T lymphocytes play a role in neuropathic pain following peripheral nerve injury in rats.
A catastrophic consequence of peripheral nerve injury is the development of abnormal, chronic neuropathic pain. The inflammatory response at the injury site is believed to contribute to the generation and maintenance of such persistent pain. However, the physiological significance and potential contribution of T cells to neuropathic pain remains unclear. Here we show that T cells infiltrate injured sciatic nerves following chronic constriction injury (CCI), but not uninjured nerves. Congenitally athymic nude rats, which lack mature T cells, developed a significantly reduced mechanical allodynia and thermal hyperalgesia following CCI, compared with their heterozygous littermates. To understand further the role played by different T-cell subsets, we generated polarized populations of type 1 and type 2 T cells, with different cytokine secretion profiles, from spleens of sciatic nerve-injured heterozygous rats. Passive transfer of type 1 T cells, which produce proinflammatory cytokines, into nude rats enhanced the recipients' pain hypersensitivity to a level similar to that of heterozygous donor rats. In contrast, passive transfer of polarized type 2 T cells, which produce anti-inflammatory cytokines, into heterozygous rats modestly though significantly attenuated their pain hypersensitivity. Thus, injection of type 1 and type 2 T-cell subsets produces opposing effects on neuropathic pain. These findings suggest the modulation of the T-cell immune response as a potential target for the treatment of neuropathic pain.


Treatment algorithm and prognostic factors for patients with stage I-III carcinoma of the anal canal: a 20-year multicenter study.
Despite a growing incidence in developed countries and a recent improved understanding of its pathogenesis, anal cancer management has not evolved over the past decades and drug combination used as first-line regimen still largely depends on clinician preferences. Aiming at paving the way for precision medicine, a large cohort of 372 HIV-negative patients diagnosed over a 20-year time period with locally advanced anal carcinoma was collected and carefully characterized at the clinical, demographic, histopathologic, immunologic, and virologic levels. Both the prognostic relevance of each clinicopathological parameter and the efficacy of different concurrent chemoradiation strategies were determined. Overall, the incidence of anal cancer peaked during the sixth decade (mean: 63.4) and females outnumbered males (ratio: 2.51). After completion of treatment, 95 (25.5%) patients experienced progression of persistent disease or local/distant recurrence and 102 (27.4%) died during the follow-up period (median: 53.8 months). Importantly, uni-multivariate analyses indicated that both negative HPV/p16ink4a status and aberrant p53 expression were far better predictors for reduced progression-free survival than traditional risk factors such as tumor size and nodal status. As for overall survival, the significant influences of age at diagnosis, p16ink4a status, cTNM classification as well as both CD3+ and CD4+ T-cell infiltrations within tumor microenvironment were highlighted. Cisplatin-based chemoradiotherapy was superior to both radiotherapy alone and other concurrent chemoradiation therapies in the treatment of HPV-positive tumors. Regarding their HPV-uninfected counterparts, frequent relapses were observed, whatever the treatment regimen administered. Taken together, our findings reveal that current anal cancer management and treatment have reached their limits. A dualistic classification according to HPV/p53 status should be considered with implications for therapy personalization and optimization.


Conflicting signals: Exploring the socioeconomic implications of gender discordant names.
We investigate the educational and employment consequences of having a gender discordant name - one that is also given to people of a different gender. People with discordant names may be more likely to experience stigma due to the conflicting signal between their gender and the perceptions of femininity or masculinity associated with their names. Our primary measure of discordance is based on the percentage of men and women with each first name, using a large administrative dataset from Brazil. We find that both men and women with gender discordant names attain significantly less education. Gender discordant names are also negatively and significantly associated with earnings though, after controlling for educational attainment, only people with the most discordant names have significantly lower earnings. These results are corroborated when using crowd-sourced gender perceptions of names in our dataset, which suggests that stereotypes and the judgments of others are a probable mechanism for the observed disparities.


Enzalutamide (formerly MDV3100) as a new therapeutic option for men with metastatic castration-resistant prostate cancer.
Enzalutamide marks the latest addition to the drugs currently approved by the US Food and Drug Administration for metastatic, castration-resistant prostate cancer (mCRPC). AFFIRMwas a phase III international randomized trial that evaluated the clinical utility of enzalutamide versus placebo in men with mCRPC who have failed prior docetaxel-containing chemotherapy. Enzalutamide showed a remarkable 37% decreased risk of death with a median overall survival of 18.4 months versus 13.6 months for those who received placebo. These findings confirm the validity of further targeting the androgen receptor as a valid therapeutic approach in prostate cancer despite emergence of castration resistance.


Characterization of organic membrane foulants in a forward osmosis membrane bioreactor treating anaerobic membrane bioreactor effluent.
In this study, two aerobic forward osmosis (FO) membrane bioreactors (MBR) were utilized to treat the effluent of mesophilic (35°C) and atmospheric (25°C) anaerobic MBRs, respectively. The results showed that the FO membrane process could significantly improve the removal efficiencies of N and P. Meanwhile, the flux decline of the FOMBR treating effluent of mesophilic AnMBR (M-FOMBR) was higher than that treating effluent of atmospheric AnMBR (P-FOMBR). The organic membrane foulants in the two FOMBRs were analyzed to understand the membrane fouling behavior in FO processes. It was found that the slightly increased accumulation of protein-like substances into external foulants did not cause faster flux decline in P-FOMBR than that in M-FOMBR. However, the quantity of organic matter tended to deposit or adsorb into FO membrane pores in P-FOMBR was less than that in M-FOMBR, which was accordance with the tendency of membrane fouling indicated by flux decline.


Hepatitis C virus modulates signal peptide peptidase to alter host protein processing.
Immunoevasins are viral proteins that prevent antigen presentation on major histocompatibility complex (MHC) class I, thus evading host immune recognition. Hepatitis C virus (HCV) evades immune surveillance to induce chronic infection; however, how HCV-infected hepatocytes affect immune cells and evade immune recognition remains unclear. Herein, we demonstrate that HCV core protein functions as an immunoevasin. Its expression interfered with the maturation of MHC class I molecules catalyzed by the signal peptide peptidase (SPP) and induced their degradation via HMG-CoA reductase degradation 1 homolog, thereby impairing antigen presentation to CD8+ T cells. The expression of MHC class I in the livers of HCV core transgenic mice and chronic hepatitis C patients was impaired but was restored in patients achieving sustained virological response. Finally, we show that the human cytomegalovirus US2 protein, possessing a transmembrane region structurally similar to the HCV core protein, targets SPP to impair MHC class I molecule expression. Thus, SPP represents a potential target for the impairment of MHC class I molecules by DNA and RNA viruses.


Hypocalcaemia induced by glucocorticoids in a child with hypoparathyroidism treated with 1-alpha-hydroxyvitamin D3.
Glucocorticoids tend to lower the intestinal absorption of calcium, leading to a negative calcium balance. A 7-year-old girl with hypoparathyroidism was maintained as normocalcaemic on 1-alpha-hydroxyvitamin D3 (1 alpha D3) and calcium gluconate lactate. During an episode of aplastic anaemia she was treated with prednisolone, with a subsequent dramatic fall of serum calcium despite 1 alpha D3 treatment and serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in the high-normal range. Glucocorticoids seem to have interfered directly with cellular events responsible for intestinal absorption of calcium.


Polydnavirus infection inhibits translation of specific growth-associated host proteins.
The wasp Campoletis sonorensis injects a polydnavirus (CsPDV) along with its egg during parasitization of Heliothis virescens larvae. CsPDV protects the wasp egg and larvae by selectively disabling the host's cellular immune response, and by altering host physiology, growth, and development. Among the changes in host physiology brought about by CsPDV infection is a rapid, and specific decline in the translation of fat body mRNAs encoding selected major plasma proteins. Translational inhibition of the synthesis of all storage protein monomers, p82 (Riboflavin binding hexamer), and p74/p76 (arylphorin), occurs upon infection with CsPDV. Moreover, the prewandering peak of the plasma enzyme juvenile hormone esterase (JHE) was blocked by CsPDV injection. Northern blotting of fat body mRNA demonstrated that transcript levels of storage proteins were not affected by infection. Plasma titers of the iron binding proteins transferrin (p72) and ferritin (p24/26), and of the plasma juvenile hormone binding protein (p25) were not changed by CsPDV infection. That storage protein and JHE synthesis are translationally suppressed, while the synthesis of other plasma proteins continues apace, suggests that CsPDV infection may lead to translational discrimination among available mRNAs in CsPDV infected fat bodies. The effect of this translational discrimination is to shunt host resources away from larval growth and adult development, which presumably makes them available to the developing endoparasitoid.


Short reaction times coupled with alkalization improves the release of phosphorus from Al-waste activated sludge.
In this study, the performance and mechanism of P release from Al-waste activated sludge (WAS) via wet-chemical treatment at different reaction times were investigated. The maximum P release (46% of TP) was achieved at 20 min when the pH was maintained at 2 during acidic treatment. During alkali treatment, the maximum P concentration (363.96 mg/L, 46.07%) was achieved at 10 min when pH was initially adjusted to 12. Acidic treatment took twice as long to achieve the same efficiency of released P as the alkali treatment. Furthermore, P release mainly originated from Al-P and Ca-P during acidic treatment and Al-P dissolution during alkali treatment. The cost of chemical consumption was 483.96 USD/ton TS sludge with acidic treatment, which was 8.49 times higher than that of alkali treatment without pH control. Thus, short reaction times (ca. 10 min) coupled with alkalization provide an effective approach for improving P release from Al-WAS.


Incorporating genetic and clinical data into the prediction of thromboembolism risk in patients with lymphoma.
The incorporation of genetic variables into risk scores for predicting venous thromboembolic events (VTE) could improve their capacity to identify those patients for whom thromboprophylaxis would be most beneficial. Proof-of-concept of this is provided by the TiC-ONCO score for predicting the risk of VTE in patients with solid tumours. Our aim was to develop a similarly improved tool-the TiC-LYMPHO score-for predicting VTE in patients with lymphoma. In a retrospective observational study of 208 patients with lymphoma, 31 (14.9%) were found to have experienced an episode of VTE either at the time of diagnosis or over the next 6 months. Clinical variables associated with VTE, determined via logistic regression analysis, plus the same genetic variables included in the TiC-ONCO score, were used to build the TiC-LYMPHO score algorithm. The sensitivity, specificity, predictive values and AUC of the TiC-LYMPHO, the Khorana and ThroLy scores were compared in the same population. The TiC-LYMPHO score showed a significantly higher AUC, sensitivity and NPV (0.783, 95.35% and 97.98% respectively) than the other scores. The ThroLy score showed a significantly higher specificity (96.43% vs. 54.49%; p < 0.0001) and PPV (37.50% vs. 26.36%; p = 0.0147) than the TiC-LYMPHO score, whereas its AUC, sensitivity and NPV were significantly lower (0.579, 19.35% and 86.48%, respectively). These results show that by incorporating genetic and clinical data into VTE risk assessment, the TiC-LYMPHO score can categorize patients with lymphoma better in terms of their risk of VTE and allow individualized thromboprophylaxis to be prescribed.


