Reconstruction of Myerson type III chronic Achilles tendon ruptures using semitendinosus tendon and gracilis tendon autograft.
Reconstruction of Myerson type III (defect size more than 5 cm) chronic Achilles tendon ruptures (CATRs) is a surgical challenge due to its large Achilles tendon defect. This study aims to describe our operative technique for Myerson type III CATR and its clinical outcomes. From May 2012 to April 2015, we treated seven patients (6 males, 1 female) with Myerson type III CATR using semitendinosus tendon and gracilis tendon autograft. The mean age was 47.3 years (range: 37-56). Patients were followed for a mean time of 31.3 months. All patients' defect size between Achilles ends after debridement was more than 5 cm and hence classified as Myerson type III. The clinical outcomes were evaluated by visual analog scale (VAS) for pain, American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot score, Achilles tendon total rupture score (ATRS), and the Short Form 36 (SF-36). All patients reported good postoperative clinical outcomes. The average AOFAS score increased from 54.29 points (range: 46-65 points) preoperatively to 97.57 points (range: 90-100 points) at last follow-up. The average ATRS increased from 51.43 points (range: 40-61 points) preoperatively to 92.71 points (range: 83-100 points) at last follow-up. And the average VAS for pain was 0 at the last follow-up. The mean value of SF-36 physical increased from 32.14 points (range: 25-35 points) to 90 points (range: 80-95 points). And the mean value of SF-36 mental was improved from 37.14 points (range: 32-40 points) to 90.86 points (range: 84-96 points). Semitendinosus tendon combined gracilis tendon autograft is a safe and effective technique in the reconstruction of Myerson type III CATR.


Erosion of an inflatable penile prosthesis reservoir into the bladder, presenting as bladder calculi.
We report a case of erosion of an inflatable penile prosthesis reservoir int the bladder 4 years after implantation for organic impotence. In contrast to previously reported cases this complication was not associated with incontinence, urinary tract infection or a revision procedure. Microscopic hematuria was present but there was no pyuria. Diagnosis evaded radiographic and cystoscopic confirmation. Bladder erosion of the reservoir was discovered incidentally during treatment of bladder calculi.


Changes with aging in the levels of amino acids in rat CNS structural elements. I. Glutamate and related amino acids.
Glutamate and related amino acids were determined in 53 discrete brain areas of 3- and 29-month-old male Fischer 344 rats microdissected with the punch technique. The levels of amino acids showed high regional variation - the ratio of the highest to lowest level was 9 for aspartate, 5 for glutamate, 6 for glutamine, and 21 for GABA. Several areas were found to have all four amino acids at very high or at very low level, but also some areas had some amino acids at high, others at low level. With age, in more than half of the areas, significant changes could be observed; decrease occurred 5 times more frequently than increase. Changes occurred more often in levels of aspartate and GABA than in those of glutamate or glutamine. The regional levels of glutamate and its related amino acids show severalfold variations, with the levels tending to decrease in the aged brain.


Multicriteria optimization in intensity-modulated radiation therapy treatment planning for locally advanced cancer of the pancreatic head.
Intensity-modulated radiation therapy (IMRT) affords the potential to decrease radiation therapy-associated toxicity by creating highly conformal dose distributions. However, the inverse planning process can create a suboptimal plan despite meeting all constraints. Multicriteria optimization (MCO) may reduce the time-consuming iteration loop necessary to develop a satisfactory plan while providing information regarding trade-offs between different treatment planning goals. In this exploratory study, we examine the feasibility and utility of MCO in physician plan selection in patients with locally advanced pancreatic cancer (LAPC). The first 10 consecutive patients with LAPC treated with IMRT were evaluated. A database of plans (Pareto surface) was created that met the inverse planning goals. The physician then navigated to an "optimal" plan from the point on the Pareto surface at which kidney dose was minimized. Pareto surfaces were created for all 10 patients. A physician was able to select a plan from the Pareto surface within 10 minutes for all cases. Compared with the original (treated) IMRT plans, the plan selected from the Pareto surface had a lower stomach mean dose in 9 of 10 patients, although often at the expense of higher kidney dose than with the treated plan. The MCO is feasible in patients with LAPC and allows the physician to choose a satisfactory plan quickly. Generally, when given the opportunity, the physician will choose a plan with a lower stomach dose. The MCO enables a physician to provide greater active clinical input into the IMRT planning process.


Characterization and immunomodulatory effect of an alkali-extracted galactomannan from Morchella esculenta.
In our continuous exploration for bioactive polysaccharides, a novel polysaccharide FMP-2 was isolated and purified from the fruiting bodies of Morchella esculenta by alkali-assisted extraction. FMP-2 had an average molecular weight of 1.09 × 106 Da and contained mannose, glucuronic acid, glucose, galactose, and arabinose in a molar ratio of 4.10:0.22:1.00:5.75:0.44. The backbone of FMP-2 mainly consisted of 1,2-α-D-Galp, 1,6-α-D-Galp, and 1,4-α-D-Manp, with branches of 1,4,6-α-D-Manp and 1,2,6-α-D-Galp. FMP-2 can stimulate phagocytosis and promote the secretion of NO, ROS, and cytokines like IL-6, IL-1β, and TNF-α in RAW264.7 cells ranging from 25 to 400 μg/mL. FMP-2 had great repairing effect on the immune injury of zebrafish induced by chloramphenicol. The phagocytosis ability of zebrafish macrophages and the proliferation of neutrophils can be greatly enhanced by polysaccharide FMP-2 with concentrations from 50 to 200 μg/mL. These findings suggest that FMP-2 might be used as a potential immunomodulator in the food and pharmaceutical industries.


Surgeon workload and survival from breast cancer.
The formation of multidisciplinary breast teams across the UK is intended to concentrate the assessment and treatment of breast cancer into the hands of high volume specialists. We undertook a retrospective population-based study in order to determine the trends in surgeon breast cancer workload in Yorkshire, UK, and to investigate whether patients treated by low-workload surgeons had poorer survival. Of 11 329 female breast cancer patients diagnosed in 1989-1994 in Yorkshire, 6% were managed by surgeons with a mean annual workload of less than 10 new patients, while surgeons with workloads of 10-29, 30-49 and >50 treated 21, 21 and 52%, respectively. Over the study period, increasing number of patients were managed by surgeons with higher workloads. Patients treated by low-workload surgeons had poorer survival. Five-year survival was 60% in the lowest workload category compared to 68% in the highest category. The relative risk of death was increased by 15% (RR=1.15, 95% CI 1.03-1.28) and by 10% (RR=1.10, 95% CI 1.02-1.18) for patients managed by surgeons with workloads <10 and 10-29 cases per annum in comparison to patients managed by surgeons with workloads of >50. The results of this study suggest increasing site specialisation in breast cancer among general surgeons. It also provides further evidence that the management of patients by surgeons with low workloads decreases overall survival.


The role of leadership in times of systems disruption: a qualitative study of health and social care integration.
To understand whether and how effective integration of health and social care might occur in the context of major system disruption (the COVID-19 pandemic), with a focus on how the initiative may overcome past barriers to integration. Rapid, descriptive case study approach with deviant case sampling to gather and analyse key informant interviews and relevant archival documents. The innovation ('COVID-19 Protect') took place in Norfolk and Waveney, UK, and aimed to foster integration across highly diverse organisations, capitalising on existing digital technology to proactively identify and support individuals most at risk of severe illness from COVID-19. Twenty-six key informants directly involved with project conceptualisation and early implementation. Participants included clinicians, executives, digital/information technology leads, and others. Final sample size was determined by theoretical saturation. Four primary recurrent themes characterised the experiences of diverse team members in the project: (1) ways of working that supported rapid collaboration, (2) leveraging diversity and clinician input for systems change, (3) allowing for both central control and local adaptation and (4) balancing risk taking and accountability. This rapid case study underscores the role of leadership in large systems change efforts, particularly in times of major disruption. Project leadership overcame barriers to integration highlighted by prior studies, including engaging with aversion to clinical/safety risk, fostering distributed leadership and developing shared organisational practices for data sharing and service delivery. These insights offer considerations for future efforts to support strategic integration of health and social care.


Adoption of new selection criteria on living donor liver transplantation for hepatocellular carcinoma and their impact on the outcome.
In cadaveric liver transplantation, the Milan criteria have been accepted as the selection criteria for HCC in considering organ allocation. However, the situation in LDLT is different. This is a retrospective study on 518 recipients who underwent LDLT. The exclusion criteria included HCC with extrahepatic spread and HCC extending to the major hepatic vessels detected during the preoperative evaluation. HCC was the indication in 96 patients (18.5%); 52/96 patients (54.2%) fulfilled Milan criteria and 44/96 patients (45.8%) did not. The 5-year survival rate among patients fulfilling Milan criteria was 40/52 (77.0%) while for those who did not 30/44 (68.0%). Although these results show better survival rates among patients with HCC within the Milan criteria, they are insignificant (p=0.01) and they clearly demonstrate that patients with HCC outside the Milan criteria have nearly the same survival rate as patients with HCC within Milan criteria. Transplantation is the best treatment option for patients with HCC if a careful search reveals no extra-hepatic disease. The application of the Milan criteria for all patients with HCC would have denied many patients who can survive after transplantation. In LDLT programs, where the patient has a special living donor, the Milan criteria are not necessarily relevant.


FGF9 from cancer-associated fibroblasts is a possible mediator of invasion and anti-apoptosis of gastric cancer cells.
Cancer-associated fibroblasts (CAFs), which reside around tumor cells, are suggested to play a pivotal role in tumor progression. Here we performed microarray analyses to compare gene expression profiles between CAFs and non-cancerous gastric fibroblasts (NGFs) from a patient with gastric cancer and found that fibroblast growth factor 9 (FGF9) was a novel growth factor overexpressed in CAFs. We then examined the biological effects of FGF9 during progression of gastric cancer. Expression of FGF9 in CAFs and NGFs, and their secreted products, were examined by Western blotting. The effects of FGF9 on AGS and MKN28 gastric cancer cells in terms of proliferation, invasion and anti-apoptosis were assessed by WST-1 assay, invasion chamber assay and FACS, respectively. Furthermore, the intracellular signaling by which FGF9 exerts its biological roles was examined in vitro. FGF9 was strongly expressed in CAFs in comparison with NGFs, being compatible with microarray data indicating that FGF9 was a novel growth factor overexpressed in CAFs. Treatment with FGF9 promoted invasion and anti-apoptosis through activation of the ERK and Akt signaling pathways in AGS and MKN28 cells, whereas these effects were attenuated by treatment with anti-FGF9 neutralizing antibody. In addition, FGF9 treatment significantly enhanced the expression of matrix metalloproteinase 7 (MMP7) in both cell lines. FGF9 is a possible mediator secreted by CAFs that promotes the anti-apoptosis and invasive capability of gastric cancer cells.


