Pathologically Benign Lymph Nodes Can Mimic Malignancy on Imaging in Patients With Angiomatoid Fibrous Histiocytoma.
Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm, and its rarity makes studying it difficult. We found that several of our patients with AFH presented with radiologically suspicious local lymph nodes that were sampled because of their imaging characteristics, but the nodes proved to be benign on pathologic evaluation. Although the frequency of this finding is unknown, it seems important for orthopaedic oncologists who care for patients with AFH to know whether suspicious-appearing associated nodes in these patients warrant aggressive management. (1) How often do patients with newly diagnosed AFH present with radiologically suspicious lymph nodes? (2) How often are the radiologically suspicious nodes malignant on pathologic evaluation? In this retrospective, Health Insurance Portability and Accountability Act-compliant study, we used a hospital database to identify all 54 patients treated at our hospital for AFH between 1993 and 2016. This study was performed with institutional review board waiver. All of the patients were considered potentially eligible for analysis. Of the patients, 19 (35%) had pretherapy imaging; during the period in question, pretherapy imaging generally was obtained when there was uncertainty regarding extent of disease. All patients who had imaging underwent MRI, and four also had fluorodeoxyglucose positron emission tomography (FDG PET/CT). Imaging reports were reviewed to identify which patients had nodes that were called suspicious in the reports. All patients with nodes described as suspicious on imaging underwent subsequent pathologic analysis for the presence or absence of metastatic AFH cells in the node. Seven of 19 patients with pretherapy imaging had local lymph nodes called suspicious for nodal metastases. Pathologic analysis of these nodes showed they were malignant in only one patient, whereas six patients had nodes that were histologically benign despite suspicious imaging findings. Benign nodes measured as much as 3.2 × 1.8 cm on MRI and showed maximum standardized uptake values up to 10.9 on FDG PET/CT. Patients with newly diagnosed AFH present with benign lymph nodes that are mistaken for malignancy on imaging. Orthopaedic surgeons and radiologists should be aware of this finding in patients with AFH. Less-invasive management of suspicious nodes, such as image-guided biopsy, may be preferable to nodal resections, as this will help decrease the aggressiveness of surgery for patients with newly diagnosed AFH. Level IV, diagnostic study.


From refugia to contact: Pine processionary moth hybrid zone in a complex biogeographic setting.
Contact zones occur at the crossroad between specific dispersal routes and are facilitated by biogeographic discontinuities. Here, we focused on two Lepidoptera sister species that come in contact near the Turkish Straits System (TSS). We aimed to infer their phylogeographic histories in the Eastern Mediterranean and finely analyze their co-occurrence and hybridization patterns in this biogeographic context. We used molecular mitochondrial and nuclear markers to study 224 individuals from 42 localities. We used discordances between markers and complementary assignment methods to identify and map hybrids and parental individuals. We confirmed the parapatric distribution of Thaumetopoea pityocampa (Lepidoptera: Notodontidae) in the west and Thaumetopoea wilkinsoni in the east and identified a narrow contact zone. We identified several glacial refugia of T. wilkinsoni in southern Turkey with a strong east-west differentiation in this species. Unexpectedly, T. pityocampa crossed the TSS and occur in northern Aegean Turkey and some eastern Greek islands. We found robust evidence of introgression between the two species in a restricted zone in northwestern Turkey, but we did not identify any F1 individuals. The identified hybrid zone was mostly bimodal. The distributions and genetic patterns of the studied species were strongly influenced both by the Quaternary climatic oscillations and the complex geological history of the Aegean region. T. pityocampa and T. wilkinsoni survived the last glacial maximum in disjoint refugia and met in western Turkey at the edge of the recolonization routes. Expanding population of T. wilkinsoni constrained T. pityocampa to the western Turkish shore. Additionally, we found evidence of recurrent introgression by T. wilkinsoni males in several T. pityocampa populations. Our results suggest that some prezygotic isolation mechanisms, such as differences in timing of the adult emergences, might be a driver of the isolation between the sister species.


Development and Validation of a Stability-Indicating UPLC Method for the Determination of Hexoprenaline in Injectable Dosage Form Using AQbD Principles.
A novel and efficient stability-indicating, reverse phase ultra-performance liquid chromatographic (UPLC®) analytical method was developed and validated for the determination of hexoprenaline in an injectable dosage form. The development of the method was performed using analytical quality by design (AQbD) principles, which are aligned with the future requirements from the regulatory agencies using AQbD principles. The method was developed by assessing the impact of ion pairing, the chromatographic column, pH and gradient elution. The development was achieved with a Waters Acquity HSS T3 (50 × 2.1 mm i.d., 1.8 µm) column at ambient temperature, using sodium dihydrogen phosphate 5 mM + octane-1-sulphonic acid sodium salt 10 mM buffer pH 3.0 (Solution A) and acetonitrile (Solution B) as mobile phases in gradient elution (t = 0 min, 5% B; t = 1 min, 5% B; t = 5 min, 50% B; t = 7 min, 5% B; t = 10 min, 5% B) at a flow rate of 0.5 mL/min and UV detection of 280 nm. The linearity was proven for hexoprenaline over a concentration range of 3.50-6.50 µg/mL (R2 = 0.9998). Forced degradation studies were performed by subjecting the samples to hydrolytic (acid and base), oxidative, and thermal stress conditions. Standard solution stability was also performed. The proposed validated method was successfully used for the quantitative analysis of bulk, stability and injectable dosage form samples of the desired drug product. Using the AQbD principles, it is possible to generate methodologies with enhanced knowledge, which can eventually lead to a reduced regulatory risk, high quality data and lower operational costs.


Randomized controlled trials in mild cognitive impairment: Sources of variability.
To examine the variability in performance among placebo groups in randomized controlled trials for mild cognitive impairment (MCI). Placebo group data were obtained from 2 National Institute on Aging (NIA) MCI randomized controlled trials, the Alzheimer's Disease Cooperative Study (ADCS) MCI trial and the Alzheimer's Disease Neuroimaging Initiative (ADNI), which is a simulated clinical trial, in addition to industry-sponsored clinical trials involving rivastigmine, galantamine, rofecoxib, and donepezil. The data were collated for common measurement instruments. The performance of the placebo participants from these studies was tracked on the Alzheimer's Disease Assessment Scale-cognitive subscale, Mini-Mental State Examination, and Clinical Dementia Rating-sum of boxes, and for progression on these measures to prespecified clinical study endpoints. APOE status, where available, was also analyzed for its effects. The progression to clinical endpoints varied a great deal among the trials. The expected performances were seen for the participants in the 2 NIA trials, ADCS and ADNI, with generally worsening of performance over time; however, the industry-sponsored trials largely showed stable or improved performance in their placebo participants. APOE4 carrier status influenced results in an expected fashion on the study outcomes, including rates of progression and cognitive subscales. In spite of apparently similar criteria for MCI being adopted by the 7 studies, the implementation of the criteria varied a great deal. Several explanations including instruments used to characterize participants and variability among study populations contributed to the findings.


Identification of the faecal indicator Escherichia coli in wastewater through the β-D-glucuronidase activity: comparison between two enumeration methods, membrane filtration with TBX agar, and Colilert®-18.
Escherichia coli (E. coli) is one of the most commonly adopted indicators for the determination of the microbiological quality in water and treated wastewater. Two main types of methods are used for the enumeration of this faecal indicator: membrane filtration (MF) and enzyme substrate tests. For both types, several substrates based on the β-D-glucuronidase activity have been commercialized. The specificity of this enzyme for E. coli bacteria has generated considerable use of methods that identify the β-D-glucuronidase activity as a definite indication of the presence of E. coli, without any further confirmation. This approach has been recently questioned for the application to wastewater. The present study compares two methods belonging to the above-mentioned types for the enumeration of E. coli in wastewater: MF with Tryptone Bile X-glucuronide agar and the Colilert®-18 test. Confirmation tests showed low average percentages of false positives and false negatives for both enumeration methods (between 4 and 11%). Moreover, the counting capabilities of these two methods were compared for a set of 70 samples of wastewater having different origins and degrees of treatment. Statistical analysis showed that the Colilert®-18 test allowed on average for a significantly higher recovery of E. coli.


Combining molecular-marker and chemical analysis of Capparis decidua (Capparaceae) in the Thar Desert of Western Rajasthan (india).
The Thar Desert, a very inhospitable place, accommodates only plant species that survive acute drought, unpredictable precipitation, and those can grow in the limited moisture of sandy soils. Capparis decidua is among one of the few plants able to grow well under these conditions. This species is highly exploited and has been naturally taken, as local people use it for various purposes like food, timber and fuel, although, no management or conservation efforts have been established. The present study was conducted in this arid area of Western Rajasthan (India) with the aim to obtain preliminary molecular information about this group of plants. We evaluated diversity among 46 samples of C. decidua using chemical parameters and random amplified polymorphic DNA (RAPD) markers. Fourteen chemical parameters and eight minerals (total 22 variables) of this species fruits were estimated. A total of 14 RAPD primers produced 235 band positions, of which 81.27% were polymorphic. Jaccard's similarity coefficients for RAPD primers ranged from 0.34 to 0.86 with a mean genetic similarity of 0.50. As per observed coefficient of variation, NDF (Neutral Detergent Fiber) content was found to be the most variable trait followed by starch and soluble carbohydrate. The Manhattan dissimilarity coefficient values for chemical parameters ranged between 0.02-0.31 with an average of 0.092. The present study revealed a very low correlation (0.01) between chemical parameters and RAPD-based matrices. The low correlation between chemical- and RAPD-based matrices indicated that the two methods were different and highly variable. The chemical-based diversity will assist in selection of nutritionally rich samples for medicinal purpose, while genetic diversity to face natural challenges and find sustainable ways to promote conservation for future use.


