Androgen receptor activation by polychlorinated biphenyls: epigenetic effects mediated by the histone demethylase Jarid1b.
The exposure to environmental endocrine disrupting compounds (EDC), as polychlorinated biphenyls (PCBs), widely diffused in the environment may produce epigenetic changes that affect the endocrine system. We found that PCBs activate AR transcriptional activity and that this effect is potentiated by the demethylase Jarid1b, a histone demethylase that catalyzes the removal of trimethylation of lysine 4 on histone H3 (H3K4me3), induced by PCB. The aim of the present study was to investigate the effect of the treatment of cultured cells (HEK293) with a mixture of the most diffused environmental PCBs and, also with dihydrotestosterone (DHT), on the functional interaction between AR and Jarid1b. Although the effect induced by DHT on the AR transactivation was considerably higher, the PCB mixture produced an AR-mediated transactivation in a dose-dependent manner. Cotransfection with plasmids expressing Jarid1b and various AR isoforms containing polyglutamine tracts (polyQ tracts) of different lengths showed that Jarid1b potentiates the AR transcriptional activity induced by PCBs but only with the shortest AR isoform. The potentiating effect of Jarid1b on the AR is mediated by a direct interaction of the enzyme with the AR promoter. In fact, utilizing constructs containing AR promoters with a different length and a luciferase reporter gene, we showed that the effect of PCBs, but not of DHT, needs the presence of Jarid1b and of at least two DNA binding sites for Jarid1b.


Treatment of subtrochanteric femoral fracture with long proximal femoral nail antirotation.
Subtrochanteric femoral fractures are severe injuries. Although many treatment methods have been developed, controversy exists regarding the optimal management of these fractures. This study evaluated the clinical outcome of subtrochanteric femoral fractures fixed with long proximal femoral nail antirotation (PFNA-long). Between October 2006 and February 2008, 25 patients with traumatic subtrochanteric fractures of the femur were treated with PFNA-long. Closed reduction and fixation were performed in 20 cases. In the remaining 5 cases, closed reduction was difficult, so limited open reduction was performed, with bone grafting in 4 cases and circumferential wiring in 4 cases. The average follow-up time was 16.1 months. All subtrochanteric femoral fractures healed uneventfully except one case of delayed union. The mean union time was 26.2 weeks. Technical difficulties with nail insertion were encountered in 3 cases. No implant failure was observed. PFNA-long is effective in treatment of subtrochanteric femoral fractures, with a high rate of bone union, minor soft tissue damage, early return to functional exercise and few implant-related complications.


The adenovirus protease is required for virus entry into host cells.
We have analyzed the mechanisms used by adenovirus to gain entry into the host cell. Using both virus infection and the ability of adenovirus particles to enhance polylysine/DNA uptake as a measure of virus entry, we have demonstrated that the adenovirus-encoded 23K protease is required for two functions in the infection process. A proteolytic processing of the capsid is required to generate a virus capsid that can increase membrane interactions at pH 5. We have found that forms of adenovirus capsid that have not undergone the processing reactions (immature capsids) are deficient in their ability to disrupt membranes at pH 5 and are unable to enhance the entry of polylysine/DNA complexes. A second role of the protease was revealed by experiments using inhibitors of the protease. Mature virus capsids lose their ability to enhance gene delivery and become noninfectious after exposure to inhibitors of the protease (1 microM N-ethylmaleimide, 100-300 microM copper chloride, 1 microM MDL28170, or anti-protease antiserum), suggesting that the viral protease activity is required during the cellular entry process.


beta4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium.
Tumor cells can evade chemotherapy by acquiring resistance to apoptosis. We investigated the molecular mechanism whereby malignant and nonmalignant mammary epithelial cells become insensitive to apoptosis. We show that regardless of growth status, formation of polarized, three-dimensional structures driven by basement membrane confers protection to apoptosis in both nonmalignant and malignant mammary epithelial cells. By contrast, irrespective of their malignant status, nonpolarized structures are sensitive to induction of apoptosis. Resistance to apoptosis requires ligation of beta4 integrins, which regulates tissue polarity, hemidesmosome formation, and NFkappaB activation. Expression of beta4 integrin that lacks the hemidesmosome targeting domain interferes with tissue polarity and NFkappaB activation and permits apoptosis. These results indicate that integrin-induced polarity may drive tumor cell resistance to apoptosis-inducing agents via effects on NFkappaB.


Higher Admission D-Dimer Values Are Associated With an Increased Risk of Nonroutine Discharge in Neurosurgery Patients.
Background D-dimers are serum acute-phase proteins with a role in mediating inflammation that may be used as biomarkers for the prediction of deep vein thrombosis. Recent studies have shown that D-dimers can be used to predict prognosis and stratify risk in neurosurgical patients; however, a comparative analysis across diagnostic subtypes has yet to be performed. Methods A bioinformatics analysis evaluated neurosurgical patients with admission D-dimer levels between 2008 and 2017. Nonroutine disposition (e.g., skilled nursing facility, rehabilitation, other hospital, mortality) was primarily evaluated. Results A total of 1,854 patients (mean age 55.1±18.2 years, 55.4% male; mean admission D-dimer 4.83±7.78 μg/ml) were identified. Patient diagnoses included vascular (27.1%), trauma (16.4%), multiple diagnoses (15.7%), spine (15.6%), tumor (13.0%), and other (12.2%) causes. Univariate analysis showed that older age (p=0.0001), higher American Society of Anesthesiologists (ASA) score (p=0.0001), lower Glasgow Coma Scale (GCS) score (p=0.0001), diagnosis type (p=0.0001), longer length of stay (LOS) (p=0.0001), higher infection rate (p=0.0001), surgery in the past year (p=0.02), and higher D-dimer levels (3.4±4.9 vs. 5.4±8.7 μg/ml, p=0.0001) were associated with nonroutine disposition. Multivariate logistic regression showed that elevated D-dimers were independently associated with a greater relative risk of nonroutine disposition (relative risk [RR] 1.026, 95% CI 1.02-1.033, p=0.0001). Conclusions Elevated admission D-dimer values were independently associated with a 3% increased risk of nonroutine disposition per D-dimer unit after accounting for other factors. These results suggest that D-dimer values may help in stratifying patient risk models despite clinical heterogeneity. Further refinement of neurosurgical patient risk models using clinical variables and biomarkers may aid in resource allocation and early warning.


Differential diagnostic features of small cell carcinoma in the uterine cervix.
Small cell carcinoma (SMCC) of the uterine cervix is rare and known to be an aggressive tumor, but there are only few reports on the cytologic features of cervical SMCC. This rare small cell lesion should be distinguished from malignant lymphoma (ML), squamous cell carcinoma in situ (SCIS), and chronic lymphocytic cervicitis (CLC). By clarifying cytologic features and reevaluating the significance of cervical cytologic smears to reveal these cervical lesions, we can improve the diagnostic specificity and patient's outcome. The clinical record and available cervical smears from 13 cases of SMCC, four cases of malignant lymphoma, 20 cases of SCIS, and five cases of CLC were analyzed. The cytologic differential diagnostic points of SMCC were nuclear molding and smearing (100%), salt and pepper chromatin (100%), exudative and necrotic background (91.7%), various architectures including individual cells (83.3%), tight clusters (75%) and feathering and strip (50%), and inconspicuous nucleoli (75%). Early diagnosis of the cervical SMCC by cytology and treatment is important for better outcome of patients.


Mistakes happen. Improved processes mean fewer mistakes.
A patient receives the wrong medication. Another waits in an exam room, forgotten. Yet another undergoes expensive imaging, only to find the pictures taken were of the wrong area. When mistakes happen in health care, repercussions range from inefficiency and a decline in profitability to human suffering and even death. In such an environment, errors can't be fixed by a quality inspector at the end of the line. By that time, the damage is done. But by improving quality all along the patient visit process, mistakes can be avoided.


Dispersion-engineered multicore fibers for distributed radiofrequency signal processing.
We report a trench-assisted heterogeneous multicore fiber optimized in terms of higher-order dispersion and crosstalk for radiofrequency true time delay operation. The analysis of the influence of the core refractive index profile on the dispersion slope and effective index reveals a tradeoff between the behavior of the crosstalk against fiber curvatures and the linearity of the propagation group delay. We investigate the optimization of the multicore fiber in the framework of this tradeoff and present a design that features a group delay relative error below 5% for an optical wavelength range up to 100 nm and a crosstalk level below -80 dB for bending radii larger than 103 mm. The performance of the true time delay line is validated in the context of microwave signal filtering and optical beamforming for phased array antennas. This work opens the way towards the development of compact fiber-integrated solutions that enable the implementation of a variety of distributed signal processing functionalities that will be key in future fiber-wireless communications networks and systems.


Systemic or topical application of plasminogen activator inhibitor with extended half-life (VLHL PAI-1) reduces bleeding time and total blood loss.
Civilian and military trauma patients consist of a disproportional number of young people, causing a considerable burden to society in terms of disability and premature death. Hemorrhage is a leading cause of mortality in this group of patients and the novel methods to reduce bleeding would be welcomed. Management of bleeding following major trauma includes hemostatic agents that offer effective clotting. However a very limited number of agents control secondary bleeding triggered by lysis of the clot. Fibrinolysis depends on the balance between tissue plasminogen activator (tPA), activating plasminogen to plasmin initiating fibrinolysis, and plasminogen activator inhibitor type 1 (PAI-1) inhibiting tPA and preventing lysis. The drugs available on the market that prevent the activation of plasminogen have been used successfully, but have some side effects and limited efficacy for the control of localized bleeding in the surgical setting. Inhibitors of tPA, initiator of clot fibrinolysis, have not yet found their way into the clinical arena. Plasminogen activator inhibitor-1, the major specific inhibitor of tPA, can be used to limit fibrinolysis. Unfortunately, PAI-1 has a short half-life of approximately 2 h and is rapidly converted to the latent form. A recombinant PAI-1 with very long half-life developed in our laboratory (a two-point mutant, VLHL PAI-1, half-life over 700 h) has clinical potential as an agent to promote hemostasis in several scenarios including surgical injury, trauma, and PAI-1 deficiency. Here we report testing of VLHL PAI-1 as a potent inactivator of fibrinolysis reducing total blood loss while applied systemically or topically in experimental animals. The very long half-life of VLHL PAI-1 may provide an advantage in the important physiological mechanism to protect clots from premature dissolution, when applied topically or systemically to prevent excessive bleeding in the surgical and trauma setting and possibly in PAI-1 deficient patients.


