Criteria indicating morbidity in tuberculous meningitis.
To work out a criterion that may indicate morbidity in tuberculous meningitis. The retrospective study was conducted at the Medical Unit of the Liaquat University of Health Sciences, Jamshoro, Pakistan, and included cases related to a period between January 2006 and June 2011. Record of 50 patients were evaluated for clinical features, chest radiograph, Mantoux test, sputum for acid fast bacilli, routine investigations, cerebrospinal fluid studies, computerised tomography scan and magnetic resonance imaging of head. All the patients in the study had been treated with conventional approach. The severity of the condition was classified in stages, I, II and III. Clinical features, laboratory findings and imaging reports were analysed through SPSS 10 to find out the criteria indicating morbidity. Mean, median, standard deviation were calculated. Student t-test was applied on variables. Of the 50 patients, 26 (52%) were male and 24 (48%) were female. Their ages ranged from 12 to 70 years. Mean age was 37.72 +/-19.65 years. Median age was 35.54 years. Of the total, 17 (34%) patients recovered completely without any complications. Their mean age was 24+/-8.98 years and their mean time interval from onset of illness to presentation in the hospital was 21.75+/-9.75 days. Besides, 30 (60%) patients persisted with neurological sequelae, including cranial nerve palsies, hemiplegia, and hydrocephalus. Patients with neurological sequelae had mean age of 48+/-17.48 years and their mean time interval from onset of illness to presentation in the hospital was 41.33+/-14.14 days. Hydrocephalus was seen in 10 (20%) patients. Three (6%) patients expired. Clinical features, laboratory findings and imaging reports analysis showed that the criteria indicating morbidity were increasing age of the patient (p=0.037), late diagnosis (p=0.044), advancing stage of disease, and development of hydrocephalus. Increasing age of the patient, late diagnosis, advancing stage of the disease and the development of hydrocephalus indicate morbidity in tuberculous meningitis.


Pathogenesis of haemophilic synovitis: clinical aspects.
Arthropathy remains a major cause of morbidity in patients with haemophilia. Frequent bleeding into the joints leads to joint damage with resultant contractures, joint deformities and arthritis. This in turn leads to muscle atrophy, limited physical activity, osteoporosis and disability. Even though several studies of prophylactic factor replacement for persons with severe haemophilia demonstrate improved joint function, this therapy is still not readily available to most people with haemophilia around the world and a universal treatment protocol has not been used. In this article, we discuss key issues in the treatment of severe haemophilia: the optimal timing of initiation and termination of therapy, dosing options and goals of therapy. The options for countries where prophylaxis is not readily available are also discussed. Most studies are small and not randomized making consensus treatment recommendations difficult to formulate. Randomized, clinical trials are needed to provide the answers regarding the optimal treatment of patients with severe haemophilia.


The 93rd Annual Meeting of the American Association for Cancer Research. 6-10 April 2002, San Francisco, California, USA.
The American Association for Cancer Research held its 93rd Annual Meeting on 6 - 10 April 2002. This was an enormous meeting with approximately 14,000 registrants and some 5750 abstracts, the vast majority of which were presented as posters. Those abstracts judged to be of particular significance or interest were presented as 15-min platform presentations in minisymposia, of which there were 36 during the meeting. In addition to this, there was a full day of 15 educational sessions (each with three to four speakers), 11 award lectures, 47 early morning Meet-the-Expert Sunrise Sessions. There was a mind-boggling array of choices for those interested in cancer research. This meeting was the largest ever convened on a single disease. We will endeavour to provide some of the highlights of this exciting meeting.


Application of Human-Induced Pluripotent Stem Cells (hiPSCs) to Study Synaptopathy of Neurodevelopmental Disorders.
Synapses are the basic structural and functional units for information processing and storage in the brain. Their diverse properties and functions ultimately underlie the complexity of human behavior. Proper development and maintenance of synapses are essential for normal functioning of the nervous system. Disruption in synaptogenesis and the consequent alteration in synaptic function have been strongly implicated to cause neurodevelopmental disorders such as autism spectrum disorders (ASDs) and schizophrenia (SCZ). The introduction of human-induced pluripotent stem cells (hiPSCs) provides a new path to elucidate disease mechanisms and potential therapies. In this review, we will discuss the advantages and limitations of using hiPSC-derived neurons to study synaptic disorders. Many mutations in genes encoding for proteins that regulate synaptogenesis have been identified in patients with ASDs and SCZ. We use Methyl-CpG binding protein 2 (MECP2), SH3 and multiple ankyrin repeat domains 3 (SHANK3) and Disrupted in schizophrenia 1 (DISC1) as examples to illustrate the promise of using hiPSCs as cellular models to elucidate the mechanisms underlying disease-related synaptopathy.


Direct measurement of intermediate-range Casimir-Polder potentials.
We present the first direct measurements of Casimir-Polder forces between solid surfaces and atomic gases in the transition regime between the electrostatic short-distance and the retarded long-distance limit. The experimental method is based on ultracold ground-state Rb atoms that are reflected from evanescent wave barriers at the surface of a dielectric glass prism. Our novel approach does not require assumptions about the potential shape. The experimental data are compared to the theoretical predictions valid in the different regimes. They agree best with a full QED calculation.


[Clinical significance of changes in quantitative expression of human leukocyte antigen DR in severely burned patients].
To investigate the clinical significance of kinetic changes in quantitative expression of human leukocyte antigen DR (HLA-DR) in severely burned patients. The blood samples of 77 extensively burned patients (>30% of total body surface area) were serially collected in the present study. The expression of HLA-DR on CD14(+) mononuclear cell surface in burned patients were quantified by flow cytometry (using monoclonal antibody, QuantiBRITETM Anti-HLA-DR PE(*)/Anti-Monocyte PerCP-Cy5.5) on days 1, 3, 5, 7, 14, 21 and 28 post burn. The expressions of HLA-DR on CD14(+) mononuclear cell surface in severely burned patients were significantly lower than those in healthy volunteers from the first day post burn (P < 0.05), and the value of HLA-DR expression was negatively correlated with the burned area (r = -0.7232, P < 0.05). The expression of HLA-DR in patients complicated with multiple organ dysfunction syndrome (MODS) was persistently decreased following major burns, and it was significantly lower than that of non-MODS patients on days 3, 14, 21 and 28 post burn (P < 0.05). The incidence rate of MODS rose markedly along with the lowering of HLA-DR expression, accompanied with poorer prognosis. Extensive burns could result in marked damage in expression of HLA-DR on CD14(+) mononuclear cell surface and immunologic dysfunction. Quantitative measurement of HLA-DR expression might be of significance in forecasting the development of MODS and prognosis in extensively burned patients.


Interleukin-10 gene promoter polymorphisms and their protein production in peritoneal fluid in patients with endometriosis.
Although associations of interleukin-10 (IL-10) gene promoter polymorphisms and their protein production with endometriosis risk have been reported, the correlations remain controversial. The objective of this study was to determine IL-10 gene promoter polymorphisms at -1082, -819 and -592 sites and their protein production in peritoneal fluid (PF) in patients with and without endometriosis. IL-10 gene promoter polymorphisms at -1082 site were detected by amplification refractory mutation system (ARMS)-PCR and that at -819 and -592 sites was genotyped by restriction fragment length polymorphism (RFLP)-PCR. Protein levels of IL-10 in PF were measured by enzyme-linked immunosorbent assay (ELISA). There were no significant differences in the genotype and allele frequencies of IL-10 gene promoter polymorphisms at position -1082 between the endometriosis and the control groups. However, the frequency of -819 or -592 C alleles was significantly increased in patients with endometriosis compared with controls. The protein levels of IL-10 in PF were statistically higher in the endometriosis group than in the control group. Moreover, the polymorphisms at -1082, -819 and -592 sites were associated with protein levels of IL-10 in PF in the endometriosis group while in the control group only the polymorphisms at position -1082 correlated with protein levels. Increased frequency of -819 or -592 C allele and increased protein production of IL-10 in PF in patients with endometriosis compared with controls and correlations of polymorphisms at -819 and -592 sites with protein levels of IL-10 in PF in patients with endometriosis may suggest that polymorphisms at -819 and -592 sites and their protein production are associated with endometriosis risk.


[Damage to a stent caused by a Shaldon catheter].
Recently, stent implantation has been used with increasing frequency in the treatment of central venous stenoses in patients undergoing chronic haemodialysis. Stent localisation may interfere with central venous catheterisation. CASE REPORT. In a 57-year-old female haemodialysis patient, a filiform stenosis of the right subclavian vein was treated by percutaneous transvenous angioplasty and stent implantation. Five weeks later, she presented with a thrombosed dialysis shunt. A Shaldon catheter was implanted via the right internal jugular vein. Post-procedure radiographs showed extensive stent damage without stent dislocation or thrombosis. CONCLUSION. Stent localisation has to be considered in the event of later central venous catheterisation. Venous puncture should be carried out under fluoroscopic control if catheter placement on the side of the stent is inevitable.


Molecular interactions in celecoxib-PVP-meglumine amorphous system.
Stabilization of the amorphous form of a drug is conferred by additives that interact with it at the molecular level. Ternary systems of celecoxib, poly(vinyl pyrrolidone) (PVP) and meglumine were studied for molecular interactions responsible for enhanced drug stability and solubility in amorphous form. Meglumine was found to lower the glass transition temperature (T(g)) of the drug due to its plasticization effect. However, the presence of PVP masked its destabilizing effect and provided net anti-plasticization to the celecoxib-PVP-meglumine (7:2:1 w/w) ternary amorphous system. Positive deviation of the experimentally determined T(g mix) value for this composition, from those predicted by the Gordon-Taylor/Kelley-Bueche equation, inferred molecular interaction between the three species, which was also supported by band shifts from their Fourier-transform infra-red (FTIR) spectra. Further, shift of differential scanning calorimetry (DSC) melting endotherms of celecoxib in its amorphous systems from those observed for crystalline celecoxib confirmed the complexation between these components, which was also substantiated by molecular modelling studies that showed H-bonding of -S=O, 2-N of the pyrazole ring and -C-F groups of celecoxib with -O-H group of meglumine. These molecular interactions of amorphous celecoxib with meglumine were found to be the potential cause for enhanced stability and solubility of the celecoxib-PVP-meglumine ternary system.