A granular perspective on inclusion: Objectively measured interactions of preschoolers with and without autism.
Children's preschool experiences have consequences for development. However, it is not clear how children's real-time interactions with peers affect their language development; nor is it clear whether these processes differ between children with autism spectrum disorder (ASD) and two other groups of children, those with general developmental delays (DD) and typically developing (TD) children. We used objective measures of movement and vocalizations to quantify children's real-time dyadic vocal interactions and quantify classroom social networks. Participants included 56 preschoolers (22 female; M = 50.14 months) in five inclusive classrooms for children with ASD or DD and their TD peers. Each class was observed monthly on two to five occasions. Overall, children vocalized more to peers who had vocalized more to them in the previous observation. These dyadic vocalization patterns were associated with group differences in social network analyses. Modularity, the cohesiveness of group ties, was lower among children with ASD than it was among TD children or children with DD. Individually, children with ASD exhibited lower total levels of vocalizations with peers (lower degree centrality) than TD children and children with DD. In an exploratory analysis with a subset of the participants, children's degree centrality was strongly associated with their end-of-year assessed language abilities, even when accounting for mean differences between groups. Findings highlight the impact peers and social networks play in real-time language use and in the developing language abilities of children with ASD in inclusion classrooms. LAY SUMMARY: This study objectively measured associations between children's peer vocal interactions and assessed language abilities in inclusion classrooms for children with autism spectrum disorder (ASD) and their peers. All children benefited from peers talking to them, but children with ASD were less central to classroom speech networks than were typically developing children. Children's centrality to social speech networks, regardless of ASD status, was associated with assessed language abilities.


Cardiac automaticity: basic concepts and clinical observations.
The purpose of this report was to review the basic mechanisms underlying cardiac automaticity. Second, we describe our clinical observations related to the anatomical and functional characteristics of sinus automaticity. We first reviewed the main discoveries regarding the mechanisms responsible for cardiac automaticity. We then analyzed our clinical experience regarding the location of sinus automaticity in two unique populations: those with inappropriate sinus tachycardia and those with a dominant pacemaker located outside the crista terminalis region. We studied 26 patients with inappropriate sinus tachycardia (age 34 ± 8 years; 21 females). Non-contact endocardial mapping (Ensite 3000, Endocardial Solutions) was performed in 19 patients and high-density contact mapping (Carto-3, Biosense Webster with PentaRay catheter) in 7 patients. The site of earliest atrial activation shifted after each RF application within and outside the crista terminalis region, indicating a wide distribution of atrial pacemaker sites. We also analyzed 11 patients with dominant pacemakers located outside the crista terminalis (age 27 ± 7 years; five females). In all patients, the rhythm was the dominant pacemaker both at rest and during exercise and located in the right atrial appendage in 6 patients, in the left atrial appendage in 4 patients, and in the mitral annulus in 1 patient. Following ablation, earliest atrial activation shifted to the region of the crista terminalis at a slower rate. Membrane and sub-membrane mechanisms interact to generate cardiac automaticity. The present observations in patients with inappropriate sinus tachycardia and dominant pacemakers are consistent with a wide distribution of pacemaker sites within and outside the boundaries of the crista terminalis.


Structural constraints on the covariance matrix derived from multiple aligned protein sequences.
Residue contact predictions were calculated based on the mutual information observed between pairs of positions in large multiple protein sequence alignments. Where previously only the statistical properties of these data have been considered important, we introduce new measures to impose constraints that make the contact map more consistent with a three dimensional structure. These included global (bulk) properties and local secondary structure properties. The latter allowed the contact constraints to be employed at the level of filtering pairs of secondary structure contacts which led to a more efficient (lower-level) implementation in the PLATO structure prediction server. Where previously the measure of success with this method had been whether the correct fold was predicted in the top 10 ranked models, with the current implementation, our summary statistic is the number of correct folds included in the top 10 models--which is on average over 50 percent.


Caregivers' perception of adults with Down syndrome willingness to participate in research.
Historically, individuals with Down syndrome have been excluded from clinical research. Our objective was to assess the degree of interest adults with Down syndrome have in participating in research from the perspective of the caregivers who care for them. We conducted an online survey of N = 390 caregivers of adults with Down syndrome and asked about interest in research participation and demographics. Caregivers were mostly family members, older than 55 years, and White. Caregivers reported that the adult with Down syndrome that they cared for would be more comfortable participating in research that was physiological, such as research involving fit bits (70.2% would participate), exercise (63.3%) or diet apps (53.9%), whereas they would be less likely to participate in clinical trials involving more invasive procedures such as injections (10.9%) and laboratory exams like MRIs (32.0%). We found little difference by age or gender of the adult with Down syndrome or by caregiver education level. Our survey identified high interest for less invasive studies, illustrating acceptability of observational and lifestyle studies. More effort may be needed to understand fear and barriers to participation and to create tools and methods to increase interest in more invasive studies.


Relationship between enteric migrating motor complex and the sleep cycle.
To address the question of synchrony between two major biorhythms with a similar periodicity, the cortical rapid eye movement (REM)/non-REM sleep cycle and the enteric migrating motor complex (MMC cycle), we recorded upper small bowel motor activity and sleep activity during nocturnal and diurnal sleep in six healthy subjects. Motility was measured continuously using a fine (2.2 mm OD) and relatively comfortable nasojejunal probe with two pressure-sensitive microtransducers positioned under fluoroscopic control on either side of the ligament of Treitz. Sleep stages were recorded while the subjects slept in a sleep laboratory. Each subject was studied twice; once during normal nocturnal sleep and then after acute reversal of sleep by advancing the time of going to bed by 4 h each night for three nights. The total duration of sleep was similar for diurnal and nocturnal sleep. There was a significantly higher number of REM episodes (P less than 0.001) and REM sleep stage shifts (P less than 0.02) during diurnal (reversed) sleep. During sleep (both diurnal and nocturnal) there was a significant reduction in the MMC cycle length (P less than 0.02, P less than 0.03) and the duration of phase II of the MMC (P less than 0.009, P less than 0.02). The distribution of MMCs among sleep stages and REM sleep was consistent with a random distribution. These data show that periodic activity in the gut is modulated by the presence or absence of sleep, but they also are consistent with the hypothesis that the two cycles are independent and that one is not contingent upon the other.


Stimulatory effects of cholecystokinin on isolated perifused islets inhibited by potent and specific antagonist L 364718 [corrected].
The influence of L 364718 on islet responsiveness to sulfated cholecystokinin (CCK-8S) was investigated. In islets whose inositol-containing phospholipids were prelabeled during a 2-h incubation period, subsequent exposure to L 364718 (1 nM) significantly impaired the secretion of insulin usually noted in response to 200 nM CCK-8S in the simultaneous presence of 7 mM glucose. A higher level of the antagonist (10 nM) completely abolished insulin secretion. L 364718 (1-10 nM) reduced the efflux of 3H from myo-[2-3H]-inositol prelabeled islets in parallel with the reduction in secretion. L 364718 (10 nM) significantly reduced the accumulation of 3H-containing inositol phosphates usually noted with CCK-8S addition. L 364718, at levels 10- to 100-fold greater than those necessary to attenuate CCK-8S-induced insulin secretion, had no adverse effect on the insulin secretory response of freshly isolated islets to 10 mM glucose alone, 5 mM D-glyceraldehyde, 15 mM alpha-ketoisocaproate, or 50 ng/ml gastric inhibitory polypeptide. L 364718 (1000 nM) had no adverse influence on carbamylcholine (1 mM)-induced phosphoinositide hydrolysis. These results establish L 364718 as a potent and highly selective antagonist of cholecystokinin's stimulatory actions on beta-cells. Because of its potency, selectivity, and oral effectiveness, in vivo studies with L 364718, aimed at unraveling the pleiotropic effects of CCK-8S on glucose and insulin homeostasis, seem feasible.


Adenosine in the treatment of stroke: yes, maybe, or absolutely not?
Agonist stimulation of adenosine A(1) receptors has been consistently shown to result in reduction of brain damage following experimentally induced global and focal brain ischaemia in animals. Unsurprisingly, the use of adenosine A(1) receptors as targets for the development of clinical therapeutics suitable for treatment of ischaemic brain disorders has been suggested by many authors. The latest studies of adenosine and its receptors indicate that adenosine-mediated actions might be far more complex than originally anticipated, casting some doubt about the rapid development of stroke treatment based on adenosine. This review discusses the possible role of adenosine receptor subtypes (A(1), A(2) and A(3)) in the context of their potential as therapeutics in stroke.


[Efficacy of cycloferon in the treatment of brucellosis].
Therapeutic potential of cyclopheron was evaluated as exemplified by the treatment of patients with chronic brucellosis. Positive clinical dynamics during combined treatment including cyclopheron is apparent as reduced duration of intoxication and inflammation, improved quality of life, decreased frequency of exacerbation of the infectious process and development of intercurrent diseases. These effects are shown to be due to immunomodulating activity of cyclopheron and suppression of lipid peroxidation. Also, the drug increases activity of antioxidants, decreases the levels of proinflammatory (and to a lesser degree of anti-inflammatory) cytokines.


Balancing selection and introgression of newt immune-response genes.
The importance of interspecific introgression as a source of adaptive variation is increasingly recognized. Theory predicts that beneficial genetic variants cross species boundaries easily even when interspecific hybridization is rare and gene flow is strongly constrained throughout the genome. However, it remains unclear whether certain classes of genes are particularly prone to adaptive introgression. Genes affected by balancing selection (BS) may constitute such a class, because forms of BS that favour novel, initially rare alleles, should facilitate introgression. We tested this hypothesis in hybridizing newts by comparing 13 genes with signatures of BS, in particular an excess of common non-synonymous polymorphisms, to the genomic background (154 genes). Parapatric hybridizing taxa were less differentiated in BS candidate genes than more closely related allopatric lineages, while the opposite was observed in the control genes. Coalescent and forward simulations that explored neutral and BS scenarios under isolation and migration showed that processes other than differential gene flow are unlikely to account for this pattern. We conclude that BS, probably involving a form of novel allele advantage, promotes introgression. This mechanism may be a source of adaptively relevant variation in hybridizing species over prolonged periods.


