Sterilization of corticosteroids for ocular and pulmonary delivery with supercritical carbon dioxide.
Glucocorticosteroids, a class of drugs widely used in the treatment of allergies, airways inflammation and inflammatory ocular diseases, are often difficult to sterilize due to their inherent sensibility to heat or irradiation induced degradation. Being often in form of suspension, obviously the final medicinal product cannot be sterilized by filtration. The effectiveness of supercritical CO2 (SC-CO2) based method for the sterilization of food and biomedical materials is well documented in the literature. Few reports are available on the sterilization of drugs especially in powder form with SC-CO2. The aim of the present work was to investigate the suitability of SC-CO2 at mild temperature for the decontamination of two model corticosteroid powders (beclometasone dipropionate and budesonide) both in dry or wet form. We found that SC treatment in wet environment reduces by at least six orders of magnitude the contamination of micronized steroidal drugs while retaining the particle size distribution. The findings of this work are of particular interest for the application in the case of aqueous suspension of steroids for aerosol therapy or ocular delivery, where the sterilization process with SC-CO2 could be carried out directly on the bulk of the final formulation.


Inhibition of the algesic effect of bradykinin and acetylcholine by mepacrine.
1. The isolated perfused rabbit ear connected to the body by its nerve only was used to investigate the influence of mepacrine on the algesic effect of bradykinin and acetylcholine. For comparison, quinidine was included in this investigation. 2. Infusion of mepacrine or quindine (2-10 microgram/ml) into the rabbit ear reduces the algesic effect of bradykinin as well as of acetylcholine in proportion to the dose. 3. Infusion of postglandin E1 (10 ng/ml) in addition to mepacrine or quinidine restores theinhibited algesic effect of bradykinin more than that of acetylcholine. 4. Mepacrine and quinidine (10 microgram/ml) reduce the brief vasoconstriction elicited by bradykinin in the rabbit ear. 5. The results suggest that mepacrine or quinidine reduce the algesic effect of bradykinin primarily by inhibiting the release of E-type prostaglandins which sensitize pain receptors and secondarily by an unspecific antagonism (local-anaesthetic action). The effect of acetylcholine, however, appears to be reduced mainly by an unspecific antagonism.


Nutrient modification of proliferation and radiation response in EMT6/Ro spheroids.
The effects of external nutrients on the growth and radiation response of EMT6/Ro spheroids were studied by maintaining spheroids in media with different concentrations of glucose, amino acids, and vitamins. Compared to spheroids grown in normal glucose concentration (5.5 mM), spheroids grown in higher glucose media (24.8 mM), demonstrated no difference in initial volume doubling time, clonogenicity, number of proliferating cells, or cell cycle distributions. However, histology sections revealed that, spheroids grown in higher glucose concentration had a thicker viable rim than spheroids grown in normal glucose media. Two-step acridine orange staining and dual parameter flow cytometric analysis, in addition to continuous [3H]-thymidine labeling techniques, showed that spheroids grown in higher glucose had 2 to 3 times the fraction of quiescent cells, when compared to normal glucose spheroids. When irradiated in ice to reoxygenate, the Do's were similar in the normal and the higher glucose spheroids, but the Dq's were reduced in the higher glucose spheroids in the presence of increased amino acids and vitamins. When irradiated in air at 37 degrees C, spheroids grown in the higher glucose media were more sensitive (decreased Do), and had a smaller hypoxic fraction than when grown in normal glucose media. For spheroids grown in the same glucose concentrations but increased concentrations of amino acids and vitamins, there was generally an increased Do under all irradiation conditions. Some of these differences in radiation sensitivity could be correlated to differences in cellular glutathione levels of these spheroid cells.


Effect of modified atmosphere packaging on shelf life and bacterial community of roast duck meat.
The purpose of this work was to assess the effect of different packaging methods on the shelf life and bacterial communities of roast duck meat. Samples were packaged under the following five conditions: overwrapped packaging (OWP), 100% N2 (100% N2-MAP), 30% CO2/70% N2 (30% CO2-MAP), 50% CO2/50% N2 (50% CO2-MAP), and 0.4% CO/30% CO2/69.6% N2 (CO-MAP). Physicochemical and microbiological parameters were monitored during 14 days of chilled storage (0-4 °C). Results showed that MAP samples obtained higher and more stable redness, better sensory scores, and lower lipid oxidation, compared with OWP, in which CO-MAP samples had the lowest TBARS values (0.13-0.22 MDA/kg) during storage. Moreover, 30% CO2-MAP, 50% CO2-MAP, and CO-MAP effectively retarded the onset of bacterial spoilage and extended shelf life by 7 days compared with 100% N2-MAP and OWP treatments. Additionally, bacterial succession was significantly affected by the gas composition used in the packages, especially the dominant biota at the end of storage, which played an important role in the spoilage of roast duck meat under specific packaging. On day 14, Pseudoalteromonas spp., Lactobacillus spp., and Pseudomonas spp. became the most predominate genera in OWP, 100% N2-MAP, and 50% CO2-MAP, respectively. Notably, Vibrio spp. was dominant in both 30% CO2-MAP and CO-MAP, indicating 0.4% CO did not exert a further inhibitory effect on this genus. Additionally, the growth inhibition of Pseudoalteromonas spp., Lactobacillus spp., and Leuconostoc spp. by high CO2 concentration might be the reason for MAP (CO2/N2) samples having lower levels of TVC. Globally, these results indicate that 30% CO2-MAP, 50% CO2-MAP, and CO-MAP are promising packaging methods to improve roast duck meat quality and achieve shelf life extension.


Symptomatic intra-cardiac metastasis complicating non-small cell lung cancer: imaging findings and clinical course.
We describe a man who was diagnosed with non-small cell lung cancer following previous treatment for small cell lung cancer. He developed dyspnoea, paroxysmal nocturnal dyspnoea and orthopnoea. Trans-thoracic echocardiogram revealed a large mass within the right atrium. The patient proceeded to thoracotomy at which time unresectable metastatic tumour was found in the right atrium infiltrating into the pericardium. Metastatic involvement of the heart by tumour is rare and is found at autopsy in 1-3% of unselected cases in various series. This translates into a finding of cardiac metastases in approximately 10% of autopsies where malignancy is diagnosed. Most cases are clinically silent and are undiagnosed in vivo. Echocardiography, CT and MRI are complementary investigations, and are all used in the evaluation of cardiac lesions. When metastatic disease is in question, MR and CT imaging offer advantages over echocardiography, chiefly a wider imaging field which allows evaluation of distant disease.


Telemedicine in the diagnosis and management of temporomandibular disorders: A systematic review conducted according to PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions.
Telemedicine (T-Med) has always been an important tool in the arsenal of clinicians worldwide. This technique has become increasingly popular in recent years, especially in light of the COVID-19 pandemic, which has made it difficult for some people to access traditional dental care. The current review aimed to analyse the usage of telemedicine in the diagnosis and management of temporomandibular disorders (TMDs) and its impact on general health. An extensive search of databases was conducted using keywords such as, "telemedicine," "teledentistry," "TMJ" and "temporomandibular disorders," resulting in a total of 482 papers to be available from which eligible studies were selected. The Risk of Bias in Observational Studies of Exposures (ROBINS-E) tool was used to evaluate methodological quality of included studies. Two studies were selected which fulfilled the eligibility criteria. All assessed studies indicated varying degrees of positive outcomes for patients who were intervened for TMDs using T-Med. T-Med shows promising results for the diagnosis and management of TMDs, especially since the advent of the COVID-19 pandemic and thereafter. Long-term clinical trials with larger samples are needed to further ascertain validity in this regard.


Ablative fractional laser treatment of hypertrophic burn and traumatic scars: a systematic review of the literature.
Hypertrophic scars (HTS) following burns and other trauma and are associated with significant functional and psychosocial impairment. Ablative fractional lasers (AFLs) are increasingly being applied in the treatment of HTS supported by a rapidly expanding multidisciplinary base of literature. The multidisciplinary authors sought to evaluate existing literature, provide context and identify gaps, and make recommendations for a path forward. A systematic review was conducted to identify literature pertinent literature through September 2019. Retrospective cohort, randomized controlled trials, quasi-randomized controlled trials, observational prospective cohort, or case series with five or more subjects with hypertrophic scars incurred from burns and related trauma were considered. Twenty-two of the 23 evaluated studies documented statistically significant and/or meaningful qualitative improvements in nearly all outcome measures. Adverse events were generally infrequent and minor. Significant heterogeneity was observed among the studies included in this systematic review, precluding metaanalysis of pooled data. There is abundant existing literature on the use of AFLs in the management of HTS but study heterogeneity limits generalizability. Future studies should prioritize standardized protocols including assessments of function and quality of life.


Association between clinical use of lansoprazole and the risk of type 2 diabetes mellitus: a pharmacoepidemiological cohort study.
Proton pump inhibitors (PPIs) are common and widely used for gastrointestinal-related disorders. Lansoprazole is one of PPIs with potential benefits of anti-inflammation, reduced oxidative stress, and anti-diabetes. The aims of this study are to determine whether lansoprazole imparts differential risk of type 2 diabetes as compared with other PPIs. A population-based retrospective cohort study was conducted using the National Health Insurance Research Database in Taiwan. Patients who received lansoprazole more than 90 days and without records of use of other PPIs between January 1, 2000 and December 31, 2005 (the exposure period) were considered as the exposed cohort (n = 1668). In comparison, patients who received other PPIs more than 90 days and without use of lansoprazole in the exposure period were treated as the comparison cohort (n = 3336).The primary outcome was the new-onset of type 2 diabetes mellitus (T2DM). The association between use of lansoprazole and the risk of T2DM was determined by hazard ratios (HRs) and 95% confidence intervals (CIs) derived from multivariable Cox proportional hazards models. The lansoprazole cohort showed a significantly reduced risk of T2DM with an adjusted HR of 0.65 (95% CI 0.56-0.76). Interestingly, the inverse association between use of lansoprazole and risk of T2DM was observed in both genders and in various age groups. The present study findings suggest that lansoprazole was associated with a reduced risk of T2DM compared with other PPIs. Further studies are needed to determine the clinical implications of the present study.


