Surgical technique for single-port laparoscopy in huge ovarian tumors: SW Kim's technique and comparison to laparotomy.
This study aimed to introduce a method to remove huge ovarian tumors (≥15 cm) intact with single-port laparoscopic surgery (SPLS) using SW Kim's technique and to compare the surgical outcomes with those of laparotomy. Medical records were retrospectively reviewed for patients who underwent either SPLS (n=21) with SW Kim's technique using a specially designed 30×30-cm2-sized 3XL LapBag or laparotomy (n=22) for a huge ovarian tumor from December 2008 to May 2016. Perioperative surgical outcomes were compared. In 19/21 (90.5%) patients, SPLS was successfully performed without any tumor spillage or conversion to multi-port laparoscopy or laparotomy. There was no significant difference in patient characteristics, including tumor diameter and total operation time, between both groups. The postoperative hospital stay was significantly shorter for the SPLS group than for the laparotomy group (median, 2 [1 to 5] vs. 4 [3 to 17] days; P<0.001). The number of postoperative general diet build-up days was also significantly shorter for the SPLS group (median, 1 [1 to 4] vs. 3 [2 to 16] days; P<0.001). Immediate post-operative pain score was lower in the SPLS group (median, 2.0 [0 to 8] vs. 4.0 [0 to 8]; P=0.045). Patient-controlled anesthesia was used less in the SPLS group (61.9% vs. 100%). SPLS was successful in removing most large ovarian tumors without rupture and showed quicker recovery and less immediate post-operative pain in comparison to laparotomy. SPLS using SW Kim's technique could be a feasible solution to removing huge ovarian tumors.


Prerequisite objectives for graduate surgical education: a study of the Graduate Medical Education Committee American College of Surgeons.
Recent changes in the educational environment and in the content of specialty surgical education have highlighted limitations, both educational and logistic, of the current system of graduate surgical education. To address these issues, the Graduate Medical Education Committee of the American College of Surgeons conducted a study of the educational competencies desired of graduating medical students, and of surgical residents completing their first postgraduate year (PGY 1). Surgeons representing all surgical specialties identified learning needs for graduating students and PGY 1 surgical residents. Responding to a questionnaire based on these learning needs, surgical educators assigned a priority of essential, desirable, or supplementary to each item. Additional questionnaires, limited to student-level items, were sent to graduating medical students matched to surgical residency programs, who assessed their competency. Questionnaires were received from 350 senior surgeons and 83 graduating medical students. General agreement was found among surgeons of all specialties of the essential and desired competencies for medical students entering any surgical residency program. Although there was considerable specialty variation in the priority given to individual items, there was also a broad general consensus on many areas of essential or desirable knowledge and skill that all surgical interns should possess before continuing in advanced education in a surgical specialty, including general surgery. The evidence that many core proficiencies are held in common by all surgical specialties argues strongly for careful coordination and cooperation among the various residency programs in an institution to achieve these objectives in a common learning program.


Mito-nuclear interactions as drivers of gene movement on and off the X-chromosome.
Mito-nuclear gene interactions regulate energy conversion, and are fundamental to eukaryotes. Generally, mito-nuclear coadaptation would be most efficient if the interacting nuclear genes were X-linked, because this maximizes the probability of favorable mito-nuclear allelic combinations co-transmitting across generations. Thus, under a coadaptation (CA) hypothesis, nuclear genes essential for mitochondrial function might be under selection to relocate to the X-chromosome. However, maternal inheritance predisposes the mitochondrial DNA (mtDNA) to accumulate variation that, while male-harming, is benign to females. Numerous nuclear genes were recently reported in Drosophila melanogaster, which exhibit male-specific patterns of differential expression when placed alongside different mtDNA haplotypes, suggesting that nuclear genes are sensitive to an underlying male-specific mitochondrial mutation load. These genes are thus candidates for involvement in mito-nuclear interactions driven by sexual conflict (SC), and selection might have moved them off the X-chromosome to facilitate an optimal evolutionary counter-response, through males, to the presence of male-harming mtDNA mutations. Furthermore, the presence of male-harming mtDNA mutations could exert selection for modifiers on the Y-chromosome, thus placing these mito-sensitive nuclear genes at the center of an evolutionary tug-of-war between mitochondrion and Y-chromosome.We test these hypotheses by examining the chromosomal distributions of three distinct sets of mitochondrial-interacting nuclear genes in D. melanogaster; the first is a list of genes with mitochondrial annotations by Gene Ontologies, the second is a list comprising the core evolutionary-conserved mitochondrial proteome, and the third is a list of genes involved in male-specific responses to maternally-inherited mitochondrial variation and which might be putative targets of Y-chromosomal regulation. Genes with mitochondrial annotations and genes representing the mitochondrial proteome do not exhibit statistically-significant biases in chromosomal representation. However, genes exhibiting sex-specific sensitivity to mtDNA are under-represented on the X-chromosome, over-represented among genes known to be sensitive to Y-chromosomal variation, and among genes previously associated with male fitness, but under-represented among genes associated with direct sexual antagonism. Our results are consistent with the SC hypothesis, suggesting that mitochondrial mutational pressure selects for gene movement off-the-X, hence enabling mito-nuclear coadaptation to proceed along trajectories that result in optimized fitness in both sexes.


Normalizing intermethod free triiodothyronine patient results: need for commutable materials.
The aim of this work was to check the suitability of control materials to normalize intermethod results for the measurement of free triiodothyronine in patient sera. In the main experiment, 108 patient sera and 11 commercially available control materials were assayed by a pair of methods. In a confirmatory experiment, two of the control materials and 142 patient sera were assayed with an alternative pair of methods. In the main experiment, the intermethod variability of 6/11 control materials differed significantly from that of patient sera (i. e. control materials were non-commutable). Recalculation of patient results using control materials as calibrators lowered the intermethod difference only if commutable materials were used. The confirmatory experiment demonstrated that the pattern of commutability changed if a different pair of methods was used. We conclude that in the case of free triiodothyronine the commutability of control materials should be tested if they are to be used to normalize patient results obtained by different methods.


(99m)Tc-GSA SPECT/CT fused images for assessment of hepatic function and hepatectomy planning.
To assure safe hepatectomy, accurate estimation of the functional reserve of the future remnant liver is crucial. The combination of indocyanine green retention rate at 15 min and CT volumetry is widely used in deciding on the extent of hepatectomy. On the other hand, there are quantitative indices calculated from (99m)Tc-GSA scintigraphy that reflect the number and function of hepatocytes. Therefore, there are many indices calculated from (99m)Tc-GSA scintigraphy that have been reported. In recent Annals of Surgical Oncology on Oct. 2014 the Uptake Index (UI) calculated from (99m)Tc-GSA scintigraphy was reported to be useful for hepatectomy planning and postoperative liver failure prediction. In this paper, we report on the usefulness and limits of quantitative indices calculated from (99m)Tc-GSA SPECT/CT for preoperative simulation.


Change of the isoelectric point of hemoglobin at the air/water interface probed by the orientational flip-flop of water molecules.
Elucidation of the molecular mechanisms of protein adsorption is of essential importance for further development of biotechnology. Here, we use interface-selective nonlinear vibrational spectroscopy to investigate protein charge at the air/water interface by probing the orientation of interfacial water molecules. We measured the Im χ(2) spectra of hemoglobin, myoglobin, serum albumin and lysozyme at the air/water interface in the CH and OH stretching regions using heterodyne-detected vibrational sum frequency generation (HD-VSFG) spectroscopy, and we deduced the isoelectric point of the protein by monitoring the orientational flip-flop of water molecules at the interface. Strikingly, our measurements indicate that the isoelectric point of hemoglobin is significantly lowered (by about one pH unit) at the air/water interface compared to that in the bulk. This can be predominantly attributed to the modifications of the protein structure at the air/water interface. Our results also suggest that a similar mechanism accounts for the modification of myoglobin charge at the air/water interface. This effect has not been reported for other model proteins at interfaces probed by conventional VSFG techniques, and it emphasizes the importance of the structural modifications of proteins at the interface, which can drastically affect their charge profiles in a protein-specific manner. The direct experimental approach using HD-VSFG can unveil the changes of the isoelectric point of adsorbed proteins at various interfaces, which is of major relevance to many biological applications and sheds new light on the effect of interfaces on protein charge.


[For the benefit of man and animals (author's transl)].
Food hygiene continues to be based on inspection of the "basic materials" which are consumed as such or after processing. In the meat sector, the work of the hygienist should continue to be based on clinical inspection before slaughter as well as on morbid-anatomical and laboratory inspection after slaughter. In recent years, however, new duties have become more clearly apparent, such as care for the welfare of the animal which is to be slaughtered (improvement of transport, improvement of treatment prior to slaughter), ensuring hygienic conditions of slaughter, the problem of slaughtered animals harbouring pathogenic micro-organisms, examination of the meat for residues of foreign substances such as pesticides, antibiotics and growth-stimulating agents, supervision of the product by the hygienist on its road from the place of production to that of consumption, promoting a minimum use (which is nevertheless justifiable from the point of view of hygiene) of water, detergents and disinfectants in the food line and drainage of the cleanest possible waste water. In the field of food hygiene, more attention should be paid to other foods such as poultry, fish and game, and increasingly close checks should be maintained on the quality of those products which are offered for sale to the consumer. In doing so, the veterinary hygienist should be prepared to co-operate. On the one hand, with those fellow-veterinarians whose activities take place at an earlier stage in the process of food production, i.e. in veterinary practice and particularly in the veterinary supervision of large fattening farms. And, on the other, with experts in a large number of other disciplines, who are in a better position to deal with the technological, chemical and toxicological aspects and, last but not least, the medical sector. The veterinary practitioner attending to productive livestock actually is also employed in the production of foods of animal origin and has to co-operate with his fellow in the public health sector to ensure the production of sound and wholesome foods.


