inferior forearm rotation. Retrospective Cohort study, Level 3.


Safety and efficacy of new potassium binders on hyperkalemia management in patients with heart failure: a systematic review and meta-analysis of randomized controlled trials.
Hyperkalemia leads to suboptimal use of evidence-based therapies in patients with heart failure (HF). Therefore, we aimed to assess whether new potassium binders are effective and safe to promote medical optimization in patients with HF. MEDLINE, Cochrane, and Embase were searched for randomized controlled trials (RCTs) that reported outcomes after initiation of Patiromer or Sodium Zirconium Cyclosilicate (SZC) versus placebo in patients with HF at high risk of hyperkalemia development. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random effects model. Quality assessment and risk of bias were performed according to Cochrane recommendations. A total of 1432 patients from 6 RCTs were included, of whom 737 (51.5%) patients received potassium binders. In patients with HF, potassium binders increased the use of renin-angiotensin-aldosterone inhibitors (RR 1.14; 95% CI 1.02-1.28; p = 0.021; I2 = 44%) and reduced the risk of hyperkalemia (RR 0.66; 95% CI 0.52-0.84; p < 0.001; I2 = 46%). The risk of hypokalemia was significantly increased in patients treated with potassium binders (RR 5.61; 95% CI 1.49-21.08; p = 0.011; I2 = 0%). There was no difference between groups in all-cause mortality rates (RR 1.13; 95% CI 0.59-2.16; p = 0.721; I2 = 0%) or in adverse events leading to drug discontinuation (RR 1.08; 95% CI 0.60-1.93; p = 0.801; I2 = 0%). The use of new potassium binders Patiromer or SZC in patients with HF at risk for hyperkalemia increased the rates of medical therapy optimization with renin-angiotensin-aldosterone inhibitors and reduced the incidence of hyperkalemia, at the cost of an increased prevalence of hypokalemia.


Recalled pain scores are not reliable after acute trauma.
Pain research in emergency settings can be problematic, as data collection is logistically difficult and pain levels are often poorly documented. Short-term recall of acute pain has been evaluated in postoperative, labour and procedural pain, with variable reported accuracy. The reliability of pain recall in trauma resuscitation patients is unknown. This study aims to determine the accuracy of short-term pain recall 1-2 days after trauma. Prospective, cohort study of trauma resuscitation patients transported by ambulance to a major trauma centre. Patients with haemodynamic instability (SBP<90, HR>120) or GCS<14 on arrival were excluded. Momentary pain scores were measured on an 11-point verbal numerical rating scale by paramedics during prehospital management. Patients were evaluated within 48 h of injury on the recall of their initial pain, pain during transport, and lowest pain score achieved by prehospital analgesia. Spearman's rank correlation and Bland-Altman tests were used to compare ambulance and hospital data. 88 trauma resuscitation patients (mean age 44 years ± 18 SD, male 74%, mean ISS: 7 ± 5 SD) were enrolled over a 5 month study period. Comparison of immediate and recalled pain scores produced Spearman's correlation coefficients of 0.71 for initial pain, 0.56 for pain during transport, and 0.45 for minimum pain scores. In our study patients did not accurately recall their pain levels 1-2 days after acute trauma. The results suggest that retrospective pain ratings are not reliable in trauma patients.


Sacral myolipoma with symptomatic contraction of the conus at standing on tiptoe.
We present a case with spinal myolipoma that was unique in its anatomical composition and symptomatology. An 18-year-old male presented with urinary retention and buttock pain exacerbated by standing on tiptoe underwent untethering of the low-set conus associated with a sacral fatty tract. Electrical stimulation of the spinal roots beside the upper conus induced anomalous caudal movement of the conus and contraction of the gastrocnemius muscle. In the lower conus, an ectopic muscle bridging the conus and dura was found, and the tissue contracted upon electrical stimulation. The histopathological diagnosis was myolipoma involving mature striated muscle and fat cells. Postoperatively his buttock pain was relieved immediately, but urinary retention persisted. We posit that his buttock pain, exacerbated by standing on tiptoe, was due to traction of the conus by contraction of the ectopic muscle that was aberrantly innervated from the sacral spinal roots.


[Vitamin D].
The authors write a short review on vitamin D : sources, needs, metabolism, actions, methods of dosage of vitamin D and its metabolites.


Optimised protocols for the identification of the murine cardiac side population.
Cardiac side population (CSP) cells, defined by their ability to efflux the vital dye Hoechst 33342, have been identified as putative cardiac stem cells based on their potential to give rise to both cardiomyocytes and endothelial cells. The CSP phenotype relies on an active metabolic pathway and cell viability to identify a rare population of cells and therefore technical differences in the CSP staining protocol can lead to inconsistent results and discrepancies between studies. Here we describe an established protocol for CSP identification and have optimised a protocol for CSP analysis utilizing an automated cardiac digestion procedure using gentleMACs dissociation and Hoechst 33342 staining followed by dual wavelength flow cytometric analysis.


3D N-doped carbon derived from zeolitic imidazole framework as heterogeneous catalysts for decomposition of pulp and paper mill effluent: Optimization and kinetics study.
Three specific catalysts, namely ZIF-67 (zeolitic imidazolate framework-67), Co@NCF (Co@Nitrogen-Doped Carbon Framework), and 3D NCF (Three-Dimensional Nitrogen-Doped Carbon Framework), were prepared and studied for pulp and paper mill effluent degradation using heterogeneous activation of peroxymonosulfate (PMS). Numerous characterizations, including scanning electron microscopy (SEM), X-ray diffraction (XRD), and N2 adsorption, were used to characterize the properties of three different catalysts. 3D NCF is remarkably effective at heterogeneous activation of PMS to generate sulfate radicals to degrade pulp and paper mill effluent (PPME) compared to the other as-prepared catalysts. The catalytic activity reveals a sequence of 3D NCF > Co@NCF > ZIF-67.3D NCF could degrade organic pollutants in 30 min at an initial COD concentration of 1146 mg/L of PPME, 0.2 g/L catalysts, 2 g/L PMS, and 50 °C. Consequently, it was observed that the degradation of PPME using 3D NCF followed first-order kinetics, with an activation energy of 40.54 kJ mol-1. Overall, 3D NCF/PMS system reveals promising performance for PPME removal.