Wheat non-specific lipid transfer protein genes display a complex pattern of expression in developing seeds.
Nine cDNA clones encoding non-specific lipid transfer proteins (nsLTPs) were isolated from Triticum aestivum and Triticum durum cDNA libraries and characterized. One cDNA is predicted to encode a type 2 nsLTP (7 kDa) while others encode type 1 nsLTPs (9 kDa). All encoded proteins contain an N-terminal signal sequence and possess the characteristic features of nsLTPs. The genomic structures of the wheat nsLtp genes show that type 2 TaLtp7.1a, TaLtp7.2a and type 1 TaLtp9.2b genes lack introns while the other type 1 genes consist of one intron. Construction of a phylogenic tree of Poaceae nsLTPs shows that wheat nsLTPs can be divided into eleven distinct groups and are closely related to barley sequences. Using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, the expression patterns of nine nsLtp genes were studied during wheat seed development and germination. We identified three different profiles of nsLtp gene transcript accumulation. Whereas TdLtp7.1a, TdLtp9.4a and TdLtp9.7a transcripts were detected during all maturation stages, TdLtp7.2a, TdLtp9.2a, TdLtp9.3a, TdLtp9.5a and TdLtp9.6a transcripts were only present in the first and TdLtp9.1a in the last stages of seed development. Moreover, these nine wheat nsLtp genes are not seed-specific and are also expressed in the coleoptile of young seedlings. The present study revealed the complexity of the wheat nsLtp gene family and showed that the expression of nsLtp genes is developmentally regulated in the seeds, suggesting a specific function for each of the corresponding proteins.


Behavioral intentions of rural farmers to recycle human excreta in agriculture.
Considerable progress has been made in developing human excreta recovery pathways and processes for maximum nutrient recovery and contaminant elimination. The demand segment has often been ignored as an area for future research, especially during the technology development. The findings from the few published articles on social acceptance show missing and inconclusive influence of demographic, sociological, and economic farmer-characteristics. This study endeavours to close this gap by using the social psychological theories, technology adoption theories and the new ecological paradigm to investigate the factors that influence the behavioral intentions of rural farmers to recycle human excreta in agriculture. Study findings show that social acceptance was driven by awareness, religiosity, income, source of income, and environmental dispositions. Perceived behavioral control represents a potential barrier to human excreta reuse. The study recommends the demographic, cultural, sociological, and economic mainstreaming of dissemination strategies of circular bioeconomy approaches within the context of agricultural innovation systems.


LCZ696 protects against doxorubicin-induced cardiotoxicity by inhibiting ferroptosis via AKT/SIRT3/SOD2 signaling pathway activation.
Doxorubicin (DOX) is an effective and widely used anticancer drug but has limited clinical applicability because of its cardiotoxicity. Ferroptosis plays a key role in DOX-induced cardiac damage and cardiomyocyte cell death. The inhibition of ferroptosis reverses DOX-induced cardiotoxicity (DIC). LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, protects against DIC. However, the mechanism of action of LCZ696, especially its effect on ferroptosis, is incompletely understood. This study investigates the cardioprotective effects of LCZ696 on DIC in vivo and in vitro.Cardiotoxicity was induced in Wistar rats by tail intravenous injection of 2.5 mg/kg DOX once a week for six weeks. Rats and H9c2 cells were treated with or without LCZ696 to determine the cardioprotective role and underlying mechanisms of LCZ696 against DIC. To assess the role of SIRT3 and correlated pathways in ferroptosis, SIRT3 knockout was performed using lentiviral vectors, and AKT was inhibited with LY294002. LCZ696 significantly attenuated DIC by decreasing the concentrations of lipid reactive oxygen species and malondialdehyde and increasing the levels of glutathione peroxidase-4 and reduced glutathione in cells and heart tissues. Moreover, LCZ696 remodeled myocardial structures and improved heart ventricular function in DOX-treated rats. LCZ696 treatment increased SIRT3 expression and deacetylated its target gene SOD2, and these changes were mediated by AKT activation. SIRT3 knockdown and AKT inhibition induced lipid peroxidation and reduced the protective effect of LCZ696 in H9c2 cells. Collectively,LCZ696 prevents DIC by inhibiting ferroptosis via AKT/SIRT3/SOD2 signaling pathway activation. Thus, LZC696 is a potential therapeutic strategy for DIC.


Uranium behaviour in an estuary polluted by mining and industrial effluents: the Ría of Huelva (SW of Spain).
This paper describes a comprehensive study of the behaviour of U in the Ría of Huelva estuary, formed by the Tinto and Odiel rivers. This ecosystem is conditioned by two hydrochemical facts: one connected with the acid mining drainage (AMD) generated in the first section of the river basins, and another one related to the fertilizer industry located at the estuary. AMD gives a singular character to these rivers; low pH and high redox potential that keep high amounts of toxic elements and radionuclides in dissolution. Most of the data for dissolved U in estuaries indicate conservative mixing, but there are examples of non-conservative behaviour attributed to oxidation/reduction processes or solubility variations. In the Ría of Huelva estuary the U shows a non-conservative behaviour due to solubility changes produced by variations in the pH. A complete removal of riverine dissolved U is observed in a pH range of 4-6. At higher pH values, U release from suspended matter, and probably also from sediments into the dissolved phase is found.


Twin vessels in von Hippel-Lindau disease.
We examined ten patients from three families with von Hippel-Lindau disease and 26 of their at-risk relatives for the presence of twin vessels, defined as a paired retinal arteriole and venule that are separated by less than the diameter of one venule and extend for a distance of more than one disk diameter. They were compared with 36 age- and sex-matched controls. Of the 36 subjects in the study group, 23 had twin vessels compared with two controls (P less than 10(-6). Of the ten patients, nine (14 eyes) had twin vessels; no twin vessels were found in their controls (P = 5.9 x 10(-5)). Fourteen at-risk relatives and two of their controls had twin vessels (P = 9.4 x 10(-4)).


Plasma Thymidine Kinase Activity as a Novel Biomarker in Metastatic Melanoma Patients Treated with Immune Checkpoint Inhibitors.
Background. Immune checkpoint inhibitors (ICI) are effective in fractions of patients with disseminated melanoma. This study is the first to analyze the plasma activity of thymidine kinase (TK), an enzyme involved in DNA synthesis and repair, as a biomarker in melanoma patients. Methods. Plasma samples were collected prior to treatment start in patients with unresectable metastatic cutaneous melanoma, treated with ICI (anti-CTLA-4 and/or anti-PD-1). Plasma TK activity (TKa) levels were determined using the DiviTum TKa ELISA assay. TKa levels were correlated with patients' baseline characteristics, response rate (RR), progression-free survival (PFS), and overall survival (OS). Results. In the 90 study patients, the median TKa level was 42 Du/L (range <20-1787 Du/L). A significantly higher plasma TKa was found in patients with ECOG performance status ≥1 (p = 0.003), M1c-d disease (p = 0.015), and elevated lactate dehydrogenase levels (p < 0.001). The RR was 63.2% and 30.3% in those with low or high TKa, respectively (p = 0.022). The median PFS was 19.9 and 12.6 months in patients with low or high TKa, respectively (hazard ratio (HR) 1.83 (95% CI, 1.08-3.08), p = 0.024). The median OS was >60 months and 18.5 months in patients with low or high TKa, respectively (HR: 2.25 (95% CI, 1.25-4.05), p = 0.011. Conclusions. High pretreatment plasma TKa levels were significantly associated with worse baseline characteristics and poor response and survival in ICI-treated melanoma patients. TKa is hence a novel and interesting plasma biomarker in melanoma and should be further studied to define its role as a prognostic and predictive marker in this disease.


Morphogenesis of silkmoth chorion: sequential modification of an early helicoidal framework through expansion and densification.
The silkmoth chorion is a helicoidally layered, fibrous structure which is constructed in four sequential morphogenetic modes, beginning with the assembly of a thin, low density lamellar framework. Subsequently, the framework expands in height by the insertion of additional fiber sheets into the preexisting lamellae. This expansion mode begins farthest from the follicular secretory cells and progresses in reverse. Individual fibers then grow in thickness, presumably through accretion of newly synthesized proteins, and eventually fuse. This third mode, which also begins in the most distant lamellae and proceeds in reverse, is called densification, as it results in an approximately two fold increase in overall chorion density without further lamellar expansion. Finally, lamellogenesis is recapitulated in miniature in a region of the chorion's surface, where very-late-forming lamellae are molded into prominent surface structures, the aeropyle crowns. The densification and especially the expansion modes suggest considerable fluidity in the developing chorion, consistent with its proposed cholesteric liquid crystalline structure. Such a structure is also consistent with numerous deviations from the ideal helicoidal array. These distortions and defects are described and discussed in terms of their possible origin and function.


Mobilization of hematopoietic progenitor cells with granulocyte colony stimulating factors for autologous transplant in hematologic malignancies: a single center experience.
In 2006 the Hematology Service of Hospital Maciel published its experience with peripheral blood progenitor cell harvesting for autologous stem cell transplantation using Filgen JP (Clausen Filgrastim). After mobilization with a mean filgrastim dose of 78 mcg/Kg, 4.7 x 10(6) CD34(+) cells/Kg were obtained by apheresis. Age above 50, multiple myeloma as underlying disease and a malignancy that was not in remission were identified as frequent characteristics among patients showing complex mobilization. The aim of this study was to compare stem cell mobilization using different brands of filgrastim. One hundred and fifty-seven mobilizations performed between 1997 and 2006 were analyzed. This retrospective analysis comparative two groups of patients: those mobilized with different brands of filgrastim (Group A) and those who received Filgen JP (Clausen Filgrastim) as mobilizing agent (Group B). A cluster analysis technique was used to identify four clusters of individuals with different behaviors differentiated by age, total dose of filgrastim required, number of apheresis and harvested CD34(+) cells. The mean total dose of filgrastim administered was 105 mcg/Kg, the median number of apheresis was 2 procedures and the mean number of harvested stem cells was 4.98 x 10(6) CD34(+) cells/Kg. No significant differences were observed between Groups A and B regarding the number of apheresis, harvested CD34(+) cells and number of mobilization failures, however the total dose of filgrastim was significantly lower in Group B. Among other factors, the origin of the cytokine used as mobilizing agent is an element to be considered when evaluating CD34(+) cell mobilization results.


Submersed macrophyte growth at low pH : I. CO2 enrichment effects with fertile sediment.
Vallisneria americana was grown for six weeks in a greenhouse on relatively fertile sediment to test for factors other than nutrient limitation which may slow growth of this submersed macrophyte at pH 5. On the basis of dry mass accumulated, (1) low pH significantly depressed Vallisneria growth at constant free CO2 levels; (2) free CO2 enrichment, however, greatly stimulated Vallisneria growth at pH 5, by 2.8-fold and 10-fold at 3.2 times and 10 times air-equilibrated CO2 levels, respectively; and (3) growth was greater by far at pH 5 than at higher pH with constant total dissolved inorganic carbon (DIC). Free CO2 availability was thus an important controller of growth at low pH by Vallisneria americana on fertile sediment, and low pH was not directly deleterious. Field surveys of acidic lakes in the Adirondack Mountains of New York state revealed that DIC levels in low pH lakes were often well above equilibrium values and could potentially support vigorous macrophyte growth. Aluminum and/or iron toxicity did not appear to impair growth at low pH, and aluminum concentrations in Vallisneria shoots significantly decreased with increasing free CO2 concentrations at pH 5.0, perhaps due to growth dilution. Rosette production (a measure of asexual reproduction), maximum leaf length, and extent of flowering within treatments were positively correlated with plant biomass, rather than with pH or free CO2 levels per se.


