Follow-up of the Post-Liver Transplantation Patient: A Primer for the Practicing Gastroenterologist.
The focus in liver transplantation in the next 10 years will likely change from preventing viral disease recurrence to minimizing the toll of rejection and fatty liver disease, minimizing the complications from immunosuppression with withdrawal strategies, and more optimal management of long-term risks, such as malignancy, cardiovascular disease, and renal failure. In addition, now that short-term results (<1 year) have improved significantly, there will be a shift toward improving long-term patient and graft survival, as well as a focus on primary care preventive strategies.


Workplace Outreach Program Improves Management of Chronic Kidney Disease.
Assess whether an employee outreach program improved management of chronic kidney disease (CKD). Participants with suspected CKD (eGFR <60 mL/min/1.73m 2 ) identified in employee health assessments in 2017 and 2018 were contacted by phone and offered physician consultation. Subsequent nephrologist visits at 11 months of follow up were compared between those who were (outreach group) and were not (control group) successfully contacted. Most CKD risk factors at baseline were similar in outreach and control groups. At the end of the follow-up, outreach participants had more than 2-fold greater incidence of visiting a nephrologist compared with controls (HR = 2.3; 95% CI 1.2-4.2, P = 0.01), after adjusting for potential confounders. Conclusions: Employee outreach program increased utilization of nephrologist care.


Spontaneous sister chromatid differentiation (SCD) and sister chromatid exchange (SCE) in mouse blastocyst chromosomes.
The phenomenon of spontaneous differentiation (without bromodeoxyuridine in the culture medium) of sister chromatids of mouse chromosomes at the blastocyst stage of embryogenesis is described. The frequency of sister chromatid exchanges in such differentiated chromosomes was calculated.


In vitro cytotoxic, antileishmanial and antifungal activities of ethnopharmacologically selected Gabonese plants.
Seventy-seven crude extracts from leaves and stem barks of 15 Gabonese plants used in traditional medicine were evaluated for their cytotoxic, antileishmanial and antifungal activities. Most of the extracts exhibited cytotoxic activities toward human monocytes, and most particularly the hydromethanolic 50% (v/v) fraction of Ganophyllum giganteum leaves (IC(50)=1.3 microg/ml) as well as the methanolic extracts of Polyalthia suaveolens, Dioscorea preussii, Augouardia letestui leaves and Cola lizae stem barks (IC(50)<5 microg/ml). The methanolic extract of Polyalthia suaveolens displayed a strong antiproliferative activity against the promastigote form of Leishmania infantum parasites and presented a good antifungal activity on all the tested strains (IC(50)<1mg/ml). This extract was divided into six fractions: fraction F6 demonstrated a cytotoxic activity stronger than those of the crude extract (IC(50)=0.6 microg/ml), fractions F4 and F5 were devoid of cytotoxicity (IC(50)>100 microg/ml) and displayed interesting antileishmanial activity against the intracellular amastigote form of the parasite (IC(50)=5.6 and 12.4 microg/ml), respectively. However, the antifungal activity observed for the crude extract could not be recovered in the corresponding fractions.


Current perceptions of 'Brazilian butt lift' (BBL) surgery in the UK: A BAAPS-led survey of BAAPS members.
The BAAPS advice against Brazilian butt lift (BBL) surgery in the UK was set in October 2018. A Delphi study conducted by BAAPS highlighted the importance of defining current practice and perceptions amongst UK surgeons, as this is currently unknown. To evaluate BAAPS members' current practice and perceptions around BBL surgery to ensure patient safety and propose better recommendations. A BAAPS-commissioned survey was emailed to all BAAPS members through an on-line link. The survey collected quantitative and qualitative information in several domains. This survey received a 44% response rate. Of 102 respondents, 32 surgeons undertook BBL surgery before the BAAPS advice to halt it. There was a wide variation in actual fat volumes injected, and in perceptions of what constituted a small or large volume. Virtually all respondents (96.9%) performed only subcutaneous fat injections. There were differences in fat harvest techniques. The majority (66.7%) felt that BAAPS should maintain its recommendation against undertaking BBL surgery until further data became available. Nearly a quarter of 102 respondents (20.6%) had been treated for BBL complications, the majority as a result of surgical tourism. The survey provides member-reported perception and experience with regard to BBL surgery in the UK. The demand for BBL surgery and its provision should be reassessed in the UK. This information will be analysed with further national and international data to better define and shape the scope of the safety of BBL surgery in the UK. BAAPS will use such data towards the production of future guidance and support for surgeons and patients.


Laparoscopic Myomectomy of a Symptomatic Uterine Leiomyoma in a 15-Year-Old Adolescent.
Although adnexal masses and ovarian torsion are common causes of acute pain in the female adolescent, fibroids are an uncommon etiology and little is reported in the literature. Because of the rarity of adolescent leiomyomas, the best surgical management is still unknown. To our knowledge, this is the first case report of a laparoscopic myomectomy in the adolescent population. The removed fibroid is one of the largest documented cases of uterine leiomyoma in adolescents. Degenerative fibroids, albeit less common, should be kept on the differential diagnosis, as a possible cause of pelvic mass and pain in the adolescent population. Fibroids in the adolescent patient, like the adult, can be managed with minimally invasive surgery with excellent clinical outcomes.


Nuclear phenomena in low-energy nuclear reaction research.
This is a comment on Storms E (2010) Status of Cold Fusion, Naturwissenschaften 97:861-881. This comment provides the following remarks to other nuclear phenomena observed in low-energy nuclear reactions aside from helium-4 make significant contributions to the overall energy balance; and normal hydrogen, not just heavy hydrogen, produces excess heat.


Growth and aflatoxin production by Aspergillus parasiticus in a medium at different pH values and with or without pimaricin.
A glucose-yeast extract-salt medium containing 0, 5, 7.5, 10, 15 or 20 micrograms pimaricin/ml with an initial pH of 3.5 or 5.5 was inoculated with Aspergillus parasiticus WB 108 and incubated at 15 degrees or 28 degrees C. The pH, weight of mycelium and amount of aflatoxin produced were determined after 3, 7, and 10 days and after 14, 21, and 30 days when incubation was at 28 degrees or 15 degrees C, respectively. Increasing the concentration of pimaricin in the medium with an initial pH of 5.5 decreased the amounts of aflatoxin B1 and G1 produced after 3 days of incubation. When the initial pH of the medium was 3.5, no growth or toxin production occurred after 3 days of incubation in the medium containing 7.5 micrograms or more of pimaricin/ml. The presence of 20 micrograms of pimaricin/ml inhibited growth and toxin production after 7 days of incubation. When cultures were incubated at 15 degrees C, there was a lag phase which extended from 9 to 16 days, and the amounts of aflatoxin produced decreased with an increasing concentration of pimaricin. Pimaricin did not completely inhibit the growth and aflatoxin production by A. parasiticus. Pimaricin, in combination with a low pH, low temperature or 4% or 6% NaCl, initially caused slow mycelial growth and low toxin production, but the mold overcame the inhibitory effects and produced substantial amounts of mycelium and toxin.


Extension of RBE-weighted 4D particle dose calculation for non-periodic motion.
Highly conformal scanned Carbon Ion Radiotherapy (CIRT) might permit dose escalation and improved local control in advanced stage thoracic tumors, but is challenged by target motion. Dose calculation algorithms typically assume a periodically repeating, regular motion. To assess the effect of realistic, irregular motion, new algorithms of validated accuracy are needed. We extended an in-house treatment planning system to calculate RBE-weighted dose distributions in CIRT on non-periodic CT image sequences. Dosimetric accuracy was validated experimentally on a moving, time-resolved ionization chamber array. Log-file based dose reconstructions were compared by gamma analysis and correlation to measurements at every intermediate detector frame during delivery. The impact of irregular motion on treatment quality was simulated on a virtual 4DCT thorax phantom. Periodic motion was compared to motion with varying amplitude and period ± baseline drift. Rescanning as a mitigation strategy was assessed on all scenarios. In experimental validation, average gamma pass rates were 99.89+-0.30% for 3%/3 mm and 88.2+-2.2% for 2%/2 mm criteria. Average correlation for integral dose distributions was 0.990±0.002. Median correlation for single 200 ms frames was 0.947±0.006. In the simulations, irregular motion deteriorated V95 target coverage to 81.2%, 76.6% and 79.0% for regular, irregular motion and irregular motion with base-line drift, respectively. Rescanning restored V95 to >98% for both scenarios without baseline drift, but not with additional baseline drift at 83.7%. The validated algorithm permits to study the effects of irregular motion and to develop and adapt appropriate motion mitigation techniques.


Reward partitioning in Capparis spp. along ecological gradient.
The genus Capparis is represented in Israel by three taxons of the section spinosa. The pollinators of the three taxa are hawkmoths, crepuscular bees of the genus Proxylocopa and various daily bees. However, the efficiency of the different pollinators is very varied with respect to the individual taxons. Hawkmoths were frequently observed as pollinators of C. spinosa var. aravensis and C. ovata, but rarely on C. spinosa var. aegyptia. All the other bees, on the other hand, were found abundantly on all three taxons, all over the country. The three taxa all provide different rewards for their particular pollinators. Bees visiting C. spinosa var. aegyptia are provided with a lot of pollen but a relatively small amount of nectar, with a low sugar content. C. spinosa var. aravensis and C. ovata (the flowers visited more by hawkmoths), have less pollen but a higher amount of nectar which has a higher concentration of sugar. In drier habitats the emphasis of the reward provided by the flowers is nectar, whilst in the Mediterranean habitats it is the pollen which is the reward, without any connection to the systematic origin of the plant.


Drug acetylation in breast cancer.
The acetylator phenotype was determined in 100 patients with breast cancer and 100 control female subjects using isoniazid. The proportion of fast acetylators in the breast cancer patients (43%) was not significantly different from the control group (43%). We conclude that acetylator phenotype is unlikely to be an important determinant of the risk of developing breast cancer.


150 years ago: First complete removal of the larynx by Theodor Billroth.
This historical vignette celebrates the first total removal of the larynx in humans, performed by Theodor Billroth 150 years ago and stresses the importance of the prior experimental study of laryngeal ablation performed in dogs by Vincent Czerny. A part of the original article, written by his assistant Carl Gussenbauer, is reproduced, to help readers immerse themselves in this operation which opened up new perspectives in the treatment of laryngeal cancer.