Toxicological effects of WS2 nanomaterials on rice plants and associated soil microbes.
As an important member of transition-metal dichalcogenides family, tungsten disulfides nanomaterials (WS2 NMs) have a wide range of applications. To date, their environmental risks remain largely unknown. In this study, rice plants were grown in soil amended with different concentrations (0, 10, and 100 mg/kg) of WS2 NMs for 4 weeks. WS2 NMs at 100 mg/kg significantly increased MDA (malondialdehyde) content and decreased total antioxidant capacities of leaves, indicating the oxidative response induced by WS2 NMs. Meanwhile, WS2 NMs at 100 mg/kg significantly decreased root biomass compared to control, indicating the negative impacts of WS2 NMs on plant growth. While exposure to 100 mg/kg WS2 NMs significantly increased soil bioavailable Cu, Fe, Zn, and Olsen-P, and increased the content of Cu, Fe, Zn, and P in rice leaves. Inductively coupled plasma-optical emission spectroscopy (ICP-OES) analysis showed that W was taken up by rice roots and translocated into leaves. The impact of WS2 on soil microbial communities was evaluated by 16S rRNA gene sequencing. WS2 NMs at 100 mg/kg significantly decreased soil microbial diversity, as indicated by decreased Shannon index. In addition, 100 mg/kg WS2 shifted the soil microbial profile, the relative abundance of the phylum Acidobacteriota decreased, and Actinobacteriota increased. Taken together, the soil microbial community's diversity and composition have been altered upon exposure to 100 mg/kg WS2 NMs. The results of this study provide some basic information regarding the environmental behavior and phytotoxicity of WS2 NMs, which is valuable for safe use of WS2 NMs.


Warfarin inhibits both procoagulant activity and metastatic capacity of Lewis lung carcinoma cells. Role of vitamin K deficiency.
Chronic vitamin K deficiency, either dietary or pharmacologically induced with warfarin, depressed significantly the growth of lung secondaries in a spontaneously metastasizing murine tumor, the Lewis Lung Carcinoma. This effect was associated with a marked depression of the procoagulant activity of cancer cells, which could contribute to fibrin deposition around the tumor. Cellular anticoagulation may thus be an important mechanism in the antimetastatic effect of warfarin.


[Photochenical and photoelectronic properties of components of the photosynthetic apparatus. II. Stationary photoconductivity in chlorophyll-acceptor and chlorophyll+protein-acceptor lamellar systems].
It has been shown that the treatment of chlorophyll a amorphous layer surface with the electron acceptor n-chloranyl leads to an increase of photocurrent by 10(1)--10(3) times. The photoinduced polarization in the lamellar system chlorophyll a--n-chloranyll is studied. It has been shown that under the effect of the red light the n-chloranyl layer is negatively charged in relation to the pigment layer. Photoconductivity was discovered in the rigid layers of chlorophyll a+human serum albumin. When a thin film of n-chloranyl is sprayed on the surface of the chlorophyll-protein layer, the photocurrent increases approximately 6--7 times. The experimental results are discussed within the scheme according to which the formation of free radical carriers in chlorophyll layers is carried out by the destruction of excited states, possibly excitons on the electron-acceptor centres of dissociation.


Electrostatic assembly of a DNA superparamagnetic nano-tool for simultaneous intracellular delivery and in situ monitoring.
A superparamagnetic γFe(2)O(3) nanocarrier was developed, characterized by spectroscopic methods and evaluated for the delivery of a decoy oligonucleotide (dODN) in human colon carcinoma SW 480 cells. This nanoparticle-dODN bioconjugate (γFe(2)O(3)@dODN) was designed to target the signal transducer and activator of transcription 3, STAT3, a key regulator of cell survival and proliferation. We exploited a simple precipitation-redispersion mechanism for the direct and one-step complexation of a labeled decoy oligonucleotide with iron oxide nanoparticles (NPs). The cell internalization of the decoy γFe(2)O(3)@dODN nanoparticles is demonstrated and suggests the potential for DNA delivery in biological applications. Despite the increasing use of NPs in biology and medicine, convenient methods to quantify them within cells are still lacking. In this work, taking advantage of the nonlinear magnetic behavior of our superparamagnetic NPs, we have developed a new method to quantify in situ their internalization by cells. In this study, the authors demonstrate methods to quantify superparamagnetic nanocarriers within cells, taking advantage of the nonlinear magnetic behavior of the studied NPs.


A rare case of tropical chronic pancreatitis with giant pseudocyst: Case report.
Tropical chronic pancreatitis (TCP) is common in developing countries and is defined as a juvenile form of chronic calcific non-alcoholic pancreatitis. Pseudocysts occur in 20-40% of chronic pancreatitis. TCP with pseudocyst has not been reported yet, so we represent this rare case to broaden the horizons regarding pancreatitis. A 16-year-old woman suffered a painful lump in the upper abdomen. She came from a low-income family and frequently consumed cassava. There was intolerance of glucose in which admission blood sugar level of the patient increased by 179 mg/dl. An abdominal CT scan showed a mass around the pancreas, 20 cm in diameter, and located in retro-gastric. There were multiple ductal calculi along the major pancreatic duct with the largest stone was 3 cm in the pancreatic head. Longitudinal pancreaticojejunostomy (Partington-Rochelle procedure) has been performed and histopathological results appropriate with a pancreatic pseudocyst. TCP with a giant pseudocyst is an interesting case report that has not been reported yet. This case met the clinical characteristics of TCP, such as young women, malnourished, history of cassava consumption, abdominal pain, and intolerance of glucose. A surgical intervention provides a satisfactory result to the patient. Tropical chronic pancreatitis is a rare case. A pseudocyst adds the uniqueness of this case that has never been reported before. Appropriate management can provide satisfactory results and improve the quality of life for patients.


The ARG8m Reporter for the Study of Yeast Mitochondrial Translation.
Mitochondrial translation is an intricate process involving both general and mRNA-specific factors. In addition, in the yeast Saccharomyces cerevisiae, translation of mitochondrial mRNAs is coupled to assembly of nascent polypeptides into the membrane. ARG8m is a reporter gene widely used to study the mechanisms of yeast mitochondrial translation. This reporter is a recodified gene that uses the mitochondrial genetic code and is inserted at the desired locus in the mitochondrial genome. After deletion of the endogenous nuclear gene, this reporter produces Arg8, an enzyme necessary for arginine biosynthesis. Since Arg8 is a soluble protein with no relation to oxidative phosphorylation, it is a reliable reporter to study mitochondrial mRNAs translation and dissect translation form assembly processes. In this chapter, we explain how to insert the ARG8m reporter in the desired spot in the mitochondrial DNA, how to analyze Arg8 synthesis inside mitochondria, and how to follow steady-state levels of the protein. We also explain how to use it to find spontaneous suppressors of translation defects.


CORR Insights™: Intramedullary nails result in more reoperations than sliding hip screws in two-part intertrochanteric fractures.
This CORR Insights™ is a commentary on the article "Intramedullary Nails Result in More Reoperations Than Sliding Hip Screws in Two-part Intertrochanteric Fractures" by Matre et al. available at DOI- 10.1007/s11999-012-2728-2 .


SLE in 2011: Deciphering the role of NETs and networks in SLE.
From neutrophil extracellular traps to genetic networks that underlie the disease and new targeted therapies, important advances in 2011 improve our understanding of the pathogenesis of systemic lupus erythematosus and mark the beginning of our ability to treat it effectively.


Comprehensive study of anxiety and depression in females with urinary incontinence.
Anxiety and depression are commonly seen with urinary incontinence (UI) and its association is strongest for urgency and mixed UI. It affects the quality of life and functional status. To assess the prevalence and severity of anxiety and depression in SUI (Stress urinary incontinence) and UUI/MUI (Urge or mixed urinary incontinence), to assess the severity of SUI and UUI/MUI and its association with anxiety and depression and to identify various factors associated with anxiety and depression. An observational study using various tools as history regarding urinary incontinence, history of other prior events which can lead to anxiety or depression, age, educational level, BMI (Body mass index), HADS scale (Hospital anxiety and depression scale) for anxiety and depression and ICIQ-UI-SF score (International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form). The Prevalence of anxiety and depression in UUI/MUI was higher. More women were overweight (BMI > 25) in the UUI/MUI group. Higher prevalence of anxiety and depression in the very severe urinary incontinence group. No association of the level of education with anxiety and depression in women with urinary incontinence. Anxiety and depression are more in UUI/MUI patients compared to SUI. In obese ladies, UUI is more prevalent compared to SUI. Anxiety and depression are more with increasing severity of incontinence. Anxiety and depression have no association with the educational status of the patients.


Inferior turbinate surgery in children: a survey of practice patterns.
A variety of techniques for inferior turbinate reduction have been used in children, but to date practice patterns have not been studied. The purpose of this survey was to study the practice of inferior turbinate surgery among pediatric otolaryngologists. Cross-sectional survey study. A questionnaire was sent electronically to American Society of Pediatric Otolaryngologists members. A total of 249 questionnaires were sent, and 103 (41%) were completed. Six questionnaires were eliminated due to incompleteness. Seventy-nine (81%) respondents performed inferior turbinate surgery. The most common reason for not performing the procedure was lack of outcomes data. Coblation was the most common technique used in 51% of respondents. A change in surgical technique in the last 2 to 5 years, most commonly to coblation or microdebridement, was reported by 53% of respondents. Nasal obstruction was the primary indication for turbinate reduction (81%), followed by sleep-disordered breathing (16%). Respondents reported that 20% of turbinate reductions were sole procedures, and 80% were with other procedures: adenotonsillectomy, septoplasty, and sinus surgery. Fifty-six (71%) responders were either satisfied or very satisfied with the results of pediatric turbinate surgery. Failure of the procedure, epistaxis, and nasal crusting were commonly reported complications, and 9% reported major complications. A high proportion of pediatric otolaryngologists perform inferior turbinate surgery, most commonly for nasal obstruction. Coblation is the most common technique used, and complications are mostly minor. Physician satisfaction rates are high despite a paucity of outcomes data on the procedure.


An aggressive lymphatic malformation (Gorham's disease) leading to death of a child.
Here in, we present a case of aggressive Gorham's disease in a 10 year old boy. We document its evolution from a seemingly benign buttock mass to a widely invasive disease that was ultimately fatal. We highlight the challenges in the management of such an aggressive, yet benign process and review the available literature on the subject.


