The associated microflora to the larvae of human bot fly Dermatobia hominis L. Jr. (Diptera: Cuterebridae) and its furuncular lesions in cattle.
The microflora associated to furuncular lesions, larvae and pupae of Dermatobia hominis, as well as the relationships between parasite, host and microflora associated, as a comprehensive microsystem, has been studied. One hundred and two furuncular myiasis due to D. hominis larvae in several breeds of cattle were studied and the following bacterial species were significant: Staphylococcus aureus, S. epidermidis, S. warneri, Bacillus subtilis and Escherichia coli. Closely related, the microflora associated to 141 samples from first, second, third instar larva and both external surface and larval cavities has been studied. The representative associated microflora to the larvae were: S. aureus, B. subtilis, S. hycus and Moraxella phenylpiruvica, Moerella wisconsiensis, Proteus mirabilis and P. vulgaris, M. phenylpiruvica, M. wisconsiensis, P. mirabilis and P. rettgeri were the representative microflora associated to 64 pupae of D. hominis.


External validation of the Hospital Frailty Risk Score and comparison with the Hospital-patient One-year Mortality Risk Score to predict outcomes in elderly hospitalised patients: a retrospective cohort study.
Frailty is an important prognostic factor in hospitalised patients but typically requires face-to-face assessment by trained observers to detect. Thus, frail patients are not readily apparent from a systems perspective for those interested in implementing quality improvement measures to optimise their outcomes. This study was designed to externally validate and compare two recently described tools using administrative data as potential markers for frailty: the Hospital Frailty Risk Score (HFRS) and the Hospital-patient One-year Mortality Risk (HOMR) Score. Retrospective cohort study. Ontario, Canada. All patients over 75 with at least one urgent non-psychiatric hospitalisation between 2004 and 2010. Prolonged hospital length of stay (>10 days), 30-day mortality after admission and 30-day postdischarge rates of urgent readmission or emergency department (ED) visits. In 452 785 patients (25.9% with intermediate or high-risk HFRS), increased HFRS was associated with higher Charlson scores, older age and decreased likelihood of baseline independence. Patients with high or intermediate HFRS had significantly increased risks of prolonged hospitalisation (70.0% (OR 8.64, 95% CI 8.30 to 8.99) or 49.7% (OR 3.66, 95% CI 3.60 to 3.71) vs 21.3% in low-risk HFRS group) and 30-day mortality (15.5% (OR 1.27, 95% CI 1.20 to 1.33) or 16.8% (OR 1.39, 95% CI 1.36 to 1.41) vs 12.7% in low-risk), but decreased risks of 30-day readmission (10.0% (OR 0.74, 95% CI 0.69 to 0.79) and 11.2% (OR 0.84, 95% CI 0.82 to 0.86) vs 13.1%) or ED visit (7.3% (OR 0.41, 95% CI 0.38 to 0.45) and 11.1% (OR 0.66, 95% CI 0.38 to 0.45) vs 16.0%). Although only loosely associated (Pearson correlation coefficient 0.265, p<0.0001), both the HFRS and HOMR Score were independently associated with each outcome-HFRS was more strongly associated with prolonged length of stay (C-statistic 0.71) and HOMR Score was more strongly associated with 30-day mortality (C-statistic 0.71). Both poorly predicted 30-day readmissions (C-statistics 0.52 for HFRS and 0.54 for HOMR Score). The HFRS best identified hospitalised older patients at higher risk of prolonged length of stay and the HOMR score better predicted 30-day mortality. However, neither score was suitable for predicting risk of readmission or ED visit in the 30 days after discharge. Thus, a single score is inadequate to prognosticate for all outcomes associated with frailty.


[Humoral factors in the stimulation of immunogenesis in a toxic lesion of the liver].
The work was aimed at the study of possibilities of passive transfer of the immunostimulating effect (with the aid of blood serum) observed in various pathological conditions of the liver. Investigations were carried out on rabbits poisoned with carbon tetrachloride (primary serum donors), healthy rabbits (primary recipients and secondary donors of the serum), and healthy rabbits (secondary serum recipients). Crude and heated (for 30 min at 56 degrees C) sera of rabbits poisoned with carbon tetrachloride stimulated production of antibodies induced with the antigen in the intact animals. Under the effect of trasilol, a polyvalent proteinase inhibitor, the sera of rabbits poisoned with carbon tetrachloride lost their immunostimulating properties. The sera of rabbits given injections of the sera obtained from the poisoned animals produced an immunostimulating action which failed to disappear under the effect of trasilol.


Therapeutic effect of Shaoyao-Gancao Decoction on TLR9-mediated NETosis in MRL/lpr mice.
Systemic lupus erythematosus (SLE) is a chronic, devastating autoimmune disorder associated with severe organ damage. The roles of Toll-like receptor 9 (TLR9) and NETosis in SLE have been described, suggesting the involvement of NETosis signaling in the development of SLE. Shaoyao-Gancao Decoction (SGT) is a potential medication for the treatment of SLE; however, its potential therapeutic mechanism remains unexplored. To determine the function of SGT in SLE, we treated MRL/lpr female mice with SGT, the main components of which were paeoniflorin (56.949 μg·mL-1) and glycyrrhizin (459.393 μg·mL-1). We found that SGT treatment relieved lymphadenectasis and splenomegaly, reduced urine protein and anti-dsDNA antibody concentrations, and relieved kidney pathology in MRL/lpr mice. SGT could also effectively regulate the oxidation/antioxidant balance, significantly reduce malondialdehyde (MDA) and nitric oxide (NO) contents and significantly increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in MRL/lpr mice. The neutrophil extracellular trap (NET) content of MRL/lpr mice also decreased to a certain extent after SGT treatment. All these results suggested that SGT might improve the inflammatory damage to tissues caused by oxygen free radicals, thereby regulating the NETosis process mediated by TLR9 and exerting a good therapeutic effect on SLE.


Intermittent attendance at breast cancer screening.
To determine why women skip rounds and factors influencing return of previous non attenders (PNAs) to breast screening. Retrospective, quantitative, structured questionnaire posted to 2500 women. First PNAs did not attend their first screening appointment in 2007/2008 but then attended in 2010; First Controls first attended in 2010 without missed previous appointments. Women who attended screening in 2006 or earlier then skipped a round but returned in 2010 were Subsequent PNAs; Subsequent Controls attended all appointments. More First Controls than First PNAs had family history of cancer (72.7% vs 63.2%; P=0.003); breast cancer (31.3% vs 24.8%; P=0.04). More PNAs lived rurally; more First PNAs had 3rd level education (33.2% vs 23.6%; P=0.002) and fewer had private insurance than First Controls (57.7% vs 64.8%; P=0.04). Excellent/good health was reported in First PNAs and First Controls (82.9% vs 83.2%), but fewer Subsequent PNAs than Subsequent Controls (72.7% vs 84.9%; P=0.000). Common considerations at time of missed appointment were had mammogram elsewhere (33% First PNA) and postponed to next round (16% First PNA, 18.8% Subsequent PNA). Considerations when returning to screening were similar for First PNAs and Subsequent PNAs: I am older (35.4%, 29.6%), I made sure I remembered (29%, 23.6%), could reschedule (17.6%, 20.6%), illness of more concern (16.5%, 19%). More First PNAs stated my family/friends advised (22.3% vs 15.2%) or my GP (12.6% vs 4.6%) advised me to attend, heard good things about BreastCheck (28.8% vs 13.6%). Intermittent attenders do not fit socio-demographic patterns of non-attenders; GP recommendation and word of mouth were important in women's return to screening. Fear and anxiety seem to act as a screening facilitator rather than an inhibitor. Significance for public healthAll breast cancer screening programmes strive to achieve and maintain a high level of attendance, as this is essential to reduce breast cancer mortality, together with cancer detection. While non-attendance has been widely studied, little is known about intermittent attenders. It is unclear why a woman chooses not to attend her breast screening appointment but then decides to respond positively to screening invitation two or more years later. The literature identifies many reasons why some women choose not to attend; but this study distinguishes those who then change their mind and return to screening. This study explores a sub-set of non-attenders which have, to date, been largely ignored, or grouped with people who never attend. This study will inform those struggling with non-attendance in their population based health programmes and will help to tackle the problem of non-attendance, which has adverse affects both economically and epidemiologically.


Headaches in older patients: Ddx and Tx of common nonvascular causes.
From this and the previous article, the following points may be offered in summary: When comparing the elderly age group with the general population, the incidence of migraine headaches decreases with age, whereas other etiologies such as glaucoma, temporal arteritis, and cerebrovascular disease may assume a more prominent role in the differential diagnosis. Patients in the geriatric population are frequently taking a multitude of medications, and it is extremely important to carefully evaluate these for possible precipitants of headache. Furthermore, in elderly patients with other potential medical problems, particular attention should be paid to the possibility of various systemic causes of headache. Therapy for specific headache disorders should be tailored to the individual patient. Consider the patient's overall general, psychological, medical, and neurologic background. The physician must be aware of possible interactions of medications with the therapeutic intervention, as well as possible poor tolerance to specific medications due to preexisting medical or neurologic disorders. A complete history, obtaining information on the temporal pattern of headache, the distribution of pain, and precipitating and alleviating factors, is extremely important in evaluating the elderly patient. A careful physical examination, paying particular attention to possible disorders of extracranial structures, is indicated. A neurologic exam, including basic tests of higher cortical function, should be obtained. Important additional laboratory investigations include a complete blood count, erythrocyte sedimentation rate, and basic blood chemistries. Arterial blood gases should be obtained in patients who have pulmonary disease, a history suggestive of sleep apnea, or other disorders that may produce hypoxia and hypercarbia, resulting in vascular headache.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical and bacteriological evaluation of tetracycline and erythromycin in acne vulgaris.
A clinical and bacteriological comparison of tetracycline and erythromycin was carried out in 40 patients with papulopustular acne vulgaris. Twenty patients received 250 mg of tetracycline BID and 20 received 250 mg of erythromycin BID for four months. Clinically, 19 (95%) of patients treated with tetracycline and 17 (85%) of those treated with erythromycin had improvement ranging from moderate to very good. Both drugs also reduced the microflora both in the pustules and on normal skin from the same patients. Three patients given tetracycline and one given erythromycin reported mild side effects. Thus both antimicrobial agents were effective and safe in treating acne vulgaris.


