Computational visual ecology in the pelagic realm.
Visual performance and visual interactions in pelagic animals are notoriously hard to investigate because of our restricted access to the habitat. The pelagic visual world is also dramatically different from benthic or terrestrial habitats, and our intuition is less helpful in understanding vision in unfamiliar environments. Here, we develop a computational approach to investigate visual ecology in the pelagic realm. Using information on eye size, key retinal properties, optical properties of the water and radiance, we develop expressions for calculating the visual range for detection of important types of pelagic targets. We also briefly apply the computations to a number of central questions in pelagic visual ecology, such as the relationship between eye size and visual performance, the maximum depth at which daylight is useful for vision, visual range relations between prey and predators, counter-illumination and the importance of various aspects of retinal physiology. We also argue that our present addition to computational visual ecology can be developed further, and that a computational approach offers plenty of unused potential for investigations of visual ecology in both aquatic and terrestrial habitats.


Association of AXL and PD-L1 Expression with Clinical Outcomes in Patients with Advanced Renal Cell Carcinoma Treated with PD-1 Blockade.
A minority of patients currently respond to single-agent immune-checkpoint blockade (ICB), and strategies to increase response rates are urgently needed. AXL is a receptor tyrosine kinase commonly associated with drug resistance and poor prognosis in many cancer types, including in clear-cell renal cell carcinoma (ccRCC). Recent experimental cues in breast, pancreatic, and lung cancer models have linked AXL with immune suppression and resistance to antitumor immunity. However, its role in intrinsic and acquired resistance to ICB remains largely unexplored. In this study, tumoral expression of AXL was examined in ccRCC specimens from 316 patients who were metastatic receiving the PD-1 inhibitor nivolumab in the GETUG AFU 26 NIVOREN trial after failure of antiangiogenic therapy. We assessed associations between AXL and patient outcomes following PD-1 blockade, as well as the relationship with various markers, including PD-L1; VEGFA; the immune markers CD3, CD8, CD163, and CD20; and the mutational status of the tumor-suppressor gene von Hippel-Lindau (VHL). Our results show that high AXL-expression level in tumor cells is associated with lower response rates and a trend to shorter progression-free survival following anti-PD-1 treatment. AXL expression was strongly associated with tumor-PD-L1 expression, especially in tumors with VHL inactivation. Moreover, patients with tumors displaying concomitant PD-L1 expression and high AXL expression had the worst overall survival. Our findings propose AXL as candidate factor of resistance to PD-1 blockade, and provide compelling support for screening both AXL and PD-L1 expression in the management of advanced ccRCC.See related commentary by Hahn et al., p. 6619.


Validity of transactional analysis and emotional intelligence in training nursing students.
Emotional intelligence (EI) is considered a critical component of a nurse's characteristic trait which is known as a significant predictor of a person's job performance and life success. Transactional Analysis (TA) plays a fundamental role in nurse-patient communication and managing emotions during difficult dialect with patients. The aim of this review is to discuss the framework of EI and TA, and how the combined theories can be utilized to further educate nurses and enhance the patient's experience. Exploring the idea of combining EI, TA, and other theories and adding these addendums to the nursing curriculum may advance the empathy and communication skills of nursing students. The method used in this review is a literature search using databases, such as Medline, EBSCO, and Google Scholar, etc. to form a critical discussion of this area. Key words such as emotional intelligence, transactional analysis, nursing curriculum, and relating theoretical models were used to identify applicable documents. Four studies involving EI and TA were sampled. A combination of data collection tools, such as lecture series and intervention programs, were used to authenticate the results. Other instruments used were ego state questionnaires, empathy, and five point Likert scales. No study design or type of literature was excluded in healthcare to substantiate the application of EI and TA into the nursing curriculum. Sixteen nurses attended a six-week psycho-education program using communication and empathy scales, and patient satisfaction surveys to improve their empathetic and communication skills. The result of the mean communication score (177.8±20) increased to (198.8±15) after training (p=0.001). The empathy score increased from 25.7±7 to 32.6±6 (p=0.001). The overall result reflects that training can improve emergency nurse's communication and empathy skills. The data suggests there are under-researched theories with futuristic topics that have value to the nursing community. Suitable evaluation of these theories is vital to nursing education. Implementation and training for nursing students and existing nurses may help shift the culture of medical education ahead by creating a more educated and empathetic work environment.


Inhaled nitric oxide therapy for pulmonary disorders of the term and preterm infant.
The 21st century began with the FDA approval of inhaled nitric oxide therapy for the treatment of neonatal hypoxic respiratory failure associated with pulmonary hypertension in recognition of the 2 randomized clinical trials demostrating a significant reduction in the need for extracorporeal support in the term and near-term infant. Inhaled nitric oxide is one of only a few therapeutic agents approved for use through clinical investigations primarily in the neonate. This article provides an overview of the pertinent biology and chemistry of nitric oxide, discusses potential toxicities, and reviews the results of pertinent clinical investigations and large randomized clinical trials including neurodevelopmental follow-up in term and preterm neonates. The clinical investigations conducted by the Eunice Kennedy Shriver NICHD Neonatal Research Network will be discussed and placed in context with other pertinent clinical investigations exploring the efficacy of inhaled nitric oxide therapy in neonatal hypoxic respiratory failure.


[Concept for treatment of pelvic ring injuries in elderly patients. A challenge].
Whereas pelvic injuries in patients in their 20s and 30s are typically caused by high energy trauma, another group suffering this injury are elderly patients between the seventh and eighth decades of life. Due to osteoporosis and co-morbidities females are particularly affected by low energy trauma. After examining the medical history a physical examination of the pelvis is performed. This is followed by imaging with X-ray and CT scanning with 3D reconstruction if necessary. If there are concomitant injuries additional diagnostics are essential (e.g. sonography, MRI, retrograde ureterography, cystography and excretion urogram). The standard AO/ATO classification (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association) has been well proven and does not depend on the age of the patient. Three different fracture types are differentiated, types A, B and C. This classification in combination with the description of the affected anatomical region (e.g. transsymphysis, transpubic, etc.) is sufficient in the daily clinical practice to decide on the necessary treatment. Often there are diagnostic difficulties in elderly patients (so-called differentiation of the A-B problem). In these patients a type A fracture is initially diagnosed and treated conservatively but due to persistent pain the imaging is repeated and an additional (insufficiency) fracture is found. With this new information the therapeutic regime has to be changed. The reconstruction of the pelvic ring is of major importance especially for elderly patients. This reduces the pain and the primary objective, an earliest possible rehabilitation without prolonged immobilization, can be achieved. In elderly patients external fixation with supra-acetabular screw positioning is an effective procedure and secondary insufficiency-instability (mostly dorsal) can be avoided. Whereas type A fractures can almost exclusively be treated non-surgically, types B and C fractures usually need surgery. As in young patients type B fractures are stabilized ventrally and C fractures dorsoventrally. In an emergency supra-acetabular external fixation and when required extraperitoneal tamponade has been established as the standard treatment for elderly patients in Germany. For the definitive surgical management standard procedures are used, but they often have to be modified depending on the bone structure.


Carriage of Haemophilus influenzae type b in children after widespread vaccination with conjugate Haemophilus influenzae type b vaccines.
Rates of invasive Haemophilus influenzae type b (Hib) disease in children decreased very rapidly after licensure of Hib conjugate vaccines. A role for a vaccine-related reduction in nasopharyngeal carriage of Hib has been suggested. We studied oropharyngeal carriage of Hib and vaccination rates in a population of 2- to 5-year-old children in metropolitan Atlanta. Among 584 children 75% were vaccinated with an Hib conjugate vaccine, 17% had not been vaccinated and 8% had no vaccination records available. Forty-one percent of the children were colonized with H. influenzae. One child was colonized with Hib. Hib carriage (0.17%; upper 95% confidence interval boundary, 0.97%) was substantially lower than the estimates of Hib carriage from prior studies of children who had not received Hib conjugate vaccines. Our data are consistent with a decline in Hib carriage induced by widespread use of conjugate Hib vaccines, which may have contributed to the decline of Hib disease in United States children.


Bayesian optimal designs for pharmacokinetic models: sensitivity to uncertainty.
We studied the sensitivity of the number of unique design points and their placement, in Bayesian optimal designs for pharmacokinetic models, with respect to the magnitude of prior uncertainty. We used two and three-parameter pharmacokinetic models with fixed and mixed effects and two Bayesian optimal design criteria, namely ED and API, using different error weighting schemes. We found that by increasing the magnitude of the uncertainty, in most cases, additional design points appear, compared to the corresponding local design, and this happens gradually, forming bifurcation patterns. These bifurcation patterns were interpreted as high sensitivity of the design from the magnitude of the uncertainty.


[Inter-radicular osteotomies. Apropos of 1 observation].
Although more common in recent years, inter-radicular osteotomies remain operations which pose the problem of the prognosis of the displaced teeth. In the light of one special case, the authors sought to assess these risks, in relation to the functional and aesthetic benefits of the surgical procedure.


Analysis of the methylation pattern of the maize opaque-2 (O2) promoter and in vitro binding studies indicate that the O2 B-Zip protein and other endosperm factors can bind to methylated target sequences.
The maize opaque-2 locus (o2) has an endosperm-specific expression and is positively autoregulated by its gene product, a b-Zip protein, to a TGACGTTG motif. The genomic sequencing method was used here to describe, in leaf and endosperm, the methylation pattern of a 390-base pair region of the o2 promoter. In leaf, 96% of the C residues are methylated, whereas in endosperm the 5-methylcytosine content is 84%. Comparison of these methylation patterns indicates that the o2 tissue-specific expression does not result from the demethylation of any specific C residue and that, in vivo, O2 interacts with a methylated target sequence. Consistently, gel-shift experiments using a CpG-methylated, partially methylated, and hemimethylated o2 promoter fragments showed that, in vitro, the O2 protein binds to the major groove of a methylated target sequence, although its binding activity decreases at increasing levels of C-methylation and is more effectively reduced by methylation of the lower strand than of the upper strand of the DNA. Using partially purified endosperm cell extracts, we also show that, besides the O2 protein, other proteins specifically bind to a partially methylated o2 promoter fragment, therefore indicating that in plants a subset of different proteins may mediate the expression of a naturally occurring methylated o2 promoter.


