Paternal allele influences high fat diet-induced obesity.
C57BL/6J (B6) mice are susceptible to high-fat diet (HFD)-induced obesity and have been used in metabolism research for many decades. However, the genetic component of HFD-induced obesity has not yet been elucidated. This study reports evidence for a paternal transmission of HFD-induced obesity and a correlated expression of Igf2 and Peg3 (paternal expressed gene 3) imprinted genes. We found that PWK mice are resistant to HFD-induced obesity compared to C57BL/6J mice. Therefore, we generated and analyzed reciprocal crosses between these mice, namely; (PWK×B6) F1 progeny with B6 father and (B6×PWK) F1 progeny with PWK father. The (PWK×B6) F1 mice were more sensitive to diet-induced obesity compared to (B6×PWK) F1 mice, suggesting a paternal transmission of diet-induced obesity. Expression analysis of imprinted genes in adipocytes revealed that HFD influences the expression of some of the imprinted genes in adipose tissue in B6 and PWK mice. Interestingly, Igf2 and Peg3, which are paternally expressed imprinted genes involved in the regulation of body fat accumulation, were down-regulated in B6 and (PWK×B6) F1 mice, which are susceptible to HFD-induced obesity, but not in PWK and (B6×PWK) F1 mice, which are resistant. Furthermore, in vitro analysis showed that Igf2, but not Peg3, had an anti-inflammatory effect on TNF-α induced MCP-1 expression in adipocytes. Taken together, our findings suggest that the down-regulation of Igf2 and Peg3 imprinted genes in adipocytes may be involved in the paternal transmission of HFD-induced obesity.


[Modernity in dreams and myths].
The very presence of myths in psychoanalysis raises questions about their scientific status: that leads to reconsider the whole issue of Freudian mythology in a non-medical manner, by envisaging it in the more general context of modern myths, both political and artistic. Special attention is then paid to Surrealism, as the only avant-garde movement at the same time focused on psychoanalysis and politics: the role played by dreams in foundering myths is examined in both Surrealism and psychoanalysis. Surrealistic myths, such as Dalí's Grand Paranoïaque Comestible, finally prove to be so non-oedipian as the Nazi Ubermensch myth; nevertheless, their comparison with Freudian mythology points out their common origin, as they all fulfilled the need of the mass society for a modern myth, able to express his deeply renewed self-awareness.


Revision cochlear implantation with different electrodes can cause incomplete electrode insertion and poor performance.
To review our experiences with revision cochlear implantation (CI), to assess revision CI efficacy, and to find factors that cause incomplete electrode insertion. Retrospective chart review of revision CI from 2004 to 2011. Academic tertiary referral center. Twenty-two patients who underwent revision CI. Revision cochlear implant surgery, explanted device analysis, electrode analysis for a newly implanted device, measurement of electrode insertion depth on postoperative radiographic evaluation, and postoperative speech perception test by open-set testing. Surgical outcomes, postoperative performance, and analysis of used electrodes. Approximately 2.7% (22/816) of CI recipients underwent revision surgery. The reasons for revision surgery were device failure (n = 14) and medical reason (n = 8). Cochlear implantation was performed at an average of 4.7 years after initial operation. Seventeen patients underwent revision CI with an electrode that was the same as or similar to the initial one, and all electrodes were fully inserted. Different electrode types were used in the remaining 5 patients. Interestingly, 4 of the 5 had incomplete electrode insertion. Among the 4 patients, 2 had poorer open set sentence scores after revision than after initial surgery. In this study, full electrode insertion was achieved in all cases where the same type of electrode was used during initial and revision CI. In contrast, we noticed incomplete insertion in 4 of 5 patients who had revision electrodes that differed from initial electrodes. While incomplete electrode insertion does not necessitate poor speech performance, some patients with incomplete electrode insertion certainly experience it. Therefore, electrode selection requires circumspection in revision CI. Choosing a thinner electrode for revision CI may reduce the possibility of incomplete electrode insertion.


[Prolonged hospital stay in patient with head and neck cancer: impact of nutritional status and pharyngeal problems].
Patients who underwent surgery for head and neck malignant neoplasms loose two important human functions: phonation and swallowing. The purpose of this study is to determine the impact of nutritional status and pharyngeal problems in hospital stay in these patients. Fifty-four patients with oral and pharyngolaryngeal carcinomas underwent surgery were prospective studied to determinate predictors of 2 weeks or longer hospital stay. We studied the impact of malnutrition, tumour location, pharyngeal postoperative problems and infections on hospital stay. 53% of the patients unwent surgery had more than two weeks of hospital stay. Postoperative pharyngeal problems was the strongest correlate of prolonged hospital stay (69% of patients) while only 23% of patients had longer stay because of severe infection (sepsis, neunoniae). Malnutrition or tumor location were not risk factors of prolonged hospitalization stay in our study. These findings suggest that swallowing problems are the strongest predictors of long hospital stay in head and neck cancer patients.


[Characterization of the foci of meningococcal infection in closed groups of males].
A total of 257 foci of meningococcal infection in groups of servicemen were selectively examined in 1982-2002. From these groups 353 patients with generalized forms of the disease underwent hospitalization. Most of the foci had a single infection, the proportion of foci with 10-40 patients was 82.6%. The meningococcal infection rate among humans in the foci was 25-37%, group A meningococci playing the leading role. In the structure of meningococcal infection generalized forms of infection constituted 16%, localized forms constituted 25% and inapparent forms (carriers)--59%. The formation of the morbidity structure was influenced by the type of the focus (with a single or multiple infection) and the character of morbidity for many years (during epidemic or at the period between epidemics). No absolute dependence of the level of meningococcal carrier state in the groups of servicemen on the appearance of the generalized forms of meningococcal infection was noted. Thus, both during epidemic and at the period between epidemics the population of meningococci, heterogeneous in its serological structure and differing in its clinical and epidemiological importance, constantly circulated with the leading role played by group A meningococci.


Somatosensory abnormalities in atypical odontalgia: A case-control study.
Somatosensory function in patients with persistent idiopathic types of orofacial pain like atypical odontalgia (AO) is not well described. This study tested the hypothesis that AO patients have significantly more somatosensory abnormalities than age- and sex-matched controls. Forty-six AO patients and 35 controls participated. Inclusion criteria for AO were pain in a region where a tooth had been endodontically or surgically treated, persistent pain >6 months, and lack of clinical and radiological findings. The examination included qualitative tests and a battery of intraoral quantitative sensory testing (QST). Most AO patients (85%) had qualitative somatosensory abnormality compared with few controls (14%). The most common qualitative abnormalities in AO patients were found with pin-prick 67.4%, cold 47.8%, and touch 46.5% compared with 11.4%, 8.6%, and 2.9%, respectively, in the control group (P<0.001). Between-group differences were seen for many intraoral QST: mechanical detection threshold, mechanical pain threshold (pinprick), dynamic mechanical allodynia (brush), dynamic mechanical allodynia (vibration), wind-up ratio, and pressure pain threshold (P<0.01). In the trigeminal area, between-group differences in thermal thresholds were nonsignificant while differences in cold detection at the thenar eminence were significant. Individual somatosensory profiles revealed complex patterns with hyper- and hyposensitivity to intraoral QST. Between-group differences in pressure pain thresholds (P<0.02) were observed at the thenar eminence. In conclusion, significant abnormalities in intraoral somatosensory function were observed in AO, which may reflect peripheral and central sensitization of trigeminal pathways. More generalized sensitization of the nociceptive system may also be part of AO pathophysiology.


Systematic Investigation of the Alucone-Coating Enhancement on Silicon Anodes.
Polyvinylidene fluoride (PVDF) is the most popular binder in commercial lithium-ion batteries but is incompatible with a silicon (Si) anode because it fails to maintain the mechanical integrity of the Si electrode upon cycling. Herein, an alucone coating synthesized by molecular layer deposition has been applied on the laminated electrode fabricated with PVDF to systematically study the sole impact of the surface modification on the electrochemical and mechanical properties of the Si electrode, without the interference of other functional polymer binders. The enhanced mechanical properties of the coated electrodes, confirmed by mechanical characterization, can help accommodate the repeated volume fluctuations, preserve the electrode structure during electrochemical reactions, and thereby, leading to a remarkable improvement of the electrochemical performance. Owing to the alucone coating, the Si electrodes achieve highly reversible cycling performance with a specific capacity of 1490 mA h g-1 (0.90 mA h cm-2) as compared to 550 mA h g-1 (0.19 mA h cm-2) observed in the uncoated Si electrode. This research elucidates the important role of surface modification in stabilizing the cycling performance and enabling a high level of material utilization at high mass loading. It also provides insights for the future development of Si anodes.


Interim monitoring of longitudinal comparative studies with recurrent event responses.
A method of interim monitoring is described for longitudinal comparative studies in which the outcome of interest is a recurrent event and treatment comparisons are based on expected numbers of events. The nonparametric methods described by Cook, Lawless, and Nadeau (1996, Biometrics 52, 116-130) are generalized to provide a robust estimate of the covariance matrix for a sequence of test statistics calculated over time. The error spending function methodology of Lan and DeMets (1983, Biometrika 70, 659-663) is adopted to control the experimental type I error rate. A simulation study indicates satisfactory frequency properties of this procedure for the moderate to large scale trials for which it is intended. Extensions of this approach to handle stratified designs and studies with multitype recurrent events are indicated. Data from a kidney transplant study (Cole et al., 1994, Transplantation 57, 60-67) are used for illustrative purposes.


Invisible grasps: Grip interference in anosognosia for hemiplegia.
Previous findings suggest that, in anosognosic patients, their illusory motor experience is based on a "normal" motor intention and planning for the paralyzed limbs. However, these studies involved proximal muscles (shoulder) that can be mediated by the ipsilateral (intact) cortex more than distal muscles (fingers). In the present study, we asked whether, in anosognosic patients, the spared motor intention for the paralyzed limb can go as far as to influence kinematic parameters of distal movements. Six hemiplegic patients (1 with and 5 without anosognosia) were required to reach and grasp with both hands targets of the same or different size, attached to a plinth. Maximum grip aperture of the right (intact) hand was recorded using an infrared motion capture system. All patients were evaluated with a specific battery for anosognosia and different neurpsychological test. In the patient affected by anosognosia for hemiplegia, the grip aperture of the healthy hand was influenced by the intended (but not executed) movement of the plegic hand when the patient was trying to reach to grasp targets of different size, F(2, 14) = 11.87, p < .001. Patients affected by hemiplegia (without anosognosia) didn't show any interference effect between the plegic and healthy hand even when they were asked to reach to grasp targets of different size. Our results confirm the hypothesis that a spared intention-programming system within the contralateral (damaged) cortex can go as far as to influence distal kinematic parameters of the healthy hand of patients affected by anosognosia for hemiplegia.


