Pyridinic nitrogen enables dechlorination of trichloroethylene to acetylene by green rust: Performance, mechanism and applications.
Carbonous materials were found to catalyze the dechlorination of trichloroethylene (TCE) by green rust (GR), but the catalytic mechanism was not fully understood. We have developed a facile ball milling method to synthesize N-doped graphene (NG) with various N species, catalyzing fast dechlorination of TCE to acetylene by GR with the highest acetylene production rate of ~0.1 d-1. The adsorption of TCE onto NG is mainly derived from the graphene region of NG, and high pyridinic N is essential for the enhanced TCE reduction by GR. Oxygen species did not enhance the TCE reduction in GR/NG system. High dechlorination rates are correlated to a high amount of defect in NG and a high electron conductivity of NG. Pyridinic N has the highest adsorption energy for TCE among all the N species, which leads to the highest catalytic performance. High electrochemically active surface area resulted from the high content of pyridinic N facilitate the NG-catalyzed dechlorination. The acetylene production rate in real groundwater is still around one-third of that in ultrapure water. This work not only reveals the catalytic mechanism of NG-catalyzed dechlorination by GR, but also provide a feasible approach for practical remediations of TCE-contaminated groundwater using GR-NG mixture.


Ischemic stroke following corrective surgery for idiopathic scoliosis in a pediatric patient: the importance of early diagnosis.
To present a rare case of a cerebral ischemic lesion of unknown etiology in a pediatric patient following idiopathic scoliosis surgery and to review the current literature regarding this complication in children. A 12-year-old female with early-onset scoliosis underwent surgery to correct a 65.6º scoliosis after a normal preoperative study. T4-L1 posterior instrumentation was performed uneventfully. Twelve hours postoperatively, she developed central left facial paresis, diplopia, and gait instability. An urgent MRI scan revealed an acute ischemic lesion in the right parasagittal subthalamic-mesencephalic region, for which she received anticoagulant therapy with close monitoring. The diagnosis of "stroke of undetermined etiology" was made according to the CASCADE (Childhood Arterial Ischemic Stroke Standardized Classification and Diagnostic Evaluation) criteria. Therefore, prophylaxis was changed to antiplatelet therapy for 3 months. Symptoms resolved within a week, except for an occasional diplopia that subsided after 2 months, being asymptomatic at 2 years of follow-up. Although a rather frequent complication in adults, there are only 2 other reported cases of ischemic stroke in pediatric patients after scoliosis surgery, both related to longer procedures and underlying disease. Even so, it is important to consider this potential perioperative spinal complication due to the importance of early diagnosis and adequate acute treatment for prognosis.


Robust FOSMC of quadrotor in the presence of slung load.
This study aims to develop a robust control for the quadrotor slung-load system that efficiently follows a reference trajectory. A fractional-order robust sliding mode control has been chosen to control the quadrotor's altitude, position, and attitude. An anti-swing controller was also installed to limit the swing angle of the suspended load. It was created via delayed feedback, in which the quadrotor's position reference trajectory is changed by the difference of the load angles within a specific delayed value. Designing an adaptive FOSMC would control the system when the system uncertainties do not know the bounds. Moreover, the control parameters and the anti-swing controller for the FOSMC can be obtained using some optimization techniques to increase the controllers' accuracy.


A novel explant outgrowth culture model for mouse pancreatic acinar cells with long-term maintenance of secretory phenotype.
The development of in vitro models able to support the long-term viability and function of acinar cells is critical for exploring pancreatic pathophysiology. Despite considerable efforts, no long-term culture models for non-transformed pancreatic acini exist. Our aim was to develop and validate culture conditions for this purpose. An explant outgrowth culture design was established in which mouse pancreatic explants were cultured at the gas-liquid interphase. An enriched culture medium, pH 7.8, was employed to promote the selective outgrowth of acinar cells and to support their differentiated phenotype. After 7 days, the outgrown primary acinar cells were subcultured and maintained up to an additional 7 days as secondary monolayers on tissue culture plastic. Measurements of basal and caerulein-induced amylase secretion, phase-contrast microscopy and immunohistochemical analyses were used to characterize the cultures. Explants retained their pancreatic cytoarchitecture for 2 days in vitro. A triphasic dose response to caerulein was detected in 7-day primary cultures. The maximal rate of secretion was 1.2-fold versus basal (p=0.009) and 1.7-fold versus 1 pM caerulein (p=0.014). In secondary cultures the response was biphasic with maximal rates of secretion being 1.9-fold in 3- to 4-day cultures at 0.01 nM (p=0.049) and 2-fold in 6- to 7-day cultures at 0.1 nM (p=0.003). The present culture model provides a means to obtain functionally competent normal mouse acinar cells for long-term in vitro experimentation.