Recognising eating disorders in older people.
Changes in eating behaviours, weight and mental health in older people may be related to psychological distress and indicate the presence of a diagnosable eating disorder, rather than 'anorexia of ageing'. Eating disorders in older people may be overlooked because signs and symptoms are assumed to be part of normal ageing. The role of nurses in the care of older people with eating disorders is likely to be detection, referral and support in accessing specialist intervention. This article offers an overview of eating disorders in older people and discusses why they may arise, why they may not be detected and how to recognise them. The authors describe a framework that nurses can use when assessing older people to determine whether they may have an eating disorder.


Population pharmacokinetics of meropenem administered as a prolonged infusion in children with cystic fibrosis.
Meropenem is frequently used to treat pulmonary exacerbations in children with cystic fibrosis (CF) in the USA. Prolonged-infusion meropenem improves the time that free drug concentrations remain above the MIC (fT> MIC) in adults, but data in CF children are sparse. We describe the population pharmacokinetics, tolerability and treatment burden of prolonged-infusion meropenem in CF children. Thirty children aged 6-17 years with a pulmonary exacerbation received 40 mg/kg meropenem every 8 h; each dose was administered as a 3 h infusion. Pharmacokinetics were determined using population methods in Pmetrics. Monte Carlo simulation was employed to compare 0.5 with 3 h infusions to estimate the probability of pharmacodynamic target attainment (PTA) at 40% fT> MIC. NCT#01429259. A two-compartment model fitted the data best with clearance and volume predicted by body weight. Clearance and volume of the central compartment were 0.41 ± 0.23 L/h/kg and 0.30 ± 0.17 L/kg, respectively. Half-life was 1.11 ± 0.38 h. At MICs of 1, 2 and 4 mg/L, PTAs for the 0.5 h infusion were 87.6%, 70.1% and 35.4%, respectively. The prolonged infusion increased PTAs to >99% for these MICs and achieved 82.8% at 8 mg/L. Of the 30 children, 18 (60%) completed treatment with prolonged infusion; 5 did so at home without any reported burden. Nine patients were changed to a 0.5 h infusion when discharged home. In these CF children, meropenem clearance was greater compared with published values from non-CF children. Prolonged infusion provided an exposure benefit against pathogens with MICs ≥1 mg/L, was well tolerated and was feasible to administer in the hospital and home settings, the latter depending on perception and family schedule.


A Case of Recurrent Respiratory Papillomatosis Successfully Removed Via Endoscopic Argon Plasma Coagulation (APC) With No Evidence of Recurrence.
Recurrent respiratory papillomatosis (RRP) is a benign disease caused by the human papilloma virus (HPV), characterized by the formation of recurrent, epithelial neoplastic lesions in the airways. While benign, they can cause significant airway obstruction in some cases. Difficulties in treatment arise from the recurrent nature of the lesions despite repeated procedures. Other known procedures that result in deep tissue damage also cause unacceptable collateral damage to the underlying airway mucosa. We describe a case of recurrent papillomatosis that was successfully treated with argon plasma coagulation ( APC) when laser and electrocautery ablation had failed in the past. After the papillomatasis was treated with APC, there is no recurrence on repeat scope at 4 months and 9 months after the initial procedure. The procedure was done as a day case and there is no complication from the procedure. The property of the APC that allows it to cause only superficial thermal damage to the tissue makes it a suitable adjunct therapy to the treatment of papillomas, which are usually superficial lesions.


Phase II study of trastuzumab plus gemcitabine in chemotherapy-pretreated patients with metastatic breast cancer.
We evaluated the efficacy and toxicity of trastuzumab plus gemcitabine in patients with HER2-positive metastatic breast cancer (MBC). Sixty-four patients were enrolled, the majority of whom (95%) had been treated with an anthracycline and a taxane before study enrollment. Eligible women were treated with gemcitabine (1200 mg/m(2) weekly for 2 weeks with the third week off on a 21-day cycle) plus weekly doses of trastuzumab (4-mg/kg loading dose; 2 mg/kg thereafter) until disease progression. The median patient age was 55 years, and the median number of previously administered (including adjuvant) chemotherapy regimens was 3. Twenty-two patients were scored as 2+ for HER2 expression by immunohistochemistry; 39 patients scored 3+. Three patients were assessed as HER2-negative on central pathology review and were ineligible for evaluation. Fifty-nine of the 61 patients remained evaluable for response. The objective response rates were 38% in the intent-to-treat population (23 of 61) and 44% among the 39 patients with HER2 3+ expression. The median response duration was 5.8 months, median overall survival was 14.7 months, and median time to disease progression was 5.8 months. Trastuzumab plus gemcitabine was well tolerated. No cases of clinical congestive heart failure occurred. Grade 3/4 toxicities included asthenia in 4 patients, fever in 4, neutropenia in 18, dyspnea in 6, abdominal or back pain in 3, and edema and nausea in 1 patient each. The combination of trastuzumab plus gemcitabine appears to be well tolerated and effective for patients with HER2-positive MBC previously treated with chemotherapy.


[Chlamydiae. 1].
Throughout the animal kingdom the Chlamydiae are among the most common and ancient pathogens, but only in the 1966 they were classified by Page in the same genus because of different nosological pictures that they cause, while more recently were identified as bacteria. Chlamydiae have been divided into two species: C. trachomatis and C. psittaci. In 1986 Grayston et al. proved the etiological role of a "new chlamydial strain", named TWAR (Taiwan-Acute Respiratory), in human pneumonia and bronchitis; TWAR is distinguishable from other Chlamydiae and possibly represents a new entity. The Chlamydiae are non-motile, metabolically poor bacteria, completely lacking of any enzimatic system for energy production (ATP) and for this reason are obligate intracellular parasites; they poses group-specific, species-specific and type-specific antigens. Four series of surface proteins were identified as responsible for their pathogenic properties, while many Authors consider a particular lipopolysaccharidical acid, group antigen, as a real LPS. These bacteria poses an unique developmental cycle with production of two type of particles different for metabolic and infecting characters: elementary body and reticulate body. The Chlamydiae have a broad spectrum of host. They cause persistent or chronic infections and their survival is insured by the elementary body. The Chlamydiae stimulate the humoral and the cellular-mediate immunity system and are capable of survival in the monocytes and macrophages.


Colorectal Cancers in Low- and Middle-Income Countries-Demographic Pattern and Clinical Profile of 970 Patients Treated at a Tertiary Care Cancer Center in India.
Globally, colorectal cancer (CRC) ranks third in terms of incidence and second in terms of mortality. A relatively low burden of CRC has been reported from low- and middle-income countries (LMIC), and there is a paucity of publications related to CRC from LMIC. A computerized comprehensive structured CRC clinical database was developed. All the patients with histopathologically proven CRC undergoing either curative and palliative multimodality management or surgical interventions between 2000 and 2019 were included in the study. A descriptive analysis of the demographic profile and clinical spectrum was performed. A total of 970 patients of CRC were treated between 2000 and 2019. Of these, 401 patients (41.3%) had colon cancer and 569 (58.7%) had rectal cancer. The male-to-female ratio was 1.79:1. The mean age at presentation was 47.7 years. A total of 337 (34.7%) patients qualified as young CRC (≤ 40 years of age at diagnosis). The commonest symptom among patients with colon cancer was abdominal pain; 55.6% of patients had a right-sided primary tumor as compared with 42.2% with left-sided tumors. The commonest symptom among patients with rectal cancer was bleeding per rectum. The predominant location of the tumor was in the lower rectum (58%). Majority of patients with CRC presented with locally advanced stage II and III disease. The most common histologic subtype encountered for both colon and rectal cancers was adenocarcinoma (84.8% and 81.2%, respectively). This study has revealed certain important findings related to CRC in LMIC including a higher burden of young colorectal cancer, a relatively higher proportion of rectal cancers in comparison with colon cancer, a high percentage of patients with low-rectal cancer, and advanced stage at presentation.


HIGH-FLOW NASAL CANNULA COMBINED WITH PRONE POSITIONING AS AN INTUBATION ALTERNATIVE IN COVID-19: A CASE REPORT AND REVIEW OF THE LITERATURE.
The use of high-flow nasal cannula (HFNC) in COVID-19 patients is a controversial topic due to the benefits and risks which may occur in patients and healthcare workers. The goal of this treatment modality is potential avoidance of invasive mechanical ventilation, but generation of aerosol and increased healthcare professional infection risk must be considered. We present a case of a SARS-CoV-2-positive 71-year-old male with acute hypoxemic respiratory failure, who was successfully treated with HFNC combined with prone positioning. Furthermore, we discuss recent literature concerning potential issues of HFNC treatment in COVID-19 patients.


Association of urinary phenolic compounds, inflammatory bowel disease and chronic diarrheal symptoms: Evidence from the National Health and Nutrition Examination Survey.
Endocrine disruptors such as phenolic compounds and parabens may be involved in chronic non-infective disease. While products incorporating these compounds are extensively utilized in consumer and personal products, little is known about their effect on bowel health. Inflammatory bowel disease (IBD) - consisting of the diseases ulcerative colitis and Crohn's disease - and irritable bowel syndrome are common chronic non-infectious diarrheal diseases. Despite limited knowledge on the etiology of IBD, these diseases have increased prevalence in industrialized countries and cause significant impairment to quality of life. In the present study we examine relationships between urinary environmental phenolic compounds, chronic diarrhea and inflammatory bowel disease. Data was obtained from the 2005-2010 US National Health and Nutrition Examination Survey (NHANES) including demographics, lifestyle factors, self-reported health conditions, inflammatory markers and urinary phenolic chemical concentrations. Only participants with complete environmental phenols & parabens component were included in our analysis. Chronic diarrheal symptoms were determined by using the 2009-2010 NHANES questionnaire which included questions pertaining to bowel health. We utilized chronic bowel leakage symptoms as a surrogate marker for chronic diarrhea. The presence of IBD was also analyzed from 2009 to 2010 NHANES data, as a sub-analysis for arthropathy directly querying the presence or absence of IBD. Among the subset of 5218 American adults aged 20-80 years in the NHANES study period who completed environmental phenols & parabens component, 25.5% reported chronic diarrheal symptoms. Abnormal markers of inflammation were present in 2200 (42.2%) of respondents. For IBD, 19 individuals with arthropathy confirmed a diagnosis of ulcerative colitis, and 1 person confirmed a Crohn's diagnosis. After adjustment for demographics, inflammatory and subsample weighing; lower paraben levels were associated with chronic bowel leakage (diarrheal) symptoms. Higher 4-tert-octylphenol levels was significantly associated with ulcerative colitis. Further study of underlying mechanisms should be considered.


