Peritoneal sclerosis in peritoneal dialysis patients.
Peritoneal sclerosis, a disorder similar to that previously identified in nonuremic patients, is being noted in peritoneal dialysis patients with increasing frequency. The etiology in dialysis patients remains unknown. An association with previous or ongoing peritoneal inflammation or irritation suggests that the incidence of peritoneal sclerosis could be reduced by rapidly controlling peritonitis and by eliminating the irritant properties of catheters, dialysate, and other materials used in performing peritoneal dialysis. If peritoneal sclerosis does supervene, weight loss, abdominal pain, and intestinal obstruction may occur and further peritoneal dialysis may become impossible because of abdominal pain or poor fluid and solute transfer.


HIV and conflict in Nepal: relation and strategy for response.
Conflict and displacement make affected population more vulnerable to HIV infection. Refugees and internally displaced persons, in particular women and children, are at increased risk of exposure to HIV. In Nepal, there is considerable increase in the number of HIV infection since 1996 when conflict started. Along with poverty, stigma and lack of awareness, conflict related displacement, economic migration, and closure of HIV programmes have exacerbated the HIV situation in Nepal. Government has established "National AIDS Council" and launched HIV/AIDS Strategy. The strategy has not included the specific needs of displaced persons. While launching an HIV prevention programme in the conflict situation, the guidelines developed by Inter Agency Standing Committee (IASS) are important tools. This led to suggestion of an approach with implementations steps in the case of Nepal in this report.


Stoichiometry of microtubule-associated protein (MAP2):tubulin and the localisation of the phosphorylation and cysteine residues along the MAP2 primary sequence.
The stoichiometry of the dimer between microtubule-associated protein 2 (MAP2) and tubulin has been determined by quantitative dodecylsulphate/polyacrylamide gel electrophoresis to be 1:12 mol X mol-1, a value equal to the number of phosphorylation sites that can be labelled in vitro. The distribution of these sites along the MAP2 primary sequence has been determined by cleaving pre-labelled MAP2 with either alpha-chymotrypsin or at the five cysteine residues with nitrothiocyanobenzoic acid. The phosphorylation sites lie in two clusters: ten within the known tubulin-binding domain at one end of the primary sequence, and a pair midway along the sequence. It is postulated that the tertiary structure of MAP2 is folded to bring all twelve sites into association with the twelve tubulin dimers.


Hearing an illusory vowel in noise: suppression of auditory cortical activity.
Human hearing is constructive. For example, when a voice is partially replaced by an extraneous sound (e.g., on the telephone due to a transmission problem), the auditory system may restore the missing portion so that the voice can be perceived as continuous (Miller and Licklider, 1950; for review, see Bregman, 1990; Warren, 1999). The neural mechanisms underlying this continuity illusion have been studied mostly with schematic stimuli (e.g., simple tones) and are still a matter of debate (for review, see Petkov and Sutter, 2011). The goal of the present study was to elucidate how these mechanisms operate under more natural conditions. Using psychophysics and electroencephalography (EEG), we assessed simultaneously the perceived continuity of a human vowel sound through interrupting noise and the concurrent neural activity. We found that vowel continuity illusions were accompanied by a suppression of the 4 Hz EEG power in auditory cortex (AC) that was evoked by the vowel interruption. This suppression was stronger than the suppression accompanying continuity illusions of a simple tone. Finally, continuity perception and 4 Hz power depended on the intactness of the sound that preceded the vowel (i.e., the auditory context). These findings show that a natural sound may be restored during noise due to the suppression of 4 Hz AC activity evoked early during the noise. This mechanism may attenuate sudden pitch changes, adapt the resistance of the auditory system to extraneous sounds across auditory scenes, and provide a useful model for assisted hearing devices.


Tumour necrosis factor-alpha released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis.
Experimental autoimmune orchitis (EAO) is a model of chronic inflammation and infertility useful for studying testicular immune and germ cell (GC) interactions. In this model, EAO was induced in rats by immunization with testicular homogenate and adjuvants; Control (C) rats were injected with adjuvants. EAO was characterized by an interstitial infiltrate of lymphomonocytes and seminiferous tubule damage, moderate 50 days (focal orchitis) and severe 80 days after the first immunization (severe orchitis). Based on the previous results showing that the number of macrophages and apoptotic GC expressing tumour necrosis factor (TNF) receptor 1 increased in EAO, we studied the role of macrophages and TNF-alpha in GC apoptosis. Conditioned media of testicular macrophages (CMTM) obtained from rats killed on Days 50 and 80 decreased the viability (MTS, P < 0.01) and induced apoptosis (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labelling, TUNEL) of GC obtained from EAO but not from non-immunized, N rats (P < 0.001). TNF-alpha content (enzyme-linked immunosorbent assay) was significantly higher in the CMTM from EAO versus C rats on Day 80 (P < 0.05). The apoptotic effect of CMTM from Day 80 rats was abrogated by a selective TNF-alpha blocker (Etanercept). Moreover, TNF-alpha in vitro induced GC apoptosis. TNF-alpha expression (by immunofluorescence) was observed in testicular (ED2(+)) and non-resident (ED1(+)) macrophages, the percentage of TNF-alpha(+) macrophages being similar in focal and severe orchitis. Results demonstrated that soluble factors released from testicular EAO macrophages induce apoptosis of GC, biased by the local inflammatory environment, and that TNF-alpha is a relevant cytokine involved in testicular damage during severe orchitis.


[Follow-up studies of rheumatoid arthritis patients with the presence of antiphospholipid antibodies].
The aim of the study was 2 years follow-up observation of clinical course in RA patients with the presence of anticardiolipin antibodies (aCL). Among 395 patients with RA hospitalized in the Clinic of Rheumatology from January 2003 to December 2004 (2 years), in 39 patients with suspicion of antiphopspholipid syndrome the aCL antibodies were determined. In 7 cases we confirm the presence of aCL antibodies. Patients positive for antiphospholipid antibodies were invited to the Clinic on the beginning of 2006 (after 2 years from previous hospitalization) to analyze clinical course of disease and to perform laboratory examination. In the group of patients with RA positive for antiphospholipid antibodies, 3 had active RA with vascular changes. Aggressive therapy with disease modifying antirheumatic drugs (DMARDs) and corticosteroids caused conversion of anticardiolipin antibodies. Analogically antibiotic therapy in 2 patients with concomitant infections (urinary tract, respiratory system) caused conversion of aCL antibodies. 1 patient developed blastic coat cell lymphoma. 1 patient died because of cardiovascular complications. Presence of anticardiolipin antibodies can be the indicator of serious prognosis, it can predict vasculitis, persistent infections, cardiovascular complications or neoplasmatic disease. We suggest that antiphospholipid antibodies should be measure in patient with aggressive course of rheumatoid arthritis.


[Zinc in the therapy of the attention-deficit/hyperactivity disorder in children. A preliminar randomized controlled trial].
The attention-deficit/hyperactivity disorder (ADHD) is a neurological/behavioral disorder which begins in childhood. Zinc has a potential role as an adjuvant therapy for ADHD. The objective was to evaluate the effect ofZn supplementation on behavior, as a complementary therapy to metylphenidate, in pediatrics patients with ADHD. In a controlled, double blind design, 40 patients with clinical criteria ofADHD (DSM-IV) and psychometric evaluation (WISC-R), were selected (31 boys and 9 girls, 7-14 years of age). They were randomized to receive methylphenidate 0.3 mg/kg/d + placebo (sucrose) (group placebo, GPL) or methylphenidate 0.3 mg/kg/d + zinc (sulfate) 10 mg/d (group Zn, GZN) for 6 weeks. A blood sample was drawn at time 0 and 6 weeks, for plasma Zn analysis. The teacher and parent ADHD rating scale (Conners' global index, CGI) was applied at both times. Among the results, plasma Zn was normal at time 0, decreasing especially in the GPL after 6 weeks (GPL: 95.9 +/- 21.5 to 77.9 +/- 15.5; GZN: 90.3 +/- 9.1 to 85.0 +/- 12.0 microg/dL; NS). The CGI by teachers showed a non-significant improvement with Zn: GPL: 18 (9-28) to 16 points (2-26); GZN: 19 (6-24) to 11 points (3-23) (p = 0.07); no significant difference in the CGI by parents by groups was found: GPL: 19 (7-25) to 13 (3-22); GZN: 19(7-25) to 11(2-19). We conclude that a decrease in plasma Zn levels in both groups was found, greater in the placebo group. An apparent improvement in ADHD signs in children was observed with the Zn supplementation, according to the Conners global index by teachers.


Biomarkers of Ionizing Radiation Exposure: A Multiparametric Approach.
Humans are exposed to ionizing radiation not only through background radiation but also through the ubiquitous presence of devices and sources that generate radiation. With the expanded use of radiation in day-to-day life, the chances of accidents or misuse only increase. Therefore, a thorough understanding of the dynamic effects of radiation exposure on biological entities is necessary. The biological effects of radiation exposure on human cells depend on much variability such as level of exposure, dose rate, and the physiological state of the cells. During potential scenarios of a large-scale radiological event which results in mass casualties, dose estimates are essential to assign medical attention according to individual needs. Many attempts have been made to identify biomarkers which can be used for high throughput biodosimetry screening. In this study, we compare the results of different biodosimetry methods on the same irradiated cells to assess the suitability of current biomarkers and push forward the idea of employing a multiparametric approach to achieve an accurate dose and risk estimation.


Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2014.
This study presents the 2014 nationwide cancer statistics in Korea, including cancer incidence, survival, prevalence, and mortality. Cancer incidence data from 1999 to 2014 was obtained from the Korea National Cancer Incidence Database and followed until December 31, 2015. Mortality data from 1983 to 2014 were obtained from Statistics Korea. The prevalence was defined as the number of cancer patients alive on January 1, 2015, among all cancer patients diagnosed since 1999. Crude and age-standardized rates (ASRs) for incidence, mortality, prevalence, and 5-year relative survivals were also calculated. In 2014, 217,057 and 76,611 Koreans were newly diagnosed and died from cancer respectively. The ASRs for cancer incidence and mortality in 2014 were 270.7 and 85.1 per 100,000, respectively. The all-cancer incidence rate has increased significantly by 3.4% annually from 1999 to 2012, and started to decrease after 2012 (2012-2014; annual percent change, -6.6%). However, overall cancer mortality has decreased 2.7% annually since 2002. The 5-year relative survival rate for patients diagnosed with cancer between 2010 and 2014 was 70.3%, an improvement from the 41.2% for patients diagnosed between 1993 and 1995. Age-standardized cancer incidence rates have decreased since 2012 and mortality rates have also declined since 2002, while 5-year survival rates have improved remarkably from 1993-1995 to 2010-2014 in Korea.