Graphonomics and its contribution to the field of motor behavior: A position statement.
The term graphonomics was conceived in the early 1980s; it defined a multidisciplinary emerging field focused on handwriting and drawing movements. Researchers in the field of graphonomics have made important contribution to the field of motor behavior by developing models aimed to conceptualize the production of fine motor movements using graphical tools. Although skeptics have argued that recent technological advancements would reduce the impact of graphonomic research, a shift of focus within in the field of graphonomics into fine motor tasks in general proves the resilience of the field. Moreover, it has been suggested that the use of fine motor movements due to technological advances has increased in importance in everyday life. It is concluded that the International Graphonomics Society can have a leading role in fostering collaborative multidisciplinary efforts and can help with the dissemination of findings contributing to the field of human movement sciences to a larger public.


Characterization of a model of chronic orofacial hyperalgesia in the rat: contribution of NA(V) 1.8.
The purpose of this study was to develop and characterize a model of orofacial inflammatory hyperalgesia. Injection of complete Freund's adjuvant (CFA) into the upper lip/whisker pad of the rat produced significant and long-lasting thermal (> or =14 days) and mechanical (> or =28 days) hyperalgesia in the area of CFA injection. Both indomethacin and morphine, given systemically, significantly attenuated thermal hyperalgesia; the effect of morphine was shown to be opioid receptor-mediated. We also examined the contribution of the tetrodotoxin-resistant voltage-gated sodium channel Na(v)1.8 in CFA-produced orofacial mechanical hypersensitivity. Na(v)1.8 mRNA was increased > or =2.5-fold in trigeminal ganglion neurons 1 and 2 weeks after CFA treatment, and Na(v)1.8 protein was increased in the infraorbital nerve over a similar time course. The changes observed were time-dependent and had returned to baseline when examined 2 months after inflammation; there were no changes in Na(v)1.9 mRNA in trigeminal ganglion neurons after CFA treatment. In support of this, Na(v)1.8 antisense oligodeoxynucleotide treatment significantly attenuated CFA-produced mechanical hypersensitivity. These results document development of a model of inflammatory orofacial hyperalgesia, which, consistent with other reports, indicate a contribution of tetrodotoxin-resistant, voltage-gated sodium channel Na(v)1.8. Orofacial hypersensitivity develops postoperatively as a routine course of orofacial surgery, and mechanical allodynia is characteristic of temporomandibular joint disorder. The results described in this report are novel with respect to the duration of orofacial hypersensitivity produced and suggest that pharmacological targeting of the voltage-gated sodium channel Na(v)1.8 may be useful in managing hypersensitivity.


High-sensitive molecularly imprinted sensor with multilayer nanocomposite for 2,6-dichlorophenol detection based on surface-enhanced Raman scattering.
This study describes the preparation of a novel multilayer sensor based on molecularly imprinted polymers (MIPs) for the detection of trace-level chlorophenols by surface-enhanced Raman scattering (SERS). Composites of SiO2/reduced graphene oxide/gold (SiO2/rGO/Au, SGA) are chosen as the SERS substrates. The fabricated composites are able to enhance the SERS sensitivity, and the addition of MIPs improves the selectivity of traditional SERS substrates. Furthermore, the sensor's detection sensitivity and selectivity are improved by including two functional monomers, namely methacrylic acid (MAA) and acrylamide (AM) containing different functional groups. Finally, in to more effectively balance the selectivity of MIPs shell and the sensitivity of SERS detection, the prepared substrates are surface-modified with polydopamine (pDA) and prepared by atom transfer radical polymerization (ATRP). It is confirmed that the prepared SGA-MIPs exhibits relatively good sensitivity and selectivity in the detection of chlorophenols. Importantly, all the investigations are conducted in environmentally friendly aqueous solution, which enables scaling-up without causing pollution.