Biophysical characterization of α-amylase inhibitor Parvulustat (Z-2685) and comparison with Tendamistat (HOE-467).
Parvulustat is a small, highly active proteinaceous α-amylase inhibitor whose high-resolution NMR structure was recently solved in Frankfurt. Here, we present its biochemical and biophysical characterization. Several spectroscopic methods such as UV, fluorescence and CD were utilized to extract conformational changes upon modification of pH, temperature and chemical denaturant. Parvulustat revealed native like behavior over a wide range of denaturizing agents as reflected in terms of activity and thermodynamic data. In addition, spectroscopic and thermodynamic properties of Parvulustat were compared to the well-characterized Tendamistat. Despite the overall structural similarity, the thermodynamic stability of the two proteins is different. Our analysis led to the conclusion that Parvulustat is even more stable than Tendamistat. Furthermore, investigations on three C-terminally truncated Parvulustat derivatives indicate that the higher stability is caused by the long flexible C-terminus.


[Neurosurgical treatment of patients with severe thyroid-associated ophthalmopathy. Transcranial two-wall orbital decompression].
Thyroid-associated ophthalmopathy is most often seen in patients with Graves' disease. Surgical decompression is rarely used in Denmark. We report the results of neurosurgical two-wall orbital decompression in a consecutive group of patients. From 1997 to 2000 we used a uniform technique and a standardised follow-up of 52 orbital decompressions in 27 patients. All the patients were assessed preoperatively, and at one month and one year postoperatively. Visual acuity, proptosis (Hertel ophthalmometry), soft tissue involvement, and eye motility were recorded and graded according to a modified NOSPECS scale. As reduced visual acuity was present in only a few patients, it was not significantly changed during follow-up. No case with worsening was seen. Proptosis had decreased by a mean of 3.4 mm (0-9 mm) in the first month and by 3.9 mm (0-9 mm) at one year. Twenty-three patients had reduced eye motility before and 15 one month after operation. Eye motility improved in all 15 patients. Soft tissue involvement was present in 21 patients (40 eyes) before and in 10 patients (19 eyes) one month after operation and improved in all ten patients. Soft tissue involvement was further reduced one year after operation. A total of ten patients received glucocorticoid treatment before and during the operation. The corresponding figures were six at one month and four at one year. One patient had a lesion of one frontal branch of the facial nerve. No other side effects were encountered. Transcranial two-wall orbital decompression is effective in patients with thyroid-associated ophthalmopathy and complications seem rare. This surgical method is superior to other surgical approaches as regards the effect on eye motility.


Delayed diagnosis of intraperitoneal bladder perforation after blunt trauma.
Intraperitoneal urinary bladder perforation due to blunt trauma in intoxicated patients requires quick and accurate diagnosis. However, this is difficult to correctly diagnose in intoxicated patients because their symptoms can be masked. We describe a rare case of intraperitoneal urinary bladder perforation that occurred after blunt trauma. A 66-year-old intoxicated man stumbled, tripped on a stone step and landed on his lower abdomen, but felt no pain at the time. Two days later, he was diagnosed with intraperitoneal urinary bladder perforation, which was repaired by open surgery. Urinary bladder perforation should be considered when patients present with abdominal pain and decrease in urine volume following trauma.


Oxygen and Metabolism: Digesting Determinants of Antibiotic Susceptibility in the Gut.
Microbial metabolism is a major determinant of antibiotic susceptibility. Environmental conditions that modify metabolism, notably oxygen availability and redox potential, can directly fine-tune susceptibility to antibiotics. Despite this, relatively few studies have discussed these modifications within the gastrointestinal tract and their implication on in vivo drug activity and the off-target effects of antibiotics in the gut. In this review, we discuss the environmental and biogeographical complexity of the gastrointestinal tract in regard to oxygen availability and redox potential, addressing how the heterogeneity of gut microhabitats may modify antibiotic activity in vivo. We contextualize the current literature surrounding oxygen availability and antibiotic efficacy and discuss empirical treatments. We end by discussing predicted patterns of antibiotic activity in prominent microbiome taxa, given gut heterogeneity, oxygen availability, and polymicrobial interactions. We also propose additional work required to fully elucidate the role of oxygen metabolism on antibiotic susceptibility in the context of the gut.


Giant primary vaginal calculus secondary to vesicovaginal fistula with partial vaginal outlet obstruction in a 12-year-old girl.
A vesicovaginal fistula with vagina obstruction associated with vaginal calculi is an extremely rare medical condition. We report a giant primary vaginal calculus resulting from vesicovaginal fistula with partial vaginal outlet obstruction secondary to perineum trauma and surgery in a 12-year-old girl. Episiotomy was performed and the adhesive labia minora was split. After the removal of a giant calculus in the vagina, approximately 8 cm in diameter, the fistula tract was completely excised, followed by the repair of the vesicovagina fistula and the vagina. The patient was symptom-free at 6-month follow-up examination.


The impact of concussion on subsequent injury risk in elite junior Australian football athletes.
Concussion increases injury risk. However, this has not been investigated in junior Australian football and it is unknown whether the location, severity, and mechanism of subsequent injuries differ after concussion vs. non-concussion injury. Prospective cohort. 1455 elite adolescent male Australian footballers were tracked across seven seasons to determine whether subsequent injury risk was greater after concussion compared to non-concussion index injury using multilevel survival analysis. Mixed-effects logistic regression compared location and mechanism. Mixed-effects Poisson regression compared severity. Of 1455 athletes, 632 were injured and included in subsequent-injury analysis. There were no differences in injury incidence after a concussion compared to upper- (hazard ratio = 1.0, 0.6 to 1.9, P = 0.892; trivial effect) and lower (hazard ratio = 1.1, 0.6 to 1.9, P = 0.810; trivial effect) index injury, or in location. Subsequent injuries were more likely to be contact-based after a non-concussion injury than concussion (odds ratio = 4.6, 1.3 to 16.0; P = 0.017; large effect). There was no difference in subsequent injury severity after lower- (3.4 ± 3.0 missed matches; incidence rate ratio = 1.4, 0.9 to 2.1; P ≤ 0.117; small effect) and upper-limb injuries (3.4 ± 3.1 missed matches; incidence rate ratio = 1.4, 0.9 to 2.2; P = 0.189; small effect) compared to concussion (2.4 ± 2.0 missed matches). Subsequent injury risk, severity, and location in junior Australian football are similar following concussion compared to non-concussion index injuries, although contact injuries are less likely.


Anthropogenic protection alters the microbiome in intertidal mangrove wetlands in Hainan Island.
Intertidal mangrove wetlands are of great economic and ecological importance. The regular influence of tides has led to the microbial communities in these wetlands differing significantly from those in other habitats. In this study, we investigated the microbiomes of the two largest mangrove wetlands in Hainan Island, China, which have different levels of anthropogenic protection. Soil samples were collected from the root zone of 13 mangrove species. The microbial composition, including key functional groups, was assessed using Illumina sequencing. Bioinformatics analysis showed that there was a significant difference in the microbiomes between the protected Bamen Bay and the unprotected Dongzhai Bay. The overall microbiome was assigned into 78 phyla and Proteobacteria was the most abundant phylum at both sites. In the protected wetland, there were fewer marine-related microbial communities, such as sulfate-reducing bacteria, and more terrestrial-related communities, such as Verrucomicrobia methanotrophs. We also observed distinct microbial compositions among the different mangrove species at the protected site. Our data suggest that the different microbiomes of the two mangrove wetlands are the result of a complex interaction of the different environmental variables at the two sites.


The relationship between gastric emptying, plasma cholecystokinin, and peptide YY in critically ill patients.
Cholecystokinin (CCK) and peptide YY (PYY) are released in response to intestinal nutrients and play an important physiological role in regulation of gastric emptying (GE). Plasma CCK and PYY concentrations are elevated in critically ill patients, particularly in those with a history of feed intolerance. This study aimed to evaluate the relationship between CCK and PYY concentrations and GE in critical illness. GE of 100 mL of Ensure meal (106 kcal, 21% fat) was measured using a 13C-octanoate breath test in 39 mechanically ventilated, critically ill patients (24 males; 55.8 +/- 2.7 years old). Breath samples for 13CO2 levels were collected over the course of 4 hours, and the GE coefficient (GEC) (normal = 3.2 to 3.8) was calculated. Measurements of plasma CCK, PYY, and glucose concentrations were obtained immediately before and at 60 and 120 minutes after administration of Ensure. GE was delayed in 64% (25/39) of the patients. Baseline plasma CCK (8.5 +/- 1.0 versus 6.1 +/- 0.4 pmol/L; P = 0.045) and PYY (22.8 +/- 2.2 versus 15.6 +/- 1.3 pmol/L; P = 0.03) concentrations were higher in patients with delayed GE and were inversely correlated with GEC (CCK: r = -0.33, P = 0.04, and PYY: r = -0.36, P = 0.02). After gastric Ensure, while both plasma CCK (P = 0.03) and PYY (P = 0.02) concentrations were higher in patients with delayed GE, there was a direct relationship between the rise in plasma CCK (r = 0.40, P = 0.01) and PYY (r = 0.42, P < 0.01) from baseline at 60 minutes after the meal and the GEC. In critical illness, there is a complex interaction between plasma CCK, PYY, and GE. Whilst plasma CCK and PYY correlated moderately with impaired GE, the pathogenetic role of these gut hormones in delayed GE requires further evaluation with specific antagonists.


