Relationship of uric acid concentrations and severe intraventricular hemorrhage/leukomalacia in the premature infant.
The purine metabolite hypoxanthine accumulates with hypoxia ischemia and with reperfusion is converted to uric acid (UA). We hypothesized that elevated UA concentration is a marker of previous hypoxia ischemia and would identify infants at greatest risk for having subsequent intraventricular hemorrhage (IVH)/periventricular leukomalacia (PVL). We determined the relationship between UA concentrations in the first postnatal day and the development of severe IVH, PVL, or both in 58 infants of birth weight 865 +/- 177 gm and gestational age 27 +/- 2 weeks. Severe IVH developed in 10 (17%) infants and PVL in 3 (5.1%) infants. UA concentrations on day 1 (obtained at 16 +/- 4 hours) were 7.9 +/- 2.8 mg/dl and increased to 9.5 +/- 2.58 mg/dl on day 2. UA concentrations on day 1 were higher in infants with severe IVH/PVL versus those in infants with neither condition: 10.2 vs 7.3 mg/dl (p = 0.005). Infants with hyperkalemia on the second postnatal day had higher UA concentrations on the first day versus infants with normal potassium levels: 11.7 +/- 2 mg/dl versus 6.8 +/- 1.8 mg/dl (p < 0.0005). Infants with severe IVH/PVL had higher potassium levels on day 2 versus infants with neither condition: 11.9 vs 6.9 mg/dl (p < 0.048). By univariate analysis UA concentrations were significantly related to gestational age (p = 0.005) and birth weight (p = 0.03). Only UA concentration (p = 0.004) and gestational age (p = 0.02) were related to IVH/PVL. By multivariate analysis UA remained significantly related to IVH/PVL even when adjusted for other clinical variables, with an odds ratio estimate of 1.63 (95% confidence interval 1.16 to 2.31). In conclusion, higher UA concentrations on the first postnatal day were associated with the subsequent development of severe IVH/PVL and with subsequent hyperkalemia. Elevated UA concentrations in the first postnatal day may help to identify a subset of premature infants at greatest risk for having subsequent hemorrhagic ischemic injury.


Approach to hypertension among primary care physicians in the West Region of Cameroon: substantial room for improvement.
This study was conducted to assess the knowledge and approach of primary care physician (PCP) towards the management of hypertension in Cameroon. In 2012 we surveyed 77 PCPs among the 111 working in the West region of Cameroon. We used a standardized questionnaire assessing practices regarding the detection, evaluation and treatment of hypertension, and source of information about updates on hypertension. Participants had a mean duration of practice of 10.1 (SD 7.6) years, and received an average of 10.5 (SD 5.8) patients daily. Most of the PCPs (80.5%, n=62) measured blood pressure (BP) for all adult patients in consultation, however, only 63.6% (n=49) used correct BP thresholds to diagnose hypertension. Sixty-seven PCPs (87.0%) ordered a minimal work-up for each newly diagnosed hypertensive patient, but only the work-up offered by 8 (10.4%) PCPs was adequate. Regarding treatment, the most commonly prescribed medications as monotherapy were loop diuretics (49.3%). Bitherapy mostly included the combination of a diuretic with other drug classes. Most of PCPs used incorrect target BP, with a general tendency of using higher target levels. PCPs received updates on hypertension management mostly through drug companies representatives (53.2%, n=41). Up to 97.4% were willing to receive continuing medical training on hypertension. PCPs' knowledge and management of hypertension is poor in this region of Cameroon. Our data point to a need for continually updating the teaching curricula of medical schools with regard to the management of hypertension, and physicians in the field should receive continuing medical education.


Antigens recognized by monoclonal antibody to mouse acrosomal components differ in guinea pig spermatogenic cells and sperm.
Monoclonal antibody 1D4 reacts with a glycoconjugate antigen of the developing mouse spermatid acrosome until the terminal steps of spermiogenesis. Although 1D4 does not label the acrosome of mouse epididymal spermatozoa, it does bind to the acrosomal region of guinea pig epididymal sperm. Here we report that the antigens recognized in extracts of guinea pig spermatogenic cells and sperm are different from those detected in mouse spermatids. Three major bands of reactivity with apparent molecular weights (Mr) of 97,000-145,000, 180,000, and greater than 200,000 were detected in extracts of guinea pig sperm. Soluble antigens with the same molecular weights were released after the acrosome reaction was induced with ionophore A23187. On two-dimensional immunoblots, 1D4 recognized a microheterogeneous population of molecules in guinea pig sperm extracts. The molecules recognized by this antibody are not major Concanavalin A receptors and do not react strongly with periodic acid-Schiff's stain or periodic acid-dansylhydrazine. However, comparisons of immunoblots of sperm extracts indicate that 1D4 reacted with antigens having similar molecular weights to glycoconjugates recognized by antibodies J1 and C6. Immunofluorescent labeling of guinea pig germ cells showed that 1D4 reacted only with the acrosomes of developing spermatids and sperm, and occasionally with the juxtanuclear region of spermatocytes. In general, staining was associated with the periphery of the acrosome and not with the acrosomal granule. Immunoblots of extracts of guinea pig spermatocytes, round spermatids, condensing spermatids, and sperm demonstrated that the antigens change during germ cell differentiation. Thus, 1D4 can be used as a marker of the developing acrosome for studies of the synthesis, structure, and assembly of the sperm organelle.


Selection of reference genes for expression analysis using quantitative real-time PCR in the pea aphid, Acyrthosiphon pisum (Harris) (Hemiptera, Aphidiae).
To facilitate gene expression study and obtain accurate qRT-PCR analysis, normalization relative to stable expressed housekeeping genes is required. In this study, expression profiles of 11 candidate reference genes, including actin (Actin), elongation factor 1 α (EF1A), TATA-box-binding protein (TATA), ribosomal protein L12 (RPL12), β-tubulin (Tubulin), NADH dehydrogenase (NADH), vacuolar-type H+-ATPase (v-ATPase), succinate dehydrogenase B (SDHB), 28S ribosomal RNA (28S), 16S ribosomal RNA (16S), and 18S ribosomal RNA (18S) from the pea aphid Acyrthosiphon pisum, under different developmental stages and temperature conditions, were investigated. A total of four analytical tools, geNorm, Normfinder, BestKeeper, and the ΔCt method, were used to evaluate the suitability of these genes as endogenous controls. According to RefFinder, a web-based software tool which integrates all four above-mentioned algorithms to compare and rank the reference genes, SDHB, 16S, and NADH were the three most stable house-keeping genes under different developmental stages and temperatures. This work is intended to establish a standardized qRT-PCR protocol in pea aphid and serves as a starting point for the genomics and functional genomics research in this emerging insect model.


[Liposarcoma of the spermatic cord: a clinical case].
A case of spermatic cord liposarcoma is reviewed. Radical orchiectomy is an adequate form of treatment while retroperitoneal lymphadenectomy and adjunctive radiotherapy or chemotherapy appear to be controversial. A close follow-up is mandatory to detect early relapses or distant metastasis.


Expression of dentatorubral-pallidoluysian atrophy (DRPLA) proteins in patients.
The genetic defect dentatorubral-pallidoluysian atrophy (DRPLA) is caused by expansion of a CAG trinucleotide repeat. The mutant gene is translated into protein whose electrophoretic mobility correlates to the number of expanded CAG trinucleotide repeats, indicating that the protein carries an expanded glutamine repeat. Using two polyclonal antibodies raised against the DRPLA gene product in immunoblotting, we determined the untruncated DRPLA proteins, and showed that the amounts of mutant and wild-type DRPLA proteins were similar in DRPLA brain tissues and lymphoblastoid cells, suggesting that regulation of the level of translation of the DRPLA gene is not central to the development of the disease.


A dynamical system that describes vein graft adaptation and failure.
Adaptation of vein bypass grafts to the mechanical stresses imposed by the arterial circulation is thought to be the primary determinant for lesion development, yet an understanding of how the various forces dictate local wall remodeling is lacking. We develop a dynamical system that summarizes the complex interplay between the mechanical environment and cell/matrix kinetics, ultimately dictating changes in the vein graft architecture. Based on a systematic mapping of the parameter space, three general remodeling response patterns are observed: (1) shear stabilized intimal thickening, (2) tension induced wall thinning and lumen expansion, and (3) tension stabilized wall thickening. Notable is our observation that the integration of multiple feedback mechanisms leads to a variety of non-linear responses that would be unanticipated by an analysis of each system component independently. This dynamic analysis supports the clinical observation that the majority of vein grafts proceed along an adaptive trajectory, where grafts dilate and mildly thicken in response to the increased tension and shear, but a small portion of the grafts demonstrate a maladaptive phenotype, where progressive inward remodeling and accentuated wall thickening lead to graft failure.


Negative HCV-RNA 2 weeks after initiation of treatment predicts sustained virological response to pegylated interferon alfa-2a and ribavirin in patients with chronic hepatitis C.
The aim of this study was to examine the early viral kinetics as predictor for sustained virological response (SVR) during hepatitis C treatment. We included patients with biopsy-proven chronic hepatitis C and ALT above the upper limit of normal, who received a standard treatment of pegylated interferon alfa-2a and ribavirin. The HCV-RNA concentration (limit of detection 20 IU/mL) was determined at days 0, 1, 2, 3, 4, 7, 14, 21 and monthly thereafter. Among 46 patients who completed the trial, 30 (65%) had SVR. Low baseline viral load, IL28B genotype CC and absence of cirrhosis were statistically associated with SVR. In multivariate analysis only absence of cirrhosis and HCV-RNA negativity at day 14 were independent predictors for SVR. Eight patients who became HCV-RNA negative on day 14 as well as 13 of 14 patients (93%) with HCV-RNA levels of <1000 IU/mL at day 7 obtained a SVR. Among 8 of 18 (44%) genotype 1 and 4 patients with more than a one log drop in HCV-RNA titer at day 7, 75% achieved SVR. We observed a correlation between low HCV-RNA titers in week 2 and SVR during pegylated interferon/ribavirin-based treatment. This may help identify a group of patients for whom SVR may be obtained without the addition of directly acting antivirals, and thereby save the patients for unnecessary side effects and the health care system for additional costs.


