Antigen-induced suppression of mitogen responses and resistance to experimental autoimmune encephalomyelitis.
Random-bred Hartley and inbred Strain 2 and Strain 13 guinea pigs were inoculated for acute experimental autoimmune encephalomyelitis (EAE). Sixty-six percent (69/103) of the Hartleys developed signs of EAE while the remaining 34% (34/103) were resistant. No Strain 2 and all Strain 13 guinea pigs developed EAE. Histologic examination of nervous tissue revealed that susceptible Hartleys and Strain 13 and Strain 2 animals had lesions characteristic of EAE. Tissue from resistant Hartleys showed fewer and less severe changes. Lymphocyte-transformation assays with EAE-inducing and noninducing antigens and T-cell mitogens revealed three different sets of responses in vitro: (i) lymphocytes from all animals responded to mitogens; (ii) lymphocytes from susceptible animals responded to EAE-inducing antigens; and (iii) lymphocytes from resistant Hartleys were suppressed from responding to the mitogens solely by EAE-inducing antigens. Plasmas from all EAE-sensitized animals had equivalent anti-myelin basic proteins (MBP) antibody titers and skin tests of EAE-inoculated Hartleys were all positive for MBP sensitization. Therefore, resistance and reduced histologic changes characteristic of EAE correlated with a disease-specific antigen-induced suppression of lymphocyte responses to T-cell mitogens. This suggests that clinical resistance to EAE in Hartley guinea pigs is mediated by an immunologic suppressor mechanism.


Ultrasensitive detection of small molecule-protein interaction via terminal protection of small molecule linked DNA and Exo III-aided DNA recycling amplification.
Terminal protection of small molecule linked DNA assays amplified by Exo III-aided DNA recycling is developed for the detection of streptavidin-biotin interaction, with a detection limit of 0.8 fM streptavidin in the "turn-on" state, indicating that the proposed method is an ultrasensitive platform for the detection of small molecule-protein interactions.


Clinical effectiveness of a novel intense pulsed light source on facial pigmentary lesions.
Intense pulsed light (IPL) therapy improves various clinical symptoms of photoaging skin. In this study we have investigated clinical effects of a novel IPL, Lumenis One (LUMENIS, Tokyo) on facial pigmentary lesions in 18 Japanese female patients. Measurement was performed after 3-5 treatments. IPL showed marked and slight improvements in 28 and 39%, respectively. The data of melanin index demonstrated the improvement after IPL therapy. These results indicated that IPL therapy using Lumenis One may be useful to treat solar lentigines and ephelides on the face.


A medically staffed emergency ambulance service. Report of a 5-year prospective study.
The results of a prospective 5-year study of a medically staffed ambulance service are presented. There was a total of 558 turn-outs distributed among a mixed patient material. In 192 cases, resuscitation was attempted and this proved primarily successful in 59 patients. A total of 23 of these resuscitated patients could be discharged, 19 without cerebral sequelae, two with slight brain damage and two with severe brain damage. In 44 further cases, other relevant forms of emergency treatment were administered. It is concluded that prehospital treatment at the scene of accident seems beneficial to patients with life-threatening conditions.


Maternal serum alpha-fetoprotein measurement: a screening test for Down syndrome.
The median maternal serum alpha-fetoprotein (AFP) level at 14-20 weeks' gestation in 61 pregnancies associated with Down syndrome was 0.72 multiples of the median (MoM) value for a series of 36 652 singleton pregnancies unaffected by Down syndrome or neural-tube defect--a statistically significant reduction. The difference is great enough to form the basis of a screening test. By selecting for amniocentesis women with serum AFP levels less than or equal to 0.5 MoM at 14-20 weeks' gestation (excluding any of these that ultrasound cephalometry shows to have been due to the overestimation of gestational age) 21% of pregnancies with Down syndrome would be identified as well as 5% of unaffected pregnancies. If amniocentesis were offered to all women aged 38 years or more and, in addition, to younger women with serum AFP below specified maternal age-dependent cut-off levels (less than or equal to 1.0 MoM at 37 years, less than or equal to 0.9 at 36, less than or equal to 0.8 at 35, less than or equal to 0.7 at 34, less than or equal to 0.6 at 32-33, less than or equal to 0.5 at 25-31) 40% of pregnancies with Down syndrome and 6.8% unaffected pregnancies would be selected.


Mental health system in Saudi Arabia: an overview.
There is evidence that mapping mental health systems (MHSs) helps in planning and developing mental health care services for users, families, and other caregivers. The General Administration of Mental Health and Social Services of the Ministry of Health over the past 4 years has sought to streamline the delivery of mental health care services to health consumers in Saudi Arabia. We overview here the outcome of a survey that assessed the Saudi MHS and suggest strategic steps for its further improvement. The World Health Organization Assessment Instrument for Mental Health Systems was used systematically to collect information on the Saudi MHS in 2009-2010, 4 years after a baseline assessment. Several mental health care milestones, especially provision of inpatient mental health services supported by a ratified Mental Health Act, were achieved during this period. However, community mental health care services are needed to match international trends evident in developed countries. Similarly, a larger well-trained mental health workforce is needed at all levels to meet the ever-increasing demand of Saudi society. This updated MHS information, discussed in light of international data, will help guide further development of the MHS in Saudi Arabia in the future, and other countries in the Eastern Mediterranean region may also benefit from Saudi experience.


Response to comment on "Exceptional preservation of organs in Devonian placoderms from the Gogo largerstätte".
Jensen et al. (1) question evidence presented of a chambered heart within placoderms, citing its small size and apparently ventral atrium. However, they fail to note the belly-up orientation of the placoderm within one nodule, and the variability of heart morphology within extant taxa. Thus, we remain confident in our interpretation of the mineralized organ as the heart.


Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration.
The effectiveness of therapeutic monoclonal antibodies (mAbs) against variants of the SARS-CoV-2 virus is highly variable. As target recognition of mAbs relies on tight binding affinity, we assessed the affinities of five therapeutic mAbs to the receptor binding domain (RBD) of wild type (A), Delta (B.1.617.2), and Omicron BA.1 SARS-CoV-2 (B.1.1.529.1) spike using microfluidic diffusional sizing (MDS). Four therapeutic mAbs showed strongly reduced affinity to Omicron BA.1 RBD, whereas one (sotrovimab) was less impacted. These affinity reductions correlate with reduced antiviral activities suggesting that affinity could serve as a rapid indicator for activity before time-consuming virus neutralization assays are performed. We also compared the same mAbs to serological fingerprints (affinity and concentration) obtained by MDS of antibodies in sera of 65 convalescent individuals. The affinities of the therapeutic mAbs to wild type and Delta RBD were similar to the serum antibody response, indicating high antiviral activities. For Omicron BA.1 RBD, only sotrovimab retained affinities within the range of the serum antibody response, in agreement with high antiviral activity. These results suggest that serological fingerprints provide a route to evaluating affinity and antiviral activity of mAb drugs and could guide the development of new therapeutics.


Understanding the perspective of women who use the Billings Ovulation Method®: a focus group study.
The Billings Ovulation Method®(the Billings Method) is a fertility awareness-based method (FABM) of family planning that relies on the observation of patterns of fertility and infertility based on vulvar sensations and appearance of discharges. This allows people to choose when to have intercourse, depending on whether they want to avoid or achieve pregnancy. Few studies have documented user experiences with FABMs. We conducted four virtual focus groups (FGs) in May and June 2021 with current adult women users of the Billings Method. We asked questions about users' reasons for selecting a FABM and the Billings Method, positive experiences and challenges learning and using the Billings Method, and suggestions for improving the user experience. We performed a content analysis of the transcribed FGs to explore key themes from the discussions. COREQ guidelines were followed. Twenty women between the ages of 23 and 43 participated in the FGs. Reasons women described choosing a FABM included to follow religious beliefs, to avoid side effects of hormonal contraception, and/or to learn more about their bodies. Reasons for selecting the Billings Method included perceiving it as more precise and easier to understand than other FABMs, having a scientific basis, and being recommended by family and friends. Experiences related to learning and using the Billings Method were mainly positive. They included finding the method easy to use and learn, successfully using it to either postpone or achieve a pregnancy and increasing their awareness of their bodies. Challenges for participants included the inherent learning curve for identifying sensations at the vulva and the required periods of abstinence. Participants provided suggestions and recommendations for improving users' experience, including raising awareness of the Billings Method among healthcare providers. Users of the Billings Method expressed an overall positive experience when learning and using it for family planning and body awareness. Some challenges were identified that offer opportunities to improve how the Billings Method is taught and delivered. These findings can also enhance healthcare providers' interactions with FABM users, including those of the Billings Method.


Therapeutic Advances in Eosinophilic Granulomatosis with Polyangiitis.
Eosinophilic granulomatosis with polyangiitis (EGPA) is an eosinophilic vasculitis that affects a variety of organ systems. Historically, glucocorticoids and a variety of other immunosuppressants were used to abrogate the inflammation and tissue injury associated with EGPA. The management of EGPA has evolved greatly during the last decade with the development of novel targeted therapeutics that have resulted in significantly improved outcomes for these patients, with many more novel targeted therapies emerging.


The sequence of 3'-termini of mRNAs from early region III of adenovirus 2.
The cloned cDNA sequences corresponding to early region III transcripts (76.6-86.0 map units) of adenovirus 2 were analyzed with a view to determine the structure of their 3'-termini. The clones pE7, pE22 and pE34, which contain a part of or the entire coding sequence for the Mr 19000 glycoprotein, showed microheterogeneity with respect to the poly(A) addition site, with the polyadenylation occurring 17, 26, or 29 nucleotides downstream from the hexanucleotide, 5'-ATTAAA-3'. The clone pE17 which represents a copy of the mRNA ending at 86.0 map units showed the presence of the sequence 5'-AATAAA-3', 16 nucleotides before the poly(A) tail.


Contribution to scientific research in paediatrics in The Netherlands: evaluation according to subspeciality over a 10-year period.
The board of the Dutch Paediatric Association requested a survey of the scientific research performed in all academic and non-academic paediatric hospitals, authorized to train medical doctors in paediatrics in the Netherlands. Contributions to the international and the Dutch scientific literature, in the form of regular publications, chapters in books, contributions to proceedings and Ph.D. theses were counted over two 5-year periods, i.e. 1981-1985 and 1986-1990. The quality of publications in the international journals was assessed using the average impact factor of the journals over the 10-year period. The number of publications in the international literature doubled during the observation period 1986-1990 compared to the period 1981-1985. Nevertheless, the quality of the publications remained the same. Metabolism, oncology/haematology, immunology/infectious diseases and cardiology are the subspecializations in which scientific research takes place in four or more academic paediatric hospitals. In total, 84 Ph.D. theses were produced in which a paediatrician was either the project leader (mostly a professor in paediatrics) or the investigator-in-charge. Insight into structure and major research efforts of paediatric hospitals in other countries of Europe may lead to exchange of views and, maybe, profitable co-operation.