Osteoporosis in Frail Patients: A Consensus Paper of the Belgian Bone Club.
In this consensus paper, the Belgian Bone Club aims to provide a state of the art on the epidemiology, diagnosis, and management of osteoporosis in frail individuals, including patients with anorexia nervosa, patients on dialysis, cancer patients, persons with sarcopenia, and the oldest old. All these conditions may indeed induce bone loss that is superimposed on physiological bone loss and often remains under-recognized and under-treated. This is of particular concern because of the major burden of osteoporotic fractures in terms of morbidity, mortality, and economic cost. Therefore, there is an urgent need to appreciate bone loss associated with these conditions, as this may improve diagnosis and management of bone loss and fracture risk in clinical practice.


Use of ultrasound localization to improve results of fine needle aspiration cytology of breast masses.
A prospective randomized controlled trial of 116 patients with breast masses was conducted to compare the accuracy of 'blind' aspiration cytology performed in the clinic with aspiration cytology using ultrasound localization. The unsatisfactory aspiration cytology rate was significantly reduced by ultrasound localization (P = 0.028). This was mainly due to an improvement in the unsatisfactory rate for tumours less than 3 cm in diameter (P = 0.036). The results were influenced by the number of needle manoeuvres performed, less than 10 needle manoeuvres being associated with a 54% unsatisfactory aspiration rate compared with 25% when greater than 10 manoeuvres were performed (P = less than 0.02). One experienced aspirator in the clinic had results comparable to those achieved with ultrasound localization. It is concluded that experience and technique are the most important factors in obtaining a satisfactory aspirate from breast masses. Routine ultrasound localization prior to aspiration confers some benefit. Consideration should be given to the use of the ultrasound-assisted technique following a previous unsatisfactory aspiration, particularly if the tumour is less than 3 cm in diameter.


Epidemiology and mortality in older patients treated by reverse shoulder arthroplasty for displaced proximal humerus fractures.
Reverse shoulder arthroplasty (RSA) is rapidly becoming the preferred treatment for displaced proximal humerus fractures in older patients. However, few studies have analyzed the target population and the effect of RSA on survival, although the socioeconomic impact of this type of surgery is considerable. This was a retrospective epidemiological study of all patients with a displaced proximal humeral fracture treated by RSA in 14 public and private hospitals throughout France between 1995 and 2016. The French hospital discharge database (PMSI) was analyzed to isolate an 898-patient cohort who underwent RSA within 6 weeks of the fracture event. In 87% of cases, this was a 3- or 4-fragment fracture. We analyzed the epidemiological characteristics of the patients at the time of fracture, their survival (Kaplan-Meier estimate) and factors that may impact survival. The mean age at the time of fracture and surgery was 79 years (46-98 years). Eighty percent of the cohort was female (sex ratio: 0.18 [p=0.0042], with 21% obesity rate [BMI>30]) and 60% of patients were ASA 1-2. The most common comorbidities were cardiovascular and neurological. The survival rate after RSA was 94% at 1 year and 73% at 5years. At the latest follow-up of 19 years, 42% of patients were still alive. In 18% of cases, the patient died within the first 15 days. The presence of comorbidities (ASA score>3-4) (p<0.004) and/or cognitive disorders (p<0.0001) were risk factors for early mortality. The time to surgery, type of fracture, associated fractures and discharge destination (return home, transfer to nursing home) had no effect on postoperative mortality in our cohort. Despite being older (79 years) at the time of proximal humerus fracture, patients who underwent RSA treatment had a high survival rate (94% at 1 year, 73% at 5years), which is better than the survivorship reported after surgical treatment of femoral neck fractures (81-87% at 1 year, 38% at 5years). The presence of comorbidities (ASA>3-4) and/or cognitive disorders are risk factors for early mortality and should be taken into account to prevent early death. IV, Retrospective study.


Directed C-H Bond Functionalization: A Unified Approach to Formal Syntheses of Amorfrutin A, Cajaninstilbene Acid, Hydrangenol, and Macrophyllol.
Formal syntheses of natural products amorfrutin A, cajaninstilbene acid, hydrangenol, and macrophyllol have been accomplished on the basis of successive C-H bond functionalization of ready-stock benzoic acids. This concise strategy involves transition-metal-catalyzed directed C-H olefination, C-H hydroxylation, and acid-mediated C-H prenylation as key steps.


Effect of protein aggregates on properties and structure of rice bran protein-based film at different pH.
Rice bran protein (RBP) aggregates were prepared by heating of RBP solution at 90 °C for 4 h at pH 2, 7, or 11 and used for preparing of packaging films. The structure and properties of RBP aggregates and RBP-based films were characterized with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transmission electron microscopy, scanning electron microscope, differential scanning calorimetry, Fourier transform infrared spectroscopy and circular dichroism. The results showed formation of fibrillar, globular, and large molecular protein aggregates during the heating at pH 2, 7 and 11. The heat-aggregated RBP-based films exhibited lower opacity, moisture content, water solubility, and water vapor permeability than those of untreated RBP-based films. Also, improved mechanical and thermal properties were found for the heat-aggregated RBP-based films. In addition, the heat-aggregated RBP-based film at pH 11 showed homogenous and smooth surface as well as compact appearance compared with the untreated RBP-based films or heat-aggregated RBP-based film at pH 2 or 7. Furthermore, the secondary structure of heat-aggregated RBP film exhibited an increase in β-sheet content and molecular interactions through non-covalent bonds. The obtained results indicated that formation of protein aggregates could improve physical, mechanical, and thermal properties of RBP-based film, especially at pH 11.


The relationship between cholesterol and stroke: implications for antihyperlipidaemic therapy in older patients.
Various studies on the relationship between serum cholesterol level and the risk of stroke have been published recently. Subsequent reviews have extrapolated information on stroke from the clinical trials originally aimed at lowering cholesterol for the primary and secondary prevention of myocardial infarction (MI) in middle-aged patients. We have reviewed the epidemiological knowledge on the relationship between serum cholesterol levels and stroke, and also focused on possible reduction of the risk of stroke with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor treatment. Possible benefits from such therapy are particularly relevant for the elderly population which is at particularly high risk for stroke. The effects of serum cholesterol levels on the risk for haemorrhagic and ischaemic stroke have been evaluated. Indirect epidemiological evidence indicates that serum levels of total cholesterol and its subfractions are determinants of stroke, but their associations are relatively weak. When exploring the possible association of serum cholesterol levels with the increased risk of stroke with aging, we concluded that, as in younger adults, elevated total cholesterol and decreased high density lipoprotein-cholesterol levels predispose to ischaemic stroke in the elderly. The mechanism through which serum cholesterol levels increase stroke risk is based on its actions on the artery walls. Indirect evidence suggests that the reduction in the stroke risk with HMG-CoA reductase inhibitors is larger than would be expected with reduction of elevated serum cholesterol level alone. Therefore, antioxidant and endothelium-stabilising properties of HMG-CoA reductase inhibitors may contribute in reducing the risk of stroke in recipients. Lowering high serum cholesterol with HMG-CoA reductase inhibitors has been beneficial in the primary and secondary prevention of MI. No trials have specifically tested the effect of cholesterol lowering with HMG-CoA reductase inhibitors on stroke occurrence. High serum cholesterol levels are a risk factor for ischaemic stroke, although the risk imparted is lower than that for MI. Although the relative risk of stroke associated with elevated serum cholesterol levels is only moderate, its population attributable risk is high given the increase in the elderly population worldwide. The effect of cholesterol reduction with HMG-CoA reductase inhibitors on prevention of ischaemic stroke should be evaluated in prospective, randomised, placebo-controlled trials in the elderly. The tolerability of lipid-lowering drugs in the elderly and the cost effectiveness of primary prevention of stroke using lipid-lowering drugs also needs to be assessed in the elderly.


Great Plains American Indians' Perspectives on Patient and Family Needs Throughout the Cancer Journey.
To explore the perspectives on patient and family needs during cancer treatment and survivorship of American Indian (AI) cancer survivors, caregivers, Tribal leaders, and healers. 36 AI cancer survivors from three reservations in the Great Plains region. A community-based participatory research design was employed. Postcolonial Indigenous research techniques of talking circles and semistructured interviews were used to gather qualitative data. Data were analyzed using content analysis to identify themes. The overarching theme of accompaniment was identified. The following themes were intertwined with this theme: (a) the need for home health care, with the subthemes of family support and symptom management; and (b) patient and family education. To provide high-quality cancer care to AI patients in their home communities, oncology clinicians should collaborate with local care providers, relevant organizations, and the Indian Health Service to identify and develop essential services. Future efforts must emphasize culturally responsive interventions in which Tribal community health workers serve as navigators to accompany patients and families during treatment and in survivorship.


Legislation on the Roles of the Pharmacist and Pharmacy in the Revision of the Pharmaceutical and Medical Device Act and the Pharmacists Act in Japan.
Japan's rapidly aging population has prompted a change in the country's pharmaceutical care framework from a drug-oriented to a patient-oriented approach. Pharmacies and pharmacists are expected to play central roles in this new patient-oriented approach by reconciling medication and managing polypharmacy, conducting home visits, and providing care to patients in collaboration with local clinics and hospitals. These additional roles are expected to lead to a reduction in the prevalence of adverse effects and improve the quality of life of patients in Japan's aging society. To promote patient-oriented care by pharmacists, these additional roles were legislated in a revision of the Japanese Pharmaceutical and Medical Device Act and other related Act in December 2019. Here, we overview how the revisions affect pharmacies, pharmacists, medical institutions, and outpatients.


[Continuing education through the European Heart Rhythm Association (EHRA): chance for European standardization?].
Standardization of training with an examination in cardiac electrophysiology represents a milestone in the unification and improvement in the quality of electrophysiological therapy within the member countries of the European Society of Cardiology (ESC). Since 2004 the European Heart Rhythm Association (EHRA) has established an Educational Committee with the mission of improving training in device therapy and electrophysiology in the ESC with accredited materials and educational initiatives. The Educational Committee established Europe-wide courses for continuous medical education in 1. invasive electrophysiology and catheter ablation, 2. pacemaker, ICD and cardiac resynchronization therapy and 3. case-based tutorials to prepare for the EHRA examinations for electrophysiology/ablation and device therapy. Independent from participation in EHRA examinations these courses represent a useful aid for daily practice in cardiac electrophysiology and help to bring young and advanced European cardiologists with an interest in electrophysiology together.