Bayesian estimation of optimal craniofacial reconstructions.
Forensic craniofacial reconstruction (CFR) aims at estimating the facial outlook associated to an unknown skull for victim identification. Computerized CFR techniques are essentially a virtual mimicking of manual CFR techniques and all share the same conceptual model-based framework. We propose a fully automated Bayesian based statistical framework estimating the most probable face, according to a known craniofacial model (CFM), given the, possibly inaccurate, skull data. A multivariate Gaussian distribution is assumed for the shape parameters of the CFM, only allowing face-like solutions. The CFM is improved by encoding tissue depth differently as an extra value for 52 landmarks on the face and by incorporating gray-valued texture information. A fully automated and consistent technique is obtained by the use of an implicit target skull representation (TSR). The most plausible face associated to the target skull is calculated using an expectation-maximization procedure that is robust to small (noise) and/or gross errors (outliers). A clinical database of 12 individuals is used for simulating realistic reconstruction scenarios. Validation is performed in terms of reconstruction accuracy and recognition success. Within the same EM reconstruction framework, the proposed procedure is compared to alternative reconstructions using different target skull representations and different CFMs incorporating various amounts of covariance. The results indicate that the proposed CFM performs better than the other models. Furthermore, the use of the implicit TSR generates more consistent and better results compared to a realistic landmark based skull representation. Finally, these results also confirm that the Bayesian framework formulation is indeed robust against noise and outliers in the skull data.


Stool microbiome dataset of the critically endangered Puerto Rican parrot (Amazona vittata).
The Puerto Rican parrot (Amazona vittata), endemic to Puerto Rico, is the only native parrot in the United States and is classified as a critically endangered species. There are two captive populations of A. vittata in Puerto Rico located in the Iguaca Aviary in El Yunque National Rainforest and the José L. Vivaldi Aviary in the Río Abajo Forest. To characterize the microbial communities of A. vittata's stool, 21 stool samples from captive birds were collected, DNA extracted and sequenced using Illumina MiSeq. Sequences were processed by removing host sequences (A. vittata genome) and low-quality reads. Taxonomic and functional profiles were generated using MG-RAST. The most abundant domain was Bacteria (96%), followed by Virus (3%), and Eukaryota (0.6%). Among the functions in the microbiome, the most abundant was related to carbohydrates (14%), followed by clustering-based subsystems (12%), protein metabolism (8%), and amino acids and derivatives (7%). This dataset describes the stool microbiome of A. vittata using a metagenomics approach. Data can be used to develop holistic conservation strategies for A. vittata and other endangered birds, as well as to search for bioprospects with potential biomedical and biotechnological applications.


L-1416, a novel MDR reversing agent with possible reduced calcium antagonism.
Multidrug efflux transporter P-glycoprotein (P-gp) is highly expressed on membrane of tumor cells and supposed to be implicated in the resistance to tumor chemotherapy. However, currently none of P-gp inhibitors has been approved by Food and Drug Administration not only due to toxicity but also lack of efficacy in clinical trials. To solve the problem, our lab synthesized a novel compound named 1416 [1-(2,6-dimethylphenoxy)-3,4-dimethoxyphenylethylamino) propane hydrochloride] with the hope of high P-gp inhibition and low side effects. Caco-2 cell monolayer and tumor bearing mice were used to evaluate the P-gp inhibition of 1416 in vitro and in vivo, respectively. One of its potential side effects, calcium antagonism was also evaluated. Results showed that 1416 showed a similar P-gp inhibition as verapamil in Caco-2 cell monolayer. No significant difference was observed in antitumor enhancement when the optical isomers of 1416 (D-1416 and L-1416) were co-administered with vinblastine. In calcium antagonism, L-1416 showed less calcium inhibition than both D-1416 and verapamil. The novel compound 1416 could significantly increase the antitumor effects of cytotoxic drugs and one of its optical isomers, L-1416, might be more promising due to its potential low calcium antagonism.


Coverage, determinants of use and repurposing of long-lasting insecticidal nets two years after a mass distribution in Lihir Islands, Papua New Guinea: a cross-sectional study.
Universal coverage with long-lasting insecticidal nets (LLINs) is an essential component of malaria control programmes. Three-yearly mass distribution of LLINs in Papua New Guinea (PNG) has been successful in reducing infection transmission since 2009, but malaria prevalence ramped up from 2015 onwards. Although LLIN universal coverage is mostly achieved during these campaigns, it may not be related with net use over time. Uses given to LLINs and non-compliance of this strategy were evaluated. A knowledge, attitude and practice (KAP) cross-sectional study was conducted in Lihir Islands, PNG, 2-2.5 years after the last LLIN mass distribution campaign. Data on bed net ownership, use and maintenance behaviour was collected using a household questionnaire administered by trained community volunteers. Logistic regression models were used to identify factors associated with owning at least one LLIN and sleeping under a LLIN the previous night. Among 2694 households surveyed, 27.4 % (95 % CI: 25.8-29.2) owned at least one LLIN and 8.7 % (95 % CI: 7.6-9.8) had an adequate LLIN coverage (at least one LLIN for every two people). Out of 13,595 individuals in the surveyed households, 13.6 % (95 % CI: 13.0--4.2) reported having slept under a LLIN the preceding night. Determinants for sleeping under LLIN included living in a household with adequate LLIN coverage [adjusted OR (aOR) = 5.82 (95 % CI: 3.23-10.49)], household heads knowledge about LLINs [aOR = 16.44 (95 % CI: 8.29-32.58)], and female gender [aOR = 1.92 (95 % CI: 1.53-2.40)] (all p-values < 0.001). LLIN use decreased with older age [aOR = 0.29 (95 % CI: 0.21-0.40) for ≥ 15 year-olds, aOR = 0.38 (95 % CI: 0.27-0.55) for 5-14 year-olds] compared to < 5 year-olds (p-value < 0.001). Knowledge on the use of LLIN was good in 37.0 % of the household heads. Repurposed nets were reported serving as fishing nets (30.4 %), fruits and seedlings protection (26.6 %), covering up food (19.0 %) and bed linen (11.5 %). Two years after mass distribution, LLIN coverage and use in Lihir Islands is extremely low. Three yearly distribution campaigns may not suffice to maintain an acceptable LLIN coverage unless knowledge on maintenance and use is promoted trough educational campaigns.


Prevalence of gastrointestinal nematodes in growing pigs in Kabale District in Uganda.
During the last 30 years, pig production in Uganda and neighbouring counties has increased markedly. Pigs are mainly kept as a source of income for small-scale farmers; however, the pig production is subject to several constraints, one of them being worm infections. A study was carried out in rural communities in Kabale District in the South Western part of Uganda in September and October 2007 in order to estimate the prevalence of gastrointestinal nematode parasites in pigs based on coprological examination. Fifty-six households were randomly selected and visited. Housing system and deworming history were recorded. Faeces was sampled from rectum of one to five pigs (age, 3-12 months) per household. A total of 106 pigs were examined coprologically of which 91% excreted nematode eggs. The following prevalences of nematode eggs were recorded: strongyles (89%), Ascaris suum (40%), Trichuris suis (17%) and spiruroid eggs (48%). On household level, rearing pigs on slatted floors in pens significantly reduced the faecal egg excretion of strongyle eggs with almost 80% (p=0.010) and a significant interaction between floor type and anthelmintic treatment was found for spiruroids (p=0.037). Fifteen T. suis egg positive pigs were selected for post-mortem examination of the gastrointestinal tract. The post-mortem examinations revealed that 93% pigs were infected with Oesophagostomum spp. (worm burden, min-max 10-2,180), 73% with A. suum (1-36), 67% with T. suis (6-58), and 20% with Hyostrongylus rubidus (worms not quantified). In general, nematode infections were widespread and polyparasitism common in pigs in Uganda. However, worm burdens were moderate which may be related to recent deworming or to the practice of rearing pigs on slatted floors in wooden elevated pens.


Anticalcification strategies to increase bioprosthetic valve durability.
In recent years, there has been a revival in the use of bioprosthetic valves as aortic substitutes. For example, during 2008 in Germany, among 12,397 patients who underwent isolated aortic valve procedures, 78% received a biological prosthesis and 21% a mechanical valve, while only 1% underwent valve repair. However, whilst this situation is the reverse of that during the 1990s, the question must be asked as to whether this is simply a fluctuating fashion, or a reflection of other factors.


The role of patient-physician relationship on health-related quality of life and pain in cancer patients.
Health-related quality of life (HRQOL) and pain are important supportive cancer care outcomes. The patient-provider relationship, a modifiable care experience, has been linked to healthcare outcomes; however, less is known about associations between patient-provider relationship and supportive care outcomes in cancer patients. We examined the role of multiple aspects of the patient-provider relationship in explaining patterns of HRQOL and pain among breast and lung cancer patients. Our analysis included 283 breast and lung cancer patients from two cancer centers. Clinical data and survey data on patient sociodemographic factors, physical and mental HRQOL, pain, and patient-physician relationship (i.e., doctor's respectfulness, time spent with doctors, patient involvement in decision-making, satisfaction with care, and following doctor's advice/treatment plan) were collected at baseline and during treatment. We estimated adjusted modified Poisson regression models to assess associations between patient-physician relationship factors and physical and mental HRQOL and pain. Compared with patients reporting suboptimal respect from doctors, patients reporting optimal respect were less likely to report below average physical HRQOL (adjusted risk ratio (ARR), 0.73; 95%CI, 0.62-0.86), below average mental HRQOL (ARR, 0.71; 95%CI, 0.54-0.93), and moderate-to-severe pain (ARR, 0.53; 95%CI, 0.35-0.79). Patients reporting optimal involvement in care decision-making and patients who reported following their doctor's advice/treatment plan were less likely to report below average mental HRQOL than their respective counterparts (ARR, 0.64; 95%CI, 0.50-0.83; ARR, 0.65; 95%CI, 0.48-0.86). Multiple patient-physician relationship factors account for variations in HRQOL and pain in cancer patients. These findings provide insight into potential targets for improving the patient-provider relationship and supportive cancer care outcomes.


Wound healing of grafts in congenitally opaque infant corneas.
Wound healing, determined by uneventful suture removal, was evaluated in 28 corneal transplants (20 eyes) with congenital corneal opacities. Seven transplants in seven eyes with the typical central corneal opacities of Peters' anomaly had suture removal between 17 and 90 days postoperatively. All seven transplants remained transparent. Corneal grafts for sclerocornea or regrafts in sclerocornea healed much more quickly than those in eyes with Peters' anomaly (as early as four days postoperatively in the 13 most recent cases). In these corneas suture microabscesses and superficial neovascularization of the wound were signs indicating wound healing and also a host inflammatory response that led to graft rejection if the sutures were not removed.