Factors associated with insensitivity to pyridostigmine therapy in Thai patients with ocular myasthenia gravis.
The objective of this study was to determine factors associated with pyridostigmine therapy in patients with ocular myasthenia gravis (OMG). This retrospective study included eighty-five patients with OMG who have been treated with pyridostigmine. Patients were excluded if they were diagnosed as generalized myasthenia gravis within a month after diagnosis or were treated with other medications. Forty-two patients responded to pyridostigmine and 43 patients did not. There were no significant differences in gender, age, the duration of symptoms before treatment, the dosage of pyridostigmine, and the initial presentations of ptosis or diplopia between the two groups. However, an initial presentation of concurrent ptosis and diplopia and the presence of systemic involvement after follow up were significant factors associated with an insensitivity to pyridostigmine in patients with OMG (p = 0.001 and p = 0.01, respectively). Determining these factors could help predict the pyridostigmine response in patients with OMG.


Exon-Skipping Oligonucleotides Restore Functional Collagen VI by Correcting a Common COL6A1 Mutation in Ullrich CMD.
Collagen VI-related congenital muscular dystrophies (COL6-CMDs) are the second most common form of congenital muscular dystrophy. Currently, there is no effective treatment available. COL6-CMDs are caused by recessive or dominant mutations in one of the three genes encoding for the α chains of collagen type VI (COL6A1, COL6A2, and COL6A3). One of the most common mutations in COL6-CMD patients is a de novo deep intronic c.930+189C > T mutation in COL6A1 gene. This mutation creates a cryptic donor splice site and induces incorporation of a novel in-frame pseudo-exon in the mature transcripts. In this study, we systematically evaluated the splice switching approach using antisense oligonucleotides (ASOs) to correct this mutation. Fifteen ASOs were designed using the RNA-tiling approach to target the misspliced pseudo-exon and its flanking sequences. The efficiency of ASOs was evaluated at RNA, protein, and structural levels in skin fibroblasts established from four patients carrying the c.930+189C > T mutation. We identified two additional lead ASO candidates that efficiently induce pseudo-exon exclusion from the mature transcripts, thus allowing for the restoration of a functional collagen VI microfibrillar matrix. Our findings provide further evidence for ASO exon skipping as a therapeutic approach for COL6-CMD patients carrying this common intronic mutation.


Epitope mapping of human aromatic L-amino acid decarboxylase.
Autoimmune polyendocrine syndrome type I (APS I) is a rare hereditary condition considered a model disease for organ specific autoimmunity. A wide range of autoantibodies targeting antigens present in the affected organs have been identified. Autoantibodies against aromatic L-amino acid decarboxylase (AADC) are present in about 50% of APS I patients. In order to increase our understanding of autoantibody specificity in APS I, the aim of the present study was to localize target regions on AADC recognized by sera from APS I patients. Using several complementing strategies, we have shown that autoantibodies against AADC mainly recognize conformational epitopes. The major antigenic determinants were detected N-terminally to amino acid residue 237. Replacement of amino acids 227-230 (ERDK) with alanine residues reduced the reactivity towards AADC by >80% in all patient sera tested, suggesting that amino acids 227-230 are an important part of an immunodominant epitope.


Approximate Representations of Shaped Pulses Using the Homotopy Analysis Method.
The evolution of nuclear spin magnetization during a radiofrequency pulse in the absence of relaxation or coupling interactions can be described by three Euler angles. The Euler angles in turn can be obtained from the solution of a Riccati differential equation; however, analytic solutions exist only for rectangular and chirp pulses. The Homotopy Analysis Method is used to obtain new approximate solutions to the Riccati equation for shaped radiofrequency pulses in NMR spectroscopy. The results of even relatively low orders of approximation are highly accurate and can be calculated very efficiently. The results are extended in a second application of the Homotopy Analysis Method to represent relaxation as a perturbation of the magnetization trajectory calculated in the absence of relaxation. The Homotopy Analysis Method is powerful and flexible and is likely to have other applications in magnetic resonance.


Where is the nerve? Review of operation note documentation practice for inguinal hernia repair.
Careful identification and management of inguinal nerves during inguinal hernia repair is important to avoid iatrogenic injury. Documentation of this practice may inform postoperative clinical management. We set out to investigate how often surgeons identify inguinal nerves and document findings and management in their operation notes. We carried out a retrospective review of operation notes at a single district general hospital. We analysed operation notes for documentation of identification and intraoperative management (preservation or sacrifice) of the inguinal nerves (iliohypogastric, ilioinguinal, genital branch of genitofemoral nerve). We collected data on the baseline characteristics of the patients, hernia characteristics and primary operating surgeons for subgroup analysis. A total of 100 patients were included in the analysis. Identification of any inguinal nerves (generic 'nerve') was documented in 17% of operation notes. Documentation in the operation notes of named individual nerves was limited. No documentation of intraoperative management of inguinal nerves was found in 83% of operation notes. Preservation of the inguinal nerves (generic 'nerve') was recorded in 8% and sacrifice recorded in 9% of cases. Subgroup analysis revealed similar incidence of documentation of identification and management of inguinal nerves across grades of primary surgeon, with overall incidence low for all grades. This study reveals a lack of appreciation of the importance of documenting identification and management of inguinal nerves in operation notes. Further consideration of the potential implications of poor documentation would be beneficial to improve standards.


Return to play decision after shoulder dislocation in upper limb athletes: critical analysis between the habits of medical professionals and the literature.
The return to field is a critical moment for an athlete who has dislocated his shoulder as there is a significant risk of recurrence. The decision to return to field made by the doctor will therefore be crucial for the smooth continuation of the athlete's career. This objective is to compare the criteria most used by specialists in clearing an overhead athlete to return to competition after a first episode of antero-internal dislocation of the glenohumeral joint with or without surgery and those mentioned in the literature. The target population consisted of French-speaking physicians in orthopaedic surgery, physical medicine and rehabilitation or sports medicine. This study was conducted by the means of a questionnaire. The questionnaire was validated by 3 experts in sports medicine and published on an online survey website. Sixty-three medical specialists responded to the questionnaire. On average, they use more than 9 criteria to decide if an athlete is fit to return to competition. Over the 12 criteria proposed, 4 are used by more than 90% of respondents: laxity/instability, pain, range of motion and patient's subjective feeling. The methods used to evaluate certain criteria such as pain, joint range or muscular strength are often subjective and very often not validated by the literature. Doctors use a set of criteria to allow an overhead athlete to return to competition. This study highlights that the techniques employed to evaluate these criteria are not always thoroughly validated by literature reviews. III; Observational study.


Dependence of electron transfer among alpha cages on the chemical compositions of zeolite LTAs including K clusters.
K atoms are loaded in diluted amount into K-form LTA zeolites whose framework compositions are Al(x)Si(24-x)O(48) (6<x<or=12) per alpha cage. The optical and electron spin resonance (ESR) properties of K clusters formed in the alpha cages of the LTAs were investigated to elucidate the influence of the LTA compositions on the transfer of a 4s electron of a loaded K atom among the cages. Optical absorption spectra showed notable absorption at approximately 1 eV originating from cationic K clusters in the alpha cages independent of the x value. The linewidths of the ESR spectra showed a minimum value at x approximately 10. A motional narrowing effect induced by the electron transfer among the alpha cages is the origin of the sharp ESR spectra at x approximately 10. The gradual narrowing of the ESR spectral linewidth that occurred from x=12 to 10 can be explained with the assistance of numerical calculations of the periodic potential for an electron introduced into the LTAs. The potential inside the alpha cage becomes monotonously shallower with decreasing x value. On the other hand, the potential of an eight-membered ring shared with the adjacent alpha cages was insensitive to the x value. The calculation results demonstrate that the electron mobility becomes larger at smaller x values. The discrepancy between the actual ESR results and the calculation results for x<10 might be due to the aggregation of K+ ions to stabilize 4s electrons in the alpha cage in actual systems.


Spatial working memory in neurofibromatosis 1: Altered neural activity and functional connectivity.
Neurofibromatosis Type 1 (NF1) is a genetic disorder that disrupts central nervous system development and neuronal function. Cognitively, NF1 is characterized by difficulties with executive control and visuospatial abilities. Little is known about the neural substrates underlying these deficits. The current study utilized Blood-Oxygen-Level-Dependent (BOLD) functional MRI (fMRI) to explore the neural correlates of spatial working memory (WM) deficits in patients with NF1. BOLD images were acquired from 23 adults with NF1 (age M = 32.69; 61% male) and 25 matched healthy controls (age M = 33.08; 64% male) during an in-scanner visuo-spatial WM task. Whole brain functional and psycho-physiological interaction analyses were utilized to investigate neural activity and functional connectivity, respectively, during visuo-spatial WM performance. Participants also completed behavioral measures of spatial reasoning and verbal WM. Relative to healthy controls, participants with NF1 showed reduced recruitment of key components of WM circuitry, the left dorsolateral prefrontal cortex and right parietal cortex. In addition, healthy controls exhibited greater simultaneous deactivation between the posterior cingulate cortex (PCC) and temporal regions than NF1 patients. In contrast, NF1 patients showed greater PCC and bilateral parietal connectivity with visual cortices as well as between the PCC and the cerebellum. In NF1 participants, increased functional coupling of the PCC with frontal and parietal regions was associated with better spatial reasoning and WM performance, respectively; these relationships were not observed in controls. Dysfunctional engagement of WM circuitry, and aberrant functional connectivity of 'task-negative' regions in NF1 patients may underlie spatial WM difficulties characteristic of the disorder.


CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis.
Protective immunity against Mycobacterium tuberculosis is primarily mediated by the interaction of antigen-specific T cells and antigen presenting cells, which often depends on the interplay of cytokines produced by these cells. Costimulatory signals represent a complex network of receptor-ligand interactions that qualitatively and quantitatively influence immune responses. Thus, here we investigated the function of CD137 and CD137L, molecules known to have a central role in immune regulation, during human tuberculosis (TB). We demonstrated that M. tuberculosis antigen stimulation increased both CD137 and CD137L expression on monocytes and NK cells from TB patients and healthy donors, but only up-regulated CD137 on T lymphocytes. Blockage of the CD137 pathway enhanced the levels of interferon (IFN)-γ and tumor necrosis factor (TNF)-α produced by monocytes and NK against M. tuberculosis. In contrast, CD137 blockage significantly decreased the specific degranulation of CD8(+) T cells and the percentage of specific IFN-γ and TNF-α producing lymphocytes against the pathogen. Furthermore, inhibition of the CD137 pathway markedly increased T-cell apoptosis. Taken together, our results demonstrate that CD137:CD137L interactions regulate the innate and adaptive immune response of the host against M. tuberculosis.


Studies of mdx mice.
Cerebral water accumulation-clinically denoted as brain edema-is a potentially life threatening complication of almost every intracranial neuropathological state. The molecular membrane water channel aquaporin-4 (AQP4) has been shown to be present at the blood-brain barrier (BBB) where it plays pivotal role in the transport of water between the tissue water compartments of the brain. Accumulating evidence indicates that the blockade of AQP4 function at the BBB would be a new therapeutic approach to the treatment and prevention of brain swelling. The cytoskeletal protein dystrophin has been shown to be involved in the maintenance of the polarized expression of AQP4 at the BBB. In order to further elucidate the mechanisms responsible for the highly polarized AQP4 expression, we studied brain tissue water accumulation during induction of brain edema in dystrophin-null transgenic mice (mdx-bgeo) and control mice. Immunofluorescence and immunoelectron microscopic analyses of dystrophin-null brains revealed a dramatic reduction of AQP4 in astroglial end-feet surrounding capillaries (BBB) and at the glia limitans (cerebrospinal fluid-brain interface). The AQP4 protein is mislocalized, because immunoblotting showed that the total AQP4 protein abundance was unaltered. Brain edema was induced by i.p. injection of distilled water and 8-deamino-arginine vasopressin. Changes in cerebral water compartments were assessed by diffusion-weighted MRI (DWI) with determination of the apparent diffusion coefficient (ADC). In dystrophin-null mice and control mice, ADC gradually decreased by 5-6% from baseline levels during the first 35 min, indicating the initial phase of intracellular water accumulation is similar in the two groups. At this point, the control mice sustained an abrupt, rapid decline in ADC to 58%+/-2.2% of the baseline at 52.5 min, and all of the animals were dead by 56 min. After a consistent delay, the dystrophin-null mice sustained a similar decline in ADC to 55%+/-3.4% at 66.5 min, when all of the mice were dead. These results demonstrate that dystrophin is necessary for polarized distribution of AQP4 protein in brain where facilitated movements of water occur across the BBB and cerebrospinal fluid-brain interface. Moreover, these results predict that interference with the subcellular localization of AQP4 may have therapeutic potential for delaying the onset of impending brain edema.


The Expert Consensus Guidelines for treating depression in bipolar disorder.
We present expert consensus guideline recommendations for the treatment of bipolar depression. These were arrived at through the statistical aggregation of the survey responses of 61 leading clinical researchers to eight questions about the key decision points in the management of bipolar depression. The experts' first-line recommendation for treating psychotic depression in bipolar disorder is to provide a combination of mood stabilizer, antidepressant, and neuroleptic medication. For severe, but nonpsychotic bipolar depression, the experts recommend the combination of a mood stabilizer and an antidepressant. For milder bipolar depression, a mood stabilizer and an antidepressant together or a mood stabilizer alone would be first line. The experts' antidepressant dose and dosing schedule recommendations are equivalent for unipolar and bipolar depression, but the experts recommend a faster discontinuation of antidepressants during the maintenance phase in bipolar patients--probably to reduce the risk of rapid cycling. Among the antidepressants, the experts prefer bupropion and the serotonin reuptake inhibitors as first line. They also believe that bupropion is least likely among antidepressants to cause switches to mania. Among mood stabilizers, the experts rate lithium as most likely to have a direct antidepressant effect.


Egon Schiele and dystonia.
Egon Schiele was a leading Austrian Expressionist painter who, after the era of Gustav Klimt, strongly influenced the artistic scene in Vienna in the early 20th century. Schiele's depiction of his body in his self-portraits in a twisted, contorted, dystonia-like pose raised questions about the possibility of his suffering from dystonia. However, there are no grounds whatsoever for such a hypothesis. Schiele's conception of distorted, at times bizarre, body postures reflects a concourse of the Expressionist formal style of displaying extroverted emotions and psychic confl icts with the emerging perception of photographs of patients with movement disorders in Vienna's art scene and intellectual circles. There are reliable indications that Schiele knew the images of diseases published in the 'Iconographie Photographique de la Salpetriere' and the later 'Nouvelle Iconographie de la Salpetriere' including hysterical and dystonic postures. The brevity of Schiele's life adds to the popular fantasy of the outlaw who lived fast and died young. In fact, however, his drawings sold well to discerning collectors, and his exhibitions were a financial success, so the myth of Schiele as a sacrificial outcast does not tell the whole story. It may be speculated that the figuration of the pathological body in Schiele's self-portraiture was part of modernist strategizing.


Retention of ova in oviducts of senescent mice and hamsters.
Young (3-5 months of age) and senescent (12-17 months of age depending on the species) female mice, hamsters and rats were mated with young mature males and examined for numbers of degenerating ova. Young female mice, hamsters, rats and senescent rats exhibited normal numbers of ova following ovulation and, in general, normal numbers of blastocysts before implantation. In contrast, on the morning of ovulation some senescent mice and hamsters exhibited degenerating ova in the isthmus or isthmic-utero-tubal region of the oviduct, while normal ova were found in the ampulla. Degenerating ova were also located in the uterine horns of one mouse and hamster before implantation (day 3 of preganacy). Another hamster at the same stage of pregnancy exhibited 24 degenerating ova and nine blastocysts, all of which remained in the oviducts except for one blastocysts recovered from the uterus. In a previous study (Parkening and Soderwall, '75) a histological examination of the number of copora lutea from ovaries removed from senescent female hamsters whose oviducts contained large numbers of degenerating ova indicated the deteriorating ova were not ovulated following mating. Why ova from the previous unmated estrous cycle(s) remain in the oviducts of some senescent mice and hamsters remains to be determined.


Short term results in a population based study indicate advantage for laparoscopic colon cancer surgery versus open.
The aim of this study was to compare LAP with OPEN regarding short-term mortality, morbidity and completeness of the cancer resection for colon cancer in a routine health care setting using population based register data. All 13,683 patients who were diagnosed 2012-2018 and underwent elective surgery for right-sided or sigmoid colon cancer were included from the Swedish Colorectal Cancer Registry and the National Patient Registry. Primary outcome was 30-day mortality. Secondary outcomes were 90-day mortality, length of hospital stay, reoperation, readmission and positive resection margin (R1). Weighted and unweighted multi regression analyses were performed. There were no difference in 30-day mortality: LAP (0.9%) and OPEN (1.3%) (OR 0.89, 95% CI 0.62-1.29, P = 0.545). The weighted analyses showed an increased 90-day mortality following OPEN, P < 0.001. Re-operations and re-admission were more frequent after OPEN and length of hospital stay was 2.9 days shorter following LAP (P < 0.001). R1 resections were significantly more common in the OPEN group in the unweighted and weighted analysis with P = 0.004 and P < 0.001 respectively. Therefore, the favourable short-term outcomes following elective LAP versus OPEN resection for colon cancer in routine health care indicate an advantage of laparoscopic surgery.


The role of chelators in preventing biofilm formation and catheter-related bloodstream infections.
As metallic cations are essential to microbial adherence, biofilm formation, and bacterial growth, efforts have been directed toward utilizing metal-binding chelators that have the capability of inhibiting bacterial growth by disrupting surface adherence and preventing biofilm production. This review focuses on recent advances in the role of chelators in biofilm disruption and prevention of catheter-related bloodstream infections. The most important factor in the pathogenesis of catheter-related bloodstream infections is the intraluminal colonization of the central venous catheters through the formation of bacterial biofilm matrix in which microbial organisms embed themselves and eventually become a source of catheter-related bloodstream infections. It has been demonstrated that high-affinity metal-binding chelators including ethylenediamine-tetraacetic acid and citrate have the capacity of inhibiting microbial growth by disrupting surface adherence and preventing biofilm production. Furthermore, ethylenediamine-tetraacetic acid and citrate have been clinically shown to be highly effective and outperform heparin in the prevention and treatment of catheter-related bloodstream infections when used as a component of antimicrobial catheter lock solutions. It is suggested that the addition of chelators such as ethylenediamine-tetraacetic acid and citrate to antimicrobial lock solutions provides an innovative and superior alternative to heparin lock solution in the prevention and treatment of catheter-related bloodstream infections.


Clinical Outcomes Following the Latarjet Procedure in Contact and Collision Athletes.
Few studies have evaluated the success of the Latarjet procedure for recurrent anterior glenohumeral instability in the contact or collision athlete. The purpose of this study was to evaluate the return-to-sport and functional results of the Latarjet procedure in this select group. One hundred and nine consecutive contact or collision athletes (112 shoulders) treated with an open Latarjet procedure for recurrent anterior glenohumeral instability were retrospectively identified. Seventy-three shoulders in 73 patients (67%) were evaluated at a mean follow-up of 52 months (range, 24 to 120 months). The average age at surgery was 25.8 years (range, 15 to 54 years). The primary outcomes were the scores on the Western Ontario Shoulder Instability Index (WOSI), the American Shoulder and Elbow Surgeons (ASES) questionnaire, a visual analog scale (VAS) for pain, and return to sport. Predictors of return to sport were analyzed. Six (8%) of the 73 patients experienced ≥1 postoperative dislocations. Ten additional patients (14%) experienced a perception of instability without a dislocation. The median postoperative WOSI and ASES scores were 382 (range, 0 to 2,016) and 93.3 (range, 21.7 to 100), respectively. The median postoperative VAS pain score was 0 (range, 0 to 10). Forty-nine percent (36) of the 73 patients returned to their preoperative sports level, 14% (10) decreased their activity level in the same sport, 12% (9) changed sports, and 25% (18) decreased their level of activity and changed sports or stopped participating in sports altogether. Patients with ≥2 stabilization procedures prior to the Latarjet procedure demonstrated a lower likelihood of returning to their original sport (p = 0.019; relative risk = 2.84; 95% confidence interval = 1.34 to 6.06). The percentage of glenoid bone loss showed no association with the return-to-sport rate (p = 0.507). The outcome of the Latarjet procedure in high-risk contact or collision athletes is variable. Patients who have fewer prior stabilization surgical procedures are more likely to successfully return to their original sport. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


New picropodophyllin analogs via palladium-catalyzed allylic alkylation-Hiyama cross-coupling sequences.
Unsaturated malonyl esters underwent Pd-catalyzed intramolecular allylic alkylation to give 4-vinyl-substituted gamma-lactones. In contrast to the formerly studied cyclization of malonamides, this reaction could be achieved only with a substrate incorporating a suitably positioned silicon moiety, which directs the ionization toward the desired eta(3)-allylpalladium complex. The resulting 4-[dimethyl-(2-thienyl)silylvinyl]lactone could be subsequently engaged into Hiyama couplings with various iodoarenes, to give the corresponding 4-(alpha-styryl)-gamma-lactones. The use of a specifically substituted iodoarene generated an advanced tetracyclic lactone intermediate incorporating rings A-D of lignans belonging to the podophyllotoxin family. Subsequent electrophilic aromatic substitution with a variety of electron-rich arenes afforded the target picropodophyllin analogs.


