Metastatic prostatic carcinoma to supradiaphragmatic lymph nodes. A clinicopathologic and immunohistochemical study.
We identified 26 cases of metastatic prostatic carcinoma in supradiaphragmatic lymph nodes from 1972-1987. All involved nodes (15 supraclavicular, eight cervical, two axillary, and one mediastinal) were taken from the left side. Of those cases with available data, serum acid phosphatase was normal in five of 21 (24%). Seven of 20 (35%) had no evidence of bone metastases. Rectal examination was normal in eight of 19 cases (42%). While seven cases had a history of prostate cancer, the rest presented with enlarged nodes alone or with simultaneous urinary obstructive symptoms. Eighteen patients died following node biopsy (mean 19.8 months, range 1-46 months). Twenty-two of 26 metastases were high grade and often were not histologically suggestive of prostate carcinoma. In general, immunohistochemical staining for prostate-specific acid phosphatase (PSAP) was more intense than for prostate-specific antigen (PSA), in contrast to several other reports using these antisera. Metastatic prostate carcinoma should be ruled out by using immunoperoxidase for PSA and PSAP in all men over 45 presenting with carcinoma of unknown primary origin in left-sided supradiaphragmatic lymph nodes, even in the absence of bony disease, elevated serum acid phosphatase (SAP), abnormal rectal examination, and a histologic picture suggesting prostate carcinoma.


Applications of Office-Based 445 nm Blue Laser Transnasal Flexible Laser Surgery: A Case Series and Review of Practice.
The recent introduction of 445 nm blue laser to office-based laryngology presents potential advantages. These include a desirable combination of cutting and photoangiolytic qualities and a lightweight, shock-resistant design. Despite its increasing use, current evidence is limited to experimental data and case reports. The authors present a case series and overview of office blue laser transnasal flexible laser surgery (TNFLS), considering indications, patient selection, safety, technique, and surgical outcomes. We also review the safety and relevance of TNFLS to the ongoing coronavirus pandemic. Retrospective case series and narrative review. Our primary outcome measure was preoperative and postoperative Voice Handicap Index (VHI-10) score. Complications were documented by nature and severity. Thirty-six cases of office blue laser TNFLS were performed. A statistically significant improvement in VHI-10 score was demonstrated in cases of recurrent respiratory papillomatosis (RRP) and benign laryngeal lesions causing dysphonia (P < 0.01 and 0.045). Blue laser also proved effective in assisting office biopsy procedures. A minor and self-limiting complication was reported. Office blue laser TNFLS is safe and effective in the treatment of RRP and a range of benign laryngeal lesions. Future research should compare the efficacy and safety of blue laser with potassium titanyl phosphate laser in office-based treatment of these conditions. Further assessment of the cutting qualities of blue laser, initially in the theater environment, is necessary to refine our understanding of future applications.


Maternal antigen avoidance during lactation for preventing atopic disease in infants of women at high risk.
To assess the effects of prescribing an antigen avoidance diet during lactation on the nutritional status of the mother and newborn and on the development of atopic disease in the child. The main focus is on women whose infants are at high risk for developing an atopic condition, based on a history of atopic disease in the mother, father, or a previous child. The register of clinical trials maintained and updated by the Cochrane Pregnancy and Childbirth Group. All acceptably controlled comparisons of maternal antigen avoidance prescribed to lactating women at high risk, regardless of the degree of antigen avoidance (number of foods eliminated from the diet) or its duration. Trials of multimodal interventions that include manipulation of the infant's diet other than breast milk or of other nondietary aspects of the infant's environment (eg, exposure to inhaled allergens) have been excluded from the review. Data were extracted by the author from published reports, and supplemented by additional information from trialists contacted by the author. Three trials involving 209 women were included. The combined data from the three available trials suggest a strong protective effect of maternal antigen avoidance on the incidence of atopic eczema during the child's first 12-18 months of life. Methodologic shortcomings in all three trials, however, argue for caution in applying these encouraging results. In particular, the high incidence of atopic eczema in the control groups of all three trials might be explained by nonblinding or de-blinding of the examining physicians. Prescription of an antigen avoidance diet to a high-risk woman during lactation may substantially reduce her child's risk of developing atopic eczema, but better trials are needed.


Risk of ESRD in the United States.
Although incidence rates of end-stage renal disease (ESRD) in the United States are reported routinely by the US Renal Data System (USRDS), risks (probabilities) are not reported. Short- and long-term risk estimates need to be updated and expanded to minority populations, including Native Americans, Asian/Pacific Islanders, and Hispanics. Risk estimation from surveillance data in large populations using life-table methods. A competing-risks framework was applied by constructing a hypothetical cohort followed from birth to death. Total US population. Incidence and mortality rates of ESRD were obtained from the USRDS; all-cause mortality rates were obtained from CDC WONDER. Age, sex, race/ethnicity, and year. 10-year to lifetime risks (cumulative incidence) of ESRD. Among males, lifetime risks of ESRD from birth using 2013 data were 3.1% (95% CI, 3.0%-3.1%) for non-Hispanic whites, 8.0% (95% CI, 7.9%-8.2%) for non-Hispanic blacks, 3.8% (95% CI, 3.4%-4.9%) for non-Hispanic Native Americans, 5.1% (95% CI, 4.8%-5.4%) for non-Hispanic Asians/Pacific Islanders, and 6.2% (95% CI, 6.1%-6.4%) for Hispanics. Among females, lifetime risks were 2.0% (95% CI, 2.0%-2.1%) for non-Hispanic whites, 6.8% (95% CI, 6.7%-6.9%) for non-Hispanic blacks, 3.6% (95% CI, 3.3%-4.2%) for non-Hispanic Native Americans, 3.8% (95% CI, 3.6%-4.0%) for non-Hispanic Asian/Pacific Islanders, and 4.3% (95% CI, 4.2%-4.5%) for Hispanics. Lifetime risk of ESRD from birth increased from 3.5% in 2000 to 4.0% in 2013 in males and decreased from 3.0% to 2.8% in females. Standard life-time assumption of fixed age-specific rates over time and possible ESRD misclassification. To be useful in clinical practice, this application will require additional predictors (eg, comorbid conditions and chronic kidney disease stage). ESRD risk in the United States varies more than 2-fold among racial/ethnic groups for both sexes.


How do genes regulate simple behaviours? Understanding how different neurons in the vertebrate spinal cord are genetically specified.
Understanding how the vertebrate central nervous system develops and functions is a major goal of a large body of biological research. This research is driven both by intellectual curiosity about this amazing organ that coordinates our conscious and unconscious bodily processes, perceptions and actions and by the practical desire to develop effective treatments for people with spinal cord injuries or neurological diseases. In recent years, we have learnt an impressive amount about how the nerve cells that communicate with muscles, motoneurons, are made in a developing embryo and this knowledge has enabled researchers to grow motoneurons from stem cells. Building on the success of these studies, researchers have now started to unravel how most of the other nerve cells in the spinal cord are made and function. This review will describe what we currently know about spinal cord nerve cell development, concentrating on the largest category of nerve cells, which are called interneurons. I will then discuss how we can build and expand upon this knowledge base to elucidate the complete genetic programme that determines how different spinal cord nerve cells are made and connected up into neural circuits with particular functions.


Development of an ex vivo model to investigate the effects of altered haemodynamics on human bypass grafts.
The insertion of vein grafts into the arterial circulation may contribute to vessel wall thickening and accelerated atherosclerosis, a common feature of late vein graft failure. We aimed to develop a model suitable for investigation of the effects of altered haemodynamics on human saphenous vein following its implantation into the arterial circulation. Segments of human saphenous vein obtained from patients undergoing coronary artery bypass surgery were sutured at each end to PTFE and placed into a flow system. Pressure and flow rates to stimulate the arterial and venous systems were achieved. A theoretical model of the flow chamber was created and computational fluid dynamics software (FLOTRAN, Swanson Analysis Systems) was used to determine the flow profile within the model. In summary, a flow model has been developed to investigate the effect of altered haemodynamics on the molecular and pathological changes that occur in vein grafts incorporated into the arterial circulation.


Inhibitors in hemophilia A: advances in elucidation of inhibitory mechanisms and in inhibitor management with bypassing agents.
Development of inhibitory antibodies (inhibitors) to factor VIII (FVIII) is the most serious adverse event in replacement therapy of hemophilia A patients. The etiology and management of this condition remain major challenges for both researchers and clinicians. In the present review, we discuss recent advances in understanding the molecular mechanisms by which inhibitors inactivate FVIII and experimental approaches used for the mapping of inhibitor epitopes. We also present a comparative analysis of treatment of hemophilia A patients with inhibitors with currently available bypassing agents-activated prothrombin complex concentrate (FEIBA VH; Baxter Healthcare Corp., Westlake Village, CA) and recombinant activated factor VII (NovoSeven; Novo Nordisk, Princeton, NJ)-and describe some ongoing research programs aimed at developing new treatment options for these patients. Availability of sensitive and standardized laboratory assays that would assist in monitoring the effectiveness of bypass therapies is essential for designing customized treatment regimens and improvement in the management of health conditions of hemophilia patients with inhibitors.


Capsule-like assemblies in polar solvents.
Calix[4]arene derivatives with four anionic groups at their upper rim form discrete 1:1 complexes with complementary calix[4]arene derivatives bearing four cationic groups at their upper rim. Each cation is bound by two anions, and vice versa, in a mutual chelate arrangement, reinforced by a network of ionic hydrogen bonds. These multiple electrostatic interactions lead to the formation of highly stable capsule-like assemblies even in polar protic solvents such as methanol and water. In the capsule interior a cavity is formed that is in principle large enough for the encapsulation of small aliphatic and aromatic guests (170-230 A(3)). Monte Carlo simulations in water reproducibly lead to the same regular opimized structures. These differ mainly by their inner volume and flexibility, as demonstrated by molecular dynamics calculations. Most half-spheres can be synthesized by way of the tetrakis(chloromethyl) or the tetrabromocalix[4]arene intermediate. Oppositely charged calix[6]arenes also form strong complexes, but no indication was found for a lock in the cone conformation. The formation of the ball-shaped complexes from calix[4]arene building blocks was studied with Job plots, NMR titrations, NOESY, and variable-temperature experiments, as well as ESI-MS measurements. Investigations aimed at the inclusion of various guest molecules were carried out with alcohols, sulfoxides, benzene derivatives, and ammonium, as well as pyrazinium guests. Although binding isotherms were generated with cationic guests, these must be considered to be loosely associated around the seam rather than included inside the capsule.