The circulating ANGPTL8 levels show differences among novel subgroups of adult patients with diabetes and are associated with mortality in the subsequent 5 years.
ANGPTL8, an important regulator of glucose and lipid metabolism, is associated with diabetes, but the role of ANGPTL8 in the outcomes of novel subgroups of diabetes remains unclear. To assess the circulating ANGPTL8 levels in novel subgroups of diabetes and their association with health outcomes, we performed a data-driven cluster analysis (k-means) of patients with newly diagnosed diabetes (741 patients enrolled from 2011 through 2016) from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a longitudinal (REACTION) study. The primary outcomes were mortality from all causes and cardiovascular diseases (CVD), and the secondary outcome was any cardiovascular event. Comparisons among groups were performed using the Kruskal-Wallis test, and the correlations between variables were assessed using the Pearson correlation test. Logistic regression was used to detect associations between the risk of outcomes and the ANGPTL8 levels. We identified four replicable clusters of patients with diabetes that exhibited significantly different patient characteristics and risks of all-cause mortality. The serum ANGPTL8 levels in the cluster of mild age-related diabetes (MARD), severe insulin-resistant diabetes (SIRD), and severe insulin-deficient diabetes (SIDD) were significantly higher than those in the mild obesity-related diabetes (MOD) cluster (685.01 ± 24.50 vs. 533.5 ± 18.39, p < 0.001; 649.69 ± 55.83 vs. 533.5 ± 18.39, = 0.040; 643.29 ± 30.89 vs. 533.5 ± 18.39, p = 0.001). High circulating ANGPTL8 levels were more highly associated with a greater hazard of all-cause mortality (quartile 4 vs 1: risk ratio [RR] 3.23, 95% CI 1.13-9.22; per unit increase in the Z score: RR 1.53, 95% CI 1.17-2.01) than low circulating ANGPTL8 levels. In conclusion, this 5-year follow-up REACTION study revealed that the circulating ANGPTL8 levels show differences among novel subgroups of adult patients with diabetes and are associated with all-cause mortality in the subsequent 5 years.


Efficacy of seasonal pandemic influenza hemagglutinin DNA vaccines delivered by electroporation against a seasonal H1N1 virus challenge in mice.
Prophylactic DNA vaccines against the influenza virus are promising alternatives to conventional vaccines. In this study, we generated two candidate gene-based influenza vaccines encoding either the seasonal or pandemic hemagglutinin antigen (HA) from the strains A/New Caledonia/20/99 (H1N1) (pV1A5) and A/California/04/2009 (H1N1) (pVEH1), respectively. After verifying antigen expression, the immunogenicity of the vaccines delivered intramuscularly with electroporation was tested in a mouse model. Sera of immunized animals were tested in hemagglutination inhibition assays and by ELISA for the presence of HA-specific antibodies. HA-specific T-cells were also measured in IFN-γ ELISpot assays. The protective efficacy of the candidate influenza vaccines was evaluated by measuring mortality rates and body weight after a challenge with 100 LD(50) of mouse-adapted A/New Caledonia/20/99 (H1N1). Mice immunized with either one of the two vaccines showed significantly higher T cell and humoral immune responses (P<0.05) than the pVAX1 control group. Additionally, the pV1A5 vaccine effectively protected the mice against a lethal homologous mouse-adapted virus challenge with a survival rate of 100% compared with a 40% survival rate in the pVEH1 vaccinated group (P<0.05). Our study indicates that the seasonal influenza DNA vaccine completely protects against the homologous A/New Caledonia/20/99 virus (H1N1), while the pandemic influenza DNA vaccine only partially protects against this virus.


The landscape of tumors-infiltrate immune cells in papillary thyroid carcinoma and its prognostic value.
Thyroid cancer is a very common malignant tumor in the endocrine system, while the incidence of papillary thyroid carcinoma (PTC) throughout the world also shows a trend of increase year by year. In this study, we constructed two models: ICIscore and Riskscore. Combined with these two models, we can make more accurate and reasonable inferences about the prognosis of PTC patients. We selected 481 PTC samples from TCGA and 147 PTC samples from GEO (49 samples in GSE33630, 65 samples in GSE35570 and 33 samples in GSE60542). We performed consistent clustering for them and divided them into three subgroups and screened differentially expressed genes from these three subgroups. Then we divided the differential genes into three subtypes. We also distinguished the up-regulated and down-regulated genes and calculated ICIscore for each PTC sample. ICIscore consists of two parts: (1) the PCAu was calculated from up-regulated genes. (2) the PCAd was calculated from down-regulated genes. The PCAu and PCAd of each sample were the first principal component of the relevant gene. What's more, we divided the patients into two groups and constructed mRNA prognostic signatures. Additionally we also verified the independent prognostic value of the signature. Though ICIscore, we were able to observe the relationship between immune infiltration and prognosis. The result suggests that the activation of the immune system may have both positive and negative consequences. Though Riskscore, we could make more accurate predictions about the prognosis of patients with PTC. Meanwhile, we also generated and validated the ICIscore group and Riskscore group respectively. All the research results show that by combining the two models constructed, ICIscore and Riskscore, we can make a more accurate and reasonable inference about the prognosis of patients with clinical PTC patients. This suggests that we can provide more effective and reasonable treatment plan for clinical PTC patients.


Childhood survivors of high-risk neuroblastoma show signs of immune recovery and not immunosenescence.
Neuroblastoma survivors show signs of immunosenescence early after therapy in CD8+ T cell compartment and elevated plasma TNF-α but in later follow-up immune recovery comes into play. Whether the recovery phenotype is long lasting or transient remains to be elucidated, however, late adverse effects often occur in childhood cancer survivors.


Effects of preoperative oral carbohydrate administration combined with postoperative early oral intake in elderly patients undergoing hepatectomy with acute-phase inflammation and subjective symptom burden: A prospective randomized controlled study.
Enhanced recovery after surgery (ERAS) has received increasing attention. Preoperative oral carbohydrate and postoperative early oral feeding (POC-PEOF) as the basic nutrition administration in the ERAS program suffers from low adherence. The role and benefits of administering POC-PEOF in elderly patients with hepatocellular carcinoma (HCC) are unclear. Therefore, the randomized controlled trial evaluated the effects of POC-PEOF in elderly patients with HCC undergoing hepatectomy with inflammation and patient self-reported symptom burden compared with the corresponding outcomes of traditional fasting protocols. Elderly patients with HCC (n = 126) were randomly assigned to two groups using the sealed envelope technique. Sixty-three patients were included in the intervention (POC-PEOF) group and received POC-PEOF administration, whereas the 63 patients in the control (FAST) group underwent conventional fasting. Acute-phase inflammation markers, patient self-reported symptom burdens, and postoperative outcomes were compared between the two groups. The average age was 69.60 ± 5.00 years in the POC-PEOF group and 70.44 ± 6.15 years in the FAST group. Compared to prolonged fasting, POC-PEOF achieved significant positive results, including lower overall levels of inflammatory response mediators (CRP, IL-6) on postoperative day (POD) 1, POD 3, and POD 5 (P < 0.05), lower patient self-reported symptom burdens of thirst, hunger, anxiety and nausea (P < 0.05), faster gastrointestinal function return with shortened times to first flatus and first defecation (48.31 ± 13.24 h vs. 96.26 ± 23.12 h and 72.87 ± 21.12 h vs. 144.34 ± 23.31 h, and P = 0.034 and P = 0.013, respectively). Furthermore, the average postoperative hospitalization duration in the POC-PEOF group was shorter than that in the FAST group (6.93 ± 0.98 d vs. 8.12 ± 1.15 d, P = 0.042). There was no significant difference of total complications between the groups (25.39 % vs 36.51 %, RR 0.696, 95 % CI 0.408-0.187, P = 0.177). POC-PEOF helps lessen acute-phase inflammation and relieves the subjective symptom burden, which can ensure better positive postoperative outcomes in elderly HCC patients undergoing hepatectomy.


Outcomes of young active patients with displaced clavicle fractures treated with Rockwood pin.
Various fixation techniques have been described for midshaft clavicle fractures in the literature. We hypothesized that use of the Rockwood pin for fixation of displaced midshaft clavicle fractures would result in favorable outcomes in a young active cohort. Patients aged 10-35 years who underwent Rockwood clavicle pin fixation at a single institution were identified. Preoperative and postoperative radiographs were reviewed and assessed for fracture characteristics, postoperative alignment, and radiographic union. Postoperative outcome scores were obtained. A total of 39 patients (age 17.3 ± 3.9 years) with clavicle fracture treated with Rockwood pin were identified. Radiographic review demonstrated that 88% of fractures were 100%, or more, displaced, and surgery achieved near-anatomic reduction in 92% of cases. Average time to radiographic union was 2.3 ± 0.8 months, and average time to clinical union was 2.5 ± 0.3 months. One patient required revision for nonunion (3%). Complete outcome responses were obtained for 24 patients, with an average 40 ± 27.7 months of follow-up. Mean Total Clavicle Functional score was 2.75 ± 3.6 for minor patients. For adult patients, Nottingham Clavicle score was 90.7 ± 10.7, mean American Shoulder and Elbow Society score was 92.4 ± 11.2, and mean Single Assessment Numerical Evaluation score was 88.8 ± 21.5. 77% of adults reported no long-term functional limitation; 54% reported a bump at the prior fracture site, but 100% reported satisfaction with shoulder appearance. In our cohort of young active patients, treatment with Rockwood pin allowed for anatomic reduction, healing with a low nonunion rate, and favorable patient reported outcomes.


The nervous control of rat glucagon secretion in vivo.
In order to study the efferent pathways of the nervous regulation of rat A and B cells, portal blood samples were obtained in vivo without interruption of the blood flow. Glucagon, insulin and catecholamines were determined and hepatic blood flow (EHBF) was estimated by a Brome-Sulfone-Phtaleine extraction method. Carotid blood pressure was monitored and a normal volaemia was maintained. Stimulation of the right vagus nerve increased EHBF and the releases of glucagon and insulin. Stimulation of splanchnic nerve increased the glucagon and catecholamine secretions and decreased that of insulin. Acute hypovolaemia as induced by blood withdrawal, caused hormonal consequences similar to those of splanchnic stimulation. It is suggested that the nervous control of pancreatic islets plays an important role in the rat species. Assessment of the haemodynamic status is critical for the valid interpretation of pancreatic hormone concentrations in experimental conditions. A sympathetic stimulation can account for the high glucagon and relatively low insulin secretions which characterize the hormonal pattern of stress.