The Prediction of Infectious Diseases: A Bibliometric Analysis.
The outbreak of infectious diseases has a negative influence on public health and the economy. The prediction of infectious diseases can effectively control large-scale outbreaks and reduce transmission of epidemics in rapid response to serious public health events. Therefore, experts and scholars are increasingly concerned with the prediction of infectious diseases. However, a knowledge mapping analysis of literature regarding the prediction of infectious diseases using rigorous bibliometric tools, which are supposed to offer further knowledge structure and distribution, has been conducted infrequently. Therefore, we implement a bibliometric analysis about the prediction of infectious diseases to objectively analyze the current status and research hotspots, in order to provide a reference for related researchers. We viewed "infectious disease*" and "prediction" or "forecasting" as search theme in the core collection of Web of Science from inception to 1 May 2020. We used two effective bibliometric tools, i.e., CiteSpace (Drexel University, Philadelphia, PA, USA) and VOSviewer (Leiden University, Leiden, The Netherlands) to objectively analyze the data of the prediction of infectious disease domain based on related publications, which can be downloaded from the core collection of Web of Science. Then, the leading publications of the prediction of infectious diseases were identified to detect the historical progress based on collaboration analysis, co-citation analysis, and co-occurrence analysis. 1880 documents that met the inclusion criteria were extracted from Web of Science in this study. The number of documents exhibited a growing trend, which can be expressed an increasing number of experts and scholars paying attention to the field year by year. These publications were published in 427 different journals with 11 different document types, and the most frequently studied types were articles 1618 (83%). In addition, as the most productive country, the United States has provided a lot of scientific research achievements in the field of infectious diseases. Our study provides a systematic and objective view of the field, which can be useful for readers to evaluate the characteristics of publications involving the prediction of infectious diseases and for policymakers to take timely scientific responses.


The chemical organization of signaling interactions.
Cellular chemical signaling pathways form complex networks that are beginning to be studied at the level of chemical kinetics and databases of reactions. Chemical reaction details are traditionally represented as lists of reactions and rates. This does not map readily to the block diagram representation familiar to biologists, and obscures the functional organization of signaling networks. This study examines motifs in signaling chemistry and reports common features that may help to formalize such a mapping between pathway block diagrams and the chemistry. The same motifs may facilitate data representation and provide functional abstraction of the chemistry. I classified 74 interactions between 25 signaling pathways in terms of shared chemical motifs. All interactions in this dataset consist of a few communicating molecules from one set of pathways, and a replicating set of reactions and molecules from another. Each unique combination of interacting pathways duplicates the chemical reaction scheme of this replicating set, but involves different rate constants. Signaling pathways can therefore be described in an object-oriented manner as sets of core reactions with well-defined interfaces between pathways. This generalization lends itself to designing simulators and databases for signaling networks. Software and example models are freely available from http://www.ncbs.res.in/~bhalla/examples/EGFR_example.html.


Response of barley aleurone layers to abscisic Acid.
Cordycepin, an inhibitor of RNA synthesis in barley (Hordeum vulgare L.) aleurone cells, does not inhibit the gibberellic acid-enhanced alpha-amylase (EC 18.104.22.168.) synthesis in barley aleurone layers if it is added 12 hours or more after the addition of the hormone. However, the accumulation of alpha-amylase activity after 12 hours of gibberellic acid can be decreased by abscisic acid. The accumulation of alpha-amylase activity is sustained or quickly restored when cordycepin is added simultaneously or some time after abscisic acid, indicating that the response of aleurone layers to abscisic acid depends on the continuous synthesis of a short lived RNA. By analysis of the newly synthesized proteins by gel electrophoresis with sodium dodecylsulfate, we observed that the synthesis of alpha-amylase is decreased in the presence of abscisic acid while the synthesis of most of the other proteins remains unchanged. From the rate of resumption of alpha-amylase production in the presence of cordycepin and abscisic acid, it appears that abscisic acid does not have a measurable effect on the stability of alpha-amylase mRNA.


Inflammatory gene expression in cerebral ischemia and trauma. Potential new therapeutic targets.
This review summarized evidence in support for the case that ischemia elicits an inflammatory condition in the injured brain. The inflammatory condition consists of cells (neutrophils at the onset and later monocytes) and mediators (cytokines, chemokines, others). It is clear that de novo upregulation of proinflammatory cytokines, chemokines and endothelial-leukocyte adhesion molecules in the brain follow soon after the ischemic insult and at a time when the cellular component is evolving. The significance of the inflammatory response to brain ischemia is not fully understood. Evidence is emerging in support of the possibility that the acute inflammatory reaction to brain ischemia may be causally related to brain damage. This evidence includes: 1) the capacity of cytokines to exacerbate brain damage; 2) the capacity of specific cytokine antagonists such as IL-1ra to reduce ischemic brain damage; 3) that depletion of circulating neutrophils reduces ischemic brain injury; 4) and that antagonists of the endothelial-leukocyte adhesion interactions (e.g., anti-ICAM-1) reduce ischemic brain injury. However, it should be kept in mind that cytokines were also argued to provide beneficial effects in brain injury as inferred from studies with TNF-receptor knock-out mice (p55 and p75 knock-out), which display increased sensitivity to brain ischemia, and the capacity of IL-1 to elicit the state of ischemic tolerance upon repeated administration. Nevertheless, the recent revelation on the capacity of ischemia to induce acute inflammation in the brain provides a new and fertile ground for new explorations for novel therapeutic agents that could confine the neuronal damage that follows ischemia. Furthermore, many of the genes that are upregulated by ischemia have growth-promotion capacity and therefore raise the possibility that such gene products may be useful in counteracting brain damage by enhancing repair and establishing compensatory mechanisms that enhance histological and functional recovery.


Ethnobotanical study of medicinal plants in the Adrar Province, Mauritania.
Mauritania is a country in which few ethnobotanical studies have been conducted and consequently the ethnomedical data is scarce. Since the geographical region reflects the transition between tropical and Northern Africa, influenced by the Mediterranean floristic region, the traditional knowledge was influenced by several cultures from tropical Africa as well as Arab, Berber and Islamic societies. This paper aims to explore and compile the diversity of ethnomedical knowledge in one of the regions of Mauritania and to compare the data with similar studies from surrounding territories. Surveys and interviews were carried out in 11 villages of Adrar province in northern Mauritania. Data were collected through open, semi-structured interviews (with individuals and focus groups). A sample of 120 people aged between 20 and 70 years, including 24 herbalists and 28 traditional healers was included. Ethnomedical data for 68 plant species belonging to 27 families were obtained. They are used to treat 50 health conditions grouped in 14 pathological groups. Remedies for digestive system disorders, skin problems and respiratory ailments were among the most frequent indications. Leaves were the most frequently used plant part and remedies generally used as a powder for the various applications and a total of 2'317 use reports were gathered. About 55% of the reported species were not cited previously in the literature focusing on Mauritania and neighbouring countries. Moreover, only 6 species are also cited by Ibn al-Baytar (13th century CE). This work shows a promising perspective for future studies, shedding light on the richness and the risk for conservation of traditional knowledge of herbal medicine in Mauritania.


Pelvic fractures in children (pelvic ring and acetabulum).
Pelvic fractures in children are rare and often the result of high-energy trauma. The possibility of associated lesions cannot be ignored. Treatment at a specialized children's hospital is a must. The multidisciplinary care team must include a paediatric orthopaedic surgeon. In the emergency room, the surgeon contributes to haemodynamic stabilization of the child by reducing and stabilizing posterior arch fractures and restoring the skeletal cohesion to make it easier to move the child and allow other examinations to be performed. Imaging modalities are used to determine the stability of the pelvic ring fracture, the risk of epiphysiodesis of an acetabulum fracture if the triradiate cartilage is open and the joint congruency if the triradiate cartilage is closed. Internal fixation can be used if surgery is being performed for associated non-orthopaedic injuries. Most vertically stable fractures are treated non-surgically. Fractures that are unstable vertically will require surgical treatment. Treatment of acetabulum fractures depends on the status of the triradiate cartilage. In older children, it is similar to the treatments used in adults. In children with open growth plates, the goal is to make sure the acetabulum continues growing. In all cases, the patients must be instructed to start physical therapy as soon as possible. Full recovery can be expected after stable pelvic fractures. Unstable pelvic fractures can lead to sequelae, the severity of which depend on the residual pelvic displacement and involvement of the growth plates that can cause epiphysiodesis. Surgery to correct these deformities is challenging. The most serious occur when the vertical displacement of the hemipelvis must be corrected. After an acetabulum fracture, removal of the growth blocker can be done in children under 10 years of age. In older children, acetabular dysplasia requires periacetabular osteotomy.


Endotoxins of enteric pathogens are chemotactic factors for human neutrophils.
Early activation of human peripheral blood polymorphonuclear neutrophils is characterized by their morphological changes from spherical to polarized shapes. The endotoxins from enteric pathogens (S. dysenteriae type 1, V. cholerae Inaba 569B, S. typhimurium, and K. pneumoniae) were assessed by their ability to induce morphological polarization of the neutrophils as measures of early activation. Phagocytic activity, adhesion, chemokinetic locomotion, and nitroblue tetrazolium (NBT) dye-reduction ability measured the later activation of the cells. Neutrophils showed distinct morphological polarization in suspension over a wide range of concentrations of these endotoxins when were compared with those that were induced by the standard chemotactic factor, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). It was discovered that all of the endotoxins induced locomotor responses in neutrophils in suspension that were dose- and time-dependent. The optimum concentration for the endotoxins of S. dysenteriae, V. cholerae, and K. pneumoniae was 1 mg/ml in which 71, 69, and 66% of the neutrophils were polarized. However, the S. typhimurium dose was 2 mg/ml in which 50% of the cells responded. Neutrophils that were stimulated with endotoxins also showed increased random locomotion (p<0.005) through cellulose nitrate filters, but an enhanced adhesion of the cells to glass surfaces (p<0.03). These are important functions of these cells to reach and phagocytose damaged cells, as well as invading microorganisms. Interestingly, the endotoxins had a highly-significant inhibitory effect upon the proportions of neutrophils phagocytosing opsonized yeast (p<0.01) with a small number of yeast that were engulfed by the cells (p<0.02). Further, endotoxin-treated cells showed an enhanced ability to reduce NBT dye (p<0.03). Therefore, we concluded that endotoxins of enteric pathogens are neutrophil chemotactic factors.