Validating the SMART2 Score in a Racially Diverse High-Risk Nationwide Cohort of Patients Receiving Coronary Artery Bypass Grafting.
Background We tested the potential of the Secondary Manifestations of Arterial Disease (SMART2) risk score for use in patients undergoing coronary artery bypass grafting. Methods and Results We conducted an external validation of the SMART2 score in a racially diverse high-risk national cohort (2010-2019) that underwent isolated coronary artery bypass grafting. We calculated the preoperative SMART2 score and modeled the 5-year major adverse cardiovascular event (cardiovascular mortality+myocardial infarction+stroke) incidence. We evaluated SMART2 score discrimination at 5 years using c-statistic and calibration with observed/expected ratio and calibration plots. We analyzed the potential clinical benefit using decision curves. We repeated these analyses in clinical subgroups, diabetes, chronic kidney disease, and polyvascular disease, and separately in White and Black patients. In 27 443 (mean age, 65 years; 10% Black individuals) US veterans undergoing coronary artery bypass grafting (2010-2019) nationwide, the 5-year major adverse cardiovascular event rate was 25%; 27% patients were in high predicted risk (>30% 5-year major adverse cardiovascular events). SMART2 score discrimination (c-statistic: 64) was comparable to the original study (c-statistic: 67) and was best in patients with chronic kidney disease (c-statistic: 66). However, it underpredicted major adverse cardiovascular event rates in the whole cohort (observed/expected ratio, 1.45) as well as in all studied subgroups. The SMART2 score performed better in White than Black patients. On decision curve analysis, the SMART2 score provides a net benefit over a wide range of risk thresholds. Conclusions The SMART2 model performs well in a racially diverse coronary artery bypass grafting cohort, with better predictive capabilities at the upper range of baseline risk, and can therefore be used to guide secondary preventive pharmacotherapy.


Endothelial lipase modulates susceptibility to atherosclerosis in apolipoprotein-E-deficient mice.
Endothelial lipase (EL) expression correlates inversely with circulating high density lipoprotein (HDL) cholesterol levels in genetic mouse models, and human genetic variation in this locus has been linked to differences in HDL cholesterol levels. These data suggest a role for EL in the development of atherosclerotic vascular disease. To investigate this possibility, LIPG-null alleles were bred onto the apoE knockout background, and the homozygous double knockout animals were characterized. Both apoE knockout and double knockout mice had low HDL cholesterol levels when compared with wild-type mice, but the HDL cholesterol levels of the double knockout mice were higher than those of apoE knockout mice. Atherogenic very low density lipoprotein and intermediate density lipoprotein/low density lipoprotein cholesterol levels of the double knockout mice were also greater than those of the apoE knockout animals. Despite this lipid profile, there was a significant approximately 70% decrease in atherosclerotic disease area in double knockout mice on a regular diet. Immunohistochemistry and protein blot studies revealed increased EL expression in the atherosclerotic aortas of the apoE knockout animals. An observed decrease in macrophage content in vessels lacking EL correlated with ex vivo vascular monocyte adhesion assays, suggesting that this protein can modulate monocyte adhesion and infiltration into diseased tissues. These data suggest that EL may have indirect atherogenic actions in vivo through its effect on circulating HDL cholesterol and direct atherogenic actions through vascular wall processes such as monocyte recruitment and cholesterol uptake.


Stroke and bleeding risk in atrial fibrillation with CHA2DS2-VASC risk score of one: the Norwegian AFNOR study.
The benefit of oral anticoagulant (OAC) therapy in atrial fibrillation (AF) and intermediate stroke risk is debated. In a nationwide Norwegian cohort with a non-sex CHA2DS2-VASc risk score of one, this study aimed to investigate (i) stroke and bleeding risk in AF patients with and without OAC treatment, and (ii) the risk of stroke in non-anticoagulated individuals with and without AF. A total of 1 118 762 individuals including 34 460 AF patients were followed during 2011-18 until ischaemic stroke, intracranial haemorrhage, increased CHA2DS2-VASc score, or study end. One-year incidence rates (IRs) were calculated as events per 100 person-years (%/py). Cox regression models provided adjusted hazard ratios (aHRs [95% confidence intervals]). Among AF patients, the ischaemic stroke IR was 0.51%/py in OAC users and 1.05%/py in non-users (aHR 0.47 [0.37-0.59]). Intracranial haemorrhage IR was 0.28%/py in OAC users and 0.19%/py in non-users (aHR 1.23 [0.88-1.72]). Oral anticoagulant use was associated with an increased risk of major bleeding (aHR 1.37 [1.16-1.63]) but lower risk of the combined outcome of ischaemic stroke, major bleeding, and mortality (aHR 0.57 [0.51-0.63]). Non-anticoagulated individuals with AF had higher risk of ischaemic stroke compared to non-AF individuals with the same risk profile (aHR 2.47 [2.17-2.81]). In AF patients at intermediate risk of stroke, OAC use was associated with overall favourable clinical outcomes. Non-anticoagulated AF patients had higher risk of ischaemic stroke compared to the general population without AF with the same risk profile.


Emergency medical services in St. Vincent and the Grenadines.
This descriptive study reports the status of the health care infrastructure and the emergency medical services system in the nation of St. Vincent and the Grenadines, an eastern Caribbean nation made up of a series of small islands located 1,600 miles southeast of Miami. Data regarding the health care system and emergency medical services in the nation were gathered from various sources, including the Ministry of Health, government publications, hospital records, accident and emergency department logbooks, and interviews with physicians, nurses, and ambulance workers. The health system is similar in structure to that of the United Kingdom. Generally, the health infrastructure and available staffing are adequate and comparable to those of developed nations. However, out-of-hospital emergency medical services are lacking in both equipment and trained personnel. These data should be useful to both policymakers and health professionals in formulating strategies for advancing emergency medical services in St. Vincent and the Grenadines, and may also be instructive to other countries with developing emergency medical services systems.


Understand the overlap between FMLA and COBRA.
An employer's obligation to continue an eligible employee's medical insurance under the Family and Medical Leave Act overlaps with the employee's right to continued medical insurance coverage under the provisions of the Consolidated Omnibus Budget Reconciliation Act of 1985 (COBRA). To avoid liability traps resulting from the overlap, employers, plan sponsors and plan administrators must have a good understanding of the two laws and keep accurate records.


Mutual interferences and design principles for mechatronic devices in magnetic resonance imaging.
Robotic and mechatronic devices that work compatibly with magnetic resonance imaging (MRI) are applied in diagnostic MRI, image-guided surgery, neurorehabilitation and neuroscience. MRI-compatible mechatronic systems must address the challenges imposed by the scanner's electromagnetic fields. We have developed objective quantitative evaluation criteria for device characteristics needed to formulate design guidelines that ensure MRI-compatibility based on safety, device functionality and image quality. The mutual interferences between an MRI system and mechatronic devices working in its vicinity are modeled and tested. For each interference, the involved components are listed, and a numerical measure for "MRI-compatibility" is proposed. These interferences are categorized into an MRI-compatibility matrix, with each element representing possible interactions between one part of the mechatronic system and one component of the electromagnetic fields. Based on this formulation, design principles for MRI-compatible mechatronic systems are proposed. Furthermore, test methods are developed to examine whether a mechatronic device indeed works without interferences within an MRI system. Finally, the proposed MRI-compatibility criteria and design guidelines have been applied to an actual design process that has been validated by the test procedures. Objective and quantitative MRI-compatibility measures for mechatronic and robotic devices have been established. Applying the proposed design principles, potential problems in safety, device functionality and image quality can be considered in the design phase to ensure that the mechatronic system will fulfill the MRI-compatibility criteria. New guidelines and test procedures for MRI instrument compatibility provide a rational basis for design and evaluation of mechatronic devices in various MRI applications. Designers can apply these criteria and use the tests, so that MRI-compatibility results can accrue to build an experiential database.


The SENIC Project. Study on the efficacy of nosocomial infection control (SENIC Project). Summary of study design.
With the emergence of nosocomial infections as a serious problem among US hospitals, the Center for Disease Control undertook in 1974 a nationwide study to evaluate approaches to infection control. The three-phased project, now known as the Study on the Efficacy of Nosocomial Infection Control, or SENIC Project, was designed with three primary objectives: 1) to determine whether (and, if so, to what degree) the implementation of infection surveillance and control programs (ISCPs) has lowered the rate ofnosocomi al infection, 2) to describe the current status of ISCPs and infection rates, and 3) to demonstrate the relationships among characteristics of hospitals and patients, components of ISCPs, and changes in the infection rate. With data collection completed in a nationally representative sample of hospitals, analysis is underway to identify approaches to infection control that are most effective for the least cost to hospitals and to point out additional specific questions to be answered by future research.


Treatment With Cholecalciferol Leads to Increase Of Selected Semen Parameters in Young Infertile Males: Results of a 6-month Interventional Study.
High incidence of infertility along with low vitamin D levels was detected in otherwise healthy young men. The aim is to observe the effect of vitamin D supplementation on semen parameters as assessed by semen analysis in infertile men. In total, 45 men (mean age 36.6 years) in consecutive order were included, of whom 34 finished the study. Subjects were supplemented by vitamin D (cholecalciferol) 2500 IU/day. Vitamin D levels were assessed by HPLC. Semen analysis was performed strictly following 2010 WHO guidelines. Study periods were baseline and month 6. During follow-up, 20 %, 7.4 %, 22 % and 0.7 % increase in serum vitamin D levels, progressive sperm motility, sperm concentration and sperm morphology, respectively, were observed (all p<0.05). At follow-up end, 9 patients (26 %) reached normal sperm parameters of whom 2 fertilized their partner. There was no correlation between vitamin D and semen parameters observed. This study proves that vitamin D supplementation is possibly a modulator of sperm parameters in vitamin D deficient, otherwise healthy men. Although a direct relationship between vitamin D and sperm parameters was not observed obtaining adequate vitamin D levels could likely play a role in the male factor of infertility.


