Women's disclosure of HIV status: experiences of mistreatment and violence in an urban setting.
Women represent an increasing proportion of AIDS cases and anecdotal reports suggest some face substantial risks when others learn they are HIV-positive. The purpose of this paper is to describe women's fears and experiences regarding disclosure of their HIV status. Fifty HIV-positive women, ages 16-45 from urban teaching hospital outpatient clinics, were interviewed using an in-depth, qualitative interview. Eighty-six percent of the women were African American and 56% were current or former IVDU. At the time of the interview, 88% of the women had known their HIV status for a year or more. All but one woman had disclosed her HIV status to at least one person and 82% had disclosed to multiple people. Although two-thirds of the women had been afraid to disclose to others because of concerns about rejection, discrimination or violence, three-quarters of the sample reported only supportive and understanding responses to their disclosure. One-quarter of the sample reported negative consequences of disclosure, including rejection, abandonment, verbal abuse and physical assault. Disclosure-related violence was discussed by nine women (18%): two who feared violence were relieved to find a supportive response; four chose not to disclose their status because they feared violence; and three women were verbally or physically assaulted. Fear of mistreatment figured prominently in decisions about disclosure among this sample. That many women found supportive and understanding responses is encouraging. However, there were sufficient examples of negative consequences, including violence, to suggest individualized approaches to post-test counseling, enhanced support services for HIV-positive women, and public education to destigmatize HIV-disease.


Site-specific mutagenesis of Drosophila proliferating cell nuclear antigen enhances its effects on calf thymus DNA polymerase delta.
We and others have shown four distinct and presumably related effects of mammalian proliferating cell nuclear antigen (PCNA) on DNA synthesis catalyzed by mammalian DNA polymerase delta(pol delta). In the presence of homologous PCNA, pol delta exhibits 1) increased absolute activity; 2) increased processivity of DNA synthesis; 3) stable binding of synthetic oligonucleotide template-primers (t1/2 of the pol deltaPCNAtemplate-primer complex >/=2.5 h); and 4) enhanced synthesis of DNA opposite and beyond template base lesions. This last effect is potentially mutagenic in vivo. Biochemical studies performed in parallel with in vivo genetic analyses, would represent an extremely powerful approach to investigate further, both DNA replication and repair in eukaryotes. Drosophila PCNA, although highly similar in structure to mammalian PCNA (e.g., it is >70% identical to human PCNA in amino acid sequence), can only substitute poorly for either calf thymus or human PCNA (approximately 10% as well) in affecting calf thymus pol delta. However, by mutating one or only a few amino acids in the region of Drosophila PCNA thought to interact with pol delta, all four effects can be enhanced dramatically. Our results therefore suggest that all four above effects depend at least in part on the PCNA-pol delta interaction. Moreover unlike mammals, Drosophila offers the potential for immediate in vivo genetic analyses. Although it has proven difficult to obtain sufficient amounts of homologous pol delta for parallel in vitro biochemical studies, by altering Drosophila PCNA using site-directed mutagenesis as suggested by our results, in vitro biochemical studies may now be performed using human and/or calf thymus pol delta preparations.


The premenstrual syndrome. A survey of current treatment practices.
Interest in the premenstrual syndrome (PMS) has increased rapidly in both the lay and professional communities during the past few years. Research on the causes, diagnosis and treatment of the disorder continues to expand. An area that has received little attention, however, is the current treatment practices of physicians who recognize PMS as a treatable disorder. Our study was a survey of 502 physicians from the United States and Canada regarding diagnostic and treatment services provided to their PMS patients. Descriptive results of the survey, as well as breakdowns by medical specialty and region, were obtained. The results have implications for current practice and future research.


Characteristics of the NICU work environment associated with breastfeeding support.
The provision of breastfeeding support in the neonatal intensive care unit (NICU) may assist a mother to develop a milk supply for the NICU infant. Human milk offers unique benefits and its provision unique challenges in this highly vulnerable population. The provision of breastfeeding support in this setting has not been studied in a large, multihospital study. We describe the frequency of breastfeeding support provided by nurses and examined relationships between NICU nursing characteristics, the availability of a lactation consultant (LC), and breastfeeding support. This was a secondary analysis of 2008 survey data from 6060 registered nurses in 104 NICUs nationally. Nurse managers provided data on LCs. These NICUs were members of the Vermont Oxford Network, a voluntary quality and safety collaborative. Nurses reported on the infants (n = 15,233) they cared for on their last shift, including whether breastfeeding support was provided to parents. Breastfeeding support was measured as a percentage of infants on the unit. The denominator was all infants assigned to all nurse respondents on that NICU. The numerator was the number of infants that nurses reported providing breastfeeding support. Nurses also completed the Practice Environment Scale of the Nursing Work Index (PES-NWI), a nationally endorsed nursing care performance measure. The NICU nursing characteristics include the percentages of nurses with a BSN or higher degree and with 5 or more years of NICU experience, an acuity-adjusted staffing ratio, and PES-NWI subscale scores. Lactation consultant availability was measured as any/none and in full-time equivalent positions per 10 beds. The parents of 14% of infants received breastfeeding support from the nurse. Half of the NICUs had an LC. Multiple regression analysis showed a significant relationship between 2 measures of nurse staffing and breastfeeding support. A 1 SD higher acuity-adjusted staffing ratio was associated with a 2% increase in infants provided breastfeeding support. A 1 SD higher score on the Staffing and Resource Adequacy PES-NWI subscale was associated with a 2% increase in infants provided breastfeeding support. There was no association between other NICU nursing characteristics or LCs and nurse-provided breastfeeding support. Nurses provide breastfeeding support around the clock. On a typical shift, about 1 in 7 NICU infants receives breastfeeding support from a nurse. Lactation consultants are not routinely available in NICUs, and their presence does not influence whether nurses provide breastfeeding support. Better nurse staffing fosters nurse provision of breastfeeding support.


Dynamic respiratory videoendoscopy in ridden sport horses: effect of head flexion, riding and airway inflammation in 129 cases.
Dynamic upper airway obstruction (UAO) is a cause of respiratory noise and sometimes poor performance in sport horses. Riding, head flexion and airway inflammation may impact upper respiratory tract stability during exercise. To evaluate upper airway mechanical behaviour in ridden sport horses using overground endoscopy and the effect of head flexion, rider intervention and underlying airway inflammation on the pharynx and larynx. Resting and exercising videoendoscopic recordings during ridden exercise were obtained in 129 sport horses referred mainly for respiratory noise, poor performance or routine evaluation. The rider modified poll flexion and way of riding during the test and associated changes in UAO were recorded. Presence of upper and lower airway inflammation was also assessed. Dynamic UAO was diagnosed in 91% (64/70) of the horses referred for respiratory noise and in 71% (29/41) of horses referred for poor performance. Pharyngeal instability was the most frequently diagnosed problem. However, differences were observed between dressage horses and showjumpers. Rider interaction and head flexion exacerbated upper airway instability and promoted the occurrence of complex UAO. Both lower airway inflammation and pharyngeal lymphoid hyperplasia were associated with pharyngeal instability, but not with any other UAO. Rider intervention during ridden exercise (i.e. the various movements a horse might be asked to perform) influences upper airway morphology and function and, in cases of upper airway dynamic obstruction, can contribute to increasing laryngeal and/or pharyngeal instability in sport horses. As these are changes that would not usually be seen with treadmill videoendoscopy, ridden videoendoscopy should be the preferred method for evaluation of the upper airway in sport horses.


Update on PARP1 inhibitors in ovarian cancer.
The clinical development of PARP inhibitors for the treatment of tumors deficient in BRCA1 or BRCA2 is based on the concept of synthetic lethality. From the initial proof of concept study with the PARP1 inhibitor olaparib (AZD2281) in BRCA mutation carriers, in which 28% of ovarian cancer patients achieved an objective response, the target population of ovarian patients potentially sensitive to treatment with PARP inhibitors has greatly increased. Objective responses have been observed in both platinum-sensitive and platinum-resistant BRCA mutation carriers but, more recently, also in BRCA negative 'BRCAness' patients, those with no BRCA mutations but with a dysfunction of the homologous recombination (HR) system, which makes them more sensitive to the antitumor agents which cause double strand breaks of DNA. The recent results achieved with olaparib, given as maintenance in platinum sensitive recurrent high grade serous ovarian cancer, in response after reinduction with platinum, confirm the antitumor effect of single agent olaparib in BRCAness patients. Main topics of investigations in this field are the identification of BRCAness phenotype and the definition of tests to identify BRCAness patients. More in general, additional preclinical studies are needed to further improve clinical results in order to define the optimal regimen of combination with PARP1 inhibitor and cytotoxics or molecular targeted agents (sequence of administration, interval between dosing of the agents, duration of treatment).


Approaches for improving patient safety through a safety clearinghouse.
Creating this type of a program is a challenge and takes the time and commitment of key players. Most healthcare facilities have had systems and processes in place for years to "ensure quality." Inherent in those systems has been some ability to detect errors and to identify opportunities for improving quality of care. The next evolution of ensuring quality requires healthcare organizations to become far more proactive with error detection and correction systems. How? Becoming more openly and honestly communicative internally is an important first step. That means creating a nonpunitive environment that encourages staff members to report known or suspected problems. To do this most successfully requires not only involving members of the hospital staff who become aware of concerns, but also engaging patients and families as partners in the process. Healthcare organizations can learn much from patients and families about things that actually or almost go wrong. In turn, healthcare organizations owe patients and their families honesty when they know something has gone wrong that could or should have been prevented. Many healthcare organizations throughout the country are struggling with these new expectations from accreditors and consumers about disclosing medical errors to patients (and/or their families). Some may still even be questioning the need and/or the value of doing so. The Lexington VA Medical Center has been disclosing errors for approximately 10 years. The center has also been piloting proactive approaches to identifying and eliminating threats to patient safety (i.e., error-prone systems and processes). VAMC's experiences have demonstrated that both are clearly worth the effort.