Autotransplants for Hodgkin's disease in first relapse or second remission: a report from the autologous blood and marrow transplant registry (ABMTR).
Although patients with relapsed Hodgkin's disease have a poor prognosis with conventional therapies, high-dose chemotherapy and autologous hematopoietic stem cell transplantation (autotransplantation) may provide long-term progression-free survival. We reviewed data from the Autologous Blood and Marrow Transplant Registry (ABMTR) to determine relapse, disease-free survival, overall survival, and prognostic factors in this group of patients. Detailed records from the ABMTR on 414 patients with Hodgkin's disease in first relapse (n = 295) or second complete remission (CR) (n = 119) receiving an autotransplant from 1989 to 1995 were reviewed. Median age was 29 (range, 7-64) years. Median time from diagnosis to relapse was 18 (range, 6-219) months; median time from relapse to transplant was 5 (range, <1-215) months. Most patients received high-dose chemotherapy without total body irradiation for conditioning (n = 370). The most frequently used high-dose regimen was cyclophosphamide, BCNU, VP-16 (CBV) (n = 240). The graft consisted of bone marrow (n = 246), blood stem cells (n = 112), or both (n = 56). Median follow-up was 46 (range, 5-96) months. One hundred-day mortality (95% confidence interval) was 7 (5-9)%. One hundred and sixty-five of 295 patients (56%) transplanted in relapse achieved CR after autotransplantation. Of these, 61 (37%) recurred. Twenty-four of 119 patients (20%) transplanted in CR recurred. The probability of disease-free survival at 3 years was 46 (40-52)% for transplants in first relapse and 64 (53-72)% for those in second remission (P < 0.001). Overall survival at 3 years was 58 (52-64)% after transplantation in first relapse and 75 (66-83)% after transplantation in second CR (P < 0.001). In multivariate analysis, Karnofsky performance score <90% at transplant, abnormal serum LDH at transplant, and chemotherapy resistance were adverse prognostic factors for outcome. Progression of Hodgkin's disease accounted for 69% of all deaths. Autotransplantation should be considered for patients with Hodgkin's disease in first relapse or second remission. Future investigations should focus on strategies designed to decrease relapse after autotransplantation, particularly in patients at high risk for relapse.


[Clinical-functional state of the retina and optic nerve in contusions of the eyeball].
The function of the retina and optic nerve was studied in 79 patients with contusions of the eyeball of various severity. A complex electrophysiological method was used, consisting of recording of visual evoked potentials and of the general and macular electroretinograms, assessment of the threshold electrical sensitivity and lability. Changes were detected in all the layers of the retina and optic nerve, the degree of these changes augmenting with the severity of injury. Changes in the functional parameters of the paired intact eyes, similar in the trend, were observed.


Transient expression in tobacco leaves of an aglycosylated recombinant antibody against the epidermal growth factor receptor.
When generating stably transformed transgenic plants, transient gene expression experiments are especially useful to rapidly confirm that the foreign molecule of interest is correctly assembled and retains its biological activity. TheraCIM(R) (CIMAB S.A., Havana) is a recombinant humanized antibody against the Epidermal Growth Factor receptor (EGF-R), now in clinical trials for cancer therapy in Cuba and other countries. An aglycosylated version (Asn 297 was mutated for Gln 297) of this antibody was transiently expressed in tobacco leaves after vacuum-mediated infiltration of recombinant Agrobacterium tumefaciens that carried a binary plasmid bearing the antibody heavy and light chain genes and plant regulation signals. Protein extracts from "agroinfiltrated" leaves were tested by ELISA and Western blot, showing that the fully assembled antibody was accumulated in plant tissues. The absence of plant specific glycans did not interfere in the assembling or in the activity of the plantibody, as demonstrated in this work. Indirect immunofluorescence demonstrated that the aglycosylated antibody expressed in plants recognizes the EGF-R expressed on the surface of A431 human tumor culture cells.


Interferon and delayed-type hypersensitivity to a viral antigen.
Delayed hypersensitivity to Newcastle disease virus was measured with use of a footpad test in mice. When tissue culture interferon was administered 24 hr before sensitization, footpad swelling upon subsequent challenge with the virus was significantly decreased. In animals already sensitized to the virus, footpad swelling was similarly decreased if interferon was administered a few hours before footpad challenge. This result indicates that interferon can affect both the afferent and the efferent pathways of delayed hypersensitivity to Newcastle disease virus and is in agreement with previous results obtained with nonviral antigens.


Autonomic stimulation.
Therapeutic stimulation of the autonomic nervous system has been limited by lack of qualitative or quantitative evaluation of autonomic mechanisms. This article provides an historical review of knowledge about autonomic pathways and critical evaluation of available tests of autonomic function. Recent developments in evaluation of autonomic dysfunction and improvement in techniques of neurostimulation have facilitated the development of a number of clinically useful treatments for bladder control, sexual problems, peripheral vascular disease, angina pectoris, and seizure disorders. Future therapeutic measures may allow specific control of hypertension, pain, cardiac arrhythmias, trophic disorders and balance.


The relationship between greenhouse gas emissions and the intensity of milk production in Ireland.
European Union agri-environmental schemes aim to reduce the environmental impact of agricultural production, but were developed before consideration of greenhouse gas emissions from agriculture. Life cycle assessment methodology provided a framework for comparing emissions as kg CO2 equivalent per kg of energy corrected milk (ECM) (kg CO2 kg(-1) ECM yr(-1)) and per hectare (kg CO2 ha(-1) yr(-1)) for farms both within and outside the Irish agri-environmental scheme. The agri-environmental scheme farms operate extensive systems from 40 to 120 cows producing between 3032 and 5946 kg ECM cow(-1) lactation(-1). The cows are fed on grass, conserved silage, and concentrates. Supplementation ranged between 250 and 620 kg cow(-1) yr(-1). The conventional farms had between 30 and 77 milking cows producing 4736 to 6944 kg ECM cow(-1) lactation(-1). Supplementation ranged from 400 to 1000 kg cow(-1) yr(-1). The emissions from each unit were estimated using published emissions factors and possible error was evaluated by using ranges for each factor. Calculated emissions ranged from 0.92 to 1.51 kg CO2 kg(-1) ECM yr(-1) and 5924 to 8323 kg CO2 ha(-1). On average, total emissions from conventional farms were around 18% (p = 0.01) greater than the agri-environmental scheme farms and emissions per hectare (total area required) were 17% greater (p = 0.02) but there was no significant difference (p = 0.335) in terms of emission per unit milk produced. To evaluate greenhouse gas emissions for each farm in terms of the system intensity it was necessary to define a measure of intensification and area per liter of milk produced that was best.


Expression of keratinocyte growth factor and its receptor in human breast cancer.
The level of expression of keratinocyte growth factor (KGF) mRNA has been measured in human breast cell lines, purified populations of epithelial cells, myoepithelial cells and fibroblasts from reduction mammoplasty tissue and a panel of 42 breast cancers and 30 non-malignant human breast tissues using a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) procedure. We found similar levels of KGF mRNA in malignant and non-malignant breast tissues. The study of the amount of KGF mRNA in breast cell lines and purified populations of cells revealed that fibroblasts are the predominant source of KGF with malignant and non-malignant epithelial cells containing very low levels of KGF mRNA. We have examined the distribution of fibroblast growth factor receptor (FGFR)-2-IIIb, which is a high-affinity receptor for KGF and find that it is present on malignant and non-malignant epithelial cells. The level of FGFR-2-IIIb present on breast cancer cell lines was sufficient for KGF stimulation of breast cancer cell proliferation. Other members of the fibroblast growth factor family have been either not expressed in the human breast (FGF3, FGF4) or have been found at much reduced levels in breast cancer (FGF1, FGF2) and this is the first member of the family to potentially influence the progression of breast cancer through stimulation of cell division.


Resection of pulmonary metastases from nonseminomatous testicular tumors. Correlation of clinical and histological features with treatment outcome.
Clinical and histological correlates of survival in patients undergoing complete resection of pulmonary metastases from nonseminomatous testicular carcinoma were determined in 25 Stage C patients aged 17-38 years treated from 1969-1978. All patients had orchiectomy and retroperitoneal lymphadenectomy. Nineteen patients received combination chemotherapy before resection, and all received chemotherapy after resection. Three patients had four additional thoracotomies for pulmonary recurrence. Survival was measured from time of first thoracotomy to time of last followup or death. Actuarial survival for the entire group at one, two, and five years was 80, 63, and 59%, respectively. Median follow-up of the survivors was 3.5 years. Patients in low tumor burden groups such as those with no tumor in retroperitoneal nodes, with unilateral metastases, or with single metastases had better prognosis, as did patients whose primary tumors were moderately well differentiated. Characteristics of pulmonary metastases that favorably influenced the prognosis were the presence of mature teratoma, presence of few mitoses, lack of mononuclear infiltrate, and lack of desmoplastic response. These findings confirm the effectiveness of multimodality therapy which includes the resection of pulmonary metastases for Stage C nonseminomatous carcinoma of the testes. In addition, they suggest that consideration should be given to the stratification of prospective clinical trials on the basis of tumor burden and histologic characteristics of the primary and metastatic lesions.


Nebulized hypertonic saline for bronchiolitis in the emergency department: a randomized clinical trial.
Acute bronchiolitis is the most frequent lower respiratory tract infection in infants, yet there are no effective therapies available. Current evidence is unclear about the role of hypertonic saline (HS) for the acute treatment of bronchiolitis. To determine whether nebulized 3% HS compared with normal saline (NS) improves respiratory distress in infants with bronchiolitis not responding to standard treatments in the emergency department. A randomized clinical trial with blinding of investigators, health care providers, and parents was conducted at a single urban pediatric ED. The participants included children aged 2 to less than 24 months with their first episode of bronchiolitis and a Respiratory Distress Assessment Instrument score of 4 to 15 after nasal suctioning and a trial of nebulized albuterol. Patients were randomized to receive either nebulized 3% HS (HS group) or NS (NS group). The primary outcome was change in respiratory distress at 1 hour after the intervention, as measured by the Respiratory Assessment Change Score (a decrease indicates improvement). Secondary outcomes included vital signs, oxygen saturation, hospitalization, physician clinical impression, parental assessment, and adverse events. The 31 patients enrolled in each treatment arm had similar baseline demographic and clinical characteristics. At 1 hour after the intervention, the HS group demonstrated significantly less improvement in the median Respiratory Assessment Change Score compared with the NS group (HS, -1 [interquartile range, -5 to 1] vs. NS, -5 [interquartile range, -6 to -2]; P = .01). There were no significant differences in heart rate, oxygen saturation, hospitalization rate, or other outcomes. There were no adverse events. Infants with bronchiolitis and persistent respiratory distress after standard treatment in the emergency department had less improvement after receiving 3% HS compared with those who received NS. Based on these results and the existing evidence, administration of a single dose of 3% HS does not appear to be indicated to treat bronchiolitis in the acute care setting. clinicaltrials.gov Identifier: NCT01247064.