Exploring soil erosion trajectories and their divergent responses to driving factors: a model-based contrasting study in highly eroded mountain areas.
Soil erosion threatens environmental sustainability worldwide. Exploring the trajectories of soil erosion and associated drivers is of great significance for combating land degradation. This study selected the highly eroded Loess Plateau (LP) and Karst Plateau (KP) as contrasting regions to monitor soil erosion dynamics. Monitoring was performed by applying the Revised Universal Soil Loss Equation based on a GIS platform and multi-source input data to investigate associated drivers. The results established that soil erosion in both regions was substantially reduced by ecological restoration projects and significant land use/cover conversions. Landscape and geomorphological variables were found to be the dominant factors controlling soil erosion in the LP and KP, as they influenced land use patches and geomorphological patterns, respectively. The correlations between fragmentation metric indices and soil erosion indicated that the appropriately intensive fragmentation in the LP could mitigate or prevent soil erosion by disturbing its formation and transportation and ultimately positively influenced soil erosion control. Geomorphological patterns were also determinative factors, particularly for the KP, where almost all geomorphological variables were significantly correlated with the erosion modulus. Owing to the peculiar landform and landscape conditions in karst areas and loess hilly-gully areas, geomorphological and landscape variables should be considered when determining the main factors affecting soil erosion processes and integrated into the forecasting model to improve the accuracy of the simulation. The findings of this study are expected to (i) improve the efficacy of soil erosion control and (ii) promote the sustainable planning and management of land and soil resources.


Proteoglycan production in Drosophila egg development: effect of beta-D-xyloside on proteoglycan synthesis and larvae motility.
1. Proteoglycans (PGs) of the extracellular matrix (ECM) play an important role in several morphogenetic and differentiation events that occur during embryonic development. 2. The purpose of this work was to characterize the ECM PGs present during development of Drosophila melanogaster, in an attempt to elucidate their functional relevance. 3. The major 35SO4 incorporation into PGs occurred during the first instar larvae. Sulfated PGs (90%) from both first and second instar larvae were degraded by HNO2 treatment. 4. This result indicated that heparan sulfate proteoglycans (HSPG) are present in Drosophila ECM throughout early development. 5. Charge fractionation of PGs on DEAE-Sephacel columns indicated that most of them eluted at 0.45 M NaCl and were sensitive to HNO2. 6. The administration of beta-D-xyloside, a drug that competes with core proteins for the glycosaminoglycan synthetic apparatus, generated biochemical modifications in the ECM PGs together with alterations in larval locomotor behavior.


Heterogeneity in the Association of Citizenship Status on Self-Rated Health Among Asians in California.
Citizenship is considered an egalitarian legal identity but may function differently among minorities because of racial/ethnic stratification and historical context. Using Asians, I examine whether the association between citizenship and self-rated health differs by ethnicity. I examine the moderating effect of Asian ethnic group (Chinese, Filipino, Korean, Vietnamese, and Other Asian) on citizenship and self-rated health using the 2012-2016 California Health Interview Survey (n = 11,084). Models account for demographics, socioeconomic status, healthcare, and English proficiency. Adjusting for demographics, naturalized citizens and non-citizens were statistically significantly more likely to report fair/poor health compared to U.S.-born citizens. Naturalized and non-citizen Vietnamese reported statistically significantly poorer health to all U.S.-born groups. These trends largely disappear when controlling for all covariates. Citizenship status can be useful in considering structural barriers for immigrants. Future work should interrogate the non-citizen category and why trends are seen among Vietnamese, but not others.


Progression of renal failure in diabetic nephropathy.
The onset of renal damage in diabetes mellitus may be influenced by several factors which largely result from genetic predisposition, hereditary factors and the early appearance of microalbuminuria and/or systemic hypertension. Most of these factors are also implicated in the progression of nephropathy from microalbuminuria to overt proteinuria and to end-stage renal failure (ESRF). Over the last few years, the role of hyperglycaemia has emerged as critical in mediating the progressive renal damage in diabetes. However, hyperglycaemia leads to increased formation of glycated proteins which may act as promoters of progression by localizing in renal tissue. In addition, hyperglycaemia may have a synergistic effect with some other risk factors, such as growth factors and the renin angiotensin system, in accelerating renal deterioration.


Rules governing pharmaceuticals in the European Community.
In the interest of public health, the European community has progressively established common scientific criteria for the evaluation of human and veterinary medicines and harmonized the national authorization procedures. One major consequence of this has been that neither the tests and trials carried out to obtain authorization nor batch controls need be repeated within the European community. Henceforth the pharmaceutical industry may benefit from two types of procedures intended to facilitate the registration of their medicinal products in the member states. One, reserved for biotechnology/high technology medicinal products, involves community coordination prior to any national decision together with special protection against copies for ten years, irrespective of the position under patent law. The other enables firms to request the recognition by the other member states of an authorization previously granted by one member state. The experience gained from these two procedures will lead to the choice of the most appropriate European registration procedure for the next decade. In the interests of the European consumer, cooperation between the 12 member states and the Commission of the European Communities has progressively increased within the Committee for Proprietary Medicinal Products (adverse effects of medicines/pharmacovigilance) and the Committee for Veterinary Medicinal Products (residues). In association with these committees, several working groups of experts attempt to approximate and codify practices in the evaluation of the quality, safety, and efficacy of medicinal products (guidelines).(ABSTRACT TRUNCATED AT 250 WORDS)


[A caloric vestibular test with increased positive evidence (author's transl)].
The positive evidence of the caloric test increases, when the time-course of the induced heat wave in the petrous bone was eliminated, which differs from man to man. This is possible by changing head position during calorisation, so that a nearly rectangular stimulus results.


Efficacious, nontoxigenic Bacillus anthracis spore vaccines based on strains expressing mutant variants of lethal toxin components.
We reported previously on the development of a Bacillus anthracis vaccine strain expressing high levels of recombinant protective antigen (rPA) [Cohen et al., Infec Immun 2000;68(8):4549-58]. To further explore the potential of the B. anthracis platform, we generated several attenuated strains expressing lethal toxin components PA and LF, which are biologically inactive, yet retain their antigenic properties. A single injection of 5 x 10(7) spores of one of these strains, carrying PA mutation at a site involved in effector translocation (residues 313-314) was shown to resemble wild type PA in inducing production of high levels of anti-PA neutralizing antibodies and producing effective protective immunity for 12 months. Long-term protection and persistence of functional antibody titers was observed after the gradual elimination of spores from guinea pig tissues 3 months after injection and in the measurable absence of bacteria in tissues. The mutant toxin components could, thus be an effective alternatives to their native counterparts when presented to the immune system in context of a live B. anthracis strain. These live vaccine prototypes may serve as a platform for future multi-component vaccines.


[Detection and its clinical value of CCR5 and CCR7 in dendritic cells from patients with active rheumatoid arthritis].
To detect the expressions of CCR5 and CCR7 on dendritic cells (DCs) in patients with rheumatoid arthritis (RA) in different phases of disease activity, and explore the relationship between the disease activity and the expression of chemokine receptors. Twenty-eight patients with low, moderate and high disease activity and 10 normal control subjects were enrolled in this study. Peripheral blood was obtained from the subjects and the DCs were isolated. The expression of CCR5 and CCR7 on DCs were detected by flow cytometry, and the serum levels of rheumatoid factor (RF), C-reactive protein (CRP) and anti-CCP antibody (ACPA) were assessed. The correlation of the expressions of CCR5 and CCR7 to serum RF, CRP, and ACPA levels of the RA patients were analyzed. Compared to the normal control group, RA patients showed enhanced expressions of CCR5 and CCR7 on the DCs. A linear correlation was noted between CCR5 and CCR7 expressions on the DCs and the serum levels of RF and CRP, but not ACPA, in the RA patients. The expressions of CCR5 and CCR7 on the DCs may correlate to the disease activity of RA, and may serve as valuable indices in monitoring the disease activity and the efficacy of the treatment.


Transfer of antibiotics from goat's milk to rennet curd and whey fractions during cheese-making.
The transfer of 35 antibiotics from milk to curd and whey was evaluated. Cheeses were produced at laboratory scale, from antibiotic-free goat's milk spiked with different antibiotic concentrations between 0.25 and 4 times the Maximum Residue Limits established in milk. Drug concentrations in milk, curd and whey were analysed by UHPLC-HRMS. Results indicated that most antibiotics were mainly transferred from milk to whey (up to 85.9%), with retention percentages in the curd lower than 50%, except for ceftiofur (59.7%) and dicloxacillin (52.8%). In most cases, drug distribution was unaffected by the antibiotic concentration in milk and correlated significantly to the drug lipophilicity (Log P) for β-lactams (R2 = 0.54) and sulfonamides (R2 = 0.62). When drug ionization was considered (Log D), improved correlation coefficients were obtained for macrolides (R2 = 0.98). However, other factors besides the drug solubility should be considered to explain and predict the partitioning of antibiotics during cheese-making.


Analysis of F9 embryonal carcinoma cell lactosaminoglycans in relation to their differential expression during induction of differentiation.
Teratocarcinoma stem cells can be used to study the events related to early differentiation, and many cell surface changes have been described which correlate with the different stages of early embryogenesis. In this work we analyze the [3H]galactose-labeled glycopeptides derived from the mouse embryonal carcinoma cell line F9. We show that the high-molecular-weight glycopeptides typical of embryonal carcinoma cells are composed of two distinct molecular weight classes, namely H1 and H3, and that retinoic acid-induced differentiation determines a relative increase of the larger peak (H1) which is mainly due to a decrease in the expression of H3 species. We also show that, beside this decrease, there is a greater increase in the expression of lower-molecular-weight species. Furthermore, we present evidence that H1 and H3 species are polylactosaminoglycans N-linked to the peptidic backbone, and that induction of differentiation determines slight modifications in the structure of such species.


Bell's Palsy and Its Semantic Change over Time.
From 1821 to 1829, Sir Charles Bell presented cases of facial paralysis from infection, trauma, and unknown causes. As such, "Bell's palsy" initially referred to facial palsy of any etiology. Today, the term is reserved for idiopathic peripheral facial palsy. The objectives of this analysis were to establish when the eponym came to vogue and delineate the semantic shift from its original definition to its current one. Extensive review of available 19th and 20th century literature mentioning "Bell's palsy" and "Bell's paralysis." Historical accounts have eponymously attached Bell's name to facial paralysis as early as the 1840s-Bell's palsy was first used to describe cases of facial palsy of any cause. In 1886, Gowers characterized Bell's palsy as a "neuritis usually within the Fallopian Canal," distinguishing it as a separate etiology. Over the next decades, the definition narrowed to peripheral facial paralysis from cold exposure or unknown causes. By the 1940s, its natural history was well described-an acute, unilateral, idiopathic, and usually self-limited peripheral facial palsy. The semantic change of a word over time can tell us a remarkable story of its history and origins. Absence of a discrete lesion, lack of proven treatment, and good prognosis without intervention distinguished Bell's palsy from other causes of facial paralysis. Over time, the definition has narrowed from a facial palsy of any cause to an idiopathic peripheral facial palsy. Recent evidence supporting Bell's palsy as a viral mononeuritis may have driven its recent semantic change toward this specific etiology.