Association analysis of common genetic variations in MUC5AC gene with the risk of non-cardia gastric cancer in a Chinese population.
Several lines of evidence suggest that genetic variation in MUC5AC gene might contribute to the risk of gastric cancer. We conducted a case-control study to evaluate the relationship between common genetic variations in MUC5AC gene and non-cardia gastric cancer using an LD-based tagSNP approach in Baotou, north-western China. We genotyped 12 tagSNPs by TaqMan method among 288 cases with non-cardia gastric cancer and 281 normal controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for non-cardia gastric cancer risk in association with alleles, genotypes and haplotypes. We observed that the frequencies of rs3793964 C allele and rs11040869 A allele were significantly lower in cases than in controls. Meanwhile, minor allele homozygotes of rs3793964 and rs11040869 were significantly associated with a decreased risk of non-cardia gastric cancer when compared with their major allele homozygotes. Furthermore, a statistically significantly protective effect of rs885454 genotypes on non-cardia gastric cancer was also observed (for CT vs. CC: OR=0.581, 95%CI=0.408-0.829; for CT/TT vs. CC: OR=0.623, 95%CI=0.451-0.884). Our results indicated that some common genetic variations in the MUC5AC gene might have effects on the risk of non-cardia gastric cancer in our studied population.


Dynamic transition of Dnmt3b expression in mouse pre- and early post-implantation embryos.
The de novo DNA methyltransferases, Dnmt3a and Dnmt3b, are responsible for the creation of DNA methylation patterns in mouse development. Dnmt3b is more highly expressed in early developmental stages than Dnmt3a, and is thought to have an important role in the epigenetic gene regulation during early embryogenesis. Previous reports suggest that Dnmt3b is expressed preferentially in the embryonic lineage, but less in the extra-embryonic lineage, in early post-implantation embryos. However, it is unclear when this lineage-specific differential expression is established. Here we demonstrate that Dnmt3b shows a dynamic expression change during pre- and early post-implantation development. Contrary to the expectation, Dnmt3b is preferentially expressed in the trophectoderm rather than the inner cell mass at the mid blastocyst stage. Subsequently, the spatial Dnmt3b expression gradually changes during pre- and early post-implantation development, and finally Dnmt3b expression is settled in the embryonic lineage at the epiblast stage. The findings are consistent with the role for Dnmt3b in cell-lineage specification and the creation of lineage-specific DNA methylation patterns.


A lake-centric geospatial database to guide research and inform management decisions in an Arctic watershed in northern Alaska experiencing climate and land-use changes.
Lakes are dominant and diverse landscape features in the Arctic, but conventional land cover classification schemes typically map them as a single uniform class. Here, we present a detailed lake-centric geospatial database for an Arctic watershed in northern Alaska. We developed a GIS dataset consisting of 4362 lakes that provides information on lake morphometry, hydrologic connectivity, surface area dynamics, surrounding terrestrial ecotypes, and other important conditions describing Arctic lakes. Analyzing the geospatial database relative to fish and bird survey data shows relations to lake depth and hydrologic connectivity, which are being used to guide research and aid in the management of aquatic resources in the National Petroleum Reserve in Alaska. Further development of similar geospatial databases is needed to better understand and plan for the impacts of ongoing climate and land-use changes occurring across lake-rich landscapes in the Arctic.


Factors influencing adult carer support planning for unpaid caregiving at the end of life in Scotland: Qualitative insights from triangulated interviews and focus groups.
Caring for a relative or friend at the end of life can be rewarding but all-encompassing. These caregivers are often not identified, meaning their diverse needs remain unmet, and the lack of assessment, support and planning increases the likelihood of crisis and burnout. The Carers (Scotland) Act 2016 places responsibility on local authorities to implement such a plan, which will be fast-tracked for carers supporting someone at the end of life. Our research described the factors which might influence this planning, triangulating primary focus groups with 15 carers and secondary qualitative data from transcripts with 30 carers, all of whom who had looked after someone with a terminal illness. Analysis was iterative, and constant comparative analysis of the secondary data informed the primary focus groups. Three main themes were identified; 1. The importance of early identification as a carer to enable timely assessment and support. 2. Carers experience isolation and loneliness which limits opportunities for support. 3. Responding in a timely fashion to carer assessment and support is vital to avoid crises. This research confirms that identifying carers early in the illness trajectory, ideally at diagnosis, is vital to avoid carer burnout. Health and social care providers have a key role in identification and should ensure, where possible, that carer needs are dynamically assessed, supported and documented. Finally, caring does not end after death, it extends into bereavement. Thus, we need to consider system and cultural change to ensure the experiences and needs of carers are addressed and valued.


Parallel evaluation of serological tests applied in african trypanosomiasis: a WHO collaborative study.
Previously, the most commonly used serological tests for the indirect diagnosis of African trypanosomiasis were the indirect fluorescent antibody test, immunodiffusion test, and the determination of IgM levels in serum and cerebrospinal fluid. Recently, the capillary passive haemagglutination test and the enzyme-linked immunosorbent assay (ELISA) have been used in diagnosing trypanosomiasis. However, a parallel evaluation was needed to indicate the comparative diagnostic value of these various serological tests. A double-blind study conducted by WHO with the collaboration of three European and four African laboratories using well-documented serum samples provides a reasonable basis for determining in parallel the sensitivities of the various techniques.


Observing atomic collapse resonances in artificial nuclei on graphene.
Relativistic quantum mechanics predicts that when the charge of a superheavy atomic nucleus surpasses a certain threshold, the resulting strong Coulomb field causes an unusual atomic collapse state; this state exhibits an electron wave function component that falls toward the nucleus, as well as a positron component that escapes to infinity. In graphene, where charge carriers behave as massless relativistic particles, it has been predicted that highly charged impurities should exhibit resonances corresponding to these atomic collapse states. We have observed the formation of such resonances around artificial nuclei (clusters of charged calcium dimers) fabricated on gated graphene devices via atomic manipulation with a scanning tunneling microscope. The energy and spatial dependence of the atomic collapse state measured with scanning tunneling microscopy revealed unexpected behavior when occupied by electrons.


Genetic association between the HLA-G 14-bp insertion/deletion polymorphism and the recurrent spontaneous abortions in Saudi Arabian women.
The non-classical class I human leukocyte antigen (HLA)-G molecule was found to be predominately expressed in the extravillous cytotrophoblasts at the fetal-maternal interface during pregnancy. This molecule is critically important for successful implantation during human pregnancy. The polymorphic insertion-deletion (indel) 14-base pair (bp) site localized at the 3' untranslated region was associated with HLA-G mRNA stability and isoform alternative splicing patterns, and thus may influence HLA-G function during pregnancy. We studied the association between the 14-bp indel polymorphism (rs16375) at the 3' untranslated region with recurrent spontaneous abortions in a Saudi population living in Riyadh. A group of 64 women with 2-11 successive abortions were included in this study. The control group included 62 women without reported abortions and at least 2 pregnancies, all visiting the King Khaled Hospital in Riyadh. The 14-bp indel was genotyped in the case and control groups. The frequency of the genotype +14/+14 was slightly higher in women with recurrent spontaneous abortions, but no significant differences were observed in the distribution of alleles and genotypes.


Maternal stress does not exacerbate long-term bone deficits in female rats born growth restricted, with differential effects on offspring bone health.
Females born growth restricted have poor adult bone health. Stress exposure during pregnancy increases risk of pregnancy complications. We determined whether maternal stress exposure in growth-restricted females exacerbates long-term maternal and offspring bone phenotypes. On gestational day 18, bilateral uterine vessel ligation (restricted) or sham (control) surgery was performed on Wistar-Kyoto rats. At 4 mo, control and restricted females were mated and allocated to unstressed or stressed pregnancies. Stressed pregnancies had physiological measurements performed; unstressed females were not handled. After birth, mothers were aged to 13 mo. Second-generation (F2) offspring generated four experimental groups: control unstressed, restricted unstressed, control stressed and restricted stressed. F2 offspring were studied at postnatal day 35 (PN35), 6, 12, and 16 mo. Peripheral quantitative computed tomography was performed on maternal and F2 offspring femurs. Restricted females, irrespective of stress during pregnancy, had decreased endosteal circumference, bending strength, and increased osteocalcin concentrations after pregnancy at 13 mo. F2 offspring of stressed mothers were born lighter. F2 male offspring from stressed pregnancies had decreased trabecular content at 6 mo and decreased endosteal circumference at 16 mo. F2 female offspring from growth-restricted mothers had reduced cortical thickness at PN35 and reduced endosteal circumference at 6 mo. At 12 mo, females from unstressed restricted and stressed control mothers had decreased trabecular content. Low birth weight females had long-term bone changes, highlighting programming effects on bone health. Stress during pregnancy did not exacerbate these programmed effects. Male and female offspring responded differently to maternal growth restriction and stress, indicating gender-specific programming effects.


A Scalable Method for Thickness and Lateral Engineering of 2D Materials.
The physical properties of two-dimensional (2D) materials depend strongly on the number of layers. Hence, methods for controlling their thickness with atomic layer precision are highly desirable, yet still too rare, and demonstrated for only a limited number of 2D materials. Here, we present a simple and scalable method for the continuous layer-by-layer thinning that works for a large class of 2D materials, notably layered germanium pnictides and chalcogenides. It is based on a simple oxidation/etching process, which selectively occurs on the topmost layers. Through a combination of atomic force microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and X-ray diffraction experiments we demonstrate the thinning method on germanium arsenide (GeAs), germanium sulfide (GeS), and germanium disulfide (GeS2). We use first-principles simulation to provide insights into the oxidation mechanism. Our strategy, which could be applied to other classes of 2D materials upon proper choice of the oxidation/etching reagent, supports 2D material-based device applications, e.g., in electronics or optoelectronics, where a precise control over the number of layers (hence over the material's physical properties) is needed. Finally, we also show that when used in combination with lithography, our method can be used to make precise patterns in the 2D materials.


