[Investigation on antitumor mechanism of polysaccharide from medicinal fungus Penicillium jiangxiense].
To investigate the possible antitumor mechanism of polysaccharide from medicinal fungus Penicillium jiangxiense. The cytotoxic effect was measured by MTT assay, and the cell cycle was analyzed by flow cytometry with Propidium iodide (PI) staining. To apoptotic detections, Hoechst 33258 staining for chromatin, annexin-V FITC/PI double staining for early phase cell apoptosis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) for late phase cell apoptosis. Both MPPJ4 and MPPJ5, the fine polysaccharide fractions from P. jiangxiense, showed slight cytotoxic effects to inhibit human gastric adenocarcinoma SGC-7901 cells proliferation, but significantly caused cell cycle arrest at the S phase, and the rate of cell population at the subG1 phase was evidently increased. In apoptotic assays, MPPJ5 was more potent than MMPJ4 in inducing tumor cells in a time-dependent manner at the range from 0 to 72 hours, comparable to the negative control. The antitumor acting mechanism of P. jiangxiense polysaccharide is associated with the induction of apoptotic cell death and cell cycle arrest.


Past-users of HRT are osteopenic four months after discontinuation:an observational and cross-sectional study.
Hormonal replacement therapy (HRT) helps to prevent osteoporosis. The effect of short-term discontinuation of a long-term HRT on bone mineral density (BMD) in healthy post-menopausal women is unknown. Fifteen women on HRT (HRT users), 17 who never used HRT (non-users) and 8 former HRT users (past-HRT users) were recruited. BMD was measured by DXA. Our results allow to hypothesize that BMD may decline after short-term HRT discontinuation, which would increase the fracture risks. Indeed, our results show that past-HRT users are osteopenic just as non-users. However, these results should be re-examined using a prospective trial and a larger sample size.


Isoliquiritin treatment of osteoporosis by promoting osteogenic differentiation and autophagy of bone marrow mesenchymal stem cells.
Osteoporosis is a chronic progressive bone disease characterized by the decreased osteogenic ability of osteoblasts coupled with increased osteoclast activity. Natural products showing promising therapeutic potential for postmenopausal osteoporosis remain underexplored. In this study, we aimed to analyze the therapeutic effects of isoliquiritin (ISL) on osteoporosis in mice and its possible mechanism of action. An ovariectomy-induced osteoporosis mouse model and bone marrow mesenchymal stem cells (BMSCs) were used to analyze the effects of ISL on bone regeneration in vivo and in vitro, respectively. Mitogen-activated protein kinase (MAPK) and autophagy inhibitors were used, to investigate whether the MAPK signaling pathway and autophagy affect the osteogenic differentiation of BMSCs. ISL significantly improved bone formation and reduced bone resorption in mouse femurs without inducing any detectable toxicity in critical organs such as the liver, kidney, brain, heart, and spleen. In vitro experiments showed that ISL enhanced the proliferation and osteogenic differentiation of BMSCs and that its osteogenic effect was attenuated by p38/extracellular regulated protein kinase (ERK) and autophagy inhibitors. Further studies showed that the inhibition of phosphorylated p38/ERK blocked ISL autophagy in BMSCs. ISL promoted the osteogenic differentiation of BMSCs through the p38/ERK-autophagy pathway and was therapeutically effective in treating osteoporosis in ovariectomized mice without any observed toxicity to vital organs. These results strongly suggest the promising potential of ISL as a safe and efficacious candidate drug for the treatment of osteoporosis.


Right heart failure due to loss of right ventricular capture in a patient with atrioventricular junction ablation and biventricular pacing.
We describe the case of a patient with atrioventricular (AV) junction ablation and chronic biventricular pacing in which intermittent dysfunction of the right ventricular (RV) lead resulted in left ventricular (LV) stimulation alone and onset of severe right heart failure. Restoration of biventricular pacing by increasing device output and then performing lead revision resolved the issue. This case provides evidence that LV pacing alone in patients with AV junction ablation may lead to severe right heart failure, most likely as a result of iatrogenic mechanical dyssynchrony within the RV. Thus, probably this pacing mode should be avoided in pacemaker-dependent patients with heart failure.


Unicameral (simple) bone cysts.
Since their original description by Virchow, simple bone cysts have been studied repeatedly. Although these defects are not true neoplasms, simple bone cysts may create major structural defects of the humerus, femur, and os calcis. They are commonly discovered incidentally when x-rays are taken for other reasons or on presentation due to a pathologic fracture. Various treatment strategies have been employed, but the only reliable predictor of success of any treatment strategy is the age of the patient; those being older than 10 years of age heal their cysts at a higher rate than those under age 10. The goal of management is the formation of a bone that can withstand the stresses of use by the patient without evidence of continued bone destruction as determined by serial radiographic follow-up. The goal is not a normal-appearing x-ray, but a functionally stable bone.


[Enterococcal meningitis].
104 cases of enterococcal meningitis from the literature of the last 35 years have been reviewed: 70% are pediatric patients, 30% are adults. Malformations or concomitant conditions favour the outbreak of the disease. Mixed infections are frequent (15%). The average lethality is about 40% with a variation of +/- 22% depending on the patients prior state of health. Treatment is still very difficult even with the latest antibiotics.


Clinical predictors for the selective use of chest radiographs in pediatric blunt trauma evaluations.
Chest radiographs continue to be a routine part of the evaluation of children sustaining blunt trauma. This study sought to determine those clinical markers associated with an abnormal chest radiograph in nonintubated, pediatric, blunt trauma victims. A retrospective case-control study was performed for severely injured pediatric trauma patients presenting to our emergency department between January 1, 1996, and December 31, 1997. Abnormal chest radiographs were identified through the trauma registry and four controls were matched to each case. Radiographs were reevaluated by our study radiologist. Variables associated with an abnormal chest radiograph were grouped to develop a set of clinical markers that could predict an abnormal chest radiograph with a high degree of sensitivity. An initial chest radiograph was obtained in 457 of 587 trauma patients. Thirty study patients with an abnormal radiograph that met inclusion criteria were analyzed with 133 controls. The presence of either an abnormal respiratory rate for age, chest tenderness, or back abrasions had a sensitivity of 1.0 (95% confidence interval, 0.86-1.0) and a specificity of 0.38 (95% confidence interval, 0.30-0.47). In pediatric trauma patients, the presence of chest tenderness, back abrasions, or an abnormal respiratory rate identified all abnormal chest radiographs.


A comparison of five immunohistochemical biomarkers and HER-2/neu gene amplification by fluorescence in situ hybridization in white and Korean patients with early-onset breast carcinoma.
The objective of this article was to compare five tumor markers between white women in the U.S. and native Korean women with early-onset breast carcinoma. Sixty Korean women who were diagnosed with breast carcinoma at age 45 years or younger and 60 white women with breast carcinoma who were matched by age were selected for this study. The median age of both groups was 37 years. Paraffin embedded blocks of the primary tumor were processed for immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PR), p53, cyclin D1, and HER-2/neu. The proportion of tumors that stained positive for ER, PR, p53, and cyclin D1 in the Korean women were 47.5%, 42.4%, 28.8%, and 40.9%, respectively; in the white women, the proportions were 43.9%, 52.6%, 21.1%, and 59.1%, respectively. The differences between the white patients and the Korean patients were not statistically significant with respect to any of those variables. A significant difference was found in the expression of HER-2/neu. Specifically, positive HER-2/neu status was observed in 47.5% of Korean women, compared with overexpression in only 15.8% of white women (P < 0.001). Fluorescence in situ hybridization analysis for HER-2/neu gene amplification on all HER-2/neu positive samples that scored 2 + and 3 + demonstrated a significant difference (P = 0.007) in gene amplification between the two populations. Differences in HER-2/neu positivity were observed for the entire cohort as well as among the subsets of patients with negative and positive lymph node status. No association was found between immunoreactivity for the five markers and axillary lymph node metastasis. The findings of high positivity of HER-2/neu expression and gene amplification in Korean women with early-onset breast carcinoma may have potential implications for local and systemic management of breast carcinoma, especially anti-HER-2/neu therapy for patients with hormone receptor negativity. Further research will be needed to identify biologic and genetic factors and their effects on the survival between different racial groups.


Entomological surveillance with viral tracking demonstrates a migrated viral strain caused dengue epidemic in July, 2017 in Sri Lanka.
Dengue is the most important mosquito-borne viral infection disease in Sri Lanka triggering extensive economic and social burden in the country. Even after numerous source reduction programmes, more than 30,000 incidences are reporting in the country every year. The last and greatest dengue epidemic in the country was reported in July, 2017 with more than 300 dengue related deaths and the highest number of dengue incidences were reported from the District of Gampaha. There is no Dengue Virus (DENV) detection system in field specimens in the district yet and therefore the aim of the study is development of entomological surveillance approach through vector survey programmes together with molecular and phylogenetic methods to identify detection of DENV serotypes circulation in order to minimize adverse effects of imminent dengue outbreaks. Entomological surveys were conducted in five study areas in the district for 36 months and altogether, 10,616 potential breeding places were investigated and 423 were positive for immature stages of dengue vector mosquitoes. During adult collections, 2,718 dengue vector mosquitoes were collected and 4.6% (n = 124) were Aedes aegypti. While entomological indices demonstrate various correlations with meteorological variables and reported dengue incidences, the mosquito pools collected during the epidemic in 2017 were positive for DENV. The results of the phylogenetic analysis illustrated that Envelope (E) gene sequences derived from the isolated DENV belongs to the Clade Ib of Cosmopolitan genotype of the DENV serotype 2 which has been the dominant stain in South-East Asian evidencing that a recent migration of DENV strain to Sri Lanka.


Copper-catalyzed 1,2-hydroxysulfenylation of alkene using disulfide via cleavage of the S-S bond.
Copper-catalyzed 1,2-hydroxysulfenylation of alkenes can be carried out by the use of disulfides and acetic acid in air. This reaction regio- and anti-selectively gave the corresponding 1,2-acetoxysulfides. Furthermore, the present method enables the use of both organosulfide groups of disulfide.


