Children's Intake of Food from Non-Fast-Food Outlets and Child-Specific Menus: A Survey of Parents.
Eating out-of-home is associated with higher energy intakes in children. The continued high prevalence of childhood obesity requires a greater understanding of child menu options and eating out frequency to inform appropriate regulatory initiatives. The majority of studies to date have focused on menus from fast-food outlets with few focused on non-fast-food outlets. This study aimed to describe parents' reports of their child(ren)'s (aged up to 6 years) frequency of consuming foods at non-fast-food outlets, observations of child menus at these outlets, and their purchasing behaviours and future preferences regarding these menus; and if their responses were influenced by sociodemographic characteristics. Ninety-five parents completed a 15-item cross-sectional survey. Overall, children from 54% of families consumed food from non-fast-food outlets at least monthly. Of the 87 parents who reported that their child eats at a non-fast-food restaurant, 71 had children who ordered from child menus every time (7%, n = 5), often (29%, n = 22), sometimes (42%, n = 32) or rarely (16%, n = 12), with a further 7% (n = 5) never ordering from these menus. All parents indicated that they would like to see a higher proportion of healthy child menu items than is currently offered. Parents' responses were not influenced by sociodemographic characteristics. Parents' views support implementation of initiatives to increase availability of healthy options on child menus at non-fast-food outlets.


Ultralow-threshold Raman laser using a spherical dielectric microcavity.
The ability to confine and store optical energy in small volumes has implications in fields ranging from cavity quantum electrodynamics to photonics. Of all cavity geometries, micrometre-sized dielectric spherical resonators are the best in terms of their ability to store energy for long periods of time within small volumes. In the sphere, light orbits near the surface, where long confinement times (high Q) effectively wrap a large interaction distance into a tiny volume. This characteristic makes such resonators uniquely suited for studies of nonlinear coupling of light with matter. Early work recognized these attributes through Raman excitation in microdroplets-but microdroplets have not been used in practical applications. Here we demonstrate a micrometre-scale, nonlinear Raman source that has a highly efficient pump-signal conversion (higher than 35%) and pump thresholds nearly 1,000 times lower than shown before. This represents a route to compact, ultralow-threshold sources for numerous wavelength bands that are usually difficult to access. Equally important, this system can provide a compact and simple building block for studying nonlinear optical effects and the quantum aspects of light.


Abnormalities of basal cell keratin in epidermolysis bullosa simplex do not affect the expression patterns of suprabasal keratins and cornified cell envelope proteins.
Basal keratins, suprabasal keratins, filaggrin, and cornified cell envelope (CCE) precursor proteins are expressed during the differentiation of epidermal keratinocytes. These molecules are coordinately expressed during epidermal differentiation. The present study investigated the expression patterns of keratins and CCE precursor proteins in 15 patients with epidermolysis bullosa simplex (EBS), which is caused by mutations in the genes that encode for the basal keratins, keratins 5 and 14. The patterns of expression of keratins 5, 14, 1 and 10, filaggrin, and of the three major CCE precursor proteins, involucrin, loricrin and small proline-rich proteins 1 and 2 (SPRs), were studied immunohistochemically and by electron microscopy. In 14 of the 15 patients with EBS, the distribution pattern of keratins was not altered. In one neonate with EBS, basal cell keratins were expressed in the suprabasal layers. Ultrastructurally, numerous clumped tonofilaments were observed in the basal and suprabasal cells. In all cases, findings were positive for filaggrin in the granular cells, with positivity for involucrin in the upper spinous and granular cells. The upper spinous cells and granular cells were positive for SPRs 1 and 2, and loricrin was expressed in granular cells. Ultrastructurally, no marked abnormality was observed in the suprabasal layers such as a decrease in, or agglutination of, keratin filaments, except in one neonate. A CCE about 15 nm thick was formed normally in the cell membrane of cornified cells. The patterns of distributions of basal cell keratins, suprabasal keratins, filaggrin, and CCE precursor proteins, as well as the ultrastructural findings, resembled those of normal skin. Thus, the abnormality in basal cell keratins in patients with EBS did not appear to alter the patterns of expression of the keratins and CCE precursor proteins.


Short- and long-term results of a programme for the prevention of readmissions and mortality in patients with heart failure: are effects maintained after stopping the programme?
The objective of the study was to evaluate whether improvements obtained during an intervention programme were maintained after the programme was stopped. 153 patients discharged with a diagnosis of heart failure (HF) were randomized to either usual care or an intervention programme, which included patient education, consultation with the cardiologist and monitoring in the Heart Failure Unit. After an average period of 16+/-8 months, the intervention programme was stopped. One year later, all the patients were re-examined to assess HF readmissions, all-cause mortality, quality of life, and prescribed medical treatment. During the 16+/-8-month treatment period, patients in the intervention group had a lower rate of HF readmissions (17% vs. 51%, p<0.01), less all-cause mortality (13% vs. 27%, p=0.03), improvement in quality of life (1.5+/-0.8 vs. 1.9+/-1, p=0.03) and optimisation of medical treatment was achieved. One year after stopping the intervention, there was no difference in HF readmissions (28% vs. 25%, p=0.72), all-cause mortality (14% vs. 17%, p=0.64) and quality of life (1.7+/-0.9 vs. 1.8+/-1, p=0.24) between the groups. Survival and the probability of not being readmitted due to HF were similar in both groups. There was also a reduction in the use of beta-blockers and spironolactone in the intervention group. The positive effects of an intervention programme are clearly reduced when it is stopped, due to less strict control of the patients and a decrease in the use of drugs with proven efficacy in HF.


Systematics, conservation and morphology of the spider genus Tayshaneta (Araneae, Leptonetidae) in Central Texas Caves.
The spider genus Tayshaneta is revised based on results from a three gene phylogenetic analysis (Ledford et al. 2011) and a comprehensive morphological survey using scanning electron (SEM) and compound light microscopy. The morphology and relationships within Tayshaneta are discussed and five species-groups are supported by phylogenetic analyses: the anopica group, the coeca group, the myopica group, the microps group and the sandersi group. Short branch lengths within Tayshaneta contrast sharply with the remaining North American genera and are viewed as evidence for a relatively recent radiation of species. Variation in troglomorphic morphology is discussed and compared to patterns found in other Texas cave invertebrates. Several species previously known as single cave endemics have wider ranges than expected, suggesting that some caves are not isolated habitats but instead form part of interconnected karst networks. Distribution maps are compared with karst faunal regions (KFR's) in Central Texas and the implications for the conservation and recovery of Tayshaneta species are discussed. Ten new species are described: Tayshaneta archambaultisp. n., Tayshaneta emeraldaesp. n., Tayshaneta fawcettisp. n., Tayshaneta grubbsisp. n., Tayshaneta madlasp. n., Tayshaneta oconnoraesp. n., Tayshaneta sandersisp. n., Tayshaneta sprouseisp. n., Tayshaneta vidriosp. n. and Tayshaneta whiteisp. n. The males for three species, Tayshaneta anopica (Gertsch, 1974), Tayshaneta devia (Gertsch, 1974) and Tayshaneta microps (Gertsch, 1974) are described for the first time. Tayshaneta furtiva (Gertsch, 1974) and Tayshaneta uvaldea (Gertsch, 1974) are declared nomina dubia as the female holotypes are not diagnosable and efforts to locate specimens at the type localities were unsuccessful. All Tayshaneta species are thoroughly illustrated, diagnosed and keyed. Distribution maps are also provided highlighting areas of taxonomic ambiguity in need of additional sampling.


Cationic cellulose nanofibers from waste pulp residues and their nitrate, fluoride, sulphate and phosphate adsorption properties.
Cationic cellulose nanofibers (CNF) having 3 different contents of positively charged quaternary ammonium groups have been prepared from waste pulp residues according to a water-based modification method involving first the etherification of the pulp with glycidyltrimethylammonium chloride followed by mechanical disintegration. The cationic nanofibers obtained were observed by scanning electron microscopy and the extent of the reaction was evaluated by conductometric titration, ζ-potential measurements, and thermogravimetric analyses. The cationic CNF had a maximum cationic charge content of 1.2mmolg(-1) and positive ζ-potential at various pH values. Sorption of negatively charged contaminants (fluoride, nitrate, phosphate and sulphate ions) and their selectivity onto cationic CNF have been evaluated. Maximum sorption of ∼0.6mmolg(-1) of these ions by CNF was achieved and selectivity adsorption studies showed that cationic CNF are more selective toward multivalent ions (PO4(3-) and SO4(2-)) than monovalent ions (F(-) and NO3(-)). In addition, we demonstrated that cationic CNF can be manufactured into permeable membranes capable of dynamic nitrate adsorption by utilizing a simple paper-making process.


Neural Correlates of Spatial Navigation in Primate Hippocampus.
The hippocampus has been extensively implicated in spatial navigation in rodents and more recently in bats. Numerous studies have revealed that various kinds of spatial information are encoded across hippocampal regions. In contrast, investigations of spatial behavioral correlates in the primate hippocampus are scarce and have been mostly limited to head-restrained subjects during virtual navigation. However, recent advances made in freely-moving primates suggest marked differences in spatial representations from rodents, albeit some similarities. Here, we review empirical studies examining the neural correlates of spatial navigation in the primate (including human) hippocampus at the levels of local field potentials and single units. The lower frequency theta oscillations are often intermittent. Single neuron responses are highly mixed and task-dependent. We also discuss neuronal selectivity in the eye and head coordinates. Finally, we propose that future studies should focus on investigating both intrinsic and extrinsic population activity and examining spatial coding properties in large-scale hippocampal-neocortical networks across tasks.


Scorpion Stings in Minas Gerais (Brazil): A Monocentric Retrospective Study Evaluating All Envenoming Cases of Local Scorpionism.
We aim to provide better insights into the demographic, epidemiological, and seasonal characteristics of scorpion envenomation reported in the Rio Doce Valley, Brazil. We conducted this monocentric retrospective descriptive study with data on Investigation Forms of Accidents by Venomous Animals, only envenoming cases of scorpion stings, between January 1, 2017 and December 31, 2020, belonging to the compulsory notification system of the Municipal Hospital of Governador Valadares. There were 3032 accidents, and the male-to-female ratio was 1.17:1 (male, 54%; females, 46%). Accidents occurred every month, but there was an increase in June, July, and October to January. In most cases, the time between the scorpion sting and medical care was between 1 and 3 h (n=1304; 43%). The most frequent clinical and systemic manifestations were pain at the bite site (94%) and vagal symptoms (7%). Cases were mild (n=2750, 91%), moderate (n=221, 7%), and severe (n=56, 2%). Children younger than 10 y constituted the most cases, 522 (17%). There was a significant difference between clinical severity and age (P<0.01). Ten patients developed acute pulmonary edema. Two 4-y-old children died. All severely envenomated patients as well as 74% and 2% of mild and moderately envenomated patients, respectively, received specific scorpion antivenoms. Scorpion envenomation is of greater severity in children aged <10 y. The clinical presentation includes mainly local pain associated with vagal symptoms. Accidents occur every month, but there was an increase in June, July, and October to January.