A pilot study comparing the efficacy of two formulations of botulinum toxin type A for muscular calves contouring.
Enlarged, hypertrophy calf muscles are common in Asian women and can cause psychological burden. Botulinum toxin A (BTA) has been widely used in treating masseteric muscle hypertrophy and it's efficacious as a noninvasive method for calf-contouring has been reported. Food and Drug Administration has approved onabotulinumtoxin A (ONA, Botox; Allergan Inc, Irvine, CA, USA) for upper face rejuvenation and it has off-label uses for calf-contouring. A recently introduced Prabotulinumtoxin A (NABOTA® , PRA; Daewoong Pharmaceutical, Seoul, Korea) demonstrated a comparable efficacy and safety to ONA for masseter reduction. To compare the efficacy and safety of PRA and ONA gastrocnemius muscle reduction. This is an experimental, randomized, controlled double-blind study. Twenty-two patients were randomized to receive 100 units PRA and ONA on each calf and were asked to come for follow-up visit for up to 6 months. Clinical photographic documentation, calf circumference measurement (upright position and tiptoe), isokinetic analysis, and ultrasonographic imaging were performed to evaluate the treatment result. In addition, patients' satisfaction and side effect were also recorded. All patients completed the study without serious side effect occurred during the whole study period. The mean calf circumference of the ONA- and PRA-treated patients in upright position at baseline was 35.42 ± 1.35 cm and 36.49 ± 2.98 cm, respectively (P = 0.137). The mean calf circumference in upright position decreased significantly as early as 2 weeks after treatment, both in ONA group and in PRA group (P = 0.004 and P = 0.003, respectively), and continued to decrease until 6 months after treatment (P = 0.002 and P < 0.001, respectively). There was no statistically significant difference in mean calf circumference when comparing between ONA and PRA group at any time of follow-up period. For the tiptoe position, only in the PRA group that showed significant reduction as early as two weeks and lasted up to 6 months of follow-up (P < 0.001). The isokinetic analysis showed no significant reduction on both maximum torque and average work value in two groups. The ultrasonographic imaging revealed that the mean thickness of the lateral head of the gastrocnemius showed significant only in PRA-treated group at 2-, 3-, and 6-months of follow-up; meanwhile, the mean thickness of the medial head showed significant reduction at 2- and 6-months, with a slight increase at 3-months follow-up in two groups. The patients' satisfaction rate and doctor's evaluation also showed no statistically significant difference between both groups. This study demonstrated that PRA and ONA provided comparable efficacy and safety in gastrocnemius muscle reduction.


Evaluation of a novel commercial rapid test for dengue diagnosis based on specific IgA detection.
The performance of the novel commercial test ASSURE® Dengue IgA Rapid test (MP Diagnostics) was evaluated using a panel of 172 sera collected from dengue patients and 47 sera from healthy blood donors. The overall specificity and sensitivity were 61.0% and 85.1%, respectively. However, the positivity rate for IgA went from 33.3% for sera collected the same day of fever onset to 81.2% for sera collected 5 days after fever onset. Infections with serotype 2 viruses were detected more efficiently than those with serotype 1 viruses, and no sera from infections with serotypes 3 and 4 were available. In addition, the kit was twice more efficient at detecting secondary infections than at detecting primary infections. Finally, the ASSURE® test showed good repeatability and reproducibility. The results of this study suggest that the ASSURE® Dengue IgA Rapid test may become a useful and easy-to-use test for early dengue diagnosis.