[Tactics of surgical treatment for an inflammatory process of C0-C(I)-C(II) segments in the craniovertebral joint instability].
Pathological processes of C0-C(I)-C(II) segments, such as the clivus, atlas arch, dens, and body of the C, vertebra pose major problems for diagnosis and treatment. On removal of a sizable pathological focus, there may be instability of the craniovertebral segment, secondary displacement, and spinal compression syndrome. Therefore these patients frequently need stabilization of the craniovertebral transition. Patients with initial instability of the craniovertebral junction and subluxation of C(I)-C(II) segments are an intricate problem. The authors describe a rare case of an inflammatory process of C0-C(I)-C(II) segments with craniovertebtal junction instability. A differential diagnosis was made between chordoma, osteoblastoma, and an inflammatory focus at the above site. The following tactics was undertaken: the first stage was occipitospondylosynthesis with "Vertex" system with osteoplasty under Halo-traction; the second stage included transoral removal of a pathological removal of the dens and body of the C(II) vertebra, left lateral mass of the CI vertebra, and lower clivus. After removal of the pathological focus, there were portions of the abnormally changed bone with rarefaction without tumor tissue. Histologic studies revealed the signs of a chronic inflammatory process. A five-month follow-up showed that neurological symptoms and craniovertebral junction instability regressed. The control computed tomography made 5 months after surgery demonstrated the radical elimination of the pathology and the absence of C, vertebral subluxation. Thus, there is evidence for the tactics of successive operations (a stabilizing operation--posterior occipitospondylosynthesis (desirably under Halo-traction), followed by removal of a pathological focus via transoral access) in pathological processes of the craniovertebral C0-C(I)-C(II) in cases of initial craniovertebral junction instability.


Translocation reaction promoted by polypeptide chain elongation factor-2 from pig liver.
Translocation of peptidyl-tRNA from the ribosomal A- to the P-site in the eukaryotic system was extensively investigated using a model system, in which translocation of Phe-tRNA from the A- to the P-site was examined by using the puromycin reaction, and the following results were obtained. 1) The puromycin reaction but not the translocation reaction proceeded at 0 degrees C. Since the latter could be demonstrated at 30 degrees C, it was possible to analyze translocation per se separately from the puromycin reaction. 2) Translocation was completely dependent on the elongation factor-2 (EF-2) and required the presence of GTP, which could be replaced by GMP-P(NH)P provided that the stoichiometric amount of EF-2 with respect to the amount or ribosomes was present. It was further demonstrated that translocation observed in the presence of GTP was catalytic, while that in the presence of GMP-P(NH)P was stoichiometric, indicating that hydrolysis of GTP was required for the catalytic reutilization of EF-2. 3) Translocation promoted by EF-2 in the presence of GMP-P(NH)P could be reversed, which suggests that hydrolysis of GTP is indispensable of the translocation reaction to proceed catalytically and unidirectionally forward.


Living with myotonic dystrophy; what can be learned from couples? A qualitative study.
Myotonic dystrophy type 1 (MD1) is one of the most prevalent neuromuscular diseases, yet very little is known about how MD1 affects the lives of couples and how they themselves manage individually and together. To better match health care to their problems, concerns and needs, it is important to understand their perspective of living with this hereditary, systemic disease. A qualitative study was carried out with a purposive sample of five middle-aged couples, including three men and two women with MD1 and their partners. Fifteen in-depth interviews with persons with MD1, with their partners and with both of them as a couple took place in the homes of the couples in two cities and three villages in the Netherlands in 2009. People with MD1 associate this progressive, neuromuscular condition with decreasing abilities, describing physical, cognitive and psychosocial barriers to everyday activities and social participation. Partners highlighted the increasing care giving burden, giving directions and using reminders to compensate for the lack of initiative and avoidant behaviour due to MD1. Couples portrayed the dilemmas and frustrations of renegotiating roles and responsibilities; stressing the importance of achieving a balance between individual and shared activities. All participants experienced a lack of understanding from relatives, friends, and society, including health care, leading to withdrawal and isolation. Health care was perceived as fragmentary, with specialists focusing on specific aspects of the disease rather than seeking to understand the implications of the systemic disorder on daily life. Learning from these couples has resulted in recommendations that challenge the tendency to treat MD1 as a condition with primarily physical impairments. It is vital to listen to couples, to elicit the impact of MD1, as a multisystem disorder that influences every aspect of their life together. Couple management, supporting the self-management skills of both partners is proposed as a way of reducing the mismatch between health services and health needs.


Colon cancer metastasis to mediastinal lymph nodes without liver or lung involvement: A case report.
Colon cancer is the second most common type of cancer in females and the third in males, worldwide. The most common sites of colon cancer metastasis are the regional lymph nodes, liver, lung, bone and brain. In this study, an extremely rare case of colon adenocarcinoma with extensive metastasis to the mediastinal lymph nodes without any other organ involvement is presented. A 44-year-old Caucasian male presented with abdominal pain, a change in bowel habits, melena and weight loss. Colonoscopy revealed a large friable, ulcerated, circumferential mass in the ascending colon. Biopsies were consistent with the diagnosis of invasive moderately differentiated adenocarcinoma. Subsequently, right colon resection was performed, and pathological analysis revealed moderately differentiated adenocarcinoma of the right colon with extensive regional lymph node involvement. Computed tomography (CT) scans of the chest, abdomen and pelvis were performed preoperatively as part of routine staging for colon cancer. No liver or lung pathology was identified; however, multiple pathologically enlarged mediastinal lymph nodes were observed. Endoscopic ultrasound with fine needle aspiration of the largest mediastinal lymph node, which measured 5.2×3.5 cm on CT scans, was performed. The pathology was again consistent with the diagnosis of metastatic colorectal primary adenocarcinoma. At present, no optimum treatment has been identified for metastatic colon cancer to the mediastinal lymph nodes. The patient in the current case received chemotherapy with folinic acid, fluorouracil and oxaliplatin (FOLFOX), as well as with bevacizumab. Initial follow-up CT scans of the chest revealed a positive response to treatment. Physicians, in particular, radiologists, must consider the mediastinum during the first evaluation and further follow-up of patients with colorectal carcinoma even in the absence of metastasis.


Identification of Biomarkers of Exposure to FTOHs and PAPs in Humans Using a Targeted and Nontargeted Analysis Approach.
Although historic perfluorinated compounds are currently under scrutiny and growing regulatory control in the world, little is known about human exposure to other polyfluorinated compounds presently in use. Fluorotelomer alcohols (FTOHs) and polyfluoroalkyl phosphate esters (PAPs) are known to degrade to terminal perfluorinated acids and toxic reactive intermediates through metabolic pathways. Therefore, it is important to characterize their human exposure by the identification of unique biomarkers. With the use of liquid chromatography-mass spectrometry-time-of-flight analysis (LC-MS-TOF), we developed a workflow for the identification of metabolites for the 8:2 FTOH and 8:2 diPAP. Analysis of serum and urine of dosed rats indicated the 8:2 FTOH-sulfate and the 8:2 diPAP as potential biomarkers. These compounds, as well as 25 other fluorinated compounds and metabolites, were analyzed in human serum and urine samples from the general population (n = 100) and office workers (n = 30). The 8:2 FTOH-sulfate was measured for the first time in human samples in 5 to 10% of the serum samples, ranging from 50 to 80 pg/mL. The 8:2 diPAP was measured in 58% of the samples, ranging from 100 to 800 pg/mL. This study indicates the FTOH-sulfate conjugate as a biomarker of exposure to FTOHs and PAPs in humans.


Taking guidance from parents involved in a longitudinal birth cohort - the ROLO family advisory committee.
The ROLO Study (Randomised cOntrol trial of a Low glycaemic index diet in pregnancy to prevent macrosomia) was a randomised control trial conducted between 2007 and 2011 to examine if a low glycaemic index (GI) diet could reduce the incidence of macrosomia. The ROLO Family Advisory Committee is a self-selected group of parents who are involved in the longitudinal follow-up of the ROLO Study. The committee was established in 2017 and the goal is to achieve a partnership between ROLO families and researchers, leading to improved research quality, relevance, and outcomes. This research method is termed "Public and patient involvement (PPI)" and describes how researchers collaborate and engage with the public in order to make research more relevant to them. The ROLO study mothers and children have been prospectively followed-up at multiple time points post-pregnancy. In October 2017, all women were invited to join the ROLO Family Advisory Committee via email or via advertisement on the ROLO Study Facebook page. Fathers and other guardians of the study children were also invited to join. Two annual meetings with the research team and parents were held in 2018 and 2019. The meetings were recorded, transcribed verbatim by researchers, and thematically analysed. Parents provided opinions on the areas they felt should be explored within the ROLO study using information that was collected up to the current follow-up point. They also shared views on research interests which were of importance to them. These topics included; child mental health, fussy eating in childhood and healthy eating policies in schools. Mothers were much more concerned about factors which influenced their child's health rather than their own. Incorporating an element of PPI to this study was found to be a positive learning experience for participants and researchers. The involvement of parents has enriched the research agenda at the UCD Perinatal Research Centre. We will continue to engage with the parents of the ROLO Study and plan to involve the children to explore their opinions at the next opportunity.


Protective Effect of Edaravone against Carbon Monoxide Induced Apoptosis in Rat Primary Cultured Astrocytes.
Objective. To observe the protective effect of edaravone (Eda) on astrocytes after prolonged exposure to carbon monoxide (CO) and further to investigate the potential mechanisms of Eda against CO-induced apoptosis. Methods. The rat primary cultured astrocytes were cultured in vitro and exposed to 1% CO for 24 h after being cultured with different concentrations of Eda. MTT assay was used to detect the cytotoxicity of CO. Flow cytometry was used to detect the apoptosis rate, membrane potential of mitochondria, and ROS level. The mRNA and protein expressions of Bcl-2, Bax, and caspase-3 were assessed by real-time PCR and Western blotting analysis, respectively. Results. Eda can significantly suppress cytotoxicity of CO, and it can significantly increase membrane potential of mitochondria and Bcl-2 expressions and significantly suppress the apoptosis rate, ROS level, Bax, and caspase-3 expressions. Conclusion. Eda protects against CO-induced apoptosis in rat primary cultured astrocytes through decreasing ROS production and subsequently inhibiting mitochondrial apoptosis pathway.


Bridging the gap between measurements and modelling: a cardiovascular functional avatar.
Lumped parameter models of the cardiovascular system have the potential to assist researchers and clinicians to better understand cardiovascular function. The value of such models increases when they are subject specific. However, most approaches to personalize lumped parameter models have thus far required invasive measurements or fall short of being subject specific due to a lack of the necessary clinical data. Here, we propose an approach to personalize parameters in a model of the heart and the systemic circulation using exclusively non-invasive measurements. The personalized model is created using flow data from four-dimensional magnetic resonance imaging and cuff pressure measurements in the brachial artery. We term this personalized model the cardiovascular avatar. In our proof-of-concept study, we evaluated the capability of the avatar to reproduce pressures and flows in a group of eight healthy subjects. Both quantitatively and qualitatively, the model-based results agreed well with the pressure and flow measurements obtained in vivo for each subject. This non-invasive and personalized approach can synthesize medical data into clinically relevant indicators of cardiovascular function, and estimate hemodynamic variables that cannot be assessed directly from clinical measurements.