Vascular tortuosity is related to reduced thalamic volume after middle cerebral artery occlusion.
The mechanisms underlying secondary brain injury in remote areas remains unclear. This study aimed to investigate the relationship between vascular tortuosity and thalamic volume. In this study, we retrospectively analyzed sixty-five patients with unilateral middle cerebral artery occlusion (MCAO) who underwent magnetic resonance angiography. We compared the vascular tortuosity in patients with MCAO and controls, and analyzed the relationship between vascular tortuosity and thalamic volume. Compared with controls, the MCAO group exhibited a significantly smaller thalamus volume on the affected side (5874 ± 183 mm3 vs. 5635 ± 383 mm3, p < 0.0001). The vascular tortuosity of the posterior cerebral artery (PCA) was higher in the MCAO group than in the controls (82.8 ± 17.3 vs. 76.7 ± 17.3, p = 0.040). Logistic regression analysis revealed that PCA tortuosity was an independent risk factor for reduced thalamic volume after MCAO (p = 0.034). In the subgroup analysis, only the 4-7-day group was not statistically different in thalamic volume between the MCAO and control groups. In the MCAO group, patients older than 60 years and female patients had a more tortuous PCA. Reduced thalamic volume after MCAO was associated with a tortuous PCA. After MCAO, PCA tortuosity increased more significantly in patients aged >60 years and in female patients.


In vitro and in silico study on the effect of carvedilol and sorafenib alone and in combination on the growth and inflammatory response of melanoma cells.
Melanoma is an aggressive skin cancer. Increasing evidence has shown the role of β-adrenergic receptors in the pathogenesis of melanoma. Carvedilol is a widely used non-selective β-AR antagonist with potential anticancer activity. The purpose of the study was to estimate the influence of carvedilol and sorafenib alone and in combination on the growth and inflammatory response of C32 and A2058 melanoma cells. Furthermore, this study also aimed to predict the probable interaction of carvedilol and sorafenib when administered together. Predictive study of the interaction of carvedilol and sorafenib was performed using the ChemDIS-Mixture system. Carvedilol and sorafenib alone and in combination showed a growth inhibitory effect on cells. The greatest synergistic antiproliferative effect on both cell lines was observed at Car 5 μM combined with Sor 5 μM. Analysis in silico identified diseases, proteins, and metabolic pathways that can be affected by the interaction of carvedilol and sorafenib. The results obtained demonstrated that carvedilol and sorafenib modulated the secretion of IL-8 by IL-1β-stimulated by melanoma cell lines but the use of a combination of both drugs did not intensify the effect. In summary, the results presented indicate that the combination of carvedilol and sorafenib may have a promising anticancer effect on melanoma cells.


Calciphylaxis and metastatic calcification associated with nephrogenic fibrosing dermopathy.
Calciphylaxis and metastatic calcification are known complications of chronic renal failure. Recently, a sclerosing condition of the skin termed nephrogenic fibrosing dermopathy (NFD) has been described in patients with renal disease, many of whom have undergone hemodialysis and/or renal transplantation. To our knowledge, the simultaneous occurrence of both conditions in the same patient, in the same lesion, has not been previously reported. We report the clinical, microscopic, and immunohistochemical features of two patients with chronic renal failure whose lesional skin biopsies showed both subcutaneous calcification and NFD. We consider the possible mechanisms that might explain the coexistence of these two disorders. Both patients presented with erythematous, indurated skin over the lower extremities. Purpuric, reticulated patches, necrosis, or ulceration were not observed. Microscopic examination showed the characteristic changes of NFD involving dermis and subcutaneous septa. In addition, biopsies of both individuals showed subcutaneous calcification, one in a diffuse distribution and the other involving the walls of subcutaneous vessels, as seen in calciphylaxis. Calcification was not suspected clinically in either case. Metastatic calcification or calciphylaxis and NFD can occur simultaneously in patients with chronic renal failure and may be found together in the same lesion. Because subcutaneous calcification may not be suspected clinically in these cases, and in view of the adverse outcomes frequently associated with calciphylaxis, we recommend deep incisional biopsy of patients presenting with the clinical features of NFD. Both the fibrosis and the calcification of chronic renal failure may be related to the activity of transforming growth factor-beta/Smad signaling cascades.


Psychosocial factors and public health: a suitable case for treatment?
Adverse psychosocial exposure or "misery" is associated with physical disease. This association may not be causal. Rather it may reflect issues of reverse causation, reporting bias, and confounding by aspects of the material environment typically associated with misery. A non-causal relation will not form the basis of effective public health interventions. This may be why psychosocial interventions have, so far, showed little effect on objective physical health outcomes. This paper reviews evidence for the "psychosocial hypothesis" and suggests strategies for clarifying these issues. It concludes that, although misery is clearly a bad thing as it erodes people's quality of life, there is little evidence that psychosocial factors cause physical disease. In the absence of better evidence, suggestions that psychosocial interventions are needed to improve population physical health, in both absolute and relative terms, seem premature.


Three dimensional-printed patient-specific cutting guides for femoral varization osteotomy: Do it yourself.
In valgus knees of young patients, opening-wedge distal femoral osteotomy is a valid treatment option for axial corrections. It allows the surgeon to achieve accurate correction, which is directly related to the functional outcome and survivorship of the osteotomy. This study presents a new technique based on three-dimensional (3D)-printed cutting guides for opening-wedge distal femoral osteotomies, in which pre-operative planning and intraoperative executional accuracy play a major role. Pursuing axial correction accuracy, 3D-printed patient-specific positioning guides and wedge spacers were both created and used by the surgeon to implement the femoral osteotomy. The proposed technique was performed in 12 consecutive patients (cases). The results were compared with 20 patients (controls) in which opening-wedge distal femoral osteotomies were performed following the traditional technique. Accuracy of the axial correction, surgical time, fluoroscopic time and costs were measured. More accurate axial correction with reduced surgical time (32min less), intraoperative fluoroscopic images (59 images less) and costs (estimated €412 less) were achieved with the use of the customized guides when compared with the traditional technique. Accurate correction of the axial alignment of the limb is a critical step in survivorship of the osteotomy. Improving the technique to enhance accuracy focused on this issue. The use of patient-customized cutting guides minimised human error; therefore, surgical time was reduced and accurate axial correction was achieved. The surgeon mastered all steps in a do-it-yourself philosophy style.


Evaluation of continuous labelling data by a practical mathematical method with application to a virus-induced sarcoma of the rat.
A simple mathematical function is established which renders the increase of the labelling index during continuous labelling of an exponentially growing tumor. By known values of proliferative fraction, mean cell cycle time and tumor doubling time, the mode and extent of cell loss is determined. Three models for different modes of cell loss are introduced: Model A for cell loss equally affecting proliferative and resting cells; Model B for cell loss predominantly affecting one of the two cell compartments; Model C for cell loss during mitosis. The range of validity of the model function is specified. Experimental data of a Polyoma virus-induced renal sarcoma of the rat provide an example of applicability of the theoretical model.


Navigating immunosuppression in a pandemic: A guide for the dermatologist from the COVID Task Force of the Medical Dermatology Society and Society of Dermatology Hospitalists.
Dermatologists treating immune-mediated skin disease must now contend with the uncertainties associated with immunosuppressive use in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Although the risk of infection with many commonly used immunosuppressive agents remains low, direct data evaluating the safety of such agents in coronavirus disease 2019 (COVID-19) are scarce. This article reviews and offers guidance based on currently available safety data and the most recent COVID-19 outcome data in patients with immune-mediated dermatologic disease. The interdisciplinary panel of experts emphasizes a stepwise, shared decision-making approach in the management of immunosuppressive therapy. The goal of this article is to help providers minimize the risk of disease flares while simultaneously minimizing the risk of iatrogenic harm during an evolving pandemic.


Ipsilateral breast tumor recurrence after breast conservation therapy: outcomes of salvage mastectomy vs. salvage breast-conserving surgery and prognostic factors for salvage breast preservation.
To compare outcomes of salvage mastectomy (SM) and salvage breast-conserving surgery (SBCS) and study the feasibility of SBCS. Of 2,038 patients treated with breast-conserving therapy at Yale-New Haven Hospital before 1999, 166 sustained an ipsilateral breast tumor recurrence (IBTR). Outcomes and prognostic factors of patients treated with SM or SBCS were compared. Patients were considered amenable to SBCS if the recurrence was localized on mammogram and physical examination, and had pathologic size < 3 cm, confined to the biopsy site, without skin or lymphovascular invasion, and with < or = 3 positive nodes. Of the 146 patients definitively managed at IBTR, surgery was SM (n = 116) or SBCS (n = 30). The median length of follow-up after IBTR was 13.8 years. The SM and SBCS cohorts had no significant differences, except at IBTR the SM cohort had a greater tumor size (p = 0.049). Of the SM cohort, 65.5% were considered appropriate for SBCS, and a localized relapse was predicted by estrogen-receptor positive, diploid, and detection of recurrence by mammogram. Multicentric disease correlated with BRCA1/2 mutation, estrogen-receptor negative, lymph node positive at relapse, and detection of recurrence by physical examination. Survival after IBTR was 64.5% at 10 years, with no significant difference between SM (65.7%) and SBCS (58.0%). Only 2 patients in the SBCS cohort subsequently had a second IBTR, and were salvaged with mastectomy. While mastectomy is considered the standard surgical salvage of IBTR, SBCS is feasible and prognostic factors are related to favorable tumor biology and early detection. Patients with BRCA1/2 germline mutations may be less appropriate for SBCS, as multicentric disease was more prevalent. Patients who underwent SBCS had comparable outcomes as those who underwent SM, but remain at continued risk for IBTR. A prospective trial evaluating repeat lumpectomy and partial breast reirradiation is discussed.