The Way Forward for Montreal Protocol Science.
The Montreal Protocol has controlled the production and consumption of ozone depleting substances (ODSs) since its signing in 1987. The levels of most of these ODSs are now declining in the atmosphere, and there are now initial signs that ozone levels are increasing in the stratosphere. Scientific challenges remain for the Montreal Protocol. The science community projected large ozone losses if ODSs continued to increase, and that ozone levels would increase if ODSs were controlled and their levels declined. Scientists remain accountable for these projections, while they continue to refine their scientific basis. The science community remains vigilant for emerging threats to the ozone layer and seeks scientific evidence that demonstrates compliance with Montreal Protocol. As ODSs decrease, the largest impact on stratospheric ozone by the end of the 21st century will be increases in greenhouse gases. The associated climate forcings, and the human responses to these forcings, represent major uncertainties for the future of the stratospheric ozone layer.


Efficacy of Soy-Based Formulas in Alleviating Gastrointestinal Symptoms in Infants With Milk-Based Formula Intolerance: A Randomized Clinical Trial.
A randomized, blinded pilot clinical study was conducted to assess gastrointestinal (GI) tolerance in healthy, full-term infants (2-9 weeks old), whose pediatricians recommended a formula change due to perceived cow's milk formula intolerance. Infants were randomized and exclusively fed either a commercial control soy formula (SF; n = 22), an experimental partially hydrolyzed SF (10% hydrolyzed, n = 23), or a 5% hydrolyzed SF (n = 26) for 2 weeks. Age-matched reference cohorts (n = 72) with no GI intolerance on milk-based formula were assessed in parallel. Results indicated that all SF-fed groups contributed to reduction (P < .05) in common GI tolerance symptoms to levels not different from the non-symptomatic reference cohort at study end. The control SF group had more reduced fussiness, gas, and crying and higher formed stools versus hydrolyzed SF groups. In conclusion, the study suggests that SFs reduced GI intolerance symptoms in otherwise healthy infants with poor tolerance on milk-based formulas.


Time to act: lessons learnt from the first pilot school-based intervention study from Lebanon to prevent and reduce childhood obesity.
Today, childhood overweight and obesity are serious public health problems that the world faces. Obese children suffer from both short-term and long-term health consequences, and poorer adult health. Despite the rising prevalence of childhood obesity in the Eastern Mediterranean Region, including Lebanon, no intervention research studies have been undertaken. This paper summarizes the main challenges and lessons learned emanating from the first evidence-based multicomponent school intervention aimed at promoting Healthy Eating and Physical Activity in Lebanese School children (Health-E-PALS). Health-E-PALS, which includes three components (class curriculum, family involvement, and food service) and relies on interactive fun learning activities, achieved an increase in students' nutritional knowledge and self-efficacy, and a decrease in their purchase and consumption of high energy dense snacks and beverages. Recommendations for future school-based programs are also highlighted.


Emerging roles of PHLPP phosphatases in the nervous system.
It has been more than a decade since the discovery of a novel class of phosphatase, the Pleckstrin Homology (PH) domain Leucine-rich repeat Protein Phosphatases (PHLPP). Over time, they have been recognized as crucial regulators of various cellular processes, such as memory formation, cellular survival and proliferation, maintenance of circadian rhythm, and others, with any deregulation in their expression or cellular localization causing havoc in any cellular system. With the ever-growing number of downstream substrates across multiple tissue systems, a web is emerging wherein the central point is PHLPP. A slight nick in the normal signaling cascade of the two isoforms of PHLPP, namely PHLPP1 and PHLPP2, has been recently found to invoke a variety of neurological disorders including Alzheimer's disease, epileptic seizures, Parkinson's disease, and others, in the neuronal system. Improper regulation of the two isoforms has also been associated with various disease pathologies such as diabetes, cardiovascular disorders, cancer, musculoskeletal disorders, etc. In this review, we have summarized all the current knowledge about PHLPP1 (PHLPP1α and PHLPP1β) and PHLPP2 and their emerging roles in regulating various neuronal signaling pathways to pave the way for a better understanding of the complexities. This would in turn aid in providing context for the development of possible future therapeutic strategies.


Successful transesophageal pacing in a very-low-birth-weight-infant with atrioventricular block.
A baby with complete atrioventricular block was born with a birth weight of 1403 g. Isoproterenol was ineffective and emergency pacing was required. Since transcutaneous pacing was ineffective and transvenous pacing was untenable due to small body size, transesophageal pacing was performed for 3.5 hours until permanent pacemaker implantation. There were no complications. This is the first report of continuous transesophageal pacing in a very-low-birth-weight infant.