Tamoxifen for the prevention of breast cancer: psychosocial impact on women participating in two randomized controlled trials.
The purpose of this study was to evaluate the psychosocial implications of tamoxifen versus placebo in women who are at increased risk of breast cancer. The 488 women in the psychosocial study were recruited from participants in two placebo-controlled, double-blind, randomized, controlled trials that investigated the efficacy of tamoxifen in the prevention of breast cancer in women who are at high familial risk. During a 5-year period, repeated assessments were made of anxiety, psychological distress, and sexual functioning using standardized questionnaires before treatment at baseline and at 6-month intervals during the trial. Questionnaire completion over 5 years was good, with 71.1% of women returning at least 8 of 10 follow-up assessments. Although scores from individuals showed considerable fluctuation and variation over time, changes in anxiety, mood, and sexual functioning were not associated with treatment group. The number of symptoms reported at 48 months via a self-report checklist were not associated with treatment group, but vasomotor symptoms were more frequent among tamoxifen-treated women. Symptoms of low energy, breast sensitivity, and visual blurring were reported most frequently in the placebo group. In general, these results are comparable to those from the National Surgical Adjuvant Breast and Bowel Project psychosocial study despite differences in study populations, methodology, and instruments. The long-term use of tamoxifen and other selective estrogen response modulators as preventive agents in high-risk groups has been questioned, but we found no evidence of treatment-related side effects that affect women's psychosocial and sexual functioning.


Local delivery systems need strong I/S strategy.
The advent of "local delivery systems" now occurring throughout the nation will require a new applications portfolio for successful providers. These applications must address the key needs of the provider and patient community, including hospital information systems, physician practice systems, managed-care and insurance systems, electronic data interchange and the automated patient record. Any less just won't do.


Tattooing and the risk of transmission of hepatitis C: a systematic review and meta-analysis.
In this systematic literature review we sought to determine whether tattooing is a risk factor for the transmission of hepatitis C. A comprehensive search was performed to identify all case-control, cohort or cross sectional studies published prior to November 2008 that evaluated risks related to tattooing or risk factors of transmission of hepatitis C infection. A total of 124 studies were included in this systematic review, of which 83 were included in the meta-analysis. The pooled odds ratio (OR) and 95% confidence interval (CI) of the association of tattooing and hepatitis C from all studies was 2.74 (2.38-3.15). In a subgroup analysis we found the strongest association between tattooing and risk of hepatitis C for samples derived from non-injection drug users (OR 5.74, 95% CI 1.98-16.66). Findings from the current meta-analysis indicate that tattooing is associated with a higher risk of hepatitis C infection. Because tattooing is more common among the youth and young adults and hepatitis C is very common in the imprisoned population, prevention programs must focus on youngsters and prisoners to lower the spread of hepatitis infection.


IGF-1 Gene Transfer to Human Synovial MSCs Promotes Their Chondrogenic Differentiation Potential without Induction of the Hypertrophic Phenotype.
Mesenchymal stem cell- (MSC-) based therapy is a promising treatment for cartilage. However, repair tissue in general fails to regenerate an original hyaline-like tissue. In this study, we focused on increasing the expression levels for insulin-like growth factor-1 (IGF-1) to improve repair tissue quality. The IGF-1 gene was introduced into human synovial MSCs with a lentiviral vector and examined the levels of gene expression and morphological status of MSCs under chondrogenic differentiation condition using pellet cultures. The size of the pellets derived from IGF-1-MSCs were significantly larger than those of the control group. The abundance of glycosaminoglycan (GAG) was also significantly higher in the IGF-1-MSC group. The histology of the IGF-1-induced pellets demonstrated similarities to hyaline cartilage without exhibiting features of a hypertrophic chondrocyte phenotype. Expression levels for the Col2A1 gene and protein were significantly higher in the IGF-1 pellets than in the control pellets, but expression levels for Col10, MMP-13, ALP, and Osterix were not higher. Thus, IGF-1 gene transfer to human synovial MSCs led to an improved chondrogenic differentiation capacity without the detectable induction of a hypertrophic or osteogenic phenotype.


A psychoanalytic reading of Peter Høeg's novel Miss Smilla's Feeling for Snow.
The author presents a psychoanalytic reading of the Danish author Peter Høeg's masterpiece 'Miss Smilla's Feeling for Snow', focusing on the special linguistic style of the novel. Further, the author puts forward an interpretation of the heroine, seeing her as a literary example of female bisexuality. Investigating the heroine's fate, the author discusses Miss Smilla's phallic defence and identity. The narrative technique in Høeg's novel is analysed through Lacan's concepts of the Real, the Imaginary and the Symbolic. The main figure is interpreted as an imaginary example of female bisexuality. Miss Smilla has neither an unambiguous gender identity nor ethnicity. The heroine is pictured in a conflict between two cultures: the Greenlandish and the western European, and her bisexuality both reflects this and is part of it. The author proposes to interpret a significant memory from Smilla's early childhood as an example of a castration phantasy, which retroactively gives new significance to the little girl's pre-oedipal frustration.


[From evidence to expertise: concordance in the topical management of psoriasis].
Vulgar psoriasis is an inflammatory cutaneous-systemic disease, chronic and intermittent. Its etiology is not defined, and it has a higher risk of comorbidities which affect the patients' quality of life. The objectives of this trial were establishing the concordance between Guía de Práctica Clínica (GPC) of the plaque psoriasis pharmacological treatment and the clinical practice of a group of Mexican dermatologists, experts in the psoriasis topical treatment; as well as weighing up the interest and knowledge of quality of life and adherence to treatment. A Delphi questionnaire was applied to 30 experts to explore their therapeutic behavior and attitudes toward the assessment of quality of life and treatment adherence. A meeting was held with a subgroup of 10 dermatologists to analyze the results. A second questionnaire was responded to distinguish the decisions taken for topical treatment in institutional and private practice, as well as other items unexplored in the first questionnaire. After analyzing the questionnaires results, it was clear that the data published in the Guía de Práctica Clínica and the prescriptive attitude of the experts are consistent with respect to the topical treatment for plaque psoriasis. There is also agreement on the attitude about drug prescriptions between the physicians in the private and institutional medical care, although in the private practice it is more common to use vitamin D analogues and corticosteroids and the salicylic acid replaces corticosteroids in the institutions.


Determinants of spatial and temporal coding by semicircular canal afferents.
The vestibular semicircular canals are internal sensors that signal the magnitude, direction, and temporal properties of angular head motion. Fluid mechanics within the 3-canal labyrinth code the direction of movement and integrate angular acceleration stimuli over time. Directional coding is accomplished by decomposition of complex angular accelerations into 3 biomechanical components-one component exciting each of the 3 ampullary organs and associated afferent nerve bundles separately. For low-frequency angular motion stimuli, fluid displacement within each canal is proportional to angular acceleration. At higher frequencies, above the lower corner frequency, real-time integration is accomplished by viscous forces arising from the movement of fluid within the slender lumen of each canal. This results in angular velocity sensitive fluid displacements. Reflecting this, a subset of afferent fibers indeed report angular acceleration to the brain for low frequencies of head movement and report angular velocity for higher frequencies. However, a substantial number of afferent fibers also report angular acceleration, or a signal between acceleration and velocity, even at frequencies where the endolymph displacement is known to follow angular head velocity. These non-velocity-sensitive afferent signals cannot be attributed to canal biomechanics alone. The responses of non-velocity-sensitive cells include a mathematical differentiation (first-order or fractional) imparted by hair-cell and/or afferent complexes. This mathematical differentiation from velocity to acceleration cannot be attributed to hair cell ionic currents, but occurs as a result of the dynamics of synaptic transmission between hair cells and their primary afferent fibers. The evidence for this conclusion is reviewed below.


A Place for Sexual Dysfunctions in an Empirical Taxonomy of Psychopathology.
Sexual dysfunctions commonly co-occur with various depressive and anxiety disorders. An emerging framework for understanding the classification of mental disorders suggests that such comorbidity is a manifestation of underlying dimensions of psychopathology (or "spectra"). In this review, we synthesize the evidence that sexual dysfunctions should be included in the empirical taxonomy of psychopathology as part of the internalizing spectrum, which accounts for comorbidity among the depressive and anxiety disorders. The review has four parts. Part 1 summarizes the empirical basis and utility of the empirical taxonomy of psychopathology. Part 2 reviews the prima facie evidence for the hypothesis that sexual dysfunctions are part of the internalizing spectrum (i.e., high rates of comorbidity; shared cognitive, affective, and temperament characteristics; common neural substrates and biomarkers; shared course and treatment response; and the lack of causal relationships between them). Part 3 critically analyzes and integrates the results of the eight studies that have addressed this hypothesis. Finally, Part 4 examines the implications of reconceptualizing sexual dysfunctions as part of the internalizing spectrum, and explores avenues for future research.


Developing risk management dashboards using risk and quality measures: A visual best practices approach.
Because quality measures are ubiquitous, health care risk management leaders often use them as a proxy for risk management measures. While certain quality measures adequately reflect some aspects of risk management, they are neither a perfect nor complete substitute for well-developed and comprehensive risk management measures. Using a comprehensive approach consisting of quality measures, risk measures, and measures that are less amenable to classification would be the best approach. Identifying the most powerful and informative measures, designing the most appropriate dashboards, and incorporating visual best practices are crucial steps required for evaluating the effectiveness and value of an enterprise risk management program. The authors explain the terms and concepts, review the measures available in the literature, propose new measures, discuss visual best practices, and provide sample dashboard components.


A randomized controlled trial of the effectiveness of planning strategies in the adherence to medication for coronary artery disease.
To examine the effect of action and coping planning strategies in the adherence to medication among outpatients with coronary artery disease. Action and coping planning strategies are based on implementation intention, which requires self-regulation by the individual, to prioritize intentionally planned responses over learned or habitual ones, from daily routines to stressful situations. Randomized controlled trial. Participants (n = 115) were randomized into intervention (use of action and coping planning strategies, n = 59) or control (usual care, n = 56) groups. The study was conducted between June 2010-May 2011 in two in-person visits: baseline and 2-month follow-up. Participants in the intervention group received telephone reinforcement between baseline and 2-month follow-up. Adherence to medication for cardioprotection and symptoms relief was evaluated by proportion of adherence, global measure of adherence evaluation and Morisky Self-Reported Measure of Medication Adherence Scale at both baseline and 2-month follow-up. When using the measure of global measure of adherence, participants in the intervention group reported adherence to therapy more often than controls (odds ratio = 5.3), but no statistically significant change was observed in the other two outcome measures. This study has shown that individuals who use action and coping planning report higher adherence to drug treatment, when measured by the global adherence evaluation. Further studies with longer follow-ups are needed to assess if the effect of planning strategies has long-term duration.