The influence of prorenin/(pro)renin receptor on progesterone secretion by the bovine corpus luteum.
The aim of this study was to evaluate the role of prorenin/(pro)renin receptor activation on luteal progesterone (P4) secretion. Our hypothesis was that the nonproteolytic activation of (pro)renin receptor [P(RR)] is part of the regulatory mechanism responsible for corpus luteum (CL) function. In the first three experiments, prorenin was found to stimulate the production of P4, which is not inhibited by an angiotensin receptor antagonist (saralasin), but rather by a renin/prorenin inhibitor (aliskiren), a MAPK1/3 inhibitor (PD325901) or an EGFR inhibitor (AG1478), which are evidence of nonproteolytic activation of prorenin. Moreover, prorenin induced phosphorylation of MAPK1/3 in luteal cells. Following these in vitro experiments, a sequence of in vivo experiments was performed demonstrating that the intrafollicular injection of aliskiren in preovulatory follicles impaired P4 secretion in cows that ovulated. Furthermore, all profibrotic genes studied were present in the CL and TGFB1 and FN1 mRNA were upregulated from day 5-10 post-ovulation. During luteolysis, REN was downregulated at 48 h, whereas TGFB1 and SERPINE1 were dramatically upregulated in luteal tissue at 12 h after PGF. In summary, these data are evidence that nonproteolytic activation of (P)RR is involved in luteal function.


The rodent model of impaired gastric motility induced by allyl isothiocyanate, a pungent ingredient of wasabi, to evaluate therapeutic agents for functional dyspepsia.
Functional dyspepsia (FD) is thought to be mainly based on gastric motility dysfunction and chronic hypersensitivity, yet FD animal models has been reported a few. We studied to establish the mouse model of impaired gastric motility induced by a pungent ingredient of wasabi allyl isothiocyanate (AITC), which is reliable to evaluate prokinetic agents. Male ddY mice were used. Gastric motility was measured by 13C-acetic acid breath test in conscious mice. AITC (80 mM) was given 60 min before the measurement of motility. Prokinetic agents including itopride (30, 100 mg/kg), mosapride (0.1-1 mg/kg), neostigmine (30 μg/kg), acotiamide (10-100 mg/kg), and daikenchuto (100-1000 mg/kg) were given 40 min before the measurement. AITC impaired gastric motility without mucosal damages, which reverted 24 h after AITC treatment. The decreased motility induced by AITC was restored by prokinetic agents such as itopride, mosapride, neostigmine, and acotiamide. In separate experiment, daikenchuto recovered the decreased motility induced by AITC, although daikenchuto had no effect on motility in normal condition. In conclusion, it is considered that the AITC-induced impaired gastric motility mouse model is useful to develop new prokinetic agents for treatment of FD, and to re-evaluate traditional Japanese herbal medicines.


Critical roasting level determines bioactive content and antioxidant activity of Robusta coffee beans.
Indonesian Lampung Robusta coffee green beans were roasted at eight roasting levels (green bean, early yellow, brown, 1st crack done, very light, light, medium, and dark), followed by grinding and brewing. The physical properties of ground coffee and chemical properties of brewed coffee were analyzed. The resulting data were mapped in order to investigate the critical roasting level. It was observed that major alterations for physicochemical properties of coffee happened after "first crack" roasting level (when water activity (Aw) of bean decreased from 0.22 to 0.15). This cracking is defined as popping sound of the bean during roasting. Continuous formation of melanoidins under low Aw (< 0.15) was followed by slow degradation of chlorogenic acid (5-CQA) and total phenolic compounds. Caffeine was stable during roasting, while antioxidant activity slightly decreased. The "first crack" was determined to be the critical roasting level to produce roasted coffee beans containing high concentrations of phenolics.


3D-printed stators & drive caps for magic-angle spinning NMR.
3D printing has evolved into an invaluable tool for rapid and cost-effective production of intricate parts. In this paper we describe 3D printing and other rapid prototyping methods to fabricate 3.2 mm stators and drive caps for use in magic angle spinning (MAS) NMR experiments. These components can be fabricated with the assistance of computer-aided design (CAD) software and at a fraction of the cost of commercial parts. Additionally, we show that the performance of these 3D printed stators and drive caps is comparable to commercially available systems and that they have significant advantages over their machined counterparts.


Synthesis of a novel nitroimidazole-spermidine derivative as a tumor-targeted hypoxia-selective cytotoxin.
A four-step synthesis of (R,S)-N(4)-[3-(2-nitro-1-imidazolyl)-2-hydroxypropyl]-spermidine trihydrochloride (4) is described and the utilization of the polyamine active transport system for the uptake of this compound in cells is demonstrated. Thus, V79 cells pretreated with an inhibitor of spermidine biosynthesis, alpha-difluoromethylornithine (DFMO), are ca. 2-fold more sensitive to 4 under hypoxic conditions, compared to untreated cells. Similarly, radiosensitization of hypoxic V79 cells by 4 is improved in DFMO-pretreated cells.


On an empirical calculus of reinforcement magnitude.
Current available measures of sexual orientation are briefly reviewed. A novel sexual orientation measure is proposed, based on experiments in operant psychology. Previous relevant studies are reviewed, and it is suggested that a deficiency is their reliance on a single response as the dependent variable. The matching law is introduced, and it is argued that this provides a potentially powerful framework within which the relative reinforcement magnitudes of sexual stimuli may be computed, using as the dependent variable the relative rates of two responses. The proposed assessment method provides a means of answering the question "What is the reinforcement magnitude of various classes of erotic stimuli for a given individual?"


Extraction of instantaneous changes in arterial walls with sequential ultrasound images.
Many structural and dynamic properties of the arterial wall, e.g., lumen diameter and wall thickness, can be measured with non-invasive ultrasound techniques. We present a new computerized analysis method for measurement of instantaneous changes in far and near arterial walls in sequential ultrasound images. In this method, two algorithms, i.e., maximum gradient and dynamic programming, were composed and implemented. Reference points and cost function were based on dynamic programming and maximum gradient, respectively. To evaluate this method, B-mode abdominal aorta ultrasound examinations were obtained for ten New Zealand White rabbits. Approximately 70 sequential ultrasound images spanning three cardiac cycles were analyzed from each examination to detect instantaneous changes in the far and near walls and lumen diameter of rabbit abdominal aorta. The maximum, minimum, and mean diameters extracted by the automated method were compared with the same parameters measured by manual tracing. There was no significant differences between the manual and automated methods according to paired t test analysis (p > 0.05). In a verification study, the correlation between the two methods was calculated (R (2) = 0.98, p < 0.05). Agreement between the automated and manual methods as determined by the Bland-Altman approach was excellent. It is concluded that the new computerized analysis method is a reliable technique to assess instantaneous changes in the rabbit arterial wall in sequential B-mode images. The variability between different laboratories will be reduced if the same analysis program is used. By using this method, not only was variation in the results of manual tracing by several observers eliminated, but the duration of image processing was also considerably reduced.


Subacute oral toxicity study of di(2-ethylhexyl)adipate based on the draft protocol for the "Enhanced OECD Test Guideline no. 407".
We performed a 28-day repeated-dose toxicity study of di(2-ethylhexyl)adipate (DEHA) based on the draft protocol of the "Enhanced OECD Test Guideline 407" to investigate whether it has endocrine-mediated properties according to this assay. DEHA was orally administered to SD rats at doses of 0, 40, 200 and 1,000 mg/kg/day for at least 28 days, and disturbance of the estrous cycle and increased ovarian follicle atresia were detected in the 1,000 mg/kg group.


Distinct apoptotic phenotypes induced by radiation and ceramide in both p53-wild-type and p53-mutated lymphoblastoid cells.
The tumour suppressor gene p53 and the intracellular signalling molecule ceramide have both been shown to play crucial roles in the induction of apoptosis by ionising radiation. In this study we examined whether p53 and ceramide are involved in independent signal pathways, inducing different types of apoptosis. TK6 (p53wt/wt) and WTK1 (p53mut/mut) lymphoblastoid cells were treated with ionising radiation or N-acetyl-D-sphingosine (C2-ceramide). Flow cytometry and fluorescence microscopy studies were performed to characterise the time kinetics and morphological features of induced apoptosis. Ceramide- and radiation-induced apoptotic cells display characteristic differences in morphology and DNA staining and ceramide-induced apoptosis is expressed much faster than radiation-induced apoptosis. Radiation-induced apoptosis is p53-dependent and ceramide-induced apoptosis is p53-independent. The p53 pathway and the ceramide pathway are two independent signal pathways leading to distinct types of apoptosis. Since p53 is very often dysfunctional in tumour cells, modifying the ceramide pathway is a promising strategy to increase tumour sensitivity to radiation and other anticancer agents.


Application of multivariate image analysis in modeling (13) C-NMR chemical shifts of mono substituted pyridines.
Multivariate image analysis (MIA) descriptors have been applied to the quantitative structure-property relationship (QSPR) study of (13) C-NMR chemical shifts of 2-mono substituted pyridines. In this method, descriptors are generated from pixels of images and are analyzed with different multivariate methods. Correlation ranking-principal component regression and correlation ranking-principal component-artificial neural networks were applied in constructing predictor models. In this article, the role of weight update function in artificial neural networks was investigated too. Obtained results using the correlation ranking-principal component-artificial neural network method showed high performance for predicting of (13) C-NMR chemical shifts of pyridine derivatives. Also, these results indicated that MIA descriptors may be useful to predict (13) C-NMR chemical shifts. Finally, The MIA-QSPR approach coupled to artificial neural networks revealed that the predictive ability of MIA descriptors is comparable or even superior for the pyridine derivatives when compared with the ChemDraw program or gauge included atomic orbital procedure for (13) C chemical shifts calculations.


Transient ischaemia affects plasma membrane glutamate transporter, not vesicular glutamate transporter, expressions in the gerbil hippocampus.
In the present study, we investigated expressions of vesicular glutamate transporter (VGLUT) and of the plasma membrane glutamate transporters [glutamate transporter 1 (GLT-1), glutamate/aspartate transporter (GLAST) and excitatory amino acid carrier 1 (EAAC-1)] in the gerbil hippocampus following transient ischaemia. The expressional levels and distribution patterns of VGLUT immunoreactivities were unaltered until 3 days after ischaemic-insults. However, VGLUT-2 immunoreactivity in the CA1 region was reduced at 4 days after ischaemia due to delayed neuronal death. In addition, both GLT-1 and GLAST immunoreactivities in the CA1 region were enhanced at 30 min - 12 h after ischaemia-reperfusion and their expression began to reduce at 24 h after ischaemia-reperfusion. In contrast, EAAC-1 immunoreactivity was transiently reduced in the CA1 region at 30 min after ischaemia, re-enhanced at 3-12 h after ischaemia, and re-reduced at 24 h after ischaemia. These findings suggest that malfunctions of plasma membrane glutamate transporters, not of VGLUT, may play an important role in the elevation of extracellular glutamate concentration following ischaemic insults.


Mycetoma caused by Exophiala jeanselmei. Report of a case successfully treated with itraconazole and review of the literature.
We report a case of black grain mycetoma in a 74-years-old man who presented with a 50-yr. history of sinus-tract formation in the right foot. This is the first case of an Exophiala jeanselmeimycetoma successfully treated with itraconazole. In addition a review of the literature on this subject was done.