Family murder followed by suicide.
Four examples of family murder followed by suicide are presented with relevant clinical data from the coroners' reports. In retrospect it would appear that three of the offenders were suffering from severe depression, and the fourth showed features of morbid jealousy. In each case there were factors suggestive of mental illness apparent before the tragedy. This is consistent with recent studies of murder followed by suicide and of suicide alone, and raises the possibility that psychiatric intervention may have altered the course of events. Though such tragedies may never be totally eliminated it is considered that close co-operation between coroner, forensic pathologist and psychiatrist may promote greater professional understanding of these tragedies, and provide the impetus for the detection and treatment of potentially remediable psychiatric illness.


Membrane localization of endopeptidase-24.11 and peptidyl dipeptidase A (angiotensin converting enzyme) in the pig brain: a study using subcellular fractionation and electron microscopic immunocytochemistry.
Brains from piglets were dissected and a block of tissue including the substantia nigra, globus pallidus, and entopeduncular nucleus was homogenized and then fractionated on discontinuous Percoll gradients. Ligand-binding assays using (-)-[3H]nicotine and [3H]quinuclidinyl benzilate served to delineate fractions containing nicotinic and muscarinic acetylcholine receptors. In this system endopeptidase-24.11 exhibited a biphasic distribution, consistent with its presence on both pre- and postsynaptic membranes. Peptidyl dipeptidase A (angiotensin converting enzyme; ACE) was associated with membrane fractions containing muscarinic receptors. An immunoblot of these fractions with an affinity-purified polyclonal antibody to ACE revealed only the neuronal form of ACE (Mr 170,000), the endothelial form (Mr 180,000) being undetectable. Electron microscopic immunoperoxidase staining of the substantia nigra, with an affinity-purified antibody to endopeptidase-24.11 at the preembedding stage, showed this antigen to be confined to the plasma membranes of boutons, axons, and some dendrites. Both pre- and postsynaptic membranes were stained, and occasionally other regions of the dendritic membrane were positive. No staining of synaptic vesicles within the boutons was observed. Thus, two independent approaches indicate that endopeptidase-24.11 is present on both pre- and postsynaptic membranes in the pig substantia nigra. The subcellular fractionation suggests that neuronal ACE is confined to dendritic membranes.


Pregnancy a short time after multimodal therapy for bilateral breast cancer: a case report and review of literature.
Pregnancy occurring after multimodal therapy in a woman with breast cancer with a 1-year follow-up period is a relatively rare condition and has been defined as pregnancy-associated breast cancer. A patient can become pregnant after chemotherapy for breast cancer while she is on tamoxifen. However, the effects of tamoxifen on fetus and on the course of the pregnancy are still unknown. Here, we present a 39-year-old woman treated with chemotherapy and radiotherapy for bilateral breast cancer, and who became pregnant while taking tamoxifen.


[Fatal transmural colitis caused by Entamoeba histolytica. Differential diagnosis of chronic inflammatory bowel disease and colon cancer].
Perforation of the colon is a rare but frequently fatal complication of amoebiasis. We report a case of a 53 year-old male, with no history of travel abroad, who was admitted to hospital with haematochezia. A tumor of the rectum was diagnosed clinically. Due to acute intestinal obstruction, laparotomy was performed, revealing multiple perforations of the large bowel and severe peritonitis leading to subtotal colectomy. The histological examinations revealed transmural amoebic colitis. The patient died due to multi-organ failure.


Localization of 5-HT(2A) receptors on dopamine cells in subnuclei of the midbrain A10 cell group.
Considerable evidence suggests that a dysfunction of the dopamine and serotonin (5-hydroxytryptamine or 5-HT) neurotransmitter systems contributes to a diverse range of pathological conditions including schizophrenia, depression and drug abuse. Recent electrophysiological and behavioral studies suggest that 5-HT modulates dopaminergic neurons in the ventral tegmental area via activation of 5-HT(2A) receptors. It is currently unknown if 5-HT(2A) receptors mediate their actions on dopaminergic neurons in the ventral tegmental area via direct or indirect mechanisms. This study investigated whether 5-HT(2A) receptors were localized on dopamine cells within the A10 dopamine subnuclei of the rat, including the ventral tegmental area. We discovered that 5-HT(2A) receptor-like immunoreactivity colocalized with tyrosine hydroxylase, a marker for dopamine neurons, throughout the A10 dopamine cell population. Colocalization was most prominent in rostral and mid A10 regions, including the paranigral, parabrachial, and interfascicular subnuclei. Though more rare, non-dopaminergic neurons also expressed 5-HT(2A) receptor immunoreactivity in the ventral tegmental area. Additionally, although a dense population of 5-HT(2A) immunoreactive cells was observed in the rostral dorsal raphe nucleus, rarely were these cells immunoreactive for tyrosine hydroxylase. The linear raphe A10 dopamine subdivisions also displayed a low degree of 5-HT(2A) receptor and tyrosine hydroxylase colocalization. These findings provide an anatomical basis for the physiological modulation of dopamine neurons in the rostral ventral tegmental area either directly, by 5-HT(2A) receptors localized on dopamine cells, or indirectly, through a non-dopaminergic mechanism. Interestingly, 5-HT(2A) receptors were expressed on dopamine neurons in several A10 subnuclei that project to mesolimbic forebrain regions implicated in drug addiction, and recent evidence indicates that ventral tegmental area 5-HT(2A) receptor activation may modulate reward-related behavior in rodents. 5-HT(2A) receptors were also expressed on dopamine cells in A10 subnuclei that project to forebrain areas that have been implicated in schizophrenia, and atypical antipsychotic drugs have high affinities for 5-HT(2A) receptors. Thus, findings in this study could have important implications for understanding 5-HT and dopamine circuitry dysfunction in schizophrenia.


Screening of sperm antigen epitopes by phage display technique and its preliminary clinical application.
At present, there is a lack of standardized preparation methods of sperm antigen for the detection of antisperm antibody (AsAb). To screen sperm antigen mimotopes from a phage display random peptide library and use them to establish an enzyme-linked immunosorbent assay (ELISA) for the detection of AsAb, immunoglobulins were extracted from the sera of rabbits with positive AsAb and negative AsAb, respectively, by the saturated ammonium sulfate method, and a phage display 12-mer peptide library was affinity panned by the extracted immunoglobins coated on the ELISA plate. Then, the obtained positive phage clones were identified by ELISA and sent for sequencing and peptides synthesis. Last, a diagnostic ELISA was established to detect clinical serum and seminal plasma samples. A total of sixty phage clones were chosen by affinity panning, and sixteen of them reacted positively with AsAb in indirect ELISA and sandwich ELISA. Following DNA sequencing and translation, the peptide sequences of the sixteen positive clones were obtained. By comparison in Blast database, four of sixteen positive clones were found to be closely related to male reproduction. Two (#1 and #25) of four mimotopes were synthesized, and an ELISA method was established using the two mimotopes as sperm specific antigens. One hundred and thirty-four serum samples and seventy-four seminal plasma samples from infertile couples were analyzed by the established ELISA with #1 and #25 mimotopes, respectively. The positive rates of AsAb in serum samples were 20.15% (27/134) for #1 and 11.19% (15/134) for #25, respectively, and the coincidence rate between them was 91.04% (122/134). The positive rates of AsAb in seminal plasma samples were 1.35% (1/74) for both #1 and #25, and the coincidence rate was 100%. Sperm antigen mimotopes can be obtained successfully by the phage display technique, and can be used as standard sperm specific antigens to establish an ELISA method for the detection of AsAb.


Study of nonlinear resonance effect in Paul trap.
In this article, we investigated the nonlinear resonance effect in the Paul trap with a superimposed hexapole field, which was assumed as a perturbation to the quadrupole field. On the basis of the Poincare-Lighthill-Kuo (PLK) perturbation method, ion motional equation, known as nonlinear Mathieu equation (NME) was expressed as the addition of approximation equations in terms of perturbation order. We discussed the frequency characteristics of ion axial-radial (z-r) coupled motion in the nonlinear field, derived the expressions of ion trajectories and nonlinear resonance conditions, and found that the mechanism of nonlinear resonance is similar to the normal resonance. The frequency spectrum of ion motion in nonlinear field includes not only the natural frequency series but also nonlinear introduced frequency series, which provide the driving force for the nonlinear resonance. The nonlinear field and the nonlinear effects are inevitable in practical ion trap experiments. Our method provides better understanding of these nonlinear effects and would be helpful for the instrumentation for ion trap mass spectrometers.


Muscle trophic factor: II. Ontogenic development of activity of a muscle trophic factor in chicken serum.
The activity of chicken skeletal muscle cell trophic factor was greater in chicken serum than in other tissues examined. The variation of this activity in chicken serum was studied pre- and post hatching. The activity of the factor in the embryo was high from day 11 to day 13 of incubation and then decreased, reaching a minimum on day 16. It subsequently increased again, reaching a peak around the day of hatching. After hatching, the activity in serum began to decrease on day 4, reaching a minimum at day 18. In the hen, activity did not very significantly beyond day 18. In the rooster, however, activity increased gradually from about day 50, reached a new maximum by day 110, and was maintained at this level thereafter. The ratio of the average activity of serum from roosters older than 110 days to that of hens of the same age was about 4:3. The time course of activity of the trophic factor closely parallels that of the growth and differentiation of the muscle in vivo.


Equilibrium studies of lecithin-cholesterol interactions. II. Phase relations in surface films: analysis of the "condensing" effect of cholesterol.
From measurements of the equilibrium spreading pressure pie for dispersions of lecithin--dimyristoyl (DML) or dioleoyl (DOL)--and cholesterol (CHOL) in water, we have deduced the phase relations in both the aqueous dispersions and the equilibrium surface films. At 29.5 degrees C, when the mole fraction of cholesterol in the dispersion chi(CHOL) is 0 chi(CHOL) less than chi(CHOL) less than 0.33, pie is constant and equal to the value for pure lecithin (DOL or DML). The phase rule predicts than two bulk lipid phases coexist; these are pure lecithin and lecithin:cholesterol 2:1 complex. The equilibrium surface film contants only lecithin and therefore lecithin and 2:1 complex are immiscible in surface films. When 0.33 less than chi/CHOL) less than 1.0, pie is also contant with a value intermediate between that for pure lecithin and cholesterol. In this range of lipid composition two bulk lipid phases also coexist: lecithin:cholesterol 2:1 complex and pure cholesterol. However, the equilibrium surface film contains only the 2:1 complex and, therefore, 2:1 complex is also immiscible with cholesterol in surface films. When pi less than pie, as in the case of spread films, we deduce that two surface phases may coexist; the composition of the phases will depend on chi(CHOL). When 0 less than chi(CHOL) less than 0.33, both lecithin and 2:1 complex coexist, and when 0.33 less than chi(CHOL) less than 1.0, 2:1 complex and cholesterol coexist. The "condensing" effect of cholesterol in lecithin surface films is reexamined. The effect is attributed to formation of the lecithin:cholesterol 2:1 complex and nonequilibrium conditions in the two-phase surface film.