Assessment of risk and economic burden of surgical site infection (SSI) posthysterectomy using a U.S. longitudinal database.
Surgical site infection posthysterectomy has significant impact on patient morbidity, mortality, and health care costs. This study evaluates incidence, risk factors, and total payer costs of surgical site infection after hysterectomy in commercial, Medicare, and Medicaid populations using a nationwide claims database. IBM MarketScan databases identified women having hysterectomy between 2014 and 2018. Deep-incisional/organ space (DI/OS) and superficial infections were identified over 6 months postoperatively with risk factors and direct infection-associated payments by insurance type over a 24-month postoperative period. Analysis identified 141,869 women; 7.8% Medicaid, 5.8% Medicare, and 3.9% commercially insured women developed deep-incisional/organ space surgical site infection, whereas 3.9% Medicaid, 3.2% Medicare, and 2.1% commercially insured women developed superficial infection within 6 months of index procedure. Deep-incisional/organ space risk factors were open approach (hazard ratio, 1.6; 95% confidence interval, 1.5-1.8) and payer type (Medicaid versus commercial [hazard ratio, 1.4; 95% confidence interval, 1.3-1.5]); superficial risk factors were payer type (Medicaid versus commercial [hazard ratio, 1.4; 95% confidence interval, 1.3-1.6]) and solid tumor without metastasis (hazard ratio, 1.4; 95% confidence interval, 1.3-1.6). Highest payments occurred with Medicare ($44,436, 95% confidence interval: $33,967-$56,422) followed by commercial ($27,140, 95% confidence interval: $25,990-$28,317) and Medicaid patients ($17,265, 95% confidence interval: $15,247-$19,426) for deep-incisional/organ space infection at 24-month posthysterectomy. Real-world cost of managing superficial, deep-incisional/organ space infection after hysterectomy was significantly higher than previously reported. Surgical approach, payer type, and comorbid risk factors contributed to increased risk of infection and economic burden. Medicaid patients experienced the highest risk of infection, followed by Medicare patients. The study suggests adoption of a robust evidence-based surgical care bundle to mitigate risk of surgical site infection and economic burden is warranted.


Who Asks About HIV/STI Status?: An Analysis of Women Who Sell Sex and Inject Drugs.
Communication about HIV and sexually transmitted infections (STI) is a cornerstone of risk reduction, yet there is a dearth of research that examines communication patterns among persons with dual risks for HIV/STI acquisition, such as women who sell sex and inject drugs (WSSID). We used logistic regression to identify factors associated with WSSID (N = 211) in Baltimore, Maryland always asking new clients about their HIV/STI status. Most WSSID were non-Hispanic White (73%) and 74% reported current homelessness. 50% of WSSID reported always asking new clients about their HIV/STI status. Experiencing depressive symptoms (adjusted odds ratio [aOR]: 0.53; 95% confidence interval [CI]: 0.29, 0.96) and having condomless sex with clients (aOR 0.31; 95% CI: 0.17, 0.57) were inversely associated with WSSID always asking new clients about their HIV/STI status. Recent entry into sex work (aOR 2.99; 95% CI: 1.30, 6.87) was positively associated with always asking new clients about their HIV/STI status. Enhancing HIV/STI communication in combination with engagement in other risk mitigation strategies may decrease disease incidence among WSSID.


The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα.
Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. This study aimed to solve this problem in view of cellular metabolism. Three recognized PPARγ agonists (synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin) were used as the tools to activate PPARγ. The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. They significantly promoted FAO in differentiating Treg cells by up-regulating the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses. Moreover, PPARγ agonists enhanced UDP-GlcNAc biosynthesis and subsequent N-linked glycosylation, but did not affect the expressions of N-glycan branching enzymes Mgat1, 2, 4 and 5. Notably, the enzyme activity of phosphofructokinase (PFK) was inhibited by PPARγ agonists and the effect was limited by siCD36 or siCPT1, implying PFK to be a link between PPARγ agonists-promoted FAO and UDP-GlcNAc biosynthesis aside from acetyl-CoA. Furthermore, PPARγ agonists facilitated the cell surface abundance of TβRII and IL-2Rα via N-linked glycosylation, thereby activating TGF-β/Smads and IL-2/STAT5 signaling, and the connection between N-linked glycosylation and Treg responses was revealed by tunicamycin. However, the increased surface abundance of CD36 was demonstrated to be mainly owing to PPARγ agonists-up-regulated overall expression. Finally, PPARγ antagonist GW9662 or CRISPR/Cas9-mediated knockout of PPARγ constrained the effects of rosiglitazone, 15d-PGJ2 and morin, confirming the exact role of PPARγ. The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα, which is beneficial for inflammatory and autoimmune diseases. Video Abstract.


Antitumor and scavenging radicals activities of some polyphenols related to dehydroabietylamine derivatives.
A novel series of polyphenols 4-9 were synthesized by the reaction of catechol with dehydroabietylamine derivatives. The antitumor activities of these compounds against L02 and HepG2 cells were investigated. Among them, compounds 4, 5, and 9 can inhibit HepG2 cells viability, but have lower inhibitory effect on L02 cells in the same concentration, indicating their potential for further development. Meanwhile, the novel series of polyphenols exhibited stronger radical-scavenging activities than the control groups.


Distinct expressions for synaptic potentiation induced by calcium through voltage-gated calcium and N-methyl-D-aspartate receptor channels in the hippocampal CA1 region.
Brief elevation in postsynaptic calcium in hippocampal CA1 neurons leads to prolonged changes in synaptic strength. The calcium may enter the postsynaptic neuron via different routes, such as voltage-gated calcium channels or glutamate receptor channels of N-methyl-D-aspartate type, and/or be released from intracellular stores. The manner in which the synapse is altered, leading to the expression of an enhanced/depressed synaptic strength, is still unclear. The present study, performed using whole-cell recording from CA1 pyramidal cells of three- to five-week-old guinea-pigs, shows that postsynaptic depolarization alone, allowing for calcium influx through voltage-gated calcium channels, leads to a synaptic potentiation characterized by an altered time-course of the evoked excitatory synaptic response, an unaltered coefficient of variation of that response and a decreased paired-pulse facilitation likely related to a postsynaptic mechanism. These characteristics contrasted with those of long-term potentiation induced via activation of N-methyl-D-aspartate receptor channels, where the time-course was unaltered, the coefficient of variation was decreased and no change in paired-pulse facilitation was observed. Synapses can thus have mechanistically separate, but co-existent, potentiations of synaptic transmission initiated from separate sources for postsynaptic calcium.


Chronic inflammatory diseases, subclinical atherosclerosis, and cardiovascular diseases: Design, objectives, and baseline characteristics of a prospective case-cohort study ‒ ELSA-Brasil.
This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.


Involvement of protein kinase C in the Ca2+-dependent vesicular release of GABA from central and enteric neurons of the guinea pig.
The involvement of protein kinase C (PKC) in the release of endogenous gamma-aminobutyric acid (GABA) was studied using slices of deep cerebellar nucleus and strips of small intestine from the guinea pig. 12-O-tetradecanoylphorbol 13-acetate (TPA), but not 4 alpha-phorbol-12,13-didecanoate (4 alpha-PDD), potentiated the high K+-evoked release of GABA from both preparations in the presence of tetrodotoxin. Ouabain evoked the release of GABA from both preparations, and this release was not altered by TPA. Therefore, the activation of protein kinase C potentiates the Ca2+-dependent vesicular release of GABA from nerve terminals of the central and enteric GABAergic neurons of the guinea pig.