Midgut malrotation in adulthood.
A 29-year-old man was admitted to our hospital with a history of recurrent right upper quadrant abdominal pain and vomiting. These symptoms appeared intermittently for 7 years. Various examinations revealed a diagnosis of midgut malrotation. Laparotomy was performed and revealed reverse rotation of the duodenum with paraduodenal hernia and a normal rotating colon. This case suggests that recurrent abdominal complaints in an adult should arouse suspicion of midgut malrotation.


Role of Adenosine Receptor(s) in the Control of Vascular Tone in the Mouse Pudendal Artery.
Activation of adenosine receptors (ARs) has been implicated in the modulation of renal and cardiovascular systems, as well as erectile functions. Recent studies suggest that adenosine-mediated regulation of erectile function is mainly mediated through A2BAR activation. However, no studies have been conducted to determine the contribution of AR subtype in the regulation of the vascular tone of the pudendal artery (PA), the major artery supplying and controlling blood flow to the penis. Our aim was to characterize the contribution of AR subtypes and identify signaling mechanisms involved in adenosine-mediated vascular tone regulation in the PA. We used a DMT wire myograph for muscle tension measurements in isolated PAs from wild-type, A2AAR knockout, A2BAR knockout, and A2A/A2BAR double-knockout mice. Real-time reverse transcription-polymerase chain reaction was used to determine the expression of the AR subtypes. Data from our pharmacologic and genetic approaches suggest that AR activation-mediated vasodilation in the PA is mediated by both the A2AAR and A2BAR, whereas neither the A1AR nor A3AR play a role in vascular tone regulation of the PA. In addition, we showed that A2AAR- and A2BAR-mediated vasorelaxation requires activation of nitric oxide and potassium channels; however, only the A2AAR-mediated response requires protein kinase A activation. Our data are complemented by mRNA expression showing the expression of all AR subtypes with the exception of the A3AR. AR signaling in the PA may play an important role in mediating erection and represent a promising therapeutic option for the treatment of erectile dysfunction.


Pulmonary oncocytoma: a case report.
A 70-year-old man complained of no discomfort was admitted to our hospital because of a nodules was found in his lung. Chest computer tomography showed a nodules arising from the upper lobe of the left lung, and the lesion became larger in 2 years follow-up period. The patient underwent video-assisted thoracoscopic surgery of lobectomy to remove the nodules. Histologically, the tumor specimen contained multiple glandular structures with oncocytic cells lining. Immunohistochemical staining showed the tissue did not include some neuroendocrine granules. Finally, He was diagnosed as pulmonary oncocytoma. The patient discharged from our hospital after surgery and with no recurrence in 29 months period.


How do i participate in T-cell immunotherapy?
T cells play a key role in the adaptive immune response, and the ability to manipulate T cells for therapeutic uses has advanced in the past decade. Infusion of expanded or engineered T cells can potentially be used to treat cancer, viral infections, graft-versus-host disease, and organ transplant rejection. The role that blood banks play in the manufacture and distribution of T-cell therapeutics is still being defined. Given the regulatory framework of blood banks, they are well positioned to collect raw material for manufacture of T-cell therapies and to distribute finished product to hospitals in support of clinical trials or eventually for licensed products. A deeper level of involvement in manufacture of T-cell therapeutics is also possible, although that requires more substantial investment in physical facilities and personnel with the regulatory and scientific expertise to prepare and produce cellular therapy products. Examples of physical infrastructure needed would be a laboratory with a clean room for culture of T cells, specialized equipment for expansion of the cells, and adequate administrative and storage support space. Processes that would need to be developed to produce T-cell therapeutics would include development of standard operating procedures and an appropriate quality assurance program. As blood banks consider supporting this novel class of therapies, they will need to weigh capital and expertise requirements with the benefits of providing a novel therapy and the potential of growth for their operations.


Novel sensory adaptation mechanism in bacterial chemotaxis to oxygen and phosphotransferase substrates.
The involvement of methylation in the chemosensory response of bacteria to many attractants has been clearly established by studies in several laboratories. It has been assumed that adaptation of Salmonella typhimurium and Escherichia coli to all attractants involves methylation of a transmembrane methyl-accepting chemotaxis protein. The methyl donor in this reaction is S-adenosyl-L-methionine, and the protein methyltransferase is the product of the cheR gene. In contrast, adaptation to oxygen and phosphotransferase substrates were found to be independent of this methylation system. In E. coli AW660 (tsr tar trg), which lacks the known methyl-accepting chemotaxis proteins, chemotaxis was normal to oxygen and to substrates of the phosphotransferase system such as D-mannose, D-glucose, and N-acetyl-D-glucosamine. When S-adenosyl-L-methionine was depleted by methionine starvation or by addition of 1-aminocyclopentane-1-carboxylic acid, methylation-dependent adaptation to serine, aspartate, and ribose was defective in wild-type E. coli and S. typhimurium. However, adaptation to oxygen and phosphotransferase substrates was independent of S-adenosyl-L-methionine and the cheR product. These results suggest that there are methylation-independent and methylation-dependent mechanisms for sensory adaptation in bacteria.


Influence of personal preferences for life-sustaining treatment on medical decision making among pediatric intensivists.
Withholding and withdrawal of life-sustaining treatment by physicians is influenced by a variety of factors; the role of physicians' personal preferences for life-sustaining treatments has not previously been explored. We sought to examine the relationship between personal preferences for life-sustaining treatment and medical decision making among pediatric intensivists. Cross-sectional national anonymous mail survey. All board-certified/eligible pediatric intensivists identified by the American Medical Association Masterfile. None. A total of 471 (30%) surveys were returned. A Personal Preference Score was calculated from responses to personal-preference questions for life-sustaining treatments adapted from "Your Life, Your Choices," by Pearlman et al. Physicians were asked to consider the "acceptability" of offering and recommending treatment options involving life-sustaining treatments in a hypothetical scenario of a 2-yr old with a high cervical spinal-cord transection. Logistic regression controlling for sociodemographic characteristics found significant relationships (p<.01) between physicians' own preferences modeled as a one standard deviation change in their own Personal Preference Score (preference for life-sustaining treatment) and whether they offered more or less aggressive care (OR [95%CI]). Physicians who had a higher Personal Preference Score (higher preference for their own life-sustaining treatment) were more likely to recommend a tracheostomy (1.38 [1.35-1.41]) and reintubation if the patient failed extubation (1.87 [1.81-1.94]). Pediatric intensivists who had a lower Personal Preference Score (lower preference for life-sustaining treatment) were more likely to recommend that the patient not be reintubated if extubation failed (1.42 [1.39-1.46]) and to recommend Do Not Resuscitate status (1.34 [1.31-1.37]). Among pediatric intensivists, personal preferences for life-sustaining treatment were significantly associated with scenario-based responses to acceptability of withholding and withdrawal of life-sustaining treatment. Physicians should be aware of the potential for personal preferences to influence practice recommendations, and endeavor to elicit and respect family preferences in collaborative decision making.


Primary central nervous system lymphoma and 5-aminolevulinic acid.
Despite surgical resection of primary central nervous system lymphomas (PCNSL) having been always discouraged, recent evidence supports that it might improve prognosis in this patient population. Five- aminolevulinic acid-derived fluorescence is widely used for the resection of malignant gliomas, but its role in PCNSL surgery remains unclear. We present two patients with a solitary solid intraparenchymal mass. As high-grade glioma leaded the list of differential diagnosis (other possibilities were metastasis, abscess, and PCNSL), a five- aminolevulinic acid-guided complete resection (with strong fluorescence in both cases) was done. Surgery was uneventfully carried on with complete resection until five-aminolevulinic acid-induced fluorescence was no longer evident. After surgery, patients have no neurological deficits and had good recovery. Pathological examination revealed that both tumors were PCNSL. Adjuvant radiotherapy and chemotherapy were started. After 1 year of follow-up, patients have good evolution and have no recurrences. These cases add to the growing literature which shows that surgery might play an important role in the management of PCNSL with an accessible and single lesion. Five-aminolevulinic acid could also be a useful tool to achieve complete resection and improve prognosis in this group of patients.


Filling of extraction sockets of feline maxillary canine teeth with autogenous bone or bioactive glass.
To evaluate bone healing in the extraction socket of the feline maxillary canine tooth after grafting. Eighteen adult cats were submitted to unilateral extraction of maxillary canine tooth and divided into three groups. In group 1 (n=6), control, the extraction socket was left empty. In group 2 (n=6), the extraction socket was filled with autogenous cancellous bone from the iliac crest and in group 3 (n=6), with bioactive glass particulate material. Cats were euthanized at four weeks postoperative. The radiographic examinations performed four weeks after surgery showed that in all groups the healing process converged to a radiopacity similar to that observed in the surrounding bones. Histological examination showed formation of woven bone within the extraction socket. The percentage of newly formed bone within the extraction socket, measured by the histometry, showed no statistically significant difference among the values of the three groups (Kruskal-Wallis'test p>0.05) (group 1: 63.96 ± 5.85, group 2: 66.84 ± 11.67, group 3: 59.28 ± 15.50). The bone regeneration observed in the extraction sockets filled with autogenous cancellous bone or bioactive glass was similar to that observed in the control sites, given an observation period of four weeks after extraction of the maxillary canine tooth.