Myxoid liposarcoma with negative features on bone scan and [18F]-2-fluoro-2-deoxy-D-glucose-positron emission tomography.
Myxoid liposarcoma occurs in middle age, and is characterized by extrapulmonary metastasis, including bone metastasis. Bone scans and [18F]-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) are widely used for assessment of tumor extension, including vertebral metastasis. However, both methods have a low positive rate with regard to vertebral metastasis arising from myxoid liposarcoma. This is particularly true for bone scans for intramedullary lesions that have no cortical involvement. We present the case of a 53-year-old male with myxoid liposarcoma in the leg. He had been treated for multiple metastases over a ten-year period, and was experiencing back pain due to a pathological fracture in the second lumbar vertebra (L2). Magnetic resonance imaging of all the vertebrae showed abnormal signal intensity suggestive of metastasis in eight vertebrae, and revealed extraskeletal extension in three vertebrae. Bone scans and FDG-PET were negative except for the L2 fracture which was indicated on a bone scan. Both bone scans and FDG-PET can be negative in cases of vertebral metastasis that arise from myxoid liposarcoma, even when extraskeletal extensions are present. Similarly, even a fractured vertebra may not always be visible on FDG-PET.


Cost-effectiveness analysis of interferon beta-1b for the treatment of patients with a first clinical event suggestive of multiple sclerosis.
To assess, from a Swedish societal perspective, the cost effectiveness of interferon β-1b (IFNB-1b) after an initial clinical event suggestive of multiple sclerosis (MS) (ie, early treatment) compared with treatment after onset of clinically definite MS (CDMS) (ie, delayed treatment). A Markov model was developed, using patient level data from the BENEFIT trial and published literature, to estimate health outcomes and costs associated with IFNB-1b for hypothetical cohorts of patients after an initial clinical event suggestive of MS. Health states were defined by Kurtzke Expanded Disability Status Scale (EDSS) scores. Model outcomes included quality-adjusted life years (QALYs), total costs (including both direct and indirect costs), and incremental cost-effectiveness ratios. Sensitivity analyses were performed on key model parameters to assess the robustness of model results. In the base case scenario, early IFNB-1b treatment was economically dominant (ie, less costly and more effective) versus delayed IFNB-1b treatment when QALYs were used as the effectiveness metric. Sensitivity analyses showed that the cost-effectiveness results were sensitive to model time horizon. Compared with the delayed treatment strategy, early treatment of MS was also associated with delayed EDSS progressions, prolonged time to CDMS diagnosis, and a reduction in frequency of relapse. Early treatment with IFNB-1b for a first clinical event suggestive of MS was found to improve patient outcomes while controlling costs.


Sleep duration and its association with adiposity markers in adolescence: a cross-sectional and longitudinal study.
Large studies linking adolescents' objectively measured sleep duration and adiposity markers are lacking. We characterized sleep duration and its cross-sectional and longitudinal associations with adiposity markers in adolescence. Seven-day accelerometry was performed in a cohort of adolescents enrolled in the SI! Program for Secondary Schools trial in Spain at approximately ages 12 (1216 adolescents, 49.6% girls), 14 (1026 adolescents, 51.3% girls), and 16 (872 adolescents, 51.7% girls) years. Participants were classified as very short sleepers (VSS; <7 h), short sleepers (SS; 7-<8 h), or recommended-time sleepers (RTS; 8-10 h). Adjusted associations between sleep duration and adiposity markers were analysed using generalized linear and Poisson models. At ∼12 years, 33.7% of adolescents met sleep recommendations, and this percentage decreased with advancing age (22.6% at ∼14 and 18.7% at ∼16 years). Compared with RTS, overweight/obesity prevalence ratios at ∼12, 14, and 16 years among SS were 1.19 [95% confidence interval (CI): 1.09-1.30], 1.41 (95% CI: 1.34-1.48), and 0.99 (95% CI: 0.77-1.26) and among VSS were 1.30 (95% CI: 1.28-1.32), 1.93 (95% CI: 1.41-2.64), and 1.32 (95% CI: 1.26-1.37). Compared with adolescents who always met sleep recommendations, the prevalence of overweight/obesity was ∼5 times higher in those never meeting recommendations or meeting them only once. Similar trends were observed for the waist-to-height ratio (P = 0.010) and fat mass index (P = 0.024). Most adolescents did not meet sleep recommendations. Shorter sleep duration was independently associated with unfavourable adiposity markers, and such adverse impact was cumulative. Health promotion programmes should emphasize the importance of good sleep habits.


Vitamin A and retinoid signaling in the kidneys.
Vitamin A (VA, retinol) and its metabolites (commonly called retinoids) are required for the proper development of the kidney during embryogenesis, but retinoids also play key roles in the function and repair of the kidney in adults. Kidneys filter 180-200 liters of blood per day and each kidney contains approximately 1 million nephrons, which are often referred to as the 'functional units' of the kidney. Each nephron consists of a glomerulus and a series of tubules (proximal tubule, loop of Henle, distal tubule, and collecting duct) surrounded by a network of capillaries. VA is stored in the liver and converted to active metabolites, most notably retinoic acid (RA), which acts as an agonist for the retinoic acid receptors ((RARs α, β, and γ) to regulate gene transcription. In this review we discuss some of the actions of retinoids in the kidney after injury. For example, in an ischemia-reperfusion model in mice, injury-associated loss of proximal tubule (PT) differentiation markers occurs, followed by re-expression of these differentiation markers during PT repair. Notably, healthy proximal tubules express ALDH1a2, the enzyme that metabolizes retinaldehyde to RA, but transiently lose ALDH1a2 expression after injury, while nearby myofibroblasts transiently acquire RA-producing capabilities after injury. These results indicate that RA is important for renal tubular injury repair and that compensatory mechanisms exist for the generation of endogenous RA by other cell types upon proximal tubule injury. ALDH1a2 levels also increase in podocytes, epithelial cells of the glomeruli, after injury, and RA promotes podocyte differentiation. We also review the ability of exogenous, pharmacological doses of RA and receptor selective retinoids to treat numerous kidney diseases, including kidney cancer and diabetic kidney disease, and the emerging genetic evidence for the importance of retinoids and their receptors in maintaining or restoring kidney function after injury. In general, RA has a protective effect on the kidney after various types of injuries (eg. ischemia, cytotoxic actions of chemicals, hyperglycemia related to diabetes). As more research into the actions of each of the three RARs in the kidney is carried out, a greater understanding of the actions of vitamin A is likely to lead to new insights into the pathology of kidney disorders and the development of new therapies for kidney diseases.


Gene therapy restores mitochondrial function and protects retinal ganglion cells in optic neuropathy induced by a mito-targeted mutant ND1 gene.
Therapies for genetic disorders caused by mutated mitochondrial DNA are an unmet need, in large part due barriers in delivering DNA to the organelle and the absence of relevant animal models. We injected into mouse eyes a mitochondrially targeted Adeno-Associated-Virus (MTS-AAV) to deliver the mutant human NADH ubiquinone oxidoreductase subunit I (hND1/m.3460 G > A) responsible for Leber's hereditary optic neuropathy, the most common primary mitochondrial genetic disease. We show that the expression of the mutant hND1 delivered to retinal ganglion cells (RGC) layer colocalizes with the mitochondrial marker PORIN and the assembly of the expressed hND1 protein into host respiration complex I. The hND1-injected eyes exhibit hallmarks of the human disease with progressive loss of RGC function and number, as well as optic nerve degeneration. We also show that gene therapy in the hND1 eyes by means of an injection of a second MTS-AAV vector carrying wild-type human ND1 restores mitochondrial respiratory complex I activity, the rate of ATP synthesis and protects RGCs and their axons from dysfunction and degeneration. These results prove that MTS-AAV is a highly efficient gene delivery approach with the ability to create mito-animal models and has the therapeutic potential to treat mitochondrial genetic diseases.


Transgene expression in mammary glands of newborn rats.
Transgene expression in the mammary glands of newborn rats was studied to establish an early selection system for transgenic animals producing exogenous proteins in their milk during lactation. A fusion gene composed of the bovine alpha S1 casein gene promoter and the human growth hormone gene was microinjected into rat embryos. Transgenic lines that produced human growth hormone in their milk were established and used in this study. Immediately after birth, and without any hormone treatment, human growth hormone was found in the extracts of mammary glands from both male and female rats derived from the line secreting human growth hormone in their milk. The expression of the transgene in mammary glands of newborn rats was also detected by the presence of human growth hormone mRNA. Nontransgenic newborn rats did not express the human growth hormone gene in their mammary glands, while the mRNA for rat alpha casein, an endogenous milk protein, was found in all mammary glands from both transgenic and nontransgenic neonates. These results show that analyzing the expression of transgenes in the mammary glands of neonates is a valuable tool to select the desired transgenic animals and to shorten the selection schedules establishing the transgenic animals.


Sensitive and handy detection of pesticide residue on fruit surface based on single microsphere surface-enhanced Raman spectroscopy technique.
Surface-enhanced Raman spectroscopy (SERS) has become an emerging and reliable tool for detecting pesticide residues due to its high sensitivity, fast testing speed and easy sample handling. SERS active substrates are the key to achieve efficient and sensitive detection. However, for the most widely used noble metal nanoparticles, there are problems of high noble metal nanoparticle usage and random aggregation. The micron-scale Raman spot is focused on multiple randomly aggregated nanoparticles during the test, resulting in poor reproducibility. Therefore, the development of micron-scale cost-effective SERS substrates with good reproducibility and simple detecting method is of great significance in practical detection. Through deposition of silver nanoparticles (Ag-NPs) by chemical reduction on the surface of monodisperse sulfonated polystyrene (SPS) microspheres, micron-sized PS@Ag-NPs core-shell microspheres were prepared with excellent SERS activity. After that, two simple protocols (Method I and Method II) were explored for the determination of thiram on apple epidermis. Based on our developed strategy of the single microsphere SERS technique, we successfully fabricated uniform PS@Ag-NPs substrate with high SERS activity and excellent detection sensitivity. The single microsphere SERS technique possesses the capability of anti-dilutability and the utilization of ultra-low PS@Ag-NPs microsphere dosage, realizing qualitative and quantitative detection of thiram on apple with detection limits far below the standard stipulated by China and the European Union.


