Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia.
Granulocyte colony-stimulating factor (G-CSF) is a neuroprotective agent and activates endothelial proliferation and bone marrow stem cell mobilization. We studied the effect of G-CSF on angiogenesis and neurological recovery after focal cerebral ischemia. After the induction of transient focal ischemia in rats, G-CSF (50 micro/day, i.p.) or PBS was administered for 3 days. We evaluated the functional recovery, infarct volume, inflammatory infiltration, blood-brain barrier (BBB) disruption, hemispheric atrophy, protein expressions of endothelial nitric oxide synthase (eNOS) and angiopoietins, and the therapeutic time window of G-CSF administration. We then analyzed endothelial cell proliferation, the vascular surface area, the number of branch points, and the vascular length. G-CSF treatment improved behavioral recovery and reduced the infarct volume, the inflammatory infiltration, the BBB disruption, and the hemispheric atrophy. G-CSF injection, starting at 2 h, 1 day, or 4 days after ischemia, resulted in a better functional recovery and a greater reduction in hemispheric atrophy than injection starting at day 7. The vascular surface area, the vascular branch points, the vascular length, the number of BrdU(+) endothelial cells, and eNOS/angiopoietin-2 expression were significantly increased in the G-CSF group compared with the ischemia-only group. G-CSF injection starting at 1 day induced larger endothelial proliferation compared with injection starting at 7 days. In this study, we provide evidences that G-CSF enhances the angiogenesis and reduces the ischemic damage, which promotes the long-term functional recovery.


Organotin speciation in Bizerte lagoon (Tunisia).
For the first time, organotins have been assessed in samples collected from Bizerte lagoon, in Tunisia, during two seasons (summer and winter). The organotin distribution was studied in marine sediments and mussels tissues of this lagoon. Butyl-, phenyl- and octyltins were determined using a rapid speciation analytical method based on one-step ethylation/extraction with sodium tetraethylborate in aqueous phase. Simultaneously to the ethylation, the extraction was performed by either liquid/liquid extraction (LLE) or head-space solid phase microextraction (HS-SPME). Gas chromatography with pulsed flame photometric detection (GC-PFPD) was used to perform quantitative determination. The technique has been validated using biological and sediment reference materials. The different samples from Bizerte lagoon were found to be moderately contaminated, especially by butyltins. This pollution was attributed to industrial activities, which are very important in this area. Organotins appeared accumulated in both sediments and mussels, while significant degradations of triorganotins to monosubstituted ones was observed in water.


Seasonal rhythms of salivary cortisol secretion in captive Asian elephants (Elephas maximus).
Salivary cortisol has been recently used to assess welfare of captive and free-ranging animals. However, rhythms of cortisol secretion may vary annually and thus, it is necessary to take into account these rhythms when evaluating the physiological significance of fluctuations of this hormone throughout the year as stress indicator in animals. Here, we analyze monthly differences in cortisol secretion in Asian elephants (Elephas maximus) during a year. Saliva samples of eight adult female Asian elephants were collected and analyzed using Radioimmunoassay. Results revealed an overall seasonal pattern of salivary cortisol secretion and significant differences in cortisol concentration among months were found. Overall, the highest cortisol levels were recorded in October, and then decreased until reaching the lowest concentration in April. However, some individual variations were found respect this annual overall trend. The occurrence of this annual pattern of cortisol secretion should be taken into account when using cortisol as a tool to assess animal welfare in captive animal at zoological parks, as well as it opens new questions to further analyze this pattern and its variations, as well as the endogenous mechanisms controlling it.


Integrated Construction of a Long-Life Stretchable Zinc-Ion Capacitor.
The major challenge in achieving high-performance stretchable zinc-ion energy-storage devices is the combination of stretchable dendrite-free zinc negative electrodes and sufficient bonding between components (current collector, electrode, separator, and package). Herein, based on a series of physicochemically tunable self-healing polyurethanes, an elastic current collector is prepared through a swelling-induced wrinkling method, and then a stretchable zinc negative electrode prepared through in situ confined electroplating. The elastic current collector has a nano-network structure with polyurethane encapsulation, and exhibits both geometric and intrinsic stretchability. The stretchable zinc negative electrode formed in situ has high electrochemical activity and exhibits an excellent cycle life under the protection of a Zn2+ -permeable coating. Furthermore, fully polyurethane-based stretchable zinc-ion capacitors are assembled through in situ electrospinning and hot-pressing techniques. Due to the high stretchability of the components and the interfusion of the matrixes, the integrated device exhibits excellent deformability and desirable electrochemical stability. This work provides a systematic construction plan for stretchable zinc-ion energy-storage devices in three aspects: material synthesis, component preparation, and device assembly.


Familial hypocalciuric hypercalcaemia. III: Bone mineral metabolism.
Bone mineral metabolism was studied in 10 subjects with familial hypocalciuric hypercalcaemia (FHH) and 10 age-, sex- and surface area matched healthy controls. Bone turnover was estimated by urinary calcium and hydroxyproline excretions relative to creatinine (Ca/Creat and OHPr/Creat, respectively), serum bone Gla-protein (S-BGP) and serum alkaline phosphatase (S-ALP). Bone status was evaluated by measurement of bone mineral content (BMC) on both forearms and X-ray examinations of the hands. Ca/Creat and OHPr/Creat (indices of bone resorption) were both significantly higher in the FHH group than in the controls. S-BGP and S-ALP (indices of bone formation) tended towards a higher level in the FHH subjects, but the differences were not significant. The BMC values were similar in the two study groups and did not change with time. We conclude that these patients with FHH might have a bone turnover higher than normal, and that the increased bone resorption must be paralleled by an increased bone formation.


Prophylactic strategies for hand-foot syndrome/skin reaction associated with systemic cancer treatment: a meta-analysis of randomized controlled trials.
Hand-foot syndrome (HFS) and hand-foot skin reaction (HFSR) are common toxicities of several systemic cancer treatments. Multikinase inhibitor-induced HFSR is distinguished from chemotherapy-induced HFS in terms of pathogenesis, symptomatology, and treatment. Multiple trials have investigated the efficacy of preventive strategies such as COX-inhibitors, pyridoxine, and urea cream; however, no consensus has been made. This meta-analysis evaluated data from high-quality trials to provide strong evidence in forming recommendations to prevent systemic cancer therapy-induced HFS/HFSR. A systematic search of PubMed, Embase, Cochrane, clinical trials databases, and hand searching were utilized to identify randomized trials (RCTs) investigating prophylactic strategies for HFS/HFSR in cancer patients receiving systemic treatment. Trials published until August 2021 were included. Using the random effects model, pooled odds ratios were calculated for rates of all-grade and severe HFS/HFSR. Subgroup analysis based on type of cancer treatment given was done. Sixteen RCTs were included (N=2814). For all-grade HFS/HFSR, celecoxib (OR 0.52, 95% CI 0.32-0.85, p=0.009) and urea cream (OR 0.48, 95% CI 0.39-0.60, p<0.00001) both showed statistically significant risk reduction. Celecoxib was effective in preventing HFS in patients who received capecitabine (50.5% vs 65%, p=0.05), while urea cream was effective in both capecitabine HFS (22.3% vs 39.5%, p=0.02) and sorafenib-induced HFSR (54.9% vs 71.4%, p<0.00001). Pyridoxine at higher doses showed a trend towards benefit in preventing all grade HFS (69.6% vs 74.1%, p=0.23). Urea cream and celecoxib are both effective in preventing HFS/HFSR in patients receiving systemic cancer treatment. Particularly, celecoxib is more effective in preventing all-grade capecitabine-induced HFS, while urea cream shows more benefit in preventing moderate to severe sorafenib-induced HFSR. Studies investigating optimal dosing for celecoxib and urea cream are recommended. There is inadequate evidence to make recommendations regarding pyridoxine.


Sex differences in DNA methylation and expression in zebrafish brain: a test of an extended 'male sex drive' hypothesis.
The sex drive hypothesis predicts that stronger selection on male traits has resulted in masculinization of the genome. Here we test whether such masculinizing effects can be detected at the level of the transcriptome and methylome in the adult zebrafish brain. Although methylation is globally similar, we identified 914 specific differentially methylated CpGs (DMCs) between males and females (435 were hypermethylated and 479 were hypomethylated in males compared to females). These DMCs were prevalent in gene body, intergenic regions and CpG island shores. We also discovered 15 distinct CpG clusters with striking sex-specific DNA methylation differences. In contrast, at transcriptome level, more female-biased genes than male-biased genes were expressed, giving little support for the male sex drive hypothesis. Our study provides genome-wide methylome and transcriptome assessment and sheds light on sex-specific epigenetic patterns and in zebrafish for the first time.


Extended medial approach to the popliteal artery without muscular division.
This technique allows wide access to the entire popliteal artery by detaching the tendons of the pes anserinus and semimembranosus muscles, without any muscular division. The tendons are reinserted anatomically upon completion of the vascular procedure. This technique was used in 14 patients, without complication. This technique is of particular value when it is necessary to inspect the popliteal artery to determine the etiology of the occlusion in the young subject. It is invaluable when direct access to the midpopliteal artery is required.


Tendon injuries in dance.
Professional ballet dancers require an extraordinary anatomic, physiologic, and psychologic makeup to achieve and sustain their level of ability and activity. They are subject to a myriad of injuries as a result of the extreme demands of this profession. Tendon injuries are common and often coexist with other pathologies of the bone, ligaments, and psyche. It is critical that the dance doctor not examine the tendon injury in isolation, but rather the cause of the injury, either intrinsic from anatomic malalignment or from external sources, including poor form.


Osteoporosis of pregnancy: long-term follow-up of patients and their offspring.
The usual course of osteoporosis of pregnancy is complete resolution without recurrence. We report the 10-year follow-up of two patients with osteoporosis of pregnancy and their offspring. A 30-year-old woman presented with right hip pain at 30 weeks' gestation. Single-photon absorptiometry of the distal radius showed osteopenia, which persisted on 10-year follow-up. A dual-energy x-ray absorptiometry performed on the 11-year-old daughter of this pregnancy showed osteopenia. A 26-year-old woman presented with left hip pain at 16 weeks' gestation. Single-photon absorptiometry of the distal radius showed osteopenia, which persisted on 10-year follow-up. Dual-energy x-ray absorptiometry performed on the 13-year-old daughter of this pregnancy showed osteopenia. Osteoporosis of the hip discovered during pregnancy may not be a transient process and should prompt a search for osteopenia in both mother and offspring.