Failure to Compensate: Patients With Nerve Injury Use Their Injured Dominant Hand, Even When Their Nondominant Is More Dexterous.
To identify how individuals respond to unilateral upper extremity peripheral nerve injury via compensation (increased use of the nondominant hand). We hypothesized that injury to the dominant hand would have a greater effect on hand use (left vs right choices). We also hypothesized that compensation would not depend on current (postinjury) nondominant hand performance because many patients undergo rehabilitation that is not designed to alter hand use. Observational survey, single-arm. Academic research institution and referral center. A total of 48 adults (N=48) with unilateral upper extremity peripheral nerve injury. Another 14 declined participation. Referred sample, including all eligible patients from 16 months at 1 nerve injury clinic and 1 hand therapy clinic. Not applicable. Hand use (% of actions with each hand) via Block Building Task. Dexterity via Jebsen-Taylor Hand Function. Participants preferred their dominant hand regardless of whether it was injured: hand usage (dominant/nondominant) did not differ from typical adults, regardless of injured side (P>.07), even though most participants (77%) were more dexterous with their uninjured nondominant hand (mean asymmetry index, -0.16±0.25). The Block Building Task was sensitive to hand dominance (P=2 × 10-4) and moderately correlated with Motor Activity Log amount scores (r2=0.33, P<.0001). Compensation was associated only with dominant hand dexterity (P=3.9 × 10-3), not on nondominant hand dexterity, rehabilitation, or other patient and/or injury factors (P>.1). Patients with peripheral nerve injury with dominant hand injury do not compensate with their unaffected nondominant hand, even if it is more dexterous. For the subset of patients unlikely to recover function with the injured hand, they could benefit from rehabilitation that encourages compensation with the nondominant hand.


Palliative Care Consultation Utilization Among Patient Undergoing Surgery for Metastatic Spinal Tumors.
In patients undergoing surgery for spinal metastasis, we sought to: (1) describe patterns of palliative care consultation, (2) evaluate the factors that trigger palliative care consultation, and (3) determine the association of palliative care consultation on longer-term outcomes. A single-center, retrospective, case-control study was conducted for patients undergoing spinal metastasis surgery from February 2010 to January 2021. The primary outcome was receiving a palliative care consultation, and the timing of consultation was divided into same hospital stay consultation, preoperative versus postoperative consultation, and early (<Postoperative day 7) versus late (≥Postoperative day 7) consultation. Of 363 patients undergoing surgery for spinal metastasis, 62 (17.0%) patients received palliative care consultation during the same hospitalization, 11 (17.7%) were preoperative, and 51 (82.2%) were postoperative. Among same-stay consultations, 32 (51.6%) were early and 30 (48.4%) were late. Palliative care consultation recipients had worse preoperative Karnofsky Performance Scale (KPS) score (P < 0.001), were more likely to have other organ metastases (P = 0.005) or cord compression (P = 0.026), had longer hospitalization (P < 0.001), and were less likely to be discharged home (P < 0.001). Patients presenting with mechanical pain were more likely to receive preoperative consults compared with postoperative (P = 0.029), and earlier compared with later consultations (P = 0.046). Regarding long-term outcomes, patients with same-stay palliative care consultation had significantly shorter overall survival (log-rank; P < 0.001), worse KPS postoperatively (P = 0.017), and worse KPS and Modified McCormick Scale at the last follow-up (P < 0.001). Only 1 in 6 patients received palliative care consultation. Patients receiving same-stay palliative care consultation had more advanced local and systemic disease burden. Increased utilization of palliative care consultation in patients with spine metastasis is needed.


Family physicians and HIV infection.
We aimed to describe the current and desired involvement of family physicians (FPs) in the treatment of HIV patients (screening practices, potential training and patient follow-up) to reduce the duration and frequency of their hospital treatment. We conducted a descriptive cross-sectional survey between 2011 and 2012 with the support of COREVIH (Regional Coordinating Committee on HIV). We sent a self-assessment questionnaire to all FPs of the Pays de la Loire region to enquire about their HIV screening practices and expectations for the management of HIV patients. A total of 871 FPs completed the questionnaire (response rate: 30.4%). A total of 54.2% said to provide care to HIV patients; the mean number of HIV patients per FP was estimated at 1.4. With regard to HIV screening, 12.2% systematically suggest an HIV serology to their patients and 72.7% always suggest it to pregnant women. About 45.4% of responding FPs said to be willing to manage HIV patients (clinical and biological monitoring, compliance checks and prescription renewal). FPs mainly reported the lack of training and the low number of HIV patients as a barrier to their further involvement in the management of HIV patients. The responding FPs provide care to very few HIV patients. They are, however, willing to be more involved in the routine care of these patients. Medical training provided by COREVIH would help improve HIV screening. The management of HIV patients could thus be handed over to willing FPs.


Familial co-segregation and the emerging role of long-read sequencing to re-classify variants of uncertain significance in inherited retinal diseases.
Phasing genetic variants is essential in determining those that are potentially disease-causing. In autosomal recessive inherited retinal diseases (IRDs), reclassification of variants of uncertain significance (VUS) can provide a genetic diagnosis in indeterminate compound heterozygote cases. We report four cases in which familial co-segregation demonstrated a VUS resided in trans to a known pathogenic variant, which in concert with other supporting criteria, led to the reclassification of the VUS to likely pathogenic, thereby providing a genetic diagnosis in each case. We also demonstrate in a simplex patient without access to family members for co-segregation analysis that targeted long-read sequencing can provide haplotagged variant calling. This can elucidate if variants reside in trans and provide phase of genetic variants from the proband alone without parental testing. This emerging method can alleviate the bottleneck of haplotype analysis in cases where genetic testing of family members is unfeasible to provide a complete genetic diagnosis.


Using model explanations to guide deep learning models towards consistent explanations for EHR data.
It has been shown that identical deep learning (DL) architectures will produce distinct explanations when trained with different hyperparameters that are orthogonal to the task (e.g. random seed, training set order). In domains such as healthcare and finance, where transparency and explainability is paramount, this can be a significant barrier to DL adoption. In this study we present a further analysis of explanation (in)consistency on 6 tabular datasets/tasks, with a focus on Electronic Health Records data. We propose a novel deep learning ensemble architecture that trains its sub-models to produce consistent explanations, improving explanation consistency by as much as 315% (e.g. from 0.02433 to 0.1011 on MIMIC-IV), and on average by 124% (e.g. from 0.12282 to 0.4450 on the BCW dataset). We evaluate the effectiveness of our proposed technique and discuss the implications our results have for both industrial applications of DL and explainability as well as future methodological work.


[Vascular myeloproliferative neoplasm with normal cell blood count: Exploration and medical management].
Negative BCR ABL myeloproliferative neoplasm (MPN) such as polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (MFP) are clonal hematological malignancies and may lead to a high risk of venous, arterial or microcirculatory thrombosis. Atypical sites of thrombosis can sometimes reveal the neoplasm disorder. Their diagnoses are a major issue because of the propensity to develop acute myeloid leukemia and/or myelofibrosis. The acquired JAK2V617F variant (Janus kinase 2; 9p24) is a prevalent MPN and also a sensitive marker for PV diagnosis (95% positive mutation), but not specific since found in approximately 50% of patients with ET and MFP. We present a diagnostic and a therapeutic approach based on one patient with microcirculatory ischemic manifestations in the toes, and who had strictly normal cell blood counts and was positive for JAK2V617F mutation: thrombotic risk factor evaluation; bone marrow biopsy; red cell adhesion assays. These experimental assays are promising for the development of new therapeutics in MPN; they assess red cell adherence to the vascular endothelium after the phosphorylation of Lu/BCAM subsequent to a positive JAK2V617F mutation. Compared with controls, our patient exhibited increased Lu/BCAM receptor phosphorylation and red blood cell adhesion. This development may lead to improved care for patients with thrombotic manifestations, normal blood cell counts, and a positive JAK2V617F mutation: multidisciplinary management, including regular hematological monitoring, could lead to the introduction of a cytoreductive treatment.


Pharmacologic treatment of gastroparesis: What is (still) on the horizon?
Gastroparesis is a neuromuscular disorder of the upper gastrointestinal tract. Patients typically complain about early satiety, postprandial fullness, nausea and vomiting. Etiology is multifactorial. Treatment strategies include nutritional support, pharmacologic agents or surgery for refractory cases. Metoclopramide is the first and only FDA approved pharmacologic agent for (diabetic) Gastroparesis. A couple of compounds are currently in clinical testing. Some beacons of hope have failed recently, however. Here we present an update on possible future treatment options.


Preoperative and postoperative technetium-99m pyrophosphate myocardial scintigraphy in the assessment of operative infarction in coronary artery surgery.
The incidence of operative myocardial infarction was assessed by electrocardiogram (ECG) and technetium-99m pyrophosphate (99mTc-PyP) myocardial scintigrams in 89 consecutive patients undergoing coronary artery bypass grafting (CABG). Myocardial scintigrams were performed on the day before operation and repeated 2 to 3 days postoperatively. All patients survived operation, with three in-hospital deaths not related to myocardial infarction (mortality rate 3 percent). Operative infarction was assessed to have occurred in four of 89 patients (4 percent). Two had new Q waves and positive scintigrams; one, major ST-T wave changes and a positive scintigram; and the fourth, new Q waves without a positive scintigram. Three further patients (3 percent) had Q waves and positive scintigrams postoperatively, but myocardial infarction was evolving before anesthesia and operation. Twenty-seven of 89 patients (30 percent) were found to have abnormal scintigrams preoperatively. In two patients, both operated upon with evolving myocardial infarction, the scintigram was worse postoperatively. In 13 patients the scintigram was improved after operation. In 12 patients (13 percent) the abnormal preoperative scintigram was unchanged after operation. Preoperative and postoperative myocardial scintigrams and ECG's must be compared to assess the incidence of operative myocardial infarction in patients undergoing CABG.


Callous-unemotional traits in adolescents moderate neural network associations with empathy.
Callous-unemotional (CU) traits in adolescents are a dimensional construct involving a symptom subset of empathy impairments amongst broader affective deficits. Higher CU trait scores associate with less cognitive and affective empathy; and brain regions linked with cognitive and affective empathy show aberrant function in those with CU traits. How CU traits impact the relationship between brain function and both cognitive and affective empathy in adolescents is less clear. Here we examine how functional properties of networks that support cognitive and affective empathy is moderated by CU traits. Eighty-four adolescents underwent resting-state fMRI scanning and completed self-reports for empathy (Interpersonal Reactivity Index) and CU traits (Inventory of Callous-Unemotional Traits). Analysis revealed that CU traits moderate the association between affective empathy and connectivity between the default mode-frontoparietal networks. Weaker between default mode-frontoparietal anticorrelation negatively associated with affective empathy at low to moderate CU traits. Those highest in CU traits had the lowest affective empathy; and negative associations for those highest in CU traits were insignificant as default mode-frontoparietal anticorrelation weakened. Our results indicate that functional properties of networks that support affective empathy is different at varying levels of CU traits. This novel finding demonstrates that CU traits presence changes the relationship between the brain and empathy.