Analysis of Comorbidities, Clinical Outcomes, and Parathyroidectomy in Adults With Primary Hyperparathyroidism.
Patients with primary hyperparathyroidism (pHPT) appear to have an increased risk of fractures and other comorbidities, such as cardiovascular disease, although results from previous studies have been inconsistent. Evidence of the association of parathyroidectomy (PTX) with these outcomes is also limited because of the lack of large well-controlled trials. To investigate whether untreated pHPT was associated with an increased risk of incident fractures and cardiovascular events (CVEs) and whether PTX was associated with a reduced risk of these outcomes. This cohort study included all patients who were diagnosed with pHPT at hospitals in Sweden between July 1, 2006, and December 31, 2017. Each patient was matched with 10 control individuals from the general population by sex, birth year, and county of residence. The patients were followed up until December 31, 2017. Data analyses were performed from October 2021 to April 2022. The primary outcomes were fractures, CVEs, and death. Cumulative incidence of events was estimated using the 1-minus Kaplan-Meier estimator of corresponding survival function. Cox proportional hazards regression models were used to calculate hazard ratios (HRs). A total of 16 374 patients with pHPT were identified (mean [SD] age, 67.5 [12.9] years; 12 806 women [78.2%]), with 163 740 control individuals. The follow-up time was 42 310 person-years for the pHPT group and 803 522 person-years for the control group. Compared with the control group, the pHPT group had a higher risk of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), CVEs (unadjusted HR, 1.45; 95% CI, 1.34-1.57), and death (unadjusted HR, 1.72; 95% CI, 1.65-1.80). In a time-dependent Poisson regression model, PTX was associated with a reduced risk of any fracture (HR, 0.83; 95% CI, 0.75-0.93), hip fracture (HR, 0.78; 95% CI, 0.61-0.98), CVEs (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65). Results of this study suggest that pHPT is associated with increased risk of fractures, CVEs, and death, highlighting the importance of identifying patients with this condition to prevent serious unfavorable outcomes. The reduced risk of these outcomes associated with PTX suggests a clinical benefit of surgery.


The isolation of cDNA clones for human apolipoprotein E and the detection of apoE RNA in hepatic and extra-hepatic tissues.
We have isolated cDNA clones coding for apolipoprotein E (apoE) from a cDNA library prepared from adult human liver mRNA. Mixtures of 128 different oligonucleotides, 17 residues long were synthesised to be complementary to regions of the mRNA corresponding to amino acids 1-6 and 151-156. Five independent apoE clones were selected by direct screening of 5000 recombinants with the two oligonucleotide mixtures. Two overlapping clones contain the 3'-untranslated sequence, the entire coding sequence and an additional 30 bases 5' to the amino terminus of the mature protein. The DNA sequence has been determined spanning the known sites of amino acid substitutions which account for the observed protein polymorphism of apoE. Using the clones as probes in Northern blot analysis of total human liver and kidney RNAs and leucocyte poly(A)+ RNA we have detected a single species of mRNA in liver and kidney of 1.2 kb and two larger species in leucocyte RNA. The level of expression of the mRNA in kidney is approximately 10% of that in liver while the level of apoE RNA sequences in the leucocytes is less than 1% of that in the liver.


Efficacy and safety of roflumilast in patients with stable chronic obstructive pulmonary disease: a meta-analysis.
Currently, several large studies showed that roflumilast has been demonstrated efficacy during treatment chronic obstructive pulmonary disease (COPD) patients, but also caused some side effects. To assess the efficacy and safety of roflumilast in COPD patients. A computerized search through electronic databases included PubMed, EMBASE, CINAHL, the Cochrane clinical trials database, Physiotherapy Evidence Database and ClinicalTrials.gov was performed to identify randomized controlled trials. The primary outcomes were trough forced expiratory volume in 1 s (FEV(1)) (reported pre-bronchodilator values) and exacerbation rate. Secondary outcomes included other spirometric parameters, health-related quality of life, the overall mortality rate and adverse events. Weighted mean differences (WMDs), relative risks (RRs) and 95% confidence intervals (CIs) were calculated and pooled using a random effects model. Eleven trials involving 9675 patients met the inclusion criteria. Roflumilast significantly reduced the mean exacerbation rate (mild, moderate or severe) (WMD = -0.23; 95% CI = -0.33 to -0.13; p < 0.00001) and improved trough FEV(1) (WMD = 53.52 ml; 95% CI = 42.49 to 64.55; p < 0.00001), and other post-bronchodilator spirometric parameters (e.g., forced vital capacity, etc.). Roflumilast did not improve St George's Respiratory Questionnaire total score (WMD = -0.70 units; 95% CI = -2.65 to 1.26; p = 0.49) and decrease the overall mortality rate (RR = 0.90; 95% CI = 0.63 to 1.29; p = 0.56). Roflumilast increased some adverse events including diarrhea, headache, nausea, weight loss, and insomnia. Roflumilast significantly reduces the mean exacerbation rate in COPD patients. Although there are insufficient clinical evidence on other clinical endpoints and high risk of some adverse events, roflumilast therapy may benefit COPD patients. Further studies are needed to pay more attention to the long-term efficacy and safety of roflumilast.


[A German version of the Palliative Performance Scale (PPS) as a supportive structure to assess survival in palliative patients].
The original English version of the palliative performance scale (PPS) has been used for two decades to describe the functional status of palliative patients. Based on clinical parameters PPS helps to estimate the survival time of palliative patients: the higher the functional status the longer the survival. This is interesting for patients, their family caregivers and health care professionals in order to plan for care. Until now there has not been published an official German version of the PPS.The functional status via a German version of the PPS of 394 patients of a palliative consulting team and their survival times were analyzed. Kaplan-Meier-curves were drawn and tested for differences. The hypothesis was tested if functional status using the German version of the PPS and survival are correlated. In this population differences in survival could clearly be shown for any category of PPS.This German version of the PPS is a useful and possible tool to estimate survival time of palliative patients using just clinical information.


Identification of amino acids in the HA of H3 influenza viruses that determine infectivity levels in primary swine respiratory epithelial cells.
In the late 1990s, triple reassortant H3N2 influenza A viruses emerged and spread widely within the swine population of the United States. We have shown previously that an isolate representative of this lineage of viruses, A/Swine/Minnesota/593/99 (Sw/MN), has higher infectivity and accelerated replication kinetics in pigs, compared to a human-lineage H3N2 virus isolated from a pig during the same time period, A/Swine/Ontario/00130/97 (Sw/ONT [Landolt, G.A., Karasin, A.I., Phillips, L., Olsen, C.W., 2003. Comparison of the pathogenesis of two genetically different H3N2 influenza A viruses in pigs. J. Clin. Microbiol. 41, 1936-1941]). Additional in vivo experiments using reverse genetics-generated reassortant viruses demonstrated that these phenotypes are dependent upon the HA and/or NA genes (Landolt, G.A., Karasin, A.I., Schutten, M.M., Olsen, C.W., 2006. Restricted infectivity of a human-lineage H3N2 influenza A virus in pigs is hemagglutinin and neuraminidase gene dependent. J. Clin. Microbiol. 44, 297-301). To further study the infectivity of influenza viruses for pigs, we developed a primary swine respiratory epithelial cell (SREC) culture model. In SRECs, Sw/MN infects a significantly higher number of cells compared to Sw/ONT. Using reverse genetics-generated Sw/MN x Sw/ONT reassortant viruses we demonstrate that the infectivity phenotypes of these viruses in SRECs are strongly dependent upon the HA gene. Using chimeras and point directed mutations within the HA genes, we have identified amino acids that, either alone or in combination with other amino acids, impact infectivity. In particular, amino acid 138 is the dominant factor in determining infectivity levels in SRECs.


Estimating utility data from clinical indicators for patients with stable angina.
This study estimated a model from which data routinely collected in clinical trials of angina patients can be mapped to a utility scale and used to estimate quality-adjusted life years (QALYs). Patients with stable angina attending four cardiac out-patient clinics in the UK were included in the study. Data collected included information on patients' health-related quality of life (HRQL) using the EQ-5D, and severity of angina symptoms using two cardiac-specific measures [Breathlessness Grade and Canadian Cardiovascular Society (CCS) classification of angina]. Regression analysis was used to predict EQ-5D index values from the data. Data were obtained from 510 patients. For CCS grades, mean EQ-5D scores ranged from 0.36 (95% confidence interval 0.25-0.48) for grade 4 to 0.81 (0.77-0.85) for grade 0, and for breathlessness grades, EQ-5D scores ranged from 0.31 (0.06-0.55) for grade 0 to 0.84 (0.79-0.88) for grade 5. The final model used data on CCS grades, breathlessness grades, and patients' current medications to predict EQ-5D scores. The model had an R2 value of 0.37, and predictions for less severe angina were considered more reliable than the estimates for severe angina. In the absence of utility data collected as part of a clinical trial it is possible to map HRQL utility data from samples of patients with similar characteristics to those in the original trial. The uncertainty surrounding the estimates should be considered when using the results to estimate QALYs for purposes of economic evaluation.


Intravenous nutritional support in pregnancy. Experience following biliopancreatic diversion.
11 pregnant women with protein malnutrition following biliopancreatic diversion for obesity were supported by parenteral nutrition (PN). In 2 cases high concentration glucose, lipid emulsions and standard aminoacid mixtures were infused via a central venous catheter; in the other subjects, because oral intake was normal or increased, only aminoacids with or without lipids were administered through a peripheral vein. PN promoted foetal growth and was very well tolerated and totally safe both for mother and infant.


Psychiatric Morbidity Among a School Sample of Syrian Refugee Children in Turkey: A Cross-Sectional, Semistructured, Standardized Interview-Based Study.
Now in its eighth year, the Syrian civil war has caused displacement of more than half the population before the war and is viewed as the single largest contributing factor to many of the worsening global trends of children living in areas affected by conflict.1.