The 18-item Swedish version of Ryff's psychological wellbeing scale: psychometric properties based on classical test theory and item response theory.
Psychological wellbeing is conceptualized as the full engagement and optimal performance in existential challenges of life. Our understanding of psychological wellbeing is important for us humans to survive, adapt, and thrive during the challenges of the 21st century. Hence, the measurement of psychological wellbeing is one cornerstone for the identification and treatment of both mental illness and health promotion. In this context, Ryff operationalized psychological wellbeing as a six-dimensional model of human characteristics: self-acceptance, positive relations with others, environmental mastery, personal growth, autonomy, and purpose in life. Ryff's Psychological Wellbeing Scale has been developed and translated into different versions. Here, we examine and describe the psychometric properties of the 18-item Swedish version of Ryff's Psychological Wellbeing Scale using both Classical Test Theory (CTT) and Item Response Theory (IRT). The data used in the present study was earlier published elsewhere and consists of 768 participants (279 women and 489 men). In addition to the 18-item version of the scale, participants answered the Temporal Satisfaction with Life Scale, the Positive Affect Negative Affect Schedule, and the Background and Health Questionnaire. We examined, the 18-item version's factor structure using different models and its relationship with subjective wellbeing, sociodemographic factors (e.g., education level, gender, age), lifestyle habits (i.e., smoking, frequency of doing exercise, and exercise intensity), and health issues (i.e., pain and sleeping problems). We also analyzed measurement invariance with regard to gender. Moreover, as an addition to the existing literature, we analyzed the properties of the 18 items using Graded Response Model (GRM). Although the original six-factor structure showed a good fit, both CTT and IRT indicated that a five-factor model, without the purpose in life subscale, provided a better fit. The results supported the internal consistency and concurrent validity of the 18-item Swedish version. Moreover, invariance testing showed similar measurement precision by the scale across gender. Finally, we found several items, especially the purpose in life's item "I live life one day at a time and do not really think about the future," that might need revision or modification in order to improve measurement. A five-factor solution is a valid and reliable measure for the assessment of psychological wellbeing in the general Swedish population. With some modifications, the scale might achieve enough accuracy to measure the more appropriate and correct six-dimensional theoretical framework as detailed by Ryff. Fortunately, Ryff's original version contains 20 items per subscale and should therefore act as a perfect pool of items in this endeavor.


International importance of robust breast device registries.
Breast implants are high-risk devices that have been at the epicenter of much debate and controversy. In light of the Poly Implant Prothèse crisis, data registries among 11 national societies around the world are cooperatively calling for the urgent need to establish robust national clinical quality registries based on international best practice within a framework of international collaboration. A survey was conducted on the historic and current status of national breast device registries. Eleven countries participated in the study, illustrating different data collection systems and registries around the world. Data collection was designed to illustrate the capabilities of current national registries, with particular focus on capture rate and outcome reporting mechanisms. A study of national breast implant registries revealed that less than half of the participating countries had operational registries and that none of these had adequately high data capture to enable reliable outcome analysis. The study revealed that the two most common problems that discouraged participation are the complexity of data sets and the opt-in consent model. Recent implant crises have highlighted the need for robust registries. This article argues the importance of securing at least 90 percent data capture, which is achievable through the opt-out consent model. Since adopting this model, the Australian Breast Device Registry has increased data capture from 4 percent to over 97 percent. Simultaneously, it is important to foster international collaboration from the outset to avoid duplication of efforts and enable the development of effective international early warning systems.


Profile: Iora Health Transactional vs. relationship-based care.
Last November, Nursing Management Congress2016 attendees experienced a one-of-a-kind keynote address when Zubin Damania, MD, took the stage. Through self-produced song and video, he explored the ethics of delivering compassionate care in our challenging healthcare system. Here, read about the Iora Health model that Dr. Damania celebrates as "having it right."


VCIP135 associates with both the N- and C-terminal regions of p97 ATPase.
Two distinct p97ATPase-mediated membrane fusion pathways are required for Golgi and endoplasmic reticulum (ER) biogenesis; namely, the p97/p47 pathway and the p97/p37 pathway. p97(VCP)/p47 complex-interacting protein, p135 (VCIP135) is necessary for both of these pathways. Although VCIP135 is known to form a complex with p97 in the cytosol, the role of this complex in Golgi and ER biogenesis has remained unclear. In this study, we demonstrated that VCIP135 has two distinct p97-binding sites at its N- and C-terminal regions. In particular, the C-terminal binding site includes the SHP motif, which is also found in other p97-binding proteins, such as p47, p37 and Ufd1. We also clarified that VCIP135 binds to both the N- and C-terminal regions of p97; i.e., the N- and C-terminal binding sites in VCIP135 interact with the C- and N-terminal regions of p97, respectively. These two interactions within the complex are synchronously controlled by the nucleotide state of p97. We next generated VCIP135 mutants lacking each of the p97-binding sites to investigate their functions in living cells, and clarified that VCIP135 is involved in Golgi and ER biogenesis through its two distinct interactions with p97. VCIP135 is hence a unique p97-binding protein that functions by interacting with both the N-and C-terminal regions of p97, which strongly suggests that it plays crucial roles in p97-mediated events.


Morning headache in sleep apnoea: clinical and polysomnographic evaluation and response to nasal continuous positive airway pressure.
Morning headache is accepted as part of clinical findings of obstructive sleep apnoea syndrome (OSAS). The prevalence of morning headache is at variable levels from 18% to 74% in patients with OSAS. However, there is controversy over the association of morning headache and OSAS. We studied morning headache prevalence and characteristics in 101 controls with apnoea-hypnoea index (AHI) < 5 and 462 OSAS patients with AHI > or = 5. Morning headache was reported by only nine (8.9%) subjects in a control group compared with 156 (33.6%) of OSAS patients (P < 0.01). Morning headache prevalence was significantly higher in severe and moderate OSAS groups. AHI was significantly higher in OSAS patients with morning headache compared with patients without morning headaches. Oxygen saturation nadir during rapid eye movement and non-rapid eye movement sleep as well as mean oxygen saturation value during total sleep time were also found to be significantly lower in morning headache group. However, none of the sleep parameters was found to be determinants of morning headache. Morning headache was more frequently reported by patients of female gender and with primary headache history. Morning headache was totally resolved in 90% of patients treated with nasal continuous positive airway pressure. The history of OSAS should be considered in the differential diagnosis of morning headache.


Report from the 2013 AOA North American Traveling Fellowship.
Focused on young surgeons starting their careers in academic orthopaedics, the John J. Fahey, MD, Memorial North American Traveling Fellowship (NATF) has served to promote clinical, intellectual, and scientific exchange in orthopaedic surgery for the last forty-five years. The 2013 NATF was a tremendous experience for each and every one of us. We quickly developed very tight bonds with each other and friendships that will undoubtedly last throughout our careers and lives. At each site on the fellowship tour, we were made to feel special by our hosts and everyone with whom we came into contact. We each feel that we achieved the goals set out by the AOA (American Orthopaedic Association), making the most of this phenomenal experience through academic exchange, socialization, and networking and developing an appreciation of the various paths to success in orthopaedic surgery.


Establishment of a Molding Procedure to Facilitate Formulation Development for Co-extrudates.
Co-extrusion offers a number of advantages over conventional manufacturing techniques. However, the setup of a co-extrusion line is cost- and time-intense and formulation development is challenging. This work introduces a novel procedure to test the applicability of a co-extruded reservoir-type system at an early product development stage. We propose vacuum compression molding (VCM), a fast procedure that requires only small material amounts, for the manufacturing of cylindrical reservoir-type system. To this end, the commercially available co-extruded product NuvaRing® and variations thereof were used as test systems. All VCM systems showed a homogeneous skin thickness that adhered well to the core, thereby providing a precise core/skin interface. As drug release is a key criterion for pharmaceutical products, a modified in vitro dissolution method was set up to test the VCM systems. The drug release from the VCM systems was in the same order of magnitude as the corresponding co-extruded strands and followed the same release kinetics. Moreover, the VCM systems were capable of indicating the relative effect of formulation-related modifications on drug release. Overall, this shows that this system is a powerful tool that facilitates formulation tailoring and co-extrusion process setup at the earliest stage.


Revision and reannotation of the Halomonas elongata DSM 2581T genome.
The genome of the Halomonas elongata type strain DSM 2581, an industrial producer, was reevaluated using the Illumina HiSeq2500 technology. To resolve duplication-associated ambiguities, PCR products were generated and sequenced. Outside of duplications, 72 sequence corrections were required, of which 24 were point mutations and 48 were indels of one or few bases. Most of these were associated with polynucleotide stretches (poly-T stretch overestimated in 19 cases, poly-C underestimated in 15 cases). These problems may be attributed to using 454 technology for original genome sequencing. On average, the original genome sequence had only one error in 56 kb. There were 23 frameshift error corrections in the 29 protein-coding genes affected by sequence revision. The genome has been subjected to major reannotation in order to substantially increase the annotation quality.


Vitamin D status and hyperparathyroisism in postmenopausal osteoporotic patients in Cipto Mangunkusumo hospital Jakarta.
to determine the profile of vitamin D and parathyroid hormone (PTH) and the proportion of vitamin D inadequacy in a population of postmenopausal osteoporotic patients from a rheumatologic outpatient clinic. a cross sectional study was conducted between October and December 2006 in the Rheumatology Clinic, Cipto Mangunkusumo Hospital with osteoporosis confirmed by bone mineral densitometry (T score less than -2.5 at the lumbar spine or hip). Patients were excluded if there was a history of oral glucocorticoid treatment within 30 days, vitamin D supplementation, and have renal and/or liver function impairments. Forty-two postmenopausal osteoporotic patients aged 51-77 years old who had been postmenopausal for 5-28 years were included in this study. Vitamin D inadequacy was defined as the plasma levels of 25(OH)D less than 50 nmol/L whereas hyperparathyroidism was defined as the PTH level more than 69 pg/dL. vitamin D inadequacy was found in 61.9% of patients and 34.6% of them or 23.8% of total patients were also having high PTH level. There was an inverse correlation between 25(OH)D with PTH levels and positive correlation between duration of menopause and PTH level. Vitamin D inadequacy is common (61.9%) in postmenopausal osteoporotic patients who visited Rheumatology outpatient clinic of Cipto Mangunkusumo Hospital Jakarta. the low concentration of 25(OH)D was correlated with PTH level and duration of menopause. This finding should be confirmed in a larger epidemiological study, either hospital-or community-based to assess vitamin D status among postmenopausal women in Indonesia.