Transient inhibition of connective tissue infiltration and collagen deposition into porous poly(lactic-co-glycolic acid) discs.
Connective tissue rapidly proliferates on and around biomaterials implanted in vivo, which impairs the function of the engineered tissues, biosensors, and devices. Glucocorticoids can be utilized to suppress tissue ingrowth, but can only be used for a limited time because they nonselectively arrest cell proliferation in the local environment. The present study examined use of a prolyl-4-hydroxylase inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), to suppress connective tissue ingrowth in porous PLGA discs implanted in the peritoneal cavity for 28 days. The prolyl-4-hydroxylase inhibitor was found to be effective at inhibiting collagen deposition within and on the outer surface of the disc, and also limited connective tissue ingrowth, but not to the extent of glucocorticoid inhibition. Finally, it was discovered that 1,4-DPCA suppressed Scavenger Receptor A expression on a macrophage-like cell culture, which may account for the drug's ability to limit connective tissue ingrowth in vivo.


Diagnostic and therapeutic role of endoscopic retrograde pancreatography in the management of traumatic pancreatic duct injury patients: Single center experience for 34 years.
Traumatic pancreatic injuries are rare and present diagnostic and therapeutic difficulties. We evaluated the usefulness of endoscopic retrograde pancreatography and transpapillary pancreatic stent in the diagnosis and treatment of pancreatic trauma patients. We reviewed medical records of 83 pancreas trauma patients who underwent endoscopic retrograde pancreatography for the suspicion of pancreas duct injury between January 1983 and December 2016. Patient notes, radiologic findings, laboratory investigations, operative records, and endoscopic retrograde pancreatography reports were reviewed. Pre-endoscopic retrograde pancreatography abdominal computed tomography was performed in 52 patients. Twenty-seven patients of them were diagnosed with a major pancreatic duct injury by subsequent endoscopic retrograde pancreatography. Eleven major pancreatic duct injuries (40.7%) were missed by the pre-endoscopic retrograde pancreatography abdominal CT. Major pancreatic duct injury was confirmed by endoscopic retrograde pancreatography in 43 patients. These 43 major pancreatic duct injury patients were classified into the Operative (n = 21), Stent (n = 15), and Conservative (n = 7) groups according to the first treatment modality which was chosen by attending surgeon. Age, initial white blood cell count, initial serum amylase, associated injury, and major pancreatic duct injury site were similar among groups, while the rate of parenchymal leakage (Dye leakage confined to pancreatic capsule) on endoscopic retrograde pancreatography findings differed. Parenchymal leakage was most common in the Conservative group. Pancreas related mortality occurred in 1 (4.76%) Operative group, 2 (13.33%) Stent group, and 0 (0%) Conservative group. Pancreas related complication occurred in 16 (76.19%) Operative group, 10 (66.67%), Stent group and 5 (71.43%) Conservative group. There were no statistically significant differences in the occurrence rate of pancreas related complications and mortalities among three groups. Endoscopic retrograde pancreatography helps clinicians choose a treatment modality for major pancreatic duct injury since it provides information about the precise condition of the major pancreatic duct injury. Endoscopic retrograde pancreatography with transpapillary pancreatic stenting also shows promise as a substitute for laparotomy or pancreatic resection in selected patients.


Biomarkers of body iron stores and risk of developing type 2 diabetes.
Iron may contribute to the pathogenesis of type 2 diabetes mellitus (DM) by inducing oxidative stress and interfering with insulin secretion. Elevated ferritin levels are associated with increased DM risk among healthy individuals. However, it is yet unknown if ferritin predicts DM incidence among high-risk individuals with impaired glucose tolerance (IGT). Furthermore, the association between soluble transferrin receptors (sTfR), a novel marker of iron status, and DM risk has not yet been prospectively investigated in these individuals. We conducted this study to evaluate the association between baseline levels of ferritin and sTfR and the risk of developing DM among overweight and obese individuals at high risk of DM. This nested case-control study (280 cases and 280 matched controls) was conducted within the placebo arm of the Diabetes Prevention Program, is a clinical trial conducted among overweight/obese individuals with IGT. Ferritin and sTfR levels were measured by immunoturbidimetric assays. Incident DM was ascertained by annual 75-g oral glucose tolerance test and semi-annual fasting glucose. Compared with controls, cases had higher sTfR levels (3.50 +/- 0.07 vs. 3.30 +/- 0.06 mg/l; p = 0.03), but ferritin levels were not statistically different. The multivariable odds ratios (OR) and 95% confidence intervals (95% CI) for DM incidence comparing highest with the lowest quartiles of sTfR was 2.26 (1.37-4.01) (p-trend: 0.008). Modestly elevated sTfR levels are associated with increased DM risk among overweight and obese individuals with IGT. Future studies should evaluate factors determining sTfR levels and examine if interventions that lower body iron stores reduce DM incidence.


Using a multidisciplinary classification in nursing: the International Classification of Functioning Disability and Health.
This paper reports a study to explore systematically the usefulness of the International Classification of Functioning, Disability and Health to nurses giving patient care. The International Classification of Functioning, Disability and Health has a history of more than 20 years. Although this World Health Organization classification offers multidisciplinary use, nurses are not familiar with it. Applications of the International Classification for nursing practice were developed and evaluated in a multi-centre project, composed of a series of 10 projects in a variety of settings. These applications were a variety of tools, such as assessment forms, care plans and transfer forms. The study used information from 653 patients, 469 nurses and 178 others (International Classification experts; other professionals with whom nurses communicate or discuss patient data). Large sections of the International Classification were used in the 10 projects, revealing a predominant focus on body functions (53% of all three-digit codes and corresponding terms used). Although large sections of the Classification were useful in practice applications, some items were identified that could be added, improved or described with more detail. Positive remarks made by nurses referred to the scope of the International Classification, which encouraged assessing beyond a patient's functional impairments. The International Classification of Functioning, Disability and Health can be a useful tool in classifying and communicating aspects of patient functioning by nurses. A level of moderate detail within the Classification (three-digit level) seems appropriate for most nursing purposes. Our results on items that could be added or improved can serve as input in future revisions of the Classification. Future use of the International Classification should be encouraged, because of its relevance to nursing and its potential for multidisciplinary use in patient care.


Prevalence of lameness in high-producing holstein cows housed in freestall barns in Minnesota.
A cross-sectional study was conducted to estimate the prevalence of clinical lameness in high-producing Holstein cows housed in 50 freestall barns in Minnesota during summer. Locomotion and body condition scoring were performed on a total of 5,626 cows in 53 high-production groups. Cow records were collected from the nearest Dairy Herd Improvement Association test date, and herd characteristics were collected at the time of the visit. The mean prevalence of clinical lameness (proportion of cows with locomotion score >or=3 on a 1-to-5 scale, where 1 = normal and 5 = severely lame), and its association with lactation number, month of lactation, body condition score, and type of stall surface were evaluated. The mean prevalence of clinical lameness was 24.6%, which was 3.1 times greater, on average, than the prevalence estimated by the herd managers on each farm. The prevalence of lameness in first-lactation cows was 12.8% and prevalence increased on average at a rate of 8 percentage units per lactation. There was no association between the mean prevalence of clinical lameness and month of lactation (for months 1 to 10). Underconditioned cows had a higher prevalence of clinical lameness than normal or overconditioned cows. The prevalence of lameness was lower in freestall herds with sand stalls (17.1%) than in freestall herds with mattress stall surfaces (27.9%). Data indicate that the best 10th percentile of dairy farms had a mean prevalence of lameness of 5.4% with only 1.47% of cows with locomotion score = 4 and no cows with locomotion score = 5.


Cu-Catalyzed Oxidative C(sp2)-H Cycloetherification of o-Alkenyl Arenols for the Preparation of Fused Furans.
A practically efficient, copper-catalyzed approach for the synthesis of functionally embellished indeno-naphthofurans is developed from 1-(1H-inden-3-yl)naphthalen-2-ols. This intramolecular cycloetherification proceeds via C(sp2)-H oxygenation (C-H bond breaking and C-O bond forming), which enables the atom-economical synthesis of poly fused furans in high yields with large substrate diversity in the open air.


Infectious keratoconjunctivitis and occurrence of Mycoplasma conjunctivae and Chlamydiaceae in small domestic ruminants from Central Karakoram, Pakistan.
Infectious keratoconjunctivitis (IKC) is a contagious eye disease primarily caused by Mycoplasma conjunctivae in domestic and wild Caprinae. Chlamydophila species have also been detected in ruminants with IKC. The objectives of this study are to investigate the ocular infection of M. conjunctivae and Chlamydiaceae and assess its interaction in relation to IKC in sheep and goats from remote communities around the Central Karakoram National Park in Pakistan, performing a combination of cross-sectional and case-control study design. Mostly asymptomatic and endemic infections of M. conjunctivae and Chlamydiaceae were found in sheep (19.3 per cent and 4.5 per cent, respectively) and goats (9.5 per cent and 1.9 per cent, respectively) from all communities, assessed by qPCR. Prevalence significantly differed between species only for M. conjunctivae (P=0.0184), which was also more prevalent in younger sheep (P<0.01). Chlamydophila pecorum was identified by sequencing and was related with IKC only when coinfection with M. conjunctivae occurred, which suggest a synergic interaction. Cluster analysis of M. conjunctivae strains revealed higher diversity of strains than expected, evidenced interspecific transmission and suggested a higher local livestock trade than previously assumed. These results highlight the widespread occurrence of M conjunctivae in sheep worldwide and its implications for wildlife should be assessed from a conservation perspective.


