Genotyping analysis of 3 RET polymorphisms demonstrates low somatic mutation rate in Chinese Hirschsprung disease patients.
Genetic mosaicism has been reported for both coding and non-coding sequences in the RET gene in Hirschsprung disease (HSCR) patients. This study aimed to investigate somatic mutation rate in Chinese population by comparing both homozygous genotype percentage and risk allele frequency of 3 RET single nucleotide polymorphisms (SNPs) among blood and colon samples. DNA was extracted from 59 HSCR blood samples, 59 control blood samples and 76 fresh frozen colon tissue samples (grouped into ganglionic, transitional and aganglionic level). Genotype status of rs2435357 and rs2506030 was examined by competitive allele specific hydrolysis probes (Taqman) PCR technology, and rs2506004 was examined by Sanger sequencing. Homozygous genotype percentage and risk allele frequency were calculated for each type of sample and compared by chi-square test. P<0.05 was regarded as being statistically significant. Colon tissue DNA samples showed similar frequency of SNPs as that of the blood DNA samples in HSCR patients, both of which are significantly higher than the control blood group (rs2435357 TT genotype: 71.2%, 74.7% versus 22.0% in HSCR blood, HSCR colon and control blood DNA respectively, P=0.000; rs2506004 AA genotype: 72.4%, 83.1% versus 25.5%, P=0.000; rs2506030 GG genotype: 79.7%, 77.2% versus 54.2%, P=0.000 and 0.004). With respect to DNA extracted from ganglionic, transitional and aganglionic levels, no statistically significant difference was demonstrated in those 3 regions (rs2435357: P=0.897; rs2506004: P=0.740; rs2506030: P=0.901). Our data does not support the notion that high frequency of somatic changes as an underlying etiology of Chinese HSCR population.


Soliton bending and routing induced by interaction with curved surfaces in nematic liquid crystals.
We study experimentally the interaction of spatial optical solitons with curved dielectric surfaces in unbiased nematic liquid crystals. We demonstrate that this interaction depends on the curvature of the surface and the walk-off, and it can be employed for efficient routing and control of the soliton trajectories. We also observe a large-angle total internal reflection of the soliton beam from an interface between liquid crystal and air.


Analysis of the top 100 most influential papers in benign prostatic hyperplasia.
The fund of knowledge on benign prostatic hypertrophy (BPH) has been growing since the 1970s. Citation analysis is a tool by which we can quantify influence of specific articles and assess the growth of a certain topic. This paper seeks to identify trends, as well as draw attention to the most influential papers, authors, and journals. Many analogous studies have been done, but none have been done in the field of BPH. We used Thomson Reuters Web of Science to collect articles pertaining to BPH in a two-step fashion. We identified 117 keywords relevant to BPH and using these 117 words, we were able to identify 7302 total articles. These articles were organized by number of citations. Of the top 200 articles, 100 articles were excluded based on title and abstract analysis. One hundred articles were included for final analysis, as this is the standard of citation analysis. Overall, total citations were slightly correlated with journal impact factor. Author analysis revealed no significant difference between authorship and average citations. Topic analysis showed the most cited topic was surgical management with 657.35 citations per year. Study design analysis showed the predominant study design was the randomized control trial. By using the two-step methodology, we were able to create a list of the top 100 most influential articles in the field of BPH. In doing so, we illustrated the growth of the field over time and paid tribute to the myriad of papers, authors, and journals that have shaped the field to this day.


Biomechanical Stability of Volar Plate Only Versus Addition of Dorsal Ulnar Pin Plate: A Dorsal Ulnar Fragment, C-3-Type, Distal Radius, Cadaver Fracture Model.
To determine if the addition of a dorsal ulnar pin plate provides improved stability characteristics in the management of intra-articular distal radius fractures with an associated dorsal ulnar fragment. OTA/AO type C3 fractures, with a dorsal ulnar fragment of one-third or one-half the width of the distal radius, were simulated in 9 matched pairs of fresh-frozen cadaveric arms randomized between fixed-angle volar plate only versus volar plate with addition of a dorsal ulnar pin plate. Prepared specimens were mounted in a custom load frame and loaded in extension with stepwise cyclic load increase. Dorsal plane interfragmentary displacements were compared between the 2 fixation constructs at 50-N and 100-N cyclic load. The addition of the dorsal ulnar pin plate significantly reduced interfragmentary displacements for the dorsal ulnar fragment at the 50 N load application, resulting in mean interfragmentary displacements of -0.1 ± 0.2 mm in comparison to -0.3 ± 0.2 mm with the volar plate-only construct. No other interfragmentary displacement comparisons were significant. No differences were found comparing the one-third and one-half size fragments. The addition of a dorsal ulnar pin plate improved stability characteristics with respect to the dorsal ulnar fragment. The addition of the dorsal ulnar pin plate, although statistically significant, improved displacement by less than 0.3 mm on average and thus may not prove to be important in clinical scenarios.


Computational study of SENP1 in cancer by novel natural compounds and ZINC database screening.
Introduction: Sentrin-specific protease 1 (SENP1) is a protein whose main function is deSUMOylation. SENP1 inhibits apoptosis, and increases angiogenesis, estrogen and androgen receptor transcription and c-Jun transcription factor, proliferation, growth, cell migration, and invasion of cancer. The in vivo and in vitro studies also demonstrated which natural compounds, especially phytochemicals, minerals, and vitamins, prevent cancer. More than 3,000 plant species have been reported in modern medicine. Natural compounds have many anti-cancerous andanti-turmeric properties such as antioxidative, antiangiogenic, antiproliferative, and pro-apoptotic properties. Methods: In this study, we investigated the interaction of some natural compounds with SENP1 to inhibit its activity. We also screened the ZINC database including natural compounds. Molecular docking was performed, and toxicity of compounds was determined; then, molecular dynamics simulation (MDS) and essential dynamics (ED) were performed on natural compounds with higher free binding energies and minimal side effects. By searching in a large library, virtual screening of the ZINC database was performed using LibDock and CDOCKER, and the final top 20 compounds were allowed for docking against SENP1. According to the docking study, the top three leading molecules were selected and further analyzed by MDS and ED. Results: The results suggest that resveratrol (from the selected compounds) and ZINC33916875 (from the ZINC database) could be more promising SENP1 inhibitory ligands. Discussion: Because these compounds can inhibit SENP1 activity, then they can be novel candidates for cancer treatment. However, wet laboratory experiments are needed to validate their efficacy as SENP1 inhibitors.


Differential Gene Expression Profile of Renin-Angiotensin System in the Left Atrium in Mitral Regurgitation Patients.
Left atrial enlargement is a mortality and heart failure risk factor in primary mitral regurgitation (MR) patients. Pig models of MR have shown differential expression of genes linked to the renin-angiotensin system. Therefore, the aim of this study was to investigate the key genes of the renin-angiotensin that are expressed differentially in the left atrial myocardium in MR patients. Quantitative RT-PCR was used to compare gene expression in the renin-angiotensin system in the left atrium in MR patients, aortic valve disease patients, and normal subjects. Plasma angiotensin II concentrations did not significantly differ between MR patients and aortic valve disease patients (P = 0.582). Compared to normal controls, however, MR patients had significantly downregulated expressions of angiotensin-converting enzyme, angiotensin I converting enzyme 2, type 1 angiotensin II receptor, glutamyl aminopeptidase, angiotensinogen, cathepsin A (CTSA), thimet oligopeptidase 1, neurolysin, alanyl aminopeptidase, cathepsin G, leucyl/cystinyl aminopeptidase (LNPEP), neprilysin, and carboxypeptidase A3 in the left atrium. The MR patients also had significantly upregulated expressions of MAS1 oncogene (MAS1) and mineralocorticoid receptor compared to normal controls. Additionally, in comparison with aortic valve disease patients, MR patients had significantly downregulated CTSA and LNPEP expression and significantly upregulated MAS1 expression in the left atrium. Expressions of genes in the renin-angiotensin system, especially CTSA, LNPEP, and MAS1, in the left atrium in MR patients significantly differed from expressions of these genes in aortic valve disease patients and normal controls. Notably, differences in expression were independent of circulating angiotensin II levels. The results of this study provide a rationale for pharmacological therapies or posttranslational regulation therapies targeting genes expressed differentially in the renin-angiotensin system to remedy structural remodeling associated with atrial enlargement and heart failure progression in patients with MR.


Socio-demographic, migratory and health-related determinants of food insecurity among Venezuelan migrants in Peru.
To evaluate the factors associated with food insecurity (FI) among Venezuelan migrants residing in Peru. Secondarily, to evaluate the psychometric properties of the Food Insecurity Experience Scale (FIES). A cross-sectional study based on secondary data analysis of the 2022 Venezuelan Population Residing in Peru Survey (ENPOVE-2022, from the Spanish acronym) was conducted. FI was measured with the FIES, whose properties were tested using the Rasch model. Multinomial logistic regression was performed to estimate relative prevalence ratios with their corresponding 95 % confidence intervals. This survey was conducted in February and March 2022 in the eight cities most populated by Venezuelan migrants and refugees in Peru. Venezuelan migrants and refugees over the age of 18 years living in Peru. A total of 7727 participants were included. Rasch reliability was adequate (0·73). The prevalence of mild, moderate and severe FI was 36·71 %, 31·14 % and 10·48 %, respectively. Being aged 25-34 and 35-44 years, unemployed, uninsured, having no formal education or secondary, illegal status, living in a dwelling with 2-4 and more than 4 people, presenting one or more than one chronic disease, residing in Peru for 0-6 months and perceived discrimination were associated with a higher probability of moderate FI. Furthermore, having secondary education, being unemployed, uninsured, never married, illegal, residing in Tumbes, presenting one or more than one chronic disease and perceived discrimination were significantly associated with severe FI. Four out of ten Venezuelan migrants residing in Peru presented moderate to severe FI. The FIES showed adequate psychometric properties. Differences in the socio-demographic, health and migratory factors associated with FI levels were found. Inter-sectoral and multi-sectoral interventions are needed and should be focused on addressing the determinants of FI.


Opioid-Induced Hyperalgesia: Clinical Implications for Advanced Practice Nurses in Oncology.
Opioid-induced hyperalgesia (OIH) is a key factor in the clinical management of patients experiencing pain. However, limited knowledge exists regarding the specific mechanisms involved in OIH and its treatment. A thorough assessment is usually required, and clinical diagnosis is mainly determined by exclusion in medical practice. Patients who are taking opioids should receive ongoing, comprehensive assessment by a clinician. Early identification of OIH will lead to improved patient outcomes. .