Internal-external correlation investigations of respiratory induced motion of lung tumors.
In gated radiation therapy procedures, the lung tumor position is used directly (by implanted radiopaque markers) or indirectly (by external surrogate methods) to decrease the volume of irradiated healthy tissue. Due to a risk of pneumothorax, many clinics do not implant fiducials, and the gated treatment is primarily based on a respiratory induced external signal. The external surrogate method relies upon the assumption that the internal tumor motion is well correlated with the external respiratory induced motion, and that this correlation is constant in time. Using a set of data that contains synchronous internal and external motion traces, we have developed a dynamic data analysis technique to study the internal-external correlation, and to quantitatively estimate its underlying time behavior. The work presented here quantifies the time dependent behavior of the correlation between external respiratory signals and lung implanted fiducial motion. The corresponding amplitude mismatch is also reported for the lung patients studied. The information obtained can be used to improve the accuracy of tumor tracking. For the ten patients in this study, the SI internal-external motion is well correlated, with small time shifts and corresponding amplitude mismatches. Although the AP internal-external motion reveals larger time shifts than along the SI direction, the corresponding amplitude mismatches are below 5 mm.


Predicting temporal fluctuations in an intracellular signalling pathway.
We used a newly developed stochastic-based program to predict the fluctuations in numbers of molecules in a chemotactic signalling pathway of coliform bacteria. Specifically, we examined temporal changes in molecules of CheYp, a cytoplasmic protein known to influence the direction of rotation of the flagellar motor. Signalling molecules in the vicinity of a flagellar motor were represented as individual software objects interacting according to probabilities derived from experimentally-observed concentrations rate constants. The simulated CheYp molecules were found to undergo random fluctuations in number about an average corresponding to the deterministically calculated concentration. Both the relative amplitude of the fluctuations, as a proportion of the total number of molecules, and their average duration, increased as the simulated volume was reduced. In a simulation corresponding to 10% of the volume of a bacterium, the average duration of fluctuations was found to be 80.7 ms, which is much shorter than the observed alternations between clockwise and counter clockwise rotations of tethered bacteria (typically 2.6 s). Our results are therefore not in agreement with a simple threshold-crossing model for motor switching. However, it is possible to filter the CheYp fluctuations to produce temporal distributions closer to the observed swimming behaviour and we discuss the possible implications for the control of motor rotation.


Vaccine prospect of Kaposi sarcoma-associated herpesvirus.
Infection of Kaposi sarcoma-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8) is estimated to account for 34,000 new cancer cases globally. Unlike other herpesviruses, KSHV is not ubiquitous but is highly prevalent in some areas, such as sub-Saharan Africa where Kaposi sarcoma is the leading cancer among adults. While latent infection of KSHV plays a major and direct role in tumorigenesis, viral lytic replication also makes significant contributions to this process. Efforts to develop a KSHV vaccine are limited, but studies with EBV have provided important lessons. Informative vaccine research has been conducted in the mouse infection model of a closely related rodent virus, murine gammaherpesvirus-68 (MHV-68 or γHV-68). This mouse model has generated fundamental principles for an effective vaccination strategy. KSHV vaccines designed to prevent a naïve host from infection and to boost the immune control of KSHV in persistently infected people will have major impact on individuals who are at a high risk of developing KSHV-associated diseases.


Effect of a cage divider permitting social stimuli on stress and food intake in rats.
The need to obtain data from individual laboratory animals has forced many researchers to singly-house small animals. This is costly to the researcher and isolation can adversely affect animal physiology and behavior which in turn may threaten the validity and generalization of experiment results to humans. We assessed the practical use of a housing device - dubbed "Buddy Barrier" (BB) - that allows social stimulation in a paired-housing situation while at the same time permitting the collection of individual measures that traditionally require individual-housing. To assess stress responses to the BB, adult male rats were single or pair-housed for several days with and without a BB in the cage. Fecal corticosterone metabolites (fCORT), food intake and body weight were monitored daily. Plasma CORT and adrenal catecholamine levels were assessed at the end of the housing manipulation. Stress hormone measures did not differ in paired vs. singly-housed rats and paired rats quickly habituated to introduction and removal of the BB. Barring a trend for paired rats to eat more in the first 4 h of the dark, there was no difference in 24 h intakes or body weight gain between singly and paired-housed rats. While the BB attenuated 24 h intakes in both groups, intakes normalized to non-BB conditions by the third BB reintroduction. A device such as the BB can enhance the welfare of animals by providing social enrichment without compromising the integrity of experimental protocols traditionally requiring single-housing. In times of lagging research funding it can also substantially reduce housing costs.


Emotional suppression, caregiving burden, mastery, coping strategies and mental health in spousal caregivers.
The main aim was to explore the multiple mediation effects of personal resources (mastery, engagement and disengagement coping strategies) between caregiving burden and depression in spousal caregivers, based on integrated stress process models. A further aim was to examine whether emotional suppression moderates the relationship between perceived burden and depression. Cross-sectional data were collected in 2010-2011 by structured interviews from a sample of 110 spousal caregivers. Coefficients strategy with bootstrapping tested the strength and significance of the conditional indirect effects of simultaneous multiple mediators; and the conditional effect of burden on depression at different emotional suppression values. Caregiving burden was indirectly associated with depression, through mastery and disengagement coping, but not through engagement coping. Mastery was negatively associated with depression, while disengagement coping was positively associated with depression. Emotional suppression and functional disability were positively associated with depressive symptoms. A significant burden-by-emotional suppression interaction was found for predicting depressive symptoms. The study supports the conditional indirect effect in which burden can affect depression by reducing the mastery and increasing the disengagement coping simultaneously. The study provides also initial support for the moderating effect of emotional suppression, which can increase the deleterious effects of burden on depression. Researchers and practitioners should be aware of these issues of family care in spousal caregivers.


Efficacy of bendamustine and rituximab in unfit patients with previously untreated chronic lymphocytic leukemia. Indirect comparison with ibrutinib in a real-world setting. A GIMEMA-ERIC and US study.
Limited information is available on the efficacy of front-line bendamustine and rituximab (BR) in chronic lymphocytic leukemia (CLL) with reduced renal function or coexisting conditions. We therefore analyzed a cohort of real-world patients and performed a matched adjusted indirect comparison with a cohort of patients treated with ibrutinib. One hundred and fifty-seven patients with creatinine clearance (CrCl) <70 mL/min and/or CIRS score >6 were treated with BR. The median age was 72 years; 69% of patients had ≥2 comorbidities and the median CrCl was 59.8 mL/min. 17.6% of patients carried TP53 disruption. The median progression-free survival (PFS) was 45 months; TP53 disruption was associated with a shorter PFS (P = 0.05). The overall survival (OS) at 12, 24, and 36 months was 96.2%, 90.1%, and 79.5%, respectively. TP53 disruption was associated with an increased risk of death (P = 0.01). Data on 162 patients ≥65 years treated with ibrutinib were analyzed and compared with 165 patients ≥65 years treated with BR. Factors predicting for a longer PFS at multivariable analysis in the total patient population treated with BR and ibrutinib were age (HR 1.06, 95% CI 1.02-1.10, P < 0.01) and treatment with ibrutinib (HR 0.55, 95% CI 0.33-0.93, P = 0.03). In a post hoc analysis of patients in advanced stage, a significant PFS advantage was observed in patient who had received ibrutinib (P = 0.03), who showed a trend for OS advantage (P = 0.08). We arrived at the following conclusions: (a) BR is a relatively effective first-line regimen in a real-world population of unfit patients without TP53 disruption, (b) ibrutinib provided longer disease control than BR in patients with advanced disease stage.


Unravelling kinetic and thermodynamic effects on the growth of gold nanoplates by liquid transmission electron microscopy.
The growth of colloidal nanoparticles is simultaneously driven by kinetic and thermodynamic effects that are difficult to distinguish. We have exploited in situ scanning transmission electron microscopy in liquid to study the growth of Au nanoplates by radiolysis and unravel the mechanisms influencing their formation and shape. The electron dose provides a straightforward control of the growth rate that allows quantifying the kinetic effects on the planar nanoparticles formation. Indeed, we demonstrate that the surface-reaction rate per unit area has the same dose-rate dependent behavior than the concentration of reducing agents in the liquid cell. Interestingly, we also determine a critical supply rate of gold monomers for nanoparticle faceting, corresponding to three layers per second, above which the formation of nanoplates is not possible because the growth is then dominated by kinetic effects. At lower electron dose, the growth is driven by thermodynamic and the formation and shape of nanoplates are directly related to the twin-planes formed during the growth.


Timescales alter the inferred strength and temporal consistency of intraspecific diet specialization.
Many populations consist of individuals that differ substantially in their diets. Quantification of the magnitude and temporal consistency of such intraspecific diet variation is needed to understand its importance, but the extent to which different approaches for doing so reflect instantaneous vs. time-aggregated measures of individual diets may bias inferences. We used direct observations of sea otter individuals (Enhydra lutris nereis) to assess how: (1) the timescale of sampling, (2) under-sampling, and (3) the incidence- vs. frequency-based consideration of prey species affect the inferred strength and consistency of intraspecific diet variation. Analyses of feeding observations aggregated over hourly to annual intervals revealed a substantial bias associated with time aggregation that decreases the inferred magnitude of specialization and increases the inferred consistency of individuals' diets. Time aggregation also made estimates of specialization more sensitive to the consideration of prey frequency, which decreased estimates relative to the use of prey incidence; time aggregation did not affect the extent to which under-sampling contributed to its overestimation. Our analyses demonstrate the importance of studying intraspecific diet variation with an explicit consideration of time and thereby suggest guidelines for future empirical efforts. Failure to consider time will likely produce inconsistent predictions regarding the effects of intraspecific variation on predator-prey interactions.


Radioactive seed localization breast biopsy and lumpectomy: can specimen radiographs be eliminated?
Wire localization (WL) is the current standard for surgical diagnosis of nonpalpable breast lesions. Many disadvantages inherent to WL are solved with radioactive seed localization (RSL). This trial investigated the ability of RSL to reduce the need for specimen radiographs and operating room delays associated with WL. A total of 134 women were entered onto an institutional review board-approved study. RSL was performed by placing a titanium seed containing.29 to 20 mCi of iodine-125 to within 1 cm of the suggestive breast lesion. The surgeon used a handheld gamma detector to locate and excise the iodine-125 seed and the lesion. Specimen radiographs were eliminated in 98 (79%) of 124 patients. Surgical seed retrieval was 100% in 124 patients. No seed migration occurred after correct radiographical placement. A total of 26 (21%) of 124 patients required a specimen radiograph; 22 (85%) of these 26 were performed for microcalcifications. After surgical removal, RSL can eliminate specimen radiographs when the radiologist accurately places the seed and the pathologist grossly identifies the lesion. If small microcalcifications are noted before surgery, then specimen radiographs may be necessary. RSL reduced requirements for specimen radiographs, decreased OR time, improved incision placement, and improved resections to clear margins.