Diazoxide in the treatment of schizophrenia: novel application of potassium channel openers in the treatment of schizophrenia.
Schizophrenia is a very common disorder, affecting 1% of the world population. People who develop schizophrenia experience severe suffering and approximately 10% commit suicide. The causes of schizophrenia are still largely unknown. The relative ineffectiveness of dopamine antagonists to treat some symptoms of schizophrenia has promoted many investigators to postulate the involvement of the neuronal system in the pathophysiology of this disease. It has been suggested that the dopamine-coupled adenosine triphosphate (ATP)-sensitive channels may function by hyperpolarizing cells during metabolic stress, a function that may be disrupted in people with schizophrenia. Therefore, application of potassium channel openers/activators may be beneficial in schizophrenia. Diazoxide is a benzothiadiazine derivative related to the thiazide diuretics and a potassium channel opener. The purpose of the present investigation was to assess the efficacy of diazoxide, as an adjuvant agent in the treatment of schizophrenia. Forty-two patients who met the DSM IV criteria for chronic schizophrenia completed the study. Patients were randomized to haloperidol 20 mg/day plus diazoxide 200 mg/day (21 subjects) or to haloperidol 20 mg/day plus placebo (21 subjects) in this 8-week double-blind study. Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of haloperidol and diazoxide showed a significant superiority over haloperidol alone in the treatment of positive and general psychopathology symptoms as well as positive and negative syndrome scale (PANSS) total scores. In addition, in the diazoxide group a rapid onset of action on the positive symptoms was observed in week 2, whereas in the placebo group there was no significant effect at week 2. No significant differences were observed between the two protocols on the negative scores. The results of this study present a novel application for potassium channel openers/activators in the neuropsychiatric disorders and diazoxide may be an effective adjuvant agent in the management of schizophrenia.


Public Attitudes Toward Xenotransplantation: A Theological Perspective.
Among the myriad factors contributing to public attitudes toward xenotransplantation, religious belief offers a complex picture. In April 2019, xenotransplantation researchers at the University of Alabama-Birmingham conducted a focus group conversation among 12 area religious leaders. This article offers a theological analysis of the transcript of this conversation. The details of the interactions among the focus group participants sheds light on the manner in which theological belief shapes attitudes toward xenotransplantation. While participants generally recognized and affirmed the potential benefits of xenotransplantation, their support was tempered by an array of concerns emerging from a theological narrative that shaped their moral assessment.


Severe Clostridium difficile-associated disease in populations previously at low risk--four states, 2005.
Clostridium difficile is a spore-forming, gram-positive bacillus that produces exotoxins that are pathogenic to humans. C. difficile-associated disease (CDAD) ranges in severity from mild diarrhea to fulminant colitis and death. Antimicrobial use is the primary risk factor for development of CDAD because it disrupts normal bowel flora and promotes C. difficile overgrowth. C. difficile typically has affected older or severely ill patients who are hospital inpatients or residents of long-term-care facilities. Recently, however, both the frequency and severity of health-care-associated CDAD has increased; from 2000 to 2001, the rate of U.S. hospital discharge diagnoses of CDAD increased by 26%. One possible explanation for these increases is the emergence of a previously uncommon strain of C. difficile responsible for severe hospital outbreaks. Although individual cases of CDAD are not nationally reportable, in 2005, the Pennsylvania Department of Health (PADOH) and CDC received several case reports of serious CDAD in otherwise healthy patients with minimal or no exposure to a health-care setting. An investigation was initiated by the Philadelphia Department of Public Health (PDPH), PADOH, and CDC to determine the scope of the problem and explore a possible change in CDAD epidemiology. This report summarizes the results of the investigation in Pennsylvania and three other states, which indicated the presence of severe CDAD in healthy persons living in the community and peripartum women, two populations previously thought to be at low risk. The findings underscore the importance of judicious antimicrobial use, the need for community clinicians to maintain a higher index of suspicion for CDAD, and the need for surveillance to better understand the changing epidemiology of CDAD.


Pancreatic laceration and portal vein thrombosis in blunt trauma abdomen.
Injuries to the pancreas by blunt trauma are uncommon. The association of pancreatic injury with acute portal vein thrombosis secondary to blunt trauma abdomen is furthermore rare. The early diagnosis of the pancreas with injury to the portal vein is challenging and difficult. These injuries are associated with high morbidity and mortality, particularly if the diagnosis is delayed. Accurate and early diagnosis is therefore imperative and computed tomography plays a key role in detection. We present a case of child with a rare combination of pancreatic laceration and acute portal vein thrombosis following a blunt trauma to the abdomen. With extensive literature search we found no such cases has been described previously.


Emerging drying techniques for food safety and quality: A review.
The new trends in drying technology seek a promising alternative to synthetic preservatives to improve the shelf-life and storage stability of food products. On the other hand, the drying process can result in deformation and degradation of phytoconstituents due to their thermal sensitivity. The main purpose of this review is to give a general overview of common drying techniques with special attention to food industrial applications, focusing on recent advances to maintain the features of the active phytoconstituents and nutrients, and improve their release and storage stability. Furthermore, a drying technique that extends the shelf-life of food products by reducing trapped water, will negatively affect the spoilage of microorganisms and enzymes that are responsible for undesired chemical composition changes, but can protect beneficial microorganisms like probiotics. This paper also explores recent efficient improvements in drying technologies that produce high-quality and low-cost final products compared to conventional methods. However, despite the recent advances in drying technologies, hybrid drying (a combination of different drying techniques) and spray drying (drying with the help of encapsulation methods) are still promising techniques in food industries. In conclusion, spray drying encapsulation can improve the morphology and texture of dry materials, preserve natural components for a long time, and increase storage times (shelf-life). Optimizing a drying technique and using a suitable drying agent should also be a promising solution to preserve probiotic bacteria and antimicrobial compounds.


Frontonasal dysplasia: a family presenting autosomal dominant inheritance pattern.
Frontonasal dysplasia (FND, also called frontonasal dysostosis or median cleft face syndrome) includes a spectrum of abnormalities affecting the eyes, forehead and nose, and resulting from midfacial dysraphia. The clinical picture is highly variable, but major findings in FND include ocular hypertelorism, a broad nasal root, median cleft affecting nose or both the nose and upper lip, and widow's peak. It is usually a sporadic disorder, although a few familial cases have been reported. We report here a three-generation family with multiple affected members with frontonasal dysplasia. This observation suggests autosomal dominant inheritance. Furthermore, some of the features e.g. over-riding toes, nail changes, vertical crease on plantar region of the feet in the index patient were not reported up to now.


An analysis of changes in sensory thresholds to mild tactile and cold stimuli after experimental spinal cord injury in the rat.
Changes in sensory function including chronic pain and allodynia are common sequelae of spinal cord injury (SCI) in humans. The present study documents the extent and time course of mechanical allodynia and cold hyperalgesia after contusion SCI in the rat using stimulation with graded von Frey filaments (4.97-50.45 g force) and ice probes. Fore- and hind-paw withdrawal thresholds to plantar skin stimulation were determined in rats with a range of SCI severities (10-g weight dropped from 6.25, 12.5, or 25 mm using the MASCIS injury device); animals with 25-mm injuries most consistently showed decreased hind-paw withdrawal thresholds to touch and cold, which developed over several weeks after surgery. Stimulation of the torso with graded von Frey hairs was performed at specified locations on the back and sides from the neck to the haunch. Suprasegmental responses (orientation, vocalization, or escape) to mechanical stimulation of these sites were elicited infrequently in the laminectomy control rats and only during the first 3 weeks after surgery, whereas in 25-mm SCI rats, such responses were obtained for the entire 10 weeks of the study. These data suggest that rats with contusion SCI may exhibit sensory alterations relevant to human spinal cord injuries.


Evaluation of Biological, Textural, and Physicochemical Parameters of Panela Cheese Added with Probiotics.
Biological, physicochemical and textural parameters of a Panela cheese with and without probiotics (LSB-c and C-c) were analyzed during 15 days of storage at 4 °C. Changes in cohesiveness, hardness, springiness, and chewiness were measured by texture profile analysis. Additionally, moisture, pH, nitrogenous fractions (nitrogen soluble in pH 4.6, non-protein nitrogen, 70% ethanol-soluble nitrogen, and water-soluble extract) were evaluated. The peptide profile of nitrogenous fractions was also analyzed. Finally, biological activity was evaluated by ABTS (2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) and DPPH (2,2-diphenyl-1-picrylhydrazyl), as well as the Inhibition of Angiotensin-Converting Enzyme. Analysis of variance showed significant differences for most of the evaluated parameters. By principal component analysis (PCA), two groups were separated, one corresponding to LSB-c and the other corresponding to C-c. The separation was given mostly by hardness, chewiness, and ABTS of all nitrogenous fractions. LSB-c showed higher biological activities than C-c.


Filial cannibalism in teleost fish.
This review summarizes information on filial cannibalism (the act of eating one's own offspring) in teleost fish. Cannibalistic parents can either consume their whole brood (total filial cannibalism), or eat only some of the eggs in the nest (partial filial cannibalism). Offspring consumption has been argued to be adaptive under the assumption that offspring survival is traded against feeding, and that offspring can act as an alternative food source for the parents. The evidence supporting the basic predictions formulated under these assumptions is summarized for both total and partial filial cannibalism. These two forms of cannibalism differ significantly since the former represents an investment only in future reproductive success, whereas the latter can affect both present and future reproductive success. Despite a few inconsistencies in the data from laboratory and field studies, the energy-based explanation appears valid for both forms of cannibalism. Alternative non-energy-based explanations are considered, but they are unable to account for the wide distribution of this behaviour in teleosts. The intersexual conflict arising from attempts of the non-cannibal sex to minimize the cost of filial cannibalism is also discussed, together with the potential effect of this behaviour on the operational sex ratio at a population level.