Spatiotemporal effects of logging and fire on tall, wet temperate eucalypt forest birds.
Forests globally are subject to disturbances such as logging and fire that create complex temporal variation in spatial patterns of forest cover and stand age. However, investigations that quantify temporal changes in biodiversity in response to multiple forms of disturbance in space and time are relatively uncommon. Over a 10-yr period, we investigated the response of bird species to spatiotemporal changes in forest cover associated with logging and wildfire in the mountain ash (Eucalyptus regnans) forests of southeastern Australia. Specifically, we examined how bird occurrence changed with shifts in the proportion of area burned or logged in a 4.5 km radius surrounding our 88 long-term field survey sites, each measuring 1 ha in size. Overall species richness was greatest in older forest patches, but declined as the amount of fire around each site increased. At the individual species level, 31 of the 37 bird species we modeled exhibited a negative response to the amount of fire in the surrounding landscape, while one species responded positively to fire. Only nine species exhibited signs of recovery in the 6 yr of surveys following the fire. Five species were more likely to be detected as the proportion of logged forest surrounding a site increased, suggesting a possible "concentration effect" with displaced birds moving into unlogged areas following harvesting of adjacent areas. We also identified relationships between the coefficients of life history attributes and spatiotemporal changes in forest cover and stand age. Large-bodied birds and migratory species were associated with landscapes subject to large amounts of fire in 2009. There were associations between old growth stands and small-bodied bird species and species that were not insectivores. Our study shows that birds in mountain ash forests are strongly associated with old growth stands and exhibit complex, time-dependent, and species-specific responses to landscape disturbance. Despite logging and fire both being high-severity perturbations, no bird species exhibited similar responses to fire and logging in the landscape surrounding our sites. Thus, species responses to one kind of landscape-scale disturbance are not readily predictable based on an understanding of the responses to another kind of (albeit superficially similar) disturbance.


Attend and Guide (AG-Net): A Keypoints-Driven Attention-Based Deep Network for Image Recognition.
This article presents a novel keypoints-based attention mechanism for visual recognition in still images. Deep Convolutional Neural Networks (CNNs) for recognizing images with distinctive classes have shown great success, but their performance in discriminating fine-grained changes is not at the same level. We address this by proposing an end-to-end CNN model, which learns meaningful features linking fine-grained changes using our novel attention mechanism. It captures the spatial structures in images by identifying semantic regions (SRs) and their spatial distributions, and is proved to be the key to modeling subtle changes in images. We automatically identify these SRs by grouping the detected keypoints in a given image. The "usefulness" of these SRs for image recognition is measured using our innovative attentional mechanism focusing on parts of the image that are most relevant to a given task. This framework applies to traditional and fine-grained image recognition tasks and does not require manually annotated regions (e.g. bounding-box of body parts, objects, etc.) for learning and prediction. Moreover, the proposed keypoints-driven attention mechanism can be easily integrated into the existing CNN models. The framework is evaluated on six diverse benchmark datasets. The model outperforms the state-of-the-art approaches by a considerable margin using Distracted Driver V1 (Acc: 3.39%), Distracted Driver V2 (Acc: 6.58%), Stanford-40 Actions (mAP: 2.15%), People Playing Musical Instruments (mAP: 16.05%), Food-101 (Acc: 6.30%) and Caltech-256 (Acc: 2.59%) datasets.


On aspects of skull form in African apes and orangutans, with implications for hominoid evolution.
The study of hominoid phylogeny is currently in a state of controversy and debate due to the discovery of new fossil material and reanalysis of the morphology of extant apes. An important key to the resolution of these debates lies in attaining a fuller understanding of the morphological differences in skull form between the African and Asian great apes. In this paper I have analyzed aspects of facial morphology and internal cranial anatomy in the great apes. Results from this study and previous ones suggest that Pongo is characterized by a marked dorsal deflection of the face relative to the basicranium. Many aspects of circumorbital, midfacial, palatal, and mandibular morphology in Pongo may be related to this airorynchous condition. This hypothesis is supported by Enlow's work on form and pattern in the primate and mammalian skull. The position of the face in known Sivapithecus appears to be similar to that seen in Pongo. Although Pongo may be specialized in its marked degree of airorynchy, it seems likely that an important derived feature linking African apes and hominids is a ventral rotation of the splanchnocranium on the neurocranium. The appearance of marked supraorbital tori and ethmofrontal sinuses are probably correlated developments. Additional implications of this work for debates about hominoid phylogeny are discussed.


Regulation of AQP2 localization by S256 and S261 phosphorylation and ubiquitination.
Vasopressin-induced water reabsorption coincides with phosphorylation of aquaporin-2 (AQP2) at S256 (pS256), dephosphorylation at S261, and its translocation to the apical membrane, whereas treatment with the phorbol ester 12-tetradecanoylphorbol-13-acetate (TPA) induces AQP2 ubiquitination at K270, its internalization, and lysosomal degradation. In this study we investigated the relationship between S256 and S261 phosphorylation in AQP2 and its ubiquitination and trafficking in MDCK cells. Forskolin stimulation associated with increased pS256 and decreased pS261 AQP2, indicating that MDCK cells are a good model. After forskolin stimulation, TPA-induced ubiquitination of AQP2 preceded phosphorylation of AQP2 at S261, which in the first instance occurred predominantly on ubiquitinated AQP2. Forskolin-induced changes in pS261 were also observed for AQP2-S256A and AQP2-S256D, which constitutively localize in vesicles and the apical membrane, respectively. Although pS261 varies with forskolin as with wild-type AQP2, AQP2-S256A is not increased in its ubiquitination. Our data reveal that pS261 occurred independently of AQP2 localization and suggest that pS261 follows ubiquitination and endocytosis and may stabilize AQP2 ubiquitination and intracellular localization. The absence of increased ubiquitination of AQP2-S256A indicates that its intracellular location is due to the lack of pS256. Furthermore, AQP2-S261A and AQP2-S261D localized to vesicles, which was due to their increased ubiquitination, because changing K270 into Arg in both mutants resulted in their localization in the apical membrane. Although still increased in its ubiquitination, AQP2-S256D-S261D localized in the apical membrane. AQP2-S256D-K270R-Ub, however, localized to intracellular vesicles. Although our localization of AQP2-S261A/D is different from that of others, these data indicate that constitutive S256 phosphorylation counterbalances S261D-induced ubiquitination and internalization or changes its structure to allow distribution to the apical membrane. The vesicular localization of AQP2-S256D-K270R-Ub, however, indicates that the dominant apical sorting of S256D can again be overruled by constitutive ubiquitination. These data indicate that the membrane localization of AQP2 is determined by the balance of the extents of phosphorylation and ubiquitination.


[Energy expenditure and the actual nutrition of students in institutions of higher education].
Twenty-four hours' energy expenditure, actual nutrition and incidence of excessive body weight were studied in 100 students (85 females and 15 males), aged 19-29. Twenty-four hours' energy expenditure in males comprised 2585.2 +/- 16.3 kcal, in females - 2434.5 +/- 7.9 kcal, calorific value was 2591.3 +/- 18.9 kcal and 2587.5 +/- 12.6 kcal, respectively. The diet of males consisted of 95.1 +/- 3.9 g protein (including 72.4 g animal protein), 122.9 +/- 8.1 g fats (including 9.7 +/- 0.9 g vegetable fats) and 276.2 +/- 7.4 g carbohydrates. The diet of females contained 93.3 +/- 2.1 g protein (including 63.8 +/- 2.7 g animal protein), 111.9 +/- 4.1 g fats (including 14.6 +/- 1.0 g vegetable fats) and 301.8 +/- 5.0 g carbohydrates. Deficiency of vitamin B, ascorbic acid, calcium and magnium (in females) was recorded in the diets of the students investigated. Their twenty-four hours' rations consisted of great amount of pastry and free animal fat, little bread (especially, brown bread), and lactic acid foods (with a low content of fat), vegetables and fruit. Excessive body weight was detected in 18% of the students.


Structure, antigenic determinants of some clinically important insect allergens: chironomid hemoglobins.
Determination of the molecular structure and properties of allergens that elicit severe immediate-type hypersensitivity diseases in humans and a knowledge of the structure of their antibody-binding sites should provide new insight into the pathogenetic mechanisms of allergic diseases. Monomeric and homodimeric hemoglobins (CTT I to X) have been identified as potent allergenic components of Chironomidae, a family of Diptera. Immunologic investigations of peptides of three of these hemoglobins (CTT IV, CTT VI, and CTT VIII) showed that human antibodies of the E and G classes recognize at least two different sites within each molecule. Individual hemoglobin peptides were aligned with homologous regions of chironomid hemoglobin CTT III, whose tertiary structure has been determined by x-ray analysis at a resolution of 1.4 angstroms. The antigenic site CTT IV(91 to 101) showed the following characteristics: (i) seven polar or hydroxylated amino acids, from a total of eleven, occupying predominantly superficial regions; (ii) the property of linkage to other molecules by hydrogen bonds or solvent clusters; and (iii) high thermal mobility factors. In contrast, peptide CTT IV(102 to 108), which does not bind human antibodies, contained no polar amino acids and had low thermal mobility factors. These results support the idea that the antigenicity of clinically relevant proteins is related to regions with a predominance of polar amino acids and with low energy barriers between different conformations, which allow high flexibility, including site-specific adaptation in antibody binding.


Management and treatment recommendations for World Health Organization Grade III and IV gliomas.
The treatment recommendations provided in this manuscript are intended to serve as a knowledge base for clinicians and health personals involved in treating patients with high-grade malignant glioma. In newly diagnosed patients, complete resection or biopsy is required for histological characterization of the tumor, which in turn is essential to decide the treatment strategy. In patients with good or borderline performance score, radiotherapy (RT), and chemotherapy are the preferred management. In patients with poor performance score, RT with best possible supportive care is the mainstay of the management. All patients have to undergo brain magnetic resonance imaging procedure quarterly or half-yearly for 5 years and then on an annual basis. In patients with recurrent malignant glioma, wherever possible re-resection or re-irradiation or chemotherapy can be considered along with supportive and palliative care. High-grade malignant glioma should be managed in a multidisciplinary center with the best of the possible care that is available based on the evidence as discussed in this manuscript.