Dipeptidyl peptidase IV and related enzymes in cell biology and liver disorders.
DP (dipeptidyl peptidase) IV is the archetypal member of its six-member gene family. Four members of this family, DPIV, FAP (fibroblast activation protein), DP8 and DP9, have a rare substrate specificity, hydrolysis of a prolyl bond two residues from the N-terminus. The ubiquitous DPIV glycoprotein has proved interesting in the fields of immunology, endocrinology, haematology and endothelial cell and cancer biology and DPIV has become a novel target for Type II diabetes therapy. The crystal structure shows that the soluble form of DPIV comprises two domains, an alpha/beta-hydrolase domain and an eight-blade beta-propeller domain. The propeller domain contains the ADA (adenosine deaminase) binding site, a dimerization site, antibody epitopes and two openings for substrate access to the internal active site. FAP is structurally very similar to DPIV, but FAP protein expression is largely confined to diseased and damaged tissue, notably the tissue remodelling interface in chronically injured liver. DPIV has a variety of peptide substrates, the best studied being GLP-1 (glucagon-like peptide-1), NPY (neuropeptide Y) and CXCL12. The DPIV family has roles in bone marrow mobilization. The functional interactions of DPIV and FAP with extracellular matrix confer roles for these proteins in cancer biology. DP8 and DP9 are widely distributed and indirectly implicated in immune function. The DPL (DP-like) glycoproteins that lack peptidase activity, DPL1 and DPL2, are brain-expressed potassium channel modulators. Thus the six members of the DPIV gene family exhibit diverse biological roles.


Chlorthalidone decreases platelet aggregation and vascular permeability and promotes angiogenesis.
Variations in diuretic-mediated inhibition of carbonic anhydrase-dependent chloride transport in platelets and vascular smooth muscle could account for the contrasting efficacy of the thiazide and thiazide-like diuretics in reducing cardiovascular morbidity in patients with hypertension. We assessed platelet carbonic anhydrase activity and catecholamine-induced platelet aggregation in the presence of a thiazide and a "thiazide-like" inhibitor of the sodium-chloride cotransporter. Individual variation in platelet carbonic anhydrase activity correlated with contrasting sensitivity to epinephrine-mediated platelet aggregation. Both chlorthalidone, which potently inhibits platelet carbonic anhydrase, and bendroflumethiazide, which has much less effect on this enzyme, increased the amount of epinephrine needed to induce platelet aggregation when compared with the absence of a diuretic. However, chlorthalidone was significantly more effective than bendroflumethiazide in reducing epinephrine-mediated platelet aggregation. Chlorthalidone also induced marked changes in the number of gene transcripts for two proteins that mediate angiogenesis and vascular permeability, vascular endothelial growth factor C and transforming growth factor-beta3; chlorthalidone and bendroflumethiazide had contrasting effects on the expression of vascular endothelial growth factor C. Chlorthalidone and bendroflumethiazide reduced vascular permeability to albumin, but only chlorthalidone increased angiogenesis. Thiazides and thiazide-like diuretics can comparably reduce blood pressure, but the drugs in this class are not all alike. It can be suggested from our findings that thiazide and thiazide-like diuretics vary in their pleiotropic effects on platelets and in the vasculature, and these differences could explain the contrasting ability of these drugs to reduce cardiovascular morbidity despite comparable reduction in blood pressure.


[W-shaped Resection and Suture of the Posterior Mitral Leaflet in a Patient with Barlow's Disease].
A 72-year-old female presented with congestive heart failure. Ultrasound cardiogram revealed billowing mitral leaflets and severe mitral regurgitation. We diagnosed her with Barlow's disease and performed mitral valve repair. The posterior leaflet was large, and the leaflet height was more than 26 mm. Leaflet height reduction was necessary in order to prevent systolic anterior movement (SAM). The middle scallop was resected in a" W" shape, and its center vertex was designed to have a height of 18 mm, which was the final height of the posterior leaflet. SAM and major leaks were not seen by transesophageal echocardiography after weaning the patient from cardiopulmonary bypass. The use of a W-shaped resection is a simple technique that can be used to reduce the volume and height of the posterior mitral leaflet.


Multiple noncovalent interactions mediated one-pot therapeutic assemblies for the effective treatment of atherosclerosis.
Atherosclerosis may cause life-threatening coronary artery disease, carotid artery disease, stroke, and peripheral vascular disease, while its effective therapy remains challenging thus far. With the aim of facilely constructing efficacious and translational oral delivery systems for an anti-atherosclerotic drug of rapamycin (RAP), an all-in-one approach was created. This strategy involves a carboxyl-bearing compound (serves as a guest molecule) mediated self-assembly of a structurally simple host polymer of poly(N-isopropylacrylamide) (PNIPAm). The formation of microspheres and highly efficient packaging of RAP could be simultaneously achieved by this host-guest self-assembly, affording cost-effective therapeutic assemblies with particularly robust drug loading capacity, desirable drug dissolution, relative manufacturing simplicity, good lyophilization-reconstitution character, and facile scalability. Besides these pharmaceutical characteristics superior over control microspheres based on poly(lactide-co-glycolide) or a enteric coating material, therapeutic RAP microspheres fabricated by this assembly approach had high oral bioavailability. More importantly, assembled RAP microspheres displayed significant therapeutic advantages upon treatment of atherosclerosis in an apolipoprotein E-deficient mouse model. In addition, a long-term treatment with either RAP-containing assemblies or the carrier material PNIPAm revealed a good safety profile in mice post oral delivery. Accordingly, RAP microspheres developed herein are promising and translational therapeutics for atherosclerotic diseases. This study also provides new insights into the design of effective carrier materials for various lipophilic therapeutics.


Limited susceptibility of rhesus macaques to a cowpox virus isolated from a lethal outbreak among New World monkeys.
This study was undertaken to investigate the susceptibility of rhesus monkeys to the calpox virus, an orthopoxvirus (OPXV) of the Cowpox virus species (CPXV), which is uniformly lethal in common marmosets. Six rhesus monkeys were either intravenously (i.v.) or intranasally (i.n.) exposed to the virus. Monitoring of the macaques after viral exposure included physical examinations, the determination of viral load by real-time PCR and plaque assay, and the analysis of humoral responses. Two i.v. inoculated animals developed numerous classical pox lesions that started after inoculation at days 7 and 10. Both animals became viremic and seroconverted. They exhibited maximal numbers of lesions of approximately 50 and 140 by day 21. One animal completely recovered, while the other one suffered from a phlegmonous inflammation of a leg initially induced by a secondarily infected pox lesion and was euthanized for animal welfare reasons. In contrast to previous pathogenicity studies with the calpox virus in marmosets, none of the four animals inoculated intranasally with doses of the calpox virus exceeding those used in marmosets by orders of magnitude showed typical clinical symptoms. No viral DNA was detectable in the blood of those animals, but three animals seroconverted. In two of these three animals, infectious virus was sporadically isolated from saliva. This indicates that rhesus monkeys are less susceptible to calpox virus infection, which limits their use in further intervention studies with OPXV.


Cannabis use for Sleep Disturbance Among Older Patients in a Geriatrics Clinic.
Cannabis use is growing among older adults to manage medical concerns including poor sleep. In this study, we characterized how patients seen at a geriatrics clinic use cannabis to address sleep disturbance. Specifically, we conducted an anonymous survey of 568 adults, including 83 who reported cannabis use within the past 3 years, to inquire about such use. We compared cannabis use characteristics between those using it for sleep disturbance versus all other conditions. We considered a p-value <.10 to be statistically significant. Among the cannabis users in our sample, 29% reported using cannabis for sleep disturbance (N = 24). They were more likely than other users to be female (p = .07), consume cannabis more frequently (p = .01), use products containing tetrahydrocannabinol (THC) (vs. cannabidiol [CBD]-only; p < .01), and use cannabis to target more symptoms (p < .01). As cannabis use continues to grow in older populations, it is essential to delineate better how cannabis may be used safely and effectively to improve older adults' sleep health.


Mixed-valent neptunium oligomer complexes based on cation-cation interactions.
Mixed-valent tri- and tetranuclear complexes of neptunium, [{NpIVCl4}{NpVO2Cl(THF)3}2]·THF and [{NpIVCl3}{NpVO2(μ2-Cl)(THF)2}3{μ3-Cl}] (THF = tetrahydrofuran), were synthesised and characterised. Both the complexes are formed via the cation-cation interactions between the Np(iv) centre and the axial oxygens of the neptunyl(v) unit (i.e. trans-dioxo NpO2+ cation), demonstrating the potential of cation-cation interactions for further exploring the oligomer/cluster chemistry of actinides.


A Curated Cancer Clinical Outcomes Database (C3OD) for accelerating patient recruitment in cancer clinical trials.
Data used to determine patient eligibility for cancer clinical trials often come from disparate sources that are typically maintained by different groups within an institution, use differing technologies, and are stored in different formats. Collecting data and resolving inconsistencies across sources increase the time it takes to screen eligible patients, potentially delaying study completion. To address these challenges, the Biostatistics and Informatics Shared Resource at The University of Kansas Cancer Center developed the Curated Cancer Clinical Outcomes Database (C3OD). C3OD merges data from the electronic medical record, tumor registry, bio-specimen and data registry, and allows querying through a single unified platform. By centralizing access and maintaining appropriate controls, C3OD allows researchers to more rapidly obtain detailed information about each patient in order to accelerate eligibility screening. This case report describes the design of this informatics platform as well as initial assessments of its reliability and usability.