Treatment of autoimmune ovarian disease by co-administration with mouse zona pellucida protein 3 and DNA vaccine through induction of adaptive regulatory T cells.
Autoimmune ovarian disease (AOD) caused by auto-reactive T cells is considered a major reason for human premature ovarian failure, which affects 5% of women worldwide. To develop an effective treatment for AOD, we showed that the co-administration of mouse zona pellucida protein 3 (mZP3) protein and DNA vaccine encoding the mZP3 was able to meliorate AOD in an AOD murine model induced by the mZP3. We observed that established AOD in mice reverted to a normal ovarian morphology without notable T-cell infiltration in the co-administrated group; whereas mice in the control groups developed severe AOD. The amelioration appears to be antigen specific because other co-administration combinations failed to reverse AOD and correlates with significant reductions of pathogenic T-cell responses and productions of tumor necrosis factor-alpha and interferon-gamma. Furthermore, the melioration is apparently associated with the induction of mZP3 specific regulatory T cells that exhibit a phenotypic CD4(+)CD25(-)FoxP3(+)IL-10(+) in the co-administrated group, which can be transferred to reverse AOD in vivo. Thus, co-administration of mZP3 DNA and protein vaccines can be used to treat established AOD, and may provide a novel immunotherapy strategy to treat other autoimmune diseases.


Evidence for a norepinephrine-dependent brain-stem substrate in the development of kindling antagonism.
Kindling antagonism' is a modification of the standard kindling paradigm in which two limbic system structures are stimulated on alternate trials. The consistent outcome of this procedure is that one site ('dominant site') develops typical generalized seizures, while kindled seizure development from the other site ('suppressed site') is arrested at an intermediate stage. Our recent research suggests that kindling antagonism is dependent on hindbrain norepinephrine (NE) systems. The present study explores this relationship further. Neonatal rats were treated with intracerebral injections of 6-hydroxydopamine (6-OHDA). At adulthood, these animals received either (1) a low dose of 6-OHDA (75 micrograms), (2) a high dose of 6-OHDA (200 micrograms), or (3) vehicle. Regional NE concentrations were determined by high pressure liquid chromatography. Neonatal 6-OHDA followed by vehicle resulted in decreases in forebrain and increases in hindbrain NE concentrations. Low dose 6-OHDA at adulthood depleted cerebellar, but not pontine-medullary NE. High dose 6-OHDA resulted in depletions of both cerebellar and pontine-medullary NE. Only high dose 6-OHDA significantly interfered with the development of antagonism. Neonatal 6-OHDA facilitated the rate of dominant site kindling independently of subsequent adult treatment regimens. Results suggest that the influence of NE on kindling antagonism is mediated through a brain-stem substrate and that the influence of NE on kindling rate is mediated through a forebrain substrate.


Ambient fine particulate matter exposures and oxidative protein damage in early pregnant women.
The association between oxidative protein damage in early pregnant women and ambient fine particulate matter (PM2.5) is unknown. We estimated the effect of PM2.5 exposures within seven days before blood collection on serum 3-nitrotyrosine (3-NT) and advanced oxidation protein products (AOPP) in 100 women with normal early pregnancy (NEP) and 100 women with clinically recognized early pregnancy loss (CREPL). Temporally-adjusted land use regression model was applied for estimation of maternal daily PM2.5 exposure. Daily nitrogen dioxide (NO2) exposure of each participant was estimated using city-level concentrations of NO2. Single-day lag effect of PM2.5 was analyzed using multivariable linear regression model. Net cumulative effect and distributed lag effect of PM2.5 and NO2 within seven days were analyzed using distributed lag non-linear model. In all 200 subjects, the serum 3-NT were significantly increased with the single-day lag effects (4.72%-8.04% increased at lag 0-2), distributed lag effects (2.32%-3.49% increased at lag 0-2), and cumulative effect within seven days (16.91% increased). The single-day lag effects (7.41%-10.48% increased at lag 0-1), distributed lag effects (3.42%-5.52% increased at lag 0-2), and cumulative effect within seven days (24.51% increased) of PM2.5 significantly increased serum 3-NT in CREPL group but not in NEP group. The distributed lag effects (2.62%-4.54% increased at lag 0-2) and cumulative effect within seven days (20.25% increased) of PM2.5 significantly increased serum AOPP in early pregnant women before the coronavirus disease (COVID-19) pandemic but not after that, similarly to the effects of NO2 exposures. In conclusion, PM2.5 exposures were associated with oxidative stress to protein in pregnant women in the first trimester, especially in CREPL women. Analysis of NO2 exposures suggested that combustion PM2.5 was the crucial PM2.5 component. Wearing masks may be potentially preventive in PM2.5 exposure and its related oxidative protein damage.


Unilateral acoustic tumors: how often do they recur after translabyrinthine removal?
Unilateral acoustic tumors rarely recur after total translabyrinthine removal. Review of the patient records of the House Ear Clinic revealed five recurrent tumors, for an approximate incidence of 0.3%. A questionnaire was mailed to 857 patients who were at least 9 years postoperative and failed to find any additional recurrent tumors. No preoperative or intraoperative factors were identified to predict recurrence. The average time interval from initial removal to recurrence was approximately 10 years. Flow cytometric analysis did not reveal any fundamental differences between the recurrent acoustic tumor group and a larger group of 112 acoustic tumors. Based on observed growth rates of the recurrent acoustic tumors, a single gadolinium-enhanced magnetic resonance image 5 years after surgery is advised. To prevent recurrence, a margin of normal-appearing proximal eighth cranial nerve should be removed and the nerve stump cauterized.


The prognostic significance of bromodomain protein 4 expression in solid tumor patients: A meta-analysis.
Cancer is a leading cause of death worldwide. At present, several inhibitors of bromodomain protein 4 have shown promising anti-tumor responses in clinical trials. Numerous studies have reported the value of bromodomain protein 4 expression in predicting the prognosis of patients with cancers, but their conclusions remain controversial. Therefore, we conducted a meta-analysis to explore the association between bromodomain protein 4 and patient prognosis with the aim to provide new directions for the development of strategies for targeted cancer therapy. The meta-analysis was registered in the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/prospero/; Registration No. CRD42020184948) and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. PubMed Central, PubMed, Cochrane Library and Embase were thoroughly searched to identify eligible studies published through March 31, 2021. Odds ratios with 95% confidence intervals were calculated to demonstrate the relationship between bromodomain protein 4 expression and clinicopathological features. We computed pooled estimated hazard ratios with 95% confidence intervals using Stata 12.0 software to clarify the relationship between bromodomain protein 4 expression and overall survival of various cancers. A quality assessment of the eligible articles was performed based on the Newcastle-Ottawa scale. A total of 974 patients from 10 studies were enrolled in the meta-analysis. Our results revealed that compared to low bromodomain protein 4 expression, high bromodomain protein 4 expression in cancer tissues was significantly associated with lymph node metastasis (Odds ratio = 3.59, 95% confidence interval: 2.62-4.91), distant metastasis (Odds ratio = 4.22, 95% confidence interval: 2.40-7.45), advanced TNM stage (III+IV vs. I+II: Odds ratio = 3.23, 95% confidence interval: 1.29-8.08), and poorly differentiated tumors (Odds ratio = 1.87, 95% confidence interval: 1.33-2.63). In addition, an elevated expression of bromodomain protein 4 tended to shorten survival time (Hazard ratio = 2.23, 95% confidence interval: 1.62-3.07). The subgroup analysis results showed that bromodomain protein 4 upregulation was related to poor prognosis in patients with digestive system cancers (Hazard ratio = 2.54, 95% confidence interval: 1.85-3.50). This meta-analysis indicated that bromodomain protein 4 may serve as a promising prognostic biomarker for cancers and a direct effective cancer treatment target.


Concomitant apical suspensory procedures in women with anterior vaginal wall prolapse in the United States in 2011.
Although the surgical restoration of apical support has been shown to decrease reoperation rates, it is unclear whether this has been incorporated into current practice. The aims of this study were to determine the rate of concomitant apical suspensory procedures in women with anterior vaginal wall prolapse undergoing surgical repair in 2011 and to identify associated factors. This cross-sectional study queried the Nationwide Inpatient Sample for women with a primary diagnosis of cystocele who underwent prolapse repair in 2011. The study cohort was analyzed for demographics, concomitant procedures, and hospital characteristics. The rate of apical suspensory procedures was determined. Factors potentially associated with receiving concomitant apical suspensory procedure were evaluated using univariate analysis and multivariate logistic regression. A total of 2,900 women in the database had a primary diagnosis of cystocele and underwent surgical prolapse repair in 2011. 925 (31.9 %) subjects underwent a concomitant apical suspensory procedure. The mean age in the study cohort was 61.9 ± 12.8 years. Hysterectomies were performed in 11.1 % of subjects. 61.1 % were performed vaginally, 26.5 % laparoscopically, and 12.5 % abdominally. On multivariate analysis, age greater than 50 years, Caucasian race, concomitant hysterectomy, and an urban teaching hospital setting were independently associated with receiving concomitant apical suspensory procedure in 2011. Despite evidence that the restoration of apical support is important for optimal anterior support, the overall rate of concomitant apical suspensory procedures is low. Several factors may play a role in whether or not women receive an apical suspensory procedure. This study highlights opportunities to improve the quality of surgical care provided to women with anterior vaginal prolapse.


Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 5: correlation between radiographic and functional outcome.
At the present time, there is no Class I or II medical evidence to indicate that the appearance of a radiographic fusion is significantly associated with improved functional outcomes. The majority of Class III medical evidence does suggest that successful radiographic fusion is associated with improved clinical outcomes. It is widely acknowledged that this relationship is not perfect.