Inhibitory phenotype of HBV-specific CD4+ T-cells is characterized by high PD-1 expression but absent coregulation of multiple inhibitory molecules.
T-cell exhaustion seems to play a critical role in CD8+ T-cell dysfunction during chronic viral infections. However, up to now little is known about the mechanisms underlying CD4+ T-cell dysfunction during chronic hepatitis B virus (CHB) infection and the role of inhibitory molecules such as programmed death 1 (PD-1) for CD4+ T-cell failure. The expression of multiple inhibitory molecules such as PD-1, CTLA-4, TIM-3, CD244, KLRG1 and markers defining the grade of T-cell differentiation as CCR7, CD45RA, CD57 and CD127 were analyzed on virus-specific CD4+ T-cells from peripheral blood using a newly established DRB1*01-restricted MHC class II Tetramer. Effects of in vitro PD-L1/2 blockade were defined by investigating changes in CD4+ T-cell proliferation and cytokine production. CD4+ T-cell responses during chronic HBV infection was characterized by reduced Tetramer+CD4+ T-cell frequencies, effector memory phenotype, sustained PD-1 but low levels of CTLA-4, TIM-3, KLRG1 and CD244 expression. PD-1 blockade revealed individualized patterns of in vitro responsiveness with partly increased IFN-γ, IL-2 and TNF-α secretion as well as enhanced CD4+ T-cell expansion almost in treated patients with viral control. HBV-specific CD4+ T-cells are reliably detectable during different courses of HBV infection by MHC class II Tetramer technology. CD4+ T-cell dysfunction during chronic HBV is basically linked to strong PD-1 upregulation but absent coregulation of multiple inhibitory receptors. PD-L1/2 neutralization partly leads to enhanced CD4+ T-cell functionality with heterogeneous patterns of CD4+ T-cell rejunivation.


Measuring the impact of medicines regulatory interventions - Systematic review and methodological considerations.
Evaluating the public health impact of regulatory interventions is important but there is currently no common methodological approach to guide this evaluation. This systematic review provides a descriptive overview of the analytical methods for impact research. We searched MEDLINE and EMBASE for articles with an empirical analysis evaluating the impact of European Union or non-European Union regulatory actions to safeguard public health published until March 2017. References from systematic reviews and articles from other known sources were added. Regulatory interventions, data sources, outcomes of interest, methodology and key findings were extracted. From 1246 screened articles, 229 were eligible for full-text review and 153 articles in English language were included in the descriptive analysis. Over a third of articles studied analgesics and antidepressants. Interventions most frequently evaluated are regulatory safety communications (28.8%), black box warnings (23.5%) and direct healthcare professional communications (10.5%); 55% of studies measured changes in drug utilization patterns, 27% evaluated health outcomes, and 18% targeted knowledge, behaviour or changes in clinical practice. Unintended consequences like switching therapies or spill-over effects were rarely evaluated. Two-thirds used before-after time series and 15.7% before-after cross-sectional study designs. Various analytical approaches were applied including interrupted time series regression (31.4%), simple descriptive analysis (28.8%) and descriptive analysis with significance tests (23.5%). Whilst impact evaluation of pharmacovigilance and product-specific regulatory interventions is increasing, the marked heterogeneity in study conduct and reporting highlights the need for scientific guidance to ensure robust methodologies are applied and systematic dissemination of results occurs.


Impediments to research in pediatric dermatology: the results of a survey of the members of the society for pediatric dermatology.
A research task force of the Society for Pediatric Dermatology (SPD) was established to investigate the barriers to expanding research in the field of pediatric dermatology. A survey was designed to address constraints limiting research activities among members of the SPD. A nine-question survey was distributed to SPD members at the annual meeting in 2007. Of the 70 respondents, 99% reported limitations to research activities. Of those, 90% (62/69) cited time constraints as a cause, 71% lack of funding, 38% lack of training, 35% lack of research infrastructure, 10% (7/69) lack of mentoring, and 25% (17/69) cited other reasons. SPD members face many challenges that curtail their bench and clinical research, although time constraints are most common. The high demand for clinic-directed activity and continuing workforce issues in the specialty likely contribute to the time constraints.


Long-term results of percutaneous management for anastomotic biliary stricture after orthotopic liver transplantation.
The purpose of this study was to evaluate the results of percutaneous transhepatic management (PTM) of anastomotic biliary strictures (BS). Among 168 liver transplant adult recipients, BS was identified in 30 patients. In 6 patients, narrowing of the anastomosis was found early, and in all cases disappeared spontaneously with prolonged draining of the bile tube. Within a mean time of 14 months after transplantation, 24 patients had symptomatic BSs, revealed by cholestasis (n = 17) or cholangitis (n = 7). Twenty-two patients underwent PTM as first treatment of BS (balloon dilatation or stent placement). We evaluated the primary and secondary patency rate of PTM. In 1 patient, PTM failed because the stricture could not be passed with the guide wire, necessitating conversion to a Roux-en-Y choledochojejunostomy (CDJ). Fourteen patients were treated by percutaneous balloon dilatation from which 8 patients (57.2%) were recurrence-free with a mean follow-up of 61 months. One patient with a patent biliary anastomosis underwent retransplantation for acute rejection. Twelve patients received metallic expandable stent placement as their primary treatment (n = 7) or after failure of balloon dilatation (n = 5). Recurrent stricture was found in 7 cases (58%) and was treated by PTM (n = 6) or surgery (n = 1). The primary patency rate for PTM was 58.8% at 12 months and the secondary patency rate 88.4%, with a mean follow-up of 47 months (median: 44 months). The mortality rate was 3.5% (one death). PTM with balloon dilatation, stent placement, or both, represent a safe method to treat anastomotic BSs after orthotopic liver transplantation (OLT) resulting in a secondary patency rate of 88% at 5 years.


Atrioventricular septal defect with common valvar orifice and tetralogy of Fallot revisited: making a case for primary repair in infancy.
Atrioventricular septal defect with common valvar orifice and tetralogy of Fallot is a rare combination of congenital cardiac anomalies. Approaches to this lesion have tended to emphasize either staged repair or complete repair beyond infancy. Between July 1992 and August 1997, nine patients underwent repair of complete atrioventricular septal defect with tetralogy of Fallot. One patient, aged 9.6 years at the time of repair, had previously undergone construction of a modified Blalock-Taussig shunt. Primary complete repair was performed in the other 8 patients at ages ranging from 2.5 to 16 months (median 4.6 months), and all but one were infants. All patients had a Rastelli type C defect, a single ventricular septal defect with inlet and outlet components, and malalignment of the muscular outlet septum with subpulmonary stenosis. A single patch technique, with closure of the zone of apposition ('cleft') in the left atrioventricular valve, was used in all eight patients undergoing primary repair, while a double patch was employed in the previously palliated older patient. In all cases of repair using a single patch, the anterosuperior bridging leaflet was divided obliquely to the right, following the malaligned outlet septum, in order to avoid subaortic obstruction. Repair of the right ventricular outflow tract included infundibular myectomy in eight, pulmonary valvotomy in four, infundibular or transannular patching in three and one, respectively, and reconstruction with a valved allograft conduit in two patients. There was no early mortality or significant morbidity. At a median follow-up of 45 months, there had been one death related to non-cardiac causes and no reinterventions. Left atrioventricular valvar regurgitation was moderate or mild in two patients, and right atrioventricular valvar regurgitation was mild in one patient. No patient had more than mild pulmonary regurgitation or a gradient across the right ventricular outflow tract in excess of 18 mm Hg. Our results demonstrate that primary repair of atrioventricular septal defect with tetralogy of Fallot can be performed with excellent early and mid-term results in young infants. Although it has been suggested that a technique utilizing oblique division of the anterosuperior bridging leaflet may lead to high rates of atrioventricular valvar regurgitation, medium-term atrioventricular valvar function in the present cohort of patients has been excellent.


Metastatic adenocarcinoma to the brain: an immunohistochemical approach.
The diagnosis of metastatic adenocarcinoma to the brain of unknown primary is problematic, and the role of immunohistochemistry in identifying a source has not been fully characterized. Sixty-eight metastatic adenocarcinomas of the brain with known primaries were immunostained with antibodies to cytokeratin 7 (CK7), cytokeratin 20 (CK20), CAM 5.2, wide-spectrum keratin (WSK), gross cystic disease fluid protein-15 (GCDFP-15), glial fibrillary acidic protein (GFAP), estrogen receptor (ER), and progesterone receptor (PR). True positive staining was defined as CK7 in lung or breast; CK20 in gastrointestinal; and GCDFP-15, ER, and PR in breast carcinomas. CK7 immunoreactivity was present in all 27 lung carcinomas and 14 of 15 breast carcinomas with a sensitivity of 98% and specificity of 78%. CK20 stained 15 of 16 GI carcinomas with a sensitivity and specificity of 94%. None of the cytokeratins stained surrounding brain tissue. GCDFP-15, ER, and PR had sensitivities of 33%, 33%, and 87%, with specificities of 92%, 84%, and 28%, respectively. PR often stained nuclei of normal brain tissue and was accentuated in areas of necrosis or cautery artifact. CK7 and CK20 are highly sensitive and specific in patients with metastatic adenocarcinoma to the brain of unknown primary. GCDFP-15 and ER are relatively specific, but insensitive markers, and PR is nonspecific and difficult to interpret.


Modulation of gene expression from the arabinose-inducible araBAD promoter.
The arabinose-inducible P(BAD) promoter suffers from all-or-none gene expression in which cells harboring the natively controlled arabinose transport gene (araE) are either induced or uninduced, the relative fraction of which is controlled by the concentration of arabinose. The population-averaged variation in expression from P(BAD) as a function of inducer concentration is proportional to the percentage of cells that are fully induced (vs. uninduced) rather than the level of expression in individual cells. Because of its undesirable effects on the expression of heterologous genes, the all-or-none phenomenon was eliminated in Escherichia coli by expression of araE from arabinose-independent (either the Lactococcus lactis constitutive or IPTG-inducible lac) promoters. In these arabinose-transport engineered cells, variation in P(BAD) expression with arabinose concentration was a result of variation of the expression level in individual cells with all cells in the population having approximately the same induction level.