Monoclonal IgM gammopathy with anti-myelin associated glycoprotein (MAG) activity and polyneuropathy. A study of three cases.
The authors describe three patients with a chronic sensory-motor polyneuropathy associated with a monoclonal IgM gammopathy. In each case, the M-component was shown to display an antibody activity against the Myelin-Associated Glycoprotein (MAG) in a western blot technique. Sera from the three patients stained specifically the myelin sheaths of normal human peripheral nerves after incubation with rabbit anti-IgM. Motor conduction velocities were very low in each case. Morphological studies of the sural nerve from one patient revealed a moderate loss of myelinated fibres, some onion-bulbs but also a microangiopathy and signs of axonal degeneration.


[Superficial siderosis of the CNS. 2 cases and a review of the literature].
Superficial siderosis of the CNS is a rare disease. The superficial deposition of haemosiderin in the cerebrum, cerebellum and spinal cord is due to chronic and recurrent subarachnoidal haemorrhage (SAH). Known sources of bleeding are vascular CNS-tumours, CSF-cavity lesions, vascular malformations, nerve root lesions and neurosurgical interventions. Detection of the source of bleeding is successful in only about 50% of cases. The clinical syndrome is characterized by sensorineural deafness, cerebellar ataxia and pyramidal signs. CSF-investigation might be indicative for SAH, while ferritin and ionic iron can be elevated in the CSF. CT is unspecific and insensitive but MR imaging of the brain and spinal cord is very sensitive and specific. The elimination of the source of bleeding alone might prevent the progression of the disease, therefore, an early and extensive search for this source is highly recommended.


Complexin-I-deficient sperm are subfertile due to a defect in zona pellucida penetration.
Upon adhesion to the zona pellucida, sperm undergo regulated exocytosis of the acrosome. Although it is necessary for sperm to penetrate the zona pellucida and fertilize an egg, the acrosomal membrane fusion process is poorly understood. Complexins I and II are small, cytosolic proteins that bind to a complex of proteins termed the soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex to regulate synaptic vesicle exocytosis. Complexin-II-deficient mice are fertile but the fertility of sperm from complexin-I-deficient male mice is unclear because the mice have ataxia and cannot mate. Here, we show that the genes encoding complexins I and II are expressed in primary spermatocytes and spermatids. Complexin proteins were found in/near the developing acrosome in spermatids and in or around the acrosome of mature sperm. Cell fractionation demonstrated that complexins I and II were predominantly found in the cytosolic fraction. Furthermore, sperm from complexin-I-deficient mice had normal morphology, number, and only small differences in motility, as assessed by computer-assisted semen analysis. Complexin-I-deficient sperm capacitated normally and bound to the zona pellucida. But when sperm from complexin-I-deficient mice were inseminated into females, a defect in fertility was observed, in concordance with previous data showing that in vitro fertilization rate was also reduced. If the zona pellucida was removed prior to in vitro fertilization, fertility was normal, demonstrating that zona pellucida penetration was defective, a step requiring acrosomal exocytosis. Therefore, complexin-I-deficient sperm are subfertile due to faulty zona pellucida penetration.


Dental implant therapy in the treatment of an oroantral communication after exodontia.
A new technique in which a dental implant was the ultimate therapy for the treatment of an oroantral communication (OAC) that was created subsequent to the extraction of a maxillary first molar is described. A search of the English-speaking literature has not revealed implant therapy as part of documented modalities for the treatment of an OAC created following dental extraction. The OAC was closed by a sandwich technique that uses two resorbable membrane materials (Bio-Gide, Osteohealth, Shirley, NY) that surround a bone substitute (Bio-Oss, Osteohealth). This procedure, together with additional onlay grafting with the same bone substitute, was used also to regenerate subantral bone to enable the subsequent placement of an endosseous implant after 12 months. An 8-month postoperative radiograph showed creation of a new maxillary sinus bony floor and subantral bone of good quality, and height that can permit the placement of an endosseous dental implant.


Management of hereditary antithrombin deficiency in pregnancy.
Antithrombin (AT) deficiency is a high-risk thrombophilia and a rare condition. Despite full anticoagulation during pregnancy and the postpartum period, women with AT deficiency may still be vulnerable to developing venous thromboembolism (VTE), including fatal events. There is limited guidance on the management of AT deficiency in pregnancy, including the role of AT concentrates. Following a comprehensive review of the state of the art with respect to recommendations and guidelines, our expert panel in maternal-fetal medicine, hematology and basic science reached consensus on key issues in the recognition and management of AT deficiency in pregnancy. This paper summarizes the state of the art and summarizes what we believe are best practices with special emphasis on a multidisciplinary approach involving obstetrics and hematology in the care of women with AT deficiency.


Effects of exercise on mortality rates of individuals with severe mental illness.
Persons with severe mental illness have a 10-to-20-year shorter life span than the general public. Excess morbidity and mortality in this patient population has been described as a major public health challenge worldwide. Despite robust extant literature on the role of exercise in reducing morbidity and mortality, especially from cardiovascular disease and diabetes (highly prevalent in this patient population), Very few clinical programs or clinical research projects currently exist to implement and study the effects of exercise on decreasing morbidity and mortality in this highly vulnerable patient population. Given the global lack of trained mental health providers, the need to integrate healthcare providers from different disciplines, such as nurses, physical therapists, occupational therapists, physician assistants, cannot be overstated. This mini-review will provide an historic perspective and current data supporting the need to establish exercise, and other Lifestyle Psychiatry interventions, as a key component of treatment for all patients with serious mental illness.


A Comparison between Thromboelastography and Conventional Clotting Tests in Pediatric Patients After Cardiopulmonary Bypass Procedure.
The coagulation system is more complicated in younger infants because the hemostatic system is not completely mature before 6 months. There is confusion among pediatricians to choose conventional coagulation tests and thromboelastography (TEG) to evaluate coagulation function for infants in major surgery. This study was undertaken to perform a comparison between the two methods for pediatric patients who underwent cardio-pulmonary bypass (CPB) surgery. Infant patients who underwent CPB surgery were divided into two groups - younger group (age < 6 months old, n = 72) and older group (age from 6 months old to 12 years old, n = 76). Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (Fib) of conventional coagulation tests and reaction time (R-time), speed of fibrin building up (ɑ-Angle), clot conformation time (K-time), maximum colt amplitude (MA) of TEG results before and after CPB, as well as increasing or decreasing rate of all the values after CPB, were compared between the two groups. Postoperative transfusion details were summarized. PT, APTT, R-time, and K-time markedly increased (p < 0.05) and Fib, ɑ-Angle, and MA decreased (p < 0.05) after CPB in both groups. The younger group had a much higher rate of postoperative transfusion with suspended red cells (54.17% vs. 17.11%), fresh frozen plasma (29.17% vs. 9.21%), cryoprecipitate (9.72% vs. 1.32%), and apheresis platelet (5.56% vs. 0) than the older group. Increasing rate of R-time and K-time and decreasing rate of ɑ-Angle and MA after CPB in the younger group were significantly higher than that in the older group (p < 0.01), whereas no significant differences were observed in conventional coagulation tests (p > 0.2). TEG was more sensitive than conventional coagulation tests in response to variation of coagulation function for younger infants after major surgery.


Effect of silver ions on transport and retention of phosphate by Escherichia coli.
Silver ions inhibited phosphate uptake and exchange in Escherichia coli and caused efflux of accumulated phosphate as well as of mannitol, succinate, glutamine, and proline. The effects of Ag+ were reversed by thiols and, to a lesser extent, by bromide. In the presence of N-ethylmaleimide and several uncouplers, Ag+ failed to cause phosphate efflux, but still inhibited exchange of intracellular and extracellular phosphate, indicating an interaction at more than one site. It is unlikely that Ag+ caused metabolite efflux by acting solely as an uncoupler, as an inhibitor of the respiratory chain, or as a thiol reagent.


DYSLIPIDEMIA IN MEXICO, A CALL FOR ACTION.
The purpose of this manuscript is to highlight the peculiarities of the Mexican population regarding the clinical expression, genetics, and treatment of lipid disorders. Furthermore, it is a call for action to address the existing gaps in care and research of dyslipidemias. The Mexican Mestizos are highly susceptible to metabolic disorders (i.e., low high-density lipoprotein cholesterol concentrations, hypertriglyceridemia, abdominal obesity, and type 2 diabetes); these conditions are associated with ethnic-specific genetic variants. On the other hand, despite the high prevalence of dyslipidemia in Mexican adults, there is a lack of awareness of these conditions. The public is not informed about the need for screening and the potential benefit of the lipid-lowering treatments. Underdiagnosis and undertreatment are two of the main challenges to be solved. Dyslipidemias are not among the priorities of the health systems for the prevention of cardiovascular disease; access to laboratory resources and medications is insufficient in primary care units despite the proven cost-benefit of the treatment of lipid disorders. Evidence-based public policies are needed to change the practice and allocation of assets to be capable of preventing cardiovascular diseases. Treatment of dyslipidemia should have a prominent role in any effort to decrease the number of preventable deaths caused by non-communicable diseases.


The safety and efficacy of bridging full-dose IV-IA thrombolysis in acute ischemic stroke patients with MCA occlusion: a comparison with IV thrombolysis alone.
Early recanalization of the occluded cerebral artery is substantial for clinical improvement in acute ischemic stroke (IS) patients. The rate of achieved recanalizations using IVT is low. The aim of this study was to compare the safety and efficacy of bridging full-dose intravenous-intraarterial (IV-IA) thrombolysis to IVT alone in acute IS patients with occluded MCA. Seventy-nine consecutive IS patients with MCA occlusion were treated either with IVT alone (historic controls, Group 1) or with full-dose IV-IA thrombolysis (Group 2). Stroke severity was evaluated using NIHSS, achieved recanalizations using transcranial Doppler (Group 1) or angiography (Group 2). Occurrence of ICH including SICH was evaluated after 24 hours. 90-day clinical outcome was evaluated using modified Rankin Scale (mRS). Group 1 consisted of 50 patients (24 males, mean age 70.8±10.2 years) and Group 2 of 29 patients (14 males, mean age 67.8±10.0 years). No difference was found in the initial NIHSS (median 16 vs. 17) and other baseline parameters including time from stroke onset to IVT. Patients treated with bridging therapy had a higher number of achieved MCA recanalization (75.9 vs. 32.0%, P=0.0002), similar number of SICH (6.0 vs. 6.9%, P=1.000) and 34.5% of them achieved mRS 0-2 versus 28.0% of patients treated with IVT (P=0.546). Patients with shorter TR had significantly better clinical outcome (P=0.019). Bridging IV-IA thrombolysis seems to be safe and more effective than IVT alone in acute stroke patients with MCA occlusion.