Living versus cadaveric-donor renal transplant recipients: a comparison on sexual function.
Erectile dysfunction is experienced by 50% of men with end-stage renal disease (ESRD) and uremia. The origin of this dysfunction is multifactorial. The aim of this study was to compare living donor versus cadaveric donor transplant recipients regarding male sexual function. Seventy-seven sexually active male kidney transplant recipients (44 from living donors; 33 from cadaveric donors) were randomly selected from our single-center prospective database of 2016 renal transplants. Epidemiological and clinical data were collected between June 2010 and June 2011. Male sexual function was evaluated with the International Index of Erectile Function questionnaire (IIEF-15). We assessed the prevalence of male sexual dysfunction according to established cutoff points for each of the IIEF-15 domains. Mann-Whitney and Pearson's chi- square statistical tests were used to compare continuous and categorical variables, respectively. The median age at the time of completion of the questionnaires was 43 and 51 years (P = .003) with median times from transplantation was of 36 and 42 months for living donor and cadaveric donor recipients, respectively (P = .31). Median durations of ESRD before surgery were 17.5 and 57 months for living donor and cadaveric donor recipients, respectively (P < .001). Living donor and cadaveric donor recipients had median creatinine clearance values of 55 and 57 mL/min, respectively (P = .44). Median time after renal transplantation for first sexual intercourse was 1 and 2 months for living donor and cadaveric donor recipients, respectively (P = .35). Median body mass indices for living donor and cadaveric donor recipients were 24.8 and 24, respectively (P = .31). Regarding sexual function domains, there were significant differences only for intercourse satisfaction. In our cohort, living donor recipients tended to be younger, have shorter time of ESRD, and less incidence of hypertension or diabetes mellitus but with greater tobacco use. In conclusion, living donor transplantation exerted a favorable impact on sexual function.


Migration and transformation of Sb are affected by Mn(III/IV) associated with lepidocrocite originating from Fe(II) oxidation.
Antimony (Sb) is a recognized priority pollutant with toxicity that is influenced by its migration and transformation processes. Oxidation of Fe(II) to Fe(III) oxides, which is a common phenomenon in the environment, is often accompanied by the formation of Mn(III/IV) and might affect the fate of Sb. In this study, incorporated Mn(III) and sorbed/precipitated Mn(III/IV) associated with lepidocrocite were prepared by adding Mn(II) during and after Fe(II) oxidation, respectively, and the effects of these Mn species on Sb fate were investigated. Our results indicated that the association of these Mn species with lepidocrocite obviously enhanced Sb(III) oxidation to Sb(V), while concomitantly inhibiting Sb sorption due to the lower sorption capacity of lepidocrocite for Sb(V) than Sb(III). Additionally, Mn oxide equivalents increased in the presence of Sb, indicating that Sb oxidation by Mn(III/IV) associated with lepidocrocite was a continuous recycling process in which Mn(II) released from Mn(III/IV) reduction by Sb(III) could be oxidized to Mn(III/IV) again. This recycling process was favorable for effective Sb(III) oxidation. Moreover, Sb(V) generated from Sb(III) oxidation by Mn(III/IV) enhanced Mn(II) sorption at the beginning of the process, and thus favored Mn(III/IV) formation, which could further promote Sb(III) oxidation to Sb(V). Overall, this study elucidated the effects of Mn(III/IV) associated with lepidocrocite arisen from Fe(II) oxidation on Sb migration and transformation and revealed the underlying reaction mechanisms, contributing to a better understanding of the geochemical dynamics of Sb.


The CRISPR-Cas toolbox and gene editing technologies.
The emergence of CRISPR-Cas systems has accelerated the development of gene editing technologies, which are widely used in the life sciences. To improve the performance of these systems, workers have engineered and developed a variety of CRISPR-Cas tools with a broader range of targets, higher efficiency and specificity, and greater precision. Moreover, CRISPR-Cas-related technologies have also been expanded beyond making cuts in DNA by introducing functional elements that permit precise gene modification, control gene expression, make epigenetic changes, and so on. In this review, we introduce and summarize the characteristics and applications of different types of CRISPR-Cas tools. We discuss certain limitations of current approaches and future prospects for optimizing CRISPR-Cas systems.


Implementation of clinical decision support in young children with acute gastroenteritis: a randomized controlled trial at the emergency department.
Acute gastroenteritis (AGE) is one of the most frequent reasons for young children to visit emergency departments (EDs). We aimed to evaluate (1) feasibility of a nurse-guided clinical decision support system for rehydration treatment in children with AGE and (2) the impact on diagnostics, treatment, and costs compared with usual care by attending physician. A randomized controlled trial was performed in 222 children, aged 1 month to 5 years at the ED of the Erasmus MC-Sophia Children's hospital in The Netherlands ( 2010-2012). Outcome included (1) feasibility, measured by compliance of the nurses, and (2) length of stay (LOS) at the ED, the number of diagnostic tests, treatment, follow-up, and costs. Due to failure of post-ED weight measurement, we could not evaluate weight difference as measure for dehydration. Patient characteristics were comparable between the intervention (N = 113) and the usual care group (N = 109). Implementation of the clinical decision support system proved a high compliance rate. The standardized use of oral ORS (oral rehydration solution) significantly increased from 52 to 65%(RR2.2, 95%CI 1.09-4.31 p < 0.05). We observed no differences in other outcome measures. Implementation of nurse-guided clinical decision support system on rehydration treatment in children with AGE showed high compliance and increase standardized use of ORS, without differences in other outcome measures. What is Known: • Acute gastroenteritis is one of the most frequently encountered problems in pediatric emergency departments. • Guidelines advocate standardized oral treatment in children with mild to moderate dehydration, but appear to be applied infrequently in clinical practice. What is New: • Implementation of a nurse-guided clinical decision support system on treatment of AGE in young children showed good feasibility, resulting in a more standardized ORS use in children with mild to moderate dehydration, compared to usual care. • Given the challenges to perform research in emergency care setting, the ED should be experienced and adequately equipped, especially during peak times.


Anti-biofilm and wound-healing activity of chitosan-immobilized Ficin.
Biofouling is among the key factors slowing down healing of acute and chronic wounds. Here we report both anti-biofilm and wound-healing properties of the chitosan-immobilized Ficin. The proposed chitosan-adsorption approach allowed preserving ~90% of the initial total activity of the enzyme (when using azocasein as a substrate) with stabilization factor of 4.9, and ~70% of its specific enzymatic activity. In vitro, the chitosan-immobilized Ficin degraded staphylococcal biofilms, this way increasing the efficacy of antimicrobials against biofilm-embedded bacteria. In vivo, in the presence of Ficin (either soluble or immobilized), the S.aureus-infected skin wound areas in rats reduced twofold after 4 instead of 6 days treatment. Moreover, topical application of the immobilized enzyme resulted in a 3-log reduction of S. aureus cell count on the wound surfaces in 6 days, compared to more than 10 days required to achieve the same effect in control. Additional advantages include smoother reepithelisation, and new tissue formation exhibiting collagen structure characteristics closely reminiscent of those observed in the native tissue. Taken together, our data suggest that both soluble and immobilized Ficin appear beneficial for the treatment of biofilm-associated infections, as well as speeding up wound healing and microbial decontamination.


The role of sulfatide lipid domains in the membrane pore-forming activity of cobra cardiotoxin.
Cobra CTX A3, the major cardiotoxin (CTX) from Naja atra, is a cytotoxic, basic β-sheet polypeptide that is known to induce a transient membrane leakage of cardiomyocytes through a sulfatide-dependent CTX membrane pore formation and internalization mechanism. The molecular specificity of CTX A3-sulfatide interaction at atomic levels has also been shown by both nuclear magnetic resonance (NMR) and X-ray diffraction techniques to reveal a role of CTX-induced sulfatide conformational changes for CTX A3 binding and dimer formation. In this study, we investigate the role of sulfatide lipid domains in CTX pore formation by various biophysical methods, including fluorescence imaging and atomic force microscopy, and suggest an important role of liquid-disordered (ld) and solid-ordered (so) phase boundary in lipid domains to facilitate the process. Fluorescence spectroscopic studies on the kinetics of membrane leakage and CTX oligomerization further reveal that, although most CTXs can oligomerize on membranes, only a small fraction of CTXs oligomerizations form leakage pores. We therefore suggest that CTX binding at the boundary between the so and so/ld phase coexistence sulfatide lipid domains could form effective pores to significantly enhance the CTX-induced membrane leakage of sulfatide-containing phosphatidylcholine vesicles. The model is consistent with our earlier observations that CTX may penetrate and lyse the bilayers into small aggregates at a lipid/protein molar ratio of about 20 in the ripple P(β)' phase of phosphatidylcholine bilayers and suggest a novel mechanism for the synergistic action of cobra secretary phospholipase A2 and CTXs.


Elevated plasma levels of vascular endothelial cell markers in patients with hypercholesterolemia.
Hypercholesterolemia is associated with an increased incidence of vascular complications. To assess the actual degree of activation of coagulation systems and vascular disorders in hypercholesterolemia, plasma levels of vascular endothelial cell markers, such as thrombomodulin (TM), tissue-type plasminogen activator, plasminogen activator inhibitor-I (PAI-I), and von Willebrand factor, were measured in 51 patients with hypercholesterolemia. We also investigated the effects of Pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on plasma lipid, lipoprotein a, and hemostatic markers. The mean plasma levels of thrombin-antithrombin III complex (TAT), fibrinopeptide A (FPA), TM, and PAI-I were significantly elevated in hypercholesterolemia. Of the hemostatic markers, only TM was significantly increased in patients with ischemic heart diseases (IHD). The mean concentration of total cholesterol and levels of TAT, FPA, PAI-I, and TM were significantly reduced after the Pravastatin treatment. The PIC/TAT ratio was significantly increased in non-IHD patients after treatment, this was not the case in IHD patients. These findings suggested the presence of a thrombogenic state and vascular endothelial cell disorders in hypercholesterolemia; such a state might well be related to hypofibrinolysis.