A simplified digital workflow for the prosthetic finishing of implant rehabilitations: a case report.
The aim of this article is to describe how, during the provisional and definitive prosthetic phases, using new digital technologies, it is possible to improve the ergonomics of the prosthetist's work and reduce the discomfort of patients, subjecting them to the fewest possible appointments at the dentist. The proposal of a full digital protocol, described by the following case report, for the realization of a definitive prosthetic rehabilitation supported by a reduced number of implants, in fact, allows to considerably reduce the number of appointments and reduce any bias. A 67-year-old male patient presents for the first visit to the Department of Dentistry of the San Raffaele Hospital, wearing a removable upper prosthesis and with the request to heal the aesthetic and functional situation through prosthetics fixed. An initial panoramic radiograph was performed, intra and extra oral photos were taken and also intraoral impressions. A stereo-lithographic models are obtained from intraoral scans, and two total prostheses, upper and lower, were packaged for the provisional post-surgical phase was performed. In accordance with the All-on-4 method 8 implant fixtures were placed. For the final prosthetic phase, the patient underwent only two operative sessions. In the first session, scans were taken with the provisionals in situ, of the patient's mucous membranes and with the Scan-abutments in place. In the second session using specific CADSoftware the matching of the STL files of the three scans were created, the opposing arches of the patient were related on a digital articulator, and the milled titanium bars were immediately constructed and finished with the resin. Finally, the definitive prostheses were delivered to the patient without any other test. Digital technology has allowed a clear reduction in working times and costs and has allowed the reduction of stress for patients who undergo invasive and extensive treatments to recover aesthetics and function, and for clinicians who must manage complex cases with fewer appointments possible.


Volumetric gray matter findings in autonomic network regions of people with focal epilepsy.
Voxel-based morphometry (VBM) studies of people with focal epilepsies revealed gray matter (GM) alterations in brain regions involved in cardiorespiratory regulation, which have been linked to the risk of sudden unexpected death in epilepsy (SUDEP). It remains unclear whether the type and localization of epileptogenic lesions influence the occurrence of such alterations. To test the hypothesis that VBM alterations of autonomic network regions are independent of epileptogenic lesions and that they reveal structural underpinnings of SUDEP risk, VBM was performed in 100 people with focal epilepsies without an epileptogenic lesion identifiable on MRI (mean age ± standard deviation = 35 ± 11 years, 56 female). The group was further stratified in high (sample size n = 29) and low risk of SUDEP (n = 71). GM volumes were compared between these two subgroups and to 100 matched controls. People with epilepsy displayed higher GM volume in both amygdalae and parahippocampal gyri and lower GM volume in the cerebellum and occipital (p<.05, familywise error corrected). There were no significant volumetric differences between high and low SUDEP risk subgroups. Our findings confirm that autonomic networks are structurally altered in people with focal epilepsy and they question VBM as a suitable method to show structural correlates of the SUDEP risk score.


[A case of multifocal Langerhans cell granulomatosis: a BAL follow up study].
Langerhans cell granulomatosis, once called histiocytosis X, is a rare disease. A case of multifocal Langerhans cell granulomatosis in the bone, lymph nodes, skin and lungs of an 18-year-old man is described. Head CT and MRI showed a soft tissue mass of the left temporal bone. Lymph node and skin biopsies substantiated a diagnosis of Langerhans cell granulomatosis. A High resolution CT scan of the lung revealed a small cystic lesion, and bronchoalveolar lavage (BAL) showed an increased number of S-100 positive cells. Steroid therapy resulted in complete resolution, and no S-100 positive cells were obtained in the follow-up BAL study.


[Review of 30 digital ring avulsions].
Thirty cases of digital avulsions caused by a ring have were reviewed after a period of eighteen months. The average age of the patients was 30 years, ranging from 5 to 60 years. Fourteen vascular survivals were obtained. In this series the ring finger was the most frequently affected one (21 cases). In 20 cases, the people involved were long distance lorry drivers. The operating techniques were direct micro arterial and venous anastomosis in 2 cases, and isolated arterial bypass grafts in 6 cases, combined arterial and venous bypass graft in 18 cases. No surviving finger was amputated, but 3 patients, including 2 women, asked the amputation of an unsightly stump. This series confirms the extreme seriousness of digital avulsion caused by rings and the value of a microsurgical treatment of vascular lesions by anastomosis or by arterial and venous bypass grafts from stage 2 onwards.


Why are some pamphlets hard for patients to read?
In this study with lung cancer patients, we describe not only text characteristics that hinder comprehension, including unfamiliar words and poor organization, but also reader characteristics that hinder comprehension, such as educational level, and what the patient wants to know. Based on our and other's research we recommend writing what the reader wants to know, relating new learning to what the learner already knows, and using organizational cues for clarity and emphasis.


A Hepatitis B Virus Reactivation Case Potentially Triggered by the Onset of Diffuse Large B Cell Lymphoma.
An 81-year-old man underwent rituximab-containing chemotherapy for chronic lymphocytic leukemia (CLL). Thirteen years after his last chemotherapy, he was diagnosed with hepatitis B virus (HBV) reactivation. He was then treated with entecavir, and improvement was seen in his liver injury. He developed diffuse large B cell lymphoma (DLBCL) after improvement in his hepatitis. Despite chemotherapy, he contracted the coronavirus disease 2019 (COVID-19) and died of COVID-19. We suspect that HBV reactivation was triggered by DLBCL. When HBV reactivation occurs a long time after chemotherapy has concluded, the onset of DLBCL should be considered.


A hybrid phase-space and histogram source model for GPU-based Monte Carlo radiotherapy dose calculation.
In GPU-based Monte Carlo simulations for radiotherapy dose calculation, source modelling from a phase-space source can be an efficiency bottleneck. Previously, this has been addressed using phase-space-let (PSL) sources, which provided significant efficiency enhancement. We propose that additional speed-up can be achieved through the use of a hybrid primary photon point source model combined with a secondary PSL source. A novel phase-space derived and histogram-based implementation of this model has been integrated into gDPM v3.0. Additionally, a simple method for approximately deriving target photon source characteristics from a phase-space that does not contain inheritable particle history variables (LATCH) has been demonstrated to succeed in selecting over 99% of the true target photons with only ~0.3% contamination (for a Varian 21EX 18 MV machine). The hybrid source model was tested using an array of open fields for various Varian 21EX and TrueBeam energies, and all cases achieved greater than 97% chi-test agreement (the mean was 99%) above the 2% isodose with 1% / 1 mm criteria. The root mean square deviations (RMSDs) were less than 1%, with a mean of 0.5%, and the source generation time was 4-5 times faster. A seven-field intensity modulated radiation therapy patient treatment achieved 95% chi-test agreement above the 10% isodose with 1% / 1 mm criteria, 99.8% for 2% / 2 mm, a RMSD of 0.8%, and source generation speed-up factor of 2.5.


[Chronic digital wound: epidermoid cyst, osteomyelitis or both? Presentation of two clinical cases and review of the literature].
when faced with a chronic digital injury, the differential diagnosis between osteomyelitis or primary tumor is raised. Coexistence between osteomyelitis and epidermoid bone cyst is not uncommon. in this article, we describe two cases of epidermoid cysts in distal phalanx of the hand associated with osteomyelitis and a review of the literature is presented. both osteomyelitis and epidermoid bone cyst have been related to the presence of previous trauma at the site of the lesion, nail alterations and chronic phlogotic signs, so it is important to reach a diagnosis of certainty through an anatomopathological study and to perform a good surgical debridement to ensure the healing of both entities. surgical debridement associated with curettage and filling of the bone defect with bone substitute with antibiotic is a good therapeutic option in the treatment of these lesions.


Factor XII and uPAR upregulate neutrophil functions to influence wound healing.
Coagulation factor XII (FXII) deficiency is associated with decreased neutrophil migration, but the mechanisms remain uncharacterized. Here, we examine how FXII contributes to the inflammatory response. In 2 models of sterile inflammation, FXII-deficient mice (F12-/-) had fewer neutrophils recruited than WT mice. We discovered that neutrophils produced a pool of FXII that is functionally distinct from hepatic-derived FXII and contributes to neutrophil trafficking at sites of inflammation. FXII signals in neutrophils through urokinase plasminogen activator receptor-mediated (uPAR-mediated) Akt2 phosphorylation at S474 (pAktS474). Downstream of pAkt2S474, FXII stimulation of neutrophils upregulated surface expression of αMβ2 integrin, increased intracellular calcium, and promoted extracellular DNA release. The sum of these activities contributed to neutrophil cell adhesion, migration, and release of neutrophil extracellular traps in a process called NETosis. Decreased neutrophil signaling in F12-/- mice resulted in less inflammation and faster wound healing. Targeting hepatic F12 with siRNA did not affect neutrophil migration, whereas WT BM transplanted into F12-/- hosts was sufficient to correct the neutrophil migration defect in F12-/- mice and restore wound inflammation. Importantly, these activities were a zymogen FXII function and independent of FXIIa and contact activation, highlighting that FXII has a sophisticated role in vivo that has not been previously appreciated.


A comparative trial of a controlled-release formulation of ketoprofen ('Oruvail') and a conventional capsule formulation of ketoprofen ('Orudis') in patients with osteoarthritis of the hip.
An open study was carried out in 46 patients with osteoarthritis of the hip to compare the efficacy and tolerance of treatment with ketoprofen given either as 100 mg capsules twice daily or as 2 capsules of 100 mg ketoprofen in a controlled-release formulation given once daily. The results of subjective and objective assessments before and during 3-months' treatment in the 48 patients who completed the trial showed both treatments produced improvement in all parameters, except for the time taken for inactivity stiffness to develop, and there was no significant difference between treatments in terms of efficacy. The controlled-release preparation, however, was significantly better tolerated than the ordinary capsule form. Minor haematological and biochemical changes during treatment were noted but these were not of clinical importance. Six patients, 2 receiving the controlled-release and 4 receiving the ordinary formulation of ketoprofen, were withdrawn because of lack of efficacy or unacceptable side-effects.