Transforming growth factor beta-1 expression in macrophages of human chronic periapical diseases.
The objective of this study was to observe the distribution of macrophages (MPs) expressing transforming growth factor beta-1 (TGF-β1) in tissue samples from patients with different human chronic periapical diseases. In this study, samples were collected from 75 volunteers, who were divided into three groups according to classified standards, namely, healthy control (N = 25), periapical granuloma (N = 25), and periapical cyst (N = 25). The samples were fixed in 10% buffered formalin for more than 48 h, dehydrated, embedded, and stained with hematoxylin and eosin for histopathology. Double immunofluorescence was conducted to analyze the expression of TGF-β-CD14 double-positive MPs in periapical tissues. The number of double-positive cells (cells/mm2) were significantly higher in the chronic periapical disease tissues (P < 0.01) compared to that in the control tissue; in addition, the density of TGF-β1-CD14 double positive cells was significantly higher in the periapical cyst group than in the periapical granuloma group (P < 0.01). The number of TGF-β1 expressing macrophages varied with human chronic periapical diseases. The TGF-β1-CD14 double-positive cells might play an important role in the pathology of human chronic periapical diseases.


A review of twenty-one rectal mucosectomy and ileal pouch pull through procedures.
Twenty-one patients with chronic ulcerative colitis (CUC) or familial polyposis underwent total colectomy, rectal mucosectomy, ileal pouch formation and anastomosis of the pouch to the dentate line. Eleven (52%) intraoperative problems occurred. No deaths resulted. Ten (48%) postoperative complications were treated without operative intervention. Ten postoperative complications required a minor or major procedure to remedy the problem. The most common major complications were four small bowel obstructions. The only septic complication was a single wound infection. Functional results have been satisfactory with 14 of 19 (74%) having six or fewer bowel movements per day. Most patients do not wear perineal pads either day or night. Only one patient felt his lifestyle had worsened. Seventeen of 19 (90%) patients were satisfied with their result and would choose to have the operation again. Frequent diarrheal stools associated with incontinence was the primary reason for a failure and excision of one pouch. This procedure is becoming the alternative of choice for CUC and polyposis because of the ability to cure the disease as well as preserve anal sphincter function.


A Systematic Review on the Impact of Genetic Testing for Familial Melanoma II: Psychosocial Outcomes and Attitudes.
Although genetic testing for known familial melanoma genes is commercially available, clinical implementation has been restrained as utility is unclear, concerns of causing psychological distress are often cited, and consumer interest and perceptions are not well understood. A review of studies exploring participant-reported psychosocial outcomes and attitudes towards genetic testing for familial melanoma will provide insight into common emotional and cognitive responses. Database searches of PubMed, Embase, CINAHL, PsycINFO and the Cochrane Library were conducted using a date range of January 1995 to June 2020. Studies examining any psychosocial outcomes alongside genetic testing (real or hypothetical), in participants described as having a high risk of melanoma, were eligible. A narrative synthesis of results was used to describe psychosocial outcomes and summarise participant beliefs and attitudes towards genetic testing. Limited evidence of adverse psychosocial outcomes was found. No impacts on perceived risk or control were reported, and minimal decisional regret was recorded. Generalised distress was comparable between both genetic mutation carriers and non-carriers, often decreasing over time from pretesting levels. Melanoma-specific distress was frequently higher in carriers than non-carriers; however, this difference was present prior to testing and often associated with personal melanoma history. Overall, participants' attitudes towards testing were largely positive, with benefits more frequently described than limitations, and support for testing minors was strong. This review has found evidence of few adverse psychological outcomes following genetic testing. There was no indication of increased distress after genetic test results had been disclosed. If these findings were replicated in additional, larger, diverse populations over a longer follow-up period, this would be compelling evidence to guide clinical recommendations.


Treating amblyopia with liquid crystal glasses: a pilot study.
PURPOSE. To evaluate the use of liquid crystal glasses (LCG) for the treatment of amblyopia caused by refractive errors, strabismus, or both. METHODS. In this noncomparative, prospective, interventional case series, 28 children (age range, 4-7.8 years) with monocular amblyopia participated, of which 24 completed the study. In the LCG, the occluding and nonoccluding phases of the flicker were electronically set in all patients at a fixed rate. The rate was set so that accumulated occlusion was 5 hours during 8 hours' weartime. Occlusion was applied only to the good eye. All 24 children were followed up regularly for 9 months. Best corrected VA for distance and near, fixation patterns, and binocular function were measured. VA for distance was measured with the Snellen chart and for near with the Rossano/Weiss chart. RESULTS. Mean VA for distance at the end of the study (after 9 months) was 0.59 (SD, 0.16) compared with 0.27 (SD, 0.09) at the beginning (P < 0.001). Most of the children (92%) complied well with the treatment. (Good compliance was defined as wearing the LCG for at least 8 hours per day.) Stereopsis at the end of treatment was good (better than 60 sec arc) in 21% of the children compared with 8% at the beginning. No serious adverse events were recorded. CONCLUSIONS. The use of LCG in patients with amblyopia yielded an improvement in near and distance VA and in stereopsis. Treatment was well accepted by children and parents.


Effectiveness of training in disease management for patients with type 2 diabetes mellitus: A systematic review.
Diabetes mellitus (DM) is included in the disease group described as the pandemic of the century. Although disease management is possible, it can significantly reduce the quality of life when glycaemic control is poor. The objective of this systematic review was to examine the effectiveness of different educational programmes on the management of the disease among type 2 DM patients. In the literature review, the flow chart of PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) was used. A literature search was conducted from 2010 to 2020 using the Ulakbim National Database, Google Scholar, Scopus, PubMed, Library, Science Direct, Web of Science, Medline, Ebscohost and Cochrane Library, and 18 English randomised controlled studies were included. Within the scope of these studies, it was found that individualised and face-to-face training and long-term follow-up after the training were effective on metabolic control. Peer support was also determined as an important factor in the efficacy of the training. In line with the training, the self-management and quality-of-life scores of the individuals with diabetes were positively affected. It can be suggested that planned and regular training has a positive effect on metabolic control variables, self-management behaviours and quality of life of individuals with diabetes. Regular training for individuals with diabetes and follow-up for more than 6 months are recommended since they have a positive effect on the disease. It is also recommended to integrate peer support into training programmes.


Rectal neuroendocrine tumors: Current advances in management, treatment, and surveillance.
Rectal neuroendocrine neoplasms (r-NENs) are considered among the most frequent digestive NENs, together with small bowel NENs. Their incidence has increased over the past few years, and this is probably due to the widespread use of endoscopic screening for colorectal cancer and the advanced endoscopic procedures available nowadays. According to the current European Neuroendocrine Tumor Society (ENETS) guidelines, well-differentiated r-NENs smaller than 10 mm should be endoscopically removed in view of their low risk of local and distant invasion. R-NENs larger than 20 mm are candidates for surgical resection because of their high risk of distant spreading and the involvement of the muscularis propria. There is an area of uncertainty regarding tumors between 10 and 20 mm, in which the metastatic risk is intermediate and the endoscopic treatment can be challenging. Once removed, the indications for surveillance are scarce and poorly codified by international guidelines, therefore in this paper, a possible algorithm is proposed.


Drug-drug relationship based on target information: application to drug target identification.
Drugs that bind to common targets likely exert similar activities. In this target-centric view, the inclusion of richer target information may better represent the relationships between drugs and their activities. Under this assumption, we expanded the "common binding rule" assumption of QSAR to create a new drug-drug relationship score (DRS). Our method uses various chemical features to encode drug target information into the drug-drug relationship information. Specifically, drug pairs were transformed into numerical vectors containing the basal drug properties and their differences. After that, machine learning techniques such as data cleaning, dimension reduction, and ensemble classifier were used to prioritize drug pairs bound to a common target. In other words, the estimation of the drug-drug relationship is restated as a large-scale classification problem, which provides the framework for using state-of-the-art machine learning techniques with thousands of chemical features for newly defining drug-drug relationships. Various aspects of the presented score were examined to determine its reliability and usefulness: the abundance of common domains for the predicted drug pairs, c.a. 80% coverage for known targets, successful identifications of unknown targets, and a meaningful correlation with another cutting-edge method for analyzing drug similarities. The most significant strength of our method is that the DRS can be used to describe phenotypic similarities, such as pharmacological effects.


Myths and facts about safe patient handling in rehabilitation.
As the incidence of injuries associated with patient-handling tasks remains high in the rehabilitation community, interdisciplinary discussions on optimal methods for preventing injuries and ensuring good care continue. A national task force consisting of representatives from the Association of Rehabilitation Nurses, the American Physical Therapy Association, and the Veterans Health Administration identified myths that have been promulgated on both sides of the discussion, focusing especially on rehabilitation practices. The purpose of this article is to dispel these myths by using evidence-based methods. Evidence should be applied in discussions of safe patient handling, and although concern about patient outcomes is critical, there is no evidence that the use of patient-handling technology undermines rehabilitation goals and strong evidence that these practices enhance the safety of rehabilitation care providers. Further research on the impact of safe patient-handling practices on rehabilitation goals and continued communication between rehabilitation providers are recommended.


A plasmid-encoded UmuD homologue regulates expression of Pseudomonas aeruginosa SOS genes.
The Pseudomonas aeruginosa plasmid pUM505 contains the umuDC operon that encodes proteins similar to error-prone repair DNA polymerase V. The umuC gene appears to be truncated and its product is probably not functional. The umuD gene, renamed umuDpR, possesses an SOS box overlapped with a Sigma factor 70 type promoter; accordingly, transcriptional fusions revealed that the umuDpR gene promoter is activated by mitomycin C. The predicted sequence of the UmuDpR protein displays 23 % identity with the Ps. aeruginosa SOS-response LexA repressor. The umuDpR gene caused increased MMC sensitivity when transferred to the Ps. aeruginosa PAO1 strain. As expected, PAO1-derived knockout lexA- mutant PW6037 showed resistance to MMC; however, when the umuDpR gene was transferred to PW6037, MMC resistance level was reduced. These data suggested that UmuDpR represses the expression of SOS genes, as LexA does. To test whether UmuDpR exerts regulatory functions, expression of PAO1 SOS genes was evaluated by reverse transcription quantitative PCR assays in the lexA- mutant with or without the pUC_umuD recombinant plasmid. Expression of lexA, imuA and recA genes increased 3.4-5.3 times in the lexA- mutant, relative to transcription of the corresponding genes in the lexA+ strain, but decreased significantly in the lexA- /umuDpR transformant. These results confirmed that the UmuDpR protein is a repressor of Ps. aeruginosa SOS genes controlled by LexA. Electrophoretic mobility shift assays, however, did not show binding of UmuDpR to 5' regions of SOS genes, suggesting an indirect mechanism of regulation.