An unusual medieval mandibular pathology.
A medieval mandible with an unusual bilateral periosteal reaction, probably related to chronic inflammation or infection, is presented.


Identification of QTLs involved in open-field behavior in young and adult laying hens.
Line differences for open-field behavior in chickens have been observed, and it has been shown that this behavior has a genetic component. The aim of this study was to detect quantitative trait loci (QTL) involved in open-field behavior. For this purpose, open-field behavior was studied at 5 and 29 weeks of age in F(2) hens coming from an intercross between two commercial White Leghorn laying lines selected for egg production traits. Latencies, durations, and frequencies of general activity (sitting, standing, walking, and stepping), defecation, and vocalizations were recorded individually for each bird, and a factor score was calculated. All animals (F(0), F(1), and F(2)) were screened with 180 microsatellite markers. Regression interval mapping was applied using both a paternal half-sib analysis and a line-cross analysis method. For general activity at 5 weeks of age, a significant QTL was detected on GGA4 and a suggestive QTL on GGA2 under the line-cross model. For general activity at 29 weeks of age, a significant QTL was detected on GGA4 and two suggestive QTLs were detected on GGA1 and on GGA10, respectively, also using the line-cross analysis. The QTL on GGA4 at 5 weeks of age did not overlap with the QTL on GGA4 at 29 weeks of age. The current study indicated that open-field behavior in young chickens was regulated by QTL that differ from the QTL for open-field behavior in adult chickens.


Correspondence in relation to the case report "Capnography as an aid in localizing the phrenic nerve in brachial plexus surgery. Technical note." published in May issue of Journal of Brachial Plexus and Peripheral Nerve Injury.
Comment on 'Capnography as an aid in localizing the phrenic nerve in brachial plexus surgery. Technical note' Bhagat H, Agarwal A, Sharma MSJournal of Brachial Plexus and Peripheral Nerve Injury 2008, 3:14 (22 May 2008).


Prepulse inhibition of the startle response in risperidone-treated patients: comparison with typical antipsychotics.
Individuals with schizophrenia are known to show deficits in prepulse inhibition (PPI) of the startle response. PPI refers to a response suppression in reaction to a strong startling stimulus, if preceded briefly by a weak non-startling stimulus and represents a well-established animal model to investigate information processing deficits in schizophrenia. This study examined PPI of the startle acoustic response in schizophrenic patients given typical antipsychotics or a second generation atypical antipsychotic, risperidone, using a naturalistic between-subjects design. Two groups of male schizophrenic patients: (i) stable on a range of typical antipsychotics (n = 20), and (ii) stable on risperidone (n = 10) were tested for PPI (prepulse-to-pulse intervals: 30, 60, and 120 ms, prepulses 15 dB above the background) of the acoustic startle response, and compared with a group of healthy male subjects (n = 20). Patients on typical antipsychotics showed significantly less PPI with 30 and 60 ms prepulse trials than healthy subjects. Risperidone-treated patients did not differ from healthy subjects for PPI with any prepulse trials. Further longitudinal within-subject studies are now required to examine whether risperidone is superior to typical antipsychotics in improving information processing functions, as assessed by PPI of the acoustic startle response, in treatment-responsive male patients with schizophrenia.


Deciphering Intrinsic Inter-subunit Couplings that Lead to Sequential Hydrolysis of F1-ATPase Ring.
Rotary sequential hydrolysis of the metabolic machine F1-ATPase is a prominent manifestation of high coordination among multiple chemical sites in ring-shaped molecular machines, and it is also functionally essential for F1 to tightly couple chemical reactions and central γ-shaft rotation. High-speed AFM experiments have identified that sequential hydrolysis is maintained in the F1 stator ring even in the absence of the γ-rotor. To explore the origins of intrinsic sequential performance, we computationally investigated essential inter-subunit couplings on the hexameric ring of mitochondrial and bacterial F1. We first reproduced in stochastic Monte Carlo simulations the experimentally determined sequential hydrolysis schemes by kinetically imposing inter-subunit couplings and following subsequent tri-site ATP hydrolysis cycles on the F1 ring. We found that the key couplings to support the sequential hydrolysis are those that accelerate neighbor-site ADP and Pi release upon a certain ATP binding or hydrolysis reaction. The kinetically identified couplings were then examined in atomistic molecular dynamics simulations at a coarse-grained level to reveal the underlying structural mechanisms. To do that, we enforced targeted conformational changes of ATP binding or hydrolysis to one chemical site on the F1 ring and monitored the ensuing conformational responses of the neighboring sites using structure-based simulations. Notably, we found asymmetrical neighbor-site opening that facilitates ADP release upon enforced ATP binding. We also captured a complete charge-hopping process of the Pi release subsequent to enforced ATP hydrolysis in the neighbor site, confirming recent single-molecule analyses with regard to the role of ATP hydrolysis in F1. Our studies therefore elucidate both the coordinated chemical kinetics and structural dynamics mechanisms underpinning the sequential operation of the F1 ring.


Hypoxia induces apoptosis in human neuroblastoma SK-N-MC cells by caspase activation accompanying cytochrome c release from mitochondria.
We have attempted to elucidate the mechanism of apoptotic cell death induced by hypoxia (very low oxygen conditions) in neuronal cells. Human neuroblastoma SK-N-MC cells under hypoxic conditions resulted in apoptosis in a time-dependent manner estimated by DNA fragmentation assay and nuclear morphology stained with fluorescent chromatin dye. Pretreatment with Z-Asp-CH2-DCB, a caspase inhibitor, suppressed the DNA ladder in response to hypoxia in a concentration-dependent manner. An increase in caspase-3-like protease (DEVDase) activity was observed during apoptosis, but no caspase-1 activity (YVADase) was detected. To confirm the involvement of caspase-3 during apoptosis, Western blot analysis was performed using anti-caspase-3 antibody. The 20- and 17-kDa proteins, corresponding to the active products of caspase-3, were generated in hypoxia-challenged lysates in which processing of the full length form of caspase-3 was evident. With a time course similar to this caspase-3 activation, hypoxic stress caused the cleavage of PARP, yielding an 85-kDa fragment typical of caspase activity. In addition, caspase-2 was also activated by hypoxia, and the stress elicited the release of cytochrome c into the cytosol during apoptosis. These results suggest that caspase activation and cytochrome c release play roles in hypoxia-induced neuronal apoptosis.


Effects of hot water extract of Curcuma longa on human epidermal keratinocytes in vitro and skin conditions in healthy participants: A randomized, double-blind, placebo-controlled trial.
Curcuma longa has been reported to have anti-inflammatory effects. Skin inflammation impairs skin functions. Our aim was to investigate the effect of a hot water extract of C longa (WEC) on skin conditions in cell studies using keratinocytes and in clinical trials. We measured proinflammatory cytokine levels in ultraviolet B-irradiated keratinocytes in the presence or absence of WEC. The effects of WEC on hyaluronan production in keratinocytes were also determined. In a randomized, double-blind, placebo-controlled trial, 47 healthy participants were assigned to 8-week intervention groups with daily intakes of WEC with or without curcumin or a placebo. The water content and transepidermal water loss in the face and minimal erythema dose on the back after ultraviolet B irradiation were evaluated every 4 weeks. Hot water extract of C longa significantly inhibited increases in ultraviolet B-induced tumor necrosis factor α and interleukin 1β at the mRNA and protein levels. WEC also significantly increased hyaluronan production from nonstimulated keratinocytes. In the randomized, double-blind, placebo-controlled trial, increases from baseline in the water content of the face were significantly greater at weeks 4 and 8 in the WEC group, but not in the WEC + curcumin group, than in the placebo group. There were no significant differences in transepidermal water loss and minimal erythema dose among the groups. The cell studies confirmed that WEC has anti-inflammatory effects and augments hyaluronan production in the skin. The results of clinical trials suggest that WEC may be useful for moisturizing facial skin. UMIN Clinical Trials Registry 000028510. Retrospectively registered.


Activation by lithium ions of the inside sodium sites in (Na+ + K+)-ATPase.
1. Purified pig kidney ATPase was incubated in 30--160 mM Tris-HCl with various monovalent cations. 130 mM LiCl stimulated a ouabain-sensitive ATP hydrolysis (about 5% of the maximal (Na+ + K) activity), whereas 160 mM Tris-HCl did not stimulate hydrolysis. Similar results were obtained with human red blood cell broken membranes. 2. In the absence of Na+ and with 130 mM LiCl, the ATPase activity as a function of KCl concentration showed an initial slight inhibition (50 micrometer KCl) followed by an activation (maximal at 0.2 mM KCl) and a further inhibition, which was total at mM KCl. In the absence of LiCl, the rate of hydrolysis was not affected by any of the KCl concentrations investigated. 3. The lithium-activation curve for ATPase activity in the absence of both Na+ and K+ had sigmoid characteristics. It also showed a marked dependence on the total LiCl + Tris-HCl concentration, being inhibited at high concentrations. This inhibition was more noticeable at low LiCl concentrations. 4. In the absence of Na+, 130 mM Li+ showed promoted phosphorylation of ATPase from 1 to 3 mM ATP in the presence of Mg2+. In enzyme treated with N-ethylmaleimide, the levels of phosphorylation in Li+-containing solutions, amounted to 40% of those in Na+- and up to 7 times of those in K+-containing solutions. 5. The total (Na+ + K+)-ATPase activity was markedly inhibited at high buffer concentrations (Tris-HCl, Imidazole-HCl and tetramethylammonium-HEPES gave similar results) in cases when either the concentration of Na+ or K+ (or both) was below saturation. On the other hand, the maximal (Na+ + K+)-ATPase activity was not affected (or very slightly) by the buffer concentration. 6. Under standard conditions (Tris-HCl + NaCl = 160 mM) the Na+-activation curve of Na+-ATPase had a steep rise between 0 and 2.5 mM, a fall between 2.5 and 20 mM and a further increase between 20 and 130 mM. With 30 mM Tris-HCl, the curve rose more steeply, inhibition was noticeable at 2.5 mM Na+ and was completed at 5 mM Na+. With Tris-HCl + NaCl = 280 mM, the amount of activation decreased and inhibition at intermediate Na+ concentrations was not detected.