A-ring substituted estrogens as inhibitors of the MXT transplantable mammary ductal carcinoma.
A-ring substituted estrogens have been examined as growth inhibitors of the hormone dependent MXT murine mammary tumor. Certain of these estrogen analogues inhibited the growth of newly implanted as well as established MXT tumors when administered either by s.c. or i.p. injections or by intubation. These compounds were nontoxic over a broad range of active levels. Amino and nitro groups, introduced at position-4 of estrone 3-methyl ether were particularly carcinostatic, a property not shared by 4-bromoestrone 3-methyl ether. In addition tumor inhibition was greatly diminished by placing the nitro group at the other ortho position (i.e., carbon-2). Evidence indicates that the A-ring substituted estrogens may function as growth inhibitors via the estrogen receptor mechanism in the case of 4-nitro- and 4-aminoestrone. The 3-methyl ethers of these compounds also blocked tumor growth, possibly through in vivo dealkylation leading to the free phenolic A-ring substituted estrogens. On the other hand, A-ring substituted 3-deoxyestrogens (particularly 4-nitro- and 4-aminoestratrien-17 beta-ol), which do not bind to receptor, were also excellent inhibitors of hormone dependent MXT breast tumors and therefore must express their activity by mechanisms other than that mediated by receptor. The A-ring substituted estrogens are unlike tamoxifen and diethylstilbestrol which (a) display toxicity at optimum inhibitory doses and (b) are inactive or marginally active in rodent breast cancer models.


Parturition care planning.
Nursing care planning is not a new concept, but in contemporary nursing, this tool is taking on new meaning. In an area such as labor and delivery, the concept of the nursing process must be scrutinized and adapted to facilitate its usefulness in providing optimum care of the parturient. A perspective on the scope of care planning, its benefits to the parturient, and its value and implications is presented.


Production and characterization of monoclonal antibodies to Mobiluncus species.
Members of the genus Mobiluncus are anaerobic motile curved rods which are associated with bacterial vaginosis (BV). Murine monoclonal antibodies (MAbs) to the ATCC type strains of M. curtisii subsp. curtisii, M. curtisii subsp. holmesii, and M. mulieris were produced and characterized by enzyme-linked immunosorbent assay and indirect immunofluorescence assay. Four MAbs were subspecies specific and reacted with M. curtisii subsp. curtisii but not with M. curtisii subsp. holmesii; four were specific for M. mulieris. The remaining antibodies demonstrated some cross-reactivity: three were species specific and reacted with both subspecies of M. curtisii, and one defined an epitope shared by M. curtisii subsp. holmesii and M. mulieris but not by M. curtisii subsp. curtisii. None of the MAbs reacted with a panel of other bacteria commonly present in the vaginas of normal women or women with BV. Examination of the molecular specificities of the antibodies by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting revealed four antibodies which were specific for an 82,000-dalton molecule of M. curtisii subsp. curtisii and five antibodies which bound a major band of M. mulieris at 93,000 daltons. Selected MAbs reacted in the indirect immunofluorescence assay with 24 of 25 Mobiluncus spp. clinical isolates from local women with BV and could be used for direct detection of Mobiluncus spp. in vaginal fluid from a patient with BV.


A Qualitative Examination of the Detroit Community Food Response to COVID-19.
The COVID-19 pandemic increased the need for food assistance due to surging unemployment, the closure of in-person schooling, and other factors. This posed a historic challenge to organizations that address food insecurity: meeting the surging need for food while minimizing COVID-19 transmission. This study aimed to identify how food insecurity program operations changed during the pandemic and to examine the facilitators/successes and barriers/challenges to operations. Semi-structured interviews were conducted with staff at 13 organizations involved in addressing food insecurity in Detroit during the pandemic. Interviews were coded by two coders, summarized, and then used to create matrices and concept map displays for each organization. We found that nearly all programs changed to a contactless food distribution format, and most programs experienced an increase in demand for food. Common successes/facilitators included keeping clients and staff safe from COVID-19 and waivers that eased program rules. Common challenges/barriers included the increased need for labor and food. Lack of funding was a barrier for some organizations, and others that experienced an increase in funding reported that it facilitated their work. This research identified the needs of programs addressing food insecurity during the COVID-19 pandemic, which can inform future disaster planning.


Total colpocleisis for severe pelvic organ prolapse.
To describe the complications and efficacy of total colpoclesis for severe pelvic organ prolapse. In this descriptive study, we analyzed the complications and efficacy of total colpoclesis in 41 consecutive women with pelvic organ prolapse at Temple University Hospital between November 1994 and June 2001. The mean followup period was 28.7 months (range, 5-65). Vaginal hysterectomy was performed in 12 patients. All but 10 patients underwent concomitant modified paravaginal cystourethropexy. Modified perineorraphy was standard in every case. There was no recurrence of prolapse and a very low complication rate. The cure rate for urinary incontinence was 53.1% in 32 patients with preoperative urinary incontinence. Total colpocleisis combined with site-specific reconstructive surgery is an effective and safe treatment of severe pelvic organ prolapse in high-risk, elderly women.


Motor Plans under Uncertainty Reflect a Trade-Off between Maximizing Reward and Success.
When faced with multiple potential movement options, individuals either reach directly to one of the options, or initiate a reach intermediate between the options. It remains unclear why people generate these two types of behaviors. Using the go-before-you-know task (commonly used to study behavior under choice uncertainty) in humans, we examined two key questions. First, do these two types of responses actually reflect distinct movement strategies? If so, the relative desirability (i.e., weighing the success likelihood vs the attainable reward) of the two target options would not need to be computed identically for direct and intermediate reaches. We showed that indeed, when reward and success likelihood differed between the two options, reach direction was preferentially biased toward different directions for direct versus intermediate reaches. Importantly, this suggests that the computation of subjective values depends on the choice of movement strategy. Second, what drives individual differences in how people respond under uncertainty? We found that risk/reward-seeking individuals tended to generate more intermediate reaches and were more responsive to changes in reward, suggesting these movements may reflect a strategy to maximize reward versus success. Together, these findings suggest that when faced with choice uncertainty, individuals adopt movement strategies consistent with their risk/reward attitude, preferentially biasing behavior toward exogenous rewards or endogenous success and consequently modulating the relative desirability of the available options.


The Arabidopsis PeptideAtlas: Harnessing worldwide proteomics data to create a comprehensive community proteomics resource.
We developed a resource, the Arabidopsis PeptideAtlas (www.peptideatlas.org/builds/arabidopsis/), to solve central questions about the Arabidopsis thaliana proteome, such as the significance of protein splice forms and post-translational modifications (PTMs), or simply to obtain reliable information about specific proteins. PeptideAtlas is based on published mass spectrometry (MS) data collected through ProteomeXchange and reanalyzed through a uniform processing and metadata annotation pipeline. All matched MS-derived peptide data are linked to spectral, technical, and biological metadata. Nearly 40 million out of ∼143 million MS/MS (tandem MS) spectra were matched to the reference genome Araport11, identifying ∼0.5 million unique peptides and 17,858 uniquely identified proteins (only isoform per gene) at the highest confidence level (false discovery rate 0.0004; 2 non-nested peptides ≥9 amino acid each), assigned canonical proteins, and 3,543 lower-confidence proteins. Physicochemical protein properties were evaluated for targeted identification of unobserved proteins. Additional proteins and isoforms currently not in Araport11 were identified that were generated from pseudogenes, alternative start, stops, and/or splice variants, and small Open Reading Frames; these features should be considered when updating the Arabidopsis genome. Phosphorylation can be inspected through a sophisticated PTM viewer. PeptideAtlas is integrated with community resources including TAIR, tracks in JBrowse, PPDB, and UniProtKB. Subsequent PeptideAtlas builds will incorporate millions more MS/MS data.


Rett syndrome: review and discussion of current diagnostic criteria.
Rett syndrome is a mental retardation syndrome that occurs only in females and consists of normal pre-, peri-, and neonatal growth and development. It is followed by rapid neurobehavioral deterioration in late infancy or early childhood, a developmental arrest, plateauing, and then either a course of retarded development or continued deterioration. The period of rapid neuro-behavioral deterioration manifests as a partial autistic syndrome, with loss of production and comprehension of language, hyperactivity, hyperventilation, hand-wringing, and ataxic gait. Current diagnostic criteria are discussed and suggestions for further research are presented.


A comparative study of serological tests used in the diagnosis of Toxoplasma gondii infection in small ruminants evidenced the importance of cross-reactions for harmonizing diagnostic performance.
Toxoplasma gondii is a major foodborne zoonotic pathogen that can be transmitted through the consumption of raw or undercooked meat of small ruminants, among others. Serology has been suggested as an epidemiological indicator and several tests are available nowadays. However, there is no comparative study with the most used ones. Therefore, the objective of this study was to develop and validate two in-house tests (Western blot -TgSALUVET WB- and ELISA -TgSALUVET ELISA 2.0-) and perform a comparative study including such tests and four commercial ELISA kits (IDScreen®, PrioCHECK®, Pigtype® and IDEXX). First, a specific pattern of recognition of immunodominant antigens by TgSALUVET WB was determined with serum panels of noninfected sheep and sheep infected with T. gondii or Neospora caninum. Next, TgSALUVET WB was used as a reference to preliminary validate TgSALUVET ELISA 2.0 using sera from sheep and goats naturally infected with T. gondii. Then, the abovementioned sheep serum panels were analyzed by all tests and subjected to TG-ROC analyses and agreement tests, and cross-reactivity with the anti-N. caninum IgGs was studied. All the techniques were accurate enough for the cutoff values initially suggested with all serum panels (Se and Sp ≥ 94%), except for PrioCHECK®, which showed 83% Sp. However, a cutoff readjustment improved their diagnostic performance. Additionally, cross-reactions between anti-N. caninum antibodies and T. gondii antigens were detected with all tests. Thus, a second cutoff readjustment was carried out and the use of both readjusted cutoff values is recommended to obtain comparable data and avoid false-positive results.


Technical aspects of robotic proctectomy.
Robotic proctectomy is at the forefront of surgical innovation, and interest in this technique is rapidly increasing. The advantages of robotic techniques, such as enhanced visualization and improved dexterity along with tireless retraction and the addition of a "fourth arm" are reported to confer an advantage in the pelvis. It is unknown what long-term outcomes may emerge from ongoing clinical trials; however, early studies suggest improved perioperative and oncologic outcomes. Proponents of robotics suggest that robot-assisted procedures are associated with decreased complication rates and fewer conversions to open. This article reviews the pertinent literature on robotic total mesorectal excision and the early reported outcomes. The 3-arm, 4-arm laparoscopic-assisted, and the 4-arm totally robotic techniques for performing robotic proctectomy are described in detail, including port placement and patient position as well as robot docking.