Cementation reactions in the presence of nitrogen compounds.
The effect of aniline derivatives on the rate of cementation of copper from dilute copper sulfate solution on iron rods was investigated. The variables studied were concentration of CuSO(4), temperature, organic additives, and their concentrations. It was found that the cementation reaction was first-order in the presence and in the absence of additives. Nitrogen compounds were found to decrease the rate of cementation by 10 to 80% depending on the type of inhibitor as well as its concentration.The adsorption isotherm, the effect of temperature, and the percentage inhibition show that the order of inhibition is p-chloroaniline>o-chloroaniline>m-chloroaniline and p-chloroaniline>p-aminobenzoic acid>p-aminoacetophenone. The thermodynamic parameters DeltaS( not equal ), DeltaG( not equal ), DeltaH( not equal ) were given.


The dowelklip: a device for dowel pin placement.
While no system of dowel pin placement satisfies all the desired requirements in every situation, the dowelklip is an original design that meets most of the requirements for many routine treatment procedures. For dentists who do not do a large enough volume of fixed restorative procedures to justify the expense of complex die positioning systems but are dissatisfied with sticky wax and match sticks, the dowelklip offers an alternative approach.


Anaesthetics modulate tumour necrosis factor alpha: effects of L-carnitine supplementation in surgical patients. Preliminary results.
Both anaesthetics and surgical trauma could strongly affect the production of tumour necrosis factor alpha (TNFalpha). During in vitro experiments the authors found that anaesthetics modulate the production of TNFalpha by peripheral blood mononuclear cells. Notably, Pentothal strongly increased the production of the cytokine as compared to both lipopolysacchride treated and control mononuclear cells, whereas in supernatants from Leptofen driven mononuclear cells TNFalpha was strongly reduced. On the other hand, Pavulon did not significantly affect the cytokine production. In the in vivo study, in an attempt to ameliorate the metabolic response to surgical trauma, L-carnitine was administered to 20 surgical patients, then the circulating TNFalpha was measured. The results indicate that the levels of circulating TNFalpha were strongly increased following surgery and that L-carnitine administration resulted in a strong reduction of TNFalpha. Thus, the data suggest that L-carnitine could be helpful in protecting surgical patients against dysmetabolism dependent on dysregulated production of TNFalpha.


Prioritisation of patients awaiting hip and knee arthroplasty: Lower pre-operative EQ-5D is associated with greater improvement in quality of life and joint function.
The COVID-19 pandemic has led to unprecedented delays for those awaiting elective hip and knee arthroplasty. Current demand far exceeds available resource, and therefore it is integral that healthcare resource is fairly rationed to those who need it most. We therefore set out to determine if pre-operative health-related quality of life assessment (HRQoL) could be used to triage arthroplasty waiting lists. Data regarding demographics, perioperative variables and patient reported outcome measures (PROMs) (pre-operative and 1-year post-operative EuroQOL five dimension (EQ-5D-3L) and Oxford hip and knee scores (OHS/OKS) were retrospectively extracted from electronic patient health records at a large university teaching hospital. Patients were split into two equal groups based on pre-operative EQ-5D TTO scores and compared (Group1 [worse HRQoL] = -0.239 to 0.487; Group2 [better HRQoL] = 0.516-1 [best]). 513 patients were included. Patients in Group1 had significantly greater improvement in post-operative EQ-5D-3L scores compared to Group2 (Median 0.67 vs. 0.19; p < 0.0001), as well as greater improvement in OHS/OKS (Mean 22.4 vs. 16.4; p < 0.0001). Those in Group2 were significantly less likely to achieve the EQ-5D-3L minimum clinically important difference (MCID) attainment (OR 0.13, 95%CI 0.07-0.23; p < 0.0001) with a trend towards lower OHS/OKS MCID attainment (OR 0.66, 95%CI 0.37-1.19; p = 0.168). There was no clinically significant difference in length of stay (Median 3-days both groups), and no statistically significant difference in adverse events (30 days and 1 year readmission/reoperation). A pre-operative EQ-5D-3L cut-off of ≤0.487 for hip and knee arthroplasty prioritisation may help to maximise clinical utility and cost-effectiveness in a limited resource setting post COVID-19.


A comparison of some methods for determining oxygen dissociation curves of fish blood.
A brief description is given of four different methods for determining the oxygen dissociation curve of trout blood at pH 7.8 and 15 degrees C. A comparison of the results obtained indicates that the methods give similar results, especially when used by experienced workers. The relative advantages and disadvantages of the methods for determination of some O2-carrying parameters of fish blood are discussed.


Pattern of growth hormone response to insulin, arginine and haemodialysis in uraemic children.
Plasma growth hormone (GH) concentrations after insulin and arginine stimulation were estimated in 11 dialyzed and 6 non-dialyzed children with chronic renal failure. Twenty healthy children served as controls. Plasma GH peak concentration and estimation of the total area under the plasma GH concentration-time curve by the trapezoidal rule were used to evaluate results. Elevated basal GH levels and an exaggerated response to the stimuli were seen in several of the patients. The causes of the abnormal GH secretion and the role of high GH levels in carbohydrate intolerance are discussed. No consistent pattern was seen in GH secretion during haemodialysis without glucose in the dialysate. In children undergoing haemodialysis with a fluid containing glucose, plasma GH fell considerably.


The Impact of FKBP5 Deficiency in Glucocorticoid Receptor Mediated Regulation of Synaptic Transmission in the Medial Prefrontal Cortex.
Exposure to stress activates glucocorticoid receptors in the brain and facilitates the onset of multitude psychiatric disorders. It has been shown that FK506 binding protein 51 (FKBP5) expression increases during glucocorticoid receptor (GR) activation in various brain regions including the medial prefrontal cortex (mPFC). FKBP5 knockout (KO) mice are reported to be resilient to stress, however, it remains uninvestigated whether FKBP5 loss affects neurotransmission and if so, what the functional consequences are. Here, we examined the impact of FKBP5 deletion in synaptic transmission of the mPFC. We found that GR activation significantly decreased excitatory neurotransmission in the mPFC, which was completely abolished upon FKBP5 deletion, in consistent with behavioral resilience observed in FKBP5 KO mice. Even though FKBP5 loss has minimal impact on neural excitability, we found that FKBP5 deletion distorts the excitatory/inhibitory balance in the mPFC. Our study suggests that FKBP5 deficiency leads to the mPFC insensitive to GR activation and provides a neurophysiological explanation for how FKBP5 deficiency may mediate stress resilience.


Ranitidine, 75 mg, over-the-counter dose: pharmacokinetic and pharmacodynamic effects in children with symptoms of gastro-oesophageal reflux.
The use of over-the-counter antacids has increased in children under the age of 12 years, and has been followed by an apparent increase in the use of over-the-counter histamine-2 receptor antagonists. However, the pharmacokinetic and pharmacodynamic effects of over-the-counter histamine-2 receptor antagonists in the paediatric population are largely unknown. To evaluate the pharmacokinetics and pharmacodynamics of a single dose of the over-the-counter histamine-2 receptor antagonist, ranitidine, 75 mg, in children with symptoms of gastro-oesophageal reflux disease. Children aged between 4 and 11 years with symptoms of heartburn suspected to be due to gastro-oesophageal reflux disease were recruited at six clinical centres. Following a single dose of either oral ranitidine, 75 mg (n=19), or placebo (n=10), recording of intragastric pH and serial blood sampling were carried out for 6 h. The estimated pharmacokinetic parameters of ranitidine, 75 mg, were as follows: the median Cmax value of 477 ng/mL occurred within a median of 2.5 h after dosing, and the median half-life was 2.0 h. The intragastric pH began to rise approximately 30 min after dosing with ranitidine to a peak of pH; 4. The pH in the ranitidine group remained higher than that in the placebo group throughout the 6-h evaluation period. Adverse events were generally mild. Ranitidine, 75 mg, significantly increased the intragastric pH in children aged 4-11 years. The pharmacokinetic and pharmacodynamic profiles were similar to those in adults. Ranitidine, 75 mg, appears to be effective for the control of intragastric acidity for 5-6 h in children aged 4-11 years.


Global Assessment of Drug Target Engagement and Selectivity of Covalent Cysteine-Reactive Inhibitors Using Alkyne-Functionalized Probes.
Covalent inhibitors are emerging as a promising therapeutic means for efficient and sustained targeting of key disease-driving proteins. As for classic non-covalent inhibitors, understanding target engagement and selectivity is essential for determining optimal dosing and limiting potential on- or off-target toxicity. Here, we present a complementary activity-based protein profiling (ABPP) strategy for unbiased proteome-wide profiling of cysteine-reactive inhibitors based on two orthogonal approaches. We illustrate the use of clickable alkyne probes for in-gel fluorescence and mass spectrometry studies using a series of therapeutic XPO1 inhibitors as an example.


In-depth study of the workers' perspectives to enhance sustainable working life: comparison between workers with and without a chronic health condition.
To gain in-depth understanding of the number and type of experienced ageing problems, obstacles to perform work tasks, retention factors to maintain work and support needs to continue working life in the next years among workers aged 45 years and older with and without a chronic health condition. A survey of workers' perspectives on problems, obstacles, retention factors and needs due to ageing was carried out in 3,008 workers aged 45 years and older in nine different companies. To classify the open-ended questions we used the International Classification of Functioning and disability (ICF). Older workers with a chronic health condition reported more problems due to ageing (56 vs 34 %; p < .001), more obstacles (42 vs 16 %; p < .001) and more needs (51 vs 31 %; p < .001) compared to those without a chronic health condition. No relevant differences were found on type of experienced problems, obstacles, retention factors and needs between both groups. Problems and obstacles were found on physiological and psychological functions. Retention factors and needs to enhance sustainable working life were particularly reported on work-related environmental factors. Because workers with a chronic health condition experienced more problems, obstacles and needs, the largest gain of occupational intervention can be achieved in these workers. However, our findings suggest that interventions aimed to enhance sustainable working life of older workers can be similar in content for persons with and without chronic health conditions and should have a central focus on work-related factors.


Prospective randomized trial of single dose cefuroxime against mezlocillin in elective gastric surgery.
A prospective randomized control trial was made in 78 patients undergoing elective operations on the stomach where the viscus was opened at operation, and the efficacy of single dose intravenous prophylaxis with cefuroxime 1.5 g or mezlocillin 2 g was compared. The overall rate of sepsis was 10.2 per cent. Infection in the cefuroxime group was significantly lower (2.5 per cent) than in the mezlocillin group (18 per cent) (P less than 0.05). Four of the seven patients with infections in the mezlocillin group were due to antibiotic resistant staphylococci. The only infections in the cefuroxime group were due to an antibiotic resistant strain of Pseudomonas aeruginosa. One case of pseudomembranous colitis occurred in the cefuroxime group. In view of the high rate of resistant organisms in patients receiving mezlocillin we believe that cefuroxime remains the antibiotic of choice for patients undergoing elective gastric operations.