Dual lanthanide-doped complexes: the development of a time-resolved ratiometric fluorescent probe for anthrax biomarker and a paper-based visual sensor.
In this work, a novel time-resolved ratiometric fluorescent probe based on dual lanthanide (Tb: terbium, and Eu: europium)-doped complexes (Tb/DPA@SiO2-Eu/GMP) has been designed for detecting anthrax biomarker (dipicolinic acid, DPA), a unique and major component of anthrax spores. In such complexes-based probe, Tb/DPA@SiO2 can serve as a stable reference signal with green fluorescence and Eu/GMP act as a sensitive response signal with red fluorescence for ratiometric fluorescent sensing DPA. Additionally, the probe exhibits long fluorescence lifetime, which can significantly reduce the autofluorescence interferences from biological samples by using time-resolved fluorescence measurement. More significantly, a paper-based visual sensor for DPA has been devised by using filter paper embedded with Tb/DPA@SiO2-Eu/GMP, and we have proved its utility for fluorescent detection of DPA, in which only a handheld UV lamp is used. In the presence of DPA, the paper-based visual sensor, illuminated by a handheld UV lamp, would result in an obvious fluorescence color change from green to red, which can be easily observed with naked eyes. The paper-based visual sensor is stable, portable, disposable, cost-effective and easy-to-use. The feasibility of using a smartphone with easy-to-access color-scanning APP as the detection platform for quantitative scanometric assays has been also demonstrated by coupled with our proposed paper-based visual sensor. This work unveils an effective method for accurate, sensitive and selective monitoring anthrax biomarker with backgroud-free and self-calibrating properties.


Deletion-pattern analysis of alpha-particle and X-ray induced mutations at the HPRT locus of V79 Chinese hamster cells.
To investigate the mutagenic mechanisms of low-energy alpha particles V79 Chinese hamster cells were irradiated with 241Am-alpha particles (mean LET of 112 keV/micron). Parallel experiments were performed using 300 kV X-rays. Cell inactivation and mutation induction cross sections were measured. At approximately 20%--survival level, DNA deletions were analysed at the HPRT locus by multiplex-PCR-analysis of all nine exons of 47 alpha-irradiated and 36 background mutants. 92 HPRT- mutants isolated after 300 kV-X-irradiation were analysed similarly for comparison, along with 15 corresponding background mutants. The resulting mutant deletion-pattern distributions were corrected for background mutations. alpha Particles induced a larger fraction of deletions than X-rays. Furthermore, non-contiguous partial deletions were present among the alpha-induced mutants, a type not found after X-irradiation.


Aging and cancer cell biology, 2008.
There is increasing support for the idea that aging and cancer are intimately connected by the activity of specific genes and the cellular responses to potentially oncogenic insults. This Hot Topics review discusses some recently published articles that shed light on both the commonalities--and intricacies--of the cancer-aging relationship. These articles reveal the expected complexities, but also surprising conservation, in mechanisms that link cancer and aging.


NTRK fusion events and targeted treatment of advanced radioiodine refractory thyroid cancer.
Pathogenic fusion events involving neurotrophic receptor tyrosine kinase (NTRK) have been described in ~ 2% of differentiated thyroid cancer (DTC). The selective tropomyosin receptor kinase (TRK) inhibitors entrectinib and larotrectinib have been approved in a tumor agnostic manner based on phase 1/2 clinical trials. In a real-world setting at five referral centers, we aimed to describe the prevalence of NTRK gene fusions and the efficacy and safety of TRK inhibitor treatment for non-medullary, advanced thyroid cancer (TC). A total of 184 TC patients with testing for NTRK gene fusions were included. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated using the Kaplan-Meier method in six patients with NTRK fusion-positive TC who underwent TRK inhibitor therapy. 8/184 (4%) patients harbored NTRK gene fusions. Six patients with radioiodine (RAI)-refractory TC harboring NTRK1 (n = 4) and NTRK3 (n = 2) gene fusions were treated with larotrectinib. Five patients (83%) had received ≥ 1 prior systemic therapy and one patient did not receive prior systemic therapy. All patients had morphologically progressive disease before treatment initiation. Objective response rate was 83%, including two complete remissions. Median PFS from start of TRK inhibitor treatment was 23 months (95% confidence interval [CI], 0-57.4) and median OS was not reached (NR) (95% CI, NR). Adverse events were of grade 1-3. The prevalence of NTRK gene fusions in our cohort of RAI-refractory TC is slightly higher than reported for all TC patients. Larotrectinib is an effective treatment option in the majority of NTRK gene fusion-positive advanced TC patients after prior systemic treatment and has a favorable safety profile.


Factors associated with caregiver help seeking behavior among at-risk children.
Few at-risk school-age children receive needed psychological help, and our understanding of predictors of service use in this population is limited. Many broader contextual factors have received little attention including caregiver's trauma history and social support, father involvement, family functioning, and neighborhood satisfaction. The links between types of and cumulative maltreatment have also been inconsistent, and prior work has not always accounted for children's symptoms. The current study examined child, caregiver, family, neighborhood, and maltreatment factors in relation to past-year mental health service use among at-risk eight-year-old children. Cumulative and types of maltreatment were both investigated to help elucidate the role of these experiences. Eight hundred and forty-five eight-year-old at-risk children (48.3 % male; 59.5 % Black) from the Longitudinal Studies in Child Abuse and Neglect (LONGSCAN) were included. A small portion of children (12.4 %) received psychological help in the previous year. Children's externalizing symptoms, residing with a non-biological caregiver, cumulative maltreatment and sexual and emotional abuse were associated with seeking psychological services, whereas physical abuse, neglect, and domestic violence exposure were not. Other caregiver factors, and family and neighborhood factors were also unrelated. Non-biological caregivers as well as caregivers of children with higher levels of externalizing symptoms may be more inclined to seek out mental health services, along with greater, and specific, maltreatment experiences. These findings indicate that child factors may be key in understanding help seeking, however, it is important to further consider other broader contextual factors in future work.


Underdeveloped trabecular bone microarchitecture is detected in children with cerebral palsy using high-resolution magnetic resonance imaging.
Using high resolution magnetic resonance imaging, we detected severely underdeveloped trabecular bone microarchitecture in the distal femur of children with cerebral palsy who can not ambulate independently vs. typically developing controls. Furthermore, very good short-term reliability of trabecular bone microarchitecture measurements was observed in both groups of children. Severe forms of cerebral palsy (CP) are associated with very low areal bone mineral density and a very high incidence of fracture in the distal femur; however, the state of trabecular bone microarchitecture has not been evaluated. Furthermore, the short-term reliability of trabecular bone microarchitecture assessment in children using high-resolution magnetic resonance imaging (MRI) has not been determined. Apparent bone volume to total volume (appBV/TV), trabecular number, (appTb.N), trabecular thickness (appTb.Th) and trabecular separation (appTb.Sp) were determined in the distal femur of non-ambulatory children with CP and typically developing children using MRI. Children with CP had a 30% lower appBV/TV, a 21% lower appTb.N, a 12% lower appTb.Th and a 48% higher appTb.Sp in the distal femur than controls (n = 10/group; P < 0.001). The short-term reliability of the trabecular bone microarchitecture measures was very good, with coefficients of variation ranging from 2.0 to 3.0% in children with CP (n = 6) and 1.8 to 3.5% in control children (n = 6). Underdeveloped trabecular bone microarchitecture can be detected in the distal femur of children with CP who can not ambulate independently using high-resolution MRI. Furthermore, MRI can be used to assess trabecular bone microarchitecture in children with a high degree of reliability.


Nuclear expression of N-cadherin correlates with poor prognosis of nasopharyngeal carcinoma.
To investigate the aberrant expression of N-cadherin in nasopharyngeal carcinoma (NPC) and its prognostic significance. Immunohistochemical staining for N-cadherin protein was performed on tissue microarray (TMA) from 122 NPC patients. Cytoplasmic N-cadherin was observed in 42.6% and nuclear N-cadherin in 45.1% of NPC tissues. High expression of cytoplasmic and nuclear N-cadherin was associated with a majority of the clinicopathological variables, including lymph node metastasis, distant metastasis and clinical stage. Cytoplasmic N-cadherin was associated positively with nuclear N-cadherin expression (P = 0.000). In univariate analysis, cytoplasmic N-cadherin showed no significant impact on patient prognosis. In contrast, the overall survival was significantly shorter in patients with high nuclear N-cadherin than those with low levels of staining (P = 0.002). A high expression of nuclear N-cadherin predicted poorer survival in patients with late stage disease (P = 0.033), but not those with early tumour stage. In addition, multivariate analysis showed nuclear N-cadherin to bean independent prognostic marker for NPC patients (P = 0.024). Nuclear N-cadherin expression may represent a valuable prognostic marker in NPC patients, especially those with late stage disease.


Persistence of rat virus in seropositive rats as detected by explant culture. Brief report.
Rat virus (RV) was detected by explant culture for up to 14 weeks in rats inoculated as infants and for up to 7 weeks in rats inoculated as juveniles, although both groups were seropositive by 3 weeks post-inoculation.


Quantitative imaging approaches to understanding biological processing of metal ions.
Faster, more sensitive, and higher resolution quantitative instrumentation are aiding a deeper understanding of how inorganic chemistry regulates key biological processes. Researchers can now image and quantify metals with subcellular resolution, leading to a vast array of new discoveries in organismal development, pathology, and disease. Metals have recently been implicated in several diseases such as Parkinson's, Alzheimers, ischemic stroke, and colorectal cancer that would not be possible without these advancements. In this review, instead of focusing on instrumentation we focus on recent applications of label-free elemental imaging and quantification and how these tools can lead to a broader understanding of metals role in systems biology and human pathology.


A new approach for bio-jet fuel generation from palm oil and limonene in the absence of hydrogen.
The traditional methodology includes a carbon-chain shortening strategy to produce bio-jet fuel from lipids via a two-stage process with hydrogen. Here, we propose a new solution using a carbon-chain filling strategy to convert C10 terpene and lipids to jet fuel ranged hydrocarbons with aromatic hydrocarbon ingredients in the absence of hydrogen.