European Practical and Patient-Centred Guidelines for Adult Obesity Management in Primary Care.
The first contact for patients with obesity for any medical treatment or other issues is generally with General Practitioners (GPs). Therefore, given the complexity of the disease, continuing GPs' education on obesity management is essential. This article aims to provide obesity management guidelines specifically tailored to GPs, favouring a practical patient-centred approach. The focus is on GP communication and motivational interviewing as well as on therapeutic patient education. The new guidelines highlight the importance of avoiding stigmatization, something frequently seen in different health care settings. In addition, managing the psychological aspects of the disease, such as improving self-esteem, body image and quality of life must not be neglected. Finally, the report considers that achieving maximum weight loss in the shortest possible time is not the key to successful treatment. It suggests that 5-10% weight loss is sufficient to obtain substantial health benefits from decreasing comorbidities. Reducing waist circumference should be considered even more important than weight loss per se, as it is linked to a decrease in visceral fat and associated cardiometabolic risks. Finally, preventing weight regain is the cornerstone of lifelong treatment, for any weight loss techniques used (behavioural or pharmaceutical treatments or bariatric surgery).


The Incidence of Neurologic Susceptibility to a Skull Defect.
To determine whether there is a measureable change in neurologic function after cranioplasty. This is a prospective single-surgeon, single-center study. Fifty patients who required a cranioplasty procedure were assessed neurologically within 72 hours before and 7 days after surgery. The assessment tools were the Functional Independence Measure (FIM) and the Cognitive assessment report (Cognistat). The scores for both assessments were calculated and then compared before and after surgery. FIM assessment was performed on all fifty patients, and a Cognistat assessment was performed on 47 patients. Most improvements were seen in the Cognistat scores; however, there appeared to be no specific areas in which there was consistent improvement. There were substantial improvements in the Cognistat assessment in 9 patients. One patient had a much-improved FIM assessment (improved from 18 to 34), but a Cognistat assessment was not possible because of poor neurologic function. These results suggested that improvements after cranioplasty were more likely to occur in the domain of cognitive function than motor function, although overall these results did not reach statistically significance. Bifrontal (vs. unilateral) cranioplasty, timing between decompression and cranioplasty, and age of the patients did not appear to affect the postoperative FIM scores, after we adjusted for preoperative FIM scores and surgical complications. A small but significant number of patients appear to improve clinically after cranioplasty. Neurologic susceptibility to a skull defect may be more common than had been appreciated previously.


Predictors of meningococcal vaccination among university students.
Invasive disease secondary to Neisseria meningitidis is a rare but devastating illness among university students. The Advisory Committee on Immunization Practices recommends educating college freshmen about meningococcal disease and vaccinating all college freshmen who live in residence halls. We conducted this survey to gain a better understanding of current immunization rates and factors associated with vaccination.


Herpes simplex virus in postradiation cervical smears. A morphologic and immunocytochemical study.
From January 1987 to August 1988, cytomorphologic criteria of both herpes simplex virus (HSV) and radiation effects were observed in Papanicolaou smears from 3 of 1,340 patients who had received radiotherapy for squamous cell carcinoma of the cervix. Avidin-biotin immunoperoxidase staining, using a rabbit IgG polyclonal HSV antibody, confirmed the presence of HSV antigen in those three postradiation smears. Both multinucleated molded cells and epithelial cells that lacked cytopathic effects were positive for HSV. Three other postradiation smears from these cases were similarly positive for HSV antigen; the one preradiation smear was negative. In situ hybridization and immunoperoxidase studies on sections from the preradiation biopsies were negative: severely altered neoplastic cells showed no reactivity. The absence of HSV markers in the preradiation specimens suggests that the HSV infections were secondary to the radiotherapy; further studies are needed to prove this association and to assess the possible mechanisms. These cases clearly indicate that the overlapping features of radiation and viral effects (such as multinucleation) may be present simultaneously.


Development of senile plaques. Relationships of neuronal abnormalities and amyloid deposits.
The evolution of senile plaques and the relationships among neuritic elements, extracellular deposits of the beta-amyloid protein (beta/A4), and vascular beta/A4 are poorly understood. Immunocytochemical methods were used to examine fixed-frozen prefrontal cortices of 14 rhesus monkeys (Macaca mulatta) (14 to 37 years of age) for the presence of abnormal fibers/neurites, alpha 1-antichymotrypsin (alpha-ACT), and beta/A4. Age-associated alterations included abnormal fibers/neurites, presence of beta/A4, and association of alpha-ACT with beta/A4 in plaques and blood vessels. Vascular amyloid was present only in the oldest monkeys. The topographic distribution of abnormal fibers/neurites was mapped with acetylcholinesterase (AChE) histochemistry, and deposits of amyloid were visualized with immunocytochemistry for beta/A4. beta/A4 often was associated with neurites, but many neurites lacked demonstrable beta/A4. Thus in aged monkeys, abnormal neurites may provide one type of focus for the accumulation of the amyloid precursor, which is subsequently abnormally processed to form beta/A4. Our data in rhesus monkeys suggest that fiber and neuritic abnormalities increase with age and that they may precede the majority of beta/A4 deposits; the initial stages of neurite formation and parenchymal amyloid deposits may be independent of the appearance of vascular amyloid; and these processes may be synergistic with advanced age.


Influenza vaccine uptake in Tunisia from two high-risk groups' perception and attitudes: a qualitative study.
Pregnant women (PW) and older adult with chronic diseases (ECD) are priority groups for the influenza vaccination. This study was designed to have a better insight into the influenza perceptions and barriers of the vaccine uptake from these groups' perspectives. This qualitative study consisted of 20 focus group discussions (FGDs) enrolled from five governorates across the country (north, center, and south) between March 18 and July 10, 2019, in urban and rural areas. FGDs were conducted in Arabic (Tunisian dialect) and following the topic guide. Data were transcribed in the local language then translated into English and analyzed using Nvivo12 Software. This permitted the analysis thematic approach, using codes determined by the focus groups. A total of 170 individuals participated in the FGDs (84 ECD and 86 PW). Both groups recognized the weakness of the immune system as key determinant for severity. While PW raised the lack of information about the vaccine, the ECD emphasized accessibility problems. Five main barriers to influenza vaccination were identified: cultural barriers and use of traditional medicine, misleading or lack of information about influenza and the vaccine, advice against its uptake, problems of availability and accessibility of the vaccine as well as mistrust towards the vaccine including adverse effects, vaccine composition and effectiveness. The study provided refined information from the perspectives of users to orient the policies regarding the promotion of influenza vaccine by decision makers among these two high risk groups.


Detecting ancient codispersals and host shifts by double dating of host and parasite phylogenies: Application in proctophyllodid feather mites associated with passerine birds.
Inferring cophylogeographic events requires matching the timing of these events on both host and symbiont (e.g., parasites) phylogenies because divergences of hosts and their symbionts may not temporally coincide, and host switches may occur. We investigate a large radiation of birds (Passeriformes) and their permanent symbionts, the proctophyllodid feather mites (117 species from 116 bird species; six genes, 11,468 nt aligned) using two time-calibration strategies for mites: fossils only and host phylogeography only. Out of 10 putative cophylogeographic events 4 agree in timing for both symbiont and host events being synchronous co-origins or codispersals; three were based on host shifts, but agree in timing being very close to the origin of modern hosts; two disagree; and one large basal mite split was seemingly independent from host phylogeography. Among these events was an ancient (21-25.3 Mya), synchronous codispersal from the Old World leading to the origin and diversifications of New World emberizoid passerids and their mites, the thraupis + quadratus species groups of Proctophyllodes. Our framework offers a more robust detection of host and symbiont cophylogeographic events (as compared to host-symbiont reconciliation analysis and using host phylogeography for time-calibration) and provides independent data for testing alternative hypotheses on timing of host diversification and dispersal.


A monoclonal antibody specific for two-chain urokinase-type plasminogen activator. Application to the study of the mechanism of clot lysis with single-chain urokinase-type plasminogen activator in plasma.
A murine monoclonal antibody (MA-12E6A8) was raised against human urokinase-type plasminogen activator (u-PA), which, in an enzyme-linked immunosorbent assay (ELISA), reacted 15,000-fold better with recombinant two-chain u-PA (rtcu-PA) than with recombinant single-chain u-PA (rscu-PA). The antibody had no effect on the activity of rtcu-PA or on its inhibition by a chloromethylketone, but reduced the inhibition of rtcu-PA by recombinant plasminogen activator inhibitor-1 (rPAI-1) at least 10-fold. The dissociation constant of the rtcu-PA/MA-12E6A8 complex was 7 nmol/L. An ELISA was developed using MA-12E6A8 as capture antibody and a horseradish peroxidase conjugated u-PA specific antibody for tagging. It recognized free and active site blocked rtcu-PA but not rtcu-PA in complex with rPAI-1 or with alpha 2-antiplasmin. This ELISA was used to monitor the generation of rtcu-PA during fibrin clot lysis with rscu-PA in human plasma. Addition of 5 micrograms/mL rscu-PA to 3 mL plasma containing a 0.2 mL 125I-fibrin labeled plasma clot caused 50% clot lysis in 62 +/- 13 minutes (mean +/- SD, n = 6), at which time 99 +/- 28 ng/mL rtcu-PA was detected but no fibrinogen breakdown had occurred. Fifty percent fibrinogen breakdown did occur only when rtcu-PA had reached a level of 1,000 +/- 270 ng/mL (at 150 +/- 21 minutes). rscu-PA, 2 micrograms/mL, induced 50% clot lysis in 160 +/- 41 minutes (n = 6); no fibrinogen degradation occurred within 4 hours and rtcu-PA levels did not exceed 80 ng/mL. In the absence of a fibrin clot, 5 micrograms/mL rscu-PA added to human plasma did not result in significant generation of rtcu-PA (less than 50 ng/mL after 4 hours) and no fibrinogen degradation was observed. These results indicate that clot lysis with rscu-PA in a plasma milieu does not require extensive systemic conversion of rscu-PA to rtcu-PA, and that fibrinogen degradation occurs secondarily to systemic conversion of rscu-PA to rtcu-PA.