A trial of autologous ex vivo-expanded NK cell-enriched lymphocytes with docetaxel in patients with advanced non-small cell lung cancer as second- or third-line treatment: phase IIa study.
New strategies are still needed to enhance the treatment outcome for advanced non-small cell lung cancer, in spite of recent remarkable developments. Cancer immunotherapy has been attractive since a long time, with diverse clinical attempts and results. In particular, natural killer (NK) cells have received considerable attention because of their potential role in immune surveillance in vivo by destroying infected or transformed cells. Major histocompatibility complex class I-related chain A/B (MICA/B) on tumor cells, known as the representative ligand for NKG2D receptor on NK cells, has been reported to be modulated by a variety of stress factors, including some chemotherapeutic agents, and it is anticipated that enhancing MICA/B expression will be contributory to anticancer treatment. With recent development of expanding autologous ex vivo NK cell-enriched lymphocytes (NKL), we designed a trial to augment the anticancer effect by co-administering NKL and docetaxel, one of the second-line agents used for treatment of patients with advanced non-small cell lung cancer (NSCLC). Eligible patients were between the age of 20 and 75 years, with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, and previously received one chemotherapy or two regimens including one epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, stage IIIB/IV, histologically- or cytologically-proven NSCLC with measurable lesions. NKL were kindly prepared and provided from NKBIO Co. (Seongnam City, Korea). Feasibility, adverse effects, progression-free survival (PFS) were evaluated and compared with the historical control of weekly docetaxel regimen. Nineteen patients were enrolled before early closure. NKL production and administration were feasible in all cases, even in those with disseminated disease. No additional adverse events were observed in addition to those reported for docetaxel-alone. PFS of 3 months and 10.5% response rate (RR), with two cases of partial response, were observed and were similar to the historical control (PFS=2.9 months, RR=8.0%). To our knowledge, this is the first report on the combination of NKL with docetaxel in patients with advanced NSCLC. Autologous NKL production and co-administration with docetaxel were feasible without further toxicity or complication. Benefit in PFS and RR, as compared with the historical control, was not detected in this study population with advanced NSCLC. In order to determine whether the combination of NKL and chemotherapy has any anticancer effect, an additional study should be performed in patients with low tumor burden, such as those with less advanced disease or those in remission.


A redox-active crosslinker reveals an essential and inhibitable oxidative folding network in the endoplasmic reticulum of malaria parasites.
Malaria remains a major global health problem, creating a constant need for research to identify druggable weaknesses in P. falciparum biology. As important components of cellular redox biology, members of the Thioredoxin (Trx) superfamily of proteins have received interest as potential drug targets in Apicomplexans. However, the function and essentiality of endoplasmic reticulum (ER)-localized Trx-domain proteins within P. falciparum has not been investigated. We generated conditional mutants of the protein PfJ2-an ER chaperone and member of the Trx superfamily-and show that it is essential for asexual parasite survival. Using a crosslinker specific for redox-active cysteines, we identified PfJ2 substrates as PfPDI8 and PfPDI11, both members of the Trx superfamily as well, which suggests a redox-regulatory role for PfJ2. Knockdown of these PDIs in PfJ2 conditional mutants show that PfPDI11 may not be essential. However, PfPDI8 is required for asexual growth and our data suggest it may work in a complex with PfJ2 and other ER chaperones. Finally, we show that the redox interactions between these Trx-domain proteins in the parasite ER and their substrates are sensitive to small molecule inhibition. Together these data build a model for how Trx-domain proteins in the P. falciparum ER work together to assist protein folding and demonstrate the suitability of ER-localized Trx-domain proteins for antimalarial drug development.


Impingement and dislocation in total hip arthroplasty: mechanisms and consequences.
In contemporary total hip arthroplasty, instability has been a complication in approximately 2% to 5% of primary surgeries and 5% to 10% of revisions. Due to the reduction in the incidence of wear-induced osteolysis that has been achieved over the last decade, instability now stands as the single most common reason for revision surgery. Moreover, even without frank dislocation, impingement and subluxation are implicated in a set of new concerns arising with advanced bearings, associated with the relatively unforgiving nature of many of those designs. Against that backdrop, the biomechanical factors responsible for impingement, subluxation, and dislocation remain under-investigated relative to their burden of morbidity. This manuscript outlines a 15-year program of laboratory and clinical research undertaken to improve the scientific basis for understanding total hip impingement and dislocation. The broad theme has been to systematically evaluate the role of surgical factors, implant design factors, and patient factors in predisposing total hip constructs to impinge, sublux, and/or dislocate. Because this class of adverse biomechanical events had not lent itself well to study with existing approaches, it was necessary to develop (and validate) a series of new research methodologies, relying heavily on advanced finite element formulations. Specific areas of focus have included identifying the biomechanical challenges posed by dislocation-prone patient activities, quantifying design parameter effects and component surgical positioning effects for conventional metal-on-polyethylene implant constructs, and the impingement/dislocation behavior of non-conventional constructs, quantifying the stabilizing role of the hip capsule (and of surgical repairs of capsule defects), and systematically studying impingement and edge loading of hard-on-hard bearings, fracture of ceramic liners, confounding effects of patient obesity, and subluxation-mediated worsening of third body particle challenge.


Association of midlife body composition with old-age health-related quality of life, mortality, and reaching 90 years of age: a 32-year follow-up of a male cohort.
Overweight and obesity increase the risk of morbidity and mortality. The relations between body composition at midlife, health-related quality of life (HRQoL) in old age, and longevity are, however, less studied. We examined the association of midlife body composition with successful aging, defined as high HRQoL and reaching 90 y of age, during 32 y follow-up. Participants were 1354 men from the Helsinki Businessmen Study, born 1919-1934. In 1985/1986 (mean age: 60 y) various health measurements were performed. Percentages of body fat (BF) and skeletal muscle mass (SM) were calculated using validated formulas (including waist and hip circumferences, weight, and age) and divided into quartiles. In 2000 and 2007 (mean ages: 74 and 80 y, respectively), HRQoL was assessed using RAND-36/Short Form-36 scales. Mortality was retrieved from registers through 2018, and longevity determined by calculating the proportion of participants reaching 90 y. Logistic regression was used to assess ORs with 95% CIs. Higher SM% at midlife in 1985/1986 was associated (P < 0.05) with higher scores in the RAND-36 scales of physical functioning, role limitations caused by physical health problems, vitality, social functioning, and general health in old age in 2000. In 2007 only the association with physical domain (physical functioning, role limitations caused by physical health problems) remained statistically significant (P < 0.01). BF% quartiles in 1985/1986 were inversely associated with several RAND-36 scales in 2000 and 2007. During the 32-y follow-up, 982 participants died and 281 reached 90 y of age. Being in the highest SM% quartile at midlife increased (adjusted OR: 2.32; 95% CI: 1.53, 3.53; lowest SM% quartile as reference) and being in the highest BF% quartile decreased (OR: 0.43; 95% CI: 0.28, 0.66; lowest BF% quartile as reference) the odds of reaching 90 y. Desirable body composition in terms of both fat and skeletal muscle mass at midlife was associated with successful aging in men.This trial was registered at clinicaltrials.gov as NCT02526082.


[Effect of QTY06 on lipopolysaccharide-induced chronic airway inflammation and MUC5ac secretion in rats].
To investigate the effect of synthetic drug QTY06 on chronic airway inflammation and mucoprotein expression induced by intratracheal (i.t) instillation of lipopolysaccharide (LPS). Chronic airway inflammation was induced by i.t instillation of LPS in rats. Phospholipids content and the number of leucocytes in bronchoalveolar lavage fluid (BALF), pathological and immunochemical changes were examined 3 weeks after LPS instillation. The effect of QTY06 on chronic airway inflammation was observed. After treatment with QTY06, phospholipids in BALF was significantly increased, and the percentages of neutrophils and lymphocytes were decreased as well as the total number of leucocytes. Compared with the model group, pathological examination showed that tracheitis, bronchitis and pulmonary interstitial inflammation in QTY06 groups were significantly attenuated; epithelial damage was alleviated, infiltration of inflammatory cells reduced and the number of goblet cells decreased. QTY06 significantly decreased MUC5ac expression in trachea and bronchiole epithelium, and reduced the optical density and mucins area (%) as detected by image analysis in rats with chronic airway inflammation. QTY06 can reduce and inhibit the chronic airway inflammation induced by LPS in rats, and increase the content of phospholipids in pulmonary surfactant and inhibit the hypersecretion of airway mucins.


Carcinoma in the porcelain gallbladder: a relationship revisited.
Gallbladder cancer is the most common biliary tract malignancy. Calcification of the gallbladder wall is reported to be associated with gallbladder cancer. In the literature, the incidence is quoted to be between 12% and 61%. This study aims to clarify the risk of cancer in a calcified gallbladder. The charts and pathology reports at the Massachusetts General Hospital were reviewed, and patients with either gallbladder cancer or a calcified gallbladder were included in the study. The Fisher exact test was used to test for the association between cancer and gallbladder wall calcifications. From 1962 to 1999, there were approximately 25,900 gallbladder specimens analyzed at the Massachusetts General Hospital. There were 150 patients with gallbladder cancer and 44 patients with calcified gallbladders. Two types of calcified gallbladders were noted: those with complete intramural calcification (n = 17) and those with selective mucosal calcification (n = 27). The incidence of cancer arising in a gallbladder with selective mucosal wall calcification was approximately 7%. There was a significant association between gallbladder cancer and selective mucosal calcification with an odds ratio of 13.89 (P =.01). There were no patients with diffuse intramural calcification and cancer. A calcified gallbladder is associated with an increased risk of gallbladder cancer, but at a much lower rate than previously estimated. The incidence of cancer depends on the pattern of calcification; selective mucosal calcification poses a significant risk of cancer whereas diffuse intramural calcification does not.


