Tradeoffs in hyphal traits determine mycelium architecture in saprobic fungi.
The fungal mycelium represents the essence of the fungal lifestyle, and understanding how a mycelium is constructed is of fundamental importance in fungal biology and ecology. Previous studies have examined initial developmental patterns or focused on a few strains, often mutants of model species, and frequently grown under non-harmonized growth conditions; these factors currently collectively hamper systematic insights into rules of mycelium architecture. To address this, we here use a broader suite of fungi (31 species including members of the Ascomycota, Basidiomycota and Mucoromycota), all isolated from the same soil, and tested for ten architectural traits under standardized laboratory conditions. We find great variability in traits among the saprobic fungal species, and detect several clear tradeoffs in mycelial architecture, for example between internodal length and hyphal diameter. Within the constraints so identified, we document otherwise great versatility in mycelium architecture in this set of fungi, and there was no evidence of trait 'syndromes' as might be expected. Our results point to an important dimension of fungal properties with likely consequences for coexistence within local communities, as well as for functional complementarity (e.g. decomposition, soil aggregation).


Fission power: an evolutionary strategy.
Motivated by concerns about the difficulty of safeguarding the large flows of plutonium in a breeder reactor fuel cycle, we explore the resource and economic implications of a strategy in which there is no nuclear weapons-usable material in fresh reactor fuel. The strategy involves the deployment of already developed types of advanced converter reactors which, unlike the breeder, can be operated effectively on proliferation-resistant once-through fuel cycles. Advanced converter reactors could be much more uranium-efficient on once-through fuel cycles than current systems and therefore could compete economically with breeders up to very high uranium prices. If necessary, the uranium requirements of an advanced converter reactor system could be reduced much further with the recycling of isotopically denatured uranium, but any commitment to a closed fuel cycle would be unnecessary for many decades.


Modulation of subgenual anterior cingulate cortex activity with real-time neurofeedback.
The advent of real-time neurofeedback techniques has allowed us to begin to map the controllability of sensory and cognitive and, more recently, affective centers in the brain. The subgenual anterior cingulate cortex (sACC) is thought to be involved in generation of affective states and has been implicated in psychopathology. In this study, we examined whether individuals could use real-time fMRI neurofeedback to modulate sACC activity. Following a localizer task used to identify an sACC region of interest, an experimental group of eight women participated in four scans: (1) a pretraining scan in which they were asked to decrease activity in the sACC without neurofeedback; (2) two training scans in which sACC neurofeedback was presented along with instructions to decrease sACC activity; and (3) a neurofeedback-free post-training scan. An additional nine women in a yoked feedback control group saw sACC activity from the participants in the experimental group. Activity in the sACC was significantly reduced during neurofeedback training in the experimental group, but not in the control group. This training effect in the experimental group, however, did not generalize to the neurofeedback-free post-training scan. A psychophysiological interaction analysis showed decreased correlation in the experimental group relative to the sham control group between activity in the sACC and the posterior cingulate cortex during neurofeedback training relative to neurofeedback-free scans. The finding that individuals can down-modulate the sACC shows that a primary emotion center in which functional abnormality has been strongly implicated in affective disorders can be controlled with the aid of neurofeedback.


Factors associated with establishment-based female sex workers accessing health care services in Shanghai.
Female sex workers are a priority population for HIV prevention and health promotion in China. This paper examines the patterns of and factors associated with the utilisation of HIV-related and general health services by establishment-based sex workers in Hongkou District, Shanghai. Participants were recruited through a three-stage sampling strategy and invited to self-complete a brief survey in 2012. The median age of the 400 participants included in the analyses was 33 years (range = 18-52 years old), with over three-quarters being married at the time of the survey. Participants were mostly internal migrants, more than half had lived in Shanghai for six months or longer and nearly two-thirds were working in an establishment with a total of less than five female sex workers. Routine physical examination and HIV testing were the most commonly accessed health services in the previous 12 months. Altogether, 347 women (86.8%) had actively sought, including 157 women had obtained, free health services mainly from local Community Health Service Centres (CHSCs) in the previous 12 months. The active seeking of free, largely CHSC-provided health services was associated with a longer duration of residence in Shanghai (adjusted odds ratio [AOR] = 2.55, 95% CI = 1.32-4.93; p < 0.01) and having tested for HIV in the previous 12 months (AOR = 3.68, 95% CI = 1.84-7.38; p < 0.001). Conversely, a higher annual income (AOR = 0.41, 95% CI = 0.21-0.80; p < 0.01), working in a larger establishment (AOR = 0.40, 95% CI = 0.20-0.79; p < 0.01) and knowing that HIV can be transmitted through blood transfusion with unscreened blood (AOR = 0.21, 95% CI = 0.05-0.91; p < 0.05) were associated with not actively seeking such services. Free, community-based health services are highly demanded by establishment-based female sex workers in Shanghai. Scaling-up of free and integrated health services provided by community-based health service providers in metropolitan areas in China and beyond holds promise for promoting health and well-being of female sex workers.


Supplemental vitamin D3 concentration and biological type of steers. II. Tenderness, quality, and residues of beef.
Vitamin D3 was orally supplemented to determine the supplemental dose that improved beef tenderness in different cattle breed types. Feedlot steers (n = 142) were arranged in a 4 x 3 factorial arrangement consisting of four levels of supplemental vitamin D3 (0, 0.5, 1, and 5 million IU/steer daily) administered for eight consecutive days antemortem using three biological types (Bos indicus, Bos Taurus-Continental, and Bos Taurus-English). Warner-Bratzler shear force (WBSF) was measured at 3, 7, 10, 14, and 21 d postmortem, and trained sensory analysis was conducted at 7 d postmortem on LM, semimembranosus, gluteus medius, and supraspinatus steaks. Concentrations of vitamin D3 and the metabolites 25-hydroxyvitamin D3, and 1,25-dihydroxyvitamin D3 were determined in the LM, liver, kidney, and plasma. Biological type of cattle did not interact (P > 0.10) with vitamin D3 supplementation for sensory or tenderness traits, suggesting that feeding vitamin D3 for 8 d before slaughter affected the different biological types of cattle similarly. Supplementing steers with 0.5, 1, or 5 million IU/(steer(d) decreased (P < 0.05) LM WBSF at 7, 10, 14, and 21 d postmortem compared with controls, and vitamin D3 treatments of 0.5, 1, and 5 million IU decreased (P < 0.05) semimembranosus WBSF at 3, 7, and 14 d postmortem. In general, vitamin D3-induced improvements in WBSF were most consistent and intense in LM steaks. Sensory panel tenderness was improved (P < 0.05) by all vitamin D3 treatments in LM steaks. Sensory traits ofjuiciness, flavor, connective tissue, and off-flavor were not (P > 0.05) affected by vitamin D3 treatments. All vitamin D3 treatments decreased micro-calpain activity and increased muscle Ca concentrations (P < 0.05). Vitamin D3 concentrations were increased (P < 0.05) by supplementation in all tissues tested (liver, kidney, LM, and plasma); however, cooking steaks to 71 degrees C decreased (P < 0.05) treatment residue effects. The vitamin D metabolite 1,25-dihydroxyvitamin D3 was increased (P < 0.05) only in plasma samples as a result of the vitamin D3 treatments. These results indicate that supplementation with vitamin D3 at 0.5 million IU/steer daily for eight consecutive days before slaughter improved tenderness in steaks from different subprimal cuts by affecting muscle Ca concentrations, micro-calpain activities, and muscle proteolysis, with only a small effect on tissue residues of vitamin D3.


Sub-Sampled Cross-Component Prediction for Emerging Video Coding Standards.
Cross-component linear model (CCLM) prediction has been repeatedly proven to be effective in reducing the inter-channel redundancies in video compression. Essentially speaking, the linear model is identically trained by employing accessible luma and chroma reference samples at both encoder and decoder, elevating the level of operational complexity due to the least square regression or max-min based model parameter derivation. In this paper, we investigate the capability of the linear model in the context of sub-sampled based cross-component correlation mining, as a means of significantly releasing the operation burden and facilitating the hardware and software design for both encoder and decoder. In particular, the sub-sampling ratios and positions are elaborately designed by exploiting the spatial correlation and the inter-channel correlation. Extensive experiments verify that the proposed method is characterized by its simplicity in operation and robustness in terms of rate-distortion performance, leading to the adoption by Versatile Video Coding (VVC) standard and the third generation of Audio Video Coding Standard (AVS3).


Differential sensitivity and responsiveness of three human cell lines HepG2, 1321N1 and HEK 293 to cadmium.
Cadmium (Cd) is a toxic heavy metal with no uniform mechanism of toxicity. In this the present study, the toxic effect of 5, 10 and 50 microM of Cd chloride was compared in three human cell lines; a human hepatoma cell line HepG2, a human astrocytoma cell line 1321N1, and a human embryonic kidney cell HEK 293. The results indicate a decrease in the viability of all three cell lines following exposure to Cd with HepG2 cells (IC50=13.96 microM) showing the most sensitivity when measured using the MTT assay. There was significant increase in lactate dehydrogenase leakage, DNA damage, malondialdeyde and antioxidant enzymes activities in all three cell lines especially at 50 microM Cd. Significant decreases in ATP production were also observed at all Cd concentrations in HepG2 and HEK 293 cell lines. ROS levels significantly increase and GSH/GSSG ratio significantly decrease in all the three cell lines after Cd exposure, but these effects were attenuated by the presence of N-acetylcysteine (NAC). The present study therefore shows that ROS production and glutathione (GSH) depletion may play a role in Cd-induced toxicity in all the three cell lines. The endogenous levels of protective enzymes as well as their responsiveness are likely to determine a cell's susceptibility to Cd.