A newly recognized polyosteolysis/hyperostosis syndrome.
We report a newly recognized bone disorder consisting of polyostotic expansile osteolysis affecting long bones and iliac bones; hyperostosis of the skull, thoracic cage, and medial portion of both clavicles; pectus carinatum; gigantiform synovial masses of the elbows and knees; atrial septal defect; cardiomegaly; unilateral cryptorchidism; and mental deficiency. Affected bones can be grouped into four general types of skeletal pathology: (1) expansile osteolysis, (2) osteolysis without expansion, (3) expansion without osteolysis, and (4) hyperostosis. Some bones remained unaffected. We have named the condition "polyosteolysis/hyperostosis syndrome." It is clearly at variance with any previously reported bone disorder, including familial expansile osteolysis, juvenile Paget disease, and McCune-Albright syndrome (and polyostotic fibrous dysplasia). Because our patient shared some features in common with juvenile Paget disease, we thought that mutational analysis of TNFRSF11B was indicated, even though our patient had some manifestations not found in juvenile Paget disease. Direct sequencing failed to identify a TNFRSF11B mutation. Because the parents of our propositus were first cousins suggests that polyosteolysis/hyperostosis syndrome may possibly have autosomal recessive inheritance.


Glomerulonephritis as a Type of Kidney Injury in Multiple Myeloma: a Report of 2 Cases.
Renal involvement in multiple myeloma has multiple etiologies. Glomerulonephritis rarely occurs in multiple myeloma and numerous case reports in the literature explain their correlation. We report 2 cases of glomerulonephritis, one membranous glomerulonephritis and the other focal segmental glomerulosclerosis, in which multiple myeloma was confirmed after several months in the first case and synchronous with the second. Glomerulonephritis can be an uncommon, but not rare, cause of proteinuria in multiple myeloma.


Common modifications of trimeric G proteins and ras protein: involvement of polyisoprenylation.
The heterotrimeric guanine nucleotide-binding regulatory proteins act at the inner surface of the plasma membrane to relay information from cell surface receptors to effectors inside the cell. These G proteins are not integral membrane proteins, yet are membrane associated. The processing and function of the gamma subunit of the yeast G protein involved in mating-pheromone signal transduction was found to be affected by the same mutations that block ras processing. The nature of these mutations implied that the gamma subunit was polyisoprenylated and that this modification was necessary for membrane association and biological activity. A microbial screen was developed for pharmacological agents that inhibit polyisoprenylation and that have potential application in cancer therapy.


Evidence for active immunological regulation in prevention of testicular autoimmune disease independent of the blood-testis barrier.
It has long been considered that autoimmune disease of the testis is prevented by sequestration of testis-specific autoantigens on germ cells behind the blood-testis (BT) barrier. However, we now have evidence that not all such antigens are sequestered. Some appear to reside on germ cells in the basal compartment of the seminiferous tubule where they are accessible to antibodies and to circulating activated T cells. Mice immunized with syngeneic testis homogenate are found to have immunoglobulin G (IgG) bound to cells in the basal compartment before onset of orchitis. This IgG is absorbed from circulation by the testis and, therefore, found only in the serum of mice orchiectomized before immunization. When the IgG is eluted from the testis, it is found to react preferentially with testicular cells enriched in preleptotene spermatocytes. T cells from mice immunized with testis can be transferred to naive syngeneic mice where they infiltrate the testis to cause orchitis. This implies that the BT barrier does not need to be breached directly for specific T cells to have access to testicular autoantigens on antigen presenting cells. Thus, active systemic and/or local immunoregulatory mechanisms must operate to prevent testicular autoimmune disease. These mechanisms may operate at the level of suppressor T cells, nonspecific suppression in the local environment of the testis, antigen presentation in the testis, or lymphocyte trafficking in the testis. These mechanisms probably operate only on the afferent limb of the immune response since they are overridden and orchitis occurs once testis-specific activated T cells are generated.


Qualitative and quantitative evaluation of in vivo SD-OCT measurement of rat brain.
OCT has been demonstrated as an efficient imaging modality in various biomedical and clinical applications. However, there is a missing link with respect to the source of contrast between OCT and other modern imaging modalities, no quantitative comparison has been demonstrated between them, yet. We evaluated, to our knowledge, for the first time in vivo OCT measurement of rat brain with our previously proposed forward imaging method by both qualitatively and quantitatively correlating OCT with the corresponding T1-weighted and T2-weighted magnetic resonance images, fiber density map (FDM), and two types of histology staining (cresyl violet and acetylcholinesterase AchE), respectively. Brain anatomical structures were identified and compared across OCT, MRI and histology imaging modalities. Noticeable resemblances corresponding to certain anatomical structures were found between OCT and other image profiles. Correlation was quantitatively assessed by estimating correlation coefficient (R) and mutual information (MI). Results show that the 1-D OCT measurements in regards to the intensity profile and estimated attenuation factor, do not have profound linear correlation with the other image modalities suggested from correlation coefficient estimation. However, findings in mutual information analysis demonstrate that there are markedly high MI values in OCT-MRI signals.


Olfactory function in chemical workers exposed to acrylate and methacrylate vapors.
An investigation of the olfactory function of 731 workers at a chemical facility which manufacturers acrylates and methacrylates was undertaken using a standardized quantitative test. In a cross-sectional analysis of the data, no associations of chemical exposure with olfactory test scores were observed. A nested case-control study designed to evaluate the cumulative effects of exposure on olfactory function, however, revealed elevated crude exposure odds ratios (95% confidence interval) of 2.0 (1.1, 3.8) for all workers and 6.0 (1.7, 21.5) for workers who never smoked cigarettes. Logistic regression analysis, adjusting for multiple confounders, revealed exposure odds ratios of 2.8 (1.1, 7.0) and 13.5 (2.1, 87.6) in these same groups, respectively, and a dose-response relationship between olfactory dysfunction and cumulative exposure scores--semi-quantitative indices of lifetime exposure to the acrylates. The data also revealed decreasing exposure odds ratios with increasing duration since last exposure to these chemicals, suggesting that the effects may be reversible.


Activity-dependent peptidergic modulation of the plateau-generating neuron B64 in the feeding network of Aplysia.
Many behaviors display various forms of activity-dependent plasticity. An example of such plasticity is the progressive shortening of the duration of protraction phase of feeding responses of Aplysia that occurs when feeding responses are repeatedly elicited. A similar protraction-duration shortening is observed in isolated ganglia of Aplysia when feeding-like motor programs are elicited through a prolonged stimulation of the command-like neuron CBI-2. Here, we investigate a cellular mechanism that may underlie this activity-dependent shortening of protraction duration of feeding motor programs. CBI-2 contains two neuropeptides, CP2 and FCAP. Previous work showed that CP2 shortens protraction duration of CBI-2 elicited programs. We show here that the same is true for FCAP. We also show that both CP2 and FCAP modulated the biophysical properties of a plateau-generating neuron, B64, that plays an important role in terminating the protraction phase of feeding motor programs. We find that prestimulation of CBI-2, as well as superfusion of CP2 and FCAP, lowered the threshold for activation of the plateau potential in B64. The threshold-lowering actions of CBI-2 prestimulation were occluded by superfusion of FCAP and CP2. Furthermore, at elevated temperature, conditions under which peptide release is prevented in Aplysia, prestimulation of CBI-2 does not lower the plateau-potential threshold, whereas superfusion of CP2 and FCAP does. Our findings are consistent with the hypothesis that peptides released from CBI-2 lower the threshold for activation of plateau potential in B64, thereby contributing to the shortening of protraction duration when CBI-2 is repeatedly activated.


Pentoxifylline Inhibits TNF-α/TGF-β1-Induced Epithelial-Mesenchymal Transition via Suppressing the NF-κB Pathway and SERPINE1 Expression in CaSki Cells.
Cervical cancer (CC) is one of the most common and deadly types of female cancer worldwide. Late diagnosis in CC increases the risk of tumor cells spreading to distant organs (metastasis). The epithelial-mesenchymal transition (EMT) is a fundamental process of cancer metastasis. Inflammation can lead to tumor progression, EMT induction, and metastasis. The inflammatory microenvironment is a potent inducer of EMT; inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α) and Transforming growth factor-beta (TGF-β1) activate transcriptional factors such as STAT3, Snail, Smad, and the Nuclear Factor kappa light-chain-enhancer of activated beta cells (NF-κΒ), which drive EMT. Anti-inflammatory compounds may be an option in the disruption of EMT. PenToXifylline (PTX) possesses potent anti-inflammatory effects by inhibiting NF-κB activity. In addition, PTX exerts an anti-fibrotic effect by decreasing Smad2/3/4. We hypothesize that PTX could exert anti-EMT effects. CaSki human cervical tumor cells were exposed to TNF-α 10 ng/mL and TGF-β1 alone or in combination for 5 days. Our results revealed that TNF-α and TGF-β1 induced N-cadherin and Vimentin, confirming the induction of EMT. Furthermore, the combination of cytokines synergized the expression of mesenchymal proteins, enhanced IκBα and p65 phosphorylation, and upregulated Serpin family E member 1 (SERPINE1) mRNA. PTX pretreatment prior to the addition of TNF-α and TGF-β1 significantly reduced N-cadherin and Vimentin levels. To our knowledge, this is the first time that this effect of PTX has been reported. Additionally, PTX reduced the phosphorylation of IκB-α and p65 and significantly decreased SERPINE1 expression, cell proliferation, migration, and invasion. In conclusion, PTX may counteract EMT in cervical cancer cells by decreasing the NF-κB and SERPINE1.


Tools for health: the efficacy of a tailored intervention targeted for construction laborers.
Novel approaches to worksite health promotion are needed for high-risk workers who change job sites frequently, and thus may have limited access to worksite health promotion efforts. The objective of this study was to test a behavioral intervention among construction laborers. Using a randomized-controlled design, we tested the efficacy of a tailored telephone-delivered and mailed intervention to promote smoking cessation and increased fruit and vegetable consumption (n = 582). At baseline, 40% of control group participants and 45% of intervention group participants reported using any tobacco in the last seven days. At final, 8% of baseline cigarette smokers in the control group had quit, compared to 19% in the intervention group (p = 0.03). In both groups, the mean consumption of fruits and vegetables at baseline was over five servings per day. At final, the intervention group had increased consumption by approximately one and one-half servings, compared to a slight decrease in consumption in the control group (p < 0.001). A tailored intervention can be efficacious in promoting tobacco use cessation and increased fruit and vegetable consumption among construction laborers, a high-risk, mobile workforce.