Profiling of rice Cd-tolerant genes through yeast-based cDNA library survival screening.
The bioaccumulation of cadmium (Cd) in crop and the subsequent food chain has aroused extensive concerns. However, the underlying molecular mechanisms of plant Cd tolerance remain to be clarified from the viewpoint of novel candidate genes. Here we described a highly efficient approach for preliminary identifying rice Cd-tolerant genes through the yeast-based cDNA library survival screening combined with high-throughput sequencing strategy. About 690 gene isoforms were identified as being Cd-tolerant candidates using this shotgun approach. Among the Cd-tolerant genes identified, several categories of genes such as BAX inhibitor (BI), NAC transcription factors and Rapid ALkalinization Factors (RALFs) were of particular interest, and their function of Cd tolerance was further validated via heterologous expression, which suggested that SNAC1, RALF12, OsBI-1 can confer Cd tolerance in yeast and tobacco leaves. Regarding the genes involved in ion transport, the validated Cd-tolerant heavy metal-associated domain (HMAD) isoprenylated protein HIPP42 was particularly noteworthy. Further elucidation of these genes associated with Cd tolerance in rice will benefit agricultural activities.


Second-line antirheumatic drugs in the elderly with rheumatoid arthritis: a post hoc analysis of three controlled trials.
This study assessed the relative efficacy and toxicity of second-line antirheumatic drugs in patients 65 years of age or older compared to younger counterparts. The results of three prospective, double-blind, parallel, randomized, multicenter trials were reanalyzed, stratifying outcomes by intervention and patient age. Efficacy was assessed by categorizing patient responses as follows: important improvement, no meaningful change, or progressive disease. Toxicity was analyzed by comparing withdrawal rates due to adverse effects. The three trials compared the following treatments: (1) D-penicillamine 10-12 mg/day versus azathioprine 1.25-1.5 mg/kg/day; (2) gold sodium thiomalate 50 mg intramuscularly weekly versus auranofin 6 mg/day versus placebo; and (3) pulse oral methotrexate 7.5-15.0 mg weekly versus placebo. At baseline, 103 patients age 65 or older were similar to 485 patients less than 65 years of age, with the exception of disease duration in all studies and erythrocyte sedimentation rate in one study. For patients completing each study, efficacy outcomes based on age were not significantly different. Withdrawal rates due to adverse drug reactions were also not significantly different.


Increased stress reactivity as a possible factor of early degenerative changes in OXYS rats.
After stress (immobilization in cages) plasma corticosterone level in prematurely aging OXYS rats was higher, while the content of NO metabolites was much lower than in Wistar rats. Stress increased blood pressure in OXYS and Wistar rats, the maximum values were observed in control and stressed OXYS rats. The concentration of reduced glutathione in the brain of OXYS rats was lower than in Wistar rats. After immobilization the concentration of reduced glutathione decreased in animals of both strains. The concentration of oxidized protein increased by 1.5 times only in OXYS rats. SOD activity remained unchanged, but in OXYS rats this parameter was higher than in Wistar rats. It can be hypothesized that high blood pressure, low NO content, high corticosterone concentration, and stress-induced deficiency of the antioxidant system (or combined effects of these factors) contribute to the development of neurodegenerative changes in the brain of OXYS rats.


Estimating SNP proportions in populations of malaria parasites by sequencing: validation and applications.
We have developed a rapid and simple method for determining accurately the proportions of alleles or individual malaria clones in a mixed infection. The technique uses a nested PCR reaction to amplify, from parasite mixtures, alleles of genes differing by single nucleotide polymorphisms, simultaneously, using common primers to non-polymorphic sequences. The mixed products are sequenced, and the heights of fluorescence peaks associated with different nucleotides at the polymorphic site used to quantitate the proportions of each allele in the mixture. We have confirmed the accuracy and precision of the method using a set of well-validated mixtures of genetically different malaria parasites. This technique can be used in the mapping of genetic loci underlying phenotypic traits and in the evaluation of the effects of different alleles upon the reproductive success (fitness) of parasites.


The role of phytochemicals in sepsis: A mechanistic and therapeutic perspective.
Sepsis and septic shock are still a leading cause of mortality and morbidity in intensive care units worldwide. Sepsis is an uncontrolled and excessive response of the innate immune system toward the invading infectious microbes, characterized by the hyper-production of pro-inflammatory mediators such as interleukin (IL)-1β, IL-6, tumor-necrosis factor (TNF)-α, and high-mobility group box 1 (HMGB1). In severe sepsis, the overwhelming production of pro-inflammatory cytokines and reactive oxygen species may compromise organ function and lead to the induction of abnormal apoptosis in different organs, resulting in multiple organ dysfunction syndrome and death. Hence, compounds that are able to attenuate inflammatory responses may have therapeutic potential for sepsis treatment. Understanding the pathophysiology and underlying molecular mechanisms of sepsis may provide useful insights in the discovery and development of new effective therapeutics. Therefore, numerous studies have invested much effort into elucidating the mechanisms involved with the onset and development of sepsis. The present review mainly focuses on the molecules and signaling pathways involved in the pathogenicity of sepsis. Additionally, several well-known natural bioactive herbal compounds and phytochemicals, which have shown protective and therapeutic effects with regard to sepsis, as well as their mechanisms of action, are presented. This review suggests that these phytochemicals are able to attenuate the overwhelming inflammatory responses developed during sepsis by modulating different signaling pathways. Moreover, the anti-inflammatory and cytoprotective activities of phytochemicals make them potent compounds to be included as complementary therapeutic agents in the diets of patients suffering from sepsis in an effort to alleviate sepsis and its life-threatening complications, such as multi-organ failure.


Age-specific detection and false-positive rates: an aid to counseling in Down syndrome risk screening.
To determine whether the serum screening test for Down syndrome provides equal detection efficacy for women of all ages, to improve the data available for patient counseling both before testing and afterward in the event of a positive result. We examined the effect of age on Down screening by generating a set of "normal" and "Down syndrome" likelihood ratios by computer simulation. The expected false-positive and detection rates were derived for different age groups by counting the proportion of cases in which the likelihood ratio could modify the age-specific risk to be greater than the cutoff risk of one in 300 (equivalent to an incidence of 3.33 per 1000). The predictive value of a positive result was calculated using Baye's theorem. Detection rates, false-positive rates, and predictive values were shown to be age-dependent. Knowledge of the age dependency of Down syndrome screening results may be useful in explaining to patients that the Down screen can only detect a proportion of cases and that a negative result does not guarantee normality. This knowledge may also be helpful in minimizing psychological stress, as a positive result indicates only a small chance that the fetus will have Down syndrome.


Clinical evaluation of a new temporary pacemaker wire.
A newly designed temporary pacemaker wire has been tested in 20 patients who underwent open-heart operations. This new device has a small tip that stays securely buried in the myocardium, thus greatly reducing the risk of accidental dislodgment. In addition, the increase in thresholds during the postoperative period is slighter than with the standard electrode.


Abundance, diversity and mobility potential of antibiotic resistance genes in pristine Tibetan Plateau soil as revealed by soil metagenomics.
Widespread occurrence of antibiotic resistance genes (ARGs) has become an important clinical issue. Studying ARGs in pristine soil environments can help to better understand the intrinsic soil resistome. In this study, 10 soil samples were collected from a high elevation and relatively pristine Tibetan area, and metagenomic sequencing and bioinformatic analyses were conducted to investigate the microbial diversity, the abundance and diversity of ARGs and the mobility potential of ARGs as indicated by different mobile genetic elements (MGEs). A total of 48 ARG types with a relative abundance of 0.05-0.28 copies of ARG/copy of 16S rRNA genes were detected in Tibetan soil samples. The observed ARGs were mainly associated with antibiotics that included glycopeptide and rifamycin; the most abundant ARGs were vanRO and vanSO. Low abundance of MGEs and potentially plasmid-related ARGs indicated a low horizontal gene transfer risk of ARGs in the pristine soil. Pearson correlation and redundancy analyses showed that temperature and total organic carbon were the major environmental factors controlling both microbial diversity and ARG abundance and diversity.


Relationship between dietary pattern and depressive symptoms: an international multicohort study.
Several previous studies have shown that dietary patterns are associated with the incidence of depressive symptoms. However, the results have been inconsistent. This study aimed to prospectively investigate the association between dietary patterns and the risk of depressive symptoms in two large cohort studies. The Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort study included a total of 7,094 participants living in Tianjin, China from 2013 to 2019, and the UK Biobank cohort study includes 96,810 participants who were recruited from 22 assessment centers across the UK taken between 2006 and 2010. All participants were free of a history of cardiovascular disease (CVD), cancer, and depressive symptoms at baseline. Dietary patterns at baseline were identified with factor analysis based on responses to a validated food frequency questionnaire in TCLSIH or Oxford WebQ in UK Biobank. Depressive symptoms were evaluated using the Chinese version of the Zung Self-Rating Depression Scale (SDS) in TCLSIH or hospital inpatient records in UK Biobank. Cox proportional hazards regression models were used to estimate the association between dietary patterns and depressive symptoms. A total of 989, and 1,303 participants developed depressive symptoms during 17,410 and 709,931 person-years of follow-up. After adjusting for several potential confounders, the multivariable HRs (95% CIs) of the depressive symptoms were 0.71 (0.57, 0.88) for traditional Chinese dietary pattern, 1.29 (1.07, 1.55) for processed animal offal included animal food dietary pattern, and 1.22 (1.02, 1.46) for sugar rich dietary pattern in TCLSIH (all Q4 vs Q1). In the UK Biobank, the HRs (95% CIs) of depressive symptoms were 1.39 (1.16, 1.68) for processed food dietary pattern (Q4 vs Q1), 0.90 (0.77, 1.00) for healthy dietary pattern (Q3 vs Q1), and 0.89 (0.75, 1.05) for meat dietary pattern (Q4 vs Q1) in the final adjusted model. Dietary patterns rich in processed foods were associated with a higher risk of depressive symptoms, and following a traditional Chinese dietary pattern or healthy dietary pattern was associated with a lower risk of depressive symptoms, whereas meat dietary pattern was not associated.


The effect of postocclusion reactive hyperaemia, papaverine and nifedipine on duplex derived haemodynamic parameters of infrainguinal bypass grafts.
The aim of the present study was to analyse the effects of various vasodilating stimuli on postoperative infrainguinal graft haemodynamics. Duplex derived haemodynamic parameters of infrainguinal bypass grafts were measured at rest and after postocclusion reactive hyperaemia, intraarterial papaverine (40 mgm) injection and peroral nifedipine (10 mg) administration. Department of Surgery, University Hospital. Twenty-nine patients with infrainguinal bypass grafts were studied by Duplex scanner after a median of 25 months postoperatively. Peak systolic velocity (PSV), mean velocity (MV) and volume flow (VF) were measured at rest and after various stimuli. VF at rest increased from 125 +/- 16 ml/min (mean +/- S.E.M.) to 271 +/- 26 ml/min after papaverine administration and to 205 +/- 19 ml/min during reactive hyperaemia (p < 0.001). PSV, MV and VF increased significantly during postocclusion reactive hyperaemia and papaverine injection. After nifedipine administration VF increased to 154 +/- 21 ml/min after 30 min (p < 0.001) and there was a significant increase in MV (p < 0.05). Duplex derived flow measurement of infrainguinal bypass grafts can evaluate graft and limb haemodynamics in the postoperative period. Pharmacological manipulations, such as vasodilation, can influence the physiological runoff with subsequent increase in volume flow through the graft.