Diagnostic Criteria in Intraepithelial Pagetoid Neoplasms: A Histopathologic Study and Evaluation of Select Features in Paget Disease, Bowen Disease, and Melanoma In Situ.
Paget disease, Bowen disease, and malignant melanoma in situ are intraepidermal neoplasms, characterized by the presence of pagetoid scatter of atypical cells in the epidermis. This study reviewed the frequency of select histologic criteria to validate their usefulness in the histologic distinction between these entities. One hundred forty-four specimens with the diagnosis of Bowen disease, 144 specimens with Paget disease (mammary and extramammary), and 144 specimens with malignant melanoma in situ were examined microscopically to define frequencies of select histologic criteria present in each disease. Comparison between mammary Paget and extramammary Paget disease showed no significant differences in the features studied. Crushing of basal keratinocytes, presence of atypical cells in the corneum, and presence of large cells with amphophilic cytoplasm were significantly noted in Paget disease. Transition between the atypical clear cells and surrounding keratinocytes was absent in all cases of melanoma in situ and in 87 (60.4%) cases of Paget disease, but it was significantly associated with Bowen disease (98.6%). Dyskeratotic cells were significantly associated with Bowen disease cases. Our study demonstrated a practical histologic approach to differentiate between intraepidermal pagetoid neoplasms. Careful histologic study of the proposed criteria may reduce reliance on immunohistochemical stains.


A lysosome-targeted near-infrared fluorescent probe for imaging endogenous cysteine (Cys) in living cells.
Cysteine (Cys) is one of the most important essential biothiols in lysosomes. Highly selective probes for specific detection and imaging of lysosomal Cys over other biological thiols are rare. Herein, we developed a lysosome-targeted near-infrared fluorescent probe SHCy-C based on a novel NIR-emitting thioxanthene-indolium dye. Due to the turn-on fluorescence response elicited by the intramolecular charge transfer (ICT) processes before and after the reaction with Cys, probe SHCy-C exhibits high selectivity and sensitivity (16 nM) for the detection of Cys. More importantly, probe SHCy-C is found to precisely target lysosomes and achieves the "turn-on" detection and imaging of endogenous Cys in lysosomes.


Increased risk of cancer among 3663 patients with cutaneous lupus erythematosus: a Swedish nationwide cohort study.
Other autoimmune diseases have been associated with higher risks for cancer, and numerous case reports of cutaneous lupus erythematosus (CLE) and different cancer types are available. To estimate the overall and specific cancer risks in a nationwide cohort study of patients diagnosed with CLE in Sweden and compare that risk with that in a control cohort without CLE. A cohort of 3663 individuals with CLE and a matched control cohort from the general population (three controls to each CLE case) without a diagnosis of CLE were derived from the Swedish National Patient Register, 1997-2007, and were electronically linked to the Swedish Cancer Register and the Swedish Cause of Death Register. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to compare the observed vs. the expected numbers of cancers. A total of 183 incident cancers occurred within the observation interval, yielding a HR of 1·8 (95% CI 1·5-2·2) for cancer overall. Median follow-up was 4·1 years. About a fourfold risk increase was seen for buccal cancer, lymphomas, respiratory cancer and nonmelanoma skin cancer. Patients with CLE appear to have an elevated risk for certain cancer types, an increase that remains when excluding patients also diagnosed with systemic lupus erythematosus. Our findings point to the importance of counselling about not smoking and sun avoidance, and underscore the need for specialized monitoring of this patient group along with bench-to-bedside research efforts to clarify pathogenesis.


Budd-Chiari syndrome in a young patient with celiac sprue: a case report.
Budd-Chiari syndrome is thrombosis of the hepatic veins, and associated conditions vary. Budd-Chiari and celiac sprue association is a rare condition. A 24-year-old woman was admitted to the clinic with complaints of weakness, distended abdomen and weight loss for four months. Results of investigation showed Budd-Chiari syndrome and malabsorption with endomysial antibodies and intestinal villous atrophy. All known etiological factors for Budd-Chiari syndrome were negative. Three months after initiation of a gluten-free diet and replacement therapy, she died from infection of ascitic fluid and renal failure following umbilical hernia rupture. Celiac sprue must be remembered especially in the event of Budd-Chiari syndrome and malabsorption.


Coronary constriction impairs cardiac function and induces myocardial damage and ventricular remodeling in mice.
To establish whether coronary artery narrowing (CAN) in mice was accompanied by depressed ventricular function, tissue injury, and modifications in cardiac anatomy, the left coronary artery was constricted in FVB/N mice and the animals were killed 7 days later. CAN consisted of a 53% reduction in luminal diameter, which resulted in a twofold increase in left ventricular end-diastolic pressure. Left ventricular systolic pressure and left ventricular + and -dP/dt decreased 15, 21, and 11%, respectively. Left ventricular weight-to-body weight ratio increased 33%. This hypertrophic adaptation was characterized by a 9 and 20% increase in the longitudinal and transverse cavitary diameters, which provoked a 1.5-fold expansion in chamber volume. In contrast, wall thickness decreased 15%. These anatomic and functional changes induced a threefold elevation in diastolic stress. Foci of reparative fibrosis were found in the endomyocardium and epimyocardium, involving 2-3% of the tissue. Finally, myocyte loss in the ventricle was 15%, and myocyte hypertrophy was 38%. Impaired ventricular function, diastolic Laplace overloading, myocyte loss, and decompensated eccentric hypertrophy in mice after CAN mimic the ischemic cardiomyopathic heart in humans.


Amifostine protects against chemotherapy-induced neurotoxicity: an in vitro investigation.
Peripheral neurotoxicity is a dose-limiting side-effect of a number of effective chemotherapeutic agents. Neuroprotective agents may help to reduce neurotoxicity, thus allowing the intensification of cytostatic therapy in patients. In this in vitro study, using the rat pheochromocytoma cell line PC-12 neurite-outgrowth assay, the potential of amifostine to protect against cisplatin-, paclitaxel- and vincristine-induced neurotoxicity was investigated Amifostine is described as selectively protecting normal tissue and not tumour tissue. The effect of amifostine on tumour cell kill was investigated using the XTT and colony forming assay. Paclitaxel and vincristine both caused a significant reduction in the percentage of cells expressing neurites. Co-incubation with amifostine significantly increased this percentage of neurites in paclitaxel-induced neurotoxicity, but not in vincristine-induced neurotoxicity. Post-incubation of amifostine also proved to partly reverse already existing cisplatin-induced neurotoxicity, but not paclitaxel-, or vincristine-induced neurotoxicity. Amifostine did not protect tumour cells against cisplatin- and paclitaxel-induced tumour cytotoxicity, using the XTT assay. However, a stimulation of clonogenic capacity was observed when amifostine was coincubated with cisplatin. Amifostine protects against paclitaxel-induced neurotoxicity, but not against vincristine-induced neurotoxicity in this in vitro model. Furthermore, amifostine has potential to reverse already existing cisplatin-induced neurotoxicity. The role of amifostine in the proliferative potential of tumour cells in vitro needs further investigation.


Neurotrophins and their receptors stimulate melanoma cell proliferation and migration.
Melanoma is a highly aggressive skin tumor that originates in the epidermis from melanocytes. As melanocytes share with the nervous system a common neuroectodermal origin and express all neurotrophins (NTs), we evaluated the expression and function of NTs and their receptors in melanoma. We report that primary and metastatic melanoma cell lines synthesize and secrete all NTs. Moreover, melanoma cells express the low-affinity (p75NTR) and the high-affinity tyrosine kinase NT receptors (Trk). The inhibition of Trk receptors by either K252a or Trk/Fc chimeras prevents proliferation, indicating that autocrine NTs are responsible for this effect. NT-3, NT-4, and nerve growth factor (NGF) induce cell migration, with a stronger effect on metastatic cell lines. Transfection with p75NTR small interfering RNA (p75NTRsiRNA) or treatment with K252a inhibits NT-induced melanoma cell migration, indicating that both the low- and high-affinity NT receptors mediate this effect. All melanoma cell lines express the p75NTR coreceptor sortilin by which proNGF stimulates migration in melanoma cells, but not in cells transfected with p75NTRsiRNA. These results indicate that NTs, through their receptors, play a critical role in the progression of melanoma.


Families Improving Together (FIT) for weight loss: a resource for translation of a positive climate-based intervention into community settings.
Climate-based weight loss interventions, or those that foster a nurturing family environment, address important ecological influences typically ignored by the traditional biomedical treatments. Promoting a climate characterized by positive communication, autonomy support, and parental warmth supports adolescents in making healthy behavioral changes. In addition, encouraging these skills within the family may have additional benefits of improved family functioning and other mental and physical health outcomes. Although several programs have identified essential elements and established the evidence base for the efficacy of these interventions, few have offered resources for the translation of these constructs from theoretical concepts to tangible practice. This paper provides strategies and resources utilized in the Families Improving Together (FIT) for weight loss randomized controlled trial to create a warm, supportive climate characterized by positive communication within the parent-child relationship. Detailed descriptions of how Project FIT emphasized these constructs through facilitator training, intervention curriculum, and process evaluation are provided as a resource for clinical and community interventions. Researchers are encouraged to provide resources to promote translation of evidence-based interventions for programs aiming to utilize a positive climate-based family approach for lifestyle modification.


Impact of Synchronous Telemedicine Models on Clinical Outcomes in Pediatric Acute Care Settings: A Systematic Review.
To evaluate the impact of synchronous telemedicine models on the clinical outcomes in pediatric acute care settings. Citations from EBM Reviews, MEDLINE, EMBASE, Global Health, PubMed, and CINAHL. We identified studies that evaluated the impact of synchronous telemedicine on clinical outcomes between January 2000 and April 2018. All studies involving acutely ill children in PICUs, pediatric cardiac ICUs, neonatal ICUs, and pediatric emergency departments were included. Publication inclusion criteria were study design, participants characteristics, technology type, interventions, settings, outcome measures, and languages. Two authors independently screened each article for inclusion and extracted information, including telecommunication method, intervention characteristics, sample characteristics and size, outcomes, and settings. Out of the 789 studies initially identified, 24 were included. The six main outcomes of interest published were quality of care, hospital and standardized mortality rate, transfer rate, complications and illness severity, change in medical management, and length of stay. The use of synchronous telemedicine results improved quality of care and resulted in a decrease in the transfer rate (31-87.5%) (four studies), a shorter length of stay (8.2 vs 15.1 d) (six studies), a change or reinforcement of the medical care plan, a reduction in complications and illness severity, and a low hospital and standardized mortality rate. Overall, the quality of the included studies was weak. Despite the broad recommendations found for using telemedicine in pediatric acute care settings, high-quality evidence of its impacts is still lacking. Further robust studies are needed to better determine the clinical effectiveness and the associated impacts of telemedicine in pediatric acute care settings.