Comparison of Diagnostic Accuracy for the Low-Type Imperforate Anus Between Prone Cross-Table Radiography and Sonography.
To compare the diagnostic accuracy for the low-type imperforate anus between prone cross-table radiography and sonography. We included 20 neonates with imperforate anus: 13 with a surgically proven low type and 7 with an intermediate or high type. The distance between the distal rectal pouch and the perineum (pouch-perineum distance) was measured by both sonography and prone cross-table radiography. A previously established pouch-perineum distance of 10 mm was used as the cutoff for diagnosis of a low-type imperforate anus. The fistula location was also determined with sonography. We then compared the diagnostic accuracy of the imaging methods for a low-type imperforate anus using the cutoff value of the pouch-perineum distance alone and both the cutoff value of the pouch-perineum distance and fistula location. The McNemar test was used for statistical analysis. With the use of only the pouch-perineum distance, the diagnostic accuracy for the low-type imperforate anus based on sonographic measurements was comparable with the accuracy achieved by prone cross-table radiographic measurements (60.0% [12 of 20] versus 45.0% [9 of 20]; P = .625). With the use of the pouch-perineum distance and fistula location, the diagnostic accuracy of sonography was significantly better than the accuracy of prone cross-table radiography (90.0% [18 of 20] versus 45% [9 of 20]; P = .012). The diagnostic accuracy of sonography for the low-type imperforate anus based on both the pouch-perineum distance and fistula location is better than that of prone cross-table radiography. If the pouch-perineum distance on prone cross-table radiography is greater than 10 mm, a sonographic examination to determine the fistula location could be recommended.


Exostosis of the external auditory canal: a technical note.
To describe the author's method of managing occlusive exostosis of the external auditory canal. Retrospective chart review. Tertiary referral ambulatory otology clinic. A case series of patients treated sequentially by the author over 15 years, all of whom had occlusive external auditory canal exostoses that could not be treated by medical management. Permeatal surgical removal of the anterior exostosis only. Surgical relief of occlusive external auditory canal disease by restoration of hearing and absence of infection with persistence of an external auditory canal and no symptoms of recurrence. A total of 8 men were treated by anterior exostosis removal. Follow-up continued on these patients for a period of 5 to 15 years after the operation, and none showed any evidence of recurrence or tendency to narrowing of the deep ear canal. One patient incurred a tympanic membrane perforation at escostosis surgery that was repaired during the operation. Anterior exostosis removal by a permeatal route is a safe, rapid, and effective method of relieving patients of occlusive external auditory canal exostosis. By leaving the posterior exostosis intact, patients are not put at risk for injury to the facial nerve, chorda tympani nerve, or ossicles. When the deep ear canal is drilled blind, there are no landmarks to indicate the true path of the external canal.


Receptors for maleylated proteins regulate secretion of neutral proteases by murine macrophages.
Receptors for maleylated or acetylated proteins as well as for alpha-2-macroglobulin-protease complexes on macrophages serve as scavengers by mediating the uptake of macromolecules from the extracellular compartment. Described in this report is a novel function of these receptors on macrophages: regulation of neutral protease secretion. The binding of maleylated bovine serum albumin to macrophages triggered secretion of three neutral proteases: neutral caseinases, plasminogen activator, and cytolytic proteinase. Release of acid phosphatase, however, was not induced. An important biological consequence of protease secretion by macrophages, tumor-cytolysis, was also triggered by engagement of the receptor for maleylated bovine serum albumin. By contrast, the binding of alpha-2-macroglobulin-protease complexes to the macrophages suppressed secretion of all three proteases. Thus two receptors heretofore believed to serve principally as scavengers also regulate secretory functions of macrophages.


Apparent co-operative effect of hydrogen carbonate (HCO-3) on pigeon kidney pyruvate carboxylase.
Kinetic methods have been used to determine the interrelationship between HCO-3, pyruvate and acetyl-CoA and their effect on pigeon kidney pyruvate carboxylase (pyruvate: CO2 ligase [ADP], EC 126.96.36.199). HCO-3 shows a negative co-operative effect (biphasic kinetics with two different Km values). Pyruvate influences the attachment of HCO-3 to this enzyme. The same has been shown for acetyl-CoA. Contrary to the results of other investigators no co-operative effect was seen with pyruvate even at different concentrations of acetyl-CoA. HCO-3 itself shows hardly any effect on the homotropic positive co-operativity (sigmoidal kinetics) of acetyl-CoA. The negative co-operative effect of HCO-3 could not be removed even at saturating concentrations of pyruvate and/or acetyl-CoA, which is also supported by the n and Rs values. The results of this communication bring out differences between pigeon kidney pyruvate carboxylase and pyruvate carboxylase from other sources. It is also suggested that there may be different allosteric and regulatory sites for acetyl-CoA, HCO-3 and pyruvate.


Swallowing disorders and 1-year functional decline in community-dwelling older adults receiving home care.
The purpose of this study was to clarify the effect of swallowing disorders on functional decline in community-dwelling older adults receiving home care. This was a 1-year follow-up survey of 176 individuals ≥60 years living at home and receiving homecare services, without total dependence in basic daily living activities, in two mid-sized municipalities in Fukuoka, Japan. Functional decline was measured using the Barthel index (BI), and the primary outcome was total dependence in basic daily living activities (BI ≤ 20 points). Swallowing function was assessed using cervical auscultation, and the primary predictor was swallowing disorders. Logistic regression models were used to assess univariate and multivariate associations between baseline swallowing function and functional decline during follow-up. During follow-up 16 (9.1%), the participants became totally dependent in basic daily living activities. The participants with swallowing disorders had 6.41 times higher odds of total dependence in basic daily living activities compared to participants with normal swallowing function. After adjusting for potential confounders, swallowing disorders were significantly associated with higher odds of total dependence in basic daily living activities (odds ratio = 5.21, 95% confidence interval = 1.33-20.44). Regarding swallowing disorders, the corresponding population attributable fraction (%) of the incidence of total dependence in basic daily living activities was 50.4%. The current findings demonstrated that swallowing disorders were associated with greater risk of functional decline in basic daily living activities among older adults living at home and receiving home nursing care. Maintenance and improvement of swallowing function may prevent late-life functional decline.


Evaluation of Finnish Diabetes Risk Score in screening undiagnosed diabetes and prediabetes among U.S. adults by gender and race: NHANES 1999-2010.
To evaluate the performance of Finnish Diabetes Risk Score (FINDRISC) in detecting undiagnosed diabetes and prediabetes among U.S. adults by gender and race. This cross-sectional analysis included participants (aged ≥20 years) from the National Health and Nutrition Examination Survey (NHANES) 1999-2010. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve and the optimal cutoff points for identifying undiagnosed diabetes and prediabetes were calculated for FINDRISC by gender and race/ethnicity. Among the 20,633 adults (≥20 years), 49.8% were women and 53.0% were non-Hispanic White. The prevalence of undiagnosed diabetes and prediabetes was 4.1% and 35.6%, respectively. FINDRISC was positively associated with the prevalence of diabetes (OR = 1.48 for 1 unit increase, p<0.001) and prediabetes (OR = 1.15 for 1 unit increase, p<0.001). The area under ROC for detecting undiagnosed diabetes was 0.75 for total population, 0.74 for men and 0.78 for women (p = 0.04); 0.76 for White, 0.76 for Black and 0.72 for Hispanics (p = 0.03 for White vs. Hispanics). The area under ROC for detecting prediabetes was 0.67 for total population, 0.66 for men and 0.70 for women (p<0.001); 0.68 for White, 0.67 for Black and 0.65 for Hispanics (p<0.001 for White vs. Hispanics). The optimal cutoff point was 10 (sensitivity = 0.75) for men and 12 (sensitivity = 0.72) for women for detecting undiagnosed diabetes; 9 (sensitivity = 0.61) for men and 10 (sensitivity = 0.69) for women for detecting prediabetes. FINDRISC is a simple and non-invasive screening tool to identify individuals at high risk for diabetes in the U.S. adults.


Antidiabetic and Antioxidant Activity of Scoparia dulcis Linn.
The hypoglycaemic activity of methanol extract of Scoparia dulcis was performed on both in vitro and in vivo models along with determination of total extractable polyphenol. Methanol extract of Scoparia dulcis contains 4.9% and water extract contains 3.2% of total extractable polyphenol. The antioxidant activity showed very promising result in both the tested methods that is 2,2-diphenyl-1-picrylhydrazyl and ferric ion reducing capacity. The antioxidant activity is directly correlated to the antidiabetic potential of drug. The two enzymes (amylase and glycosidase) found in intestine are responsible for the increasing postprandial glucose in body. In vitro model was performed on these enzymes and the results showed that methanol extract of Scoparia dulcis was effective to check the postprandial glucose level. The in vivo hypoglycaemic activity of methanol extract of Scoparia dulcis was performed on streptozotocin-induced diabetes mellitus showed significant inhibition of blood glucose level as compared to control and similar to that of standard glibenclamide. The overall data potentiates the traditional value of Scoparia dulcis as an antidiabetic drug.


Droplet Microfluidics for the ex Vivo Expansion of Human Primary Multiple Myeloma Cells.
We previously reported a new approach for micromanipulation and encapsulation of human stem cells using a droplet-based microfluidic device We demonstrated the possibility of encapsulating and culturing difficult-to-preserve primary human hematopoietic stem cells using an engineered double layered bead composed by an inner layer of alginate and an outer layer of puramatrix constructed using a soft technology without the use of any external force. In this work, we use this micro manipulation technique to build a 3D scaffold as a biomimetic model to recapitulate the niche of patient-derived multiple myeloma cells (MM cell) using a multilayered 3D tissue scaffold constructed in a microfluidic device and cultured in 10% FBS culture medium. In the current study, we included the use of this biomimetic model comprising supporting human Mesenchymal stem cells to show the mid-term survival of MM cells in the proposed structures. We found that the generated microniches were suitable for the maintenance of MM cells with and without supporting cells. Additionally, cultured MM cells in droplets were exposed to both Bortezomib and Lenalidomide to test their toxicity in the cultured patient derived cells. Results indicate that the maintained MM cells were consistently responding to the applied medication, opening a wide field of possibilities to use the presented micro device as an ex vivo platform for drug screening.


[Intravascular radiologically-guided surgery in the treatment of congenital heart defects].
The article discusses the experience of the Bakulev Institute of Cardiovascular Surgery, USSR AMS, in catheter endovascular radiologically-guided surgery of some congenital heart diseases in the period from 1967 to 1990. A total of 505 operations were performed at the department of radiologically-guided examination and treatment of the heart and vessels: 307 Rashkind's and 35 Park's operations in total transposition of the great vessels, 110 balloon dilatations in valvular stenosis of the pulmonary trunk and 13 in valvular stenosis of the aorta, 7 embolizations in coronary-cardiac fistulas, 2 balloon dilatations in constrictions of Blalock-Taussig anastomosis, 14 balloon dilatations in peripheral stenoses of the pulmonary arteries, etc. The methodical aspects and the results of endovascular interventions are discussed in detail. The data of foreign researchers on the promising methods of radiologically-guided surgery are also shown.