Prevention of gestational diabetes: feasibility issues for an exercise intervention in obese pregnant women.
To examine the feasibility of an individualized exercise program to prevent gestational diabetes mellitus (GDM) in obese pregnant women. The study was a pilot randomized controlled trial with obese pregnant women (intervention group, individualized exercise program [n = 25]; control group, usual care [n = 25]). Average weekly energy expenditure (MET hours per week and kilocalories per week) of exercise-specific activity was assessed during pregnancy using the Pregnancy Physical Activity Questionnaire. Fasting glucose and insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were assessed at baseline and 20, 28, and 36 weeks' gestation. Of the women in the intervention group, 16 of 22 (73%) achieved more than 900 kcal/week of exercise-based activity at 28 weeks compared with 8 of 19 women in the control group (42%), P = 0.047. However, insulin resistance (HOMA-IR) did not differ between the groups. This intervention was feasible and prompted a modest increase in physical activity. However, we are not confident that this intervention would be sufficient to prevent GDM.


Successful resection of thymoma directly invading the right atrium under cardiopulmonary bypass.
We present the case of an invasive thymoma with severe compression of the right atrium, and infiltration of the atrial wall, causing a superior vena cava (SVC) syndrome. The tumour was resected under cardiopulmonary bypass en bloc with the atrial wall. A bovine pericardial patch was used for atrial reconstruction. We obtained a complete resection of the tumour and regression of symptoms, and, after 1 year of the follow-up, no signs of recurrence are evident. To our knowledge, this is the first case of thymoma directly invading the right atrium, without involvement of the SVC. In this setting, the aggressive surgical approach led to an immediate resolution of the symptoms and contributed to prolonged long-term survival.


Evolution and biogeography of the slipper orchids: Eocene vicariance of the conduplicate genera in the Old and New World Tropics.
Intercontinental disjunctions between tropical regions, which harbor two-thirds of the flowering plants, have drawn great interest from biologists and biogeographers. Most previous studies on these distribution patterns focused on woody plants, and paid little attention to herbs. The Orchidaceae is one of the largest families of angiosperms, with a herbaceous habit and a high species diversity in the Tropics. Here we investigate the evolutionary and biogeographical history of the slipper orchids, which represents a monophyletic subfamily (Cypripedioideae) of the orchid family and comprises five genera that are disjunctly distributed in tropical to temperate regions. A relatively well-resolved and highly supported phylogeny of slipper orchids was reconstructed based on sequence analyses of six maternally inherited chloroplast and two low-copy nuclear genes (LFY and ACO). We found that the genus Cypripedium with a wide distribution in the northern temperate and subtropical zones diverged first, followed by Selenipedium endemic to South America, and finally conduplicate-leaved genera in the Tropics. Mexipedium and Phragmipedium from the neotropics are most closely related, and form a clade sister to Paphiopedilum from tropical Asia. According to molecular clock estimates, the genus Selenipedium originated in Palaeocene, while the most recent common ancestor of conduplicate-leaved slipper orchids could be dated back to the Eocene. Ancestral area reconstruction indicates that vicariance is responsible for the disjunct distribution of conduplicate slipper orchids in palaeotropical and neotropical regions. Our study sheds some light on mechanisms underlying generic and species diversification in the orchid family and tropical disjunctions of herbaceous plant groups. In addition, we suggest that the biogeographical study should sample both regional endemics and their widespread relatives.


Burden and cost of multiple sclerosis in Brazil.
The objective of this study was to estimate costs to society and patients' quality of life (QoL) at all levels of disease severity (measured with the Expanded Disability Status Scale, EDSS) in Brazil. The study was part of an international, cross-sectional burden-of-illness study carried out in collaboration with national MS patient organizations. All information was collected directly from patients using a validated questionnaire. Direct costs were estimated both from societal and payer perspectives, while total costs are presented as societal costs. The survey included 694 patients (response rate 21%; mean age 40.8 years). 95% of patients were of working age, and around half were working. The mean EDSS score was 3.2 (62.5% of patients with EDSS <3). Relapses were reported by 18.9% of patients. Fatigue affected almost all patients (94%) regardless of EDSS level, and cognitive difficulties were reported by 69.1% of patients. Mean utility ranged from 0.77 at EDSS 0 to negative values at EDSS 9, with a mean score of 0.58; utility was affected by relapses. Total mean annual cost was R$33,872 (€ 8,000) per patient in the societal perspective, with direct costs representing 81% (R$ 27,355, € 6,500). Direct costs for the payer amounted to R$ 16,793 (€ 4,000)/patient. This study included a population with relatively mild and early disease, with a majority of patients with relapsing disease and thus on DMD treatment. It is not possible to conclude directly on the total cost of MS in Brazil. Nevertheless, resource quantities used, QoL and MS symptoms are very similar to what was seen in the European survey.


Pioglitazone Confers Neuroprotection Against Ischemia-Induced Pyroptosis due to its Inhibitory Effects on HMGB-1/RAGE and Rac1/ROS Pathway by Activating PPAR-ɤ.
Recent researches highlighted the protective potential of pioglitazone, a PPAR-γ agonist, in the progression of cerebral ischemia-reperfusion injury. However, there has been no study on the application of pioglitazone in treating ischemic stroke through mechanisms involving pyroptosis. The cerebral injury was established by middle cerebral artery occlusion (MCAO). in vitro ischemia in primary cultured astrocytes was induced by the oxygen-glucose deprivation (OGD). ELISA and Western Blot analysis were employed to the levels of PPAR-γ, pyroptosis-related biomarkers and cytoplasmic translocation of HMGB-1 and RAGE expression as well as Rac1 activity, respectively. We demonstrated that repeated intraperitoneal administration of pioglitazone remarkably reduced the infarct volume, improved neurological deficits and suppressed the Rac1 activity with significant reduction of excessive ROS in rat model of middle cerebral artery occlusion (MCAO). Moreover, pioglitazone alleviated the up-regulation of pyroptosis-related biomarkers and the increased cytoplasmic translocation of HMGB-1 and RAGE expression in cerebral penumbra cortex. Similarly, the protective effects of pioglitazone on cultured astrocytes were characterized by reduced Rac1 activity, pyroptosis related protein expressions and lactate dehydrogenase (LDH) release. However, these protective effects of pioglitazone were neutralized with the use of GW9662, a PPAR-γ inhibitor. Interestingly, Rac1 knockdown in lentivirus with the Rac1 small hair RNA (shRNA) could inhibit the OGD-induced pyroptosis of primary cultured astrocytes. Furthermore, the combination of Rac1-shRNA and pioglitazone can further strengthen the inhibitory effects on pyroptosis induced by OGD. The neuroprotection of pioglitazone was attributable to the alleviated ischemia/hypoxia-induced pyroptosis and was also associated with the PPARγ-mediated suppression of HGMB-1/RAGE signaling pathway. Moreover, the inhibition of Rac1 promoted this function.


Anticancer effect of myristicin on hepatic carcinoma and related molecular mechanism.
Myristicin is a natural active compound that has inflammatory, antimicrobial and anti-proliferative properties. Yet, its effect on hepatic carcinoma has not been investigated. To explore the role and related molecular mechanism of myristicin in hepatic carcinoma in vitro. Human hepatic carcinoma cell lines (Huh-7 and HCCLM3 cells) were treated with different concentrations of myristicin (0.5, 1 and 5 mM) for 24, 48 and 72 h. Then, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium assay (MTT), flow cytometer (FCM) analysis and transwell assay were performed to determine cell proliferation, apoptosis and migration/invasion, respectively. Protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X (Bax), E-cadherin, N-cadherin and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway-related proteins were detected using Western blot assay. Gene expression was determined using quantitative real time-polymerase chain reaction (qRT-PCR). Myristicin inhibited cell proliferation and induced apoptosis in Huh-7 and HCCLM3 cells; suppressed cell migration and invasion ability, and increased E-cadherin expression and decreased N-cadherin expression, thereby inhibiting epithelial-mesenchymal transition (EMT). Finally, the findings indicated that myristicin decreased phosphorylated (p)-mTOR and p-AKT expression at the protein level. Myristicin exerts an efficient therapeutic effect on hepatic carcinoma by suppressing PI3K/Akt/mTOR signalling pathway; thus, it may be used as a new potential drug for hepatic carcinoma treatment.


Taltirelin alleviates fatigue-like behavior in mouse models of cancer-related fatigue.
Fatigue affects most cancer patients and has numerous potential causes, including cancer itself and cancer treatment. Cancer-related fatigue (CRF) is not relieved by rest, can decrease quality of life, and has no FDA-approved therapy. Thyrotropin-releasing hormone (TRH) has been proposed as a potential novel treatment for CRF, but its efficacy against CRF remains largely untested. Thus, we tested the TRH analog, taltirelin (TAL), in mouse models of CRF. To model fatigue, we used a mouse model of chemotherapy, a mouse model of radiation therapy, and mice bearing colon 26 carcinoma tumors. We used the treadmill fatigue test to assess fatigue-like behavior after treatment with TAL. Additionally, we used wild-type and TRH receptor knockout mice to determine which TRH receptor was necessary for the actions of TAL. Tumor-bearing mice displayed muscle wasting and all models caused fatigue-like behavior, with mice running a shorter distance in the treadmill fatigue test than controls. TAL reversed fatigue-like behavior in all three models and the mouse TRH1 receptor was necessary for the effects of TAL. These data suggest that TAL may be useful in alleviating fatigue in all cancer patients and provide further support for evaluating TAL as a potential therapy for CRF in humans.


Subwavelength grating microlens with taper-resistant characteristics.
The subwavelength grating microlens has attracted much attention due to its variety of potential applications. Instead of the vertical sidewall profile normally considered by most recent works, a tapered sidewall profile is often obtained during current fabrication processes, especially during the fabrication of high aspect ratio structures. In this work, we have discovered that a tapered sidewall profile may have a significant destructive effect on the concentration properties of subwavelength concentrating lenses/metasurfaces. This is caused by the phase shift from the tapered profile that affects each individual phase shifter. More interestingly, we have further discovered that there exist some period/fill-factor combinations for phase shifters that "resist" the phase shift from the tapered structure. This study will provide an important avenue for the design of subwavelength concentrating lenses/metasurfaces when dealing with the tapered sidewall profile.