Familiarity, Navigation, and Comprehension: Key Dimensions of Health Literacy in Pap Test Use among Korean American Women.
Health literacy consists of multiple dimensions such as print and oral literacy or numeracy. Different dimensions of health literacy may have more salient impact on certain health behaviors and outcomes. Yet, evidence is limited regarding which dimensions particularly affect cervical cancer screening. The objective of this study was to examine the role of different dimensions of health literacy in cervical cancer screening among Korean American women. We used baseline data obtained from 560 Korean American women in a community-based health literacy-focused intervention study. Backward stepwise logistic regression analysis revealed that familiarity (adjusted odds ratio [AOR] = 1.20, 95% confidence interval [CI] = 1.11-1.31) and navigational health literacy (AOR = 1.10, 95% CI = 1.04-1.16) were associated with lifetime Pap test use and comprehension (AOR = 1.08, 95% CI = 1.02-1.14) with triennial Pap test screening. Prior exposure to healthcare settings and knowing how to navigate the healthcare system were more important than other health literacy dimensions for lifetime Pap test use. Understanding cancer screening-related words was most relevant to triennial Pap test use. In addition to addressing system factors such as insurance and physicians' recommendations, interventions to increase Pap test screening targeted at Korean American women are needed to address certain dimensions of health literacy such as familiarity, navigation, and comprehension.


[Multimodal therapy of tumors of the upper gastrointestinal tract].
Adjuvant and neoadjuvant therapeutic principles have in recent years received increasing attention in the management of patients with carcinoma of the upper gastrointestinal tract. A series of randomized prospective trials has demonstrated that adjuvant postoperative radiation or chemotherapy does not result in a convincing survival advantage after complete tumor resection in gastric or esophageal cancer. The available data on the role of neoadjuvant preoperative therapy in these patients as yet permit no conclusion. While neoadjuvant therapy may reduce the tumor mass in a substantial portion of patients, a series of randomized controlled trials has shown that, compared to primary resection, a multimodal approach does not result in a survival benefit in patients with loco-regional, i.e. potentially resectable, tumors. In contrast, in patients with locally advanced tumors, i.e. tumors for which complete removal with primary surgery appears unlikely, neoadjuvant therapy increases the chance for complete tumor resection on subsequent surgery. However, only patients with objective histopathologic response to preoperative therapy appear to benefit from this approach. Compared to preoperative chemotherapy alone, combined radio-chemotherapy increases the rate of response, particularly in squamous cell esophageal cancer, but may also increase postoperative morbidity and mortality. Neoadjuvant therapy should therefore currently only be performed in experienced centers within the context of prospective clinical trials. The identification of factors that would allow prediction of response to neoadjuvant or adjuvant therapy is the focus of ongoing studies.


Modeling of the thermal properties of SARS-CoV-2 S-protein.
We calculate the thermal and conformational states of the spike glycoprotein (S-protein) of SARS-CoV-2 at seven temperatures ranging from 3°C to 95°C by all-atom molecular dynamics (MD) µs-scale simulations with the objectives to understand the structural variations on the temperatures and to determine the potential phase transition while trying to correlate such findings of the S-protein with the observed properties of the SARS-CoV2. Our simulations revealed the following thermal properties of the S-protein: 1) It is structurally stable at 3°C, agreeing with observations that the virus stays active for more than two weeks in the cold supply chain; 2) Its structure varies more significantly at temperature values of 60°C-80°C; 3) The sharpest structural variations occur near 60°C, signaling a plausible critical temperature nearby; 4) The maximum deviation of the receptor-binding domain at 37°C, corroborating the anecdotal observations that the virus is most infective at 37°C; 5) The in silico data agree with reported experiments of the SARS-CoV-2 survival times from weeks to seconds by our clustering approach analysis. Our MD simulations at µs scales demonstrated the S-protein's thermodynamics of the critical states at around 60°C, and the stable and denatured states for temperatures below and above this value, respectively.


[The influence of strategy of treatment of obturation colonic tumor obstruction on short-term results and quality of life of patients].
The results of treatment of 120 patients with colonic tumor obstruction, included in the main group, with the formation at the first stage of decompressive double-barrel colostomy were analyzed as well as resection of the colon with ablation of the tumor and simultaneous liquidation of the stoma on the second stage. The overall postoperative lethality was 1.6%. Operations of the second stage were made in 96.7% of the patients. The interval between operations was 18.3 days. The control group consisted of 182 patients with Hartmann operations fulfilled at the first stage and liquidation of the double-barrel colostomy at the second stage. Postoperative lethality was 9.9%. Restorative operation was made in 83.5% of patients. The average term of colostomy was 196.3 days. A comparative assessment of quality of life of the patients fulfilled with the MOS SF-36 questionnaire demonstrated better results in the main group of the patients.


Effects of Linalool on glutamatergic system in the rat cerebral cortex.
Linalool is a monoterpene compound reported to be a major component of essential oils in various aromatic species. Several Linalool-producing species are used in traditional medical systems, including Aeolanthus suaveolens G. Dom (Labiatae) used as anticonvulsant in the Brazilian Amazon. Psychopharmacological in vivo evaluation of Linalool showed that this compound have dose-dependent marked sedative effects at the Central Nervous System, including hypnotic, anticonvulsant and hypothermic properties. The present study reports an inhibitory effect of Linalool on Glutamate binding in rat cortex. It is suggested that this neurochemical effect might be underlining Linalool psychopharmacological effects. These findings provide a rational basis for many of the traditional medical use of Linalool producing plant species.


Transcatheter embolization of coronary artery fistula: a case report.
Coronary artery fistula is rare, but it is the most common congenital coronary artery anomaly with hemodynamic significance. It usually causes no symptoms in young patients but may be associated with symptoms and complications in older patients. Surgery has been the traditional treatment. In this report, a 7-year-old girl who had a coronary artery fistula from the left circumflex coronary artery to the right atrium was successfully treated by percutaneous transcatheter technique.


Site-specific cross-linking of proteins to DNA via a new bioorthogonal approach employing oxime ligation.
DNA-protein cross-links (DPCs) are super-bulky DNA adducts induced by common chemotherapeutic agents, reactive oxygen species, and aldehydes, and also formed endogenously as part of epigenetic regulation. Despite their presence in most cells and tissues, the biological effects of DPCs are poorly understood due to the difficulty of constructing site-specific DNA-protein conjugates. In the present work, a new approach of conjugating proteins to DNA using oxime ligation was used to generate model DPCs structurally analogous to lesions formed in cells. In our approach, proteins and peptides containing an unnatural oxy-Lys amino acid were cross-linked to DNA strands functionalized with 5-formyl-dC or 7-(2-oxoethyl)-7-deaza-dG residues using oxime ligation. The conjugation reaction was site-specific with respect to both protein and DNA, provided excellent reaction yields, and formed stable DPCs amenable to biological evaluation.


Influenza A(H1N1)pdm09 outbreak detected in inter-seasonal months during the surveillance of influenza-like illness in Pune, India, 2012-2015.
An outbreak of influenza A(H1N1)pdm09 was detected during the ongoing community-based surveillance of influenza-like illness (ILI). Among reported 119 influenza A(H1N1)pdm09 cases (59 cases in the year 2012 and 60 cases in 2015) in summer months, common clinical features were fever (100%), cough (90·7%), sore throat (85·7%), nasal discharge (48·7%), headache (55·5%), fatigue (18·5%), breathlessness (3·4%), and ear discharge (1·7%). Rise in ILI cases were negatively correlated with the seasonal factors such as relative humidity (Karl Pearson's correlation coefficient, i.e. r = -0·71 in the year 2012 and r = -0·44 in the year 2015), while rise in ILI cases were positively correlated with the temperature difference (r = 0·44 in the year 2012 and r = 0·77 in the year 2015). The effective reproduction number R, was estimated to be 1·30 in 2012 and 1·64 in 2015. The study highlights the rise in unusual influenza activity in summer month with high attack rate of ILI among children aged ⩽9 years. Children in this age group may need special attention for influenza vaccination. Influenza A(H1N1)pdm09 outbreak was confirmed in inter-seasonal months during the surveillance of ILI in Pune, India, 2012-2015.


One lab, two firms, many possibilities: On R&D outsourcing in the biopharmaceutical industry.
We draw from documented characteristics of the biopharmaceutical industry to construct a model where two firms can choose to outsource R&D to an external unit, and/or engage in internal R&D, before competing in a final market. We investigate the distribution of profits among market participants, and the incentives to coordinate outsourcing activities or to integrate R&D and production. Consistent with the empirical evidence, we find that the sign and magnitude of an aggregate measure of direct (inter-firm) and indirect (through the external unit) technological externalities drives the distribution of industry profits, with higher returns to the external unit when involved in development (clinical trials) than in early-stage research (drug discovery). In the latter case, the delinkage of investment incentives from industry value, together with the ability of firms to transfer risks to the external unit, imply a vulnerability of early-stage investors' returns to negative shocks, and the likely abandonment of projects with economic and medical value. We also find that competition in the equity market makes a buyout by one of the two firms more profitable to a research biotech than to a clinical services unit, and can stimulate early-stage investments. However, this long-term incentive can be minimal, notably if the superior efficiency of outsourced operations originates from economies of scope that can hardly be exploited when a firm takes control of the external unit exclusively for itself. R&D outsourcing thus does not always qualify as a relevant pathway to address the declining productivity in innovation that has characterized the industry over several decades.