Development of a phosphorous-based biorefinery process for producing lignocellulosic functional materials from coconut wastes.
This work aimed to develop a phosphorous-based biorefinery process for obtaining phosphorylated lignocellulosic fractions in a one-pot protocol from coconut fiber. Natural coconut fiber (NCF) was mixed with 85 % m/m H3PO4 at 70 °C for 1 h to yield the modified coconut fiber (MCF), aqueous phase (AP), and coconut fiber lignin (CFL). MCF was characterized by its TAPPI, FTIR, SEM, EDX, TGA, WCA, and P content. AP was characterized regarding its pH, conductivity, glucose, furfural, HMF, total sugars and ASL contents. CFL structure was evaluated by FTIR, 1H, 31P and 1H-13C HSQC NMR, TGA and P content and was compared to that of milled wood lignin (MWL). It was observed that MCF and CFL were phosphorylated during the pulping (0.54 and 0.23 % wt., respectively), while AP has shown high sugar levels, low inhibitor content, and some remaining phosphorous. The phosphorylation of MCF and CFL also showed an enhancement of their thermal and thermo-oxidative properties. The results show that a platform of functional materials such as biosorbents, biofuels, flame retardants, and biocomposites can be created through an eco-friendly, simple, fast, and novel biorefinery process.


Isokinetic analysis of ankle and ground reaction forces in runners and triathletes.
To analyze and compare the vertical component of ground reaction forces and isokinetic muscle parameters for plantar flexion and dorsiflexion of the ankle between long-distance runners, triathletes, and nonathletes. Seventy-five males with a mean age of 30.26 (±6.5) years were divided into three groups: a triathlete group (n=26), a long-distance runner group (n = 23), and a non-athlete control group. The kinetic parameters were measured during running using a force platform, and the isokinetic parameters were measured using an isokinetic dynamometer. The non-athlete control group and the triathlete group exhibited smaller vertical forces, a greater ground contact time, and a greater application of force during maximum vertical acceleration than the long-distance runner group. The total work (180º/s) was greater in eccentric dorsiflexion and concentric plantar flexion for the non-athlete control group and the triathlete group than the long-distance runner group. The peak torque (60º/s) was greater in eccentric plantar flexion and concentric dorsiflexion for the control group than the athlete groups. The athlete groups exhibited less muscle strength and resistance than the control group, and the triathletes exhibited less impact and better endurance performance than the runners.


Aurora B kinase: a potential drug target for cancer therapy.
Ensuring genetic integrity is essential during the cell cycle to avoid aneuploidy, one of the underlying causes of malignancies. Aurora kinases are serine/threonine kinase that play a vital role in maintaining the genomic integrity of the cells. There are three forms of aurora kinases in the mammalian cells, which are highly conserved and act together with several other proteins to control chromosome alignment and its equal distribution to daughter cells in mitosis and meiosis. We provide here a detailed analysis of Aurora B kinase (ABK) in terms of its expression, structure, function, disease association and potential therapeutic implications. ABK plays an instrumental in mitotic entry, chromosome condensation, spindle assembly, cytokinesis, and abscission. Small-molecule inhibitors of ABK are designed and synthesized to control cancer progression. A detailed understanding of ABK pathophysiology in different cancers is of great significance in designing and developing effective therapeutic strategies. In this review, we have discussed the physiological significance of ABK followed by its role in cancer progression. We further highlighted available small-molecule inhibitors to control the tumor proliferation and their mechanistic insights.


Sclerosing-cholangitis-like changes in pancreatic disease.
In a retrospective analysis of endoscopic cholangiograms in 66 patients with pancreatic disease we found sclerosing-cholangitis-like changes in 83% of cases. Excluding patients with intrapancreatic constriction of the distal common bile duct, 70% of patients with chronic pancreatitis, 60% with acute pancreatitis and 100% with pancreatic cancer had these abnormalities. The possible significance of these changes, which are unlikely to be secondary to pancreatic disease, are discussed with reference to the published literature on sclerosing cholangitis.


COVID-19 pandemic in Africa: Is it time for water, sanitation and hygiene to climb up the ladder of global priorities?
In the current pandemic context, it is necessary to remember the lessons learned from previous outbreaks in Africa, where the incidence of other diseases could rise if most resources are directed to tackle the emergency. Improving the access to water, sanitation and hygiene (WASH) could be a win-win strategy, because the lack of these services not only hampers the implementation of preventive measures against SARS-CoV-2 (e.g. proper handwashing), but it is also connected to high mortality diseases (for example, diarrhoea and lower respiratory infections (LRI)). This study aims to build on the evidence-based link between other LRI and WASH as a proxy for exploring the potential vulnerability of African countries to COVID-19, as well as the role of other socioeconomic variables such as financial sources or demographic factors. The selected methodology combines several machine learning techniques to single out the most representative variables for the analysis, classify the countries according to their capacity to tackle public health emergencies and identify behavioural patterns for each group. Besides, conditional dependences between variables are inferred through a Bayesian network. Results show a strong relationship between low access to WASH services and high LRI mortality rates, and that migrant remittances could significantly improve the access to healthcare and WASH services. However, the role of Official Development Assistance (ODA) in enhancing WASH facilities in the most vulnerable countries cannot be disregarded, but it is unevenly distributed: for each 50-100 US$ of ODA per capita, the probability of directing more than 3 US$ to WASH ranges between 48% (Western Africa) and 8% (Central Africa).


Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved.
Inflammatory bowel diseases (IBD), represented by ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic inflammation of the gastrointestinal tract, what leads to diarrhea, malnutrition, and weight loss. Depression of the growth hormone-insulin-like growth factor-1 axis (GH-IGF-1 axis) could be responsible of these symptoms. We demonstrate that long-term treatment (54 weeks) of adult CD patients with adalimumab (ADA) results in a decrease in serum IGF-1 without changes in serum IGF-1 binding protein (IGF1BP4). These results prompted us to conduct a preclinical study to test the efficiency of IGF-1 in the medication for experimental colitis. IGF-1 treatment of rats with DSS-induced colitis has a beneficial effect on the following circulating biochemical parameters: glucose, albumin, and total protein levels. In this experimental group we also observed healthy maintenance of colon size, body weight, and lean mass in comparison with the DSS-only group. Histological analysis revealed restoration of the mucosal barrier with the IGF-1 treatment, which was characterized by healthy quantities of mucin production, structural maintenance of adherers junctions (AJs), recuperation of E-cadherin and β-catenin levels and decrease in infiltrating immune cells and in metalloproteinase-2 levels. The experimentally induced colitis caused activation of apoptosis markers, including cleaved caspase 3, caspase 8, and PARP and decreases cell-cycle checkpoint activators including phosphorylated Rb, cyclin E, and E2F1. The IGF-1 treatment inhibited cyclin E depletion and partially protects PARP levels. The beneficial effects of IGF-1 in experimental colitis could be explained by a re-sensitization of the IGF-1/IRS-1/AKT cascade to exogenous IGF-1. Given these results, we postulate that IGF-1 treatment of IBD patients could prove to be successful in reducing disease pathology.


The effects of conventional, warm and cold acupressure on the pain perceptions and beta-endorphin plasma levels of primiparous women in labor: A randomized controlled trial.
This study was performed to determine the impact of different acupressure procedures, performed on women's hands during labor, on β-endorphin plasma levels and labor pain perception. Randomized controlled experimental trial SETTING AND PARTICIPANTS: This study was conducted with 140 pregnant women in the delivery rooms of a university research and training hospital and a state hospital in a province in the Black Sea Region of Turkey. This study was conducted with three experimental groups (who had conventional, warm and cold acupressure on their LI4 acupressure point) and one control group (no acupressure). Each group included 35 pregnant women. The data were collected using a personal information form, the Labor Intervention Follow-up Form, the Visual Analog Scale (VAS) and the Verbal Category Scale (VCS). Its main outcomes were the women's labor pain perceptions and β-endorphin plasma levels. The experimental and control groups had homogeneous introductory characteristics. The experimental groups had significantly higher mean VAS and VCS posttest scores than the control group (p<0.001). The experimental groups' mean posttest β-endorphin plasma levels were also significantly higher (p<0.05). In this study, conventional, warm and cold acupressure reduced the women's labor pain and increased their β-endorphin plasma levels. Midwives can use acupressure to reduce labor pain.


Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry serum protein profiling to identify nasopharyngeal carcinoma.
Diagnosis of nasopharyngeal carcinoma (NPC) at an early disease stage is important for successful treatment and improving the outcome of patients. The use of serum protein profiles and a classification tree algorithm were explored to distinguish NPC from noncancer. Serum samples were applied to metal affinity protein chips to generate mass spectra by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Protein peak identification and clustering were performed using the Biomarker Wizard software. Proteomic spectra of serum samples from 50 NPC patients and 54 noncancer controls were used as a training set and a classification tree with 6 distinct protein masses was generated by using Biomarker Pattern software. The validity of the classification tree was then challenged with a blind test set including another 20 NPC patients and 25 noncancer controls. The software identified an average of 93 mass peaks/spectrum and 6 of the identified peaks were used to construct the classification tree. The classification tree correctly determined 83% (123 of 149) of the test samples with 83% (58 of 70) of the NPC samples and 82% (65 of 79) of the noncancer samples. In a combination of the serum protein profiles with Epstein-Barr (EBV) nuclear antigen 1 (EBNA1 IgA) test, the diagnostic sensitivity and specificity were increased to 99% and 96%, respectively. The results suggest that SELDI-TOF-MS serum protein profiles could discriminate NPC from noncancer. The combination of serum protein profiles with an EBV antibody serology test could further improve the accuracy of NPC screening.


A correlational study of socioeconomic factors and the prevalence of hikikomori in Japan from 2010 to 2019.
Although several surveys have suggested that socioeconomic factors function as background variables for the incidence of hikikomori (prolonged social withdrawal), no research has directly examined whether socioeconomic indicators increase the incidence of hikikomori. This study aimed to examine the relationship between socioeconomic factors and the incidence of hikikomori using data from eight cross-sectional studies conducted by our group between 2010 and 2019. We used socio-economic data from national surveys and collected the demographic data of members of a multi-branch Japanese association for family members of hikikomori patients for the period of 2010-2019. The results of the partial correlation analysis showed that the incidence probability of hikikomori increased in tandem with unemployment rates and household income. Further, the associations were positively strong in the 2010-2015 research period; however, they were absent, weak, or medium in the 2016-2019 research period. The findings suggest that socioeconomic factors relate to the increase in hikikomori, and that these factors should be considered when identifying the individual or cultural factors that cause hikikomori.