Surgical Treatment of Bullous Exudative Retinal Detachment Secondary to Atypical Bilateral Central Serous Chorioretinopathy.
This study aimed to report the diagnostic process, treatment, and follow-up of a patient with bullous exudative retinal detachment (RD) associated with an atypical variant of bilateral central serous chorioretinopathy (CSCR). A 28-year-old woman was referred to our clinic for total bullous RD in the right eye with a vision level of light perception only. She had been previously diagnosed with idiopathic uveal effusion syndrome and treated with systemic corticosteroid therapy with no response, and was referred to us for scleral window surgery. Four-quadrant scleral window surgery with external drainage of the subretinal fluid was performed, resulting in a transient partial attachment of the retina. RD started to progress again within 3 weeks, which prompted comprehensive imaging together with more advanced systemic workup for systemic lupus erythematosus and other rheumatological and immunological diseases. Systemic corticosteroid therapy was initiated during this period but did not stop the progression and was discontinued after a short time. Fluorescein angiography and indocyanine green angiography revealed multifocal choroidal leakage foci and large choroidal vessels without any intraocular inflammation findings and led to the diagnosis of atypical CSCR. Pars plana vitrectomy (PPV), internal drainage of the subretinal fluid, endolaser to the focal leakage areas, and intravitreal aflibercept injection were performed. Visual acuity increased to 0.8 within 8 months after the surgery with no recurrence. Bullous exudative RD is a very rare and atypical form of CSCR, and a favorable outcome can be obtained with PPV and surgical drainage of subretinal fluid followed by laser photocoagulation.


[Gastrointestinal surgery and gastroenterology. I. Introduction].
The enormous increase in theoretical knowledge and technical possibilities in general surgery has led to differentiation and subspecialization. Gastrointestinal surgery is now recognized as a distinguished area of specific interest within the field of general surgery. It covers the surgical diagnosis and treatment of benign and malignant diseases of the digestive tract, including liver and pancreas. Most gastrointestinal diseases require a multidisciplinary approach in which the gastroenterologist and the gastrointestinal surgeon are key figures. This Journal is planning a series of articles highlighting the recent developments and current state of the art of gastrointestinal surgery, with special emphasis on the close connection with gastroenterology.


Treatment of advanced hepatocellular carcinoma: intraarterial infusion chemotherapy combined with interferon.
Because of the difficulties of low sensitivity for anticancer agents and giving a sufficient dose because of chronic liver dysfunction, chemotherapy may not play a central role in the treatment of hepatocellular carcinoma (HCC), especially those with liver cirrhosis. However, chemotherapy must be one of the important possibilities of multimodal treatment for advanced HCC, for which hepatic resection, percutaneous ablation, transcatheter arterial embolization and other general therapies would not be effective or even possible. Also, intraarterial perfusion chemotherapy is a common therapy for HCC and it is not difficult to maintain; but the effective rate is not sufficient. Recently, the combination therapy of subcutaneous interferon (IFN)-alpha and intraarterial 5-fluorouracil (5-FU) showed an outstanding response rate for intractable HCC (with portal vein thrombosis). In addition, recent preclinical and clinical studies have revealed that the mechanism of combination therapy may concern direct antitumor effects (through cell-cycle arrest and induction of apoptosis) and indirect actions (through immunocompetent cells and antiangiogenic effect). For the further advance of HCC treatment and prognosis, this therapy might be a promising treatment modality and is expected to develop. In this review, we summarize recent clinical and preclinical data regarding IFN-alpha and 5-FU combination therapy and discuss the further prospects of this therapy.


Zipf and Heaps laws from dependency structures in component systems.
Complex natural and technological systems can be considered, on a coarse-grained level, as assemblies of elementary components: for example, genomes as sets of genes or texts as sets of words. On one hand, the joint occurrence of components emerges from architectural and specific constraints in such systems. On the other hand, general regularities may unify different systems, such as the broadly studied Zipf and Heaps laws, respectively concerning the distribution of component frequencies and their number as a function of system size. Dependency structures (i.e., directed networks encoding the dependency relations between the components in a system) were proposed recently as a possible organizing principles underlying some of the regularities observed. However, the consequences of this assumption were explored only in binary component systems, where solely the presence or absence of components is considered, and multiple copies of the same component are not allowed. Here we consider a simple model that generates, from a given ensemble of dependency structures, a statistical ensemble of sets of components, allowing for components to appear with any multiplicity. Our model is a minimal extension that is memoryless and therefore accessible to analytical calculations. A mean-field analytical approach (analogous to the "Zipfian ensemble" in the linguistics literature) captures the relevant laws describing the component statistics as we show by comparison with numerical computations. In particular, we recover a power-law Zipf rank plot, with a set of core components, and a Heaps law displaying three consecutive regimes (linear, sublinear, and saturating) that we characterize quantitatively.


Comparing Propensity Score Methods Versus Traditional Regression Analysis for the Evaluation of Observational Data: A Case Study Evaluating the Treatment of Gram-Negative Bloodstream Infections.
Propensity score methods are increasingly being used in the infectious diseases literature to estimate causal effects from observational data. However, there remains a general gap in understanding among clinicians on how to critically review observational studies that have incorporated these analytic techniques. Using a cohort of 4967 unique patients with Enterobacterales bloodstream infections, we sought to answer the question "Does transitioning patients with gram-negative bloodstream infections from intravenous to oral therapy impact 30-day mortality?" We conducted separate analyses using traditional multivariable logistic regression, propensity score matching, propensity score inverse probability of treatment weighting, and propensity score stratification using this clinical question as a case study to guide the reader through (1) the pros and cons of each approach, (2) the general steps of each approach, and (3) the interpretation of the results of each approach. 2161 patients met eligibility criteria with 876 (41%) transitioned to oral therapy while 1285 (59%) remained on intravenous therapy. After repeating the analysis using the 4 aforementioned methods, we found that the odds ratios were broadly similar, ranging from 0.84-0.95. However, there were some relevant differences between the interpretations of the findings of each approach. Propensity score analysis is overall a more favorable approach than traditional regression analysis when estimating causal effects using observational data. However, as with all analytic methods using observational data, residual confounding will remain; only variables that are measured can be accounted for. Moreover, propensity score analysis does not compensate for poor study design or questionable data accuracy.


Physical activity level is impaired and diet dependent in preterm newborn pigs.
Preterm infants show delayed development of motor function after birth. This may relate to functional immaturity of many organs, including the gut and brain. Using pigs as model for preterm infants, we hypothesized that early initiation of enteral feeding stimulates both gut growth and neonatal physical activity. In experiment 1, preterm and term pigs were fed parenteral nutrition (PN) or PN plus bovine colostrum (BC, 16-64 ml/kg/d enterally) for 5 d. In experiment 2, preterm pigs were fed PN+BC or PN+formula for 5 d. In experiment 3, preterm pigs were fed BC, formula, or human milk (HM) for 10 d. Incubator home cage activity (HCA) was quantified by continuous camera recordings. Preterm birth was associated with reduced intestinal weight and HCA (experiment 1), and BC or formula supplementation increased intestinal weights and HCA (experiments 1+2). Enteral BC and HM feeding increased HCA, intestinal weights, and necrotizing enteritis resistance, relative to formula (experiment 3). Preterm pigs show decreased physical activity, and the first enteral feeds diet dependently stimulate both gut growth and physical activity. The effects may arise from maturation of digestive, metabolic, and neurological functions, including gut serotonin production, by the first enteral feeds and milk bioactive factors.


Cofactor bypass variants reveal a conformational control mechanism governing cell wall polymerase activity.
To fortify their cytoplasmic membrane and protect it from osmotic rupture, most bacteria surround themselves with a peptidoglycan (PG) exoskeleton synthesized by the penicillin-binding proteins (PBPs). As their name implies, these proteins are the targets of penicillin and related antibiotics. We and others have shown that the PG synthases PBP1b and PBP1a of Escherichia coli require the outer membrane lipoproteins LpoA and LpoB, respectively, for their in vivo function. Although it has been demonstrated that LpoB activates the PG polymerization activity of PBP1b in vitro, the mechanism of activation and its physiological relevance have remained unclear. We therefore selected for variants of PBP1b (PBP1b*) that bypass the LpoB requirement for in vivo function, reasoning that they would shed light on LpoB function and its activation mechanism. Several of these PBP1b variants were isolated and displayed elevated polymerization activity in vitro, indicating that the activation of glycan polymer growth is indeed one of the relevant functions of LpoB in vivo. Moreover, the location of amino acid substitutions causing the bypass phenotype on the PBP1b structure support a model in which polymerization activation proceeds via the induction of a conformational change in PBP1b initiated by LpoB binding to its UB2H domain, followed by its transmission to the glycosyl transferase active site. Finally, phenotypic analysis of strains carrying a PBP1b* variant revealed that the PBP1b-LpoB complex is most likely not providing an important physical link between the inner and outer membranes at the division site, as has been previously proposed.


Technical Note: A benchtop cone-beam x-ray fluorescence computed tomography (XFCT) system with a high-power x-ray source and transmission CT imaging capability.
This report describes upgrades and performance characterization of an experimental benchtop cone-beam x-ray fluorescence computed tomography (XFCT) system capable of determining the spatial distribution and concentration of metal probes such as gold nanoparticles (GNPs). Specifically, a high-power (~3 kW) industrial x-ray source and transmission CT capability were deployed in the same platform under the cone-beam geometry. All components of the system are described in detail, including the x-ray source, imaging stage, cadmium-telluride detector for XFCT, and flat-panel detector for transmission CT imaging. The general data acquisition scheme for XFCT and transmission CT is also explicated. The detection limit of the system was determined using calibration samples containing water and GNPs at various concentrations. Samples were then embedded in a small-animal-sized phantom and imaged with XFCT and CT. The reconstructed XFCT and CT images were compared and analyzed using the contrast-to-noise ratio for each GNP-containing region of interest. Also, measurements of the incident beam spectra used for XFCT and CT imaging were made and the corresponding x-ray dose rates were estimated, along with the imaging dose. The present configuration produced a GNP detection limit of 0.03 wt. % with the delivery of an effective dose of 1.87 cGy per projection. XFCT scan of an animal-sized phantom containing low concentrations (down to 0.03 wt. %) of GNP-loaded inserts can be performed within an hour. The high performance of the system combined with the ability to perform transmission CT in tandem with XFCT suggests that the currently developed benchtop cone-beam XFCT/CT system, in conjunction with GNPs, can be used for routine multimodal preclinical imaging tasks with less stringent dose constraints such as ex vivo imaging. With further effort to minimize XFCT imaging dose as discussed in this report, it may also be used for in vivo imaging.