Adoptive immunotherapy: good habits instilled at youth have long-term benefits.
Many recent advances in basic cell biology and immunology are a harbinger of progress in adoptive cell therapy (ACT) including (1) the finding that host lymphodepletion enhances engraftment and efficacy, (2) the recognition that in vitro T cell functions may not correlate with in vivo efficacy, and (3) the development of advanced ex vivo culture methods to expand lymphocytes to therapeutically effective numbers. In this article, we focus on the development of artificial antigen presenting cells (aAPCs) in our laboratory and their applicability to augment ACT protocols. We also describe how aAPCs can be used to broaden ACT to treat patients with a wide variety of cancers, chronic infectious diseases, and autoimmune manifestations.


An HIV-Positive Patient Presenting with Malignant Bone Tumor in Left Tibia Treated with Microwave Ablation for Limb Salvage.
We report on a patient with human immunodeficiency virus (HIV)-positive disease with a malignant bone tumor in the left proximal tibia treated with surgery using microwave ablation (MWA). A 50-year-old Chinese male presented with sudden pain in the left knee and weight loss that had begun 2 months prior to his visit. The preoperative X-ray and MRI scan both demonstrated significant osteolytic destruction in the left proximal tibia surrounded with soft tissue mass. The patient underwent limb salvage surgery for his left leg with the technique of microwave ablation in situ. The pathology revealed myofibroblastic sarcoma with no positive margins, stage T2N0M0. The patient has a satisfactory functional and cosmetic limb with no evidence of disease at a follow-up time of 2 years. MWA is a feasible and effective surgical method for the limb salvage operation, especially for the patient with poor immunological function, e.g., HIV infection. It might offer an innovative and distinctive therapeutic alternative for malignant bone tumors, while avoiding prosthesis replacement.


Differences in the late components of the event-related potential due to age and to semantic and non-semantic tasks.
Recent work in event-related potentials (ERPs) has revealed differences between ERPs elicited during the performance of semantic and nonsemantic tasks. This experiment examined age differences in the late components of the ERP as a function of these tasks. Young and elderly males were presented with 5-word strings on each trial. The subject's task was to decide whether or not the fifth word matched the other four. In one condition, the first 4 words were identical to one another and the fifth word was either the same or different. In the other condition, the first 4 words were different from one another but were drawn from from the same semantic category. The fifth word was either from the category or from a different category. Matches occurred in 15% of the trials and mismatches in 85%. The ERP to the fifth word was analyzed. All ERPs evidenced a late positive component (LPC), the latency of which was greater for the Category task and for mismatches. LPC amplitude was greater in the Identity task. In addition, young subjects' LPC amplitudes were greater for matches than for mismatches, whereas the reverse was true for the elderly. In agreement with previous research, our results indicated that an N400 wave is evident only in response to semantic incongruity and that variables affecting late positive activity seem to be independent of those producing N400. The N400 wave was seen at a greater latency in the elderly. Our results extend previous work (e.g., Kutas and Hillyard 1980) by finding an N400 in a semantic context other than sentences, and in concluding that this component is relatively insensitive to stimulus frequency.


Substrate specificity and transport mechanism of amino-acid transceptor Slimfast from Aedes aegypti.
Anautogenous mosquitoes depend on vertebrate blood as nutrient source for their eggs. A highly efficient set of membrane transporters mediates the massive movement of nutrient amino acids between mosquito tissues after a blood meal. Here we report the characterization of the amino-acid transporter Slimfast (Slif) from the yellow-fever mosquito Aedes aegypti using codon-optimized heterologous expression. Slif is a well-known component of the target-of-rapamycin signalling pathway and fat body nutrient sensor, but its substrate specificity and transport mechanism were unknown. We found that Slif transports essential cationic and neutral amino acids with preference for arginine. It has an unusual dual-affinity mechanism with only the high affinity being Na(+) dependent. Tissue-specific expression and blood meal-dependent regulation of Slif are consistent with conveyance of essential amino acids from gut to fat body. Slif represents a novel transport system and type of transceptor for sensing and transporting essential amino acids during mosquito reproduction.