Sensor Information Fusion by Integrated AI to Control Public Emotion in a Cyber-Physical Environment.
The cyber-physical system (CPS) is a next-generation smart system that combines computing with physical space. It has been applied in various fields because the uncertainty of the physical world can be ideally controlled using cyber technology. In terms of environmental control, studies have been conducted to enhance the effectiveness of the service by inducing ideal emotions in the service space. This paper proposes a CPS control system for inducing emotion based on multiple sensors. The CPS can expand the constrained environmental sensors of the physical space variously by combining the virtual space with the physical space. The cyber space is constructed in a Unity 3D space that can be experienced through virtual reality devices. We collect the temperature, humidity, dust concentration, and current emotion in the physical space as an environmental control elements, and the control illumination, color temperature, video, sound and volume in the cyber space. The proposed system consists of an emotion prediction module using modular Bayesian networks and an optimal stimulus decision module for deriving the predicted emotion to the target emotion based on utility theory and reinforcement learning. To verify the system, the performance is evaluated using the data collected from real situations.


Noninvasive evaluation of extra-/intracranial anastomoses by dynamic CT and Doppler sonography.
In order to find a reliable noninvasive method of evaluating patency and function of extra-/intracranial arterial bypass, pre- and postoperative angiograms were compared with the results of pre- and postoperative dynamic computed tomographic (CT) scans and Doppler sonographic findings. Doppler sonography alone is a reliable method for determining patency and relative function of the anastomosis. Dynamic CT permits qualitative evaluation of cerebral perfusion and, by comparison of pre- and postoperative scans, assessment of the contribution of the extra-/intracranial bypass to the circulation of the affected hemisphere. Combined use of Doppler sonography and dynamic CT provides sufficient information about the postoperative status of cerebral perfusion to obviate the use of conventional angiography in routine cases.


Fast calculation method for computer-generated cylindrical holograms.
Since a general flat hologram has a limited viewable area, we usually cannot see the other side of a reconstructed object. There are some holograms that can solve this problem. A cylindrical hologram is well known to be viewable in 360 deg. Most cylindrical holograms are optical holograms, but there are few reports of computer-generated cylindrical holograms. The lack of computer-generated cylindrical holograms is because the spatial resolution of output devices is not great enough; therefore, we have to make a large hologram or use a small object to fulfill the sampling theorem. In addition, in calculating the large fringe, the calculation amount increases in proportion to the hologram size. Therefore, we propose what we believe to be a new calculation method for fast calculation. Then, we print these fringes with our prototype fringe printer. As a result, we obtain a good reconstructed image from a computer-generated cylindrical hologram.


On the possibility of determining an effective energy spectrum of clinical electron beams from percentage depth dose (PDD) data of broad beams.
Experiments have already shown that obvious differences exist between the dose distribution of electron beams of a clinical accelerator in a water phantom and the dose distribution of monoenergetic electrons of nominal energy of the clinical accelerator in water, because the electron beams which reach the water surface travelling through the collimation system of the accelerator are no longer monoenergetic. It is evident that, while calculating precisely the dose distribution of any incident electron beams, the energy spectrum of the incident electron beam must be taken into consideration. In this note we shall present a method for determining an effective energy spectrum of clinical electron beams from PDD data (percentage depth dose data). It is well known that there is an integral equation of the first kind which links the energy spectrum of an incident electron beam with PDD through the dose distribution of monoenergetic electrons in the medium, as a kernel function in the integral equation. In this note, the integral equation of the first kind will be solved by using the regularization method. The bipartition model of electron transport will be used to calculate the kernel function, namely the energy deposition due to monoenergetic electron beams in the medium.


Scleritis: a paradoxical effect of etanercept? Etanercept-associated inflammatory eye disease.
To describe 3 cases of scleritis associated with etanercept use for rheumatoid arthritis (RA) and to review the literature related to inflammatory eye diseases associated with the use of etanercept. Three cases of severe scleritis during etanercept therapy were analyzed. A systematic review of the literature in PubMed, Embase, and the Cochrane Library was performed, from 1962 to July 2010. Three patients with seropositive RA developed scleritis 7-28 months after initiation of etanercept, for the first time during their long-lasting disease. In all patients the underlying disease had responded well to anti-tumor necrosis factor therapy. Ocular inflammation went into remission after discontinuation of etanercept, and no other relapses were observed. One patient experienced a dechallenge-rechallenge phenomenon (improvement in symptoms following discontinuation of the agent, then reappearance or worsening of symptoms on reexposure to the agent). Forty-two cases of inflammatory eye diseases believed to be associated with the use of etanercept have been reported in the literature: 33 uveitis, 8 scleritis, 1 orbital myositis, concerning 16 patients with RA, 10 with juvenile idiopathic arthritis, 14 with ankylosing spondylitis, and 2 with psoriatic spondyloarthropathy. Dechallenge was performed in 28 patients, leading to resolution of symptoms. Rechallenge was done in 6 cases, with clear exacerbation. Ocular inflammation is paradoxically a potential adverse effect of etanercept, even in previously uninvolved eyes.


Changes in gene expression in human meibomian gland dysfunction.
Meibomian gland dysfunction (MGD) may be the leading cause of dry eye syndrome throughout the world. However, the precise mechanism(s) underlying the pathogenesis of this disease is unclear. This study was conducted to identify meibomian gland genes that may promote the development and/or progression of human MGD. Lid tissues were obtained from male and female MGD patients and age-matched controls after eyelid surgeries (e.g., to correct entropion or ectropion). Meibomian glands were isolated and processed for RNA extraction and the analysis of gene expression. The results show that MGD is associated with significant alterations in the expression of almost 400 genes in the human meibomian gland. The levels of 197 transcripts, including those encoding various small proline-rich proteins and S100 calcium-binding proteins, are significantly increased, whereas the expression of 194 genes, such as claudin 3 and cell adhesion molecule 1, is significantly decreased. These changes, which cannot be accounted for by sex differences, are accompanied by alterations in many gene ontologies (e.g., keratinization, cell cycle, and DNA repair). The findings also show that the human meibomian gland contains several highly expressed genes that are distinct from those in an adjacent tissue (i.e., conjunctival epithelium). The results demonstrate that MGD is accompanied by multiple changes in gene expression in the meibomian gland. The nature of these alterations, including the upregulation of genes encoding small proline-rich proteins and S100 calcium-binding proteins, suggest that keratinization plays an important role in the pathogenesis of MGD.


Alcohol consumption under lockdown measures during the COVID-19 pandemic in three Nordic countries.
At the beginning of the COVID-19 pandemic, concerns arose about a possible rise in alcohol consumption. Early surveys, however, more commonly pointed towards a decrease of alcohol use. But studies based on self-reports may underestimate alcohol use. They also depend on the population sampled. Because of border closures and gastronomy restrictions, countries with centralised alcohol sales provided a unique opportunity to study total domestic consumption during the pandemic without influence of private import or reliance on self-reports. We examined the correlation between alcohol sales and national COVID-19 restrictions in three such countries, Finland, Norway and Sweden. We conducted this study as a mirror image study, comparing alcohol sales during the first 2 years of the COVID-19 pandemic with the two preceding years. We explored hours of daylight/season as potential confounders. We found no relevant change in alcohol sales during the pandemic years for Finland or Sweden. For Norway, there was a level-change in sales, which could be explained by decreased imports. Sales followed a seasonal pattern. In all three countries, the initial pandemic increase in alcohol sales coincided with an underlying annually recurring seasonal variation. The COVID-19 pandemic had less of an impact on alcohol consumption in the three Nordic countries than could intuitively be expected. The increase of alcohol sales at the beginning of the COVID-19 pandemic coincided with a seasonal rise following a pre-pandemic pattern. Therefore, caution should be exercised with drawing conclusions from data with a short time perspective to avoid attribution bias.


Listeria monocytogenes-infected human dendritic cells: uptake and host cell response.
Dendritic cells (DCs) are potent antigen-presenting cells and play a crucial role in initiation and modulation of specific immune responses. Various pathogens are able to persist inside DCs. However, internalization of the gram-positive bacterium Listeria monocytogenes into human DCs has not yet been shown. In the present study, we demonstrate that human monocyte-derived immature DCs can efficiently phagocytose L. monocytogenes. This uptake is independent of listerial adhesion factors internalin A and internalin B but requires cytoskeletal motion and factors present in human plasma. A major portion of internalized bacteria is found in membrane-bound phagosomes and is rarely free in the cytosol, as shown by transmission electron microscopy and by using an L. monocytogenes strain expressing green fluorescent protein when in the host cell cytosol. The infection caused maturation of the immature DCs into mature DCs displaying high levels of CD83, CD25, major histocompatibility complex class II, and the CD86 costimulator molecule. This effect appeared to be largely mediated by listerial lipoteichoic acid. Although L. monocytogenes infection is known to induce death in other cell types, infection of human DCs was found to induce necrotic but not apoptotic death in fewer than 20% of DCs. Therefore, the ability of DCs to act as effective antigen-presenting cells for listerial immunity is probably enhanced by their resistance to cell death, as well as their ability to rapidly differentiate into mature, immunostimulatory DCs upon encountering bacteria.


The risk of gastric carcinoma and carcinoid tumours in patients with pernicious anaemia. A prospective follow-up study.
This endoscopic follow-up study was undertaken to evaluate the risk of gastric cancer (GC) and carcinoids in patients with pernicious anaemia (PA) and to analyse whether early detection of GC could be provided by regular endoscopic follow-up. Screening gastroscopy was performed in 71 patients with pernicious anaemia, and thereafter they were followed up with gastroscopies at 3-year intervals for a mean time of 5.8 years. Standardized incidence ratios (SIR) were calculated, the expected number being based on incidence rates in the whole Finnish population. Two GCs were found during the follow-up period; one of these patients was asymptomatic and the other had abdominal symptoms. The SIR was 5.0 (95% confidence interval, 0.6-18). Eight carcinoids were detected, and all but one were removed endoscopically, and no metastases were found. The patients who had carcinoid tumours were younger at the diagnosis of PA than those who did not develop carcinoids (mean, 40 versus 55 years). Additionally, the patients with carcinoids had longer duration of PA (mean, 11 versus 5 years). During the follow-up period the risk of GC was increased. The risk of gastric carcinoids seems to be very high in patients with pernicious anaemia when compared with a normal population, but they are mostly relatively benign tumours. Regular routine gastroscopic follow-up is not indicated in patients with pernicious anaemia.