Distinct Roles of the Chromosomal Passenger Complex in the Detection of and Response to Errors in Kinetochore-Microtubule Attachment.
The chromosomal passenger complex (CPC) localizes to centromeres in early mitosis to activate its subunit Aurora B kinase. However, it is unclear whether centromeric CPC localization contributes to CPC functions beyond Aurora B activation. Here, we show that an activated CPC that cannot localize to centromeres supports functional assembly of the outer kinetochore but is unable to correct errors in kinetochore-microtubule attachment in Xenopus egg extracts. We find that CPC has two distinct roles at centromeres: one to selectively phosphorylate Ndc80 to regulate attachment and a second, conserved kinase-independent role in the proper composition of inner kinetochore proteins. Although a fully assembled inner kinetochore is not required for outer kinetochore assembly, we find it is essential to recruit tension indicators, such as BubR1 and 3F3/2, to erroneous attachments. We conclude centromeric CPC is necessary for tension-dependent removal of erroneous attachments and for the kinetochore composition required to detect tension loss.


Non-random Mating Patterns in Education, Mental, and Somatic Health: A Population Study on Within- and Cross-Trait Associations.
Partners resemble each other on many traits, such as health and education. The traits are usually studied one by one in data from established couples and with potential participation bias. We studied all Norwegian parents who had their first child between 2016 and 2020 (N=187,926) and the siblings of these parents. We analysed grade point averages (GPA), educational attainment (EA), and medical records with prospective diagnostic data on 10 mental and 10 somatic health conditions measured 10 to 5 years before childbirth. We found stronger partner similarity in mental (median r=0.14) than in somatic health conditions (median r=0.04), with ubiquitous cross-trait correlations for mental health conditions (median r=0.13). GPA correlated 0.43 and EA 0.47 between partners. High GPA or EA was associated with better mental (median r=-0.16) and somatic (median r=-0.08) health in partners. Elevated correlations for mental health (median r=0.25) in established couples indicated convergence. Analyses of data on siblings and in-laws revealed deviations from direct assortment, suggesting instead indirect assortment based on related traits. GPA and EA accounted for 30-40% of the partner correlations in health. This has implications for the distribution of risk factors among children and for studies of intergenerational transmission.


Combined pars plana vitrectomy, phacoemulsification, and intraocular lens implantation in the capsular bag: a comparison to vitrectomy and subsequent cataract surgery as a two-step procedure.
To evaluate the effectiveness and safety of combined surgery. Combined surgery (CS) consisting of pars plana vitrectomy (PPV), phacoemulsification, and implantation of a posterior chamber intraocular lens (PC IOL) in the capsular bag was performed on 26 patients. Another 26 had phacoemulsification with PC IOL insertion one to 84 months (mean 17.3) after PPV (sequential surgery, SS). Mean follow-up was 21.9 months after CS and 19.5 months after the cataract surgery in the SS group. The data were analyzed in a prospective, nonrandomized fashion. Visual acuity and refraction, astigmatism, accuracy of biometry, intraocular pressure, intraoperative, postoperative and long-term complications, and medical treatment were comparable in the two groups. Among the four uveitis patients in each group, transient fibrin formation was more frequent with CS (100%) than with SS (25%). The advantages of CS are that only one operation is needed, intraoperative working conditions are good, macular recovery is not masked by postvitrectomy cataract formation, and ideal lens centration is achievable. Potential disadvantages of CS include a longer operative time and increased technical demand, shrinkage of the anterior capsular opening, which may interfere with fundus view, and increased inflammation may be seen in patients with preexisting uveitis. Combined surgery in selected patients is a safe and effective approach, and outcomes are comparable to sequential surgery.


Complementary and alternative medicine use by older Australians.
Complementary and alternative medicine (CAM) use by Australians is substantial and increasing, but little is known about its use by the elderly. We here present the findings for the elderly cohort in our recently conducted national survey on CAM use by adult Australians. In May and June 2005, computer-assisted telephone interviews, using random-digit telephone dialing, were employed to gather data on CAM use in the last 12 months. Of 1067 adult participants interviewed, 178 were 65 or older. More than half of these (57.8%; 95% CI, 50.7%-64.9%) had used at least one of 17 common forms of CAM and 60.4% of the CAM users had consulted CAM practitioners. Clinical nutrition, chiropractic, massage therapy, meditation, and herbal medicine were the most common forms of CAM used by the elderly. A higher proportion of the elderly had always used both CAM and conventional medical treatments (37.9%) than had those aged 18-34 (15.7%) and 35-64 (26.9%). Elderly CAM users (60.2%) were more likely than younger users to discuss their use with their doctors. Of those who did not do so, 24.1% were not asked by their doctors and 16.0% considered that their doctor would disapprove. In conclusion, we found that a substantial proportion of older Australians use CAM. The elderly are also more likely than younger adults to discuss their use of CAM with their doctors, but doctors need to play a more active role in initiating such communication.


Pyclen-Based Ligands Bearing Pendant Picolinate Arms for Gadolinium Complexation.
We report the synthesis of two pyclen-based regioisomer ligands (pyclen = 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene) functionalized with picolinic acid pendant arms either at positions 3,9-pc2pa (L5) or 3,6-pc2pa (L6) of the macrocyclic fragment. The ligands were prepared by the regiospecific protection of one of the amine nitrogen atoms of the macrocycle using Boc and Alloc protecting groups, respectively. The X-ray structure of the Gd(III) complex of L5 contains trinuclear [(GdL5)3(H2O)3]3+ entities in which the monomeric units are joined by μ2-η1:η1-carboxylate groups. However, the 1H and 89Y NMR spectra of its Y(III) analogue support the formation of monomeric complexes in solution. The Tb(III) complexes are highly luminescent, with emission quantum yields of up to 28% for [TbL5]+. The luminescence lifetimes recorded in H2O and D2O solutions indicate the presence of a water molecule coordinated to the metal ion, as also evidenced by the 1H relaxivities measured for the Gd(III) analogues. The Gd(III) complexes present very different exchange rates of the coordinated water molecule (kex298 = 87.1 × 106 and 1.06 × 106 s-1 for [GdL5]+ and [GdL6]+, respectively). The very high water exchange rate of [GdL5]+ is associated with the steric hindrance originating from the coordination of the ligand around the water binding site, which favors a dissociatively activated water exchange process. The Gd(III) complexes present rather high thermodynamic stabilities (log KGdL = 20.47 and 19.77 for [GdL5]+ and [GdL6]+, respectively). Furthermore, these complexes are remarkably inert with respect to their acid-assisted dissociation, in particular the complex of L5.


Salsolinol produces reinforcing effects in the nucleus accumbens shell of alcohol-preferring (P) rats.
The formation of salsolinol (SAL) has been hypothesized to be a factor contributing to alcoholism and alcohol abuse. If SAL is formed under chronic alcohol-drinking conditions, then it may contribute to alcohol addiction by being rewarding itself. Because SAL can be formed by the nonenzymatic condensation of acetaldehyde with dopamine, the reinforcing effects of SAL were tested in the nucleus accumbens shell, a dopamine-rich site considered to be involved in regulating alcohol-drinking behavior. The intracranial self-administration technique was used to test the reinforcing properties of SAL. Adult, female alcohol-preferring (P) rats were stereotaxically implanted with guide cannulae aimed at the nucleus accumbens shell. After 7 to 10 days to allow recovery from surgery, P rats were attached to the electrolytic microinfusion transducer system, placed in two-lever experimental chambers, and allowed to respond for the self-infusion of 100 nl of modified artificial cerebrospinal fluid (aCSF) or 0.03, 0.3, 3.0, or 12.5 microM SAL (3-1250 fmol/100 nl). Sessions were 4 hr in duration and were conducted in the dark cycle every 48 hr. The effects of coinfusing 10 to 400 microM sulpiride (given in sessions 5 and 6 after four acquisition sessions) on the intracranial self-administration of 3.0 microM SAL were tested in a separate experiment. P rats given 0.3 to 12.5 microM SAL received significantly more infusions per session than did the group given aCSF alone (e.g., 50 infusions for 3.0 microM SAL versus 10 or fewer infusions for the aCSF group) and responded significantly more on the active than inactive lever. Coinfusion of 100 or 400 microM sulpiride reduced the responding on the active lever (80-100 responses/session without sulpiride) to levels observed for the inactive lever (fewer than 10 responses/session with sulpiride). This effect was reversible because giving SAL alone in session 7 reinstated responding on the active lever. SAL is reinforcing in the nucleus accumbens shell of P rats at concentrations that are pharmacologically possible, and these reinforcing actions are mediated in part by D2/D3-like receptors.


The experiences of COVID-19 preprint authors: a survey of researchers about publishing and receiving feedback on their work during the pandemic.
The COVID-19 pandemic caused a rise in preprinting, triggered by the need for open and rapid dissemination of research outputs. We surveyed authors of COVID-19 preprints to learn about their experiences with preprinting their work and also with publishing their work in a peer-reviewed journal. Our research had the following objectives: 1. to learn about authors' experiences with preprinting, their motivations, and future intentions; 2. to consider preprints in terms of their effectiveness in enabling authors to receive feedback on their work; 3. to compare the impact of feedback on preprints with the impact of comments of editors and reviewers on papers submitted to journals. In our survey, 78% of the new adopters of preprinting reported the intention to also preprint their future work. The boost in preprinting may therefore have a structural effect that will last after the pandemic, although future developments will also depend on other factors, including the broader growth in the adoption of open science practices. A total of 53% of the respondents reported that they had received feedback on their preprints. However, more than half of the feedback was received through "closed" channels-privately to the authors. This means that preprinting was a useful way to receive feedback on research, but the value of feedback could be increased further by facilitating and promoting "open" channels for preprint feedback. Almost a quarter of the feedback received by respondents consisted of detailed comments, showing the potential of preprint feedback to provide valuable comments on research. Respondents also reported that, compared to preprint feedback, journal peer review was more likely to lead to major changes to their work, suggesting that journal peer review provides significant added value compared to feedback received on preprints.