Evolved RNA secondary structure and the rooting of the universal tree of life.
The origin and diversification of RNA secondary structure were traced using cladistic methods. Structural components were coded as polarized and ordered multi-state characters, following a model of character state transformation outlined by considerations in statistical mechanics. Several classes of functional RNA were analyzed, including ribosomal RNA (rRNA). Considerable phylogenetic signal was present in their secondary structure. The intrinsically rooted phylogenies reconstructed from evolved RNA structure depicted those derived from nucleic acid sequence at all taxonomical levels, and grouped organisms in concordance with traditional classification, especially in the archaeal and eukaryal domains. Natural selection appears therefore to operate early in the information flow that originates in sequence and ends in an adapted phenotype. When examining the hierarchical classification of the living world, phylogenetic analysis of secondary structure of the small and large rRNA subunits reconstructed a universal tree of life that branched in three monophyletic groups corresponding to Eucarya, Archaea, and Bacteria, and was rooted in the eukaryotic branch. Ribosomal characters involved in the translational cycle could be easily traced and showed that transfer RNA (tRNA) binding domains in the large rRNA subunit evolved concurrently with the rest of the rRNA molecule. Results suggest it is equally parsimonious to consider that ancestral unicellular eukaryotes or prokaryotes gave rise to all extant life forms and provide a rare insight into the early evolution of nucleic acid and protein biosynthesis.


Enhanced visible-light photocatalytic degradation of tetracycline by a novel hollow BiOCl@CeO2 heterostructured microspheres: Structural characterization and reaction mechanism.
A high-efficiency hollow BiOCl@CeO2 heterostructured microspheres with type-II staggered-gap type was successfully synthesized by precipitation-hydrothermal process loaded with BiOCl nanoparticles on CeO2 microspheres. XRD, FT-IR, EDS, SEM, HRTEM and XPS results show that the prepared materials have good crystallization, morphology and retain hollow spherical structure of CeO2. Batch experiments indicate that the photocatalytic performance of BiOCl@CeO2 towards Tetracycline (TC) is superior to pure BiOCl or CeO2 owing to the distinctive hollow structures and the formed heterostructure between BiOCl and CeO2. Cyclic experiment exhibits that the optimal BiOCl@CeO2 photocatalyst can still photodegrade more than 80% of TC in 120 min after 4 cycles. Additionally, the reactive oxidation species (ROS) trapping experiments reveal that the critical ROS include photogenerated holes (h+) and superoxide radical anions (O2-). Finally, the possible degradation pathways of TC and enhanced photodegradation mechanism was systematically discussed. On this basis, the hollow BiOCl@CeO2 heterostructured microspheres provide a new alternative with great potential in efficient visible-light-driven photodegradation of persistent organic pollutants.


Normal Values for Left Ventricular Mass in Relation to Lean Body Mass in Child and Adolescent Athletes.
It has been demonstrated that regular sport activity in children leads to physiological changes in the heart including increased left ventricular (LV) myocardial thickness and mass (LVM). The aim of the study was to establish the first specific normal values of LVM for child and adolescent athletes. Parasternal long-axis, 2D-guided echocardiographic measurements were obtained from a group of 791 Caucasian child athletes (age 5-18 years, 58.7% boys). For the preparation of normative data, LVM-for-lean body mass (LBM) reference curves were constructed using the LMS method. Then, a simple correlation plot was constructed to analyse the concordant and discordant indications of left ventricular hypertrophy (LVH), defined as LVM-for-LBM above the 95th percentile, according to the newly created and previously published normative data on LVM-for-LBM in the general population of children. Reference scatter plots of LVM-for-LBM for boys and girls in the analysed group of children practicing sports were presented, showing mean values of LVM and z-scores. The application to the studied group of reference centiles established for the general population of children would lead to false positive misclassification of increased LVH in 5.8% of the girls and 17.0% of the boys. We present the first specific normative data for LV mass in relation to lean body mass in Caucasian children and adolescents engaged in regular sport activities. The application of specific normative data for LV mass results in fewer false positive findings of left ventricular hypertrophy in this group than that of reference values for general paediatric population.


Clinical outcomes in breast cancer expander-implant reconstructive patients with radiation therapy.
Immediate expander-implant breast reconstruction (EIBR) with external beam radiation therapy (XRT) is pursued by many breast cancer patients; however, there is still a lack of consensus on the expected clinical outcomes. We performed a critical analysis of postoperative outcomes in EIBR patients with XRT exposure through a retrospective review from January 2007 to December 2013. Patients were stratified into three groups: exposure to preoperative XRT (XRT-pre), postoperative XRT (XRT-post), or no XRT (control). A subset of XRT patients with bilateral EIBR was assessed using a matched-pair analysis with the patients serving as their own controls. A total of 76 patients were included in the study. Major complications were observed in 6 of 8, 26 of 38, and 14 of 30 patients in the XRT-pre, XRT-post, and control groups, respectively, and were not statistically different (p > 0.05). EIBR failure rates were 13.3% in the control group compared to 50.0% in the XRT-pre group (p = 0.044) and 26.3% in the XRT-post group (p > 0.05). In the matched-pair analysis, 16 of 26 irradiated breasts developed complications compared to only 7 of 26 contralateral non-irradiated breasts (p = 0.043). In conclusion, we detected a significantly increased risk of complications in patients with pre-mastectomy radiotherapy. Patients with this history of XRT should strongly consider autologous reconstruction instead of EIBR to avoid the high risk of developing complications and subsequently losing their implant. Increased complications in irradiated breasts when compared to the contralateral non-irradiated breasts in bilateral EIBR patients confirmed the detrimental role of XRT in the setting of EIBR.


Fluorene-9-bisphenol regulates steroidogenic hormone synthesis in H295R cells through the AC/cAMP/PKA signaling pathway.
Fluorene-9-bisphenol (BHPF), which has been used as a substitute for bisphenol A (BPA) in consumer goods and industrial products, can be detected in environmental media and human urine. BHPF has been reported to have endocrine-disrupting effects, whereas deleterious effects on steroidogenesis in H295R cells and underlying mechanisms are still unclear. Here, we investigated effects of BHPF on steroidogenesis using human adrenocortical carcinoma cells (H295R). Cytotoxicity was initially assessed and half-maximal inhibitory concentration (IC50) was determined based on proliferation of cells. Responses of four steroid hormones, aldosterone, cortisol, testosterone and 17β-estradiol (E2), and ten critical genes, StAR, HMGR, CYP11A1, CYP11B1, CYP11B1, HSD3B2, CYP21, CYP17, 17β-HSD, and CYP19, involved in steroidogenesis after exposure to non-cytotoxic concentrations of BHPF were determined in the presence or absence of 100 μM dbcAMP. Adenylate cyclase (AC) activity, intracellular concentrations of cAMP, PKA activity and amounts of steroidogenic factor-1 (SF-1) gene and expressions of proteins were determined to elucidate underlying mechanisms of effects on steroidogenesis. BHPF was cytotoxic to H295R cells in a dose- and time-dependent manner. Effects on production of hormones results demonstrated that exposure to greater concentrations of BHPF inhibited productions of aldosterone, cortisol, testosterone and E2 by down-regulation of steroidogenic genes. Inhibition of AC activity, intercellular cAMP content and PKA activity after exposure to BHPF implied that the AC/cAMP/PKA signaling pathway was involved in BHPF-induced suppression of steroidogenesis in H295R cells. Additionally, BHPF inhibited steroidogenesis and expressions of steroidogenic genes via decreasing expression of SF-1 protein, both in basal and dbcAMP-induced treatment. These results contributed to understanding molecular mechanisms of BHPF-induced effects on steroidogenesis and advancing the comprehensive risk assessment of BPs.


Knockdown of synapse-associated protein Dlg1 reduces syncytium formation induced by human T-cell leukemia virus type 1.
Human T-cell leukemia virus type 1 (HTLV-1) spreads through cell-to-cell contact by forming a virological synapse. Based on the finding that HTLV-1 envelope glycoprotein (Env) binds to a PDZ domain containing scaffold protein Dlg1, whose function has been implicated in the organization of neuronal and immunological synapses, we examined the role of Dlg1 in the cell-cell infection by HTLV-1. The coculture of an HTLV-1-infected T-cell line MT-2 with an uninfected MOLT-4 induced syncytium, a marker of cell-cell HTLV-1 infection, but an RNA interference-mediated knockdown of Dlg1 in both cells cooperatively reduced the syncytium formation. In HTLV-1-uninfected 293T cells, Dlg1 induced the clustering of GLUT1, a cellular receptor for HTLV-1, but such clustering was abrogated by a deletion of the PDZ domain binding motif of GLUT1 (GLUT1DeltaC). GLUT1 expression in MDBK cells induced HTLV-1-mediated syncytium formation, and the activity was much greater than that of GLUT1DeltaC. These results suggest that Dlg1, through the interaction with GLUT1 as well as Env, plays a positive role in the syncytium formation induced by HTLV-1.


Regulation of tubulin expression by micro-RNAs: implications for drug resistance.
In this chapter, we provide an overview of methods for studying micro-RNA regulation of tubulin isotypes. In clinical studies, β-tubulin isotypes were found to be biomarkers for tumor formation. In addition, because changes in the levels of specific β-tubulin isotypes alter the stability of microtubules in mitotic spindles in vitro, it has been hypothesized that changes in microtubule protein levels could contribute to chemotherapy resistance. Over the past 15 years, micro-RNAs have been shown to target mRNAs in signaling pathways involved in tumor suppression, as well as tumorigenesis. Investigating micro-RNA regulation of tubulin isotypes will shed light on the mechanisms underlying the processes that implicate tubulin isotypes as biomarkers for aggressive tumors or chemotherapy resistance. The methods discussed in this chapter include the use of micro-RNA superarrays, next-generation sequencing, real-time PCR experiments, upregulation of micro-RNAs, and immunoprecipitation of RNA-induced silencing complex. We will show examples of data collected using these methods and how these data contribute to understanding paclitaxel resistance.


Joint Effect of Early Microvascular Damage in the Eye &Kidney on Risk of Cardiovascular Events.
Microalbuminuria is associated with an increased risk of cardiovascular disease (CVD), but not all individuals require treatment. Retinal microvascular abnormalities and microalbuminuria reflect early systemic microvascular changes. We examined the joint effect of retinal abnormalities and microalbuminuria on CVD risk in an Asian cohort. We conducted a prospective, population-based study. Retinal abnormalities were defined as presence of retinopathy and/or retinal venular widening. Microalbuminuria was defined as urinary albumin: creatinine ratio between 30-300 mg/g. Incident CVD was defined as newly diagnosed clinical stroke, acute myocardial infarction or CVD death. Cox regression models were performed to determine the associations between retinal abnormalities and microalbuminuria with risk of CVD, while controlling for established risk factors. 3,496 participants (aged ≥ 40) were free of prevalent CVD. During the follow-up (5.8 years), 126 (3.60%) participants developed CVD. Persons presenting with both retinal abnormalities and microalbuminuria were 6.71 times (95% CI, 2.68, 16.79) as likely to have incident CVD compared with those without either abnormalities. There was a significant interaction effect between retinal abnormalities and microalbuminuria on incident CVD. Assessment of retinal abnormalities in patients with microalbuminuria may provide additional value in identifying persons at risk of developing CVD.