Recovery from acute glucagon challenge in isolated rat hepatocytes: is protein dephosphorylation synchronous or asynchronous?
One-dimensional SDS-PAGE of cytosolic phosphopeptides confirms that glucagon promotes the phosphorylation of 11 phosphopeptides in isolated rat hepatocytes pre-equilibrated with 32PO4(3-). Nine of these phosphopeptides are tentatively identified, whereas two phosphopeptides (48 kDa and 46 kDa) remain unidentified. Transfer of the glucagon-challenged hepatocytes to medium free of 32PO4(3-) and glucagon led to the rapid net dephosphorylation of the phosphopeptides and to a rapid decline in the specific radioactivity of the [32P]ATP pool. There were profound differences between the post-glucagon rates of net dephosphorylation of the different hepatic phosphopeptides, consistent with net dephosphorylation being asynchronous during the recovery phase from acute glucagon challenge. On the basis of descending rates of dephosphorylation, four major groups of phosphopeptides were delineated. Okadaic acid, a potent inhibitor of protein phosphatase 2A and to a lesser extent protein phosphatase 1, inhibited the dephosphorylation of all of the phosphopeptides. A role for protein phosphatase 2A in protein dephosphorylation may be indicated by the observation that spermine, a specific activator of protein phosphatase 2A, stimulates the dephosphorylation of some, but not all, of the glucagon-stimulated phosphopeptides. Although phosphorylation during the recovery phase from glucagon challenge may be a complicating factor, the results suggest that post-glucagon dephosphorylation is a complex asynchronous process. The physiological consequences of this asynchrony may be that the suppression of glycogenolysis and gluconeogenesis and the activation of glycolysis are early events in the recovery process.


A crossover control study of three methods of heat acclimation on the magnitude and kinetics of adaptation.
What is the central question to the study? Are primary indices of heat adaptation (e.g., expansion of plasma volume and reduction in resting core temperature) differentially affected by the three major modes of short-term heat acclimation, that is, exercise in the heat, hot water immersion and sauna? What it the main finding and its importance? The three modes elicited typical adaptations expected with short-term heat acclimation, but these were not significantly different between modes. This comparison has not previously been made and highlights that individuals can expect similar adaptation to heat regardless of the mode used. Heat acclimation (HA) can improve heat tolerance and cardiovascular health. The mode of HA potentially impacts the magnitude and time course of adaptations, but almost no comparative data exist. We therefore investigated adaptive responses to three common modes of HA, particularly with respect to plasma volume. Within a crossover repeated-measures design, 13 physically active participants (five female) undertook four, 5-day HA regimes (60 min/day) in randomised order, separated by ≥4 weeks. Rectal temperature (Tre ) was clamped at neutrality via 36.6°C (thermoneutral) water immersion (TWI; i.e., control condition), or raised by 1.5°C via heat stress in 40°C water, sauna (55°C, 52% relative humidity), or exercise in humid heat (40°C, 52% relative humidity; ExH). Adaptation magnitude was assessed as the pooled response across days 4-6, while kinetics was assessed via the 6-day time series. Plasma volume expansion was similar in all heated conditions but only higher than TWI in exercise in the heat (ExH) (by 4%, P = 0.036). Approximately two-thirds of the expansion was attained within the initial 24 h and was moderately related to that present on day 6, regardless of HA mode (r = 0.560-0.887). Expansion was mediated by conservation of both sodium and albumin content, with little evidence for these having differential roles between modes (P = 0.706 and 0.320, respectively). Resting Tre decreased by 0.1-0.3°C in all heated conditions, and systolic blood pressure decreased by 4 mmHg, but not differentially between conditions (P ≥ 0.137). In conclusion, HA mode did not substantially affect the magnitude or rate of adaptation in key resting markers of short-term HA.


Explaining risks and benefits of loco-regional treatments to patients.
Treatment for early-stage breast cancer is complex, requiring multidisciplinary care with a multitude of treatment options available for each patient. Coupled with the rising importance of shared decision-making, patient-physician conversations are progressively more complicated. These conversations require frank disclosure of risks and benefits of the different treatment modalities in a way that is individualized for each patient and simple to understand. In most patients, breast conserving therapy with radiation should be presented as the gold-standard local treatment given similar long-term and improved quality of life outcomes. De-escalation is currently at the forefront of research in loco-regional treatments, and further investigations are required to best determine the optimal patient populations for reduced sentinel lymph node sampling, omission of sentinel lymph node biopsy altogether and omission of radiation treatment. For future trials, better endpoints need to be established considering patient-centered outcomes as well as recurrence.


Platelet release of beta-thromboglobulin within the coronary circulation during cold pressor stress.
Cold stress by increasing circulating catecholamines may sensitize blood platelets to aggregate and release their constituents. This study investigates the effect of cold stress on the release of the platelet-specific protein beta-thromboglobulin into the coronary venous blood of 12 subjects with atherosclerotic coronary artery disease (CAD) and 7 subjects with angiographically normal coronary arteries (NCA). Cold pressor stress caused a greater increase in systolic arterial pressure in patients with CAD than in subjects with NCA (p less than 0.05). There was no significant difference between the platelet counts in the arterial or coronary venous blood either before or during cold stress. Arterial beta-thromboglobulin was higher in the group with CAD (77 +/- 18 ng/ml) than in subjects with NCA (49 +/- 12 ng/ml, p less than 0.01). Although there was no arteriovenous difference of beta-thromboglobulin at rest in either group, during cold stress, coronary venous beta-thromboglobulin increased in both the NCA (53 +/- 16 to 95 +/- 26 ng/ml, p less than 0.05) and CAD groups (76 +/- 13 to 117 +/- 53 ng/ml, p less than 0.025) despite no change in arterial beta-thromboglobulin. Release of beta-thromboglobulin, although not related to the presence of angiographic arterial disease, correlated with the systolic arterial pressure during cold stress (r = 0.66) and inversely with the platelet's ability to generate cyclic adenosine monophosphate (r = 0.69). The release of platelet constituents in the coronary circulation is provoked by cold stress and may play a role in stress-induced acute coronary occlusion in patients with atherosclerotic disease and in those with apparently normal vessels.


[Cost analysis of the treatment of acute decompensated heart failure. Levosimendan versus dobutamine].
To assess whether the treatment with levosimendan is more expensive than the usual one with dobutamine, since price of medications does not usually represent the greatest expense in the treatment of cardiac decompensation. The cost of treatment of 18 inpatients with cardiac decompensation, 9 of which treated with dobutamine (dobuta group) and 9 with levosimendan (levo group), was compared. Groups were similar concerning age, sex, functional class and cardiac function. Treatment costs were similar for both groups. In the levo group, the costs with the drug were higher than in the dobuta group, but those related to the length of stay in intensive care unit and to the material used during admission were lower. Levo-drug: R$ 5,414.00; material: R$ 399.90; hospital daily rates: R$ 5,061.20; professional honorarium: R$ 3,241.80; total costs: R$ 14,117.00. Dobuta-drug: R$ 2,320.10; materials: R$ 1,665.70; hospital daily rates: R$ 6,261.90; professional honorarium: R$ 3,894.30; total costs: R$ 14,142.00. Despite the higher price of levosimendan, the global cost of the treatment was similar for patients who were treated either with dobutamine or levosimendan. Patients who were treated with levosimendan had a shorter length of stay in intensive care unit.