Evidence-based planning and costing palliative care services for children: novel multi-method epidemiological and economic exemplar.
Children's palliative care is a relatively new clinical specialty. Its nature is multi-dimensional and its delivery necessarily multi-professional. Numerous diverse public and not-for-profit organisations typically provide services and support. Because services are not centrally coordinated, they are provided in a manner that is inconsistent and incoherent. Since the first children's hospice opened in 1982, the epidemiology of life-limiting conditions has changed with more children living longer, and many requiring transfer to adult services. Very little is known about the number of children living within any given geographical locality, costs of care, or experiences of children with ongoing palliative care needs and their families. We integrated evidence, and undertook and used novel methodological epidemiological work to develop the first evidence-based and costed commissioning exemplar. Multi-method epidemiological and economic exemplar from a health and not-for-profit organisation perspective, to estimate numbers of children under 19 years with life-limiting conditions, cost current services, determine child/parent care preferences, and cost choice of end-of-life care at home. The exemplar locality (North Wales) had important gaps in service provision and the clinical network. The estimated annual total cost of current children's palliative care was about £5.5 million; average annual care cost per child was £22,771 using 2007 prevalence estimates and £2,437- £11,045 using new 2012/13 population-based prevalence estimates. Using population-based prevalence, we estimate 2271 children with a life-limiting condition in the general exemplar population and around 501 children per year with ongoing palliative care needs in contact with hospital services. Around 24 children with a wide range of life-limiting conditions require end-of-life care per year. Choice of end-of-life care at home was requested, which is not currently universally available. We estimated a minimum (based on 1 week of end-of-life care) additional cost of £336,000 per year to provide end-of-life support at home. Were end-of-life care to span 4 weeks, the total annual additional costs increases to £536,500 (2010/11 prices). Findings make a significant contribution to population-based needs assessment and commissioning methodology in children's palliative care. Further work is needed to determine with greater precision which children in the total population require access to services and when. Half of children who died 2002-7 did not have conditions that met the globally used children's palliative care condition categories, which need revision in light of findings.


A paradigm of integrative care: healing with curing throughout life, "being with" and "doing to".
We are presenting an integrative paradigm of care. We will review the basis for its evolution from prior series and parallel models. In this paradigm, healing and palliation (when indicated) are introduced in parallel with curative measures as soon as any diagnosis, especially a critical one, is made. Frequently palliative measures address patient symptoms, such as pain, anxiety, delirium, or depression, and are geared towards comfort care at the end of life. Our view of healing care is that it actively addresses the cognitive, emotional and spiritual needs of the patient and family, and includes the elements of palliative care as a complement. Because a loss is often experienced in many conditions, even in the absence of death, bereavement is represented in our model as an ongoing, continual process throughout a disease process. While we will be drawing mainly from experiences with children, the proposed model is applicable to all ages. In order to implement this model most effectively, it will be important to shift from our mindset of "doing to" to one that includes "being with" our patients and their families. The uniqueness of this paradigm, in contrast to other models, is its comprehensiveness and universality. It is appropriate for patients of any age, at any stage of their disease or illness, regardless of the severity or duration of their condition.


Autoradiography of 14C-choline uptake in endplates and skeletal muscle of mice.
The uptake of 14C-choline into the axonal part of the motor endplate and muscle of mouse diaphragms was investigated by autoradiography. With i.v. doses of 0.1 microgram/g choline chloride, the uptake into the nerve endings is fast (less than 2 min) and into muscle slower (greater than 2 min). With higher doses (1.0 microgram/g) the uptake into muscle tissue is accelerated. The radioactivity in the endplates decreases with a halflife time of 20 min and remains constant in the muscle fibres over 60 min. Denervation by cutting the phrenic nerve reduces the uptake into endplates by 40% within 14 h, but probably induces uptake into regenerating Schwann cells during 30 days. Som compounds with choline-like structure (hemicholinium-3, decamethylen-dicholine, triethyl-choline) reduce the high-affinity uptake of choline into the nerve endings with sublethal doses, whereas tetraethylammonium and N-hydroxyethyl-4-(1-naphthylvinyl)-pyridinium, an inhibitor of cholinacetyltransferase, are less active. Half lethal doses of cocaine, imipramine and reserpine have no significant action on uptake of choline into the endplates. Chlorpromazine slightly diminishes the uptake into endplates. Chlorpromazine and imipramine reduce uptake into the muscle fibres.


Use of Sm(III)-{1,2-propanediamine-N,N,N',N'-tetra(alpha,alpha-dideuterioacetate)} complex for NMR determination of absolute configuration of each alpha-amino acid in peptide hydrolysate mixtures.
(1)H NMR analyses of individual alpha-amino acids in their mixture were simultaneously conducted in the presence of Sm-(pdta-d(8)) in water: high regularity, promising for direct simultaneous determination of absolute configurations of each alpha-amino acids in peptide hydrolysate mixtures, was observed between absolute configuration and the induced shifts.


Hepatobiliary fascioliasis in non-endemic zones: a surprise diagnosis.
Fascioliasis is a zoonotic infection caused by Fasciola hepatica. Because of population migration and international food trade, human fascioliasis is being an increasingly recognised entity in nonendemic zones. In most parts of Asia, hepatobiliary fascioliasis is sporadic. Human hepatobiliary infection by this trematode has two distinct phases: an acute hepatic phase and a chronic biliary phase. Hepatobiliary infection is mostly associated with intense peripheral eosinophilia. In addition to classically defined hepatic phase and biliary phase fascioliasis, some cases may have an overlap of these two phases. Chronic liver abscess formation is a rare presentation. We describe a surprise case of hepatobiliary fascioliasis who presented to us with liver abscess without intense peripheral eosinophilia, a rare presentation of human fascioliasis especially in non-endemic zones.


Therapeutic targeting of FLT3 and associated drug resistance in acute myeloid leukemia.
Acute myeloid leukemia (AML) is a heterogeneous disease caused by several gene mutations and cytogenetic abnormalities affecting differentiation and proliferation of myeloid lineage cells. FLT3 is a receptor tyrosine kinase commonly overexpressed or mutated, and its mutations are associated with poor prognosis in AML. Although aggressive chemotherapy often followed by hematopoietic stem cell transplant is the current standard of care, the recent approval of FLT3-targeted drugs is revolutionizing AML treatment that had remained unchanged since the 1970s. However, despite the dramatic clinical response to targeted agents, such as FLT3 inhibitors, remission is almost invariably short-lived and ensued by relapse and drug resistance. Hence, there is an urgent need to understand the molecular mechanisms driving drug resistance in order to prevent relapse. In this review, we discuss FLT3 as a target and highlight current understanding of FLT3 inhibitor resistance.


Ribosomal DNA ITS-1 intergenic spacer polymorphism in triatomines (Triatominae, Heteroptera).
The length polymorphism of ribosomal DNA ITS-1 intergenic spacer was analyzed in eight species of triatomines belonging to Triatoma, Rhodnius, and Panstrongylus genera. The analyzed species were Rhodnius domesticus, R. neivai, R. robustus, Triatoma brasiliensis, T. infestans, T. vitticeps, Panstrongylus megistus, and P. herreri. These insects are vectors of Chagas' disease, one of the most prominent public health problems among South American countries. This work allowed the differentiation between species of the Triatomini and Rhodniini tribes through the analysis of ITS-1 length polymorphism by PCR and RFLP techniques. The species of the Triatoma and Panstrongylus genera presented an amplified ITS-1 fragment between 600 and 1000 bp, whereas Rhodnius presented a less variable ITS-1 length fragment, around 300 bp, which could reflect the monophyletic origin of the Rhodniini tribe. Species belonging to this genus were further differentiated by RFLP with HaeIII and AluI endonucleases. Our results corroborate the hypothesis of polyphyletic origin in this group of insects and contribute to knowledge about evolutionary relationships in triatomines.


Nanoplatforms: The future of oral cancer treatment.
Cytotoxicity is a key disadvantage of using chemotherapeutic drugs to treat cancer. This can be overcome by encapsulating chemotherapeutic drugs in suitable carriers for targeted delivery, allowing them to be released only at the cancerous sites. Herein, we aim to review the recent scientific developments in the utilization of nanotechnology-based drug delivery systems for treating oral malignancies that can lead to further improvements in clinical practice. A comprehensive literature search was conducted on PubMed, Google Scholar, ScienceDirect, and other notable databases to identify recent peer-reviewed clinical trials, reviews, and research articles related to nanoplatforms and their applications in oral cancer treatment. Nanoplatforms offer a revolutionary strategy to overcome the challenges associated with conventional oral cancer treatments, such as poor drug solubility, non-specific targeting, and systemic toxicity. These nanoscale drug delivery systems encompass various formulations, including liposomes, polymeric nanoparticles, dendrimers, and hydrogels, which facilitate controlled release and targeted delivery of therapeutic agents to oral cancer sites. By exploiting the enhanced permeability and retention effect, Nanoplatforms accumulate preferentially in the tumor microenvironment, increasing drug concentration and minimizing damage to healthy tissues. Additionally, nanoplatforms can be engineered to carry multiple drugs or a combination of drugs and diagnostic agents, enabling personalized and precise treatment approaches. The utilization of nanoplatforms in oral cancer treatment holds significant promise in revolutionizing therapeutic strategies. Despite the promising results in preclinical studies, further research is required to evaluate the safety, efficacy, and long-term effects of nanoformulations in clinical settings. If successfully translated into clinical practice, nanoplatform-based therapies have the potential to improve patient outcomes, reduce side effects, and pave the way for more personalized and effective oral cancer treatments.


A Thrombus on a Journey: A Massive Thrombus in Transit With Cerebral, Coronary, and Pulmonary Embolization.
Impending paradoxical embolism is a biatrial thrombus in transit across a patent foramen ovale. It constitutes a rare clinical condition, possibly associated with multiple embolization and high mortality. We report the exceptional case of a 71-year-old-man presenting a giant impending paradoxical thrombus, complicated with pulmonary, cerebral, and coronary embolization. The patient underwent urgent surgery and was finally discharged without complications.