Investigation of the genes associated with a male sterility mutant (msm) in Chinese cabbage (Brassica campestris ssp. pekinensis) using RNA-Seq.
In Chinese cabbage, hybrid seed production is performed using male sterility lines, an important approach to heterosis utilization. In this study, a stably inherited male sterile mutant msm was obtained from the 'FT'-doubled haploid line of Chinese cabbage using isolated microspore culture combined with 60Co γ-ray mutagenesis. The genetic backgrounds of 'FT' and msm were highly consistent; however, compared with wild-type 'FT', msm exhibited completely degenerated stamens and no pollen phenotype. Other characters showed no significant differences. Cytological observations revealed that stamen abortion in msm begins during the tetrad period and that tapetum cells were abnormally expanded and highly vacuolated, leading to microspore abortion. Genetic analysis indicated that the msm mutant phenotype is controlled by a single recessive nuclear gene. Comparative transcriptome analysis of 'FT' and msm flower buds using RNA-Seq technology revealed 1653 differentially expressed genes, among which, a large number associated with male sterility were detected, including 64 pollen development- and pollen tube growth-related genes, 94 pollen wall development-related genes, 11 phytohormone-related genes, and 16 transcription factor-related genes. An overwhelming majority of these genes were down-regulated in msm compared with 'FT'. Furthermore, KEGG pathway analysis indicated that a variety of carbohydrate metabolic and lipid metabolic pathways were significantly enriched, which may be related to pollen abortion. The expression patterns of 24 male sterility-related genes were analyzed using qRT-PCR. In addition, 24,476 single-nucleotide polymorphisms and 413,073 insertion-deletion events were specifically detected in msm. These results will facilitate elucidation of the regulatory mechanisms underlying male sterility in Chinese cabbage.


Galectin-1 is overexpressed in nasal polyps under budesonide and inhibits eosinophil migration.
Because of the importance of galectins for various cellular activities, the influence of the glucocorticoid budesonide on the level of expression of galectins-1 and -3 was investigated in human nasal polyposis. Ten nasal polyps obtained from surgical resection were maintained for 24 hours in the presence of various concentrations of budesonide. As quantitatively demonstrated by means of computer-assisted microscopy, 250 ng/ml (the highest dose tested) induced a pronounced increase of galectin-1 expression. This feature was observed in nasal polyps from allergic patients but not in those from nonallergic patients. Since eosinophils represent the main inflammatory cell population in nasal polyps, we investigated the effect of galectin-1 on their migration levels by means of quantitative phase-contrast computer-assisted videomicroscopy. Our results show that galectin-1 (coated on plastic supports) markedly reduced the migration levels of eosinophils in comparison to P-selectin. On the cellular level, marked modifications in the polymerization/depolymerization dynamics of the actin cytoskeleton (as revealed by means of computer-assisted fluorescence microscopy) and, to a much lesser extent, an increase in the adhesiveness of eosinophils to tested substrata were detectable. The present study therefore reveals a new galectin-1-mediated mechanism of action for glucocorticoid-mediated anti-inflammatory effects.


Physician advice to quit smoking: results from the 1990 California Tobacco Survey.
To estimate the percentage of California smokers who visit physicians each year and thus determine the extent of the opportunity for physicians to advise their smoking patients to quit; to identify sociodemographic and other characteristics related to smokers' reporting that advice was given; and to look for evidence that physician advice influences quitting behavior. Data were collected as part of the 1990 California Tobacco Survey, a large (n = 24,296) population-based telephone survey. 9,796 current smokers, including 5,559 daily smokers who had visited a physician in the preceding year. Two-thirds of all smokers had visited a physician in the year before the interview, but only about 50% of Hispanic and Asian smokers had done so. Multivariate analysis showed that advice at the last visit was independently related to older age, higher cigarette consumption, and poorer perceived health. Compared with smokers never advised to quite by a physician, those advised to quit at the last visit were 1.61 (95% confidence interval, 1.31-1.98) times more likely to report a quit attempt in the preceding year and 1.90 (95% confidence interval, 1.45-2.48) times more likely to be preparing to quit; however, those advised previously but not at the last visit showed no more quitting activity than did smokers never advised to quit. Physicians have considerable opportunity to reach all demographic subgroups of the population, but the nature of the subgroups advised most (those who are older, have high consumption of cigarettes, or have poor health) suggests that physicians tend to treat such advice as a therapeutic rather than a preventive intervention. Physician advice at the most recent visit encourages patients to think about quitting and probably leads to quit attempts. Thus, it is vital that physicians perform the simple intervention of advising every smoker to quit at every visit.


Distribution of intracytoplasmic acidophilic granule-containing neurons in the human brain.
Using four autopsied brains, we studied the anatomic locations of the intracytoplasmic acidophilic granule (IAG)-containing neurons. These neurons occurred in the hypothalamus, zona incerta, insular cortex, and the other 23 nuclei. However, IAGs were not observed in neurons of the Ammon's horn, thalamus, dentate nucleus, or in Purkinje cells of the cerebellum. The distribution of IAG-containing neurons does not exactly correspond to that of the neuromelanin- or monoamine-forming neurons. There is, however, a striking parallelism between the IAG-containing neurons map and the Lewy bodies map. It is suggested by the superimposition of both maps that IAG-containing neurons may have a certain metabolic relation to the formation of Lewy bodies.


Sclerosing Encapsulated Peritonitis: A devastating and infrequent disease complicating kidney transplantation, case report and literature review.
Sclerosing Encapsulating Peritonitis (SEP) is a rare condition with an incidence of up to 3% and a mortality of up to 51% among peritoneal dialysis (PD) patients (Brown et al., Korte et al. and Kawanishi et al.). In the last ten years, the incidence of SEP in kidney transplant recipients has increased (Nakamoto, de Sousa et al. and Korte et al.). A 31-year old male with a 15 years history of PD and later kidney retransplantation was admitted to the emergency service after experiencing several weeks of diffuse abdominal pain which had escalated to include vomiting and diarrhea during the 24h previous to admission. The patient underwent an exploratory laparotomy where severe peritoneal thickening was found, in addition to signs of chronic inflammation and blocked intestinal loops. Histopathologic findings were suggestive of sclerosing peritonitis. After two months of treatment in hospital, the patient presented an obstructed intestine, with a rigid and thickened peritoneum compromising all the intestinal loops. Despite being rare, SEP, represents a significant complication due to its high mortality and recurrence. It is insidious in its early stages and culminates in an intestinal obstruction (Fieren). Risk factors for its development in kidney transplant recipients include a history of prolonged treatment with PD and the use of calcineurin inhibitors as an immunosuppressive treatment (Korte et al.). Given the increase in the incidence of SEP in kidney transplant recipients, the clinician should be alert to the presence of this complication. A greater number of multi-centre studies are required to identify the risk factors for SEP that are inherent in renal transplant recipients.


Evaluation of oil-gelling properties and crystallization behavior of sorghum wax in fish oil.
Inspired by the potential opportunities offered by sorghum as a natural wax source, the objective of this study was to investigate for the first time the potential of three types of sorghum waxes, namely, sorghum bran wax (SBW), sorghum DDGS wax (SDW), and sorghum kernel wax (SKW), as an oleogelator. All the three sorghum waxes showed good gelation properties with minor differences. Fast cooling rate and ultrasonic treatment favored the oil-gelling capacity and reduced oil loss by reducing the crystal size. All sorghum wax oleogels exhibited two common x-ray diffraction peaks around d-value of 0.415 nm and 0.374 nm, suggesting the evidence of a hexagonal symmetry and β' crystals. Faster cooling rate resulted in an earlier onset of crystallization and ultrasonic treatment narrowed the melting range. Oxidation of fish oil in the sorghum wax oleogels were delayed considerably compared to free fish oil, while SDW generated the most stable oleogels.


Prediction of postoperative pain from assessment of pain induced by venous cannulation and propofol infusion.
Postoperative pain may lead to delayed mobilization, persisting pain, and psychosocial distress. There are no simple and reliable techniques for prediction of postoperative pain. This study was designed to evaluate if pain induced by venous cannulation or propofol injection can be used to predict postoperative pain. This prospective study included 180 patients scheduled for laparoscopic cholecystectomy. Pain intensity associated with peripheral venous cannulation and administration of propofol preoperatively and pain intensity, and use of opioid postoperatively was recorded. Patients scoring cannulation-induced pain intensity > 2.0 VAS units were given postoperative opioid more often (65% vs. 36%; P < 0.001), earlier (12 min vs. 90 min; P < 0.001), and in higher doses (4.8 mg vs. 0 mg; P < 0.001), and also reported higher levels of postoperative pain intensity (5.8 vs. 2.9 VAS units; P < 0.001). There were also significant (P < 0.01) correlations with postoperative pain intensity (rs = 0.24), time to opioid administration (rs = -0.26), and total dose of opioid (rs = 0.25). Propofol-induced pain intensity correlated significantly (P < 0.05) with postoperative pain intensity (rs = 0.19). Pain intensity associated with venous cannulation and propofol infusion can easily be evaluated at bedside before surgery without specific equipment or training. Patients scoring > 2.0 VAS units on venous cannulation were found to have 3.4 times higher risk of postoperative pain after laparoscopic cholecystectomy. Low pain intensity associated with venous cannulation and propofol infusion indicate lower risk of postoperative pain.


Monoclonal antibodies against a plant virus.
Eight stable hybridoma clones derived from fusion of spleen cells of Tobacco Mosaic Virus (TMV) immunized mice with murine myeloma cells were grown in mass culture. They were obtained by 2 subsequent limiting dilution cloning cycles and subcultivation. Five of these clones secreted monoclonal antibodies which reacted with TMV nucleocapsid but not with capsid monomers and the monoclonal antibodies secreted by 3 other clones reacted with the TMV capsid monomer but not with the nucleocapsid. The specificity was determined by Enzyme Linked Immunosorbent Assay (ELISA) adjusted for the detection of antibodies in hybridoma culture supernatants.


Enhanced adipose-derived stem cells with IGF-1-modified mRNA promote wound healing following corneal injury.
The cornea serves as an important barrier structure to the eyeball and is vulnerable to injuries, which may lead to scarring and blindness if not treated promptly. To explore an effective treatment that could achieve multi-dimensional repair of the injured cornea, the study herein innovatively combined modified mRNA (modRNA) technologies with adipose-derived mesenchymal stem cells (ADSCs) therapy, and applied IGF-1 modRNA (modIGF1)-engineered ADSCs (ADSCmodIGF1) to alkali-burned corneas in mice. The therapeutic results showed that ADSCmodIGF1 treatment could achieve the most extensive recovery of corneal morphology and function when compared not only with simple ADSCs but also IGF-1 protein eyedrops, which was reflected by the healing of corneal epithelium and limbus, the inhibition of corneal stromal fibrosis, angiogenesis and lymphangiogenesis, and also the repair of corneal nerves. In vitro experiments further proved that ADSCmodIGF1 could more significantly promote the activity of trigeminal ganglion cells and maintain the stemness of limbal stem cells than simple ADSCs, which were also essential for reconstructing corneal homeostasis. Through a combinatorial treatment regimen of cell-based therapy with mRNA technology, this study highlighted comprehensive repair in the damaged cornea and showed the outstanding application prospect in the treatment of corneal injury.