Effects of Combat Deployment on Anthropometrics and Physiological Status of U.S. Army Special Operations Forces Soldiers.
U.S. Army Special Operations Forces (SOF) soldiers deploy frequently and conduct military operations through special warfare and surgical strike capabilities. Tasks required to execute these capabilities may induce physical and mental stress and have the potential to degrade soldier physiological status. No investigations have longitudinally characterized whether combat deployment alters anthropometrics or biochemical markers of physiological status in a SOF population of frequent deployers. Effects of modern combat deployment on longitudinal changes in anthropometrics and physiological status of elite U.S. Army SOF soldiers (n = 50) were assessed. Changes in measures of body composition, grip strength, physiological status, and health behaviors from baseline to postdeployment were determined with paired t test and McNemar's statistic. Baseline measures were obtained between 4 and 8 weeks before deployment. Deployment length was a uniform duration of time between 3 and 6 months (all soldiers completed the same length of deployment). Post hoc analyses determined change in body mass within quartiles of baseline body mass with paired t test and associations between change in sex hormone-binding globulin (SHBG) and change in body mass with correlation coefficient. The study was approved by the Human Use Review Committee at the U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts. In response to deployment, increases in lean mass (77.1 ± 7.6 to 77.8 ± 7.5 kg), maximum grip strength (57.9 ± 7.2 to 61.6 ± 8.8 kg), and conduct of aerobic (156 ± 106 to 250 ± 182 minutes/week) and strength training (190 ± 101 to 336 ± 251 minutes/week) exercise were observed (p < 0.05). Increases in serum SHBG (35.42 ± 10.68 to 38.77 ± 12.26 nmol/L) and decreases in serum cortisol (443.2 ± 79.3 to 381.9 ± 111.6 nmol/L) were also observed (p < 0.05). Body mass changes were dependent on baseline body mass. Soldiers in the lowest quartile of baseline body mass increased body mass (75.6 ± 2.6 vs. 76.6 ± 2.8 kg, p = 0.03), as did those in the second quartile (81.6 ± 2.0 vs. 83.7 ± 3.5 kg, p = 0.02). Those in the third quartile also tended to increase body mass (89.2 ± 2.6 vs. 90.9 ± 3.3 kg, p = 0.05), while those in the upper quartile tended to decrease body mass (98.5 ± 3.6 vs. 96.7 kg, p = 0.06). Change in SHBG was inversely correlated with change in body mass (r = -0.33, p = 0.02). There were no changes in fat mass, body fat percentage, waist circumference, neck circumference, total testosterone, calculated bioavailable or free testosterone, high-sensitivity C-reactive protein, tumor necrosis factor-α, interleukin-1β, or interleukin-6. Inflammatory markers were skewed toward lower values. Overall, physiological status of elite SOF soldiers characterized by multiple prior deployments was minimally impacted by combat deployment, in the absence of major unit casualties. The majority experienced some adaptive changes, including increased lean mass, grip strength, time spent engaged in exercise, and decreased levels of the stress hormone cortisol. Mechanisms contributing to inverse correlations between change in SHBG and change in body mass may be further clarified. Future investigations may also more fully characterize the degradation and optimization of health and physiological status of SOF training and deployment cycles with in-theater data collection and repeated measures.


Leukocytoclastic vasculitis and gastric adenocarcinoma.
Cutaneous vasculitis has been mainly associated with hematologic cancer. The association of solid neoplasms with cutaneous paraneoplastic vasculitis is rare. We report a case of cutaneous leucocytoclastic vasculitis that revealed a gastric adenocarcinoma. A 72-year-old man presented with an acute diffuse polymorphic eruption, with erythematous, vesicular, and necrotic lesions predominating on the lower limbs, which had developed within the past 8 days. The medical history revealed abdominal pain and weight loss over the previous 6 months. A skin biopsy noted typical leucocytoclastic vasculitis. A workup including GI tract investigations revealed an antral adenocarcinoma. Complete excision of the gastric tumor was followed by resolution of the skin lesions. No tumor recurrence or cutaneous vasculitis was noted during 2 years of follow-up. To our knowledge, the association of leucocytoclastic vasculitis with gastric cancer has never been reported previously. The failure of vasculitis to respond to conventional therapy should suggest an underlying malignancy.


Renal Lymphangiectasia in a Pediatric Patient.
Renal lymphatic abnormalities are rare, and the understanding of pathophysiology involving renal lymphatics is limited. Symptoms can include hypertension, hematuria, proteinuria, chyluria, and abdominal and lumbar pain. Imaging techniques specific to the renal lymphatics have not been clarified. We review the intrahospital imaging evaluation/workup and clinical course of a 6-year-old male who presented to our institution with a large perirenal cyst. His presentation presented a diagnostic and management challenge. The cyst was determined to be lymphatic in origin and required multiple interventional radiology and surgical procedures for management.


Purification and characterization of S-adenosyl-L-methionine: norcoclaurine 6-O-methyltransferase from cultured Coptis japonica cells.
S-adenosyl-L-methionine:norcoclaurine 6-O-methyltransferase (norcoclaurine 6-O-methyltransferase), which catalyzes the transfer of the S-methyl group of S-adenosyl-L-methionine to the 6-hydroxyl group of 1,2,3,4-tetrahydro-1-[(4-hydroxyphenyl)methyl]-6,7- isoquinolinediol (norcoclaurine), was purified from cultured Coptis japonica cells and its enzymic properties were characterized. Purified norcoclaurine 6-O-methyltransferase had apparent pI 4.7, a native molecular mass of 95 kDa (determined by gel filtration) and subunit molecular mass of 40 kDa (SDS/PAGE). The enzyme did not require a divalent cation for activity, and the addition of Fe2+, Cu2+, Co2+, Zn2+, Mn2+, or Ni2+ at 5 mM severely inhibited enzyme activity. Neither p-chloromercuribenzoate, N-methylmaleimide nor iodoacetamide inhibited enzyme activity at 1 mM. 5,6-Dihydro-9,10-dimethoxybenzo[g]-1,3-benzodioxolo[5,6-a]qu inolizinium (berberine, the end-product of the biosynthetic pathway in which norcoclurine 6-O-methyltransferase catalyzes an intermediate step) also inhibited the activity by 50% at 10 mM. Norcoclaurine 6-O-methyltransferase methylated both (S)-norcoclaurine and (R)-norcoclaurine and (R,S)-norlaudanosoline. Further characterization of substrate-saturation kinetics and product inhibition of the purified enzyme indicated that norcoclaurine 6-O-methyltransferase follows a bi-bi ping-pong mechanism with Km values of 2.23 mM and 3.95 mM for (R,S)-norlaudanosoline and S-adenosyl-L-methionine, respectively, while Ki values for S-adenosylhomocysteine versus S-adenosyl-L-methionine and (R,S)-norlaudanosoline were 2.1 mM and 0.18 mM, respectively.


The acceptability of evidence-informed guidance for parents in talking to their children about weight.
Many parents express concern about the impact of talking to children about weight on their self-esteem and wellbeing. The aim of this study was to explore the perceived relevance, utility and acceptability of new guidance for parents on talking to children about weight, developed to apply theory, evidence and expert advice into practice. For this qualitative study, parents and public health practitioners (PHPs) were recruited from ten local authorities in England, through the National Child Measurement Programme between June and September 2021. Participants were sent a copy of the guidance document and took part in an interview approximately one week later. Interviews were transcribed verbatim and explored using thematic analysis. 12 parents and 15 PHPs took part, and were similar in their responses reporting the guidance to be acceptable, relevant and helpful. Theme 1 explored how the guidance reduced perceptions of stigma and blame through the perspective and tone that was adopted. Theme 2 explored how the guidance could provide reassurance and increase confidence as a result of case study examples, and specific tips and advice. Theme 3 explored the extent to which participants perceived the advice to be realistic and how it could fit with existing PHP practice. Suggestions for improvement included adapting for relevance for lower income families and providing separate advice for parents of older and younger children. The guidance was perceived as relevant and needed; it showed potential to reduce parents' negative affect and concerns, and improve confidence around talking to children about weight.


Effect of acetylcholinesterase inhibitors on AChE-induced PrP106-126 aggregation.
Transmissible spongiform encephalopaties are caused by an extracellular surface protein, the scrapie prion protein (PrPsc), which is an aberrant form of normal and functional cellular PrP (PrPc). The pathological hallmarks of these diseases are the accumulation and deposition of PrPsc in the form of amyloid fibrils in the central nervous system (Tateishi et al., 1988), similar to amyloid-beta (Abeta) protein in Alzheimer's disease (AD). In some patients, Abeta and prion pathology can coexist (Hainfellner et al., 1998), and a common spatial pattern of protein deposition has been described (Armstrong et al., 2001). In addition, it is well-known that acetylcholinesterase (AChE) colocalizes with Abeta deposits of brains in AD patients and accelerates assembly of Abeta peptides through the peripheral site of the enzyme (Inestrosa et al., 1996). The aim of the present study was to analyze time course and concentration dependence of the AChE proaggregating effect on synthetic peptide-spanning residues 106-126 of human PrP (PrP106-126) and the reversion of this effect by different AChE inhibitors (AChEIs).


Plasma sodium: ignored and underestimated.
Salt intake is a major regulator of blood pressure. There is evidence that those who develop high blood pressure have an underlying defect in the ability of the kidney to excrete salt. It has been suggested that this results in a greater tendency to retain sodium and an increased compensatory response that is responsible for the rise in blood pressure. There is also evidence suggesting that small increases in plasma sodium may directly affect blood pressure, independent of the associated expansion in extracellular volume. We reanalyzed 3 types of studies of changing salt intake. (1) An acute and large reduction in salt intake from 350 mmol/d to 10 to 20 mmol/d for 5 days in hypertensives and normotensives was associated with a fall in plasma sodium of approximately 3 mmol/L (P<0.001). (2) Progressive increases in salt intake from 10 to 250 mmol/d by a daily amount of 50 mmol in normotensives caused increases in plasma sodium (P<0.001). (3) Longer-term modest reduction in salt intake in hypertensives was studied in double-blind randomized crossover studies; 1 month of usual salt intake ( approximately 170 mmol/d) compared with reduced salt intake ( approximately 100 mmol/d). There was a decrease in plasma sodium of 0.4+/-0.2 mmol/L (P<0.05), which was weakly but significantly correlated with the fall in systolic blood pressure (r=0.18; P<0.05). These studies demonstrate that an increase or a decrease in salt intake causes changes in plasma sodium. Small changes in plasma sodium alter extracellular volume, which may influence blood pressure. Changes in plasma sodium may also affect blood pressure directly.