Outcomes after Falls Continue to Worsen Despite Trauma and Geriatric Care Advancements.
The most common mechanism of traumatic injury is ground-level fall. The objective of this study was to understand how patients sustaining falls and their outcomes have evolved. An institutional trauma database was used to identify adult patients who suffered a fall and were admitted to a Level I trauma center during two distinct time periods: 1998 to 2003 (past) and 2008 to 2013 (current). Data on anticoagulant use and comorbidities was gathered by retrospective chart review of patients treated during 2003 and 2013. Univariable analyses and multivariable regression were used to evaluate demographics and outcomes. A total of 6116 patients were identified, with a 24 per cent increase in number of falls between groups. Current fall patients are older (70 vs 66 years, P < 0.001), more often admitted to intensive care (28 vs 12%, P < 0.001), have longer lengths of stay (5 vs 4 days, P < 0.001), are frequently discharged to skilled nursing facilities (24 vs 8%, P < 0.001), and have higher mortality (5 vs 3%, P = 0.002). The adjusted odds of mortality for patients treated during 2003 and 2013 was associated with age, gender, injury severity score, and Glasgow Coma Scale score. Current fall patients use more health care resources and have worse outcomes, despite advances in trauma and geriatric care.


Occlusive colon carcinoma: virtual colonoscopy in the preoperative evaluation of the proximal colon.
To evaluate the use of preoperative virtual colonoscopy to examine the proximal colon in patients with distal occlusive carcinomas, defined as cancers that cannot be traversed endoscopically. Twenty-nine patients with occlusive colorectal carcinomas underwent preoperative virtual colonoscopy with use of a standard protocol. Patients with acute bowel obstruction were excluded. Results of virtual colonoscopy were compared with the findings of preoperative colonoscopy, preoperative barium enema examination, intraoperative colon palpation, histopathologic outcome, and postoperative colonoscopy and barium enema examination, where possible. Virtual colonoscopy helped identify all 29 occlusive carcinomas and demonstrated two cancers and 24 polyps in the proximal colon. Both synchronous cancers were confirmed intraoperatively and resected. Postoperative conventional colonoscopy in 12 patients confirmed 16 polyps identified at virtual colonoscopy and demonstrated two subcentimeter polyps missed at virtual colonoscopy. Postoperative barium enema examination was performed in two patients and helped confirm two polyps identified at virtual colonoscopy. Virtual colonoscopy successfully demonstrated the proximal colon in 26 of 29 patients examined compared with preoperative barium enema examination, which failed to adequately demonstrate the proximal colon in any patient examined. Virtual colonoscopy is a feasible and useful method for evaluating the entire colon before surgery in patients with occlusive carcinomas.


How specialized volatiles respond to chronic and short-term physiological and shock heat stress in Brassica nigra.
Brassicales release volatile glucosinolate breakdown products upon tissue mechanical damage, but it is unclear how the release of glucosinolate volatiles responds to abiotic stresses such as heat stress. We used three different heat treatments, simulating different dynamic temperature conditions in the field to gain insight into stress-dependent changes in volatile blends and photosynthetic characteristics in the annual herb Brassica nigra (L.) Koch. Heat stress was applied by either heating leaves through temperature response curve measurements from 20 to 40 °C (mild stress), exposing plants for 4 h to temperatures 25-44 °C (long-term stress) or shock-heating leaves to 45-50 °C. Photosynthetic reduction through temperature response curves was associated with decreased stomatal conductance, while the reduction due to long-term stress and collapse of photosynthetic activity after heat shock stress were associated with non-stomatal processes. Mild stress decreased constitutive monoterpene emissions, while long-term stress and shock stress resulted in emissions of the lipoxygenase pathway and glucosinolate volatiles. Glucosinolate volatile release was more strongly elicited by long-term stress and lipoxygenase product released by heat shock. These results demonstrate that glucosinolate volatiles constitute a major part of emission blend in heat-stressed B. nigra plants, especially upon chronic stress that leads to induction responses.


Conceptualizing how couples talk about cancer.
Scholarship on couple communication about cancer employs variable conceptualizations of communication, and common measurement strategies make questionable assumptions about communication. This study provides a descriptive foundation for a multiple-topic, multidimensional approach to studying couple talk about cancer. Based on interviews with persons treated for cancer in the last 5 years and partners, we identified 16 topics and 5 dimensions of talk. "Talk about cancer" covers a broad range of issues. The frequency, openness, difficulty, and focus of talk vary considerably for different topics and can change over time or differ between partners. Disagreements were rare but highly salient, and satisfaction with talk tended to be high. These findings suggest we move away from abstract, general measures of couple communication and that we develop descriptive advice for couples, rather than simply prescribing "be open."


Total synthesis of cyclic heptapeptide Rolloamide B.
The first total synthesis of Rolloamide B, a cyclic proline-enriched heptapeptide, is reported. This work features solution phase benzotriazole-mediated peptide synthesis ligating native amino acids.


Controlled release of BMP-2 from a sintered polymer scaffold enhances bone repair in a mouse calvarial defect model.
Sustained and controlled delivery of growth factors, such as bone morphogenetic protein 2 (BMP-2), from polymer scaffolds has excellent potential for enhancing bone regeneration. The present study investigated the use of novel sintered polymer scaffolds prepared using temperature-sensitive PLGA/PEG particles. Growth factors can be incorporated into these scaffolds by mixing the reconstituted growth factor with the particles prior to sintering. The ability of the PLGA/PEG scaffolds to deliver BMP-2 in a controlled and sustained manner was assessed and the osteogenic potential of these scaffolds was determined in a mouse calvarial defect model. BMP-2 was released from the scaffolds in vitro over 3 weeks. On average, ca. 70% of the BMP-2 loaded into the scaffolds was released by the end of this time period. The released BMP-2 was shown to be active and to induce osteogenesis when used in a cell culture assay. A substantial increase in new bone volume of 55% was observed in a mouse calvarial defect model for BMP-2-loaded PLGA/PEG scaffolds compared to empty defect controls. An increase in new bone volume of 31% was observed for PLGA/PEG scaffolds without BMP-2, compared to empty defect controls. These results demonstrate the potential of novel PLGA/PEG scaffolds for sustained BMP-2 delivery for bone-regeneration applications.


Quantitative Aspects of Communicative Impairment Ascertained in a Large National Survey of Japanese Children.
The Japanese version of the Children's Communication Checklist-2 (CCC-2) was rated by caregivers in a large national population sample of 22,871 children aged 3-15 years. The General Communication Composite (GCC) of the CCC-2 exhibited a distribution with a single-factor structure. The GCC distribution between autism spectrum disorders (ASD) and language impairment (LI) groups in the general population fit inside a bell curve with significant overlap with the general population, and a continuum was evident between groups. No evidence of a natural cutoff that would differentiate categorically affected from unaffected children was seen. The Social Interaction Deviance Composite (SIDC) supported the notion that ASD and LI are on the opposite endpoints of a SIDC continuum of communication impairment.


Quinoline Thiourea-Based Zinc Ionophores with Antibacterial Activity.
The increasing resistance of bacteria to commercially available antibiotics threatens patient safety in healthcare settings. Perturbation of ion homeostasis has emerged as a potential therapeutic strategy to fight against antibacterial resistance and other channelopathies. This study reports the development of 8-aminoquinoline (QN) derivatives and their transmembrane Zn2+ transport activities. Our findings showed that a potent QN-based Zn2+ transporter exhibits promising antibacterial properties against Gram-positive bacteria with reduced hemolytic activity and cytotoxicity to mammalian cells. Furthermore, this combination showed excellent in vivo efficacy against Staphylococcus aureus. Interestingly, this combination prevented bacterial resistance and restored susceptibility of gentamicin and methicillin-resistant S. aureus to commercially available β-lactam and other antibiotics that had lost their activity against the drug-resistant bacterial strain. Our findings suggest that the transmembrane transport of Zn2+ by QN derivatives could be a promising strategy to combat bacterial infections and restore the activity of other antibiotics.


Autonomous Navigation System of Greenhouse Mobile Robot Based on 3D Lidar and 2D Lidar SLAM.
The application of mobile robots is an important link in the development of intelligent greenhouses. In view of the complex environment of a greenhouse, achieving precise positioning and navigation by robots has become the primary problem to be solved. Simultaneous localization and mapping (SLAM) technology is a hot spot in solving the positioning and navigation in an unknown indoor environment in recent years. Among them, the SLAM based on a two-dimensional (2D) Lidar can only collect the environmental information at the level of Lidar, while the SLAM based on a 3D Lidar demands a high computation cost; hence, it has higher requirements for the industrial computers. In this study, the robot navigation control system initially filtered the information of a 3D greenhouse environment collected by a 3D Lidar and fused the information into 2D information, and then, based on the robot odometers and inertial measurement unit information, the system has achieved a timely positioning and construction of the greenhouse environment by a robot using a 2D Lidar SLAM algorithm in Cartographer. This method not only ensures the accuracy of a greenhouse environmental map but also reduces the performance requirements on the industrial computer. In terms of path planning, the Dijkstra algorithm was used to plan the global navigation path of the robot while the Dynamic Window Approach (DWA) algorithm was used to plan the local navigation path of the robot. Through the positioning test, the average position deviation of the robot from the target positioning point is less than 8 cm with a standard deviation (SD) of less than 3 cm; the average course deviation is less than 3° with an SD of less than 1° at the moving speed of 0.4 m/s. The robot moves at the speed of 0.2, 0.4, and 0.6 m/s, respectively; the average lateral deviation between the actual movement path and the target movement path is less than 10 cm, and the SD is less than 6 cm; the average course deviation is <3°, and the SD is <1.5°. Both the positioning accuracy and the navigation accuracy of the robot can meet the requirements of mobile navigation and positioning in the greenhouse environment.