A missense mutation in myelin oligodendrocyte glycoprotein as a cause of familial narcolepsy with cataplexy.
Narcolepsy is a rare sleep disorder characterized by excessive daytime sleepiness and cataplexy. Familial narcolepsy accounts for less than 10% of all narcolepsy cases. However, documented multiplex families are very rare and causative mutations have not been identified to date. To identify a causative mutation in familial narcolepsy, we performed linkage analysis in the largest ever reported family, which has 12 affected members, and sequenced coding regions of the genome (exome sequencing) of three affected members with narcolepsy and cataplexy. We successfully mapped a candidate locus on chromosomal region 6p22.1 (LOD score ¼ 3.85) by linkage analysis. Exome sequencing identified a missense mutation in the second exon of MOG within the linkage region. A c.398C>G mutation was present in all affected family members but absent in unaffected members and 775 unrelated control subjects. Transient expression of mutant myelin oligodendrocyte glycoprotein (MOG) in mouse oligodendrocytes showed abnormal subcellular localization, suggesting an altered function of the mutant MOG. MOG has recently been linked to various neuropsychiatric disorders and is considered as a key autoantigen in multiple sclerosis and in its animal model, experimental autoimmune encephalitis. Our finding of a pathogenic MOG mutation highlights a major role for myelin and oligodendrocytes in narcolepsy and further emphasizes glial involvement in neurodegeneration and neurobehavioral disorders. [corrected].


Hurricane impacts on US forest carbon sequestration.
Recent focus has been given to US forests as a sink for increases in atmospheric carbon dioxide. Current estimates of US forest carbon sequestration average approximately 20 Tg (i.e. 10(12) g) year. However, predictions of forest carbon sequestration often do not include the influence of hurricanes on forest carbon storage. Intense hurricanes occur two out of three years across the eastern US. A single storm can convert the equivalent of 10% of the total annual carbon sequestrated by US forests into dead and downed biomass. Given that forests require at least 15 years to recover from a severe storm, a large amount of forest carbon is lost either directly (through biomass destruction) or indirectly (through lost carbon sequestration capacity) due to hurricanes. Only 15% of the total carbon in destroyed timber is salvaged following a major hurricane. The remainder of the carbon is left to decompose and eventually return to the atmosphere. Short-term increases in forest productivity due to increased nutrient inputs from detritus are not fully compensated by reduced stem stocking, and the recovery time needed to recover leaf area. Therefore, hurricanes are a significant factor in reducing short-term carbon storage in US forests.


Maternal care in rural China: a case study from Anhui province.
Studies on prenatal care in China have focused on the timing and frequency of prenatal care and relatively little information can be found on how maternal care has been organized and funded or on the actual content of the visits, especially in the less developed rural areas. This study explored maternal care in a rural county from Anhui province in terms of care organization, provision and utilization. A total of 699 mothers of infants under one year of age were interviewed with structured questionnaires; the county health bureau officials and managers of township hospitals (n = 10) and county level hospitals (n = 2) were interviewed; the process of the maternal care services was observed by the researchers. In addition, statistics from the local government were used. The county level hospitals were well staffed and equipped and served as a referral centre for women with a high-risk pregnancy. Township hospitals had, on average, 1.7 midwives serving an average population of 15,000 people. Only 10-20% of the current costs in county level hospitals and township hospitals were funded by the local government, and women paid for delivery care. There was no systematic organized prenatal care and referrals were not mandatory. About half of the women had their first prenatal visit before the 13th gestational week, 36% had fewer than 5 prenatal visits, and about 9% had no prenatal visits. A major reason for not having prenatal care visits was that women considered it unnecessary. Most women (87%) gave birth in public health facilities, and the rest in a private clinic or at home. A total of 8% of births were delivered by caesarean section. Very few women had any postnatal visits. About half of the women received the recommended number of prenatal blood pressure and haemoglobin measurements. Delivery care was better provided than both prenatal and postnatal care in the study area. Reliance on user fees gave the hospitals an incentive to put more emphasis on revenue generating activities such as delivery care instead of prenatal and postnatal care.


Influenza in patients with cancer after 2009 pandemic AH1N1: An 8-year follow-up study in Mexico.
Immunosupressed patients are at high risk of influenza-related complications. Influenza AH1N1 has been hypothesized to induce worse outcomes in patients with malignancies, but after the A(H1N1)pdm09 few publications have analyzed the presentation and complications related to influenza afterward. We aimed to describe the characteristics, risk factors, and outcomes of influenza in an oncologic center after the 2009 pandemic and to compare our case distribution to the National community acquired influenza databases in Mexico and the United States. We reviewed the cases of confirmed influenza in patients with cancer from an oncological center in Mexico from April 2009 to April 2017. Data on severity and influenza type, malignancy, comorbidities, and outcomes were recorded. We correlated data between the Centers for Disease Control and Prevention (CDC) in the United States and SISVEFLU (Influenza Surveillance Program) in Mexico. One hundred eighty-eight patients were included; 75 (39.9%) had a solid neoplasm and 113 (60.1%) had hematologic malignancies. AH1N1 was the most frequent influenza type (54.2%). Patients with hematologic malignancies had more pneumonia (55% vs 25%, P < .001), needed more hospitalizations (75% vs 39% P < .001), had higher all-cause mortality at 30 days (20% vs 9% P = .048) and influenza-associated mortality (17% vs 7% P = .041). Thirty (16%) patients died within 30 days, and 24 (12.7%) were related to influenza. Influenza type was not associated with worse outcomes. Yearly occurrence of influenza reported by the CDC and SISVEFLU showed a significant correlation (ρ = 0.823, P = .006). AH1N1 was the dominant serotype. Patients with hematologic malignancies had more severe influenza and presented worse outcomes. Annual SISVEFLU and CDC surveillance information showed a similar distribution of cases along time but influenza serotypes did not match for all seasons.


Dengue NS1 induces phospholipase A2 enzyme activity, prostaglandins, and inflammatory cytokines in monocytes.
Dengue virus (DENV) NS1 is a non-structural secretory protein associated with severe disease and known to cause vascular leak leading to dengue haemorrhagic fever (DHF). As phospholipases A2 (PLA2) enzymes, platelet activating factor, and leukotrienes are elevated in dengue, we sought to investigate whether NS1 potentially contributes to disease pathogenesis by inducing PLA2s. THP-1 cells and primary human monocytes of healthy adults (n = 6) were co-cultured with DENV1 NS1, LPS and media alone. The latter two were used as positive and negative controls. The cell culture supernatants and lysates were harvested at 12 and 24 h and the activity of secretory and cytoplasmic PLA2, prostaglandins (PGE2 and PGD2) were measured by ELISA and cytokines levels were measured using a magnetic Luminex assay. Expression of PLA2G4A, PLA2G2A, PLA2G5, PLA2G10, PLA2G7, GAPDH, NLRP3 and DDX58 genes were assessed using quantitative RT-PCR. cPLA2 (p = 0.005), sPLA2 (p = 0.04), PGE2 metabolite (p = 0.02) and PGD2 metabolite (p = 0.04) levels were significantly higher at 12 h in monocytes co-cultured with NS1. Levels of IP-10 (p = 0.005) and IL-10 (p = 0.009) was significantly higher at 24 h, whereas IFNα level was significantly higher (p = 0.013) only at 12 h. IL-1β (p = 0.028 and p = 0.031) and TNFα (p = 0.007 and p = 0.011) showed significantly higher levels at both time points. At 12 h significant upregulation of PLA2G4A (p < 0.0001) was seen, whereas PLA2G7 (p = <0.0001), NLRP3 (p = 0.0009) and DDX58 (p = 0.0056) were significantly downregulated. This pattern changed at 24 h with PLA2G4A (p = 0.0069) showing a marked downregulation and PLA2G7, DDX58 and NLRP3 showing an upregulation, although not significant. Dengue NS1 induces the production of PLA2 enzymes, prostaglandins and inflammatory cytokines from primary human monocytes, which could play a role in vascular leak in dengue.


The protective effects of EGCG was associated with HO-1 active and microglia pyroptosis inhibition in experimental intracerebral hemorrhage.
Intracerebral hemorrhage (ICH), which has high mortality and disability rate is associated with microglial pyroptosis and neuroinflammation, and the effective treatment methods are limited Epigallocatechin-3-gallate (EGCG) has been found to play a cytoprotective role by regulating the anti-inflammatory response to pyroptosis in other systemic diseases. However, the role of EGCG in microglial pyroptosis and neuroinflammation after ICH remains unclear. In this study, we investigated the effects of EGCG pretreatment on neuroinflammation-mediated neuronal pyroptosis and the underlying neuroprotective mechanisms in experimental ICH. EGCG pretreatment was found to remarkably improved neurobehavioral performance, and decreased the hematoma volume and cerebral edema in mice. We found that EGCG pretreatment attenuated the release of hemin-induced inflammatory cytokines (IL-1β, IL-18, and TNF-α). EGCG significantly upregulated the expression of heme oxygenase-1 (HO-1), and downregulated the levels of pyroptotic molecules and inflammatory cytokines including Caspase-1, GSDMD, NLRP3, mature IL-1β, and IL-18. EGCG pretreatment also decreased the number of Caspase-1-positive microglia and GSDMD along with NLRP3-positive microglia after ICH. Conversely, an HO-1-specific inhibitor (ZnPP), significantly inhibited the anti-pyroptosis and anti-neuroinflammation effects of EGCG. Therefore, EGCG pretreatment alleviated microglial pyroptosis and neuroinflammation, at least in part through the Caspase-1/GSDMD/NLRP3 pathway by upregulating HO-1 expression after ICH. In addition, EGCG pretreatment promoted the polarization of microglia from the M1 phenotype to M2 phenotype after ICH. The results suggest that EGCG is a potential agent to attenuate neuroinflammation via its anti-pyroptosis effect after ICH.


Biochemical thresholds for pathological presentation of ATP synthase deficiencies.
Mitochondrial ATP synthase is responsible for production of the majority of cellular ATP. Disorders of ATP synthase in humans can be caused by numerous mutations in both structural subunits and specific assembly factors. They are associated with variable pathogenicity and clinical phenotypes ranging from mild to the most severe mitochondrial diseases. To shed light on primary/pivotal functional consequences of ATP synthase deficiency, we explored human HEK 293 cells with a varying content of fully assembled ATP synthase, selectively downregulated to 15-80% of controls by the knockdown of F1 subunits γ, δ and ε. Examination of cellular respiration and glycolytic flux revealed that enhanced glycolysis compensates for insufficient mitochondrial ATP production while reduced dissipation of mitochondrial membrane potential leads to elevated ROS production. Both insufficient energy provision and increased oxidative stress contribute to the resulting pathological phenotype. The threshold for manifestation of the ATP synthase defect and subsequent metabolic remodelling equals to 10-30% of residual ATP synthase activity. The metabolic adaptations are not able to sustain proliferation in a galactose medium, although sufficient under glucose-rich conditions. As metabolic alterations occur when the content of ATP synthase drops below 30%, some milder ATP synthase defects may not necessarily manifest with a mitochondrial disease phenotype, as long as the threshold level is not exceeded.