Ultrasound-guided ethanol ablation versus the Sistrunk operation as a primary treatment for thyroglossal duct cysts.
This study compared ethanol ablation (EA) with the Sistrunk operation (SO) with regard to feasibility, treatment efficacy, and cost-effectiveness. The goal was to evaluate whether EA could replace SO as a primary treatment modality for thyroglossal duct cysts (TGDCs). This retrospective case-control study included patients with TGDCs who were treated with either EA or SO between 2016 and 2022. The primary outcome variables evaluated were treatment efficacy (as measured by the volume reduction rate [VRR] and treatment success rate), complications, and cost-effectiveness. A total of 72 patients were enrolled, with 33 in the EA group and 39 in the SO group. The procedure or operation times for the EA and SO groups were 9 and 82 minutes, respectively (P<0.001). At the final follow-up appointment, the VRR was 94.1% for the EA group and 100.0% for the SO group (P<0.001). Treatment success was achieved for 32 patients (97.0%) in the EA group and for all 39 patients (100.0%) in the SO group (P=0.458). The overall complication rates were 0.0% and 17.9% in the EA and SO groups, respectively (P=0.013). The total costs, including all treatment procedures and follow-up ultrasound examinations, were $485 and $1,081.7 for the EA and SO groups, respectively (P<0.001). EA demonstrates superiority over SO in terms of feasibility, safety, and costeffectiveness, while maintaining comparable treatment efficacy. Despite the need for multiple treatment sessions in approximately one-quarter of patients, EA can serve as a primary treatment modality for selected patients with TGDCs, supplanting SO.


Effect of gemcitabine on the expression of apoptosis-related genes in human pancreatic cancer cells.
To investigate the expression of genes involved in the gemcitabine-induced cytotoxicity in human pancreatic cancer cells. A human pancreatic cancer cell line, PANC-1, was cultured. 1x10(4) PANC-1 cells were plated in 96-well microtiter plates. After being incubated for 24 h, gemcitabine was added to the medium at concentrations ranging 2.5-1000 mg/L. The AlamarBlue dye method was used for cell growth analysis. DNA fragmentation was quantitatively assayed using a DNA fragmentation enzyme-linked immunosorbent assay (ELISA) kit. PAP and TP53INP1 mRNA expression was determined using the reverse transcription-polymerase chain reaction with semi-quantitative analysis. The expression of GSK-3beta and phospho-GSK-3beta proteins was examined with Western blot analysis. The IC50 for the drug after a 48-h exposure to gemcitabine was 16 mg/L. The growth of PANC-1 cells was inhibited by gemcitabine in a concentration-dependent manner (P<0.0001) and the cell growth was also inhibited throughout the time course (P<0.0001). The DNA fragmentation rate in the gemcitabine-treated group at 48 h was 44.7%, whereas it was 25.3% in the untreated group. The PAP mRNA expression was decreased after being treated with gemcitabine, whereas the TP53INP1 mRNA was increased by the gemcitabine treatment. Western blot analysis showed that phospho- GSK-3beta (ser9) was induced by the gemcitabine treatment. Gemcitabine suppresses PANC-1 cell proliferation and induces apoptosis. Apoptosis is considered to be associated with the inhibition of PAP and GSK-3beta, and the activation of TP53INP1 and pospho-GSK-3beta (ser9).


Gender and age are associated with healthy food purchases via grocery voucher redemption.
Grocery vouchers that specifically target foods associated with reduced cardiovascular disease (CVD) risk result in increased consumption of those foods. In regions with disproportionately high CVD rates, there is little research concerning the impact of vouchers on purchases of risk-reducing foods when there are no restrictions placed on grocery voucher redemption. Since many food assistance programs place few restrictions on type of foods that can be purchased, identifying demographic factors associated with purchasing habits is a prerequisite to promoting healthy eating. The purpose of this study was to determine the associations of age, gender, education and income level with purchasing of healthful foods through the use of a grocery voucher in a rural food desert (poverty rate of ≥20% and ≥33% of residents living >16 km from a large grocery store) with high rates of chronic disease. The effectiveness of an intervention that included a media campaign, a $5 grocery voucher, local heart healthy food branding and a grocery store event was tested. Brief nutritional articles were published in both local newspapers during four consecutive weeks. These articles explained the physiological actions of healthy foods and listed a health-promoting recipe. During the fourth week of the media campaign, a voucher for a $5 grocery gift card redeemable at one of either community grocery stores was also printed in both local newspapers. In each store, foods that are known to be associated with a reduced risk of CVD were marked with a blue logo. Participants (N=311) completed a questionnaire that assessed demographics and usual servings of fruits, vegetables and grains. Participants received a $5 grocery card and a list of labelled foods. Returned grocery receipts were stapled to the questionnaires to analyse the relationship between demographics and food choices. Participants who bought at least one labelled food item were older (M=48.5, SD=14.7) than those who did not buy any of these items (M=42.3, SD=16.4; p=0.0008). There was a significant association between labelled food purchases and gender, with 47% of male participants purchasing at least one labelled food item compared with 63% of females in the study (p = 0.008). There were no significant associations between purchase of labelled food items and either education or income. The significant predictors were age (p=0.003) and gender (p=0.01). For every 10 year increase in age, there was a 29% increase in the likelihood that at least one labelled food item would be purchased. Male participants were 48% less likely to purchase at least one designated food item than female participants were. Younger adults and men may be less responsive to media-based educational strategies, heart-healthy food labelling and grocery vouchers to defray the cost of healthy eating than older adults and women. Previous studies show that concerns about cost and availability of foods are greater factors in the decision to purchase these foods than demographic characteristics. However, age and gender are associated with the likelihood of using grocery vouchers for the purchase of healthful foods. Additional research is needed to determine whether different educational strategies paired with food labelling and grocery vouchers may be successful strategies to promote purchase of healthful foods, particularly for men and younger adults.


A comparison of spreading and motility behaviour of 8701-BC breast carcinoma cells on type I, I-trimer and type V collagen substrata. Evidence for a permissive effect of type I-trimer collagen on cell locomotion.
Ductal infiltrating carcinoma (d.i.c.) of human breast is a highly invasive neoplasm characterized by enhanced deposition of collagen. Paradoxically, enhanced collagen deposition is not correlated with inhibition of the migration of tumour cells into the host tissue. d.i.c. is characterized by the reappearance of 'embryonic' type I-trimer collagen and an increase in type V collagen content in the matrix. The effects of these two collagen types were compared with type I collagen as culture substrata on the spreading pattern, cytoskeletal organization and motile behaviour of 8701-BC breast carcinoma cells using rhodamine-phalloidin staining, a DNAase I-competition assay, scanning electron microscopy and time-lapse video-microscopy. Cells grown on type I collagen were stationary, showing a well-spread morphology and an extensive stress fibre pattern. Cells grown on type V collagen were also stationary, but displayed a poorly spread and elongated morphology. In contrast, cells grown on trimer collagen were motile and displayed a compact morphology and a reduced content of stress fibres. Both single-cell and group motility were detectable on trimer collagen substratum. These data are consistent with the existence of two opposite local signals, type I-trimer and type V collagens, which may confer a more or a less metastatic phenotype on breast carcinoma cells. Moreover, the synthesis of trimer collagen in d.i.c. is conceivably instrumental in providing new stromal pathways permitting tumour cells to infiltrate the host tissue.


Host Genetics of Cytomegalovirus Pathogenesis.
Human cytomegalovirus (HCMV) is a ubiquitous herpes virus (human herpes virus 5) with the highest morbidity and mortality rates compared to other herpes viruses. Risk groups include very young, elderly, transplant recipient, and immunocompromised individuals. HCMV may cause retinitis, encephalitis, hepatitis, esophagitis, colitis, pneumonia, neonatal infection sequelae, inflammatory, and age-related diseases. With an arsenal of genes in its large genome dedicated to host immune evasion, HCMV can block intrinsic cellular defenses and interfere with cellular immune responses. HCMV also encodes chemokines, chemokine receptors, and cytokines. Therefore, genes involved in human viral defense mechanisms and those encoding proteins targeted by the CMV proteins are candidates for host control of CMV infection and reactivation. Although still few in number, host genetic studies are producing valuable insights into biological processes involved in HCMV pathogenesis and HCMV-related diseases. For example, genetic variants in the immunoglobulin GM light chain can influence the antibody responsiveness to CMV glycoprotein B and modify risk of HCMV-related diseases. Moreover, CMV infection following organ transplantation has been associated with variants in genes encoding toll-like receptors (TLRs), programmed death-1 (PD-1), and interleukin-12p40 (IL-12B). A KIR haplotype (2DS4+) is proposed to be protective for CMV activation among hematopoietic stem cell transplant patients. Polymorphisms in the interferon lambda 3/4 (IFNL3/4) region are shown to influence susceptibility to CMV replication among solid organ transplant patients. Interestingly, the IFNL3/4 region is also associated with AIDS-related CMV retinitis susceptibility in HIV-infected patients. Likewise, interleukin-10 receptor 1 (IL-10R1) variants are shown to influence CMV retinitis development in patients with AIDS. Results from genome-wide association studies suggest a possible role for microtubule network and retinol metabolism in anti-CMV antibody response. Nevertheless, further genetic epidemiological studies with large cohorts, functional studies on the numerous HCMV genes, and immune response to chronic and latent states of infection that contribute to HCMV persistence are clearly necessary to elucidate the genetic mechanisms of CMV infection, reactivation, and pathogenesis.