[World war I as seen by Franciscans of Slavonski Brod].
There is a profound and permanent connection between Franciscans and Slavonski Brod (formerly known as Brod na Savi). It has lasted for centuries, as Franciscans were present in the town even during the Turkish occupation. They were the first town pastors after its independence from the Turks in 1691 and are present today with churches, monasteries, and the Franciscan High School, which opened in 1995. Their chronicles describing the events from 1706 to 1932 are an important source of historical information, especially for local historians. This article describes the life of Franciscans in Brod na Savi during the First World War. Initially, they were loyal Austro-Hungarian citizens who passionately believed in the ultimate victory on all fronts. However, war circumstances quickly lead to a disappointment and doubt. Slavic solidarity increased as the war progressed, and in the end Franciscans were delighted with the establishment of the new country of South Slavs, which they perceived as a means to free the nation from the Austrian and Hungarian authorities. Throughout the war, the Convent served as a reserve military hospital with 145 beds for the soldiers and 21 beds for officers.


Local administration of high-dose diabetes medicine exendin-4 inhibits orthodontic tooth movement in mice.
To investigate the effects of exendin-4 on orthodontic tooth movement distance, root resorption, and expression levels of osteoclast-related cytokines in a mouse model. A 10-g NiTi coil spring was placed between the anterior alveolar bone and upper left first molar of 8-week-old male C57BL/6 mice. Twenty microliters of exendin-4 solution (containing 0.2 μg, 4 μg, or 20 μg exendin-4) or phosphate-buffered saline (PBS) were injected on the buccal side of the upper left first molar at 2-day intervals (4 mice per group). Mice were sacrificed on day 12; silicone impressions were taken to record tooth movement distance. The left maxillae of the PBS and 20 μg exendin-4 groups were also excised for histological analysis and quantitative reverse transcription polymerase chain reaction analysis. Orthodontic tooth movement distance was smaller in the 20 μg exendin-4 group than in the PBS group (P < .01). Compared with the PBS group, the 20 μg exendin-4 group showed lower osteoclast number (P < .05), odontoclast number (P < .05), and root resorption surface percentage (P < .05). Relative to maxillae with PBS injections, maxillae with 20 μg exendin-4 injections had lower receptor activator of nuclear factor kappa-B ligand (RANKL) mRNA expression (P < .05), TNF-α mRNA expression (P < .05), and RANKL/osteoprotegerin (OPG) ratio (P < .01). There were no differences in the expression of OPG mRNA. Exendin-4 inhibits orthodontic tooth movement. Therefore, additional attention is needed for orthodontic patients who receive exendin-4 for diabetes treatment. GLP-1 receptor may be a treatment target for patients with severe root resorption.


Overcoming the hurdle of implementation: putting human resources for health tools into action.
The global human resources for health (HRH) challenge remains persistent. In 2006, the World Health Report identified 57 crisis countries, and, despite increased attention and investment in strengthening the workforce, those countries are still in crisis. While chronic HRH problems still exist, progress has been made in some countries where innovative programs have been implemented that show promise, or specific initiatives have been scaled up. Yet, these have not been substantive enough to move countries out of the "crisis" category. While many countries have HRH plans, this paper asserts that a major reason countries remain in crisis is the lack of sustained implementation to achieve concrete workforce strengthening results. This is true despite the fact that there have been major investments in a broad range of tools and resources aimed to support implementation of plans and initiatives.Given this picture, the paper states that it is critical for HRH leaders to take action to ensure that already available tools are disseminated, adapted and used to foster effective implementation at the country level. The paper highlights four such tools as examples that can be used to build implementation capacity, and acknowledges more like them. Having highlighted these tools, the paper concludes by offering recommendations as to how to support more results-oriented implementation. These recommendations are organized around three linked components: 1) providing sufficient advocacy to leadership at the national level to mobilize and commit them to implementation action, 2) assembling and managing the requisite assets (including the institutional arrangements, people and money) into a coherent and powerful whole, and 3) using accountability as a foundational tool to assess progress in implementation, track key indicators, celebrate achieving key milestones and identify problems when indicators are not achieved.


N-(1,3-Thia-zol-2-yl)-N'-[(thio-phen-2-yl)carbon-yl]thio-urea hemihydrate.
The title compound, C9H7N3OS3·0.5H2O, crystallizes with two independent but similar mol-ecules in the asymmetric unit, both of which are linked by a water mol-ecule through O-H⋯N hydrogen bonds. In addition the water O atom is further linked by N-H⋯O hydrogen bonds to two additional main mol-ecules, forming a tetra-meric unit. These tetra-meric units then form infinite ribbons parallel to the ac plane.The dihedral angle between the thio-phenoyl and thia-zolyl rings is 12.15 (10) and 21.69 (11)° in mol-ecules A and B, respectively. The central thio-urea core makes dihedral angles of 5.77 (11) and 8.61 (9)°, respectively, with the thio--phen-oyl and thia-zolyl rings in mol-ecule A and 8.41 (10) and 13.43 (12)° in mol-ecule B. Each mol-ecule adopts a trans-cis geometry with respect to the position of thio-phenoyl and thia-zole groups relative to the S atom across the thio-urea C-N bonds. This geometry is stabilized by intra-molecular N-H⋯O hydrogen bonds.


Local and systemic effects of phosphorus and nitrogen on nodulation and nodule function in Alnus incana.
Phosphorus (P) and nitrogen (N) effects on nodulation, nitrogenase activity and plant growth were studied in the root-hair-infected actinorhizal plant Alnus incana (L.) Moench. A split-root experiment, as well as a short-term experiment with entire root systems and a broader range of P concentrations, showed that P effects were specific on nodulation and not a general stimulation via a plant growth effect. These results indicate that nodule initiation and nodule growth have a high P demand. The split-root assay, comprising seven combinations of two N and two P levels, showed that P could counteract systemic N inhibition of nodulation, but did not counteract N inhibition of nitrogenase activity.


Heterogeneous Origins of Human Sleep Spindles in Different Cortical Layers.
Sleep spindles are a cardinal feature in human NREM sleep and may be important for memory consolidation. We studied the intracortical organization of spindles in men and women by recording spontaneous sleep spindles from different cortical layers using linear microelectrode arrays. Two patterns of spindle generation were identified using visual inspection, and confirmed with factor analysis. Spindles (10-16 Hz) were largest and most common in upper and middle channels, with limited involvement of deep channels. Many spindles were observed in only upper or only middle channels, but approximately half occurred in both. In spindles involving both middle and upper channels, the spindle envelope onset in middle channels led upper by ∼25-50 ms on average. The phase relationship between spindle waves in upper and middle channels varied dynamically within spindle epochs, and across individuals. Current source density analysis demonstrated that upper and middle channel spindles were both generated by an excitatory supragranular current sink while an additional deep source was present for middle channel spindles only. Only middle channel spindles were accompanied by deep low (25-50 Hz) and high (70-170 Hz) gamma activity. These results suggest that upper channel spindles are generated by supragranular pyramids, and middle channel by infragranular. Possibly, middle channel spindles are generated by core thalamocortical afferents, and upper channel by matrix. The concurrence of these patterns could reflect engagement of cortical circuits in the integration of more focal (core) and distributed (matrix) aspects of memory. These results demonstrate that at least two distinct intracortical systems generate human sleep spindles.SIGNIFICANCE STATEMENT Bursts of ∼14 Hz oscillations, lasting ∼1 s, have been recognized for over 80 years as cardinal features of mammalian sleep. Recent findings suggest that they play a key role in organizing cortical activity during memory consolidation. We used linear microelectrode arrays to study their intracortical organization in humans. We found that spindles could be divided into two types. One mainly engages upper layers of the cortex, which are considered to be specialized for associative activity. The other engages both upper and middle layers, including those devoted to sensory input. The interaction of these two spindle types may help organize the interaction of sensory and associative aspects of memory consolidation.


National wealth, individualism, generalised trust, and religiosity as moderators of the relationship between helping strangers and life satisfaction in 137 societies.
We predicted that the relationship between helping strangers and life satisfaction would depend partially on the wealth of the country in which one lives. We argue that wealthy societies provide a wide range of welfare provisions for assisting their citizens. By contrast, people living in poorer countries with associated lower individualism, lower generalised trust, and higher religiosity have fewer financial and institutional supports for their daily welfare. They thus receive greater personal and interpersonal rewards for helping strangers in their societies and experience greater life satisfaction. Using a 137-country sample, we found that the relationship between helping strangers and life satisfaction was weaker in wealthier nations and in nations with more individualistic, more trusting, but less religious citizens. When all four moderators were used, only trust and religiosity remained significant moderators. In a supplementary mediated moderation model, we also found that trust and religiosity mediated the effect of national wealth on the relationship between kindness and life satisfaction. We conclude that the relationship between kindness and life satisfaction depends on various aspects of national culture that may reduce or increase people's dependence in their daily lives on the help of others as opposed to dependence on welfare institutions.


cDNA clones of Japanese hepatitis C virus genomes derived from a single patient show sequence heterogeneity.
Twelve cDNA clones of Japanese hepatitis C virus (HCV) have been isolated from liver tissue of a single non-A, non-B hepatitis patient. These clones represented the non-structural domains of HCV. The degree of substitution in the nucleotide sequences and deduced amino acid sequences between these clones was 9.5 and 7.7%, respectively. This high level of substitution suggested that repeated infections of different HCVs may have occurred in the patient.


Semantic-hierarchical model improves classification of spoken-word evoked electrocorticography.
Classification of spoken word-evoked potentials is useful for both neuroscientific and clinical applications including brain-computer interfaces (BCIs). By evaluating whether adopting a biology-based structure improves a classifier's accuracy, we can investigate the importance of such structure in human brain circuitry, and advance BCI performance. In this study, we propose a semantic-hierarchical structure for classifying spoken word-evoked cortical responses. The proposed structure decodes the semantic grouping of the words first (e.g., a body part vs. a number) and then decodes which exact word was heard. The proposed classifier structure exhibited a consistent ∼10% improvement of classification accuracy when compared with a non-hierarchical structure. Our result provides a tool for investigating the neural representation of semantic hierarchy and the acoustic properties of spoken words in human brains. Our results suggest an improved algorithm for BCIs operated by decoding heard, and possibly imagined, words.