[Antidiabetic drugs prescription patterns among a group of patients in Colombia].
To identify prescription patterns for diabetes treatment among a group of individuals covered by Colombia's universal health care, the General System for Social Security in Health (SGSSS). The study included 7 308 patients covered by SGSSS who had diabetes mellitus type 1 or 2, were of either sex, any age, and had been undergoing treatment for at least three months (May-July 2005) in 19 cities in Colombia. A database was compiled from the medication usage records maintained by the dispensing pharmacy. Data were analyzed using SPSS 13.0 (SPSS Inc., Chicago, Illinois, United States of America). Student's t-test and analysis of variance (ANOVA) were employed to compare quantitative variables, and the chi-square test was applied to compare categorical variables. The patients' mean age was 60.7 +/- 12.7 years. Women made up 56.6% of the group and had a mean age significantly higher than that of the men (P < 0.05). Forty-eight percent of the group had been prescribed one diabetes medication, while 52% had been prescribed from two to four. The medications prescribed were: biguanides (67.5%), sulphonylureas (64.9%), insulin (23.5%), and thiazolidinediones (0.1%). The most common oral combination-therapies were: glibenclamide and metformin (n = 2 847), metformin and insulin (n = 510), glibenclamide and insulin (n = 148), and metformin, insulin, and glibenclamide (n = 288). Of the total, 94.3% had comorbid conditions for which they had been prescribed medication: antihypertensive drugs (in 74.4% of the cases), anti-inflammatories (61.5%), hypolipemiants (45.5%), antiulcer medications (21.0%), psychoactive drugs (16.8%), antimicrobials (14.4%), asthma medication (5.3%), and salicylic acid (2.8%). Prescriptions for comorbid conditions were more common among women than men (95.6% vs. 92.7%, P < 0.001). Undertreatment with certain medications (metformin, thiazolidinediones, alpha-glucosidase inhibitors, and salicylic acid), and overtreatment with others (antiulcer drugs), probably exist. There are significant differences in oral therapies prescribed for diabetes across the 19 cities studied, but overall, prescription patterns are appropriate. Educational strategies should be developed to address those prescribing practices that are not appropriate, and the clinical results of the medications studied should be explored.


A cost analysis of a sports-based sexual health education programme for adolescent girls in South African schools.
Studies have shown that school-based sexual health promotion interventions can improve adolescent sexual and reproductive health outcomes. However, there has been insufficient evidence on the cost and cost-effectiveness of such programmes, driving poor and inconsistent investment and prioritization. This paper analyses the costs of the SKILLZ Health for Girls programme, a sports-based sexual education intervention targeted at adolescent girls in the secondary school environment. Costs were collected alongside a cluster-randomized trial, including 38 secondary schools in Cape Town, South Africa. The analysis was conducted from a provider (multi-sector) perspective and used a mixed-methods costing approach. We developed a cost data collection tool to compile cost information from one-on-one interviews, administrative data and non-participant observations of the intervention. Costs were analysed for 2019, representing a full academic year of programme implementation. The intention-to-treat analysis revealed an average cost per learner per session of $9.92, and the cost per learner reached was estimated at $69.43. Sensitivity analysis indicated that these costs were sensitive to the participation rates of the learners who did not complete the intervention. The cumulative cost for the scale-up scenario for the Western Cape Province based on the base-case analysis (maximizing coverage of schools but only including 30% of eligible learners within schools) was estimated at $5 311 453.00 for a 3-year period, which exceeds the provincial conditional grant allocation dedicated to the human immunodeficiency virus and acquired immune deficiency syndrome (life skills education) for the same period, yet is comparable to the expenditure for a similar donor-funded programme within the province. The study's results will contribute to decision-making for implementing sexual education interventions in schools in South Africa and similar contexts.


[Exerience with 3000 endoscopies of the upper digestive tract].
A study is presented of over 3,000 upper gastrointestinal endoscopies over a 4 year period. The principal findings were: 1.282 normal 42,73%), 349 gastric ulcers (11,63%), 314 duodenal ulcers (10,47%), and 208 gastric cancers (6,90%). Endoscopy is an important method for the study of upper gastrointestinal tract diseases. Specially for nonconclusive X-ray study, locating the site of a hemorrhage, differentiating between a benign and a malignant lesion, recommending continuation of medical treatment or surgery, and indicating the zone of surgical resection. The routine use for endoscopy should be insisted upon in patients with vague chronic symptoms to increase the diagnosis of incipient lesions. We have obtained more advantages with endoscopy than with X-rays. However, both methods are complementary and give a more certain diagnosis of digestive diseases. It is a method that when done by experts is innocuous and free of complications. Although the cost of the fibroscope instruments is high, the invaluable services they render to gastroenterology more than compensate their cost.


High-resolution behavioral economic analysis of cigarette demand to inform tax policy.
Novel methods in behavioral economics permit the systematic assessment of the relationship between cigarette consumption and price. Towards informing tax policy, the goals of this study were to conduct a high-resolution analysis of cigarette demand in a large sample of adult smokers and to use the data to estimate the effects of tax increases in 10 US States. In-person descriptive survey assessment. Academic departments at three universities. Adult daily smokers (i.e. more than five cigarettes/day; 18+ years old; ≥8th grade education); n = 1056. Estimated cigarette demand, demographics, expired carbon monoxide. The cigarette demand curve exhibited highly variable levels of price sensitivity, especially in the form of 'left-digit effects' (i.e. very high price sensitivity as pack prices transitioned from one whole number to the next; e.g. $5.80-6/pack). A $1 tax increase in the 10 states was projected to reduce the economic burden of smoking by an average of $530.6 million (range: $93.6-976.5 million) and increase gross tax revenue by an average of 162% (range: 114-247%). Tobacco price sensitivity is non-linear across the demand curve and in particular for pack-level left-digit price transitions. Tax increases in US states with similar price and tax rates to the sample are projected to result in substantial decreases in smoking-related costs and substantial increases in tax revenues.


Combined effects of inversion and feature removal on N170 responses elicited by faces and car fronts.
The face-sensitive N170 is typically enhanced for inverted compared to upright faces. Itier, Alain, Sedore, and McIntosh (2007) recently suggested that this N170 inversion effect is mainly driven by the eye region which becomes salient when the face configuration is disrupted. Here we tested whether similar effects could be observed with non-face objects that are structurally similar to faces in terms of possessing a homogeneous within-class first-order feature configuration. We presented upright and inverted pictures of intact car fronts, car fronts without lights, and isolated lights, in addition to analogous face conditions. Upright cars elicited substantial N170 responses of similar amplitude to those evoked by upright faces. In strong contrast to face conditions however, the car-elicited N170 was mainly driven by the global shape rather than the presence or absence of lights, and was dramatically reduced for isolated lights. Overall, our data confirm a differential influence of the eye region in upright and inverted faces. Results for car fronts do not suggest similar interactive encoding of eye-like features and configuration for non-face objects, even when these objects possess a similar feature configuration as faces.


Time of day effects on the incidence of anesthetic adverse events.
We hypothesized that time of day of surgery would influence the incidence of anesthetic adverse events (AEs). Clinical observations reported in a quality improvement database were categorized into different AEs that reflected (1) error, (2) harm, and (3) other AEs (error or harm could not be determined) and were analyzed for effects related to start hour of care. As expected, there were differences in the rate of AEs depending on start hour of care. Compared with a reference start hour of 7 am, other AEs were more frequent for cases starting during the 3 pm and 4 pm hours (p < 0.0001). Post hoc inspection of data revealed that the predicted probability increased from a low of 1.0% at 9 am to a high of 4.2% at 4 pm. The two most common event types (pain management and postoperative nausea and vomiting) may be primary determinants of these effects. Our results indicate that clinical outcomes may be different for patients anesthetized at the end of the work day compared with the beginning of the day. Although this may result from patient related factors, medical care delivery factors such as case load, fatigue, and care transitions may also be influencing the rate of anesthetic AEs for cases that start in the late afternoon.


Anti-Neuroinflammatory Property of Phlorotannins from Ecklonia cava on Aβ25-35-Induced Damage in PC12 Cells.
Alzheimer disease (AD) is a neurodegenerative disorder characterized by excessive accumulation of amyloid-beta peptide (Aβ) and progressive loss of neurons. Therefore, the inhibition of Aβ-induced neurotoxicity is a potential therapeutic approach for the treatment of AD. Ecklonia cava is an edible brown seaweed, which has been recognized as a rich source of bioactive derivatives, mainly phlorotannins. In this study, phlorotannins including eckol, dieckol, 8,8'-bieckol were used as potential neuroprotective candidates for their anti-apoptotic and anti-inflammatory effects against Aβ25-35-induced damage in PC12 cells. Among the tested compounds, dieckol showed the highest effect in both suppressing intracellular oxidative stress and mitochondrial dysfunction and activation of caspase family. Three phlorotannins were found to inhibit TNF-α, IL-1β and PGE₂ production at the protein levels. These result showed that the anti-inflammatory properties of our compounds are related to the down-regulation of proinflammatory enzymes, iNOS and COX-2, through the negative regulation of the NF-κB pathway in Aβ25-35-stimulated PC12 cells. Especially, dieckol showed the strong anti-inflammatory effects via suppression of p38, ERK and JNK. However, 8,8'-bieckol markedly decreased the phosphorylation of p38 and JNK and eckol suppressed the activation of p38. Therefore, the results of this study indicated that dieckol from E. cava might be applied as a drug candidate for the development of new generation therapeutic agents against AD.