Long Term Outcome of Avulsed Immature Mandibular Incisor with Progressive External Root Resorption: 9 Years Follow-Up.
Avulsion of permanent teeth is the most common in young permanent dentition. Replantation of immature teeth after avulsion represents a major challenge in terms of treatment management and long-term prognosis. This case report describes 9 years of follow-up for an avulsed and replanted immature mandibular lateral incisor with progressive external root resorption. A 7-year-old patient following an accident in which his mandibular left central incisor was avulsed and replanted within one hour after being stored in a physiological storage medium. However, radiographic examination conducted six weeks after the dental injury revealed inflammatory root resorption of the replanted tooth #31. To address root resorption, endodontic treatment was performed involving the use of calcium hydroxide as an intracanal medication for a short period of time, followed by root canal obturation with mineral trioxide aggregate placed below the crestal bone margin. Three months later the root resorption had progressed. Consequently, a decision was made to perform periodontal surgery. While the long-term follow-up revealed that the inflammatory root resorption had damaged half of the root, the tooth remained functional and aesthetically favourable. Despite the challenges associated with replantation of an immature tooth following avulsion, this case demonstrated favourable outcomes. The tooth maintained its functionality, exhibited favourable aesthetic, and the dimensions of the alveolar ridge were preserved, allowing for the physiological expansion of the dental arch.


Should the presence of an antiphospholipid antibody affect the duration of anticoagulant treatment in patients with venous thromboembolism?
A 44-year-old otherwise healthy woman has completed 3 months of anticoagulation therapy for a first episode of unprovoked pulmonary embolism. At the time of diagnosis and before the initiation of anticoagulation, she was found to have an elevated IgG anticardiolipin antibody (ACLA), which was measured at 42 IgG phospholipid (GPL) units (reference range, <15 GPL units) with negative lupus anticoagulant (LAC) testing. Should this laboratory finding affect the recommended duration of anticoagulant therapy?


Remote controls illusion: strange interactions across space cannot be explained by simple contrast filters.
The visual system has separable visual encoding for luminance and for contrast modulation [J. Vis.8(1), B152 (2008)1534-736210.1167/8.6.1]; the two dimensions can be represented with a luminance contrast versus luminance plane. Here we use a contrast asynchrony paradigm to explore contextual effects on luminance contrast modulation: two identical rectangular bars (0.5°×2.5°) have luminance levels that modulate at 2 Hz; when one bar is placed on a bright field and the other bar on a dark field, observers perceive the bars modulating in antiphase with each other and yet becoming light and dark at the same time. The antiphase perception corresponds to the change in contrast between the bars and their surrounds (a change along the contrast axis of the plane); the in-phase perception corresponds to the luminance modulation (a change along the luminance axis of the plane). We examine spatial interaction by adding bright rectangular (0.5°×2.5°) flankers on both sides of the dark-field bar and dark flankers on both sides of the bright-field bar. Remarkably, flankers produce an in-phase appearance when separated from the bars by between 2' and 4' of visual angle, and produce antiphase appearance when they directly adjoin the bars or are separated by more than 8'. To estimate the dimensions of the spatial interaction, we parametrically adjust the size of the gap between bars and flankers and the length of the flankers. We attempt to account for the results with models based on rectified difference of Gaussian filters and with rectified oriented difference of Gaussian filters. The models can account for the results when the flankers are the same height as bars, but are unable to account for the effects of increasing the flanker length. The models therefore suggest that the spatial interaction across distances requires more complex interactions of contrast filters.


Hydrogen storage in mesoporous titanium oxide-alkali fulleride composites.
Mesoporous titanium oxide-alkali fulleride composites were synthesized and characterized by X-ray diffraction, nitrogen adsorption, Raman spectroscopy, and elemental analysis. The hydrogen sorption properties of these composites were investigated at 77 K, room temperature, and 200 degrees C. A maximum overall volumetric uptake of 27.35 kg/m(3) was obtained for the lithium fulleride composite at 77 K and 100 atm, compared with 25.48 kg/m(3) for the pristine unreduced material under the same conditions. This value was less than those previously reported for bis(toluene)titanium- and bis(benzene)vanadium-reduced materials (40.46 and 33.42 kg/m(3), respectively) and also less than those found for the fulleride-free Li- and Na-reduced materials in this study (28.10 and 28.19 kg/m(3), respectively). At room temperature and 100 atm, the maximum gravimetric storage and adsorption values of fulleride-impregnated composites were 0.99 and 0.11 wt %, respectively, while the corresponding amounts for unreduced material were 0.94 and 0.10 wt %. At 200 degrees C and 100 atm, the maximum gravimetric storage and adsorption capacities of fulleride composites were less than those of the unreduced material, which were 0.62 and 0.06 wt %, respectively. Thus, inclusion of fulleride units in the pores lowered the overall gravimetric and volumetric storage relative to the fulleride-free Na- and Li-reduced counterparts. Like other reduced composites studied in our group, the enthalpies of the reduced composites showed an unusual increasing trend with surface coverage, with the greatest value (6.55 kJ/mol) measured for the Na-reduced fulleride composite. This suggests that the reduced titanium oxide surface provides the majority of the binding sites in these materials.


Do nitrogen fertilizers stimulate or inhibit methane emissions from rice fields?
In rice cultivation, there are controversial reports on net impacts of nitrogen (N) fertilizers on methane (CH 4 ) emissions. Nitrogen fertilizers increase crop growth as well as alter CH 4 producing (Methanogens) and consuming (Methanotrophs) microbes, and thereby produce complex effects on CH 4 emissions. Objectives of this study were to determine net impact of N fertilizers on CH 4 emissions and to identify their underlying mechanisms in the rice soils. Database was obtained from 33 published papers that contained CH 4 emissions observations from N fertilizer (28-406 kg N ha-1 ) treatment and its control. Results have indicated that N fertilizers increased CH 4 emissions in 98 of 155 data pairs in rice soils. Response of CH 4 emissions per kg N fertilizer was significantly (P < 0.05) greater at < 140 kg N ha-1 than > 140 kg N ha-1 indicating that substrate switch from CH 4 to ammonia by Methanotrophs may not be a dominant mechanism for increased CH 4 emissions. On the contrary, decreased CH 4 emission in intermittent drainage by N fertilizers has suggested the stimulation of Methanotrophs in rice soils. Effects of N fertilizer stimulated Methanotrophs in reducing CH 4 emissions were modified by the continuous flood irrigation due to limitation of oxygen to Methanotrophs. Greater response of CH 4 emissions per kg N fertilizer in urea than ammonia sulfate probably indicated the interference of sulfate in the CH 4 production process. Overall, response of CH 4 emissions to N fertilizers was correlated with N-induced crop yield (r = +0.39; P < 0.01), probably due to increased carbon substrates for Methanogens. Using CH 4 emission observations, this meta-analysis has identified dominant microbial processes that control net effects of N fertilizers on CH 4 emissions in rice soils. Finally, we have provided a conceptual model that included microbial processes and controlling factors to predict effects of N fertilizers on CH 4 emissions in rice soils.


11 beta-hydroxy-9 beta-estrone.
C18H22O3, Mr = 286.37, trigonal, P3(2), a = 10.091 (1), c = 12.271 (1) A, V = 1082.1 A3, Z = 3, Dx = 1.318 Mg m-3, lambda(Cu K alpha) = 1.5418 A, mu = 0.667 mm-1, T = 298 K, F(000) = 462, final R = 0.056 for 1468 observed reflections. The pattern of intermolecular interaction associated with 11 beta-hydroxy substitution differs from that observed in more potent estrogens.


Autoradiographic evidence for a calcitonin receptor on testicular Leydig cells.
Previous studies have indicated that there is a relation between testicular function and adequate concentrations of zinc in testicular cells, and that calcitonin alters cellular zinc transfer in the testis. The present studies provide autoradiographic evidence that calcitonin binds in vivo to the cell membrane of testicular Leydig cells. The data thus confirm the presence of the testicular cell membrane calcitonin receptors that were previously demonstrated indirectly by Scatchard analysis of data collected from binding studies.


Regulating general mutation rates: examination of the hypermutable state model for Cairnsian adaptive mutation.
In the lac adaptive mutation system of Cairns, selected mutant colonies but not unselected mutant types appear to arise from a nongrowing population of Escherichia coli. The general mutagenesis suffered by the selected mutants has been interpreted as support for the idea that E. coli possesses an evolved (and therefore beneficial) mechanism that increases the mutation rate in response to stress (the hypermutable state model, HSM). This mechanism is proposed to allow faster genetic adaptation to stressful conditions and to explain why mutations appear directed to useful sites. Analysis of the HSM reveals that it requires implausibly intense mutagenesis (10(5) times the unselected rate) and even then cannot account for the behavior of the Cairns system. The assumptions of the HSM predict that selected revertants will carry an average of eight deleterious null mutations and thus seem unlikely to be successful in long-term evolution. The experimentally observed 35-fold increase in the level of general mutagenesis cannot account for even one Lac(+) revertant from a mutagenized subpopulation of 10(5) cells (the number proposed to enter the hypermutable state). We conclude that temporary general mutagenesis during stress is unlikely to provide a long-term selective advantage in this or any similar genetic system.


Chemical technology principles for selective bioconjugation of proteins and antibodies.
Proteins are multifunctional large organic compounds that constitute an essential component of a living system. Hence, control over their bioconjugation impacts science at the chemistry-biology-medicine interface. A chemical toolbox for their precision engineering can boost healthcare and open a gateway for directed or precision therapeutics. Such a chemical toolbox remained elusive for a long time due to the complexity presented by the large pool of functional groups. The precise single-site modification of a protein requires a method to address a combination of selectivity attributes. This review focuses on guiding principles that can segregate them to simplify the task for a chemical method. Such a disintegration systematically employs a multi-step chemical transformation to deconvolute the selectivity challenges. It constitutes a disintegrate (DIN) theory that offers additional control parameters for tuning precision in protein bioconjugation. This review outlines the selectivity hurdles faced by chemical methods. It elaborates on the developments in the perspective of DIN theory to demonstrate simultaneous regulation of reactivity, chemoselectivity, site-selectivity, modularity, residue specificity, and protein specificity. It discusses the progress of such methods to construct protein and antibody conjugates for biologics, including antibody-fluorophore and antibody-drug conjugates (AFCs and ADCs). It also briefs how this knowledge can assist in developing small molecule-based covalent inhibitors. In the process, it highlights an opportunity for hypothesis-driven routes to accelerate discoveries of selective methods and establish new targetome in the precision engineering of proteins and antibodies.