Quantum noise as an entanglement meter.
Transport in a quantum point contact (QPC) can be used to generate many-body entanglement of Fermi seas in the leads. A universal relation is found between the generated entanglement entropy and the fluctuations of electric current, which is valid for any protocol of driving the QPC. This relation offers a basis for direct electric measurement of entanglement entropy. In particular, by utilizing space-time duality of 1D systems, we relate electric noise generated by opening and closing the QPC periodically in time with the seminal S=1/3logL prediction of conformal field theory.


Benchmarking definitions of false-positive alerts during computer-aided polyp detection in colonoscopy.
The occurrence of false-positive alerts is an important outcome measure in computer-aided colon polyp detection (CADe) studies. However, there is no consensus definition of a false positive in clinical trials evaluating CADe in colonoscopy. We aimed to study the diagnostic performance of CADe based on different threshold definitions for false-positive alerts. A previously validated CADe system was applied to screening/surveillance colonoscopy videos. Different thresholds for false-positive alerts were defined based on the time an alert box was continuously traced by the system. Primary outcomes were false-positive results and specificity using different threshold definitions of false positive. 62 colonoscopies were analyzed. CADe specificity and accuracy were 93.2 % and 97.8 %, respectively, for a threshold definition of ≥ 0.5 seconds, 98.6 % and 99.5 % for a threshold definition of ≥ 1 second, and 99.8 % and 99.9 % for a threshold definition of ≥ 2 seconds. Our analysis demonstrated how different threshold definitions of false positive can impact the reported diagnostic performance of CADe for colon polyp detection.


Copper-catalyzed C-C bond-forming transformation of CO2 to alcohol oxidation level: selective synthesis of homoallylic alcohols from allenes, CO2, and hydrosilanes.
A highly selective carbon-carbon bond-forming transformation of carbon dioxide (CO2) to alcohol oxidation level has been disclosed. By employing a copper/bisphosphine catalyst system and hydrosilanes as mild and easy-to-handle reducing agents, various allenes can be reacted with CO2 to regioselectively obtain homoallylic alcohols. Esters and other reducible functionalities on the allenes remain intact during the reaction, whereas CO2 is reduced to alcohol oxidation level.


Insomnia: a primary care perspective.
Primary care physicians once considered insomnia a nuisance diagnosis with which they had little concern. A complaint of insomnia is often brought to a physician's attention as a last-minute secondary complaint, which may be dismissed as unimportant by the physician. However, chronic insomnia is prevalent, associated with a decrease in quality of life, and can be an exacerbating factor in other psychiatric and medical conditions. Primary care physicians therefore should be aware of the signs of insomnia and include the detection of it in the evaluation of patients who present with other complaints or as part of annual physical examinations. Physicians can assess insomnia with tools they already use, such as a patient's initial history. If insomnia is detected, primary care physicians should work with patients to educate them. Management necessitates the inclusion of education and patient counseling about sleep hygiene and correction of dysfunctional beliefs and behaviors. It may also include pharmacologic treatment, nonpharmacologic treatment, or a combination of both.


Bone integration capability of alkali- and heat-treated nanobimorphic Ti-15Mo-5Zr-3Al.
The role of nanofeatured titanium surfaces in a number of aspects of in vivo bone-implant integration, and, in particular, their potential advantages over microfeatured titanium surfaces, as well as their specific contribution to osteoconductivity, is largely unknown. This study reports the creation of a unique nanobimorphic titanium surface comprised of nanotrabecular and nanotuft-like structures and determines how the addition of this nanofeature to a microroughened surface affects bone-implant integration. Machined surfaces without microroughness, sandblasted microroughened surfaces, and micro-nano hybrid surfaces created by sandblasting and alkali and heat treatment of Ti-15Mo-5Zr-3Al alloy were subjected to biomechanical, interfacial and histological analyses in a rat model. The presence of microroughness enabled accelerated establishment of biomechanical implant fixation in the early stages of healing compared to the non-microroughened surfaces; however, it did not increase the implant fixation at the late stages of healing. The addition of nanobimorphic features to the microroughened surfaces further increased the implant fixation by as much as 60-100% over the healing time. Bone area within 50 μm of the implant surface, but not beyond this distance, was significantly increased by the presence of nanobimorphic features. Although the percentage of bone-implant contact was also significantly increased by the addition of nanobimorphic features, the greatest improvement was found in the soft tissue intervention between the bone and the implant, which was reduced from >30% to <5%. Mineralized tissue densely deposited with calcium-binding globular proteins was observed in an extensive area of nanobimorphic surfaces after biomechanical testing. This study clearly demonstrates the nanofeature-enhanced osteoconductivity of titanium by an alkali- and heat-treated nanobimorphic surface compared to that by microfeatured surfaces, which results not only in an acceleration but also an improvement of bone-implant integration. The identified biological parameters that successfully detect the advantages of nanofeatures over microfeatures will be useful in evaluating new implant surfaces in future studies.


Jasmonate action in plant defense against insects.
Herbivorous insects represent one of the major threats to sessile plants. To cope with herbivore challenges, plants have evolved sophisticated defense systems, in which the lipid-derived phytohormone jasmonate plays a crucial role. Perception of insect attack locally and systemically elicits rapid synthesis of jasmonate, which is perceived by the F-box protein COI1 to further recruit JAZ repressors for ubiquitination and degradation, thereby releasing transcription factors that subsequently activate plant defense against insect attack. Here, we review recent progress in understanding the molecular basis of jasmonate action in plant defense against insects.


Efforts to incorporate social justice perspectives into a family training program.
This paper describes the efforts of the faculty of the Family Institute of New Jersey in recent years to develop a collaborative family training program that takes into account issues of gender, race, culture, class, and sexual orientation. We have come to realize how strongly traditional approaches have been skewed in the direction of the dominant culture--white, male, heterosexist, and prioritizing the needs and experience of the middle and upper classes. We have attempted to modify our teaching, supervision, reading lists, and overall training approach to challenge trainees and ourselves to move toward broader, strength-based, and equity-based multicultural perspectives in our training. We describe our vision, how we incorporate it into our program structure, and a few of our training initiatives.


Discrimination of temporal jitter in patterned sequences of tones.
The perception of pure tone sequences in highly dependent on the serial pattern of tone frequencies. We propose that this phenomenon is mediated by a frequency-selective mechanism. Three models of the selective mechanism were evaluated in a temporal discrimination task. The observer was required to discriminate between two sequences of tone bursts. In one sequence the time interval between each tone burst was constant; in the other sequence the time interval was a random variable. A set of fixed and random pattern rules determined the frequency of each tone in the sequence. Discrimination performance was studied as a function of the magnitude of the time interval jitter and the serial pattern of tone frequency. Performance in the fixed pattern conditions was well described by a multiple-channel model in which timing information is available between tones within the same frequency region. The influence of higher order attentional factors was randomly determined. The frequency-selective mechanism appears to be sensitive to uncertainty about the frequency pattern of the input. Repeating the random pattern within each trial effectively eliminated this uncertainty. This result is consistent with experiments on the discrimination of word-length auditory patterns and temporal cues in speech.


Epidemiological studies of neural tube defects in Newfoundland.
A 9-year survey of neural tube defects in Newfoundland showed (1) evidence for secular variation, with a peak in 1980, but no general downward trend as seen in some other populations; (2) significant geographic variation which did not correlate with hardness or nitrate content of the lake water; (3) a tendency for the proportion of females among anencephalic births to increase with increasing frequency of anencephaly among geographic regions. This supports previous evidence for a female-specific contribution to the causes of increased liability to neural tube defect.


Magnetic resonance imaging features of dogs with incomplete recovery after acute, severe spinal cord injury.
Retrospective case series. Describe the magnetic resonance imaging (MRI) features of dogs chronically impaired after severe spinal cord injury (SCI) and investigate associations between imaging variables and residual motor function. United States of America. Thoracolumbar MRI from dogs with incomplete recovery months to years after clinically complete (paralysis with loss of pain perception) thoracolumbar SCI were reviewed. Lesion features were described and quantified. Gait was quantified using an ordinal, open field scale (OFS). Associations between imaging features and gait scores, duration of injury (DOI), or SCI treatment were determined. Thirty-five dogs were included. Median OFS was 2 (0-6), median DOI was 13 months (3-83), and intervertebral disk herniation was the most common diagnosis (n = 27). Myelomalacia was the most common qualitative feature followed by cystic change; syringomyelia and fibrosis were uncommon. Lesion length corrected to L2 length (LL:L2) was variable (median LL:L2 = 3.5 (1.34-11.54)). Twenty-nine dogs had 100% maximum cross-sectional spinal cord compromise (MSCC) at the lesion epicenter and the length of 100% compromised area varied widely (median length 100% MSCC:L2 = 1.29 (0.39-7.64)). Length 100% MSCC:L2 was associated with OFS (p = 0.012). OFS was not associated with any qualitative features. DOI or treatment type were not associated with imaging features or lesion quantification. Lesion characteristics on MRI in dogs with incomplete recovery after severe SCI were established. Length of 100% MSCC was associated with hind limb motor function. Findings demonstrate a spectrum of injury severity on MRI among severely affected dogs, which is related to functional status.


Immunoproteasome and Non-Covalent Inhibition: Exploration by Advanced Molecular Dynamics and Docking Methods.
The selective inhibition of immunoproteasome is a valuable strategy to treat autoimmune, inflammatory diseases, and hematologic malignancies. Recently, a new series of amide derivatives as non-covalent inhibitors of the β1i subunit with Ki values in the low/submicromolar ranges have been identified. Here, we investigated the binding mechanism of the most potent and selective inhibitor, N-benzyl-2-(2-oxopyridin-1(2H)-yl)propanamide (1), to elucidate the steps from the ligand entrance into the binding pocket to the ligand-induced conformational changes. We carried out a total of 400 ns of MD-binding analyses, followed by 200 ns of plain MD. The trajectories clustering allowed identifying three representative poses evidencing new key interactions with Phe31 and Lys33 together in a flipped orientation of a representative pose. Further, Binding Pose MetaDynamics (BPMD) studies were performed to evaluate the binding stability, comparing 1 with four other inhibitors of the β1i subunit: N-benzyl-2-(2-oxopyridin-1(2H)-yl)acetamide (2), N-cyclohexyl-3-(2-oxopyridin-1(2H)-yl)propenamide (3), N-butyl-3-(2-oxopyridin-1(2H)-yl)propanamide (4), and (S)-2-(2-oxopyridin-1(2H)-yl)-N,4-diphenylbutanamide (5). The obtained results in terms of free binding energy were consistent with the experimental values of inhibition, confirming 1 as a lead compound of this series. The adopted methods provided a full dynamic description of the binding events, and the information obtained could be exploited for the rational design of new and more active inhibitors.