Behavioral surveillance study: sexual risk taking behaviour in UK HIV outpatient attendees.
This study aimed to determine demographic, behavioural and self-report disease/treatment variables among HIV-infected individuals (n = 666) that predict unprotected intercourse with a partner of unknown/discordant status. Sexual risk behaviour was reported by 12.8%. In multivariable analysis, risk was more likely to be reported by gay men compared to women or heterosexual men, and for those with higher psychological symptom burden. Psychological symptoms should be assessed and managed in the HIV outpatient setting to ensure integrated care that enhances prevention.


Management of Ankylotic Root Resorption Following Dental Trauma: A Short Review and Proposal of a Treatment Protocol.
Ankylotic root resorption is a serious complication following traumatic dental injuries. The aetiology of root resorption includes acute injury to the cementum and periodontal ligament, and subsequent biological processes that propagate the harm. The aim of the present paper is to present a structured treatment protocol for teeth that have experienced trauma and are at risk of developing ankylotic root resorption, followed by a decoronation protocol for situations in which ankylotic root resorption developed. This protocol provides a structured road map from the primary dental trauma, through the initial development of ankylosis detected radiographically, to the clinical manifestation that results in significant infra-occlusion. The current protocol integrates the best available evidence from the literature and from published guidelines. Ample contradictory data, which mainly consists of case reports related to the treatment of ankylotic root resorption, is available in the current literature. No accepted protocol or uniform guidelines for treatment in these cases exist, and many clinicians prefer avoiding replantation of an avulsed tooth that seems to have an uncertain longterm prognosis, or performing decoronation when infra-occlusion developed. As a result, young patients lose the benefits associated with replantation and decoronation procedures. The option of re-implantation of the avulsed teeth should be considered irrespective of the negative long-term prognosis. Following ankylosis development, the goal of submerging the tooth root (decoronation) is to maintain the horizontal dimension of the alveolar ridge and also to gain vertical dimension, allowing implant placement in the future.


A solanesol-derived scaffold for multimerization of bioactive peptides.
A flexible molecular scaffold bearing varying numbers of terminal alkyne groups was synthesized in five steps from solanesol. R(CO)-MSH(4)-NH(2) ligands, which have a relatively low affinity for binding at the human melanocortin 4 receptor (hMC4R), were prepared by solid phase synthesis and were N-terminally acylated with 6-azidohexanoic acid. Multiple copies of the azide N(3)(CH(2))(5)(CO)-MSH(4)-NH(2) were attached to the alkyne-bearing, solanesol-derived molecular scaffold via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Control studies showed that the binding affinity of the triazole-containing ligand, CH(3)(CH(2))(3)(C(2)N(3))(CH(2))(5)(CO)-MSH(4)-NH(2), was not significantly diminished relative to the corresponding parental ligand, CH(3)(CO)-MSH(4)-NH(2). In a competitive binding assay with a Eu-labeled probe based on the superpotent ligand NDP-alpha-MSH, the monovalent and multivalent constructs appear to bind to hMC4R as monovalent species. In a similar assay with a Eu-labeled probe based on MSH(4), modest increases in binding potency with increased MSH(4) content per scaffold were observed.


Chlorine Disinfection of Legionella spp., L. pneumophila, and Acanthamoeba under Warm Water Premise Plumbing Conditions.
Premise plumbing conditions can contribute to low chlorine or chloramine disinfectant residuals and reactions that encourage opportunistic pathogen growth and create risk of Legionnaires' Disease outbreaks. This bench-scale study investigated the growth of Legionella spp. and Acanthamoeba in direct contact with premise plumbing materials-glass-only control, cross-linked polyethylene (PEX) pipe, magnesium anode rods, iron pipe, iron oxide, pH 10, or a combination of factors. Simulated glass water heaters (SGWHs) were colonized by Legionella pneumophila and exposed to a sequence of 0, 0.1, 0.25, and 0.5 mg/L chlorine or chloramine, at two levels of total organic carbon (TOC), over 8 weeks. Legionella pneumophila thrived in the presence of the magnesium anode by itself and or combination with other factors. In most cases, 0.5 mg/L Cl2 caused a significant rapid reduction of L. pneumophila, Legionella spp., or total bacteria (16S rRNA) gene copy numbers, but at higher TOC (>1.0 mg C/L), a chlorine residual of 0.5 mg/L Cl2 was not effective. Notably, Acanthamoeba was not significantly reduced by the 0.5 mg/L chlorine dose.


Omega-3 fatty acids and schizophrenia: evidences and recommendations.
Schizophrenia is a brain disease that represents a not rare condition, in fact the lifetime risk of developing schizophrenia is widely accepted to be around 1 in 100. Schizophrenia clinically manifests with acute episodes which are associated with hallucinations, delirium, behavioral disorders and a variable range of chronic persistent symptoms, which can be debilitating. The causes of schizophrenia are not clearly understood. It seems that genetic factors may produce a vulnerability to schizophrenia, along with environmental factors that contribute in a different way from individual to individual. In this context schizophrenia constitutes the outcome of a complex interaction between multiple genes and environmental risk factors, none of which on its own causes the disorder itself. Antipsychotic medications represent the first line of psychiatric treatment for schizophrenia. But there is a growing body of evidence that omega-3 fatty acids can prevent the disease or at least mitigate the course and symptoms. Probably, an appropriate dietary supplementation can play a partially therapeutic effect, even in more severe patients, improving some behavioral aspects and, mainly, reducing the cognitive deterioration. In this context the role of omega-3 fatty acids as a treatment for schizophrenia will strengthen the thrust of researchers and clinicians to the integrated approach to the prevention and cure of a disease that for more than a century challenging researchers.


Evaluating the capacity of plant DNA barcodes to discriminate species of cotton (Gossypium: Malvaceae).
Although two plastid regions have been adopted as the standard markers for plant DNA barcoding, their limited resolution has provoked the consideration of other gene regions, especially in taxonomically diverse genera. The genus Gossypium (cotton) includes eight diploid genome groups (A-G, and K) and five allotetraploid species which are difficult to discriminate morphologically. In this study, we tested the effectiveness of three widely used markers (matK, rbcL, and ITS2) in the discrimination of 20 diploid and five tetraploid species of cotton. Sequences were analysed locus-wise and in combinations to determine the most effective strategy for species identification. Sequence recovery was high, ranging from 92% to 100% with mean pairwise interspecific distance highest for ITS2 (3.68%) and lowest for rbcL (0.43%). At a 0.5% threshold, the combination of matK+ITS2 produced the greatest number of species clusters. Based on 'best match' analysis, the combination of matK+ITS2 was best, while based on 'all species barcodes' analysis, ITS2 gave the highest percentage of correct species identifications (98.93%). The combination of sequences for all three markers produced the best resolved tree. The disparity index test based on matK+rbcL+ITS2 was significant (P < 0.05) for a higher number of species pairs than the individual gene sequences. Although all three barcodes separated the species with respect to their genome type, no single combination of barcodes could differentiate all the Gossypium species, and tetraploid species were particularly difficult.


Finding neuroelectric activity under magnetic-field oscillations (NAMO) with magnetic resonance imaging in vivo.
Neuroimaging techniques are among the most important tools for investigating the function of the human nervous system and for improving the clinical diagnosis of neurological disorders. However, most commonly used techniques are limited by their invasiveness or their inability to accurately localize neural activity in space or time. Previous attempts at using MRI to directly image neuroelectric activity in vivo through the detection of magnetic field changes induced by neuronal currents have been challenging because of the extremely small signal changes and confounding factors such as hemodynamic modulations. Here we describe an MRI technique that uses oscillating magnetic field gradients to significantly amplify and detect the Lorentz effect induced by neuroelectric activity, and we demonstrate its effectiveness in imaging sensory nerve activation in vivo in the human median nerve during electrical stimulation of the wrist. This direct, real-time, and noninvasive neuroimaging technique may potentially find broad applications in neurosciences.


Changes in left ventricular stroke volume measured by Doppler echocardiography.
Cardiac stroke volume was measured simultaneously by Doppler echocardiography and thermodilution in 20 patients with coronary artery disease. Stroke volume as determined by ultrasound was calculated from the area of the aortic orifice and the flow velocity just distal to the aortic cusps. The recordings were made twice at rest. Ten patients were given dobutamine (2.5 and 5.0 micrograms/kg/min) by infusion to induce rapid changes in stroke volume from the resting state. The individual Doppler data before, during, and after dobutamine infusion correlated closely with the thermodilution data (r = 0.92). These results suggest that Doppler echocardiography reliably detects changes in stroke volume.


Aerobic and resistance exercise improves Reynolds risk score in overweight or obese breast cancer survivors.
Breast cancer survivors have double the risk of mortality from cardiovascular disease than age-matched women without a cancer history. Reynolds risk score (RRS) is a validated algorithm for the assessment of cardiovascular disease risk. This secondary analysis sought to examine the effects of a 16-week aerobic and resistance exercise intervention on RRS in overweight or obese breast cancer survivors. One hundred overweight or obese (BMI > 25 kg/m2) breast cancer survivors were randomized to exercise or usual care. The exercise group underwent aerobic and resistance exercise sessions for 16 weeks. RRS was calculated using a validated equation. Group differences in mean change for RRS were evaluated using repeated-measures analyses of variance. Post-intervention, RRS was significantly reduced (7.9 ± 0.9% to 1.0 ± 0.5%; p < 0.001) in the exercise group compared to a significant increase (9.0 ± 0.8% to 11.6 ± 1.2%; p = 0.002%) in the usual care group (p < 0.01). RRS was significantly reduced in exercise vs usual care (between group difference, - 10.6; 95% CI, - 16.3 to - 7.4; p < 0.001). A 16-week aerobic and resistance exercise intervention is an effective approach to reduce the risk of cardiovascular disease in breast cancer survivors. Exercise during cancer survivorship should be considered to reduce the risk for cardiovascular disease risk in overweight women breast cancer survivors. ClinicalTrials.gov: NCT01140282 . Registered 9 June 2010.