Large granules in the peripheral blood smear and bone marrow aspirate of a 3-year-old male with lymphadenopathy and fever.
A 3-year-old male with oculocutaneous albinism presented with lymphadenopathy and fever. Serological testing revealed Epstein-Barr virus (EBV)-specific immunoglobulin M (IgM) and a diagnosis of infectious mononucleosis was made. A complete blood count and peripheral blood smear demonstrated mild anemia, thrombocytopenia, and neutropenia with leukocytes that contained large azurophilic and eosinophilic granules. Bone marrow examination demonstrated increased hemophagocytic histiocytes along with granulocytes that contained large eosinophilic granules. In addition to hemophagocytic lymphohistiocytosis, presumably due to acute EBV infection, the patient was diagnosed with Chediak-Higashi syndrome based on the pathognomonic granules within peripheral leukocytes and precursors. The differential diagnosis of a young patient with oculocutaneous albinism presenting with an acute viral infection includes a relatively narrow range of genetic syndromes based solely on the history of albinism. This case demonstrates the application of clinical laboratory data to presumptively diagnose Chediak-Higashi syndrome in the midst of a presentation of hemophagocytic lymphohistiocytosis secondary to acute EBV infection.


Validation of fast MR thermometry at 1.5 T with gradient-echo echo planar imaging sequences: phantom and clinical feasibility studies.
The purpose of this work was to validate in phantom studies and demonstrate the clinical feasibility of MR proton resonance frequency thermometry at 1.5 T with segmented gradient-echo echo planar imaging (GRE-EPI) sequences during liver tumour radiofrequency (RF) ablation. Classical GRE acquisitions and segmented GRE-EPI acquisitions were performed at 1.5 T during simultaneous RF heating with an MR-compatible RF electrode placed in an agar gel phantom. Temperature increments were calculated and compared with four optical temperature probe measurements using Bland- Altman analysis. In a preliminary clinical feasibility study, the rapid GRE-EPI sequence (echo train length = 13) was used for MR temperature monitoring of RF ablation of liver tumours in three patient procedures. For phantom experiments, the Bland-Altman mean of differences between MR and optical probe temperature measurements was <0.4 degrees C, and the 95% limits of agreement value was <1.4 degrees C. For the in vivo studies, respiratory-triggered GRE-EPI acquisitions yielded a temperature accuracy of 1.3 +/- 0.4 degrees C (acquisition time = 0.6 s/image, spatial coverage of three slices/respiratory cycle). MR proton resonance frequency thermometry at 1.5 T yields precise and accurate measurements of temperature increment with both classical GRE and rapid GRE-EPI sequences. Rapid GRE-EPI sequences minimize intra-scan motion effects and can be used for MR thermometry during RF ablation in moving organs.


Effects of vitamin E supplementation on recovery from repeated bouts of resistance exercise.
The purpose of this study was to examine the effects of vitamin E (VE) supplementation (1200 IU/day) on recovery responses to repeated bouts of resistance exercise. Non-resistance trained men were assigned to supplement with VE (n = 9) or placebo (PL; n = 9) for 3 weeks and then perform 3 resistance exercise sessions separated by 3 days of recovery (EX-1, EX-2, and EX-3). Performance was assessed at EX-1, EX-2, and EX-3. Fasting morning blood samples and perceived muscle soreness were obtained before EX-1 and for 10 consecutive days. Muscle soreness peaked after EX-1 and gradually returned to baseline values by day 6. Lower and upper body maximal strength and explosive power were significantly (p < or = 0.05) decreased at EX-2 and EX-3 (approximately 10%). Plasma malondialdehyde (MDA) was significantly elevated on days 7 and 8. There were no significant differences between VE and PL in muscle soreness, performance measures, or plasma MDA. Creatine kinase (CK) area under the curve from day 1 to day 10 was significantly greater for VE because of a nearly 2-fold greater increase in CK after EX-1 in VE, compared with PL (404 +/- 146 and 214 +/- 179 U/L, respectively). VE supplementation was not effective at attenuating putative markers of membrane damage, oxidative stress, and performance decrements after repeated bouts of whole-body concentric/eccentric resistance exercise.


Moving beyond genetics: is FAM13A a major biological contributor in lung physiology and chronic lung diseases?
Variants in FAM13A have been found in genome-wide association studies (GWAS) to associate with lung function in the general population as well as in several common chronic lung diseases (CLD) such as chronic obstructive pulmonary disease (COPD), asthma, as well as in idiopathic interstitial pneumonias (IIP). The gene was cloned in 2004, yet the encoded protein has not been characterised and its function is unknown. The redundancy of its genetic contribution in CLD suggests a major function of this gene both in lung physiology and CLD. This review provides a brief summary of the current knowledge of FAM13A, and demonstrates the necessity to resolve its biological function besides its well accepted genetic contribution. Further interpretations of FAM13A variants may help in the understanding of CLD mechanisms and reveal opportunity for intervention.


Fos Expression in the Olfactory Pathway of High- and Low-Sexually Performing Rams Exposed to Urine from Estrous or Ovariectomized Ewes.
Exposure to estrous ewe urine stimulates investigation and mounting activity in sexually active but not sexually inactive rams. It was hypothesized sexual indifference may result from an inability to detect olfactory cues or an interruption of the pathway from detection of the olfactory stimulus to the motor response. Sexually active (n=4) and inactive (n=3) rams were exposed to urine from estrous ewes. An additional group of sexually active rams (n=3) were exposed to urine from ovariectomized ewes. Rams were exsanguinated following 1 h of exposure to stimulus. Neural activity was determined in tissues of interest by the presence of fos and fos-related proteins detected by immunohistochemistry procedures. Sexually active rams exposed to urine from ovariectomized ewes had more (P ≤ 0.05) fos-positive cells in the olfactory bulb, but fewer (P = 0.03) fos-positive cells in the cortical amygdala compared to sexually active rams exposed to urine from estrous ewes. Sexually inactive rams had similar (P ≥ 0.13) numbers of fos positive neurons in the olfactory bulb and medial amygdala but fewer (P ≤ 0.04) in the central amygdala, bed nucleus of the stria terminalis and the medial preoptic area compared to sexually active rams exposed to urine from estrous ewes. Sexual inactivity was not associated with decreased hypothalamic function since fos activity was similar (P ≥ 0.14) among groups in the suprachiasmatic and ventral medial nucleus. Sexual inactivity is not likely due to an impaired ability to detect or process olfactory stimuli by the main olfactory bulb and medial-cortical amygdala. Sexually inactive rams may have reduced attentiveness to sexual stimuli and/or decreased responsiveness of regions in the brain which regulate reproductive behaviors.


Robo1: a potential role in ocular angiogenesis.
Robo1, a member of the roundabout (Robo) family, serves as neuronal guidance receptors and has been reported to mediate tumor angiogenesis. In this study, we investigated the function of Robo1 and its possible role in retinal angiogenesis in vitro and in vivo. Expression of Robo1 in relation to retinal neovascularization was studied in an animal model of retinopathy of prematurity (ROP). siRNA technology was used to knockdown Robo1 expression to study its effects on monkey choroidal retinal endothelial cells (RF/6A) in vitro. Cell proliferation, migration, spreading, cycling, and apoptosis were assessed with the methyl thiazolyl tetrazolium (MTT), Boyden chamber, immunohistochemistry, and flow cytometry assay. Tube formation by RF/6A on Matrigel was also analyzed. Robo1 expression was elevated in the ROP murine eyes (P < 0.01). Knockdown of Robo1 expression inhibited cell proliferation and migration. Tube formation by RF/6A was also disturbed. Our results show that Robo1 inhibits choroidal and retinal angiogenesis in vitro. Further studies are ongoing to evaluate Robo1 as a potential target for the treatment of choroidal or retinal angiogenesis.


Effects of Freeze-Thaw Cycle with and without Proteolysis Inhibitors and Cryopreservant on the Biochemical and Biomechanical Properties of Articular Cartilage.
We investigated the effects of freeze-thawing on the properties of articular cartilage. The reproducibility of repeated biomechanical assay of the same osteochondral sample was first verified with 11 patellar plugs from 3 animals. Then, 4 osteochondral samples from 15 bovine patellae were divided into 4 groups. The reference samples were immersed in phosphate-buffered saline (PBS) containing proteolysis inhibitors and biomechanically tested before storage for further analyses. Samples of group 1 were biomechanically tested before and after freeze-thawing in PBS in the absence and those of group 2 in the presence of inhibitors. Samples of the group 3 were biomechanically tested in PBS-containing inhibitors, but frozen in 30% dimethyl sulfoxide/PBS and subsequently tested in PBS supplemented with the inhibitors. Glycosaminoglycan contents of the samples and immersion solutions were analyzed, and proteoglycan structures examined with SDS-agarose gel electrophoresis. Freeze-thawing decreased slightly dynamic moduli in all 3 groups. The glycosaminoglycan contents and proteoglycan structures of the cartilage were similar in all experimental groups. Occasionally, the diffused proteoglycans were partly degraded in group 1. Digital densitometry revealed similar staining intensities for the glycosaminoglycans in all groups. Use of cryopreservant had no marked effect on the glycosaminoglycan loss during freeze-thawing. The freeze-thawed cartilage samples appear suitable for the biochemical and biomechanical studies.


The level of MHC class I expression on murine adenocarcinoma can change the antitumor effector mechanism of immunocytokine therapy.
The huKS1/4-IL2 fusion protein, directed against the human epithelial cell adhesion molecule (huEpCAM) has been shown to induce a strong CD8+ T-cell-dependent, natural killer (NK) cell-independent, antitumor response in mice bearing the huEp-CAM-transfected CT26 colon cancer CT26-EpCAM. Here we investigate the effectiveness of huKS1/4-IL2 against CT26-Ep21.6, a subclone of CT26-EpCAM, expressing low levels of MHC class I. In vitro antibody-dependent cellular cytotoxicity (ADCC) assays in the presence of huKS1/4-IL2 demonstrate that murine NK cells from spleen and blood can kill CT26-Ep21.6 significantly better than they kill CT26-EpCAM. NK-mediated ADCC of CT26-EpCAM can be enhanced by blocking the murine NK cell-inhibitory receptor, Ly-49C. A potent in vivo antitumor effect was observed when BALB/c mice bearing experimental metastases of CT26-Ep21.6 were treated with huKS1/4-IL2. The depletion of NK cells during huKS1/4-IL2 treatment significantly reduced the antitumor effect against CT26-Ep21.6. Together our in vitro and in vivo data in the huEp-CAM-transfected CT26 models indicate that the amount of MHC class I expressed on the tumor target cell plays a critical role in the in vivo antitumor mechanism of huKS1/4-IL2 immunotherapy. A low MHC class I level favors NK cells as effectors, whereas a high level of MHC class I favors T cells as effectors. Given the heterogeneity of MHC class I expression seen in human tumors and the prevailing T-cell suppression in many cancer patients, the observation that huKS1/4-IL2 has the potential to effectively activate an NK cell-based antitumor response may be of potential clinical relevance.