Application of a lanthanide fluorescent chelate label for detection of single-nucleotide mutations with peptide nucleic acid probes.
We developed the approach to detect single-nucleotide mutation with peptide nucleic acid (PNA) probes and time-resolved fluorometry using a fluorescence lanthanide chelate label, {2,2',2'',2'''-{4'-{[(4,6-dichloro-1,3,5-triazin-2-yl)amino]biphenyl-4-yl}-2,2': 6',2''-terpyridine-6,6''-diyl}bis(methylenenitrilo)}tetrakis(acetato)}europium(III) (DTBTA-Eu3+). Compared with DNA probes, PNA probes showed lower mismatch signals and gave higher signal/noise (S/N) ratios. Using the system, we examined the single-nucleotide mutations of codon 12 in the c-Ha-ras gene of PCR amplicons of genome DNAs isolated from human umbilical vein endothelial cells (HUVECs) and T24 cells.


Effect of mastication evaluation and intervention on body composition and biochemical indices in female patients with obesity: a randomized controlled trial.
A limited number of studies have evaluated the masticatory indices of individuals with obesity who only chew their food a few times and for shorter duration or who were provided with an instructional intervention. This study aimed to examine the effects of a 6-month instructional mastication intervention on the body composition and biochemical indices in female patients with obesity. Female patients with obesity were randomly classified into a conventional treatment group (CTG; 12 individuals), which only received normal nutritional and exercise guidance, and a mastication intervention group (MIG; 16 individuals), which received an additional mastication guidance. The MIG received guidance on foods requiring increased number of chews and chewing duration, eating techniques, and the proper method of cutting foods. Changes in the masticatory, body composition, and biochemical indices were compared before and after the 6-month intervention. The values of body composition indices decreased significantly in both groups; however, the rate of change in body mass index significantly decreased in the MIG. In addition, the values of biochemical indices were significantly decreased in the MIG compared with that in the CTG, which is attributed to the addition of mastication instruction to female patients with obesity. Increasing the number of chews and duration of chewing times for carbohydrates, which are staple foods, possibly contributed to weight loss and improvement of glucose metabolism. UMIN, UMIN000025875. Registered on 27 Jan 2017.


Bile acids and neurological disease.
This review will focus on how bile acids are being used in clinical trials to treat neurological diseases due to their central involvement with the gut-liver-brain axis and their physiological and pathophysiological roles in both normal brain function and multiple neurological diseases. The synthesis of primary and secondary bile acids species and how the regulation of the bile acid pool may differ between the gut and brain is discussed. The expression of several bile acid receptors in brain and their currently known functions along with the tools available to manipulate them pharmacologically are examined, together with discussion of the interaction of bile acids with the gut microbiome and their lesser-known effects upon brain glucose and lipid metabolism. How dysregulation of the gut microbiome, aging and sex differences may lead to disruption of bile acid signalling and possible causal roles in a number of neurological disorders are also considered. Finally, we discuss how pharmacological treatments targeting bile acid receptors are currently being tested in an array of clinical trials for several different neurodegenerative diseases.


Gene cloning and transcriptional regulation of the alkaline and acid phosphatase genes in Scylla paramamosain.
In crustaceans, innate immunity serves as the frontline of defense against microbes. Alkaline phosphatases (ALPs) and acid phosphatases (ACPs) are essential enzymes that play a significant role in crustaceans' immune defenses. However, the function and transcriptional regulation of the alp and acp genes in the Scylla paramamosain, an important aquaculture species in China, have not been elucidated. In this study, the full-length cDNAs of Spalp and Spacp were identified, which consist of 2,718 bp and 3,768 bp, encoding 579 and 452 amino acids, respectively. Multiple sequence alignment and phylogenetic analysis showed that these two genes were conserved among different species and shared high homology with crustaceans. The mRNA expression of Spalp and Spacp were examined in eight tested tissues, with the highest levels in the hepatopancreas. The 5'-flanking regions of Spalp and Spacp were cloned and sequenced. The core promoter region of the Spalp and Spacp was -39 bp∼+8 bp and -39 bp∼+10 bp, respectively. Potential binding sequences for SOX-2, c-fos, SP1, NF-κB, GATA-1, YY1, and AP-1 transcription factors were found in the 5'-flanking regions of Spalp and Spacp. The NF-κB binding site located between -1,223 bp and -972 bp in Spalp while SP1 and AP-1 binding sites located between -1,249 bp and -514 bp in Spacp. Mutation analysis confirmed that NF-κB negatively regulated the expression of Spalp gene, and SP1 and AP-1 positively regulated Spacp gene expression. These results provide us with essential information to elucidate the function of the Spalp and Spacp in S. paramamosain. This study is the first one to analyze the activity of Spalp and Spacp promoters.


Successful reoperation for diffuse supravalvular aortic stenosis.
We reoperated for diffuse supravalvular aortic stenosis using a modified technique of patch plasty described by Brom. A 36-year-old woman admitted to our hospital with a peak systolic pressure gradient of 92 mmHg across the ascending aorta had previously undergone Doty's operation at another hospital. Aortography showed an ascending aorta diffusely stenotic from the sinotubular junction to the aortic arch. We transected the ascending aorta just above the stenotic portion and incised the proximal wall to the sinus of Valsalva. Three patches were sewn to each sinus to expand them and the ascending aorta. The pressure gradient decreased postoperatively to 11 mmHg, and we conclude that this technique sufficiently relieves diffuse supravalvular aortic stenosis.


Insulin and growth hormone function as minor growth factors that potentiate lymphocyte activation.
The small resting lymphocyte is devoid of cell surface receptors for endocrine peptides such as insulin and growth hormone. During the process of activating these cells by either specific antigen or mitogenic agents the lymphocyte has been shown to display receptors for insulin. The present paper reviews work that indicates a functional role for both insulin and growth hormone during the process of lymphocyte activation. The results of these studies point to potentially important interactions between the immune and neuroendocrine systems and are discussed in terms of endocrine peptides playing a supportive role during the complex series of events that occur during lymphocyte activation.


The antimicrobial efficacy of copper, cobalt, zinc and silver nanoparticles: alone and in combination.
With the advent of nanotechnology, there has been an extensive interest in the antimicrobial potential of metals. The rapid and widespread development of antimicrobial-resistant and multidrug-resistant bacteria has prompted recent research into developing novel or alternative antimicrobial agents. In this study, the antimicrobial efficacy of metallic copper, cobalt, silver and zinc nanoparticles was assessed againstEscherichia coli(NCTC 10538),S. aureus(ATCC 6538) along with three clinical isolates ofStaphylococcus epidermidis(A37, A57 and A91) and three clinical isolates ofE. coli(Strains 1, 2 and 3) recovered from bone marrow transplant patients and patients with cystitis respectively. Antimicrobial sensitivity assays, including agar diffusion and broth macro-dilution to determine minimum inhibitory and bactericidal concentrations (MIC/MBC) and time-kill/synergy assays, were used to assess the antimicrobial efficacy of the agents. The panel of test microorganisms, including antibiotic-resistant strains, demonstrated a broad range of sensitivity to the metals investigated. MICs of the type culture strains were in the range of 0.625-5.0 mg ml-1. While copper and cobalt exhibited no difference in sensitivity between Gram-positive and Gram-negative microorganisms, silver and zinc showed strain specificity. A significant decrease (p< 0.001) in the bacterial density ofE. coliandS. aureuswas demonstrated by silver, copper and zinc in as little as two hours. Furthermore, combining metal nanoparticles reduced the time required to achieve a complete kill.


Basilar artery occlusion after multifactor coagulopathy including Rhizopus oryzae infection in burns.
The authors report a case of a 29-year-old male patient with severe burn injuries (54% TBSA) and inhalation injury. He developed a candidemia and a cutaneous zygomycotic superinfection with Rhizopus oryzae while he received burn intensive care. Despite aggressive surgery, sepsis persisted, and therapy was limited by uncontrollable coagulopathy and catecholamine refractory shock after 15 days. Autopsy revealed a thromboembolic occlusion of the basilar artery that resulted in liquefactive necrosis of the basal brain tissue and the brain stem. Because cerebral vessel occlusions after burn injuries are reported rarely, the current literature was reviewed, and possible pathophysiological aspects are discussed.


Unsaturated Copolyesters from Macrolactone/Norbornene: Toward Reaction Kinetics of Metathesis Copolymerization Using Ruthenium Carbene Catalysts.
Unsaturated copolyesters are of great interest in polymer science due to their broad potential applications and sustainability. Copolyesters were synthesized from the ring-opening metathesis copolymerization of ω-6-hexadecenlactone (HDL) and norbornene (NB) using ruthenium-alkylidene [Ru(Cl2)(=CHPh)(1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)(PCy3)] (Ru1), [Ru(Cl)2(=CHPh)(PCy3)2] (Ru2), and ruthenium-vinylidene [RuCl2(=C=CH(p-C6H4CF3))(PCy3)2] (Ru3) catalysts, respectively, yielding HDL-NB copolymers with different ratios of the monomer HDL in the feed. The activity of N-heterocyclic-carbene (NHC) (Ru1) and phosphine (Ru2 and Ru3) ligands containing ruthenium-carbene catalysts were evaluated in the synthesis of copolymer HDL-NB. The catalysts Ru1 with an NHC ligand showed superior activity and stability over catalysts Ru2 and Ru3 bearing PCy3 ligands. The incorporation of the monomers in the copolymers determined by 1H-NMR spectroscopy was similar to that of the HDL-NB values in the feed. Experiments, at distinct monomer molar ratios, were carried out using the catalysts Ru1-Ru3 to determine the copolymerization reactivity constants by applying the Mayo-Lewis and Fineman-Ross methods. The copolymer distribution under equilibrium conditions was studied by the 13C NMR spectra, indicating that the copolymer HDL-NB is a gradient copolymer. The main factor determining the decrease in melting temperature is the inclusion of norbornene units, indicating that the PNB units permeate trough the HDL chains. The copolymers with different molar ratios [HDL]/[NB] have good thermal stability up to 411 °C in comparison with the homopolymer PHDL (384 °C). Further, the stress-strain measurements in tension for these copolymers depicted the appreciable increment in stress values as the NB content increases.