A nonparametric approach to the analysis of longitudinal data via a set of level crossing problems with application to the analysis of microarray time course experiments.
Here we develop a completely nonparametric method for comparing two groups on a set of longitudinal measurements. No assumptions are made about the form of the mean response function, the covariance structure or the distributional form of disturbances around the mean response function. The solution proposed here is based on the realization that every longitudinal data set can also be thought of as a collection of survival data sets where the events of interest are level crossings. The method for testing for differences in the longitudinal measurements then is as follows: for an arbitrarily large set of levels, for each subject determine the first time the subject has an upcrossing and a downcrossing for each level. For each level one then computes the log rank statistic and uses the maximum in absolute value of all these statistics as the test statistic. By permuting group labels we obtain a permutation test of the hypothesis that the joint distribution of the measurements over time does not depend on group membership. Simulations are performed to investigate the power and it is applied to the area that motivated the method-the analysis of microarrays. In this area small sample sizes, few time points and far too many genes to consider genuine gene level longitudinal modeling have created a need for a simple, model free test to screen for interesting features in the data.


Building community networks: a road trauma education and training program for rural areas.
The work of the Road Trauma Support Team highlights the ongoing impact of road trauma on rural communities. Small population size and close social networks mean that road trauma can have a negative effect on social relations across the whole community. Much of the 'flow-on' effect of road trauma, in the form of community distress, can be alleviated by increased skills, information about responding to road trauma, and the establishment of supportive community networks. This paper reports on the implementation and evaluation of a project that addressed knowledge, skills and awareness of road trauma in rural communities. Funded by the Rural Health Support Education and Training (RHSET) program and conducted by the Road Trauma Support Team, the project focused on the impact of traumatic events in small communities and strategies to maximise effective participation of community members and health workers in response to trauma. Piloted in six rural communities in northern Tasmania, the project has developed an educational resource package.


Psychological and adjustment problems due to acquired brain lesions in pediatric patients: a comparison of vascular, infectious, and other origins.
The aim of this study was to describe psychological, behavioral, and adjustment problems in children and adolescents with acquired brain lesions of different origins. Three groups of patients with acquired brain lesions (15 patients with infectious origin, 37 with vascular origin, and 15 with other origin), ranging in age from 4 to 18 years, received a psychological evaluation, including the Child Behavior Checklist for ages 4 to 18 and the Vineland Adaptive Behavior Scale. About half of the total sample (47.8%) showed psychological problems. Difficulties varied according to the cause of the brain lesions. The most problematic patients were children with brain lesions of infectious origin, whereas children with brain lesions of vascular origin scored lower on most of the Child Behavior Checklist scales. The authors conclude that psychological and behavioral difficulties are very common among school-aged children with acquired brain lesions, and their relevance and impact must necessarily be considered.


Chlorpropamide alcohol flush and circulating met-enkephalin: a positive link.
Chlorpropamide-alcohol flushing may be due to sensitivity to endogenous opiates. To investigate this possibility the plasma met-enkephalin and beta-endorphin responses to sherry with and without chlorpropamide were studied in six patients with non-insulin dependent diabetes and in six normal subjects. After chlorpropamide all patients showed a rise in met-enkephalin concentrations from a basal level of 50 +/- 7.2 ng/l to a peak of 75 +/- 8.1 ng/l (p less than 0.001). In contrast, before chlorpropamide treatment was started met-enkephalin values did not change after alcohol. No significant changes in beta-endorphin values were observed. In six normal subjects pretreated with chlorpropamide the met-enkephalin concentration also rose from a basal level of 72 +/- 15 ng/l to a peak of 103 +/- 9.4 ng/l (p less than 0.002). Again, the met-enkephalin rise was not observed after placebo. Neither beta-endorphin concentrations nor facial temperature changed significantly. These data suggest that endogenous opiates may be implicated in CPAF. Furthermore, this is the first study in which a significant change in circulating met-enkephalin values has occurred.


Postoperative cognitive dysfunction after total joint arthroplasty in the elderly: a meta-analysis.
This meta-analysis consolidated the research on postoperative cognitive dysfunction (POCD) following total joint arthroplasty (TJA). Data from 17 studies that assessed cognition pre- and post-surgery in TJA patients alone (15 studies) or matched TJA and control groups (2 studies) were analysed. Results were grouped by cognitive domain (memory, attention, language, speed, general cognition) and follow-up interval (pre-discharge, 3-6 months post-surgery). The TJA data revealed small declines in reaction time and general cognition pre-discharge, but no evidence of decline 3-6 months post-surgery. Very limited TJA and Control data indicated no group differences in the changes to performance over time; however, the TJA group was cognitively compromised pre- and post-surgery compared to Controls. Further appropriately controlled research is required to clarify whether POCD commonly occurs after TJA.


The impact of COVID-19 on the mental health of older sexual minority Canadians in the CLSA.
Limited research has examined the mental health impacts of the COVID-19 pandemic on sexual minority (i.e., lesbian, gay, bisexual; LGB) older adults using a longitudinal approach. This study aimed to compare the mental health trajectories (i.e., reported symptoms of depression and loneliness) of LGB and heterosexual participants across four time points. Data were drawn from the Canadian Longitudinal Study on Aging (CLSA), an ongoing study on the experiences of adults between 45 to 85 at Baseline. Data included for analysis were collected at Baseline (2011-2015), Follow-up 1 (2015-2018), and two time points during the COVID-19 pandemic (April-December 2020). We used General Estimating Equations (GEE) to model changes in depression symptoms (CESD-10; n = 47,728) and loneliness (UCLA 3-item loneliness scale; n = 41,698), adjusting for covariates (i.e., age, sex, race/ethnicity, education, and income). Results indicated that LGB participants reported more symptoms of depression (B = .595, p < .001) and loneliness (B = .313, p < .001) in comparison to heterosexual peers across the four time points. Mean depression and loneliness scores increased regardless of sexual orientation. This study highlighted the detrimental effects of the pandemic on the mental health of older adults regardless of sexual orientation. It also showed that LGB older adults experienced more loneliness and depression symptoms than heterosexual older adults both before and during the pandemic. Understanding diverse identities, needs, and disparities in mental health is critical to promoting equitable aging experiences for everyone.


The effect of tramadol on blood glucose concentrations: a systematic review.
Studies comprehensively summarizing the impact of tramadol use on glucose homeostasis are very sparse. Thus, the present study was performed to collect and summarize the latest information about this issue in a systematic way. An exhaustive literature search was carried out using relevant keywords. Web of Sciences, PubMed, Scopus, and Google scholar were interrogated until 30 June 2019. Case-control, cohort, cross-sectional, clinical trial, case report, and animal studies that focused on the objective of the study were retrieved. This review summarizes the results of 761 papers on glycemic changes due to tramadol exposure. Thirty-six publications reported hypoglycemia and 17 hyperglycemia during tramadol use. Twenty-two studies either reported normal blood glucose concentrations, or did not observe any difference in the blood glucose levels following tramadol use. Finally, hypoglycemia was reported in diabetic individuals exposed to tramadol in 12 studies. The data suggest that primarily hypoglycemia but some degree of hyperglycemia has been reported with tramadol use. Importantly, all studies on tramadol use in diabetes reported hypoglycemia. Tramadol-induced hypoglycemia may be severe in some cases. The risk of alterations in glucose homeostasis accompanying tramadol exposure indicates time importance of careful blood glucose monitoring during tramadol use.


[Case management based multidiscıplinary care protocol in the palliative care of cancer patients].
Today, multifaceted approach is needed for the palliative care of advanced stage cancer patients. The main objective for these patients, elimination of pain and other symptoms, psychosocial and spiritual needs are met and to increase the quality of life. We are also faced with the challenge of meeting the physical and psychosocial needs of family members. The purpose of a holistic approach to patient and family who provide effective and quality care, care coordination and case management of a multidisciplinary team approach is based on cooperation. Care protocols specified patient care activities to be carried by the related disciplines to achieve results on a timeline that shows a certain, a multidisciplinary clinical management tool. A lot of care guidelines and protocols developed by a team of experts to contribute to the palliative care activities, and this is thought to be a guiding team members, working with patients.


Effectiveness of antimicrobial hospital curtains on reducing bacterial contamination-A multicenter study.
To determine the efficacy of 2 types of antimicrobial privacy curtains in clinical settings and the costs involved in replacing standard curtains with antimicrobial curtains. A prospective, open-labeled, multicenter study with a follow-up duration of 6 months. This study included 12 rooms of patients with multidrug-resistant organisms (MDROs) (668 patient bed days) and 10 cubicles (8,839 patient bed days) in the medical, surgical, neurosurgical, orthopedics, and rehabilitation units of 10 hospitals. Culture samples were collected from curtain surfaces twice a week for 2 weeks, followed by weekly intervals. With a median hanging time of 173 days, antimicrobial curtain B (quaternary ammonium chlorides [QAC] plus polyorganosiloxane) was highly effective in reducing the bioburden (colony-forming units/100 cm2, 1 vs 57; P < .001) compared with the standard curtain. The percentages of MDRO contamination were also significantly lower on antimicrobial curtain B than the standard curtain: methicillin-resistant Staphylococcus aureus, 0.5% vs 24% (P < .001); carbapenem-resistant Acinetobacter spp, 0.2% vs 22.1% (P < .001); multidrug-resistant Acinetobacter spp, 0% vs 13.2% (P < .001). Notably, the median time to first contamination by MDROs was 27.6 times longer for antimicrobial curtain B than for the standard curtain (138 days vs 5 days; P = .001). Antimicrobial curtain B (QAC plus polyorganosiloxane) but not antimicrobial curtain A (built-in silver) effectively reduced the microbial burden and MDRO contamination compared with the standard curtain, even after extended use in an active clinical setting. The antimicrobial curtain provided an opportunity to avert indirect costs related to curtain changing and laundering in addition to improving patient safety.


Disparities in Follow-Up After Low-Dose Lung Cancer Screening.
The National Lung Cancer Screening Trial (NLST) demonstrated an improvement in overall survival with lung cancer screening. Achieving follow-up for a positive screen is essential to impact early intervention for lung cancer. The objective of this study was to determine predictors of follow-up after a positive lung cancer screening test. The NLST database was queried for participants with a positive lung cancer screening exam. This cohort was then subdivided into patients who had follow-up and those who did not. Pairwise comparison was performed within different subgroups. A logistic regression model was then utilized to identify predictive factors associated with follow-up. Of the 53,454 patients who participated in the study, we identified 14,000 patients who had a positive lung cancer screening test. Of those patients, 12,503 followed up appropriately (89.3%). Women had a statistically higher follow-up rate compared to men (90% vs 88.8%, P ≤ 0.05). Patients reported as married or living as married also showed a higher rate of follow-up compared to patients reported as never married, divorced, separated, or widowed (90.2% vs 87.5%, P ≤ 0.05). The rate of follow-up among African-American patients was 82.8%, while those in white patients was 89.6%, this was statistically significant (P ≤ 0.05). Education level was not a significant factor in follow-up rates. Current smokers followed up at lower rates compared to former smokers (87.9 % vs 90.6%, P ≤ 0.05). Logistic regression determined gender, marital status, race, and smoking status to be predictors of follow-up. Follow-up rates after a positive lung cancer screening test were associated with a patient's gender, marital status, race, and smoking status.