A case of Poland Syndrome associated with dextroposition.
Classical Poland Syndrome (PS) is characterized by unilateral, partial or complete absence of the sternocostal head of the major pectoral muscle and brachysyndactyly of fingers on the same side. We report the case of a newborn infant with dextrocardia and PS located on the left side. This association is very rare: to date only 19 cases have been described in scientific literature. In all reported cases, as in the present, the Poland defect involved the left side and was associated to rib defects, whereas most cases of PS are on the right side and few have rib defects. This case supports the view that dextrocardia follows the loss of volume of the left hemithorax caused by Poland sequence and that the combination of PS and dextrocardia is not coincidental.


Purinergic mechanosensory transduction and visceral pain.
In this review, evidence is presented to support the hypothesis that mechanosensory transduction occurs in tubes and sacs and can initiate visceral pain. Experimental evidence for this mechanism in urinary bladder, ureter, gut, lung, uterus, tooth-pulp and tongue is reviewed. Potential therapeutic strategies are considered for the treatment of visceral pain in such conditions as renal colic, interstitial cystitis and inflammatory bowel disease by agents that interfere with mechanosensory transduction in the organs considered, including P2X3 and P2X2/3 receptor antagonists that are orally bioavailable and stable in vivo and agents that inhibit or enhance ATP release and breakdown.


Identifying Optimal Acute Care Comparators to Inform the Evaluation of an Advanced Care at Home Pilot Program.
Background Hospital at Home (H@H) programs-which seek to deliver acute care within a patient's home-have become more prevalent over time. However, existing literature exhibits heterogeneity in program structure, evaluation design, and target population size, making it difficult to draw generalizable conclusions to inform future H@H program design. Objective The objective of this work was to develop a quality improvement evaluation strategy for a H@H program-the Kaiser Permanente Advanced Care at Home (KPACAH) program in Northern California-leveraging electronic health record data, chart review, and patient surveys to compare KPACAH patients with inpatients in traditional hospital settings. Methods The authors developed a 3-step recruitment workflow that used electronic health record filtering tools to generate a daily list of potential comparators, a manual chart review of potentially eligible comparator patients to assess individual clinical and social criteria, and a phone interview with patients to affirm eligibility and interest from potential comparator patients. Results This workflow successfully identified and enrolled a population of 446 comparator patients in a 5-month period who exhibited similar demographics, reasons for hospitalization, comorbidity burden, and utilization measures to patients enrolled in the KPACAH program. Conclusion These initial findings provide promise for a workflow that can facilitate the identification of similar inpatients hospitalized at traditional brick and mortar facilities to enhance outcomes evaluations for the H@H programs, as well as to identify the potential volume of enrollees as the program expands.


The immune microenvironment of HPV-negative oral squamous cell carcinoma from never-smokers and never-drinkers patients suggests higher clinical benefit of IDO1 and PD1/PD-L1 blockade.
Never-smokers and never-drinkers patients (NSND) suffering from oral squamous cell carcinoma (OSCC) are epidemiologically different from smokers drinkers (SD). We therefore hypothesized that they harbored distinct targetable molecular alterations. Data from The Cancer Genome Atlas (TCGA) (discovery set), Gene Expression Omnibus and Centre Léon Bérard (CLB) (three validation sets) with available gene expression profiles of HPV-negative OSCC from NSND and SD were mined. Protein expression profiles and genomic alterations were also analyzed from TCGA, and a functional pathway enrichment analysis was carried out. Formalin-fixed paraffin-embedded samples from 44 OSCC including 20 NSND and 24 SD treated at CLB were retrospectively collected to perform targeted-sequencing of 2559 transcripts (HTG EdgeSeq system), and CD3, CD4, CD8, IDO1, and PD-L1 expression analyses by immunohistochemistry (IHC). Enrichment of a six-gene interferon-γ signature of clinical response to pembrozulimab (PD-1 inhibitor) was evaluated in each sample from all cohorts, using the single sample gene set enrichment analysis method. A total of 854 genes and 29 proteins were found to be differentially expressed between NSND and SD in TCGA. Functional pathway analysis highlighted an overall enrichment for immune-related pathways in OSCC from NSND, especially involving T-cell activation. Interferon-γ response and PD1 signaling were strongly enriched in NSND. IDO1 and PD-L1 were overexpressed and the score of response to pembrolizumab was higher in NSND than in SD, although the mutational load was lower in NSND. IHC analyses in the CLB cohort evidenced IDO1 and PD-L1 overexpression in tumor cells that was associated with a higher rate of tumor-infiltrating T-cells in NSND compared with SD. The main biological and actionable difference between OSCC from NSND and SD lies in the immune microenvironment, suggesting a higher clinical benefit of PD-L1 and IDO1 inhibition in OSCC from NSND.


Production of matrix metalloproteinase 3 (stromelysin) by cultured ovine endometrial cells.
Ovine endometrial cells (stromal plus epithelial) in primary culture release matrix metalloproteinase 3 (stromelysin, MMP-3), the enzyme that degrades various extracellular components including the basement membrane components collagen IV and laminin. The enzyme was detected in tissue culture medium by specific enzyme assay. A low level of MMP-3 activity was released from the cells (0.12 +/- 0.02 unit per 10(6) cells per 48 h; 1 unit degrades 1 microgram of reduced, carboxymethylated transferrin min-1 at 37 degrees C), but following stimulation by phorbol myristate acetate (PMA) a mean 4.4-fold increase in MMP-3 production was observed (to 0.53 +/- 0.13 unit per 10(6) cells per 48 h). The enzyme was released primarily in the form of its proenzyme, which could be activated in vitro by (4-aminophenyl)mercuric acetate (APMA). Stimulation of enzyme release from cells by PMA was not seen before 24 h and required PMA at a dose of 10 nM or higher. This finding was substantiated by Western blot analysis. Immunocytochemistry of cells that had been treated with PMA for 48 h, and with the ionophore, monensin, for 4 h, confirmed the potential of the endometrial cells to produce stromelysin. The release of MMP-3 from ovine endometrial cells suggests that this enzyme may have a role in assisting the passage of syncytial processes through the basement membrane during the process of implantation.


Evaluating the ability of a predictive vision-based machine learning model to measure changes in gait in response to medication and DBS within individuals with Parkinson's disease.
Gait impairments in Parkinson's disease (PD) are treated with dopaminergic medication or deep-brain stimulation (DBS), although the magnitude of the response is variable between individuals. Computer vision-based approaches have previously been evaluated for measuring the severity of parkinsonian gait in videos, but have not been evaluated for their ability to identify changes within individuals in response to treatment. This pilot study examines whether a vision-based model, trained on videos of parkinsonism, is able to detect improvement in parkinsonian gait in people with PD in response to medication and DBS use. A spatial-temporal graph convolutional model was trained to predict MDS-UPDRS-gait scores in 362 videos from 14 older adults with drug-induced parkinsonism. This model was then used to predict MDS-UPDRS-gait scores on a different dataset of 42 paired videos from 13 individuals with PD, recorded while ON and OFF medication and DBS treatment during the same clinical visit. Statistical methods were used to assess whether the model was responsive to changes in gait in the ON and OFF states. The MDS-UPDRS-gait scores predicted by the model were lower on average (representing improved gait; p = 0.017, Cohen's d = 0.495) during the ON medication and DBS treatment conditions. The magnitude of the differences between ON and OFF state was significantly correlated between model predictions and clinician annotations (p = 0.004). The predicted scores were significantly correlated with the clinician scores (Kendall's tau-b = 0.301, p = 0.010), but were distributed in a smaller range as compared to the clinician scores. A vision-based model trained on parkinsonian gait did not accurately predict MDS-UPDRS-gait scores in a different PD cohort, but detected weak, but statistically significant proportional changes in response to medication and DBS use. Large, clinically validated datasets of videos captured in many different settings and treatment conditions are required to develop accurate vision-based models of parkinsonian gait.


Fertility preservation in young female lymphoma patients: review of available options and initial experiences with their implementation in clinical routine.
High cure rates in women suffering from Hodgkin's disease or aggressive non-Hodgkin's lymphoma are often achieved at the cost of impaired ovarian function or infertility. Different strategies can be offered to protect fertility. Early experiences with the implementation of a specialised fertility preservation clinic are analysed with the aim to assess the need for and acceptance of the clinic, as well as the delay of treatment caused by the different approaches. Available options are reviewed. Data on underlying malignancy and fertility preservation measures in women of childbearing age treated for aggressive lymphoma and Hodgkin's disease with curative intent between November 2006 and January 2010 were retrospectively analysed. Among 111 female lymphoma patients, 30 were eligible for counselling. Nineteen accepted the offer. The main reason for declining was completed family planning. Eight further patients were referred from elsewhere. Of the counselled patients, 96% decided to pursue at least 1 protective strategy, 39% chose an invasive procedure (cryopreservation of ovarian tissue or oocyte aspiration following hormonal stimulation). These procedures deferred the start of systemic treatment within the expected range, no undue delays were observed. Female lymphoma patients have a large demand for counselling about measures to protect fertility. In a proper setting, counselling and intervention can be offered without undue delays menacing the chance for cure.


Assessment of Heart Rate Variability Thresholds from Incremental Treadmill Tests in Five Cross-Country Skiing Techniques.
The assessment of heart rate variability (HRV) thresholds (HRVTs) as an alternative of Ventilatory thresholds (VTs) is a relatively new approach with increasing popularity which has not been conducted in cross-country (XC) skiing yet. The main purpose of the present study was to assess HRVTs in the five main XC skiing-related techniques, double poling (DP), diagonal striding (DS), Nordic walking (NW), V1 skating (V1), and V2 skating (V2).Ten competitive skiers completed these incremental treadmill tests until exhaustion with a minimum of one to two recovery days in between each test. Ventilatory gases, HRV and poling frequencies were measured. The first HRV threshold (HRVT1) was assessed using two time-domain analysis methods, and the second HRV threshold (HRVT2) was assessed using two non-time varying frequency-domain analysis methods. HRVT1 was assessed by plotting the mean successive difference (MSD) and standard deviation (SD) of normalized R-R intervals to workload. HRVT1 was assessed by plotting high frequency power (HFP) and the HFP relative to respiratory sinus arrhythmia (HFPRSA) with workload. HRVTs were named after their methods (HRVT1-SD; HRVT1-MSD; HRVT2-HFP; HRVT2-HFP-RSA). The results showed that the only cases where the proposed HRVTs were good assessors of VTs were the HRVT1-SD of the DS test, the HRVT1-MSD of the DS and V2 tests, and the HRVT2-HFP-RSA of the NW test. The lack of a wider success of the assessment of HRVTs was reasoned to be mostly due to the high entrainment between the breathing and poling frequencies. As secondary finding, a novel Cardiolocomotor coupling mode was observed in the NW test. This new Cardiolocoomtor coupling mode corresponded to the whole bilateral poling cycle instead of corresponding to each poling action as it was reported to the date by the existing literature.