The use of real-time digital video in the assessment of post-operative outcomes of breast reconstruction.
Outcome measures of breast reconstruction have used panel assessment of photographs. This provides limited information to the assessor as these images are static.. The aim of this study was to assess whether the use of digital video was a valid assessment tool and to compare its use against photography. 35 patients post-reconstruction underwent photography, digital video capture and completed Breast Cancer Treatment Outcomes Scale (BCTOS) questionnaires. The photographs/video clips were randomised and shown to a 21 member panel. Opinions on aesthetic aspects of the reconstruction were assessed using the BCTOS and Harris scale. Panel inter-rater agreement and patient-panel correlation was assessed using Kendall's Coefficient of Concordance and Spearman's rank correlation tests respectively. There was a "moderate" degree of inter-rater agreement amongst panel members in all categories. Greater agreement occurred using video footage to assess overall cosmesis (0.548 vs 0.507) and shape (0.505 vs 0.486). Video showed a greater degree of correlation with patient self-assessment scores in comparison to photography (0.311 vs 0.281). Video footage coupled with panel assessment is a valid method of assessing post-operative outcomes of breast reconstruction and appears superior to still photographs in terms of inter-rater agreement and correlation with patient self-assessment.


Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency.
Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM). Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade. Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.


Cerebral hemodynamics predicts the cortical area and coding scheme in the human brain for force generation by wrist muscles.
The goal of this study is to identify the cortical area maximally active over the primary sensorimotor cortex (SM1) and characterize the cortical encoding for force production by wrist muscles in the human brain. The technique of functional near-infrared spectroscopy (fNIRS) was used to continuously monitor the changes in hemoglobin concentrations from the left hemisphere during isometric contractions of wrist flexion muscles over a broad range of load forces (0 ∼ 8 kgf) on the right hand. As previously shown in primate studies, this action produced hemodynamic activity predominantly in the wrist area localized dorsally to the finger region over SM1 and the hemodynamic response was systematically related to the level of load intensity. The coding scheme for force production in terms of hemodynamic signals was characterized defining eight trajectory parameters (four for amplitude coding and four for temporal coding) and analyzed for the area maximally activated over SM1. The trajectory parameter representing the oxygenated hemoglobin concentration change at the end of motor task (amplitude coding) and the timing of maximum change in oxygenated hemoglobin concentration (temporal coding) was most strongly correlated with the load variation in a superliner manner. All these results indicate the applicability of fNIRS to monitor and decode cortical activity that is correlated with low-level motor control such as isometric muscle contractions. This study may provide not only insights into cortical neural control of muscle force but also predictors of muscle force in clinical diagnostics and neural interfaces for the human brain.


Clock circadian regulator (CLOCK) gene network expression patterns in bovine adipose, liver, and mammary gland at 3 time points during the transition from pregnancy into lactation.
The transition from late gestation to early lactation is the most critical phase of the lactation cycle for mammals. Research in rodents has revealed changes in the clock circadian regulator (CLOCK) gene network expression around parturition. However, their expression profiles and putative functions during the periparturient period in ruminants remain to be determined. The present study aimed to investigate the expression pattern of the CLOCK network and selected metabolic genes simultaneously in mammary gland (MG), liver (LIV), and subcutaneous adipose tissue (AT). Seven dairy cows were biopsied at -10 (±2), 7, and 21 d relative to parturition. A day × tissue interaction was observed for ARNTL, CRY1, and PER2 due to upregulation at 7 and 21 d postpartum, with their expression being greater in AT and MG compared with LIV. No interaction was detected for CLOCK, CRY2, PER1, and PER3. In general, the expression of NPAS2, NR1D1, NR2F2, ALAS1, FECH, FBXW11, CCRN4L, PPARA, PPARGC1A, and FGF21 was lower at -10 d but increased postpartum in all tissues. The interaction detected for CSNK1D was associated with increased expression postpartum in AT and MG but not LIV. The interaction detected for CPT1A was due to upregulation in AT and LIV postpartum without a change in MG. In contrast, the interaction for PPARG was due to upregulation in AT and MG postpartum but a downregulation in LIV. Leptin was barely detectable in LIV, but there was an interaction effect in AT and MG associated with upregulation postpartum in MG and downregulation in AT. Together, these results suggest that the control of metabolic adaptations in LIV, MG, and AT around parturition might be partly regulated through the CLOCK gene network. Although the present study did not specifically address rhythmic control of tissue metabolism via the CLOCK gene network, the difference in expression of genes studied among tissues confirms that the behavior of circadian-controlled metabolic genes around parturition differs by tissue and, as such, is closely associated with the metabolic function of the organ.


Regulation of inwardly rectifying K+ channels in retinal pigment epithelial cells by intracellular pH.
Inwardly rectifying K+ (Kir) channels in the apical membrane of the retinal pigment epithelium (RPE) play a key role in the transport of K+ into and out of the subretinal space (SRS), a small extracellular compartment surrounding photoreceptor outer segments. Recent molecular and functional evidence indicates that these channels comprise Kir7.1 channel subunits. The purpose of this study was to determine whether Kir channels in the RPE are modulated by extracellular (pHo) or intracellular pH (pHi), both of which change upon illumination of the dark-adapted retina. The Kir current (IKir) in acutely dissociated bovine RPE cells was recorded in the whole-cell configuration while altering pHo or pHi. In cells dialysed with pipette solution buffered to pH 7.2, step changes in pHo from 7.4 to 8.0, 7.0 or 6.5 had little effect on IKir. Acidification to pHo 6.0, however, caused a transient activation of IKir followed by a slower inhibition. To determine the dependence of IKir on pHi, we altered pHi within individual RPE cells at constant pHo by imposing transmembrane acetate concentration gradients. These experiments revealed a biphasic relationship between IKir and pHi: IKir was maximal at about pHi 7.1, but decreased sharply at more acidic or alkaline levels. To evaluate the role of Kir7.1 channels in the pHi-dependent changes in IKir, we tested the effect of transmembrane acetate concentration gradients on Rb+ currents, which are 10-fold larger than K+ currents for this channel subtype. Inwardly rectifying Rb+ currents were maximal at about pHi 7.0 and were inhibited by intracellular alkalinization or acidification. We conclude that the Kir conductance in the RPE is modulated by intracellular pH in the physiological range and that this reflects the behaviour of Kir7.1 channels. This sensitivity to pHi may provide an important mechanism linking photoreceptor activity and RPE function.


The Effect of Clinical Pilates on Functional Movement in Recreational Runners.
Biomechanical imbalances and inefficient functional movements are considered contributing factors to running-related injuries. Clinical Pilates uses a series of exercises focused on retraining normal movement patterns. This study investigated whether a 6-week course of Clinical Pilates improves functional movement and thereby, potentially, reduces the risk of running-related injuries associated with movement dysfunction. A modified functional movement screen was used to analyze the functional movement ability of forty runners. Forty participants completed a 6-week course of Clinical Pilates delivered by a Clinical Pilates instructor. The movement screen was carried out 3 times for each runner: 6 weeks pre-intervention (baseline), within one week pre-intervention (pre) and within one week post-intervention (post). Repeated-measures analysis of variance and post-hoc tests found significant increases in scores between baseline and post (mean±SD; 13.4±2.4 vs. 17.0±1.7, p<0.01) and pre and post (mean±SD; 13.5±2.5 vs. 17.0±1.7, p<0.01), but no significant difference between baseline and pre (p=0.3). A 6-week course of Clinical Pilates significantly improves functional movement in recreational runners, and this may lead to a reduction in the risk of running-related injuries.


Black tea theaflavins induce programmed cell death in cultured human stomach cancer cells.
The exposure of human stomach cancer KATO III cells to black tea theaflavin extract, free theaflavin, and theaflavin digallate that are main components of the extract, led to both growth inhibition and the induction of programmed cell death (apoptosis). Morphological changes showing apoptotic bodies were observed in the cells treated with black tea theaflavin extract, theaflavin and theaflavin digallate. The fragmentations by these theaflavin compounds of DNA to oligonucleosomal-sized fragments that are characteristics of apoptosis were observed to be concentration- and time-dependent. These data suggest that drinking of black tea in large amounts is recommended to protect humans from stomach cancer.


The pharmacology of cephalexin.
Cephalexin has an antimicrobial spectrum that includes those pathogens most frequently encountered in clinical practice. It is useful in the treatment of infections of the upper and lower respiratory tract, skin and soft tissue, and the genitourinary tract. It can be administered in relatively high oral doses without gastrointestinal irritation, and because it is absorbed high in the intestinal tract, it does not disturb the lower bowel flora. Because of its stability and chemical configuration, it causes a very low incidence of allergy. Cephalexin is not absorbed from the stomach but is totally and rapidly absorbed in the upper intestine. Children, because of their greater body water turnover, may need higher doses per kilogram than those used in treating adults. Distribution to the tissues, other than the spinal fluid and aqueous humour, is rapidly achieved. Cephalexin does not penetrate into the host tissue cells, which probably accounts for its low incidence of side effects. Binding to human serum proteins is low, and there is no measurable destruction or metabolism of cephalexin during its sojourn in the body fluids. Cephalexin is rapidly cleared from the body by the kidneys. Seventy to 100% of the dose is found in the urine 6-8 hr after each dose. Concentrations of 500-1000 micrograms/ml of urine follow 250 to 500 mg oral doses of cephalexin, many times greater than the minimum inhibitory concentration for the usual urinary tract pathogens. Patients with creatinine clearances less than 30 ml/min require a reduction in cephalexin dosage. This reduction should be proportional to the reduced function which may be established by determination of creatinine clearance or serum creatinine.


Wear performance of self-mating contact pairs of TiN and TiAlN coatings on orthopedic grade Ti-6Al-4V.
Both titanium nitride (TiN) and titanium aluminum nitride (TiAlN) have shown great wear resistance potential in metallic medical devices as protective, hard thin film coatings. In the present study, the effects of TiN and TiAlN coating layers on the wear performance of Ti-6Al-4V were compared and analyzed. TiN and TiAlN coatings with a thickness of 3 microm were deposited by a cathodic vacuum arc ion plating technique on the surface of Ti-6Al-4V. Wear tests were conducted by using a pin-on-disk-type tribotester with a point contact self-mating pair in a linear reciprocal motion. A sliding distance of 20 mm per cycle at 1 Hz was used under a load of 15 N under ambient conditions with no lubricant. The wear resistance of TiN and TiAlN coatings is superior to that of uncoated Ti-6Al-4V at the early stage of sliding contact. Until a measurable amount of wear was detected, the number of sliding cycles of the TiAlN coating pair was longer than TiN. After the first detection of wear from the coating layers, the rate of wear of the TiN coating pairs was significantly higher than that of TiAlN (p < 0.05), and it was close to that of the uncoated pairs. In conclusion, the TiAlN coating is superior to TiN from the viewpoint of wear resistance under the test conditions used in this study.