De novo assembly and transcriptome analysis of two contrary tillering mutants to learn the mechanisms of tillers outgrowth in switchgrass (Panicum virgatum L.).
Tillering is an important trait in monocotyledon plants. The switchgrass (Panicum virgatum), studied usually as a source of biomass for energy production, can produce hundreds of tillers in its lifetime. Studying the tillering of switchgrass also provides information for other monocot crops. High-tillering and low-tillering mutants were produced by ethyl methanesulfonate mutagenesis. Alteration of tillering ability resulted from different tiller buds outgrowth in the two mutants. We sequenced the tiller buds transcriptomes of high-tillering and low-tillering plants using next-generation sequencing technology, and generated 34 G data in total. In the de novo assembly results, 133,828 unigenes were detected with an average length of 1,238 bp, and 5,290 unigenes were differentially expressed between the two mutants, including 3,225 up-regulated genes and 2,065 down-regulated genes. Differentially expressed gene analysis with functional annotations was performed to identify candidate genes involved in tiller bud outgrowth processes using Gene Ontology classification, Cluster of Orthologous Groups of proteins, and Kyoto Encyclopedia of Genes and Genomes pathway analysis. This is the first study to explore the tillering transcriptome in two types of tillering mutants by de novo sequencing.


Molecular basis for C-degron recognition by CRL2APPBP2 ubiquitin ligase.
E3 ubiquitin ligases determine the specificity of eukaryotic protein degradation by selective binding to destabilizing protein motifs, termed degrons, in substrates for ubiquitin-mediated proteolysis. The exposed C-terminal residues of proteins can act as C-degrons that are recognized by distinct substrate receptors (SRs) as part of dedicated cullin-RING E3 ubiquitin ligase (CRL) complexes. APPBP2, an SR of Cullin 2-RING ligase (CRL2), has been shown to recognize R-x-x-G/C-degron; however, the molecular mechanism of recognition remains elusive. By solving several cryogenic electron microscopy structures of active CRL2APPBP2 bound with different R-x-x-G/C-degrons, we unveiled the molecular mechanisms underlying the assembly of the CRL2APPBP2 dimer and tetramer, as well as C-degron recognition. The structural study, complemented by binding experiments and cell-based assays, demonstrates that APPBP2 specifically recognizes the R-x-x-G/C-degron via a bipartite mechanism; arginine and glycine, which play critical roles in C-degron recognition, accommodate distinct pockets that are spaced by two residues. In addition, the binding pocket is deep enough to enable the interaction of APPBP2 with the motif placed at or up to three residues upstream of the C-end. Overall, our study not only provides structural insight into CRL2APPBP2-mediated protein turnover but also serves as the basis for future structure-based chemical probe design.


ER-stress-associated functional link between Parkin and DJ-1 via a transcriptional cascade involving the tumor suppressor p53 and the spliced X-box binding protein XBP-1.
Parkin and DJ-1 are two multi-functional proteins linked to autosomal recessive early-onset Parkinson's disease (PD) that have been shown to functionally interact by as-yet-unknown mechanisms. We have delineated the mechanisms by which parkin controls DJ-1. Parkin modulates DJ-1 transcription and protein levels via a signaling cascade involving p53 and the endoplasmic reticulum (ER)-stress-induced active X-box-binding protein-1S (XBP-1S). Parkin triggers the transcriptional repression of p53 while p53 downregulates DJ-1 protein and mRNA expressions. We show that parkin-mediated control of DJ-1 is fully p53-dependent. Furthermore, we establish that p53 lowers the protein and mRNA levels of XBP-1S. Accordingly, we show that parkin ultimately upregulates XBP-1 levels. Subsequently, XBP-1S physically interacts with the DJ-1 promoter, thereby enhancing its promoter trans-activation, mRNA levels and protein expression. This data was corroborated by the examination of DJ-1 in both parkin- and p53-null mice brains. This transcriptional cascade is abolished by pathogenic parkin mutations and is independent of its ubiquitin-ligase activity. Our data establish a parkin-dependent ER-stress-associated modulation of DJ-1 and identifies p53 and XBP-1 as two major actors acting downstream of parkin in this signaling cascade in cells and in vivo. This work provides a mechanistic explanation for the increase in the unfolded protein response observed in PD pathology, i.e. that it is due to a defect in parkin-associated control of DJ-1.


Neuroligin-associated microRNA-932 targets actin and regulates memory in the honeybee.
Increasing evidence suggests small non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) control levels of mRNA expression during experience-related remodelling of the brain. Here we use an associative olfactory learning paradigm in the honeybee Apis mellifera to examine gene expression changes in the brain during memory formation. Brain transcriptome analysis reveals a general downregulation of protein-coding genes, including asparagine synthetase and actin, and upregulation of ncRNAs. miRNA-mRNA network predictions together with PCR validation suggest miRNAs including miR-210 and miR-932 target the downregulated protein-coding genes. Feeding cholesterol-conjugated antisense RNA to bees results in the inhibition of miR-210 and of miR-932. Loss of miR-932 impairs long-term memory formation, but not memory acquisition. Functional analyses show that miR-932 interacts with Act5C, providing evidence for direct regulation of actin expression by an miRNA. An activity-dependent increase in miR-932 expression may therefore control actin-related plasticity mechanisms and affect memory formation in the brain.


Structure, stability, and infrared spectroscopy of (H2O)nNH4(+) clusters: a theoretical study at zero and finite temperature.
The combined effects of size and temperature on the stable structures of water clusters doped with one ammonium molecule have been investigated theoretically using an empirical potential and density-functional theory (DFT) calculations. Global optimization with Monte Carlo methods has been performed using an explicit intermolecular potential based on the Kozack-Jordan polarizable model. Putative lowest-energy structures based on this empirical potential are reported. Our results indicate a high propensity for the NH(4)(+) impurity to be fully solvated by water molecules. Clathratelike patterns are formed for clusters containing more than 11 molecules. Local reoptimizations of candidate structures carried out at the DFT level with the B3LYP hybrid functional and the 6-311++G(d,p) basis set confirm the general trends obtained with the intermolecular potential. However, some reorderings between isomers often due to zero-point energy corrections are found in small clusters, leading to stable geometries in agreement with other first-principles studies. Temperature effects have been assessed using a simple harmonic superposition approximation for selected cluster sizes and using dedicated Monte Carlo simulations for (H(2)O)(20)NH(4)(+). The clusters are found to melt near 200 K, and possibly isomerize already below 50 K. The free energy barrier for core/surface isomerization of the impurity in the 21-molecule cluster is estimated to be only a few kcal/mol at 150 K. The vibrational spectroscopic signatures of the clusters obtained from the electronic structure calculations show the usual four O-H stretching bands. As the cluster size increases, the double acceptor-single donor band near 3700 cm(-1) increasingly dominates over the three other bands. While we do not find conclusive evidence for a O-H stretching spectroscopic signature of the ammonium impurity to be in the core or at the surface in the 20-molecule cluster, a possible signature via the N-H stretching bands is suggested near 2800-2900 cm(-1). In the larger (H(2)O)(49)NH(4)(+) cluster, the impurity is slightly more stable at the surface.


Polymorphisms of xenobiotic metabolizing genes in oropharyngeal carcinoma.
The objective was to determine the prevalence of the polymorphisms of the microsomal epoxide hydrolase (Ephx1), glutathione S-transferase mu1 (GSTM ), theta1 (GSTT1), and pi1 (GSTP1) genes in patients with oropharyngeal carcinoma. Gene polymorphisms in 137 patients with oropharyngeal carcinoma were determined by polymerase chain reaction and restriction enzyme digestion for xenobiotic metabolizing enzymes that have been implicated in the carcinogenesis of tobacco-related neoplasias and compared with a population sample of 99 persons. At Ephx1 (microsomal epoxide hydrolase) codon 113, an overrepresentation of the greater activity genotype (Tyr/Tyr) was observed for male ever-smokers alone, both male and female ever-smokers, female never-smokers alone, and in both male and female never-smokers, compared with a control population sample. At codon 139, Ephx1 showed no differences. There was an overrepresentation of homozygosity for the GSTT1 (glutathione S-transferase theta1) null allele [but not for the GSTM1 (glutathione S-transferase mu1) null allele] in ever-smokers, when compared with controls. Polymorphisms at the GSTP1 (glutathione S-transferase pi1) locus did not show differences versus controls, although in the never-smoker cancer sample there was a higher prevalence of the B/B genotype compared with ever-smokers. The Ephx1 codon 113 Tyr/Tyr variant, as well as homozygosity for the GSTT1 null allele, is associated with oropharyngeal carcinogenesis.


Haplotype analysis of the mitochondrial DNA d-loop region reveals the maternal origin and historical dynamics among the indigenous goat populations in east and west of the Democratic Republic of Congo.
This study aimed at assessing haplotype diversity and population dynamics of three Congolese indigenous goat populations that included Kasai goat (KG), small goat (SG), and dwarf goat (DG) of the Democratic Republic of Congo (DRC). The 1169 bp d-loop region of mitochondrial DNA (mtDNA) was sequenced for 339 Congolese indigenous goats. The total length of sequences was used to generate the haplotypes and evaluate their diversities, whereas the hypervariable region (HVI, 453 bp) was analyzed to define the maternal variation and the demographic dynamic. A total of 568 segregating sites that generated 192 haplotypes were observed from the entire d-loop region (1169 bp d-loop). Phylogenetic analyses using reference haplotypes from the six globally defined goat mtDNA haplogroups showed that all the three Congolese indigenous goat populations studied clustered into the dominant haplogroup A, as revealed by the neighbor-joining (NJ) tree and median-joining (MJ) network. Nine haplotypes were shared between the studied goats and goat populations from Pakistan (1 haplotype), Kenya, Ethiopia and Algeria (1 haplotype), Zimbabwe (1 haplotype), Cameroon (3 haplotypes), and Mozambique (3 haplotypes). The population pairwise analysis (FST ) indicated a weak differentiation between the Congolese indigenous goat populations. Negative and significant (p-value <.05) values for Fu's Fs (-20.418) and Tajima's (-2.189) tests showed the expansion in the history of the three Congolese indigenous goat populations. These results suggest a weak differentiation and a single maternal origin for the studied goats. This information will contribute to the improvement of the management strategies and long-term conservation of indigenous goats in DRC.