A New Fixation Technique for French-Door Cervical Laminoplasty: Surgical Results With a Minimum Follow-up of 6 Years.
A case series of 5 patients with multilevel cervical myelopathy treated by French-door cervical laminoplasty (FDCL) and use of unicortical iliac crest graft as spacer fixed with titanium miniplates and screws is described. To report a minimum of 6-year follow-up results of our new plate-screw fixation technique for FDCL. Hardware-assisted laminoplasty has the potential advantage of preventing restenosis by holding the laminar door "open" while healing progresses and also prevents spacer dislodgement. The use of titanium miniplates as internal fixation device for FDCL by our novel technique has not been reported. Five patients suffering from multilevel cervical myelopathy harboring constitutionally narrow cervical canal (3) and multilevel cervical spondylotic myelopathy (2) who underwent 2-3 level FDCL and followed up prospectively for 6 years is presented. Modified Kurokawa and colleague's technique of FDCL was performed and autologous iliac crest bone graft was interposed between the sagittaly split spinous processes. A 12- to 15-hole titanium miniplate was contoured into a trapezoidal shape to sit flush with the posterior elements. The plate was anchored to bone graft and posterior elements with screws and patients mobilized without any external orthosis. The mean follow-up was 90.5 months. The mean improvement in Neck disability index at final follow-up was 35% and mean improvement in Visual analog scale was 4 points. Japanese orthopaedic association score improved from a mean of 10 to a mean of 14.8 postoperatively. The final outcome was good (3) and excellent (2) by Odom's criteria. All patients improved to Nurick's grade 0 or I and reported significant relief from their myelopathic symptoms and axial neck pain. There were no postoperative hardware-related complications or pseudoarthrosis. Titanium miniplates are excellent devices for stabilizing the interspinous spacers used in FDCL. They prevent cervical canal deformation, restenosis, spacer dislodgement and are durable, cost-effective in facilitating early mobilization at intermediate-term follow-up of 6 years.


The prevalence and impact of arthritis in older persons.
To review that what is known about the prevalence and impact of arthritis on disability and health care expenditures incurred by older persons. The current prevalence estimates of osteoarthritis and osteoporosis in the US are examined, and what is known about the relationship of arthritis, broadly defined to disability, and the impact of arthritis-specific disability on home care and nursing home use by older persons are reviewed. Arthritis is a major contributor to disability among older people and is especially disabling for older women, who have higher prevalence rates and greater disability than their male counterparts. Studies of the relationship of arthritis to long-term care use indicate that arthritis can be a risk factor insofar as it can cause disability that results in homeboundedness, which, in turn is a risk factor for nursing home use. It is possible that previous analyses that included arthritis and disability as competing risk factors for nursing home use underestimate the contribution of arthritis because arthritis is a risk factor for disability; thus, the two variables may be strongly correlated. More study is needed to understand the contribution of sex to prevalence of arthritis and severity of arthritis-specific disability. The route through which arthritis affects long-term care use also needs careful longitudinal study. If arthritis is confirmed to be a major risk factor for disability that leads to long-term care use, the development and testing of interventions to prevent/minimize arthritis-specific disability should be a major research priority.


Experimental evolution reveals sex-specific dominance for surviving bacterial infection in laboratory populations of Drosophila melanogaster.
Males and females are subjected to distinct kinds of selection pressures, often leading to the evolution of sex-specific genetic architecture, an example being sex-specific dominance. Sex-specific dominance reversals (SSDRs), where alleles at sexually antagonistic loci are at least partially dominant in the sex they benefit, have been documented in Atlantic salmon, rainbow trout, and seed beetles. Another interesting feature of many sexually reproducing organisms is the asymmetric inheritance pattern of X chromosomes, which often leads to distinct evolutionary outcomes on X chromosomes compared to autosomes. Examples include the higher efficacy of sexually concordant selection on X chromosomes, and X chromosomes being more conducive to the maintenance of sexually antagonistic polymorphisms under certain conditions. Immunocompetence is a trait that has been extensively investigated for sexual dimorphism with growing evidence for sex-specific or sexually antagonistic variation. X chromosomes have been shown to harbor substantial immunity-related genetic variation in the fruit fly, Drosophila melanogaster. Here, using interpopulation crosses and cytogenetic cloning, we investigated sex-specific dominance and the role of the X chromosome in improved postinfection survivorship of laboratory populations of D. melanogaster selected against pathogenic challenge by Pseudomonas entomophila. We could not detect any contribution of the X chromosome to the evolved immunocompetence of our selected populations, as well as to within-population variation in immunocompetence. However, we found strong evidence of sex-specific dominance related to surviving bacterial infection. Our results indicate that alleles that confer a survival advantage to the selected populations are, on average, partially dominant in females but partially recessive in males. This could also imply an SSDR for overall fitness, given the putative evidence for sexually antagonistic selection affecting immunocompetence in Drosophila melanogaster. We also highlight sex-specific dominance as a potential mechanism of sex differences in immunocompetence, with population-level sex differences primarily driven by sex differences in heterozygotes.


Duration of over- and under-treatment of hypothyroidism is associated with increased cardiovascular risk.
Objective To investigate the association between hypothyroidism and cardiovascular disease (CVD) in both treated and untreated hypothyroid patients, and the consequences of over- and under-treatment with respect to cardiovascular risk. Design A registry-based case-control study nested within a population-based cohort of 275 467 individuals with at least one serum thyroid stimulating hormone (TSH) measurement in the period of 1995-2011. Methods Incident cases of CVD were matched with controls according to gender, age and year of birth. Conditional logistic regression analyses were performed to calculate CVD risks associated with exposure to hypothyroidism, with adjustment for 19 pre-existing comorbidities, including cardiovascular disease and diabetes, using the Charlson Comorbidity Index. Results Overall, 20 487 individuals experienced CVD (9.4%, incidence rate 13.1 per 1000 person-years, 95% confidence interval (CI), 13.0-13.3). Risk of CVD was increased in untreated hypothyroidism compared to euthyroidism (odds ratio (OR): 1.83 (95% CI: 1.43-2.35; P < 0.001)). Cardiovascular risk was increased in both treated and untreated hypothyroid individuals per half year of elevated TSH (OR: 1.11 (95% CI: 1.06-1.16; P < 0.001) and OR: 1.15 (95% CI: 1.09-1.23; P = 0.001), respectively). In patients treated with levothyroxine, OR for CVD was 1.12 (95% CI: 1.06-1.18; P < 0.001) for each 6 months of decreased TSH. Conclusion Cardiovascular risk is increased in untreated, but not in treated hypothyroid patients. Among those with treated hypothyroidism, duration of decreased TSH (overtreatment) had a similar impact on cardiovascular risk as duration of elevated TSH (under-treatment), highlighting the importance of initiating treatment and maintaining biochemical euthyroidism in hypothyroid patients in order to reduce the risk of CVD and death.


In vitro and in vivo anti-platelet effects of enzymatic hydrolysates of collagen and collagen-related peptides.
Collagen-related peptides, Gly-Pro-Arg and its analogues, were examined for their inhibitory effects on platelet aggregation induced by the addition of ADP. Human platelet aggregation was suppressed by more than 50% with each of Gly-Pro-Arg and such Gly-Pro-Arg-containing peptides as Gly-Pro-Arg-Gly, Gly-Pro-Arg-Gly-Pro, Gly-Pro-Arg-Pro-Pro, and Gly-Pro-Arg-Pro-Pro-Pro at a concentration of 0.3 mM. The inhibitory effects of these peptides were about 10 times higher in human PRP than in rat PRP. Other Gly-Pro-Arg analogues such as Sar-Pro-Arg, Gly-Pro-Lys, Gly-Ala-Arg, and Ala-Gly-Pro-Arg had no inhibitory effect at a concentration from 0.1 to 0.8 mM even in human PRP. Intravenous and oral administrations of Gly-Pro-Arg and enzymatic hydrolysates of collagen suppressed the decrease in platelet count for endotoxin-induced DIC in rats. Collagen itself has been regarded as a potent inducer of platelet aggregation, but these findings suggest that collagen-related peptides and enzymatic hydrolysates of collagen prevent platelet aggregation.


Septic arthritis of the shoulder in a dental patient.
Septic arthritis of the glenohumoral joint is rare following dental procedures, comprising approximately 3% of all joint infections. Septic arthritis following bacteremia from dental procedures is uncommon and generally occurs in prosthetic joints. Predisposing causes may include immunocompromising diseases such as diabetes, HIV infection, renal failure and intravenous drug abuse. We report a rare case of unilateral glenohumoral joint septic arthritis in a 60-year-old male patient (without a prosthetic joint) secondary to a dental procedure. The insidious nature of the presentation is highlighted. Septic arthritis infections, though rare, require a high level of clinical suspicion. Vague symptoms of shoulder pain may mask the initial diagnosis, as was the case in our patient. Incision and drainage via surgical intervention are often required, followed by parenteral antibiotics.


Single-atom doping of MoS2 with manganese enables ultrasensitive detection of dopamine: Experimental and computational approach.
Two-dimensional transition metal dichalcogenides (TMDs) emerged as a promising platform to construct sensitive biosensors. We report an ultrasensitive electrochemical dopamine sensor based on manganese-doped MoS2 synthesized via a scalable two-step approach (with Mn ~2.15 atomic %). Selective dopamine detection is achieved with a detection limit of 50 pM in buffer solution, 5 nM in 10% serum, and 50 nM in artificial sweat. Density functional theory calculations and scanning transmission electron microscopy show that two types of Mn defects are dominant: Mn on top of a Mo atom (MntopMo) and Mn substituting a Mo atom (MnMo). At low dopamine concentrations, physisorption on MnMo dominates. At higher concentrations, dopamine chemisorbs on MntopMo, which is consistent with calculations of the dopamine binding energy (2.91 eV for MntopMo versus 0.65 eV for MnMo). Our results demonstrate that metal-doped layered materials, such as TMDs, constitute an emergent platform to construct ultrasensitive and tunable biosensors.