The importance of methane breath testing: a review.
Sugar malabsorption in the bowel can lead to bloating, cramps, diarrhea and other symptoms of irritable bowel syndrome as well as affecting absorption of other nutrients. The hydrogen breath test is now a well established noninvasive test for assessing malabsorption of sugars in the small intestine. However, there are patients who can suffer from the same spectrum of malabsorption issues but who produce little or no hydrogen, instead producing relatively large amounts of methane. These patients will avoid detection with the traditional breath test for malabsorption based on hydrogen detection. Likewise the hydrogen breath test is an established method for small intestinal bacterial overgrowth (SIBO) diagnoses. Therefore, a number of false negatives would be expected for patients who solely produce methane. Usually patients produce either hydrogen or methane, and only rarely there are significant co-producers, as typically the methane is produced at the expense of hydrogen by microbial conversion of carbon dioxide. Various studies show that methanogens occur in about a third of all adult humans; therefore, there is significant potential for malabsorbers to remain undiagnosed if a simple hydrogen breath test is used. As an example, the hydrogen-based lactose malabsorption test is considered to result in about 5-15% false negatives mainly due to methane production. Until recently methane measurements were more in the domain of research laboratories, unlike hydrogen analyses which can now be undertaken at a relatively low cost mainly due to the invention of reliable electrochemical hydrogen sensors. More recently, simpler lower cost instrumentation has become commercially available which can directly measure both hydrogen and methane simultaneously on human breath. This makes more widespread clinical testing a realistic possibility. The production of small amounts of hydrogen and/or methane does not normally produce symptoms, whereas the production of higher levels can lead to a wide range of symptoms ranging from functional disorders of the bowel to low level depression. It is possible that excess methane levels may have more health consequences than excess hydrogen levels. This review describes the health consequences of methane production in humans and animals including a summary of the state of the art in detection methods. In conclusion, the combined measurement of hydrogen and methane should offer considerable improvement in the diagnosis of malabsorption syndromes and SIBO when compared with a single hydrogen breath test.


Evaluation of a Precision Approach to Intraoperative Ropivacaine Nerve Block to Improve Postoperative Analgesia in 120 Patients Undergoing Thyroid Surgery.
BACKGROUND This study aimed to compare a precision approach to intraoperative nerve block with traditional analgesia to reduce postoperative pain in 120 patients during thyroid surgery. The precision intraoperative technique used 0.3% ropivacaine to block the lower branch of the transverse cervical nerve and the inner branches of the supraclavicular nerve. MATERIAL AND METHODS A total of 120 patients were prospectively enrolled in this study. All patients were randomly and evenly divided into 3 groups. In the precision group, 0.3% ropivacaine was used through the wound during surgery. In the traditional group, a superficial cervical plexus nerve block was performed before surgery. Saline was injected in the control group. The valuation of postoperative pain was assessed using the visual analogue scale (VAS). RESULTS Two hours after surgery, the VAS scores in the precision group, traditional group, and control group were 1.4±0.5, 1.6±0.7, and 2.8±1.0 (P<0.001), respectively. Then, the pain improvement was more significant after 6 h, as the VAS scores in the precision, traditional, and control groups were 1.0±0.5, 1.2±0.6, and 2.6±1.1 (P<0.001), respectively. Twenty-four hours after surgery, the VAS scores in the precision, traditional, and control groups were 0.7±0.3, 0.6±0.4, and 1.9±1.1 (P<0.001), respectively. CONCLUSIONS At a single center, the use of a precision intraoperative ropivacaine nerve block significantly reduced postoperative pain when compared with traditional analgesia for patients undergoing thyroid surgery.


Midterm Results of Primary Exeter Cemented Stem in a Select Patient Population.
Most North American surgeons predominantly use uncemented stems in primary total hip arthroplasties (THAs) and reserve cemented stems for selected older patients and those with poor bone quality. However, data on this "selective use" strategy for cemented stems in the population at risk for periprosthetic fracture and implant loosening are limited. The purpose of this study was to describe implant survivorship, complications, and radiographic results of a specific collarless, polished, tapered cemented stem (Exeter; Stryker) used selectively in a predominantly elderly population undergoing primary THA. We identified 386 patients who underwent a total of 423 primary THAs with selectively utilized Exeter stems for the treatment of osteoarthritis between 2006 and 2017. In the same time period, 11,010 primary THAs were performed with uncemented stems and 961 with non-Exeter cemented stems. The mean patient age was 77 years, 71% were female, and the mean body mass index was 29 kg/m2. Competing risk analysis accounting for death was utilized to determine cumulative incidences of revision and reoperation. The mean follow-up was 5 years (range, 2 to 12 years). The 10-year cumulative incidence of any femoral component revision in this patient cohort was 4%, with 10 stems revised at the time of the latest follow-up. There were no intraoperative femoral fractures. The indications for revision were postoperative periprosthetic femoral fracture (n = 6), dislocation (n = 3), and infection (n = 1). There were no revisions for femoral loosening. The 10-year cumulative incidence of reoperation was 10%. The 10-year cumulative incidence of Vancouver B periprosthetic femoral fracture was 2%. Radiographically, there were no cases of aseptic loosening or osteolysis. There was a significant improvement in median Harris hip score, from 53 preoperatively to 92 at a mean follow-up of 5 years (p < 0.001). The strategy of selectively utilizing a collarless, polished, tapered cemented stem produced a low (4%) cumulative incidence of stem revision at 10 years postoperatively and resulted in no cases of aseptic loosening. The use of the Exeter stem did not eliminate postoperative femoral fractures in this predominantly elderly, female patient population. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


The distribution of somatic symptom disorder and bodily distress syndrome in general hospital outpatients in China: A multicenter cross-sectional study.
To investigate the distribution of somatic symptom disorder (SSD) and bodily distress syndrome (BDS) and analyze the differences in psychosocial characteristics of patients with the two diagnoses. A total of 694 general hospital outpatients completed the diagnostic interviews for SSD and BDS, and a set of questionnaires evaluating their psychosocial characteristics. A secondary analysis of these data is done. SSD and BDS had a moderate overlap (kappa value = 0.43). Patients who fulfilled both SSD and BDS diagnosis showed significantly higher levels of symptom-related psychological distress (SSD-12), somatic symptom severity (PHQ-15), depression (PHQ-9), and general anxiety (GAD-7), as well as lower mental and physical quality of life (SF-12) compared to patients with neither diagnosis and patients with only one diagnosis. Patients with either diagnosis were associated with significantly higher psychosocial impairments as compared to those with neither diagnosis. Patients who only met SSD had higher SSD-12 scores, whereas those with only BDS had higher PHQ-15 scores (p<0.001). SSD and BDS appear to represent somewhat different psychopathologies, with SSD more associated with psychological distress and BDS associated with greater experience of somatic symptoms. Patients fulfilling both diagnosis show higher symptom severity in various psychosocial aspects.


Changes in brown adipose tissue lipid mediator signatures with aging, obesity, and DHA supplementation in female mice.
Brown adipose tissue (BAT) dysfunction in aging and obesity has been related to chronic unresolved inflammation, which could be mediated by an impaired production of specialized proresolving lipid mediators (SPMs), such as Lipoxins-LXs, Resolvins-Rvs, Protectins-PDs, and Maresins-MaRs. Our aim was to characterize the changes in BAT SPMs signatures and their association with BAT dysfunction during aging, especially under obesogenic conditions, and their modulation by a docosahexaenoic acid (DHA)-rich diet. Lipidomic, functional, and molecular studies were performed in BAT of 2- and 18-month-old lean (CT) female mice and in 18-month-old diet-induced obese (DIO) mice fed with a high-fat diet (HFD), or a DHA-enriched HFD. Aging downregulated Prdm16 and UCP1 levels, especially in DIO mice, while DHA partially restored them. Arachidonic acid (AA)-derived LXs and DHA-derived MaRs and PDs were the most abundant SPMs in BAT of young CT mice. Interestingly, the sum of LXs and of PDs were significantly lower in aged DIO mice compared to young CT mice. Some of the SPMs most significantly reduced in obese-aged mice included LXB4 , MaR2, 4S,14S-diHDHA, 10S,17S-diHDHA (a.k.a. PDX), and RvD6. In contrast, DHA increased DHA-derived SPMs, without modifying LXs. However, MicroPET studies showed that DHA was not able to counteract the impaired cold exposure response in BAT of obese-aged mice. Our data suggest that a defective SPMs production could underlie the decrease of BAT activity observed in obese-aged mice, and highlight the relevance to further characterize the physiological role and therapeutic potential of specific SPMs on BAT development and function.


Thirty percent of ductal carcinoma in situ of the breast in Japan is extremely low-grade ER(+)/HER2(-) type without comedo necrosis.
Background Overdiagnosis in mammography (MMG) is a problem. Combination of MMG and ultrasonography for breast cancer screening may increase overdiagnosis. Most cases of overdiagnosis are low-grade ductal carcinoma in situ (LGD), but no reports have focused on them. Materials and methods We immunostained 169 ductal carcinoma in situ (DCIS) cases for ER, PgR, HER2 and Ki67 and classified them into 4 subtypes: ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(-) and ER(-)/HER2(+). The Ki67 index was used to evaluate the grade of malignancy and examined for correlations with each ER/HER2 subtype and the nuclear grade (NG), with/without comedo necrosis. Results The Ki67 index correlated significantly with NG, both with/without comedo necrosis, and reliably evaluated the grade of malignancy. The index for ER(+)/HER2(-) (n=117, 69.2%) was 7.45±7.10, which was significantly lower than for each of the other types. The index was 5.71±6.94 for ER(+)/HER2(-) without comedo necrosis (n=52, 30.8%), which was significantly lower than with comedo necrosis. This was considered LGD, characterized by absence of microcalcification in MMG and either presence of a solid mass or cystic lesion or absence of hypoechoic areas in ultrasound. Conclusion In Japan, ER(+)/HER2(-) without comedo necrosis accounts for about 30% of DCIS and is LGD. This may be being overdiagnosed. J. Med. Invest. 63: 192-198, August, 2016.