Sulphasalazine and lung toxicity.
Sulphasalazine prescribing is on the increase. Pulmonary toxicity and blood dyscrasias are rare side-effects. Numerous case reports have been published implicating sulphasalazine in pulmonary toxicity. The authors searched the literature for cases of sulphasalazine induced lung toxicity and the 50 cases identified are discussed here. All published case reports/letters referring to sulphasalazine and lung toxicity were studied. The search terms "sulphasalazine" and "sulfasalazine" were combined with the terms "lung", "pulmonary disease", "pneumonitis" and "pleuritis" using Medline and PubMed databases. Typical presentation of sulphasalazine-induced lung disease was with new onset dyspnoea and infiltrates on chest radiography. Common symptoms were cough and fever. Crepitations on auscultation and peripheral eosinophilia were noted in half of the cases. Sputum production, allergy history, rash, chest pain and weight loss were inconsistent findings. Pulmonary pathology was variable, the commonest being eosinophilic pneumonia with peripheral eosinophilia and interstitial inflammation with or without fibrosis. Fatal reports were infrequent. Most patients were managed by drug withdrawal with 40% prescribed corticosteroids. In conclusion, sulphasalazine lung disease should be distinguished from interstitial lung disease due to underlying primary disease. Despite the increase in sulphasalazine prescribing, pulmonary toxicity remains rare. The majority of patients with suspected sulphasalazine-induced lung disease improved within weeks of drug withdrawal and the need for corticosteroids is debatable.


Clinical severity of human infections with avian influenza A(H7N9) virus, China, 2013/14.
Assessing the severity of emerging infections is challenging because of potential biases in case ascertainment. The first human case of infection with influenza A(H7N9) virus was identified in China in March 2013; since then, the virus has caused two epidemic waves in the country. There were 134 laboratory-confirmed cases detected in the first epidemic wave from January to September 2013. In the second epidemic wave of human infections with avian influenza A(H7N9) virus in China from October 2013 to October 2014, we estimated that the risk of death among hospitalised cases of infection with influenza A(H7N9) virus was 48% (95% credibility interval: 42-54%), slightly higher than the corresponding risk in the first wave. Age-specific risks of death among hospitalised cases were also significantly higher in the second wave. Using data on symptomatic cases identified through national sentinel influenza-like illness surveillance, we estimated that the risk of death among symptomatic cases of infection with influenza A(H7N9) virus was 0.10% (95% credibility interval: 0.029-3.6%), which was similar to previous estimates for the first epidemic wave of human infections with influenza A(H7N9) virus in 2013. An increase in the risk of death among hospitalised cases in the second wave could be real because of changes in the virus, because of seasonal changes in host susceptibility to severe infection, or because of variation in treatment practices between hospitals, while the increase could be artefactual because of changes in ascertainment of cases in different areas at different times.


Synthesis and application of glutaric dihydrazide modified multiwalled carbon nanotubes for selective solid-phase extraction and preconcentration of Cu(II), Zn(II), Ni(II), and Fe(III).
An SPE method for selective separation-preconcentration of Cu(ll), Zn(II), Ni(II), and Fe(III) on multiwalled carbon nanotubes (MWCNTs) modified by glutaric dihydrazide prior to flame atomic absorption spectrometric determination was investigated. The adsorption was achieved quantitatively on MWCNTs at pH 5.0, and then the retained metal ions on the adsorbent were eluted with 1 M HNO3. The effects of analytical parameters including pH of the solution, eluent type, sample volume, and matrix ions were investigated for optimization of the presented procedure. The adsorption capacity of the adsorbent at optimum conditions was found to be 33.6, 29.2, 22.1, and 36.0 mg/g for Cu(ll), Zn(ll), Ni(ll), and Fe(lll), respectively. The LOD values of the method were 0.21, 0.11, 0.24, and 0.27 microg/L for Cu(ll), Zn(ll), Ni(ll), and Fe(lll), respectively. The RSDs were lower than 3.01%. The method was applied for the determination of analytes in soil, river water, and wastewater samples with satisfactory results.


Status of insecticide resistance in Anopheles mosquitoes in Ubon Ratchathani province, Northeastern Thailand.
Malaria is common in hilly, forested areas along national borders in Southeast Asia. Insecticide resistance in malaria vectors has been detected in a few countries in the Greater Mekong sub-region (GMS), representing a threat to malaria control and prevention. This study aims to determine the insecticide resistance status of Anopheles mosquitoes in Ubon Ratchathani province, northeastern Thailand, where increasing number of malaria cases were reported recently. Mosquitoes were collected in 2013-2015 using human landing and cattle bait collections in six sites during both the rainy and dry seasons. Mosquitoes were first morphologically identified to species and their susceptibility status to deltamethrin (0.05%), permethrin (0.75%) and DDT (4%) investigated, according to WHO guidelines. Bioassays with the synergists PBO and DEF were carried out to address the role of detoxifying enzymes in insecticide resistance. DNA sequencing of a fragment of the voltage-gated sodium channel gene was carried out to detect knock-down resistance (kdr) substitutions at position 1014 in resistant species. Due to low vector abundance, complete bioassays (n ≥ 100 mosquitoes) were only achieved for Anopheles hyrcanus s.l., which was resistant to all insecticides tested (mortality ranged from 45 to 87%). Suspected resistance to DDT was found in Anopheles barbirostris s.l. (mortality 69%), but it was susceptible to deltamethrin (mortality 97-100%) and permethrin (mortality 100%). Although insufficient number of primary vectors were collected, results showed that Anopheles dirus s.l. and Anopheles maculatus s.l. were susceptible to deltamethrin (mortality 100%). Anopheles nivipes and Anopheles philippinensis were susceptible to all three insecticides. PBO significantly increased mortality to deltamethrin and permethrin in pyrethroid-resistant An. hyrcanus s.l. None of the sequenced specimens presented the L1014F or L1014S mutation. This study shows that insecticide resistance is present in potential malaria vectors in northeastern Thailand. The absence of kdr mutations in all Anopheles species tested suggests that metabolic resistance is the main mechanism of pyrethroid resistance. This study provides new findings about insecticide susceptibility status of potential malaria vectors in northeastern Thailand that are deemed important to guide malaria vector control.


Th17-related cytokines in mucositis: is there any difference between peri-implantitis and periodontitis patients?
This study aimed to compare Th17-related cytokines named IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, sCD40L and TNF-α in peri-implant fluid (PIF) from mucositis sites in patients having either peri-implantitis, periodontitis or without interproximal alveolar bone loss. Thirty-three patients diagnosed with peri-implant mucositis were divided into three groups: individuals with peri-implant mucositis but without any signs of interproximal alveolar bone loss (group 1, n = 10), individuals with peri-implantitis (group 2, n = 14) and individuals with periodontitis (group 3, n = 9). Probing depth (PD), clinical attachment level (CAL), visible plaque index and bleeding on probing were measured. PIF was collected from mucositis sites in patients from the three groups and from peri-implantitis (group 2) and periodontitis sites (group 3). Cytokines were measured by a bead-based multiplex assay. Probing depth was significantly lower in group 1 when compared to both groups 2 and 3 (P < 0.001 and P = 0.01, respectively). There was no significant difference in cytokine levels in mucositis sites among the three groups. In group 2, IL-21 level was significantly higher in mucositis compared to peri-implantitis sites (P = 0.04). The expression of Th17-related cytokines in PIF from mucositis sites seems to be similar regardless the presence or not of alveolar bone loss around implants or teeth.


Methylation level of potato gene OMT30376 regulates tuber anthocyanin transformations.
After anthocyanin synthesis, a variety of anthocyanin compounds are produced through further methylation, glycosylation, and acylation. However, the effect of the potato methylase gene on anthocyanin biosynthesis has not been reported. Red and purple mutation types appear in tubers of the potato cultivar 'Purple Viking' with chimeric skin phenotypes. In this study, transcriptome and anthocyanin metabolome analyses were performed on skin of Purple Viking tubers and associated mutants. According to the metabolome analysis, the transformation of delphinidin into malvidin-3-O-glucoside and petunidin 3-O-glucoside and that of cyanidin into rosinidin O-hexoside and peonidin-3-O-glucoside were hindered in red tubers. Expression of methyltransferase gene OMT30376 was significantly lower in red tubers than in purple ones, whereas the methylation level of OMT30376 was significantly higher in red tubers. In addition, red skin appeared in tubers from purple tuber plants treated with S-adenosylmethionine (SAM), indicating the difference between purple and red was caused by the methylation degree of the gene OMT30376. Thus, the results of the study suggest that the OMT30376 gene is involved in the transformation of anthocyanins in potato tubers. The results also provide an important reference to reveal the regulatory mechanisms of anthocyanin biosynthesis and transformation.


Polymer curing assisted formation of optically visible sub-micron blisters of multilayer graphene for local strain engineering.
The local or global straining techniques are used to modulate the electronic, vibrational and optical properties of the two-dimensional (2D) materials. However, manipulating the physical properties of a 2D material under a local strain is comparatively more challenging. In this work, we demonstrate an easy and efficient polymer curing assisted technique for the formation of optically visible multilayer graphene (MLG) blisters of different shapes and sizes. The detailed spectroscopic and morphological analyses have been employed for exploring the dynamics of the confined matter inside the sub-micron blisters, which confirms that the confined matter inside the blister is liquid (water). From further analyses, we find the nonlinear elastic plate model as an acceptable model under certain limits for the mechanical analyses of the MLG blisters over the (poly)vinyl alcohol (PVA) polymer film to estimate the MLG-substrate interfacial adhesion energy and confinement pressure inside the blisters. The findings open new pathways for exploiting the technique for the formation of sub-micron blisters of the 2D materials for local strain-engineering applications, as well as the temperature-controlled release of the confined matter.


The short-term safety of adjuvant paclitaxel plus trastuzumab - A single centre experience.
HER2-amplified breast cancer (BC) has a poor prognosis. The combination of trastuzumab with chemotherapy in the adjuvant setting decreases recurrence and improves overall survival in HER2-positive BC. However, the role of adjuvant treatment in patients with HER2-amplified small BC without lymph node involvement is still under debate. The purpose of this study was to investigate the safety of adjuvant paclitaxel and trastuzumab (APT) in this group of patients. A total of 87 operated early BC patients without lymph node involvement (N0) were treated with APT for 12 weeks followed by trastuzumab alone for a total of 9 months. Clinicopathological features and adverse events were analyzed. The median patient age was 50 years (range 28- 82), and 51% of them were postmenopausal. The median tumor diameter was 2.4 cm (range 0.5-6), with 51% of the patients having tumor size between 2 and 3 cm. Eighty-one percent of patients had invasive ductal carcinoma (IDC), and 64% had grade 3 tumors. Adjuvant hormone therapy and adjuvant radiotherapy were administered to 65 and 54% of patients, respectively. At a median follow up of 13 months (range 6-38), one patient (1.1%, 95% CI 0-3.4) experienced an asymptomatic decrease in left ventricular ejection fraction (LVEF) and 3 patients (3.4%, 95% CI 0-6.9) experienced grade 3 neuropathy. APT appears to be a safe combination in early-stage, HER2-amplified and node-negative BC.