Thermal degradation characteristics and gasification kinetics of camel manure using thermogravimetric analysis.
In this work, the sustainable valorisation of camel manure has been studied using thermogravimetric analysis. The gasification tests were performed from ambient conditions to 950 °C at 10, 20, and 50 °C/min under an O2 environment. The TGA data were applied to determine the kinetics of the O2 gasification. Single-heating rate models (Arrhenius and Coats-Redfern) and multi-heating rate models (Distributed activation energy, Friedman, Flynn-Wall-Ozawa, Starink, and Kissinger-Akahira-Sunose) were applied to estimate the kinetics of the process. Between the two single-heating rate models, the Coats-Redfern method fitted best with the experimental data. Among the multi-heating rate models, the Flynn-Wall-Ozawa model fitted best with the experimental results. The kinetic parameters-frequency factor, activation energy, and order of reaction were estimated using the Flynn-Wall-Ozawa model (the best-fitting model) and the estimated kinetic parameters were used to calculate the thermodynamic properties-Gibbs free energy, enthalpy, and entropy. The information on these kinetic and thermodynamic properties can be useful for the design of gasifiers and for optimising the O2 gasification operating conditions.


Role of calcium and albumin in the autoregulation of renal perfusate flow.
1. We investigated the role of calcium and albumin on the perfusate flow in isolated perfused rat kidneys. The initial perfusion medium was Krebs-Henseleit bicarbonate solution with 1.82 mm-calcium without albumin. Perfusate flow autoregulation occurred above 100 mmHg.2. Raising albumin concentration to 20 and 60 g/l. abolished autoregulation and increased perfusate flow.3. Keeping ionized calcium at 1.82 mm restored autoregulation in medium containing 20 and 60 g albumin/l. However, in 60 g albumin/l. autoregulation occurred at a significantly higher flow.4. 1.82 mm-ionized calcium appears to be a critical level for autoregulation of flow in these experiments, for autoregulation was not obtained in 60 g albumin/l. medium containing 1.80 mm-ionized calcium. On the other hand, autoregulation occurred in medium containing 1.83 mm-ionized calcium, but at a lower perfusate flow.5. Raising albumin concentration to 120 g/l. increased perfusate flow from 14.6+/-0.8 to 20.8+/-0.7 ml./min.g (n = 5, P < 0.01) in the presence of 1.82 mm-total calcium, and from 11.6+/-1.0 to 15.8+/-0.7 ml./min.g (n = 5, P < 0.01) in 1.82 mm-ionized calcium. The effect of raising albumin concentration was reversible.6. Removing the capsule from the kidneys abolished the increased flow in response to raising albumin concentration.7. We conclude that (a) the mechanism for the autoregulation of renal perfusate flow in isolated perfused kidneys is critically dependent on an extremely narrow range of ionized calcium concentration in the perfusion medium, below this range, autoregulation is not achieved; above it, however, autoregulation is achieved, but during intense vasoconstriction; (b) raising albumin concentration in the perfusion medium increases perfusate flow and abolishes autoregulation by lowering extracellular ionized calcium and by raising intrarenal tissue pressure.


Effect of tamsulosin versus prazosin on clinical and urodynamic parameters in women with voiding difficulty: a randomized clinical trial.
To compare the effects of tamsulosin and prazosin on clinical and urodynamic parameters in women with voiding dysfunction. Forty women aged 20-65 years with a clinical diagnosis of voiding dysfunction were blindly randomized to two equal groups for treatment with tamsulosin 0.4 mg or 1-2 mg of prazosin daily. Symptom assessment with the American Urological Association Symptom Score (AUASS) and urodynamic evaluation was performed initially and after three months of treatment. Patient satisfaction was evaluated and severe adverse drug effects recorded. Statistical analysis was carried out using the Student's t-test and Mann-Whitney U test. Although AUASS improved in both groups, the rate of improvement was larger in the tamsulosin group. Urodynamic parameters improved but did not normalize in both groups. Adverse side effects from medication in the prazosin group were more common than in the tamsulosin group. Most of the patients in the tamsulosin group (80%) were satisfied with their treatment compared with those in the prazosin group (45%). Tamsulosin and prazosin are both effective in palliating symptoms of women with voiding dysfunction and improving their urodynamic parameters. Tamsulosin may be the preferred drug to prescribe because of its more amenable side effect profile and greater patient satisfaction.


[Hair alterations in trichophytosis of roe deer--a differential diagnosis for hair parakeratosis].
A rare case of mycosis (ringworm) in a female roedeer is described and compared with parakeratosis of hair. It seems that in game, parakeratosis--as a primary lesion--predisposes to mycosis.


Rationale and design of the AMULET study: A new Model of telemedical care in patients with heart failure.
Heart failure (HF) is characterized by high mortality and hospital readmission rates. Limited access to cardiologists restricts the application of guideline-directed, patient-tailored medical therapy. Some telemedicine solutions and novel non-invasive diagnostic tools may facilitate real-time detection of early HF decompensation symptoms, prompt initiation of appropriate treatment, and optimal management of medical resources. We describe the rationale and design of the AMULET trial, which investigates the effect of comprehensive outpatient intervention, based on individualized haemodynamic assessment and teleconsultations, on cardiovascular mortality and unplanned hospitalizations in HF patients. The AMULET trial is a multicentre, prospective, randomized, open-label, and controlled parallel group trial (ClinicalTrials.gov Identifier: NCT03476590). Six hundred and five eligible patients with HF (left ventricular ejection fraction ≤49%, at least one hospitalization due to acute HF decompensation within 6 months prior to enrolment) were randomly assigned in a 1:1 ratio to either an intervention group or a standard care group. The planned follow-up is 12 months. The AMULET interventions are performed in ambulatory care points operated by nurses, with the remote support of cardiologists. The comprehensive clinical evaluation comprises measurements of heart rate, blood pressure, body mass, thoracic fluid content, and total body water. A recommendation support module based on these objective parameters is implemented in remote therapeutic decision-making. The primary complex endpoints are cardiovascular mortality and unplanned HF hospitalization. The AMULET trial will provide a prospective assessment of the effect of comprehensive ambulatory intervention, based on telemedicine and haemodynamically guided therapy, on mortality and readmissions in HF patients.


Guidance for doctors on the assessment of mental health for the purpose of recommending on appropriate adult under PACE.
This is a new feature for the Journal. A case report is described and those with a particular interest in the field are asked to comment. Further submissions are invited and welcomed.


Studies on the correct quantitative relations of antigen components in mono-, bi- and trivalent foot-and-mouth disease vaccine preparations.
Waldmann and frenkel type mono-, bi- and trivalent FMD vaccines, with different quantitative relations of the antigen components, were prepared and tested by the E, K and S index methods. Potency tests in adult mice showed that the antigen components of the bivalent vaccines are usually synergistic, but a 47-57% excess of antigen "O1" over the other two types is always required for a similar immunogenic action (E index value). For the same reason, the "O1" content of the trivalent vaccine should be as high as the total quantity of its other two components. Trivalent FMD vaccines in which the quantitative relations of the antigen components correspond with the proportions assessed as optimal in the mouse test prove also to be satisfactorily immunogenic in cattle in respect of all three components.


Anterior cruciate ligament femoral-tunnel drilling through an anteromedial portal: 3-dimensional plane drilling angle affects tunnel length relative to notchplasty.
Notchplasty is a surgical technique often performed during anterior cruciate ligament reconstruction (ACLR) with widening of the intercondylar notch of the lateral distal femur to avoid graft impingement. The purpose of this study was to correlate femoral-tunnel length with 3-dimensional (3D) drilling angle through the anteromedial (AM) portal with and without notchplasty. Computer data were collected from an anatomical study using 16 cadaveric knees. The anterior cruciate ligament (ACL) femoral insertion was dissected and outlined for gross anatomical observation. The dissected cadaveric knees were scanned by computed tomography (CT). Three-dimensional measurements were calculated using software (Geomagic, Inc., Research Triangle Park, NC, USA) and included the center of the ACL footprint and the size of the ACL femoral footprint. The femoral-tunnel aperture centers were measured in the anatomical posterior-to-anterior and proximal-to-distal directions using Bernard's quadrant method. The ACL tunnel was created 3-demensionally in the anatomical center of femoral foot print of ACL using software (SolidWorks®, Corp., Waltham, MA, USA). The 8-mm cylinder shaped ACL tunnel was rested upon the anatomical center of the ACL footprint and placed in three different positions: the coronal plane, the sagittal plane, and the axial plane. Finally, the effect of notchplasty on the femoral-tunnel length and center of the ACL footprint were measured. All the above-mentioned studies performed ACLR using the AM portal. The length of the femoral tunnels produced using the low coronal and high axial angles with 5-mm notchplasty became significantly shorter as the femoral starting position became more horizontal. The result was 30.38 ± 2.11 mm on average at 20° in the coronal plane/70° in the axial plane/45° in the sagittal plane and 31.26 ± 2.08 mm at 30° in the coronal plane/60° in the axial plane/45° in the sagittal plane, respectively, comparing the standard technique of 45° in the coronal/45° in the axial/45° in the sagittal plane of 32.98 ± 3.04 mm (P < 0.001). The tunnels made using the high coronal and low axial angles with notchplasty became longer than those made using the standard technique: 40.31 ± 3.36 mm at 60° in the coronal plane/30° in the axial plane/45° in the sagittal plane and 50.46 ± 3.13 mm at 75° in the coronal plane/15° in the axial plane/45° in the sagittal plane (P < 0.001). Our results show that excessive notchplasty causes the femoral tunnel to be located in the non-anatomical center of the ACL footprint and reduces the femoral-tunnel length. Therefore, care should be taken to avoid excessive notchplasty when performing this operation.


A method of producing improved scars following excision of small lesions of the back.
Twelve benign lesions were excised from the back using the accepted elliptical excisions with suturing. At follow-up, all scars had stretched to become much larger than the original lesion. By contrast, 12 lesions of similar size were excised with minimal margin and the resultant defect allowed to heal by contraction and epithelialization. This method was quicker and less painful, and produced significantly smaller scars than the conventional method.


Effects of nursing intervention on lung infection prevention in patients with tracheotomy.
This study will evaluate the effects of nursing intervention (NIV) on lung infection prevention (LIP) in patients with tracheotomy. The electronic databases of MEDLINE, Cochrane Library, EMBASE, Web of Science, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be retrieved from inception to the June 1, 2019 for randomized controlled trials investigating the effects of NIV on LIP in patients with tracheotomy without any language limitations. In addition, we will also search grey literature to avoid missing any potential studies. Two independent authors will perform study selection, data extraction, and risk of bias evaluation. This study will investigate the effects of NIV on LIP in patients with tracheotomy. The primary outcome is incidence of lung infection. The secondary outcomes include pulmonary function, quality of life, and complications post-surgery. The results of this study will summarize recent evidence for the effects of NIV on LIP in patients with tracheotomy.No ethic approval is needed in this study, because it will not need any individual data. The results of this study will be published at a peer-reviewed journal.