Metastatic melanoma presenting as a breast mass - role of radiologist as a clinician.
Breast tissue can be the host of not only many benign and malignant tumors but can also be a metastatic site for various tumors such as leukemia, lung cancer, and melanoma. This report describes an unusual case of a 43-year-old female who presented with a new palpable breast lump and several similar extramammary lumps on her skin. A melanoma panel, consisting of S100, HMB45, and Melan-A stains, was included in the pathology evaluation due to diagnostic suspicion of the radiologist and revealed metastatic melanoma. This case highlights the importance of detailed history and relevant physical exam as well as clinical and imaging correlation. It serves as a reminder to radiologists to include metastatic melanoma in the differential of suspicious subcutaneous breast masses, especially in patients with multiple subcutaneous lumps in the body or abnormal skin findings.


Dry chemical processing and ensiling of rice straw to improve its quality for use as ruminant feed.
In this study, changes in the chemical composition, pH, cell wall and degradability of ensiled rice straw were investigated when treated with alkali, acid, oxidant agents (1-11 %, w/w) and a combination of an oxidant with either an alkali (ALHP) or an acid (ACHP). The findings of the study revealed that ALHP had a lower efficiency in enhancing fibre degradability compared to alkali alone. Oxidant treatment showed no detectable changes in pH, dry matter (DM) and phenolic compound (PC) solubility, or in silica and fibre content, but led to increased esterified groups formed within the cell wall constituents (hemicellulose and lignin). Increasing acid concentration led to an exponential change in both pH and solubility of DM and hemicelluloses while it quadratically increased PC and silica solubility. Moreover, crystallinity, hydrogen bonding and esterification were enhanced under high acid concentrations (11 %), but decreased under mild acid conditions (5 %). Increased alkalinity led to the linear enhancement of DM and PC solubility. Solubility of silica and hemicellulose did not exhibit any significant changes with alkali concentration above 7 %. A gradual enhancement (29 %) was observed in ruminal DM degradability with increasing oxidant concentration, whereas exponential (91 %) and quadratic (23 %) enhancements were observed with alkaline and acid treatments, respectively. Treatment with acid showed observable reductions in the degradability of both cellulose and hemicellulose, whereas oxidant treatment reduced only that of hemicellulose. Treatment with 7 % alkali (pH ∼ 12) followed by ensiling appeared to be a promising process for improving rice straw quality.


The relationship between focal seizures and sleep: an analysis of the cyclic alternating pattern.
The aim of this study was to examine the relationship between focal epileptic seizures and sleep through analysis of the cyclic alternating pattern (CAP). We analyzed the recordings of a total of 56 nocturnal partial seizures (13 occurring as isolated events and 43 "in clusters" during a full-night ambulatory polysomnography) in 12 adult patients affected by localization-related focal epilepsy (7 males, 5 females; mean age 35+12.8 years; range 25-71). On exact binomial distribution analysis, seizures were more frequent in CAP than in non-CAP sleep, and in CAP phase A than in CAP phase B (p<0.001). Seizures occurring in clusters were more frequently associated with CAP sleep (p<0.05) than isolated seizures and first seizures of seizure clusters. Increase of CAP rate during the 30-min of sleep period after the occurrence of a seizure was documented in both cluster and isolated seizures. Our data indicate that an intra-sleep condition of highly fluctuating vigilance constitutes the real substrate for the occurrence of epileptic seizures regardless of the NREM stage in which they occur. The occurrence of partial seizures during sleep appears to induce sleep instability, which may in turn result in the facilitation of clusters of seizures. Together, these data highlight the potential of sleep fragmentation to modulate intra-sleep seizure occurrence.


Effects of next-generation, dual-active-ingredient, long-lasting insecticidal net deployment on insecticide resistance in malaria vectors in Tanzania: an analysis of a 3-year, cluster-randomised controlled trial.
Insecticide resistance among malaria-vector species is a pervasive problem that might jeopardise global disease-control efforts. Novel vector-control tools with different modes of action, including long-lasting insecticidal nets (LLINs) incorporating new active ingredients, are urgently needed to delay the evolution and spread of insecticide resistance. We aimed to measure phenotypic and genotypic insecticide-resistance profiles among wild Anopheles collected over 3 years to assess the longitudinal effects of dual-active-ingredient LLINs on insecticide resistance. For this analysis, data nested in a 3-year, four parallel-arm, superiority cluster-randomised controlled trial (cRCT) in Tanzania, collected from 84 clusters (39 307 households) formed of 72 villages in the Misungwi district, were used to measure insecticide-resistance profiles among female Anopheles mosquitoes via insecticide-resistance bioassays and quantitative RT-PCR of metabolic-resistance genes. Wild, blood-fed, indoor-resting mosquitoes were collected annually during the rainy seasons from house walls in clusters from all four trial groups. Mosquitoes were morphologically identified as An gambiae sensu lato (SL) or An funestus SL before separate bioassay testing. The primary outcomes were lethal-dose values for α-cypermethrin, permethrin, and piperonyl butoxide pre-exposure plus permethrin-resistance intensity bioassays, mortality 72 h after insecticidal exposure for chlorfenapyr bioassays, fertility reduction 72 h after insecticidal exposure for pyriproxyfen bioassays, and fold change in metabolic-enzyme expression relative to an insecticide-susceptible laboratory strain. All primary outcomes were measured in An funestus SL 1 year, 2 years, and 3 years after LLIN distribution. Primary outcomes were also assessed in An gambiae SL if enough mosquitoes were collected. The cRCT is registered with ClinicalTrials.gov (NCT03554616). Between May 24, 2019, and Oct 25, 2021, 47 224 female Anopheles were collected for resistance monitoring. In the pyrethroid (PY)-LLIN group, there were significant increases in α-cypermethrin-resistance intensity (year 1 LD50=9·52 vs year 2 76·20, p<0·0001) and permethrin-resistance intensity (year 1 13·27 vs year 2 35·83, p=0·0019) in An funestus SL. In the pyriproxyfen PY-LLIN group, there was similar increase in α-cypermethrin-resistance intensity (year 1 0·71 vs year 2 81·56, p<0·0001) and permethrin-resistance intensity (year 1 5·68 vs year 2 50·14, p<0·0001). In the piperonyl butoxide PY-LLIN group, α-cypermethrin-resistance intensity (year 1 33·26 vs year 3 70·22, p=0·0071) and permethrin-resistance intensity (year 1 47·09 vs year 3 2635·29, p<0·0001) also increased over time. In the chlorfenapyr PY-LLIN group, there were no effects on α-cypermethrin-resistance intensity (year 1 0·42 vs year 3 0·99, p=0·54) or permethrin-resistance intensity (data were not estimable due to nearly 100% mortality). There were also minimal reductions in chlorfenapyr susceptibility. However, in the chlorfenapyr PY-LLIN group, a significant decline in piperonyl-butoxide synergy was seen by year 3 (year 1 0·02 vs year 3 0·26, p=0·020). Highly over-expressed detoxification enzymes showed dynamic patterns of selection throughout the trial. Our phenotypic data supports trial epidemiological findings; chlorfenapyr PY-LLINs provided superior protection from malaria across multiple transmission seasons, with few effects on insecticide-resistance selection. Rapid pyrethroid-resistance intensification in the piperonyl butoxide PY-LLIN group and pre-existing tolerance of pyriproxyfen in vector populations might explain the poorer performance of these two interventions regarding malaria outcomes. Further work is required to elucidate the potential mechanisms driving cross-resistance between pyrethroids and novel active ingredients to better inform the design of pre-emptive resistance-management strategies. UK Department for International Development; UK Medical Research Council; Wellcome Trust; UK Department of Health and Social Care; UK Foreign, Commonwealth and Development Office; and The Bill and Melinda Gates Foundation via the Innovative Vector Control Consortium.


Behavioral treatment of children with recurrent headaches.
The effectiveness of relaxation and biofeedback treatment for adults who suffer from headaches is well documented. By contrast, only several case study reports have been published describing these procedures applied to childhood headaches. This report describes the treatment of 15 children, aged 10-17 years, treated in a behavioral medicine clinic by using relaxation, biofeedback and behavioral counseling. At the end of treatment, 8 of 15 children were headache-free and 5 others exhibited a marked reduction in headache frequency and severity. Improvements were then maintained at follow-up. These results are comparable to results obtained when similar procedures are used to treat chronic adult headache sufferers.


Acute ischemic syndromes. Chest pain center concept.
CPCs have been developed to meet the clinical challenge posed by the diverse group of patients presenting to the ED with findings suggestive of a coronary event. Using a protocol-driven approach, high- and low-risk patients can be identified on presentation, facilitating urgent therapy in the former and triage of the latter to more deliberate management. Most CPCs focus on low-risk patients who are being increasingly managed by accelerated diagnostic protocols. These methods comprise systematic strategies that include innovative diagnostic approaches during a 6 to 12 hour period of observation with serial ECGs, continuous monitoring and cardiac biomarker measurements. A negative evaluation is usually followed by predischarge stress testing, and positive findings mandate admission. An essential aspect of the CPC strategy is continuity of care for patients with negative cardiac evaluations. Current data indicate that management of low-risk patients with chest pain in a CPC is safe accurate, and appears to be cost-effective.


Space-time correlations of neuronal firing related to memory storage capacity.
Most viable theories of memory require some form of synaptic modification dependent on the correlation of pre- and postsynaptic neuronal firing (which we will denote as the Hebb hypothesis). We show here that a possible consequence of this hypothesis is that the storage capacity of a network of highly interconnected neurons is related to the number of synapses and that this implies that the network can be excited into many different time sequence of firing patterns of assemblies of neurons. The important role played by the assembly (as defined by E. R. John) is discussed in detail. A modified Hebb hypothesis is proposed. The crucial experiments to test the model involve the use of two (or more) extracellular microelectrodes to record, simultaneously, the firing activity of several neurons and thus determine the spatial and temporal cross correlations after presenting a mature animal with a variety of stimuli.