Calf Spleen Extractive Injection (CSEI), a small peptides enriched extraction, induces human hepatocellular carcinoma cell apoptosis via ROS/MAPKs dependent mitochondrial pathway.
Calf Spleen Extractive Injection (CSEI), a small peptides enriched extraction, performs immunomodulatory activity on cancer patients suffering from radiotherapy or chemotherapy. The present study aims to investigate the anti-hepatocellular carcinoma effects of CSEI in cells and tumor-xenografted mouse models. In HepG2 and SMMC-7721 cells, CSEI reduced cell viability, enhanced apoptosis rate, caused reactive oxygen species (ROS) accumulation, inhibited migration ability, and induced caspases cascade and mitochondrial membrane potential dissipation. CSEI significantly inhibited HepG2-xenografted tumor growth in nude mice. In cell and animal experiments, CSEI increased the activations of pro-apoptotic proteins including caspase 8, caspase 9 and caspase 3; meanwhile, it suppressed the expressions of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) and anti-oxidation proteins, such as nuclear factor-erythroid 2 related factor 2 (Nrf2) and catalase (CAT). The enhanced phosphorylation of P38 and c-JunN-terminalkinase (JNK), and decreased phosphorylation of extra cellular signal-regulated protein kinase (ERKs) were observed in CSEI-treated cells and tumor tissues. CSEI-induced cell viability reduction was significantly attenuated by N-Acetyl-l-cysteine (a ROS inhibitor) pretreatment. All data demonstrated that the upregulated oxidative stress status and the altered mitogen-activated protein kinases (MAPKs) phosphorylation contributed to CSEI-driven mitochondrial dysfunction. Taken together, CSEI exactly induced apoptosis in human hepatocellular carcinoma cells via ROS/MAPKs dependent mitochondrial pathway.


Percutaneous edge-to-edge mitral valve repair in high-surgical-risk patients: do we hit the target?
This study sought to assess the feasibility and safety of percutaneous edge-to-edge mitral valve (MV) repair in patients with an unacceptably high operative risk. MV repair for mitral regurgitation (MR) can be accomplished by use of a clip that approximates the free edges of the mitral leaflets. All patients were declined for surgery because of a high logistic EuroSCORE (>20%) or the presence of other specific surgical risk factors. Transthoracic echocardiography was performed before and 6 months after the procedure. Differences in New York Heart Association (NYHA) functional class, quality of life (QoL) using the Minnesota questionnaire, and 6-min walk test (6-MWT) distances were reported. Fifty-five procedures were performed in 52 patients (69.2% male, age 73.2 ± 10.1 years, logistic EuroSCORE 27.1 ± 17.0%). In 3 patients, partial clip detachment occurred; a second clip was placed successfully. One patient experienced cardiac tamponade. Two patients developed inguinal bleeding, of whom 1 needed surgery. Six patients (11.5%) died during 6-month follow-up (5 patients as a result of progressive heart failure and 1 noncardiac death). The MR grade before repair was ≥3 in 100%; after 6 months, a reduction in MR grade to ≤2 was present in 79% of the patients. Left ventricular (LV) end-diastolic diameter, LV ejection fraction, and systolic pulmonary artery pressure improved significantly. Accompanied improvements in NYHA functional class, QoL index, 6-MWT distances, and log N-terminal pro-B-type natriuretic peptide were observed. In a high-risk population, MR reduction can be achieved by percutaneous edge-to-edge valve repair, resulting in LV remodeling with improvement of functional capacity after 6 months.


Brain tumors on slice: A novel platform for personalized therapeutic screening.
Mann and Zhang et al. developed a robust ex vivo slice culture platform consisting of resected patient high- and low-grade glioma tissue engrafted onto rat organotypic brain slices, and interrogated tumor responses to clinically relevant therapeutics with a novel treatment-response algorithm.


Computer Simulation of Skin Permeability of Hydrophobic and Hydrophilic Chemicals - Influence of Follicular Pathway.
A recently published mechanistic skin permeability model (Kasting et al., 2019. J Pharm Sci 108:337-349) that included a follicular diffusion pathway has been extended to describe transient diffusion and finite dose applications. The model follows the disposition of two components, solute and solvent, so that solvent deposition processes can be explicitly represented. Experimentally-calibrated permeability characteristics of the follicular pathway leading to the permeation of highly hydrophilic permeants are further refined. Details of the refinements and a comparison with the earlier model using two large experimental datasets are presented. An example calculation shows the marked difference between the time scales for achievement of near steady-state diffusion for large hydrophilic and lipophilic compounds, with the former being more than 100-fold faster than the latter. However, the true steady state for the hydrophilic compound is not reached until much later due to the very slow filling of the corneocyte phase.


Redox-driven proton pumping by heme-copper oxidases.
One of the key problems of molecular bioenergetics is the understanding of the function of redox-driven proton pumps on a molecular level. One such class of proton pumps are the heme-copper oxidases. These enzymes are integral membrane proteins in which proton translocation across the membrane is driven by electron transfer from a low-potential donor, such as, e.g. cytochrome c, to a high-potential acceptor, O(2). Proton pumping is associated with distinct exergonic reaction steps that involve gradual reduction of oxygen to water. During the process of O(2) reduction, unprotonated high pK(a) proton acceptors are created at the catalytic site. Initially, these proton acceptors become protonated as a result of intramolecular proton transfer from a residue(s) located in the membrane-spanning part of the enzyme, but removed from the catalytic site. This residue is then reprotonated from the bulk solution. In cytochrome c oxidase from Rhodobacter sphaeroides, the proton is initially transferred from a glutamate, E(I-286), which has an apparent pK(a) of 9.4. According to a recently published structure of the enzyme, the deprotonation of E(I-286) is likely to result in minor structural changes that propagate to protonatable groups on the proton output (positive) side of the protein. We propose that in this way, the free energy available from the O(2) reduction is conserved during the proton transfer. On the basis of the observation of these structural changes, a possible proton-pumping model is presented in this paper. Initially, the structural changes associated with deprotonation of E(I-286) result in the transfer of a proton to an acceptor for pumped protons from the input (negative) side of the membrane. After reprotonation of E(I-286) this acceptor releases a proton to the output side of the membrane.


Esophageal vascular impression in total anomalous pulmonary venous return below the diaphragm.
This paper discusses a new oblique posterior to anterior extrinsic vascular impression on the distal esophagus in total anomalous pulmonary venous return (TAPVR) below the diaphragm caused by a right common pulmonary vein.


Low-level, progestogen-releasing vaginal contraceptive devices.
Silicone rubber vaginal contraceptive devices of four different formulations, which release predetermined, controlled doses of three progestogens at four distinct levels, were designed and fabricated, and tested in 90-day clinical trials. Data obtained with 70 of the devices indicated that in vivo release rates (microgram/day +/- S.D.) for the formulations were: progesterone, 1400 +/- 30; norethindrone (two levels), 49.4 +/- 2.4, 196 +/- 21; d-norgestrel, 21.6 +/- 1.4. Clinical studies with these devices indicate that the women usually ovulate (with the exception of the high-dose norethindrone-releasing devices) while sperm penetration of the cervix was inhibited by all four fromulations, most consistently by the norgestrel-releasing devices.


Biomineral armor in leaf-cutter ants.
Although calcareous anatomical structures have evolved in diverse animal groups, such structures have been unknown in insects. Here, we report the discovery of high-magnesium calcite [CaMg(CO3)2] armor overlaying the exoskeletons of major workers of the leaf-cutter ant Acromyrmex echinatior. Live-rearing and in vitro synthesis experiments indicate that the biomineral layer accumulates rapidly as ant workers mature, that the layer is continuously distributed, covering nearly the entire integument, and that the ant epicuticle catalyzes biomineral nucleation and growth. In situ nanoindentation demonstrates that the biomineral layer significantly hardens the exoskeleton. Increased survival of ant workers with biomineralized exoskeletons during aggressive encounters with other ants and reduced infection by entomopathogenic fungi demonstrate the protective role of the biomineral layer. The discovery of biogenic high-magnesium calcite in the relatively well-studied leaf-cutting ants suggests that calcareous biominerals enriched in magnesium may be more common in metazoans than previously recognized.


Sex-specific metabolic dysregulation in digestive glands of green mussels following exposure to triazophos.
As a ubiquitous environmental pollutant in China, triazophos (TP) is known to have neurotoxicity, oxidative stress, and reproductive toxicity to mussels. To investigate the molecular mechanisms of TP toxicity, metabolic changes in the digestive glands of Perna viridis in different sexes were examined after treated with 35 μg/L TP. Notably, 158 significant different metabolites (SDMs) were detected in TP-treated mussels and more than half of the SDMs were lipids and lipid-like molecules, which suggested that TP disturbed the lipid metabolism of P. viridis. In addition, metabolites associated with neurotoxicity and reproductive disturbance were also detected in female and male mussels. Moreover, a larger number of SDMs were found in male mussels (120 SDMs) than females (99 SDMs), and 60 common metabolites exhibited consistent variation tendency and similar magnitude in both sexes. The metabolic alternations in female and male mussels displayed similar protective mechanisms and also sex-specific responses, male mussels were more sensitive to TP exposure. This research provided new data about the molecular mechanisms of TP toxicity and the gender specific changes in mussels after treated by chemicals.


Molecular detection of plasmid mediated blaTEM, blaCTX-M,and blaSHV genes in Extended Spectrum β-Lactamase (ESBL) Escherichia coli from clinical samples.
Extended spectrum β-lactamases (ESBLs) are a group of beta-lactamase enzymes that confer resistance to the oxyimino-cephalosporins and monobactams. The emergence of ESBL - producing genes possesses a serious threat for treating infections since it is associated with multi-drug resistance. This study was focused to identify the ESBLs producing genes from Escherichia coli isolates from clinical samples from a referral-level tertiary care hospital in Lalitpur. This was a cross-sectional study conducted from September 2018 to April 2020 at the Microbiology Laboratory of Nepal Mediciti Hospital. Clinical samples were processed, and culture isolates were identified and characterized following standard microbiological techniques. An antibiotic susceptibility test was performed by a modified Kirby-Bauer disc diffusion method as recommended by Clinical and Laboratory Standard Institute guidelines.Extended -spectrum beta-lactamases were phenotypically confirmed by the combined disc method. The ESBL-producing genes blaTEM, blaCTX-M and blaSHV were confirmed by PCR. Of the 1449 total E. coli isolates, 22.29% (323/1449) isolates were multi-drug resistant (MDR). Among the total MDR E. coli isolates, 66.56% (215/323) were ESBL producers. The maximum number of ESBL E. coli was isolated from urine 90.23% (194) followed by sputum 5.58% (12), swab 2.32% (5), pus 0.93% (2), and blood 0.93% (2). The antibiotic susceptibility pattern of ESBL E. coli producers showed the highest sensitivity toward tigecycline (100%) followed by polymyxin b, colistin and meropenem. Out of 215 phenotypically confirmed ESBL E. coli, only 86.51% (186) isolates were found to be positive by PCR for either blaTEM or blaCTX-M genes. Among the ESBL genotypes, the most common were blaTEM 63.4% (118) followed by blaCTX-M 36.6% (68). The emergence of MDR and ESBL - producing E. coli isolates with high antibiotic - resistant rates to commonly used antibiotics and increased predominance of major gene types blaTEM is a serious concern to the clinicians and microbiologists. Periodic monitoring of antibiotic susceptibility and associated genes would help guide the rationale use of antibiotics for treating the predominant pathogen E. coli in the hospitals and healthcare facilities of the communities.