Determination of total dietary fiber in selected foods containing resistant maltodextrin by enzymatic-gravimetric method and liquid chromatography: collaborative study.
A method was developed for determination of total dietary fiber (TDF) in foods containing resistant maltodextrin (RMD) which includes nondigestible carbohydrates that are not fully recovered as dietary fiber by conventional TDF methods such as AOAC 985.29 or 991.43. Because the average molecular weight (MW) of RMD is 2000 daltons, lower MW soluble dietary fiber components do not precipitate in 78% ethanol; therefore, RMD is not completely quantitated as dietary fiber by current AOAC methods. The accuracy and precision of the method was evaluated through an AOAC collaborative study. Ten laboratories participated and assayed 12 test portions (6 blind duplicates) containing RMD. The 6 test pairs ranged from 1.5 to 100% RMD. The method consisted of the following steps: (1) The insoluble dietary fiber (IDF) and high MW soluble dietary fiber (HMWSDF) were determined by AOAC 985.29. (2) Ion exchange resins were used to remove salts and proteins contained in the AOAC 985.29 filtrates (including ethanol and acetone). (3) The amount of low MWRMD (LMWRMD) in the filtrates were determined by liquid chromatography. (4) The TDF was calculated by summation of the IDF, HMWSDF, and LMWRMD fractions having nondigestible carbohydrates with a degree of polymerization of 3 and higher. Repeatability standard deviations (RSDr) were 1.33-7.46%, calculated by including outliers, and 1.33-6.10%, calculated by not including outliers. Reproducibility standard deviations (RSDR) were 2.48-9.39%, calculated by including outliers, and 1.79-9.39%, calculated by not including outliers. This method is recommended for adoption as Official First Action.


Radionuclide I-131 Labeled Albumin-Paclitaxel Nanoparticles for Synergistic Combined Chemo-radioisotope Therapy of Cancer.
Development of biocompatible/biodegradable materials with multiple functionalities via simple methods for cancer combination therapy has attracted great attention in recent years. Herein, paclitaxel (PTX), a popular anti-tumor chemotherapeutic drug, is used to induce the self-assembly of human serum albumin (HSA) pre-labeled with radionuclide I-131, obtaining 131I-HSA-PTX nanoparticles for combined chemotherapy and radioisotope therapy (RIT) of cancer. Such 131I-HSA-PTX nanoparticles show prolonged blood circulation time, high tumor specific uptake and excellent intra-tumor penetration ability. Interestingly, as revealed by in vivo photoacoustic imaging and ex vivo immunofluorescence staining, PTX delivered into the tumor by HSA-nanoparticle transportation can remarkably enhance the tumor local oxygen level and suppress the expression of HIF-1α, leading to greatly relieved tumor hypoxia. As the results, the combined in vivo chemotherapy & RIT with 131I-HSA-PTX nanoparticles in the animal tumor model offers excellent synergistic therapeutic efficacy, likely owing to the greatly modulated tumor microenvironment associated with PTX-based chemotherapy. Therefore, in this work, a simple yet effective therapeutic agent is developed for synergistic chemo-RIT of cancer, promising for future clinic translations in cancer treatment.


Odynophagia in sickle cell anemia: pain is not always a crisis.
This report describes the case of a 30-year-old African American male with sickle cell anemia who presented with odynophagia and chest pain. Clinical examination revealed tachypnea, conjunctival congestion, icterus, facial swelling, engorged neck veins, induration over the upper part of chest and arms and a right chest wall port-a-cath. Subsequent imaging revealed occlusion of both brachiocephalic veins and proximal superior vena cava with a metallic SVC stent in-situ. Recanalization was attempted but guidewires could not be passed across the site ofocclusion. He was then treated with catheter guided t-PA boluses delivered to the site of occlusion and oral anticoagulation.


Spectrophotometric method for simultaneous estimation of escitalopram oxalate and clonazepam in tablet dosage form.
A simple, accurate and precise spectrophotometric method has been developed for simultaneous estimation of escitalopram oxalate and clonazepam in combined dosage form. Simultaneous equation method is employed for simultaneous determination of escitalopram oxalate and clonazepam from combined dosage forms. In this method, the absorbance was measured at 238 nm for escitalopram oxalate and 273 nm for clonazepam. Linearity was observed in range of 5-100 mug/ml and 5-50 mug/ml for escitalopram and clonazepam respectively. Recovery studies confirmed the accuracy of proposed method and results were validated as per ICH guidelines. The method can be used for routine quality control of pharmaceutical formulation containing escitalopram and clonazepam.


Molecular identification of cDNA, immunolocalization, and expression of a putative odorant-binding protein from an Asian honey bee, Apis cerana cerana.
An odorant-binding protein cDNA (Acer-ASP2) was cloned and characterized from antennae of adult workers of an Asian honey bee, Apis cerana cerana F. (Hymenoptera: Apidae). The full-length open reading frame of Acer-ASP2 cDNA was 429 bp, encoding 142 amino acids. Protein signature analyses revealed that it contained six conserved cysteines with an N-terminal signal sequence of 19 amino acids. The deduced protein sequence shares high homology with Amel-ASP2 from the honey bee, Apis mellifera L., and low similarity with odorant-binding proteins from other species of insects. Immunocytochemical localization showed that Acer-ASP2 was concentrated in the lymph of olfactory sensilla, such as sensilla placodea and sensilla trichodea A. Real-time polymerase chain reaction of Acer-ASP2 transcripts showed that Acer-ASP2 was expressed on antennae but not in other general anatomical regions of the body. Temporally, Acer-ASP2 was expressed at a relatively high level in adults during two periods (9 and 27 vs. 1, 15, and 30 days). This timing is correlated with the production of beeswax and searching behavior for nectar/pollen, respectively. Thus, Acer-ASP2 is a species-specific gene that we propose to be involved in the acquisition of odorant molecules from nectar, pollen, and other general odorant sources.


Measuring raft size as a function of membrane composition in PC-based systems: Part 1--binary systems.
This work applied two steady-state fluorescence techniques to detect nanoscopic membrane domains in a binary dimyristoylphosphocholine (DMPC)-cholesterol system and a ternary dioleoylphosphocholine (DOPC)-dipalmitoylphosphocholine (DPPC)-cholesterol system. A polarity-induced spectral shift in the emission spectra of 1-myristoyl-2-[12-[(5-dimethylamino-1-naphthalenesulfonyl)amino]dodecanoyl]-sn-glycero-3-phosphocholine (DAN-PC) in combination with a Förster resonance energy transfer (FRET) assay agreed with the phase diagrams that have been published for these systems and were observed to be useful tools in the detection of membrane heterogeneities. The DAN-PC/dehydroergosterol (DHE) FRET pair was found to be best suited for use with these steady-state techniques because of their differential partitioning between phases, although a high acceptor concentration was needed to obtain accurate measurements. In the binary system, this high probe concentration was found to be perturbing, but in more representative ternary systems, the high probe concentration no longer disrupted the phase behavior of the system. This FRET pair allowed for the calculation of nanometer-scale domain sizes in model ternary systems, using the two steady-state fluorescence techniques along with a clear and straightforward model.


Evaluation of ribavirin in the treatment of acute hepatitis.
In this double-blind, placebo-controlled study, treatment of 60 acute hepatitis patients with ribavirin resulted in a more rapid reduction of abnormal laboratory values when compared with the placebo group. Moreover, improved clinical status as reflected by increased appetite with resultant weight gain was noted to be significantly greater in the ribavirin-treated patients. Ribavirin was well tolerated. With this dosage regimen, there were no side effects or changes in laboratory values that could be associated with drug-related toxicity. Since hepatitis A is one of the most common viral infections afflicting the Indian population, the use of a safe and effective therapeutic agent, such as ribavirin, will be necessary to treat these cases.


Reproductive risk factors related to socioeconomic status in pregnant women in southern Brazil.
To evaluate patterns of drug use during pregnancy and other potential reproductive risks in pregnant women, we applied a standard questionnaire to 412 pregnant women classified as low socioeconomic status (SES) or as middle/high SES, in two cities of South Brazil. 77% of the women used at least one medication during pregnancy. We observed significant differences, when comparing low SES and middle/high SES groups, for the following variables: teenage pregnancies (28.4 vs. 12.4%); self-medication (21.8 vs. 13.1%); smoking habits (21.5 vs. 5.1%); unplanned pregnancies (69.5 vs. 51.8%); unwanted pregnancies (31.3 vs. 10.9%), and abortion attempts (13.1 vs. 5.8%). The average number of drugs consumed, however, was not different between low SES and middle/high SES. We believe that better education and conditions for family planning are key points to improve this scenario.


Evaluation of hands-on seminar for reduced port surgery using fresh porcine cadaver model.
The use of various biological and non-biological simulators is playing an important role in training modern surgeons with laparoscopic skills. However, there have been few reports of the use of a fresh porcine cadaver model for training in laparoscopic surgical skills. The purpose of this study was to report on a surgical training seminar on reduced port surgery using a fresh cadaver porcine model and to assess its feasibility and efficacy. The hands-on seminar had 10 fresh porcine cadaver models and two dry boxes. Each table was provided with a unique access port and devices used in reduced port surgery. Each group of 2 surgeons spent 30 min at each station, performing different tasks assisted by the instructor. The questionnaire survey was done immediately after the seminar and 8 months after the seminar. All the tasks were completed as planned. Both instructors and participants were highly satisfied with the seminar. There was a concern about the time allocated for the seminar. In the post-seminar survey, the participants felt that the number of reduced port surgeries performed by them had increased. The fresh cadaver porcine model requires no special animal facility and can be used for training in laparoscopic procedures.


Severe neurological impairment: legal aspects of decisions to reduce care.
Decisions to reduce care for patients with severe neurological impairment may raise legal questions. The laws of most states now authorize physicians to stop care for those who have suffered irreversible cessation of all functions of the brain ("brain death"). Where state law is not explicit, it is nevertheless probably lawful to regard brain death as death for legal purposes so long as currently accepted criteria are satisfied. Several courts have ruled that it is lawful to reduce care for patients in vegetative states, but have prescribed differing standards and procedures for implementing such decisions. The issue of whether parents can authorize physicians to reduce care for neurologically impaired children is the focus of current litigation. Implicit in this litigation is the question of how severe neurological impairment must be before parents and physicians may lawfully agree to reduce care. For severely impaired but not vegetative adults, there is some legal authority to justify certain decisions to reduce care. The issue of whether withholding feeding from a severely demented patient with life-threatening medical problems constitutes criminal behavior is now being considered by a state supreme court.


[Evolution and effectiveness of therapeutic patient education for obesity and diabetes].
Therapeutic patient education (TPE) aims to help patients acquire or maintain the skills they need to best manage their lives with a chronic disease. Through a scientometric analysis of the literature, we identified the most influential bibliographic data related to TPE research that have strengthened the field and increased its effectiveness. These were studies from the fields of education, philosophy, psychology, anthropology and medical sociology. We have conducted a meta-analysis that has demonstrated the effectiveness of TPE for the management of obesity and diabetes on biological and psychological parameters. It allowed patients to improve their knowledge, their therapeutic adherence and their sense of self-efficacy.