Quantitative assessment of the synovial membrane in the rheumatoid wrist: an easily obtained MRI score reflects the synovial volume.
Determination of the synovial membrane volume in the rheumatoid arthritis (RA) wrist by gadolinium-DTPA-enhanced MRI is introduced. Moreover, dynamic imaging and an MRI score of synovial hypertrophy, based on gradings in six regions, are evaluated as substitutes of the time-consuming volume calculations. Twenty-six RA wrists were examined. Synovial membrane volumes ranged from 1 to 20 ml (median 9 ml). Synovial hypertrophy scores were highly correlated to synovial volumes (Spearman r = 0.88; P < 10(-8) for uncorrelated values). The volumes and scores were significantly higher in wrists with joint swelling and/or joint tenderness than in wrists without these signs (Mann-Whitney, both P < 0.05). Suboptimal slice selection made dynamic imaging uninformative. MRI allows quantification of the synovial volume in the rheumatoid wrist. The volume is related to clinical signs of inflammation, but may also give information about the cumulated synovial proliferation in the joint. An easily obtained score of synovial hypertrophy reflects the synovial volume and may thus be a useful marker of synovial involvement.


An Arabidopsis thaliana cDNA encoding PS II-X, a 4.1 kDa component of photosystem II: a bipartite presequence mediates SecA/delta pH-independent targeting into thylakoids.
Higher plant photosystem II preparations contain a 4.1 kDa polypeptide (subunit X) associated with the oxygen-evolving core complex. We describe the isolation of a cDNA encoding PS II-X from Arabidopsis thaliana, in which the C-terminal region is highly homologous to partially sequenced PS II-X from wheat and spinach. The mature protein of 42 residues is preceded by a 74-residue, bipartite presequence similar to those involved in the targeting of nuclear-encoded thylakoid lumen proteins, although hydrophobicity analysis indicates the presence of a single transmembrane span in the mature protein. Moreover, import of pre-PS II-X into the thylakoid membrane of isolated chloroplasts is unaffected by inhibitors of either the Sec- or delta pH-dependent thylakoidal protein translocases, suggesting a spontaneous insertion mechanism. PS II-X appears to be encoded as a mature protein by the plastid genome in the chlorophyll a+c- containing alga, Odontella sinensis. We thus propose that the thylakoid transfer signal of Arabidopsis pre-PS II-X represents a recent acquisition, in phylogenetic terms, compared with signals of Sec-dependent lumenal proteins.


A Single Surgeon's Experience With Transgender Female-to-Male Chest Surgery.
Chest wall recontouring is a common surgical treatment of gender dysphoria in transmen and nonbinary individuals assigned female at birth. This study reviews more than 20 years of cases to identify risk factors for postoperative complications and likelihood of preservation of nipple sensation. One hundred thirty-seven cases of female-to-male chest wall recontouring by a single surgeon from 1994 to 2016 were reviewed, 99 of which were included for final analysis. Double-incision free nipple graft and double incision with nipple transposition on a pedicle were the most common techniques used. Complication rates between these 2 techniques were compared, and multivariate analysis was used to identify possible predictors of major complications, and minor complications. No significant risk factors for major complications were identified. With regard to minor complications, advanced patient age (odds ratio [OR], 1.67; P = 0.03) and early surgical experience (OR, 5.08; P = 0.001) were found to be associated with increased risk. Preoperative hormonal treatment was found to trend toward a protective effect (OR, 0.13; P = 0.07). Any of the reviewed techniques are safe in practice; however, there is a learning curve associated with their use, and longer follow-up will allow for the identification of late complications. The double incision with nipple transposition on a pedicle technique can be considered for patients for whom depigmentation of the nipple-areola complex is a significant concern, especially if they are willing to tolerate a potentially suboptimal chest contour.


Role of non-neuronal cells in body weight and appetite control.
The brain is composed of neurons and non-neuronal cells, with the latter encompassing glial, ependymal and endothelial cells, as well as pericytes and progenitor cells. Studies aimed at understanding how the brain operates have traditionally focused on neurons, but the importance of non-neuronal cells has become increasingly evident. Once relegated to supporting roles, it is now indubitable that these diverse cell types are fundamental for brain development and function, including that of metabolic circuits, and they may play a significant role in obesity onset and complications. They participate in processes of neurogenesis, synaptogenesis, and synaptic plasticity of metabolic circuits both during development and in adulthood. Some glial cells, such as tanycytes and astrocytes, transport circulating nutrients and metabolic factors that are fundamental for neuronal viability and activity into and within the hypothalamus. All of these cell types express receptors for a variety of metabolic factors and hormones, suggesting that they participate in metabolic function. They are the first line of defense against any assault to neurons. Indeed, microglia and astrocytes participate in the hypothalamic inflammatory response to high fat diet (HFD)-induced obesity, with this process contributing to inflammatory-related insulin and leptin resistance. Moreover, HFD-induced obesity and hyperleptinemia modify hypothalamic astroglial morphology, which is associated with changes in the synaptic inputs to neuronal metabolic circuits. Astrocytic contact with the microvasculature is increased by HFD intake and this could modify nutrient/hormonal uptake into the brain. In addition, progenitor cells in the hypothalamus are now known to have the capacity to renew metabolic circuits, and this can be affected by HFD intake and obesity. Here, we discuss our current understanding of how non-neuronal cells participate in physiological and physiopathological metabolic control.


Catalase, a specific antigen in the feces of human subjects infected with Helicobacter pylori.
Recently, we reported the production of three new monoclonal antibodies with high specificity for a Helicobacter pylori antigen suitable for diagnosis of H. pylori infection. The aim of the present study was to identify the antigen recognized by these monoclonal antibodies concerning both H. pylori and the feces of human subjects infected with H. pylori. The cellular antigen was purified from an H. pylori cell extract by immunoaffinity column chromatography with the monoclonal antibody as a ligand. The amino-terminal amino acid sequences (eight residues) of the purified antigen and H. pylori catalase were the same. The molecular weights of native and subunit, specific catalase activity, and UV and visible spectra of the purified antigen were in good agreement with those of H. pylori catalase. The human fecal antigens were purified from two fecal samples of two H. pylori-positive subjects by ammonium sulfate precipitation, CM-Sephadex C(50) chromatography, and the same immunoaffinity chromatography used for the H. pylori cellular antigen. The fecal antigens had catalase activity. The amino-terminal amino acid sequences (five residues) of the human fecal antigen and H. pylori catalase were the same. The monoclonal antibodies reacted with the native cellular antigen, but did not react with the denatured antigen, human catalase, and bovine catalase. The results show that the target antigen of the monoclonal antibodies is native H. pylori catalase and that the monoclonal antibodies are able to specifically detect the antigen, which exists in an intact form, retaining the catalase activity in human feces.


Clinical and economic impact of methicillin resistance in patients with Staphylococcus aureus bacteremia.
We performed a retrospective cohort study to determine the morbidity, mortality, and hospital costs attributable to methicillin resistance in patients with S. aureus bacteremia (SAB). Episodes of SAB occurring at the Detroit Receiving Hospital in 1999-2001 were evaluated. Controlling for confounding variables, patients with methicillin-resistant Staphylococcus aureus (MRSA) had a 1.5-fold longer length of stay (19.1 versus 14.2 days, P = 0.005) and a 2-fold increased cost of hospitalization (dollar 21577 versus dollar 11668, P = 0.001) compared with methicillin-susceptible S. aureus (MSSA). MRSA patients were at increased risk for delayed treatment, and delayed therapy was an independent predictor of mortality. Efforts should be made to ensure that appropriate therapy is initiated promptly in patients at risk for MRSA. Infection control policies must be strictly enforced to limit the spread of MRSA and potentially minimize excess hospital expenditures incurred with MRSA. With the advent of new treatment options, the impact of MRSA will need to be revisited to determine if these therapies can remedy the increased morbidity associated with MRSA.


Skill-based job descriptions for sterile processing technicians--a total quality approach.
Rochester General Hospital in Rochester, NY, included as part of its total quality management effort the task of revising job descriptions for its sterile processing technicians as a way to decrease turnover and increase job satisfaction, teamwork and quality output. The department's quality team developed "skill banding," a tool that combines skill-based pay with large salary ranges that span job classifications normally covered by several separate salary ranges. They defined the necessary competencies needed to move through five skill bands and worked with the rest of the department to fine-tune the details. The process has only recently been implemented, but department employees are enthusiastic about it.


Quantification of colloid retention and release by straining and energy minima in variably saturated porous media.
The prediction of colloid transport in unsaturated porous media in the presence of large energy barrier is hampered by scant information of the proportional retention by straining and attractive interactions at surface energy minima. This study aims to fill this gap by performing saturated and unsaturated column experiments in which colloid pulses were added at various ionic strengths (ISs) from 0.1 to 50 mM. Subsequent flushing with deionized water released colloids held at the secondary minimum. Next, destruction of the column freed colloids held by straining. Colloids not recovered at the end of the experiment were quantified as retained at the primary minimum. Results showed that net colloid retention increased with IS and was independent of saturation degree under identical IS and Darcian velocity. Attachment rates were greater in unsaturated columns, despite an over 3-fold increase in pore water velocity relative to saturated columns, because additional retention at the readily available air-associated interfaces (e.g., the air-water-solid [AWS] interfaces) is highly efficient. Complementary visual data showed heavy retention at the AWS interfaces. Retention by secondary minima ranged between 8% and 46% as IS increased, and was greater for saturated conditions. Straining accounted for an average of 57% of the retained colloids with insignificant differences among the treatments. Finally, retention by primary minima ranged between 14% and 35% with increasing IS, and was greater for unsaturated conditions due to capillary pinning.


Gambling Marketing Strategies and the Internet: What Do We Know? A Systematic Review.
Background: The gambling industry has developed many types of gambling on Internet in recent years. Gambling is a social activity for a majority of the world population, but problem gambling (PG) can emerge. The trajectories of gamblers from initiation to PG development are influenced by many variables, including individual and environmental variables and also variables linked to the gambling characteristics. Marketing has been reported to influence gamblers' perceptions and behaviors, but this is not as clear for digital marketing. Digital gambling marketing is broad, ranging from the marketing of gambling websites to communication and advertising on the social media and networks. The objective of this article was to fill this gap by conducting a systematic literature review in order to answer the following questions: (1) What are the strategies of digital gambling marketing? (2) What is the effect of this exposure on gambling representations, intentions and practices? Method: A systematic review was conducted following the PRISMA guidelines on Pubmed database (Medline) from February 2020 to March 2020 and Scopus. Existing papers published between January 2000 and February 2020 were identified by searching with this algorithm: ((("internet"[MeSH Major Topic] OR (communications[All Fields] AND media[All Fields])) OR ("social media"[MeSH Terms] OR ("social"[All Fields] AND "media"[All Fields]) OR "social media"[All Fields])) AND "gambling"[MeSH Major Topic]) AND ("marketing"[MeSH Terms] OR "marketing"[All Fields]), in title, keywords or abstract. Results: Ninety-one candidate studies were selected, 21 studies were selected for the systematic review. Sport appeared as a specific target of online gambling marketing. A growing range of platforms for online sport betting and the development of strategies on the social media were identified. Regarding content, a systematic association between sport and gambling was highlighted. Vulnerable populations, such as young people, appeared to be at high risk of exposure to gambling marketing. Conclusion: Little data is available on the strategies of digital gambling marketing or on exposure to it. Sport could be the first target for future research to understand how the industry is targeting specific populations, and what influence these strategies could have on PG development.