Evaluation of the use of an induced puripotent stem cell sheet for the construction of tissue-engineered vascular grafts.
The development of a living, tissue-engineered vascular graft (TEVG) holds great promise for advancing the field of cardiovascular surgery. However, the ultimate source and time needed to procure these cells remain problematic. Induced puripotent stem (iPS) cells have recently been developed and have the potential for creating a pluripotent cell line from a patient's own somatic cells. In the present study, we evaluated the use of a sheet created from iPS cell-derived vascular cells as a potential source for the construction of TEVG. Male mouse iPS cells were differentiated into embryoid bodies using the hanging-drop method. Cell differentiation was confirmed by a decrease in the proportion of SSEA-1-positive cells over time using fluorescence-activated cell sorting. The expression of endothelial cell and smooth muscle cell markers was detected using real-time polymerase chain reaction (PCR). The differentiated iPS cell sheet was made using temperature-responsive dishes and then seeded onto a biodegradable scaffold composed of polyglycolic acid-poly-l-lactide and poly(l-lactide-co-ε-caprolactone) with a diameter of 0.8 mm. These scaffolds were implanted as interposition grafts in the inferior vena cava of female severe combined immunodeficiency/beige mice (n = 15). Graft function was serially monitored using ultrasonography. The grafts were analyzed at 1, 4, and 10 weeks with histologic examination and immunohistochemistry. The behavior of seeded differentiated iPS cells was tracked using Y-chromosome fluorescent in situ hybridization and SRY real-time PCR. All mice survived without thrombosis, aneurysm formation, graft rupture, or calcification. PCR evaluation of iPS cell sheets in vitro demonstrated increased expression of endothelial cell markers. Histologic evaluation of the grafts demonstrated endothelialization with von Willebrand factor and an inner layer with smooth muscle actin- and calponin-positive cells at 10 weeks. The number of seeded differentiated iPS cells was found to decrease over time using real-time PCR (42.2% at 1 week, 10.4% at 4 weeks, 9.8% at 10 weeks). A fraction of the iPS cells were found to be Y-chromosome fluorescent positive at 1 week. No iPS cells were found to co-localize with von Willebrand factor or smooth muscle actin-positive cells at 10 weeks. Differentiated iPS cells offer an alternative cell source for constructing TEVG. Seeded iPS cells exerted a paracrine effect to induce neotissue formation in the acute phase and were reduced in number by apoptosis at later time points. Sheet seeding of our TEVG represents a viable mode of iPS cell delivery over time.


Grossesse et psoriasis : le point de vue du gynécologue-obstétricien.
Psoriasis is a common chronic inflammatory disorder which worries a lot of women of childbearing age. The questions are abundant about heredity of psoriasis, its effects on the pregnancy and the future child and the risks of the used treatments. The best way to reassure them is to work closely together with the dermatologists. A préconceptionnel consultation by an expert in pathologic pregnancies obstetrician gynaecologist is strongly recommended for a first contact to explain the following pregnancy. Psoriasis is not dangerous for the pregnancy but some treatments will be prohibited. This will justify advices as soon as the patient has a desire to have a baby. The first trimester is the highest- risk period and the obstetrical complications seem increasing when the psoriasis is severe.


Acute microcystin-LR exposure interfere thyroid hormones homeostasis in adult zebrafish (Danio rerio).
Microcystin-LR (MC-LR) in the aquatic environment may disturb thyroid hormone (TH) homeostasis. It is not clear how MC-LR affects downstream biological processes after TH disturbance. After exposure to 50, 100, 200 and 400 μg/L MC-LR for 24, 48, 72, or 96 h, alterations of the TH metabolism of adult zebrafish at thyroxine (T4), triiodothyronine (T3) levels, and iodothyronine deiodinase (Dio) activity, were observed. After exposure to MC-LR at 400 μg/L, T3 and T4 levels decreased significantly in females (p < 0.05) and returned to normal levels at 96 h. In males, T4 levels were not significantly different between groups. The expression of corticotropin releasing hormone, thyroid-stimulating hormone beta subunit, transthyretin, sodium/iodide cotransporter, thrombopoietin, thyroid hormone receptor alpha and beta changed, but not in a dose-dependent manner. Acute MC-LR exposure induced a negative feedback regulation of the hypothalamic-pituitary-thyroid axis in adult zebrafish, and females were more sensitive than males. In conclusion, acute MC-LR exposure disrupted the TH metabolism by altering Dio activity and gene expression of the HPT axis; these changes may affect the complement system through regulation of c9 mRNA synthesis.


Choline acetyltransferase and acetylcholinesterase in muscular dystrophic mice.
The activities of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) were assayed in various tissues of dystrophic (dy/dy) and normal mice of Bar Harbor strain 129. The brain weights of these dystrophic mice were not significantly different from those of normal mice, but the average body weight of these dystrophic mice was only 66.8% of that of the controls. The activity of CAT (expressed as unit activity per mg of protein) was very similar in the brains of both groups of animals, but the CAT activity (per mg of protein) in the hindlimb muscles of the dystrophic mice was significantly higher than that of the controls. The patterns of AChE activity, as separated by sucrose density gradient centrifugation, were distinctly different in extracts of dystrophic and normal muscle. Compared with controls, decreased activity of the 15-S and 10-S forms of AChE, with increased activity of a 4.3-S formed of AChE, was observed in dystrophic muscle.


Self-rated health in centenarians: a nation-wide cross-sectional Greek study.
Self-rated health (SRH) is an inclusive measure of public health that is correlated with quality of life and subsequent mortality. Extensive literature has identified multiple determinants of SRH in different populations. However, such studies on centenarians are scarce and parsimonious. Our objective is to identify SRH determinants in centenarians. This is a nationwide cross-sectional study on 400 Greek centenarians that was carried out between 2007 and 2010. SRH was evaluated by a simple question with a 5-point scale. Three categories of SRH were formed (very good/good/poor), which served as the dependent variable in multinomial regression models. Various sociodemographic, disease-related, lifestyle and psychosocial variables were assessed as candidate determinants of SRH. According to our results, SRH ratings among centenarians were better than that expected according to previous studies showing worse SRH ratings with increasing age in Greece. The 22.4% of the variance in SRH among centenarians was predicted by gender, habitat region and status, financial problems, disease presence and autonomy. Among lifestyle and psychosocial variables, obesity, good relationships with children, lack of feelings of loneliness, high optimism, adaptability and an internal health locus of control profile were independently associated with good SRH. These results indicate that SRH in individuals of extreme longevity were related to specific personal psychosocial factors that contribute to healthy aging and thus support the biopsychosocial model of health promotion.


High diagnostic performance of plasma and cerebrospinal fluid beta-synuclein for sporadic Creutzfeldt-Jakob disease.
Beta-synuclein is a promising cerebrospinal fluid and blood biomarker of synaptic damage. Here we analysed its accuracy in the discrimination between sporadic Creutzfeldt-Jakob disease (n = 150) and non-prion rapidly progressive dementias (n = 106). In cerebrospinal fluid, beta-synuclein performed better than protein 14-3-3 (AUC 0.95 vs. 0.89) and, to a lesser extent, than total tau (AUC 0.92). Further, the diagnostic value of plasma beta-synuclein (AUC 0.91) outperformed that of plasma tau (AUC 0.79) and neurofilament light chain protein (AUC 0.65) and was comparable to that of cerebrospinal fluid biomarkers. Beta-synuclein might represent the first highly accurate blood biomarker for the diagnosis of sporadic Creutzfeldt-Jakob disease.


On the history of Ludwig von Bertalanffy's "General Systemology", and on its relationship to cybernetics - part III: convergences and divergences.
Bertalanffy's so-called "general system theory" (GST) and cybernetics were and are often confused: this calls for clarification. In this article, Bertalanffy's conceptions and ideas are compared with those developed in cybernetics in order to investigate the differences and convergences. Bertalanffy was concerned with first order cybernetics. Nonetheless, his perspectivist epistemology is also relevant with regard to developments in second order cybernetics, and the latter is therefore also considered to some extent. W. Ross Ashby's important role as mediator between GST and cybernetics is analysed. The respective basic epistemological approaches, scientific approaches and inherent world views are discussed. We underline the complementarity of cybernetic and "organismic" trends in systems research within the unitary hermeneutical framework of "general systemology".


Prevalence of and factors associated with postnatal depression and anxiety among parents of preterm infants: A systematic review and meta-analysis.
This study aimed to determine the prevalence of and factors associated with postpartum depression and anxiety among mothers and fathers of preterm infants and to examine the relationships between maternal and paternal symptoms. Six electronic databases were searched to identify eligible studies reporting parental depression and anxiety within 1 year postpartum. Data were extracted for a random-effects meta-analysis to estimate the prevalence with 95 % confidence intervals (CIs). Subgroup and meta-regression analyses were conducted to analyze associations between study characteristics and prevalence estimates. In total, 79 studies were included. The meta-analysis of studies on mothers generated estimates of prevalence for depression (29.2 %, 95 % CI, 21.8 %-37.9 %) and anxiety (37.7 %, 95 % CI, 24.1 %-53.6 %). The meta-analysis of fathers indicated a pooled depression prevalence of 17.4 % (95 % CI, 12.5 %-23.8 %) and an anxiety estimate of 18.3 % (95 % CI, 8.1 %-36.3 %). Assessment time points and methods as well as the geographic continent in which the study was conducted were significant moderators of depression and anxiety. Significant inter-correlations were found between mothers' and fathers' depression and anxiety symptoms (p < 0.05). Limited data from specific geographic continents, including Africa and Asia. Prevalence of depression and anxiety among preterm infants' parents was high, highlighting the need for early psychological screening and assessment. Further research is required to improve services that focus on parents' postpartum psychological needs in the family context.


Keyword-augmented and semi-automatic generation of FESS reports: a proof-of-concept study.
Surgical reports are usually written after a procedure and must often be reproduced from memory. Thus, this is an error-prone, and time-consuming task which increases the workload of physicians. In this proof-of-concept study, we developed and evaluated a software tool using Artificial Intelligence (AI) for semi-automatic intraoperative generation of surgical reports for functional endoscopic sinus surgery (FESS). A vocabulary of keywords for developing a neural language model was created. With an encoder-decoder-architecture, artificially coherent sentence structures, as they would be expected in general operation reports, were generated. A first set of 48 conventional operation reports were used for model training. After training, the reports were generated again and compared to those before training. Established metrics were used to measure optimization of the model objectively. A cohort of 16 physicians corrected and evaluated three randomly selected, generated reports in four categories: "quality of the generated operation reports," "time-saving," "clinical benefits" and "comparison with the conventional reports." The corrections of the generated reports were counted and categorized. Objective parameters showed improvement in performance after training the language model (p < 0.001). 27.78% estimated a timesaving of 1-15 and 61.11% of 16-30 min per day. 66.66% claimed to see a clinical benefit and 61.11% a relevant workload reduction. Similarity in content between generated and conventional reports was seen by 33.33%, similarity in form by 27.78%. 66.67% would use this tool in the future. An average of 23.25 ± 12.5 corrections was needed for a subjectively appropriate surgery report. The results indicate existing limitations of applying deep learning to text generation of operation reports and show a high acceptance by the physicians. By taking over this time-consuming task, the tool could reduce workload, optimize clinical workflows and improve the quality of patient care. Further training of the language model is needed.