Evaluation of protease-activated receptor 2 in murine models of arthritis.
Protease-activated receptor 2 (PAR-2) activation has been linked to pro- and antiinflammatory cellular responses. We undertook this study to explore the importance of PAR-2 activation in 4 murine models of arthritis and to analyze the expression of PAR-2 in human arthritic synovium. Zymosan-induced arthritis (ZIA), K/BxN serum-induced arthritis, and Freund's complete adjuvant (CFA)-induced arthritis were generated in naive PAR-2(-/-) mice and PAR-2(+/+) littermates. Antigen-induced arthritis (AIA) was generated in immunized mice using methylated bovine serum albumin (mBSA). The severity of arthritis was assessed by clinical scoring, technetium uptake measurement, and histologic analysis. Immune responses to mBSA were also evaluated from AIA. The expression of PAR-2 in synovial tissues from rheumatoid arthritis (RA) and osteoarthritis (OA) patients was compared. In AIA, arthritis was significantly decreased in PAR-2-deficient mice and was associated with decreased levels of anti-mBSA IgG antibodies and lymph node cell proliferation. No difference in arthritis severity was seen in mice with ZIA, K/BxN serum-induced arthritis, and CFA-induced arthritis. Synovial biopsy specimens from RA patients demonstrated significantly increased expression of PAR-2 compared with those from OA patients. PAR-2 deficiency was found to modulate articular inflammation in murine models of arthritis that require prior immunization and was associated with reduced levels of anti-mBSA IgG and lymph node cell proliferation in AIA. Expression of PAR-2 in RA synovium was significantly higher than that in OA synovium, and this suggests that PAR-2 is implicated in the pathogenesis of immune-mediated forms of arthritis.


Advances in small-molecule drug discovery for triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is a subtype of poor prognosis, highly invasive and difficult-to-treat breast cancers accounting for approximately 15% of clinical cases. Given the poor outlook and lack of sustained response to conventional therapies, TNBC has been the subject of intense studies on new therapeutic approaches in recent years. The development of targeted cancer therapies, often in combination with established chemotherapy, has been applied to a number of new clinical studies in this setting in recent years. This review will highlight recent therapeutic advances in TNBC, focusing on small-molecule drugs and their associated biological mechanisms of action, and offering the possibility of improved prospects for this patient group in the near future.


Pharmacological Inhibition of Exosome Machinery: An Emerging Prospect in Cancer Therapeutics.
Exosomes are nanocarriers that mediate intercellular communication crucial for normal physiological functions. However, exponentially emerging reports have correlated their dysregulated release with various pathologies, including cancer. In cancer, from stromal remodeling to metastasis, where tumor cells bypass the immune surveillance and show drug resistivity, it has been established to be mediated via tumor-derived exosomes. Owing to their role in cancer pathogenicity, exosomebased strategies offer enormous potential in treatment regimens. These strategies include the use of exosomes as a drug carrier or as an immunotherapeutic agent, which requires advanced nanotechnologies for exosome isolation and characterization. In contrast, pharmacological inhibition of exosome machinery surpasses the requisites of nanotechnology and thus emerges as an essential prospect in cancer therapeutics. In this line, researchers are currently trying to dissect the molecular pathways to reveal the involvement of key regulatory proteins that facilitate the release of tumor-derived exosomes. Subsequently, screening of various molecules in targeting these proteins, with eventual abatement of exosome-induced cancer pathogenicity, is being done. However, their clinical translation requires more extensive studies. Here, we comprehensively review the molecular mechanisms regulating exosome release in cancer. Moreover, we provide insight into the key findings that highlight the effect of various drugs as exosome blockers, which will add to the route of drug development in cancer management.


Assessment of energy intake underreporting by doubly labeled water and observations on reported nutrient intakes in children.
To compare reported energy intake with energy expenditure using doubly labeled water (DLW). Additionally, we compared reported nutrient intakes of our subject population with national survey population data from the third National Health and Nutrition Examination Survey (NHANES III). This was a cross-sectional study of children, balanced by race and gender, primarily characterized by 4 body types: lean, obese, centrally fat, or peripherally fat. Children (n=118; mean age=10 years) kept 8-day food records, with nutritionists recording weekday school lunch intakes. These subjects, assisted by their parents, recorded all breakfasts, dinners, snacks, and weekend lunches. Data were analyzed using least squares analysis of variance with the general linear models procedure. Tukey's test was used for multiple comparisons of predicted treatment means. Mean daily energy intake was underreported by 17% to 33% of energy expenditure. The tendency to underreport increased with age. Underreporting occurred in all groups and subgroups studied. Reported mean intakes of vitamin A, vitamin E, vitamin B-6, calcium, zinc, and copper were less than 70% of the Recommended Dietary Allowance (RDA) for African-American girls, whereas African-American boys reported similarly low intakes of copper. On average, white girls reported intakes less than 70% of the RDA for zinc and copper, whereas white boys reported low intakes of copper (60% of the RDA). Reported intakes in general were somewhat lower than those reported in NHANES III. Dietetics professionals may modify the nutritional advice they give to patients/subjects based on food intake records and other data. For children, particularly, it is imperative that ethnic and gender differences be taken into consideration and that all foods eaten be accounted for as much as possible.


Effect of a Text-Messaging Intervention on Oral Self-Care Practices in Antenatal Women in Delhi, India: A Pilot Randomized Control Trial.
This study aimed to determine the effect of a mHealth (text message) intervention compared with a structured health educational session on the oral care and hygiene practices of pregnant women. We conducted a pilot randomized control trial, parallel design superiority trial, with a 1:1 allocation ratio. A total of 76 pregnant women up to 20 weeks of gestational age and capable of reading mobile phone text messages were recruited during August-October 2020 from the antenatal clinic of a primary health center in a low-income urban agglomeration in Delhi, India. The mHealth intervention arm participants were sent a daily text message for 30 days, while all participants were provided a one-time, face-face, brief didactic structured educational session toward oral health promotion. The baseline characteristics of both groups were comparable in terms of age structure, education, parity, and oral hygiene but differed in terms of oral health problems. Postintervention, although the twice-brushing frequency increased in both arms, only the mHealth arm revealed a statistically significant reduction in the incidence of missed twice-daily brushing episodes (P = 0.016). A mHealth-based daily text-message intervention for 1 month was not superior to a one-time brief didactic structured educational intervention for oral health promotion in antenatal women.


Shifting paradigms: biopharmaceuticals versus low molecular weight drugs.
Biopharmaceuticals are pharmaceutical products consisting of (glyco)proteins. Nowadays a substantial part of the FDA-approved drugs belong to this class of drugs. Biopharmaceuticals deserve special attention as they have a number of characteristics that set them aside from low molecular weight drugs. Their activity depends on their complicated shape based on secondary, tertiary and (sometimes) quaternary structures. These structures cannot be fully defined with our present set of analytical techniques and approaches for potency testing. They often are the same as (or closely resemble) endogenous proteins. This means that in safety testing and clinical test programs questions have to be addressed regarding species specific responses, selection of dosing schedules and route of administration, and the possible occurrence of immunogenicity. As the conformational structure of a protein is easily disturbed, formulation and handling of biopharmaceuticals needs special attention in order to optimize the therapeutic effect and minimize adverse reaction, among which immune responses. The issue of biogenerics is gaining more and more interest and different critical elements in the development of biogenerics are touched upon. In conclusion, biopharmaceuticals cannot be characterized fully in terms of their structure like low molecular weight drugs. The performance of biopharmaceuticals relies on strict production protocols and close monitoring of their activity in the clinical situation.


Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads.
Mechanosensitive cell surface adhesion complexes allow cells to sense the mechanical properties of their surroundings. Recent studies have identified both force-sensing molecules at adhesion sites, and force-dependent transcription factors that regulate lineage-specific gene expression and drive phenotypic outputs. However, the signaling networks converting mechanical tension into biochemical pathways have remained elusive. To explore the signaling pathways engaged upon mechanical tension applied to cell surface receptor, superparamagnetic microbeads can be used. Here we present a protocol for using magnetic beads to apply forces to cell surface adhesion proteins. Using this approach, it is possible to investigate not only force-dependent cytoplasmic signaling pathways by various biochemical approaches, but also adhesion remodeling by magnetic isolation of adhesion complexes attached to the ligand-coated beads. This protocol includes the preparation of ligand-coated superparamagnetic beads, and the application of define tensile forces followed by biochemical analyses. Additionally, we provide a representative sample of data demonstrating that tension applied to integrin-based adhesion triggers adhesion remodeling and alters protein tyrosine phosphorylation.


The effects of vitamin D deficiency and insufficiency on the endocrine and paracrine systems.
Individuals are capable of producing vitamin D with proper exposure to sunlight. However, several factors can interfere with the effectiveness of this process. Most sunscreens filter out UVB light, thus inhibiting vitamin D production. Individuals with more darkly pigmented skin have greater difficulty producing vitamin D because melanin acts as an effective natural sunscreen, requiring longer sun exposure to produce an adequate daily allotment of vitamin D. Additionally, solely breastfed infants whose mothers suffered from vitamin D deficiency or insufficiency when pregnant have smaller reserves of the nutrient and are at greater risk of developing nutritional rickets. Vitamin D deficiency leads to rickets, osteomalacia, and osteoporosis. Long-term vitamin D insufficiency can lead to paracrine effects such as type 1 diabetes, cancer, and multiple sclerosis. This article reviews the current literature on vitamin D deficiency and insufficiency and their relation to different disease states. Potential areas for research are discussed.


The effects of oral and enteric Campylobacter concisus strains on expression of TLR4, MD-2, TLR2, TLR5 and COX-2 in HT-29 cells.
Campylobacter concisus, a Gram-negative bacterium that colonizes the human oral cavity, has been shown to be associated with inflammatory bowel diseases (IBD). The effects of different C. concisus strains on intestinal epithelial expression of Toll like receptors (TLR) have not been investigated. This study examined the effects of C. concisus strains isolated from patients with IBD and controls on expression of TLR4, its co-receptor myeloid differentiation factor (MD)-2; TLR2, TLR5, cyclooxygenase-2 (COX-2) and interleukin (IL)-8 in HT-29 cells.Fourteen oral and enteric C. concisus strains isolated from patients with IBD and healthy controls were co-incubated with HT-29 cells. Expression of TLR4, MD-2, TLR2, TLR5 and COX-2 in HT-29 cells in response to C. concisus infection was examined by Western blot, flow cytometry analysis and immunofluorescent staining visualized by confocal microscope. Production of IL-8 was evaluated by enzyme-linked immunosorbent assay.Both oral and enteric C. concisus strains upregulated expression of TLR4 in HT-29 cells. The levels of glycosylated TLR4 (Gly-TLR4) and surface TLR4 induced by C. concisus strains isolated from patients with IBD were significantly higher than those induced by C. concisus strains isolated from the healthy controls. Four C. concisus strains isolated from patients with IBD induced more than two-fold increase of surface expression of MD-2. C. concisus did not affect expression of TLR2 and TLR5. All C. concisus strains induced production of IL-8 and COX-2 in HT-29 cells.This study shows that some C. concisus strains, most from patients with IBD, upregulate surface expression of TLR4 and MD-2 in HT-29 cells. These data suggest that a potential role of specific C. concisus strains in modulating the intestinal epithelial responses to bacterial LPS needs to be investigated.