Oil-in-water Pickering emulsion stabilization with oppositely charged polysaccharide particles: chitin nanocrystals/fucoidan complexes.
Chitin nanocrystals (ChN) are insoluble particles that can be used as stabilizers for Pickering emulsions. Their unique cationic properties and antibacterial activity have generated considerable interest among researchers. However, ChN have remained largely underexplored. Furthermore, the droplets of the emulsions stabilized by ChN are as large as 10-100 μm, and their physical stability requires further improvement. Some studies have shown that the spontaneous reaction of oppositely charged particles can effectively stabilize the emulsions. Positively charged ChN and negatively charged fucoidan (F) were therefore compounded to stabilize Pickering emulsions, and the stability of these emulsions was analyzed qualitatively. The results showed that the composite particles comprising two polysaccharides in a mass ratio of 1:1 and at a pH of 2 (ChN1 -F1 -pH 2) possessed the lowest sulfate content (20.1%) and almost zero potential (-3 mV), indicating a high degree of neutralization of the positively charged amino group in ChN and the negatively charged sulfate group in F. Meanwhile, ChN1 -F1 -pH 2 displayed a dense network structure that improved the dispersibility and wettability (contact angle = 9.3°). Fourier transform infrared spectroscopy results confirmed that ChN and F were effectively combined through electrostatic interaction or neutralization to produce a polyelectrolyte complex. Furthermore, the particle size of the Pickering emulsion stabilized by ChN-F was significantly reduced, and the maximum size did not exceed 10 μm; the physical and storage stability also improved. The ChN1 -F1 -pH 2 emulsion presented excellent storage stability; in particular, the emulsions stabilized by ChN1 -F1 -pH 5 and ChN1 -F1 -pH 6 exhibited excellent flocculation stabilities. The size of the emulsion droplets stabilized by the oppositely charged polysaccharide particles (ChN-F complexes) reduced significantly. Furthermore, by changing the mass ratio and pH, the microstructure and binding degree of the complexes can be adjusted, thereby promoting their adsorption on the oil-water interface and improving the stability of the Pickering emulsion. © 2020 Society of Chemical Industry.


Regulation of cellulolytic genes by McmA, the SRF-MADS box protein in Aspergillus nidulans.
Cellobiose triggers the production of two endoglucanases, EglA and EglB, in Aspergillus nidulans. The cellulose responsive element (CeRE) cis-element that is essential for induction has been identified on the eglA promoter, but transcription factors that bind to CeRE have not yet been identified. CeRE contained a consensus sequence CC(A/T)6GG for binding of the SRF-type MADS box proteins. Introduction of a missense mutation into mcmA, encoding for the sole SRF-MADS protein in A. nidulans, caused a significant reduction in cellulase induction. Real-time RT-PCR analysis revealed that inductive expression of not only eglA but also eglB and cbhA by cellobiose were under control of McmA. The McmA protein expressed in Escherichia coli specifically bound to two regions of the eglA promoter: CeRE and its upstream proximal region. These results, together with our previous study on the eglA promoter structure, imply that McmA regulates eglA expression by binding directly to its promoter. This is the first evidence for participation of an SRF-MADS protein in cellulase regulation.


[Huntington chorea in a boy aged 14 years].
The authors present a case of Huntington disease in a 14 year old boy. The basis of genetic, pathoetiology, clinical course of disease, significance of molecular analysis of DNA are discussed.


Barriers and Enablers of Second-Order Problem-Solving Behavior: How Nurses Can Break Away From the Workaround Culture.
Nurses are challenged by numerous day-to-day unexpected problems due to poorly performing work systems that hinder patient care. These operational failures persist in hospitals, partly because nurses tend to prefer quick fixes or workarounds over real improvements that prevent recurrence. The aim of this review is to shed light on the barriers to and enablers of nurses' second-order problem-solving behavior and their consequences, so that hospitals can learn from failure and improve organizational outcomes. We conducted a systematic review, with quantitative, qualitative, and mixed-method articles, searching 6 databases (PubMed, Embase, Web of Science, CINAHL, and Google Scholar) following the Preferred Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Quality assessment for inclusion was performed by 2 independent authors using the Mixed Methods Appraisal Tool (MMAT). A descriptive synthesis was used for analysis. This study reveals the barriers and enablers for second-order problem-solving behavior, and synthesizes improvement proposals within 3 perspectives, namely the "empowerment" perspective, the "process improvement" perspective, and the "time" perspective. Furthermore, we found that limited attention is given to the patient's perspective, and the existence of a no-action behavior. Although operational failures have several important consequences for hospital staff and organizations, there has been hardly any research into the barriers and enablers that initiate second-order problem-solving behavior; stemming this nursing behavior has thus rarely appeared as a suggestion for improvement.


Atypical Scheuermann's disease with severe kyphosis and negative sagittal balance in the thoracolumbar region: A case report and literature review.
Scheuermann's kyphosis is a structural deformity of the thoracolumbar spine that is classified in typical (thoracic) and atypical (lumbar and thoracolumbar) Scheuermann's disease. Surgical intervention is reserved for those with progressive kyphosis, intractable pain and neurological impairment. Although, previous literature focuses on the correction of the thoracic kyphosis (TK), recent lines of evidence recommend considering all the sagittal balance parameters when performing a surgery. We herein, report a posterior-only approach in a patient with Scheuermann's kyphosis, considering all the sagittal balance parameters. The patient was a 17-year-old boy with a kyphotic deformity in the lumbar region, with urinary retention and upper back intractable pain. The preoperative physical examination was normal except for a kyphotic gait. The patient was first treated with thoracic lumbosacral orthoses (TLSO) brace that was not effective; consequently, the patient underwent posterior only approach (pedicular screw fixation along with Smith-Peterson osteotomy) with correction of the sagittal balance and kyphosis. The patient's sign and symptoms improved significantly. The surgery was uneventful and no complication was recorded. The 1-year follow-up revealed normal neurological examination and normal sagittal balance parameters. Atypical Scheuermann's kyphosis with neurological impairment and progressive kyphosis should be treated with surgical intervention. Considering the sagittal parameters of the spine, the surgical intervention should be designed to correct the kyphosis and the other indices of the sagittal balance. Posterior-only approach is safe and effective method for correction of the TK and improving the signs and symptoms of the patients.


Significant bone loss after stopping long-term denosumab treatment: a post FREEDOM study.
We evaluate 38 elderly women who had received long-term denosumab treatment after stopping the drug. Taking into account the gain during treatment and the loss after stopping treatment, they lost 35.5% of the total gain in the spine, 44.6% of the total gain in the femoral neck, and 103.3% in the total hip. Denosumab (DMAb) is a soluble inhibitor of the receptor activator of nuclear factor-kappaB ligand (RANKL) and, therefore, does not incorporate into the bone matrix. Consistently, DMAb discontinuation is associated with reversal of the effects attained with treatment. The aim of this study is to assess changes in BMD after a year of discontinuation of DMAb in a group of postmenopausal women treated with DMAb for 7 or 10 years. Secondly, is to evaluate the occurrence of fragility fractures. Women who had participated in the FREEDOM study and its extension were invited to participate in this follow-up study. BMD at LS and hip and spine X-rays were obtained. Results were compared to the last value obtained while in treatment to assess changes after discontinuation. Thirty-eight women, mean age: 81 ± 3.4 years completed study procedures; none had received bisphosphonates after stopping DMAb. Mean gap time between DMAb last dose and the follow-up visit was 17 months (range 16-20 months). Bone mineral density (BMD) decreased significantly in all regions: - 8.1% in LS, - 6% in FN, and - 8.4% in TH. Five (5/38, 13.15%) patients had a fragility fracture, one suffered a wrist fracture, and four experienced vertebral fractures. Three patients suffered one vertebral fracture and one of them had two vertebral fractures. Laboratory results showed the following mean values: CTX = 996 ± 307 pg/ml (normal values 550 ± 226 pg/ml); osteocalcin = 55.2 ± 18.6 ng/ml (normal value 42 ng/ml); and 25 OH vitamin D = 23.7 ± 6.9 ng/ml. Our results describe the rapid bone loss occurring after cessation of denosumab treatment. Further studies are needed to assess if patients have a higher risk of fracture after stopping DMAb and if so, which patients have the highest risk, and assess the role of transitioning to bisphosphonates in the long term.


Case report: acute pancreatitis following corticosteroid and azathioprine therapy.
Several drugs have been implicated as causes of acute pancreatitis. This report presents four patients, three with lupus nephritis and one with membranous glomerulopathy, who developed acute pancreatitis while being treated with corticosteroids alone or in combination with azathioprine. Two of the reported patients died with a hemorrhagic pancreatitis and one of the patients developed a pancreatic pseudocyst. The pathogenesis of corticosteroid and/or azathioprine-induced pancreatitis is discussed.


The evolution of the neocortex in mammals: how is phenotypic diversity generated?
Evolution of the mammalian neocortex is difficult to examine directly. For this reason, comparative studies and developmental studies are the best way of gaining insight into the evolutionary process. Comparative studies indicate that neocortical evolution is constrained, and that the types of systems-level modifications made to the neocortex are limited. Developmental studies of gene expression suggest that genetic contingencies set up aspects of cortical organization and connectivity, and that the complex spatial and temporal interactions of genes constrain development and evolution. Although genes obviously contribute to phenotypic variability, variability can also be achieved through alterations in the sensory receptor arrays, or changes in sensory driven activity. The intracellular mechanisms that enable phenotypic variability might evolve, but often the phenotypic characteristic in question is context-dependent.


Evaluation of contact precautions discharges in an acute care setting.
The health care environment is increasingly discussed as a source of health care-associated infections. We evaluated patterns of discharges among patients on contact precautions (CP) and assessed correlation of CP discharges with health care acquisition of organisms requiring CP and evaluated the feasibility of targeting CP discharges for additional monitoring.


Combined endoscopic and laparoscopic approach to a gastroesophageal tumor.
Smooth muscle tumors of the stomach, especially when benign, are a common clinical entity and can represent a therapeutic challenge. Classically the removal of such a tumor requires open laparotomy. We sought to perform this surgery utilizing minimally invasive technology. We describe a minimally invasive technique combining laparoscopy with endoscopy to remove a sub-mucosal leiomyoma at the gastroesophageal junction. A 3.3-cm smooth muscle tumor of the gastroesophageal junction was removed completely and safely with the described procedure and thus saved the patient from requiring a laparotomy. Minimally invasive techniques can be used in combination to tackle difficult problems in general surgery leading to shorter hospital stays and improved patient satisfaction.


Neurostimulation for the treatment of functional neurological disorder: A systematic review.
Functional Neurological Disorder (FND), also known as conversion disorder, is characterized by neurological symptoms that are incompatible with any known structural disorder and best explained by a biopsychosocial model. Evidence-based treatments for FND are limited, with cognitive behavioral therapy (CBT) and physiotherapy being the most effective interventions [1]. In recent years, functional neuroimaging studies have provided robust evidence of alterations in activity and connectivity in multiple brain networks in FND. This body of evidence suggests that neurocircuitry-based interventions, such as non-invasive brain stimulation techniques (NIBS), may also represent an effective therapeutic option for patients with FND. In this systematic review, we outline the current state of knowledge of NIBS in FND, and discuss limitations and future directions that may help establish the efficacy of NIBS as a therapeutic option for FND.