Rabbit anti-human leukocyte polyclonal antibody inhibits xenogeneic cell-mediated immune responses.
We studied the interactions between human monocytes and porcine endothelial cells (PEC) as well as the effects of a new generation of rabbit anti-human leukocyte polyclonal antibody (newRALG) to inhibit xenogeneic cell-mediated immune responses. Human peripheral blood mononuclear cells (PBMC) were cocultured with the florescent dye PKH-26 labeled-PEC, which showed membrane uptake by monocytes detected by florescence activated cell scanning (FACS). Scavenger receptor (SR) ligand poly-(G) or the newRALG or Thymoglobulin was added into the cocultures followed by FACS. Lymphocyte proliferation upon exposure to PEC with or without newRALG or thymoglobulin was evaluated by a xenogeneic mixed-lymphocyte-endothelial cell reaction (xMLER). FACS analysis demonstrated that CD14+ monocytes became positive for PKH-26 following their interaction with PKH-26-labeled PEC. These PKH-26+ monocytes displayed up-regulated CD40 and CD80 expression during the PBMC-PEC interaction. Furthermore, SR blockade with poly-(G) prevented PEC membrane uptake by CD14+ monocytes. The newRALG from rabbits immunized with activated human monocytes and lymphocytes greatly reduced SR-mediated PEC membrane uptake. xMLER demonstrated strong lymphocyte proliferation in response to PEC. Lymphocyte proliferation was dramatically inhibited in dose-dependent manner by the newRALG. In summary, monocytes up-regulate costimulatory molecules during xenogeneic interactions, indicating that they may serve as a source of T-cell costimulation during xenogeneic reactions, enguling PEC membranes. This phenomenon was inhibited by poly (G), suggesting that PEC membrane uptake was via SR. The newRALG inhibited monocyte SR-mediated PEC membrane uptake and lymphocyte proliferation in response to PEC suggesting that this new polyclonal preparation may impair the initiation of xeno-specific immune responses.


The Nesbit operation for Peyronie's disease: 16-year experience.
We analyze the long-term outcome of the Nesbit operation for the correction of the penile deformity due to Peyronie's disease. Between 1977 and 1992, the penile deformity due to Peyronie's disease was corrected in 359 patients using the Nesbit operation. The overall success rate was 82%, which increased to 90% during the last 8 years with better patient selection due to improved preoperative investigation. Complications were minimal and only 6 patients had significant penile shortening that precluded sexual intercourse. The Nesbit operation remains the procedure of choice to correct the penile curvature of Peyronie's disease.


Precipitate labour.
In Turku University Central Hospital there were 4976 deliveries in the years 1974--75. Among them there were 106 spontaneous, nonaugmented labours with a duration of two hours or less, giving an incidence of 2.1% precipitate labour. The most important aetiological factor was multiparity. 35% of precipitate labours commenced with spontaneous rupture of the membranes. The incidence of prematurity after precipitate labour was 8.5% and thus significantly (p less than 0.05) higher than in a control group, where mothers were matched according to age and parity. After precipitate labour the newborn fared as well as those in the control groups. It is our conclusion therefore, that precipitate labour need not be considered as an intrapartum risk factor, when neonatal well-being is considered.


How good are support vector machines?
Support vector (SV) machines are useful tools to classify populations characterized by abrupt decreases in density functions. At least for one class of Gaussian data model the SV classifier is not an optimal one according to a mean generalization error criterion. In real world problems, we have neither Gaussian populations nor data with sharp linear boundaries. Thus, the SV (maximal margin) classifiers can lose against other methods where more than a fixed number of supporting vectors contribute in determining the final weights of the classification and prediction rules. A good alternative to the linear SV machine is a specially trained and optimally stopped SLP in a transformed feature space obtained after decorrelating and scaling the multivariate data.


Mutagenic and clastogenic activity of nitracrine analogues in cultured V79 Chinese hamster cells.
Nitracrine is used clinically as an antitumour agent, and analogues are actively being developed in some laboratories. The mutagenic activity of 9-[(3-dimethylaminopropyl)amino]-acridine and its 1-nitro (nitracrine), 2-, 3- and 4-nitro derivatives was evaluated at the 6-thioguanine and ouabain resistance loci in cultured Chinese hamster fibroblasts (V79-171b cell line). The des-nitro, 2- and 3-nitro caused no statistically significant mutagenic activity at either locus. Each of these 3 compounds weakly increased (approximately 2-fold) the incidence of micronuclei in the same cell line when tested at cytotoxic doses. Both the 1- and 4-nitro compounds increased the incidence of 6-thioguanine resistant cells from around 1 in 10(-6) to approximately 1 in 10(-4). The former compound significantly increased the frequency of ouabain-resistant cells. Both of these compounds were potent inducers of micronuclei in V79-171b cells, indicating high clastogenic activity. It would appear prudent to regard both of these compounds as potential human carcinogens.


The Future of Ischemic Stroke Diagnosis and a Review of Underrecognized Ischemic Stroke Etiologies.
Accurate ischemic stroke etiologic determination and diagnosis form the foundation of excellent cerebrovascular care as from it stems initiation of the appropriate secondary prevention strategy as well as appropriate patient education regarding specific risk factors for that subtype. Recurrent stroke rates are highest among those patients who receive an incorrect initial stroke diagnosis. Patient distrust and patient reported depression are also higher. The cause of the ischemic stroke also informs predicted patient outcomes and the anticipated recovery trajectory. Finally, determining the accurate cause of the ischemic stroke provides the patient the opportunity to enroll in appropriate research studies studying mechanism, or targeting treatment approaches for that particular disease process. Advances in ischemic stroke research, imaging techniques, biomarkers, and the ability to rapidly perform genetic sequencing over the past decade have shown that classifying patients into large etiologic buckets may not always be appropriate and may represent one reason why some patients are labeled as cryptogenic, or for whom an underlying etiology is never found. Aside from the more traditional stroke mechanisms, there is new research emerging regarding clinical findings that are not normative, but the contributions to ischemic stroke are unclear. In this article, we first review the essential steps to accurate ischemic stroke etiologic classification and then transition to a discussion of embolic stroke of undetermined source (ESUS) and other new entities that have been postulated as causal in ischemic stroke (i.e., genetics and subclinical atherosclerosis). We also discuss the limitations that are inherent in the current ischemic stroke diagnostic algorithms and finally review the most recent studies regarding more uncommon diagnoses and the future of stroke diagnostics and classification.


Antidromic mapping of descending axons of respiratory bulbospinal neurons in the nucleus tractus solitarius of the rabbit.
Antidromic mapping of the descending axons of the respiratory bulbospinal neurons in the region of the nucleus tractus solitarius (NTS) was performed on rabbits anesthetized with urethane. Among 177 units tested, 29 out of 87 inspiratory (I), 27 out of 84 expiratory (E) and 2 out of 6 phase-spanning units were identified as bulbospinal. A prominent feature of the bulbospinal pathway from the NTS in the rabbit is the abundance of ipsilateral descending axons. The axons rising from one side are situated in the ventrolateral and ventral funiculi of both sides. The axonal conduction velocities are about 25-35 m/s. Both I and E bulbospinal neurons can be divided into R alpha and R beta types according to 'no I inflation' and 'maintained E inflation' tests.