Atopic diseases by filaggrin mutations and birth year.
The prevalence of atopic disorders has increased in recent years. The pathogenesis is complex with genetic and environmental risk factors. Filaggrin loss-of-function mutations are common and associated with atopic disorders. We investigated whether the prevalence of filaggrin mutations increased in different birth cohorts in adults from the general population in Denmark. Cross-sectional questionnaire and filaggrin gene mutation (R501X and 2282del4) data from 3335 18- to 69-year-old adults were available for analyses. The effect of filaggrin mutations on the prevalence of atopic diseases, albeit not statistically significant, depended mostly on birth year for atopic dermatitis (AD). A nonsignificant increase in the prevalence of filaggrin mutations was noted across birth year groups reporting AD, with 12.9% in adults born in 1936-1949 and 19.0% born in 1976-1988. If confirmed in other populations, the observed increase suggests that mutation carriers have been more susceptible to environmental changes accentuating the rise in AD prevalence.


Design, formulation and evaluation of a mucoadhesive gel from Quercus brantii L. and coriandrum sativum L. as periodontal drug delivery.
Periodontitis is inflammation of the supporting tissues of the teeth caused by specific microorganisms. Intra-periodontal pocket, mucoadhesive drug delivery systems have been shown to be clinically effective in the treatment of periodontitis. The aim of this study was to formulate a mucoadhesive gel from the seed hull of Quercus brantii and fruits of Coriandrum sativum for the treatment of periodontitis. The semisolid concentrated extracts were incorporated in gel base. Mucoadhesive gels were prepared using carbopol 940, sodium carboxymethylcellulose (sodium CMC) and hydroxypropyl methylcellulose K4M (HPMC) as bioadhesive polymers. Physicochemical tests, mucoadhesive strength measurement and in vitro drug release study were carried out on two formulations containing carbopol 940 and sodium CMC polymers (Formulations F4 and F5). We investigated the antibacterial activity of formulation F5 against Porphyromonas gingivalis using the disk diffusion method on supplemented Brucella agar. Eight gel formulations were prepared. Physical appearance, homogeneity and consistency of F4 and F5 were good. Mucoadhesion and viscosity of F5 (1% carbopol 940 and 3% sodium CMC) was more than F4 (0.5% carbopol 940 and 3% sodium CMC). Drug release from F5 was slower. Both of formulations were syringeable through 21 G needle. In the disk diffusion method, F5 produced significant growth inhibition zones against P. gingivalis. The ideal formulation for the treatment of periodontitis should exhibit high value of mucoadhesion, show controlled release of drug and be easily delivered into the periodontal pocket preferably using a syringe. Based on in vitro release and mucoadhesion studies, F5 was selected as the best formulation.


Prediction of the treatment outcome using intravoxel incoherent motion and diffusional kurtosis imaging in nasal or sinonasal squamous cell carcinoma patients.
To evaluate the diagnostic value of intravoxel incoherent motion (IVIM) and diffusional kurtosis imaging (DKI) parameters in nasal or sinonasal squamous cell carcinoma (SCC) patients to determine local control/failure. Twenty-eight patients were evaluated. MR acquisition used single-shot spin-echo EPI with 12 b-values. Quantitative parameters (mean value, 25th, 50th and 75th percentiles) of IVIM (perfusion fraction f, pseudo-diffusion coefficient D*, and true-diffusion coefficient D), DKI (kurtosis value K, kurtosis corrected diffusion coefficient Dk) and apparent diffusion coefficient (ADC) were calculated. Parameter values at both the pretreatment and early-treatment period, and the percentage change between these two periods were obtained. Multivariate logistic regression analysis: the percentage changes of D (mean, 25th, 50th, 75th), K (mean, 50th, 75th), Dk (mean, 25th, 50th), and ADC (mean, 25th, 50th) were predictors of local control. ROC curve analysis: the parameter with the highest accuracy = the percentage change of D value with the histogram 25th percentile (0.93 diagnostic accuracy). Multivariate Cox regression analyses: the percentage changes of D (mean, 25th, 50th), K (mean, 50th, 75th), Dk (mean, 25th, 50th) and ADC (mean, 25th, 50th) are predictors. IVIM and DKI parameters, especially the D-value's histogram 25th percentile, are useful for predicting local control. • Noninvasive assessment of treatment outcome in SCC patients was achieved using IVIM/DKI. • Several IVIM and DKI parameters can predict the local control. • Especially, the D-value's histogram 25th percentile has high diagnostic accuracy.