PBX1 as Pioneer Factor: A Case Still Open.
Pioneer factors are proteins that can recognize their target sites in barely accessible chromatin and initiate a cascade of events that allows for later transcriptional activation of the respective genes. Pioneer factors are therefore particularly well-suited to initiate cell fate changes. To date, only a small number of pioneer factors have been identified and studied in depth, such as FOXD3/FOXA1, OCT4, or SOX2. Interestingly, several recent studies reported that the PBC transcription factor PBX1 can access transcriptionally inactive genomic loci. Here, we summarize the evidence linking PBX1 with transcriptional pioneer functions, suggest potential mechanisms involved and discuss open questions to be resolved.


Sequence of cyanogen bromide fragments D and E of B. amyloliquefaciens alpha amylase.
Alpha amylase (Sigma type IIA) was cleaved by cyanogen bromide. The sequences of two fragments, D which contains 88 amino acids and E which contains 56, are presented. By applying the Chou-Fasman rules, D is predicted to have 32% beta sheet and 37% alpha helix, and E is predicted to exhibit 11% beta sheet and 71% alpha helix.


Catalytic vs. uncatalyzed [2 + 2] photocycloadditions of quinones with alkynes.
Photoreactions of quinones with alkynes under catalytic and non-catalytic conditions were studied. In contrast to recent reports, simple irradiation with blue light is sufficient to trigger [2 + 2] photocycloadditions, which afford either fused cyclobutenes or reactive para-quinone methides (p-QMs) depending on the quinone structure. Revision of the chemo- and regioselectivity of the uncatalyzed photoreactions provided useful insight into their overlooked relatedness to the recently developed catalytic protocols. Experimental evidence indicates that the reactivity of the photochemically generated p-QMs is sufficient to perform uncatalyzed reactions with nucleophiles, which can help to explain the existing transformations and develop new cascade transformations involving quinones and alkynes.


Altered hydrogen bonding of Arg82 during the proton pump cycle of bacteriorhodopsin: a low-temperature polarized FTIR spectroscopic study.
Light-driven proton transport in bacteriorhodopsin (BR) is achieved by dynamic rearrangement of the hydrogen-bonding network inside the membrane protein. Arg82 is located between the Schiff base region and proton release group, and has a major influence on the pK(a) values of these groups. It is believed that Arg82 changes its hydrogen-bonding acceptors during the pump cycle of BR, stages of which are correlated with proton movement along the transport pathway. In this study, we compare low-temperature polarized FTIR spectra of [eta(1,2)-(15)N]arginine-labeled BR in the 2750-2000 cm(-1) region with those of unlabeled BR for the K, L, M, and N intermediates. In the K-minus-BR difference spectra, (15)N-shifted modes were found at 2292 (-)/2266 (+) cm(-1) and at 2579 (-)/2567 (+) cm(-1). The former corresponds to strong hydrogen bonding, while the latter corresponds to very weak hydrogen bonding. Both N-D stretches probably originate from Arg82, the former oriented toward water 406 and the latter toward the extracellular side, and both hydrogen bonds are somewhat strengthened upon retinal photoisomerization. This perturbation of arginine hydrogen bonding is entirely relaxed in the L intermediate where no (15)N-isotope shifts are observed in the difference spectrum. In the M intermediate, the frequency is not significantly altered from that in BR. However, the polarized FTIR spectra strongly suggest that the dipolar orientation of the strongly hydrogen bonded N-D group of Arg82 is changed from perpendicular to parallel to the membrane plane. Such a change is presumably related to the motion of the Arg82 side chain from the Schiff base region to the extracellular proton release group. Additional bands corresponding to weak hydrogen bonding were observed in both the M-minus-BR and N-minus-BR spectra. Changes in hydrogen-bonding structures involving Arg82 are discussed on the basis of these FTIR observations.


[Stigmatisation : a widespread problem with multiple consequences].
Stigmatisation is a well known social phenomenon based on the discrimination of an individual or a sub-group of individuals by a dominant or majority group. Often discussed in the frame of psychiatry, it is also observed in other domains of medicine. It impacts not only patients, but their relatives and their children, as well as the health professionals taking care of them. Moreover, it is detrimental to the implementation of preventive strategies and induces depressive reactions, loss of self esteem and reduction of patients' quality of life. Finally, it keeps researchers away from certain domains of medicine and has a negative impact on funding for research and treatment. It is therefore important to understand its underlying mechanisms in order to fight it more efficiently.


Mechanisms of Degradation and Strategies for the Stabilization of Cathode-Electrolyte Interfaces in Li-Ion Batteries.
Undesired reactions at the interface between a transition metal oxide cathode and a nonaqueous electrolyte bring about challenges to the performance of Li-ion batteries in the form of compromised durability. These challenges are especially severe in extreme conditions, such as above room temperature or at high potentials. The ongoing push to increase the energy density of Li-ion batteries to break through the existing barriers of application in electric vehicles creates a compelling need to address these inefficiencies. This goal requires a combination of deep knowledge of the mechanisms underpinning reactivity, and the ability to assemble multifunctional electrode systems where different components synergistically extend cycle life by imparting interfacial stability, while maintaining, or even increasing, capacity and potential of operation. The barriers toward energy storage at high density apply equally in Li-ion, the leading technology in the battery market, and in related, emerging concepts for high energy density, such as Na-ion and Mg-ion, because they also conceptually rely on electroactive transition metal oxides. Therefore, their relevance is broad and the quest for solutions inevitable. In this Account, we describe mechanisms of reaction that can degrade the interface between a Li-ion battery electrolyte and the cathode, based on an oxide with transition metals that can reach high formal oxidation states. The focus is placed on cathodes that deliver high capacity and operate at high potential because their development would enable Li-ion battery technologies with high capacity for energy storage. Electrode-electrolyte instabilities will be identified beyond the intrinsic potential windows of stability, by linking them to the electroactive transition metals present at the surface of the electrode. These instabilities result in irreversible transformations at these interfaces, with formation of insulating layers that impede transport or material loss due to corrosion. As a result, strategies that screen the reactive surface of the oxide, while reducing the transition metal content by introducing inactive ions emerge as a logical means toward interfacial stability. Yet they must be implemented in the form of thin passivating barriers to avoid unacceptable losses in storage capacity. This Account subsequently describes our current ability to build composite structures that include the active material and phases designed to address deleterious reactions. We will discuss emerging strategies that move beyond the application of such barriers on premade agglomerated powders of the material of interest. The need for these strategies will be rationalized by the goal to effectively passivate all interfaces while fully controlling the chemistry that results at the surface and its homogeneity. Such outcomes would successfully minimize interfacial losses, thereby leading to materials that exceed the charge storage and life capabilities possible today. Practically speaking, it would create opportunities to design batteries that break the existing barriers of energy density.


Menopause Rating Scale as a screening tool in rural Turkey.
Women living in rural areas of Turkey experience difficulties in accessing healthcare services, and this is attributed to distance from urban healthcare centers, financial barriers and poverty, a low education level, and gender discrimination. The purpose of this study was to test the applicability of the menopause rating scale (MRS) as a screening tool by primary healthcare professionals for identifying women with severe menopausal symptoms. The objectives of the study were to test the validity and reliability of the MRS in rural areas of Turkey, to determine estimation values for referral to the secondary level of healthcare, and to assess the prevalence of severe menopausal symptoms among rural Turkish women. The sample size was 600 women. The Turkish version of the MRS and the Kupperman index were used to evaluate the severity of symptoms. The internal consistency coefficient (Cronbach's alpha) of the MRS was computed using the test-retest method. The influence of the MRS with regard to the decision to seek medical advice due to menopausal symptoms was considered the validity criterion, and the sensitivity and specificity of the test were established according to this criterion. Estimation values of the test were determined by ROC analysis. Independent variables for the severity of menopausal symptoms were determined using a logistic regression model. A positive correlation between the MRS and the Kupperman index was revealed (r=0.86, p=0.000). The estimation value or the MRS score that would predict whether a woman had visited a gynecologist at least once due to the severity of menopause symptoms was found to be 16, its sensitivity and specificity were both 60%. The MRS score was higher among participants who evaluated their general health as 'unfit' or who had advanced age, chronic disease, a history of dysmenorrhea, or who had had two or more miscarriages. This evaluation of the MRS indicates that the instrument is a comprehensible, useable, reliable screening test for the identification of women with severe menopausal symptoms. By screening using the MRS it is possible for primary healthcare workers in rural areas to identify women in need of referral to an upper-level healthcare institution.


In vivo proton MR three-dimensional T1rho mapping of human articular cartilage: initial experience.
The purpose of this study was to demonstrate the feasibility of computing three-dimensional relaxation maps of spin-lattice relaxation time in the rotating frame (T1rho) from in vivo magnetic resonance (MR) images of the human patellofemoral joint. T1rho was measured by applying a three-dimensional gradient-echo pulse sequence in six healthy subjects and one symptomatic subject by using a 1.5-T MR imager and a 15-cm-diameter transmit-receive quadrature birdcage radiofrequency coil. Average T1rho measured in healthy patellar cartilage was 49.7 msec +/- 3.2 (mean +/- SD). Two-dimensional T1rho-weighted images were obtained with a fast spin-echo pulse sequence for comparison. There was good correlation between two-dimensional and three-dimensional T1rho values for the six healthy subjects (R2 = 0.88, slope = 1.16).