Dental anesthesia for patients with special needs.
To offer individualized dental treatment to certain patients who cannot tolerate dental treatment, sedation or general anesthesia is required. The needs could be either medical, mental, or psychological. The most common indications for sedation or general anesthesia are lack of cooperation, multiple morbidities, and pediatric autism. In adults, cognitive impairment and multiple morbidities are most commonly encountered indications. Because of suboptimal home care, incomplete medical history, poor preoperative management, lack of cooperation, and developmental abnormalities, it is a challenge to prepare anesthesia for patients with special needs. The American Society of Anesthesiology (ASA) has proposed guidelines for office-based anesthesia for ambulatory surgery. In patients with ASA physical status IV and V, sedation or general anesthesia for treatment in the dental office is not recommended. The distinction between sedation levels and general anesthesia is not clear. If intravenous general anesthesia without tracheal intubation is chosen for dental procedures, full cooperation between the dentist, dental assistant, and anesthesiologist is needed. Teamwork between the dentist and healthcare provider is key to achieve safe and successful dental treatment under sedation or general anesthesia in the patient with special needs.


Interplay of host and infectious agents.
In this group we would like to answer the question why people show a different response against certain pathogens. In many infections the course of the disease can range from asymptomatic carriage to the severest forms even death. In the past we have analysed candidate genes and their role in the course of malaria and could detect some polymorphisms influencing infectious diseases in the genes encoding NOS2, MBL2, IFNa, FCN2, and receptors for IFNg and IFNa. Having worked initially mainly on malaria we broadened our spectrum also to other infectious diseases like hepatitis B, Leprosy, schistosomiasis. Here we give a short overview about ongoing projects.


A GIS approach to prioritizing habitat for restoration using neotropical migrant songbird criteria.
Restoration efforts to increase wildlife habitat quality in agricultural landscapes have limited funding and are typically done on a first come, first serve basis. In order to increase the efficiency of these restoration efforts, a prioritized ranking system is needed to obtain the greatest increase in habitat quality possible for the fewest amount of hectares restored. This project examines the use of a GIS based multi-criteria approach to prioritize lands for reforestation along the Kaskaskia River in Illinois. Loss of forested area and corresponding increase in forest fragmentation has decreased songbird habitat quality across the Midwestern United States. We prioritized areas for reforestation based on nine landscape metrics: available agricultural land, forest cover gaps, edge density, proximity to river, 200 m corridor area, total forest core area, fringe core area, distance to primary core value, and primary core area. The multi-criteria analysis revealed that high priority areas for reforestation were most likely to be close to the riparian corridor and existing large blocks of forest. Analysis of simulated reforestation (0, 0.5, 1.0, 5.0 10.0, 25.0, and 50.0% of highest priority parcels reforested) revealed different responses for multiple landscape metrics used to quantify forest fragmentation following reforestation, but indicated that the study area would get the greatest rate of return on reforestation efforts by reforesting 10.0% of the highest priority areas. This project demonstrates how GIS and a multi-criteria analysis approach can be used to increase the efficiency of restoration projects. This approach should be considered by land managers when attempting to identify the location and quantity of area for restoration within a landscape.


An outbreak of acute respiratory disease caused by HAdV-55 in Beijing, China, 2020.
Human adenoviruses (HAdVs) can cause acute respiratory diseases (ARDs) worldwide, and HAdV-55 is a reemergent pathogen in recent years. In the study, we investigated an outbreak of ARD at a school due to HAdV-55 in Beijing, China, during the early outbreak of coronavirus disease 2019 (COVID-19). The epidemic prevention team was dispatched to the school to collect epidemiologic data and nasopharyngeal samples. Then, real-time reverse transcription polymerase chain reaction (PCR) and multiplex PCR assays were used to detect severe acute respiratory syndrome coronavirus 2 and other respiratory pathogens, respectively. One representative HAdV-55 isolate was selected and submitted for whole-genome sequencing using a MiSeq system and the whole-genome phylogenetic tree was conducted based on the maximum likelihood method. The outbreak lasted from January 27 to February 6, 2020, and 108 students developed fever, among whom 60 (55.56%) cases were diagnosed with HAdV-55 infection in the laboratory using real-time PCR and 56 cases were hospitalized. All the confirmed cases had a fever and 11 cases (18.33%) presented with a fever above 39°C. Other main clinical symptoms included sore throat (43.33%) and headache (43.33%). We obtained and assembled the full genome of one isolate, BJ-446, with 34 761 nucleotides in length. HAdV-55 isolate BJ-446 was 99.85% identical to strain QS-DLL, which was the first HAdV-55 strain in China isolated from an ARD outbreak in Shanxi in 2006. One and four amino acid mutations were observed in the hexon gene and the coding region of L2 pV 40.1 kDa protein, respectively. We identified the first HAdV-55 infection associated with the ARD outbreak in Beijing since the emergence of COVID-19. The study suggests that improved surveillance of HAdV is needed, although COVID-19 is still prevalent in the world.


Microstructured liposome subunit vaccines reduce lung inflammation and bacterial load after Mycobacterium tuberculosis infection.
Tuberculosis is a disease affecting millions of people throughout the world. One of the main problems in controlling the disease is the low efficacy of the Bacillus Calmette-Guérin (BCG) vaccine in protecting young adults. The development of new vaccines that induce a long-lasting immune response or that stimulate the immunity induced by BCG may improve the control of tuberculosis. The use of microstructured liposomes containing HspX, with or without MPL or CpG DNA adjuvants, as vaccines for tuberculosis was evaluated. The HspX-specific humoral and cellular immune responses to the different vaccine formulations were compared. All vaccines containing liposome microparticles and HspX were immunogenic. Vaccines formulated with CpG DNA and HspX induced the strongest humoral and cellular immune responses, mainly by inducing interferon-γ and tumor necrosis factor-α expression by both CD4(+) and CD8(+) T cells. HspX and MPL mainly induced CD8(+) T-cell activation and specific humoral responses. When evaluated the protective efficacy of the formulations against Mycobacterium tuberculosis challenge, the microstructured liposome containing L-HspX and L-HspX-CPG DNA reduced both lung inflammatory lesions and the bacterial load. We have thus demonstrated, for the first time, the use of microstructured liposomes as an adjuvant and delivery system for a vaccine formulation against tuberculosis.


Compulsive exercise and vaping among a sample of U.S. College students aged 18-26 years.
To determine the association between compulsive exercise and vaping among college students aged 18-26 years, and to characterize the type of vaping used among participants who report compulsive exercise. Cross-sectional, pooled data from two survey years (2018-2020; N = 2125) of the national (U.S.) Healthy Minds Study were analyzed. Compulsive exercise was measured based on number of occurrences in the past 28 days (analyzed continuously and among those who reported ≥ 1 and ≥ 20 occurrences). Vaping was measured based on reported use in the past 30 days. Most recent type of vaping was assessed only among participants who reported vaping. Logistic regression analyses were conducted to estimate the associations between compulsive exercise and vaping, while adjusting for covariates. For every additional occurrence of compulsive exercise reported by participants, their odds of also reporting vaping increased by 5% (95% CI 1.01-1.09). Participants who reported 20 or more occurrences of compulsive exercise in the past 28 days, a clinical threshold, had 3.71 (95% CI 1.28-10.76) higher odds of vaping in the past 30 days. Among participants who endorsed vaping, nicotine vaping was the most common recent type for those who reported any (76.2%) or 20 or more (50.2%) occurrences of compulsive exercise. Compulsive exercise is associated with vaping in a national, U.S. sample of college students, with nicotine vaping being the most common type used. Screening for both compulsive exercise and vaping, particularly if either is reported, among college-age young adults is necessary to implement prevention and intervention strategies. V, cross-sectional descriptive study.


SARS-CoV-2 Detection by Digital Polymerase Chain Reaction and Immunohistochemistry in Skin Biopsies from 52 Patients with Different COVID-19-Associated Cutaneous Phenotypes.
COronaVIrus Disease 19 (COVID-19) is associated with a wide spectrum of skin manifestations, but SARS-CoV-2 RNA in lesional skin has been demonstrated only in few cases. The objective of this study was to demonstrate SARS-CoV-2 presence in skin samples from patients with different COVID-19-related cutaneous phenotypes. Demographic and clinical data from 52 patients with COVID-19-associated cutaneous manifestations were collected. Immunohistochemistry and digital PCR (dPCR) were performed in all skin samples. RNA in situ hybridization (ISH) was used to confirm the presence of SARS-CoV-2 RNA. Twenty out of 52 (38%) patients presented SARS-CoV-2 positivity in the skin. Among these, 10/52 (19%) patients tested positive for spike protein on immunohistochemistry, five of whom had also positive testing on dPCR. Of the latter, one tested positive both for ISH and ACE-2 on immunohistochemistry while another one tested positive for nucleocapsid protein. Twelve patients showed positivity only for nucleocapsid protein on immunohistochemistry. SARS-CoV-2 was detected only in 38% of patients, without any association with a specific cutaneous phenotype, suggesting that the pathophysiology of cutaneous lesions mostly depends on the activation of the immune system. The combination of spike and nucleocapsid immunohistochemistry has higher diagnostic yield than dPCR. Skin persistence of SARS-CoV-2 may depend on timing of skin lesions, viral load, and immune response.


Roadmap to cure multiple myeloma.
Despite significant advances in the treatment of multiple myeloma which had led to unprecedented rates of response and survival, patients still relapse, and cure remains elusive. We propose in this review a roadmap to achieve the dream of cure for multiple myeloma based on five complementary strategies. First, to increase knowledge about disease pathogenesis with a focus on the biology of circulating tumor cells, responsible for dissemination and extramedullary disease, and minimal residual disease clones who represent the reservoir of clonal evolution and disease recurrence. Second, to consider undetectable measurable residual disease (MRD), defined by high-sensitive techniques, as the new endpoint of therapy. Third, to treat disease causation instead of symptomatology through early detection and intervention. Thereby, by treating high-risk smoldering myeloma patients early, we may not only contribute to delay disease progression into active disease but also to increase the cure rates. Fourth, to use the most active scheme in standard-risk patients if the cure is in the horizon. Fifth, to investigate experimental therapies in newly diagnosed patients with high-risk MM, implementing early rescue intervention strategies with the goal of eradicating all tumor clones, and achieving minimal residual disease negativity.