Development of a Polymeric Pharmacological Nanocarrier System as a Potential Therapy for Spinocerebellar Ataxia Type 7.
Spinocerebellar ataxia type 7 (SCA7) is an autosomal-dominant inherited disease characterized by progressive ataxia and retinal degeneration. SCA7 belongs to a group of neurodegenerative diseases caused by an expanded CAG repeat in the disease-causing gene, resulting in aberrant polyglutamine (polyQ) protein synthesis. PolyQ ataxin-7 is prone to aggregate in intracellular inclusions, perturbing cellular processes leading to neuronal death in specific regions of the central nervous system (CNS). Currently, there is no treatment for SCA7; however, a promising approach successfully applied to other polyQ diseases involves the clearance of polyQ protein aggregates through pharmacological activation of autophagy. Nonetheless, the blood-brain barrier (BBB) poses a challenge for delivering drugs to the CNS, limiting treatment effectiveness. This study aimed to develop a polymeric nanocarrier system to deliver therapeutic agents across the BBB into the CNS. We prepared poly(lactic-co-glycolic acid) nanoparticles (NPs) modified with Poloxamer188 and loaded with rapamycin to enable NPs to activate autophagy. We demonstrated that these rapamycin-loaded NPs were successfully taken up by neuronal and glial cells, demonstrating high biocompatibility without adverse effects. Remarkably, rapamycin-loaded NPs effectively cleared mutant ataxin-7 aggregates in a SCA7 glial cell model, highlighting their potential as a therapeutic approach to fight SCA7 and other polyQ diseases.


Mitochondrial aldehyde dehydrogenase, a potential drug target for protection of heart and brain from ischemia/reperfusion injury.
Mitochondrial aldehyde dehydrogenase (ALDH2) is an isoenzyme of aldehyde dehydrogenases (ALDH), a group of enzymes that are responsible for clearance of aldehydes in the body. In animal myocardial or cerebral ischemia/ reperfusion (I/R) models, accumulation of toxic aldehydes, such as 4-hydroxy-2-nonenal and malondialdehyde, is thought to be an important mechanism for myocardial and cerebral I/R injury. Among the isoenzymes of ALDH, ALDH2 is believed to play a major role in clearance of toxic aldehydes. Thus, ALDH2 might be a potential drug target for protection of the heart or brain from I/R injury. Indeed, some of the newly identified ALDH2 activators (such as Alda-1) have demonstrated beneficial effects on heart and brain I/R injury. In addition, ALDH activity is present at high levels in some stem or progenitor cells, known as ALDH bright (ALDH(br)) cells, which possess potential value in treating patients with myocardial ischemia. The main purpose of this review is 1) to summarize recent findings regarding the role of ALDH2 in protection of heart or brain from I/R injury, 2) to list the available ALDH2 activators with their potency, selectivity and clinical potentials, and 3) to provide a rationale for ALDH(br) cells in clinical therapeutic value.


A new ether bond-splitting enzyme found in Gram-positive polyethylene glycol 6000-utilizing bacterium, Pseudonocardia sp. strain K1.
Pseudonocardia sp. strain K1 is the only Gram-positive bacterium among the bacteria aerobically metabolizing polyethylene glycol (PEG). Generally, PEG is metabolized by an oxidative pathway in which a terminal alcohol group of PEG is oxidized to aldehyde and to carboxylic acid and then an ether bond is oxidatively cleaved. As the cell-free extract of Pseudonocardia sp. strain K1 has PEG dehydrogenase, PEG aldehyde dehydrogenase and diglycolic acid (DGA) dehydrogenase (DGADH) activities, all of which are constitutively formed, the strain has a metabolic pathway similar to that so far known. We purified an ether bond-splitting enzyme as DGADH. The molecular mass of the enzyme was estimated to be 55 kDa; and it consisted of two identical subunits. The enzyme oxidatively cleaved both an ether bond of PEG 3000 dicarboxylic acid and DGA. The N-terminal amino acid sequence of the purified enzyme had high homology with various superoxide dismutases and the enzyme had also superoxide dismutase activity. The atomic absorption spectrum showed that approximately one atom of Fe was included in each subunit of the enzyme. DGADH activity increased in the cells grown in a PEG medium supplemented with FeCl(3). Thus, we concluded that the enzyme purified from Pseudonocardia sp. strain K1 is a new ether bond-splitting enzyme.


Effect of dietary electrolyte balance on nutrient digestibility determined at the end of the small intestine and over the total digestive tract in growing pigs.
A replicated 4 x 4 Latin square digestion trial was conducted to determine the effect of electrolyte balance (EB = Na + K - Cl meq/kg of the diet) on apparent nutrient digestibilities in pigs fitted with ileal T-cannulas. Experimental diets were composed of corn and soybean meal with dietary EB altered by the substitution of CaCl2 for CaCO3, or NaHCO3 for corn and soybean meal. Electrolyte balance levels examined were -50, 100, 250 or 400 meq/kg of the diet. Increasing dietary EB concentration linearly increased (P less than .05 to P less than .02) apparent ileal digestibility of N, energy, DM and all amino acids, except alanine and methionine. However, nutrient and amino acid digestibilities measured over the total digestive tract were similar (P greater than .16) among EB levels. Increasing dietary EB resulted in a linear and quadratic (P less than .03) effect on daily urinary N excretion, resulting in a linear (P less than .05) improvement in N retention expressed both as a percentage of N intake and of absorbed N. Blood pH, total CO2, HCO3 and base excess concentrations increased linearly (P less than .02 to P less than .001) with increasing dietary EB. Dietary EB concentrations influenced nutrient and amino acid absorption measured near the end of the small intestine. Additionally, the N balance data per unit of N intake or N absorbed are indicative of an improved N utilization in pigs fed increasing dietary EB concentrations from -50 to 400 meq/kg.


Action of polystyrene nanoparticles of different sizes on lysosomal function and integrity.
Data from environmental exposure to nanoparticles (NPs) suggest that chronic exposure may increase the incidence of lung, cardiovascular and neurodegenerative diseases. Impairment of cell function by intracellular accumulation of NPs is also suspected. Many types of NPs have been detected in the endosomal-lysosomal system and, upon repeated exposure, alterations of the endosomal-lysosomal system may occur. To identify such effects we compared the effect of carboxyl polystyrene particles (CPS) of different sizes (20-500 nm) on lysosomes of the endothelial cell line EAhy926 after short (24h) and long (72h-96h) exposure times. Lysosomal localization of CPS, as well as lysosomal pH, lysosomal membrane integrity, morphology of the endosomal-lysosomal system and activities of the lysosomal enzymes,cathepsin B and sulfatases, upon exposure to CPS were recorded. CPS in sizes ≤100 nm showed high co-localization with lysosomes already after 4h, larger CPS after 24h. None of the particles at non-cytotoxic concentrations caused marked changes in lysosomal pH or destroyed lysosomal membrane integrity. At 24h of exposure, 20 nm CPS induced significant dilatation of the endosomal-lysosomal system and reduced activity of lysosomal sulfatases. After 72h, these alterations were less pronounced. Despite accumulation in lysosomes CPS induced only small changes in lysosomes. Upon longer contact, these changes are even less pronounced. The presented panel of assays may serve to identify effects on lysosomes also for other NPs.


Blur identification by the method of generalized cross-validation.
The point spread function (PSF) of a blurred image is often unknown a priori; the blur must first be identified from the degraded image data before restoring the image. Generalized cross-validation (GCV) is introduced to address the blur identification problem. The GCV criterion identifies model parameters for the blur, the image, and the regularization parameter, providing all the information necessary to restore the image. Experiments are presented which show that GVC is capable of yielding good identification results. A comparison of the GCV criterion with maximum-likelihood (ML) estimation shows the GCV often outperforms ML in identifying the blur and image model parameters.


Obesity in children.
Obesity is the result of long-term energy imbalances, where daily energy intake exceeds daily energy expenditure. Along with long-term health problems, obesity in children may also be associated with psychosocial problems, including social marginalisation, low self-esteem, and impaired quality of life. Most obese adolescents stay obese as adults. Obesity is increasing among children and adolescents, with 16.8% of boys and 15.2% of girls in the UK aged 2 to 15 years obese in 2008. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of lifestyle interventions for the treatment of childhood obesity? What are the effects of surgical interventions for the treatment of childhood obesity? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 14 systematic reviews and RCTs that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following lifestyle interventions: behavioural, diet, and multifactorial interventions; physical activity; and bariatric surgery.


Guided bone regeneration in long-bone defects with a structural hydroxyapatite graft and collagen membrane.
There are few synthetic graft alternatives to treat large long-bone defects resulting from trauma or disease that do not incorporate osteogenic or osteoinductive factors. The aim of this study was to test the additional benefit of including a permeable collagen membrane guide in conjunction with a preformed porous hydroxyapatite bone graft to serve as an improved osteoconductive scaffold for bone regeneration. A 10-mm-segmental long-bone defect model in the rabbit radius was used. The hydroxyapatite scaffolds alone or with a collagen wrap were compared as experimental treatment groups to an empty untreated defect as a negative control or a defect filled with autologous bone grafts as a positive control. All groups were evaluated after 4 and 8 weeks of in vivo implantation using microcomputed tomography, mechanical testing in flexure, and histomorphometry. It was observed that the use of the wrap resulted in an increased bone volume regenerated when compared to the scaffold-only group (59% greater at 4 weeks and 27% greater after 8 weeks). Additionally, the increase in density of the regenerated bone from 4 to 8 weeks in the wrap group was threefold than that in the scaffold group. The use of the collagen wrap showed significant benefits of increased interfacial bone in-growth (149% greater) and periosteal remodeling (49%) after 4 weeks compared to the scaffold-alone with the two groups being comparable after 8 weeks, by when the collagen membrane showed close-to-complete resorption. While the autograft and wrap groups showed significantly greater flexural strength than the defect group after 8 weeks, the scaffold-alone group was not significantly different from the other three groups. It is most likely that the wrap shows improvement of function by acting like a scaffold for periosteal callus ossification, maintaining the local bone-healing environment while reducing fibrous infiltration (15% less than scaffold only at 4 weeks). This study indicates that the use of a collagen membrane with a hydroxyapatite structural graft provides benefits for bone tissue regeneration in terms of early interfacial integration.