Chorioamnionitis and Management of Asymptomatic Infants ≥35 Weeks Without Empiric Antibiotics.
Management of asymptomatic infants ≥35 weeks' gestation born to mothers with chorioamnionitis remains controversial, with many clinicians considering the need for changes to the current guidelines. The study objective was to evaluate the outcomes of asymptomatic chorioamnionitis-exposed neonates without the use of immediate empirical antibiotics. A retrospective data review was conducted from May 2008 to December 2014, including asymptomatic infants ≥35 weeks' gestation with a maternal diagnosis of clinical chorioamnionitis. A total of 240 asymptomatic infants with chorioamnionitis exposure were identified. The majority of asymptomatic chorioamnionitis-exposed infants, 162 (67.5%), remained well in the mother-infant unit with a median stay of 2 days. There were 78 (32.5%) infants admitted to the NICU and exposed to antibiotics due to abnormal laboratory data or development of clinical symptoms. Of those infants admitted to the NICU, 19 (24%) received antibiotics for <72 hours, 47 (60%) were treated for culture-negative clinical sepsis, and 12 (15%) for culture-positive sepsis, with a median NICU stay of 7 days. Nonroutine use of empirical antibiotics in asymptomatic newborns ≥35 weeks' gestation with maternal chorioamninonitis prevented NICU admission in two-thirds of these infants. This prevented unnecessary antibiotic exposure, increased hospitalization costs, and disruption of mother-infant bonding and breastfeeding. Laboratory evaluation and clinical observation without immediate antibiotic administration may be incorporated into a management approach in asymptomatic chorioamnionitis-exposed neonates. Additional studies are needed to establish the safety of this approach.


Eukaryotic initiation factor 6 is rate-limiting in translation, growth and transformation.
Cell growth and proliferation require coordinated ribosomal biogenesis and translation. Eukaryotic initiation factors (eIFs) control translation at the rate-limiting step of initiation. So far, only two eIFs connect extracellular stimuli to global translation rates: eIF4E acts in the eIF4F complex and regulates binding of capped messenger RNA to 40S subunits, downstream of growth factors, and eIF2 controls loading of the ternary complex on the 40S subunit and is inhibited on stress stimuli. No eIFs have been found to link extracellular stimuli to the activity of the large 60S ribosomal subunit. eIF6 binds 60S ribosomes precluding ribosome joining in vitro. However, studies in yeasts showed that eIF6 is required for ribosome biogenesis rather than translation. Here we show that mammalian eIF6 is required for efficient initiation of translation, in vivo. eIF6 null embryos are lethal at preimplantation. Heterozygous mice have 50% reduction of eIF6 levels in all tissues, and show reduced mass of hepatic and adipose tissues due to a lower number of cells and to impaired G1/S cell cycle progression. eIF6(+/-) cells retain sufficient nucleolar eIF6 and normal ribosome biogenesis. The liver of eIF6(+/-) mice displays an increase of 80S in polysomal profiles, indicating a defect in initiation of translation. Consistently, isolated hepatocytes have impaired insulin-stimulated translation. Heterozygous mouse embryonic fibroblasts recapitulate the organism phenotype and have normal ribosome biogenesis, reduced insulin-stimulated translation, and delayed G1/S phase progression. Furthermore, eIF6(+/-) cells are resistant to oncogene-induced transformation. Thus, eIF6 is the first eIF associated with the large 60S subunit that regulates translation in response to extracellular signals.


Overdispersed molecular clock at the major histocompatibility complex loci.
The extent of amino acid differences of major histocompatibility complex molecules within species is unusually high, consistent with the finding that some pairs of alleles have persisted for more than ten million years and the view that the polymorphism has been maintained by natural selection. The disparity between synonymous and non-synonymous substitutions in the antigen recognition site, however, suggests that some non-synonymous sites have undergone a number of substitutions whereas others have little or none. To describe statistically such an overdispersed underlying process, commonly used Poisson processes are inadequate. An alternative process leads to the surprising conclusion that each non-synonymous site has accumulated as many as 2.6 substitutions, on the average, in the two lineages leading to humans and mice. The standard deviation is also very large (6.6) and the dispersion index (the ratio of the variance to the mean) is at least 17. The substitution process thus inferred qualitatively agrees with the disposition (a boomerang pattern) of substitutions between HLA-A2 and Aw68 alleles, and quantitatively agrees well with that expected where the evolution of major histocompatibility complex molecules has long been driven mostly by balancing selection.


Sorghum forage in precision-fed dairy heifer diets.
Sorghum forage is an alternative crop that is more adapted to drier conditions and more resistant than corn to drought conditions. Thus, sorghum forage maximizes water utilization. The objective of this study was to evaluate sorghum silage (SS), including digestibility and fermentation parameters, in precision-fed dairy heifers. Eight Holstein heifers (13.7±0.6mo of age and 364.8±17.64kg of body weight) fitted with rumen cannulas were used in a replicated 4×4 Latin Square design; treatments were 4 levels of forage to concentrate ratios (85:15, 75:25, 65:35, and 55:45). Rumen contents were sampled at various times to determine pH and volatile fatty acid concentrations. Dry matter (DM) and neutral detergent fiber (NDF) in situ degradation kinetics were compared between SS and corn silage (CS) diets. Fecal total collection was used to estimate apparent total-tract digestibility. Fecal grab samples at 0, 6, 12, and 18h after feeding were used to estimate total-tract starch digestibility. Amount of concentrate in the diet affected the time that heifers spent eating as well as rumen pH. When the concentrate proportion of the diet increased, eating time and rumen pH decreased linearly. Total volatile fatty acid concentrations were not affected by treatment, but butyrate increased as the proportion of concentrate increased in the diet. Digestibility of DM and starch were higher in diets with lower forage to concentrate ratio, but NDF, acid detergent fiber, and hemicellulose digestibility were not affected. Corn silage had greater DM and NDF digestibility than SS. Also, fractional rate of digestion was faster for CS than SS (2.78 vs. 2.42% per hour, respectively). We conclude that fecal grab samples are suitable for predicting starch digestibility in heifers given the starch levels studied. In addition, SS was an adequate alternative forage in precision-fed dairy heifers with outcomes very similar to CS-based rations.


Excoriation (skin-picking) disorder: a systematic review of treatment options.
Although pathological skin-picking has been documented in the medical literature since the 19th century, it has only recently been included as a distinct entity in psychiatric classification systems. In the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition and the proposed International Classification of Diseases, Eleventh Revision, excoriation (skin-picking) disorder (ED), also known as neurotic excoriation, psychogenic excoriation, or dermatillomania), is described as recurrent picking of skin, leading to skin lesions and significant distress or functional impairment. ED is listed as one of the obsessive-compulsive and related disorders, given its overlap with conditions such as trichotillomania (hair-pulling disorder). Arguably, its inclusion and delineation in the diagnostic nomenclature will lead to increased awareness of the condition, more research, and ultimately in treatment advances. This systematic review aims to provide readers with an up-to-date view of current treatment options for ED. A MEDLINE search of the ED treatment literature was conducted to collate relevant articles published between 1996 and 2017. The findings indicate that a number of randomized controlled trails on ED have now been published, and that current management options include behavioral therapy (habit reversal or acceptance-enhanced behavior therapy), and medication (selective serotonin reuptake inhibitors or N-acetyl cysteine).


Sociodemographic factors and the use of outpatient mental health services.
What are the effects of sociodemographic factors on the use of outpatient mental health services when different demographic groups have identical health insurance coverage? The authors answer this question using data from the Rand Health Insurance Experiment. Health insurance was randomly assigned to families representative of the nonaged, noninstitutionalized civilian population in six U.S. sites. Income has no significant total effect on use when all income groups have the same coverage. When the effects of variables correlated with socioeconomic status are removed, users with higher socioeconomic status are significantly more likely to choose a mental health specialist rather than only general medical providers for their mental health care (P less than 0.05); among those who visit mental health specialists, those with higher socioeconomic status incur significantly greater expenses (P less than 0.10). Women use significantly more mental health services than men (P less than 0.05), who in turn use significantly more mental health services than children (P less than 0.05), even after controlling for demographic factors, health status, and insurance coverage. Similarly, there are large differences (roughly sixfold) by site in outpatient mental health expenses even when all sites have identical coverage.


Promoting equity at the population level: Putting the foundational principles into practice through disability advocacy.
Rehabilitation psychology is based on foundational principles that can guide us toward health equity among disabled and nondisabled communities. We summarize the literature on disparities in the disability community and underscore the urgency to address underlying inequities to eliminate disparities. We include examples of population-level interventions that promote equity in the disability community. We conclude with a call for a broader mission for rehabilitation psychologists based on the field's foundational principles, and outline emerging opportunities to widen our impact and advance equity. Our foundational principles, built on systems theory, call on rehabilitation psychologist to work at macrosystemic levels. As rehabilitation psychologists, we need to widen our focus from the micro (individual) to the macro (population) level. We need to bring the respect, dignity, and collaborative spirit that inspire our work with individuals to the broader community by advocating for structures and policies that promote equity for disabled persons. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Estimating the Proportion of True Null Hypotheses Using the Pattern of Observed p-values.
Estimating the proportion of true null hypotheses, π0, has attracted much attention in the recent statistical literature. Besides its apparent relevance for a set of specific scientific hypotheses, an accurate estimate of this parameter is key for many multiple testing procedures. Most existing methods for estimating π0 in the literature are motivated from the independence assumption of test statistics, which is often not true in reality. Simulations indicate that most existing estimators in the presence of the dependence among test statistics can be poor, mainly due to the increase of variation in these estimators. In this paper, we propose several data-driven methods for estimating π0 by incorporating the distribution pattern of the observed p-values as a practical approach to address potential dependence among test statistics. Specifically, we use a linear fit to give a data-driven estimate for the proportion of true-null p-values in (λ, 1] over the whole range [0, 1] instead of using the expected proportion at 1 - λ. We find that the proposed estimators may substantially decrease the variance of the estimated true null proportion and thus improve the overall performance.


Long noncoding RNA HOXA-AS2 acts as an oncogene by targeting miR-145-3p in human non-small cell lung cancer.
Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA HOXA-AS2 acts as an oncogene by targeting miR-145-3p in human non-small cell lung cancer, by Y.-B. Shi, S.-L. Liu, X.-R. Mou, J. Liao, J.-P. Che, X.-Q. Fei, A.-R. Wang, published in Eur Rev Med Pharmacol Sci 2020; 24 (3): 1243-1249-DOI: 10.26355/eurrev_202002_20177-PMID: 32096154" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20177.