"Ex vivo" release of eicosanoid from human brain tissue: its relevance in the development of brain edema.
The specific mechanism underlying the genesis of vasogenic brain edema is still debated: the role of arachidonic acid is considered extremely important, as it is a possible activator of self-maintaining reactions enhancing the release of vasoactive and cytotoxic compounds. The relationship between arachidonic acid metabolism and brain edema has been studied primarily in brain tissue samples or in the extracellular fluid, whereas the residual capacity of perilesional tissue to synthesize and release eicosanoids has not been investigated. In the present study, perilesional samples of brain tissue were available from 4 patients operated on for brain metastasis, from 8 patients who had malignant neuroepithelial tumors, from 4 with meningiomas, and from 5 with subarachnoid hemorrhage. A brain edema index was calculated from the preoperative computed tomographic scan. The "ex vivo" method allowed determination of the residual capacity of endogenous arachidonic acid metabolism. The edema index is significantly higher in patients with brain metastasis (6.5 +/- 0.8) and neuroepithelial tumors (3.6 +/- 0.2) than in those with meningiomas (1.5 +/- 0.06), subarachnoid hemorrhage (1.7 +/- 0.18), and in controls. In patients with metastatic and neuroepithelial tumors there is a significant correlation between peritumoral brain edema and the capacity to synthesize leukotriene C4 (P less than 0.05); the capacity to synthesize leukotriene C4 is also significantly elevated after subarachnoid hemorrhage (13.91 +/- 2.6 ng/ml of incubation medium) when compared with control cases (5.56 +/- 0.91). The capacity to synthesize prostacyclin is significantly higher in patients with brain metastasis than in those with neuroepithelial tumors and meningiomas (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Hordein Accumulation in Developing Barley Grains.
The temporal pattern of accumulation of hordein storage proteins in developing barley grains was studied by enzyme-linked immunosorbent assay (ELISA), western blot and liquid chromatography tandem mass spectrometry (LC-MS/MS). Hordein accumulation was compared to the pattern seen for two abundant control proteins, serpin Z4 (an early accumulator) and lipid transferase protein (LTP1, a late accumulator). Hordeins were detected from 6 days post-anthesis (DPA) and peaked at 30 DPA. Changes in fresh weight indicate that desiccation begins at 20 DPA and by 37 DPA fresh weight had decreased by 35%. ELISA analysis of hordein content, expressed on a protein basis, increased to a maximum at 30 DPA followed by a 17% decrease by 37 DPA. The accumulation of 39 tryptic and 29 chymotryptic hordein peptides representing all classes of hordein was studied by LC-MS/MS. Most peptides increased to a maximum at 30 DPA, and either remained at the maximum or did not decrease significantly. Only five tryptic peptides, members of the related B1- and γ1-hordeins decreased significantly by 21-51% at 37 DPA. Thus, the concentration of some specific peptides was reduced while remaining members of the same family were not affected. The N-terminal signal region was removed by proteolysis during co-translation. In addition to a suite of previously characterized hordeins, two novel barley B-hordein isoforms mapping to wheat low molecular weight glutenins (LMW-GS-like B-hordeins), and two avenin-like proteins (ALPs) sharing homology with wheat ALPs, were identified. These identified isoforms have not previously been mapped in the barley genome. Cereal storage proteins provide significant nutritional content for human consumption and seed germination. In barley, the bulk of the storage proteins comprise the hordein family and the final hordein concentration affects the quality of baked and brewed products. It is therefore important to study the accumulation of hordeins as this knowledge may assist plant breeding for improved health outcomes (by minimizing triggering of detrimental immune responses), nutrition and food processing properties.


Brains, innovations, tools and cultural transmission in birds, non-human primates, and fossil hominins.
Recent work on birds and non-human primates has shown that taxonomic differences in field measures of innovation, tool use and social learning are associated with size of the mammalian cortex and avian mesopallium and nidopallium, as well as ecological traits like colonization success. Here, I review this literature and suggest that many of its findings are relevant to hominin intelligence. In particular, our large brains and increased intelligence may be partly independent of our ape phylogeny and the result of convergent processes similar to those that have molded avian and platyrrhine intelligence. Tool use, innovativeness and cultural transmission might be linked over our past and in our brains as operations of domain-general intelligence. Finally, colonization of new areas may have accompanied increases in both brain size and innovativeness in hominins as they have in other mammals and in birds, potentially accelerating hominin evolution via behavioral drive.


Neoplastic angioendotheliosis. Immunohistochemical and electron microscopic findings in three cases.
Three cases of neoplastic angioendotheliosis (NAE) presenting with central nervous system (CNS) disease but no skin lesions are described. The histogenesis of the neoplastic cells is discussed. Microscopic examination showed accumulation of neoplastic cells in the vascular system throughout the body and their extravascular proliferation in several organs. Electron microscopic and immunohistochemical studies revealed the presence of Weibel-Palade bodies and factor VIII-related antigen in intravascular and extravascular neoplastic cells in two of the three cases. In the first case the neoplastic cells did not have any T-cell markers. However, in one case no specific markers were found in the neoplastic cells by electron microscopic, enzyme histochemical, or immunohistochemical examination. These findings, although supporting the endothelial origin of the neoplastic cells, indicate the need for further consideration of whether NAE is actually a single disease entity or several different diseases.


Continuous-wave operation of monolithically grown 1.5-microm optically pumped vertical-external-cavity surface-emitting lasers.
Continuous-wave operation, to as high as 7 degrees C, of 1.5-microm optically pumped vertical-external-cavity surface-emitting lasers is reported. The epitaxial structure, monolithically grown on InP by metal-organic chemical vapor deposition, consists of an InAlAs/GaInAlAs Bragg reflector, an InGaAs/InGaAsP active region, and an InP capping layer. The threshold incident pump intensity is <9 kW/cm2.


IGFBP7 functions as a potential lymphangiogenesis inducer in non-small cell lung carcinoma.
Lymphangiogenesis is not only involved in the processes of embryonic development, tissue repair and chronic inflammation, but also in tumor lymphatic metastasis. Metastatic tumor cells spreading through lymphatic vessels occur in non-small cell lung carcinoma (NSCLC), with regional lymph node metastasis often being the most important prognostic factor for carcinoma patients. Recent research has identified a range of lymphangiogenic growth factors that could conceivably play a great role in promoting tumor lymphangiogenesis and lymphatic metastasis. The most extensively accepted signaling pathways promoting lymphangiogenesis in tumors include the secreted lymphangiogenic proteins: vascular endothelial growth factor-C (VEGF-C) and VEGF-D, and their cognate receptor on lymphatic endothelium VEGF receptor-3 (VEGFR-3). Targeting VEGF pathway strategy sometimes failed to decrease tumor metastasis in vivo experiments and clinical trials. It is unclear whether the tumor cells induced the lymphangiogenesis process, while VEGF pathway could not completely illustrate the mechanism of tumor cell lymphatic metastasis. To explore the novel tumor lymphangiogenesis targets, we screened 181 candidate genes between high lymphatic vascular density (LVD) and low LVD in lung adenocarcinomas using Human Genome U133 Plus 2.0 Microarray. Insulin-like growth factor binding protein 7 (IGFBP7) was proven to be associated with metastatic clinicopathological features and high LVD. Furthermore, by assessing the capability of lymphatic endothelial cell forming lymphatic vessel-like structures in vitro, it appears to enhance lymphangiogenesis.


Epidemiological and economic impact of human papillomavirus vaccines.
Despite screening, cervical cancer (CC) remains a serious health care problem. Because human papillomavirus (HPV) is the necessary cause of CC, the development of 2 new vaccines can have a tremendous impact on CC and other HPV-related conditions. In this systematic review, the epidemiological and economic impacts of HPV are evaluated. A literature search was conducted through MEDLINE, Web of Science, Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature. Articles were selected based on inclusion and exclusion criteria. Economic evaluations were submitted to a quality assessment. Sixteen articles were selected to review the epidemiological impact of HPV vaccines, and 11 were selected to review the economic impact. The studies were very heterogeneous because of different assumptions. Nevertheless, a substantial reduction in CC is reported consistently and a (smaller) reduction in precancerous lesions and HPV prevalence. Cost-effectiveness ratios are also very diverse and dependent on the assumptions made. An HPV vaccine can be profitable if duration of vaccine-related immunity is high, efficacy is high, price is low, screening is reduced, administration is before sexual activity, discount rate is not too high, or if there is herd immunity. Human papillomavirus vaccines have the potential to reduce CC by at least approximately half of its current incidence, and this might be cost-effective if there is high efficacy with a long-lasting immunity.


[Hairy cell leukemia and pregnancy].
The paper presents experience in following up and treating hairy cell leukemia (HCL) during pregnancy. The combination of HCL and pregnancy was observed in 5 patients. The patients' median age was 35 years (range, 28-42 years). The diagnosis of HCL was based on a conventional examination protocol: clinical blood analysis with the morphological assessment of lymphocytes, a myelogram and trepanobiopsy, immunophenotypic analysis of lymphocytes or bone marrow (in all the patients), cytochemical determination of tartrate-resistant acid phosphatase in 3 patients, and identification of BRAFV600E mutation in 3 patients. Three pregnant women were treated for HCL in the postpartum period. In one patient with HCL, pregnancy was seen in remission after treatment with cladribine. In one patient with HCL detected at 11 weeks' gestation, interferon-α therapy during the second trimester of pregnancy was performed for increased cytopenia, which was followed by cladribine therapy after delivery. Pregnancy and delivery were uncomplicated in all the patients; 3 patients had vaginal delivery and 2 patients underwent cesarean section. All infants were healthy, with no developmental abnormalities during a follow-up period of 6-140 months (median 30 months). All the patients with HCL are currently in remission: 4 patients in first remission at a follow-up of 10 to 48 months (median 15 months) and one patient in second remission at a follow-up of 88 months. Possible observational tactics is possible when HCL is detected during pregnancy. Treatment of HCL during pregnancy is necessary in cases of deep or progressive cytopenia and/or splenomegaly. The use of interferon-α or splenectomy is preferable.