Perspectives of healthcare providers and HIV-affected individuals and couples during the development of a Safer Conception Counseling Toolkit in Kenya: stigma, fears, and recommendations for the delivery of services.
Reproduction is important to many HIV-affected individuals and couples and healthcare providers (HCPs) are responsible for providing resources to help them safely conceive while minimizing the risk of sexual and perinatal HIV transmission. In order to fulfill their reproductive goals, HIV-affected individuals and their partners need access to information regarding safer methods of conception. The objective of this qualitative study was to develop a Safer Conception Counseling Toolkit that can be used to train HCPs and counsel HIV-affected individuals and couples in HIV care and treatment clinics in Kenya. We conducted a two-phased qualitative study among HCPs and HIV-affected individuals and couples from eight HIV care and treatment sites in Kisumu, Kenya. We conducted in-depth interviews (IDIs) and focus group discussions (FGDs) to assess the perspectives of HCPs and HIV-affected individuals and couples in order to develop and refine the content of the Toolkit. Subsequently, IDIs were conducted among HCPs who were trained using the Toolkit and FGDs among HIV-affected individuals and couples who were counseled with the Toolkit. HIV-related stigma, fears, and recommendations for delivery of safer conception counseling were assessed during the discussions. One hundred and six individuals participated in FGDs and IDIs; 29 HCPs, 49 HIV-affected women and men, and 14 HIV-serodiscordant couples. Participants indicated that a safer conception counseling and training program for HCPs is needed and that routine provision of safer conception counseling may promote maternal and child health by enhancing reproductive autonomy among HIV-affected couples. They also reported that the Toolkit may help dispel the stigma and fears associated with reproduction in HIV-affected couples, while supporting them in achieving their reproductive goals. Additional research is needed to evaluate the Safer Conception Toolkit in order to support its implementation and use in HIV care and treatment programs in Kenya and other HIV endemic regions of sub-Saharan Africa.


Autonomous replicating sequences from mouse cells which can replicate in mouse cells in vivo and in vitro.
We have already reported that the cloned mouse DNA fragment (pMU65) could replicate in a simian virus 40 T antigen-dependent system in vivo and in vitro (H. Ariga, Z. Tsuchihashi, M. Naruto, and M. Yamada, Mol. Cell. Biol. 5:563-568, 1985). The plasmid p65-tk, containing the thymidine kinase (tk) gene of herpes simplex virus and the BglII-EcoRI region of pMU65 homologous to the simian virus 40 origin of DNA replication, was constructed. The p65-tk persisted episomally in tk+ transformants after the transfection of p65-tk into mouse FM3Atk- cells. The copy numbers of p65-tk in FM3Atk+ cells were 100 to 200 copies per cell. Furthermore, the p65-tk replicated semiconservatively, and the initiation of DNA replication started from the mouse DNA sequences when the replicating activity of p65-tk was tested in the in vitro DNA replication system developed from the FM3A cells. These results show that a 2.5-kilobase fragment of mouse DNA contains the autonomously replicating sequences.


Empiric Transcatheter Embolization for Acute Arterial Upper Gastrointestinal Bleeding: A Meta-Analysis.
OBJECTIVE. The purpose of this study was to conduct a meta-analysis to assess the safety and efficacy of empiric embolization compared with targeted embolization in the treatment of acute upper gastrointestinal bleeding (UGIB). MATERIALS AND METHODS. We searched the PubMed and Cochrane Library databases for studies performed without language restrictions from January 2000 to November 2019. Only clinical studies with a sample size of five or more were included. Clinical success, rebleeding and complication rates, survival rates, bleeding cause, embolic materials, and vessels embolized were recorded. Empiric embolization and targeted embolization (i.e., embolization performed based on angiographic evidence of ongoing bleeding) were compared when possible. Meta-analysis was performed. RESULTS. Among 13 included studies (12 retrospective and 1 prospective), a total of 357 of 725 patients (49.2%) underwent empiric embolization for UGIB. The clinical success rate of empiric embolization was 74.7% (95% CI, 63.1-86.3%) among the 13 studies, and the survival rate was 80.9% (95% CI, 73.8-88.0%) for 10 studies. On the basis of comparative studies, no statistically significant difference was observed between empiric and targeted embolization in terms of rebleeding rate in 111 studies (36.5% vs 29.6%; odds ratio [OR], 1.13; 95% CI, 0.77-1.65; p = .53), mortality in eight studies (23.3% vs 18.0%; OR, 1.44; 95% CI, 0.89-2.33; p = .14), and need for surgery to control rebleeding in four studies (17.8% vs 13.4%; OR, 1.34; 95% CI, 0.58-3.07; p = .49). The pooled embolization-specific complications were 1.9% (empiric) and 2.4% (targeted). CONCLUSION. According to all available published evidence, empiric embolization assessed with endoscopic or preprocedural imaging findings (or both) appears to be as effective as targeted embolization in preventing rebleeding and mortality in patients with angiographically negative acute UGIB. Because of its favorable safety profile, empiric embolization should be considered for patients in this clinical scenario.


Prooxidant-antioxidant balance in pregnancy: a randomized double-blind placebo-controlled trial of selenium supplementation.
We assessed the impact of selenium, a trace element with antioxidant properties on a simple measure of oxidative stress in pregnant women. A novel assay of prooxidant-antioxidant balance (PAB) was applied in a double-blind, placebo-controlled study of selenium supplementation in pregnancy. We measured the prooxidant burden and the antioxidant capacity simultaneously in one assay, thereby calculating a redox index. A total of 166 primigravid pregnant women in the first trimester of pregnancy, were randomized to receive 100 microg of selenium (n=83) or placebo (n=83) per day until delivery. PAB values and serum selenium concentrations were measured at baseline and at the end of study. Pretreatment demographic data and biochemical indices including serum selenium concentrations did not differ significantly between the groups. The drop-out rates for the groups were 22/83 and 19/83 for the selenium and placebo groups, respectively. Supplementation with selenium was associated with a significant increase in mean serum selenium concentration (P<0.001) but without significant change in mean PAB value. In contrast, mean serum selenium concentration remained unchanged and mean PAB values increased significantly (P<0.05 in the control group). Our findings suggest that selenium supplementation may reduce oxidative stress associated with pregnancy.


Sulforaphane: Expected to Become a Novel Antitumor Compound.
Natural products are becoming increasingly popular in a variety of traditional, complementary, and alternative systems due to their potency and slight side effects. Natural compounds have been shown to be effective against many human diseases, especially cancers. Sulforaphane (SFE) is a traditional Chinese herbal medicine. In recent years, an increasing number of studies have been conducted to evaluate the antitumor effect of SFE. The roles of SFE in cancers are mainly through the regulation of potential biomarkers to activate or inhibit related signaling pathways. SFE has exhibited promising inhibitory effects on breast cancer, lung cancer, liver cancer, and other malignant tumors. In this review, we summarized the reports on the activity and functional mechanisms of SFE in cancer treatment and explored the efficacy and toxicity of SFE.


Dysbiosis of gut microbiota in patients with protein-losing enteropathy after the Fontan procedure.
There is a lack of predictive biomarkers for the onset or activity of protein-losing enteropathy (PLE), a Fontan procedure-associated complication. Here, we aimed to identify the gut microbiota composition of patients with active PLE and investigate its relationship with PLE activity. This multicenter case-control study involved patients who developed PLE (n = 16) after the Fontan procedure and those who did not (non-PLE; n = 20). Patients with PLE who maintained a serum albumin level of ≥3 g/dL for >1 year were included in the remissive-stage-PLE group (n = 9) and those who did not maintain this level were included in the active-PLE group (n = 7). 16S rRNA gene sequencing analysis of fecal samples was performed using QIIME2 pipeline. Alpha (Shannon and Faith's phylogenetic diversity indices) and beta diversity was assessed using principal coordinate analysis based on unweighted UniFrac distances. Shannon and Faith's phylogenetic diversity indices were lower in the active-PLE group than in the remissive-stage- (q = 0.028 and 0.025, respectively) and non-PLE (q = 0.028 and 0.017, respectively) groups. Analysis of beta diversity revealed a difference in the microbiota composition between the active-PLE and the other two groups. Linear discriminant effect size analysis demonstrated differences in the relative abundance of Bifidobacterium and Granulicatella spp., and Ruminococcus torques between patients with active- and those with remissive-stage-PLE. Gut microbiota dysbiosis was observed in patients with active PLE. Changes in the bacterial composition of the gut microbiota and decreased diversity may be associated with the severity of PLE.


Second quantization of many-body dispersion interactions for chemical and biological systems.
The many-body dispersion (MBD) framework is a successful approach for modeling the long-range electronic correlation energy and optical response of systems with thousands of atoms. Inspired by field theory, here we develop a second-quantized MBD formalism (SQ-MBD) that recasts a system of atomic quantum Drude oscillators in a Fock-space representation. SQ-MBD provides: (i) tools for projecting observables (interaction energy, transition multipoles, polarizability tensors) on coarse-grained representations of the atomistic system ranging from single atoms to large structural motifs, (ii) a quantum-information framework to analyze correlations and (non)separability among fragments in a given molecular complex, and (iii) a path toward the applicability of the MBD framework to molecular complexes with even larger number of atoms. The SQ-MBD approach offers conceptual insights into quantum fluctuations in molecular systems and enables direct coupling of collective plasmon-like MBD degrees of freedom with arbitrary environments, providing a tractable computational framework to treat dispersion interactions and polarization response in intricate systems.


Increased mortality exposure within the family rather than individual mortality experiences triggers faster life-history strategies in historic human populations.
Life History Theory predicts that extrinsic mortality risk is one of the most important factors shaping (human) life histories. Evidence from contemporary populations suggests that individuals confronted with high mortality environments show characteristic traits of fast life-history strategies: they marry and reproduce earlier, have shorter birth intervals and invest less in their offspring. However, little is known of the impact of mortality experiences on the speed of life histories in historical human populations with generally higher mortality risk, and on male life histories in particular. Furthermore, it remains unknown whether individual-level mortality experiences within the family have a greater effect on life-history decisions or family membership explains life-history variation. In a comparative approach using event history analyses, we study the impact of family versus individual-level effects of mortality exposure on two central life-history parameters, ages at first marriage and first birth, in three historical human populations (Germany, Finland, Canada). Mortality experience is measured as the confrontation with sibling deaths within the natal family up to an individual's age of 15. Results show that the speed of life histories is not adjusted according to individual-level mortality experiences but is due to family-level effects. The general finding of lower ages at marriage/reproduction after exposure to higher mortality in the family holds for both females and males. This study provides evidence for the importance of the family environment for reproductive timing while individual-level mortality experiences seem to play only a minor role in reproductive life history decisions in humans.