Yeast Mpo1 Is a Novel Dioxygenase That Catalyzes the α-Oxidation of a 2-Hydroxy Fatty Acid in an Fe2+-Dependent Manner.
Phytosphingosine (PHS) is the major long-chain base component of sphingolipids in Saccharomyces cerevisiae The PHS metabolic pathway includes a fatty acid (FA) α-oxidation reaction. Recently, we identified the novel protein Mpo1, which is involved in PHS metabolism. However, the details of the FA α-oxidation reaction and the role of Mpo1 in PHS metabolism remained unclear. In the present study, we revealed that Mpo1 is involved in the α-oxidation of 2-hydroxy (2-OH) palmitic acid (C16:0-COOH) in the PHS metabolic pathway. Our in vitro assay revealed that not only the Mpo1-containing membrane fraction but also the soluble fraction was required for the α-oxidation of 2-OH C16:0-COOH. The addition of Fe2+ eliminated the need for the soluble fraction. Purified Mpo1 converted 2-OH C16:0-COOH to C15:0-COOH in the presence of Fe2+, indicating that Mpo1 is the enzyme body responsible for catalyzing the FA α-oxidation reaction. This reaction was also found to require an oxygen molecule. Our findings indicate that Mpo1 catalyzes the FA α-oxidation reaction as 2-OH fatty acid dioxygenase, mediated by iron(IV) peroxide. Although numerous Mpo1 homologs exist in bacteria, fungi, protozoa, and plants, their functions had not yet been clarified. However, our findings suggest that these family members function as dioxygenases.


The Relationship Between Child Maltreatment and Partner Violence Victimization and Perpetration Among College Students: Focus on Auditory Status and Gender.
Partner violence is a pervasive public health concern that has received significant attention over the past three decades. Although a number of studies have reported that college students who are Deaf or hard of hearing are at an increased risk of experiencing partner violence compared with their hearing counterparts, little is known about partner violence perpetration among college students who are Deaf or hard of hearing. Furthermore, beyond disability, studies examining partner violence among students with disabilities tend to ignore other potential risk factors that may increase the risk of partner violence as a victim and/or a perpetrator. This exploratory study examines the extent of partner violence among male and female college students by auditory status and the relationship between experiencing and perpetrating partner abuse (i.e., physical abuse and psychological abuse) and child maltreatment (i.e., witnessing abuse and experiencing child physical abuse). The study also examines gender differences in the relationship between child maltreatment and physical and psychological abuse victimization and perpetration. Data were collected from a sample of approximately 680 college students at a northeastern university. Findings indicate that having witnessed interparental abuse as a child was only significant for being an adult victim of physical abuse. Having been a child victim of parental abuse was not significant for any of the abuse measures. Gender was only significant for being an adult victim of physical abuse. Deaf students were significantly more likely to report all abuse measures. Implications and directions for further research are discussed.


Simvastatin attenuates leucocyte-endothelial interactions after coronary revascularisation with cardiopulmonary bypass.
To investigate the effects of preoperative simvastatin treatment on leucocyte-endothelial interactions following coronary artery bypass surgery with cardiopulmonary bypass. Double blind crossover study. Experiments on polymorphonuclear cells (neutrophils) were done at the end of cardiopulmonary bypass and one hour postoperatively. Endothelial P-selectin expression and neutrophil/endothelial adhesion were evaluated under either normoxic or hypoxic conditions. University hospital (tertiary referral centre). Three groups of patients undergoing coronary bypass surgery: 20 patients taking simvastatin for cholesterol control, 16 patients not responsive to simvastatin, and 20 controls. Expression of neutrophil CD11b and endothelial P-selectin; adhesion of neutrophils to endothelium. Cardiopulmonary bypass resulted in a significant increase in neutrophil CD11b expression in all groups. Similarly, the exposure of saphenous vein to hypoxia/reoxygenation induced an augmentation of endothelial P-selectin. However, both neutrophil CD11b expression and endothelial P-selectin exocytosis were less in the simvastatin groups than in the controls. Cardiopulmonary bypass and controlled hypoxia/reoxygenation stimulated neutrophil/endothelial adhesion, but the number of adhering cells was less in the simvastatin groups than in the controls, irrespective of the cholesterol concentration. Treatment of endothelial cells with L-NAME completely reversed the effects of simvastatin. Pretreatment with simvastatin reduces neutrophil adhesion to the venous endothelium in patients undergoing coronary surgery, irrespective of its efficacy at lowering cholesterol concentration.


Oral consumption of green tea polyphenols inhibits insulin-like growth factor-I-induced signaling in an autochthonous mouse model of prostate cancer.
We earlier demonstrated that oral infusion of green tea polyphenols inhibits development and progression of prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Evidence indicates that elevated levels of IGF-I with concomitant lowering of IGF binding protein (IGFBP)-3 are associated with increased risk for prostate cancer development and progression. In this study, we examined the role of IGF/IGFBP-3 signaling and its downstream and other associated events during chemoprevention of prostate cancer by green tea polyphenols in TRAMP mice. Our data demonstrated an increase in the levels of IGF-I, phosphatidylinositol 3'-kinase, phosphorylated Akt (Thr-308), and extracellular signal-regulated kinase 1/2 with concomitant decrease in IGFBP-3 in dorso-lateral prostate of TRAMP mice during the course of cancer progression, i.e., as a function of age. Continuous green tea polyphenol infusion for 24 weeks to these mice resulted in substantial reduction in the levels of IGF-I and significant increase in the levels of IGFBP-3 in the dorso-lateral prostate. This modulation of IGF/IGFBP-3 was found to be associated with an inhibition of protein expression of phosphatidylinositol 3'-kinase, phosphorylated forms of Akt (Thr-308) and extracellular signal-regulated kinase 1/2. Furthermore, green tea polyphenol infusion resulted in marked inhibition of markers of angiogenesis and metastasis most notably vascular endothelial growth factor, urokinase plasminogen activator, and matrix metalloproteinases 2 and 9. Based on our data, we suggest that IGF-I/IGFBP-3 signaling pathway is a prime pathway for green tea polyphenol-mediated inhibition of prostate cancer that limits the progression of cancer through inhibition of angiogenesis and metastasis.


Spontaneous closure of a dural arteriovenous fistula.
Spontaneous closure of a dural arteriovenous fistula (dAVF) is a rare condition and only a few cases have been reported since its first description in 1976. We report delayed and progressive spontaneous closure of a dAVF after massive intracerebral hemorrhage documented by angiographic studies before and after bleeding. To our knowledge, this is the first report to document gradual closure of a dAVF by serial angiographic studies. The mechanism of spontaneous closure of dAVFs has not been fully elucidated. We suggest different factors for consideration from previously published data and show how each of these factors can influence the others.


Oxaliplatin added to fluoropyrimidine for adjuvant treatment of colorectal cancer is associated with long-term impairment of peripheral nerve sensory function and quality of life.
Oxaliplatin-induced peripheral neuropathy (OIPN) of acute and chronic type is well known, but long-term chronic type OIPN and its impact on quality of life (QoL) has not been extensively studied. Clinical experience indicates that oxaliplatin tolerance might vary with climate. Patient-reported chronic type OIPN and QoL among patients treated with oxaliplatin added to a fluoropyrimidine (Folfox or Capox) in the adjuvant setting of colorectal cancer (CRC) were assessed in a single center cross-sectional study by using the EORTC QLQ-CIPN20 and QLQ-C30 questionnaires. Comparison was made to patients treated with a fluoropyrimidine (5-FU or capecitabine) alone during the same time period. Of 161 patients being disease-free 1-8 years after stop of treatment and invited, 84% participated; 65 treated with oxaliplatin and 71 with a fluoropyrimidine alone. Mean cumulative oxaliplatin dose was 567 mg/m2 (55% of planned dose). Oxaliplatin-treated patients reported statistically and clinically significant worse sensory as well as motor scale scores, dominated by symptoms from the feet. Severe tingling and numbness in toes/feet was reported by 38% and 37%, respectively, by oxaliplatin-treated patients compared with 8% for both by fluoropyrimidine alone patients (p < 0.001). Subgroup analyses indicated no impact of gender, age, regimen, time since stop of treatment or cumulated oxaliplatin dose for severity of the chronic type OIPN. The oxaliplatin compared with the fluoropyrimidine group reported worse QoL scores throughout all domains, with statistically and clinically significant differences for role and social function, nausea/loss of appetite and financial problems. Oxaliplatin added to a fluoropyrimidine for adjuvant treatment of CRC in a country with subarctic climate is associated with long-term, seemingly chronic, sensory neuropathy and impairment of QoL. This should be taken into account in clinical decision making on oxaliplatin treatment in the adjuvant setting.


Acquisition of Paleolithic toolmaking abilities involves structural remodeling to inferior frontoparietal regions.
Human ancestors first modified stones into tools 2.6 million years ago, initiating a cascading increase in technological complexity that continues today. A parallel trend of brain expansion during the Paleolithic has motivated over 100 years of theorizing linking stone toolmaking and human brain evolution, but empirical support remains limited. Our study provides the first direct experimental evidence identifying likely neuroanatomical targets of natural selection acting on toolmaking ability. Subjects received MRI and DTI scans before, during, and after a 2-year Paleolithic toolmaking training program. White matter fractional anisotropy (FA) showed changes in branches of the superior longitudinal fasciculus leading into left supramarginal gyrus, bilateral ventral precentral gyri, and right inferior frontal gyrus pars triangularis. FA increased from Scan 1-2, a period of intense training, and decreased from Scan 2-3, a period of reduced training. Voxel-based morphometry found a similar trend toward gray matter expansion in the left supramarginal gyrus from Scan 1-2 and a reversal of this effect from Scan 2-3. FA changes correlated with training hours and with motor performance, and probabilistic tractography confirmed that white matter changes projected to gray matter changes and to regions that activate during Paleolithic toolmaking. These results show that acquisition of Paleolithic toolmaking skills elicits structural remodeling of recently evolved brain regions supporting human tool use, providing a mechanistic link between stone toolmaking and human brain evolution. These regions participate not only in toolmaking, but also in other complex functions including action planning and language, in keeping with the hypothesized co-evolution of these functions.


Q fever after a journey in Syria: a diagnosis suggested by bone marrow biopsy.
A Belgian patient developed Q fever after a journey in Syria. Coxiella burnetii infection was diagnosed because of the presence of granulomas with a central vacuole in a bone marrow biopsy. During doxycycline treatment all his symptoms disappeared.