Effect of pioglitazone and its combination with statins in coronary artery disease patients with hyperinsulinemia.
The objective of the study was to demonstrate the effect of pioglitazone and pioglitazone in combination with statin on East Indian patients with hyperinsulinemia and hyperlipidemia. It was a randomized, placebo-controlled, double-blind study with a parallel-group design comprising 83 patients. Patients of either sex with cardiac complications, including hyperlipidemia and (or) diabetes mellitus with or without hyperinsulinemia, were enrolled. Patients over 70 years of age, with renal or hepatic failure, or with severe diabetes mellitus (total glucose >400 mg/dL) were excluded from the study. Enrolled patients were randomly assigned to 4 groups that received placebo, pioglitazone, atorvastatin, or both. Blood samples were collected before and after treatment for analysis of serum glucose, insulin, lipid profile, apolipoprotein (apo) A1, apo B, and fibrinogen. Data were compared with that of patients with normal insulin or hyperinsulinemia. The patients with hyperinsulinemia receiving only pioglitazone showed a significant decrease in insulin levels compared with those with normal insulin levels. These patients also showed a significant increase in HDL levels. However, no significant change was observed in patients treated with both atorvastatin and pioglitazone. Pioglitazone was also found to increase significantly the apo A1 levels in patients with hyperinsulinemia, but there was no significant increase in patients given both atorvastatin and pioglitazone. Our data suggests that pioglitazone should be given preferably to the patients with hyperinsulinemia and statin should not be coadministered.


Diagnosis of mesothelioma with deep learning.
Malignant mesothelioma (MM) is a rare but aggressive cancer. The definitive diagnosis of MM is critical for effective treatment and has important medicolegal significance. However, the definitive diagnosis of MM is challenging due to its composite epithelial/mesenchymal pattern. The aim of the current study was to develop a deep learning method to automatically diagnose MM. A retrospective analysis of 324 participants with or without MM was performed. Significant features were selected using a genetic algorithm (GA) or a ReliefF algorithm performed in MATLAB software. Subsequently, the current study constructed and trained several models based on a backpropagation (BP) algorithm, extreme learning machine algorithm and stacked sparse autoencoder (SSAE) to diagnose MM. A confusion matrix, F-measure and a receiver operating characteristic (ROC) curve were used to evaluate the performance of each model. A total of 34 potential variables were analyzed, while the GA and ReliefF algorithms selected 19 and 5 effective features, respectively. The selected features were used as the inputs of the three models. SSAE and GA+SSAE demonstrated the highest performance in terms of classification accuracy, specificity, F-measure and the area under the ROC curve. Overall, the GA+SSAE model was the preferred model since it required a shorter CPU time and fewer variables. Therefore, the SSAE with GA feature selection was selected as the most accurate model for the diagnosis of MM. The deep learning methods developed based on the GA+SSAE model may assist physicians with the diagnosis of MM.


Fungicin M4: a narrow spectrum peptide antibiotic from Bacillus licheniformis M-4.
The strain Bacillus licheniformis M-4 produces a 3.4 kDa hydrophilic peptide with antifungal activity, named fungicin M4. Analysis of the purified peptide shows that it contains the amino acids Glu (8), Arg (5), Pro (4), Tyr (8), Val (3), Met (2) and Orn (4). Its inhibitory spectrum is restricted to Microsporum canis CECT 2797, Mucor mucedo CECT 2653, Mucor plumbeus CCM 443, Sporothrix schenckii CECT 2799, Bacillus megaterium and Corynebacterium glutamicum CECT 78. Fungicin M4 exerts biocidal activity on liquid cultures of Sporothrix schenckii CECT 2799.


Group-level self-definition and self-investment: a hierarchical (multicomponent) model of in-group identification.
Recent research shows individuals' identification with in-groups to be psychologically important and socially consequential. However, there is little agreement about how identification should be conceptualized or measured. On the basis of previous work, the authors identified 5 specific components of in-group identification and offered a hierarchical 2-dimensional model within which these components are organized. Studies 1 and 2 used confirmatory factor analysis to validate the proposed model of self-definition (individual self-stereotyping, in-group homogeneity) and self-investment (solidarity, satisfaction, and centrality) dimensions, across 3 different group identities. Studies 3 and 4 demonstrated the construct validity of the 5 components by examining their (concurrent) correlations with established measures of in-group identification. Studies 5-7 demonstrated the predictive and discriminant validity of the 5 components by examining their (prospective) prediction of individuals' orientation to, and emotions about, real intergroup relations. Together, these studies illustrate the conceptual and empirical value of a hierarchical multicomponent model of in-group identification.


THE BIOLOGICAL ACTIVITIES OF MOLTKIA AUREA BOISS., AN ENDEMIC SPECIES TO TURKEY.
Staphylococcus aureus is the direct reason of mastitis. Mastitis is a disease characterized by pathological changes in mammary glands as well as physical, chemical, bacteriological changes in milk. This disease causes loses in milk yield and quality. In recent years, it is reported that mastitis pathogens have developed a resistance to antibiotics as a natural consequence of widespread use of it. Today's researches are focused on discovering and using new antibiotics against bacteria. The aim of this paper is to examine the antibacterial properties of Moltkia aurea Boiss.][o] (an endemic species to Turkey), and its other biological activities. All of the extracts were tested by disc diffusion assay in order to screen antibacterial activity. MIC values were evaluated as antibacterial activities of plant extracts. The non-enzymatic antioxidative activities including DPPH radical scavenging effects were studied in vitro. Results shown that the extracts had strong antibacterial effects on three bacteria (S. aureus- 17, S. aureus-18 and CNS-37) and the range of inhibition zone was 4-6mm. This three bacteria screened the lowest sensitivity to 65000 μg /mL concentration. Besides, the extracts were tested for non-enzymatic antioxidant activities. As a result, the methanol extract of the flower displayed a strong antioxidant activity. The various extracts of Moltkia aurea have different antibacterial and antioxidant properties.


But it's doctor recommended and I read the fine print: antecedents to drug companies' perceived credibility.
Using 2009 National Consumer Survey data from Experian Simmons, the authors found that dependence on doctor recommendations to assess the integrity of advertised drugs and the extent of reading small print in direct-to-consumer prescription drug advertising positively related to consumers' perceived credibility of health information from pharmaceutical companies, which in turn positively influenced willingness to ask their doctor for a specific medicine they saw or heard advertised. The potential effect of small print reading on willingness to request prescription was partially mediated by perceived credibility of information from drug companies. The findings are discussed in light of their practical implications.


A simplified intensity modulated radiation therapy technique for the breast.
A simplified intensity modulated radiation therapy (sIMRT) technique for the breast is presented. The technique aims to produce a uniform dose distribution in the entire breast volume. Using the standard tangential beam arrangement, we first determine for each pencil beam the midpoint of the segment that intersects the treatment volume. The dose to the midpoint from the open field is then calculated. The intensity of the pencil beam is determined as proportional to the inverse of the open field dose. With this intensity modulated beam, the dose delivered to the midpoint of each pencil beam segment that intersects the treatment volume is now equalized. The dose distribution in the entire treatment volume is nearly as uniform as can be achieved under the given beam arrangement. Fifteen left breast patients were planned with the sIMRT technique. For comparison, the same group of patients was also planned with the standard wedged pair technique and the full-fledged volume-based IMRT (vIMRT) technique. Both the sIMRT and the vIMRT techniques achieved more homogeneous dose in the treatment volume than the standard plan. Doses to the heart, the ipsilateral lung, and the contralateral breast were also reduced. The planning time and the treatment time for the sIMRT technique were comparable to that of the standard technique, and significantly less than that required by the vIMRT technique. The sIMRT technique is practical for large-scale implementation in a busy clinic without requiring significant increase of resources.


Role of Stereotactic Body Radiotherapy in the Treatment of Elderly and Poor Performance Status Patients With Pancreatic Cancer.
Literature on the management of nonmetastatic pancreatic ductal adenocarcinoma in patients who are elderly or have poor performance status is sparse. The median survival of this unique cohort of patients is < 6 months, and most patients are only offered single-agent gemcitabine or supportive care. Recently, adding nanoparticle albumin-bound paclitaxel to gemcitabine was shown to improve survival of patients with metastatic disease with Eastern Cooperative Group performance status of 2. Although standard chemoradiotherapy provides long-term locoregional control in locally advanced pancreatic cancer, it is difficult for this group of patients to tolerate 6 weeks of therapy. Stereotactic body radiotherapy (SBRT) can be delivered in only 3 to 5 days, does not require concurrent chemotherapy, and has limited toxicity, and tumor control rates appear to be equivalent to or better than those achieved with standard chemoradiotherapy. Additionally, SBRT has been shown to improve cancer-related pain and patient-reported quality of life. Given the favorable toxicity profile, SBRT seems like an obvious choice for patients who are elderly, have multiple comorbidities, or have poor performance status. Herein, we review the literature on SBRT in this unique patient population and discuss future directions.


Is frequency of family meals associated with fruit and vegetable intake among preschoolers? A logistic regression analysis.
The present study aimed to examine the associations between frequency of family meals and low fruit and vegetable intake in preschool children. Promoting healthy nutrition early in life is recommended for combating childhood obesity. Frequency of family meals is associated with fruit and vegetable intake in school-age children and adolescents; the relationship in young children is less clear. We completed a secondary analysis using data from the Early Childhood Longitudinal Study-Birth Cohort. Participants included children, born in the year 2001, to mothers who were >15 years old (n = 8 950). Data were extracted from structured parent interviews during the year prior to kindergarten. We used hierarchical logistic regression to describe the relationships between frequency of family meals and low fruit and vegetable intake. Frequency of family meals was associated with low fruit and vegetable intake. The odds of low fruit and vegetable intake were greater for preschoolers who shared less than three evening family meals per week (odds ratio = 1.5, β = 0.376, P < 0.001) than preschoolers who shared the evening meal with family every night. Fruit and vegetable intake is related to frequency of family meals in preschool-age children. Educating parents about the potential benefits of frequent shared meals may lead to a higher fruit and vegetable consumption among preschoolers. Future studies should address other factors that likely contribute to eating patterns during the preschool years.