A necropsy technique for cattle to eliminate contamination of lymph nodes by mycobacteria.
A field necropsy technique for cattle is described which avoids contamination by environmental mycobacteria of tissues intended for bacteriological examination. Settling the dust by hosing on and around the carcase, using sterile instruments for the collection of each tissue, excising lymph nodes without incising the capsule and submitting the nodes to the laboratory intact in saturated tetraborate solution resulted in uncontaminated samples even under adverse field conditions. The procedure is recommended for future investigations into the role of mycobacteria other than Mycobacterium bovis in the sensitisation of cattle to the intradermal test for tuberculosis.


Effects of a feeding intervention in patients with Alzheimer's disease and dysphagia.
This study aimed to investigate the effects of a feeding intervention in patients with Alzheimer's disease with dysphagia. In patients with Alzheimer's disease, inadequate food and fluid intake can result in malnutrition, dehydration and increased morbidity and mortality. Patients may lose self-care abilities such as self-feeding. A prospective cohort study. A three-month self-control feeding intervention was conducted prospectively in 30 nursing home residents with Alzheimer's disease with dysphagia. Pre- and post-intervention measures included the Kubota water swallow test, type and amount of food intake and assessment of nutritional status by triceps skinfold thickness, upper arm circumference, serum albumin and haemoglobin. We used the Edinburgh Feeding Evaluation in Dementia scale to evaluate eating compliance and the Mini- Mental State Examination to evaluate cognitive function. Pre- and post-intervention results were compared to evaluate the effects of nursing intervention. Patients' eating/feeding abilities improved overall, including significantly increased food intake (p < 0·001), decreased levels on the Kubota water swallow test (p < 0·001) and significant differences in skinfold thickness, arm circumference, serum albumin and haemoglobin (all p < 0·01), indicating improved nutritional status. Edinburgh Feeding Evaluation in Dementia scale scores decreased significantly, showing improved eating compliance. No changes were noted in cognition post-intervention. Among 22 patients who initially required feeding, five patients resumed self-feeding after the intervention (p = 0·06). Results of this study show that a feeding intervention can improve food intake, eating compliance and nutritional status in patients with Alzheimer's disease with dysphagia and prevent further decline in swallowing function. The significant improvement in eating/feeding measures suggest that this feeding intervention model could be developed as a feeding skills programme to improve both the eating/feeding care by nursing staff and the eating/feeding abilities and nutritional status of Alzheimer's disease patients.


Rvs161p interacts with Fus2p to promote cell fusion in Saccharomyces cerevisiae.
FUS7 was previously identified by a mutation that causes a defect in cell fusion in a screen for bilateral mating defects. Here we show that FUS7 is allelic to RVS161/END6, a gene implicated in a variety of processes including viability after starvation, endocytosis, and actin cytoskeletal organization. Two lines of evidence indicate that RVS161/END6's endocytic function is not required for cell fusion. First, several other endocytic mutants showed no cell fusion defects. Second, we isolated five function-specific alleles of RVS161/FUS7 that were defective for endocytosis, but not mating, and three alleles that were defective for cell fusion but not endocytosis. The organization of the actin cytoskeleton was normal in the cell fusion mutants, indicating that Rvs161p's function in cell fusion is independent of actin organization. The three to fourfold induction of RVS161 by mating pheromone and the localization of Rvs161p-GFP to the cell fusion zone suggested that Rvs161p plays a direct role in cell fusion. The phenotypes of double mutants, the coprecipitation of Rvs161p and Fus2p, and the fact that the stability of Fus2p was strongly dependent on Rvs161p's mating function lead to the conclusion that Rvs161p is required to interact with Fus2p for efficient cell fusion.


Subcutaneous abatacept for the treatment of rheumatoid arthritis.
The efficacy, safety and tolerability of i.v. abatacept are well established in patients with active RA. A s.c. abatacept formulation is now available in some countries. Here, we review clinical data for s.c. abatacept. Six trials are presented (Phase II dose-finding study, ACQUIRE, ALLOW, ACCOMPANY, ATTUNE and AMPLE) and issues important to both patients and clinicians are addressed. The primary focus assesses whether the i.v. and s.c. abatacept formulations have similar efficacy, including whether the recommended fixed dose of s.c. abatacept is comparable to the weight-tiered i.v. dosing and whether efficacy is sustained with long-term treatment. Safety and immunogenicity are also discussed, including the short- and long-term safety of s.c. abatacept, and whether immunogenicity is increased following a switch from i.v. to s.c. abatacept, after withdrawal or reintroduction of s.c. abatacept or in the absence of MTX. Year 1 data from the AMPLE study, comparing s.c. abatacept with the TNF antagonist adalimumab, are discussed. Although fewer patient-years of exposure are available for s.c. compared with i.v. abatacept, observations suggest that s.c. abatacept has a similar long-term efficacy to the i.v. formulation, improving the signs, symptoms, disease activity and physical function in patients with RA. With continued treatment, these improvements are maintained over time with high retention rates, similar to i.v. abatacept. s.c. abatacept is associated with low immunogenicity and short- and long-term safety that is consistent with i.v. abatacept. In addition, s.c. abatacept demonstrates comparable efficacy, kinetics of response, safety and radiographic inhibition to adalimumab.


[Current and future prospects of endovascular treatment for acute ischemic stroke].
Recently, remarkable progress has been made in the field of endovascular treatment, and endovascular treatment for acute ischemic stroke due to large vessel occlusion has been an effective and therapeutic option. However, there is no randomized control trial as to superiority of endovascular treatment for acute ischemic stroke compared to the standard treatment including intravenous rt-PA. Inclusion criteria for the performance of endovascular treatment for acute ischemic stroke will need to be defined more precisely, and high rates of fast recanalization will be needed in future. We expect the evidence that endovascular treatment for acute ischemic stroke due to large vessel occlusion is superior to standard treatment by the detailed images of the brain, more strict indications and novel endovascular devices such as percutaneous transluminal mechanical thrombectomy devices.


High-throughput identification of reference genes for research and clinical RT-qPCR analysis of breast cancer samples.
Quantification and normalization of RT-qPCR data critically depends on the expression of so called reference genes. Our goal was to develop a strategy for the selection of reference genes that utilizes microarray data analysis and combines known approaches for gene stability evaluation and to select a set of appropriate reference genes for research and clinical analysis of breast samples with different receptor and cancer status using this strategy. A preliminary search of reference genes was based on high-throughput analysis of microarray datasets. The final selection and validation of the candidate genes were based on the RT-qPCR data analysis using several known methods for expression stability evaluation: comparative ∆Ct method, geNorm, NormFinder and Haller equivalence test. A set of five reference genes was identified: ACTB, RPS23, HUWE1, EEF1A1 and SF3A1. The initial selection was based on the analysis of publically available well-annotated microarray datasets containing different breast cancers and normal breast epithelium from breast cancer patients and epithelium from cancer-free patients. The final selection and validation were performed using RT-qPCR data from 39 breast cancer biopsy samples. Three genes from the final set were identified by the means of microarray analysis and were novel in the context of breast cancer assay. We showed that the selected set of reference genes is more stable in comparison not only with individual genes, but also with a system of reference genes used in commercial OncotypeDX test. A selection of reference genes for RT-qPCR can be efficiently performed by combining a preliminary search based on the high-throughput analysis of microarray datasets and final selection and validation based on the analysis of RT-qPCR data with a simultaneous examination of different expression stability measures. The identified set of reference genes proved to be less variable and thus potentially more efficient for research and clinical analysis of breast samples comparing to individual genes and the set of reference genes used in OncotypeDX assay.


Effect of chain flexibility on master curve behavior for diffusion coefficient.
The diffusion coefficients of simple chain models are analyzed as a function of packing fraction, η, and as a function of a parameter C that is the density raised to a power divided by temperature to look at scalar metrics to find master curves. The central feature in the analysis is the mapping onto an effective hard site diameter, d. For the molecular models lacking restrictions on dihedral angle (e.g., freely jointed), simple mappings of molecular potential to d work very well, and the reduced diffusion coefficient, D*, collapses into a single-valued function of η. Although this does not work for the dihedral angle restriction case, assuming that d is inversely proportional to temperature to a power results in collapse behavior for an empirically selected value of the power. This is equivalent to D* being a single-valued function of C. The diffusion coefficient of a single-site penetrant in the chain systems also is found to be a scalar metric that can reduce the chain diffusion data for a given system to a single master curve.


STAT3 contributes to the mitogenic response of hepatocytes during liver regeneration.
STAT3 is rapidly induced during liver regeneration in an interleukin 6 (IL-6)-dependent fashion, and IL-6 is required for normal liver regeneration. We wanted to know whether STAT3 was also required for liver regeneration but disruption of the STAT3 gene during embryonic stages causes lethality. Therefore, an albumin promoter-driven Cre-loxP recombination system was used to create a STAT3 deletion in the adult mouse liver to study the role of STAT3 in liver regeneration. After partial hepatectomy, there was virtually no STAT3 RNA or protein induction in Alb(+) STAT3(fl/fl) livers. STAT3 DNA binding activity was also absent in Alb(+) STAT3(fl/fl) livers. Unlike in control livers, STAT1 was activated in STAT3 conditional-mutant livers posthepatectomy. Hepatocyte DNA synthesis at 40 h posthepatectomy in Alb(+) STAT3(fl/fl) livers was reduced to approximately one-third of the control. Alb(+) STAT3(fl/fl) livers had abnormalities in immediate-early gene activation that largely correlated with but were not identical to those seen in IL-6-/- livers. G(1) phase cyclins including cyclins D1 and E had lower expression levels in Alb(+) STAT3(fl/fl) livers, indicating an abnormal G(1) to S phase transition. Therefore, STAT3 accounts for part of the DNA synthetic response of the hepatocytes during liver regeneration, which cannot be compensated for by induction of STAT1. Normal activation of the MAPK pathway in Alb(+) STAT3(fl/fl) livers reinforces the fact that at least part of the effect of IL-6 on hepatocyte proliferation is not mediated by STAT3. This study provides the first in vivo evidence that STAT3 promotes cell cycle progression and cell proliferation under physiological growth conditions.