[Construction of left ventricle-aorta conduits (review of the literature)].
The development prospectives of the design problem for extracardial conduits, which lies in creation of different sizes series of conduits design for left and right part of the heart relating to the age of the patient, type of obstruction lesion and anatomic peculiarities of its heart is discussed.


Morphological study of the teeth of Ambystoma maculatum, Salamandra salamandra and Aneides lugubris: fine structure and chemistry of enamel.
The functional teeth of adult salamander (Caudata): Ambystoma maculatum, Salamandra salamandra and Aneides lugubris were prepared for transmission electron microscopy and electron microprobe analysis of the elements and trace elements of the enamel layer. The arrangement of enamel crystals in these species is variable. The outer part of the enamel layer in which hydroxyapatite elements (Ca, P) and trace elements (e.g., F, Fe, Mg) are concentrated, is most mineralized. The concentration of trace elements are arrangement of crystals in the enamel layer differed in these species, may be related to the pattern of mineralization of enamel.


Influence of mismatched and bulged nucleotides on SNP-preferential RNase H cleavage of RNA-antisense gapmer heteroduplexes.
This study focused on determining design rules for gapmer-type antisense oligonucleotides (ASOs), that can differentiate cleavability of two SNP variants of RNA in the presence of ribonuclease H based on the mismatch type and position in the heteroduplex. We describe the influence of structural motifs formed by several arrangements of multiple mismatches (various types of mismatches and their position within the ASO/target RNA duplex) on RNase H cleavage selectivity of five different SNP types. The targets were mRNA fragments of APP, SCA3, SNCA and SOD1 genes, carrying C-to-G, G-to-C, G-to-A, A-to-G and C-to-U substitutions. The results show that certain arrangements of mismatches enhance discrimination between wild type and mutant SNP alleles of RNA in vitro as well as in HeLa cells. Among the over 120 gapmers tested, we found two gapmers that caused preferential degradation of the mutant allele APP 692 G and one that led to preferential cleavage of the mutant SNCA 53 A allele, both in vitro and in cells. However, several gapmers promoted selective cleavage of mRNA mutant alleles in in vitro experiments only.


Diagnosis of infant synostotic and nonsynostotic cranial deformities: a review for pediatricians.
To review the current comprehensive care for nonsyndromic craniosynostosis and nonsynostotic cranial deformity and to offer an overall view of these craniofacial conditions. The review was conducted in the PubMed, SciELO, and LILACS databases without time or language restrictions. Relevant articles were selected for the review. We included the anatomy and physiology of normal skull development of children, discussing nuances related to nomenclature, epidemiology, etiology, and treatment of the most common forms of nonsyndromic craniosynostosis. The clinical criteria for the differential diagnosis between positional deformities and nonsyndromic craniosynostosis were also discussed, giving to the pediatrician subsidies for a quick and safe clinical diagnosis. If positional deformity is accurately diagnosed, it can be treated successfully with behavior modification. Diagnostic doubts and craniosynostosis patients should be referred straightaway to a multidisciplinary craniofacial center. Pediatricians are in the forefront of the diagnosis of patients with cranial deformities. Thus, it is of paramount importance that they recognize subtle cranial deformities as it may be related to premature fusion of cranial sutures.


Serological diagnosis of bovine neosporosis: a comparative study of commercially available ELISA tests.
Bovine neosporosis control programs are currently based on herd management and serodiagnosis because effective treatments and vaccines are unavailable. Although a wide variety of serological tools have been developed, enzyme-linked immunosorbent assays (ELISAs) are the most commonly commercialized tests. Partial comparative studies have been performed in the past, and the panel of available ELISAs has notably changed in the last few years. Therefore, diagnostic laboratories are requesting updated information about the performance of these tests. Accordingly, the aim of this study was to compare all of the commercially available ELISAs (n=10) by evaluating their performance and to re-standardize them based on TG-ROC analyses when necessary. For this purpose, a well-characterized serum panel from experimentally and naturally infected bovines and non-infected bovines (n=458) was used. Two different definitions of gold standard were considered: (i) the result of the majority of tests and (ii) pre-test information based on epidemiological, clinical and serological data. Most of the tests displayed high sensitivity (Se) and specificity (Sp) values when both gold standard criteria were considered. Furthermore, all the tests showed near perfect agreement, with the exception of the pair-wise comparisons that included the VMRD and SVANOVIR. The best-adjusted ELISAs were the HIPRA-CIVTEST, IDVET, BIOVET and IDEXX Rum (Se and Sp>95%). After the TG-ROC analyses, higher Se and Sp values were obtained for the BIO-X, LSI Bov, LSI Rum and IDEXX Bov, though the increases were more significant for the SVANOVIR and VMRD. The Kappa values also increased with the new adjusted cut-offs. This is the first study that offers updated performance evaluations of commercially available ELISAs. Such analyses are essential for diagnostic laboratories and are valuable to the companies that develop and distribute these tests.


Sites of lanthanum occlusion in the testis of the crayfish Procambarus paeninsulanus (Crustacea: Cambaridae).
The presence of stage-dependent occlusive junctions between adjacent Sertoli cells in the seminiferous epithelium of the crayfish testis was demonstrated by a lanthanum tracer study. The germinal epithelium did not appear to be compartmentalized, as evidenced by access of lanthanum to spermatogonia, spermatocytes, and spermatids. During late spermiogenesis, when encapsulated stage VI spermatids were concentrated in the center of an acinus, lanthanum was excluded apically, coincident with lumen formation. This is the first study examining occluding junctions using a barrier penetration method in the testis of a crustacean.


Sexual size dimorphism in the ontogeny of the solitary predatory wasp Symmorphus allobrogus (Hymenoptera: Vespidae).
Sex-specific patterns of individual growth, resulting in sexual size dimorphism (SSD), are a little studied aspect of the ontogeny related to the evolutionary history and affected by the ecology of a species. We used empirical data on the development of the predatory wasp Symmorphus allobrogus (Hymenoptera, Vespidae) to test the hypotheses that sexual differences of growth resulting in the female-biased SSD embrace the difference in (1) the egg size and the starting size of larva, (2) the larval development duration, and (3) the larval growth rate. We found that eggs developing into males and females have significant differences in size. There was no significant difference between the sexes in the duration of larval development. The relative growth rate and the food assimilation efficiency of female larvae were significantly higher than compared to those of male larvae. Thus, the SSD of S. allobrogus is mediated mainly by sexual differences in egg size and larval growth rate.


Relationship between psychophysical tuning curves and critical bandwidths.
In Experiment I, band noises were used as signals and pure tones were used as maskers. The conventional psychophysical tuning curves (PTCs) present the following characteristics depending on the signal level; slopes of the PTC are steeper than those of the auditory nerve fibers frequency threshold curve (FTC). This result from the large effect of the combination tones and, especially, of the off-frequency listening. Bandwidths of PTC do not depend on both signal levels and duration, but they are narrower than the equivalent rectangular bandwidth (ERB) of auditory filters. Masked thresholds at tips of PTC are affected by the temporal integration of signal sound at signal levels of 10- and 20-dB SL, but are not affected at 30-dB SL. This implies a close relation between PTCs and critical bandwidths (CB-widths). In Experiment II, pure tones were used as signals and band noise were used as maskers. The low- and high-frequency slopes were steeper in Experiment I. The flat parts of the masked threshold at the tips of curves become broader as the signal duration increased. No such flattening was found at a 30-dB signal level, irrespective of signal duration. The results of Experiment II coincide with the prediction derived from the excitation-pattern model. Masked thresholds at the tip of PTC were the same as in Experiment I. The conventional PTC represents the psychological frequency selectivity, and its 3-dB bandwidth corresponds to the CB-width. However, the quantitative properties depend greatly upon the bandwidths of the band noises used as signals or maskers.


The effect of twice daily nadolol on intraocular pressure.
The 12-hour control of intraocular pressure obtained with 10 and 20 mg of nadolol twice daily was studied in a placebo-controlled trial. In this ten-week study involving 17 patients a significant reduction in intraocular pressure was obtained with both doses. The effect of 20 mg of nadolol twice daily on intraocular pressure, resting pulse rate, and blood pressure was consistently slightly greater than 10 mg twice daily, but the difference was not significant.


Cross-sectional study of neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratios in mood disorders.
Neutrophil-lymphocyte, monocyte-lymphocyte and platelet-lymphocyte ratio are inexpensive and reproducible biomarkers of inflammation found to be elevated in mood disorders. This study aimed to compare inflammatory ratios between bipolar disorder and major depressive disorder and between bipolar disorder manic episodes and bipolar disorder depressive episodes. We included 142 Caucasian patients (major depressive disorder: n = 36; bipolar disorder manic episode: n = 66; bipolar disorder depressive episode: n = 40). We measured white blood cells, neutrophils, lymphocytes, monocytes, platelets, glucose, and total cholesterol. Neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio, and platelet-lymphocyte ratio were calculated. Neutrophil-lymphocyte ratio and monocyte-lymphocyte ratio were significantly higher in bipolar disorder manic episodes when compared to bipolar disorder depressive episodes and major depressive disorder episodes after adjustment for age, sex, body mass index, and smoking. To our knowledge, our study is the first one to compare inflammatory ratios between different bipolar disorder phases and major depressive disorder episodes. In accord with previous studies on other inflammatory mediators, we found higher neutrophil-lymphocyte and monocyte-lymphocyte ratios in bipolar manic episodes, suggesting that inflammatory changes occur especially during acute episodes of mania.


Extended-spectrum-beta-lactamase-producing Escherichia coli strains isolated from farm animals from 1999 to 2002: report from the Japanese Veterinary Antimicrobial Resistance Monitoring Program.
A nationwide surveillance for antimicrobial susceptibility in Escherichia coli strains isolated from food-producing animals in Japan was conducted from 1999 to 2002. Eighteen cefazolin-resistant E. coli strains were isolated from broilers. Six were CTX-M-type producing, and eight were CMY-2 producing, while eight had mutations at the ampC promoter region.