Sequential response of milk leukocytes, albumin, immunoglobulins, monovalent ions, citrate, and lactose in cows given infusions of Escherichia coli endotoxin into the mammary gland.
Changes in concentrations of both the cellular and the humoral components of milk are known to occur during mastitis. This study was conducted to determine temporal changes in the concentrations of leukocytes, albumin, immunoglobulins (Ig), monovalent ions, lactose, and citrate in milk during the initial phases of simulated mastitis. Ten cows whose udders were pathogen free and had milk leukocyte counts of less than 0.5 X 10(6)/ml were used. Two dosages of Escherichia coli endotoxin were administered to simulate various degrees of mastitis. Two quarters in each cow were infused with the endotoxin and the other 2 served as controls. Quarter milk samples were collected frequently before and after infusion. Within 2 hours after infusion of a 100-micrograms dose of endotoxin, clinical mastitis was observed in most of the infused quarters. Leukocytes, albumin, IgG1, and conductivity showed significant increases. Values before infusion and at postinfusion (PI) hour 2 were as follows: leukocytes, 0.33 and 3.65 X 10(6)/ml, respectively; albumin, 0.38 and 4.49 mg/ml; IgG1, 0.34 and 0.79 mg/ml; and conductivity, 6.0 and 6.9 mmho. Average of the peak values and their average relative time of appearance after infusion were as follows: leukocytes, 28.82 X 10(6)/ml at 16 hours; albumin, 9.37 mg/ml at 4 hours; IgG1, 1.35 mg/ml at 4 hours; and conductivity, 95.5 mmho at 10 hours. The IgG1 values tended to remain high in the presence of rapidly declining albumin concentrations, indicating the possibility of an active, rather than a passive, transfer of IgG1 from the circulation. The response to the 10-micrograms dose of endotoxin ranged from subclinical to clinically mild mastitis with lesser cellular and humoral responses.


Ground- and excited-state electronic structure of an iron-containing molecular spin photoswitch.
The electronic structure of the cation of [Fe(ptz)(6)](BF(4))(2), a prototype of a class of complexes that display light-induced excited-state spin trapping (LIESST), has been investigated by time-independent and time-dependent density-functional theories. The density of states of the singlet ground state reveals that the highest occupied orbitals are metal centered and give rise to a low spin configuration Fe(2+)(3d(xy) ( upward arrow downward arrow)3d(xz) ( upward arrow downward arrow)3d(yz) ( upward arrow downward arrow)) in agreement with experiment. Upon excitation with light in the 2.3-3.3 eV range, metal-centered spin-allowed but parity-forbidden ligand field (LF) antibonding states are populated which, in conjunction with electron-phonon coupling, explain the experimental absorption intensities. The computed excitation energies are in excellent agreement with experiment. Contrary to simpler models we show that the LF absorption bands, which are important for LIESST, do not originate in transitions from the ground to a single excited state but from transitions to manifolds of nearly degenerate excited singlets. Consistent with crystallography, population of the LF states promotes a drastic dilation of the ligand cage surrounding the iron.


Endoscopic anatomy of the skull base explored through the nose.
Different surgical approaches have been used over the years in order to access skull base. The endoscopic endonasal approach represents a direct and minimally invasive approach to the suprasellar, retrosellar, and retroclival space, with the advantage of avoid brain retraction and visualize safely and effectively the surgical target. The present contribution aims to provide anatomical details of the skull base as seen from below (i.e., via an endoscopic endonasal approach). Five human cadaver heads were dissected. The anatomical neurovascular structures within the skull base were visualized and carefully described from an endoscopic endonasal view. The advantages and limitations of the endoscopic endonasal route were discussed as well. The entire skull base region, as seen from the endoscopic endonasal viewpoint, has been divided in 4 main regions: anterior skull base, middle skull base, posterior skull base and parasellar area. The development of endoscopic techniques has opened different perspectives over the skull base surgery. Endonasal surgery provides access to a wide range of skull base lesions via a natural surgical corridor (i.e., the nasal cavities).


Synthesis and properties study of the uniform nonspherical styrene/methacrylic acid copolymer latex particles.
A facile method to prepare the nonspherical amphiphilic random copolymer of poly(styrene-co-methacrylic acid) (poly(St-co-PMAA)) latex particles with well-defined shapes and high yields by one-step batch emulsifier-free polymerization was demonstrated. In our strategy, only varying the molar ratio of styrene (St) to methacrylic acid (MAA), no seed-particles, no cross-linker, and no multistep control procedures were needed. Due to the presence of carboxyl groups on the surface of (poly(St-co-PMAA) latex particles, these latex particles can be used as templates for fabricating core-shell nonspherical functional materials, such as poly(St-co-PMAA)@SiO2 and poly(St-co-PMAA)@polypyrrole). The corresponding nonspherical hollow structures (SiO2 and polypyrrole) could be obtained after removal of the templates. In addition, poly(St-co-PMAA) latex particles exhibit interesting morphologies in ethanol.


Impacts of the late adulthood diet-induced obesity onset on behavior, immune function, redox state and life span of male and female mice.
The aim of the present study was to investigate whether the late onset of diet-induced obesity (DIO) in middle-aged mice affected behavioral, immunological and oxidative stress parameters as well as life span of male and female mice. Also, it was analyzed whether the late DIO onset aggravated immunosenescence in old female mice. Late-adult male and female ICR/CD1 mice (28 weeks old) were fed either a high-fat diet or a standard diet during 14 weeks. After that, in these middle-aged (42 weeks old) diet-induced obese (DIO) and non-DIO controls, behavior as well as functions and redox state of peritoneal leukocytes were evaluated. These same parameters (excepting behavioral tests) were repeated when female mice were old (72 weeks old). The results showed lower exploratory activity and higher anxiety-like behavior in middle-aged male and female DIO than in controls. Moreover, these DIO animals from both sexes exhibited statistically significant impaired immune cell functions, such as chemotaxis of macrophages and lymphocytes, phagocytosis of macrophages, natural killer activity and lymphoproliferation in response to ConA and LPS, as well as an oxidative stress state in comparison with controls. Male DIO mice exhibited higher impairments in a variety of the evaluated parameters and a shorter life span than their female counterparts. In addition, female DIO mice, at old age, showed aggravated immunosenescence. In conclusion, the late DIO onset leads to impairments in behavior as well as in immune system functions of middle-aged male and female mice, males being significantly more affected than females.


Early nasoduodenal feeding for the post-biliary surgical patient.
The effects of early postoperative nasoduodenal feeding on nutrition and metabolic response were studied using 24 patients after biliary surgery. The patients were randomly divided into two groups with 12 in each group. Group I was fed via a nasoduodenal tube from the first postoperative day but control group II was not fed until the fourth postoperative day. The hospital blenderized tube feeding diet provided the enteric nutrition (17% protein, 33% fat and 50% carbohydrate). The nutritional status of the 2 groups was compared over a one week period. The changes in nitrogen balance were measured daily for 8 days. The group fed early had a significantly reduced negative nitrogen balance when compared to the group whose feeding was started later. (-1.91 +/- 1.05 g/day vs -5.84 +/- 0.48 g/day). There was no difference in serum albumin and transferrin levels, but serum prealbumin levels in the group fed early were more desirable than those of the control group (from 15.8 +/- 2.5 mg/dl to 28.9 +/- 3.8 mg/dl vs from 18.0 +/- 2.0 mg/dl to 25.9 +/- 3.9 mg/dl). Total lymphocyte count was also better in the group fed early than in the controls (from 1,325 +/- 204 cells/mm3 to 2,655 +/- 584 cells/mm3 vs from 1,277 +/- 188 cells/mm3 to 1,877 +/- 440 cells/mm3). All the patients in group I felt better than those in group II during the study course. These results indicated that those patients provided with early nasoduodenal feeding after a biliary operation displayed a better nitrogen balance, and a faster increase in short half life visceral protein and total lymphocyte count.


Effect of fish and olive oil on mitochondrial ATPase activity and membrane fluidity in patients with relapsing-remitting multiple sclerosis treated with interferon beta 1-b.
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system associated with increased oxidative stress (OS) and mitochondrial alterations. Fish oil consumption has neuroprotective, antioxidant and anti-inflammatory effects in patients with relapsing-recurrent MS (RR-MS). To evaluate changes in the hydrolytic activity of ATP synthase and mitochondrial membrane fluidity in patients with RR-MS who receive fish oil or olive oil as a dietary supplement. Clinical, controlled, randomized, double-blind trial. Patients consumed fish oil or olive oil for one year. The hydrolytic activity of ATPase and the fluidity of the mitochondrial membrane of platelets were quantified. In patients with RR-MS, a decrease in the fluidity of mitochondrial membranes and an increase in the hydrolytic activity of ATP synthase was observed in comparison with healthy controls. After 6 or 9 months of treatment with fish oil or olive oil, respectively, these values were normalized. The consumption of fish oil and olive oil increases the fluidity of the mitochondrial membranes and decreases the catabolic activity of ATP synthase in platelets from patients with RR-MS.


Endothelial progenitor cells and abdominal aortic aneurysms.
Endothelial progenitor cells (EPCs) are a population of circulating stem cells that hone in to sites of vascular injury where they undergo differentiation to become incorporated into damaged tissue. The aim of this study was to enumerate EPCs in patients with abdominal aortic aneurysms (AAA). CD133(+) peripheral blood mononuclear cells were immunomagnetically selected and CD34/CD133 was used as a marker of EPCs. EPCs were detected using flow cytometry. AAA patients had significantly higher levels of circulating EPCs than age-matched controls (2.43% vs. 1.25% of all events, P = 0.008). The role and function of EPCs in AAA remain to be determined, but their implication with angiogenesis may represent one plausible mechanism.


Use of the brief psychiatric rating scale by nurses.
1. Nurses are intimately involved in the assessment of patients in inpatient clinical settings and in community settings--and nurses have a role to play in the systematic rating of severe psychopathology. 2. The Brief Psychiatric Rating Scale (BPRS) provides a means of assessing mental health status from an interview using 16 rating concepts. Analysis of BPRS rating profiles obtained from a variety of patients and settings have consistently revealed four syndromes: withdrawal-retardation, anxious depression, hostile-suspiciousness, and thinking disturbance. 3. Once properly trained regarding the BPRS, nurses can use the scale effectively in the assessment and ongoing monitoring of patient conditions. The scale is an added tool for nurses to use in monitoring the effectiveness and outcome of both medical and nursing interventions.