Individualized PEEP without Recruitment Maneuvers Improves Intraoperative Oxygenation: A Randomized Controlled Study.
Individualized positive end-expiratory pressure (PEEP) combined with recruitment maneuvers improves intraoperative oxygenation in individuals undergoing robot-assisted prostatectomy. However, whether electrical impedance tomography (EIT)-guided individualized PEEP without recruitment maneuvers can also improve intraoperative oxygenation is unknown. To test this, fifty-six male patients undergoing elective robot-assisted laparoscopic prostatectomy were randomly assigned to either individualized PEEP (Group PEEPIND, n = 28) or a control with a fixed PEEP of 5 cm H2O (Group PEEP5, n = 28). Individualized PEEP was guided by EIT after placing the patients in the Trendelenburg position and performing intraperitoneal insufflation. Patients in Group PEEPIND maintained individualized PEEP without intermittent recruitment maneuvers, and those in Group PEEP5 maintained a PEEP of 5 cm H2O intraoperatively. Both groups were extubated in a semi-sitting position once the extubation criteria were met. The primary outcome was arterial oxygen partial pressure (PaO2)/inspiratory oxygen fraction (FiO2) prior to extubation. Other outcomes included intraoperative driving pressure, plateau pressure and dynamic, respiratory system compliance, and the incidence of postoperative hypoxemia in the post-operative care unit (PACU). Our results showed that the intraoperative median for PEEPIND was 16 cm H2O (ranging from 12 to 18 cm H2O). EIT-guided PEEPIND was associated with higher PaO2/FiO2 before extubation compared to PEEP5 (71.6 ± 10.7 vs. 56.8 ± 14.1 kPa, p = 0.003). Improved oxygenation extended into the PACU with a lower incidence of postoperative hypoxemia (3.8% vs. 26.9%, p = 0.021). Additionally, PEEPIND was associated with lower driving pressures (12.0 ± 3.0 vs. 15.0 ± 4.4 cm H2O, p = 0.044) and better compliance (44.5 ± 12.8 vs. 33.6 ± 9.1 mL/cm H2O, p = 0.017). Our data indicated that individualized PEEP guided by EIT without intraoperative recruitment maneuvers also improved perioperative oxygenation in patients undergoing robot-assisted laparoscopic radical prostatectomy, which could benefit patients with the risk of intraoperative hemodynamic instability caused by recruitment maneuvers. Trial registration: China Clinical Trial Registration Center Identifier: ChiCTR2100053839. This study was registered on 1 December 2021. The first patient was recruited on 15 December 2021.


[Clinical course and diagnosis of the acute craniocervical injury].
Combined observation and treatment of 126 patients (80 men, 46 women) aged 15-67 years were carried out in the acute period of craniocerebral trauma of mild or moderate severity. Diagnostic methods including neurological examination, manual testing and X-ray investigation are discussed. The conclusion is made that craniocerebral trauma should be considered as craniocervical trauma as an indirect damage of the neck was revealed in each case in the form of myofascial syndrome pronounced in different degree; cervical syndrome of vertebral artery was also frequent. These data must be taken into consideration in pathogenetic treatment of patients with craniocerebral trauma.


Multiparametric deep learning tissue signatures for a radiological biomarker of breast cancer: Preliminary results.
Deep learning is emerging in radiology due to the increased computational capabilities available to reading rooms. These computational developments have the ability to mimic the radiologist and may allow for more accurate tissue characterization of normal and pathological lesion tissue to assist radiologists in defining different diseases. We introduce a novel tissue signature model based on tissue characteristics in breast tissue from multiparametric magnetic resonance imaging (mpMRI). The breast tissue signatures are used as inputs in a stacked sparse autoencoder (SSAE) multiparametric deep learning (MPDL) network for segmentation of breast mpMRI. We constructed the MPDL network from SSAE with 5 layers with 10 nodes at each layer. A total cohort of 195 breast cancer subjects were used for training and testing of the MPDL network. The cohort consisted of a training dataset of 145 subjects and an independent validation set of 50 subjects. After segmentation, we used a combined SAE-support vector machine (SAE-SVM) learning method for classification. Dice similarity (DS) metrics were calculated between the segmented MPDL and dynamic contrast enhancement (DCE) MRI-defined lesions. Sensitivity, specificity, and area under the curve (AUC) metrics were used to classify benign from malignant lesions. The MPDL segmentation resulted in a high DS of 0.87 ± 0.05 for malignant lesions and 0.84 ± 0.07 for benign lesions. The MPDL had excellent sensitivity and specificity of 86% and 86% with positive predictive and negative predictive values of 92% and 73%, respectively, and an AUC of 0.90. Using a new tissue signature model as inputs into the MPDL algorithm, we have successfully validated MPDL in a large cohort of subjects and achieved results similar to radiologists.


Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenzaa.
These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America (IDSA) in 2009, prior to the 2009 H1N1 influenza pandemic. This document addresses new information regarding diagnostic testing, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal influenza. It is intended for use by primary care clinicians, obstetricians, emergency medicine providers, hospitalists, laboratorians, and infectious disease specialists, as well as other clinicians managing patients with suspected or laboratory-confirmed influenza. The guidelines consider the care of children and adults, including special populations such as pregnant and postpartum women and immunocompromised patients.


Relapsing Cutaneous Multiple Myeloma Responding to Immunochemotherapy: A Rare Case Report.
Multiple myeloma (MM) is characterized by the neoplastic proliferation of plasma cells. The diagnosis of this disease is often suspected through a constellation of clinical signs and symptoms of hypercalcemia, renal failure, anemia, and M-spike proteins. It is the second most common hematological malignancy after non-Hodgkin lymphomas. However, cutaneous MM is an extremely rare entity, and it is associated with poor prognosis. It presents as diffuse erythematous rash or violaceous nodules on the skin. Most common sites of involvement are chest, lower extremities and back. It can be triggered by a local extension of the tumor which is the most common way, surgical procedures and hematogenous spread. An 82-year-old African American male was diagnosed with MM since 2008. He underwent autologous peripheral stem cell transplantation (ASCT) twice in 2010 and 2014; and he had a history of multiple chemotherapy regimens in the past. He had violaceus chest nodules, and the biopsy confirmed the diagnosis of cutaneous MM in 2013. The patient was treated with pomalidomide, panobinostat and dexamethasone with a complete response (CR) to treatment. One year later, the patient developed new skin nodules. Repeat biopsy confirmed the diagnosis of MM again. Patient was treated with daratumumab and had CR to treatment without any new M-spike. Cutaneous lesion is an exceedingly rare presentation of MM. It either present as reddish rash or violaceous nodules involving chest, lower extremities and back. It has a poor prognosis and can be rapidly fatal. Our case is unique because our patient responded to the newer chemotherapy, and lesions resolved despite poor prognosis of this condition.


Prevalence of Mycobacterium abscessus among the Patients with Nontuberculous Mycobacteria.
Considering the importance of the increasing incidence of non-tuberculous mycobacteria, especially Mycobacterium abscessus worldwide, we conducted a study to evaluate the incidence of these diseases in our area. The aim of this study was to evaluate the prevalence of M. abscessus in patients with non-tuberculous mycobacteria. This descriptive study was performed on 18,083 samples isolated from patients with non-tuberculous mycobacteria during 2011-2017 at the Mycobacteriology Research Center (MRC), Tehran, Iran. To identify the Mycobacterium species, a 439 bp fragment of the IS6110 gene was first amplified using primers TB1 and TB2. Samples with a negative polymerase chain reaction (PCR) result were analyzed to investigate non-tuberculosis mycobacteria (NTM), especially M. abscessus using the RFLP method. Of the 18,083 samples, 5513 (30.49%, 95% CI, 12.95) strains of Complex Tuberculosis and 236 (1.31%, 95% CI, 1.84) strains of NTM were identified. The mean age of the patients with NTM was 18 years, and most of them were male. The most commonly identified species in this study were M. abscessus type Ι 32 (13.56%, 95% CI, 18.36) and M. abscessus type II 13 (5.51%, 95%CI, 20.04). In this study, we observed a high prevalence of Mycobacterium abscessus type 1 in patients. As the treatment protocol for non-TB mycobacteria is different from M. abscessus complex, the diagnosis of these species as soon as possible will be significant for physicians.


Aerobic exercise training in an AIDS risk group.
Increases in physical fitness are often associated with improvements in certain chronic diseases, such as hypertension and coronary heart disease. Recent evidence has shown that exercise also influences the neuroendocrine and immune systems, resulting in a potential to benefit those with chronic immunodeficiency diseases. Therefore, exercise may prove to have a profound impact on the management of the acquired immunodeficiency syndrome (AIDS). Our current work includes the investigation of the immunologic and stress-attenuating effects of an aerobic exercise training program for individuals at risk for AIDS. Upon completion of training, the subjects showed a significant increase in helper/inducer (CD4) cells and the inducer subset (CD45RA+CD4+) which activate suppressor/cytotoxic (CD8) cells. These increases, which average about 50 cells per cubic millimeter, are comparable to those observed in some studies of the AIDS drug comparable to those observed in some studies of the AIDS drug azidothymidine (AZT), but without the accompanying side effects. Also, individuals undergoing aerobic training reported no increases in anxiety and depression in response to notification of a positive HIV-1 serologic status. These findings taken together indicate that an aerobic exercise training program may enhance certain critical components of cellular immunity as well as acting as a buffer for the detrimental mood changes that typically accompany stress, thus providing a timely, promising behavioral approach to helping HIV-1-infected individuals.