Ductal shunting, high pulmonary blood flow, and pulmonary hemorrhage.
To describe the relationship among ductal shunting, estimated pulmonary blood flow, and pulmonary hemorrhage in very preterm infants. A total of 126 babies born before 30 weeks' gestation (median gestation 27 weeks, range 23 to 29 weeks) underwent echocardiography at 5, 12, 24, and 48 hours of age; measurements included right and left ventricular output, superior vena cava flow, and color Doppler diameter of any ductal shunt. Pulmonary blood flow was derived from the sum of right ventricular output and estimated ductal shunt flow. Twelve (9.5%) babies had a pulmonary hemorrhage at a mean age of 38 hours. Compared with the rest of the cohort, these 12 babies were less likely to have had antenatal steroids (59% vs 90%) and were less mature (26 weeks vs 27 weeks). At the echocardiogram closest to the pulmonary hemorrhage, 11 (92%) of the 12 babies had a significant patent ductus arteriosus >1.6 mm in diameter (median 2 mm, range 0.7 to 2.4 mm), and the median pulmonary blood flow was 326 mL/kg/min (range 210 to 598 mL/kg/min). These measurements were significantly higher than those found in the rest of the cohort in the same period (median duct diameter 0.5 mm [range 0 to 2.9 mm], median pulmonary blood flow 237 mL/kg/min [range 107 to 569 mL/kg/min]). At 5-hour echocardiography the babies with pulmonary hemorrhage had significantly larger diameter ducts but similar pulmonary blood flow. Pulmonary hemorrhage in preterm babies is associated with significant ductal shunting and high estimated pulmonary blood flow.


Essay: a cancer patient's perspective on how and why care providers should pursue healing partnerships.
This essay is based on the author's experiences as a cancer patient who underwent the grueling treatment known as a bone marrow transplant. An unintended consequence of the author's war with cancer is that he now "enjoys" more empathy for and insights into the challenging service encounters experienced by acutely ill individuals. This essay discusses why cancer patients and health service providers should each benefit when healing partnerships are developed. It also describes how such healing partnerships should be pursued. The content delivered in this essay is intended to help health care professionals better manage the means by which they deliver health services to acutely ill patients.


Midterm outcomes of the Zenith Renu AAA Ancillary Graft.
The Zenith Renu abdominal aortic aneurysm (AAA) Ancillary Graft (Cook Medical Inc, Bloomington, Ind) provides active proximal fixation for treatment of pre-existing endografts with failed or failing proximal fixation or seal. The purpose of this study was to evaluate the midterm outcomes of treatment with this device. From September 2005 to November 2006, a prospective, nonrandomized, multicenter, postmarket registry was utilized to collect physician experiences from 151 cases (89 converters and 62 main body extensions) at 95 institutions. Preoperative indications and procedural and postimplantation outcomes were collected and analyzed. Technical success and clinical success were determined as defined by the Society of Vascular Surgery reporting standards. Patients were predominantly male (87%) with a mean age of 77 years. The interval between the original endograft implantation to Renu treatment was 43.4 ± 18.7 months. The indications for treatment were endoleak (n = 111), migration (n = 136), or both (n = 94). Technical success was 98.0% with two cases of intraoperative conversion and one case of persistent type IA endoleak. The median follow-up for the cohort was 45.0 months (range, 0-56 months; interquartile range, 25.0 months). Overall, 32 cases had treatment failures that included at least one of the following: death (n = 5), type I/III endoleak (n = 18), graft infection (n = 1), thrombosis (n = 1), aneurysm enlargement >5 mm (n = 9), rupture (n = 4), conversion (n = 9, with 7 after 30 days), and migration (n = 1). Overall, the clinical success for the entire cohort during the follow-up period was 78.8% (119/151). The postmarket registry data confirm that the Zenith Renu AAA Ancillary Graft can be used to treat endovascular repairs that failed due to proximal attachment failures. The salvage treatment with the Renu device had high technical success rate and resulted in clinical success in a majority of patients (78.8%). While failed endovascular repairs can be salvaged, a clinical failure in one of five patients still emphasizes the importance of patient and device selection during initial endovascular aneurysm repair to ensure durable success.


Defining excess resource utilization and identifying associated factors for trauma victims.
Trauma system evaluation addresses aspects of the process, structure, and outcomes of trauma care. This approach may not identify all opportunities for trauma system improvement. Hospital length of stay (LOS) represents a meaningful measure of resource utilization and may help focus efforts to improve care. The purpose of this study is to estimate expected hospital LOS after trauma and determine the consequences of excessive LOS. Patients admitted during a 2-year period (January 1, 1993 to December 31, 1994) were retrospectively reviewed, and expected LOS was estimated. Excess LOS was defined as an observed LOS > or =100% of expected. Injuries, complications, and American College of Surgeons' Committee on Trauma audit filters were compared between the groups. Observed LOS exceeded expected by 100% or more for 568 of 5,226 patients (10.9%), and most survived (98.3%). Complications predicted excess LOS, whereas audit filters did not. Median costs for these 568 patients were $30,315 and totaled 30% of the expenditures for the entire cohort of 5,226 patients. Prolonged LOS represents an adverse outcome. Estimation of LOS and evaluation of outliers represents an important method for the evaluation of care within established trauma systems and centers.


Roberts syndrome: antenatal ultrasound--a case report.
There is obvious confusion and overlap involving these various syndromes, i.e., Roberts syndrome, SC phocomelia, and TAR syndrome. However, the patient reported here seemed to exhibit the features of shortened upper extremities, clefting, and microbrachycephaly characteristic of Roberts syndrome. Antenatal detection of Roberts syndrome may be important in that early neonatal death can be expected. Other similar syndromes may have much longer survival. Cytogenetic abnormalities may be detected as well. It appears that routine ultrasonographic assessment of humerus length in addition to femur length may yield certain diagnoses that otherwise would be missed. The parents can be counselled concerning antenatal management including the possibility of not performing a cesarean section for some abnormal presentations.


Diurnal variations in first lapses to smoking for nicotine patch users.
Amongst those not using nicotine replacement therapy (NRT), first lapses to smoking have been shown to be more common in the afternoons and evenings than the mornings. The present study investigated whether first lapses amongst those using 16 h nicotine patches follow a similar pattern. This is of interest because 16 h patches may not provide sufficient nicotine early in the morning to meet the needs of smokers. 200 male and female smokers attended a cessation programme combining behavioural support and 16 h nicotine patches. During the first 2 weeks of smoking abstinence 70 smokers reported first lapses. The frequency of first lapses was significantly higher in the afternoons (12.00-18.00 h, 30 lapses) and evenings (18.00-24.00, 35 lapses) than in the mornings (24.00-12.00, five lapses, p < 0.001 for both comparisons). There was no detectable difference between the rates of first lapse in the afternoon and evening. In conclusion, abstaining smokers using 16 h nicotine patches are more likely to experience their first lapse in the afternoon or evening rather than in the morning. Despite nicotine patches providing limited nicotine replacement for the first few hours after waking, there is no evidence that this undermines quit attempts by failing to prevent lapses during that time.


Development and characterization of 41 novel EST-SSR markers for Pisum sativum (Leguminosae).
Expressed sequence tag (EST)-derived simple sequence repeat (SSR) markers were developed in Pisum sativum for further use in genetic studies and breeding programs. Forty-one novel EST-SSR primers were developed and characterized for size polymorphism in 32 Pisum sativum individuals from four populations from China. In each population, the number of alleles per locus ranged from one to seven, with observed heterozygosity and expected heterozygosity ranging from 0 to 0.8889 and 0 to 0.8400, respectively. Furthermore, 53.7% of these markers could be transferred to the related species, Vicia faba. The developed markers have potential for application in the study of genetic diversity, germplasm appraisal, and marker-assisted breeding in pea and other legume species.


Selenium-containing nanoparticles synergistically enhance Pemetrexed&NK cell-based chemoimmunotherapy.
NK cell-based immunotherapy and pemetrexed (Pem)-based chemotherapy have broad application prospects in cancer treatment. However, the over-expressed NK cell inhibitory receptor on the surface of cancer cells and the low cell internalization efficiency of Pem greatly limit their clinical application. Herein, we construct a series of selenium-containing nanoparticles to synergistically enhance Pem-based chemotherapy and NK cell-based immunotherapy. The nanoparticles could deliver Pem to tumor sites and strengthen the chemotherapy efficiency of Pem by seleninic acid, which is produced by the oxidation of β-seleno ester. Moreover, seleninic acid can block the expression of inhibitory receptors against NK cells, thereby activating the immunocompetence of NK cells. The in vitro and in vivo experiments reveal the potential chemo-enhancing and immune-activating mechanism of seleninic acid, emphasizing the promising prospects of this strategy in effective chemoimmunotherapy.


Metal Knitting: A New Strategy for Cold Gas Spray Additive Manufacturing.
Cold Spray Additive Manufacturing (CSAM) is an emergent technique to produce parts by the additive method, and, like other technologies, it has pros and cons. Some advantages are using oxygen-sensitive materials to make parts, such as Ti alloys, with fast production due to the high deposition rate, and lower harmful residual stress levels. However, the limitation in the range of the parts' geometries is a huge CSAM con. This work presents a new conceptual strategy for CSAM spraying. The controlled manipulation of the robot arm combined with the proper spraying parameters aims to optimize the deposition efficiency and the adhesion of particles on the part sidewalls, resulting in geometries from thin straight walls, less than 5 mm thick, up to large bulks. This new strategy, Metal Knitting, is presented regarding its fundamentals and by comparing the parts' geometries produced by Metal Knitting with the traditional strategy. The Metal Knitting described here made parts with vertical sidewalls, in contrast to the 40 degrees of inclination obtained by the traditional strategy. Their mechanical properties, microstructures, hardness, and porosity are also compared for Cu, Ti, Ti6Al4V, 316L stainless steel, and Al.