Free-form V-groove reflector design with the SMS method in three dimensions.
The Simultaneous Multiple Surface design method in three dimensions (SMS3D) is applied to the design of free-form V-groove reflectors. The general design problem is how to achieve the coupling of two wavefronts after two reflections at the V-groove, no matter which side of the groove the rays hit first. This paper also explains a design procedure for thin dielectric grooved-reflector substitutes for conventional mirrored surfaces. Some canonical V-groove designs are ray-traced in detail.


Testing for Trenbolone, an Anabolic Steroid, in Biological Fluids and Head Hair in a Post-Mortem Case.
A 60-year-old man was found dead at home by his wife. The man was known to be a regular trainer in a fitness center and was described as a long-term user of anabolic steroids. The autopsy revealed heart failure with a cardiomegaly, a visceral congestion and a pulmonary edema. The local prosecutor ordered toxicological analyses but no anatomic pathology test. Initial analyses by UPLC-q-TOF-MS system indicated the presence in femoral blood of trenbolone, an anabolic steroid. Trenbolone was quantified with a liquid chromatography system coupled with a tandem mass spectrometer in various autopsy specimens, including hair. Concentrations of trenbolone were 3.9, 3.2, 231 and lower than 0.5 ng/mL in femoral blood, cardiac blood, bile and vitreous humor, respectively. Moreover, in head hair the concentration was 9 pg/mg. The presence of trenbolone in hair can be interpreted as repetitive exposures when compared to the limited literature data. Repetitive misuse of trenbolone can explain the advanced heart failure. This paper highlights the importance to test biological specimens for anabolic steroids in case of heart failure.


VITRECTOMY FOR INTERMEDIATE AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH TANGENTIAL VITREOMACULAR TRACTION: A CLINICOPATHOLOGIC CORRELATION.
To describe the morphologic characteristics of the vitreomacular interface in intermediate age-related macular degeneration associated with tangential traction due to premacular membrane formation and to correlate with optical coherence tomography (OCT) findings and clinical data. Premacular membrane specimens were removed sequentially with the internal limiting membrane from 27 eyes of 26 patients with intermediate age-related macular degeneration during standard vitrectomy. Specimens were processed for immunocytochemical staining of epiretinal cells and extracellular matrix components. Ultrastructural analysis was performed using transmission electron microscopy. Spectral domain optical coherence tomography images and patient charts were evaluated in retrospect. Immunocytochemistry revealed hyalocytes and myofibroblasts as predominant cell types. Ultrastructural analysis demonstrated evidence of vitreoschisis in all eyes. Myofibroblasts with contractile properties were observed to span between folds of the internal limiting membrane and vitreous cortex collagen. Retinal pigment epithelial cells or inflammatory cells were not detected. Mean visual acuity (Snellen) showed significant improvement from 20/72 ± 20/36 to 20/41 ± 20/32 (P < 0.001) after a mean follow-up period of 19 months (median, 17 months). During this period, none of the eyes required anti-vascular endothelial growth factor therapy. Fibrocellular premacular proliferation in intermediate age-related macular degeneration predominantly consists of vitreous collagen, hyalocytes, and myofibroblasts with contractile properties. Vitreoschisis and vitreous-derived cells appear to play an important role in traction formation of this subgroup of eyes. In patients with intermediate age-related macular degeneration and contractile premacular membrane, release of traction by vitrectomy with internal limiting membrane peeling results in significantly functional and anatomical improvement.


Intraoperative CT-guided cochlear implantation in congenital ear deformity.
Intraoperative computed tomography (iCT)-guided cochlear implantation is practical and effective for correct electrode placement in the cochlea of patients with congenital inner ear and/or complex middle ear malformation. The operation in patients with inner ear and/or complex middle ear malformation including abnormal facial nerve course is difficult. This study evaluated the efficacy of cochlear implantation under the guidance of iCT to insure correct electrode placement. This was a prospective interventional case series. Ten patients with severe to profound sensorineural hearing loss due to ear malformations were enrolled, and iCT was used to confirm the right placement of electrodes. Intraoperative CT was performed three times in one patient, twice in two, and once in the others. Interruption of the surgical process for each iCT until resumption of surgery was 9.64 ± 0.63 min. iCT revealed incorrectly positioned cochlear implants in two patients, which were immediately corrected. There were no reoperations due to misplacement of electrodes. iCT helped locate the cochlea in the middle ear of one patient with an abnormal facial nerve course. The overall intervention rate based on iCT findings was 30%. level 4.


A novel pestivirus associated with deaths in Pyrenean chamois (Rupicapra pyrenaica pyrenaica).
During investigations into recent population decreases in Pyrenean chamois (Rupicapra pyrenaica pyrenaica) 21 animals found dead or dying were necropsied. Immunohistochemistry revealed the presence of a pestivirus in organs from two of the 21 chamois. From one of these animals a pestivirus was isolated from the spleen, skin and serum. The virus had better growth in ovine than in bovine cells and was neutralized most effectively by an anti-border disease virus (BDV) reference antiserum. Using panpestivirus and genotype-specific primers selected from 5'-untranslated region (UTR) of the pestivirus genome, BDV RNA was demonstrated by RT-PCR. Comparison of the chamois sequences from 5'-UTR, entire N(pro) and E2 gene coding regions with those of other pestivirus genotypes revealed that this virus did not fall into any of the pestivirus genotypes identified so far. Results of phylogenetic analysis suggested that the chamois pestivirus was closely related to BDV and it was typed as BDV-4 genotype.


Platinum complexes as radiosensitizers of hypoxic mammalian cells.
Cis-dichlorodiammineplatinum (II), or cis-PDD, has recently been shown to be a potent radiosensitizer of bacteria, particularly under conditions of acute hypoxia. This study extends this observation to include the radiosensitization of mammalian cell (V-79) by low concentrations of cis-PDD, cis-dichlorobis(aziridine) platinum (II), and the trans-isomer of PDD as measured from survival curve analysis. This radiosensitization was obtained at concentrations of 10 micrometer, 60 micrometer, and 100 micrometer for the cis-PDD, aziridine-platinum, and trans-isomer respectively. The corresponding drug toxicity survival levels were 8, 40 and 50%. Dose modification factors of around 1.3 to 1.4 were observed.


Asymmetric Three-Component Cyclizations toward Structurally Spiro Pyrrolidines via Bifunctional Phosphonium Salt Catalysis.
Asymmetric multicomponent reactions toward optically pure compounds are highly attractive but extremely challenging. Presented herein is a highly diastereo- and enantioselective three-component cyclization of exocyclic alkenes with aldehydes and amino esters, which was enabled by bifunctional phosphonium salt catalysts. A wide range of multiply substituted spiro pyrrolidine derivatives were prepared in high yields with excellent stereoselectivities. Of note, this is the first example of a catalytic asymmetric three-component reaction with a phase-transfer catalysis system.


NMR metabolomics of planktonic and biofilm modes of growth in Pseudomonas aeruginosa.
Bacteria often reside in communities where the cells have secreted sticky, polymeric compounds that allow them to attach to surfaces. This sessile lifestyle, referred to as a biofilm, affords the cells within these communities a tolerance of antibiotics and antimicrobial treatments. Biofilms of the bacterium Pseudomonas aeruginosa have been implicated in cystic fibrosis and are capable of colonizing medical implant devices, such as heart valves and catheters, where treatment of the infection often requires the removal of the infected device. This mode of growth is in stark contrast to planktonic, free floating cells, which are more easily eradicated with antibiotics. The mechanisms contributing to a biofilm's tenacity and a planktonic cell's susceptibility are just beginning to be explored. In this study, we have used a metabolomic approach employing nuclear magnetic resonance (NMR) techniques to study the metabolic distinctions between these two modes of growth in P. aeruginosa. One-dimensional 1H NMR spectra of fresh growth medium were compared with spent medium supernatants from batch and chemostat planktonic and biofilms generated in continual flow system culture. In addition, 1H high-resolution magic angle spinning NMR techniques were employed to collect 1H NMR spectra of the corresponding cells. Principal component analysis and spectral comparisons revealed that the overall metabolism of planktonic and biofilm modes of growth appeared similar for the spent media, while the planktonic and biofilm cells displayed marked differences. To determine the robustness of this technique, we prepared cell samples under slightly different preparation methods. Both techniques showed similar results. These feasibility studies show that there exist chemical differences between planktonic and biofilm cells; however, in order to identify these metabolomic differences, more extensive studies would have to be performed, including 1H-1H total correlated spectroscopy.


Down-regulation of ubiquitin ligase Cbl induced by twist haploinsufficiency in Saethre-Chotzen syndrome results in increased PI3K/Akt signaling and osteoblast proliferation.
Genetic mutations of Twist, a basic helix-loop-helix transcription factor, induce premature fusion of cranial sutures in Saethre-Chotzen syndrome (SCS). We report here a previously undescribed mechanism involved in the altered osteoblastogenesis in SCS. Cranial osteoblasts from an SCS patient with a Twist mutation causing basic helix-loop-helix deletion exhibited decreased expression of E3 ubiquitin ligase Cbl compared with wild-type osteoblasts. This was associated with decreased ubiquitin-mediated degradation of phosphatidyl inositol 3 kinase (PI3K) and increased PI3K expression and PI3K/Akt signaling. Increased PI3K immunoreactivity was also found in osteoblasts in histological sections of affected cranial sutures from SCS patients. Transfection with Twist or Cbl abolished the increased PI3K/Akt signaling in Twist mutant osteoblasts. Forced overexpression of Cbl did not correct the altered expression of osteoblast differentiation markers in Twist mutant cells. In contrast, pharmacological inhibition of PI3K/Akt, but not ERK signaling, corrected the increased cell growth in Twist mutant osteoblasts. The results show that Twist haploinsufficiency results in decreased Cbl-mediated PI3K degradation in osteoblasts, causing PI3K accumulation and activation of PI3K/Akt-dependent osteoblast growth. This provides genetic and biochemical evidence for a role for Cbl-mediated PI3K signaling in the altered osteoblast phenotype induced by Twist haploinsufficiency in SCS.


Invasive pulmonary aspergillosis.
Invasive pulmonary aspergillosis is the most common fungal pulmonary infection in certain immunocompromised patients. The most commonly affected patients are hematopoietic stem cell transplant recipients and patients with hematological malignancies undergoing intensive chemotherapy. The survival of patients with invasive pulmonary aspergillosis is very poor because of difficulties in early diagnosis and lack of effective treatment options. Research efforts are being made constantly to improve different diagnostic techniques. Early, repeated, high resolution computed tomography of the chest, and sequential nonculture-based monitoring of Aspergillus antigen and DNA can improve earlier diagnosis. New antifungal drugs for treatment and prevention of invasive pulmonary aspergillosis continue to emerge, with better safety, efficacy, and pharmacologic profiles.