Retroperitoneal cystic schwannoma mimics liquefied hematoma.
Schwannomas are nerve sheath tumors that seldom occur in the retroperitoneal region. Herein, we describe an incidentally detected retroperitoneal schwannoma that mimicked liquefied hematoma on computed tomography. A 61-year-old man was admitted to the emergency department with chest pain caused by a fall at a construction site. Chest computed tomography incidentally revealed a retroperitoneal cystic mass measuring 10 cm, in addition to multiple rib fractures and hemopneumothorax. The patient frequently consumed alcohol and had a history of repeated trauma; therefore, we considered the following 2 conditions: retroperitoneal cystic tumor and liquefied hematoma. He underwent complete surgical excision, and a histopathological examination confirmed the mass as a schwannoma. Experience and knowledge regarding the computed tomography findings of retroperitoneal cystic schwannoma are useful for the differential diagnosis of infrequent retroperitoneal tumors.


Afferent receptors in the airways and cough.
The roles of airway rapidly adapting receptors (RARs) and of C-fibre receptors in the induction of cough are reviewed. It is concluded that, while there is substantial evidence that irritant receptors in the laryngeal wall and RARs in the tracheobronchial mucosa can cause cough, the evidence for such a similar direct role for C-fibre receptors is tenuous. Indeed there is accumulating evidence that the C-fibre receptors may cause apnoea and rapid shallow breathing, and also reflexly inhibit cough. However the C-fibre receptors may release tachykinins when stimulated, and these in turn may cause plasma extravasation from mucosal postcapillary venules. RARs are excited by increases in interstitial liquid volume, so C-fibre receptors may indirectly enhance cough via the RARs.


Total versus subtotal thyroidectomy in the management of multinodular goiter.
The choice between subtotal and total thyroidectomy for multinodular goiter is controversial. Subtotal and total thyroidectomy have been respectively performed in 108 and 451 euthyroid patients with multinodular goiter. After subtotal and total thyroidectomy, transient recurrent laryngeal nerve (RLN) palsy occurred in 1 patient (0.9%) and 3 (0.6%), transient asymptomatic hypoparathyroidism in 27 (25%) and 131 (29%), and transient symptomatic hypoparathyroidism in 2 (1.8%) and 13 (2.9%), respectively (P = NS). After subtotal thyroidectomy, recurrence occurred in 27 patients (26%) Re-operation in 14 patients resulted in transient RLN palsy in 2 patients (14%), transient asymptomatic hypoparathyroidism in 6 (43 %) and transient symptomatic hypoparathyroidism in 2 (14%). The failure to demonstrate any 'hormonal advantage' in preserving thyroid tissue by subtotal thyroidectomy, and the low morbidity rate and no need for re-operation after primary total thyroidectomy, make the latter the procedure of choice for the management of non-toxic multinodular goiter.


Diagnostic performance of direct latex agglutination, post-enrichment latex agglutination and culture methods in screening of group B streptococci in late pregnancy: a comparative study.
Group B streptococcus (GBS) is one of the main causes of neonatal sepsis. Evaluation of the diagnostic performance of direct latex agglutination test (DLA), post-enrichment latex agglutination (LA) test, and direct culture on chromogenic media in rapid identification of GBS carrier in pregnant women in comparison with the conventional post-enrichment CDC-recommended culture method and further to estimate GBS carriage prevalence and its antimicrobial susceptibility. Two hundred pregnant women at gestational age (35-37 weeks) were enrolled. Three low vaginal swabs were obtained from each participant. One swab was directly inoculated into Strep B Select (SBS) agar. The second swab was inoculated in enrichment Lim broth for immunological antigen detection by post-enrichment latex agglutination (5 h and 24 h) and subculture for bacteriological detection. The third swab was used for immunological detection of GBS antigen by direct latex agglutination. The isolated GBS was subjected to antimicrobial susceptibility testing. Among 200 pregnant women, 47 (23.5%) were GBS carriers. Considering post-enrichment subculture on SBS medium as a gold standard, the sensitivities for post-enrichment 5 h and 24 h LA were 66% and 95.7%, respectively. However, direct cultivation of the vaginal swabs on SBS medium and DLA recorded 83% and 4.3%, respectively, for sensitivity. All GBS isolates (100%) were sensitive to penicillin G, ampicillin, ceftriaxone, and vancomycin. In contrast, 21.3% and 12.8% of isolated GBS were resistant to erythromycin and clindamycin, respectively. Group B streptococcal antigen detection by latex agglutination after 5 h enrichment is a reliable, easy, and relatively rapid method for screening of GBS carriage in pregnant woman not in labor. Latex agglutination after 18-24 h enrichment can be used alternative to standard subculture method for screening GBS carriage.


Impact of illegal mining activities on forest ecosystem services: local communities' attitudes and willingness to participate in restoration activities in Ghana.
Understanding local communities' willingness to participate in environmental restoration activities can help assess the level of volunteerism that can be expected for restoration projects. This study ascertained local communities' perception of the importance of non-market ecosystem services, the impact of illegal mining on ecosystem services, and their likeliness to participate in restoration of degraded lands resulting from illegal mining. Fifty respondents each were purposefully selected from three mining communities (Ntakam, Asawinso No.1 and Nkatieso) in a survey. Analysis of variance (ANOVA) tests results indicated there were no difference in views of respondents regarding the importance of forest for various non-market services. Illegal mining activities were identified as the cause of environmental problems such as water pollution, deforestation, poor soil fertility and limited access to land for agriculture productivity. Majority of respondents across the three communities indicated that forest is very important for non-market environmental services. Logistic regression results indicated that factors that affect likeliness to participate in restoration financing included income, embracing non-market ecosystem services as important, confidence in PES schemes and positive value motivation for restoration (altruistic, use and bequest values).


Autonomic nervous system control of multiple myeloma.
The autonomic nervous system (ANS), which consists of antagonistic sympathetic (adrenergic) and parasympathetic (cholinergic) arms, has emerged as an important regulator of neoplastic development, yet little is known about its role in multiple myeloma (MM). Clinical findings that anti-adrenergic β-blocker intake reduces risk of disease-specific death and overall mortality in patients with MM have indicated that adrenergic input may worsen myeloma outcome. However, preclinical studies using β-adrenergic receptor agonists or antagonists produced controversial results as to whether sympathetic pathways promote or inhibit myeloma. Retrospective outcome data demonstrating that high message levels of cholinergic receptor genes predict inferior survival in the Multiple Myeloma Research Foundation CoMMpass trial suggest that parasympathetic input may drive myeloma progression in a subset of patients. Here we review the ill-defined role of the ANS in MM, put myeloma in the context of other cancers, and discuss knowledge gaps that may afford exciting research opportunities going forward.


Embryonic stress hypothesis of teratogenesis.
Cells and tissues of essentially all eukaryotes respond uniformly to a variety of stressful situations. Immediately following the onset of several types of environmental insult (e.g., hyperthermia), genes for the so-called heat-shock proteins become unusually active; simultaneously, other genetic loci that were engaged in transcription at the onset of the insult become relatively less active. The biologic significance of the heat-shock response is unknown, as is its role, if any, in maintaining human health. In fact, the heat-shock response seems not to have been invoked previously to explain any aspect of human health or disease. Herein, the proposal is made that induction of the heat-shock response in the mammalian embryo during the critical period of organogenesis can alter the established program of activation and inactivation of genetic loci essential for normal intrauterine development, the result being anatomic malformation. By this hypothesis, induction of the heat-shock response provides a common pathway by which diverse environmental agents can result in any of a variety of developmental abnormalities, the precise period during gestation when the response is induced determining the nature of the abnormalities.


Bioelectric Potential in Next-Generation Organoids: Electrical Stimulation to Enhance 3D Structures of the Central Nervous System.
Pluripotent stem cell-derived organoid models of the central nervous system represent one of the most exciting areas in in vitro tissue engineering. Classically, organoids of the brain, retina and spinal cord have been generated via recapitulation of in vivo developmental cues, including biochemical and biomechanical. However, a lesser studied cue, bioelectricity, has been shown to regulate central nervous system development and function. In particular, electrical stimulation of neural cells has generated some important phenotypes relating to development and differentiation. Emerging techniques in bioengineering and biomaterials utilise electrical stimulation using conductive polymers. However, state-of-the-art pluripotent stem cell technology has not yet merged with this exciting area of bioelectricity. Here, we discuss recent findings in the field of bioelectricity relating to the central nervous system, possible mechanisms, and how electrical stimulation may be utilised as a novel technique to engineer "next-generation" organoids.


A single serine mutation on the nuclear localization signal of hepatitis B virus core protein abolishes the inhibition of nuclear transport by surface proteins.
The nuclear localization signal of hepatitis B virus core protein contained three SPRRR motifs. Substitution of a single serine residue on the third SPRRR motif enhanced significantly the nuclear localization of core protein. By performing immunofluorescence staining assays and subcellular fractionation experiments, it was demonstrated that although nuclear transport of the wild type core protein was markedly suppressed by co-expression of hepatitis B virus surface proteins, nuclear transport of this serine mutant protein was not affected. These results indicated that the serine residue in the SPRRR motifs played an important role in regulating the nuclear transport of core protein and the interaction between core and surface proteins.


Gene expression of Toll-like receptors, cytokines and a nuclear factor and cytokine secretion in DH82 canine macrophage cells infected with Brucella canis.
Canine brucellosis caused by Brucella canis infection occurs mainly in dogs, and is a zoonotic disease that also has the possibility of infection in humans. Many studies have been conducted to understand the immunopathological mechanism of B. canis infection. However, the precise immune mechanism remains to be elucidated because compared to other Brucella spp., B. canis has different immune evasion mechanisms. In this study, gene expression levels of Toll-like receptors (TLRs) and TLR-associated molecules and cytokine production were analyzed to figure out the roles of immune-related host factors in B. canis infection. Time-dependent gene expression of TLRs (1-10) and TLR-related molecules (TNF-α, IL-5, IL-23, CCL4, CD40 and NFκ-B) and release of Th1, Th2 and Th17-related cytokines (IFN-γ, IL-1β, IL-4, IL-6, IL-10 and IL-17A) were investigated in DH82 canine macrophages infected with B. canis. Time-dependent induction of TLRs 3, 7 and 8 was observed, and TLR 7 had the highest expression level (p <0.05). The expression levels of all TLR-related genes were significantly increased after infection. In particular, the expression of the CCL4 and IL-23 genes was highly induced. The amounts of IL-1β, IL-6 and IL-10 were significantly increased by B. canis infection, but the amounts of IL-4 and IL-17A were not. The production of IL-1β and IL-6 was the highest at 24 hr after B. canis infection (p <0.05). This study demonstrates that TLRs 3, 7 and 8 are prominent sites of to immune response induction with the production of related cytokines and a nuclear factor in DH82 cells infected with B. canis. These results suggest a sequential immune mechanism of B. canis infection, involving TLRs, cytokines and their associated factors.