Thrombin generation in patients with a first acute myocardial infarction.
Despite improved treatment options, myocardial infarction is still an important cause of morbidity and mortality. One of the contributing mechanisms in the acute myocardial infarction (AMI) is plasma hypercoagulability. We investigated hypercoagulability in 135 (first) patients with AMI using thrombin generation (TG) testing. TG testing was performed in plasmas, drawn upon admission and before medication administration, and subsequently after 4 days, 3 and 6 months. Further, we evaluated determinants of thrombin generation using multiple regression analysis of major coagulation proteins and inhibitors. Admission TG results were also related to 1-year outcome: cardiovascular death, recurrent myocardial infarction, a second coronary intervention [percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)] and ischemic stroke. At day 0, the TG parameters peak height, endogenous thrombin potential (ETP) and lag time were increased compared with a reference population. Peak height and lag time stayed persistently increased in patients. The lowest half of the ETP values was statistically not significantly associated with an occurrence of endpoints. The lowest half of the ETP values combined with the upper half of the D-dimer values were associated with endpoints; odds ratio 5.8 (1.1-30.7). Tissue factor pathway inhibitor (TFPI) seems to be an important determinant of TG in AMI and healthy persons. TG reflects acute hypercoagulability during AMI and partly also in the 6-month period after the acute event. TG shows a trend of an inverse association with risk of recurrent ischemic cardiovascular complications. Unraveling mechanisms in TG might improve our understanding of the pathophysiology of AMI and direct future improvements in medical care.


[The main etiologic groups of congenital developmental defects and the problems of diagnosis and thanatogenesis].
The proportion of congenital developmental defects (CDD) in children decreased in perinatal or early age is increasing. According to national and foreign data this figure is in the range of 21-41%. The etiologic structure of CDD for the last 5 years (1980-1984) basing on the data from the Minsk Teratologic Center has not practically changed. As in the previous 5 years, 50.8% of CDD belong to multifactorial ones, 14.3% are due to single gene mutations (8.4% of them are inherited according to dominant type and 5.9%--according to recessive type). Chromosome and gene mutations caused 7.9% of CDD. About 2% of CDD are induced by the effect of environmental factors on the embryo (less frequently on the fetus). Etiology of 25.1% of CDD is not clear.


Perceived helpfulness of websites for mental health information: a national survey of young Australians.
Despite the high risk of developing a mental disorder during adolescence, many young people fail to receive appropriate treatment from mental health professionals. Recent studies have found certain mental health information websites have improved mental health literacy and reduced symptoms of depression. However, studies exploring young people's perceptions of such resources still remain scarce. The current paper compared young people's preference for a website with self-help books and two face-to-face services-counselling and mental health services. The factors associated with believing in the perceived helpfulness of each intervention were also explored. A national telephone survey was carried out with 3,746 people aged 12-25 years and 2005 co-resident parents. Perceived helpfulness of each intervention was assessed in relation to four vignettes (depression, social phobia, psychosis and depression with alcohol misuse). Approximately 71% of respondents rated websites and books as likely to be helpful, which was less than for counselling, but more than for mental health services. Predictors of rating a website as likely to be helpful were older age (18-25 years), belief in seeking help, less social distance from peers like the one in the vignette, and being presented with the vignettes depicting either social phobia or depression with alcohol misuse. Predictors of rating a book as helpful included belief in seeking help, awareness of the national depression initiative beyondblue, less social distance, being presented with the social phobia vignette, and the belief that the person in the vignette is 'weak not sick'. Most young people are open to the idea of accessing mental health information online, especially for disorders that are often perceived as behavioural problems. These young people also believe in help-seeking in general and are more willing to associate with peers who have mental health problems.


Relations between biochemical markers of osteoarthritis and other disease parameters in a population of dogs with naturally acquired osteoarthritis of the genual joint.
To investigate the hypothesis that concentrations of the keratan sulfate epitope, 1/20/5D4 (5D4) and total sulfated glycosaminoglycans (S-GAG) in synovial fluids, and of 5D4 in serum of dogs with naturally acquired osteoarthritis of the genual joint (stifle), secondary to cranial cruciate ligament deficiency, are associated with other disease parameters of osteoarthritis. 58 dogs with stifle osteoarthritis secondary to naturally acquired cranial cruciate ligament (CCL) deficiency. All dogs were examined clinically, radiographically and, in some instances, scintigraphically. Serum and synovial fluid from both stifles were assayed for 5D4 concentration, using an inhibition ELISA, and for S-GAG, using a direct dye-binding assay. Serum 5D4 concentration was not significantly associated with other disease features. Total S-GAG values were high, and 5D4 values were low, in synovial fluid from clinically active, compared with contralateral joints. The S-GAG concentration in synovial fluid from clinically active joints was negatively correlated with radiographic severity score (rs = -0.389, P = 0.004, Spearman's rank correlation). Other associations between marker concentrations and disease parameters could not be detected. Serum 5D4 concentration is not a useful marker of stifle osteoarthritis in dogs; however, synovial fluid S-GAG and 5D4 values may hold more promise as disease measures.


Osimertinib as first-line treatment for elderly patients with advanced EGFR mutation-positive non-small cell lung cancer in a real-world setting (OSI-FACT-EP).
Osimertinib is the primary treatment for patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer. However, evidence of the outcomes of osimertinib treatment in patients over 75 years of age in the real-world setting is limited. This retrospective study analyzed the data of 538 patients (203 elderly and 335 non-elderly) with EGFR mutation-positive lung cancer in whom osimertinib was initiated as first-line treatment between August 2018 and December 2019. Patients over 75 years of age were classified as elderly. The data cut-off date was February 28, 2022. The progression-free survival (PFS) did not significantly differ between the elderly and non-elderly groups [elderly group: median PFS, 16.9 months (95 % confidence interval (CI), 14.3-20.2); non-elderly group: median PFS, 22.1 months (95 % CI: 19.5-26.3); hazard ratio (HR) for the elderly against the non-elderly: 1.21 (95 % CI: 0.98-1.50), p = 0.079]. However, the time to treatment failure (TTF) was significantly shorter in the elderly than in the non-elderly [elderly group: median TTF, 14.0 months (95 % CI: 0.98-1.50); non-elderly group: median TTF, 21.8 months (95 % CI: 18.2-24.6); HR for the elderly against the non-elderly: 1.46 (95 % CI: 1.20-1.77), p < 0.001]. Furthermore, the rate of treatment discontinuation because of adverse events was 28.6 % in the elderly and 14.9 % in the non-elderly (p < 0.001). Among patients who discontinued treatment, the conversion rate to second-line treatment was 39.6 % in the elderly and 72.8 % in the non-elderly. In addition, the median overall survival was 30 months (95 % CI: 25.8-37.7) in the elderly and not reached (NR) (95 % CI: NR-NR) in the non-elderly (p < 0.001). In a real-world clinical setting, elderly patients receiving osimertinib as first-line treatment should be aware of the frequent inability to transition to second-line treatment due to adverse events.


Hypoxia tolerance of common sole juveniles depends on dietary regime and temperature at the larval stage: evidence for environmental conditioning.
An individual's environmental history may have delayed effects on its physiology and life history at later stages in life because of irreversible plastic responses of early ontogenesis to environmental conditions. We chose a marine fish, the common sole, as a model species to study these effects, because it inhabits shallow marine areas highly exposed to environmental changes. We tested whether temperature and trophic conditions experienced during the larval stage had delayed effects on life-history traits and resistance to hypoxia at the juvenile stage. We thus examined the combined effect of global warming and hypoxia in coastal waters, which are potential stressors to many estuarine and coastal marine fishes. Elevated temperature and better trophic conditions had a positive effect on larval growth and developmental rates; warmer larval temperature had a delayed positive effect on body mass and resistance to hypoxia at the juvenile stage. The latter suggests a lower oxygen demand of individuals that had experienced elevated temperatures during larval stages. We hypothesize that an irreversible plastic response to temperature occurred during early ontogeny that allowed adaptive regulation of metabolic rates and/or oxygen demand with long-lasting effects. These results could deeply affect predictions about impacts of global warming and eutrophication on marine organisms.


A novel Betaretrovirus discovered in cattle with neurological disease and encephalitis.
The majority of emerging infectious diseases in humans are of animal origin, and many of them are caused by neuropathogenic viruses. Many cases of neurological disease and encephalitis in livestock remain etiologically unresolved, posing a constant threat to animal and human health. Thus, continuous extension of our knowledge of the repertoire of viruses prone to infect the central nervous system (CNS) is vital for pathogen monitoring and the early detection of emerging viruses. Using high-throughput sequencing (HTS) and bioinformatics, we discovered a new retrovirus, bovine retrovirus CH15 (BoRV CH15), in the CNS of a cow with non-suppurative encephalitis. Phylogenetic analysis revealed the affiliation of BoRV CH15 to the genus Betaretrovirus. BoRV CH15 genomes were identified prospectively and retrospectively by PCR, RT-PCR, and HTS, with targeting of viral RNA and proviral DNA, in six additional diseased cows investigated over a period of > 20 years and of different geographical origins. The virus was not found in brain samples from healthy slaughtered control animals (n = 130). We determined the full-length proviral genomes from six of the seven investigated animals and, using in situ hybridization, identified viral RNA in the cytoplasm of cells morphologically compatible with neurons in diseased brains. Further screening of brain samples, virus isolation, and infection studies are needed to estimate the significance of these findings and the causative association of BoRV CH15 with neurological disease and encephalitis in cattle. However, with the full-length proviral sequences of BoRV CH15 genomes, we provide the basis for a molecular clone and further in vitro investigation.


Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence.
Swift elimination of undesirable cells is an important feature in tumour suppression and immunity. The tumour suppressor p53 and interferon-alpha and -beta (IFN-alpha/beta) are essential for the induction of apoptosis in cancerous cells and in antiviral immune responses, respectively, but little is known about their interrelationship. Here we show that transcription of the p53 gene is induced by IFN-alpha/beta, accompanied by an increase in p53 protein level. IFN-alpha/beta signalling itself does not activate p53; rather, it contributes to boosting p53 responses to stress signals. We show examples in which p53 gene induction by IFN-alpha/beta contributes to tumour suppression. Furthermore, we show that p53 is activated in virally infected cells to evoke an apoptotic response and that p53 is critical for antiviral defence of the host. Our study reveals a hitherto unrecognized link between p53 and IFN-alpha/beta in tumour suppression and antiviral immunity, which may have therapeutic implications.