Regioselective Rh(I)-catalyzed sequential hydrosilylation toward the assembly of silicon-based peptidomimetic analogues.
A highly regioselective Rh(I)-catalyzed hydrosilylation of enamides is presented. This mild protocol allows access to a wide variety of different arylsilanes with substitution at the β-position of the enamide and functionalization on the alkyl chain tethered to the silane. This protocol is extended to include a sequential one-pot hydrosilylation. Using diphenylsilane as the appendage point, hydrosilylation of a protected allyl alcohol followed by hydrosilylation of an enamide generates a complex organosilane in one step. This highly convergent strategy to synthesize these functionalized systems now provides a way for the rapid assembly of a diverse collection of silane-based peptidomimetic analogues.


The effect of patient reminders and gas station gift cards on patient adherence to testing guidelines for diabetes.
Analysis of the effectiveness of a small financial incentive and a written reminder to encourage test taking among persons with diabetes who have missed glycosylated hemoglobin (HbAlc) and low-density lipoprotein cholesterol (LDL-C) screenings. The analysis uses data from the University of Wisconsin Medical Foundation medical records of persons diagnosed with diabetes who had not received an HbA1c screening or had not received an LDL-C screening over the previous year (prior to October 2005). This study uses a quasi-experimental design comparing 464 diabetic patients (cases) who received a letter reminder of screening and financial incentive for undergoing screening, and 693 controls who did not receive a letter or financial incentive. The treated patients (464) all were seen in 1 of 4 clinics while those not treated used different clinics within the same system of care. Propensity scores served as the matching procedure using the following covariates: age, gender, ethnicity, marital status, number of HbA1c tests and number of LDL-C tests in the year prior to pilot program, mean HbA1c levels in the year prior to the pilot program (when available), census income data, and a comorbidity measure. During the 2 years following the pilot program, on average the target or "treated" population received significantly more screenings--3.34-compared to 2.69 screenings for the matched comparison group, and a far smaller proportion of the target population had no screening at all. The results provide evidence that a small financial incentive coupled with a written reminder work to increase test taking (especially the HbA1c screening) and suggest greater control of HbA1c levels among persons who had previously missed screenings.


Impulsive personality dimensions are associated with altered behavioral performance and neural responses in the monetary incentive delay task.
Individual differences in dimensions of impulsivity personality including disinhibition and sensation seeking modulate approach responses to reinforcing stimuli, such as drugs and money. The current study examined the effects of monetary incentive on both behavioral performance and electrophysiological activity among individuals varying in disinhibition and sensation seeking. The monetary incentive delay (MID) task was completed under electroencephalogram (EEG) recording. Behavioral data showed that higher disinhibition and sensation-seeking were associated with lower performance accuracy. Event-related potential (ERP) data showed that high reinforcement cues elicited a larger late positive component (LPC) than other conditions among high disinhibition participants, indicating its strong emotional influence. Additionally, in the neutral incentive condition, the feedback-related negativity (FRN) elicited by correct outcomes was larger than that elicited by incorrect outcomes in the high disinhibition group only. This novel finding indicates that high disinhibition participants were less likely to expect correct outcomes compared to incorrect outcomes in the neutral incentive condition. Finally, the P3 component elicited by outcome presentation showed an interaction between two impulsivity dimensions; when disinhibition level was low, the P3 was larger among high than low sensation seeking participants.


Methylamine reaction and denaturation-dependent fragmentation of complement component 3. Comparison with alpha2-macroglobulin.
Complement protein C-3 can covalently incoporate [14C]methylamine with a stoichiometry of 0.85 +/- 0.11 mol/mol of protein. The reactive site is located in the larger, Mr = 135,000 peptide subunit of C-3. The methylamine is incorporated as a derivative of glutamic acid, viz. as gamma-glutamylmethylamide, which was identified by high performance liquid chromatography and low resolution mass spectroscopy. C-3 was shown to undergo a specific, denaturation-dependent protein fragmentation in sodium dodecyl sulfate at 90 degrees C. The cleavage results in the partial conversion of the Mr = 135,000 subunit to fragments of Mr = 84,000 and 53,000. The cleavage is completely prevented by reaction of C-3 with methylamine prior to the 90 degrees C incubation. The site of methylamine incorporation (the glutamyl residue) and the peptide fragmentation reaction have been reported for alpha2-macroglobulin (Howard, J.B., Vermeulen, M., and Swenson, R. (1980) J. Biol. Chem. 255, 3820-3823). A comparison of the results for the two proteins suggests that they have a common reactive site.


Deletion of transcription factor binding motifs using the CRISPR/spCas9 system in the β-globin LCR.
Transcription factors play roles in gene transcription through direct binding to their motifs in genome, and inhibiting this binding provides an effective strategy for studying their roles. Here we applied the CRISPR/spCas9 system to mutate the binding motifs of transcription factors. Binding motifs for erythroid specific transcription factors were mutated in the locus control region hypersensitive sites of the human β-globin locus. Guide RNAs targeting binding motifs were cloned into lentiviral CRISPR vector containing the spCas9 gene, and transduced into MEL/ch11 cells carrying a human chromosome 11. DNA mutations in clonal cells were initially screened by quantitative PCR in genomic DNA and then clarified by sequencing. Mutations in binding motifs reduced occupancy by transcription factors in a chromatin environment. Characterization of mutations revealed that the CRISPR/spCas9 system mainly induced deletions in short regions of <20 bp and preferentially deleted nucleotides around the fifth nucleotide upstream of Protospacer adjacent motifs. These results indicate that the CRISPR/Cas9 system is suitable for mutating the binding motifs of transcription factors, and, consequently, would contribute to elucidate the direct roles of transcription factors.


Implications of the stereotyping and modification of sex role.
This article discusses and questions a study by Rekers and Lovaas (1974), which sought to "normalize" a young boy's sex-role behavior. The reasons given for treatment and the treatment itself are questioned. The ethical implications of the treatment and its outcome are then discussed, and alternative treatment procedures are suggested. Finally, the experimenters' description of the feminine sex-role is criticized.


Momentum transfer in nonequilibrium steady states.
When a Brownian object interacts with noninteracting gas particles under nonequilibrium conditions, energy dissipation associated with Brownian motion causes an additional force on the object as a "momentum transfer deficit." This principle is demonstrated first by a new nonequilibrium steady state model and then applied to several known models such as an adiabatic piston for which a simple explanation has been lacking.


Single-strand annealing between inverted DNA repeats: Pathway choice, participating proteins, and genome destabilizing consequences.
Double strand DNA breaks (DSBs) are dangerous events that can result from various causes including environmental assaults or the collapse of DNA replication. While the efficient and precise repair of DSBs is essential for cell survival, faulty repair can lead to genetic instability, making the choice of DSB repair an important step. Here we report that inverted DNA repeats (IRs) placed near a DSB can channel its repair from an accurate pathway that leads to gene conversion to instead a break-induced replication (BIR) pathway that leads to genetic instabilities. The effect of IRs is explained by their ability to form unusual DNA structures when present in ssDNA that is formed by DSB resection. We demonstrate that IRs can form two types of unusual DNA structures, and the choice between these structures depends on the length of the spacer separating IRs. In particular, IRs separated by a long (1-kb) spacer are predominantly involved in inter-molecular single-strand annealing (SSA) leading to the formation of inverted dimers; IRs separated by a short (12-bp) spacer participate in intra-molecular SSA, leading to the formation of fold-back (FB) structures. Both of these structures interfere with an accurate DSB repair by gene conversion and channel DSB repair into BIR, which promotes genomic destabilization. We also report that different protein complexes participate in the processing of FBs containing short (12-bp) versus long (1-kb) ssDNA loops. Specifically, FBs with short loops are processed by the MRX-Sae2 complex, whereas the Rad1-Rad10 complex is responsible for the processing of long loops. Overall, our studies uncover the mechanisms of genomic destabilization resulting from re-routing DSB repair into unusual pathways by IRs. Given the high abundance of IRs in the human genome, our findings may contribute to the understanding of IR-mediated genomic destabilization associated with human disease.


Mutational and clinical analysis of the ENG gene in patients with pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a rare vascular disorder characterized by a capillary wedge pressure ≤ 15 mmHg and a mean pulmonary arterial pressure ≥ 25 mmHg at rest. PAH can be idiopathic, heritable or associated with other conditions. The aim of this study was to analyze the Endoglin (ENG) gene and assess the influence of the c.572G > A (p.G191D) mutation in patients with idiopathic or associated PAH. The correlation between the pathogenic mutations and clinical and functional parameters was further analyzed. Sixteen different changes in the ENG gene were found in 44 out of 57 patients. After in silico analysis, we classified eight mutations as pathogenic in 16 of patients. The c.572G>A (p.G191D) variation was observed in ten patients, and the analysis for the splicing process using hybrid minigenes, with pSPL3 vector to assess splicing alterations, do not generate a new transcript. Age at diagnosis (p = 0.049) and the 6-min walking test (p = 0.041) exhibited statistically significant differences between carriers and non-carriers of pathogenic mutations. Patients with pathogenic mutations exhibited disease symptoms 8 years before non-carriers. Five patients with pathogenic mutations were carriers of another mutation in the BMPR2 or ACVRL1 genes. We present a series of PAH patients with mutations in the ENG gene, some of them not previously described, exhibiting clinical and hemodynamic alterations suggesting that the presence of these mutations may be associated with the severity of the disease. Moreover, genetic analysis in patients with PAH may be of clinical relevance and indicates the complexity of the genetic background.