Genotypic resistance profile and clinical progression of treatment-experienced HIV type 1-infected patients with virological failure.
We explored the relationship between HIV-1 drug resistance in treatment-experienced patients and disease progression in a cohort of patients undergoing resistance testing to guide treatment decisions. A total of 601 treatment-failing individuals tested for genotypic HIV-1 drug resistance between 1998 and 2004 were selected. At genotypic testing, median HIV-1 RNA levels and CD4 counts were 3.8 log copies/ml and 293 cells/mul, respectively; 84% had resistance mutations to nucleoside reverse transcriptase inhibitors (NRTIs), 42% had resistance mutations to non-NRTIs, 51% had major resistance mutations to protease inhibitors (PI), 12% had no major resistance mutations to any drug class, 22% had mutations to one class, 42% had mutations to two classes, and 23% had mutations to three classes. During a follow-up of 714.7 patients/year, 80 patients showed an AIDS-defining event or died. In multivariable models adjusting for prior AIDS, baseline CD4 counts, HIV-1 RNA, and calendar year, viral resistance variables associated with increased hazards of clinical progression were the presence of reverse transcriptase substitution T215F (p = 0.002) and the presence of three or more protease substitutions among L33F/I/V, V82A/F/L/T, I84V, and L90M (p = 0.003). Resistance to three drug classes remained independently predictive of clinical progression only when calendar year was not used as an adjustment factor. Prevention and treatment of multiple drug class resistance are clinical priorities for HIV-infected patients. In recent years, improved treatment options may have helped in reducing part of the resistance-associated clinical progression.


Clinical application of blood purification in polymyositis/dermatomyositis.
We investigated the clinical efficacy and safety of blood purification technology in patients with polymyositis/dermatomyositis. In a study of 22 patients, 10 cases received blood purification treatment (5 cases received plasma exchange, 5 cases received plasma HA280 immunoadsorption), and 12 cases served as the control group. A 3-month follow-up was conducted to compare the clinical manifestations and laboratory examination. Symptoms and signs of patients in treatment group were significantly improved, and the hormone usage was lower than the control group. For patients with normal creatine kinase level and ferritin level below three times the upper limit of normal, there was a positive correlation between their N/L values and MDAAT scores. The results of this study suggest that blood purification therapy, including plasma HA280 immunoadsorption and plasma exchange, is an effective and safe treatment for patients with polymyositis/dermatomyositis, offering assistance in reducing hormone usage in the long-term.


Improving the quality of electron backscatter diffraction (EBSD) patterns from nanoparticles.
In this study, we investigated the relative contributions of atomic number (Z) and density (rho) to the degradation of the electron backscatter diffraction (EBSD) pattern quality for nanoparticles < 500 nm in diameter. This was accomplished by minimizing the diffuse scattering from the conventional thick mounting substrate through the design of a sample holder that can accommodate particles mounted on thin-film TEM substrates. With this design, the contributions of incoherently scattered electrons that result in the diffuse background are minimized. Qualitative and quantitative comparisons were made of the EBSD pattern quality obtained from Al(2)O(3) particles approximately 200 nm in diameter mounted on both thick- and thin-film C substrates. For the quantitative comparison we developed a 'quality' factor for EBSD patterns that is based on the ratio of two Hough transforms derived from a given EBSD pattern image. The calculated quality factor is directly proportional to the signal-to-noise ratio for the EBSD pattern. In addition to the comparison of the thick and thin mounting substrates, we also estimated the effects of Z and rho by comparing the EBSD pattern quality from the Al(2)O(3) particles mounted on thin-film substrates with the quality of patterns obtained from Fe-Co nanoparticles approximately 120 nm in diameter. The results indicate that the increased background generated in EBSD patterns by the electrons escaping through the bottom of the small particles is the dominant reason for the poor EBSD pattern quality from nanoparticles < 500 nm in size. This was supported by the fact that we were able to obtain usable EBSD patterns from Al(2)O(3) particles as small as 130 nm using the thin-film mounting method.


Compensating the Influence of Tremors on Impedance Measurements Through Fourier Analysis.
Electrical mpedance measurements are a promising method for detecting structural changes in tissue and can be used in oncology to differentiate between healthy and tumorous tissue areas. The impedance measurements are so sensitive that they are not only affected by changes in the tissue itself, but also by a fluctuating contact force between sensor and tissue. In this work, the correlation between impedance measurements and movements during the measuring process, such as physiological tremors, are analyzed. To do this, impedance measurements are taken on pig bladders and the sensor-tissue contact force is simultaneously recorded. The tremor frequencies are directly visible in the Fourier transform of the impedance measurement. To counteract these effects, a Butterworth filter is used to filter out tremor frequencies and remove unwanted artefacts. Additionally, placing an spring on top of the impedance sensor helped to achieve a steadier contact force between sensor and tissue to also remove low frequency disturbances in the impedance measurements.Clinical relevance- This approach can help to obtain more reliable impedance measurements on tissue both for ex vivo and in vivo applications.


Immunoglobulin E, atopy, and nickel allergy.
Statements in the literature as to whether a relation exists between atopy and nickel allergy are contradictory. I have attempted to make the diagnosis of the two states more stringent by using immunoglobulin E (IgE) determinations and serial dilution tests with nickel sulfate. The IgE determinations proved to be of less value in cases of pure eczema, and nonspecific (?) increases were sometimes observed. The incidence of family atopy was higher in other reports, but the clinical significance of this was unclear. Serial dilution tests gave important information, and a warning is issued against uncritical acceptance of a test reaction with 5.0% nickel sulfate in a patient with suspected atopy.


Recent Progress in Drug Delivery Systems for Tyrosine Kinase Inhibitors in the Treatment of Lung Cancer.
Lung cancer ranks as the second most commonly diagnosed cancer in both men and women worldwide. Despite the availability of diverse diagnostic and treatment strategies, it remains the leading cause of cancer-related deaths globally. The current treatment approaches for lung cancer involve the utilization of first generation (e.g., erlotinib, gefitinib) and second generation (e.g., afatinib) tyrosine kinase inhibitors (TKIs). These TKIs exert their effects by inhibiting a crucial enzyme called tyrosine kinase, which is responsible for cell survival signaling. However, their clinical effectiveness is hindered by limited solubility and oral bioavailability. Nanotechnology has emerged as a significant application in modern cancer therapy. Nanoparticle-based drug delivery systems, including lipid, polymeric, hybrid, inorganic, dendrimer, and micellar nanoparticles, have been designed to enhance the bioavailability, stability, and retention of these drugs within the targeted lung area. Furthermore, these nanoparticle-based delivery systems offer several advantages, such as increased therapeutic efficacy and reduced side effects and toxicity. This review focuses on the recent advancements in drug delivery systems for some of the most important TKIs, shedding light on their potential in improving lung cancer treatment.


[Personality disorders in oncology: characteristic and management].
Confronted with a patient with a personality disorder, the oncologist must recognize it and adapt his treatment accordingly. Some pathological character types require interpersonal adjustments to ensure a good understanding of the cancer disease and also to obtain the best compliance with supportive care. Given the fact that specific pharmacological treatment does not exist, collaboration between oncologists and the psycho-oncology team is paramount. The interaction between the somatic disease and the psychiatric disorder demand collaboration among caregivers sharing explanations and recommendations. Clinical examples will illustrate each personality disorder and will focus on the several problems raised by the psychiatric disorder. Treatment principles will be addressed in a second section.


Mineral trioxide aggregate inhibits osteoclastic bone resorption.
Mineral trioxide aggregate (MTA), a commonly used endodontic repair material, is useful for both basic and clinical research, and the effect of MTA on osteoblast differentiation has been well-defined. However, the effects of MTA on osteoclastic bone resorption are not fully understood. Hence, the aim of this study is to examine the effect of MTA solution in the regulation of osteoclast bone-resorbing activity using osteoclasts formed in co-cultures of primary osteoblasts and bone marrow cells. MTA solution dose-dependently reduced the total area of pits formed by osteoclasts. The reduction of resorption induced by 20% MTA treatment was due to inhibition of osteoclastic bone-resorbing activity and had no effect on osteoclast number. A 20% MTA solution disrupted actin ring formation, a marker of osteoclastic bone resorption, by reducing phosphorylation and kinase activity of c-Src, and mRNA expressions of cathepsin K and mmp-9. A high concentration of MTA solution (50%) induced apoptosis of osteoclasts by increasing the expression of Bim, a member of the BH3-only (Bcl-2 homology) family of pro-apoptotic proteins. Taken together, our results suggest that MTA is a useful retrofilling material for several clinical situations because it both stimulates osteoblast differentiation and inhibits bone resorption.


Beyond Correlation: Optimal Transport Metrics For Characterizing Representational Stability and Remapping in Neurons Encoding Spatial Memory.
Spatial representations in the entorhinal cortex (EC) and hippocampus (HPC) are fundamental to cognitive functions like navigation and memory. These representations, embodied in spatial field maps, dynamically remap in response to environmental changes. However, current methods, such as Pearson's correlation coefficient, struggle to capture the complexity of these remapping events, especially when fields do not overlap, or transformations are non-linear. This limitation hinders our understanding and quantification of remapping, a key aspect of spatial memory function. To address this, we propose a family of metrics based on the Earth Mover's Distance (EMD) as a versatile framework for characterizing remapping. Applied to both normalized and unnormalized distributions, the EMD provides a granular, noise-resistant, and rate-robust description of remapping. This approach enables the identification of specific cell types and the characterization of remapping in various scenarios, including disease models. Furthermore, the EMD's properties can be manipulated to identify spatially tuned cell types and to explore remapping as it relates to alternate information forms such as spatiotemporal coding. By employing approximations of the EMD, we present a feasible, lightweight approach that complements traditional methods. Our findings underscore the potential of the EMD as a powerful tool for enhancing our understanding of remapping in the brain and its implications for spatial navigation, memory studies and beyond.