Elevated hexokinase increases cardiac glycolysis in transgenic mice.
Cardiac glucose metabolism is critical to normal and pathological function. The significance of the first committed metabolic step, glucose phosphorylation, has not been established. In this study a new transgenic model was developed in order to investigate the importance of this enzymatic step in cardiac glycolysis. Transgenic mice were produced that overexpress yeast hexokinase B under the control of a cardiac specific promoter. Yeast hexokinase B is a high affinity enzyme that is not inhibited by glucose-6-phosphate. Hexokinase enzyme activity was measured by a modified radiometric procedure. Cardiac glucose metabolism and contractility were measured in the Langendorff mode. Cardiac glycogen content and glucose-6-phosphate independent glycogen synthase activity were also determined. In transgenic hearts hexokinase activity was significantly elevated and increased glucose metabolism, particularly in the presence of insulin and during cardiac reperfusion. However during ischemic perfusion the effect of the transgene on glycolysis was minimal. Under all conditions tested there was no effect of hexokinase on contractility. Glycogen content of transgenic hearts was elevated 2-fold and glucose-6-phosphate independent glycogen synthase was also increased. These results demonstrate that glucose phosphorylation is a key step in determining cardiac glucose metabolism under oxidative conditions.


Preferential human eosinophil chemotactic activity of the platelet-activating factor (PAF) 1-0-hexadecyl-2-acetyl-sn-glyceryl-3-phosphocholine (AGEPC).
The chemotactic responses of human blood neutrophils and of eosinophils of two different densities, which were resolved by centrifugation on gradients of polyvinylpyrrolidone-coated silica gel (Percoll), were quantified in modified Boyden micropore filter chambers using highly purified synthetic 1-0-hexadecyl-2-acetyl-sn-glyceryl-3-phosphocholine (AGEPC or PAFacether) and leukotriene B4 (LTB4) as stimuli. Maximal chemotactic responses of the densest eosinophils, less dense eosinophils, and neutrophils were evoked by 1 nM, 100 nM, and 1 microM PAFacether, respectively, and by 30-100, 30-100, and 10 nM LTB4. The magnitude of the maximal chemotactic response to PAFacether of the densest eosinophils was significantly greater than that of neutrophils. The eosinophil responses to PAFacether were chemotactic, as distinguished from chemokinetic, and were not influenced by the percentage of contaminating neutrophils. PAFacether is a more potent chemotactic factor for eosinophils than neutrophils and selectively attracts the densest population of human blood eosinophils.


New insights in the coordinated amidase and glucosaminidase activity of the major autolysin (Atl) in Staphylococcus aureus.
After bacterial cell division, the daughter cells are still covalently interlinked by the peptidoglycan network which is resolved by specific hydrolases (autolysins) to release the daughter cells. In staphylococci, the major autolysin (Atl) with its two domain enzymes, N-acetylmuramyl-L-alanine amidase (AmiA) and β-N-acetylglucosaminidase (GlcA), resolves the peptidoglycan to release the daughter cells. Internal deletions in each of the enzyme domains revealed defined morphological alterations such as cell cluster formation in ΔamiA, ΔglcA and Δatl, and asymmetric cell division in the ΔglcA. A most important finding was that GlcA activity requires the prior removal of the stem peptide by AmiA for its activity thus the naked glycan strand is its substrate. Furthermore, GlcA is not an endo-β-N-acetylglucosaminidase but an exo-enzyme that cuts the glycan backbone to disaccharides independent of its O-acetylation modification. Our results shed new light into the sequential peptidoglycan hydrolysis by AmiA and GlcA during cell division in staphylococci.


Rapid synthesis of Ti-MCM-41 by microwave-assisted hydrothermal method towards photocatalytic degradation of oxytetracycline.
This study employed microwave-assisted hydrothermal method to synthesize Ti-MCM-41, which are mesoporous materials with a high surface area and excellent photocatalytic ability. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and ultraviolet-visible spectroscopy (UV-Vis) were employed. The XRD findings showed that Ti-MCM-41 exhibited a peak at 2θ of 2.2°, which was attributed to the hexagonal MCM-41 structure. The BET (Brunauer-Emmett-Teller) results agreed with the TEM findings that Ti-MCM-41 has a pore size of about 3-5nm and a high surface area of 883m(2)/g. FTIR results illustrated the existence of Si-O-Si and Si-O-Ti bonds in Ti-MCM-41. The appearance of Ti 2p peaks in the XPS results confirmed the FTIR findings that the Ti was successfully doped into the MCM-41 structure. Zeta (ζ)-potential results indicated that the iso-electric point (IEP) of Ti-MCM-41 was at about pH3.02. In this study, the photocatalytic degradation of oxytetracycline (OTC) at different pH was investigated under Hg lamp irradiation (wavelength 365nm). The rate constant (K'obs) for OTC degradation was 0.012min(-1) at pH3. Furthermore, TOC (total organic carbon) and high resolution LC-MS (liquid chromatography-mass spectrometry) analyses were conducted to elucidate the possible intermediate products and degradation pathway for OTC. The TOC removal efficiency of OTC degradation was 87.0%, 74.4% and 50.9% at pH3, 7 and 10, respectively. LC-MS analysis results showed that the degradation products from OTC resulted from the removal of functional groups from the OTC ring.


Long-term alkaline volatile fatty acids production from waste streams: Impact of pH and dominance of Dysgonomonadaceae.
Alkaline co-fermentation of primary sludge and external organic waste (OW) was studied to elucidate the influence of substrate ratios and long-term system robustness and microbial community dynamics using batch and semi-continuous reactors. Volatile fatty acid (VFA) production increased with increasing OW fraction in the substrate due to synergistic effects of co-degradation. VFA production at pH 10 increased up to 30,300 mgCOD/L (yield of 630 mg COD/gVSfed) but reduced over time to ≈10,000 mgCOD/L. Lowering pH to 9 led to the restoration of VFA production with a maximum of 32,000 mg COD/L (676 mg COD/g VSfed) due to changes in microbial structure. VFA was composed mainly of acetic acid, but propionic acid increased at pH 9. The microbial community was dominated by Bacillaceae (34 ± 10%) and Proteinivoracales_uncultured (16 ± 11%) at pH 10, while Dysgonomonadaceae (52 ± 8%) was enriched at pH 9. The study demonstrated a zero-waste strategy that turns organic wastes into bio-based products.


[Influence of dental caries prophylaxis using fluor-vigantoletten 1000 on plasma fluoride levels in infants (author's transl)].
A group of 57 newborns was divided into two: group I (27 subjects) received solely 1,000 I.U. vitamin D3 per day for 6 months, whereas group II (30 subjects) were given a combination of 1,000 I.U. vitamin D3 and 0.25 mg fluoride. At the end of the time of observation there was a significant difference between the plasma concentrations in the two groups. The median value was 13.06 microgram/l (range: 8:18-39.4 microgram/l) in group I and 16.54 microgram/l (range: 9.9--41.2 microgram/l) in group II. Fluoride is obviously available to infants when administered in combination with Vitamin D3. In addition, it could be proven, that after 6 month administration of fluoride there are no signs of cumulation, overdosage or even intoxication.


Leishmania mexicana: temperature sensitivity of isolated amastigotes and of amastigotes infecting macrophages in culture.
Different temperature requirements for intracellular growth of Leishmania spp. may account for the predominantly peripheral or visceral localization of the parasites in the vertebrate host. We show here that Leishmania mexicana amazonensis, an agent of cutaneous disease, is growth restricted in vitro at 37.5 C and viable at 34 C. This temperature sensitivity has been observed in both infected macrophage cultures and isolated amastigotes. Counts of the percentage of infected macrophages and of the number of amastigotes per infected cell documented that at 34 C the parasites progressively proliferated for at least 11 days. In contrast, no amastigotes were found in infected cells 48 to 72 hr after the cultures were shifted to the restrictive temperature of 37.5 C. This effect was reversible within the first 24 hr of temperature shift. Incorporation of [3H]uracil into parasite RNA was used to monitor the viability of intracellular and of isolated amastigotes. The trichloroacetic acid-precipitable incorporation of [3H]uracil by infected macrophages was markedly reduced as early as 6 hr after the monolayers were placed at 37.5 C. This decrease was also reversible within the first 24 hr at the restrictive temperature. In order to determine whether the restrictive temperature could directly affect the parasites, isolated amastigotes were incubated at either 34 C or 37.5 C and assayed for [3H]uracil incorporation. The results indicated that by 3 hr of incubation at the restrictive temperature the incorporation was significantly decreased and remained low for at least 9 hr.


The efficacy of the supramolecular complexes of niclosamide obtained by mechanochemical technology and targeted delivery against cestode infection of animals.
Niclosamide is an anthelmintic that is widely used to treat cestode infection of animals. The efficacy of the supramolecular complexes of niclosamide obtained by mechanochemical technology and targeted delivery was studied in hymenolepiosis of mice and monieziosis of sheep. The efficacy of new substances of niclosamide with polyvinylpyrrolidone polymer in different ratios (1:10; 1:5; 1:2) was determined by the results of helminthological necropsy of the small intestine of sheep and mice. Pre-treatment eggs per gram (EPG) were not significantly different (P>0.1) among groups. The controlled test was used to evaluate the efficacy. A high efficacy (>95% efficacy) of the supramolecular complexes of niclosamide with PVP (SCoNwPVP) was shown in different ratios (1:10; 1:5 and 1:2) at a dose of 20mg/kg of body weight at oral administration against Hymenolepis nana in mice and Moniezia expansa in sheep. Whereas the basic drug - substance of niclosamide was effective at a dose of 100mg/kg of b/w. No adverse effects of the drugs on animal health were detected during the study.


Lectins and lectibodies: potential promising antiviral agents.
In nature, lectins are widely dispersed proteins that selectively recognize and bind to carbohydrates and glycoconjugates via reversible bonds at specific binding sites. Many viral diseases have been treated with lectins due to their wide range of structures, specificity for carbohydrates, and ability to bind carbohydrates. Through hemagglutination assays, these proteins can be detected interacting with various carbohydrates on the surface of cells and viral envelopes. This review discusses the most robust lectins and their rationally engineered versions, such as lectibodies, as antiviral proteins. Fusion of lectin and antibody's crystallizable fragment (Fc) of immunoglobulin G (IgG) produces a molecule called a "lectibody" that can act as a carbohydrate-targeting antibody. Lectibodies can not only bind to the surface glycoproteins via their lectins and neutralize and clear viruses or infected cells by viruses but also perform Fc-mediated antibody effector functions. These functions include complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and antibody-dependent cell-mediated phagocytosis (ADCP). In addition to entering host cells, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein S1 binds to angiotensin-converting enzyme 2 (ACE2) and downregulates it and type I interferons in a way that may lead to lung disease. The SARS-CoV-2 spike protein S1 and human immunodeficiency virus (HIV) envelope are heavily glycosylated, which could make them a major target for developing vaccines, diagnostic tests, and therapeutic drugs. Lectibodies can lead to neutralization and clearance of viruses and cells infected by viruses by binding to glycans located on the envelope surface (e.g., the heavily glycosylated SARS-CoV-2 spike protein).