Post-thymic maturation of migrating human thymic single-positive T cells: thymic CD1a- CD4+ T cells are more susceptible to anergy induction by toxic shock syndrome toxin-1 than cord blood CD4+ T cells.
To determine whether human CD4+ T cells undergo post-thymic maturation, we compared the susceptibility to anergy induction in human thymic CD1a- CD4+ single-positive (CD4+), cord blood (CB) CD4+, and adult peripheral blood (APB) CD4+ T cells by stimulation with toxic shock syndrome toxin-1 (TSST-1). Most TSST-1-induced T cell blasts derived from either T cell preparation expressed TCR Vbeta2, which determines the potential reactivity to TSST-1. Most thymic CD4+ T cell blast preparations exhibited little or no production of IL-2 and IL-4 after restimulation with TSST-1 and only marginal responses after stimulation with rIL-2 or a combination of PMA and calcium ionophore, while the APB CD4+ T cell blasts showed high responses to these stimuli. The responses of CB CD4+ T cell blasts to these stimuli varied, ranging from minimal to relatively high. Studies of DNA fragmentation showed that there was no significant cell death of thymic CD4+ T cell blasts. Most thymic CD1a- CD4+ and CB CD4+ T cells were CD38 positive. APB CD4+ T cell blasts derived from the CD38+ fraction and from the CD38- fraction exhibited equally high responses to restimulation with TSST-1. These results indicate that thymic CD1a- CD4+ and CB CD4+ T cells are inherently highly susceptible to anergy induction by bacterial superantigens and that thymic CD1a- CD4+ T cells are less mature than CB CD4+ T cells, suggesting that post-thymic maturation in thymic T cells migrating to the periphery is required for acquisition of full reactivity to antigenic stimulation.


[A case of recurrent duodenal carcinoma successfully controlled with FOLFOX treatment].
A 60-year-old woman was diagnosed as having duodenal cancer by upper gastrointestinal endoscopy and biopsy. Pylorus-preserving pancreatoduodenectomy was performed. Pathological findings suggested T4(CBD)N1M0 primary duodenal carcinoma. Adjuvant chemotherapy with S-1(80 mg/m² of S-1 administered for 2 weeks followed by a 1-week drug-free period)was administered after surgery. One year after the surgery, computed tomography(CT)scans showed swelling of the paraaortic lymph nodes. Recurrence of the duodenal carcinoma was diagnosed, and gemcitabine chemotherapy was initiated. Eight months later, CT scans revealed lung metastasis. The patient was then treated with oxaliplatin in combination with infusional 5-fluorouracil/Leucovorin(FOLFOX regimen). After completing 6 courses of the chemotherapy regimen, CT scans showed a partial response(PR). Currently, at 1 year, PR has been maintained. Therefore, we suggest that the FOLFOX regimen can be highly effective for the treatment of patients with duodenal carcinoma.


Proactive outreach smoking cessation program for Chinese employees in China.
We evaluated the first workplace intervention to help smokers quit in Hong Kong. Smoking employees (N = 642) received a 26-page self-help booklet and 15 fix SMS within 3 months and chose to receive cognitive behavioral workshop (N = 76), or face-to-face counseling (N = 11), or group health talk (N = 516), or telephone counseling (N = 39). Twenty participants were interviewed individually for their opinions about the interventions. By intention-to-treat, the overall self-reported past 7-day point prevalence quit rate was 31.0% and 32.9%, and reduction rate was 15.0% and 13.2% at 6 and 12-months, respectively. More than 20% of the unmotivated smokers at baseline (N = 399) quit in this program. Proactive outreach workplace smoking cessation programs with diverse intensity but without medications, chosen by smokers and supported by employers without further incentives, were feasible in busy working environment in Hong Kong.


Some Physical Properties of Protein Moiety of Alkali-Extracted Tea Polysaccharide Conjugates Were Shielded by Its Polysaccharide.
Polysaccharide conjugates were alkali-extracted from green tea (TPC-A). Although it contained 11.80% covalently binding proteins, TPC-A could not bind to the Coomassie Brilliant Blue dyes G250 and R250. TPC-A had no expected characteristic absorption peak of protein in the UV-vis spectrum scanning in the range of 200-700 nm. The UV-vis wavelength of 280 nm was not suitable to detect the presence of the protein portion of TPC-A. The zeta potential of TPC-A merely presented the negative charge properties of polysaccharides instead of the acid-base property of its protein section across the entire pH range. Furthermore, TPC-A was more stable when the pH of solution exceeded 4.0. In addition, no precipitation or haze was generated in the TPC-A/(-)-epigallocatechin gallate (EGCG) mixtures during 12 h storage. TPC-A has emulsifying activity, which indicated that its protein moiety formed hydrophobic groups. Thus, it was proposed that some physical properties of TPC-A protein were shielded by its olysaccharide, since the protein moiety was wrapped by its polysaccharide chains.


Phylogenetic climatic niche conservatism and evolution of climatic suitability in Neotropical Angraecinae (Vandeae, Orchidaceae) and their closest African relatives.
In the present study we investigate the concept of phylogenetic niche conservatism (PNC) within the American species of angraecoid orchids (Campylocentrum and Dendrophylax) and their closest relatives in the Old World (Angraecum) using ecological niche modelling (ENM). The predicted niche occupancy profiles were matched with the outcomes of previous phylogenetic studies to reconstruct the evolution of climatic suitability within the orchid group studied and evaluate the role of niche differentiation in the speciation of Angraecinae. No correlation between preferred niches and taxonomic relationships within the orchid group studied was revealed. The climatic suitability of the majority of the species overlapped each other, either fully or partially. This pattern is also present in the species of other orchid genera. Our research confirms a significant level of PNC in Orchidaceae, even within taxa exhibiting a transatlantic disjunction. The analysis of the evolution of climatic suitability indicated that the adaptation to various climatic conditions is not a factor that has driven speciation within orchids studied.


Cholecystectomy following the introduction of laparoscopy: more, but for the same indication.
To assess whether indications for cholecystectomy might have changed after the introduction of laparoscopic cholecystectomy (LC), the data from patients undergoing cholecystectomy at the University of South Alabama Medical Center during 1988 (before LC) and 1993 (after the introduction of LC) were retrospectively analyzed and compared. In 1993, the number of patients undergoing cholecystectomy for gallstone-related disease was 18 per cent higher than in 1988 (87 vs 103, 1.4 per cent of all noncardiac operations vs 2.7 per cent, Chi square; P = 0.003). There was no difference in the mean Preoperative Severity Index, a quantitative evaluation of symptom complex, preoperative laboratory evaluation, and radiological findings. Besides obesity, there were also no differences between the groups in associated comorbidities that might affect the decision to proceed with operation. Furthermore, pathologic findings, including the distribution of patients with gallstone pancreatitis, symptomatic cholelithiasis, chronic cholecystitis, and acute cholecystitis, were similar in both groups. The indications for cholecystectomy did not broaden after the introduction of LC, but rather, more patients with similar indications are undergoing cholecystectomy now, as compared with the pre-laparoscopic era.


The Accuracy of Common Hand Injections With and Without Ultrasound: An Anatomical Study.
The aim of the study is to determine the accuracy of hand injections with and without the aid of ultrasound (U/S) into the carpal tunnel, thumb carpometacarpal (CMC) joint, first dorsal compartment (DC) and the radiocarpal (RC) joint. Four participants of various level of experience injected the carpal tunnel, thumb CMC, first DC, and RC joint into 40 fresh frozen cadaver specimens with blue dye and radiographic contrast. Participants 1 and 2 were injected without U/S guidance, and participants 3 and 4 were injected with U/S guidance. A successful injection was determined by both fluoroscopy and dissection/direct observation. Additional information was recorded for each injection such as median nerve infiltration and evidence of thumb CMC arthrosis. The overall accuracy for carpal tunnel, thumb CMC, first DC, and RC injections were 95%, 63%, 90%, and 90%, respectively. Success was compared with and without U/S guidance. Success rates were similar for each injection site, except the thumb CMC joint, where U/S participants had 25% higher accuracy. In the setting of thumb CMC arthrosis, the incidence of success was 38% for participants with no U/S aid and 72% for participants with U/S aid. There was a significant difference between participants who used U/S with the participant with more U/S experience being more successful. Carpal tunnel, first DC, and RC injections had an accuracy of greater than 90%. Thumb CMC injections have a lower accuracy (63%) and one can improve accuracy with U/S. The accuracy of U/S-guided injections is dependent on the user and their experience.


Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor.
Cellular senescence suppresses cancer by arresting cell proliferation, essentially permanently, in response to oncogenic stimuli, including genotoxic stress. We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells. We show that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy. This senescence-associated secretory phenotype (SASP) developed slowly over several days and only after DNA damage of sufficient magnitude to induce senescence. Remarkably similar SASPs developed in normal fibroblasts, normal epithelial cells, and epithelial tumor cells after genotoxic stress in culture, and in epithelial tumor cells in vivo after treatment of prostate cancer patients with DNA-damaging chemotherapy. In cultured premalignant epithelial cells, SASPs induced an epithelial-mesenchyme transition and invasiveness, hallmarks of malignancy, by a paracrine mechanism that depended largely on the SASP factors interleukin (IL)-6 and IL-8. Strikingly, two manipulations markedly amplified, and accelerated development of, the SASPs: oncogenic RAS expression, which causes genotoxic stress and senescence in normal cells, and functional loss of the p53 tumor suppressor protein. Both loss of p53 and gain of oncogenic RAS also exacerbated the promalignant paracrine activities of the SASPs. Our findings define a central feature of genotoxic stress-induced senescence. Moreover, they suggest a cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment.


Bone SPECT in management of mandibular condyle hyperplasia. Report of a case and review of literature.
In the present paper we report the case of a 14-year-old girl suffering from condylar hyperplasia and enlargement of ipsilateral jaw body, stressing the importance of bone SPECT in the clinical management of this temporomandibular joint (TMJ) disorder. Condylar hyperplasia is an uncommon idiopathic monolateral disorder of jaw growth consistent with exuberant or persistent activity of the condyle nucleus finally involving sociopsychological aspects due to facial dysmorphism. Besides facial asymmetry our patient showed prognathism, malocclusion, worsening otalgia and headache. Conventional X-rays examinations and multislice spiral CT gave us important morphostructural information also thanks to 3D volume-rendered and virtual reconstructions, while bone SPECT by detecting an intense well focused (99m)Tc-MDP uptake allowed to achieve uninvasively the final diagnosis of primary condyle hyperplasia. In spite of the full imaging characterization of TMJ disorders, consensus on best timing and therapeutic approaches on condylar hyperplasia is yet to be reached. In the present case patient was first treated orthodontically, planning a "high" condylectomy intervention after at least 6 months.