Supratentorial arachnoid cyst mimicking a Ménière's disease attack.
Arachnoid cysts (AC) often present with symptoms depending on their anatomical location within the skull; while supratentorial cysts grow causing relatively few symptoms, infratentorial ones may impair liquor circulation at the level of the fourth ventricle, giving rise to intracranial hypertension, or may stretch the complex nerve network in the cerebello-pontine angle. We report the singular clinical history of a 54-year-old male, who suddenly began to feel dizzy while sitting at his workplace, complaining of left tinnitus and aural fullness, in a classic clinical picture of Ménière's disease. The anomalous findings at otoneurological examination (markedly the left deviation at the Fukuda test) made a magnetic resonance image (MRI) scan mandatory and a huge AC was found in the left fronto-parietal lobe. The mass provoked an evident clockwise rotation of the brainstem that we suppose to be the cause of acoustico-facial bundle stretching explaining the vestibular symptomatology.


Production of L-lactic acid from a mixture of xylose and glucose by co-cultivation of lactic acid bacteria.
The production of optically pure lactic acid in a high yield from xylose or a mixture of xylose and glucose, which is a model hydrolysate of lignocellulose, is described. In a single cultivation, Enterococcus casseliflavus produced 38 g/l of lactic acid with an optical purity of 96% enantiomeric excess (ee) and 6.4 g/l of acetic acid from 50 g/l of xylose when MRS medium was used. When a mixture of 50 g/l of xylose and 100 g/l of glucose was used as the carbon source in a cultivation of E. casseliflavus alone, glucose was converted to lactic acid in the early phase of the cultivation but xylose was hardly consumed. In a co-cultivation where E. casseliflavus and Lactobacillus casei specific for glucose were simultaneously inoculated, little or no lactic acid was produced after the glucose was almost consumed. A co-cultivation with two-stage inoculation (in which E. casseliflavus was added at a cultivation time of 40 h after L. casei cells were inoculated) resulted in complete consumption of 50 g/l of xylose and 100 g/l of glucose. In the co-cultivation, 95 g/l of lactic acid with a high optical purity of 96% ee was obtained at 192 h. Such a co-cultivation using two microorganisms specific for each sugar is considered to be one promising cultivation technique for the efficient production of lactic acid from a sugar mixture derived from lignocellulose.


Engineered Bacteria for Short-Chain-Fatty-Acid-Repressed Expression of Biotherapeutic Molecules.
Short-chain fatty acids (SCFA) such as propionate and butyrate are critical metabolites produced by the gut microbiota. Microbiome dysbiosis resulting in altered SCFA profiles is associated with certain diseases, including inflammatory bowel diseases (IBD), characterized by a reduction in butyrate concentration and active intestinal inflammation. There is an increasing interest in the use of engineered bacteria as diagnostic and therapeutic tools for gut diseases. In this study, we developed genetic circuits capable of sensing SCFA concentrations to build biosensors that express a response protein (superfolder green fluorescent protein [sfGFP]) in amounts inversely proportional to the SCFA concentration. We also built biotherapeutics expressing the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) using the same logic. The propionate biotherapeutic expressed larger amounts of mouse GM-CSF in the absence of propionate. The butyrate biotherapeutics presented the expected behavior only at the beginning of the kinetics and an accelerated response in the absence of butyrate. Overall, these genetic systems may function as complementary diagnostic tools for measuring SCFAs and as delivery vehicles for biotherapeutic molecules. IMPORTANCE Short-chain fatty acids are key molecules produced by the gut microbiome. Their concentrations are altered in certain diseases. Here, we created molecular biosensors that quantify the absence of propionate and butyrate, using logic "NOT" gates and bacterial promoters. Finally, we show that these genetic systems could be useful for the delivery of therapeutic molecules in the gut, in the absence of these acids.


Rumen fermentation in vitro as influenced by long chain fatty acids.
Responses of rumen microbes to fatty acids were evaluated by production of total volatile fatty acid and ratio of acetate to propionate. Fermentations were under carbon dioxide for 20 h in 50-ml Erlenmeyer flasks in a Dubnoff metabolic shaking incubator. Flasks contained 20 ml medium, 1 ml reducing solution, 750 mg substrate (450 mg hay plus 300 mg grain), and varying amounts of long-chain fatty acids supplied as free acids, as calcium salts, or as triglycerides. They were inoculated with 5 ml rumen fluid obtained from a cow fed 3.6 kg grass hay, 2.3 kg grain, and .2 kg tallow daily. Volatile fatty acid production was decreased by long-chain fatty acids that contained less than 18 carbon atoms and by unsaturated long-chain fatty acids with 18 carbon atoms. Lauric acid decreased volatile fatty acid production by 69% and induced unusual acetate/propionate ratio (40:1). Stearic acid, however, did not affect volatile fatty acid production or acetate/propionate ratio. Within two series of long chain fatty acids (myristic, palmitic, stearic, arachidic; stearic, oleic, linolenic), melting point accounted for 93 to 95% of the variation of volatile fatty acid production and acetate/propionate. As calcium salts, long chain fatty acids caused small changes of fermentation. Our data support the proposition that hard fats and calcium salts of long-chain fatty acids do not interfere with ruminal fermentation.


Multiple organ dysfunction syndrome in hematopoietic stem cell transplantation.
To review the data demonstrating that central nervous system, pulmonary, and hepatic dysfunctions during hematopoietic stem cell transplantation have similar laboratory correlates and clinical outcomes, suggesting that they are individual organ manifestations of a systemic disorder at presentation, a disorder similar to the multiple organ dysfunction syndrome seen in other populations of critically ill patients. Reports of clinical research studies on the natural history and laboratory correlates of central nervous system, pulmonary, and hepatic dysfunction (generally manifesting as the syndrome of hepatic veno-occlusive disease) during hematopoietic stem cell transplantation. During hematopoietic stem cell transplantation, pulmonary dysfunction (manifesting as hypoxia), central nervous system dysfunction (detected by alteration of the Mini-Mental Status Exam), and hepatic dysfunction (presenting as the syndrome of hepatic veno-occlusive disease) are all associated with significant decreases in the levels of antithrombin III and protein C and an increase in the platelet transfusion requirement. Each of these three organ dysfunctions is associated with a high likelihood of being followed by the other two and, eventually, death. Patients with these organ dysfunctions have higher levels of interleukin-6, interleukin-10, and tumor necrosis factor-alpha than patients who never develop these complications. Mortality rates for patients with these organ dysfunctions vary from 15% in patients with only one organ dysfunction to 100% in patients who have progressed to all three. Patients who develop none of these organ dysfunctions have a mortality rate that approaches zero. Central nervous system, pulmonary, and hepatic dysfunctions are intimately involved in the mortal complications of hematopoietic stem cell transplantation. Because these organ dysfunctions have similar correlates and similar outcomes, the hypothesis that they are individual parts of a systemic disorder is proposed. The additional observation that these organ dysfunctions are associated with abnormally high levels of inflammation-related cytokines raises the possibility that their pathogenesis is similar to that of multiple organ dysfunction syndrome in other populations of critically ill patients.


Vinylogous Mukaiyama-Michael Reactions of Dihydropyridinones.
An In(III)-catalyzed vinylogous addition of O-silyl vinylketene acetals to 2,3-dihydro-4-pyridinones has been developed. The method features the unprecedented employment of supersilyl groups to influence the γ versus α regiochemical control of vinylogous Mukaiyama-Michael (vM-Michael) reactions when γ-substituted O-silyl vinylketene acetals are used. We also demonstrate that these reactions allow facile access to quinolizidine-based alkaloids such as deoxynupharidine and well as lasubine I and II.


Mo Single-Atom Nanozyme Anchored to the 2D N-Doped Carbon Film: Catalytic Mechanism, Visual Monitoring of Choline, and Evaluation of Intracellular ROS Generation.
Single-atom nanozymes (SANs) have attracted great attention in constructing devices for instant biosensing due to their excellent stability and atom utilization. Here, Mo atoms were immobilized in 2D nitrogen-doped carbon films by cascade-anchored one-pot pyrolysis to obtain Mo single-atom nanozyme (Mo-SAN) with high atomic loading (4.79 wt %) and peroxidase-like activity. The coordination environment and enzyme-like activity mechanism of Mo-SAN were studied by combining synchrotron radiation and density functional theory. The strong oxophilicity of single-atom Mo makes the catalytic center more capable of transferring electrons to free radicals to selectively generate •OH in the presence of H2O2. Choline oxidase and Mo-SAN were used as signal opening unit and signal amplification unit, respectively. Combining the portability and visualization functions of smartphone and test strips, a paper-based visual sensing platform was constructed, which can accurately identify choline at a concentration of 0.5-35 μM with a limit of detection as low as 0.12 μM. The recovery of human serum samples was 96.4-102.2%, with an error of less than 5%. Furthermore, the potential of Mo-SAN to efficiently generate toxic •OH in tumor cells was intuitively confirmed. This work provides a technical and theoretical basis for designing highly active SANs and detecting neurological markers.


Air-processed MAPbI3 perovskite solar cells achieve 20.87% efficiency and excellent bending resistance enabled via a polymer dual-passivation strategy.
In recent years, air-processed MAPbI3 perovskite solar cells (PSCs) have attracted widespread interest from researchers worldwide because of their simple and low-cost fabrication process. Nonetheless, the ambient conditions usually bring about many adverse effects, such as imperfect crystallization and numerous defects in perovskite films, which seriously impact both the photoelectric performance and stability of the device. Therefore, in this work, a polymer dual-passivation strategy was employed by introducing ammonium polyphosphate (APP) as an additive to the green anti-solvent to accurately modify the perovskite layer. APP, which has abundant phosphate and ammonium groups, could simultaneously fill the I/Pb vacancies by Lewis acid-base reactions to restrain defect formation and improve the power conversion efficiency (PCE) of the ultimate device. On the other hand, the long molecular chains of the polymer with a certain flexural ability were easily congregated at the grain boundaries of the perovskite grains, thus enhancing the bending resistance. Consequently, high-quality perovskite films with a dense morphology and large grain size were obtained. Because of the reduced defect density and suppressed non-radiative recombination, the optimal PSC attained a champion PCE of 20.87% with negligible hysteresis. Furthermore, the non-encapsulated APP-modified flexible device also exhibited excellent bending resistance. Only 20% of its normalized PCE was lost after 150 bending cycles at room temperature. This simple, green, low-cost, and reliable strategy for preparing high-efficiency PSCs with good stability can facilitate its commercialization.