[The diagnosis and surgical treatment of intestinal amebiasis].
Ninety-one patients with intestinal amebiasis (IA) were studied. All had been long suffering from IA due to the fact that it had not been diagnosed in time. Indications for emergency surgery were profuse hemorrhage, perforation of amebic ulcers, gangrene, and toxic dilatation of the large intestine. Planned operations were made in pseudopolyposis, strictures of the large intestine. Surgical treatment was performed along with specific therapy. Seven patients died due to late diagnosis, ineffective therapy and profound systemic and regional changes caused by these factors. It is necessary to differentiate ulcerative colitis, polyposis, and tumors of the large intestine with IA.


Artificial embolization of carotid-cavernous fistula with post-operative patency of internal carotid artery.
This report deals with a patient of 86 who developed a carotid-cavernous fistula. Artificial embolization alone was considered the safest treatment for this patient and proved to be adequate. Post-operative preservation of the patency of the internal carotid artery was demonstrated by angiography. We believe this method is particularly appropriate for carotid-cavernous fistulas if it is demonstrated by angiography that the major blood flow of the carotid artery pours into the fistula. A soft-iron clip attached to the muscle can be used for external and forceful guidance of the embolus into the fistula with the help of an electromagnet, hence the patency of the internal carotid artery can be preserved. The embolus should be introduced through the external carotid artery. This is the only case known to us in which patency of the internal carotid artery was post-operatively maintained. We have reviewed 545 reported cases of surgically treated carotid-cavernous fistulas and analysed the results from simple cervical carotid ligation to the more sophisticated methods of artificial embolizations. The results obtained by artificial embolization have been consistently good, while the other techniques have failed in large percentages. Artificial embolization should be used as the primary treatment for carotid-cavernous fistula, since ligation of the internal carotid artery precludes its embolization at a later date.


Spouses' existential loneliness when caring for a frail partner late in life - a hermeneutical approach.
Purpose: Spouses are in a vulnerable situation when caring for a frail partner late in life. Exploring their existential loneliness can be a way to understand more about their existential needs.Method: A hermeneutic approach was used. Multistage focus group interviews were conducted with two groups consisting of five spouses, respectively, who met three times each. To work with the text, an approach was adapted where quotations are converted into poems in a linguistic manner.Results: Existential loneliness can be understood as the following: 1) being in a transition from us to merely me, 2) being forced to make decisions and feeling excluded, 3) navigating in an unfamiliar situation and questioning oneself, and 4) longing for togetherness but lacking the energy to encounter other people. The main interpretation is that existential loneliness emerges when one is in moments of inner struggle, when one is forced to make impossible choices, when one is approaching and is in limit situations, and when one is experiencing the endless loss of the other.Conclusion: For health care professionals to achieve a holistic picture, person-centeredness can be a way to make the spouses' existential needs visible and to provide support based on their needs.


Evaluation of women seeking sterilisation reversal.
A total of 1120 women attending at Regional Centre of Excellence (RCOE), RG Kar Medical College and Hospital, Calcutta from October, 1989 to July, 1998 with the request for sterilisation reversal (SR) were evaluated step by step for fitness of SR operation on the basis of history, clinical examination, pre-operative investigations, fertility status and laparoscopic findings. One thousand and sixty couples completed their evaluation. Majority of the SR seekers were young (< 30 years) and significant number (8.9%) of women came in late age (> 40 years). Most (85.8%) of the women had one or no child. The main reason for requesting reversal was death of children (91.8%). Only 43.3% were ultimately found fit for SR operation and rest (56.7%) were refused. Presence of 2 or more children in not remarried couple (13.8%), gross pelvic pathology (2.35%), advanced age (8.7%), seminopathy (4.05%), and some medical diseases (3.2%) were important reasons before pre-operative investigations for refusal. Faulty sterilisation technique (11%) was responsible for refusal at laparoscopic evaluation. The need of critical evaluation of all women seeking reversal has been emphasised in this study. Various aspects related with demand for SR and preventive measures to improve the success of this procedure have been critically discussed.


High risk fertility behaviour and health facility delivery in West Africa.
Evidence suggests that women who give birth in a health facility have lower odds of experiencing pregnancy complications and significantly reduced risk of death from pregnancy-related causes compared to women who deliver at home. Establishing the association between high-risk fertility behaviour (HRFB) and health facility delivery is imperative to inform intervention to help reduce maternal mortality. This study examined the association between HRFB and health facility delivery in West Africa. Data for the study were extracted from the most recent Demographic and Health Surveys of twelve countries in West Africa conducted from 2010 to 2020. A total of 69,479 women of reproductive age (15-49 years) were included in the study. Place of delivery was the outcome variable in this study. Three parameters were used as indicators of HRFB based on previous studies. These were age at first birth, short birth interval, and high parity. Multivariable binary logistic regression analysis was performed to examine the association between HRFB and place of delivery and the results were presented using crude odds ratio (cOR) and adjusted odds ratio (aOR), with their respective 95% confidence interval (CI). More than half (67.64%) of the women delivered in a health facility. Women who had their first birth after 34 years (aOR = 0.52; 95% CI = 0.46-0.59), those with short birth interval (aOR = 0.91; 95% CI = 0.87-0.96), and those with high parity (aOR = 0.58; 95% CI = 0.55-0.60) were less likely to deliver in a health compared to those whose age at first delivery was 18-34 years, those without short birth interval, and those with no history of high parity, respectively. The odds of health facility delivery was higher among women whose first birth occurred at an age less than 18 years compared to those whose age at first birth was 18-34 years (aOR = 1.17; 95% CI = 1.07-1.28). HRFB significantly predicts women's likelihood of delivering in a health facility in West Africa. Older age at first birth, shorter birth interval, and high parity lowered women's likelihood of delivering in a health facility. To promote health facility delivery among women in West Africa, it is imperative for policies and interventions on health facility delivery to target at risk sub-populations (i.e., multiparous women, those with shorter birth intervals and women whose first birth occurs at older maternal age). Contraceptive use and awareness creation on the importance of birth spacing should be encouraged among women of reproductive age in West Africa.


Management of adverse events associated with idelalisib treatment: expert panel opinion.
Idelalisib is a first-in-class selective, oral, phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor approved for the treatment of several types of blood cancer. Idelalisib has demonstrated significant efficacy and a tolerable safety profile in clinical trials. However, the US prescribing information contains a black box warning for fatal and/or severe diarrhea or colitis, hepatotoxicity, pneumonitis and intestinal perforation. An expert panel was convened to review the pathology of these treatment-emergent adverse events (TEAEs) to propose key management tools for patients receiving idelalisib therapy. This article provides an overview of idelalisib TEAEs reported in clinical trials, and a summary of the panel's recommendations for identification and management of idelalisib treatment-emergent diarrhea or colitis as well as a discussion of transaminitis and pneumonitis. For idelalisib-related diarrhea or colitis (including unresolved grade 2 and grade ≥ 3), after exclusion of infectious causes, the panel recommends individualized treatment with budesonide or oral or intravenous steroid therapy.


IGREX for quantifying the impact of genetically regulated expression on phenotypes.
By leveraging existing GWAS and eQTL resources, transcriptome-wide association studies (TWAS) have achieved many successes in identifying trait-associations of genetically regulated expression (GREX) levels. TWAS analysis relies on the shared GREX variation across GWAS and the reference eQTL data, which depends on the cellular conditions of the eQTL data. Considering the increasing availability of eQTL data from different conditions and the often unknown trait-relevant cell/tissue-types, we propose a method and tool, IGREX, for precisely quantifying the proportion of phenotypic variation attributed to the GREX component. IGREX takes as input a reference eQTL panel and individual-level or summary-level GWAS data. Using eQTL data of 48 tissue types from the GTEx project as a reference panel, we evaluated the tissue-specific IGREX impact on a wide spectrum of phenotypes. We observed strong GREX effects on immune-related protein biomarkers. By incorporating trans-eQTLs and analyzing genetically regulated alternative splicing events, we evaluated new potential directions for TWAS analysis.


Patterns of Hospital Performance on the Hospital-Wide 30-Day Readmission Metric: Is the Playing Field Level?
Hospital performance on the 30-day hospital-wide readmission (HWR) metric as calculated by the Centers for Medicare and Medicaid Services (CMS) is currently reported as a quality measure. Focusing on patient-level factors may provide an incomplete picture of readmission risk at the hospital level to explain variations in hospital readmission rates. To evaluate and quantify hospital-level characteristics that track with hospital performance on the current HWR metric. Retrospective cohort study. A total of 4785 US hospitals. We linked publically available data on individual hospitals published by CMS on patient-level adjusted 30-day HWR rates from July 1, 2011, through June 30, 2014, to the 2014 American Hospital Association annual survey. Primary outcome was performance in the worst CMS-calculated HWR quartile. Primary hospital-level exposure variables were defined as: size (total number of beds), safety net status (top quartile of disproportionate share), academic status [member of the Association of American Medical Colleges (AAMC)], National Cancer Institute Comprehensive Cancer Center (NCI-CCC) status, and hospital services offered (e.g., transplant, hospice, emergency department). Multilevel regression was used to evaluate the association between 30-day HWR and the hospital-level factors. Hospital-level characteristics significantly associated with performing in the worst CMS-calculated HWR quartile included: safety net status [adjusted odds ratio (aOR) 1.99, 95% confidence interval (95% CI) 1.61-2.45, p < 0.001], large size (> 400 beds, aOR 1.42, 95% CI 1.07-1.90, p = 0.016), AAMC alone status (aOR 1.95, 95% CI 1.35-2.83, p < 0.001), and AAMC plus NCI-CCC status (aOR 5.16, 95% CI 2.58-10.31, p < 0.001). Hospitals with more critical care beds (aOR 1.26, 95% CI 1.02-1.56, p = 0.033), those with transplant services (aOR 2.80, 95% CI 1.48-5.31,p = 0.001), and those with emergency room services (aOR 3.37, 95% CI 1.12-10.15, p = 0.031) demonstrated significantly worse HWR performance. Hospice service (aOR 0.64, 95% CI 0.50-0.82, p < 0.001) and having a higher proportion of total discharges being surgical cases (aOR 0.62, 95% CI 0.50-0.76, p < 0.001) were associated with better performance. The study approach was not intended to be an alternate readmission metric to compete with the existing CMS metric, which would require a re-examination of patient-level data combined with hospital-level data. A number of hospital-level characteristics (such as academic tertiary care center status) were significantly associated with worse performance on the CMS-calculated HWR metric, which may have important health policy implications. Until the reasons for readmission variability can be addressed, reporting the current HWR metric as an indicator of hospital quality should be reevaluated.