Squamous Carcinoma of the Cervix in a 15-Year-Old with Congenital HIV: A Case Report.
Human papillomavirus (HPV) is the most prevalent sexually transmitted infection (STI) worldwide. Immunocompetent hosts have intact defense mechanisms to prevent HPV infection, but immunocompromised patients are at higher risk for complications, including HPV-related cancers. Most of these cancers originate from high-risk HPV strains in sexually active patients. Here we present a case of an immunocompromised adolescent who developed cervical cancer despite no prior sexual activity and only ever having had low-risk type HPV on biopsy. To our knowledge, this is the first case report of a cervical cancer arising from a low-risk HPV strain in an immunocompromised, non-sexually active adolescent. This case highlights the importance of preventive and screening mechanisms in immunocompromised populations, as they are have a higher probability of HPV-related complications, even in the absence of traditional risk factors.


Effect of yeast extract on growth kinetics of Monascus purpureus.
Growth kinetics and red pigment production of Monascus purpureus CCT 3802 was studied. A reproducible inoculum with extremely dispersed hyphae for bioreactor runs was obtained through a two-step cultivation in a shaker. First, the spores were cultivated in a complex medium rendering a suspension of vegetative cells. In the second step these cells were grown in a semisynthetic medium. Two types of media were employed in the bioreactor runs: a semisynthetic (glucose, salts, and yeast extract), and a synthetic, without yeast extract. The inclusion of yeast extract, caused an increase in cell yield on glucose (Yx/s) as high as 40%. Also, yeast extract probably yielded a higher proportion of red pigment associated with the cell, relative to the synthetic medium. On the other hand, cells grown on the synthetic medium were slightly higher producers of red soluble pigments.


Preparation of nanocellulose from micro-crystalline cellulose: The effect on the performance and properties of agar-based composite films.
A facile approach has been performed to prepare nanocellulose (NC) from micro-crystalline cellulose (MCC) and test their effect on the performance properties of agar-based composite films. The NC was characterized by STEM, XRD, FTIR, and TGA. The NC was well dispersed in distilled water after sonication and their size was in the range of 100-500nm. The XRD results revealed the crystallinity of NC. The crystallinity index of NC (0.71) was decreased compared to the MCC (0.81). The effect of NC or MCC content (1, 3, 5 and 10wt% based on agar) on the mechanical, water vapor permeability (WVP), and thermal properties of the composites were studied. The NC obtained from MCC can be used as a reinforcing agent for the preparation of biodegradable composites films for their potential use in the development of biodegradable food packaging materials.


(2E)-2-(3,4-Di-meth-oxy-benzyl-idene)-3,4-di-hydro-naphthalen-1(2H)-one.
In the title chalcone derivative, C19H18O3, the cyclo-hexa-none ring adopts a distorted half-chair conformation and the dihedral angle between the aromatic rings is 52.20 (15)°. In the crystal, weak C-H⋯O hydrogen bonds link the mol-ecules into C(12) [001] chains.


Effect of Lower Limb Muscle Fatigue on Ground Reaction Force Components During Landing in People With Nonspecific Chronic Low Back Pain.
The link between landing parameters and lower limb muscle fatigue in association with chronic low back pain (CLBP) is not well understood. To examine the effects of fatigue on the ground reaction force components during landing in people with nonspecific CLBP. Quasi-experimental study. Clinical biomechanics laboratory. A total of 44 subjects were equally divided into a healthy group and a group with CLBP. The ground reaction force along anterior-posterior (y) and medial-lateral (x) and vertical (z) axes, time to peak (TTP), the rate of force development, and impulses for all axes were calculated. A repeated-measures analysis of variance (group × fatigue) was used to compare the data among groups. In the unfatigued conditions, the amplitudes of Fy3, Fz2, and TTP of Fy1, Fy2, Fz1, Fz2, Fz3, Fz4, rate of force development in Y in the CLBP subjects are significantly different than those in the healthy subjects (P < .05). In the fatigued conditions, the amplitudes of Fz2, Fz3, Fz4, and TTP of Fy2, Fy3, Fy4, Fz2, impulses of X2, Z in the CLBP group were significantly different than those in the healthy subjects (P < .05). Within-group comparisons of measured Fx1, Fy1, Fy2, Fz2, Fz4 and TTP of Fx1, Fy1, Fy2, Fz2, Fz3, Fz4, impulses of X2, z were significantly different from prefatigue to postfatigue in the healthy group (P < .05). Within-group comparisons of measured Fx1, Fy1, Fz1, Fz2 and TTP of Fx5, Fz1, impulses of X2 were significantly differed from prefatigue to postfatigue in the CLBP group (P < .05). It seems that TTP of ground reaction force variables in CLBP may have clinical values for rehabilitation. Muscle fatigue altered landing performance. However, patients with CLBP will respond differently to lower-extremity fatigue. These altered variables in patients with low back pain are the cause of future injuries or lower-extremity injuries that need to be addressed in further studies.


Otologic evaluation of patients with primary antibody deficiency.
Common variable immunodeficiency (CVID) represents the most frequent primary immunodeficiency, often encountered in the ENT clinical practice. The clinical spectrum of CVID is quite broad, but otitis media are certainly among the most common clinical manifestations. This prospective study enrolled 60 patients (34 males, 26 females) with a previous diagnosis of CVID with the aim of performing an otologic evaluation and a more precision characterization of incidence, diagnosis, and treatment of otitis media in this group of patients. In consideration that Eustachian tube dysfunction (ETD) could be the 'primum movens' of otitis media, we wanted to assess whether a Eustachian tube dysfunction was present in these patients. Besides, we propose a possible diagnostic algorithm of middle ear pathologies to use in all cases of primary antibody deficiency patients. Results of our otologic examination showed that: 5 % of patients had chronic suppurative otitis media, 25 % bilateral otitis media with effusion and 10 % reported unilateral OME with associated contralateral ETD. There was bilateral isolated ETD and unilateral isolated ETD in 5 and 15 % of patients, respectively. All patients with unilateral OME had associated contralateral ETD. Finally, 40 % of patients were bilaterally negative at otoscopic examination and all otologic tests.


The role of inflammatory cytokines in Meigs' syndrome.
Inflammatory cytokines are known to induce capillary leakage and third-space fluid accumulation in numerous gynecologic and nongynecologic disorders. This study aimed to assess their role in Meigs' syndrome. Evaluation of serum, peritoneal, and pleural fluids retrieved from a patient suffering from Meigs' syndrome revealed high interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha levels. After surgical removal of the ovarian tumor and with resolution of ascites and hydrothorax, serum levels of IL-1beta, IL-6, and IL-8 declined, whereas tumor necrosis factor-alpha levels remained high. The correlation between these inflammatory cytokines and the clinical course of Meigs' syndrome suggests their involvement in the formation of ascites and hydrothorax in this disorder.


Vimentin-positive cells in the villus epithelium of the rabbit small intestine.
In rabbit intestinal epithelium, vimentin intermediate filaments are selectively expressed in the M cells of follicle-associated epithelium (FAE). To find intestinal epithelial cells belonging to the M cell lineage, vimentin was detected immunohistochemically in the rabbit small and large intestines. Vimentin-positive columnar cells were scattered throughout the villus epithelium of the small intestine. In their cytoplasm, vimentin was located from the perinuclear region to the cell membrane touching intraepithelial lymphocytes. These cells had microvilli shorter than those of absorptive cells, and the alkaline phosphatase activity of the microvilli was markedly weaker than that of absorptive cell microvilli. Glycoconjugates on the surface of the microvilli were alcian blue positive and periodic acid-Schiff negative. The morphological and histochemical features of these vimentin-positive villus epithelial cells differed from those of adjacent absorptive cells and closely resembled those of the M cells in FAE covering Peyer's patches and solitary lymphatic nodules. These results suggest that the vimentin-positive cells in the villus epithelium belong to the M cell lineage.


Isolation of giant unilamellar vesicles from electroformed vesicle suspensions and their extrusion through nano-pores.
Liposomes required for drug delivery are commonly obtained by extrusion of phospholipid vesicle suspensions through track-etched membranes. The effects of trans-membrane pressure, membrane pore size and bilayer composition on extruded liposome size are well-studied. Vesicle suspensions used in these extrusion studies are highly polydisperse, ranging from 20 nm to 100 μm. Vesicle sub-populations smaller than membrane pore size do not undergo extrusion-mediated size reduction and contribute significantly to the mean radius of extruded liposomes. In the present work, giant unilamellar vesicles (GUVs) are isolated by subjecting electroformed vesicle suspensions to low-pressure filtration. The isolated GUVs are extruded through track-etched polycarbonate membranes with pore radii ranging from 25 to 200 nm. We show that, when vesicles larger than the membrane pore size are extruded, the minimum attainable value of mean radius of resulting liposomes is independent of initial vesicle size as well as the number of extrusion cycles. We also show that bilayer composition significantly influences the extruded liposome size. These results provide new insights into the possible mechanisms of vesicle size reduction during extrusion process.


Small cell lung cancer: Subtypes and therapeutic implications.
Small cell lung cancer (SCLC) is an extremely aggressive neuroendocrine tumor, accounting for approximated 13% of all lung cancer cases. SCLC is characterized by rapid growth and early metastasis. Despite marked improvements in the number and efficacy of targeted, therapeutic options and overall survival rates in SCLC have remained nearly unchanged for almost three decades. The lack of significant progress can be attributed to our poor understanding of the biology of SCLC. Although immune checkpoint inhibitors were recently approved as front-line therapies for SCLC, we still need to better understand the mechanisms responsible for the selective vulnerability of some SCLCs to these inhibitors. Recent work utilizing sequencing data and single cell analyses identified four distinct subsets of SCLC, based on the expression levels of the transcription factors ASCL1, NEUROD1, POU2F3 and YAP1. Each subset was found to have its own distinct biology and therapeutic vulnerabilities. However, these subsets appear to be phenotypically unstable, representing snapshots in the gradual evolution of a tumor that exhibits significant plasticity. Tumor evolution, a product of this plasticity, results in the emergence of significant intratumoral heterogeneity which plays an important role in multiple aspects of SCLC development and progression, including cell survival and proliferation, metastasis and angiogenesis. The recent paradigm shifting discoveries in the biology of SCLC are now beginning to inform the design of new therapeutic strategies for the management of this intractable disease.