A potential important role of skeletal muscle in human counterregulation of hypoglycemia.
During hypoglycemia, systemic glucose uptake (SGU) decreases and endogenous glucose release (EGR) increases. Skeletal muscle appears to be primarily responsible for the reduced SGU and may be important for the increased EGR by providing lactate for gluconeogenesis (GN). The objective of the study was to test the hypothesis that reduced muscle glucose uptake and increased muscle lactate release both make major contributions to glucose counterregulation using systemic isotopic techniques in combination with forearm net balance measurements. The study was conducted at the University of Giessen Clinical Research Center. Nine healthy volunteers participated in the study. A 2-h hyperinsulinemic euglycemic clamp (blood glucose approximately 4.4 mm) was followed by a 90-min hypoglycemic clamp (blood glucose approximately 2.6 mm). Compared with the euglycemic clamp, SGU decreased (21.0 +/- 2.0 vs. 29.6 +/- 1.8 micromol.kg body weight(-1).min(-1); P < 0.001), whereas EGR (11.2 +/- 1.7 vs. 4.9 +/- 1.3 micromol.kg body weight(-1) .min(-1); P < 0.003), arterial lactate concentrations (1051 +/- 162 vs. 907 +/- 115 microm; P < 0.02), systemic lactate release (23.5 +/- 0.9 vs. 17.1 +/- 0.9 micromol.kg body weight(-1).min(-1); P < 0.001), and lactate GN (4.50 +/- 0.60 vs. 2.74 +/- 0.30 micromol.kg body weight(-1).min(-1); P < 0.02) increased during hypoglycemia; the proportion of lactate used for GN remained unchanged (38 +/- 4 vs. 32 +/- 3%; P = 0.27). Whole-body muscle glucose uptake decreased approximately 50% during hypoglycemia (6.4 +/- 1.9 vs. 13.6 +/- 2.9 micromol.kg body weight(-1).min(-1); P < 0.001), which accounted for approximately 85% of the reduction of SGU. Whole-body muscle lactate release increased 6.6 +/- 1.6 micromol.kg body weight(-1). min(-1) (P < 0.01), which could have accounted for all the increase in systemic lactate release and, considering the proportion of lactate used for GN, contributed 1.4 +/- 0.4 micromol.kg body weight(-1).min(-1) (approximately 25%) to the increase in EGR. Reduced muscle glucose uptake and increased muscle lactate release both make major contributions to glucose counterregulation in humans.


Self-directed learning: the Wizard of Oz syndrome.
Every adult who embarks on a new project undergoes some self-directed learning. During the search for solutions, individuals may react in varied ways; yet, a basic syndrome of behavioral activities underlies these individual reactions. We have named this the "Wizard of Oz" syndrome because of the similarity it bears to the events in that classic fantasy. When developing interactive programs, producers should be cognizant of this behavior which characterizes the adult learner.


Results of open carpal tunnel release: a comprehensive, retrospective study of 188 hands.
Many recent reports of the results of decompression of the median nerve in the carpal tunnel have concentrated on only one aspect of recovery (numbness, grip etc.), and there are no reports of a comprehensive study of outcome. The aim of the present study was to review comprehensively the results of the direct visualization method of decompression of the carpal tunnel and to compare them with the published results of endoscopic release. Patients' perceptions of the severity of pain, numbness and paraesthesiae due to carpal tunnel syndrome (CTS), before and after open carpal tunnel release (CTR) in 188 hands were reviewed retrospectively at a minimum time of follow-up of 18 months. Motor and sensory testing, provocation testing and measurement of scar tenderness in 135 hands were performed at a clinical review. Subjective results showed that 70% experienced a reduction in the severity of pain after CTR, 78% of hands experienced a reduction in the severity of paraesthesiae and 77% experienced a reduction in the severity of numbness. A total of 49% had improvements in all three symptoms after CTR. At the clinical review, sensory testing revealed that 59% of hands had normal or slightly diminished light touch, 35% had normal static two-point discrimination and 61% had normal dynamic two-point discrimination. Results for Tinel's test, Phalen's test and pressure provocation testing were positive in 10% of hands. There was no scar tenderness in 38%, no persisting thenar atrophy in 90%. Normal grip strength was found in 93% and 91% had normal pinch strength. It was concluded that open carpal tunnel release remains a safe and reliable treatment for carpal tunnel syndrome. The very low incidence of serious complications from the open technique of CTR, when compared with endoscopic CTR as published by different authors in the literature, and the comparable clinical results, appears to make the open technique a safer and preferable option. However, a properly controlled trial of both techniques is necessary to compare them.


Epidermoid tumor of the lateral ventricle.
The authors present a case report of the successful removal of an epidermoid tumor of the temporal horn of the lateral ventricle. The tumor was confined to the ventricular cavity and was not adherent or connected to the choroid plexus. Spilling of tumor material during surgery was presumed to have contributed to the development of a postoperative acute hydrocephalus, either by obstructing the cerebospinal fluid pathways or by causing an aseptic meningitis in conjunction with cholesterol in the ventricular fluid in the postoperative period.


Non-contact lateral force microscopy.
The goal of atomic force microscopy (AFM) is to measure the short-range forces that act between the tip and the surface. The signal recorded, however, includes long-range forces that are often an unwanted background. Lateral force microscopy (LFM) is a branch of AFM in which a component of force perpendicular to the surface normal is measured. If we consider the interaction between tip and sample in terms of forces, which have both direction and magnitude, then we can make a very simple yet profound observation: over a flat surface, long-range forces that do not yield topographic contrast have no lateral component. Short-range interactions, on the other hand, do. Although contact-mode is the most common LFM technique, true non-contact AFM techniques can be applied to perform LFM without the tip depressing upon the sample. Non-contact lateral force microscopy (nc-LFM) is therefore ideal to study short-range forces of interest. One of the first applications of nc-LFM was the study of non-contact friction. A similar setup is used in magnetic resonance force microscopy to detect spin flipping. More recently, nc-LFM has been used as a true microscopy technique to systems unsuitable for normal force microscopy.


[Perception of the family health care team about the use of the Basic Health Care Information System-SIAB].
This study aimed to identify and analyze the use of the Basic Health Care Information System-SIAB by the family health care team, identifying the aim, possible difficulties and facilities of using these forms. This is an exploratory, descriptive study with a qualitative approach. We have used semi-structured taped interviews with the family health care team in Franca-São Paulo--Brazil. The analysis was structured into four groups: the usage of SIAB as a work instrument for the health care team; contradictions in the usage of SIAB; limitations as to data input; and suggestions on how to solve these problems. We will show that the team's use and involvement with SIAB is sporadic, due to difficulties in analyzing, monitoring and evaluating data for complying with local programs related to community health agents, whose high turnover directly affects the inadequate completion and interpretation of forms, as well as difficulties to understand the aim of these forms.


[Is local anesthesia necessary for venipuncture?].
We evaluated the necessity of local anesthesia for the venipuncture pain in 27 healthy adult volunteers by using a visual analogue scale (VAS) from 0 to 10. The pain scales were measured three times: at the time of percutaneous intravenous cannulation (20 G polyurethane catheter) without local anesthesia as well as the skin infiltration with local anesthetics (0.5% lidocaine 0.5 ml; 25 G needle), and after intravenous cannulation. The measurements were done twice, once by an expert staff and once by a novice staff with an interval of three days. VAS values were significantly higher (2.4 +/- 1.1) for the percutaneous intravenous cannulation without local anesthesia than both for the skin infiltration with local anesthetics (1.4 +/- 0.6) and for the evaluation after intravenous cannulation (0.7 +/- 0.8), independent of who inserted the catheter. VAS values were significantly lower (2.1 +/- 1.0) when the percutaneous intravenous cannulation without local anesthesia was performed by expert staff than when it was performed by novice staff (2.7 +/- 1.1; P < 0.05). We conclude that local anesthesia is necessary when novice staff performs the percutaneous intravenous catheterization.


The influence of pulsed electric fields and microwave pretreatments on some selected physicochemical properties of oil extracted from black cumin seed.
Application of novel technologies such as microwave and pulsed electric fields (PEF) might increase the speed and efficiency of oil extraction. In the present research, PEF (3.25 kV/cm electric field intensity and 30 pulse number) and microwave (540 W for 180 s) pretreatments were used to study the process of oil extraction from black cumin (Nigella sativa) seeds. After applying the selected pretreatments, the oil of seeds was extracted with the use of a screw press and the extraction efficiency, refractive index, oil density, color index, oxidative stability, and chemical components of oil and protein of meal were evaluated. The achieved results expressed that PEF and microwave pretreatments increased the oil extraction efficiency and its oxidative stability. Different pretreatments didn't have any significant influence on the refractive index of black cumin seed oil (p>.05). When microwave and PEF were used, the oil density showed an enhancement as the following: 1.51% and 0.96%, respectively in comparison with the samples with no pretreatments. Evaluation of the extracted oils, using GC/MS analysis indicated that thymoquinone was the dominant phenolic component in the black cumin oil. Finally, the SEM analysis revealed that microwave and PEF can be useful in the extraction of oil from black cumin seeds since these treatments damaged cell walls and facilitated the oil extraction process.