Elastic response of wire frame glasses. I. Two dimensional model.
We study the elastic response of concentrated suspensions of rigid wire frame particles to a step strain. These particles are constructed from infinitely thin, rigid rods of length L. We specifically compare straight rod-like particles to bent and branched wire frames. In dense suspensions, the wire frames are frozen in a disordered state by the topological entanglements between their arms. We present a simple, geometric method to find the scaling of the elastic stress with concentration in these glassy systems. We apply this method to a simple 2D model system where a test particle is placed on a plane and constrained by a random distribution of points with number density ν. Two striking differences between wire frame and rod suspensions are found: (1) The linear elasticity per particle for wire frames is very large, scaling like ν2L4, whereas for rods, it is much smaller and independent of concentration. (2) Rods always shear thin but wire frames shear harden for concentrations less than ∼K/kBTL4, where K is the bending modulus of the particles. The deformation of wire frames is found to be important even for small strains, with the proportion of deformed particles at a particular strain, γ, being given by (νL2)2γ2. Our results agree well with simple numerical calculations for the 2D system.


Sutureless closure for the management of gastroschisis.
Gastroschisis is a common congenital anomaly in which the midgut fails to return to the abdominal cavity resulting in exposed intestines, which are not covered by a membrane in a neonate. The incidence of gastroschisis has been increasing worldwide resulting in an evolving medical and surgical management. Gastroschisis can be either simple or complicated. Complicated gastroschisis occurs when gastroschisis is associated with gastrointestinal conditions such as intestinal atresia, volvulus, stenosis or perforation. In this instance, the mortality and morbidity of patients significantly increases. Initial management of gastroschisis requires a multi-modal, interdisciplinary approach in order to successfully care for a neonate. Patients should be managed in a neonatal intensive care unit under the care of intensivists, respiratory therapists and pediatric surgeons. Temperature regulation, hydration and protection of the bowel are of the utmost priorities. Surgical management of gastroschisis focuses on reduction of the bowel and closure of the abdominal wall defect. Initially, the defect was closed primarily with suture, however, more recently, a sutureless closure has become prevalent. This, in conjunction with use of a silo, has led to a shift from the operating room and general anesthesia to the bedside. This article aims to discuss the presentation, diagnosis and management of gastroschisis.


Miscarriage but not fecundity is associated with progression of joint destruction in rheumatoid arthritis.
To determine whether reproductive history before disease onset is associated with severity of joint destruction in rheumatoid arthritis. A special early arthritis clinic (EAC) was established at the department of rheumatology of Leiden University Medical Centre. General practitioners were encouraged to refer patients with joint complaints to this clinic, where the diagnosis of rheumatoid arthritis was made by a rheumatologist. In all, 113 female patients with definite rheumatoid arthritis were included in this study. A structured questionnaire was administered and joint damage was assessed by sequential x rays of the hands and feet, using the modified Sharp score. The length of time of unprotected intercourse until first pregnancy (fecundity) was comparable with data from earlier studies, with 16% of the patients reporting a time to first pregnancy of more than 12 months. Fecundity did not reflect the extent of joint damage over time. The miscarriage rate was 15% per pregnancy, comparable to population figures (12-15%). A significant increase in joint damage over a two year follow up was found in patients with rheumatoid arthritis who had experienced at least one miscarriage compared with those who had never had a miscarriage (mean modified Sharp scores at 2 years, 24 (95% confidence interval, 15 to 32) and 16 (10 to 23), respectively; p<0.05). At baseline, the Sharp scores were similar in the two subgroups. Miscarriage before disease onset but not fecundity is associated with the progression of joint damage in rheumatoid arthritis.


Substituting oat hay or maize silage for portion of alfalfa hay affects growth performance, ruminal fermentation, and nutrient digestibility of weaned calves.
The impact of forage feeding strategy on growth performance, ruminal fermentation and nutrient digestibility in post-weaning calves was investigated. Forty-five female Holstein calves (body weight [BW] = 79.79±0.38 kg) were enrolled in the 35-d study at one week after weaning and randomly assigned to one of three dietary treatments. All diets were fed as total mixed ration containing 60% (dry matter [DM] basis) of basal starter feed and 40% (DM basis) of forage, but varied in composition of forage source including i) alfalfa (40% DM, AH); ii) alfalfa hay (26.7% DM)+oat hay (13.3% DM; OH); iii) alfalfa hay (26.7% DM)+corn silage (13.3% DM; WS). Dry matter intake was not different among treatment groups (p>0.05). However, BW (p<0.05) and average daily gain (p<0.05) of calves fed AH and OH were greater than WS-fed calves, whereas heart girth was greater in OH-fed calves than those fed AH and WS (p<0.05). Ruminal fermentation parameters including proportion of butyric acid, acetated-to-propionate ratio, concentration of total volatile fatty acid, protozoal protein, bacterial protein, and microbial protein in rumen were the highest in OH (p<0.05) and the lowest in WS. Compared with the AH and WS, feeding oat hay to postweaning calves increased crude protein digestibility (p<0.05), and decreased duration of diarrhea (p<0.05) and fecal index (p<0.05). Our results suggested that partially replacing alfalfa hay with oat hay improved ruminal fermentation, nitrogen utilization, and reduced incidence of diarrhea in post-weaning dairy calves.


Tracking Responses to Items in Measures as a Means of Increasing Therapeutic Engagement in Clients: A Complementary Clinical Approach to Tracking Outcomes.
This article presents a novel clinical application of questionnaire feedback, which focuses on change at the individual question level rather than the total mean or clinical score level. We term the approach 'Tracking Responses to Items in Measures' (TRIM) and promote the key aims to be (1) providing both client and practitioner with feedback on areas of positive change that may be masked by numerical feedback, (2) reinforcing client strengths and self-efficacy, (3) exploring potential extra-therapeutic factors that may contribute to the lack of change or deterioration on individual questions and (4) establishing a collaborative dialogue relating clients' problems to their goals and the consequent aims of treatment. This paper profiles the clinical origins and technical development of TRIM as a clear, user-friendly display of item change across sessions using colour codes and illustrates the clinical utility through two clinical vignettes. Although the profile of the TRIM method herein uses the Clinical Outcomes in Routine Evaluation Outcome Measure, we believe the method could easily be used with other measures. These could include Generalized Anxiety Disorder 7 and Patient Health Questionnaire 9 used in English National Health Service primary care Improving Access to Psychological Therapies services, or disorder specific measures for particular problems commonly used in National Health Service specialist services. We suggest TRIM is a practical complement to existing feedback systems, especially in work with clients who may be less likely to show empirically meaningful change on mean item or clinical score levels. Using outcome questionnaires as conversational tools helps practitioners focus on change at the individual item level rather than the numeric level. Tracking Responses to Items in Measures helps provide clients and practitioners with feedback on areas of positive change that may be masked by summary score analysis. Exploring the lack of change or deterioration on particular questions helps practitioners to assess extra-therapeutic factors that may be compromising change. Using individual item change profiles as feedback for clients helps validate their progress and reinforce their strengths and self-efficacy.


Enhancing Primary Adherence to Prescribed Medications through an Organized Health Status Assessment-Based Extension of Primary Healthcare Services.
This study was part of monitoring an intervention aimed at developing a general practitioner cluster (GPC) model of primary healthcare (PHC) and testing its effectiveness in delivering preventive services integrated into the PHC system. The aim was to demonstrate whether GPC operation could increase the percentage of drugs actually dispensed. Using national reference data of the National Health Insurance Fund for each anatomical-therapeutic chemical classification ATC group of drugs, dispensed-to-prescribed ratios standardized (sDPR) for age, sex, and exemption certificate were calculated during the first quarter of 2012 (before-intervention) and the third quarter of 2015 (post-intervention). The after-to-before ratios of the sDPR as the relative dispensing ratio (RDR) were calculated to describe the impact of the intervention program. The general medication adherence increased significantly in the intervention area (RDR = 1.064; 95% confidence interval (CI): 1.054-1.073). The most significant changes were observed for cardiovascular system drugs (RDR = 1.062; 95% CI: 1.048-1.077) and for alimentary tract and metabolism-specific drugs (RDR = 1.072; 95% CI: 1.049-1.097). The integration of preventive services into a PHC without any specific medication adherence-increasing activities is beneficial for medication adherence, especially among patients with cardiovascular, alimentary tract, and metabolic disorders. Monitoring the percentage of drugs actually dispensed is a useful element of PHC-oriented intervention evaluation frames.


High cardiovascular risk in young Saudi males: cardiovascular risk factors, diet and inflammatory markers.
The relationship between coronary risk score (CRS), individual coronary risk factors and the serum inflammatory markers, high sensitivity C-reactive protein (hsCRP), ceruloplasmin (Cp), and soluble intercellular adhesion molecule-1 (sICAM-1) was studied in 140 Saudi males without clinically evident coronary heart disease (CHD). One hundred forty subjects without clinically evident CHD were categorized into age tertiles. Demographic data together with an estimate of CRS using Framingham and PROCAM algorithms were obtained, and serum lipid profile, glucose, hsCRP, sICAM-1, and Cp were measured. Macronutrient intake was assessed by a questionnaire. The relationship between CRS, biochemical markers and diet was assessed by univariate and multivariate analysis. There was no significant difference in median hsCRP, sICAM-1 or Cp between the age groups. Serum Cp was positively associated with age (r=0.224, p<0.01) and FRS score (r=0.174, p<0.05). Serum sICAM-1 was negatively associated with PROCAM score (r=-0.183, p<0.05). sICAM-1 was positively associated with HDL cholesterol (r=0.36, p<0.0001) among non-diabetics and negatively associated (r=-0.397, p<0.05) among diabetic subjects. Age and dietary intake of saturated fatty acids together explained 7.9% of the variation in serum Cp level in a stepwise multiple regression model. Similarly 6.5% of the variation in serum sICAM-1 level was explained by the total cholesterol/HDL-C ratio. The youngest tertile of the group (<30 y) had the highest dietary intake of energy, fat and saturated fatty acids (p<0.05), and also had a high prevalence of obesity, smoking and sedentary lifestyle. We have demonstrated that there is a high prevalence of coronary risk factors and poor dietary intake within a Saudi male population, and that dietary factors are associated with serum sICAM-1 and ceruloplasmin but not hsCRP concentrations in this group.