Adolescent BMI trajectory and risk of diabetes versus coronary disease.
The association of body-mass index (BMI) from adolescence to adulthood with obesity-related diseases in young adults has not been completely delineated. We conducted a prospective study in which we followed 37,674 apparently healthy young men for incident angiography-proven coronary heart disease and diabetes through the Staff Periodic Examination Center of the Israeli Army Medical Corps. The height and weight of participants were measured at regular intervals, with the first measurements taken when they were 17 years of age. During approximately 650,000 person-years of follow-up (mean follow-up, 17.4 years), we documented 1173 incident cases of type 2 diabetes and 327 of coronary heart disease. In multivariate models adjusted for age, family history, blood pressure, lifestyle factors, and biomarkers in blood, elevated adolescent BMI (the weight in kilograms divided by the square of the height in meters; mean range for the first through last deciles, 17.3 to 27.6) was a significant predictor of both diabetes (hazard ratio for the highest vs. the lowest decile, 2.76; 95% confidence interval [CI], 2.11 to 3.58) and angiography-proven coronary heart disease (hazard ratio, 5.43; 95% CI, 2.77 to 10.62). Further adjustment for BMI at adulthood completely ablated the association of adolescent BMI with diabetes (hazard ratio, 1.01; 95% CI, 0.75 to 1.37) but not the association with coronary heart disease (hazard ratio, 6.85; 95% CI, 3.30 to 14.21). After adjustment of the BMI values as continuous variables in multivariate models, only elevated BMI in adulthood was significantly associated with diabetes (β=1.115, P=0.003; P=0.89 for interaction). In contrast, elevated BMI in both adolescence (β=1.355, P=0.004) and adulthood (β=1.207, P=0.03) were independently associated with angiography-proven coronary heart disease (P=0.048 for interaction). An elevated BMI in adolescence--one that is well within the range currently considered to be normal--constitutes a substantial risk factor for obesity-related disorders in midlife. Although the risk of diabetes is mainly associated with increased BMI close to the time of diagnosis, the risk of coronary heart disease is associated with an elevated BMI both in adolescence and in adulthood, supporting the hypothesis that the processes causing incident coronary heart disease, particularly atherosclerosis, are more gradual than those resulting in incident diabetes. (Funded by the Chaim Sheba Medical Center and the Israel Defense Forces Medical Corps.).


Delayed increase in high density lipoprotein-phospholipids after ingestion of a fat load in normolipidemic patients with coronary artery disease.
We studied the effect of a single oral fat load, supplemented with retinyl palmitate (RP), on high density lipoprotein (HDL) lipids in six normolipidemic men with coronary artery disease (CAD) and in six age- and lipid-matched controls. All subjects were selected from a study group which underwent the same protocol 2 years earlier. Post-prandial total plasma lipids, plasma RP levels, and HDL lipids were evaluated at 2-h intervals up till 10 h after the meal. In most subjects the post-prandial response of plasma triglyceride (TG) and plasma RP was identical in the first and second tests. Following the fat load, control subjects showed no change in HDL total cholesterol (TC) or HDL cholesteryl ester (CE) and showed an increase in HDL-TG. CAD subjects however showed a decrease in HDL-TC and HDL-CE and an increase in HDL-TG, similar to the increase in control subjects. In control subjects an increase in HDL phospholipid (PL) was apparent between 0 and 8 h after the fat load. By contrast, in CAD subjects the increase in HDL-PL was only found after as long as 6 h. The magnitude of the post-prandial response of HDL-PL measured during the test was significantly lower in the CAD group. The effects of the fat load on HDL free cholesterol (FC) were similar to the changes in HDL-PL. These data support the hypothesis that PL and FC released during the degradation of chylomicrons as surface remnants are taken up by HDL. This process is clearly delayed in normolipidemic CAD subjects compared with controls. The data suggest that differences in the post-prandial response to an oral fat load in normolipidemic CAD patients and control subjects are not confined to the clearance of TG-rich lipoproteins, but also involve a difference in the uptake of chylomicron surface material by HDL.


Comparison of polymerase chain reaction and Warthin-Starry techniques to detect Leptospira spp. in kidneys of slaughtered cattle.
Leptospirosis is a worldwide zoonotic disease that is caused by Gram-negative spirochaetes, Leptospira species. Affected animals excrete the organism in the urine into the environment and act as a source of infection. Cattle are maintenance hosts for some serovars of leptospirosis and are important in the transmission of the infection to humans. At post mortem examination, affected cattle show white spots in their kidneys but these are not specific for leptospirosis. Sometimes it is necessary that leptospirosis be diagnosed in the carcass. Different direct methods, including polymerase chain reaction (PCR), Warthin-Starry silver stain (WS), immunofluorescence (IF) and immunohistochemistry (IHC) can be used in order to diagnose leptospirosis in the affected tissues, such as kidney. The main advantage of the WS technique is direct visualisation of the bacteria in the tissue samples. Silver staining is useful for retrospective studies on formalin-fixed and paraffin-embedded samples but little information is available on the sensitivity and specificity of the technique. The present study aimed to find a simple and inexpensive method that can be used in any laboratory and that also, if clinical samples are not available, can detect Leptospira in tissue samples post mortem. This study was performed on 19 paraffin-embedded kidneys of slaughtered cows that grossly had focal to multifocal white spots. Leptospirosis was confirmed in these samples with PCR based on the LipL32 gene. Out of 19 PCR positive kidneys, Leptospira was identified in 13 stained samples by WS. The kidneys revealed different grades of interstitial nephritis. No relationship was found between severity of lesions and presence of leptospires in the kidneys. The PCR results on the urine and blood were consistent with matching WS stained kidneys. Out of 13 kidneys that were positive with silver staining, 7 matching blood and 10 matching urine samples were confirmed positive for leptospirosis with PCR. In this study, the WS technique provided fewer positive results than PCR. This may be as a result of a low burden of Leptospira in the kidney, but the sensitivity of WS staining needs more investigation.


Pedunculopontine-induced cortical decoupling as the neurophysiological locus of dissociation.
Mounting evidence suggests an association between aberrant sleep phenomena and dissociative experiences. However, no wake-sleep boundary theory provides a compelling explanation of dissociation or specifies its physiological substrates. We present a theoretical account of dissociation that integrates theories and empirical results from multiple lines of research concerning the domain of dissociation and the regulation of rapid eye movement (REM) sleep. This theory posits that individual differences in the circuitry governing the REM sleep promoting Pedunculopontine Nucleus and Laterodorsal Tegmental Nucleus determine the degree of similarity in the cortical connectivity profiles of wakefulness and REM sleep. We propose that a latent trait characterized by elevated dissociative experiences emerges from the decoupling of frontal executive regions due to a REM sleep-like aminergic/cholinergic balance. The Pedunculopontine-Induced Cortical Decoupling Account of Dissociation (PICDAD) suggests multiple fruitful lines of inquiry and provides novel insights. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Changing Antibiotic Prescribing in a Primary Care Network: The Role of Readiness to Change and Group Dynamics in Success.
Overuse of broad-spectrum antibiotics in outpatient pediatrics remains a significant issue and there is limited evidence on how to effectively implement outpatient stewardship interventions. This study examines the relationship between readiness to change and modifiable factors affecting success of a primary care network antibiotic stewardship intervention. A survey designed to measure readiness to accept a health care innovation was administered to 209 clinicians. Practices were split in half into "high" versus "low" readiness to change. Semistructured qualitative interviews were conducted with 2 to 3 clinicians from 6 practices in each readiness group. High readiness practices trended toward greater improvements between years (8% to 26% vs 2% to 10% mean improvement). High readiness practice clinicians described more open communication, active group change process, and supportive underlying group cohesion. Low readiness practice clinicians functioned more independently and were influenced more by external forces but were developing group cohesion through the initiative. System-wide interventions should be appropriately tailored to different levels of readiness to change, specifically addressing group dynamics and their differing foci of influence.


Intra- and interexaminer reliability of the chiropractic biophysics lateral lumbar radiographic mensuration procedure.
To determine the intra- and interexaminer reliability of a specific method of mensuration commonly used to evaluate the positional configuration of the lumbopelvic spine viewed on lateral lumbar radiographs. A blind, repeated-measures design was used. Lateral lumbopelvic radiographs were presented to each of three examiners in random order. Each film was marked and measurements were recorded. The films were cleaned of all markings and randomized again for a second run by each examiner. Each examiner's measurements were unavailable to the other examiners. Private, primary-care chiropractic clinic. Anterior/posterior thoracic translation in millimeters, Ferguson's sacral-plane angle to horizontal, arcuate line angle to horizontal, L1 to L5 absolute rotation angle and four relative rotation angles for L1-L2, L2-L3, L3-L4 and L4-L5. Intra- and interrelibility of the three radiographic examiners were analyzed. Intraexaminer reliability for (a) L1-L5 absolute rotation angle was .98, with confidence intervals included in the range of 0.95-0.99, (b) anterior/posterior thorax translation [+/- Sz] was .97-.99, with confidence intervals included in the range of 0.94-1.00, (c) arcuate angle (AA) .40-.81, with confidence intervals included in the range of 0.07-0.90, (d) Ferguson's angle (FA) was .91-.97, with confidence intervals included in the range of 0.82-0.98, (e) relative rotation angle reliability ranges were L1-L2, .84-.94; L2-L3, .80-.85; L3-L4, .78-.89; L4-L5, .87-.92. Interexaminer reliabilities for the three examiners ranged from .66-.98. With the exception of the arcuate angle measurement, the reliabilities for all other measurements were at least .78. Those measurements with reliabilities approaching .80 or better would be considered accurate enough for use in future clinical studies. The arcuate angle measurement may have been least reliable because of the subjective nature of the method of affixing a best-fit line to a radiographic landmark that often takes on the appearance of a mild curvature. Establishing reliability is an important first step toward evaluating these and other similar radiographic measurements that have yet to be examined for their validity.