Uterine smooth muscle tumor analysis by comparative genomic hybridization: a useful diagnostic tool in challenging lesions.
The diagnosis and management of uterine smooth muscle tumors with uncertain malignant potential (STUMP) is often challenging, and genomic data on these lesions as well as on uterine smooth muscle lesions are limited. We tested the hypothesis that genomic profile determination by array-CGH could split STUMP into a benign group with scarce chromosomal alterations akin to leiomyoma and a malignant group with high chromosomal instability akin to leiomyosarcoma. Array-CGH genomic profile analysis was conducted for a series of 29 cases of uterine STUMP. A group of ten uterine leiomyomas and ten uterine leiomyosarcomas served as controls. The mean age was 50 years (range, 24-85) and the follow-up ranged from 12 to 156 months (average 70 months). Since STUMP is a heterogenous group of tumors with genomic profiles that can harbor few to many chromosomal alterations, we compared genomic indices in leiomyomas and leiomyosarcomas and set a genomic index=10 threshold. Tumors with a genomic index <10 were classified as nonrecurring STUMPs and those with a genomic index >10 represented STUMPs with recurrences and unfavorable outcomes. Hence, the genomic index threshold splits the STUMP category into two groups of tumors with different outcomes: a group comparable to leiomyomas and another similar to leiomyosarcomas, but more indolent. In our STUMP series, genomic analysis by array-CGH is an innovative diagnostic tool for problematic smooth muscle uterine lesions, complementary to the morphological evaluation approach. We provide an improved classification method for distinguishing truly malignant tumors from benign lesions within the category of STUMP, especially those with equivocal morphological features.


A non-contact vital sign monitoring system for ambulances using dual-frequency microwave radars.
We developed a novel non-contact monitoring system to measure the vital signs of casualties inside a moving ambulance. This system was designed to prevent exposure of patients to infectious organisms under biochemical hazard conditions. The system consists of two microwave radars: a 10-GHz respiratory-monitoring radar is positioned 20 cm away from the surface of the isolator. The 24-GHz cardiac-monitoring radar is positioned below the stretcher underneath the isolator. The subject (22.13 +/- 0.99 years) was placed inside the isolator on a stretcher in the simulated ambulance. While the ambulance was in motion at a speed of approximately 10 km/h, the heart rates determined by the cardiac-monitoring radar correlated significantly with those measured by ECG (r = 0.69, p < 0.01), and the respiratory rates derived from the respiratory-monitoring radar correlated with those measured by the respiration curves (r = 0.97, p < 0.0001). The proposed system appears promising for future on-ambulance monitoring of the vital sign of casualties exposed to toxins.


A ten-gene signature-based risk assessment model predicts the prognosis of lung adenocarcinoma.
Lung adenocarcinoma (LUAD) is a major cause of cancer death. Therefore, identifying potential prognostic risk factors is critical to improve the survival of patients with LUAD. Here, relevant datasets were downloaded from TCGA and GEO databases to screen the differentially expressed genes (DEGs). Univariate Cox analysis, LASSO regression analysis and multivariate Cox analysis were conducted on the DEGs combined with TCGA clinical data, and finally a risk assessment model based on 10 feature genes was constructed. The prognosis of patients was evaluated after the patients were grouped based on the median risk score and the results showed that the survival time of patients in the high-risk group was significantly shorter than that in the low-risk group. ROC analysis showed that the AUC values of the 1, 3, 5-year survival were 0.753, 0.724, and 0.73, respectively, indicating that the model was precise in predicting the prognosis, which was also verified in the external dataset GSE72094. In addition, a significant correlation was found between the risk score and the clinical stages of LUAD, that is, a later stage always corresponded to a higher risk score. Then, we performed survival analysis on the 10 feature genes independently in the TCGA-LUAD dataset through the GEPIA database, finding that the high expression of 6 genes (COL5A2, PLEK2, BAIAP2L2, S100P, ZIC2, SFXN1) was associated with the poor prognosis of LUAD patients. To sum, this study established a 10-gene risk assessment model and further evaluated its value in predicting LUAD prognosis, which provided a new method for the prognosis prediction of LUAD.


Anatomic variations of brachial and lumbosacral plexus models in different rat strains.
Selection of an appropriate model for preclinical assessment of new methods of peripheral nerve injury management is crucial. This report presents anatomic variations within brachial and lumbosacral plexuses in three selected rat strains Sprague Dawley (Hsd:Sprague Dawley SD), Lewis (LEW/SsNHsd), and Athymic Nude (Hsd:RH-Foxn1rnu ) rats. Based on their strain eighteen rats were divided into three groups. A total of 90 brachial plexus nerves (axillary, musculocutaneous, median, ulnar, and radial nerves) and 72 lumbosacral plexus nerves (sciatic, tibial, common peroneal, and sural nerves) were analyzed for the length, diameter and correlation with the body weight. A detailed anatomic course of each nerve within the brachial and lumbosacral plexuses was outlined. The sural nerve was the longest nerve in all studied rat strains, whereas the sciatic nerve had the largest diameter. Comparison of all the nerves' length demonstrated that the Lewis rat sciatic and sural nerves were significantly shorter (P < 0.05). No significant differences in nerve diameters were found among the analyzed rat strain groups. Significant correlation was revealed between the length of sciatic nerve and the rats' weight, which is irrelevant to the rats' genetic background. This study confirmed that nerves' length within rat's brachial and lumbosacral plexus depends on the inter-individual variations within the rat strains rather than on the differences in the peripheral nerve development, which is inherent to the specific rat strain. Correlation between the nerve length and body weight, suggests that bigger rats should be considered for studies requiring access to the long nerves. © 2016 Wiley Periodicals, Inc. Microsurgery 37:327-333, 2017.


Predictive value of low interleukin-33 in critically ill patients.
Patients admitted to a medical intensive care unit (ICU) are characterized by an activated immune system and exhibit a high mortality rate irrespective of the underlying cause of admission. Interleukin (IL)-33 has been shown to be protective in experimental sepsis models and it has been demonstrated that circulating levels of its "decoy" receptor soluble ST2 (sST2) are associated with outcome in critically ill patients. The aim of the present study was to investigate whether circulating IL-33 is associated with 30-day mortality in patients admitted to a medical ICU. In this prospective, observational study, both IL-33 and sST2 levels were assessed in 223 consecutive patients at ICU admission using specific enzyme-linked immunosorbent assays (ELISAs). During the 30-day follow-up, 58 patients (26%) died. Circulating IL-33 was detectable in 166 patients and in 57 patients, serum IL-33 was below the detection limit. Both detectable IL-33 and sST2 below the median were strong predictors of survival in critically ill patients independent of acute physiology and chronic health evaluation II (APACHE II) score. IL-33 and sST2 predicted risk independent from each other. Patients with both, non-detectable levels of IL-33 and sST2 levels above the median, showed a dramatically increased mortality risk (HR 6.9 95% CI 3.0-16.2; p<0.001). Low levels of IL-33 and increased levels of sST2 predict mortality risk in critically ill patients independent from each other and APACHE II score. Both together showed additive predictive value suggesting a pathogenic role of the IL-33/ST2 system in critically ill patients.


Calibration of the viscometric glucose sensor before its use in physiological liquids--compensation for the colloid-osmotic effect.
The function of the recently described viscometric affinity sensor (VAS), which measures glucose due to its strong effect on the viscosity of a sensitive liquid containing Concanavalin A (ConA) and dextran, was analysed for osmotic and colloid-osmotic effects on the glucose reading. The suction of low- and high-molecular weight osmotica on the membrane of the microdialysis fibre was measured using a membrane osmometer built from the microdialysis probe of the VAS. The reduction of the sensor read-out in blood plasma can be completely explained by a change in small osmotic volume fluxes through the dialysis membrane, which affect the ConA concentration and the viscosity after the flow of the sensitive liquid through the dialysis probe. The measuring error could be prevented by the presence of the polyethylene glycol 6000 at an isotonic concentration in the glucose standard solutions used for sensor calibration.