First report of Colletotrichum henanense causing anthracnose on Chinese chestnut in the United States.
Culinary chestnut production in the United States (US) is a rapidly growing industry supporting fresh market and value-added industries. An estimated 200-400 new acres of chestnuts are planted every year in the US, with most growers east of the Rocky Mountains planting Chinese chestnut (Castanea mollissima) or Chinese chestnut hybrids. In 2018, Ohio producers of Chinese chestnut reported losses of up to 80% to blossom end rot. Symptoms were like those reported by Fowler and Berry (1958), including black spots on the chestnut shell, often at the stylar end, and blackening of the kernels. Spots covered 1-100% of the kernel, however, no signs of any pathogen were present on the shell or kernel. In 2020, cankers that were brown/black in color, sunken, and ~1 cm in length were observed on 1-yr twigs of chestnut seedlings from a nursery operation on the same farm from which the symptomatic kernels were observed. In some seedlings, distal portions of the twigs died, while in other seedlings only shoots and leaves within the cankered areas died. Black acervuli were observed erupting from the cankers. Colletotrichum spp. were isolated and cultured on potato dextrose agar from surface-sterilized tissue from kernel lesions (MLI246-21 to MLI249-21) and twig cankers (MLI250-21 and MLI251-21). All isolates produced grey aerial mycelia, pink sporodochia, and cylindrical conidia with rounded ends ranging in size from 12-20 um long by 5-8 um wide. Isolates were preliminarily identified as belonging to the Colletotrichum gloeosporioides species complex (CGSC). The glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene, β-tubulin (TUB2) gene, and the intergenic spacer ApMat were amplified from genomic DNA and sequenced (Dowling et al. 2020). These genes are suitable for identifying species within the CGSC (Eaton et al. 2021). Sequences were submitted to the GenBank database (GAPDH OL687148 to OL687153, TUB2 OL741624 to OL741629 and ApMAT OL695914 to OL695919). BLASTn queries of NCBI GenBank showed that the GAPDH, TUB2, and ApMat sequences from all isolates had 98%, 98% and 99% identity with C. henanense isolates MT513015.1, MT513080.1, and MT512917.1 from apple (Martin et al. 2021). Representative isolates were used to demonstrate Koch's postulates and confirm pathogenicity on kernels (MLI246-21 and MLI249-21) and twigs (MLI250-21). Developing chestnuts in burs (n=4 per isolate) were gathered from the field and surface-sterilized with 70% ethanol. Nuts (n=12 per isolate) inside burs were inoculated by injecting 50uL of inoculum (~1.0 x 106 conidia/mL) directly into each kernel with a hypodermic needle and sterile syringe. Burs were incubated at room temperature in a moist chamber for 14 days. One-year-old seedlings (n=6) grown in containers were used for twig inoculations. Twig nodes (one/seedling) were surface sterilized with 70% ethanol and inoculated by wounding the stem with a sterile probe and dropping 100uL of inoculum into each wound. Seedlings were incubated in a glass house for 60 days and monitored daily for symptom development. Nuts (n=9) and twigs (n=3) were inoculated with sterile water using the same inoculation and incubation conditions to serve as negative controls. Inoculated kernels developed characteristic brown/black lesions at the wound site and inoculated twigs developed brown/black, slightly sunken cankers with acervuli. No symptoms developed on the control kernels or twigs. Fungi with the same colony, conidial, and molecular characteristics as C. henanense were re-isolated from inoculated kernels and twigs. Blossom end rot caused by Glomerella cingulata has been reported on chestnut kernels in Georgia (Fowler and Berry 1958), but this is the first report of C. henanense causing rot on kernels and twigs in the US. Since 2018, C. henanense has been isolated from infected nuts received from commercial orchards in Pennsylvania, Missouri, and Alabama. We propose to retire the name "blossom end rot" for the symptoms found in kernels and replace it with the name "chestnut anthracnose" for this disease that affects both twigs and kernels of Chinese chestnut.


Microalgal culture in animal cell waste medium for sustainable 'cultured food' production.
'Cultured food' has tremendous potential as a sustainable meat alternative. Increased cultured food production is increasing the amount of waste medium from cell culture. Nitrogen- and phosphorus-containing compounds in waste medium can cause eutrophication of water bodies. Currently, microalgae are used in energy production, environmental protection, agriculture and pharmaceutical and health food industries. Here, we used the microalgae, Chlorococcum littorale and Chlorella vulgaris and the waste medium of C2C12 cells for a case study. We found that 80% and 26% of ammonia and 16% and 15% of phosphorus in the waste medium were consumed by C. littorale and C. vulgaris, respectively. In addition, C. littorale and C. vulgaris proliferated 3.2 folds and 1.6 folds, respectively, after seven days in the waste medium that was enhanced by adjusting medium salt concentration. This report demonstrates the potential of sustainability for solving the issue of waste medium production during the production of cultured food.


Embolia cutis medicamentosa.
Embolia cutis medicamentosa or Nicolau syndrome is an acute necrotic condition of skin and subcutis that follows intramuscular administration of certain medicines. A young lady from rural area presented with an irregular-contoured ulceration with livedoid features on left deltoid region which she developed after receiving intramuscular injection of diclofenac sodium. The histopathological examination of the biopsied tissue demonstrated dead keratinocytes with degenerated epidermis and dermis. The condition improved on local management of wound with a residual scar.


Rat thymocyte sodium transport. Effects of changes in sodium balance and experimental hypertension.
The wide range of membrane electrolyte transport abnormalities associated with experimental, genetic, and essential hypertension may either reflect an underlying global change in the cell membrane or may be directly related to the underlying disturbance that causes hypertension or to changes in sodium balance. To investigate this further, we studied sodium transport and intracellular electrolyte composition in the thymocytes of normal rats undergoing salt loading or depletion, and in rats with renovascular, mineralocorticoid, or spontaneous hypertension compared to appropriate age-matched normotensive control rats. In normotensive rats, although there was no significant difference between the blood pressures at the two extremes of sodium balance, sodium loading caused a nonsignificant rise in sodium transport, whereas sodium depletion was associated with a significant fall in sodium transport and intracellular sodium. When cells from salt-loaded or normal animals were incubated in a medium containing their own serum, sodium transport was slightly stimulated in both, but there was no significant difference in the sodium efflux-rate constant of thymocytes obtained from rats on the normal as opposed to the high salt intake. Compared to normotensive rats, there was no significant change in the sodium efflux-rate constant in any of the hypertensive rat models studied. However, the sodium efflux-rate constant fell with age in both the spontaneously hypertensive and Wistar-Kyoto normotensive rats. The present studies show that dietary sodium intake and aging had considerable effects on rat thymocyte sodium transport, but neither of these changes was related to a change in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)


Strain-specific estimation of epidemic success provides insights into the transmission dynamics of tuberculosis.
The transmission dynamics of tuberculosis involves complex interactions of socio-economic and, possibly, microbiological factors. We describe an analytical framework to infer factors of epidemic success based on the joint analysis of epidemiological, clinical and pathogen genetic data. We derive isolate-specific, genetic distance-based estimates of epidemic success, and we represent success-related time-dependent concepts, namely epidemicity and endemicity, by restricting analysis to specific time scales. The method is applied to analyze a surveillance-based cohort of 1,641 tuberculosis patients with minisatellite-based isolate genotypes. Known predictors of isolate endemicity (older age, native status) and epidemicity (younger age, sputum smear positivity) were identified with high confidence (P < 0.001). Long-term epidemic success also correlated with the ability of Euro-American and Beijing MTBC lineages to cause active pulmonary infection, independent of patient age and country of origin. Our results demonstrate how important insights into the transmission dynamics of tuberculosis can be gained from active surveillance data.


Treatment of erythema nodosum and nodular vasculitis with potassium iodide.
Twenty-four of twenty-eight patients with erythema nodosum and sixteen of seventeen patients with nodular vasculitis responded to treatment with potassium iodide. Relief of symptoms occurred within 2 days. The average duration of treatment was 3 weeks and the lesions took an average of 2 weeks to resolve. The possible mode of action of potassium iodide is discussed and an immunosuppressive effect mediated by heparin is suggested.


Apoptotic efficacy and antiproliferative potential of silver nanoparticles synthesised from aqueous extract of sumac (Rhus coriaria L.).
Currently, nanotechnology and nanoparticles (NPs) are recognised due to their extensive applications in medicine and the treatment of certain diseases, including cancer. Silver NPs (AgNPs) synthesised by environmentally friendly method exhibit a high medical potential. This study was conducted to determine the cytotoxic and apoptotic effects of AgNPs synthesised from sumac (Anacardiaceae family) fruit aqueous extract (AgSu/NPs) on human breast cancer cells (MCF-7). The anti-proliferative effect of AgSu/NPs was determined by MTT assay. The apoptotic properties of AgSu/NPs were assessed by morphological analysis and acridine orange/propidium iodide (AO/PI) and DAPI staining. The mechanism of apoptosis induction in treated cells was investigated using molecular analysis. Overall results of morphological examination and cytotoxic assay revealed that AgSu/NPs exert a concentration-dependent inhibitory effect on the viability of MCF-7 cells (IC50 of ∼10 µmol/48 h). AO/PI staining confirmed the occurrence of apoptosis in cells treated with AgSu/NPs. In addition, molecular analysis demonstrated that the apoptosis in MCF-7 cells exposed to AgSu/NPs was induced via up-regulation of Bax and down-regulation of Bcl-2. These findings suggested the potential use of AgSu/NP as cytotoxic and pro-apoptotic efficacy and its possible application in modern medicine for treating certain disorders, such as cancer.


Using salamanders as model taxa to understand vertebrate feeding constraints during the late Devonian water-to-land transition.
The vertebrate water-to-land transition and the rise of tetrapods brought about fundamental changes for the groups undergoing these evolutionary changes (i.e. stem and early tetrapods). These groups were forced to adapt to new conditions, including the distinct physical properties of water and air, requiring fundamental changes in anatomy. Nutrition (or feeding) was one of the prime physiological processes these vertebrates had to successfully adjust to change from aquatic to terrestrial life. The basal gnathostome feeding mode involves either jaw prehension or using water flows to aid in ingestion, transportation and food orientation. Meanwhile, processing was limited primarily to simple chewing bites. However, given their comparatively massive and relatively inflexible hyobranchial system (compared to the more muscular tongue of many tetrapods), it remains fraught with speculation how stem and early tetrapods managed to feed in both media. Here, we explore ontogenetic water-to-land transitions of salamanders as functional analogues to model potential changes in the feeding behaviour of stem and early tetrapods. Our data suggest two scenarios for terrestrial feeding in stem and early tetrapods as well as the presence of complex chewing behaviours, including excursions of the jaw in more than one dimension during early developmental stages. Our results demonstrate that terrestrial feeding may have been possible before flexible tongues evolved. This article is part of the theme issue 'Food processing and nutritional assimilation in animals'.


[Evaluation of a method based on the principle of CI therapy in the correction of walking function in patients with post-stroke hemiparesis syndrome].
To develop a new, effective, affordable method of neurorehabilitation for the correction of walking functions based on the principle of CI (constraint-induced movement therapy) therapy in patients with the syndrome of hemiparesis of post-stroke origin. The study included 100 patients with moderate to marked syndrome of central hemiparesis in the recovery period of stroke. Patients were randomized into two groups. In the main group, the walk recovery was carried out using CI-therapy in complex with traditional methods of neurorehabilitation and in the comparison group, walk correction was performed by generally accepted methods of kinesiotherapy and physical therapy. Both groups were comparable by stage of stroke, the severity of paresis, age. The risk of fall significantly decreased in both groups of patients. The length and paretic step time significantly decreased in the main group. The effectiveness of the restoration of the function of walking was higher in the main group that allows us to recommend the method of correction of the walk based on the principle of CI therapy in the complex neurorehabilitation.