Prospective study of major dietary patterns and stroke risk in women.
Many foods have been suggested to influence the risk of stroke. However, no previous studies have examined the relationship between overall dietary patterns and risk of stroke. Using dietary information collected in 1984 from 71,768 women aged 38 to 63 years without a history of cardiovascular disease or diabetes in 1984, we conducted factor analysis and identified 2 major dietary patterns: "prudent" and "Western." We calculated scores for each participant for each pattern and prospectively examined their associations with stroke risk using a proportional hazard model, adjusting for other stroke risk factors. The prudent pattern was characterized by higher intakes of fruits, vegetables, legumes, fish, and whole grains, whereas the Western pattern by higher intakes of red and processed meats, refined grains, and sweets and desserts. During 14 years of follow-up, we identified 791 incidents of stroke, with 476 ischemic and 189 hemorrhagic strokes. After adjusting for potential confounders, we observed a relative risk (RR) of 1.58 (95% CI, 1.15 to 2.15; P=0.0002 for trend) for total strokes and 1.56 (95% CI, 1.05 to 2.33; P=0.02 for trend) for ischemic stroke when comparing the highest with lowest quintiles of the Western pattern. For the prudent pattern, the RRs comparing extreme quintiles were 0.78 (95% CI, 0.61 to 1.01) for total stroke and 0.74 (95% CI, 0.54 to 1.02) for ischemic stroke. These data suggest that a dietary pattern typified by higher intakes of red and processed meats, refined grains, and sweets and desserts may increase stroke risk, whereas a diet higher in fruits and vegetables, fish, and whole grains may protect against stroke.


A trillion trees: carbon capture or fuelling fires?
Afforesting grassy systems for carbon gain using flammable plantation trees could shift the fire regime from lower intensity grass-fuelled fires to high-intensity crown fires. Future changes in climate will worsen this. We highlight the fire risk of trees planted for carbon and costs of fire protection using African examples.


Hominin skeletal part abundances and claims of deliberate disposal of corpses in the Middle Pleistocene.
Humans are set apart from other organisms by the realization of their own mortality. Thus, determining the prehistoric emergence of this capacity is of significant interest to understanding the uniqueness of the human animal. Tracing that capacity chronologically is possible through archaeological investigations that focus on physical markers that reflect "mortality salience." Among these markers is the deliberate and culturally mediated disposal of corpses. Some Neandertal bone assemblages are among the earliest reasonable claims for the deliberate disposal of hominins, but even these are vigorously debated. More dramatic assertions center on the Middle Pleistocene sites of Sima de los Huesos (SH, Spain) and the Dinaledi Chamber (DC, South Africa), where the remains of multiple hominin individuals were found in deep caves, and under reported taphonomic circumstances that seem to discount the possibility that nonhominin actors and processes contributed to their formation. These claims, with significant implications for charting the evolution of the "human condition," deserve scrutiny. We test these assertions through machine-learning analyses of hominin skeletal part representation in the SH and DC assemblages. Our results indicate that nonanthropogenic agents and abiotic processes cannot yet be ruled out as significant contributors to the ultimate condition of both collections. This finding does not falsify hypotheses of deliberate disposal for the SH and DC corpses, but does indicate that the data also support partially or completely nonanthropogenic formational histories.


An analgesia-delirium-sedation protocol for critically ill trauma patients reduces ventilator days and hospital length of stay.
Analgesics and sedatives are required to maintain a calm and comfortable mechanically ventilated injured patient. Continuous sedative infusions have been shown to lengthen mechanical ventilation and hospital length of stay. Daily interruption of sedative infusions may reduce both of these variables. Implementation of an Analgesia-Delirium-Sedation (ADS) Protocol using objective assessments with a goal of maintaining an awake and comfortable patient may obviate the need for daily interruption of infusions in critically ill trauma patients. We examined the effects of such a protocol on ventilator duration, intensive care unit (ICU) length of stay, hospital slength of stay, and medication requirements. A multidisciplinary team designed the protocol. Objective measures of pain (visual/objective pain assessment scale-VAS/OPAS), agitation (Richmond Agitation-Sedation Scale-RASS), and delirium [Confusion Assessment Method {CAM-ICU}] were used. Medications were titrated to a RASS of -1 to +1 and VAS/OPAS <4. Haloperidol was used to treat delirium in CAM-ICU positive patients. Retrospective review of the local Project IMPACT database for a 6-month period in 2004 was compared with the same seasonal period in 2006 in which the ADS protocol was used. All mechanically ventilated trauma patients receiving infusions of narcotic, propofol, or benzodiazepine were included. Age, APACHE II score, Injury Severity Score, ventilator days, ventilator-free days at day 28, ICU length of stay, and hospital length of stay are reported as median values (interquartile range). Medication usage is reported as mean values (+/-SD). Differences in data were analyzed using Wilcoxon's rank-sum test or t test, as appropriate. Gender, mortality, and mechanism of injury were analyzed using chi analysis. A total of 143 patients were included. Patients who died during their hospitalization were excluded except in the analysis of ventilator-free days at day 28. After exclusions, 61 patients were in the control group and 58 in the protocol group. The median duration of mechanical ventilation in the protocol group was 1.2 days (0.5-3.0) which was significantly reduced compared with 3.2 days (1.0-12.9) in the control group (p = 0.027). Analysis of ventilator-free days at day 28 found that the protocol group had 26.4 ventilator-free days (13.9-27.4) compared with 22.8 days (10.5-26.9) in the control group (p = 0.007). The median ICU length of stay was 5.9 days (2.3-18.2) in the control group and 4.1 days (2.5-8.3) in the protocol group (p = 0.21). Hospital length of stay was 12 days (7-17) in the protocol group in contrast to 18 days (10-27) in the control group (p = 0.036). Opiate equivalents and propofol use per patient was significantly reduced in the protocol group from 2,465 mg (+/-1,242 mg) to 1,641 mg (+/-1,250 mg) and 19,232 mg (+/-22,477 mg) to 10,057 (+/-14,616 mg), respectively (p < 0.001, p = 0.01). An objective assessment- based ADS protocol without daily interruption of medication infusion decreases ventilator days and hospital length of stay in critically ill trauma patients.


Phase-sensitive time-modulated surface plasmon resonance polarimetry for wide dynamic range biosensing.
A novel polarimetry scheme is proposed to improve the performance of phase-sensitive Surface Plasmon Resonance (SPR) biosensors. The scheme uses s-polarized light, not affected by SPR, as a reference beam, while information on the phase of the p-polarized component is obtained from an analysis of phase-polarization state of light of mixed polarization. We utilize temporal modulation of the beam reflected under SPR by a photo-elastic modulator and show that, under certain birefringent geometry, the signals at the 2nd and 3rd harmonics of modulated frequency can provide ultra-sensitive phase-based response to changes of the refractive index (thickness) of thin films on gold. We also show that the proposed configuration significantly improves detection limit compared to conventional intensity-sensitive SPR, yet enables to maintain wide dynamic range of measurements, which is normally difficult with phase-sensitive SPR schemes. Biosensing applications of the proposed scheme are illustrated in a biological model reaction of avidin - biotin binding on gold.


New Agents in Non-Small Cell Lung Cancer.
Lung cancer is the leading cause of death due to cancer in the United States in both men and women over the age of 35 years. Standard chemotherapy regimens have led to a modest impact on survival, but new strategies and more effective agents are needed, particularly those that interact favorably with radiation therapy. Recently, several agents with novel mechanisms of action - paclitaxel, docetaxel, topotecan, irinotecan, 9-aminocamptothecin, edatrexate, vinorelbine, and gemcitabine - have shown significant activity in patients with non-small cell lung cancer. The results of those clinical trials and the plans for further development are discussed.


Developing a grounded theory for interprofessional collaboration acquisition using facilitator and actor perspectives in simulated wilderness medical emergencies.
Interprofessional collaboration is a complex process that has the potential to transform patient care for the better in urban, rural and remote healthcare settings. Simulation has been found to improve participants' interprofessional competencies, but the mechanisms by which interprofessionalism is learned have yet to be understood. A rural wilderness medicine conference (WildER Med) in northern Ontario, Canada with simulated medical scenarios has been demonstrated to be effective in improving participants' collaboration without formal interprofessional education (IPE) curriculum. Interprofessionalism may be taught through rural and remote medical simulation, as done in WildER Med where participants' interprofessional competencies improved without any formal IPE curriculum. This learning may be attributed to the informal and hidden curriculum. Understanding the mechanism by which this rural educational experience contributed to participants' learning to collaborate requires insight into the events before, during and after the simulations. The authors drew upon feedback from facilitators and patient actors in one-on-one interviews to develop a grounded theory for how collaboration is taught and learned. Sharing emerged as the core concept of a grounded theory to explain how team members acquired interprofessional collaboration competencies. Sharing was enacted through the strategies of developing common goals, sharing leadership, and developing mutual respect and understanding. Further analysis of the data and literature suggests that the social wilderness environment was foundational in enabling sharing to occur. Medical simulations in other rural and remote settings may offer an environment conducive to collaboration and be effective in teaching collaboration. When designing interprofessional education, health educators should consider using emergency response teams or rural community health teams to optimize the informal and hidden curriculum contributing to interprofessional learning.


Associations of Face-to-Face and Instant Messaging Family Communication and Their Contents With Family Wellbeing and Personal Happiness Amidst the COVID-19 Pandemic.
Both face-to-face and instant messaging (IM) communication are important for families, but face-to-face communication has reduced amidst the COVID-19 pandemic. We examined the use and contents of both communication methods amidst the pandemic, their associations with family wellbeing and personal happiness, and the mediation effects of communication quality in Hong Kong Chinese adults. This population-based online survey enrolled 4,921 respondents in May 2020, who reported (i) any face-to-face or IM family communication when the pandemic was severe; (ii) communication contents being classified as neutral, positive, supportive, and negative; and (iii) communication quality, family wellbeing and personal happiness (score 0-10). Associations of family wellbeing and personal happiness with communication methods and contents (no communication excluded) were examined using linear regressions (β), adjusting for each other, sex, age, socioeconomic status, and the number of cohabitants. Mediating effects of communication quality on these associations were examined. Prevalence estimates were weighted by sex, age, and education of the general population. Interactions of methods and contents were examined. Of 4,891 included respondents (female: 52.9%, 45-54 years: 37.7%, ≥65 years: 21.3%), 7.1% reported no communication, 12.7% face-to-face communication only, 26.7% IM only, and 53.4% both methods. More males and those at younger ages, had lower socioeconomic status, or fewer cohabitants showed no family communication or face-to-face only. More respondents reported neutral (83.1-99.3%) than positive (42.1-62.2%), supportive (37.5-54.8%), and negative (10.9-34.5%) contents despite communication methods. Communication quality was higher with both methods than IM only, face-to-face only, and no communication (scores: 6.7 vs. 4.5-6.6, all P ≤ 0.02). Better family wellbeing and personal happiness were associated with using IM only (adjusted βs: 0.37 and 0.48) and both methods (0.37 and 0.42) than face-to-face only, and positive (0.62 and 0.74) or supportive (0.45 and 0.46) contents (all P ≤ 0.001). Communication quality mediated 35.2-93.5% of these associations. Stronger associations between positive contents and family wellbeing showed in both methods and face-to-face only than IM only (P for interaction = 0.006). We have first shown that, amidst the COVID-19 pandemic, family IM communication and positive and supportive contents may promote family wellbeing and personal happiness. People with no family communication may need assistance.