Inhibitory effects of multicomponent, phosphonate-grafted, zwitterionic chitosan biomacromolecules on silicic acid condensation.
This article reports the inhibitory effects of phosphonated chitosan (PCH, synthesized from chitosan (CHS) by a Mannich-type reaction) on the in vitro silicic acid condensation. In particular, the ability of PCH to retard silicic acid condensation in aqueous supersaturated solutions at circumneutral pH is studied. Furthermore, the effect of anionic carboxymethyl inulin (CMI) polyelectrolyte on the inhibitory activity of PCH is systematically studied. It was discovered that when PCH is added in dosages up to 150 ppm, it can inhibit silicic acid condensation, thereby maintaining soluble silicic acid up to 300 ppm (for 8 h, from a 500 ppm initial stock solution). The addition of CMI to working solutions that already contain PCH can further enhance the inhibitory action of PCH. A combination of 150 ppm PCH and 100 ppm CMI maintains 400 ppm soluble silicic acid for 8 h. PCH and CMI combinations also affect colloidal silica particle morphology.


Porphyrins bearing stable meso-alkylidenyl double bonds. A new family of nonplanar porphyrinoids.
[Structure: see text] Unique core-modified porphyrinoids, such as oxabenziporphyrins, oxapyriporphyrins, and thiapyriporphyrins, bearing exocyclic C-C double bonds at meso-positions, have been synthesized and characterized. The synthesis was accomplished by utilizing typical "3+1"-type condensation. Two different stable tautomeric forms were isolated, and the two tautomeric forms can be interconvertible upon treatment with base. In contrast, only the structure bearing an exocyclic double bond was isolated in the case of oxapyriporphyrin and oxabenziporphyrin.


Amnesia for context fear is caused by widespread disruption of hippocampal activity.
The hippocampus plays an essential role in the formation and retrieval of episodic memories in humans and contextual memories in animals. However, amnesia is not always observed when this structure is compromised. To determine why this is the case, we compared the effects of several different circuit manipulations on memory retrieval and hippocampal activity. Mice were first trained on context fear conditioning and then optogenetic and chemogenetic tools were used to alter activity during memory retrieval. We found that retrieval was only impaired when manipulations caused widespread changes (increases or decreases) in hippocampal activity. Widespread increases occurred when pyramidal cells were excited and widespread decreases were found when GABAergic neurons were stimulated. Direct hyperpolarization of excitatory neurons only moderately reduced activity and did not produce amnesia. Surprisingly, widespread decreases in hippocampal activity did not prevent retrieval if they occurred gradually prior to testing. This suggests that intact brain regions can express contextual memories if they are given adequate time to compensate for the loss of the hippocampus.


Gene identification and recombinant protein of a lysozyme from freshwater mussel Cristaria plicata.
Lysozymes are important proteins to bivalve in the innate immune responses against bacterial infections, and provide nutrition as digestion enzymes. A new LYZ1 from the freshwater mussel Cristaria plicata was cloned by rapid amplification of cDNA ends (RACE) and nested PCR method. The full-length cDNA sequence of CpLYZ1 was 763 bp. The cDNA contained a 5'-terminal untranslated region (UTR) of 21 bp, a 3'- terminal UTR of 259 bp with a 29 bp poly(A) tail, a tailing signal (AATAAA) and the open reading frame of 483 bp. The CpLYZ1 cDNA encoded a polypeptide of 160 amino acids with a predicted molecular mass of 17.8 kDa, and a theoretical isoelectric point of 6.07. The comparison of the deduced amino acid sequences with LYZs from other species showed that the enzyme belonged to i-type lysozyme. The mRNA transcript of CpLYZ1 could be detected in all the examined tissues with the highest expression level in hepatopancreas. The expression levels of CpLYZ1 in hemocytes, hepatopancreas and gill significantly increased after Aeromonas hydrophila challenge. The expression level of CpLYZ1 in hemocytes sharply decreased from 6 h to 24 h and significantly increased at 48 h, and was the highest level in hepatopancreas at 24 h, and was the maximum level in gill at 48 h. Furthermore, the recombinant CpLYZ1 was induced to be expressed as an inclusion body form by IPTG at 37 °C for 4 h, and then was purified by using the Ni(2+) affinity chromatography. The relative enzyme activity of the recombinant CpLYZ1 was influenced on pH and temperature. The optimal pH and temperature was 5.5 and 50 °C, respectively. Against Escherichia coli, A. hydrophila, Staphyloccocus aureus, Bacillus subtilis, Streptococcus sp. and Staphylococcus epidermidis, the recombinant CpLYZ1 had bacteriolytic activity.


Addition of etoposide to CHOP chemotherapy in untreated patients with high-grade non-Hodgkin's lymphoma.
Second- and third-generation chemotherapy protocols for the treatment of aggressive non-Hodgkin's lymphomas (NHL) have considerable, and age-related, toxic effects. In addition, they do not seem to prolong overall survival in comparison to standard CHOP chemotherapy. In this phase II study we investigated the feasibility and efficacy of the addition of etoposide to the conventional CHOP regimen. Toxicity and clinical efficacy were determined in 132 patients with previously untreated high-grade NHL. There were 51 patients in clinical stage I and II and 81 patients in stage III and IV, with a median age of 54 years (range 17-85). Patients received standard-dose CHOP plus etoposide 100 mg/m2 i.v. on day 1 and 200 mg/m2 p.o. on days 2-3. The overall response rate was 84%, with 70% complete and 14% partial responses. The predicted three- and five-year survivals for the group as a whole were 60% and 53%, respectively, and the corresponding disease-free survivals for patients achieving complete remissions were 65% and 56%, respectively. Outcome was not different from that of CHOP-treated patients in a recently completed Nordic study performed during the same time period. Myelosuppression (WHO grade 3-4), observed in 87% of patients and infectious complications (WHO grade 3-4) in 33%, dominated the toxicity profile of this regimen. Fifty-seven of 92 complete responders (62%) received 6-8 CHOP-E cycles with no reductions in planned dose intensity. LDH level higher than normal, extranodal sites = 2, stage III-IV at diagnosis were all indicators of a poor survival. We conclude that CHOP-E treatment is effective in high-grade NHL. However, mainly due to severe myelosuppression frequent schedule modifications were required and the results are not obviously superior to those of conventional CHOP.


The origin of deletion 22q11 in chronic lymphocytic leukemia is related to the rearrangement of immunoglobulin lambda light chain locus.
The technology of array comparative genomic hybridization (array-CGH/aCGH) enabled the identification of novel genomic aberrations in chronic lymphocytic leukemia (CLL) including the monoallelic and biallelic deletions affecting 22q11 locus. In contrast to previous publications, we hypothesized that the described 22q11 deletions are a consequence of the rearrangement of immunoglobulin lambda light chain locus (IGL) segments surrounding several protein-coding genes located in this region. Indeed, using array-CGH and PCR analysis we show that all deletions (n=7) affecting the 22q11 locus in our cohort (n=40) are based on the physiological mechanism of IGL rearrangement. This demonstrates that this loss of genetic material is likely not pathogenic and in fact is merely a marker of IGL rearrangement.


Molecular basis of vascular anomalies.
Vascular anomalies comprise a heterogeneous group of disorders that are divided into tumors (hemangiomas) and malformations. Recent advances in biomedical research provide insights into the molecular basis of these disorders and a deeper understanding of vascular morphogenesis. In the future, this emerging knowledge will contribute to novel ways to treat vascular anomalies and to regulate pathologic angiogenesis.


Association of end-tidal carbon dioxide levels during cardiopulmonary resuscitation with survival in a large paediatric cohort.
To examine the associations between ETCO2, ROSC, and chest compression quality markers in paediatric patients during active resuscitation. This was a single-centre cohort study of data collected as part of an institutional prospective quality initiative improvement program that included all paediatric patients who received chest compressions of any duration from January 1, 2013, through July 10, 2018, in the Johns Hopkins Children's Center. Data was collected from Zoll R Series® defibrillators. Events were included if Zoll data files contained both chest compression and ETCO2 data. 2,746 minutes corresponding to 143 events were included in the analyses. The median event ETCO2 for all 143 events was 16.8 [9.3-26.3] mmHg. There was a significant difference in median event ETCO2 between events that achieved ROSC and those that did not (ROSC: 19.3 [14.4-26.6] vs. NO ROSC: 13.9 [6.6-25.5] mmHg; p < 0.05). When the events were based on patient age, this relationship held in adolescents (ROSC: 18.8 [15.5-22.3] vs. NO ROSC: 9.6 [4.4-15.9] mmHg; p < 0.05), but not in children or infants. Median event ETCO2 was significantly associated with chest compression rate less than 140 (p < 0.0001) and chest compression fraction 90-100 (p < 0.0001). This represents the largest collection of ETCO2 and chest compression data in paediatric patients to date and unadjusted analyses suggests an association between ETCO2 and ROSC in some paediatric patients.


Biosynthesis of adrenal corticosteroids by the sesterterpene pathway via 23,24-dinor-4-cholen-3-one.
Rat adrenal gland preparations were incubated with 23,24-dinor-5-cholen-3 beta-ol (Guneribol), a proposed intermediate in the sesterterpene pathway for steroid biosynthesis. Steroids were isolated, purified by thin layer and high-performance liquid chromatographies and crystallized to constant specific activity. These preparations converted the substrate to 23,24-dinor-4-cholen-3-one. Radioactive 23,24-dinor-4-cholen-3-one was synthesised and incubated with further tissue preparations and shown to be converted to corticosteroids. These findings suggest that 23,24-dinor-4-cholen-3-one is an intermediate on the sesterterpene pathway for steroidogenesis.


Outcome and factors associated with mortality in patients receiving urgent chemotherapy in the ICU: A retrospective study.
This study aimed to assess the outcome and factors associated with mortality in patients who received urgent chemotherapy (CT) in the intensive care unit (ICU) in Lyon, France. A total of 147 adult patients diagnosed with cancer and requiring urgent CT during ICU stay between October 2014 and December 2019 were included in this retrospective study. Hematological cancer was found in 77% of patients, and acute respiratory failure was the leading cause of ICU admission (46.3%). The 6-month mortality rate was 69.4%; patients with solid cancer had a higher risk of mortality. Patients who died within 6 months had a poor performance score and a higher SOFA score at admission. The multivariate analysis showed that solid tumors, sepsis on the day of CT, and SOFA score on the day of CT were associated with 6-month mortality. Additionally, 95% of patients who survived the ICU resumed conventional CT, with a higher likelihood of resuming CT among those with hematological cancer. Urgent CT in the ICU is feasible in a specific subset of patients, mainly those with hematological cancer, with resumption of the curative treatment regimen after ICU discharge.