Long non-coding RNA nuclear-enriched abundant transcript 1 inhibition blunts myocardial ischemia reperfusion injury via autophagic flux arrest and apoptosis in streptozotocin-induced diabetic rats.
This study aimed to investigate the effects of long non-coding RNA (lncRNA)-nuclear-enriched abundant transcript (Neat1) on myocardial ischemia reperfusion injury in diabetic rats ex vivo and in vivo. Screening for LncRNA Neat1 expression was performed in rat myocardial tissues using microarray analysis and verified by qRT-PCR. Cell viability of rat cardiomyocytes was analyzed by MTT assay. Levels of autophagy-related proteins Atg7, Atg5, LC3-II/LC3-I and p62 were determined by Western blot assay. Left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF) and fractioning shortening were obtained by transthoracic echocardiography. Left ventricular end systolic pressure (LVESP), left ventricular end diastolic pressure (LVEDP), maximum rate of increase or decrease of left ventricular pressure (±dp/dtmax) and heart rate were obtained by computer algorithms and an interactive videographics programme. Myocardial infarct size was determined by Evans blue and triphenyltetrazolium chloride (TTC) staining. Myocardial apoptotic index was analyzed by TUNEL assay and immunohistochemical staining. Autophagic flux was examined by evaluating fluorescent LC3 puncta. Neat1 was highly expressed in ischemia reperfusion-treated diabetic rat myocardial tissues. Overexpression of Neat1 promoted the production of lactate dehydrogenase, inhibited superoxide dismutase content and cardiomyocyte viability. Neat1 overexpression also promoted the production of serum myocardial enzymes, including creatine kinase and creatine kinase-MB, and increased infarct size. By promoting myocardial apoptosis and autophagy, Neat1 aggravated myocardial ischemia reperfusion (I/R) injury in diabetic rats. Neat1 promoted cardiomyocyte autophagy by up-regulating Foxo1 expression to increase hypoxia-reoxygenation injury. I/R treatment caused more injuries in diabetic rats compared with normal rats. Elevated Neat1 expression aggravates myocardial ischemia reperfusion injury via activation of apoptosis and autophagy in diabetic rats. Foxo1 is one of the molecular mechanisms underlying Neat1-induced autophagy.


Dicentric translocation (9;12) in acute lymphoblastic leukemia: a chromosomal abnormality with an excellent prognosis?
Recurrent chromosomal abnormalities present in the leukemic cells of pediatric patients with acute lymphoblastic leukemia (ALL) often allow us to classify patients according to their prognosis, in order to establish further treatment. The dicentric translocation (9;12) consists of the rearrangement of the short arms of chromosomes 9 and 12 generating a dicentric chromosome (9;12). Patients with this alteration present a very good response to treatment and an excellent prognosis. We present the case of an adolescent with ALL in which the dicentric translocation (9;12) was observed in the karyotype of the blasts at diagnosis. Given the excellent results of our patient and most of the series published to date, an international study is necessary to determine the true prognostic significance of this molecular alteration.


Label-free 3D characterization of cardiac fibrosis in muscular dystrophy using SHG imaging of cleared tissue.
Duchenne muscular dystrophy (DMD) is a neuromuscular disease caused by mutations in the gene encoding dystrophin. It leads to repeated cycles of muscle fiber necrosis and regeneration and progressive replacement of fibers by fibrotic and adipose tissue, with consequent muscle weakness and premature death. Fibrosis and, in particular, collagen accumulation are important pathological features of dystrophic muscle. A better understanding of the development of fibrosis is crucial to enable better management of DMD. Three-dimensional (3D) characterization of collagen organization by second harmonic generation (SHG) microscopy has already proven a highly informative means of studying the fibrotic network in tissue. Here, we combine for the first-time tissue clearing with SHG microscopy to characterize in depth the 3D cardiac fibrosis network from DMDmdx rat model. Heart sections (1-mm-thick) from 1-year-old wild-type (WT) and DMDmdx rats were cleared using the CUBIC protocol. SHG microscopy revealed significantly greater collagen deposition in DMDmdx versus WT sections. Analyses revealed a specific pattern of SHG+ segmented objects in DMDmdx cardiac muscle, characterized by a less elongated shape and increased density. Compared with the observed alignment of SHG+ collagen fibers in WT rats, profound fiber disorganization was observed in DMDmdx rats, in which we observed two distinct SHG+ collagen fiber profiles, which may reflect two distinct stages of the fibrotic process in DMD. The current work highlights the interest to combine multiphoton SHG microscopy and tissue clearing for 3D fibrosis network characterization in label free organ. It could be a relevant tool to characterize the fibrotic tissue remodeling in relation to the disease progression and/or to evaluate the efficacy of therapeutic strategies in preclinical studies in DMD model or others fibrosis-related cardiomyopathies diseases.


Gas-phase chemistry of benzyl cations in dissociation of N-benzylammonium and N-benzyliminium ions studied by mass spectrometry.
In this study, the fragmentation reactions of various N-benzylammonium and N-benzyliminium ions were investigated by electrospray ionization mass spectrometry. In general, the dissociation of N-benzylated cations generates benzyl cations easily. Formation of ion/neutral complex intermediates consisting of the benzyl cations and the neutral fragments was observed. The intra-complex reactions included electrophilic aromatic substitution, hydride transfer, electron transfer, proton transfer, and nucleophilic aromatic substitution. These five types of reactions almost covered all the potential reactivities of benzyl cations in chemical reactions. Benzyl cations are well-known as Lewis acid and electrophile in reactions, but the present study showed that the gas-phase reactivities of some suitably ring-substituted benzyl cations were far richer. The 4-methylbenzyl cation was found to react as a Brønsted acid, benzyl cations bearing a strong electron-withdrawing group were found to react as electron acceptors, and para-halogen-substituted benzyl cations could react as substrates for nucleophilic attack at the phenyl ring. The reactions of benzyl cations were also related to the neutral counterparts. For example, in electron transfer reaction, the neutral counterpart should have low ionization energy and in nucleophilic aromatic substitution reaction, the neutral counterpart should be piperazine or analogues. This study provided a panoramic view of the reactions of benzyl cations with neutral N-containing species in the gas phase.


Fish predation on Notonecta (Hemiptera): relationship between prey risk and habitat utilization.
Prey risk was examined in the laboratory to compare the ability of 6 Notonecta species to coexist with insectivorous fishes (Lepomis cyanellus, L. gibbosus). Because of their smaller size, lighter color, greater tendency to remain motionless in the presence of the predator, greater ability to avoid capture when attacked, and predicted lower profitability as prey, N. lunata and N. petrunkevitchi were estimated to have the lowest prey risk and greatest chance of coexisting with insectivorous fishes in nature. The 2 largest notonectids, N. irrorata and N. insulata, both highly melanistic and rapidly discovered by foraging sunfishes, were judged to be the most susceptible to predation by large fishes. The presence of vegetation as a potential refuge tended to decrease prey risk but did not significantly alter the relative risk among the prey species. Finally, the relative prey risk measured in the laboratory was consistent with the general distribution of these species in relation to fishes in local habitats. We suggest that fish predation is an important determinant of Notonecta habitat utilization patterns.


Tailoring surgical approach for elective ventral hernia repair based on obesity and National Surgical Quality Improvement Program outcomes.
Obesity's influence on postoperative complications in either laparoscopic ventral hernia repair (LVHR) or open ventral hernia repair (OVHR) has yet to be defined. Although 30-day postoperative complications increase with higher body mass index (BMI), we propose LVHR minimizes surgical site infections (SSIs) and surgical site occurrences (SSOs) for given BMI categories. Retrospective review of the American College of Surgeons National Surgical Quality Improvement Program database (2009 to 2012) for patients aged 18 years or more undergoing elective ventral hernia repair. Exclusion criteria included immunosuppression, disseminated malignancy, advanced liver disease, or pregnancy. Patients were stratified by BMI (20 to 25, 25 to 30, 30 to 35, 35 to 40, and >40 kg/m(2)), and 30-day SSOs evaluated across BMI groups for LVHR vs OVHR. A total of 106,968 patients met inclusion criteria, with 60% patients obese. LVHR decreased SSO for all patients (odds ratio, .4; confidence interval, .19 to .60). Obesity classes I/II/III have increased odds of superficial SSI, deep SSI, and dehiscence for OVHR compared with LVHR. Only obesity class III has increased odds of organ space SSI and reoperation for OVHR vs LVHR (P < .05). Obese patients are over-represented in VHRs. Thirty-day postoperative wound complications increase with higher BMI. LVHR minimizes both SSIs and SSOs, especially in higher obesity classes.


Hexosaminidase assays.
beta-Hexosaminidases (EC 184.108.40.206) are lysosomal enzymes that remove terminal beta-glycosidically bound N-acetylglucosamine and N-acetylgalactosamine residues from a number of glycoconjugates. Reliable assay systems are particularly important for the diagnosis of a family of lysosomal storage disorders, the GM2 gangliosidoses that result from inherited beta-hexosaminidase deficiency. More recently, aberrant hexosaminidase levels have also been found to be associated with a variety of inflammatory diseases. Apart from patient testing and carrier screening, practical in vitro assays are indispensable for the characterization of knock-out mice with potentially altered hexosaminidase activities, for detailed structure-function studies aimed at elucidating the enzymatic mechanism, and to characterize newly described enzyme variants from other organisms. The purpose of this article is to discuss convenient hexosaminidase assay procedures for these and other applications, using fluorogenic or chromogenic artificial substrates as well as the physiological glycolipid substrate GM2. Attempts are also made to provide an overview of less commonly used alternative techniques and to introduce recent developments enabling high-throughput screening for enzyme inhibitors.


Regulation of aromatase activity in bone-derived cells: possible role of mitogen-activated protein kinase.
Fetal human osteoblast-like cells and the THP-1 cell line that differentiates into macrophage/osteoblast-like cells in the presence of Vitamin D3 and which possesses high aromatase activity, constitute a useful model with which to study the regulation of aromatase in bone. We showed that dexamethasone (DEX)-induced aromatase activity in the THP-1 cell line is completely suppressed by forskolin and by dibutyryl cAMP. We therefore investigated the contribution of mitogen-activated protein kinase (MAPK) to the regulation of aromatase, because cAMP inhibits MAPK in many cells. We examined the role of MAPK on aromatase activity using PD98059, a selective inhibitor of MEK-1. PD98059 (100 microM) reduced DEX+interleukin (IL)-1beta-induced aromatase activity in human osteoblast-like cells by more than 90%, whereas 50% of the aromatase mRNA concentration was retained compared with the control incubated with DEX+IL-1beta. PD98059 (50 microM) reduced the activity of aromatase in THP-1 cells by 80% without significantly affecting the mRNA level. These results indicated that MAPK plays an important role in aromatase activation at the post-transcriptional level.