Temporal preparation strategy may inflate RT deficit in patients with Parkinson's disease.
Twelve patients with Parkinson's disease (PD) and 12 age-matched controls completed a visual reaction time (RT) task to assess the effect of temporal parameters on response preparation. Simple and choice RT conditions were presented in separate blocks. In both conditions, preparatory intervals of various durations (1, 3 and 5 s) were introduced between an auditory warning signal and the visual target. Within a block of trials, intervals varied randomly. The results indicated that PD patients responded slower than controls in both task conditions. Also, there was evidence for preparation in both groups, as RT decreased with increasing intervals. A three-way interaction indicated that PD patients' RT was longer than that of controls at the shortest interval in simple RT. This suggests that PD patients show a different pattern of temporal response preparation and that this may contribute to their deficit on RT tasks.


Evaluating mixtures of urinary phthalate metabolites and serum per-/polyfluoroalkyl substances in relation to adolescent hair cortisol: The HOME Study.
Results of toxicological studies indicate that phthalates and per-/polyfluoroalkyl substances (PFAS), two classes of endocrine disrupting chemicals, may alter the functioning of the hypothalamic-pituitary-adrenocortical (HPA) axis. We evaluated the associations of urinary phthalate metabolites and serum PFAS during gestation and childhood with adolescent hair cortisol concentrations (pg/mg hair) at age 12 years, an integrative marker of HPA axis activity (n=205 mother-child pairs; Cincinnati, Ohio; enrolled 2003-2006). We used quantile-based g-computation to estimate associations between mixtures of urinary phthalate metabolites or serum PFAS and hair cortisol. We also examined whether associations of individual phthalate metabolites or PFAS with cortisol varied by the timing of exposure. We found that a quartile increase in all childhood phthalate metabolites was associated with 35% higher adolescent hair cortisol (phthalate mixture ψ=0.13; 95% CI=0.03, 0.22); these associations were driven by MEP, MiBP and MBzP. We did not find evidence that phthalate metabolites during gestation or serum PFAS mixtures were related to adolescent hair cortisol concentrations. We found suggestive evidence that higher childhood concentrations of individual PFAS were related to higher and lower adolescent hair cortisol concentrations. Our results suggest that phthalate exposure during childhood may contribute to higher levels of chronic HPA axis activity.


CGS 9896 and ZK 91296, but not CGS 8216 and RO 15-1788, are pure benzodiazepine receptor antagonists on mouse neurons in culture.
The effects of several benzodiazepine receptor ligands on gamma-aminobutyric acid (GABA) responses and on diazepam (DZ) enhancement of GABA responses on mouse spinal cord and cerebral hemisphere neurons are reported. The neurons were grown in primary dissociated cell culture, and intracellular microelectrode recording techniques were used. DZ and Ro 15-1788 reversibly enhanced GABA responses from spinal cord neurons in a concentration-dependent manner. Maximal enhancement was obtained for DZ at 500 nM (82%) and for Ro 15-1788 at 1 microM (18%). CGS 9896 and ZK 91296, in concentrations from 1 nM to 10 microM, were devoid of intrinsic effects in spinal cord and cerebral hemisphere neurons. CGS 8216 and methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) reversibly and dose-dependently reduced GABA responses on spinal cord neurons. Maximal reduction was obtained for CGS 8216 at 50 nM (10%) and for DMCM at 1 microM (39%). CGS 8216 (IC50 = 2.6 nM), ZK 91296 (IC50 = 9 nM), CGS 9896 (IC50 = 17 nM) and Ro 15-1788 (IC50 = 40 nM) antagonized (100 nM) DZ enhancement of GABA responses in a concentration-dependent manner. In addition, CGS 9896 antagonized the effects of Ro 15-1788 and CGS 8216 on GABA responses, and CGS 9896 and ZK 91296 antagonized the reduction of GABA responses by DMCM. On the studied neurons, DZ can be classified as an agonist, Ro 15-1788 as a weak partial agonist, CGS 8216 as a weak partial inverse agonist and DMCM as an inverse agonist at the benzodiazepine receptor. CGS 9896 and ZK 91296 were pure antagonists at the benzodiazepine receptor.


Molecular Characterization and Detection of a Genetically Distinct Tomato Chlorosis Virus Strain in Taiwan.
The whitefly-transmitted tomato chlorosis virus (ToCV) belonging to the genus Crinivirus (family Closteroviridae) affects tomato production worldwide. ToCV was first recorded in Taiwan in 1998 affecting tomato production. In this study, a local virus isolate XS was obtained, after serial whitefly transmissions from a diseased tomato plant displaying general chlorosis were collected in central Taiwan. The whole genome sequence of XS was determined from cDNA fragments amplified by reverse transcription (RT)-PCR, first using the degenerate primers for viruses of Closteroviridae and followed by degenerate and specific primers designed on available sequences of the ToCV isolates. The nucleotide (nt) sequences of RNA-1 and RNA-2 of the XS shared low identities of 77.8 to 78% and 78 to 78.1%, respectively, with genome segments of other ToCV isolates. Nevertheless, the viral RNA-dependent RNA polymerase (RdRp), heat shock protein 70 homolog (Hsp70h), and major capsid protein (CP) shared 88.3 to 96.2% amino acid (aa) identities with other ToCV isolates, indicating that XS is a new strain of this virus. Phylogenetic analyses of these three proteins indicated that all ToCV isolates from different counties outside Taiwan are closely related and clustered in the same clade, whereas the XS isolate is distinct and forms a unique branch. A one tube RT-PCR assay using primers designed from the genomic sequence of the XS was able to detect the ToCV-XS in infected tomato plants and in individual whiteflies. A field survey during 2013 to 2016 revealed a high ToCV-XS prevalence of 60.5% in 172 tested tomato samples, demonstrating that ToCV-XS is becoming an emerging threat for tomato production in Taiwan.


Equine Intestinal O-Seroconverting Temperate Coliphage Hf4s: Genomic and Biological Characterization.
Tailed bacteriophages constitute the bulk of the intestinal viromes of vertebrate animals. However, the relationships between lytic and lysogenic lifestyles of phages in these ecosystems are not always clear and may vary between the species or even between the individuals. The human intestinal (fecal) viromes are dominated mostly by temperate phages, while in horse feces virulent phages are more prevalent. To our knowledge, all the previously reported isolates of horse fecal coliphages are virulent. Temperate coliphage Hf4s was isolated from horse feces, from the indigenous equine Escherichia coli 4s strain. It is a podovirus related to the Lederbergvirus genus (including the well-characterized Salmonella bacteriophage P22). Hf4s recognizes the host O antigen as its primary receptor and possesses a functional O antigen seroconversion cluster that renders the lysogens protected from superinfection by the same bacteriophage and also abolishes the adsorption of some indigenous equine virulent coliphages, such as DT57C, while other phages, such as G7C or phiKT, retain the ability to infect E. coli 4s (Hf4s) lysogens. IMPORTANCE The relationships between virulent and temperate bacteriophages and their impact on high-density symbiotic microbial ecosystems of animals are not always clear and may vary between species or even between individuals. The horse intestinal virome is dominated by virulent phages, and Hf4s is the first temperate equine intestinal coliphage characterized. It recognizes the host O antigen as its primary receptor and possesses a functional O antigen seroconversion cluster that renders the lysogens protected from superinfection by some indigenous equine virulent coliphages, such as DT57C, while other phages, such as G7C or phiKT, retain the ability to infect E. coli 4s (Hf4s) lysogens. These findings raise questions on the significance of bacteriophage-bacteriophage interactions within the ecology of microbial viruses in mammal intestinal ecosystems.


BoCluSt: Bootstrap Clustering Stability Algorithm for Community Detection.
The identification of modules or communities in sets of related variables is a key step in the analysis and modeling of biological systems. Procedures for this identification are usually designed to allow fast analyses of very large datasets and may produce suboptimal results when these sets are of a small to moderate size. This article introduces BoCluSt, a new, somewhat more computationally intensive, community detection procedure that is based on combining a clustering algorithm with a measure of stability under bootstrap resampling. Both computer simulation and analyses of experimental data showed that BoCluSt can outperform current procedures in the identification of multiple modules in data sets with a moderate number of variables. In addition, the procedure provides users with a null distribution of results to evaluate the support for the existence of community structure in the data. BoCluSt takes individual measures for a set of variables as input, and may be a valuable and robust exploratory tool of network analysis, as it provides 1) an estimation of the best partition of variables into modules, 2) a measure of the support for the existence of modular structures, and 3) an overall description of the whole structure, which may reveal hierarchical modular situations, in which modules are composed of smaller sub-modules.


Predictors of all-cause and cardiovascular-specific mortality in type 2 diabetes: A competing risk modeling of an Iranian population.
In Asian population, diabetes mellitus is increasing and has become an important health problem in recent decades. In Iran, cardiovascular disease (CVD) accounts for nearly 46% of the total costs spent for diabetes-associated diseases. Because individuals with diabetes have highly increased CVD risk compared with normal individuals, it is important to diagnosis factors that may increase CVD risk in diabetic patients. The study objective was to identify predictors associated with CVD mortality in patients with type 2 diabetes (T2D) and to develop a prediction model for cardiovascular (CV)-death using a competing risk approach. The study population consisted of 2638 T2D (male = 1110, female = 1528) patients aged ≥35 years attending from Endocrine and Metabolism Research Center in Isfahan for a mean follow-up period of 12 years; predictors for different cause of death were evaluated using cause specific Cox proportional and subdistribution hazards models. Based on competing modeling, the increase in blood pressure (BP) (spontaneously hypertensive rats [SHR]: 1.64), cholesterol (SHR: 1.55), and duration of diabetes (SHR: 2.03) were associated with CVD-death. Also, the increase in BP (SHR: 1.85), fasting blood sugar (SHR: 2.94), and duration of diabetes (SHR: 1.68) were associated with other death (consist of cerebrovascular accidents, cancer, infection, and diabetic nephropathy). This finding suggests that more attention should be paid to the management of CV risk in type 2 diabetic patients with high cholesterol, high BP, and long diabetes duration.