A comparison of four light traps for collecting Culicoides biting midges.
Epidemiological analyses of vector-associated diseases such as bluetongue (BT), African horse sickness, or epizootic hemorrhagic disease require substantiated data on the species diversity and activity patterns of vector species. To this end, Spain and Italy implemented extensive Culicoides biting midge monitoring programs since 2000, as several other countries did after the arrival of BT in northern Europe in 2006. The seasonal occurrence, spatial distribution, and abundance of Culicoides species, as the major results of such monitoring programs, are used as parameters for assessing the risk of virus introduction and transmission in a given area. However, the quality of entomological monitoring results fundamentally depends on the collection techniques. In this publication, we describe a Latin Square design trial carried out in Germany under field conditions in 2009/2010 to compare the efficacy of four commonly used light baited/suction traps in collecting Culicoides. A total of 2651 Culicoides were caught over 18 nights. In both years, the Onderstepoort and BG-Sentinel traps caught significantly more Culicoides than the Rieb and the CDC trap. Most specimens were caught by the Onderstepoort trap (1246, i.e., 76 % in 2009 and 819, i.e., 82 % in 2010). Most were classified as midges of the Culicoides obsoletus group.


A new microporous oxyfluorinated titanium(IV) phosphate as an efficient heterogeneous catalyst for the selective oxidation of cyclohexanone.
Designing a new porous nanomaterial for eco-friendly catalytic reactions is very challenging. Here, a new crystalline microporous oxyfluorinated titanium phosphate material (TIPO-1) has been synthesized under hydrothermal conditions in the absence of any structure directing agent. The triclinic crystalline phase with the unit cell parameters a=7.962Å, b=10.006Å, c=13.979Å, α=96.921°, β=95.851° and γ=93.760° has been indexed for TIPO-1 and it has been characterized through powder X-ray diffraction, nitrogen adsorption/desorption, XPS, FT-IR, 31P MAS NMR spectroscopy, UHR-TEM, FE-SEM and TGA/DTA analysis. The material exhibited excellent catalytic activity in liquid phase partial oxidation of cyclohexanone to adipic acid (up to 92% conversion) in the presence of aqueous H2O2 as oxidant together with value added side products like 1,6-hexandial and ε-caprolactone for reactions in different solvents. The material showed excellent recycling efficiency for six consecutive reaction cycles without any significant loss in catalytic activity.


TRPV5 and TRPV6 in Ca(2+) (re)absorption: regulating Ca(2+) entry at the gate.
Many physiological functions rely on the exact maintenance of body Ca(2+) balance. Therefore, the extracellular Ca(2+) concentration is tightly regulated by the concerted actions of intestinal Ca(2+) absorption, exchange of Ca(2+) to and from bone, and renal Ca(2+) reabsorption. Renal distal convoluted and connecting tubular cells as well as duodenal epithelial cells are unique in their ability to mediate transcellular (re)absorption of Ca(2+) at large and highly variable rates. Two members of the transient receptor potential (TRP) superfamily, TRP vanilloid (TRPV)5 and TRPV6, are specialized epithelial Ca(2+) channels responsible for the critical Ca(2+) entry step in transcellular Ca(2+) (re)absorption in intestine and kidney, respectively. Because transcellular Ca(2+) transport is fine-tuned to the body's specific requirements, regulation of the transmembrane Ca(2+) flux through TRPV5/6 is of particular importance and has, therefore, to be conspicuously controlled. We present an overview of the current knowledge and recent advances concerning the coordinated regulation of Ca(2+) influx through the epithelial Ca(2+) channels TRPV5 and TRPV6 in transcellular Ca(2+) (re)absorption.


Brief presentation of the story and present status of studies of the vertebrate cholinergic system.
This year marks the seventieth anniversary of Otto Loewi's demonstration of chemical transmission generally and autonomic cholinergic transmission specifically and the fortieth anniversary of John Eccles's proof of the existence of central cholinergic transmission. Following these epochal findings, the subsequent studies of the cholinergic system led to discoveries of similarly important phenomena. This review concerns these phenomena, including chemical structure and molecular biology of cholinergic receptors; electrophysiologic and ionic aspects of pre- and postsynaptic cholinergic events; the quantal expression of cholinergic postsynaptic events and activities of their subunits, the elementary events; second messengers and G proteins; synthesis, storage and release of acetylcholine; cholinesterases, anticholinesterases, and war gases; central cholinergic pathways; central cholinergic functions, behaviors, cholinergic EEG and REM sleep; cholinergic ontogeny and teratology; trophic phenomena; and the clinical aspects of the cholinergic system. This review refers to the history as well as the present status of each of these phenomena; furthermore, it describes briefly the nineteenth-century work with calabar bean, pilocarpine, muscarine, and nicotine, that is, the work performed before the promulgation of the cholinergic era.


Determination of the internal morphology of poly (D,L-lactide) microspheres using stereological methods.
The morphological characteristics of the internal structure of poly (D,L-lactide) microspheres have been determined by stereological methods in two different formulations of microspheres, with different internal structures, prepared by using a double emulsion method. In one formulation the internal emulsion was produced by homogenisation at 3000 rpm, whilst the other was prepared at 11000 rpm. As expected the formulation prepared at the lower speed contained larger and more broadly distributed pores than that prepared at the higher speed. The porosity, pore size distribution and total internal surface area of the microspheres were obtained by stereological methods from electron microscopic measurements of the sectioned microspheres. It was found that whilst the porosity of the microspheres was 0.6 in both formulations, the preparation method gave rise to large differences in their pore size distribution characteristics. The pore size distribution was simulated by computer modelling to validate and compare alternative stereological algorithms. It was found that the Saltykov unfolding method predicts the measured pore size distribution more accurately than the Cruz-Orive unfolding method (at significance level alpha=0.1). This finding was attributed to the violation of one of the basic assumptions of the Cruz-Orive unfolding method.


Can the impingement test predict outcome after arthroscopic subacromial decompression?
The impingement test, placement of local anesthetic in the subacromial space, is considered a useful tool in diagnosing impingement syndrome. The purpose of this study was to examine the predictive value of the impingement test with respect to outcome after arthroscopic subacromial decompression. Fifty-five patients who had a preoperative impingement test were evaluated at 3 and 12 months postoperatively. We noted 88% satisfactory results in patients in whom the impingement test was positive, with only 63% satisfactory results at 3 months and 60% satisfactory results at 12 months in patients in whom the impingement test was negative. Although workers' compensation patients tended to have lower scores than others, the impingement test result was more predictive of outcome than was compensation status. Impingement test results and preoperative American Shoulder and Elbow Surgeons scores were independent predictors of postoperative American Shoulder and Elbow Surgeons scores. Our evidence indicates that the impingement test can be used as a predictor of outcome for patients with impingement syndrome treated by arthroscopic subacromial decompression.


Resveratrol as MDR reversion molecule in breast cancer: An overview.
Breast cancer is the most common cause of cancer mortality among women worldwide; therefore, a strategy to defeat breast cancer is an extremely important medical issue. One of the major challenges in this regard is multidrug resistance (MDR). Resveratrol, a well-known phytoestrogen, may be helpful as part of an overall strategy to defeat breast cancer. The mixed agonist and antagonist role of resveratrol for the estrogen receptor makes it a controversial but interesting molecule in cancer therapy, especially in hormone dependent cancers. Several in vitro investigations have suggested that resveratrol can reverse multidrug resistance. However, poor bioavailability of resveratrol is a potential limitation for resveratrol treatment and cancer outcome in vivo. Fortunately, combination therapy with other selected compounds improves resveratrol's bioavailability and/or a delay in its metabolism. This review summaries the available published literature dealing with the effects of resveratrol on multidrug resistance in cancer and more specifically, breast cancer.