The staff workplace and the quality and outcome of substance abuse treatment.
The study examined the connection between the staff work environment and staff members' beliefs about treatment, the quality of the treatment environment, patients' involvement in treatment and self-help activities, and patients' improvement during treatment. Patient care staff (N = 329) in 15 substance abuse treatment programs reported on the characteristics of their work environment and on their beliefs and treatment orientations about substance abuse. Patients in these programs (N = 3,228) reported on the treatment environment, their participation in treatment and self-help activities, and their treatment goals, confidence in achieving these goals, and coping skills at intake to and discharge from treatment. Staff in supportive and goal-directed work environments were more likely to espouse disease model beliefs and a 12-step orientation toward substance abuse treatment. These work environments were associated with more supportive and goal-directed treatment environments. Patients in these treatment environments participated in more substance abuse, educational and social, and family treatment services, were more involved in self-help groups (as indicated by attending more meetings, reading 12-step materials, and having a sponsor and friends in such groups), were more satisfied with the program, improved more during treatment (as indicated by abstinence goals and confidence in maintaining abstinence, less depression, and more substance abuse and general coping skills), and were more likely to participate in outpatient mental health care after discharge. More goal-directed work environments are associated with more goal-directed treatment environments and patients' engagement in treatment and improvement. The staff work environment is an important component of the substance abuse treatment system.


Development of Culture Medium for the Isolation of Flavobacterium and Chryseobacterium from Rhizosphere Soil.
An effective medium designated phosphate separately autoclaved Reasoner's 2A supplemented with cycloheximide and tobramycin (PSR2A-C/T) has been developed for the isolation of Flavobacterium and Chryseobacterium strains from the plant rhizosphere. It consists of Reasoner's 2A agar (R2A) prepared by autoclaving phosphate and agar separately and supplementing with 50 mg L(-1) cycloheximide and 1 mg L(-1) tobramycin. A comparison was made among the following nine media: PSR2A-C/T, PSR2A-C/T supplemented with NaCl, R2A agar, R2A agar supplemented with cycloheximide and tobramycin, 1/4-strength tryptic soy agar (TSA), 1/10-strength TSA, soil-extract agar, Schaedler anaerobe agar (SAA), and SAA supplemented with gramicidin, for the recovery of Flavobacterium and Chryseobacterium strains from the Welsh onion rhizosphere. Flavobacterium strains were only isolated on PSR2A-C/T, and the recovery rate of Chryseobacterium strains was higher from PSR2A-C/T than from the eight other media. In order to confirm the effectiveness of PSR2A-C/T, bacteria were isolated from onion rhizosphere soil with this medium. Flavobacterium and Chryseobacterium strains were successfully isolated from this sample at a similar rate to that from the Welsh onion rhizosphere.


MAP and kinesin-dependent nuclear positioning is required for skeletal muscle function.
The basic unit of skeletal muscle in all metazoans is the multinucleate myofibre, within which individual nuclei are regularly positioned. The molecular machinery responsible for myonuclear positioning is not known. Improperly positioned nuclei are a hallmark of numerous diseases of muscle, including centronuclear myopathies, but it is unclear whether correct nuclear positioning is necessary for muscle function. Here we identify the microtubule-associated protein ensconsin (Ens)/microtubule-associated protein 7 (MAP7) and kinesin heavy chain (Khc)/Kif5b as essential, evolutionarily conserved regulators of myonuclear positioning in Drosophila and cultured mammalian myotubes. We find that these proteins interact physically and that expression of the Kif5b motor domain fused to the MAP7 microtubule-binding domain rescues nuclear positioning defects in MAP7-depleted cells. This suggests that MAP7 links Kif5b to the microtubule cytoskeleton to promote nuclear positioning. Finally, we show that myonuclear positioning is physiologically important. Drosophila ens mutant larvae have decreased locomotion and incorrect myonuclear positioning, and these phenotypes are rescued by muscle-specific expression of Ens. We conclude that improper nuclear positioning contributes to muscle dysfunction in a cell-autonomous fashion.


Role of Geitlerinema sp. DE2011 and Scenedesmus sp. DE2009 as Bioindicators and Immobilizers of Chromium in a Contaminated Natural Environment.
The aim of this work was to study the potential of the two phototrophic microorganisms, both isolated from Ebro Delta microbial mats, to be used as bioindicators and immobilizers of chromium. The results obtained indicated that (i) the Minimum Metal Concentration (MMC) significantly affecting Chlorophyll a intensity in Geitlerinema sp. DE2011 and Scenedesmus sp. DE2009 was 0.25 µM and 0.75 µM, respectively, these values being lower than those established by current legislation, and (ii) Scenedesmus sp. DE2009 was able to immobilize chromium externally in extracellular polymeric substances (EPS) and intracellularly in polyphosphate (PP) inclusions. Additionally, this microorganism maintained high viability, including at 500 µM. Based on these results, we postulate that Geitlerinema sp. DE2011 and Scenedesmus sp. DE2009 are good chromium-indicators of cytotoxicity and, further, that Scenedesmus sp. DE2009 plays an important role in immobilizing this metal in a contaminated natural environment.


[The Amazon Sanitation Plan (1940-1942)].
The article addresses the Amazon Sanitation Plan and the political context in which it was formulated between 1940 and 1941. It examines the role of Getúlio Vargas, the activities of the plan's main protagonists (such as Evandro Chagas, João de Barros Barreto, and Valério Konder), its key proposals, and its demise as of 1942 upon creation of the Special Public Health Service (Sesp), which grew out of cooperation agreements between Brazil and the US following both nations' involvement in World War II. A reproduction of the Plan as published in the Arquivos de Higiene in 1941 is included.


Survivorship wellness: a multidisciplinary group program for cancer survivors.
National mandates require cancer centers provide comprehensive survivorship care. We created an 8-session, group intervention, the Survivorship Wellness Group Program (SWGP), that covered 8 topics: nutrition, physical activity, stress, sleep/fatigue, sexuality/body image, emotional wellbeing/fear of cancer recurrence, spirituality/meaning, and health promotion/goal setting. This study examined the acceptability and preliminary outcomes of SWGP. We evaluated SWGP using questionnaire data collected at program entry and 15-week follow-up. Questionnaires assessed acceptability and impact on anxiety, depression, quality of life, and perceived knowledge of topics. Enrollees who consented to participate in research and completed the baseline and 15-week follow-up were included in the analysis (N = 53). We assessed acceptability and preliminary outcomes using paired-samples t-tests. Due to the COVID-19 pandemic, SWGP transitioned to telehealth partway through data collection. Post-hoc analyses compared outcomes by intervention delivery. Participants completed an average of 7.44/8 classes. Participants reported a mean response of 3.42/4 regarding overall program satisfaction and 90.6% reported being "very likely" to recommend SWGP. SWGP was associated with decreases in anxiety and depression; increases in physical, emotional, functional, and overall quality of life; and increases in knowledge of all health behavior domains. No outcomes differed significantly between delivery in person versus telehealth. SWGP offers an acceptable and replicable model for cancer centers to meet national survivorship care guidelines. SWGP provides a comprehensive service for cancer survivors post-treatment, and was associated with better quality of life, fewer mental health symptoms, and increased knowledge in multiple domains of wellness.


Connexin Mutants Compromise the Lens Circulation and Cause Cataracts through Biomineralization.
Gap junction-mediated intercellular communication facilitates the circulation of ions, small molecules, and metabolites in the avascular eye lens. Mutants of the lens fiber cell gap junction proteins, connexin46 (Cx46) and connexin50 (Cx50), cause cataracts in people and in mice. Studies in mouse models have begun to elucidate the mechanisms by which these mutants lead to cataracts. The expression of the dominant mutants causes severe decreases in connexin levels, reducing the gap junctional communication between lens fiber cells and compromising the lens circulation. The impairment of the lens circulation results in several changes, including the accumulation of Ca2+ in central lens regions, leading to the formation of precipitates that stain with Alizarin red. The cataract morphology and the distribution of Alizarin red-stained material are similar, suggesting that the cataracts result from biomineralization within the organ. In this review, we suggest that this may be a general process for the formation of cataracts of different etiologies.


Targeting PI3K in Cancer: Impact on Tumor Cells, Their Protective Stroma, Angiogenesis, and Immunotherapy.
The PI3K pathway is hyperactivated in most cancers, yet the capacity of PI3K inhibitors to induce tumor cell death is limited. The efficacy of PI3K inhibition can also derive from interference with the cancer cells' ability to respond to stromal signals, as illustrated by the approved PI3Kδ inhibitor idelalisib in B-cell malignancies. Inhibition of the leukocyte-enriched PI3Kδ or PI3Kγ may unleash antitumor T-cell responses by inhibiting regulatory T cells and immune-suppressive myeloid cells. Moreover, tumor angiogenesis may be targeted by PI3K inhibitors to enhance cancer therapy. Future work should therefore also explore the effects of PI3K inhibitors on the tumor stroma, in addition to their cancer cell-intrinsic impact. The PI3K pathway extends beyond the direct regulation of cancer cell proliferation and survival. In B-cell malignancies, targeting PI3K purges the tumor cells from their protective microenvironment. Moreover, we propose that PI3K isoform-selective inhibitors may be exploited in the context of cancer immunotherapy and by targeting angiogenesis to improve drug and immune cell delivery. Cancer Discov; 6(10); 1090-105. ©2016 AACR.


Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis.
In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB). To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA). We searched international scientific databases, trial registration websites, and references of identified articles. Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment. Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB. Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75). In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.