Identification of a TcpC-TcpQ outer membrane complex involved in the biogenesis of the toxin-coregulated pilus of Vibrio cholerae.
The toxin-coregulated pilus (TCP) of Vibrio cholerae and the soluble TcpF protein that is secreted via the TCP biogenesis apparatus are essential for intestinal colonization. The TCP biogenesis apparatus is composed of at least nine proteins but is largely uncharacterized. TcpC is an outer membrane lipoprotein required for TCP biogenesis that is a member of the secretin protein superfamily. In the present study, analysis of TcpC in a series of strains deficient in each of the TCP biogenesis proteins revealed that TcpC was absent specifically in a tcpQ mutant. TcpQ is a predicted periplasmic protein required for TCP biogenesis. Fractionation studies revealed that the protein is not localized to the periplasm but is associated predominantly with the outer membrane fraction. An analysis of the amount of TcpQ present in the series of tcp mutants demonstrated the inverse of the TcpC result (absence of TcpQ in a tcpC deletion strain). Complementation of the tcpQ deletion restored TcpC levels and TCP formation, and similarly, complementation of tcpC restored TcpQ. Metal affinity pull-down experiments performed using His-tagged TcpC or TcpQ demonstrated a direct interaction between TcpC and TcpQ. In the presence of TcpQ, TcpC was found to form a high-molecular-weight complex that is stable in 2% sodium dodecyl sulfate and at temperatures below 65 degrees C, a characteristic of secretin complexes. Fractionation studies in which TcpC was overexpressed in the absence of TcpQ showed that TcpQ is also required for proper localization of TcpC to the outer membrane.


Within-host parasite dynamics, emerging trade-off, and evolution of virulence with immune system.
Virulence is an evolutionary paradox because parasites never benefit from their host's death. The adaptive explanation of virulence is classically based upon the existence of physiological constraints that create a trade-off between parasites' epidemiological traits (virulence, transmissibility, and clearance). Here we develop an epidemiological model where infections are dynamic processes and we demonstrate how these dynamics generate a trade-off between emerging epidemiological parameters. We then study how host's immune strength modifies this trade-off and hence influences virulence evolution. We found that in acute infections, where parasites are engaged in a race with immune cells, immunity restrains more the duration of the infection than its intensity. As a consequence parasites evolve to provoke more virulent but shorter infections in strongly immunized hosts.


Ellagic Acid Enhances Apoptotic Sensitivity of Breast Cancer Cells to γ-Radiation.
Herbal polyphenols have gained increased significance because of the promises they hold in the prevention and treatment of cancer. There exists an enormous opportunity for the screening and valuation of natural dietary compounds in the development of an effective chemopreventive drug and radiosensitizer that may be of practical use for patients undergoing cancer therapy. This study describes the effect of the flavonoid ellagic acid (EA) on gamma-irradiated human breast cancer MCF-7 cells in vitro when administered alone or in combination with radiation. It was interesting to find the radioprotective effect of EA on NIH3T3, which is a normal cell line. Irradiation of breast tumor cells in the presence of EA (10 μM) to doses of 2 and 4-Gy gamma radiation produced a marked synergistic tumor cytotoxicity while it was found to aid recovery from the radiation damage to NIH3T3 cells. When cells were given a combined treatment of EA and radiation, the cell death increased to 21.7% and 20.7% in the 2 and 4-Gy-treated cells respectively, significantly (P < 0.05) reducing the capacity of MCF-7 cells to form colonies. Even at 24 h, 38 foci/cell were observed in samples that were given the combined treatment, suggesting the cells' inability in repairing the damage. Also, increased apoptosis in EA+ 2Gy (50%) and EA+ 4 Gy (62%)-treated cells was observed in the the sub-G1 phase of the cell cycle. A 6.2-fold decrease in the mitochondrial membrane potential was observed in the combined treatment of EA and IR that facilitated the upregulation of pro-apopttotic Bax and downregulation of Bcl-2, pushing the MCF-7 cells to undergo an apoptotic cell death. It is suggested that EA may be a potential drug adjuvant for improving cancer radiotherapy by increasing tumor toxicity and reducing the normal cell damage caused by irradiation.


Seasonality of anencephalic births and pre-ovulatory overripeness ovopathy.
The total number of births and the anencephaly incidence rate in the Netherlands, in the years 1951 to 1968 (both corrected to estimate the 'conception' curves), were analyzed to find their circannual fluctuations and to see whether there was a relation between the two. The results indicate that, as predicted by the seasonal preovulatory overripeness ovopathy (SPOO-) hypothesis, anencephalics are born disproportionately more often than expected during the peak months and less often during the troughs of the total birth curve. Overripeness ovopathy as a teratogenic factor, therefore, may offer a unifying aetiological concept which can also explain other epidemiological findings concerning congenital CNS-defects. This concept may challenge the genetic theories of their causation, and offer new possibilities for 'primary' prevention.


Relaxation skills for the patient, dentist, and auxiliaries.
The aforementioned stress reduction techniques can be useful for some people, but not all individuals will benefit to the same degree with a similar technique. Those who manifest severe stress symptoms, such as ulcers, hypertension, and migraine headaches, are advised to seek a medical evaluation before attempting relaxation or any other type of stress reduction method. The relaxation skill most beneficial for an individual's own needs might be best sought through a qualified therapist. Those who desire reduction in general tension, or who wish a rejuvenation during the workday, may well benefit from less controlled stress reduction techniques, such as taped instructions, breathing, and imagery methods. A trained therapist can provide the most appropriate relaxation method for an individual's needs. We, as health care providers, can enlighten our patients about methods which can aid them in dealing with anxiety and stress and thus gain better control over the pace of their lives and ours.


Endothelial shear stress from large-scale blood flow simulations.
We discuss the optimal evaluation of endothelial shear stress for real-life case studies based on anatomic data acquisition. The fluid dynamic simulations require smoothing of the geometric dataset to avoid major artefacts in the flow patterns, especially in the proximity of bifurcations. A systematic series of simulations at different corrugation levels shows that, below a smoothing length of about 0.5 mm, the numerical data are insensitive to further smoothing.


5-Fluoro-N-(2-methyl-3-oxo-1-thia-4-aza-spiro-[4.5]dec-4-yl)-3-phenyl-1H-indole-2-carboxamide.
In the title compound, C24H24FN3O2S, the 1,3-thia-zolidine ring adopts an envelope conformation with the S atom as the flap, while the cyclo-hexane ring is in a chair conformation. In the crystal, mol-ecules are linked by N-H⋯O and C-H⋯F hydrogen bonds, forming a three-dimensional network. The unit cell contains six voids of 57 Å(3), but the residual electron density (highest peak = 0.23 e Å(-3) and deepest hole = -0.19 e Å(-3)) in the difference Fourier map suggests no solvent mol-ecule occupies this void.


Pinacidil pretreatment extends ischemia tolerance of neonatal rabbit hearts.
Activating ATP-sensitive potassium (K(ATP)) channels improves ischemia tolerance of adult rabbit hearts. We hypothesize that (a) endogenous activation of the K(ATP) channel accounts for better ischemia tolerance of neonatal hearts and (b) exogenous K(ATP) channel activation with pinacidil further improves the neonatal heart's tolerance to cardioplegic ischemia. Study 1: Seven (control) neonatal rabbits received intraperitoneal saline, whereas five others (Glib) received 0.3 mg/kg glibenclamide 10 min before sacrifice. They were perfused on Langendorff with Krebs-Henseleit buffer (KHB). Baseline left ventricle (LV) performance and coronary flow (CF) were measured. After 20 min of 37 degrees C ischemia and 10 min of reperfusion, recovery was measured. Study 2: Ten (control) neonatal hearts underwent 90 min of normothermic ischemia with St. Thomas' cardioplegia (STCP) solution administered every 30 min. Ten others were pretreated with a 10-min infusion of 1 microM pinacidil in KHB and received 1 microM pinacidil-enriched STCP. Recovery of LV performance and CF were measured after 60 min of reperfusion. Study 1: Glib significantly reduced preischemia LV performance by 28%* compared to control hearts. Recovery of Glib-treated hearts was significantly less (67%*) than controls (81%*). Study 2: Pinacidil-treated hearts had significantly better recovery of LV performance (39%*) and CF (78%*) compared to 23 and 52%, respectively, in untreated controls (*P < 0.05 vs control hearts). Endogenous K(ATP) channel activation in neonatal hearts contributes to their better tolerance to ischemia. Exogenous K(ATP) channel activation by pinacidil pretreatment and cardioplegic enrichment significantly improved the neonatal rabbit heart's tolerance to cardioplegic ischemia. This may be an important addition to myocardial protection during pediatric cardiac surgery.


Three-stage revision arthroplasty for the treatment of fungal periprosthetic joint infection: outcome analysis of a novel treatment algorithm : a prospective study.
Fungal periprosthetic joint infections (fPJIs) are rare complications, constituting only 1% of all PJIs. Neither a uniform definition for fPJI has been established, nor a standardized treatment regimen. Compared to bacterial PJI, there is little evidence for fPJI in the literature with divergent results. Hence, we implemented a novel treatment algorithm based on three-stage revision arthroplasty, with local and systemic antifungal therapy to optimize treatment for fPJI. From 2015 to 2018, a total of 18 patients with fPJI were included in a prospective, single-centre study (DKRS-ID 00020409). The diagnosis of PJI is based on the European Bone and Joint Infection Society definition of periprosthetic joint infections. The baseline parameters (age, sex, and BMI) and additional data (previous surgeries, pathogen spectrum, and Charlson Comorbidity Index) were recorded. A therapy protocol with three-stage revision, including a scheduled spacer exchange, was implemented. Systemic antifungal medication was administered throughout the entire treatment period and continued for six months after reimplantation. A minimum follow-up of 24 months was defined. Eradication of infection was achieved in 16 out of 18 patients (88.8%), with a mean follow-up of 35 months (25 to 54). Mixed bacterial and fungal infections were present in seven cases (39%). The interval period, defined as the period of time from explantation to reimplantation, was 119 days (55 to 202). In five patients, a salvage procedure was performed (three cementless modular knee arthrodesis, and two Girdlestone procedures). Therapy for fPJI is complex, with low cure rates according to the literature. No uniform treatment recommendations presently exist for fPJI. Three-stage revision arthroplasty with prolonged systemic antifungal therapy showed promising results. Cite this article: Bone Jt Open 2021;2(8):671-678.