Identification and characterization of a Drosophila nuclear proteasome regulator. A homolog of human 11 S REGgamma (PA28gamma ).
We report the cloning and characterization of a Drosophila proteasome 11 S REGgamma (PA28) homolog. The 28-kDa protein shows 47% identity to the human REGgamma and strongly enhances the trypsin-like activities of both Drosophila and mammalian 20 S proteasomes. Surprisingly, the Drosophila REG was found to inhibit the proteasome's chymotrypsin-like activity against the fluorogenic peptide succinyl-LLVY-7-amino-4-methylcoumarin. Immunocytological analysis reveals that the Drosophila REG is localized to the nucleus but is distributed throughout the cell when nuclear envelope breakdown occurs during mitosis. Through site-directed mutagenesis studies, we have identified a functional nuclear localization signal present in the homolog-specific insert region. The Drosophila PA28 NLS is similar to the oncogene c-Myc nuclear localization motif. Comparison between uninduced and innate immune induced Drosophila cells suggests that the REGgamma proteasome activator has a role independent of the invertebrate immune system. Our results support the idea that gamma class proteasome activators have an ancient conserved function within metazoans and were present prior to the emergence of the alpha and beta REG classes.


Influence of monovalent metal ions on metal binding and catalytic activity of the 10-23 DNAzyme.
Deoxyribozymes (DNAzymes) are single-stranded DNA molecules that catalyze a broad range of chemical reactions. The 10-23 DNAzyme catalyzes the cleavage of RNA strands and can be designed to cleave essentially any target RNA, which makes it particularly interesting for therapeutic and biosensing applications. The activity of this DNAzyme in vitro is considerably higher than in cells, which was suggested to be a result of the low intracellular concentration of bioavailable divalent cations. While the interaction of the 10-23 DNAzyme with divalent metal ions was studied extensively, the influence of monovalent metal ions on its activity remains poorly understood. Here, we characterize the influence of monovalent and divalent cations on the 10-23 DNAzyme utilizing functional and biophysical techniques. Our results show that Na+ and K+ affect the binding of divalent metal ions to the DNAzyme:RNA complex and considerably modulate the reaction rates of RNA cleavage. We observe an opposite effect of high levels of Na+ and K+ concentrations on Mg2+- and Mn2+-induced reactions, revealing a different interplay of these metals in catalysis. Based on these findings, we propose a model for the interaction of metal ions with the DNAzyme:RNA complex.


Predictive factors associated with axillary lymph node metastases in T1a and T1b breast carcinomas: analysis in more than 900 patients.
Axillary lymph node metastasis (ALNM) represents the single most important prognostic indicator in patients diagnosed with breast cancer. The proportion of < or = 1-cm (T1a, T1b) invasive breast carcinomas is increasing. The incidence and predictive factors associated with ALNM in patients with < or = 1-cm tumors remains unclear and the role of axillary lymph node dissection in these patients has been questioned. The purpose of this study was to determine clinical and pathologic factors predictive of ALNM in patients with < or = 1-cm invasive breast carcinomas by univariate and multivariate analyses. Review analysis from a prospective database identified patients with < or = 1-cm invasive breast cancers treated at our institution between 1990 and 1996. All patients underwent a resection of the primary tumor and axillary lymph node dissections. Routine patient and tumor characteristics evaluated included: age, race, tumor size, histologic grade, estrogen and progesterone receptor status, and lymphatic and vascular invasion. Univariate and multivariate analyses were performed. Adjusted odds ratios (OR) and 95% confidence intervals (CI) are presented. A total of 919 patients were identified in this study with tumors < or = 1 cm. These included 199 patients (21.7%) with T1a tumors and 720 patients (78.3%) with T1b tumors. ALNM was detected in 165 patients with an overall incidence of 18.0%. Of the ALNM group, 32 patients (19.4%) had T1a tumors and 133 patients (80.6%) had T1b tumors. Four variables were found to be significant in univariate analysis. These included: increasing tumor size, poor histologic grade, presence of lymphatic or vascular invasion, and younger age of the patient. An increase in tumor size was associated with a significant risk of ALNM (OR = 2.66, 95% CI = 1.28 to 5.75; p = 0.01). Poor tumor grade and the presence of lymphatic or vascular invasion were also associated with an increased risk of ALNM (OR = 2.69, p = 0.003 and OR = 5.52, p = 0.0001, respectively). Patients with ALNM were more likely to have a tumor grade of 3 (25.0% ALNM versus 12.5% node-negative, p = 0.004) and lymphatic or vascular invasion (16.9% ALNM versus 3.5% node-negative, p < 0.0001). In multivariate analysis, an increased risk of ALNM was demonstrated with increasing tumor size (0.1-cm increments), poor histologic grade, and younger age. This study investigated clinical and pathologic factors influencing ALNM in patients with T1a and T1b breast carcinomas. We have identified three factors by multivariate analysis as significant independent predictors of ALNM in this group of patients. These include increasing tumor size, poor histologic grade, and younger age. Given the significant amount of ALNM demonstrated in this study (overall 18%) and the inability to identify a subgroup of patients that had an acceptable low risk of ALNM, the complete omission of assessing the axilla for metastatic disease in patients with small breast cancers cannot be advocated. Our recommendation for patients diagnosed with T1a and T1b tumors is to have their axilla investigated for metastatic disease either by traditional axillary lymph node dissections or by intraoperative lymphatic mapping and sentinel lymph node biopsy techniques.


Myofibroblasts: Biochemical and proteomic approaches to fibrosis.
Fibrosis is a state, in which excess amounts of extracellular matrix are deposited in the tissue. Fibrosis can occur in various organs, including the liver, lung, kidney and heart. The progression of fibrosis involves interstitial hypercellularity, accumulation of extracellular matrix, and atrophy of epithelial structures, resulting in a loss of normal function. Myofibroblasts play a crucial role in the development and progress of fibrosis. When stimulated, myofibroblasts actively synthesize connective tissue components and cause organ fibrosis. As a result, the process and the mechanism of myofibroblast activation represent a target for antifibrotic treatment. As yet, however, an effective treatment has not been developed, and new treatment modalities are expected. Because activation of myofibroblasts is a key event during fibrosis development, there is great interest in identifying and characterizing proteins whose expression is changed after this activation. In this review, fibrosis is outlined and the role of myofibroblasts in this disorder is described. Furthermore, the search for candidate proteins to target for treatment and the prospects of antifibrotic therapy are discussed.


Delimiting subterritories of the human subthalamic nucleus by means of microelectrode recordings and a Hidden Markov Model.
Positive therapeutic response without adverse side effects to subthalamic nucleus deep brain stimulation (STN DBS) for Parkinson's disease (PD) depends to a large extent on electrode location within the STN. The sensorimotor region of the STN (seemingly the preferred location for STN DBS) lies dorsolaterally, in a region also marked by distinct beta (13-30 Hz) oscillations in the parkinsonian state. In this study, we present a real-time method to accurately demarcate subterritories of the STN during surgery, based on microelectrode recordings (MERs) and a Hidden Markov Model (HMM). Fifty-six MER trajectories were used, obtained from 21 PD patients who underwent bilateral STN DBS implantation surgery. Root mean square (RMS) and power spectral density (PSD) of the MERs were used to train and test an HMM in identifying the dorsolateral oscillatory region (DLOR) and nonoscillatory subterritories within the STN. The HMM demarcations were compared to the decisions of a human expert. The HMM identified STN-entry, the ventral boundary of the DLOR, and STN-exit with an error of -0.09 +/- 0.35, -0.27 +/- 0.58, and -0.20 +/- 0.33 mm, respectively (mean +/- standard deviation), and with detection reliability (error < 1 mm) of 95, 86, and 91%, respectively. The HMM was successful despite a very coarse clustering method and was robust to parameter variation. Thus, using an HMM in conjunction with RMS and PSD measures of intraoperative MER can provide improved refinement of STN entry and exit in comparison with previously reported automatic methods, and introduces a novel (intra-STN) detection of a distinct DLOR-ventral boundary.


Gamma oscillations in the mPFC: A potential predictive biomarker of depression and antidepressant effects.
Gamma oscillations have attracted much attention in the field of mood disorders, but their role in depression remains poorly understood. This study aimed to investigate whether gamma oscillations in the medial prefrontal cortex (mPFC) could serve as a predictive biomarker of depression. Chronic restraint stress (CRS) or lipopolysaccharide (LPS) were used to induce depression-like behaviors in mice; local field potentials (LFPs) in the mPFC were recorded by electrophysiological techniques; We found that both CRS and LPS induced significant depression-like behaviors in mice, including increasing immobility durations in the forced swimming test (FST) and tail suspension test (TST) and increasing the latency to feed in the novelty-suppressed feeding test (NSFT). Electrophysiological results suggested that CRS and LPS significantly reduced low and high gamma oscillations in the mPFC. Furthermore, a single injection of ketamine or scopolamine for 24 h significantly increased gamma oscillations and elicited rapid-acting antidepressant-like effects. In addition, fluoxetine treatment for 21 days significantly increased gamma oscillations and elicited antidepressant-like effects. Taken together, our findings suggest that gamma oscillations are strongly associated with depression, yielding new insights into investigating the predictive biomarkers of depression and the time course of antidepressant effects.