Effect of asthma control on general health-related quality of life in patients diagnosed with adult-onset asthma.
Health-related quality of life (HRQoL) is a well-established aspect of health that can be measured by both disease-specific and general instruments. The effect of uncontrolled asthma on generic HRQoL has not been shown in patients with clinically confirmed adult-onset asthma and with asthma control defined according to the Global Initiative for Asthma, so the aim of this study was to determine this. In the 12-year follow-up cohort of the Seinäjoki Adult Asthma Study (n = 203), patients with uncontrolled and partially controlled asthma had lower generic HRQoL as determined by 15D compared to the controlled group. On 10 out of 15 dimensions of 15D, the mean scores were significantly lower in patients with uncontrolled asthma compared with those with controlled asthma. The affected dimensions were mobility, breathing, sleeping, usual activities, mental function, discomfort and symptoms, depression, distress, vitality and sexual activity. In the Tobit regression analysis, a poorer 15D score was associated with uncontrolled asthma, lower postbronchodilator FEV1, female sex, depression, treated dyspepsia and poorer 15D score at diagnosis. Our results show that uncontrolled asthma affects everyday life in several aspects, including previously unknown components such as sexual activity and vitality.


Identification of manganese superoxide dismutase as a NO-regulated gene in rat glomerular mesangial cells by 2D gel electrophoresis.
The course of inflammatory glomerular diseases is accompanied by changes in the expression of matrix-associated proteins, growth factors, and mediators in renal mesangial cells. Furthermore, the production of nitric oxide (NO) by the inducible isoform of nitric oxide synthase (iNOS) is enhanced after stimulation with pro-inflammatory cytokines. NO has been demonstrated to be a potent modulator of gene expression. To identify NO-regulated genes, we compared the expression patterns of mesangial cells treated for 24h with 500 microM (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO) with those of un-stimulated controls by applying a proteomics approach. One protein found to be NO-modulated by 2D gel electrophoresis is the manganese superoxide dismutase (Mn-SOD). Immunoblot and Northern blot analysis demonstrated a dose- and time-dependent induction of Mn-SOD expression by S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and DETA-NO on both the protein and the mRNA levels. An upregulation of Mn-SOD expression by NO was accompanied by an increased Mn-SOD activity. Immunoblots of extracts of IL-1beta-treated cells cultivated with or without the iNOS inhibitor N(G)-monomethyl-L-arginine and the inhibitor of soluble guanylyl cyclase (sGC) 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) demonstrated that the upregulation of the Mn-SOD by NO is due to a NO-dependent activation of sGC. The upregulation of Mn-SOD mRNA expression by NO was confirmed in vivo by Northern blot analysis in kidneys from rats treated with lipopolysaccharide (LPS) either in presence or absence of the iNOS inhibitor N(6)-(1-iminoethyl)-L-lysine (l-NIL).


Tridimensional models and radiographic study of dorsal laminectomy and thoracolumbar hemilaminectomy in dogs.
To create three-dimensional anatomical models of the thoracic and lumbar portions of the canine spine that reproduce the vertebral surgical approaches of dorsal laminectomy and hemilaminectomy, and to perform the respective radiographic evaluations of each approach. In a digital archive of the canine spine, digitally replicate the dorsal laminectomy and hemilaminectomy in the thoracic and lumbar portions and, then, make tridimensional prints of the vertebral models and obtain radiographs in three dorsoventral, ventrodorsal and laterolateral projections. The anatomical models of the surgical spinal canal accesses of the thoracic and lumbar portions showed great fidelity to the natural bones. The created accesses have the proper shape, location and size, and their radiographic images showed similar radiodensities. The replicas of the dorsal laminectomy and hemilaminectomy developed in the anatomical models in the thoracic and lumbar portions are able to represent the technical recommendations of the specialized literature, as well as their respective radiographic images, which have certain radiological properties that allow to make a deep radiological study. Therefore, the models are useful for neurosurgical training.


Twist-angle dependence of moiré excitons in WS2/MoSe2 heterobilayers.
Moiré lattices formed in twisted van der Waals bilayers provide a unique, tunable platform to realize coupled electron or exciton lattices unavailable before. While twist angle between the bilayer has been shown to be a critical parameter in engineering the moiré potential and enabling novel phenomena in electronic moiré systems, a systematic experimental study as a function of twist angle is still missing. Here we show that not only are moiré excitons robust in bilayers of even large twist angles, but also properties of the moiré excitons are dependant on, and controllable by, the moiré reciprocal lattice period via twist-angle tuning. From the twist-angle dependence, we furthermore obtain the effective mass of the interlayer excitons and the electron inter-layer tunneling strength, which are difficult to measure experimentally otherwise. These findings pave the way for understanding and engineering rich moiré-lattice induced phenomena in angle-twisted semiconductor van der Waals heterostructures.


Ultrastructural examination of dentin using focused ion-beam cross-sectioning and transmission electron microscopy.
Focused ion-beam (FIB) milling is a commonly used technique for transmission electron microscopy (TEM) sample preparation of inorganic materials. In this study, we seek to evaluate the FIB as a TEM preparation tool for human dentin. Two particular problems involving dentin, a structural analog of bone that makes up the bulk of the human tooth, are examined. Firstly, the process of aging is studied through an investigation of the mineralization in 'transparent' dentin, which is formed naturally due to the filling up of dentinal tubules with large mineral crystals. Next, the process of fracture is examined to evaluate incipient events that occur at the collagen fiber level. For both these cases, FIB-milling was able to generate high-quality specimens that could be used for subsequent TEM examination. The changes in the mineralization suggested a simple mechanism of mineral 'dissolution and reprecipitation', while examination of the collagen revealed incipient damage in the form of voids within the collagen fibers. These studies help shed light on the process of aging and fracture of mineralized tissues and are useful steps in developing a framework for understanding such processes.


Oncologic Outcome and Quality of Life After Hindquarter Amputation for Sarcoma: Is it Worth it?
Hindquarter amputations for bone or soft tissue sarcoma cause a high degree of disability. The goal of this study was to analyze oncologic outcome and quality of life after resection in order to better select patients who are more likely to benefit from this operation. Patients treated with a hindquarter amputation between 1989 and 2015 for a bone or soft tissue sarcoma were selected from our database. Clinical and histopathological features were analyzed for their prognostic value using Kaplan-Meier and Cox proportional hazard analysis. In addition, performance status, ambulatory status, and pain were assessed from the hospital charts for patients surviving longer than 1 year after surgery. Overall, 78 patients underwent a hindquarter amputation for sarcoma. The median hospital stay was 24 days and 49% of patients had wound complications. In-hospital mortality was 6%. Overall survival for patients with metastases at presentation was significantly worse than patients with localized disease only (p = 0.001, 5-year survival 41 vs. 0%). For patients treated for localized disease, the combination of age >65 years and tumor size ≥15 cm was significantly correlated with worse metastasis-free survival (p = 0.003) and overall survival (p = 0.01). In particular, patients younger than 65 years of age who survived more than 1 year had an acceptable performance status, with reasonable pain levels and mobility. Younger patients are more likely to benefit from hindquarter ampuations in terms of survival and functionality; however, for older patients with large tumors, a hindquarter amputation might not be beneficial.


Hypothesis for the lack of a muscular antagonist to the lateral pterygoid.
During physiological function of the temporomandibular joint, we have to rely only on elastic structures (in particular the bilaminar zone) for repositioning of the articular disc. A real muscle, however, would be functionally more reasonable. In patients, a decrease of this elasticity is possibly one of the reasons for temporomandibular joint malfunctions, which affect between 16% and 36% of the population. This study assesses the morphogenesis of the murine (Mus musculus) temporomandibular joint with particular regard to the masticatory muscles, to throw light on this topic. To that end, a collection of 11 murine heads ranging from prenatal stages E13.25 to E20 was used and early postnatal stages P0 to P4, which were prepared as histological sections (thickness 8-10 µm) and stained conventionally in order to examine them with light microscopy. Next, the temporomandibular joint and selected surrounding structures, along with the masticatory muscles, were threedimensionally reconstructed using analySIS® software. Subsequently, specific morphometric analyses were performed. The evaluation of the results led to the following conclusions.


The impacts of Covid-19 absences on workers.
We show that Covid-19 illnesses and related work absences persistently reduce labor supply. Using an event study, we estimate that workers with week-long Covid-19 absences are 7 percentage points less likely to be in the labor force one year later compared to otherwise-similar workers who do not miss a week of work for health reasons. Our estimates suggest Covid-19 absences have reduced the U.S. labor force by approximately 500,000 people (0.2 percent of adults) and imply an average labor supply loss per Covid-19 absence equivalent to $9,000 in forgone earnings, about 90 percent of which reflects losses beyond the initial absence week.


Measurement by ELISA of complement factor 4 (C4) in the rat brain: necessity for removal of cerebrovascular proteins.
Assessment of complement 4 (C4) levels in experimental animals is used as a marker for activation of the classical complement pathway. The objective of this study was to develop a method for measuring C4 concentrations in the rat brain. An ELISA (sensitivity = 0.5 ng C4/ml) was used to measure C4 in regional brain homogenates from Fischer rats cardiac-perfused with phosphate buffered saline to remove cerebrovascular contents, and from sham-perfused rats. Ventral midbrain C4 levels were increased (p < 0.001) versus frontal cortex and striatum in sham-perfused rats, whereas after perfusion there were no differences between brain regions. Removal of cerebrovascular contents decreased C4 by 43% in striatum, 52% in frontal cortex, and 69% in ventral midbrain (all p < 0.01 versus sham-perfused means). These results indicate that C4 in the rat brain can be measured quantitatively by ELISA provided that cerebrovascular proteins are removed by perfusion.