The Elasticity Coefficients Measurement of Human Dentin Based on RUS.
This paper proposed to take advantages of resonant ultrasound spectroscopy (RUS) to measure the mechanical properties of human dentin specimen. The resonant spectroscopy of the dentin specimen was obtained between the frequency bands 155 and 575 kHz, and resonant frequencies were extracted by linear predictive filter and then by Levenberg-Marquardt method. By inverse problem approach, 13 experimental resonant frequencies progressively matched to the first 30 orders of theoretical resonant frequencies calculated by Lagrangian variational method. The full second-order elastic tensor of dentin specimen was adjusted. The whole set of human dentin engineering moduli, including Young's moduli (E11 = 22.641 GPa, E33 = 13.637 GPa), shear moduli (G12 = 10.608 GPa, G23 = 7.742 Gpa), and Poisson's ratios (ν12 = 0.067, ν31 = 0.378), were finally calculated. This study demonstrates that RUS can be successfully adapted to measure the mechanical properties of low quality factor biomaterials.


Mutant p53 in head and neck squamous cell carcinoma: Molecular mechanism of gain‑of‑function and targeting therapy (Review).
Head and neck squamous cell carcinoma (HNSCC) is one of the most widespread malignancies worldwide. p53, as a transcription factor, can play its role in tumor suppression by activating the expression of numerous target genes. However, p53 is one of the most commonly mutated genes, which frequently harbors missense mutations. These missense mutations are nucleotide substitutions that result in the substitution of an amino acid in the DNA binding domain. Most p53 mutations in HNSCC are missense mutations and the mutation rate of p53 reaches 65‑85%. p53 mutation not only inhibits the tumor suppressive function of p53 but also provides novel functions to facilitate tumor recurrence, called gain‑of‑function (GOF). The present study focused on the prevalence and clinical relevance of p53 mutations in HNSCC, and further described how mutant p53 accumulates. Moreover, mutant p53 in HNSCC can interact with proteins, RNA, and exosomes to exert effects on proliferation, migration, invasion, immunosuppression, and metabolism. Finally, several treatment strategies have been proposed to abolish the tumor‑promoting function of mutant p53; these strategies include reactivation of mutant p53 into wild‑type p53, induction of mutant p53 degradation, enhancement of the synthetic lethality of mutant p53, and treatment with immunotherapy. Due to the high frequency of p53 mutations in HNSCC, a further understanding of the mechanism of mutant p53 may provide potential applications for targeted therapy in patients with HNSCC.


IgA vasculitis update: Epidemiology, pathogenesis, and biomarkers.
Immunoglobulin A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is the most common systemic vasculitis in children, characterized by diverse clinical manifestations with a wide spectrum ranging from isolated cutaneous vasculitis to systemic involvement. The incidence of IgAV is geographically and ethnically variable, with a prevalence in autumn and winter, suggesting a driving role that genetic and environmental factors play in the disease. Although IgAV has a certain degree of natural remission, it varies widely among individuals. Some patients can suffer from severe renal involvement and even progress to end-stage renal disease. Its pathogenesis is complex and has not been fully elucidated. The formation of galactose-deficient IgA1 (Gd-IgA1) and related immune complexes plays a vital role in promoting the occurrence and development of IgAV nephritis. In addition, neutrophil activation is stimulated through the binding of IgA to the Fc alpha receptor I expressed on its surface, resulting in systemic vascular inflammation and tissue damage. Starting from the epidemiological characteristics, this article will review the role of immunological factors such as Gd-IgA1, autoantibodies, circulating immune complexes, complement system, cellular immunization, and the contributions of environmental and genetic factors in the pathogenesis of IgAV, and conclude with the major biomarkers for IgAV.


[Classification of the lung conditions in cases of perinatal death].
Comparability of morphological lung findings depends on the greatest possible consistency in assessment and verbal definition. It is for that purpose that a classification of perinatal pulmonary morphology is proposed, based on latest knowledge in foetal and paediatric pathology and established with due consideration of findings from clinical and physiological research as well as of the author's own experience. The findings have been subdivided into five main groups, each of them with several sub-groups, and have been pathomorphologically so characterised that the new classification can be easily used in prosector practice.


Loss of brain volume in endogenous Cushing's syndrome and its reversibility after correction of hypercortisolism.
Chronic exposure to excess glucocorticoids results in cognitive and psychological impairment. A few studies have indicated that cerebral atrophy can be found in patients with Cushing's syndrome (CS), but its evolution after cure has not been studied extensively. We report the presence of apparent cerebral atrophy in CS and its reversibility after the correction of hypercortisolism. Thirty-eight patients with CS, including 21 with Cushing's disease and 17 with adrenal CS were studied. The control groups consisted of 18 patients with other non-ACTH-secreting sellar tumors and 20 normal controls. Twenty-two patients with CS were reevaluated after cure. Subjective loss of brain volume was present in 86% of patients with Cushing's disease and 100% of patients with adrenal CS. The values for third ventricle diameter, bicaudate diameter, and subjective evaluation were significantly increased in CS groups in comparison with the control group (P < or = 0.001). Imaging reevaluated at 39.7 +/- 34.1 months after achieving eucortisolism showed an improvement of the third ventricle diameter (P = 0.001), bicaudate diameter (P < 0.0005), and subjective evaluation (P = 0.05). We conclude that brain volume loss is highly prevalent in CS and is at least partially reversible following correction of hypercortisolism.


Embryo-uterine interactions during early stages of pregnancy in domestic mammals.
The first part of this paper presents data concerning our knowledge of uterine proteins during early pregnancy in domestic mammals; the second part gives results of in vitro biochemical studies on embryo-uterine interactions in the ewe. We have developed an in vitro technique of the co-culture of ovine uterine epithelial cells with the blastocyst or its secretory proteins. The effects of a specific trophoblastic protein (oTPB), involved in the maintenance of the corpus luteum, have been particularly studied by this system. The modifications of endometrial protein synthesis have been measured by incorporation of radiolabelled amino acids and analysed by electrophoresis (SDS-PAGE or bidimensional). The results show that the presence of the blastocyst, or of its total secretory proteins or oTPB alone, decreased overall protein synthesis by the endometrial cells. The nature of the secreted proteins was apparently not affected by the blastocyst, but the addition of oTPB alone increased the production of 3 polypeptides (MW = 150.10(3); 74.10(3); 50.10(3) and pI = 7-8.2; 5.4-5.2; 6.4, respectively) and decreased the synthesis of 2 others (MW = 57.10(3); 35.10(3) and pI = 7-6.7; 5.3, respectively). We also studied the effects of co-culture with uterine cells on blastocyst DNA and protein synthesis. In no cases we obtained stimulation of blastocyst development during the co-culture period, and DNA or protein synthesis decreased in the presence of uterine cells. In conclusion, the presence of specific uterine proteins has been established in some domestic mammals (pig, rabbit) but not in all of them. Although local modifications of uterine protein synthesis are induced by the embryo or its secretory products, the nature and the role of the proteins which are affected need to be determined by further studies.


Characteristics of patients assessed for cognitive decline in primary healthcare, compared to patients assessed in specialist healthcare.
Objective: The aim of this study was to describe patients assessed for cognitive decline in primary healthcare, compared to patients assessed in specialist healthcare and to examine factors associated with depression.Design: This was an observational study.Setting: Fourteen outpatient clinics and 33 general practitioners and municipality memory teams across Norway.Subjects: A total of 226 patients assessed in primary healthcare and 1595 patients assessed in specialist healthcare outpatient clinics.Main outcome measures: Cornell scale for depression in dementia (CSDD), Mini-Mental Status Examination (MMSE), Clock drawing test, Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Instrumental Activities of Daily Living, Personal Self-Maintenance Scale, Relatives' stress scale (RSS), and Neuropsychiatric Inventory Questionnaire (NPI-Q)Results: Patients assessed in primary healthcare were older (mean age 81.3 vs 73.0 years), less educated, had poorer cognition (MMSE median 22 vs 25), more limitations in activities of daily living (ADL), more behavioural and psychological symptoms of dementia (BPSD), more depressive symptoms (CSDD median 7 vs 5), more often lived alone (60% vs 41%) and were more often diagnosed with dementia (86% vs 47%) compared to patients diagnosed in specialist healthcare. Depression was associated with female gender, older age, more severe decline in cognitive functioning (IQCODE, OR 1.65), higher caregiver burden (RSS, OR 1.10) and with being assessed in primary healthcare (OR 1.53).Conclusion: Post-diagnostic support tailored to patients diagnosed with dementia in primary healthcare should consider their poor cognitive function and limitations in ADL and that these people often live alone, have BPSD and depression.Key pointsPeople diagnosed in Norwegian primary healthcare had more needs than people diagnosed in specialist healthcare. • They were older, less educated, had poorer cognitive functioning and activity limitations, more often lived alone, and had more BPSD and depression. • Depression was associated with being female, older, having cognitive decline, being assessed in primary care and the caregiver experiencing burden • Post diagnostic support for people with dementia should be tailored to the individual's symptoms and needs.


Structural basis for gene regulation by a B12-dependent photoreceptor.
Photoreceptor proteins enable organisms to sense and respond to light. The newly discovered CarH-type photoreceptors use a vitamin B12 derivative, adenosylcobalamin, as the light-sensing chromophore to mediate light-dependent gene regulation. Here we present crystal structures of Thermus thermophilus CarH in all three relevant states: in the dark, both free and bound to operator DNA, and after light exposure. These structures provide visualizations of how adenosylcobalamin mediates CarH tetramer formation in the dark, how this tetramer binds to the promoter -35 element to repress transcription, and how light exposure leads to a large-scale conformational change that activates transcription. In addition to the remarkable functional repurposing of adenosylcobalamin from an enzyme cofactor to a light sensor, we find that nature also repurposed two independent protein modules in assembling CarH. These results expand the biological role of vitamin B12 and provide fundamental insight into a new mode of light-dependent gene regulation.