[Faults in operations as the nasal spine and the anterior parts of the septum (author's transl)].
The nasal spine and the anterior part of the septal cartilage are problematic parts for surgery. Technical faults in this region have not only poor functional results, they are also followed by dropping of the nasal tip and by unfavourable changes of the profile line of the face. This article shows some typical faults and their effects on the exterior picture of the nose. The principles for the reconstruction of the spine and the anterior septum are demonstrated.


Audit of sweat testing: a first report from Italian Cystic Fibrosis Centres.
Cystic Fibrosis diagnosis is confirmed using sweat test. The aim of our study was to evaluate current techniques and methodologies in use at Italian CF Care Centres. A series of questions related to the performance of the sweat test was collected by all CF Care Centres in Italy. Answers were compared with UK and NCCLS guidelines. 39/41 Centres replied to the questionnaire. A good adherence to guidelines was registered for storing samples before analysis in 90.9%, while performing CF diagnosis by at least two sweat tests, and chloride analysis were reported respectively in 100% and 75.7% of Centres. Some inconsistencies were registered for minimum acceptable sweat quantity and time to collect sweat inadequate in respectively 42.5% and 24.2% of Centres, while performing quality control procedures and referring to an external quality assessment scheme were found inadequate in respectively 54.6% and 100%. 57.6% didn't provide any appropriate analytical ranges and only 15.1% of Centres offered proper information to patients/parents. A report form, including sweat quantity, reference ranges and interpretation, was adequate only for 9.4 up to 41.4% of CF Centres. Our study showed areas of inconsistencies in sweat testing current practices in Italy and highlights the need for evidence based national guidelines to improve practice and management strategies.


Patients' knowledge of new medicines after discharge from hospital: What are the effects of hospital-based discharge counseling and community-based medicines use reviews (MURs)?
Interventions to reduce medicines discontinuity at transitions during and reinforced after discharge are effective. However, few studies have linked hospital-based counseling with onward referral for community pharmacy-based follow-up to support patients' medicines use. To determine the effects of targeted hospital pharmacist counseling on discharge or targeted community pharmacy medicines reviews post-discharge on patients' knowledge of newly started medication. The study was a controlled trial of targeted medicines discharge counseling provided by hospital pharmacists or follow-up post-discharge medicines review provided by community pharmacists compared with usual care (nurse counseling). Outcomes measured using a structured telephone survey conducted at two and four weeks after patients were discharged from hospital. Patients who received hospital pharmacist counseling were significantly more likely to report being told the purpose of their new medicine and how to take it versus those receiving usual care. Fewer than half of the patients who were allocated to receive a community pharmacy medicines review received one. Patient knowledge of medicines newly prescribed in the hospital was increased by targeted counseling of hospital pharmacists. The findings suggest the need to improve the consistency of the information covered when providing counseling, perhaps by the implementation of a counseling checklist for use by all disciplines of staff involved in patient counseling. The potential of community pharmacy follow-up medicines review is currently undermined by several barriers to uptake.


The development of Amblyomma americanum and Dermacentor variabilis (Acari: Ixodidae) fed on rabbits immunized with tick hemolymph.
The possibility of interfering with the normal function of tick hemolymph using antihemolymph antibodies taken in with the bloodmeal, was investigated. Cell free hemolymph from replete Amblyomma americanum and Dermacentor variabilis ticks was used to immunize rabbits. Immunized rabbits developed high antihemolymph antibody titers (ca. 10(5)) and had no ill side effects. Rabbits were simultaneously infested with larvae, nymphs, and adult ticks. The biological performance of ticks fed on immunized rabbits was virtually identical to that of ticks fed on nonimmunized rabbits. Usually, the mean engorgement weights of nymphs and females and the weights of the egg masses of both species were slightly higher for ticks fed on the nonimmunized rabbits but differences were not significant (P greater than 0.05) due to a large standard deviation. The possibility of deactivating a single hemolymph component with specific antibodies is discussed.


Pharmacokinetic comparison of two triphasic oral contraceptive formulations containing levonorgestrel and ethinylestradiol.
The pharmacokinetics of levonorgestrel (LNG) and ethinylestradiol (EE2) were determined in 24 women (aged 21 to 35 years), following the administration of a single tablet from the second phase of two different triphasic preparations (Triphasil and Trinordiol. Each tablet contained 0.075 mg of LNG and 0.040 mg of EE2. The data were compared to the pharmacokinetics of LNG and EE2 obtained following the oral administration of a hydroalcoholic solution (standard) containing the same steroids and dose. The study consisted of a randomized design in which the three formulations were administered to each of the 24 subjects in a three-period crossover pattern. Blood samples were taken at frequent intervals after dosing. Serum levels of LNG and EE2 were measured by specific radioimmunoassays. The results show that both LNG and EE2 in the Triphasil and Trinordiol tablets are bioequivalent with respect to rate and extent of absorption. Furthermore, LNG, but not EE2, in both tablet formulations was bioequivalent to the solution dose. The serum concentration-time profiles for the three formulations showed that the range of mean peak levels was 2.3-2.8 ng/ml for LNG and 116-159 pg/ml for EE2. These levels were achieved within 2 hours in the majority of subjects. The ranges of mean values calculated for the areas under the curves were 15-16 ng.hr/ml for LNG and 1053-1390 pg.hr/ml for EE2. The ranges of mean values calculated for other pharmacokinetic parameters were: volume of distribution: LNG--1.6-1.8 L/kg, EE2--7.7-9.1 L/kg; clearance: LNG--84-88 ml/hr/kg, EE2--0.67-0.99 ml/hr/kg; half-life: LNG--13-15 hr, EE2--7-12 hrs.


Payments for health care and its effect on catastrophe and impoverishment: experience from the transition to Universal Coverage in Thailand.
Equitable health financing was embodied in the reform strategies of Thailand's health care system when the country moved towards implementing the Universal Coverage (UC) policy in 2001. This study aimed to measure the pattern of household out-of-pocket payments for health care and to examine the financial catastrophe and impoverishment due to such payments during the transitional period (pre- and post-Universal Coverage policy implementation) in Thailand. This study used the nationally representative Socioeconomic Surveys in 2000 (pre-UC), 2002, and 2004 (post-UC), which contained data from 24747, 34758 and 34843 individual households, respectively. The proportion of out-of-pocket payments for health care as a share of household living standards among Thai households shows a decreasing pattern during the observed period. Moreover, the incidence and intensity of catastrophic payments for health care decline from the pre-UC to post-UC period. The distribution of incidence and the intensity of catastrophic payments for health care across quintiles also indicate that the lower quintile group (1st and 2nd quintiles) incurs lower catastrophic health care payments compared to the higher quintile group. The UC policy is also effective in preventing impoverishment due to out-of-pocket payments for health care since both the poverty headcount and poverty gap decline from the pre-UC to post-UC period. This study provides important evidence that the UC policy implementation is a valuable social protection and safety net strategy that contributes to the prevention of financial catastrophe and impoverishment due to out-of-pocket payments for health care. In conclusion, the UC policy in Thailand achieves one of the goals of improving the health system through equitable health care financing by reducing financial catastrophe and impoverishment due to out-of-pocket payments for health care.


Strain improvement of fungal insecticides for controlling insect pests and vector-borne diseases.
Insect pathogenic fungi play an important natural role in controlling insect pests. However, few have been successfully commercialized due to low virulence and sensitivity to abiotic stresses that produce inconsistent results in field applications. These limitations are inherent in most naturally occurring biological control agents but development of recombinant DNA techniques has made it possible to significantly improve the insecticidal efficacy of fungi and their tolerance to adverse conditions, including UV. These advances have been achieved by combining new knowledge derived from basic studies of the molecular biology of these pathogens, technical developments that enable very precise regulation of gene expression, and genes encoding insecticidal proteins from other organisms, particularly spiders and scorpions. Recent coverage of genomes is helping determine the identity, origin, and evolution of traits needed for diverse lifestyles and host switching. In future, such knowledge combined with the precision and malleability of molecular techniques will allow design of multiple pathogens with different strategies and host ranges to be used for different ecosystems, and that will avoid the possibility of the host developing resistance. With increasing public concern over the continued use of synthetic chemical insecticides, these new types of biological insecticides offer a range of environmental-friendly options for cost-effective control of insect pests.


Effect of modified tapioca starch on the physicochemical and sensory properties of liquid kashk.
Three forms of modified tapioca starch, i.e. phosphorylated cross-linked tapioca starch (CLTS), octenyl succinic anhydride substituted tapioca starch (OSTS) and hydroxypropylated tapioca starch (HPTS) were studied and used as stabilizers (0.5, 1 and 1.5%) in industrial liquid kashk, and their effects on the physicochemical and sensory properties of products were examined during 60 days of refrigerated storage. When combined with the highest concentration of each stabilizer, the kashk reached its highest acidity, hardness, adhesiveness, viscosity and overall acceptability, while the lowest value of syneresis was obtained. Moreover, the highest values of viscosity was observed after incorporating CLTS into the samples, and other samples with HPTS showed the highest syneresis, hardness, adhesiveness and overall acceptability. During storage, there were significant trends of increase in the values of acidity, syneresis and hardness, whereas the viscosity, pH and adhesiveness decreased significantly. Several sensory attributes such as texture, odour value and overall acceptability were influenced by the type of stabilizer. In general, among the three kinds of modified tapioca starch, the HPTS was the most suitable form at the concentration of 1.5%, and this was most appropriate for the production of industrial liquid kashk with respect to high-quality physicochemical and sensory properties.


Anomalous photophysics of bis(hydroxystyryl)benzenes: a twist on the para/meta dichotomy.
The dianions of two isomeric bis(hydroxystyryl)benzenes show dramatically different photophysical properties.