Posterior Segment Retained Intraocular Foreign Body: A Study from Western Nepal.
Posterior segment retained Intraocular foreign body (IOFB) management is challenging. Facility of pars plana vitrectomy (PPV) and availability of well trained vitreo retina surgeons are the basic need to accomplish this work. Encircling band provide permanent 360° support to close the anterior retinal break and prevent traction on the retina. The objective of this study is to analyse the clinical characteristics and predictors of the final visual outcome and survival of the globe in cases of retained IOFB in the posterior eye segment. A hospital based retrospective observational study was conducted. All the patients of retained IOFB in the posterior segment presented from January 2016 to June 2019 were enrolled. Patients presented with visual acuity of NPL were excluded. Statistical analysis was performed using a variety of tests using SPSS version 21. Forty eyes of 40 patients were included. The mean age was 27.08±10.68 years (range 5-66). 95% of our patients were male. Most of them (52.5%) worked on the farm. 26(65%) of 40 eyes had Zone I injury. The median time spent before presentation was 13.5 day. Retinal detachment, vitreous hemorrhage, and endophthalmitis were present in 15, 23 and 5 eyes, respectively, before IOFB removal. The mean LogMAR visual acuity was improved significantly from 2.50±0.87 to 1.33± 1.01 (p=0.003). Poor presenting visual acuity, retinal detachment and large diameter of IOFB were found as the predictor of poor final visual acuity. Pars plana vitrectomy by a vitreo retinal surgeon can give encouraging results in the cases of retained posterior segment IOFB. Poor presenting visual acuity, large diameter of IOFB and RD before IOFB removal are predictors of poor visual outcome.


"In situ" endografting in the treatment of arterial and graft infections.
Endografts (eg, aortic aneurysm device or covered stent) are increasingly being used to temporize or treat arterial and graft infections in inaccessible areas, in patients with compromised anatomy, or in the presence of active bleeding or rupture. This summary examines the evidence for "in situ" endografting in the treatment these conditions. A two-level search strategy of the literature (MEDLINE, PubMed, Google Scholar, and The Cochrane Library) was performed for relevant articles listed between January 2000 and December 2015. The review was confined to patients with primary and secondary bacterial or viral arterial infections, with or without fistulization and infection of bypass grafts and arteriovenous accesses. For the purposes of this summary, endografts can be considered to be an aortic aneurysm device or a covered stent. There are no societal guidelines. Endografts have been successfully applied to mycotic arterial aneurysms, aortoenteric, aortobronchial, and arterioureteric fistulae, and to anastomotic bleeds secondary to infection. Multiple reports indicate success at the control of hemorrhage in all locations. Short-term outcomes are good, but fatal infection-related complications, especially if antibiotic therapy is halted, are well reported and necessitate a more definitive plan for the long term. Stent grafts remain an important and viable option for the treatment of mycotic aneurysms, aortoesophageal and aortobronchial fistulae, and infected pseudoaneurysms in anatomically or technically inaccessible locations. In patients with a short life span (<6 months), no further intervention is generally required. In patients with a predicted life span >6 months, careful consideration should be given to a more definitive procedure. Life-long appropriate antibiotic therapy is strongly recommended for any patient receiving an endograft in an infected field.


Challenges and Opportunities for Soil Biodiversity in the Anthropocene.
Biodiversity on Earth is strongly affected by human alterations to the environment. The majority of studies have considered aboveground biodiversity, yet little is known about whether biodiversity changes belowground follow the same patterns as those observed aboveground. It is now established that communities of soil biota have been substantially altered by direct human activities such as soil sealing, agricultural land-use intensification, and biological invasions resulting from the introduction of non-native species. In addition, altered abiotic conditions resulting from climate change have also impacted soil biodiversity. These changes in soil biodiversity can alter ecosystem functions performed by the soil biota, and therefore, human-induced global changes have a feedback effect on ecosystem services via altered soil biodiversity. Here, we highlight the major phenomena that threaten soil biodiversity, and we propose options to reverse the decline in soil biodiversity. We argue that it is essential to protect soil biodiversity as a rich reservoir that provides insurance against the changes wrought by the Anthropocene. Overall, we need to better understand the determinants of soil biodiversity and how they function, plan to avoid further losses, and restore soil biodiversity where possible. Safeguarding this rich biotic reservoir is essential for soil sustainability and, ultimately, the sustainability of human society.


Role of natural killer cells and TCR gamma delta T cells in acute autoimmune encephalomyelitis.
To elucidate the role of NK cells and TCR gamma delta+ T cells in acute experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats, the distribution, number and function of these cells were studied using several methods. Immunohistochemical and flow cytometric analysis revealed that a certain number of NK cells (17 of the total inflammatory cells) infiltrated the central nervous system (CNS) at the peak stage of EAE and were mainly located in the perivascular region. On the other hand, virtually no TCR gamma delta+ T cells were found in the CNS. NK-T (NKR-P1+TCR alpha beta+) cells were few and did not increase in number in the CNS and lymphoid organs. In the cytotoxic assay using YAC-1 cells, effector cells isolated from the spleen of rats at the peak of EAE showed essentially the same cytotoxicity as those isolated from normal controls although the total number of NK cells decreased to one fifth of that of normal rats. Furthermore, in vivo administration of anti-NK cell (3.2.3 and anti-asialo GM1), but not of anti-TCR gamma delta (V65), antibodies exacerbated the clinical features of EAE and induced fatal EAE in some rats. These findings suggest that NK cells play a suppressive role in acute EAE whereas TCR gamma delta+ T cells are not involved in the development of or recovery from the disease.


Insular resting state functional connectivity is associated with gut microbiota diversity.
The gut microbiota has recently gained attention as a possible modulator of brain activity. A number of reports suggest that the microbiota may be associated with neuropsychiatric conditions such as major depressive disorder, autism and anxiety. The gut microbiota is thought to influence the brain via vagus nerve signalling, among other possible mechanisms. The insula processes and integrates these vagal signals. To determine if microbiota diversity and structure modulate brain activity, we collected faecal samples and examined insular function using resting state functional connectivity (RSFC). Thirty healthy participants (non-smokers, tobacco smokers and electronic cigarette users, n = 10 each) were studied. We found that the RSFC between the insula and several regions (frontal pole left, lateral occipital cortex right, lingual gyrus right and cerebellum 4, 5 and vermis 9) were associated with bacterial microbiota diversity and structure. In addition, two specific bacteria genera, Prevotella and Bacteroides, were specifically different in tobacco smokers and also associated with insular connectivity. In conclusion, we show that insular connectivity is associated with microbiome diversity, structure and at least two specific bateria genera. Furthemore, this association is potentially modulated by tobacco smoking, although the sample sizes for the different smoking groups were small and this result needs validation in a larger cohort. While replication is necessary, the microbiota is a readily accessible therapeutic target for modulating insular connectivity, which has previously been shown to be abnormal in anxiety and tobacco use disorders.


Healthy Eating as Potential Mediator of Inverse Association between Purpose in Life and Waist Circumference: Emerging Evidence from US and Chilean Cohorts.
High sense of purpose in life, a fundamental domain of eudaimonic well-being, has been consistently associated with lower risk for various obesity-related chronic diseases. Although this psychological feature correlates with some health behaviors as potential mediators, its association with healthy eating remains less explored. In addition, studies of these psycho-behavioral and health relationships in the South American population are lacking. This research sought to assess: (1) the cross-sectional association between self-reported purpose in life and overall healthy eating patterns, and (2) healthy food intake as a potential mediator of the inverse relationship between purpose in life and waist circumference. Data collected of 2060 US adults from the MIDUS study (5 ± 12 years, 55% women, mostly white people, and 42.5% obese) and 223 Chilean adults from the CHILEMED study (46.6 ± 9 years, 58.3% women, and 71.3% obese) were used. Anthropometric and sociodemographic variables were collected. Sense of purpose was assessed using the purpose in life subscale of the Ryff's psychological well-being questionnaire. Diet quality was evaluated using healthy eating or low-fat diet indexes, according to extant food intake data in each cohort. The relationship between these variables was estimated by bivariate and multivariate linear regressions with appropriate adjustments. To establish whether a better diet quality could mediate a link of purpose in life and improved nutritional status (assessed by waist circumference), the association between these three variables was tested by bootstrapping-based mediation analysis. Our results show significant associations of sense of purpose with healthy eating and low-fat dietary patterns in both US and Chilean cohorts, respectively, even after adjusting for sociodemographic variables. According to the mediation analysis, the relationship between sense of purpose and waist circumference, as an indicator of abdominal obesity, appears to be partially mediated by healthier food intake in both samples. In conclusion, our findings suggest a plausible mechanism underlying the favorable impact of this well-being dimension on physical health. Given its protective effects, interventions aimed at increasing purpose in life may facilitate adherence to better dietary patterns, which, in turn, will reduce the risk for obesity-related chronic diseases.


Porous biodegradable lumbar interbody fusion cage design and fabrication using integrated global-local topology optimization with laser sintering.
Biodegradable cages have received increasing attention for their use in spinal procedures involving interbody fusion to resolve complications associated with the use of nondegradable cages, such as stress shielding and long-term foreign body reaction. However, the relatively weak initial material strength compared to permanent materials and subsequent reduction due to degradation may be problematic. To design a porous biodegradable interbody fusion cage for a preclinical large animal study that can withstand physiological loads while possessing sufficient interconnected porosity for bony bridging and fusion, we developed a multiscale topology optimization technique. Topology optimization at the macroscopic scale provides optimal structural layout that ensures mechanical strength, while optimally designed microstructures, which replace the macroscopic material layout, ensure maximum permeability. Optimally designed cages were fabricated using solid, freeform fabrication of poly(ε-caprolactone) mixed with hydroxyapatite. Compression tests revealed that the yield strength of optimized fusion cages was two times that of typical human lumbar spine loads. Computational analysis further confirmed the mechanical integrity within the human lumbar spine, although the pore structure locally underwent higher stress than yield stress. This optimization technique may be utilized to balance the complex requirements of load-bearing, stress shielding, and interconnected porosity when using biodegradable materials for fusion cages.


Enhanced pH and thermal stability, solubility and antioxidant activity of resveratrol by nanocomplexation with α-lactalbumin.
The health-promoting benefits of resveratrol (RES) have attracted significant attention. Poor water solubility and chemical stability, however, hindered its application. In this study, α-lactalbumin (ALA)-RES nanoparticles were prepared by a simple nanocomplexation protocol. The particle sizes of ALA and the ALA-RES complex were 87.8, and 95.3 nm, respectively. AFM confirmed that both nanoparticles were spherical. XRD results confirmed that RES in ALA nanoparticles was amorphous. Fluorescence spectroscopy and FTIR showed that the ALA-RES nanocomplex was formed mainly by hydrophobic interactions. The water solubility increased by 32 times, compared to that of free RES. ALA nanocomplexation also appreciably improved the chemical stability of RES under all storage conditions, especially at pH 8.0 and high temperature. The ALA-RES nanocomplex showed significantly higher in vitro antioxidant activity than free RES. The results showed that the simple ALA-RES nanocomplex has the potential to be used as an effective antioxidant. The information obtained may enable the expanded application of ALA as an effective nanoscale carrier for delivering RES or other lipophilic nutraceuticals in the functional food, biomedical, and pharmaceutical products.