Regulation by dietary essential fatty acid balance of tumor necrosis factor production in mouse macrophages.
Increasing the dietary alpha-linolenate (18:3n - 3)/linoleate (18:2n - 6) ratio results in an increase in lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) production in mouse resident and casein-induced peritoneal macrophages [3]. We found that prostaglandin E2 (PGE2) production is inversely related to TNF production and that indomethacin abolishes the effect of changing the essential fatty acid balance in resident macrophages. The resident macrophages enriched in n - 3 did not produce a significant amount of PGE3. Accordingly, the decreased production of PGE2 appears to be a major negative regulatory factor for enhancement of TNF production in the n - 3 enriched resident macrophages. In casein-induced macrophages the situation is more complex. Indomethacin decreased PGE2 production and increased TNF production; however, the differences in TNF production between the n - 6 enriched and n - 3 enriched macrophages were not completely abolished by indomethacin treatment. Lysosomal acid phosphatase activity, a marker of activation/maturation stages, was elevated in the n - 3 enriched compared to the n - 6 enriched casein-induced macrophages but was similar in the resident macrophages of the two dietary groups. Expression of CD14, which is a receptor for LPS, was not different in casein-induced macrophages of the two dietary groups. Thus, the differences in production of TNF between the n - 3 and n - 6 enriched resident macrophages can be accounted for mostly by a difference in the production of a negative feedback effector, PGE2. However, a significant portion of the TNF production in casein-induced macrophages is regulated by a factor(s) other than PGE2 and LPS receptor; advanced activation/maturation stages induced by the diet high in alpha-linolenate may underlie the enhanced TNF production in casein-induced macrophages.


Inactivation of Listeria monocytogenes ATCC 7644 on fresh-cut tomato using nisin in combinations with organic salts.
The inhibition of Listeria monocytogenes ATCC 7644 on fresh-cut tomato was investigated using nisin alone, and in combinations with organic salts. Nisin at a concentration of 5000UI/mL was introduced alone or in combination with an organic salt (sodium citrate or sodium acetate each at 3 and 5g/100mL each) on fresh-cut tomato previously inoculated with 10(8)CFU/mL of L. monocytogenes ATCC 7644. Chlorine at 200ppm was used as a control. The inoculated samples were incubated at different temperatures (4, 10 and 25°C) and examined at 0, 24, 48 and 72h. The effects of the antimicrobial treatments on quality parameters of tomato (pH, soluble solids, titratable acidity and vitamin C) were also evaluated, and colour parameters were observed at the lowest storage temperature for 10 days. Both nisin and the organic salts inhibited growth of L. monocytogenes, but the combinations of two compounds were more effective. The nisin-sodium citrate (5%) combination was significantly (p≤0.05) effective, while chlorine was least effective against L. monocytogenes. The quality parameters were substantially retained, especially at 4°C, suggesting good shelf stability at a low temperature. These results substantiate the use of the cheap and eco-friendly approach to reducing this pathogen of health concern in common fresh produce.


Genome-wide association study and genetic mapping of BhWAX conferring mature fruit cuticular wax in wax gourd.
Wax gourd [Benincasa hispida (Thunb) Cogn. (2n = 2x = 24)] is an economically important vegetable crop of genus Benincasa in the Cucurbitaceae family. Fruit is the main consumption organ of wax gourd. The mature fruit cuticular wax (MFCW) is an important trait in breeding programs, which is also of evolutionary significance in wax gourd. However, the genetic architecture of this valuable trait remains unrevealed. In this study, genetic analysis revealed that the inheritance of MFCW was controlled by a single gene, with MFCW dominant over non-MFCW, and the gene was primarily named as BhWAX. Genome-wide association study (GWAS) highlighted a 1.1 Mb interval on chromosome 9 associated with MFCW in wax gourd germplasm resources. Traditional fine genetic mapping delimited BhWAX to a 0.5 Mb region containing 12 genes. Based on the gene annotation, expression analysis and co-segregation analysis, Bhi09G001428 that encodes a membrane bound O-acyltransferase (MBOAT) was proposed as the candidate gene for BhWAX. Moreover, it was demonstrated that the efficiency of a cleaved amplified polymorphic sequences (CAPS) marker in the determination of MFCW in wax gourd reached 80%. In closing, the study identified the candidate gene controlling MFCW and provided an efficient molecular marker for the trait in wax gourd for the first time, which will not only be beneficial for functional validation of the gene and marker-assisted breeding of wax gourd, but also lay a foundation for analysis of its evolutionary meaning among cucurbits.


Sequence and in vitro expression of the phosphoprotein gene of avian pneumovirus.
The phosphoprotein (P) gene of two subgroup A strains of avian pneumovirus comprised 855 nucleotides containing only one substantial open reading frame encoding a protein of 278 amino acids, with a predicted M(r) of 30,323. In vitro translation of P mRNA in a wheat germ system resulted in the synthesis of two polypeptides of M(r) 35,000. Comparison of the deduced P protein sequence with that of the known mammalian pneumoviruses revealed overall amino acid identities ranging from 31 to 34.5%, suggesting a distant relationship. However, there was a much higher identity (63.2-68.4%) in a region of 57 residues, which included a heptad repeat sequence.


Enantioselective direct aldol-Tishchenko reaction: access to chiral stereopentads.
[reaction: see text] The aldol-Tishchenko reaction of aromatic aldehydes in the presence of titanium(IV) tertbutoxide and amino alcohols is described. When used with cinchona alkaloids, stereopentads were isolated for the first time with a high degree of diastereo- and enantioselectivity.


In Vitro Filaricidal Properties of Hydro-Methanolic Extracts of Powdery Fractions of Khaya senegalensis (Meliaceae) on Onchocerca ochengi.
Onchocerciasis is a neglected tropical disease that remains endemic in sub-Saharan African countries. Unfortunately, only a few microfilaricidal agents have been approved so far. This study aimed to assess the in vitro macro and microfilaricidal potentialities of the hydro-methanolic extracts of the different powdery fractions of Khaya senegalensis against Onchocerca ochengi. Adult male worms and microfilariae (mf) of O. ochengi were isolated from cowhides in Ngaoundere II, Cameroon. Parasites were incubated for 4 h (mf) or 48 h (adult worms) in RPMI-1640 medium in the presence or absence of ivermectin, flubendazole, or hydro-methanolic extracts of different plant powdery fractions obtained by controlled differential sieving. The filaricidal effect was evaluated using motility (mfs) and mortality tests (worms) and oxidative stress parameters. Cytotoxicity and acute toxicity tests were performed on monkey-derived kidney cell lines (LLC-MK2) and Swiss albino mice, respectively, and selectivity indexes were determined. Phytochemical screening was also carried out using high-performance liquid chromatography/UV (HPLC/UV), molecular networking, and through quantification of phenolic contents. The hydro-methanolic extracts of 0-63 µm fractions from leaves and barks exhibited the strongest macrofilaricidal activities with lethal concentrations 50 of 162.4 and 208.8 µg/mL respectively versus 22.78 µg/mL for flubendazole. These two fractions also showed the fastest microfilaricidal activities (T1/2 of 1 h), although it was low when compared to ivermectin (T1/2 < 1 h). Their macrofilaricidal effects were accompanied by a significant inhibition of nitric oxide secretion and a significant increase of glutathione and catalase activity compared to the untreated group. However, no effect was found on superoxide dismutase activity, the GABAergic and glutamatergic receptors. Although neither extract was toxic to Swiss mice until a dose of 2000 mg/kg body weight, the 0-63 µm leaf fraction hydro-methanolic extract was selectively more effective on worms than bark extract (SI = 1.28 versus 0.34). Both extracts were found to contain some flavonoids including procyanidin-, rutin-, myricetin-, and naringenin derivatives as well as new unknown compounds. However, the total polyphenol, flavonoid and tannin contents of the leaf extract were significantly greater (P < 0.05) than that of the bark extract. These results support the anti-filarial effect of K. senegalensis leaves and highlight stress oxidative markers as new therapeutic targets in O. ochengi. Further, in vivo experiments are required in understanding their anti-parasitic properties, and testing combinations of fine fractions.