Changes in rat spatial learning and memory as well as serum exosome proteins after simultaneous exposure to 1.5 GHz and 4.3 GHz microwaves.
This study aimed to elucidate the effects and biological targets sensitive to simultaneous 1.5 and 4.3 GHz microwave exposure in rats. A total of 120 male Wistar rats were divided randomly into four groups: the sham (S group), 1.5 GHz microwave exposure (L group), 4.3 GHz microwave exposure (C group) and simultaneous 1.5 and 4.3 GHz microwave exposure (LC group) groups. Spatial learning and memory, cortical electrical activity, and hippocampal ultrastructure were assessed by the Morris Water Maze, electroencephalography, and transmission electron microscopy, respectively. Additionally, serum exosomes were isolated by ultracentrifugation and assessed by Western blotting, nanoparticle tracking and transmission electron microscopy. The serum exosome protein content was assessed by label-free quantitative proteomics. Impaired spatial learning and memory decreased cortical excitability, and damage to the hippocampal ultrastructure were observed in groups exposed to microwaves, especially the L and LC groups. A total of 54, 145 and 296 exosomal proteins were differentially expressed between the S group and the L, C and LC groups, respectively. These differentially expressed proteins were involved in the synaptic vesicle cycle and SNARE interactions during vesicular transport. Additionally, VAMP8, Syn7 and VMAT are potential serum markers of simultaneous microwave exposure. Thus, exposure to 1.5 and 4.3 GHz microwaves induced impairments in spatial learning and memory, and simultaneous microwave exposure had the most severe effects.


Gene amplification correlates with sister chromatid exchange in B16 murine and human melanoma and human astrocytoma cell lines.
The incidence of double minute chromosomes and sister chromatid exchanges has been examined in four variant lines of the B16 murine melanoma, two human melanoma and two astrocytoma cell lines. The incidence of double minutes and sister chromatid exchanges appears to be strongly associated in these cell lines.


Gene expression profiling of hypoxic response in different models of senescent endothelial cells.
Endothelial cells senescence is a physiological process affecting vascular integrity. It can contribute to heart and arterial stiffening and remodeling, impaired angiogenesis, defective vascular repair, and with an increasing prevalence of atherosclerosis. Drugs used as antineoplastic therapies, targeting tumor as well as endothelial cells, can also trigger endothelial cells senescence. We demonstrated that a short pulse of axitinib, a specific inhibitor of vascular endothelial growth factor receptors, induces cell senescence of endothelial cells. Here, we performed a high-throughput gene expression analysis to characterize the response of proliferating versus senescent endothelial cells to hypoxia, the main trigger of neo-angiogenetic phenomena in tumors. We compared the response to hypoxia of replicative senescent cells, with that of axitinib or of DNA damage-induced senescence. Overall, we enlightened common and specific responses to different senescence inducers and changes in the Senescent Associated Secretory Phenotype.


Hierarchy of DNA immobilization and hybridization on poly-L-lysine using an atomic force microscopy study.
The atomic force microscopy has been used to analyze the immobilization of single stranded DNA on poly-L-lysine-coated glass and subsequent hybridization with complimentary DNA with the Z-threshold parameter and fractal analysis methods. The poly-L-lysine layer, which has a thickness of approximately 7 nm, presents nano-defects that could be critical for DNA immobilization by acting as a nucleation sites for ssDNA and subsequently for dsDNA aggregates. The Z-threshold for the dsDNA aggregates is much larger than for ssDNA, but the statistical fractal dimension is very similar, suggesting a conformal increase of the dimensions of the dsDNA aggregates mainly in the Z-direction, due to an effective ssDNA-ccDNA molecular recognition. This study demonstrates the use of fractal analysis in conjunction with the distribution of heights to evaluate the efficiency of DNA-DNA molecular recognition on surfaces and the impact of nanodefects.


Pseudohypertension masquerading as malignant hypertension. Case report and review of the literature.
An elderly man with chronic renal failure and radiologic evidence of vascular calcification was found to have severe pseudohypertension mimicking hypertensive crisis. Pathologic examination of his artery revealed severe medical calcification. The syndrome of pseudohypertension is reviewed.


Erratum: Development of Auer bodies from giant inclusions associated with rough endoplasmic reticulum in acute promyelocytic leukemia.
[This corrects the article DOI: 10.1097/BS9.0000000000000145.].


Glove-based sensors for multimodal monitoring of natural sweat.
Sweat sensors targeting exercise or chemically induced sweat have shown promise for noninvasive health monitoring. Natural thermoregulatory sweat is an attractive alternative as it can be accessed during routine and sedentary activity without impeding user lifestyles and potentially preserves correlations between sweat and blood biomarkers. We present simple glove-based sensors to accumulate natural sweat with minimal evaporation, capitalizing on high sweat gland densities to collect hundreds of microliters in just 30 min without active sweat stimulation. Sensing electrodes are patterned on nitrile gloves and finger cots for in situ detection of diverse biomarkers, including electrolytes and xenobiotics, and multiple gloves or cots are worn in sequence to track overarching analyte dynamics. Direct integration of sensors into gloves represents a simple and low-overhead scheme for natural sweat analysis, enabling sweat-based physiological monitoring to become practical and routine without requiring highly complex or miniaturized components for analyte collection and signal transduction.


Defense reaction elicited by microinjection of kainic acid into the medial hypothalamus of the rat: antagonism by a GABAA receptor agonist.
Electrical stimulation of either the midbrain central gray or the medial hypothalamus induces a defense reaction in the rat, characterized mainly by increased locomotion, rearing, and leaping. However, microinjection of the excitatory amino acid glutamate was effective only in the former region. Because excitatory amino acids do not depolarize axons of passage, it was suggested that the hypothalamus is devoid of soma/dendrites of neurons commanding the defense reaction. In the present study, we show that a subtoxic dose (60 pmol) of another excitatory amino acid, kainic acid, injected into the medial hypothalamus significantly enhanced locomotion and rearing of Wistar rats systematically observed in an open field. Similar behavioral changes have been reported following microinjection of drugs impairing GABAergic neurotransmission. Local pretreatment with the GABAA receptor agonist THIP (2 nmol) blocked the effect of kainic acid. Therefore, the medial hypothalamus of the rat seems to contain a population of neuronal cell bodies commanding the defense reaction, which is activated by excitatory amino acids and tonically inhibited by GABAergic fibers.


Potentially adverse interactions between haloperidol and valerian.
This study was designed to determine whether the treatment with haloperidol (HP), valerian or both in association impairs the liver or kidney functions. Valerian alone did not affect oxidative stress parameters in the liver or kidney of rats. HP alone only increased glutathione (GSH) depletion in liver, but not in kidney. However, when HP was associated with valerian, an increase in lipid peroxidation levels and dichlorofluorescein (DCFH) reactive species production was observed in the hepatic tissue. Superoxide dismutase (SOD) and Catalase (CAT) activities were not affected by the HP plus valerian treatment in the liver and kidney of rats. HP and valerian when administered independently did not affect the activity of hepatic and renal delta-aminolevulinate dehydratase (delta-ALA-D), however, these drugs administered concomitantly provoked an inhibition of hepatic delta-ALA-D activity. The delta-ALA-D reactivation index was higher in rats treated with HP plus valerian than other treated groups. These results strengthen the view that delta-ALA-D can be considered a marker for oxidative stress. Serum aspartate aminotransferase (AST) activity was not altered by any treatment. However, serum alanine aminotransferase (ALT) activity was higher in the HP group and HP plus valerian group. Our findings suggest adverse interactions between haloperidol and valerian.


Impact of doxofylline compared to theophylline in asthma: A pooled analysis of functional and clinical outcomes from two multicentre, double-blind, randomized studies (DOROTHEO 1 and DOROTHEO 2).
This pooled analysis of double-blind, randomized, placebo-controlled trials aimed to investigate the impact of DOxofylline compaRed tO THEOphylline (DOROTHEO 1 and DOROTHEO 2 studies) on functional and clinical outcomes in asthma. Asthmatic patients ≥16 years of age with forced expiratory volume in 1 s (FEV1) ≥50% and <80% and with ≥15% post-bronchodilator increase in FEV1 were randomized in a 1:1:1:1 ratio in DOROTHEO 1 to receive doxofylline 200 mg, doxofylline 400 mg, theophylline 250 mg, or placebo; in DOROTHEO 2 patients were randomized in a 1:1:1 ratio to receive doxofylline 400 mg, theophylline 250 mg, or placebo. All double-blind treatments were taken orally with immediate release formulations and three times daily. Data evaluating the effect of doxofylline 400 mg, theophylline 250 mg and placebo on FEV1, asthma events rate, use of salbutamol as rescue medication and adverse events (AEs) were pooled from both studies. The pooled-analysis of 483 patients demonstrated that both doxofylline 400 mg and theophylline 250 mg significantly increased FEV1, reduced the rate of asthma events and use of salbutamol to relieve asthma symptoms compared to placebo (p < 0.01). No significant differences were detected between doxofylline 400 mg and theophylline 250 mg. Doxofylline 400 mg did not significantly (p > 0.05) increase the risk of AEs compared to placebo, conversely in patients treated with theophylline 250 mg the risk of AEs was significantly (p < 0.05) greater than in those that received placebo. We conclude that doxofylline seems to offer a promising alternative to theophylline with a superior efficacy/safety profile in the management of patients with asthma.


Renovascular hypertension in a child with Degos-Köhlmeier disease.
A 7-year old boy with Degos-Köhlmeier disease developed renovascular hypertension. Arteriography showed peripheral occlusive arteriopathy of the left kidney as part of the Degos-Köhlmeier disease.


Expanded criteria for pneumatic retinopexy and potential cost savings.
To provide insight into the preoperative factors that affect outcome after pneumatic retinopexy (PR) for treatment of primary rhegmatogenous retinal detachment repair. Additionally, we sought to analyze the cost of rhegmatogenous retinal detachment repair in the United States to determine potential cost savings with pneumatic retinopexy. Single-center, retrospective, observational consecutive case series and third party payer-perspective comparative cost analysis. We included 141 eyes undergoing pneumatic retinopexy for the treatment of primary rhegmatogenous retinal detachment. Preoperative characteristics, anatomic outcomes, and best-available visual acuity were collected. Anatomic and visual outcomes were analyzed based on the presence of selected preoperative factors. The primary cohort was divided into 2 groups based on preoperative characteristics: (1) traditional pneumatic retinopexy and (2) nontraditional pneumatic retinopexy. Comparative cost analyses were performed between pneumatic retinopexy, scleral buckling, and vitrectomy. Anatomic and visual outcomes at 6 months. Overall anatomic success was 78.7% and visual acuity improved significantly (logarithm of the minimum angle of resolution [logMAR] 0.48-0.25; P <0.005). A 97.6% final anatomic success rate was achieved. Anatomic outcomes were similar between traditional versus nontraditional (84.1% vs 74.4%; P = 0.16), phakic versus pseudophakic (79.1% vs 78.0%; P = 0.88), and macula-on versus macula-off (77.9% vs 81.1%; P = 0.68) groups. Anatomic failure was predicted by the presence of an inferior retinal break (P <0.005) or visible vitreous traction on a retinal break (P = 0.04). Visual outcomes were similar between each of the traditional versus nontraditional (logMAR 0.21 vs 0.27; P >0.05) and phakic versus pseudophakic groups (logMAR 0.23 vs 0.28; P >0.05). Visual outcomes were better in macula-on detachments compared with those in which the macula was detached (logMAR 0.18 vs 0.42; P <0.005). Annual health care cost savings in the United States ranging from $6 to $30 million are theoretically possible by increasing pneumatic retinopexy utilization from the current rate of 15% to 20%-35%. Pneumatic retinopexy is an effective treatment modality for primary rhegmatogenous retinal detachment. Anatomic and visual outcomes are similar for traditional and nontraditional preoperative inclusion criteria, as well as phakic and pseudophakic eyes. Inferior breaks and visible vitreous traction on a tear predicted failure. Increased utilization of pneumatic retinopexy would achieve significant cost savings while maintaining outcomes.