Subgaleal Hemorrhage Secondary to Child Physical Abuse in a 4-Year-Old Boy.
Subgaleal hemorrhage is commonly described in the neonatal population but is a rare injury in young children and adolescents. Though infrequently seen, it can follow blunt head trauma or hair pulling. This case report details a 4-year-old African American boy with massive subgaleal hemorrhage and bilateral periorbital swelling and ecchymosis as a result of hair pulling in the setting of child physical abuse. The patient was evaluated in the emergency department for swelling of his scalp several hours after reportedly bumping his head on a chair. He was discharged home after a head computed tomography only confirmed soft tissue hematoma. The following morning, the findings progressed and he returned to the emergency department. He was triaged as a trauma and initially evaluated by the emergency physician, pediatric trauma surgeon, and pediatric neurosurgeon. Head computed tomography scan confirmed diffuse scalp edema without skull fracture or intracranial pathology. The child abuse specialty service was consulted for suspected child physical abuse. Their examination revealed numerous scattered bruises on the trunk and thighs, several of which were patterned. Local police investigation resulted in the patient's grandfather confessing to striking the patient with a belt and picking him up from the ground by his hair, the latter of which is a mechanism consistent with the patient's dramatic scalp and facial findings. The authors encourage consultation by a specialist in child abuse pediatrics for subgaleal hemorrhage and/or raccoon eyes in the presence of minor trauma, as well as thorough head-to-toe skin examination for all children presenting with injuries.


Chemical excitation and inactivation in photoreceptors of the fly mutants trp and nss.
The Drosophila and Lucilia photoreceptor mutants, trp and nss, respond like wild-type flies to a short pulse of intense light or prolonged dim light; however, upon continuous intense illumination, the trp and nss mutants are unable to maintain persistent excitation. This defect manifests itself by a decline of the receptor potential toward baseline during prolonged intense illumination with little change in the shape or amplitude of the quantal responses to single photons (quantum bumps). Previous work on the trp and nss mutants suggests that a negative feedback loop may control the rate of bump production. Chemical agents affecting different steps of the phototransduction cascade were used in conjunction with light to identify a possible branching point of the feedback loop and molecular stages which are affected by the mutation. Fluoride ions, which in the dark both excite and adapt the photoreceptors of wild-type flies, neither excite nor adapt the photoreceptors of the trp and nss mutants. The hydrolysis-resistant analogue, GTP gamma S, which excites the photoreceptors of wild-type flies, resulting in noisy depolarization, markedly reduces the light response of both mutant flies. Intracellular recordings revealed, however, that the inhibitory effect of GTP gamma S on the nss mutant was accompanied neither by any significant depolarization nor by an increase in the noise, and thus was very different from the effect of a dim background light. The combination of inositol trisphosphate and diphosphoglycerate (InsP3 + DPG), which efficiently excites the photoreceptors of wild-type Lucilia, also excites the photoreceptors of nss Lucilia mutant. The InsP3 + DPG together act synergistically with light to accelerate the decline of the response to light in the mutant flies. These results suggest that the fly phototransduction pathway involves a feedback regulatory loop, which branches subsequent to InsP3 production and regulates guanine nucleotide-binding protein (G protein)-phospholipase C activity. A defect in this regulatory loop, which may cause an unusually low level of intracellular Ca2+, severely reduces the triggering of bumps in the mutants during intense prolonged illumination.


Pain management after laminectomy: a systematic review and procedure-specific post-operative pain management (prospect) recommendations.
With lumbar laminectomy increasingly being performed on an outpatient basis, optimal pain management is critical to avoid post-operative delay in discharge and readmission. The aim of this review was to evaluate the available literature and develop recommendations for optimal pain management after one- or two-level lumbar laminectomy. A systematic review utilizing the PROcedure-SPECific Post-operative Pain ManagemenT (PROSPECT) methodology was undertaken. Randomised controlled trials (RCTs) published in the English language from 1 January 2008 until 31 March 2020-assessing post-operative pain using analgesic, anaesthetic and surgical interventions-were identified from MEDLINE, EMBASE and Cochrane Databases. Out of 65 eligible studies identified, 39 RCTs met the inclusion criteria. The analgesic regimen for lumbar laminectomy should include paracetamol and a non-steroidal anti-inflammatory drug (NSAID) or cyclooxygenase (COX)-2 selective inhibitor administered preoperatively or intraoperatively and continued post-operatively, with post-operative opioids for rescue analgesia. In addition, surgical wound instillation or infiltration with local anaesthetics prior to wound closure is recommended. Some interventions-gabapentinoids and intrathecal opioid administration-although effective, carry significant risks and consequently were omitted from the recommendations. Other interventions were also not recommended because there was insufficient, inconsistent or lack of evidence. Perioperative pain management for lumbar laminectomy should include paracetamol and NSAID- or COX-2-specific inhibitor, continued into the post-operative period, as well as intraoperative surgical wound instillation or infiltration. Opioids should be used as rescue medication post-operatively. Future studies are necessary to evaluate the efficacy of our recommendations.


Emerging therapies for the treatment of neovascular age-related macular degeneration and diabetic macular edema.
Diabetic macular edema (DME) and choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) are the leading causes of vision loss in the industrialized world. The mainstay of treatment for both conditions has been thermal laser photocoagulation, while there have been recent advances in the treatment of CNV using photodynamic therapy with verteporfin. While both of these treatments have prevented further vision loss in a subset of patients, vision improvement is rare. Anti-vascular endothelial growth factor (VEGF)-A therapy has revolutionized the treatment of both conditions. Pegaptanib, an anti-VEGF aptamer, prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment, and bevacizumab, a full-length humanized monoclonal antibody against VEGF, have both shown promising results, with improvements in visual acuity in the treatment of both diseases. VEGF trap, a modified soluble VEGF receptor analog, binds VEGF more tightly than all other anti-VEGF therapies, and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering RNA to inhibit VEGF production and VEGF receptor production. Corticosteroids have shown efficacy in controlled trials, including anacortave acetate in the treatment and prevention of CNV, and intravitreal triamcinolone acetonide and the fluocinolone acetonide implant in the treatment of DME. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Initial results are also encouraging for other growth factors, including pigment epithelium-derived factor administered via an adenoviral vector. Ruboxistaurin, which decreases protein kinase C activity, has shown positive results in the prevention of diabetic retinopathy progression, and the resolution of DME. Combination therapy has been investigated, and may prove to be quite effective in the management of both DME and AMD-associated CNV, although ongoing and future studies will be crucial to treatment optimization for each condition.


Overexpression of MicroRNA-106b-5p Attenuates Kidney Injuries after Deep Hypothermic Circulatory Arrest in Rats.
MicroRNAs (miRNA) have been identified to exert a wide range of biological functions in acute kidney injury (AKI) after deep hypothermic circulatory arrest (DHCA). We sought to investigate the renoprotection of miRNA-106b-5p in a rat model of DHCA by targeting phosphatase and tensin homolog (PTEN). Overexpression of miRNA-106b-5p in vivo was conducted by directly injection of lentivirus vectors containing pre-miRNA-106b-5p into the renal parenchyma of the animals under the ultrasound guidance 7 days before DHCA. The vehicle or control lentivirus vectors were given to the control group or the control vector group, respectively. Renal function and apoptosis activity were evaluated by serum cystatin C, serum/tissue neutrophil gelatinase-associated lipocalin (NGAL), and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay (TUNEL) at 24 hours after surgery. Expressions of miRNA-106b-5p, PTEN, and caspase-3 in the kidney were evaluated by quantitative real-time polymerase chain reaction and western blot analysis. Transfection of pre-miRNA-106b-5p significantly enhanced the expression of miRNA-106b-5p and dramatically downregulated the expressions of PTEN in the kidney compared with the control group. Renal functions were markedly protected by pretreatment with pre-miRNA-106b-5p as evidenced by decreases in serum cystatin C and serum/tissue neutrophil gelatinase-associated lipocalin at 24 hours after surgery. The pre-miRNA-106b-5p group showed significantly fewer apoptotic cells and lower levels of caspase-3 activation than the control group. Overexpression of miRNA-106b-5p attenuates kidney injuries after DHCA, possibly by inhibition of PTEN.


Clinical significance of Maspin promoter methylation and loss of its protein expression in invasive ductal breast carcinoma: correlation with VEGF-A and MTA1 expression.
Maspin is a serine protease inhibitor with tumor-suppressor activity. Maspin can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro. Previous studies indicate that the loss of Maspin expression is closely linked to aberrant methylation of the Maspin promoter. We examined the promoter methylation status of Maspin in tumor and corresponding serum of breast cancer patients. In addition, protein expression of this gene was also assessed to determine possible correlation between promoter hypermethylation and gene silencing. Further, we investigated the correlation of Maspin expression with vascular endothelial growth factor (VEGF-A) and MTA1 expression. Maspin methylation was analyzed by methylation-specific PCR in 100 invasive ductal breast carcinoma patients' tumors and circulating DNA in a prospective study. Promoter hypermethylation was correlated with expression of the encoded protein in tumors by immunohistochemistry. Significant correlation was observed between promoter hypermethylation of Maspin (r = +0.88; p ≤ 0.0001) in tumors and paired sera. Significant association was found between Maspin promoter hypermethylation and loss of its protein expression (p = 0.01, OR = 3.1, 95% CI = 1.3-7.4). The expression of VEGF-A and MTA1 was lower in tumors with high Maspin expression compared to tumors with loss of Maspin expression. Our results indicate that aberrant promoter methylation is associated with loss of Maspin immunoreactivity in breast cancer tissues. Further, loss of Maspin expression is significantly correlated with increased expression of VEGF-A and MTA1.