Reaction time, inhibition, working memory and 'delay aversion' performance: genetic influences and their interpretation.
For candidate endophenotypes to be useful for psychiatric genetic research, they first of all need to show significant genetic influences. To address the relative lack of previous data, we set to investigate the extent of genetic and environmental influences on performance in a set of theoretically driven cognitive-experimental tasks in a large twin sample. We further aimed to illustrate how test-retest reliability of the measures affects the estimates. Four-hundred 7- to 9-year-old twin pairs were assessed individually on tasks measuring reaction time, inhibition, working memory and 'delay aversion' performance. Test-retest reliability data on some of the key measures were available from a previous study. Several key measures of reaction time, inhibition and working-memory performance indicated a moderate degree of genetic influence. Combining data across theoretically related tasks increased the heritability estimates, as illustrated by the heritability estimates of 60% for mean reaction time and 50% for reaction-time variability. Psychometric properties (reliability or ceiling effects) had a substantial influence on the estimates for some measures. The data support the usefulness of several of the variables for endophenotype studies that aim to link genes to cognitive and motivational processes. Importantly, the data also illustrate specific conditions under which the true extent of genetic influences may be underestimated and hence the usefulness for genetic mapping studies compromised, and suggest ways to address this.


[Food-related lifestyles and eating habits inside and outside the home in the Metropolitan Region of Santiago, Chile].
To distinguish consumer typologies on the basis of their food-related lifestyle in the principal municipalities of the Metropolitan Region of Santiago, Chile, and to characterize these according to their food consumption habits inside and outside the home, sociodemographic characteristics and their level of satisfaction with food-related life. A structured questionnaire was administered to a sample of 951 people in the principal municipalities of the Metropolitan Region of Santiago (more than 100,000 inhabitants). The instrument for collecting data included an adaptation of the food-related life (FRL) questionnaire and the satisfaction with food-related life (SWFL) scale. The food consumption habits inside and outside the home were asked about as well as sociodemographic classification variables of those surveyed. Using a cluster analysis, five typologies were distinguished with significant differences in the five components obtained from the FRL with a factorial analysis of the principal components. The typologies presented a different gender, age and socioeconomic level profile and differed in the scores obtained on the SWFL. They differed in the frequency with which the person has lunch, tea ("once" in Chile) and dinner at home. With respect to the meals outside the home, the typologies were distinguished according to the frequency of meals in restaurants, fast food outlets and in the purchase of prepared food. A lifestyle where eating is related to low involvement and enjoyment of food is associated with a person's higher socioeconomic level and lower age. Additionally, a greater frequency of meals in restaurants and the purchase of prepared food combined with a lower frequency of meals at home is associated with unhealthy eating habits of little benefit to the person, which might have a bearing on a lower level of food-related life satisfaction.


Is dietary deficiency of calcium a factor in rickets? Use of current evidence for our understanding of the disease in the past.
Rickets is considered an indicator of vitamin D deficiency in palaeopathology, but a strand of biomedical thought maintains that dietary calcium deficiency may sometimes play a part in its causation. Our aim is to evaluate the extent to which low calcium intake should be considered as a factor in biocultural interpretations of rickets. We assess published modern epidemiological studies that provide primary data to support claims for a role for dietary calcium deficiency in rickets. We also consider how we might identify, via indicators of calcium intake, populations at risk of calcium deficiency in the past. Support for dietary calcium deficiency as a cause of rickets is equivocal. Direct measurement of dietary calcium in the past is not possible, but exposure to risk factors for low calcium intake can to some extent be identified. Whilst there is little evidence to alter the view that rickets is essentially an indicator of a population's vitamin D status, occasionally, in very low calcium intake groups, dietary calcium deficiency may play a synergistic role by accentuating the need for vitamin D. The notion that dietary calcium deficiency may be a cause of rickets appears to be gaining currency in bioarchaeological studies. This paper shows that it is unusual for this to be the case, and even then the role of vitamin D remains crucial. This paper attempts to summarise the current state of biomedical study in an area that is subject to continuing investigation.


Soil Nutrients, Enzyme Activities, and Microbial Communities along a Chronosequence of Chinese Fir Plantations in Subtropical China.
Forests undergo a long-term development process from young to mature stages, yet the variations in soil nutrients, enzyme activities, microbial diversity, and community composition related to forest ages are still unclear. In this study, the characteristics of soil bacterial and fungal communities with their corresponding soil environmental factors in the young, middle, and mature stages (7, 15, and 25-year-old) of Chinese fir plantations (CFP) in the subtropical region of China were investigated in 2021. Results showed that the alpha diversity indices (Chao1 and Shannon) of soil bacteria and fungi were higher in 15 and 25-year-old stands than in 7-year-old stand of CFP, while the soil pH, soil water content, soil organic carbon, total nitrogen, total phosphorus, sucrase, urease, acid phosphatase, catalase, and microbial biomass carbon, nitrogen, and phosphorus showed higher in 7-year-old stand than other two stands of CFP. The nonmetric multidimensional scaling analysis revealed that the soil microbial species composition was significantly different in three stand ages of CFP. The redundancy and canonical correspondence analysis indicated that the soil urease and microbial biomass nitrogen were the main factors affecting soil bacterial and fungal species composition. Our findings suggested that soil microbial diversity and community structure were inconsistent with changes in soil nutrients and enzyme activities during CFP development, and enhancing stand nurturing and soil nutrient accumulation in the mid-development stage were beneficial to the sustainable management of CFP.


Effect of early administration of alendronate after surgery for distal radial fragility fracture on radiological fracture healing time.
This multicentre prospective clinical trial aimed to determine whether early administration of alendronate (ALN) delays fracture healing after surgical treatment of fractures of the distal radius. The study population comprised 80 patients (four men and 76 women) with a mean age of 70 years (52 to 86) with acute fragility fractures of the distal radius requiring open reduction and internal fixation with a volar locking plate and screws. Two groups of 40 patients each were randomly allocated either to receive once weekly oral ALN administration (35 mg) within a few days after surgery and continued for six months, or oral ALN administration delayed until four months after surgery. Postero-anterior and lateral radiographs of the affected wrist were taken monthly for six months after surgery. No differences between groups was observed with regard to gender (p = 1.0), age (p = 0.916), fracture classification (p = 0.274) or bone mineral density measured at the spine (p = 0.714). The radiographs were assessed by three independent assessors. There were no significant differences in the mean time to complete cortical bridging observed between the ALN group (3.5 months (SE 0.16)) and the no-ALN group (3.1 months (SE 0.15)) (p = 0.068). All the fractures healed in the both groups by the last follow-up. Improvement of the Quick-Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, grip strength, wrist range of movement, and tenderness over the fracture site did not differ between the groups over the six-month period. Based on our results, early administration of ALN after surgery for distal radius fracture did not appear to delay fracture healing times either radiologically or clinically.


The EPH/Ephrin System in Colorectal Cancer.
The EPH/ephrin system constitutes a bidirectional signaling pathway comprised of a family of tyrosine kinase receptors in tandem with their plasma membrane-bound ligand (ephrins). Its significance in a wide variety of physiologic and pathologic processes has been recognized during the past decades. In carcinogenesis, EPH/ephrins coordinate a wide spectrum of pathologic processes, such as angiogenesis, vessel infiltration, and metastasis. Despite the recent advances in colorectal cancer (CRC) diagnosis and treatment, it remains a leading cause of death globally, accounting for 9.2% of all cancer deaths. A growing body of literature has been published lately revitalizing our scientific interest towards the role of EPH/ephrins in pathogenesis and the treatment of CRC. The aim of the present review is to present the recent CRC data which might lead to clinical practice changes in the future.


Primary adult T cell leukemia of bone: two patients with primary bone lesion showing monoclonal integration of HTLV-I proviral DNA.
Adult T cell leukemia (ATL), a neoplasm of mature helper T lymphocytes is etiologically associated with human T lymphotropic virus type-I (HTLV-I). ATL cells infiltrate various organs, the lung, skin, central nervous system, gastrointestinal tract, and bone, causing various clinical manifestations. Two unusual cases of ATL, in which lytic bone lesion was the primary site of ATL, are described. One patient had multiple lytic lesions in bones without any involvement of other organs, and the other patient had a bone lesion in the right radius, which disappeared after chemotherapy. In both cases, monoclonal integration of HTLV-I provirus was demonstrated in the genomic DNA from each bone lesion. Although their clinical courses and pathological findings were different, ATL in both patients began as a bone lesion, showing that primary lymphoma of bone can be manifested in ATL cases.


Spectroscopic characterization and ligand-binding properties of chlorite dismutase from the chlorate respiring bacterial strain GR-1.
Chlorite dismutase (EC 126.96.36.199), an enzyme capable of reducing chlorite to chloride while producing molecular oxygen, has been characterized using EPR and optical spectroscopy. The EPR spectrum of GR-1 chlorite dismutase shows two different high-spin ferric heme species, which we have designated 'narrow' (gx,y,z = 6.24, 5.42, 2.00) and 'broad' (gz,y,x = 6.70, 5.02, 2.00). Spectroscopic evidence is presented for a proximal histidine co-ordinating the heme iron center of the enzyme. The UV/visible spectrum of the ferrous enzyme and EPR spectra of the ferric hydroxide and imidazole adducts are characteristic of a heme protein with an axial histidine co-ordinating the iron. Furthermore, the substrate analogs nitrite and hydrogen peroxide have been found to bind to ferric chlorite dismutase. EPR spectroscopy of the hydrogen peroxide adduct shows the loss of both high-spin and low-spin ferric signals and the appearance of a sharp radical signal. The NO adduct of the ferrous enzyme exhibits a low-spin EPR signal typical of a five-co-ordinate heme iron nitrosyl adduct. It seems that the bond between the proximal histidine and the iron is weak and can be broken upon binding of NO. The midpoint potential, Em(Fe3+/2+) = -23 mV, of chlorite dismutase is higher than for most heme enzymes. The spectroscopic features and redox properties of chlorite dismutase are more similar to the gas-sensing hemoproteins, such as guanylate cyclase and the globins, than to the heme enzymes.