Transcriptional analysis of early lineage commitment in human embryonic stem cells.
The mechanisms responsible for the maintenance of pluripotency in human embryonic stem cells, and those that drive their commitment into particular differentiation lineages, are poorly understood. In fact, even our knowledge of the phenotype of hESC is limited, because the immunological and molecular criteria presently used to define this phenotype describe the properties of a heterogeneous population of cells. We used a novel approach combining immunological and transcriptional analysis (immunotranscriptional profiling) to compare gene expression in hESC populations at very early stages of differentiation. Immunotranscriptional profiling enabled us to identify novel markers of stem cells and their differentiated progeny, as well as novel potential regulators of hESC commitment and differentiation. The data show clearly that genes associated with the pluripotent state are downregulated in a coordinated fashion, and that they are co-expressed with lineage specific transcription factors in a continuum during the early stages of stem cell differentiation. These findings, that show that maintenance of pluripotency and lineage commitment are dynamic, interactive processes in hESC cultures, have important practical implications for propagation and directed differentiation of these cells, and for the interpretation of mechanistic studies of hESC renewal and commitment. Since embryonic stem cells at defined stages of commitment can be isolated in large numbers by immunological means, they provide a powerful model for studying molecular genetics of stem cell commitment in the embryo.


[Detection of transgenic proteins in maize flour marketed in Bogotá, Colombia].
Objective To detect the presence or absence of transgenic proteins derived from GM crops in maize flour marketed in Bogota D.C., Colombia. Methods 11 extraction protocols for total protein were evaluated in 17 precooked flour, two uncooked and three positive controls. Subsequently, the presence of 7 transgenic proteins (CP4-EPSPS, Cry1Ab, Cry1Ac, Cry1F, Cry2A, Cry34Ab1 and Cry3Bb1) using commercial ELISA kits was determined. Results It was determined that the best protocol for total protein extraction was buffer with Triton X-100, which allowed obtaining protein concentrations greater than 0.5 mg per gram of flour and does not generate interference with the ELISA technique. Four transgenic proteins were detected: CP4EPSPS, Cry1F, Cry1Ab and Cry34Ab1 in precooked and uncooked flour with percentages varying between 20 and 100 %. Conclusion Seven of the 19 maize flours contain traces of transgenic protein (B2,B8,A3,O3,O1,C1 and C2) that provide resistance to lepidopterans and coleopterans, and tolerance to glyphosate herbicide, (CP4EPSPS- Cry1Ab, Cry1F, Cry34Ab1 and Cry3Bb1). All detected events are approved for human consumption in Colombia, according to the Ministry of Health and Social Protection.


Cell Cycle Modulation of CHO-K1 Cells Under Genistein Treatment Correlates with Cells Senescence, Apoptosis and ROS Level but in a Dose-Dependent Manner.
Purpose: Genistein, a soy isoflavone, exhibits a biphasic effect on cells proliferation with some different effects between ER-alpha and ER-beta. The objective of this present study is to determine the modulatory effect based on cell cycle progression under genistein treatment in combination with 17-β estradiol (E2) on CHO-K1 cells. Methods: The effect of genistein 0.1-100 µM on cells proliferation was examined by MTT assay. The modulation of genistein and estradiol (E2) on cell cycle and apoptosis were observed by using flowcytometry with PI and PI/AnnexinV staining, respectively. Moreover, the effect of genistein and E2 on senescence cells, and ROS level were determined by senescence-associated β-galactosidase (SA β-gal) staining and by using flowcytometry with 2', 7'-dichlorofluorescin diacetate (DCFDA) staining, respectively. The expression level of the cell cycle and senescence protein markers were observed by immunoblotting. Results: Single treatment of genistein at physiologically achievable (low) concentration (<2 µM) induced proliferation of CHO-K1 cells while at a pharmacological (high) concentration (50 and 100 µM) suppressed cells proliferation. Interestingly, treatment of genistein at the physiological concentration in combination with E2 for 24, 48 and 72 h decreased cells viability on CHO-K1 cells compared to untreated cells. Further analysis of the cells showed that 50 µM genistein induced G2/M phase accumulation and induced apoptosis. Moreover, genistein induced cell senescence and increased ROS level. Immunoblotting analysis showed the decreasing of ERalpha, Bcl2, and ppRb protein level upon treatment of 1 µM Gen and 1 nM E2. Conclusion: Our results suggest that the cell proliferation inhibitory mechanism of genistein at pharmacological concentration involved the induction of cell senescence, and the elevation of ROS level. Moreover, the decreased of cells proliferation upon treatment of physiological concentration of genistein in combination with E2 may be correlated with the alteration of ER expression.


Assessment of different methods for shadow detection in high-resolution optical imagery and evaluation of shadow impact on calculation of NDVI, and evapotranspiration.
Significant efforts have been made recently in the application of high-resolution remote sensing imagery (i.e., sub-meter) captured by unmanned aerial vehicles (UAVs) for precision agricultural applications for high-value crops such as wine grapes. However, at such high resolution, shadows will appear in the optical imagery effectively reducing the reflectance and emission signal received by imaging sensors. To date, research that evaluates procedures to identify the occurrence of shadows in imagery produced by UAVs is limited. In this study, the performance of four different shadow detection methods used in satellite imagery was evaluated for high-resolution UAV imagery collected over a California vineyard during the Grape Remote sensing Atmospheric Profile and Evapotranspiration eXperiment (GRAPEX) field campaigns. The performance of the shadow detection methods was compared and impacts of shadowed areas on the normalized difference vegetation index (NDVI) and estimated evapotranspiration (ET) using the Two-Source Energy Balance (TSEB) model are presented. The results indicated that two of the shadow detection methods, the supervised classification and index-based methods, had better performance than two other methods. Furthermore, assessment of shadowed pixels in the vine canopy led to significant differences in the calculated NDVI and ET in areas affected by shadows in the high-resolution imagery. Shadows are shown to have the greatest impact on modeled soil heat flux, while net radiation and sensible heat flux are less affected. Shadows also have an impact on the modeled Bowen ratio (ratio of sensible to latent heat) which can be used as an indicator of vine stress level.


Accumulation and Stretching of DNA Molecules in Temperature-Induced Concentration Gradients.
Temperature fields provide a noninvasive approach for manipulating individual macromolecules in solution. Utilizing thermophoresis and other secondary effects resulting from the inhomogeneous distribution of crowding agents, one may gain valuable insights into the interactions of molecular mixtures. In this report, we examine the steady-state concentration distribution and dynamics of DNA molecules in a poly(ethylene glycol) (PEG)/water solution when exposed to localized temperature gradients generated by optical heating of a thin chrome layer at a liquid-solid boundary. This allowed us to experimentally investigate the interplay between DNA thermophoresis and PEG-induced entropic depletion effects. Our quantitative analysis demonstrates that the depletion effects dominate over DNA thermophoresis, causing the DNA polymers to migrate toward the heat source. Additionally, we explore the transient stretching of individual DNA molecules in thermally induced PEG gradients and estimate the contributing forces.


Child maltreatment as a social determinant of midlife health-related quality of life in women: do psychosocial factors explain this association?
We examined if child maltreatment (CM) is associated with worse health-related quality of life (HRQoL) in midlife women and if the association is mediated by psychosocial factors. A total of 443 women were enrolled in the Pittsburgh site of the longitudinal Study of Women's Health Across the Nation-Mental Health Study. The analytic sample included 338 women who completed the SF-36 and the Childhood Trauma Questionnaire. Generalized linear regression was used to assess the association between CM and two HRQoL component scores. Structural nested mean models were used to evaluate the contribution of each psychosocial mediator (lifetime psychiatric history, depressive symptoms, sleep problems, very upsetting life events, low social support) to the association. Thirty-eight percent of women reported CM. The mean mental (MCS) and physical (PCS) SF-36 component scores were 2.3 points (95% CI - 4.3, - 0.3) and 2.5 points (95% CI - 4.5, - 0.6) lower, respectively, in women with any CM than in those without. When number of CM types increased (0, 1, 2, 3+ types), group mean scores decreased in MCS (52, 51, 48, 47, respectively; p < .01) and PCS (52, 52, 49, 49, respectively; p = .03). In separate mediation analyses, depressive symptoms, very upsetting life events, or low social support, reduced these differences in MCS, but not PCS. CM is a social determinant of midlife HRQoL in women. The relationship between CM and MCS was partially explained by psychosocial mediators. It is important to increase awareness among health professionals that a woman's midlife well-being may be influenced by early-life adversity.


Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study.
To study the effect of systemic hyperbaric oxygenation (HBO) therapy on the healing course of nonischemic chronic diabetic foot ulcers. From 1999 to 2000, 28 patients (average age 60.2 +/- 9.7 years, diabetes duration 18.2 +/- 6.6 years), of whom 87% had type 2 diabetes, demonstrating chronic Wagner grades I-III foot ulcers without clinical symptoms of arteriopathy, were studied. They were randomized to undergo HBO because their ulcers did not improve over 3 months of full standard treatment. All the patients demonstrated signs of neuropathy. HBO was applied twice a day, 5 days a week for 2 weeks; each session lasted 90 min at 2.5 ATA (absolute temperature air). The main parameter studied was the size of the foot ulcer measured on tracing graphs with a computer. It was evaluated before HBO and at day 15 and 30 after the baseline. HBO was well tolerated in all but one patient (barotraumatic otitis). The transcutaneous oxygen pressure (TcPO(2)) measured on the dorsum of the feet of the patients was 45.6 +/- 18.1 mmHg (room air). During HBO, the TcPO(2) measured around the ulcer increased significantly from 21.9 +/- 12.1 to 454.2 +/- 128.1 mmHg (P < 0.001). At day 15 (i.e., after completion of HBO), the size of ulcers decreased significantly in the HBO group (41.8 +/- 25.5 vs. 21.7 +/- 16.9% in the control group [P = 0.037]). Such a difference could no longer be observed at day 30 (48.1 +/- 30.3 vs. 41.7 +/- 27.3%). Four weeks later, complete healing was observed in two patients having undergone HBO and none in the control group. In addition to standard multidisciplinary management, HBO doubles the mean healing rate of nonischemic chronic foot ulcers in selected diabetic patients. The time dependence of the effect of HBO warrants further investigations.