Exploring the molecular basis of heme coordination in human neuroglobin.
Neuroglobin (Ngb), a recently discovered ancient heme protein, presents the typical globin fold and is around 20% identical to myoglobin (Mb). In contrast with Mb, however, its heme is hexacoordinated (6c). It is expressed in the nervous system and has been the subject of numerous investigations in the last years, but its function is still unclear. The proposed roles include oxygen transport, reactive oxygen species (ROS) detoxification, hypoxia protection, and redox state sensing. All proposed functions require distal histidine dissociation from the heme to yield a reactive iron. With the aim of understanding the 6c to 5c transition, we have performed molecular dynamics simulations for ferrous Ngb in the 6c, 5c, and oxy states. We also computed free energy profiles associated with the transition employing an advanced sampling technique. Finally, we studied the effect of the redox state of CysCD7 and CysD5, which are known to form a disulfide bridge. Our results show that protein oxidation promotes a stabilization of the pentacoordinated species, thus favoring the protein to adopt the more reactive state and supporting the existence of a molecular mechanism whereby O2 would be released under hypoxic conditions, thereby suggesting an O(2) storage function for Ngb. Taken together, our results provide structural information not available experimentally which may shed light on the protein proposed functions, particularly as a redox sensor.


Secondary metabolites from Glycine soja and their growth inhibitory effect against Spodoptera litura.
The wild soybean (Glycine soja Sieb. et Zucc) has been reported to be relatively resistant to insect and pathogenic pests. However, the responsible secondary metabolites in the aerial part of this important plant are largely unknown. From the aerial part of G. soja, 13 compounds were isolated and identified, including seven isoflavonoids (1-7), a cyclitol (8), two sterol derivatives (9 and 10), and three triterpenoids (11-13). Compound 7 is a new isoflavonoid, and compounds 9 and 10 are reported as natural products for the first time. The growth inhibitory activity of 1, 3, 4, and 8 against the larvae of Spodoptera litura was investigated. The most abundant isoflavonoid in the aerial part of G. soja, daidzein (1), which could not be metabolized by S. litura, was found to inhibit the insect larvae growth significantly in 3 days after feeding diets containing the compound. Compounds 3, 4, and 8, which could be partially or completely metabolized, were inactive. Our results suggested that the isoflavonoid daidzein (1) might function as a constitutive defense component in G. soja against insect pests.


Functional roles of the extracellular segments of the sodium channel alpha subunit in voltage-dependent gating and modulation by beta1 subunits.
Voltage-gated sodium channels consist of a pore-forming alpha subunit associated with beta1 subunits and, for brain sodium channels, beta2 subunits. Although much is known about the structure and function of the alpha subunit, there is little information on the functional role of the 16 extracellular loops. To search for potential functional activities of these extracellular segments, chimeras were studied in which an individual extracellular loop of the rat heart (rH1) alpha subunit was substituted for the corresponding segment of the rat brain type IIA (rIIA) alpha subunit. In comparison with rH1, wild-type rIIA alpha subunits are characterized by more positive voltage-dependent activation and inactivation, a more prominent slow gating mode, and a more substantial shift to the fast gating mode upon coexpression of beta1 subunits in Xenopus oocytes. When alpha subunits were expressed alone, chimeras with substitutions from rH1 in five extracellular loops (IIS5-SS1, IISS2-S6, IIIS1-S2, IIISS2-S6, and IVS3-S4) had negatively shifted activation, and chimeras with substitutions in three of these (IISS2-S6, IIIS1-S2, and IVS3-S4) also had negatively shifted steady-state inactivation. rIIA alpha subunit chimeras with substitutions from rH1 in five extracellular loops (IS5-SS1, ISS2-S6, IISS2-S6, IIIS1-S2, and IVS3-S4) favored the fast gating mode. Like wild-type rIIA alpha subunits, all of the chimeric rIIA alpha subunits except chimera IVSS2-S6 were shifted almost entirely to the fast gating mode when coexpressed with beta1 subunits. In contrast, substitution of extracellular loop IVSS2-S6 substantially reduced the effectiveness of beta1 subunits in shifting rIIA alpha subunits to the fast gating mode. Our results show that multiple extracellular loops influence voltage-dependent activation and inactivation and gating mode of sodium channels, whereas segment IVSS2-S6 plays a dominant role in modulation of gating by beta1 subunits. Evidently, several extracellular loops are important determinants of sodium channel gating and modulation.


Sphingosine kinase (SphK) 1 and SphK2 play equivalent roles in mediating insulin's mitogenic action.
Insulin, an established mitogen that promotes breast cancer cell growth, has been implicated in the link between obesity and an increased risk of breast cancer. However, the current understanding of signaling pathways that mediate the mitogenic action of insulin remains incomplete. Here we provide the first evidence that insulin is capable of activating both sphingosine kinase (SphK) 1 and SphK 2, two isoenzymes that often exhibit opposing effects in the regulation of cell survival and growth. Insulin stimulates the phosphorylation of both SphK1 and SphK2 in a similar time- and dose-dependent manner. Interestingly, both isoenzymes are responsible equally for insulin-induced cell cycle progression and proliferation of MCF7 breast cancer cells, although SphK1 and SphK2 display different roles in mediating insulin-induced ERK1/2 and Akt activation. Moreover, the sphingosine 1-phosphate receptor 3, a key component of the SphK signaling system, is important for insulin-mediated mitogenic action in breast cancer cells. Furthermore, insulin receptor and type 1 IGF receptor (IGF1R) are responsible for the insulin-promoted mitogenic action on MCF7 breast cancer cells. Notably, IGF1R mediates insulin-stimulated phosphorylation of both SphK1 and SphK2, whereas insulin receptor is involved only in SphK1, but not SphK2, activation. Collectively the current study illustrates a new signaling system controlling the mitogenic action of insulin in breast cancer cells, suggesting a new strategy that pharmaceutically targets both isoenzymes of SphK for the management of breast cancer.


Changes in Opioid Prescribing Habits for Patients Undergoing Rhinoplasty and Septoplasty.
Opioid prescriptions have increased substantially over the last 2 decades, contributing to the opioid epidemic. Physician practices and legislative changes play a key role in decreasing prescription opioid use. To evaluate changes in opioid prescribing habits for patients undergoing rhinoplasty and/or septoplasty before and after the adoption of new opioid legislation. This single-institution case-control study examined opioid prescribing habits for 80 patients who were undergoing rhinoplasty and septoplasty with or without turbinate reduction at the University of Vermont between March 2016 and May 2018. Patients were excluded if they underwent concomitant endoscopic sinus surgery or were younger than 14 years. Patients were divided by surgery date before or after legislative changes on July 1, 2017. Rhinoplasty and septoplasty with or without turbinate reduction. Patient demographics and opioid prescriptions were recorded. Patients were evaluated if they reported pain during follow-up, called the office, or received a second prescription. The Vermont Prescription Monitoring System was queried to determine if opioid prescriptions were filled within 30 days of the procedure. The 2 groups were compared to test the hypothesis that opioid prescriptions had decreased after legislative changes. Of a total of 80 participants, the mean (SD) age in the before (15 women [37.5%]) and after (16 women [40.0%]) groups were 41.4 years and 40.6 years, respectively. There was a statistically significant decrease in the number of pills prescribed to the after group (17.5 to 9.7; P < .001) as well as a decrease in the morphine milligram equivalents that were prescribed (130.9 to 73.2; P < .001). There was no statistical difference in the number of postoperative telephone calls for pain, second prescriptions, or increased complaints of pain at the postoperative visit. Recent laws in Vermont regarding opioid prescribing were implemented in 2017 to curb the ongoing opioid epidemic. Our observations of patients undergoing septoplasties and rhinoplasties found a significant reduction in opioid prescriptions. This was not associated with an increase in patient complaints about postoperative pain or the need for a second prescription after surgery. This shows that we may safely be able to decrease the number of narcotic medications that we prescribe. 3.


Assessing regional drought impacts on vegetation and evapotranspiration: a case study in Guanacaste, Costa Rica.
This research investigates ecological responses to drought by developing a conceptual framework of vegetation response and investigating how multiple measures of drought can improve regional drought monitoring. We apply this approach to a case study of a recent drought in Guanacaste, Costa Rica. First, we assess drought severity with the Standard Precipitation Index (SPI) based on a 64-yr precipitation record derived from a combination of Global Precipitation Climatology Center data and satellite observations from Tropical Rainfall Measuring Mission and Global Precipitation Measurement. Then, we examine spatial patterns of precipitation, vegetation greenness, evapotranspiration (ET), potential evapotranspiration (PET), and evaporative stress index (ESI) during the drought years of 2013, 2014, and 2015 relative to a baseline period (2002-2012). We compute wet season (May-October) anomalies for precipitation at 0.25° spatial resolution, normalized difference vegetation index (NDVI) at 30-m spatial resolution, and ET, PET and ESI derived with the Priestley-Taylor Jet Propulsion Laboratory (PT-JPL) model at 1-km spatial resolution. We assess patterns of landscape response across years and land cover types including three kinds of forest (deciduous, old growth, and secondary), grassland, and cropland. Results show that rainfall in Guanacaste reached an all-time low in 2015 over a 64-yr record (wet season SPI = -3.46), resulting in NDVI declines. However, ET and ESI did not show significant anomalies relative to a baseline, drought-free period. Forests in the region exhibited lower water stress compared to grasslands and had smaller declines, and even some increases, in NDVI and ET during the drought period. This work highlights the value of using multiple measures to assess ecosystem responses to drought. It also suggests that agricultural land management has an opportunity to integrate these findings by emulating some of the characteristics of drought-resilient ecosystems in managed systems.