Folate receptor targeted bufalin/β-cyclodextrin supramolecular inclusion complex for enhanced solubility and anti-tumor efficiency of bufalin.
Bufalin (BF), a traditional Chinese medicine, exhibited inhibitory activities against a broad spectrum of tumor cells. The present study elaborates that bufalin was successfully encapsulated into the cavity of β-cyclodextrin (β-CD), which was determined by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (1H NMR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The best reaction mole ratio of BF/β-CD was 1:5. The solubilities of bufalin in water and phosphate buffer solution (pH=7.4) were increased up to 24 and 34 times after encapsulated into the cavity of β-CD respectively. The inclusion efficiency (IE) and drug loading (DL) of bufalin in the inclusion complex were (94.22±0.85)% and (14.11±0.20)%, respectively. Then β-CD conjugated with folic acid (FA) were further prepared and employed to improve the anti-tumor efficacy of inclusion complex. The in vitro dissolution and solubility study showed better values of inclusion complex and FA targeted inclusion complex than that of pure BF. Cytotoxicity experiments by using HCT116 cell line revealed that the antitumor efficiency of bufalin were enhanced more than two folds in the presence of β-CD and folate conjugated β-CD (FA-PEI-β-CD), which demonstrated the potential application of β-CD (FA-PEI-β-CD) as delivery vehicles of bufalin for antitumor therapy.


Reliability and sensitivity analysis of double inverted-T nano-cavity label-free Si:HfO2 ferroelectric junctionless TFET biosensors.
In this work, we propose and simulate an ultrasensitive, label-free, and charge/dielectric modulated Si:HfO2 ferroelectric junctionless tunnel field effect transistor (FE-JL-TFET) based biosensor. The proposed sensing device employs a dual inverted-T cavity and uses ferroelectric gate stacking of Si-doped HfO2, a key enabler of negative capacitance (NC) behavior. The two cavities are carved in gate-source underlap regions by a sacrificial etching technique to sense biomolecules such as streptavidin (2.1), bacteriophage T7 (6.3) and gelatin (12). Two dimensional (2D) calibrated simulations have been performed and the impact of various device parameters, including cavity length and height, on various performance measuring parameters has been studied. It has been observed that the biosensor exhibits better sensitivities for both neutral and charged biomolecules. The maximum values of the I ON/I OFF sensitivity for the neutral, positively charged and negatively charged biomolecules are as high as 3.77 × 109, 5.85 × 109, and 1.72 × 1010, respectively. It has been observed that optimizing the cavity length and height can significantly improve the sensing capability of the proposed device. The comparative analysis of the proposed biosensor and other state of the art biosensors shows a significant improvement in the sensitivity (101 to 106 times) in the proposed biosensor. The detrimental effect of interface trapped charges on the biosensor performance is also analyzed in detail.


First-Principles Design of Na-ion Superionic Conductors: Interstitial-Based Na Diffusion in NaCuZrS3.
In recent years all-solid-state sodium-ion batteries (SS-SIBs) have drawn significant attention due to their potential to be safer and lower cost than lithium-ion batteries. However, the lack of sodium solid-state electrolytes with high ionic conductivity has become one of the major challenges. Here, with first-principles computation we took NaCuZrS3 , consisting of earth-abundant and environmentally benign elements only, as an example to study Na-ion transport in the post-perovskite-like structure and used computation-guided design to improve its potential as a solid-state electrolyte. With ab initio molecular dynamics simulation and nudged elastic band calculation, we studied possible diffusion mechanisms in this material and found that Na ion interstitials have a favorable migration barrier of 0.22 eV, which is among the smallest in the literature reported values. Considering the large formation energy of Frenkel defects, we proposed doping strategy to introduce extra Na interstitials in the material. Our study suggests that the post-perovskite-like sulfides are worth of exploration for applications in SS-SIBs.


[A case of serous cystadenoma of the pancreas communicating with the main pancreatic duct synchronously diagnosed with pancreatic ductal carcinoma].
A 65-year-old woman who had been followed up for a cystic lesion of the tail of the pancreas was found to have cancer of the body of the pancreas. ERP showed stenosis of the main pancreatic duct (MPD) with dilatation of the distal side of the duct, and communication between the cystic lesion and MPD. She underwent distal pancreatectomy under a diagnosis of intraductal papillary-mucinous neoplasm associated with cancer of the body of the pancreas. Clinicopathologic investigation revealed that the diagnosis of the cystic lesion was serous cystadenoma having the communication with MPD. It was also indicated by the histopathologic findings that inflammatory changes of MPD caused by stenosis might contribute to the development of serous cystadenoma.


Sensitivity of a low energy Ge detector system for in vivo monitoring in the framework of ICRP 78 applications.
In in vivo detection of internal contamination by actinides the minimum detectable activities (MDAs) correspond to significant doses, so the sensitivity of the detection system is the key to establishing adequate individual monitoring programmes for internal exposure to these radionuclides. The whole body counting (WBC) faculty at CIEMAT uses a low-energy Ge detector system with different available counting geometries to estimate the retention of actinides in the lungs and evaluate 125I in thyroid and 241Am in bone (skull and knee). A study of the factors and uncertainties involved in estimations of MDA is presented for lung and thyroid monitoring. The dependence of detection limits on counting efficiency in the measurement of low-energy emitters in the lungs has been carefully studied, carrying out a comparison among different biometric equations obtained by ultrasound techniques for estimations of chest wall thickness. Dosimetric implications of the estimated MDAs are taken into account in the framework of ICRP 78 application and considering Spanish regulations. The main interest in lung measurements is for the assessment of occupational exposure. This work confirms the low-energy Ge detector system to be an adequate in vivo technique for the routine monitoring of internal exposure to most insoluble uranium compounds (detection of 3% enriched uranium in lungs), and also to be useful in special monitoring programmes or in the case of incidents when the detection of 241Am is required.


Hemostasis Strategies and Recent Advances in Nanomaterials for Hemostasis.
The development of materials that effectively stop bleeding and prevent wound adhesion is essential in both military and medical fields. However, traditional hemostasis methods, such as cautery, tourniquets, and gauze, have limitations. In recent years, new nanomaterials have gained popularity in medical and health fields due to their unique microstructural advantages. Compared to traditional materials, nanomaterials offer better adhesion, versatility, and improved bioavailability of traditional medicines. Nanomaterials also possess advantages such as a high degree and stability, self-degradation, fewer side effects, and improved wound healing, which make them ideal for the development of new hemostatic materials. Our review provides an overview of the currently used hemostatic strategies and materials, followed by a review of the cutting-edge nanomaterials for hemostasis, including nanoparticles and nanocomposite hydrogels. The paper also briefly describes the challenges faced by the application of nanomaterials for hemostasis and the prospects for their future development.


A revisit to the effects of zinc salt on skin burn wound healing to reflect the risks in current pharmaceutical care.
The lower limit of soluble zinc content that can possibly be applied onto a wounded skin as a healing promoter was not known. This study examined skin wound healing process of rats inflicted by partial thickness thermal burn wound as a function of applied soluble zinc contents (0.1 ml of zinc chloride solution 0.01% (w/w) or 5.0% (w/w)). The size, surface morphology and histological profiles of wound beds of untreated rats and those treated with zinc chloride solutions were characterized. A soluble zinc content as low as 10.5 μg/cm2 of skin negated skin wound healing when compared to the untreated rats. This was alarming as the commercial products currently in the market are formulated with a high level of zinc content. Albeit the zinc salt employed was water-insoluble, a minute fraction of soluble zinc might be available to the treatment sites. This could be partially responsible for the late adverse effects such as pruritis and inflammation reported with calamine/diphenhydramine lotion, medicated shampoo, Olay Complete defense moisturizing lotion and Zineryt® topical solution. The skin irritation was likely a resultant oxidative stress action of soluble zinc, where a small fraction could be adequate to negate the skin homeostasis.[Figure: see text]Key messagesZinc is essentially a cofactor for skin collagen formation.Soluble zinc content as low as 10.5 μg/cm2 of skin irritates skin and negates burn wound healing.Skin irritation of commercial products relates to minute soluble zinc content availability.


High Fat High Sugar Diet Reduces Small Intestinal Secretion by Sex-Dependent Mechanisms.
The goal of this study was to determine the influence of high-fat high-sugar diet (Western diet) on intestinal function and subsequently to determine if there were any beneficial effects of exercise, genistein (a naturally occurring phytoestrogen) or both, on the intestine. We measured transepithelial short circuit current (Isc), across freshly isolated segments of jejunum from male and female C57Bl/6J mice randomly assigned to one of the following groups for the 12-week study duration: high-fat high-sugar diet (HFS), HFS with genistein (Gen), HFS with exercise (Ex), or HFS with both genistein and exercise (Gen+Ex) and compared them to lean controls. Genistein concentration was 600 mg genistein/kg diet. Exercise comprised of moderate intensity treadmill running (150 min per week). At the completion of the study, segments of jejunum were frozen for western blot determination of key proteins involved in secretory and absorptive functions, as well as senescence. Intestinal morphology was assessed. Serum cytokine assays were performed. Basal Isc was significantly decreased (by 70%, P<0.05) in HFS females and males versus leans. This decrease was partially mitigated by exercise in both sexes. In females, the HFS-induced decrease in Isc was attributed to a significant loss of CLC2, NKCC1 and CFTR expression whereas in males this was due to a significant loss of Na/K-ATPase, KCa and NKCC1 expression (indicating sex-dependent mechanisms). Exercise mitigated most of the loss of Isc in both sexes. Our data suggested that A2BR levels were dysregulated in HFS fed mice and that concomitant treatment with Gen or Gen+Ex prevented this disruption in females only. Inflammatory state was associated with body weight changes. Our data suggests that the reduced basal jejunal Isc in HFS mice is attributed to sex-dependent mechanisms and while exercise partially mitigated this, it's mechanism of action was unclear. Improved understanding of Western diet induced intestinal dysfunctions may allow for the development of novel drug targets to treat gastrointestinal disturbances in diabetic obesity.


On Koopman mode decomposition and tensor component analysis.
Koopman mode decomposition and tensor component analysis [also known as CANDECOMP (canonical decomposition)/PARAFAC (parallel factorization)] are two popular approaches of decomposing high dimensional datasets into modes that capture the most relevant features and/or dynamics. Despite their similar goal, the two methods are largely used by different scientific communities and are formulated in distinct mathematical languages. We examine the two together and show that, under certain conditions on the data, the theoretical decomposition given by the tensor component analysis is the same as that given by Koopman mode decomposition. This provides a "bridge" with which the two communities should be able to more effectively communicate. Our work provides new possibilities for algorithmic approaches to Koopman mode decomposition and tensor component analysis and offers a principled way in which to compare the two methods. Additionally, it builds upon a growing body of work showing that dynamical systems theory and Koopman operator theory, in particular, can be useful for problems that have historically made use of optimization theory.