Advertising and availability of 'obesogenic' foods around New Zealand secondary schools: a pilot study.
To examine the extent and content of outdoor food advertisements and food availability from outlets in the vicinity of secondary schools. The sample of schools (n=10) was randomly selected from a sample frame of schools in both an urban and rural region (Wellington and Wairarapa regions respectively) and at each extreme of the socioeconomic status (SES) distribution (based on school characteristics). An area of 1-km radius around the schools was examined for food and non-food product advertisements and shops/outlets. Out of 1408 outdoor advertisements for products, 61.5% were for food (i.e. 28 per square kilometre). The major categories were soft drinks (21.6%), frozen confectionary (16.2%), savoury snacks (11.4%), and alcohol (8.1%). Overall, 70.2% of food advertisements were for foods classified as 'unhealthy' (i.e. inconsistent with the national nutritional guidelines for adolescents). A majority of the 224 outlets sold food (i.e. 56.3%). Those that primarily sold food were (on average) closer than other outlets to the secondary schools (p=0.03). Out of those schools that sold meals, the proportion of these that advertised a salad option was significantly lower in the low SES neighbourhoods (p=0.006). Other significantly different patterns for food outlet distribution, and category of advertised food were found by SES and rurality. Although only a pilot study, the information obtained suggests that food advertising and food outlets are prevalent in the vicinity of secondary schools and that the advertising is generally not compatible with nutritional guidelines for adolescents. Larger studies into such advertising are needed as well as consideration of policy options to control aspects of the 'obesogenic environment.'


Meibography: A review of techniques and technologies.
Meibomian glands play a significant role in tear production by contributing lipids to the superficial tear film.(1) Dysfunction of the meibomian glands destabilizes tears resulting in evaporative dry eye.(2,3) Historically, the meibomian glands were assessed in an ex vivo fashion through histologic studies. However, innovations in ocular imaging have advanced significantly in recent decades to include meibography. Meibography is an imaging study developed 35 years ago exclusively for the purpose of observing the morphology of meibomian glands in vivo.(4,5) In this review of meibography, we briefly describe the etiology of meibomian gland dysfunction and then discuss various meibography techniques, technologies, and methods of image analysis. We close with a review of the literature, crediting various studies for the significant contributions made toward our current understanding of the meibomian glands.


Intravesical holmium laser fragmentation and removal of detached resectoscope sheath tip.
We describe a case in which the tip of a resectoscope sheath broke off in the bladder during transurethral resection of the prostate. A holmium laser was used to fragment a detached ceramic 26Fr resectoscope sheath tip, which was dislodged into the bladder during transurethral resection of the prostate. The fragments were then retrieved using grasping forceps. This procedure caused minimal trauma. The procedure represents a novel and safe approach to the intravesical fragmentation and subsequent removal of an iatrogenic foreign body from the bladder.


Physical Mobility, Social Isolation and Cognitive Function: Are There Really Gender Differences?
This study aimed to examine the mediating role of social isolation between physical mobility and cognitive function, and whether there are gender differences in the above mediating effects among Chinese older adults. This is a prospective and cohort study. We obtained data from the 2011 (Time 1, T1), 2015 (Time 2, T2) and 2018 (Time 3, T3) waves of China Health and Retirement Longitudinal Study, including 3,395 participants aged 60 years or above. Cognition was evaluated by Telephone Interview of Cognitive Status, words recall, and figure drawing, which was widely used in previous research. We used a cross-lagged model to test the hypothesis that social isolation mediated the association between physical mobility and cognitive function among Chinese older adults. The total effects of T1 physical mobility limitations on T3 cognitive function (β = -0.055, bootstrap p < 0.001) were significantly negative. Social isolation played a mediating role among both males and females (male: β = -0.008, bootstrap p = 0.012; female: β = -0.006, bootstrap p = 0.023), demonstrating that the mediating effect of social isolation between physical mobility and cognitive function was not gender specific. This study confirmed that social isolation mediated the association between physical mobility and cognitive function among both Chinese male and female older adults. These findings indicate that reversing social isolation can be a priority intervention target for cognitive decline prevention and promote successful ageing, particularly among older adults with impaired physical mobility.


Indications for laparoscopic adrenalectomy for non-functional adrenal tumor with hypertension: usefulness of adrenocortical scintigraphy.
Laparoscopic adrenalectomy is currently indicated for biochemically and clinically functional adrenal tumors and potentially malignant tumors of the adrenal glands. Non-functional adenomas greater than 5 cm in diameter of the adrenal gland are generally considered to represent potentially malignant tumors. The present study shows indications of laparoscopic adrenalectomy for non-functional adrenal tumors with hypertension in a retrospective fashion. Between 1994 and 2004, 110 laparoscopic adrenalectomies were performed at Tokushima University Hospital. All 110 patients underwent detailed endocrinological examination before surgery. Medical and operative records of these 110 patients (57 men, 53 women), including operative parameters, histopathological findings and pre- and postoperative hypertension, were reviewed. Forty-five patients underwent laparoscopic adrenalectomy for non-functional adrenal tumors, and [(131)I]6beta-iodomethyl-19-norcholest-5(10)-en-3beta-ol (NP-59) scintigraphy was performed for patients with preoperative hypertension. Mean patient age was 55.0 years (range, 22-77 years). Mean maximum tumor diameter was 42 mm (range, 20-105 mm). All adrenal tumors were removed successfully by laparoscopic surgery. Hypertension was postoperatively improved in seven of the 11 patients with preoperative hypertension, without subclinical Cushing syndrome. Importantly, all patients who improved hypertension after adrenalectomy displayed strong accumulation in adrenal tumors with visualization of the contralateral gland on NP-59 scintigraphy. Conversely, blood pressure did not improve in four patients for whom scintigraphy yielded negative results. The indication of laparoscopic adrenalectomy for non-functional adrenal tumors is generally considered for lesions more than 5 cm diameter. However, the present study suggests that laparoscopic surgery should be considered even in patients with tumors less than 5 cm in diameter, if both hypertension and accumulation in tumors on NP-59 scintigraphy are present.