Positively charged microporous ceramic membrane for the removal of Titan Yellow through electrostatic adsorption.
To develop a depth filter based on the electrostatic adsorption principle, positively charged microporous ceramic membrane was prepared from a diatomaceous earth ceramic membrane. The internal surface of the highly porous ceramic membrane was coated with uniformly distributed electropositive nano-Y2O3 coating. The dye removal performance was evaluated through pressurized filtration tests using Titan Yellow aqueous solution. It showed that positively charged microporous ceramic membrane exhibited a flow rate of 421L/(m(2)·hr) under the trans-membrane pressure of 0.03bar. Moreover it could effectively remove Titan Yellow with feed concentration of 10mg/L between pH3 to 8. The removal rate increased with the enhancement of the surface charge properties with a maximum rejection of 99.6%. This study provides a new and feasible method of removing organic dyes in wastewater. It is convinced that there will be a broad market for the application of charged ceramic membrane in the field of dye removal or recovery from industry wastewater.


Cabbage waxes affect Trissolcus brochymenae response to short-range synomones.
We show that induced synomones, emitted as a consequence of Murgantia histrionica activity on Brassica oleracea, are adsorbed by the epicuticular waxes of leaves and perceived by the egg parasitoid Trissolcus brochymenae. Leaves were exposed to M. histrionica females placed on the abaxial leaf surface. After 24 h, the leaves were treated mechanically using gum arabic, or chemically using chloroform, on the adaxial surface, and finally the adaxial surface was assayed with T. brochymenae by two-choice tests in a closed arena. Wasp females responded to mechanically dewaxed cabbage leaf portions with feeding punctures and footprints (Ff) and with feeding punctures, oviposition and footprints (FOf), showing no effect of wax removal. In contrast, the removal of the epicuticular waxes from leaf portions close to FOf, and from leaves with oviposition and footprints (Of), determined the lack of responses by T. brochymenae. Solvent extracts of different treatments were bioassayed, but only FOf triggered parasitoid response. Thus the detection of oviposition-induced synomones by the parasitoid depends on their adsorption by the epicuticular waxes. Mechanical wax removal from leaf portions contaminated with host footprints (f) also determined a lack of wasp responses, suggesting that the footprints might trigger the induction of a "footprint-induced synomone" adsorbed onto the epicuticular waxes and exploited by the parasitoid. Leaf portions with the abaxial lamina previously dewaxed and then contaminated by footprints (D+f) of M. histrionica did not affect the parasitoid response, indicating that the abaxial epicuticular waxes are not directly involved in the chemicals induced by M. histrionica footprints.


Indraloris and Sivaladapis: Miocene adapid primates from the Siwaliks of India and Pakistan.
THE primate family Adapidae underwent a major radiation during the Eocene in Europe(1,2) and North America(3,4). Asian and African Eocene mammalian faunas are still poorly known, but there is sufficient evidence to indicate at least a modest radiation of Eocene adapids in Asia(5,6) and probably also in Africa(2). Apart from possible lemuriform and anthropoid primate derivatives, the family Adapidae was thought to have become extinct at the end of the Eocene (middle Tongrian, approximately 37 Myr (refs 2, 7, 8)). We present here new evidence which indicates that at least two genera of adapid primates, Indraloris and Sivaladapis (gen. nov.), survived into the late Miocene of India and Pakistan. These genera are little advanced over Eocene Adapidae in terms of dental adaptations and are apparently south Asian relicts of a much earlier radiation.


Evidence for O-dealkylation of 7-pentoxyresorufin by cytochrome P450 2B1/2B2 isoenzymes in brain.
O-dealkylation of 7-pentoxyresorufin (PR) was studied in rat brain to characterise the functional activity specific for cytochrome P450 2B1/2B2 isoenzymes in brain microsomes. Brain microsomes catalyzed the O-dealkylation of PR in the presence of NADPH. Pretreatment with phenobarbital (PB; 80 mg/kg body wt, i.p. x 5 days) resulted in 3-4 fold induction of pentoxyresorufin-O-dealkylase (PROD) activity while 3-methylcholanthrene (MC; 30 mg/kg body wt, i.p. x 5 days) did not produce any significant increase in enzyme activity. Kinetic studies revealed that the rate of velocity (Vmax) for the O-dealkylation of PR was significantly increased to 2.9 times higher in brain microsomes isolated from PB pretreated rats. In vitro studies using metyrapone, an inhibitor of P450 2B1/2B2 catalyzed reactions and antibody for hepatic PB inducible P450s (P450 2B1/2B2) significantly inhibited the activity of PROD in cerebral microsomes prepared from PB pretreated animals. These studies suggest that PB inducible isoenzymes of P450, i.e. P450 2B1/2B2 specifically catalyze the O-dealkylation of PR in brain microsomes.


Acid glycosidase and arylsulfatase activities of human cerebrospinal fluid as measured by concanavalin A-sepharose affinity chromatography.
An affinity chromatographic method using concanavalin A-Sepharose is described for the determination of N-acetyl-beta-D-glucosaminidase, arylsulfatase. alpha-L-Fucosidase and alpha-D-mannosidase activities in the human cerebrospinal fluid. By this method (starting with 12 to 20 ml samples of cerebrospinal fluid) the above enzymes could be obtained in a concentrated form and their activities could be determined within incubation periods of 30 min to 1 h under the assay conditions described. The pH optima of the enzymes were in the range of pH 4 to 5. About 80% of the total cerebrospinal fluid N-acetyl-beta-D-glucosaminidase was found to be the A form by DEAE-Sephadex A-50 chromatography. About 60% of the total arylsulfatase was also found to be the A form. Determination of these enzyme activities in a few samples of human cerebrospinal fluid indicated a rough proportionality between the enzyme activities and the protein concentration in the cerebrospinal fluid.


Synthesis of [(11)C]MK-1064 as a new PET radioligand for imaging of orexin-2 receptor.
The reference standard MK-1064 {5″-chloro-N-((5,6-dimethoxypyridin-2-yl)methyl)-[2,2':5',3″-terpyridine]-3'-carboxamide} was synthesized from methyl 2-chloro-5-iodonicotinate and 5-(chloropyridin-3-yl)boronic acid in 4 steps with 33% overall chemical yield. The precursor desmethyl-MK-1064 {5″-chloro-N-((5-hydroxy-6-methoxypyridin-2-yl)methyl)-[2,2':5',3″-terpyridine]-3'-carboxamide} for radiolabeling was synthesized from 2-bromopyridin-3-ol and 5″-chloro-[2,2':5',3″-terpyridine]-3'-carboxylic acid in 6 steps with 17% overall chemical yield. The target tracer [(11)C]MK-1064 {5″-chloro-N-((5-[(11)C]methoxy-6-methoxypyridin-2-yl)methyl)-[2,2':5',3″-terpyridine]-3'-carboxamide} was prepared by O-[(11)C]methylation of its corresponding precursor desmethyl-MK-1064 with [(11)C]CH3OTf under basic condition and isolated by a simplified solid-phase extraction (SPE) method in 50-60% decay corrected radiochemical yields based on [(11)C]CO2 at end of bombardment (EOB). The overall synthesis time from EOB was 23min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 185-555GBq/μmol.


A Gynecologic Oncology Group phase II study of amonafide (NSC 308847) in epithelial ovarian cancer.
In this study, 19 evaluable patients with epithelial ovarian cancer were treated with amonafide 300 mg/m2 over an hour for 5 consecutive days every 3 weeks. One partial response (5%) was seen. Hematologic toxicity was substantial with grade 3 or 4 toxicity occurring as follows: leukopenia, 10 patients (45%); thrombocytopenia, 6 patients (27%); granulocytopenia, 8 patients (36%). No other unusual or severe toxicity occurred. In view of the low response rate and high toxicity, amonafide does not warrant further investigation in epithelial ovarian cancer.


Unipolar and bipolar electrograms to predict successful ablation site of premature ventricular contractions originating from the free wall of the tricuspid annulus.
This study aimed to identify the characteristics of unipolar and bipolar electrogram (UniEGM and BiEGM) in guiding successful ablation of premature ventricular contractions (PVCs) originating from the free wall of the ventricular aspect of the tricuspid annulus (TA). We hypothesized that the negative concordance pattern (NCP) on the onset of UniEGM and BiEGM, together with the least value of the difference between the earliest BiEGM and UniEGM dV/dTmax, might improve the accuracy of conventional mapping. Thirty consecutive patients who underwent successful catheter ablation from February 2018 to July 2021 were retrospectively analyzed. The BiEGM and UniEGM for successful ablation sites were compared with those for non-successful ablation sites. Among the 30 patients, 30 successful and 26 nonsuccessful ablation sites were compared. The earliest activation time of the BiEGM (BiEGMoneset-QRS) was 25 ± 6 ms for the successful ablation sites and 21 ± 6 ms for the nonsuccessful ablation sites (p = .47). The value of the difference in the earliest BiEGM and UniEGM dV/dTmax differed between successful and nonsuccessful ablation sites (6.4 ± 3.6 ms vs. 10.4 ± 6.8 ms). NCP was observed at 90.0% and 42.3% of the successful and nonsuccessful ablation sites, respectively. Alignment of NCP and BiEGMonset-UniEGM ≤6 ms was applied as the mapping criterion for successful PVC suppression (73.1% sensitivity and 87.7% specificity). The area under the receiver-operating characteristic curve for this cutoff was 0.85. Mapping based on an NCP at the onset of the BiEGM and UniEGM and the least difference value of the earliest BiEGM and UniEGM dV/dTmax had an excellent predictive value for successful ablation. These strategies may reduce the number of radiofrequency catheter ablation (RFCA) applications for free-wall tricuspid annular PVCs.


The pro-apoptotic action of new analogs of the insect gonadoinhibiting peptide Neb-colloostatin: synthesis and structure-activity studies.
Neb-colloostatin (SIVPLGLPVPIGPIVVGPR), an insect oostatic factor found in the ovaries of the flesh fly Neobellieria bullata, strongly induces apoptosis in insect haemocytes. To explain the role of Ser(1) and Pro(4) residues of Neb-colloostatin in the pro-apoptotic activity of this peptide, the synthesis of a series of analogs was performed, such as: [Ac-Ser(1)]- (1), [d-Ser(1)]- (2), [Thr(1)]- (3), [Asp(1)]- (4), [Glu(1)]- (5), [Gln(1)]- (6), [Ala(1)]- (7), [Val(1)]- (8), [d-Pro(4)]-(9), [Hyp(4)]- (10), [Acp(4)]- (11), [Ach(4)]- (12), [Ala(4)]- (13), [Ile(4)]- (14), and [Val(4)]-colloostatin (15). All peptides were bioassayed in vivo for the pro-apoptotic action on haemocytes of Tenebrio molitor. Additionally, the structural properties of Neb-colloostatin and its analogs were examined by the circular dichroism in water and methanol. Peptides 1, 4, 5, 7, 8, 10, 12, 14, and 15 strongly induce T. molitor haemocytes to undergo apoptosis and they show about 120-230% of the Neb-colloostatin activity at a dose of 1nM. The CD conformational studies show that the investigated peptides seem to prefer the unordered conformation.