Intranasal immunotherapy with M2 macrophage soluble factors in post-COVID hyposmia: A pilot study.
Olfactory dysfunction is an early marker of COVID-19 infection. However, individuals may develop chronic olfactory impairment for more than six months in 1-10 % of cases. The study's objective is to evaluate the efficacy and safety of intranasal immunotherapy using bioactive substances produced by M2 macrophages for the treatment of people with long-term post-COVID-19 hyposmia. Seven individuals with long-term persistent hyposmia (7 to 24 months), associated with PCR-confirmed coronavirus infection were evaluated for olfactory function at baseline, one, and six to twelve months after therapy. The intranasal inhalation of M2 macrophage conditioned medum (one time per day for 28-30 days) was well tolerated. Furthermore, olfactometry demonstrated that the patients restored their capacity to perceive (Kruskal-Wallis H test 14.123, p = 0.0009) and recognize odours (H = 11.674, p = 0.0029). In addition, the subjective evaluation of smell significantly improved (H = 11.935, p = 0.0026). At the 6- to 12-month follow-up, the majority of patients (5/7) reported extremely high levels of satisfaction with the outcomes, and the remaining two patients also felt generally positive about the therapy's success. Overall, our study showed that the use of intranasal inhalations as a method of delivering bioactive factors and the conditioned medium of M2 macrophages as a therapeutic agent are both safe, well tolerated and, according to preliminary data, clinically effective in the treatment of patients with long-term post-COVID-19 hyposmia.


[Antibodies to neuroleptics and their role in the mechanisms of the development of drug resistance in psychopharmacotherapy of patients with paranoid schizophrenia].
A study was made of the content of drug antibodies (DAT) to chlorpromazine, triphthazine and haloperidol in the blood sera of 112 patients with paranoid schizophrenia (acute period, curable exacerbation associated with the chronic course, and a group of therapeutically resistant subjects). Antibodies to neuroleptics were demonstrable in all the patients' groups. However, the rate of positive reactions and the content of DAT in the therapeutically resistant patients differed significantly from the characteristics in "acute" patients and in the group of "nonresistant" ones. The maximum "antigenicity" was shown by chlorpromazine, the minimum by haloperidol. The appearance and the content of DAT agree well with the duration of the drug intake, especially if the treatment is repeated. In acute conditions, the content of DAT was found to depend on the increment of the daily dose (with the exception of haloperidol). In chronic conditions and repeated treatments, the rise of the content of DAT was feasible with the low daily doses, particularly to chlorpromazine.


Autoantibodies to human heat shock protein (hsp)60 may be induced by Escherichia coli groEL.
The 65-kD hsp from Mycobacterium tuberculosis has been reported to induce an autopathogenic subset of T cells in at least two animal models of autoimmune disease. Reports of increased expression of human hsp60 in the inflamed synovial tissue of rheumatoid arthritis (RA) patients, increased proliferation of RA synovial fluid T cells to mycobacterial hsp65, and increased levels of anti-mycobacterial hsp65 antibody in synovial fluid, have suggested that the highly homologous human (hu) hsp60 may be recognized as an autoantigen iin RA patients. In the present study, we have examined by ELISA the serum IgG antibody levels to mycobacterial hsp65 and hu hsp60, as well as to the Escherichia coli hsp60, groEL, in patients with RA, systemic lupus erythematosus (SLE), Reiter's syndrome, active tuberculosis, and normal controls. In all these groups, the levels of anti-groEL and anti-hu hsp60 were significantly higher than the anti-mycobacterial hsp65. Anti-hu hsp60 was positively correlated with anti-groEL, but not with anti-mycobacterial hsp65. Anti-hu hsp60 was competitively inhibited by either soluble groEL or hu hsp60, but little or none by mycobacterial hsp65. Reiter's sera were found to have somewhat higher levels of anti-groEL and anti-hu hsp60 than did normal controls. We conclude that IgG anti-hu hsp60 autoantibodies arise primarily as a consequence of the humoral immune response to E. coli groEL through the recognition of cross-reactive epitopes.


Transcriptional Reprogramming of Distinct Peripheral Sensory Neuron Subtypes after Axonal Injury.
Primary somatosensory neurons are specialized to transmit specific types of sensory information through differences in cell size, myelination, and the expression of distinct receptors and ion channels, which together define their transcriptional and functional identity. By profiling sensory ganglia at single-cell resolution, we find that all somatosensory neuronal subtypes undergo a similar transcriptional response to peripheral nerve injury that both promotes axonal regeneration and suppresses cell identity. This transcriptional reprogramming, which is not observed in non-neuronal cells, resolves over a similar time course as target reinnervation and is associated with the restoration of original cell identity. Injury-induced transcriptional reprogramming requires ATF3, a transcription factor that is induced rapidly after injury and necessary for axonal regeneration and functional recovery. Our findings suggest that transcription factors induced early after peripheral nerve injury confer the cellular plasticity required for sensory neurons to transform into a regenerative state.


Long-term outcomes following microwave ablation for liver malignancies.
Microwave ablation has emerged as a promising treatment for liver malignancies, but there are scant long-term follow-up data. This study evaluated long-term outcomes, with a comparison of 915-MHz and 2.4-GHz ablation systems. This was a retrospective review of patients with malignant liver tumours undergoing operative microwave ablation with or without liver resection between 2008 and 2013. Regional or systemic (neo)adjuvant therapy was given selectively. Local recurrence was analysed using competing-risk methods with clustering, and overall survival was determined from Kaplan-Meier curves. A total of 176 patients with 416 tumours were analysed. Colorectal liver metastases (CRLM) comprised 81.0 per cent of tumours, hepatocellular carcinoma 8.4 per cent, primary biliary cancer 1.7 per cent and non-CRLM 8.9 per cent. Median follow-up was 20.5 months. Local recurrence developed after treatment of 33 tumours (7.9 per cent) in 31 patients (17.6 per cent). Recurrence rates increased with tumour size, and were 1.0, 9.3 and 33 per cent for lesions smaller than 1 cm, 1-3 cm and larger than 3 cm respectively. On univariable analysis, the local recurrence rate was higher after ablation of larger tumours (hazard ratio (HR) 2.05 per cm; P < 0.001), in those with a perivascular (HR 3.71; P = 0.001) or subcapsular (HR 2.71; P = 0.008) location, or biliary or non-CRLM histology (HR 2.47; P = 0.036), and with use of the 2.4-GHz ablation system (HR 3.79; P = 0.001). Tumour size (P < 0.001) and perivascular position (P = 0.045) remained significant independent predictors on multivariable analysis. Regional chemotherapy was associated with decreased local recurrence (HR 0.49; P = 0.049). Overall survival at 4 years was 58.3 per cent for CRLM and 79.4 per cent for other pathology (P = 0.360). Microwave ablation of liver malignancies, either combined or not combined with liver resection, and selective regional and systemic therapy resulted in good long-term survival. Local recurrence rates were low after treatment of tumours smaller than 3 cm in diameter, and those remote from vessels.


Concise Review: A Safety Assessment of Adipose-Derived Cell Therapy in Clinical Trials: A Systematic Review of Reported Adverse Events.
The popularity of adipose-derived cell therapy has increased over the last decade, and the number of studies published annually is growing. However, concerns regarding safety in the setting of previous malignancy or the use of allogeneic cells have been raised. We therefore aimed to systematically review all clinical studies using adipose-derived cell therapy to identify reported adverse events with a special focus on risk of thromboembolic, immunological, and oncological safety concerns. Our systematic search resulted in 70 included studies involving more than 1,400 patients that were treated with adipose-derived cell therapy. Safety assessment method was not described in 32 of the included studies. For studies involving systemic or cardiac administration, one case of pulmonary thromboembolism and cases of both myocardial and cerebral infarctions were described. In the setting of allogeneic cell therapy studies, where the production of specific antibodies toward donor cells was examined, it was noted that 19%-34% of patients develop antibodies, but the consequence of this is unknown. With regard to oncological safety, only one case of breast cancer recurrence was identified out of 121 patients. Adipose-derived cell therapy has so far shown a favorable safety profile, but safety assessment description has, in general, been of poor quality, and only adverse events that are looked for will be found. We encourage future studies to maintain a strong focus on the safety profile of cell therapy, so its safeness can be confirmed. Stem Cells Translational Medicine 2017;6:1786-1794.


Colony geometry and structural complexity of the endangered species Acropora cervicornis partly explains the structure of their associated fish assemblage.
In the past decade, significant efforts have been made to describe fish-habitat associations. However, most studies have oversimplified actual connections between fish assemblages and their habitats by using univariate correlations. The purpose of this study was to identify the features of habitat forming corals that facilitate and influences assemblages of associated species such as fishes. For this we developed three-dimensional models of colonies of Acropora cervicornis to estimate geometry (length and height), structural complexity (i.e., volume, density of branches, etc.) and biological features of the colonies (i.e., live coral tissue, algae). We then correlated these colony characteristics with the associated fish assemblage using multivariate analyses. We found that geometry and complexity were better predictors of the structure of fish community, compared to other variables such as percentage of live coral tissue or algae. Combined, the geometry of each colony explained 40% of the variability of the fish assemblage structure associated with this coral species; 61% of the abundance and 69% of fish richness, respectively. Our study shows that three-dimensional reconstructions of discrete colonies of Acropora cervicornis provides a useful description of the colonial structural complexity and may explain a great deal of the variance in the structure of the associated coral reef fish community. This demonstration of the strongly trait-dependent ecosystem role of this threatened species has important implications for restoration and conservation efforts.