Partitioning of crude oil polycyclic aromatic hydrocarbons in aquatic systems.
This paper investigates the hypothesis that observed polycyclic aromatic hydrocarbon (PAH) concentrations in an aqueous system are equal to the sum of the organic phase and soluble phase molar concentrations. While the organic phase concentrations are proportional to the PAH mole fraction in the oil, the soluble phase molar concentrations are estimated using Raoult's law. A batch laboratory mixing vessel with a scalable mixing energy was loaded initially at various oil layer thicknesses (0.4-3.2 mm) which correspond to oil surface loadings (40-310 mg/cm2). The vessel was agitated at constant mean shear rates (Gm = 5, 20 s(-1)). Total petroleum hydrocarbon (TPH) samples were taken periodically to estimate the entrainment rate as a function of initial oil layer thickness. TPH concentrations were measured in-situ using a laser scattering instrument (LISST-100) and ex-situ using gravimetric analysis. At a steady-state TPH concentration (>72 h), additional samples were analyzed for PAH concentration using GC/MS analysis. TPH concentrations increased over time according to a first-order kinetic model. Generally, the first-order rate constant and steady-state concentration both increased with increased oil loading and with increased Gm. In addition, measured PAH concentrations correlated well (r2 > 0.96) with those predicted by a partitioning model. These results are useful for assessing the effects of mixing and oil loading conditions on crude oil entrainment and PAH partitioning.


Patterns of calcium localization in pancreatic endocrine cells.
Subcellular calcium localization in the dndocrine cells of rat pancreas was studied by the pyroantimonate precipitation technique. Calcium-containing electron-dense deposits in the endocrine cells were mostly found within secretory granules and along the plasma membrane, but their pattern of distribution in A-, B- and D-cells displayed qualitative and quantitative differences. In B-cells, numerous secretory granules contained deposits located in the halo surrounding the granule core. In A-cells, only few granules contained precipitates in their halo, whereas in D-cells, deposits were situated in the dense core of the secretory granules. Deposits along the plasma membrane occurred generally on the outer leaflet of the plasma membrane of B- and D-cells and on the inner leaflet of that of A-cells. In islets incubated at a high glucose concentration or in the presence of the calcium ionophore A23187, the number of beta granules containing precipitates was significantly increased. By contrast, only few deposits were observed in B-cells incubated in calcium-deprived medium enriched with EGTA. These findings indicate that: the pattern of calcium localization varies in different islet cell types; in B-cells the secretory granules represent one of the major stores of intracellular calcium; and that this store undergoes changes in conditions which alter insulin release.


Construction of a high-performance human fetal liver-derived lentiviral cDNA library.
The gene transduction method is a very powerful tool, not only in basic science but also in clinical medicine. Regenerative medicine is one field that has close connection with both basic and clinical. Recently, it has been reported that induced pluripotent stem (iPS) cells can be produced from somatic cells by a three or four gene transduction. We have also recently reported that lentiviral gene transfer of the tal1/scl gene can efficiently differentiate non-human primate common marmoset ES cells into hematopoietic cells without the support of stromal cells. In this study, we constructed a high-performance human fetal liver-derived lentiviral expression library, which contains a high number of individual clones, in order to develop a very helpful tool for understanding early hematopoiesis and/or hepatocytosis for future regenerative medicine. Our lentiviral cDNA library consisted of more than 8 x 10(7) individual clones, and their average insert size was >2 kb. DNA sequence analysis for each individual inserted cDNAs revealed that >60% contained the full-length protein-coding regions for many genes including cytokine receptors, cytoplasmic proteins, protein inhibitors, and nuclear factors. The transduction efficiency on 293T cells was 100% and the average size of an integrated cDNA was ~1.1 kb. These results suggest that our lentiviral human fetal liver cDNA expression library could be a very helpful tool for accelerating the discovery of novel genes that are involved in early hematopoiesis and hepatopoiesis and to make the use of iPS cells more efficient in the field of regenerative medicine.


Comparing least-squares and quantile regression approaches to analyzing median hospital charges.
Emergency department (ED) and hospital charges obtained from administrative data sets are useful descriptors of injury severity and the burden to EDs and the health care system. However, charges are typically positively skewed due to costly procedures, long hospital stays, and complicated or prolonged treatment for few patients. The median is not affected by extreme observations and is useful in describing and comparing distributions of hospital charges. A least-squares analysis employing a log transformation is one approach for estimating median hospital charges, corresponding confidence intervals (CIs), and differences between groups; however, this method requires certain distributional properties. An alternate method is quantile regression, which allows estimation and inference related to the median without making distributional assumptions. The objective was to compare the log-transformation least-squares method to the quantile regression approach for estimating median hospital charges, differences in median charges between groups, and associated CIs. The authors performed simulations using repeated sampling of observed statewide ED and hospital charges and charges randomly generated from a hypothetical lognormal distribution. The median and 95% CI and the multiplicative difference between the median charges of two groups were estimated using both least-squares and quantile regression methods. Performance of the two methods was evaluated. In contrast to least squares, quantile regression produced estimates that were unbiased and had smaller mean square errors in simulations of observed ED and hospital charges. Both methods performed well in simulations of hypothetical charges that met least-squares method assumptions. When the data did not follow the assumed distribution, least-squares estimates were often biased, and the associated CIs had lower than expected coverage as sample size increased. Quantile regression analyses of hospital charges provide unbiased estimates even when lognormal and equal variance assumptions are violated. These methods may be particularly useful in describing and analyzing hospital charges from administrative data sets.


Overlap of replication rounds disturbs the progression of replicating forks in a ribonucleotide reductase mutant of Escherichia coli.
Ribonucleotide reductase (RNR) is the only enzyme specifically required for the synthesis of deoxyribonucleotides (dNTPs). Surprisingly, Escherichia coli cells carrying the nrdA101 allele, which codes for a thermosensitive RNR101, are able to replicate entire chromosomes at 42 °C under RNA or protein synthesis inhibition. Here we show that the RNR101 protein is unstable at 42 °C and that its degradation under restrictive conditions is prevented by the presence of rifampicin. Nevertheless, the mere stability of the RNR protein at 42 °C cannot explain the completion of chromosomal DNA replication in the nrdA101 mutant. We found that inactivation of the DnaA protein by using several dnaAts alleles allows complete chromosome replication in the absence of rifampicin and suppresses the nucleoid segregation and cell division defects observed in the nrdA101 mutant at 42 °C. As both inactivation of the DnaA protein and inhibition of RNA synthesis block the occurrence of new DNA initiations, the consequent decrease in the number of forks per chromosome could be related to those effects. In support of this notion, we found that avoiding multifork replication rounds by the presence of moderate extra copies of datA sequence increases the relative amount of DNA synthesis of the nrdA101 mutant at 42 °C. We propose that a lower replication fork density results in an improvement of the progression of DNA replication, allowing replication of the entire chromosome at the restrictive temperature. The mechanism related to this effect is also discussed.


Acquisition of a runway motor learning task is impaired by a beta adrenergic antagonist in F344 rats.
Performance of rats on a motor learning paradigm that has been demonstrated to be dependent upon cerebellar norepinephrine (NE) was studied in male F344 rats treated with an alpha 1 antagonist (prazosin), an alpha 2 antagonist (yohimbine) or a beta noradrenergic antagonist (propranolol). The ability of propranolol-treated rats (10 mg/kg i.p. 30 min prior to daily testing) to acquire proficiency on the novel motor task was impaired while prazosin-treated rats' (0.5 mg/kg i.p. 30 min prior to daily testing) and yohimbine-treated rats' (1 mg/kg i.p. 30 min prior to daily testing) rates of acquisition of the novel motor task were not different from controls. In an attempt to distinguish between alterations in motor coordination and motor learning, additional tests of psychomotor performance were assessed for all groups of rats. These examinations included a walking test on 2.5 and 5 cm rods and speed of running on the motor task. The data indicate that drug-treated rats show no difference from controls on the above parameters. Some differences, however, were observed between propranolol and controls in the time spent in the goal box. Overall, the data are consistent with our hypothesis that the beta noradrenergic receptor is involved in the ability to acquire novel motor tasks.


Histopathological Investigation of Dura-like Membrane in Vestibular Schwannomas.
The dura-like membrane (DLM) is an outermost membranous structure arising from the dura mater adjacent to the internal auditory meatus (IAM) that envelops some vestibular schwannomas (VSs). Its recognition is important for the preservation of the facial and cochlear nerves during tumor resection. This study analyzes the histopathological characteristics of the DLM. The expression of CD34 and αSMA was histopathologically analyzed in tumor and DLM tissue of 10 primary VSs with and without a DLM. Tumor volume, resection volume percentage, microvessel density (MVD), and vessel diameter were analyzed. Volumetric analysis revealed that the presence of a DLM was significantly associated with lower tumor resection volume (p < 0.05). Intratumoral vessel diameter was significantly larger in the DLM group than the non-DLM group (p < 0.01). Larger VSs showed a higher intratumoral MVD in the DLM group (p < 0.05). Multilayered αSMA-positive vessels were identified in the DLM, tumor, and border; there tended to be more of these vessels within the tumor in the DLM group compared to the non-DLM group (p = 0.08). These arteriogenic characteristics suggest that the DLM is formed as the tumor induces feeding vessels from the dura mater around the IAM.


Use of complementary and alternative therapies by overweight and obese adults.
Obesity is associated with higher health-care costs due, in part, to higher use of traditional health care. Few data are available on the relationship between obesity and the use of complementary and alternative medicine (CAM). We analyzed data on CAM use from the 2002 National Health Interview Survey (NHIS) Alternative Medicine Supplement (n=31,044). We compared the use of CAM overall, within the past 12 months, between normal weight (BMI from 18 to <25), overweight (from 25 to <30), mildly obese (from 30 to <35), moderately obese (from 35 to <40), and extremely obese (>40) adults. For the primary analysis, our multivariable model was adjusted for sociodemographic factors, insurance status, medical conditions, and health behaviors. We performed additional analyses to explore the association of BMI and the use of seven CAM modalities. We found that adults with obesity have lower prevalence of use of yoga therapy, and similar prevalence of use of several CAM modalities, including relaxation techniques, natural herbs, massage, chiropractic medicine, tai chi, and acupuncture, compared to normal-weight individuals. After adjustment for sociodemographic factors, insurance status, medical conditions, and health behaviors, adults with obesity were generally less likely to use most individual CAM modalities, although the magnitude of these differences were quite modest in many cases. Even though adults with obesity have a greater illness burden and higher utilization of traditional medical care, adults with higher BMIs were no more likely to use each of the individual CAM therapies studied. Additional research is needed to improve our understanding of CAM use by adults with obesity.