Simultaneous HPLC determination of multiple components in a commercial cosmetic cream.
A high-performance liquid chromatographic method for the simultaneous determination of magnesium ascorbyl phosphate (I), imidazolidinylurea (II), a mixture of methyl-(III), ethyl-(IV), propyl-(V), butyl-(VI) parabens dissolved in phenoxyethanol, and ascorbyl palmitate (VII), was studied by using a cyano-propyl column and a methanol gradient at 220 and 240 nm. Calibration curves were found to be linear in the 0.05-5 mg ml(-1) range (compounds I, II, VII) and 0.9-160 mg ml(-1) (compounds III-VI). Linear regression analysis of the data demonstrates the efficacy of the method in terms of precision and accuracy. An extraction method is developed and validated in order to apply this chromatographic method to a commercial cosmetic cream. The precision of this method, calculated as the relative standard deviation (RSD) of the recoveries (1.57-2.21%) was excellent for all compounds I-VII.


Synthesis of raloxifene-like quinoxaline derivatives by intramolecular electrophilic cyclization with disulfides.
The intramolecular electrophilic cyclization of alkynes with disulfides to form thieno[2,3-b]quinoxaline structures and to introduce thioether substituents afforded quinoxaline derivatives (7a-7d, 8a-8d). Among obtained eight derivatives, the raloxifene analogues (7c, 8b) showed specifically high cytotoxicity against breast cancer cells (SK-BR-3), and raloxifene analogues (8a) showed the highest cytotoxicity against human leukemia cells (HL-60). None of the raloxifene analogues (7a-7d, 8a-8d) showed cytotoxicity against human lung fibroblasts (WI-38), which are normal cells.


Choreiform movements induced by anticholinergic therapy.
A case is reported where long term therapy with anticholinergic drugs caused choreiform movements in a 73-year-old man. After the therapy was ceased the movements disappeared. The elderly are particularly at risk from developing side effects from drug therapy. We believe this to be the first report of chorea produced by long-term therapy with benzhexol.


Hypocalcemia During Lenvatinib Treatment for Advanced Thyroid Cancer: Clinical Features and Management in a Real-Life Setting.
Background: Several toxicities are recorded during treatment of advanced thyroid cancer (TC) with antiangiogenic drugs, including lenvatinib (LEN). Hypocalcemia was reported in registration studies, but little data are available from real-life cohorts. The aim of our study was to describe the incidence, characteristics, and the management of hypocalcemia in patients on LEN treatment. Methods: This is a retrospective cohort study of consecutive patients with advanced TC, treated with LEN for at least six months at a single tertiary center in Italy. Phosphocalcic metabolism was evaluated during treatment. Results: We included 25 patients treated for a mean of 29 ± 19 months (range 6-68 months). Hypocalcemia occurred in 6 of the 25 patients (24% [95% confidence interval 9.36-45.13%]), being of grade ≥3 in 2 of the 25 patients (8%), and recurrent in 4 of 6 patients (67%). The median time to hypocalcemia onset was 3 months (range 0.5-13 months) from starting LEN. No differences were found between patients who developed or not hypocalcemia regarding either starting/mean dose of LEN or clinicopathological characteristics. During the hypocalcemic crisis, the 2 patients with grade ≥3 hypocalcemia had low magnesium and low or inappropriately normal parathormone (PTH) levels, while 2 of 3 patients with grade 2 hypocalcemia had a secondary hyperparathyroidism. Hypocalcemia was managed with calcium oral supplementation in most cases, although up to 10% of patients required intravenous calcium treatment and transient LEN withdrawal. Conclusions: In this relatively small cohort, we observed an incidence of hypocalcemia of 24%, which is higher than that reported in the registration trial (6.9%). Both PTH-dependent and PTH-independent mechanisms explained hypocalcemia in the present cohort. Monitoring of serum calcium levels is strongly advised during the first year of LEN treatment, as hypocalcemia may be severe. More research is needed to confirm our findings and inform possible risk factors for hypocalcemia in advanced TC patients treated with LEN.


Enhancing antigen cross-presentation and T-cell priming by complexing protein antigen to recombinant large heat-shock protein.
Large heat-shock proteins (HSPs), including hsp110 and grp170, are unique immunochaperones capable of carrying and introducing antigens into professional antigen-presenting cells for efficient cross-presentation. Therefore, reconstituted chaperone complexes of large HSPs and protein antigen may be exploited for augmentation of an antigen-specific immune response. The methods for the preparation of the recombinant protein antigen chaperone complex and characterization of its T-cell priming capability in both in vitro and in vivo settings are described.


The effects of age on second language grammar and speech production.
The current study examined the age of learning effect on second language (L2) acquisition. The research goals of the study were twofold: to test whether there is an independent age effect controlling for other potentially confounding variables, and to clarify the age effect across L2 grammar and speech production domains. The study included 118 Mandarin-speaking immigrants and 24 native English speakers. Grammar knowledge was assessed by a grammaticality judgment task, and speech production was measured by native English speaking raters' ratings of participants' foreign accents. Results from the study revealed that the age of learning effect was robust for both L2 domains even after controlling for the influences of other variables, such as length of residence and years of education in the United States. However, the age of learning variable had a stronger impact on speech production than on grammar. The current results support the framework of multiple critical/sensitive periods (Long in Int Rev Appl Linguist 43(4):287-317, 2005; Newport et al. in Language, brain and cognitive development: Essays in honor of Jacques Mehler. MIT Press, Cambridge, MA, 2001; Werker and Tees in Dev Psychobiol 46(3):233-251, 2005).


Genome Sequence of the Polycyclic Aromatic Hydrocarbon-Degrading Bacterium Strain Marinobacter nanhaiticus D15-8WT.
Marinobacter nanhaiticus strain D15-8W(T) was isolated from a phenanthrene-degrading consortium, enriched from sediment of the South China Sea. Here, we present the draft genome of strain D15-8W(T), which contains 5,358,309 bp with a G+C content of 58.53% and contains 4,829 protein-coding genes and 47 tRNA genes.


Highly selective dummy molecularly imprinted polymer as a solid-phase extraction sorbent for five bisphenols in tap and river water.
A simple and fast method for both dummy template selection and polymer composition optimization is proposed here. A series of dummy templates for bisphenols imprinting were screened by running them on a non-imprinted polymer (NIP) column with porogen solvent as mobile phase. The tested dummy templates mainly involved bisphenol S (BPS), bromobisphenol A (TBBPA), bisphenol F (BPF), bisphenol E (BPE), bisphenol B (BPB), bisphenol AF (BPAF), 2,2',6,6'-tetramethyl-4,4'-sulfonyldiphenol (BS-TM) and 4,4'-diaminodiphenylmethane (DADPM). Different monomers and porogens were also investigated for BPS and DADPM using the same method. BPS dummy template was finally selected with acetonitrile and 4-VP as porogen and monomer. The resulting dummy molecularly imprinted polymer (DMIP) achieved superior affinities for BPF, BPE, BPA, BPB and BPAF with imprinting factors 14.5, 13.8, 8.7, 5.7 and 4.2, respectively. An efficient method based on BPS-DMIP-SPE coupled with HPLC-UV was developed for selective extraction of BPF, BPE, BPA, BPB and BPAF in water samples. The method showed excellent recoveries (89.4-102.0%) and precision (RSD 0.3-4.8%, n=5) for tap and river water samples spiked at three concentration levels each (40, 200 and 1000ngL(-1)). The detection limits ranged between 2.2 and 3.8ngL(-1) with a sample volume of 500mL. The result demonstrated the superiority of the optimized method for selective extraction of BPs in water samples at the ngL(-1) level.


Development and validation of a tool to measure collaborative practice between community pharmacists and physicians from the perspective of community pharmacists: the professional collaborative practice tool.
Collaborative practice between community pharmacists and physicians is becoming increasingly common. Although tools and models to explore collaborative practice between both health care professionals have been developed, very few have been validated for their use in clinical practice. The objective of this study was to develop and validate a tool for measuring collaborative practice between community pharmacists and physicians from the perspective of community pharmacists. The DeVellis method was used to develop and validate the Professional Collaborative Practice Tool. A pool of 40 items with Likert frequency scales was generated based on previous literature and expert opinion. This study was undertaken in Spain. A sample of community pharmacists providing medication reviews with follow-up and a random sample of pharmacists providing usual care were invited to participate. Exploratory and confirmatory factor analysis was used to assess the tool's reliability and content validity. Three hundred thirty-six pharmacists were invited with an overall response rate of 84.8%. The initial 40 items selected were reduced to 14 items. Exploratory Factor Analysis provided a 3-factor solution explaining 62% of the variance. Confirmatory Factor Analysis confirmed the three factors "Activation for collaborative professional practice," the "Integration in collaborative professional practice," and the "Professional acceptance in collaborative professional practice." The tool demonstrated an adequate fit (X2/df = 1.657, GFI = 0.889 and RMSEA = 0.069) and good internal consistency (Cronbach's alpha = 0.924). The Professional Collaborative Practice Tool has shown good internal reliability and criterion validity. The tool could be used to measure the perceived level of collaborative practice between community pharmacists and physicians and monitor changes over time. Its applicability and transferability to other settings should be evaluated.


Intraoperative esmolol infusion in the absence of opioids spares postoperative fentanyl in patients undergoing ambulatory laparoscopic cholecystectomy.
The use of opioids during ambulatory surgery can delay hospital discharge or cause unexpected hospital admission. Preliminary studies using an intraoperative continuous infusion of esmolol in place of an opioid have inconsistently reported a postoperative opioid-sparing effect. In this study, we compared esmolol versus either intermittent fentanyl or continuous remifentanil on postoperative opioid-sparing, side effects, and time of discharge. Ninety patients (consisting of three groups) were enrolled in this prospective, randomized, and observer-blinded study. The control group (n = 30) received intermittent doses of fentanyl, the esmolol group (n = 30) received a continuous infusion of esmolol (5-15 microg x kg(-1) x min(-1)) and no supplemental opioids during surgery, and the remifentanil group (n = 30) received a continuous infusion of remifentanil (0.1-0.5 mixrog x kg(-1) x min(-1)). General anesthesia was standardized, and adjuvant medications included acetaminophen, ketorolac, local anesthetics in the skin incisions, dexamethasone, and droperidol. Postoperative analgesia included fentanyl. The amount of fentanyl in the postanesthesia care unit was significantly less in the esmolol group, 91.5 +/- 42.7 microg, compared with the other two groups, remifentanil, 237.8 +/- 54.7 microg, control, 168.1 +/- 96.8 microg (P < 0.0001). The incidence of nausea was more frequent in the control (66.7%) and remifentanil (67.9%) groups compared with the esmolol group (30%) (P < 0.01). The esmolol group reached the White-Song score of 12 of 14 faster than the remifentanil group (P < 0.01), and left the hospital 45-60 min earlier (P < 0.004). Intraoperative IV infusion of esmolol contributes to a significant decrease in postoperative administration of fentanyl and ondansetron and facilitates earlier discharge.