Risk Factors for Bisphosphonate-Related Osteonecrosis of the Jaws in Bone Metastatic Breast and Prostate Cancer under Zoledronate Treatment: A Retrospective Analysis from 10 Years of Evaluation.
This study aims to analyze the risk factors for BRONJ in patients taking zoledronic acid (ZA) for metastatic breast and prostate cancer. For this, a retrospective, quantitative, observational cohort study was conducted using data on adverse effects in the oral cavity in patients during chemotherapy for treatment of solid tumors available in the electronic patient record system of the Haroldo Juaçaba Hospital/Ceará Cancer Institute in the period from 2010, to 2019. Data were tabulated in Excel and exported to SPSS v20.0 software for statistical analysis, with 95% confidence. Thus, it can be observed that the prevalence of BRONJ in patients under treatment for breast cancer and prostate cancer was <7%, with age <50 years of age (p=0.009), cytotoxic chemotherapy such as methotrexate (p=0.023), paclitaxel (p=0.005), capecitabine (p<0.001), gemcitabine (p=0.007) and bicalutamide (p=0.016), amount of ZA infusions (p<0.001) and hormone therapy (p=0.007), in addition, a slight reduction in survival and increased use of antidepressants (p=0.014) were observed. The reduced overall survival and increased use of antidepressants in patients who developed BRONJ, reinforcing the need for further research to study the mechanisms involved in the unconventional risk factors for BRONJ. Thus, increasing the attention to these patients to prevent this condition from compromising the prognosis of these individuals.


Clinical features of Japanese polycythemia vera and essential thrombocythemia patients harboring CALR, JAK2V617F, JAK2Ex12del, and MPLW515L/K mutations.
The risk of complication of polycythemia vera (PV) and essential thrombocythemia (ET) by thrombosis in Japanese patients is clearly lower than in western populations, suggesting that genetic background such as race may influence the clinical features. This study aimed to clarify the relationship between genetic mutations and haplotypes and clinical features in Japanese patients with PV and ET. Clinical features were assessed prospectively among 74 PV and 303 ET patients. There were no clinical differences, including JAK2V617F allele burden, between PV patients harboring the various genetic mutations. However, CALR mutation-positive ET patients had a significantly lower WBC count, Hb value, Ht value, and neutrophil alkaline phosphatase score (NAP), and significantly more platelets, relative to JAK2V617F-positive ET patients and ET patients with no mutations. Compared to normal controls, the frequency of the JAK246/1 haplotype was significantly higher among patients with JAK2V617F, JAK2Ex12del, or MPL mutations, whereas no significant difference was found among CALR mutation-positive patients. CALR mutation-positive patients had a lower incidence of thrombosis relative to JAK2V617F-positive patients. Our findings suggest that JAK2V617F-positive ET patients and CALR mutation-positive patients have different mechanisms of occurrence and clinical features of ET, suggesting the potential need for therapy stratification in the future.


Seasonal differences in climate in the Chianti region of Tuscany and the relationship to vintage wine quality.
Climatic factors and weather type frequencies affecting Tuscany are examined to discriminate between vintages ranked into the upper- and lower-quartile years as a consensus from six rating sources of Chianti wine during the period 1980 to 2011. These rankings represent a considerable improvement on any individual publisher ranking, displaying an overall good consensus for the best and worst vintage years. Climate variables are calculated and weather type frequencies are matched between the eight highest and the eight lowest ranked vintages in the main phenological phases of Sangiovese grapevine. Results show that higher heat units; mean, maximum and minimum temperature; and more days with temperature above 35 °C were the most important discriminators between good- and poor-quality vintages in the spring and summer growth phases, with heat units important during ripening. Precipitation influences on vintage quality are significant only during veraison where low precipitation amounts and precipitation days are important for better quality vintages. In agreement with these findings, weather type analysis shows good vintages are favoured by weather type 4 (more anticyclones over central Mediterranean Europe (CME)), giving warm dry growing season conditions. Poor vintages all relate to higher frequencies of either weather type 3, which, by producing perturbation crossing CME, favours cooler and wetter conditions, and/or weather type 7 which favours cold dry continental air masses from the east and north east over CME. This approach shows there are important weather type frequency differences between good- and poor-quality vintages. Trend analysis shows that changes in weather type frequencies are more important than any due to global warming.


Adherence to diet and medication and the associated factors among patient with chronic heart failure in a multi-ethnic society.
To investigate diet adherence, medication adherence and self-care behaviour among patients with chronic heart failure (CHF) in a multi-ethnic society and identify the significant factors associated with their diet and medication adherence. A cross-sectional descriptive correlational study was conducted with a convenience sample of 107 patients with CHF recruited from two cardiology wards of a public tertiary hospital in Singapore. Study variables were measured using the Dietary Sodium Restriction Questionnaire, the Medication Adherence Rating Scale-5 items and the European Heart Failure Self-care Behaviour Scale-12 items. Our sample reported positive attitudes towards diet adherence, poor self-care behaviour, and good medication adherence. The multiple linear regression results indicated that lower income, Chinese ethnicity, diabetic complications, current smoking, lower New York Heart Association classification I and II, and poorer self-care behaviour predicted poorer diet adherence. In addition, absence of hypertension, having non-myocardial infarction as a cause of CHF, and moderately diminished ejection fraction were identified as significant predictors of poorer medication adherence. The findings from this study have established the need to improve current education and rehabilitation programmes for patients with CHF by addressing those factors significantly influencing their adherence to diet and medication.


[The chondrotoxic and apoptotic effects of levobupivacaine and bupivacaine on the rabbit knee joint].
A single dose injection or continuous infusion of local anesthetics into the joint space is considered to be a well-defined analgesia technique. The aim of this study was to investigate the chondrotoxic and apoptotic effects of single-dose intra-articular injection of levobupivacaine and bupivacaine on rabbit knee joint tissues. The animals were allocated into two groups each containing 20 rabbits. 0.5% levobupivacaine (Group L) and 0.5% bupivacaine (Group B) were applied intra-articularly to the left posterior joints of rabbits. At the same time, normal saline was applied to the right posterior leg knee joints of rabbits in both groups and used as a control (Group S). At the end of the 7th and 28th days after the intraarticular injections, ten randomly chosen rabbits in each group were killed by applying intraperitoneal thiopental. Sections of cartilage tissue samples were stained for light microscopic examinations and the TUNEL method was used to investigate apoptotic cells. As a result of immunofluorescence microscopic examination, the number of apoptotic cells in Group B at day 7 and day 28 were both significantly higher than Group L and S (p<0.05). Also, the number of apoptotic cells in Group L at day 7 and day 28 were both significantly higher than Group S (p<0.05). We found that bupivacaine is more chondrotoxic than other anesthetic agent and increases the number of apoptotic cells. These results indicated that bupivacaine caused high chondrotoxic damage and it led to more apoptotic activation than levobupivacaine.


Flavonoids in Scutellaria immaculata and S. ramosissima (Lamiaceae) and their biological activity.
The aim of this study was to investigate the flavonoid composition of Scutellaria immaculata and S. ramosissima (Lamiaceae) and the in-vitro biological activity of their extracts and flavonoids. The flavonoid composition of S. immaculata (Si) and S. ramosissima (Sr) were analysed using LC-MS. Antimicrobial activity was studied in vitro against a range of bacteria and fungi using diffusion and microdilution methods. Anti-trypanosomal and cell proliferation inhibitory activity of the extracts and flavonoids was assessed using MTT. The antioxidant activity of the flavonoids and extracts were evaluated using DPPH* test. LC-MS investigation of Si and Sr plants allowed the identification, for the first time, of an additional 9 and 16 flavonoids, respectively. The methanol, chloroform and water extracts from these plants and six flavonoids (scutellarin, chrysin, apigenin, apigenin-7-O-glucoside, cynaroside and pinocembrine) exhibited significant inhibition of cell growth against HeLa, HepG-2 and MCF-7 cells. The chloroform extract of Sr showed potent cytotoxic effects with IC50 (drug concentration which resulted in a 50% reduction in cell viability) values of 9.25 ± 1.07 µg/ml, 12.83 ± 1.49 µg/ml and 17.29 ± 1.27 µg/ml, respectively. The highest anti-trypanosomal effect against T. b. brucei was shown by the chloroform extract of Sr with an IC50 (drug concentration which resulted in a 50% inhibition of the biological activity) of 61 µg/ml. The pure flavonoids showed an IC50 range between 3 and 29 µm, with cynaroside as the most active compound with an IC50 value of 3.961 ± 0.133 µm. The chloroform extract of Sr has potent antimicrobial activity against Streptococcus pyogenes (minimum inhibitory concentration, MIC = 0.03 mg/ml). Pinocembrine exhibited a strong activity against the all bacteria except Escherichia coli and yeasts. Water extracts of Sr and Si exhibited potent antioxidant activity with IC50 values of 5.62 ± 0.51 µg/ml and 3.48 ± 0.02 µg/ml, respectively. Scutellarin exerted stronger antioxidant activity than other flavonoids. This is the first study reporting an in-vitro biological investigation for Si and Sr. Especially the chloroform extract of Sr showed potent anticancer and antimicrobial activity. Cynaroside had a highly selective and strong cytotoxicity against T. b. brucei while showing only mild effects against cancer cells.