[Early discharge of the healthy newborn from the nursery of the Hospital Español de México].
The risk-benefit of early discharge in newborns is controversial. We haven't found studies that analyze newborn variables and their impact in morbility with early postnatal discharge. We analyze the main variables and their statistical association with the need of additional therapy in early discharged newborns. Observational prolective study in full-term newborns from their birth until their discharge from August to December, 2013. It was made a telephone follow-up to know their health status. The dependent variables were the hours of hospital stay, additional therapies and treatment in the first month. 701 full-term newborns were included in the study, 41 used additional treatment, 23 had to be at the ICU (22 < 24 hours). There was a relative risk (RR) of 12.9 if the Apgar was < 8.8. Also, the risk of needing additional therapy was 9 times greater if the baby was born after a pregnancy of less than 38 weeks. Low weight for gestational age triplicated the risk for admission to ICU. The main variables that had an influence in requiring additional therapy were an Apgar < 8 at 5 minutes, having more than 38 weeks of gestation, and low weight. The elements to manage patients with early discharge are concrete signs that would cause suspicion, follow-up with pediatrician at 3 days of life, more attention to those with an Apgar < 8 at 5 minutes of life, having less than 38 weeks of gestation, or low birth weight for gestational age.


InterStim Therapy: A Contemporary Approach to Overactive Bladder.
Overactive bladder is a common and challenging condition for the practicing obstetrician-gynecologist. The prevalence of the condition is increasing with our aging population. Although some patients respond to first-line therapy, a significant number will require sacral nerve stimulation to address the underlying neurologic condition that causes overactive bladder as well as other pelvic floor conditions. This article summarizes the epidemiology and symptomatology, office evaluation, and treatment of overactive bladder with particular emphasis on sacral nerve stimulation (SNS). SNS technique, results, and future applications are also reviewed.


Patient and caregiver outcomes with levodopa-carbidopa intestinal gel in advanced Parkinson's disease.
Levodopa-carbidopa intestinal gel (LCIG) has shown to be efficacious in motor and non-motor symptoms (NMS). Nevertheless, studies with patient Quality of Life (QoL) as a primary endpoint are scarce. To assess the effect of LCIG on Advanced Parkinson's Disease (APD) patients QoL. Secondarily, the impact on motor symptoms and NMS, emotional well-being, treatment satisfaction, and caregiver QoL, stress, disease burden, anxiety, depression, and work impairment were also investigated. In this prospective, 6-month multicenter postmarketing observational study, LCIG was administered to 59 patients with APD. Endpoints were assessed using validated scales and questionnaires. LCIG significantly improved patient QoL (PDQ-39 mean change ± standard deviation from baseline, -12.8 ± 14.6; P < 0.0001), motor symptoms (UPDRS-III in "On," -6.5 ± 11.8; P = 0.0002), NMS (NMSS, -35.7 ± 31.1; P < 0.0001), mood (Norris/Bond-Lader VAS, -6.6 ± 21.1; P = 0.0297), fatigue (PFS-16, -0.6 ± 1.0; P = 0.0003), depression (BDI-II, -5.1 ± 9.4; P = 0.0002), anxiety (BAI, -6.2 ± 9.6; P < 0.0001), and patient treatment satisfaction (SATMED-Q, 16.1 ± 16.8; P < 0.0001). There were significant correlations between the change from baseline to 6 months between PDQ-39 and UPDRS-IV, NMSS, BAI, BDI-II, AS, and PFS-16 scores, and Norris/Bond-Lader alertness/sedation factor. Caregiver anxiety also improved (Goldberg anxiety scale, -1.1 ± 1.0; P = 0.0234), but the clinical relevance of this finding is questionable. The serious adverse events reported were similar to those previously described for LCIG. In patients with APD, LCIG improves QoL, motor symptoms and NMS, emotional well-being, and satisfaction with the treatment. Improvement in patient QoL is associated with improvements in motor complications, NMS, anxiety, depression, apathy and fatigue. Improvements in patients' QoL does not correspond with improvements in caregivers' QoL or burden.


The unique immunobiology of the skin: implications for tolerance of vascularized composite allografts.
Vascularized composite allograft (VCA) transplantation restores function and form following major soft tissue and musculoskeletal injury. Lifelong immunosuppression is necessary for graft function and survival but acute skin-targeted rejection episodes remain common. We review recent advances in skin immunobiology, emphasizing findings in clinical and experimental VCAs. We also highlight advances in immunotherapy and tolerance protocols with implications for the prevention of VCA rejection, and ultimately, induction of clinically applicable strategies for VCA tolerance. There is now an increasing appreciation for the role of skin-specific mechanisms, including lymphoid neogenesis, in VCA rejection. In contrast, expression of the regulatory master-switch FOXP3 was demonstrated to be significantly upregulated in the skin of tolerant VCAs in large animal models compared with normal skin and rejecting controls. Most VCA transplant centers continue to utilize antibody-mediated induction therapy and triple agent maintenance immunosuppression. Skin remains the primary target of rejection in VCAs, and current multicenter studies hope to elucidate the mechanisms involved. Proposed standardized procedures for skin biopsies, and diligent reporting of clinical data to the international registry, will be important to maximize the strength of these studies.


The use of continuous arteriovenous hemofiltration in intensive care medicine.
Acute renal failure still remains an important and challenging problem in the ICU. Hemodialysis is not always feasible because of hemodynamic instability in critically ill patients. In this circumstances continuous arteriovenous hemofiltration (CAVH) can be an efficient alternative as this method has less detrimental hemodynamic effects. Moreover, within certain limitations, CAVH proves to be an effective "artificial kidney" (control of body fluid, electrolyte and acid-base homeostasis and uremia) and this without serious side-effects. Special emphasis is made on the problem of anticoagulation, which can cause life-threatening complications in posttraumatic and surgical patients. A protamine infusion on the venous line can diminish these complications.


Vancouver type B3 periprosthetic fractures: evaluation and treatment.
Periprosthetic fracture with preexisting severe loss of bone stock is a challenging condition to treat. Available surgical options can be divided into three categories: complex reconstruction of the deficient proximal femur with secure distal fixation; segmental substitution of the proximal femur with a megaprosthesis or allograft/stem composite; and distally fixed replacement with a modular stem, which acts as a scaffold around which the remaining deficient proximal bone can be assembled, to unite and possibly reconstitute.


Nociceptive afferents to the premotor neurons that send axons simultaneously to the facial and hypoglossal motoneurons by means of axon collaterals.
It is well known that the brainstem premotor neurons of the facial nucleus and hypoglossal nucleus coordinate orofacial nociceptive reflex (ONR) responses. However, whether the brainstem PNs receive the nociceptive projection directly from the caudal spinal trigeminal nucleus is still kept unclear. Our present study focuses on the distribution of premotor neurons in the ONR pathways of rats and the collateral projection of the premotor neurons which are involved in the brainstem local pathways of the orofacial nociceptive reflexes of rat. Retrograde tracer Fluoro-gold (FG) or FG/tetramethylrhodamine-dextran amine (TMR-DA) were injected into the VII or/and XII, and anterograde tracer biotinylated dextran amine (BDA) was injected into the caudal spinal trigeminal nucleus (Vc). The tracing studies indicated that FG-labeled neurons receiving BDA-labeled fibers from the Vc were mainly distributed bilaterally in the parvicellular reticular formation (PCRt), dorsal and ventral medullary reticular formation (MdD, MdV), supratrigeminal nucleus (Vsup) and parabrachial nucleus (PBN) with an ipsilateral dominance. Some FG/TMR-DA double-labeled premotor neurons, which were observed bilaterally in the PCRt, MdD, dorsal part of the MdV, peri-motor nucleus regions, contacted with BDA-labeled axonal terminals and expressed c-fos protein-like immunoreactivity which induced by subcutaneous injection of formalin into the lip. After retrograde tracer wheat germ agglutinated horseradish peroxidase (WGA-HRP) was injected into VII or XII and BDA into Vc, electron microscopic study revealed that some BDA-labeled axonal terminals made mainly asymmetric synapses on the dendritic and somatic profiles of WGA-HRP-labeled premotor neurons. These data indicate that some premotor neurons could integrate the orofacial nociceptive input from the Vc and transfer these signals simultaneously to different brainstem motonuclei by axonal collaterals.


Opinion paper. Resistance to new anti-HIV agents: problems in the pathway of drug registration.
Resistance data are now requested by the regulatory agencies as an integral part of the approval process of new antiretroviral drugs. We examined the means by which resistance data was gathered during pre-clinical and clinical Phases I, II and III of drug development, and how the public and academic experts access these proprietary data. The analysis identified various opportunities for improvement of the current process, in particular the need for standards in generating and reporting resistance data on new antiretroviral drugs, and the need to enforce warnings in the product labelling on the drug combinations that can potentially lead to resistance and treatment failure.


Tuberculosis of the parotid gland: histology surprise.
The Parotid gland is rarely involved in tuberculosis, even in endemic countries. We report a case of a 26 year-old woman with no medical history, who presented with a swelling of the parotid lodge. Pathology performed after surgery found a tuberculous parotitis, and the patient received anti-tuberculous regimen with a satisfactory evolution. We discuss both diagnostic and therapeutic modalities for this infection.