Successful laparoscopic treatment of a ruptured primary ovarian pregnancy.
A 26-year-old woman had classic symptoms of primary ovarian pregnancy. Ultrasound examination disclosed a cystic mass surrounded by a complex mass that was compatible with hematoma in the pouch of Douglas, as well as an intrauterine device (IUD) displaced near the isthmic portion of the uterine cavity. Laparoscopy revealed a ruptured gestational sac in the cul-de-sac that was encapsulated by a hematoma originating from the right ovary. All deep-seated products of conception were excised from the ovary, and the IUD was removed. Treatment was successful and avoided more invasive intervention.


Using cultural and structural indicators to explain measurement noninvariance in gender role attitudes with multilevel structural equation modeling.
The current study explores the reasons for noninvariance of the measurements of gender role attitudes across countries. While previous studies have shown that noninvariance is a problem for comparative research and pointed out methods to alleviate the risks of drawing invalid conclusions, none has so far tried to explain why measurements of gender role attitudes are nonequivalent. Therefore, we use multilevel structural equation modeling to exploring measurement invariance and explain its absence. We use data assessing peoples' views on the specialization of roles by gender and the consequences of female employment on family's well-being from the International Social Survey Programme. We can replicate the findings from prior research indicating that scalar measurement invariance across countries is absent. Furthermore, we use two country-level variables to explain the noninvariance of particular items. The cultural value embeddedness explains noninvariance to a considerable degree while the Gender Inequality Index from the United Nations Development Programme does not. Therefore, we conclude that issues of comparability of gender role attitudes are related mainly to cultural rather than structural differences between countries.


Enriching membrane cholesterol improves stability and cryosurvival of buffalo spermatozoa.
Buffalo spermatozoa are comparatively more susceptible to freezing hazards than cattle spermatozoa. In recent times incubation of spermatozoa with cholesterol-loaded-cyclodextrins (CLC) has shown improvements in semen quality in several species. Therefore, this study was undertaken to evaluate the incubation level of CLC at which maximum benefit is derived for the buffalo spermatozoa. For the study, 120 million spermatozoa were incubated in 2, 3 and 4 mg/mL of CLC (Gr II, III and IV, respectively) and cholesterol and phospholipids content, their ratio, flow cytometric evaluation of plasma membrane integrity (PMI), plasma membrane fluidity and extent of cryoinjury (Chlortetracycline, CTC assay) were compared with an untreated control (Gr I). Additionally the ability of cholesterol-loaded-spermatozoa to undergo induced acrosome reaction (IAR) using ionophore calcium (A23187) was evaluated in frozen-thaw samples. Data show a significant and linear increase (CV=0.88) in cholesterol content of spermatozoa in Gr II, III and IV and a significant decrease in phospholipids content at frozen-thaw stage in Gr IV than Gr III spermatozoa. The study revealed a significant improvement in PMI and significant reduction in plasma membrane fluidity and cryoinjury of CLC treated spermatozoa at progressive stages in three groups compared to control. Nevertheless, spermatozoa of Gr II, III and IV were significantly less responsive to ionophore calcium (A23187) than Gr I. This study shows for the first time that incubation of buffalo bull spermatozoa with CLC (3mg/120×10(6)) prior to processing permits greater numbers of sperm to survive cryopreservation while allowing spermatozoa to capacitate and the acrosome to react to AR inducer ionophore calcium (A23187).


[Alcohol, occupational accidents and their sequelae].
Alcohol is a considerably more important risk factor for non occupational accidents than for occupational accidents, but somatic and psychosocial consequences of chronic alcohol consumption can also have very negative influences on the course of healing and professional rehabilitation. Three cases illustrate the importance of the primary and secondary prevention. They did charge the workers' compensation account of the companies involved with more than one million francs, with corresponding increases in workers' compensation premiums.


Positron emission tomography with [18F]2-fluoro-D-2-deoxyglucose (FDG-PET) predicts relapse of malignant lymphoma after high-dose therapy with stem cell transplantation.
We have determined the predictive value of [18F]2-fluoro-2-deoxy-glucose (FDG-PET) in patients with Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL) scheduled for high-dose therapy with stem cell transplantation (HDT/SCT). Inclusion criteria were the presence of an FDG-PET scan after chemotherapy (ChT) within 8 weeks prior to HDT/SCT and available follow-up data. Sixteen patients (10 NHL and six HD) were observed during a follow-up period of 4 to 28 months (median 13 months). Before SCT, five patients had a negative PET, three were weakly positive, two moderately positive, and six strongly positive. None of the five patients with a negative PET before HDT/SCT relapsed and two of three patients with a weakly positive scan are still in remission after HDT/SCT. Of eight patients with a moderate or high positive PET before HDT/SCT, seven relapsed and one died of early HDT/SCT related complications (P< 0.01). Three of eight relapsing patients died of lymphoma 5 to 10 months after SCT and in one additional patient not responding to HDT/SCT, the main cause of death was chronic toxicity 4 months after transplantation. After 12 months, in PET-negative patients the overall and relapse-free survival was 100%, in PET-positive patients 55% and 18%, respectively. In NHL, two patients with negative PET, but with an age-adjusted international prognostic index (AaIPI) of 2 and one with AaIPI = 1 are still in remission. In the seven PET-positive subjects, one patient with AaIPI = 0, three with AaIPI = 1, and two with AaIPI = 2 relapsed. We conclude that FDG-PET is accurate in the prediction of relapse prior to HDT/SCT in patients with lymphoma. It provides additional information when compared with the AaIPI.


Microstructural and Metabolic Changes in Normal Aging Human Brain Studied with Combined Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging.
This study aimed to detect age-related brain metabolic and microstructural changes in healthy human brains by the use of whole-brain proton magnetic resonance spectroscopic imaging (1H‑MRSI) and quantitative MR imaging (qMRI). In this study, 60 healthy participants with evenly distributed ages (between 21 and 69 years) and sex underwent MRI examinations at 3T including whole-brain 1H‑MRSI. The concentrations of the metabolites N‑acetylaspartate (NAA), choline-containing compounds (Cho), total creatine and phosphocreatine (tCr), glutamine and glutamate (Glx), and myo-inositol (mI), as well as the brain relaxation times T2, T2' and T1 were measured in 12 regions of interest (ROI) in each hemisphere. Correlations between measured parameters and age were estimated with linear regression analysis and Pearson's correlation test. Significant age-related changes of brain regional metabolite concentrations and tissue relaxation times were found: NAA decreased in eight of twelve ROIs, Cho increased in three ROIs, tCr in four ROIs, and mI in three ROIs. Glx displayed a significant decrease in one ROI and an increase in another ROI. T1 increased in four ROIs and T2 in one ROI, while T2' decreased in two ROIs. A negative correlation of tCr concentrations with T2' relaxation time was found in one ROI as well as the positive correlations of age-related T1 relaxation time with concentrations of tCr, mI, Glx and Cho in another ROI. Normal aging in human brain is associated with coexistent brain regional metabolic alterations and microstructural changes, which may be related to age-related decline in cognitive, affective and psychomotor domains of life in the older population.


Immunogenicity screening assay development for a novel human-mouse chimeric anti-CD147 monoclonal antibody (Metuzumab).
The clinical effect of patient immune responses to therapeutic antibodies affect product safety and efficacy, which makes the development of valid, sensitive immune assays a key aspect of antibody drug development. In this paper, we reported the generations of mouse monoclonal and Cynomolgus monkey polyclonal antibodies against the anti-CD147 antibody (Metuzumab) as the internal standards and the positive controls. Seven mouse monoclonal antibodies were shown to recognize both (Fab)2 and full length of Metuzumab, but not the control normal human IgGs, and monoclonal anti-Metuzumab, Clone 2D9 was chosen to be used as the internal standard for anti-Metuzumab study. A Bridging ELISA assay was developed by coating the wells with the antibody drug, and the anti-drug antibody (ADA) in the animal sera were detected by enzyme-labeled antibody. Its limit of detection (LOD) was determined to be 0.39ng/ml of anti-Metuzumab antibody (ADA) with linear range between 0.39-50ng/ml and R(2)=0.994. For normal monkey sera, a minimal dilution was determined to be 1:80. However, very different from peptide or other protein drugs, strong interferences from the residual antibody drugs were observed from most of the testing monkey sera in the preclinical study. It was experimentally determined that the concentration of the residual antibody drug in the assay have to be lower than 1μg/ml, so the assays were carried out at 1:100 dilution of the monkey sera. In the pre-clinical study, 32 monkeys were treated with escalating doses of Metuzumab between 0, 10, 50, 200mg/kg for 13 times over 13weeks of time period. 16 of them were terminated right after the last injection, while the other 16 were rested for additional 4weeks before termination. Afraid to miss any positive response to antibody drug, sera samples were collected at six time points, including 2-, 6- and 10-weeks post 1st dose, prior to last dose, and 2-, 4-weeks into recovery. The highest positive rates were seen with the Medium- and High-dose group 2-weeks post the first injection, 6 out 8 monkeys in the High-dose were positive for free ADA. However, no significant pathologic and clinic adversary effect was observed in those monkeys.


[Isolation of DNA from epithelial cells of the internal portion of the cheek].
It is suggested to use epithelial cells from the inner cheek surface as a source of high molecular individual genomic human DNA to be used in Southern hybridization. The method efficiency has been proved experimentally.


[Inhibin].
Chemical structure of inhibins is known: there are molecules constituted by two subunits alpha and beta (A or B). Inhibin displays actions at hypophyseal, hypothalamic and gonadal levels. Produced by granulosa cells in female and by Sertoli cells in male, inhibin synthesis is stimulated by FSH, androgens and reduced by hypophysectomy and progesterone. At the present time, there is no evidence for a signal from germinal cells to modify inhibin production. Inhibin secretion parallels with follicular maturation as aromatase activity whereas luteinization arrests its production. Sperm inhibin levels are correlated with spermatozoa number. Its administration to the sheep induces either an anovulation or an increase of ovulation rate according to the scheme of treatment.