Localization of individual area neuronal activity.
A family of methods, collectively known as independent component analysis (ICA), has recently been added to the array of methods designed to decompose a multi-channel signal into components. ICA methods have been applied to raw magnetoencephalography (MEG) and electroencephalography (EEG) signals to remove artifacts, especially when sources such as power line or cardiac activity generate strong components that dominate the signal. More recently, successful ICA extraction of stimulus-evoked responses has been reported from single-trial raw MEG and EEG signals. The extraction of weak components has often been erratic, depending on which ICA method is employed and even on what parameters are used. In this work, we show that if the emphasis is placed on individual "independent components," as is usually the case with standard ICA applications, differences in the results obtained for different components are exaggerated. We propose instead the reconstruction of regional brain activations by combining tomographic estimates of individual independent components that have been selected by appropriate spatial and temporal criteria. Such localization of individual area neuronal activity (LIANA) allows reliable semi-automatic extraction of single-trial regional activations from raw MEG data. We demonstrate the new method with three different ICA algorithms applied to both computer-generated signals and real data. We show that LIANA provides almost identical results with each ICA method despite the fact that each method yields different individual components.


Using a Gratitude Intervention to Improve the Lives of Women With Breast Cancer: A Daily Diary Study.
Gratitude can be understood in two ways: as a state of being grateful for things and people, and as a disposition. Research suggests that focusing on reasons for being grateful promotes various aspects of well-being. The present study examined the effectiveness of a gratitude intervention for women with breast cancer. Each day for 2 weeks, 42 women with breast cancer described their psychological well-being, social support, and coping strategies. Women in the intervention condition reported the reasons why they felt grateful that day. Moreover, all participants took part in a pre-test session where trait measures were taken to control for dispositional differences. Listing the reasons for gratitude led to higher levels of daily psychological functioning, greater perceived support, and greater use of adaptive coping strategies. These results suggest that gratitude interventions may improve the lives of oncological patients.


Management of Chemoradiation-Induced Mucositis in Head and Neck Cancers With Oral Glutamine.
Head and neck cancers are the third most common cancers worldwide. Oral mucositis is the most common toxicity seen in patients who receive chemoradiation to treat head and neck cancer. The aim of this study was to evaluate the efficacy and safety of oral glutamine supplementation in these patients. From December 2013 to December 2014, we randomly assigned to two arms 162 patients who had squamous cell carcinoma of the head and neck. Patients in arm A were given oral glutamine once per day, whereas those in arm B served as negative control subjects. All patients received radiotherapy given as 70 Gy in 35 fractions over 7 weeks with an injection of cisplatin once per week. Patients were assessed once per week to evaluate for the onset and severity of mucositis, pain, use of analgesics, and for Ryle tube feeding. We observed that 53.1% of patients developed mucositis toward the fifth week in the glutamine arm compared with 55.5% of patients in the control arm at the third week. None in the glutamine arm compared with 92.35% of patients in the control arm developed G3 mucositis. Rates of adverse events like pain, dysphagia, nausea, edema, and cough, as well as use of analgesics and Ryle tube feeding, were significantly lower in the glutamine arm than in the control arm. This study highlights that the onset as well as the severity of mucositis in patients receiving glutamine was significantly delayed. None of the patients receiving glutamine developed G3 mucositis. Hence, the findings emphasize the use of oral glutamine supplementation as a feasible and affordable treatment option for mucositis in patients with head and neck cancers who are receiving chemoradiation.


[Role of extracellular-signal regulated kinase cascade on cerebral ischemia and ischemic preconditioning in hippocampal neuron in gerbils].
To investigate the role of extracellular-signal regulated kinase (ERK) cascade on cerebral ischemia and ischemic preconditioning in hippocampal neuron. Male gerbils were randomly divided into sham group (SH), ischemia/reperfusion group (I/ R), ischemia preconditioning group (IP), specific antagonist of ERK-PD98059 (PD), solvent control groups (VE group), PD98059 combined with IP group (PIP). Forebrain ischemia was induced by occlusion of bilateral common carotid arteries and confirmed by isoelectricity of EEG. Observations were carried out in each group 15 min, 2 h, 4 h, 6 h, 1 d, 3 d, 5 d and 7 d after ischemia. Open field test was used to examine the spontaneous motor activity, the survival and apoptotic neurons, Fos and NF-kappaB masculine neurons in hippocampal CA1 region were counted, the expression of HSP70 in hippocampal CA1 region and p-ERK in hippocampal CA3/DG regions were detected by SABC immunocytochemical technique. The spontaneous motor activity, the number of apoptotic neurons and NF-kappaB masculine neurons at 1 d, 3 d, 5 d, 7 d in CA1 region were much less in IP group than in I/R group (P < 0.01). The number of Fos masculine neurons at 15 min, 2 h, 4 h, 6 h, 1 d in CA1 region were significant more in IP group than in I/R group (P < 0.01). The expressions of p-ERK and HSP70 were significantly higher in IP group than in I/R group. The number of Fos masculine neurons at each point were more and apoptotic neurons at 1 d, 3 d were less in PD group than in I/R group. Results of observation in PIP group were within IP group and I/R group. Activation of ERK in CA3/DG regions were related to ischemic tolerance. Induction of the expression of Fos and HSP70, decreasing of the product of NF-kB which might be one of the molecule mechanisms playing an important role in neural protection of ischemic preconditioning.


Biochemical and molecular effects of UCN-01 in combination with 5-fluorodeoxyuridine in A431 human epidermoid cancer cells.
Concurrent and pre-exposure of A431 human epidermoid cancer cells to UCN-01, an investigational anticancer drug, with 5-fluoro--2'-deoxyuridine (FdUrd), which targets thymidylate synthase, produced more than additive cytotoxicty. A 24-h exposure to 10 nM FdUrd led to inhibition of TS, a 2.5-fold increase in total thymidylate synthase protein content, profound dTTP depletion and a 6.3-fold increase in the ratio of dATP to dTTP, but did not cause single-strand breaks in DNA. However, FdUrd enhanced UCN-01-associated DNA strand breaks. Concurrent thymidine exposure led to repletion of dTTP pools, and cytoprotection against FdUrd alone and with UCN-01. UCN-01 arrested cells in G1, decreased the percentage of FdUrd-treated cells in S phase and reduced FdUrd-DNA incorporation, suggesting the latter was not important for cytotoxicity. Delayed induction of high molecular mass DNA fragmentation and poly(ADP-ribose) polymerase cleavage was observed with the combination of UCN-01 and FdUrd. These findings suggest that while FdUrd-mediated deoxynucleotide imbalance alone was insufficient to induce apoptosis in this p53-mutant cell line, it magnified UCN-01's effects, most likely by interfering with DNA repair. The clinical evaluation of UCN-01 combined with 5-fluoropyrimidines may be of interest.


Regional deprivation is associated with the distribution of vulnerable asylum seekers: a nationwide small area analysis in Germany.
Newly arriving asylum seekers in many European Union countries are assigned a place of residence based on administrative quota. This may have important consequences for the exposure to contextual health risks. We assessed the association between regional deprivation and the distribution of asylum seekers in Germany considered as vulnerable (women, children <7 years, persons >64 years) because of their increased health needs. Using nationally representative data, we analysed the rates of observed to expected numbers of asylum seekers and vulnerable subgroups in Bayesian spatial models. Regional deprivation was measured by the German Index of Multiple Deprivation. The analyses were performed at the district level (N=402) and adjusted for district population size, effects of federal states as well as spatial effects. Of the 224 993 asylum seekers, 38.7% were women, 13.8% children aged <7 years and 19.8% aged >64 years. The adjusted number of asylum seekers (totals and vulnerable subgroups) was higher in more deprived districts (Q3, Q4 and Q5) relative to districts in the lowest deprivation quintile (Q1). The adjusted rate ratios for districts with highest relative to those with lowest deprivation were 1.26 (1.03-1.53) for women, 1.28 (1.04-1.58) for children aged <7 years and 1.50 (1.08-2.08) for older asylum seekers. The adjusted number of vulnerable asylum seekers was higher in districts with medium and highest deprivation compared with districts with lowest deprivation. The disproportionate distribution was highest for older asylum seekers and children <7 years. Vulnerable subgroups tend to be exposed to more deprived places of residence, which may further increase health risks and healthcare needs.


[Primary lymphomas of the digestive tract. Therapeutic results of a series of 35 cases].
We report the results of a diagnosis and treatment scheme used in 35 patients with primary gastrointestinal lymphoma studied between 1972 and 1982. There were 17 lymphomas of the stomach, 13 of the small bowel, 6 of the colon and/or the rectum. According to the Kiel classification and/or the International Working Formulation, 10 were "good risk" lymphomas, 25 were "bad risk" lymphomas. According to the Musshoff modified Ann Arbor staging classification, 16 were localized lymphomas (stage IE and II1E), 19 were disseminated lymphomas (stages II2E, IIIE or IV). The treatment scheme included laparotomy for staging and resection, total abdominal irradiation (until 1977), and polychemotherapy with or without adriamycin depending on histologic grade. The median survival was greater than the median follow-up with a survival plateau at 0.53 after 47 months. Amongst the prognostic factors studied, the digestive initial localization had no prognostic significance; on the other hand, survival depended on abdominal extension, histologic grade according to the classifications used for lymph-nodes lymphomas, and resection possibilities, and especially on achievement of complete remission. These good results emphasize the importance of combining surgical resection with chemotherapy and early assessment of the treatment in order to rapidly obtain complete remission, the way of achieving prolonged survival.


Searching for a Lifeline: Transcriptome Profiling Studies of Influenza Susceptibility and Resistance.
Excess or dysregulated host inflammatory responses cause much of the morbidity and mortality caused by severe influenza. Given the limitations of vaccines and antiviral drugs, novel therapeutics to modulate host responses and improve outcomes in severe influenza are needed. One strategy is to learn from the direct comparison of high-survivor versus high-mortality animal models. This review surveys the results of lung transcriptome profiling studies in murine models that directly compare susceptible versus resistant hosts challenged with identical influenza infections. The potential contributions and limitations of these studies are discussed. To amplify their power, the studies are subjected to a meta-analysis, which helps identify frequently dysregulated pathways and potentially novel areas for investigation. Using connectivity map-based tools (LINCS), transcriptome signatures linked to susceptibility can identify candidate drugs that merit testing for in vivo efficacy.