Long-term tensile bond durability of two different 4-META containing resin cements to dentin.
This study was conducted to evaluate the tensile bond durability of two different types of 4-META containing resin cements over a period of 3 years. Ten bovine dentin specimens were tested for tensile bond strengths with each of the following materials: Super Bond C&B: unfilled methyl methacrylate (MMA)/polymethyl methacrylate (PMMA) resin cement, MASA Bond (experimental material): filled dimethacrylate resin cement at 1 day, 6 months, 1 and 3 years. The mean bond strengths were compared statistically by two-way ANOVA and Fisher's PLSD test (P<0.05). The mode of failure was classified by SEM observation. Results for the mode of fracture were analyzed using the Mann-Whitney U test. Although there was no statistical difference in mean bond strength between Super Bond C&B and MASA Bond (P>0.05) during the experimental periods, the 1-day bond strengths were significantly greater than those at the other experimental periods except for 6 months (P<0.05). Regarding the fracture modes, at 6 months and 1 year, statistical differences were observed between Super Bond C&B and MASA Bond (P<0.05). The bond strengths of both resin cements to dentin significantly decreased after 6 months, and the long-term failure patterns of the 4-META/TBB resin cements showed a marked change.


Evidence that UGA is read as a tryptophan codon rather than as a stop codon by Mycoplasma pneumoniae, Mycoplasma genitalium, and Mycoplasma gallisepticum.
Molecular cloning and sequencing showed that Mycoplasma gallisepticum, like Mycoplasma capricolum, contains both tRNA(UCA) and tRNA(CCA) genes, while Mycoplasma pneumoniae and Mycoplasma genitalium each appear to have only a tRNA(UCA) gene. Therefore, these mycoplasma species contain a tRNA with the anticodon UCA that can translate both UGA and UGG codons.


Production of two recognins related to malignin: recognin M from mammary MCF-7 carcinoma cells and recognin L from lymphoma P3G cells.
From the first two non-brain cancer cell types examined, mammary cancer cells (MCF-7) and lymphoma cells (P3G), two new acidic polypeptides of approximately 10,000 M.W. each have been produced, called recognin M and recognin L, respectively. These are very closely related in amino acid composition and in immunological reactions to the first two cancer recognins, astrocytin from human gliomas in vivo and malignin from malignant glial cells grown in vivo. Together with earlier findings, these observations suggest that the cancer polypeptide recognins may be produced from members of a closely related family of substances characteristic of malignant cells.


Reimbursement and use of oral anticoagulants during 2014-2022 - A register-based study.
Vitamin K antagonists, warfarin in particular, have been the mainstay of anticoagulation therapy, but their use has declined in many countries since direct oral anticoagulants (DOACs) have entered the market. To examine utilization trends of oral anticoagulants (OACs) in Finland considering the reimbursement of DOACs and changes to national treatment guidelines for the treatment of atrial fibrillation (AF). Both public, aggregated data on reimbursed OAC dispensations and individual-level data on electronic dispensations during 2014-2022 were applied. Data on electronic dispensations during 2015-2016 were used to study OAC initiations. Data on entitlements to reimbursement for DOACs came from public data. In 2014, there were almost 20,000 DOAC users, rising to 214,000 in 2022. The number of warfarin users declined since 2015 from over 181,000 to around 59,000 users in 2022, DOACs exceeding warfarin in the number of users in 2019. The total DOAC costs were higher than warfarin costs each year. Rivaroxaban was the most widely used DOAC during 2014-2018, and apixaban during 2019-2022. In 2015, there were more warfarin (56.7%) than DOAC (43.3%) initiators, but the result was opposite for 2016 (warfarin 39.4%, DOACs 60.6%). The number of individuals entitled to reimbursement for DOACs has increased steadily, and in 2022, there were over 196,000 individuals entitled to this reimbursement due to AF. The uptake of DOACs in Finland appears to have been gradual and slower than in many other countries. During the 2010s, the treatment guidelines for AF were more cautious in recommending DOACs than the European guidelines. The use of DOACs increased as their reimbursement became less restrictive.


Impact of family income on the lifestyle and physique of schoolchildren in Higashi-Osaka City, Japan.
There is limited evidence about the ways in which poverty affects the health and educational environment of schoolchildren. We investigated the impact of family income on the lifestyle and physique of children in Japan. We mailed a questionnaire to 1,000 fifth-grade elementary school and 1,000 second-grade junior high school students and their parents in Higashi-Osaka City from August to September, 2017. Physique was evaluated based on standard body weight for height. The questionnaire survey recovery rate was 31.3%. Overweight / obesity was confirmed in 8.1% of males and 3.7% of females. The prevalence of overweight / obesity was higher in children of families with incomes under the median than in families with incomes over the median only in females. The number of children with less than 1 h of studying time after school was significantly higher in children of families with incomes under the median, as well as in overweight / obese children. In children of families with incomes under the median, the rates of possessing books, exercise equipment, and their own room were lower than in children of families with incomes over the median, but there was no difference in the rates of possessing smartphones, or video games, based on income. Children of low-income families have an educational handicap, which is one of the risk factors for the "chain of poverty."


Automated detection of nonmelanoma skin cancer using digital images: a systematic review.
Computer-aided diagnosis of skin lesions is a growing area of research, but its application to nonmelanoma skin cancer (NMSC) is relatively under-studied. The purpose of this review is to synthesize the research that has been conducted on automated detection of NMSC using digital images and to assess the quality of evidence for the diagnostic accuracy of these technologies. Eight databases (PubMed, Google Scholar, Embase, IEEE Xplore, Web of Science, SpringerLink, ScienceDirect, and the ACM Digital Library) were searched to identify diagnostic studies of NMSC using image-based machine learning models. Two reviewers independently screened eligible articles. The level of evidence of each study was evaluated using a five tier rating system, and the applicability and risk of bias of each study was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Thirty-nine studies were reviewed. Twenty-four models were designed to detect basal cell carcinoma, two were designed to detect squamous cell carcinoma, and thirteen were designed to detect both. All studies were conducted in silico. The overall diagnostic accuracy of the classifiers, defined as concordance with histopathologic diagnosis, was high, with reported accuracies ranging from 72 to 100% and areas under the receiver operating characteristic curve ranging from 0.832 to 1. Most studies had substantial methodological limitations, but several were robustly designed and presented a high level of evidence. Most studies of image-based NMSC classifiers report performance greater than or equal to the reported diagnostic accuracy of the average dermatologist, but relatively few studies have presented a high level of evidence. Clinical studies are needed to assess whether these technologies can feasibly be implemented as a real-time aid for clinical diagnosis of NMSC.


Indole alkaloids from Ervatamia hainanensis with potent acetylcholinesterase inhibition activities.
Through bioassay-guided fractionation and chromatography technique, eight indole alkaloids were furnished from the stems of Ervatamia hainanensis. All isolates were evaluated for acetylcholinesterase (AChE) inhibition activities, in which compounds 1 and 3 exhibited the same level of activities as galantamine, a marketed cholinesterase inhibitor for the treatment of Alzheimer's disease. Discussion about the relationships between structure and activity of these alkaloids was also presented.


Study of optimal conditions in semi-continuous anaerobic co-digestion of table olive effluents and pig manure in a perfectly stirred reactor.
Brines from table olive elaboration were co-digested with pig manure, obtaining high methane productions. In particular, the methane yields obtained for pig manure total solid (TS) initial concentrations of 2%, 7%, 9% (wet basis, wt.) were 106, 213 and 247 mL CH4 gVS-1add, respectively, using mixtures of two types of brine (acid (A) and basic (B)) generated in the elaboration process. Moreover, an experiment with only basic brine was made, using a pig manure TS concentration of 7% wt. In this case, a methane yield of 224 mL CH4 gVS-1add was obtained. The methane production rate was calculated in experiments of 7% pig manure TS concentration and a high kinetic constant of 0.31 d-1 was obtained for the mixture of residual brine. Finally, the effect of Na+ cation concentration was evaluated in the mixture A:B during co-digestion processes with a 7% wt. pig manure TS concentration and inhibition was detected in this process with a [Na+] of 0.56% wt. of the total sample. An energy and economical study on the treatment of these wastewaters by means of anaerobic co-digestion demonstrated a great economic benefit for the producer industry, a reduction in the diesel consumption used to produce its energetic demand and a reduction cost of 3.63 €/m3 generated of A:B brines mixture with ratio 2:1.


A non-thermal modification method to promote the interaction of zein-alginate oligosaccharides composites for better encapsulation and stability-Cold plasma.
This current research explored the application of cold plasma (CP) treatment to modify zein-alginate oligosaccharide (zein-AOS) composites in an ethanol-water solution. Anti-solvent method was used to prepare zein-AOS nanoparticles (NPs), and the objective was to investigate the mechanism by which CP promotes interaction between protein and saccharides. Characterization results indicated that CP treatment improved hydrogen bonding and electrostatic interaction between zein and AOS. The CP zein-AOS NPs underwent dispersion and rearrangement, resulting in smaller aggregates with better dispersibility. Among the various induction conditions tested, the zein-AOS85 NPs (induced at 85 W for 2 min) exhibited superior performance as delivery wall materials, with smaller particle size (234.67 nm), larger specific surface area (9.443 m2/g), and higher surface charge (-35.43 mV). In addition, zein-AOS85 showed high stability when used as delivery wall material, providing more binding sites and self-assembly dynamics for nutrients. Curcumin was used as the nutrient model in this study, and CP was found to enhance hydrogen bonding, electrostatic interaction, and hydrophobic interaction between zein, AOS, and nutrients, resulting in increased encapsulation efficiency (EE) from 63.80 % to 85.17 %. The delivery system also exhibited good pH, ionic strength, storage, and dispersion stability.


Maternal and neonatal factors and mortality in children with Down syndrome born in 1973-1980 and 1995-1998.
To investigate maternal and neonatal factors in Down syndrome (DS) at birth, the impact of a congenital heart defect (CHD) on these factors and changes over time. Medical data of children with DS born in northern Sweden in the periods 1973-1980 (n = 219) and 1995-1998 (n = 88) obtained from the Swedish Medical Birth Register were compared. A comparison with the general population on a group level was also made. The main finding was a reduction in infant mortality in DS, from 14.2% to 2.3% in 1995-1998 (p < 0.001), but this was still significantly higher than in the general population. The rate of Caesarean sections increased over time (from 14.5% to 27.3%, p < 0.05) even after adjustment for increased maternal age. No change over time was detected in the following rates: premature birth (gestational age < or = 36) (25%); asphyxia (5-min Apgar score < or = 6) (8%); low birthweight (< 2500 g) (14%); or small for gestational age (SGA) (14%); all rates were significantly higher than those of the general population. A CHD did not seem to influence the rates of these factors in a logistic regression model. Infant mortality decreased substantially over time in the DS group, whereas there was no reduction in the rate of asphyxia, SGA, low birthweight or prematurity. The presence of a CHD did not influence any of the neonatal factors studied.