Amitriptyline and fluphenazine in the treatment of postherpetic neuralgia.
Postherpetic neuralgia (PHN) is a vexing problem occurring in 10 to 20 percent of people with from herpes zoster (shingles). Anecdotal reports show that fluphenazine enhances the effects of amitriptyline for the treatment of PHN. The aim of this study was to determine, in a controlled manner, whether this was the case. In a double-blind placebo-controlled study, 49 patients with PHN were randomly assigned to four treatment groups: Group 1, amitriptyline; Group 2, amitriptyline and fluphenazine; Group 3, fluphenazine; Group 4, a placebo. An active placebo was used to mimic the anticholinergic side effects of dry mouth. The study lasted 8 weeks, with weekly progress evaluations with use of visual analog scales (VAS), the McGill Pain Questionnaire (MPQ), and a side-effects scale. A statistically significant decrease was seen in pain in Groups 1 and 2, and no significant changes were seen in Groups 3 and 4. There was no significant difference when fluphenazine was added to amitriptyline. These data support the effectiveness of amitriptyline in treatment of PHN, but do not support the addition of fluphenazine.


SARS-CoV-2 Codon Usage Bias Downregulates Host Expressed Genes With Similar Codon Usage.
Severe acute respiratory syndrome has spread quickly throughout the world and was declared a pandemic by the World Health Organization (WHO). The pathogenic agent is a new coronavirus (SARS-CoV-2) that infects pulmonary cells with great effectiveness. In this study we focus on the codon composition for the viral protein synthesis and its relationship with the protein synthesis of the host. Our analysis reveals that SARS-CoV-2 preferred codons have poor representation of G or C nucleotides in the third position, a characteristic which could result in an unbalance in the tRNAs pools of the infected cells with serious implications in host protein synthesis. By integrating this observation with proteomic data from infected cells, we observe a reduced translation rate of host proteins associated with highly expressed genes and that they share the codon usage bias of the virus. The functional analysis of these genes suggests that this mechanism of epistasis can contribute to understanding how this virus evades the immune response and the etiology of some deleterious collateral effect as a result of the viral replication. In this manner, our finding contributes to the understanding of the SARS-CoV-2 pathogeny and could be useful for the design of a vaccine based on the live attenuated strategy.


Molecular and Functional Analysis of the Type IV Pilus Gene Cluster in Streptococcus sanguinis SK36.
Streptococcus sanguinis, dominant in the oral microbiome, is the only known streptococcal species possessing a pil gene cluster for the biosynthesis of type IV pili (Tfp). Although this cluster is commonly present in the genome of S. sanguinis, most of the strains do not express Tfp-mediated twitching motility. Thus, this study was designed to investigate the biological functions encoded by the cluster in the twitching-negative strain S. sanguinis SK36. We found that the cluster was transcribed as an operon, with three promoters located 5' to the cluster and one in the intergenic region between SSA_2307 and SSA_2305. Studies using promoter-cat fusion strains revealed that the transcription of the cluster was mainly driven by the distal 5' promoter, which is located more than 800 bases 5' to the first gene of the cluster, SSA_2318. Optimal expression of the cluster occurred at the early stationary growth phase in a CcpA-dependent manner, although a CcpA-binding consensus is absent in the promoter region. Expression of the cluster resulted in a short hairlike surface structure under transmission electron microscopy. Deletion of the putative pilin genes (SSA_2313 to SSA_2315) abolished the biosynthesis of this structure and significantly reduced the adherence of SK36 to HeLa and SCC-4 cells. Mutations in the pil genes downregulated biofilm formation by S. sanguinis SK36. Taken together, the results demonstrate that Tfp of SK36 are important for host cell adherence, but not for motility, and that expression of the pil cluster is subject to complex regulation.IMPORTANCE The proteins and assembly machinery of the type IV pili (Tfp) are conserved throughout bacteria and archaea, and yet the function of this surface structure differs from species to species and even from strain to strain. As seen in Streptococcus sanguinis SK36, the expression of the Tfp gene cluster results in a hairlike surface structure that is much shorter than the typical Tfp. This pilus is essential for the adherence of SK36 but is not involved in motility. Being a member of the highly diverse dental biofilm, perhaps S. sanguinis could more effectively utilize this structure to adhere to host cells and to interact with other microbes within the same niche.


Biomechanical analysis of lumbar interbody fusion supplemented with various posterior stabilization systems.
Biomechanical comparison between rigid and non-rigid posterior stabilization systems following lumbar interbody fusion has been conducted in several studies. However, most of these previous studies mainly focused on investigating biomechanics of adjacent spinal segments or spine stability. The objective of the present study was to compare biomechanical responses of the fusion devices when using different posterior instrumentations. Finite-element model of the intact human lumbar spine (L1-sacrum) was modified to simulate implantation of the fusion cage at L4-L5 level supplemented with different posterior stabilization systems including (i) pedicle screw-based fixation using rigid connecting rods (titanium rods), (ii) pedicle screw-based fixation using flexible connecting rods (PEEK rods) and (iii) dynamic interspinous spacer (DIAM). Stress responses were compared among these various models under bending moments. The highest and lowest stresses in endplate, fusion cage and bone graft were found at the fused L4-L5 level with DIAM and titanium rod stabilization systems, respectively. When using PEEK rod for the pedicle screw fixation, peak stress in the pedicle screw was lower but the ratio of peak stress in the rods to yield stress of the rod material was higher than using titanium rod. Compared with conventional rigid posterior stabilization system, the use of non-rigid stabilization system (i.e., the PEEK rod system and DIAM system) following lumbar interbody fusion might increase the risks of cage subsidence and cage damage, but promote bony fusion due to higher stress in the bone graft. For the pedicle screw-based rod stabilization system, using PEEK rod might reduce the risk of screw breakage but increased breakage risk of the rod itself.


Recent advances in functional mesoporous graphitic carbon nitride (mpg-C3N4) polymers.
Mesoporous micro-/nanostructures acting as supports for catalysts or used directly in catalysis reactions generally show fascinating performances that could lead to great potential for application. In the past few decades, extensive efforts have been devoted to the exploration and enrichment of graphitic carbon nitride (g-C3N4) based research. Especially, mesoporous g-C3N4 (mpg-C3N4) with controllable porosity and electronic/atomic structure can bring to bear unique physicochemical properties and has been widely applied in the fields of photocatalysis, adsorbents, sensors and chemical templates. However, a comprehensive summary on mpg-C3N4 micro/nanostructures is less reported and there is an urgent need to further promote the development of function-oriented mpg-C3N4-based materials. Herein, we will overview the significant advances in functional mpg-C3N4 polymers, including general synthesis strategies and growth mechanisms, modifications of electronic/atomic structures and interfacial properties (such as exfoliation, doping and hybridizing), as well as their current applications. Finally, several emerging issues and perspectives are also proposed.


Isolated Leptomeningeal Enhancement in Anti-N-Methyl D-Aspartate Receptor Encephalitis: The Diagnostic Value of Contrast-Enhanced Fluid-Attenuated Inversion Recovery Imaging.
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a common autoimmune encephalitis that is noted to be a severe but treatable disease entity. Patients with anti-NMDAR encephalitis often develop psychotic symptoms, including delusions, hallucinations, and paranoia, as well as memory impairment and persistent loss of attention. However, MRI findings in such patients show no abnormalities in most cases. Although typical brain abnormality features, known as T2 hyperintensities, involve the brain parenchyma and contrast enhancement at the cerebral cortex or overlying meninges, isolated leptomeningeal enhancement has been rarely reported in anti-NMDAR encephalitis. Herein, we report a patient with anti-NMDAR encephalitis who presented with isolated leptomeningeal enhancement, additionally showing the diagnostic value of contrast-enhanced fluid-attenuated inversion recovery imaging.


Inflammatory processes triggered by Helicobacter pylori infection cause aberrant DNA methylation in gastric epithelial cells.
Altered patterns of DNA methylation associated with Helicobacter pylori (HP) infection of gastric epithelial cells are thought to contribute to gastric cancer risk. However, it is unclear whether this increased risk reflects an infection-associated inflammatory response or the infection itself. In this study, we sought to clarify mechanisms in a gerbil model of gastric cancer where we showed that HP infection is causally involved in induction of aberrant DNA methylation. By genome-wide screening, CpG islands that were aberrantly methylated in gerbil gastric cancer cell lines were isolated, and 10 islands were shown to be specifically methylated only in gastric mucosae infected with HP. By temporal analysis, methylation levels in gastric epithelial cells started to increase at 5 to 10 weeks after infection and reached high levels by 50 weeks. When HP was eradicated, methylation levels markedly decreased 10 and 20 weeks later, but they remained higher than those in gerbils that were not infected by HP. Expression levels of several inflammation-related genes (CXCL2, IL-1beta, NOS2, and TNF-alpha) paralleled the temporal changes of methylation levels. Significantly suppressing inflammation with the immunosuppressive drug cyclosporin A did not affect colonization by HP but blocked the induction of altered DNA methylation. Our findings argue that DNA methylation alterations that occur in gastric mucosae after HP infection are composed of transient components and permanent components, and that it is the infection-associated inflammatory response, rather than HP itself, which is responsible for inducing the altered DNA methylation.


10, 15 reciprocal translocation in an infertile man: ultrastructural and fluorescence in-situ hybridization sperm study: case report.
Peculiar sperm defects are described in a sterile man heterozygous for a balanced translocation t(10;15) (q26;q12). As this structural reorganization was absent in the parents, the translocation must have appeared de novo in the present patient. Spermatozoa were analysed under light and transmission electron microscopy (TEM). Fluorescence in-situ hybridization (FISH) was performed on the lymphocyte karyotype. Aneuploidy frequencies of chromosomes 18, X and Y in sperm nuclei, not involved in the translocation, were investigated using three-colour FISH. Dual- colour FISH was used to evaluate segregation of chromosomes 10, 15 in decondensed sperm nuclei. Moreover, three-colour FISH, using telomeric probes for chromosomes 10, 15 was performed in order to distinguish balanced and unbalanced gametes. Overall, structural characteristics indicate general immaturity of the germinal cells. FISH sperm analysis detected an increase in chromosome 18 disomy (0.81%) suggesting an interchromosomal effect. A high frequency of diploidies, particularly 18,18,X,X and 18,18,X,Y, was also found. FISH segregation analysis for chromosomes 10, 15 indicated that 32.8% were balanced gametes, whereas 68.2% were unbalanced. Taken together, these data demonstrate in a male carrier of a reciprocal translocation t(10;15) the presence of diffuse ultrastructural sperm alterations and a high frequency of sperm aneuploidies. The existence of a correlation among these factors is proposed.