Pathway-based joint effects analysis of rare genetic variants using Genetic Analysis Workshop 17 exon sequence data.
Pathway-based analysis has been recently used in joint tests of association between disease and a group of common genetic variants. Here we explore this idea for the joint effects analysis of rare genetic variants and their association with quantitative traits and disease. We accumulate multiple rare minor alleles in a genetic risk score for each individual in a given pathway; this score is then used to assess association with quantitative phenotypes and disease. We demonstrate that this approach may be better than studying single rare variants or a gene risk score for identifying individuals with significantly greater risk.


Intraoperative precise localization of paravalvular mitral leak by a simple surgical maneuver.
Paravalvular leak after mitral valve replacement is a known surgical problem. Its management is controversial and challenging. The first and the most important step is to localize the leaking spot precisely. Echocardiogram is the standard technique that is used to localize the leak. The echocardiogram is accurate most of the time; however, in some occasions it does not easily provide the exact orientation of the leaking areas. A simple operative maneuver, which was used to allow the surgeon to localize the leak visually, and have accurate and solid repair, is described below.


Adherence to Antihypertensive Therapy and Elevated Blood Pressure: Should We Consider the Use of Multiple Medications?
Although a majority of patients with hypertension require a multidrug therapy, this is rarely considered when measuring adherence from refill data. Moreover, investigating the association between refill non-adherence to antihypertensive therapy (AHT) and elevated blood pressure (BP) has been advocated. Identify factors associated with non-adherence to AHT, considering the multidrug therapy, and investigate the association between non-adherence to AHT and elevated BP. A retrospective cohort study including patients with hypertension, identified from a random sample of 5025 Swedish adults. Two measures of adherence were estimated by the proportion of days covered method (PDC≥80%): (1) Adherence to any antihypertensive medication and, (2) adherence to the full AHT regimen. Multiple logistic regressions were performed to investigate the association between sociodemographic factors (age, sex, education, income), clinical factors (user profile, number of antihypertensive medications, healthcare use, cardiovascular comorbidities) and non-adherence. Moreover, the association between non-adherence (long-term and a month prior to BP measurement) and elevated BP was investigated. Non-adherence to any antihypertensive medication was higher among persons < 65 years (Odds Ratio, OR 2.75 [95% CI, 1.18-6.43]) and with the lowest income (OR 2.05 [95% CI, 1.01-4.16]). Non-adherence to the full AHT regimen was higher among new users (OR 2.04 [95% CI, 1.32-3.15]), persons using specialized healthcare (OR 1.63, [95% CI, 1.14-2.32]), and having multiple antihypertensive medications (OR 1.85 [95% CI, 1.25-2.75] and OR 5.22 [95% CI, 3.48-7.83], for 2 and ≥3 antihypertensive medications, respectively). Non-adherence to any antihypertensive medication a month prior to healthcare visit was associated with elevated BP. Sociodemographic factors were associated with non-adherence to any antihypertensive medication while clinical factors with non-adherence to the full AHT regimen. These differing findings support considering the use of multiple antihypertensive medications when measuring refill adherence. Monitoring patients' refill adherence prior to healthcare visit may facilitate interpreting elevated BP.


Relationship of apolipoproteins A-1 and B, and lipoprotein(a) to cardiovascular outcomes: the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes).
This study sought to examine the relationship between baseline and on-study apolipoproteins (apo) A-1 and B and lipoprotein(a) [Lp(a)] levels and the development of subsequent cardiovascular (CV) events in the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes) trial. Niacin has been reported to lower apoB and Lp(a) and to raise apoA-1. Individuals with CV disease and low baseline levels of high-density lipoprotein cholesterol were randomized to simvastatin plus placebo or simvastatin, plus extended-release niacin ([ERN], 1,500 to 2,000 mg/day), with ezetimibe added as needed, in both groups, to maintain an on-treatment low-density lipoprotein cholesterol in the range of 40 to 80 mg/dl. Hazard ratios (HRs) were used to evaluate the relationship between levels of apoA-1, apoB, and Lp(a), and CV events in each treatment group. Baseline apoB and the apoB/apoA-I ratio were significantly predictive of CV events only for the placebo group (HR: 1.17 [p = 0.018] and HR: 1.19 [p = 0.016]). Baseline and on-study Lp(a) were predictive of CV events in both simvastatin plus placebo (baseline HR: 1.24 [p = 0.002] and on-study HR: 1.21 [p = 0.017]) and the simvastatin plus ERN group (baseline HR: 1.25 [p = 0.001] and on-study HR: 1.18 [p = 0.028]). The ERN modestly increased 1-year apoA-1 (7%), decreased apoB (13%), decreased the ApoB/ApoA-1 ratio (19%), and decreased Lp(a) 21%, but did not reduce CV events. Lp(a) was associated with increased CV risk in both treatment groups indicating that it contributes to residual CV risk. However, there was no evidence that ERN reduced CV risk, despite favorable lipoprotein changes.


Vaccination status of COVID-19 patients followed up in the ICU in a country with heterologous vaccination policy: A multicenter national study in Turkey.
Vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-2) prevents the development of serious diseases has been shown in many studies. However, the effect of vaccination on outcomes in COVID-19 patients requiring intensive care is not clear. This is a retrospective multicenter study conducted in 17 intensive care unit (ICU) in Turkey between January 1, 2021, and December 31, 2021. Patients aged 18 years and older who were diagnosed with COVID-19 and followed in ICU were included in the study. Patients who have never been vaccinated and patients who have been vaccinated with a single dose were considered unvaccinated. Logistic regression models were fit for the two outcomes (28-day mortality and in-hospital mortality). A total of 2968 patients were included final analysis. The most of patients followed in the ICU during the study period were unvaccinated (58.5%). Vaccinated patients were older, had higher Charlson comorbidity index (CCI), and had higher APACHE-2 scores than unvaccinated patients. Risk for 28-day mortality and in-hospital mortality was similar in across the year both vaccinated and unvaccinated patients. However, risk for in-hospital mortality and 28-day mortality was higher in the unvaccinated patients in quarter 4 adjusted for gender and CCI (OR: 1.45, 95% CI: 1.06-1.99 and OR: 1.42, 95% CI: 1.03-1.96, respectively) compared to the vaccinated group. Despite effective vaccination, fully vaccinated patients may be admitted to ICU because of disease severity. Unvaccinated patients were younger and had fewer comorbid conditions. Unvaccinated patients have an increased risk of 28-day mortality when adjusted for gender and CCI.


[Correlation between cyclin-dependent kinase inhibitor p27kip1 and trastuzumab-resistance in gastric cancer].
To investigate the correlation between cyclin-dependent kinase inhibitor p27kip1 and trastuzumab-resistance in gastric cancer. We selected HER2-overexpressed human gastric cancer cell line NCI-N87 to establish trastuzumab-resistant NCI-N87/TR cell line by stepwise exposure to different doses of trastuzumab. The 50% inhibitory concentration (IC(50)) of trastuzumab and resistance index (RI) were calculated or analyzed by MTT assay. The expression levels of cdk2 and p27kip1 were detected by Western blot. After the treatment with cdk2 inhibitor (Purvalanol A), the expression levels of relevant proteins in NCI-N87/TR cells were detected by Western blot, and the sensitivity to trastuzumab was analyzed by MTT assay. Compared with NCI-N87 cells, the expression of cdk2 was significantly increased in NCI-N87/TR cells (P<0.001), while the expression of p27kip1 showed a significant decrease (P<0.001). Restoration of the p27kip1 protein expression by cdk2 inhibitor (Purvalanol A) increased the sensitivity of NCI-N87/TR to trastuzumab. Down-regulation of p27kip1 might be a mechanism for triggering trastuzumab resistance to gastric cancer cell line NCI-N87.


A novel spliced transcript of influenza A/WSN/33 virus.
It has been shown that influenza A virus M1 mRNA has two alternative 5" splice sites: a distal 5" splice site producing M3 mRNA that has the coding potential for 9 amino acids and a proximal 5" splice site producing M2 mRNA that encodes the essential M2 ion-channel protein. In this study, we demonstrated that the laboratory widely used strain A/WSN/33, but not A/Udorn/72 possessed another novel 5" splice site producing a transcript with the coding potential for 54 amino acids. We nominated this novel transcript as M4 mRNA. M4 mRNA was detected in A/WSN/33-infected cells derived from different species. Sequence comparison of M1 mRNA in both A/WSN/33 and Udorn/72 at position 143 to 151 reveals that this novel 5" splice site generated in WSN was due to one nucleotide difference at position 147. Several strains of influenza A viruses other than WSN also possess the potential M4 5" splice site by sequence analysis from the files of GenBank.


Solubilization and reconstitution of proline carrier in Escherichia coli; quantitative analysis and optimal conditions.
Proline carrier of Escherichia coli was extracted from the carrier-overproducing membranes with dodecylmaltoside in the presence of phospholipid. The solubilized carrier showed the same proline binding activity as that in normal membranes. As judged from determinations of the binding activity in the micellar state as a marker of active carrier and the radioactivity of N-[ethyl-2-3H]ethylmaleimide-labeled carrier as a marker of carrier polypeptide, 80% of the carrier molecules in the membranes were extracted. Optimal conditions for reconstitution of the solubilized carrier were established. By a combination of freeze-thawing, sonication and dilution procedures, 70% of the solubilized carrier molecules were incorporated into proteoliposomes and the restored active transport of proline showed an apparent Kt of 1 microM and turnover number of 0.6 s-1. The transport of proline was driven by a membrane potential in a Na+ (or Li+)-dependent manner.


Putting the illness in its place: discussion groups for families with chronic medical illnesses.
A new psychosocial intervention for families and patients experiencing the chronic phase of a disabling medical illness is described. The intervention, a short-term, highly structured, psychoeducationally oriented, multiple-family discussion group (MFDG), was developed within the context of a clinical research program and has been successfully applied to a heterogeneous range of disabling medical illnesses. This report includes a detailed description of the treatment model, the format and content of group meetings, and initial clinical impressions regarding MFDG efficacy.