Chromosome damage, apoptosis, and necrosis in exfoliated cells of oral mucosa from androgenic anabolic steroids users.
The aim of this study was to evaluate the potential of the androgenic anabolic steroids (AAS) for inducing chromosome damage, apoptosis, and necrosis, using the micronucleus test on exfoliated cells from the oral mucosa of AAS users. The sample consisted of 55 male individuals, practitioners of physical exercise divided into two groups: 25 individuals who were users of AAS and 30 individuals in the control group. Cytological analysis included, in addition to micronuclei, counting of broken eggs and degenerative nuclear changes indicative of apoptosis (karyorrhexis, condensed chromatin, and pyknosis) and necrosis (karyolysis in addition to these changes). The statistical analysis did not show differences in occurrences of micronuclei, karyolysis, and broken eggs between the groups. The occurrence of apoptosis was significantly higher in cells from control subjects. The results obtained showed that inhibition of apoptosis was induced by AAS, suggesting that this may be one of the mechanisms contributing toward the association that has been described between use of AAS and the carcinogenic process.


[Mechanical stimulation of soles' support zones: non-invasive method of activation of generators of stepping movements in man].
The effects of mechanical stimulation of the soles' support zones in regimens of slow and fastwalking (75 and 120 steps per minute) were studied using the model of supportlessness (legs suspension). 20 healthy subjects participated in the study. EMG activity of hip and shin muscles was recorded. Kinematic of leg movements was assessed with the use of videoanalysis system. Support stimulation was followed by leg movements in 80% of cases, in 53% it was a locomotion-like movement. EMG bursts accompanied the movements. Involvement order and alteration of bursts in muscles were similar to voluntary walking. EMG activity occurred with a delay of 5.17 ± 1.08 seconds for hip muscles and 14.01 ± 2.82 seconds for shin muscles, frequency of bursts differed from stimulation frequency. Support stimulation was followed by leg movements in 80% of cases, in 53% of which they had characteristics of locomotions being accompanied by the burst-like electromyographic activities. Involvement order of the leg muscles and organization of antagonistic muscles activities were analogous to that of voluntary walking. The latencies of electromyographic activity in hip muscles composed 5.17 ± 1.083 s and 14.01 ± 2.82 s - for shin muscles, frequency of bursts differed significantly from stimulation frequency. In 31% of cases the electromyographical activity following the stimulation of the soles' support zones was not burst-like. Its amplitude rose smoothly reaching a certain level that was subsequently maintained. Results of the study showed that soles' support zones stimulation in regimen of locomotion can activate a locomotor generator and that effect evoked by this stimulation includes not only rhythmical but also non-rhythmical (probably postural) components of walking.


An in vitro model of human placental trophoblast deportation/shedding.
Deportation of trophoblast shed from the placenta into the maternal circulation was first described over 100 years ago. Despite this, little is known about the quantity or nature of the shed and deported trophoblasts. Neither do we have a clear understanding of the fate of deported trophoblasts nor do we have a clear understanding of their effects on the maternal physiology. This deficiency is largely due to the inaccessibility of deported trophoblasts in vivo. This study aimed to produce a model that would allow us to study deported trophoblasts. We devised a system for culturing placental explants of 12-week gestation in cell culture inserts with a stainless steel mesh bottom that allowed the ready harvesting of shed/deported trophoblasts. Immunohistochemical and morphologic investigations demonstrated that these in vitro shed/deported trophoblasts are similar to those found in vivo and that apoptotic, necrotic and viable trophoblasts were shed from the explants. Inhibiting caspases induced a change from predominantly apoptotic to predominantly necrotic trophoblast shedding. We have devised an in vitro model that allows the collection of shed/deported trophoblasts which will significantly enhance our ability to study these cells. Our preliminary investigations confirm that apoptosis plays an important role in trophoblast shedding/deportation.


[A cross-sectional study on relationships between daily physical activity and concentration of serum cholesterol and body mass index in fifth grade elementary schoolchildren and their parents].
The purpose of this study was to estimate the effects of daily physical activity on serum total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C), body mass index (BMI) and atherogenic index (AI) in 240 fifth grade schoolchildren, their 174 fathers and 212 mothers. Information on daily physical activity was obtained by inquiry with a questionnaire and was also measured directly with a device sensing acceleration of physical movement. In schoolchildren, effect of physical activity on TC, HDL-C and AI was not apparent, but that on BMI was shown. In adult men, HDL-C differed by job classification and increased as the degree of physical labor increased from desk work to light and heavy work. Strength of physical activity using the quotient of total amount of measured physical activity divided by body weight had a significant positive correlation with serum HDL-C (r = 0.20, p < 0.05) and significant negative correlation with AI (r = -0.18, p < 0.05) in adult men. In adult women, daily physical activity did not have a significant correlation to TC, HDL-C, AI or BMI. These results appear to suggest that the effect of daily physical activity on serum cholesterol, AI, BMI of schoolchildren and adult women was smaller than that for adult men.


Resveratrol Supported on Magnesium DiHydroxide (Resv@MDH) Represents an Oral Formulation of Resveratrol With Better Gastric Absorption and Bioavailability Respect to Pure Resveratrol.
Resveratrol attracts great interest because of the plethora of in vitro effects at the micromolar concentration range. Unfortunately, these effects are difficult to establish in vivo, due to the low concentration of resveratrol reached. This discrepancy is due to the molecules low solubility in water that favors the propensity for an intestinal absorption rather than in the gastric compartment. To address these challenges, we developed a Solid Dispersion of Resveratrol Supported by Magnesium Di Hydroxide formulation (Resv@MDH). This formulation displays increased water solubility and better bioavailability relative to pure resveratrol in the rabbit animal model. In our study, we evaluated the pharmacokinetics profile of resveratrol in six healthy human subjects following 180 mg of oral resveratrol administration, derived from Resv@MDH or pure resveratrol. Free resveratrol was evaluated in the whole blood sample by using HPLC - MS/MS. In comparison with pure resveratrol that displays an increase of the maximum plasma concentration, Cmax at about 90 min and 2 μM, Resv@MDH displays an earlier peak of resveratrol concentration with an increase of Cmax at about 30 min and 6 μM. The different kinetics suggest a main gastric route for resveratrol absorption from Resv@MDH, where, because of its improved dissolution rate, there seems to be a higher propensity for an acidic environment, as opposed to that with pure resveratrol. This conclusion is also supported by the numerical simulation analysis, which considers the principal steps during the oral route administration. Moreover, there is a 2-fold increase in the amount of free resveratrol with respect to pure resveratrol confirming a better bioavailability observed in the animal model. The characteristic feature of the pharmacokinetic profile of Resv@MDH implies that the beneficial properties of resveratrol in human health should be capitalized on it.


Isolated right ventricular infarction mimicking anterior myocardial infarction presenting with cardiogenic shock.
This is a rare case of an isolated right ventricular infarction (RVI), presenting with cardiogenic shock and an electrocardiograph (ECG) mimicking a large anterior myocardial infarction. The patient was treated successfully with primary percutaneous coronary intervention to a sub-totally occluded co-dominant right coronary artery (RCA).


The Kі-67 marker for assessing the effectiveness of systemic or regional neoadjuvant polychemotherapy in patients with locally advanced breast cancer.
Over the past decades, breast cancer (BC) is the most common cancer and one of the key causes of mortality and disability among women in developed countries. Determination of the role of Ki-67 index in assessing the quality of neoadjuvant polychemotherapy treatment using regional or systemic delivery routes of pharmacological agents in patients with locally advanced breast cancer (LABC). The retrospective analysis of 30 clinical trials of LABC treatment based on selective intra-arterial therapy in patients with BC (T4A-DN0-3M0) was used. The decrease in Ki-67 level in LABC after selective intra-arterial polychemotherapy was more pronounced than after systemic polychemotherapy. No correlation of the tumor metastatic potential with a Ki-67 level was detected. Assessment of Ki-67 expression allows to evaluate effectively the biological properties of the tumor, predict the course of the disease and choose the optimal tactics of neoadjuvant polychemotherapy (regional or systemic variant) as part of integrated antitumor treatment.


Impairment in quality of life is directly related to the level of allergen exposure and allergic airway inflammation.
Allergic disease has been shown to impair health-related quality of life (HRQL). The relationship between HRQL and either allergen exposure or allergic inflammation has not been previously assessed. To assess the relationship between HRQL and both grass pollen exposure and airway inflammation using the Paediatric Allergic Disease Quality of Life Questionnaire (PADQLQ). This is a novel questionnaire previously developed to assess the multi-system aspects of allergic disease. Eighty-four subjects, aged 6-17 years, with seasonal allergic rhinoconjunctivitis, asthma and/or cutaneous manifestations were assessed before and during the grass pollen season. They were assessed with the PADQLQ, a visual analogue scale (VAS) to assess quality of life, symptom diary and exhaled nitric oxide (FENO). HRQL, as measured by the PADQLQ, significantly correlated with the average pollen count in the previous week (regression coefficient 0.038, 95% confidence interval (CI) 0.027-0.049, P<0.001). The PADQLQ score was also found to be significantly associated with airway inflammation as measured by FENO (regression coefficient 0.410, 95% CI 0.175-0.646, P=0.001). Additionally, PADQLQ showed a high degree of correlation with symptom scores and quality of life as measured by a VAS, good within-subject reliability and a small minimal important difference (0.20, 95% CI -0.09 to 0.49 on a seven-point scale). HRQL is related to both allergen load and allergic inflammation and the PADQLQ has excellent cross-sectional and longitudinal validity with respect to quality of life and symptoms.


Oxygen transfer and plant-wide energy assessment of primary screening in WRRFs.
Primary screening is gaining interest as a method to achieve removal performances comparable to primary clarification while reducing the footprint and increasing operational elasticity. Aeration efficiency indicators in a pilot sequential batch reactor (SBR) and a full scale water resource recovery facility (WRRF) were investigated after the implementation of rotating belt filters/screens (RBF). To compare the impact between screened (350 μm) and nonscreened primary influent, two identical treatment lines were monitored using off-gas and respirometric measurements. The study provides the first result on improved oxygen transfer efficiency due to primary screening. Consistent aeration efficiency improvements of 27% and 20% between screened and nonscreened were obtained at pilot and full scale, respectively. Changes in aeration efficiency and carbon redirection were integrated into a set of models to investigate the primary screening impact on the WRRF energy balance. While the plant-wide assessment for different scenarios improved the energy balance up to 15%, a detailed comparative analysis between various treatment schemes gained insight into the advantages and limitations of the energetic sustainability of primary screening. PRACTITIONER POINTS: Aeration efficiency improved 27% at pilot scale Aeration efficiency improved 20% at full scale. Use of primary screening can improve the energy balance up to 15 Assessment of advantages and limitations of primary screening.