Basic Concepts in Metastatic Cardiac Disease.
The involvement of the heart in metastatic cancer is a rare clinical diagnosis, as it may be asymptomatic or symptoms, when present, may be attributed to other causes. Issues regarding incidence, intracardiac location, clinical presentation, diagnosis and treatment of metastatic cardiac tumors will be discussed here.


Using an alternative fixing device for nasogastric tubes.
Nasogastric tubes are increasingly used in both the hospital and community setting, especially with patients who have had a stroke. Fixing tubes in place can be a problem and this article describes the use of a new fixing method.


P002 Psychiatric Comorbidity and Suicide in Childhood Onset Immune-Mediated Diseases -A Systematic Review and Meta-Analysis.
The course of paediatric onset immune mediated inflammatory diseases (IMID) is both physically and mentally challenging. Emotional distress with anxiety and depressive symptoms is commonly reported, however, data on diagnosed comorbid psychiatric disorders is scarce. The aim of this study was to provide a literature overview of psychiatric comorbidity, suicide rates, and their potential risk factors, in childhood onset IMID. This was a systematic review following the PRISMA guidelines. The protocol was registered at Prospero (ID: CRD42021233890). A literature search was made in the databases Pubmed, PsychINFO, and Embase. We included the following IMID: paediatric onset inflammatory bowel disease (pIBD), rheumatic diseases (RD) and autoimmune liver diseases. Studies that provided prevalence rates of diagnosed psychiatric disorders and/or suicide, were included. Pooled prevalence rates of psychiatric disorders (grouped according to ICD-10 criteria) reported by three or more studies, within the same IMID, were calculated using random-effects meta-analysis. Two authors independently evaluated risk of bias using the New-Castle Ottawa scale. Twenty-three studies met the inclusion criteria; 13 describing psychiatric disorders in pIBD and 10 in RD. No study reported on psychiatric disorders in autoimmune liver diseases. Compared to controls without somatic disease, IMID patients had an increased risk of psychiatric disorders, with anxiety and mood disorders being the most common. Prevalence rates for anxiety and mood disorders in pIBD were 6% (95% confidence interval (CI): 4%-9%) and 4% (95%CI: 2%-8%), respectively, in register-based studies, and 33% (95%CI: 25%-41%) and 18% (95%CI:12%-26%), respectively, in studies using psychiatric assessment. In RD pooled estimates were 13% (95%CI: 12%-15%) for anxiety disorders and 20% (95%CI: 15%-26%) for mood disorders. Based on single studies, risk of suicide was increased in pIBD, but not in juvenile idiopathic arthritis, the most common RD. In this systematic review, patients with childhood onset IMID had increased prevalence of psychiatric disorders compared to controls. However, only pooled estimates on emotional disorders were possible and studies investigating broad spectrum of psychiatric disorders are needed.


Management of knee osteoarthritis: an evidence-based review of treatment options.
Osteoarthritis is the most common form of arthritis, and its incidence increases rapidly with age. Osteoarthritis is a progressive degenerative disease, and treatment must evolve with disease progression. Several classes of medications and treatment modalities have been used to relieve pain and preserve function. Most have been studied extensively but results of even well-designed trials can diverge. Furthermore, effect of a drug (beneficial or adverse) in an individual patient is not always predictable and may differ from the class effect. A short treatment trial may be necessary to determine efficacy. This potential discrepancy between statistical outcome and individual result is captured in the guidelines, to whatever extent possible. A summary of recommendations for select interventions compiled from multiple guidelines is presented in table II. In closing, interpretation of guideline recommendations, and how they were derived, must be clarified, since they have been a source of confusion and misinterpretation. Level of evidence (LoE) refers to the source from which the evidence was derived. It describes the quality of evidence and academic vigor, with meta-analysis of RCT being of strongest quality and expert opinion the lowest. The strength of effect describes how much of a clinical effect (usually benefit) is expected from the intervention. The strength of recommendation incorporates LoE and strength of effect, as well as cost, safety, and feasibility. An intervention with a high LoE does not necessarily trigger a strong recommendation. For example, NSAIDs have a greater effect on pain reduction than acetaminophen in most studies, but carries a lower recommendation due to concerns with long-term safety. Total knee arthroplasty has a LoE of III since no blinded RCT have studied the procedure, yet it carries a strong recommendation in advanced OA. In the five years between the publication of the EULAR and the OARIS guidelines (2003-2008), new studies were published explaining, in part, the difference in recommendations among the agencies. Future guidelines will undoubtedly evolve further.


Do everyday problems of people with chronic illness interfere with their disease management?
Being chronically ill is a continuous process of balancing the demands of the illness and the demands of everyday life. Understanding how everyday life affects self-management might help to provide better professional support. However, little attention has been paid to the influence of everyday life on self-management. The purpose of this study is to examine to what extent problems in everyday life interfere with the self-management behaviour of people with chronic illness, i.e. their ability to manage their illness. To estimate the effects of having everyday problems on self-management, cross-sectional linear regression analyses with propensity score matching were conducted. Data was used from 1731 patients with chronic disease(s) who participated in a nationwide Dutch panel-study. One third of people with chronic illness encounter basic (e.g. financial, housing, employment) or social (e.g. partner, children, sexual or leisure) problems in their daily life. Younger people, people with poor health and people with physical limitations are more likely to have everyday problems. Experiencing basic problems is related to less active coping behaviour, while experiencing social problems is related to lower levels of symptom management and less active coping behaviour. The extent of everyday problems interfering with self-management of people with chronic illness depends on the type of everyday problems encountered, as well as on the type of self-management activities at stake. Healthcare providers should pay attention to the life context of people with chronic illness during consultations, as patients' ability to manage their illness is related to it.


Optimizing lens constants specifically for short eyes: Is it essential?
Optimization of lens constants is a critically important step that improves refractive outcomes significantly. Whether lens constants optimized for the entire range of axial length would perform equally well in short eyes is still a matter of debate. The aim of this study was to analyze whether lens constants need to be optimized specifically for short eyes. : This retrospective observational study was conducted at a tertiary care hospital in Central India. Eighty-six eyes of eighty-six patients were included. Optical biometry with IOLMaster 500 was done in all cases and lens constants were optimized using built-in software. Barrett Universal II, Haigis, Hill-RBF, Hoffer Q, Holladay 1, and SRK/T formulae were compared using optimized constants. Mean absolute error, median absolute error (MedAE), and percentage of eyes within ±0.25, ±0.50, ±1.00, and ±2.00 diopter of the predicted refraction, of each formula were analyzed using manufacturer's, ULIB, and optimized lens constants. MedAE was compared across various constants used by Wilcoxon signed-rank test and among optimized constants by Friedman's test. Cochran's Q test compared the percentage of eyes within ± 0.25, ±0.50, ±1.00, and ± 2.00 diopter of the predicted refraction. A value of P < 0.05 was considered statistically significant. : Optimized constant of Haigis had significantly lower MedAE (P < 0.00001) as compared to manufacturers. However, there was no statistically significant difference between ULIB and optimized constants. Postoptimization, there was no statistically significant difference among all formulae. : Optimizing lens constants specifically for short eyes gives no added advantage over those optimized for the entire range of axial length.


Diagnostic management of acute pulmonary embolism: a prediction model based on a patient data meta-analysis.
Risk stratification is used for decisions regarding need for imaging in patients with clinically suspected acute pulmonary embolism (PE). The aim was to develop a clinical prediction model that provides an individualized, accurate probability estimate for the presence of acute PE in patients with suspected disease based on readily available clinical items and D-dimer concentrations. An individual patient data meta-analysis was performed based on sixteen cross-sectional or prospective studies with data from 28 305 adult patients with clinically suspected PE from various clinical settings, including primary care, emergency care, hospitalized and nursing home patients. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict objectively confirmed PE at baseline or venous thromboembolism (VTE) during follow-up of 30 to 90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value <0.10. Discrimination (c-statistic with 95% confidence intervals [CI] and prediction intervals [PI]) and calibration (outcome:expected [O:E] ratio and calibration plot) were evaluated based on internal-external cross-validation. The accuracy of the model was subsequently compared with algorithms based on the Wells score and D-dimer testing. The final model included age (in years), sex, previous VTE, recent surgery or immobilization, haemoptysis, cancer, clinical signs of deep vein thrombosis, inpatient status, D-dimer (in µg/L), and an interaction term between age and D-dimer. The pooled c-statistic was 0.87 (95% CI, 0.85-0.89; 95% PI, 0.77-0.93) and overall calibration was very good (pooled O:E ratio, 0.99; 95% CI, 0.87-1.14; 95% PI, 0.55-1.79). The model slightly overestimated VTE probability in the lower range of estimated probabilities. Discrimination of the current model in the validation data sets was better than that of the Wells score combined with a D-dimer threshold based on age (c-statistic 0.73; 95% CI, 0.70-0.75) or structured clinical pretest probability (c-statistic 0.79; 95% CI, 0.76-0.81). The present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study. PROSPERO ID 89366.


A manic episode after bilateral subthalamic stimulation in a patient with advanced Parkinson's disease.
Deep brain stimulation (DBS) has proven to be an effective treatment for patients with refractory symptoms in the advanced stages of Parkinson's disease. However, different psychiatric and cognitive problems may occur after DBS. We report a case of a manic episode after DBS of the subthalamic nucleus in a patient with advanced Parkinson's disease. After slow and gradually restart of the neurostimulation using the lowest effective intensity, the motor symptoms remained sufficiently under control without causing any psychiatric problems.


Skin injuries caused by new riot control agent used against civilians on the West Bank.
A new riot control agent, used by the Israeli army against civilians protesting about the Separation Wall on the West Bank, has been reported as causing severe skin injuries. We obtained one of the munitions and have identified the contents as capsaicin with an inert carrier and a dispersal agent. This corresponds to the commercially available 'Pepperball Tactical Powder'. Skin injuries of the severity described have not previously been reported with this agent, and would be difficult to manage for clinicians who were unaware of the nature of the agent.


The role of sunscreen preparations in preventing skin cancer.
Despite health campaigns and much publicity in the media on the dangers of overexposure to the sun, the incidence of skin cancer is rising. Community nurses have a vital role in educating patients about the need to use an appropriate sunscreen for their skin type and combining this with the use of protective clothing and taking measures to avoid overexposure.