Botulinum toxin injections as salvage therapy is beneficial for management of patellofemoral pain syndrome.
Patellofemoral pain syndrome (PFPS) is a common pathology usually presenting with anterior or retropatellar pain. It is associated with a relative imbalance between the vastus medialis oblique (VMO) and the vastus lateralis (VL) muscles. This can lead to considerable morbidity and reduced quality of life (QOL). This study aims to assess the long-term functional outcome of PFPS treated with VL muscle botulinum toxin A (BoNT-A) injection. A retrospective review was performed on 26 consecutive patients (31 knees) with a mean age of 50.1 years (± 19.7 years) who were treated with BoNT-A injections to the VL muscle followed by physiotherapy between 2008 and 2015. Pre- and post-treatment pain levels (numerical rating scale, NRS), QOL (SF-6D), and functional scores (Kujala and Lysholm questionnaires) were measured. Demographics, physical therapy compliance, previous surgeries, perioperative complications, and patient satisfaction levels were collected. The mean follow-up time was 58.8 ± 36.4 months. There were significant improvements in all the examined domains. The average pain score (NRS) decreased from 7.6 to 3.2 (P < 0.01), and the Kujala, Lysholm, and SF-6D scores improved from 58.9 to 82.7 (P < 0.001), 56.2 to 83.2 (P < 0.001), and 0.6 to 0.8 (P < 0.001), respectively. Similar delta improvement was achieved irrespective of gender, age, compliance to post-treatment physical therapy, or coexisting osteoarthritis. Patients who presented with a worse pre-treatment clinical status achieved greater improvement. Prior to BoNT-A intervention, 16 patients (18 knees) were scheduled for surgery, of whom 12 (75%, 13 knees) did not require further surgical intervention at the last follow-up. A single intervention of BoNT-A injections to the VL muscle combined with physiotherapy is beneficial for the treatment of patients with persistent PFPS. Retrospective cohort study.


The effect of a simple traditional exercise programme (Baduanjin exercise) on sleep quality of older adults: a randomized controlled trial.
Sleep disturbance is a major problem for older adults, calling for the development of alternative medicine techniques to help improve sleep quality in this population. The purpose of this study was to explore the effectiveness of a Baduanjin exercise program on sleep quality in Taiwanese elderly. A randomized controlled trial, longitudinal research design was employed. This study was conducted in an urban area of northern Taiwan. The inclusion criteria for participants were as follows: (1) community-dwelling older adults age 60 years or older; (2) no regular exercise within 6 months; (3) able to communicate; and (4) independent in self-care. Subjects were excluded if they had (1) depression tendency as demonstrated by the Chinese version of the Geriatric Depression Score of eight or higher; (2) impaired mobility; or (3) unstable health status. A total of 202 older people were screened for this study, 87 of whom were eligible according to the inclusion criteria. Of these, 55 completed the 12-week study. Fifty-five participants were randomly assigned to the exercise group (27) or the control group (28). Those in the exercise group received 12 weeks of Baduanjin exercise training, while those in the control group had no intervention. The Pittsburg Sleep Quality Index was administered to subjects at four time points: before the intervention, and at the 4th, 8th, and 12th week after intervention. Subjects in the Baduanjin exercise group had significantly improved overall sleep quality, subjective sleep quality, sleep latency, sleep duration, sleep efficiency, and daytime dysfunction after 12 weeks of intervention (p<0.001), while those in control group showed no significant difference in sleep quality. Compared with the control group, the Baduanjin exercise group reported significantly better sleep quality after four weeks of intervention which was maintained throughout the 12-week exercise period. This study confirmed that the Baduanjin exercise program can improve sleep quality for Taiwanese community-dwelling older adults. We recommend application of this simple, gentle exercise program in older persons to improve their sleep quality.


Ovarian hormones, antiestrogen and pregnancy effects on the expression of class II histocompatibility antigens by N-nitroso-N-methylurea-induced rat mammary carcinomas.
Hormonal modulation of Class II histocompatibility antigen expression was studied in female Sprague-Dawley rats with N-nitroso-N-methylurea-induced mammary tumors. The effects of ovarian hormones, pregnancy and lactation were examined when cancers appeared. At this time, rats with tumors were divided into several groups. Different groups received respectively 17 beta-estradiol alone, 17 beta-estradiol in association with progesterone, and tamoxifen alone. Other groups were selected to undergo pregnancy. The control group received carcinogenic treatment only. For all removed tumors, Class II histocompatibility antigens were radiolabeled, specifically immunoprecipitated with monoclonal antibody and quantified by chromatofocusing. The amount of Class II histocompatibility antigens measured in NMU-induced rat mammary tumors without any hormonal treatment decreased significantly after treatment with estrogen alone or in association with antiestrogen and during the pregnancy. Nevertheless, Class II histocompatibility antigen expression was not changed in mammary carcinoma from rats receiving progesterone, but increased significantly during the lactation. These results demonstrated clearly that ovarian hormones change the Class II histocompatibility antigen expression of NMU-induced mammary tumors in female Sprague-Dawley rats.


Human chorionic gonadotropin, fetal sex and risk of hypertensive disorders of pregnancy: A nested case-control study.
To assess whether human chorionic gonadotropin (HCG) and fetal sex are two independent risk factors for hypertensive pregnancy in the early second-trimester of pregnancy. This was a retrospective nested case-control study based on a cohort of 2521 singleton pregnancies, among whom we recruited 98 hypertensive pregnancies (subdivided into severe preeclampsia, n=34; mild preeclampsia, n=29 and gestational hypertension, n=35) and 196 normotensive pregnancies. Maternal serum HCG levels were measured at 15-20 weeks of gestation and fetal sex was determined from the neonatal record. Mann-Whitney U and chi-square tests were performed to assess differences of HCG levels and fetal sex between groups. Logistic regressions were performed to evaluate the effect of HCG and fetal sex on hypertensive pregnancy. There were 35 male and 63 female fetuses in the hypertensive group, and 102 male and 94 female fetuses in the normotensive group (p=0.008). HCG (MoM) levels were significantly higher in only severe preeclamptic pregnancies (n=34) (p=0.013). There were no significant differences of the HCG (MoM) levels between male and female fetuses in each sub-group. aOR for increased maternal HCG levels and female fetus were 2.4 (95% CI: 1.434-3.954) and 2.9 (95% CI: 1.227-6.661) respectively in severe preeclamptic pregnancies compared with normotensive pregnancies. There is a female preponderance in hypertensive pregnancies. Increased HCG levels and female fetus are two independent risk factors for severe preeclampsia in the early second-trimester of pregnancy.


Identification of vulnerable atherosclerotic plaque using IVUS-based thermal strain imaging.
Pathology and autopsy studies have demonstrated that sudden disruption of vulnerable atherosclerotic plaque is responsible for most acute coronary syndromes. These plaques are characterized by a lipid-rich core with abundant inflammatory cells and a thin fibrous cap. Thermal strain imaging (TSI) using intravascular ultrasound (IVUS) has been proposed for high-risk arterial plaque detection, in which image contrast results from the temperature dependence of sound speed. It has the potential to distinguish a lipid-laden lesion from the arterial vascular wall due to its strong contrast between water-bearing and lipid-bearing tissue. Initial simulations indicate plaque identification is possible for a 1 degrees C temperature rise. A phantom experiment using an IVUS imaging array further supports the concept, and results agree reasonably well with prediction.


Predictors of atopic dermatitis severity over time.
Atopic dermatitis (AD) is a chronic relapsing disease that has increased in prevalence during the last 4 decades. However, little is known about factors that affect disease severity. We carried out a longitudinal observational study that included children aged 5 to 10 years recruited from general practices in the United Kingdom. General practitioners identified potential patients and the United Kingdom diagnostic criteria for AD were used to verify the diagnosis in children. The scoring AD index was used to assess disease severity. In addition, information was obtained from parents at the first interview as to age of onset, social class, ethnic group, child's atopy, family history of atopy, and other potential risk factors using a 5-page piloted questionnaire. The aim was to document risk factors for AD severity over time by sequential repeated interview and clinical examination during a 2-year period. The scoring AD index was skewed to the right so nonparametric tests were used for statistical significance. In all, 137 children (65 boys [47%] and 72 girls) with AD were recruited and seen up to 4 times; 40 in March 1998, 104 in October 1998, 116 in March 1999, and 120 at the final visit in October 1999, giving our study an 88% follow-up rate. The severity scores were ranked into 3 categories (80% mild, 18% moderate, and 2% severe) according to suggested guidelines. From this population we were able to show that those with eczema that commenced during the first year of life, which was accompanied by asthma, hay fever, or both, and associated with living in an urban area, had more severe disease independent of other potential risk factors. This study has systematically studied AD severity in a community-based design. Researchers and clinicians should be aware of those factors reported in our study as patients exposed to these factors may have a different disease outcome. Further studies on disease severity are needed.


Awake craniotomies for epileptic gliomas: intraoperative and postoperative seizure control and prognostic factors.
Awake craniotomy is well-established for tumors resected in eloquent brain areas. Whether awake craniotomy provides improved seizure control in patients with epileptic gliomas has not been well evaluated. This study analyzed the incidence, risk factors and outcome of seizures during and following awake craniotomies for patients presenting with epilepsy and glioma. Forty-one patients undergoing awake craniotomies for epileptic gliomas were retrospectively analyzed. Postoperative seizure was defined as either early (postoperative day 7 + before) or late onset (after postoperative day 7). Neurologic function was assessed with modified Rankin Scales (mRS) and seizure outcome was assessed using International League Against Epilepsy (ILAE) classification. Multivariable logistic regression was used for clinical variables associated with postoperative seizures. Three patients (7.3%) had intraoperative seizures however did not fail the awake craniotomies. Mean mRS before and after the awake craniotomies were 2.4 and 2.1, respectively (P = 0.032). Fourteen (34.1%) patients had early seizures, which caused longer hospitalization than those without early seizures (P = 0.03). Surgical resection to isocitrate dehydrogenase 1 (IDH1) mutation tumors, comparing to IDH1 wild type tumors, caused better postoperative seizure control. 6-month late seizure freedom was achieved in 33 patients (80.5%). Early seizure recurrence (odds ratio = 30.75; P = 0.039) and postoperative mRS ≥ 3 (odds ratio = 7.00; P = 0.047) were independent risk factors for late seizures. Intraoperative seizures could be well-controlled during awake craniotomies. Early postoperative seizures extended hospitalization and strongly predicted late seizure recurrence. Awake craniotomies benefited long-term seizure control in patients with epileptic gliomas.