Intra-arterial ethanol embolization augments response to TACE for treatment of HCC with portal venous tumor thrombus.
The prognosis of hepatocellular carcinoma with portal vein tumor thrombus remains extremely poor. This pilot study aimed to evaluate the technical feasibility, effectiveness and safety of transcatheter chemoembolization for tumors in the liver parenchyma plus intra-arterial ethanol embolization for portal vein tumor thrombus. A pilot study was carried out on 31 patients in the treatment group (transcatheter chemoembolization plus intra-arterial ethanol embolization) and 57 patients in the control group (transcatheter chemoembolization alone). Enhanced computed tomography/magnetic resonance images were repeated 4 weeks after the procedure to assess the response. Overall survival and complications were assessed until the patient died or was lost to follow-up. Median survival was 10.5 months in the treatment group (2.4 ± 1.7 courses) and 3.9 months in the control group (1.9 ± 1 courses) (P = 0.001). Patients in the treatment group had better overall survival (at 3, 6 and 12 months, respectively), compared to patients in the control group (90.3% vs. 59.6%, 64.5% vs. 29.8%, and 41.9% vs. 10.6%; p = 0.001). Furthermore, the rate of portal vein tumor thrombus regression was higher in the treatment group (93.1%) than in the control group (32.1%) (P < 0.001). Based on the results of this study, transcatheter chemoembolization combined with intra-arterial ethanol embolization may be more effective than transcatheter chemoembolization alone for treating hepatocellular carcinoma with portal vein tumor thrombus. Intra-arterial ethanol embolization for treating portal vein tumor thrombus is safe, feasible and prolongs overall survival.


Heparin-induced thrombocytopenia: clinical presentations and therapeutic management.
With increasing indications for heparin usage, an understanding of heparin-induced thrombocytopenia (HIT) as a complication of heparin therapy is more essential than ever. Complications of HIT can result in significant morbidity and mortality. We review the clinical presentations of HIT, laboratory and diagnostic workup, and treatment agents available or being evaluated.


Mortality differences by surgical volume among patients with stomach cancer: a threshold for a favorable volume-outcome relationship.
Many studies have assessed the volume-outcome relationship in cancer patients, but most focused on better outcomes in higher volume groups rather than identifying a specific threshold that could assist in clinical decision-making for achieving the best outcomes. The current study suggests an optimal volume for achieving good outcome, as an extension of previous studies on the volume-outcome relationship in stomach cancer patients. We used National Health Insurance Service (NHIS) Sampling Cohort data during 2004-2013, comprising healthcare claims for 2550 patients with newly diagnosed stomach cancer. We conducted survival analyses adopting the Cox proportional hazard model to investigate the association of three threshold values for surgical volume of stomach cancer patients for cancer-specific mortality using the Youden index. Overall, 17.10% of patients died due to cancer during the study period. The risk of mortality among patients who received surgical treatment gradually decreased with increasing surgical volume at the hospital, while the risk of mortality increased again in "high" surgical volume hospitals, resulting in a j-shaped curve (mid-low = hazard ratio (HR) 0.773, 95% confidence interval (CI) 0.608-0.983; mid-high = HR 0.541, 95% CI 0.372-0.788; high = HR 0.659, 95% CI 0.473-0.917; ref = low). These associations were especially significant in regions with unsubstantial surgical volumes and less severe cases. The optimal surgical volume threshold was about 727.3 surgical cases for stomach cancer per hospital over the 1-year study period in South Korea. However, such positive effects decreased after exceeding a certain volume of surgeries.


In Situ Kinetic and Thermodynamic Growth Control of Au-Pd Core-Shell Nanoparticles.
One-pot wet-chemical synthesis is a simple way to obtain nanoparticles (NPs) with a well-defined shape and composition. However, achieving good control over NP synthesis would require a comprehensive understanding of the mechanisms of NP formation, something that is challenging to obtain experimentally. Here, we study the formation of gold (Au) core-palladium (Pd) shell NPs under kinetically and thermodynamically controlled reaction conditions using in situ liquid cell transmission electron microscopy (TEM). By controlling the reaction temperature, we demonstrate that it is possible to tune the shape of Au nanorods to Au-Pd arrow-headed structures or to cuboidal core-shell NPs. Our in situ studies show that the reaction temperature can switch the Pd shell growth between the kinetically and thermodynamically dominant regimes. The mechanistic insights reported here reveal how the reaction temperature affects the packing of the capping agents and how the facet selection of depositing shell atoms drives the shell formation under different kinetic conditions, which is useful for synthesizing NPs with greater design flexibility in shape and elemental composition for various technological applications.


Effective Removal of Noisy Data Via Batch Effect Processing.
In order to have faith in the analysis of data, a key factor is to have confidence that the data is reliable. In the case of microRNA, reliability includes understanding the collection methods, ensuring that the analysis is appropriate, and ensuring that the data itself is accurate. A key element in ensuring data accuracy is the removal of noise. While there can be several sources of noise, a common source of noise is the batch effect, which can be defined as systematic variability in the data caused by non-biological factors. This chapter will present various techniques designed to remove variability caused by batch effects and the potential effectiveness.


Use of high-throughput in vitro toxicity screening data in cancer hazard evaluations by IARC Monograph Working Groups.
Evidence regarding carcinogenic mechanisms serves a critical role in International Agency for Research on Cancer (IARC) Monograph evaluations. Three recent IARC Working Groups pioneered inclusion of the US Environmental Protection Agency (EPA) ToxCast program high-throughput screening (HTS) data to supplement other mechanistic evidence. In Monograph V110, HTS profiles were compared between perfluorooctanoic acid (PFOA) and prototypical activators across multiple nuclear receptors. For Monograph V112-113, HTS assays were mapped to 10 key characteristics of carcinogens identified by an IARC expert group, and systematically considered as an additional mechanistic data stream. Both individual assay results and ToxPi-based rankings informed mechanistic evaluations. Activation of multiple nuclear receptors in HTS assays showed that PFOA targets not only peroxisome proliferator activated receptors, but also other receptors. ToxCast assays substantially covered 5 of 10 key characteristics, corroborating literature evidence of "induces oxidative stress" and "alters cell proliferation, cell death or nutrient supply" and filling gaps for "modulates receptor-mediated effects." Thus, ToxCast HTS data were useful both in evaluating specific mechanistic hypotheses and in contributing to the overall evaluation of mechanistic evidence. However, additional HTS assays are needed to provide more comprehensive coverage of the 10 key characteristics of carcinogens that form the basis of current IARC mechanistic evaluations.


Thymic epithelial cell transplantation in patients with acquired immunodeficiency syndrome. Evidence for infection by HIV-I of newly differentiated T cells at the site of transplantation.
From October 1983 to July 1984, 11 adult AIDS patients have received single or repeated thymic grafts. All have had opportunistic infections and 3 also had Kaposi's sarcoma. Thymic tissue from infants undergoing cardiac surgery was cultured to provide a thymocyte- and fibroblast-free epithelial cell inoculum. 18-21 days post-explantation, cells and explants were injected intraperitoneally, intramuscularly or intrahepatically. Transplants were well tolerated in all cases. In 7 cases liver biopsy was performed at the time of grafting and 2 months later. Ten patients have died after a mean survival time following transplantation of 8.7 months while 1 patient was lost to follow up. Clinical improvement and absence of new opportunistic infections were apparent for 4 months following transplantation. Partial immunoreconstitution was evidenced by an increase in peripheral blood lymphocytes (8 of 10 cases) and lymphocyte subsets (7 of 10 cases) as well as by presence of T4 and T8 positive cells in the liver (5 of 7 cases). In 5 of 7 patients, double-staining immunofluorescence showed that HIV-I antigens were present in T4-phenotype cells, at the site of the graft, 2 months after grafting, but were not detected in the liver at the time of grafting. Transient immunoreconstitution, therefore, maybe related to destruction of newly differentiated T lymphocytes.


Frequency and predictors of autonomic dysfunction in Parkinson's disease: a study of African patients in Lagos, Nigeria.
The degenerative changes in PD also affect the autonomic nervous system. The frequency and predictors of such involvement in Africans with PD has not been reported. i) To determine the frequency and type of autonomic dysfunction in Nigerians with idiopathic Parkinson's disease (PD). ii) To determine the predictors of autonomic dysfunction in PD. Cardiovascular autonomic function assessed in 33 study subjects with PD and 33 age-matched controls, utilising heart rate variability to deep breathing, standing and the Valsalva manoeuvre, and the blood pressure (BP) response to standing. The results were compared based on treatment category, grade of severity on the Columbia scale of Hoehn and Yahr, duration of PD, age at onset of PD, present age and occurrence of autonomic symptoms. Parasympathetic function was abnormal in 51.5% of PD subjects, significantly higher than controls (P<0.001). Of these, 76.5% had early parasympathetic involvement and 23.5% definite parasympathetic involvement. Age above 65 years (at time of study or onset of PD) was the only clinical variable associated with parasympathetic autonomic dysfunction (p<0.05). Symptoms dysfunction occurred in 60.6% of PD patients and only 6.1% of controls (p<0. 001). There was however no demonstrable relationship between the occurrence of symptoms and objective evidence of autonomic dysfunction: 41.2% of PD patients with parasympathetic dysfunction had no symptoms. Autonomic dysfunction was found to be common in Africans with PD, particularly those above 65 years and tends to affect the parasympathetic system. However, the abnormality may be detectable even before symptoms appear. As such, we recommend that cardiovascular tests of autonomic function be a routine aspect of the evaluation of PD patients, especially with advancing age.


Characterisation of seeds of a C4 phosphoenolpyruvate carboxylase-deficient mutant of Amaranthus edulis.
Seeds from the C(4) plant Amaranthus edulis were studied as part of the characterisation of a mutant (designated LaC(4) 2.16), which contains reduced amounts (5% of wild type) of the photosynthetic leaf form of phosphoenolpyruvate carboxylase (PEPC). On a per seed basis, the amount of PEPC activity was not significantly altered, while the weight and protein content of the mutant seeds were 34% lower than that of the wild type. Western gel blot analysis detected two PEPC polypeptides with molecular masses of 105 kDa (minor) and 100 kDa (major). The determination of in vitro phosphorylation in reconstituted assays revealed the presence of both calcium-dependent and calcium-independent PEPC-kinase activities in protein extracts of wild-type and mutant seeds. However, PEPC proteins were phosphorylated in dry seeds, and PEPC phosphorylation did not occur in vivo during seed imbibition in the presence of (32) P-phosphate. In contrast, (32) P-phosphate was incorporated into a range of proteins in wild-type seeds, but not in mutant seeds. In addition, ATP content was much reduced in germinating mutant seeds and this did not increase following the supply of phosphate. Collectively, these data suggest that the deficiency in C(4) PEPC in mutant A. edulis leaves has no effect on C(3) -type PEPC content and phosphorylation state in seeds, but causes impairment of energy production, thereby accounting for the reduced germination of the mutant.