Genome-wide quantitative trait loci mapping on Verticillium wilt resistance in 300 chromosome segment substitution lines from Gossypium hirsutum × Gossypium barbadense.
Cotton Verticillium wilt (VW) is a devastating disease seriously affecting fiber yield and quality, and the most effective and economical prevention measure at present is selection and extension of Gossypium varieties harboring high resistance to VW. However, multiple attempts to improve the VW resistance of the most widely cultivated upland cottons have made little significant progress. The introduction of chromosome segment substitution lines (CSSLs) provide the practical solutions for merging the superior genes related with high yield and wide adaptation from Gossypium hirsutum and VW resistance and the excellent fiber quality from Gossypium barbadense. In this study, 300 CSSLs were chosen from the developed BC5F3:5 CSSLs constructed from CCRI36 (G. hirsutum) and Hai1 (G. barbadense) to conduct quantitative trait locus (QTL) mapping of VW resistance, and a total of 40 QTL relevant to VW disease index (DI) were identified. Phenotypic data were obtained from a 2-year investigation in two fields with two replications per year. All the QTL were distributed on 21 chromosomes, with phenotypic variation of 1.05%-10.52%, and 21 stable QTL were consistent in at least two environments. Based on a meta-analysis, 34 novel QTL were identified, while 6 loci were consistent with previously identified QTL. Meanwhile, 70 QTL hotspot regions were detected, including 44 novel regions. This study concentrates on QTL identification and screening for hotspot regions related with VW in the 300 CSSLs, and the results lay a solid foundation not only for revealing the genetic and molecular mechanisms of VW resistance but also for further fine mapping, gene cloning and molecular designing in breeding programs for resistant cotton varieties.


Theoretical prediction of the impact sensitivities of energetic C-nitro compounds.
In order to design high-energetic and insensitive explosives, the frontier orbital energy gaps, surface electrostatic potentials, nitro group charges, bond dissociation energies (BDEs) of the C-NO2 trigger bonds, and intermolecular interactions obtained by the M06-2X/6-311++G(2d,p) method were quantitatively correlated with the experimental drop hammer potential energies of 10 typical C-nitro explosives. The changes of several information-theoretic quantities (ITQs) in the density functional reactivity theory were discussed upon the formation of complexes. The BDEs in the explosives with six-membered ring are larger than those with five-membered ring. The frontier orbital energy gaps of the compounds with benzene ring are larger than those with N-heterocycle. The models involving the intermolecular interaction energies and the energy gaps could be used to predict the impact sensitivity of the C-nitro explosives, while those involving ΔSS, ΔIF, and ΔSGBP are invalid. With the more and more ITQs, the further studies are needed to seek for a good correlation between impact sensitivity measurements and ITQs for the energetic C-nitro compounds. The origin of sensitivity was revealed by the reduced density gradient method.


Estradiol stimulates cadherin expression in rat granulosa cells.
We have investigated the ability of hormones to modulate cadherin expression by differentiating cells. Immunocytochemical and immunoblot techniques were employed to analyze the effects of estradiol and follicle-stimulating hormone on cadherin expression in rat granulosa cells. Estradiol was shown to stimulate the expression of cadherin by these cells. This is the first report of a hormone regulating the levels of cadherin in differentiating cells.


Is Fertility Affected in Women of Childbearing Age with Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorder?
Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system (CNS), which is more prevalent among women of childbearing age. Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune disease of the CNS with similar prevalence features to MS and has recently been considered a different entity from MS. Measuring ovarian reserve is one way of evaluating fertility. Anti-Müllerian hormone (AMH) is a peptide hormone produced by ovarian granulosa cells of early follicles and is considered to be a marker for ovarian reserve. With MS and NMOSD predominance in young women, the present study aimed to address the possibility of these diseases affecting fertility by measuring AMH levels in MS and NMOSD patients and comparing it with healthy controls. The present study included 23 relapsing-remitting MS (RRMS) patients, 23 seronegative NMOSD patients, and 23 healthy age-matched controls between 18 and 45 years of age. Serum samples of the three groups were collected, and the AMH levels were measured with AMH Gen II Enzyme-Linked Immunosorbent Assay, Beckman Coulter kit. In the present study, the AMH levels did not differ significantly between the groups (p = 0.996). The mean AMH in the RRMS group was 3.59 ± 0.55 ng/ml compared with the mean of 3.60 ± 0.50 ng/ml in healthy controls. The mean AMH levels in the NMOSD group were 3.66 ± 0.61 ng/ml. Lower levels of AMH were found to be negatively associated with annualized relapse rate (in both groups of patients) and MS severity score. However, the difference was not significant. In NMOSD patients, the serum levels of AMH were negatively associated with disease duration (r = - 0.42, p = 0.023). There had been a significant negative correlation between mean AMH serum levels with Expanded Disability Status Scale (EDSS) at the time of diagnosis and at the time of study in the NMOSD group (r = - 0.402, p = 0.03 and r = - 0.457, p = 0.014, respectively). There was not a significant difference in mean serum AMH levels between RRMS and NMOSD patients compared with that of healthy controls. Further studies with larger sample sizes should be conducted, which take more variables affecting fertility in women with either RRMS or NMOSD into account to put an end to the controversial issue of fertility in this area.


Finite Systems under Pressure: Assessing Volume Definition Models from Parallel-Tempering Monte Carlo Simulations.
We have investigated different approaches to handling parallel-tempering Monte Carlo (PTMC) simulations in the isothermal-isobaric ensemble of molecular cluster/nanoparticle systems for predicting structural phase diagram transitions. We have implemented various methodologies that consist of treating pressure implicitly through its effect on the volume. Thus, the main problem in the simulations under nonzero pressure becomes the volume definition of the finite nonperiodic system, and we considered approaches based on the particles' coordinates. Various volume models, namely container-volume, particle-volume, average-volume, ellipsoids-volume, and convex hull-volume, were employed, and the required corrections for each of them in the Monte Carlo computations were introduced. Finally, we explored the effects of volume/pressure changes for all models on structural phase transitions of a test system, such as the small "icelike" (H2O)12 water cluster. The temperature and pressure dependence of the cluster's heat capacity and energy-volume Pearson correlation coefficient were studied, phase diagrams were constructed using a multiple-histogram method, and attempts were made to identify phase transitions to particular cluster structures. Our results show significant differences between the employed volume models, and we discuss all pressure-induced, such as solid-solid-, solid-liquid-, and liquid-gas-like, phase transformations in the present study.


Finite element modeling of drug distribution in the vitreous humor of the rabbit eye.
Direct intravitreal injection of drug is a common method for treating diseases of the retina or vitreous. The stagnant nature of the vitreous humor and surrounding tissue barriers creates concentration gradients within the vitreous that must be accounted for when developing drug therapy. The objective of this research was to study drug distribution in the vitreous humor of the rabbit eye after an intravitreal injection, using a finite element model. Fluorescein and fluorescein glucuronide were selected as model compounds due to available experimental data. All required model parameters were known except for the permeability of these compounds through the retina, which was determined by fitting model predictions to experimental data. The location of the intravitreal injection in the experimental studies was not precisely known; therefore, several injection locations were considered, and best-fit retinal permeability was determined for each case. Retinal permeability of fluorescein and fluorescein glucuronide estimated by the model ranged from 1.94 x 10(-5) to 3.5 x 10(-5) cm s(-1) and from 0 to 7.62 x 10(-7) cm s(-1), respectively, depending on the assumed site of the injection. These permeability values were compared with values previously calculated from other models, and the limitations of the models are discussed. Intravitreal injection position was found to be an important variable that must be controlled in both experimental and clinical settings.


Eye-blink artifact removal from single channel EEG with k-means and SSA.
In recent years, the usage of portable electroencephalogram (EEG) devices are becoming popular for both clinical and non-clinical applications. In order to provide more comfort to the subject and measure the EEG signals for several hours, these devices usually consists of fewer EEG channels or even with a single EEG channel. However, electrooculogram (EOG) signal, also known as eye-blink artifact, produced by involuntary movement of eyelids, always contaminate the EEG signals. Very few techniques are available to remove these artifacts from single channel EEG and most of these techniques modify the uncontaminated regions of the EEG signal. In this paper, we developed a new framework that combines unsupervised machine learning algorithm (k-means) and singular spectrum analysis (SSA) technique to remove eye blink artifact without modifying actual EEG signal. The novelty of the work lies in the extraction of the eye-blink artifact based on the time-domain features of the EEG signal and the unsupervised machine learning algorithm. The extracted eye-blink artifact is further processed by the SSA method and finally subtracted from the contaminated single channel EEG signal to obtain the corrected EEG signal. Results with synthetic and real EEG signals demonstrate the superiority of the proposed method over the existing methods. Moreover, the frequency based measures [the power spectrum ratio ([Formula: see text]) and the mean absolute error (MAE)] also show that the proposed method does not modify the uncontaminated regions of the EEG signal while removing the eye-blink artifact.


GDF-15 Level Correlates with CMKLR1 and VEGF-A in Tumor-free Margin in Colorectal Cancer.
Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide, responsible for over 880 000 deaths each year. Growth/differentiation factor 15 (GDF-15) is reported to be a promising diagnostic and prognostic factor in CRC. It induces pleiotropic effects in tumor cells: proliferation, stemness, invasion and metastasis. Some studies indicate that GDF-15 may stimulate angiogenesis in malignant neoplasms. However, it has not been investigated in CRC yet. The aim of our study was to determine the level of GDF-15 and the concentrations of hypoxia-inducible factor-1α (HIF-1α), VEGF-A and chemokine-like receptor 1 (CMKLR1) in tumor and margin specimens of CRC in relation to histological grade and TNM staging. The study comprised 33 samples of tumor and margin tissues obtained from CRC patients. To assess the concentration of GDF-15, HIF-1α, VEGF-A and CMKLR1, commercially available enzyme-linked immunosorbent assay (ELISA) kits were used. We found significantly increased levels of GDF-15 and CMKLR1 in tumor tissue compared to margin tissue and higher concentrations of HIF-1α and VEGF-A in margin tissue than in tumor tissue. The levels of GDF-15 and HIF-1α were significantly correlated with VEGF-A and CMKLR1 in margin tissue. In CRC, the increased level of GDF-15 might stimulate angiogenesis through upregulation of HIF-1α, VEGF A and CMKLR1 expression. Our study is the first one to reveal the correlation between the levels of GDF-15 and CMKLR1 in CRC. The elevated levels of HIF-1α and VEGF-A in tumor-free margin tissues suggest that noncancer cells in the tumor microenvironment are an important source of proangiogenic factors.