Macrophage-Listeria interactions.
It is clear that the interaction between macrophages and the facultative intracellular bacterium Listeria monocytogenes is complex and dictated by the needs of both organisms. On the one hand, the invading pathogen has devised strategies to locate itself intracellularly in a site where host defense mechanisms are minimal; thus it escapes the phagosome and enters the cytoplasm, from which it travels to the next cell without exposing itself to the extracellular environment. On the other hand, the infected cell, potentially a highly efficient killer of microbes, is influenced by cytokines and other mediators, autocrine and exocrine, that enhance its ability to thwart the invader. Thus a macrophage, under the influence of at least IFN-gamma and TNF-alpha, can progress from being a nonlistericidal cell to one that can kill the intracellular organism. It probably does this by preventing escape of Listeria from the phagosome into the cytoplasm. The bacterium, retained in the phagosome, is killed by unknown mechanisms, which appear to be regulated by iron and may involve reactive nitrogen intermediates.


[Intrapericardial teratoma in the neonatal stage: diagnosis and evolution].
Intrapericardial teratomas in fetal and neonatal stages are rare. They invade the mediastinum compromising the venous return to the heart and leading to hydrops. We report a case of a neonate with fetal hydrops who required ventilatory support at birth and urgent surgical treatment due to severe respiratory failure. During surgery, a multicyst mass was resected in the anterior mediastinum, corresponding to an immature teratoma.


Diuretic Resistance in Cardio-Nephrology: Role of Pharmacokinetics, Hypochloremia, and Kidney Remodeling.
Diuretic resistance is among the most challenging problems that the cardio-nephrologist must address in daily clinical practice, with a considerable burden on hospital admissions and health care costs. Indeed, loop diuretics are the first-line therapy to overcome fluid overload in heart failure patients. The pathophysiological mechanisms of fluid and sodium retention are complex and depend on several neuro-hormonal signals mainly acting on sodium reabsorption along the renal tubule. Consequently, doses and administration modalities of diuretics must be carefully tailored to patients in order to overcome under- or overtreatment. The frequent and tricky development of diuretic resistance depends in part on post-diuretic sodium retention, reduced tubular secretion of the drug, and reduced sodium/chloride sensing. Sodium and chloride depletions have been recently shown to be major factors mediating these processes. Aquaretics and high-saline infusions have been recently suggested in cases of hyponatremic conditions. This review discusses the limitations and strengths of these approaches. Long-term diuretic use may lead to diuretic resistance in cardio-renal syndromes. To overcome this complication intravenous administration of loop diuretics and a combination of different diuretic classes have been proposed. In the presence of hyponatremia, high-saline solutions in addition to loop diuretics might be beneficial, whereas aquaretics require caution to avoid overcorrection. Key Messages: Diuretic resistance is a central theme for cardio-renal syndromes. Hyponatremia and hypochloremia may be part of the mechanisms for diuretic resistance. Aquaretics and high-saline solutions have been proposed as possible new therapeutic solutions.


Pancreatic islet transplantation--experimental experience and clinical potential.
New theoretic developments in transplantation biology indicate that it is possible to reduce the immunogenicity of a graft by removing antigen-presenting cells (leukocytes) from the tissue before grafting. Also becoming apparent is that cellular replacement therapy, the grafting of cells or clusters of cells, can be used to treat metabolic disorders such as type I diabetes mellitus. In the past, immune rejection has been a major problem and long-term patient immunosuppression is not warranted in patients with type I diabetes. Results of studies in animals show that under defined genetic conditions, mature islet tissue or immature fetal proislets may be transplanted across major histocompatibility barriers without a requirement for recipient immunosuppression. We are now ready to commence applying this technology clinically. These developments will initially be very experimental and limited in scope but should accelerate as data emerge from the initial trials.


Diabetic preretinal membranes. An immunohistochemical study.
Fibrovascular membranes removed during vitreous surgery from patients with proliferative diabetic retinopathy were examined using indirect immunofluorescence. Antisera against collagen types I, III, IV, and V, attachment factors fibronectin and laminin, endothelial marker factor VIII, and the glial-marker glial-fibrillary acidic protein were used to examined the membranes. Seven of ten specimens contained cells staining positively for glial-fibrillary acidic protein, either singly or in large clusters within the membrane. Four of six membranes showed a well-developed vascular bed surrounded by a dense collagenous matrix. The matrix stained strongly with antiserum against both interstitial type I collagen and its associated attachment factor, fibronectin. In contrast, only localized staining was observed when antisera against both type IV collagen and its associated attachment factor, laminin, were used, and this was concentrated in regions of blood vessels and associated internal limiting membrane.


Power-law creep from discrete dislocation dynamics.
We report two-dimensional discrete dislocation dynamics simulations of combined dislocation glide and climb leading to "power-law" creep in a model aluminum crystal. The approach fully accounts for matter transport due to vacancy diffusion and its coupling with dislocation motion. The existence of quasiequilibrium or jammed states under the applied creep stresses enables observations of diffusion and climb over time scales relevant to power-law creep. The predictions for the creep rates and stress exponents fall within experimental ranges, indicating that the underlying physics is well captured.


Fibrous tissue and angiotensin II.
Myofibroblasts (myoFb) are cells responsible for fibrous tissue formation in injured systemic organs such as the heart. Cultured myoFb, obtained from rat cardiac scar tissue, express genes that encode components requisite for angiotensin (Ang) II generation, which in turn regulates myoFb collagen turnover in an autocrine/paracrine manner. In this study, we tested the hypothesis that these wound-healing fibroblast-like cells and locally generated Ang II are involved in other repairing tissue. To test this hypothesis, we used a granuloma pouch model, where a subcutaneous air sac is created followed by injection of croton oil. Pouch tissue was collected at days 4, 7, 14 and 21. The presence of myoFb was determined by immunohistochemical alpha-smooth muscle actin (alpha-SMA) labeling and collagen accumulation by picrosirius red staining. Angiotensin converting enzyme (ACE) and Ang II receptor binding were detected by in vitro quantitative autoradiography using 125I-351A and 125I[Sar1, Ile8]Ang II, respectively, while Ang II receptor subtype was defined by displacement studies using either an AT1 (losartan) or AT2 (PD123177) receptor antagonist. Cells expressing ACE were determined by immunohistochemistry. Ang II content in pouch tissue was measured by radioimmunoassay following HPLC separation while its capacity to generate Ang II was assessed in tissue bath, with and without exogenous Ang I or lisinopril, an ACE inhibitor. Collagen accumulation in pouch tissue was examined by determining hydroxyproline content in response to lisinopril, AT1 or AT2 receptor antagonists (losartan or PD123177). In pouch tissue, we found: (1) myoFb at day 4 which became more extensive at days 7, 14 and 21; (2) morphologic evidence of collagen deposition evident at day 4, which gradually became more extensive thereafter; (3) ACE and Ang II receptor binding was evident at day 4 and remained invariant on days 7, 14 and 21; (4) the predominant Ang II receptor subtype expressed was AT1; (5) myoFb express ACE and AT1 receptors; (6) picogram quantities of Ang II (per g tissue) was evident on days 7, 14 and 21; and (7) Ang II was generated from Ang I substrate. Lisinopril and losartan, but not PD123177, significantly attenuated pouch weight and accumulation of collagen. Thus, in this model of cutaneous repair, the appearance of myoFb is associated with Ang II generation that regulates fibrogenesis by AT1 receptor binding. Signals involved in the appearance of myoFb remain uncertain. Further studies are required to address the regulation of Ang II generation in pouch tissue of the rat.


Palladium nanoparticles produced by fermentatively cultivated bacteria as catalyst for diatrizoate removal with biogenic hydrogen.
A new biological inspired method to produce nanopalladium is the precipitation of Pd on a bacterium, i.e., bio-Pd. This bio-Pd can be applied as catalyst in dehalogenation reactions. However, large amounts of hydrogen are required as electron donor in these reactions resulting in considerable costs. This study demonstrates how bacteria, cultivated under fermentative conditions, can be used to reductively precipitate bio-Pd catalysts and generate the electron donor hydrogen. In this way, one could avoid the costs coupled to hydrogen supply. The catalytic activities of Pd(0) nanoparticles produced by different strains of bacteria (bio-Pd) cultivated under fermentative conditions were compared in terms of their ability to dehalogenate the recalcitrant aqueous pollutants diatrizoate and trichloroethylene. While all of the fermentative bio-Pd preparations followed first order kinetics in the dehalogenation of diatrizoate, the catalytic activity differed systematically according to hydrogen production and starting Pd(II) concentration in solution. Batch reactors with nanoparticles formed by Citrobacter braakii showed the highest diatrizoate dehalogenation activity with first order constants of 0.45 ± 0.02 h⁻¹ and 5.58 ± 0.6 h⁻¹ in batches with initial concentrations of 10 and 50 mg L⁻¹ Pd, respectively. Nanoparticles on C. braakii, used in a membrane bioreactor treating influent containing 20 mg L⁻¹ diatrizoate, were capable of dehalogenating 22 mg diatrizoate mg⁻¹ Pd over a period of 19 days before bio-Pd catalytic activity was exhausted. This study demonstrates the possibility to use the combination of Pd(II), a carbon source and bacteria under fermentative conditions for the abatement of environmental halogenated contaminants.


Peripheral complex odontome with ghost cell epithelium. A case report.
Odontomes are malformations of dental tissues found commonly within jaw-bones and to a lesser extent in the soft tissue. A case of peripheral complex odontome exhibiting ghost cell epithelium is presented here. The significance of the ghost cells and origin of the odontome are briefly commented upon.