Characteristics of volunteers and non-volunteers for voluntary counseling and HIV testing among unmarried male undergraduates.
The 2001 HIV sero-prevalence survey in Nigeria revealed a rate of 5.8 percent with those under the age of 25 years having the highest prevalence rate. Most University students fall within this age group. This study is part of a larger study on the sexual behavior of youths and young adults and was designed to compare the characteristics of volunteers and non-volunteers for voluntary confidential counseling and HIV testing (VCT) among males. Six hundred and nine male undergraduate students were randomly selected and enrolled for the study. Data were collected using a pre-tested questionnaire. Of the 609, 51 (8.3%) volunteered to have their blood screened for HIV. All volunteers who received pre-test counseling went for the HIV test. Volunteers were significantly older than the non-volunteers (P<0.0001), and were more likely to be sexually experienced (P=0.002). Among the sexually experienced, the volunteers were older at first sexual intercourse (FSI) (P<0.0001), and were more likely to have used a condom at FSI (P=0.001). Volunteers had significantly higher knowledge scores for HIV/AIDS (P=0.006), and the attitude to HIV/AIDS in both groups was positive. The marriage pattern of their parents with regard to polygyny was similar, and fewer volunteers had fathers in the higher socio-economic class and mothers who had completed secondary education (P<0.00001, (P=0.02). Among the 51 volunteers, 8 (15.7%) tested positive. Those who tested positive were less likely to have lived with parents, and were all sexually experienced. Those who screened positive were also more likely to be currently sexually active and to have fathers with low level of education. Three (5.9%) of volunteers did not return for results and posttest counseling. One of the three was positive for HIV. Of those who tested positive, 3 (37.5%) reported not using the condom at all, while the rest were using it only occasionally. VCT among the youths is possible however, small numbers encountered in the study is a limitation and there is a need to replicate this study using larger numbers. Tertiary institutions should provide VCT services for the students where they can be counseled appropriately and continuously throughout their stay in the institution. This hopefully will reduce the number of new HIV cases seen.


Ultrasound current source density imaging.
Surgery to correct severe heart arrhythmias usually requires detailed maps of the cardiac activation wave prior to ablation. The pinpoint electrical mapping procedure is laborious and limited by its spatial resolution (5-10 mm). We propose ultrasound current source density imaging (UCSDI), a direct 3-D imaging technique that potentially facilitates existing mapping procedures with superior spatial resolution. The technique is based on a pressure-induced change in resistivity known as the acoustoelectric (AE) effect, which is spatially confined to the ultrasound focus. AE-modulated voltage recordings are used to map and reconstruct current densities. In this preliminary study, we tested UCSDI under controlled conditions and compared it with conventional electrical mapping techniques. A 2-D dipole field was produced by a pair of electrodes in a bath of 0.9% NaCl solution. Boundary electrodes detected the AE signal while a 7.5-MHz focused ultrasound transducer was scanned across the bath. UCSDI located the current source and sink to within 1 mm of their actual positions. A future UCSDI system potentially provides real-time 3-D images of the cardiac activation wave coregistered with anatomical ultrasound and would greatly facilitate corrective procedures for heart abnormalities.


Conifers have a unique small RNA silencing signature.
Plants produce small RNAs to negatively regulate genes, viral nucleic acids, and repetitive elements at either the transcriptional or post-transcriptional level in a process that is referred to as RNA silencing. While RNA silencing has been extensively studied across the different phyla of the animal kingdom (e.g., mouse, fly, worm), similar studies in the plant kingdom have focused primarily on angiosperms, thus limiting evolutionary studies of RNA silencing in plants. Here we report on an unexpected phylogenetic difference in the size distribution of small RNAs among the vascular plants. By extracting total RNA from freshly growing shoot tissue, we conducted a survey of small RNAs in 24 vascular plant species. We find that conifers, which radiated from the other seed-bearing plants approximately 260 million years ago, fail to produce significant amounts of 24-nucleotide (nt) RNAs that are known to guide DNA methylation and heterochromatin formation in angiosperms. Instead, they synthesize a diverse population of small RNAs that are exactly 21-nt long. This finding was confirmed by high-throughput sequencing of the small RNA sequences from a conifer, Pinus contorta. A conifer EST search revealed the presence of a novel Dicer-like (DCL) family, which may be responsible for the observed change in small RNA expression. No evidence for DCL3, an enzyme that matures 24-nt RNAs in angiosperms, was found. We hypothesize that the diverse class of 21-nt RNAs found in conifers may help to maintain organization of their unusually large genomes.


Stripping/sweeping the membranes for inducing labour or preventing post-term pregnancy.
Stripping or sweeping of the membranes aims to initiate labour through a cascade of physiological events. These may reduce pregnancy duration or pre-empt formal induction of labour with either oxytocin, prostaglandins or amniotomy. The objective of this review was to assess the effects of membrane sweeping to promote or induce labour on maternal and perinatal outcomes. We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register (last searched April 1998). Adequately controlled trials of digital separation of the membranes from the lower uterine segment for inducing labour or for preventing post-term pregnancy, compared to either no vaginal examination or vaginal examination for cervical assessment only without the intention to detach the membranes. Two reviewers assessed trial quality and extracted data. Fourteen trials were included. Sweeping of the membranes, performed as a general policy in women at term, was associated with reduced duration of pregnancy and the frequency of pregnancy continuing beyond 41 weeks (relative risk 0.42, 95% confidence interval 0.19 to 0.93, random effects model) and 42 weeks. After sweeping of the membranes, there was a 17% risk reduction (confidence interval 6 to 29%, random effects model) in the use of more formal methods for labour induction. There was no difference in the mode of delivery or in the risk of infection. Discomfort during vaginal examination and other adverse effects (bleeding, irregular contractions) were more frequently reported by women allocated to sweeping. Routine use of sweeping of membranes from 38 weeks of pregnancy onwards does not seem to produce clinically important benefits. When used as a means for induction of labour, the reduction in the use of more formal methods of induction needs to be balanced against women's discomfort and other adverse effects.


Correlation of glutamate binding activity with glutamate-binding protein immunoreactivity in the brain of control and alcohol-treated rats.
Specific antibodies raised against a glutamate binding protein purified from bovine brain were used to trace the immunoreactivity of this protein in rat brain subcellular fractions. In the subcellular fractions obtained from whole brain homogenates, the synaptic membranes had the highest immunochemical reactivity towards the anti-glutamate-binding protein antibodies. The combination of measurements of glutamate binding activity and glutamate-binding protein immunoreactivity indicated that in brain synaptic membranes from control animals the highest activity in these two measures was associated with a synaptic plasma membrane subfraction that was enriched with synaptic junctions. In animals treated with ethanol for 14 days, there was a significant increase in the density of synaptic membrane glutamate binding sites. This increase in glutamate binding capacity was correlated with a greater than two-fold increase in the glutamate binding activity and binding protein immunoreactivity of the light synaptic membrane subfraction, a subfraction which does not contain many recognizable synaptic junctions. Acute administration of ethanol to rats produced a moderate but non-significant decrease in glutamate binding capacity of synaptic membranes. The increase in the number of glutamate binding protein subunits in brain plasma membranes may be an adaptive response of central nervous system neurons to the acute effects of ethanol on glutamate synaptic transmission.


Brown adipose tissue genes in pericardial adipose tissue of newborn sheep are downregulated by maternal nutrient restriction in late gestation.
Brown adipose tissue (BAT) thermogenesis is essential for newborn survival. Pericardial adipose tissue is a visceral depot that promotes metabolic and cardiovascular adaptations. We determined whether BAT is present in pericardial adipose tissue in newborns and whether maternal nutrition during late gestation compromises BAT in the postnatal period. We measured uncoupling protein 1 (UCP1) and other BAT-specific genes (e.g., β3-adrenergic receptor (β3ADR) and deiodinase type 2 (DIO2)), together with markers of white adipose tissue (WAT) in sheep on either the first or 30th day after birth. These were twin offspring born to mothers fed with either 100% or nutrient restricted (NR) to 60% of their total metabolizable requirements from 110 d gestation to term. Gene expression of UCP1 and other BAT-related genes decreased significantly with age. In newborns, maternal nutrient restriction downregulated gene expression of DIO2 and the β3-adrenergic receptor with reduced UCP1 but had no effect on genes predominantly expressed in WAT. BAT is present around the heart in newborns. Exposure to a suboptimal maternal diet in late gestation specifically compromises BAT development and has the potential to place these offspring at increased risk of hypothermia after birth without effects on the subsequent appearance of WAT.


Evidence-Based Practice: Improving the Quality of Perinatal Care.
For clinical research findings to improve the quality of care and outcomes for newborn infants and their families, they need to be implemented in policy and adopted in practice. We describe the principles of effective dissemination and implementation of research findings and highlight examples of collaborative quality improvement strategies to ensure that guidelines, protocols, policies and practices reflect research-informed evidence. Passive dissemination of research findings is generally ineffective in driving change. Implementation strategies that use multi-faceted approaches acting on different barriers to change are better at driving improvements in the quality of care practices. These initiatives are increasingly embedded within regional, national and international networks of neonatal care centres that collaborate in conducting research, implementing its findings and auditing its uptake. Examples of successful network-based collaborative quality improvement programmes include efforts to increase use of evidence-based strategies to prevent hospital-acquired bloodstream infections, optimise surfactant replacement for preterm infants, reduce the incidence of bronchopulmonary dysplasia, improve antibiotic stewardship and promote the use of human milk to prevent necrotising enterocolitis in very-low-birth-weight infants. Effective dissemination and implementation are essential for research evidence to improve quality of care and outcomes for newborn infants and their families. Multifaceted initiatives within network-based collaborative quality improvement programmes facilitate continuous audit and benchmarking cycles to ensure equity of access to evidence-based care practices.


Specialty Certification Status, Performance Ratings, and Disciplinary Actions of Internal Medicine Residents.
Little is known about the attrition of physicians trained in internal medicine (IM). The authors sought to examine career paths, disciplinary actions, and American Board of Medical Specialties (ABMS) certification status of IM residents. Three datasets were combined to study 66,881 residents in Accreditation Council for Graduate Medical Education-accredited IM residency programs nationwide from 1995 to 2004. Group differences (among an American Board of Internal Medicine [ABIM]-certified cohort; an ABMS-certified cohort (but not ABIM-certified); and a noncertified cohort) in IM residency performance ratings, specialty certification status, year of initial IM training, and medical board disciplinary actions were examined. Analyses included chi-square tests, analysis of variance, pairwise comparisons, and logistic regressions. Ninety-five percent of IM residents obtained ABIM certification; 1.6% received ABMS certification in another specialty; 3.4% received no ABMS specialty certification, of which 74.3% have a current medical license; and 66.6% self-reported IM as their primary specialty. During residency, the ABIM cohort performed better than those who never obtained ABIM certification. Disciplinary actions were lowest for the ABIM cohort (1.2%), 2.4% for the ABMS cohort, and highest and more severe for the noncertified cohort (6.0%). Only 5% of IM residents do not achieve IM certification. IM resident attrition minimally impacts physician supply, though those without certification appear to contribute disproportionately to poor physician performance indicators. Improved tracking of the U.S. physician workforce could aid policy makers in predicting manpower shifts in certain specialty areas, both during and after residency training.