The role of parasite epidemiology in the management of grazing cattle.
Epidemiology of ruminant helminths is the foundation on which strategic parasite control programmes are designed. Without this information one is not able to use anthelmintics to provide the optimal benefits for controlling both the adult worm and the pasture larval populations. The absence of strategic programmes generally results in using anthelmintics at the convenience of the producer, which may have little if any impact on parasite populations. The design of a strategic parasite control programme requires a knowledge of the dynamics of egg shedding from the host and the resulting pasture larval populations. It is important to know if larvae are available when animals are turned out onto pasture, when larval populations reach their maximal numbers and when they are induced to become hypobiotic. The goal is to keep pasture larval populations as low as possible. The use of pasture rotation adds another dimension to control programmes. The longer a pasture is allowed to remain fallow, the lower the pasture larval burden will be when it is grazed next. However, when we use intensive rotational grazing, animals may return to the pasture about 28 days later, when the larvae resulting from the eggs shed in the previous grazing are infective. This practice forces cattle to eat all of the forage available, including the grass closest to the faecal pat, where most of the infective larvae are available. If we treated cattle before turning them onto a clean rotationally grazed pasture, we should be able to control parasitism. Using a long-acting anthelmintic should enhance helminth control in rotationally grazed pastures and actually help to clean the pastures. Another grazing management practice is to alternately graze different species. This programme with the strategic use of anthelmintics should reduce parasitism in both host species.


Psychometric properties of an instrument designed to measure the educational quality of graduate training programs.
To assess the quality of residency education programs at an academic medical center for purposes of enhancing individual graduate medical education programs, we asked residents and fellows (N = 419) to evaluate their training programs using a Web-based questionnaire (response rate = 70%). Kruskal-Wallis tests, factor analysis, correlations, generalizability/decision studies, and mean plots were used to examine trainee responses and to assess the questionnaire's measurement properties. Exploratory factor analysis indicated that the instrument had a three-factor structure that correlated highly with overall program rating. Cronbach's alpha exceeded .80 for all factors, and decision studies revealed that 13 to 23 raters were needed to obtain G-coefficients greater than .70. Mean plots showed that the instrument could discriminate within and among training programs at the item level and the factor level, which should help target improvements across graduate training programs within large institutions.


Activation of NOD2/RIPK2 pathway induces mitochondrial injury to oligodendrocyte precursor cells in vitro and CNS demyelination in vivo.
We examined the activation of innate immune pathway mediated by nucleotide-binding oligomerization domain-containing protein 2 (NOD2) in oligodendrocyte precursor cells (OPCs). We show that activation of NOD2 by ligand peptidoglycan (PGN) leads to the recruitment and phosphorylation of receptor-interacting serine/threonine kinase 2 (RIPK2). Phosphorylation of RIPK2 is followed by phosphorylation of neuronal nitric oxide synthase (nNOS), increase in NOS activity and subsequent accumulation of nitric oxide (NO) mediated N-tyrosinylated compounds in OPCs. The reversal of NOS activity by the nNOS inhibitor 7-nitroindazole (7-NI), but not by the iNOS inhibitor L-canavanine, supported the conclusion that the increased NOS activity was due to the selective activation of nNOS in OPCs. In addition, NO mediated injury to OPC was reflected in reduction in activity of respiratory enzymes such as complex I and IV, decrease in mitochondrial membrane potential and release of cytochrome-C from mitochondria. Furthermore, intracerebral injection of PGN into corpus callosum (CC) of rats led to the development of demyelination, which appeared as early as by day 3 post-injection, and involved the trunk of the CC by day 14. Accumulation of N-tyrosinylated proteins was seen in oligodendrocytes in regions of the CC which were in close proximity to the injection site. Taken together, these results suggest that PGN induced formation of NO, mitochondrial dysfunction and accumulation of N-tyrosinylated proteins in oligodendrocytes are likely mediators of central nervous system demyelination.


Taxonomy of coccids (Hemiptera: Coccidae: Coccus L.) associated with Crematogaster ants (Hymenoptera: Formicidae) in the stems of Macaranga plants (Euphorbiaceae) in Southeast Asia.
The Southeast Asian soft scale insects (Hemiptera: Coccomorpha: Coccidae) associated with ants of the Crematogaster borneensis-group (Hymenoptera: Formicidae) and living in the hollow stems of Macaranga plants (Euphorbiaceae) are revised taxonomically. Ten species of the genus Coccus L. are recognised: seven were described previously and three new species are described herein. The species are: Coccus caviramicolus Morrison, C. circularis Morrison, C. heckrothi Gullan Kondo sp. n., C. lambirensis Gullan Kondo sp. n., C. macarangicolus Takahashi, C. macarangae Morrison, C. penangensis Morrison, C. pseudotumuliferus Gullan Kondo sp. n., C. secretus Morrison and C. tumuliferus Morrison. All of these species are described or redescribed and newly illustrated based on the adult females, and a key to distinguish the species is provided. We designate a lectotype for C. macarangicolus. The first-instar nymphs of all species are morphologically extremely similar and therefore only the first-instar nymph of C. macarangae is described and illustrated. Seven of these species currently are known only from Macaranga, but C. macarangae, C. secretus and perhaps C. pseudotumuliferus have been recorded from the hollow stems of several other ant-plants and a few non-myrmecophytes. The Coccus species from Macaranga are closely related to C. hesperidum L., the type species of the genus, and therefore are retained in the genus Coccus even though the adult females exhibit a few morphological differences from C. hesperidum. The species of Coccus from Macaranga appear to be parthenogenetic because no male nymphs or adults have been found, despite extensive collecting.


Music as language.
This article is an inquiry into the potential role of music in helping to address and to articulate complex emotional states such as the feelings patients might experience during the process of an illness or while undergoing bereavement. The article is centered on the role music played in structuring and articulating the cancer treatment experience of my infant nephew. What is woven around that central core is a synthesis and analysis of various philosophical perspectives, autobiographical vignettes, and empirical research. The writer postulates that music has an essential, inherent capacity to scaffold and contain emotions. Music is also considered a means to help facilitate the expression of difficult emotions such as lamentation, longing, and fear of the unknown that are often otherwise isolating, ineffable, or unbearable for patients. A major point of inquiry in this article is whether music can serve as a nurturing love object, or as a transitional object, for a patient during times of intense distress. What is also woven throughout this article is a subexploration of various philosophical perspectives on the cultural meanings and metaphors of illness.


Angiokeratoma corporis diffusum.
Angiokeratoma is a dark violaceous keratotic papule which can be solitary or multiple. Generalised systemic angiokeratoma constitute angiokeratoma corporis diffusum, a rare X-linked recessive inborn error of glycosphingolipid metabolism due to deficiency of alpha galactosidase A. Patients with this disease have premature death due to the vascular complications. A case of possible Fabry's disease is presented.


Luteal support with both estradiol and progesterone after clomiphene citrate stimulation for in vitro fertilization.
To determine if pregnancy rates (PRs) for clomiphene citrate (CC)-stimulated IVF-ET can be increased by luteal support with E2 and P. Prospective randomized crossover clinical study. Infertile women volunteers in an academic research environment. Ninety-three infertile women underwent a total of 143 IVF-ET cycle using CC for ovulation induction. Each woman received either no luteal support (control group) or luteal support with both oral E2 (2 mg three times daily) starting on the day of retrieval and vaginal P suppositories (100 mg twice daily) starting on the day of ET. Clinical PR. In 79 of 143 (55%) of the cycles, at least one embryo was transferred. Compared with the control group (n = 35 cycles), the luteal support group (n = 44 cycles) had a significantly higher PR per retrieval (control: 2% versus luteal support: 16%) and were older (control: 33 +/- 4 versus luteal support: 35 +/- 4 years; mean +/- SEM). They did not differ in terms of E2 or P levels, endometrial thickness on the day of hCG, number of follicles > 16 mm in diameter, mature oocytes retrieved, or embryos transferred. Luteal support with both E2 and P significantly increase the clinical PRs for CC-stimulated IVF-ET.


Population resequencing reveals local adaptation of Arabidopsis lyrata to serpentine soils.
A powerful way to map functional genomic variation and reveal the genetic basis of local adaptation is to associate allele frequency across the genome with environmental conditions. Serpentine soils, characterized by high heavy-metal content and low calcium-to-magnesium ratios, are a classic context for studying adaptation of plants to local soil conditions. To investigate whether Arabidopsis lyrata is locally adapted to serpentine soil, and to map the polymorphisms responsible for such adaptation, we pooled DNA from individuals from serpentine and nonserpentine soils and sequenced each 'gene pool' with the Illumina Genome Analyzer. The polymorphisms that are most strongly associated with soil type are enriched at heavy-metal detoxification and calcium and magnesium transport loci, providing numerous candidate mutations for serpentine adaptation. Sequencing of three candidate loci in the European subspecies of A. lyrata indicates parallel differentiation of the same polymorphism at one locus, confirming ecological adaptation, and different polymorphisms at two other loci, which may indicate convergent evolution.


Analysis of the distribution pattern of sister chromatid exchanges in mitotic chromosomes of human T-lymphocytes.
Band locations of 344 sister chromatid exchanges (SCE), observed in chromosome preparations of peripheral T-lymphocyte cultures, were identified using a sequential Q-banding-sister chromatid differentiation staining protocol. A comparison between expected Poisson, expected negative binomial distributions and observed SCE patterns, revealed that the negative binomial distribution provided a better fit to our SCE data. The aggregated pattern of SCE distribution indicated that some bands were more prone to undergo these events. Genetic markers assigned to those bands recording a significant number of exchanges seemed to correspond with the transcriptionally active genes. The results confirm that SCE are induced at the early S-phase of the cell cycle involving the early replicating genes in these events. Potential applications of cytogenetic techniques employed in the present study are proposed.


Platform-Switching to Preserve Peri-Implant Bone: A Meta-Analysis.
The objective of this meta-analysis was to determine the literature-based evidence if platform-switching has an effect in preventing marginal bone loss around prosthodontic implants following their functional loading in comparison to conventional platform-matching. A systematic literature search was performed on PubMed, Science Direct, Google Scholar for Literature from 1950 to January 2015, human randomized clinical trials (RCTs) and prospective clinical controlled cohort studies (PCCS) reporting marginal bone loss around platform-switched and matched implants. Six RCTs with a low risk of bias revealed a significantly less mean marginal bone loss (0.57 mm [CI 95% 0.30; 0.84]) around platform-switched implants in comparison to platform-matched implants [1.14 mm (CI 95% 0.69; 1.6, p < 0.001)]. The meta-analysis revealed a significantly less peri-implant marginal bone loss with platform-switched implants as compared to platform-matched implants. The qualitative analysis depicts a trend favouring the platform-switching technique over platform- matching technique to prevent marginal bone loss. However, owing to the heterogeneity of the included studies, their results necessitate cautious interpretation.