[Cryoablation - back again?].
Primary and secondary liver tumors often limit patient outcome and only a minority of patients are eligible for potential curative surgery. Minimally invasive treatments, such as radiofrequency ablation (RFA), microwave ablation (MWA) and cryoablation are alternative treatment options in a curative and palliative setting. One major limitation of RFA and MWA is the limited size of tumor ablation. Furthermore during the procedure the ablation size can only be roughly estimated using RFA and MWA. RFA is the standard modality of minimally invasive tumor therapy. In comparison cryoablation is rarely used despite its advantages. Argon-helium-based cryoablation systems of the newest generation combine the advantage of small diameter applicators comparable with those of RFA and MWA systems with intrinsic advantages. Cryoablation is a minimally invasive treatment option with advantages, such as virtually unlimited ablation size, real-time visualization using computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound and intrinsic analgesic effects. On the other hand it is not very time-efficient in comparison to MWA. Especially in liver metastases RFA is the preferred treatment option. Cryoablation is a fascinating treatment option in minimally invasive tumor treatment. It demonstrates good results in hepatocellular carcinoma within the Milan criteria and T1a renal cell carcinoma. Furthermore it is a well-established treatment modality for palliative pain management in bone tumors.


Twice-daily fludarabine and cytarabine combination with or without gentuzumab ozogamicin is effective in patients with relapsed/refractory acute myeloid leukemia, high-risk myelodysplastic syndrome, and blast- phase chronic myeloid leukemia.
We evaluated the efficacy and safety of the combination of twice-daily fludarabine and cytarabine (BIDFA) in patients with refractory/relapsed acute myeloid leukemia (AML), high-risk myelodysplastic syndromes (MDS), and chronic myeloid leukemia in myeloid blast phase (CML-BP). One hundred seven patients were enrolled. Overall, 27 (26%) patients responded with a complete remission (CR) rate of 21% and CR without platelet recovery (CRp) of 5%. The overall 4-week mortality rate was 9%. In conclusion, BIDFA is active and safe in heavily pretreated patients with myeloid malignancies. The purpose of this study was to evaluate the efficacy and safety of the combination of twice-daily fludarabine and cytarabine (BIDFA) in patients with refractory/relapsed acute myeloid leukemia (AML), high-risk myelodysplastic syndromes (MDS), and chronic myeloid leukemia in myeloid blast phase (CML-BP). One hundred seven patients with refractory/relapsed AML, intermediate and high-risk MDS, and CML-BP, with a performance status of 3 or less and normal organ function were treated. Patients received fludarabine 15 mg/m(2) intravenously (IV) every 12 hours on days 1 to 5 and cytarabine 0.5 g/m(2) IV over 2 hours every 12 hours on days 1 to 5. Gemtuzumab ozogamicin (GO) was administered at 3 mg/m(2) IV on day 1 in the first 59 patients. Patients with CML-BP were allowed to receive concomitant tyrosine kinase inhibitors. Overall, 27 (26%) patients responded with a complete remission (CR) rate of 21% and CR without platelet recovery of 5%. The overall 4-week mortality rate was 9%. The CR rates for patients with relapsed AML with first CR duration greater than or equal to 12 months, relapsed AML with first CR duration less than 12 months, and refractory/relapsed AML beyond first salvage were 56%, 26%, and 11%, respectively. With a median follow-up of 7 months, the 6-month event-free survival, overall survival, and complete remission CR duration rates were 18%, 35%, and 70%, respectively. BIDFA is active with an overall response rate of 26% in a heavily pretreated population. This combination is safe with a low 4-week mortality rate of 9%.


[Cystic tumor on the porta hepatis].
A cystic entity from the porta hepatis of a 64-year-old female patient was sent in for rapid section diagnostics with a clinical suspicion of pancreatic cancer. The rapid section diagnostics revealed aspects of glandular proliferation with mucous-like material in the lumina which led to the suspicion of infiltration of a highly differentiated mucinous adenocarcinoma. However, conventional paraffin-section histology and the immunohistochemical marker profile could not confirm this suspicion but an adenomatoid tumor was diagnosed. In typical locations in the genital area of both genders, this entity is a current differential diagnosis to infiltrations of an adenocarcinoma.


Hepatitis B infection in the Asian and Latino communities of Alameda County, California.
The purpose of this study is to estimate the prevalence of the hepatitis B virus (HBV) infection and to examine factors related to HBV screening and vaccination among various Asian and Latino populations in Alameda County, CA. A cross-sectional study was conducted on Asian and Latino residents who registered with an HBV screening program from June 2009-February 2011. All participants completed a sociodemographic survey and were offered free HBV blood testing for the hepatitis B surface antigen (HBsAg) and antibody (HBsAb). The 3-shot vaccination series was provided for free to unprotected participants. Among the 792 registered participants, 84.4% (n = 669) received a blood test. Of the 669 tested participants, 7.9% (n = 53) tested HBV positive (HBsAg+, HBsAb -), 46.2% (n = 309) were protected (HBsAg -, HBsAb +), and 45.9% (n = 307) were susceptible to HBV infection (HBsAg -, HBsAb -). Among those unprotected, 60% completed the vaccine series. Multivariate analysis showed that being Vietnamese (OR = 5.53, 95% CI 1.54, 19.85), living in the US >10 years (OR = 2.12, 95% CI 1.13, 3.97), and having at least a college education (OR = 2.55, 95% CI 1.28, 5.07) were important predictors of vaccine completion. Given the various HBsAg + prevalence, screening, and vaccine completion rates among the different ethnic groups in this study, it is clear that different approaches in screening and vaccinating individual ethnic groups for hepatitis B are warranted.


Curcumin attenuates LPS-induced sickness behavior and fever in rats by modulating Nrf2 activity.
Lipopolysaccharide (LPS) is a potent inducer of inflammation, triggering behavioral changes and fever. The present study aimed to evaluate whether pretreatment with curcumin prevents the behavioral changes and fever induced by LPS through the modulation of nuclear factor-erythroid 2 related factor 2 (Nrf2). Male Wistar rats received either vehicle or LPS and after 2 h, the behavioral responses were assessed through open field test (OFT), social interaction test, forced swim test (FST), and food intake assessment. The febrile response was assessed by telemetry after vehicle or LPS injection to evaluate the effect of curcumin on the thermoregulatory response during the immunological challenge. The pretreatment with curcumin at doses of 50 and 100 mg/kg prevented the reduction of distance traveled on OFT, increased the immobility time of FST, impaired social withdrawal, decreased food intake, and induced fever. In addition, at these doses, it was possible to observe a significant decrease in the plasma levels of cytokines and an increase in Nrf2 translocation to the cell nucleus during the immunological challenge. Our data provide further evidence of curcumin's ability to prevent LPS-induced sickness behavior and fever possibly by a mechanism related to the modulation of Nrf2 translocation.


Simple genotype analysis of the Asp299Gly polymorphism of the Toll-like receptor-4 gene that is associated with lipopolysaccharide hyporesponsiveness.
A nonsynonymous single nucleotide polymorphism (Asp299Gly) in the Toll-like receptor-4 (TLR-4) gene affects the responsiveness to lipopolysaccharide in humans. To analyze this important polymorphism more efficiently, we developed a simple polymerase chain reaction (PCR) restriction length fragment polymorphism (RFLP) assay and examined the Asp299Gly allele frequency in a Japanese population. The PCR primer was designed with 1- or 2-bp mismatches, creating the recognition sequence for restriction enzyme BsaBI or BstXI, allowing RFLP analysis of the digested products. Genotyping was carried out with this assay for 275 DNA specimens from 107 healthy volunteers and 168 patients with various diseases, including ulcerative colitis (n = 86). The Asp299Gly allele of the TLR-4 gene was not detected in any of the specimens, suggesting that it is very rare in Japanese.


Women's preferences in screening for Down syndrome.
In this article, we seek to establish women's preferences (expressed as utility values) for a number of scenarios relating to the process and associated outcomes of first- and second-trimester screening for Down syndrome. We used the standard gamble (SG) approach with a sample of 100 pregnant women. Standard gamble is a choice-based preference elicitation technique that values scenarios on a 0-1 scale. A true negative screening test, whether obtained in the first or second trimester, had the highest utility scores (both 0.98), which were not significantly different from the scores for the false-positive scenarios leading to first- or second-trimester invasive testing but the birth of a healthy infant (0.95 and 0.94, respectively). The mean utility score for the false-negative scenario resulting in the birth of a Down syndrome infant (0.77) was lower than both the true negative scenarios and the false-positive healthy baby scenarios (p < 0.000). We did not find any differences in the values of the key scenarios regarding either the timing of reassurance of a healthy fetus or the ability to access early surgical termination, rather than later medical termination for a Down syndrome fetus.


Phase synchrony in the early preterm EEG: development of methods for estimating synchrony in both oscillations and events.
Development of neuronal connections relies on proper neuronal activity, and it starts during the time when early preterm babies are treated in the neonatal intensive care units. While synchrony has been a key element in visual assessment of neonatal EEG signals, there has been no unambiguous definitions for synchrony, and no objective measures available for neonatal signals. Estimation of phase locking value (PLV) has been an established paradigm in adults, but many unique characteristics of the neonatal EEG have precluded its applicability in them. In the present paper, we developed the existing PLV-based methods further to be applicable for neonatal signals at two different temporal scales, oscillations and events, where the latter refers technically to quantitating phase synchrony (PS) between band-specific amplitude envelopes (bafPS). In addition, we present a measure for quantitation based on assessing cumulative proportion of time with statistically significant synchrony between the given signal pair. The paper uses real EEG examples and the prior neurobiological knowledge in the process of defining optimal parameters in each step of the procedure. Finally, we apply the method to a set of dense array EEG recordings from very early preterm babies, recorded at conceptional age of less than 30 weeks. By comparing PS and bafPS from babies without and with major cerebrovascular lesion, we show that the effects of brain lesions may be selective both in space and in frequency. These findings do by nature escape visual detection in the conventional EEG reading, however they have intriguing correlates in the current concept of how somatosensory networks are thought to develop and/or become disorganized in the early preterm babies.


Circle of Willis: anatomical variations of configuration. A magnetic resonance angiography study.
The main scope of this paper is to investigate the prevalence of the anatomical variants of the circle of Willis (CoW) in the Romanian population through magnetic resonance angiography. Magnetic resonance angiography images were obtained for 126 individuals and the configurations of the anterior and posterior CoW were identified, and classified. The prevalence of each variant and the number of complete anterior or posterior parts of the circle were determined. A classical configuration of the CoW was found in 39 (30.9%) cases. The most common posterior variation was the unilateral absence of a posterior communicating artery (n = 28) while in the anterior circle it was the unilateral absence of the precommunicating segment of an anterior cerebral artery (n = 17). A complete entire CoW was found in 63 cases, while the anterior and posterior parts yielded complete configurations in 108 and 73 cases, respectively. Eight cases did not present complete configurations. A foetal posterior communicating artery was identified unilaterally in 14 cases and bilaterally in 6 cases. Unilateral variations were the most common changes found in CoW configuration. The correct assessment of the CoW configuration may prove useful in the planning and follow-up of brain surgery and interventional procedures, as well as in estimating the prognosis of patients suffering from stroke or other related cerebral vascular events.