A novel flow injection amperometric method for sensitive determination of total antioxidant capacity at cupric-neocuproine complex modified MWCNT glassy carbon electrode.
A novel amperometric method is presented for the determination of total antioxidant capacity in flow injection analysis (FIA) system using copper(II)-neocuproine complex modified on Nafion-functionalized multi-walled carbon nanotube-glassy carbon electrode ([Cu(Ncp)22+]/Nf@f-MWCNT/GCE). Cyclic voltammetric studies showed that the modified electrode exhibits a very well-formed reversible redox couple for Cu(II)-/Cu(I)-complex. In addition, the [Cu(Ncp)22+]/[Cu(Ncp)2+] redox pair shows very good electrocatalytic activity towards the oxidation of polyphenolic compounds (PPhCs) such as trolox, catechin, and quercetin due to the enhancement of the anodic peak current of the redox couple in the presence of these analytes. This electrocatalytic oxidation current at the [Cu(Ncp)22+]/Nf@f-MWCNT/GCE was used for flow injection (FI) amperometric determination of PPhCs. FI amperometric-time curves recorded under optimized conditions (applied potential: + 0.6 V vs. Ag/AgCl/KCl(0.10 M), flow rate: 2 mL/min) showed that the proposed electrode had a wide linear range (LR) with a very low detection limit (LOD) for PPhCs. LR and LOD were 0.5-800 and 0.2 µM for trolox, respectively and 0.50-250 and 0.14 µM, respectively, for both quercetin and catechin. This sensitive method was successfully applied to the amperometric measurement of total antioxidant capacity (TAC) of some herbal teas, giving compatible results with the spectrophotometric CUPRAC method. The proposed method gave higher rank to fast-reacting antioxidants; it was equally precise but had a wider linear range and lower LOD than the spectrophotometric CUPRAC assay (e.g., LOD for ascorbic acid and gallic acid were 0.07 and 0.08 μM, respectively), and similar electroanalytical methods using the CUPRAC reagent.


Helicobacter pylori infection is unlikely to be transmitted between partners: evidence from genotypic study in partners of infected patients.
We postulated that the oro-oral route of transmission between spouses could be an important route of transmission of Helicobacter pylori. To estimate the prevalence of different genotypes of H. pylori as distinguished by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in our local population, and to compare the genotypes of H. pylori isolated from patients and their spouses. Gastric biopsies were obtained from 183 dyspeptic patients during endoscopy. PCR for H. pylori was carried out using the uceC gene for amplification, and PCR products were digested further for RFLP analysis using the enzyme MboI. Spouses of H. pylori-positive index cases were screened for the infection using serological testing; if found to be positive serologically, endoscopy and gastric biopsies were performed for genotypic study of the micro-organism. For couples with indistinguishable H. pylori strain on RFLP with restriction endonuclease MboI, the process of RFLP was repeated with digestion of the PCR products using restriction endonuclease HhaI. We established our PCR technique to be 89.5% sensitive and 95.5% specific. Eighty-nine subjects were found to be H. pylori positive by PCR, and eight different genotypic strains were found according to our RFLP analysis. Two genotypes accounted for 80.8% of the cases. Sixteen of 31 spouses tested serologically for H. pylori were positive. All 13 spouses who agreed to undergo endoscopy were PCR positive for H. pylori. Five couples shared indistinguishable H. pylori genotypes, but this strain was also the commonest genotype in our local population, as based on RFLP with restriction endonuclease MboI. Further RFLP on the PCR products on these five couples using restriction endonucleases HhaI showed that the H. pylori isolated from these five couples were of different strains. The oro-oral route of transmission between spouses is unlikely to be an important mode for H. pylori infection.


Philosophical underpinnings of intersubjectivity and its significance to phenomenological research: A discussion paper.
Intersubjectivity is the proposition that human experience occurs in a world of shared and embodied understandings, mediated by culture and language. Nursing is fundamentally relational, and nursing research stems from an exchange between participants and researchers and indeed around the transaction of the patient and the nurse in the intersubjective space of clinical settings. Through the philosophical standpoints of Husserl, Merleau-Ponty, Heidegger, and Gadamer we examine these differing philosophical constructs of intersubjectivity and the contribution of these positions to phenomenological nursing inquiry. Particular framings of intersubjectivity should influence the way researchers interact with their participants and data so that the chosen philosophy sits coherently within a research plan and methodology. This exploration of philosophical standpoints is extended through examples of, and reflections upon, the authors' experiences of intersubjectivity in our published phenomenological nursing studies and through dynamic interactions that characterise interpretive activities within a research team.


State-to-state rotational relaxation rate constants for CO+Ne from IR-IR double-resonance experiments: comparing theory to experiment.
IR-IR double-resonance experiments were used to study the state-to-state rotational relaxation of CO with Ne as a collision partner. Rotational levels in the range Ji=2-9 were excited and collisional energy transfer of population to the levels Jf=2-8 was monitored. The resulting data set was analyzed by fitting to numerical solutions of the master equation. State-to-state rate constant matrices were generated using fitting law functions. Fitting laws based on the modified exponential gap (MEG) and statistical power exponential gap (SPEG) models were used; the MEG model performed better than the SPEG model. A rate constant matrix was also generated from scattering calculations that employed the ab initio potential energy surface of McBane and Cybulski [J. Chem. Phys. 110, 11 734 (1999)]. This theoretical rate constant matrix yielded kinetic simulations that agreed with the data nearly as well as the fitted MEG model and was unique in its ability to reproduce both the rotational energy transfer and pressure broadening data for Ne-CO. The theoretical rate coefficients varied more slowly with the energy gap than coefficients from either of the fitting laws.


ESTIMATION OF GENE FLOW AND GENETIC NEIGHBORHOOD SIZE BY INDIRECT METHODS IN A SELFING ANNUAL, TRITICUM DICOCCOIDES.
Rates of gene flow and neighborhood area were investigated in the selfing annual, Triticum dicoccoides. The collection of seed material was made using a spatial hierarchical sampling design in which four collection sites were 5-7 m apart, four were 15-17 m apart, and four were 100-120 m apart. Between 25 and 30 plants were scored from each site (mean sample size = 28.7). Two procedures for indirect estimation of gene flow were used on gene-frequency data from 13 polymorphic loci. The estimates of Nm using Wright's (1943a, 1943b) estimation procedure were 1.265, 0.212, and 0.357, for the closest, intermediate, and most distant distance classes, respectively. The estimates of Nm using Slatkin's (1985) private-allele procedure were 4.675 (subsample ranges: 1.544-4.675), 0.110 (subsample ranges: 0.069-0.153), and 0.670 (subsample ranges: 0.129-0.256). The results indicate a general agreement between the two procedures. Both indicate a sharp decrease in gene flow beyond the first distance class (5-7 m). The large gene-flow values and the large variation within the 5-7-m distance class are taken as evidence that a genetic neighborhood for this species may cover an area defined by a 5-m radius. The results also indicate that gene flow between populations separated by only 10 or more meters may be quite limited.


Oxidative DNA Damage and Apoptosis Induced by Aclarubicin, an Anthracycline: Role of Hydrogen Peroxide and Copper.
This study aimed to investigate aclarubicin (ACR)-induced oxidative DNA damage and apoptosis. ACR-induced apoptosis was analyzed using HL-60 leukemia cells and HP100 cells, hydrogen peroxide (H2O2)-resistant cells derived from HL-60 cells. ACR-induced DNA damage was analyzed using plasmid DNA. HL-60 cells were more sensitive to ACR than HP100 cells. In HP100 cells, DNA ladder formation and caspase-3/7 activity induced by ACR were suppressed or delayed in comparison to those in HL-60 cells. ACR-induced DNA damage occurred in the presence of Cu(II), and scavenger experiments showed that the reactive species causing DNA damage appeared to be generated from H2O2 and Cu(I). Moreover, we detected intracellular Cu(I) induced by ACR in HL-60 cells, using CopperGREEN™, a fluorescent probe for detection of Cu(I) ion specifically. ACR-induced DNA damage and apoptosis can be accounted for by the involvement of H2O2 and Cu(I).


The evolution of an uncemented acetabular component in alumina-on-alumina total hip arthroplasty has improved clinical outcome: a prospective, comparative five- to 15-year follow-up study.
To determine the effect of a change in design of a cementless ceramic acetabular component in fixation and clinical outcome after total hip arthroplasty PATIENTS AND METHODS: We compared 342 hips (302 patients) operated between 1999 and 2005 with a relatively smooth hydroxyapatite coated acetabular component (group 1), and 337 hips (310 patients) operated between 2006 and 2011 using a similar acetabular component with a macrotexture on the entire outer surface of the component (group 2). The mean age of the patients was 53.5 (14 to 70) in group 1 and 53.0 (15 to 70) in group 2. The mean follow-up was 12.7 years (10 to 17) for group 1 and 7.2 years (4 to 10) for group 2. No hips were revised due to complications related to bearing fracture or to stem loosening. A total of 15 acetabular components were revised for aseptic loosening in group 1 and two in group 2. The survival rate for acetabular component aseptic loosening at eight years was 96.8% (95% confidence interval (CI) 94.8 to 98.7) for group 1 and 99.2% (95% CI 98.0 to 100) for group 2. The risk for aseptic loosening of the acetabular component was higher in group 1 (p = 0.04, Hazard Ratio (HR) 4.99), dysplastic acetabula (p = 0.01, HR 4.12), components outside Lewinnek´s zone (p < 0.001, HR 6.13) and in those with a hip rotation centre distance greater than 5 mm (p = 0.005, HR 4.09). Alumina ceramic-on-ceramic THA is an excellent option for young patients. Although newer components appeared to improve fixation, acetabular reconstruction is essential to obtain a satisfactory outcome. Cite this article: Bone Joint J 2017;99-B:749-58.