Cost analysis of leuprorelin acetate in Japanese prostate cancer patients: comparison between 6-month and 3-month depot formulations.
This study aimed to evaluate the economic value for leuprorelin acetate 6-month depot compared with leuprorelin acetate 3-month depot from a societal perspective in Japanese prostate cancer patients. The cost analysis estimated the reduction in direct and indirect costs as well as intangible costs saved by having one less injection. Claims data were used for the analyses of direct and indirect costs reduction. A discrete choice experiment based on a web-based survey estimated the monetary value of the intangible costs for one injection. Another web-based survey of prostate cancer patients, who had received treatment with leuprorelin acetate injections, was carried out to calibrate the results of the discrete choice experiment. Reductions in medical costs and loss of productivity for having one less injection in prostate cancer patients receiving leuprorelin acetate were JPY 5,670 and JPY 1,723, respectively. Intangible costs saved by using a 6-month depot formulation instead of a 3-month depot formulation for the injection of leuprorelin acetate were estimated to be JPY 19,872, including the values for a reduction in pain (JPY 3,131), injection site reactions (JPY 11,545), waiting time (JPY 9,479), and subtracting the value of medical consultation (JPY 4,283). The total cost reduction for having one less injection was JPY 27,265. The respondents from the internet panel provided by a survey company are not necessarily a representative population of Japanese society. Leuprorelin acetate 6-month depot has an advantage in monetary value in the reduction in medical costs, loss of productivity, and intangible costs for having one less injection in prostate cancer patients compared with leuprorelin acetate 3-month depot. In the costs for treating with leuprorelin acetate, the percentage of intangible costs might not be negligible. The intangible costs will probably be actively evaluated to proceed to patient-centered healthcare in society.


Glycolaldehyde, a reactive intermediate for advanced glycation end products, plays an important role in the generation of an active ligand for the macrophage scavenger receptor.
Long-term incubation of proteins with glucose leads to the formation of advanced glycation end products (AGEs) that are recognized by AGE receptors. Glyoxal, glycolaldehyde (GA), and methylglyoxal are potential intermediates for the formation of AGE structures such as Nomega-(carboxymethyl)lysine (CML). We evaluated the contribution of these aldehydes to the formation of AGE structure(s), particularly the structure important for the receptor-mediated endocytic uptake of AGE proteins by macrophages. GA-modified bovine serum albumin (BSA), methylglyoxal-modified BSA (MG-BSA), and glyoxal-modified BSA (GO-BSA) were prepared, and their physicochemical, immunological, and biologic properties were compared with those of glucose-derived AGE-BSA. CML contents were high in GO-BSA and low in GA-modified BSA (GA-BSA) but did not exist in MG-BSA. The fluorescence patterns of GA-BSA and MG-BSA were similar to those of glucose-derived AGE-BSA but were weak in GO-BSA. Immunochemically, the antibody against non-CML structures of glucose-derived AGE-BSA reacted strongly with GA-BSA and weakly with GO-BSA but did not react with MG-BSA. The negative charge of these ligands increased to a similar extent. However, GA-BSA, but not MG-BSA or GO-BSA, underwent receptor-mediated endocytosis by the macrophage-derived cell line RAW 264.7, which was effectively inhibited by glucose-derived AGE-BSA, acetylated LDL, and oxidized LDL, which are well-known ligands for the macrophage type I and type II class A scavenger receptors (MSR-A). The endocytic uptake of GA-BSA by mouse peritoneal macrophages was also significant, but that by peritoneal macrophages from MSR-A-deficient mice was markedly reduced. Our results suggest that GA serves as an important intermediate for the generation of AGE structure(s) responsible for recognition by MSR-A.


[Case of uncommon motor reaction to administration of diprivan].
A young patient without history of epilepsy developed a pronounced motor reaction simulating an epileptic attack in response to diprivan. Possible causes of motor excitation in response to diprivan and probability of their prediction are discussed.


Associations between the use of metformin, sulphonylureas, or diet alone and cardiovascular outcomes in 6005 people with type 2 diabetes in the FIELD study.
We aimed to determine the associations between metformin or sulphonylurea monotherapy at study entry into the FIELD diabetes trial and (1) metabolic risk factors, (2) risk of a first major cardiovascular (CVD) outcome, and (3) the effect of each therapy on the risk-modifying effect of fenofibrate. Patients receiving metformin or sulphonylureas without insulin therapy were compared for the relative risk of CVD outcomes, adjusted for differences in baseline characteristics likely to affect risk. Metformin-treated patients were likely to be younger, female, or obese. Metformin was associated with higher levels of lipids (other than LDL-C) and homocysteine (P<0.001). Sulphonylurea-treated patients had a longer history of diabetes and more CVD and microvascular disease. Sulphonylurea treatment was associated with higher plasma creatinine and lower plasma HDL-C (P<0.001). The risks of all CVD outcomes were higher for those on sulphonylureas than diet alone, but were nonsignificant after adjustment for the duration and intensity of diabetes and severity of risk factors. Metformin and sulphonylureas did not significantly influence the benefits of fenofibrate on CVD outcomes. Apparent differences in the risk of CVD outcomes associated with oral hypoglycemics therapy were largely abolished by adjustment for diabetes and CVD risk factors.


RAUM-VO: Rotational Adjusted Unsupervised Monocular Visual Odometry.
Unsupervised learning for monocular camera motion and 3D scene understanding has gained popularity over traditional methods, which rely on epipolar geometry or non-linear optimization. Notably, deep learning can overcome many issues of monocular vision, such as perceptual aliasing, low-textured areas, scale drift, and degenerate motions. In addition, concerning supervised learning, we can fully leverage video stream data without the need for depth or motion labels. However, in this work, we note that rotational motion can limit the accuracy of the unsupervised pose networks more than the translational component. Therefore, we present RAUM-VO, an approach based on a model-free epipolar constraint for frame-to-frame motion estimation (F2F) to adjust the rotation during training and online inference. To this end, we match 2D keypoints between consecutive frames using pre-trained deep networks, Superpoint and Superglue, while training a network for depth and pose estimation using an unsupervised training protocol. Then, we adjust the predicted rotation with the motion estimated by F2F using the 2D matches and initializing the solver with the pose network prediction. Ultimately, RAUM-VO shows a considerable accuracy improvement compared to other unsupervised pose networks on the KITTI dataset, while reducing the complexity of other hybrid or traditional approaches and achieving comparable state-of-the-art results.


Perioperative and long-term prognostic value of dipyridamole Tc-99m sestamibi myocardial tomography in patients evaluated for elective vascular surgery.
Patients with peripheral vascular disease are at increased risk for perioperative and long-term cardiac morbidity and mortality. Substantial data exist supporting the use of preoperative clinical risk stratification and planar thallium myocardial scintigraphy. Only limited data are available assessing the role of technetium-99m (Tc-99m) single photon emission computed tomography (SPECT) for preoperative evaluation in this population. In our study 153 patients who underwent peripheral vascular surgery were followed up for up to 4 years after preoperative dipyridamole Tc-99m sestamibi SPECT to determine clinical and SPECT predictors of perioperative and long-term adverse cardiac events by multivariate analysis. There were no statistically significant clinical or SPECT predictors of perioperative risk, although no perioperative events occurred in patients with normal scans. Abnormality in the left anterior descending (LAD) territory (risk ratio = 3.1; 95% confidence interval, 1.4-7.1) was the only statistically significant univariate predictor of long-term death or myocardial infarction. Only abnormality in the LAD territory appeared to improve model fit beyond clinical risk (risk ratio = 2.9; 95% confidence interval, 1.2-7.3; P =.02). Patients with normal preoperative scans have a low risk of perioperative cardiac events and may safely undergo peripheral vascular surgery without further coronary intervention. However, scan abnormality in the LAD distribution confers poor long-term prognosis, suggesting that patients with this finding before peripheral vascular surgery should receive aggressive medical therapy and possibly invasive intervention to improve long-term survival.


Beliefs of women concerning causes and risk factors for bulimia nervosa.
To examine the beliefs of women concerning causes and risk factors for eating-disordered behaviour. Face-to-face interviews were conducted with a community sample of 208 women aged 18-45 years. Respondents were presented with a vignette describing a fictional person meeting diagnostic criteria for bulimia nervosa (BN) and were asked to indicate whether each of several factors was 'very likely', 'likely' or 'not likely' to be a cause of the problem described, which factor was most likely to be a cause, and whether particular subgroups of people would be 'more likely', 'less likely' or 'equally likely' to have or develop the problem described. 'Having low self-esteem' was considered very likely to be a cause of BN by 75.0% of respondents, and the most likely cause by 40.5% of respondents. Other factors perceived as significant were 'problems from childhood', 'portrayal of women in the media', 'being overweight as a child or adolescent' and 'day-to-day problems', while genetic factors and pre-existing psychological problems were perceived to be of minor significance. Most respondents believed that women aged under 25 years were at greatest risk of having or developing BN. Women's beliefs concerning causes and risk factors for BN are generally consistent with empirical evidence. However, information concerning the increased risk associated with pre-existing anxiety and affective disorders might usefully be included in prevention programs. Systematic investigation of the benefits of addressing individuals' beliefs concerning risk factors for eating disorders - as opposed to risk factors per se - would be of interest.


Lesion location and cognitive impact of cerebral small vessel disease.
Cerebral small vessel disease (SVD) is an important cause of cognitive impairment. Important MRI manifestations of SVD include white matter hyperintensities (WMH) and lacunes. This narrative review addresses the role of anatomical lesion location in the impact of SVD on cognition, integrating findings from early autopsy studies with emerging findings from recent studies with advanced image analysis techniques. Early autopsy and imaging studies of small case series indicate that single lacunar infarcts in, for example the thalamus, caudate nucleus or internal capsule can cause marked cognitive impairment. However, the findings of such case studies may not be generalizable. Emerging location-based image analysis approaches are now being applied to large cohorts. Recent studies show that WMH burden in strategic white matter tracts, such as the forceps minor or anterior thalamic radiation (ATR), is more relevant in explaining variance in cognitive functioning than global WMH volume. These findings suggest that the future diagnostic work-up of memory clinic patients could potentially be improved by shifting from a global assessment of WMH and lacune burden towards a quantitative assessment of lesion volumes within strategic brain regions. In this review, a summary of currently known strategic regions for SVD-related cognitive impairment is provided, highlighting recent technical developments in SVD research. The potential and challenges of location-based approaches for diagnostic purposes in clinical practice are discussed, along with their potential prognostic and therapeutic applications.