Efficacy of lycopene as a locally delivered gel in the treatment of chronic periodontitis: smokers vs nonsmokers.
The present study was carried out as a multicenter, randomized controlled, split-mouth clinical trial to evaluate the efficacy of locally delivered lycopene on periodontal health and gingival crevicular fluid (GCF) levels of 8-hydroxydeoxyguanosine (8-OHdG) in smokers and nonsmokers compared with periodontally healthy control subjects. One hundred ten subjects including 50 smokers, 50 nonsmokers, and 10 controls participated in this study. Subjects in the smoker and nonsmoker groups had contralateral sites treated with lycopene gel and a placebo. Clinical parameters included recording site-specific measures of plaque, gingivitis, probing depth, and clinical attachment level. GCF 8-OHdG values were analyzed using a commercially available ELISA kit. Compared with the placebo, lycopene-treated sites in smokers and nonsmokers showed significant reductions in probing depths and gain in the clinical attachment levels. However, there was no statistically significant difference in the clinical parameters when lycopene-treated sites in smokers and nonsmokers were compared, except for the reduction in the 8-OHdG levels. The 8-OHdG levels at 1 week and 3 months in sites treated with lycopene in the smoker and nonsmoker group were comparable with those in the periodontally healthy control group. The gel formulation was effective in increasing clinical attachment and reducing gingival inflammation, probing depth, and oxidative injury compared with the placebo in smoking and nonsmoking subjects.


A new ingestion method for long-term morphine intoxication in rat.
A new method for long-term morphine intoxication in rat was developed. It was designed to deal with the nutritional imbalance and body weight loss that generally occurs using conventional techniques for morphine treatment. The morphine is administered in a nutritionally complete diet. Also pair-feeding is used to deal with intoxicated rats that do not eat the same amount of food as controls. The technique was validated during the study of different intoxication conditions, using different initial doses, dose increments and final doses. An initial dose of 25 mg morphine/kg b.w., raised exponentially up to 340 mg/kg b.w. in 8 days, made the rats dependent, as tested by withdrawal signs, precipitated by excluding morphine from the diet, or by administration of antagonists. A final dose of up to 715 mg morphine/kg b.w. was reached in 13 days without decreased food intake. However, initial doses of 340 or 715 mg/kg led to impaired weight gain and diet consumption. Plasma morphine levels of 3 micrograms/ml serum were reached on a dose of 340 mg/kg b.w. Also, preference for morphine diet over control diet was evaluated by choice tests. The technique is simple, time-saving and inexpensive, allowing the treatment of numerous animals for long periods under standardized intoxication conditions. No animals get ill or die.


Diversity of picornaviruses detected in diarrheal samples from children in Belém, Brazilian Amazon (1982-2019).
In this investigation, fecal specimens from children with diarrhea were collected from four community studies conducted between 1982 and 2019 in Belém, Brazilian Amazon. A total of 234 samples were tested by quantitative reverse transcription polymerase chain reaction (RT-qPCR) to detect infections by picornaviruses of the Enterovirus (EV), Parechovirus (HPeV), Cosavirus (HCoSV), Kobuvirus (Aichivirus - AiV) and Salivirus (SalV) genera. The positive samples were subjected to different amplification protocols of the VP1 region of the genome, such as nested PCR or snPCR, and were subsequently genotyped by sequencing VP1 and VP3 of the viral genome. Positivity was observed in 76.5% (179/234) of the samples tested using RT-qPCR for at least one virus, and co-infection was observed in 37.4% (67/179) of the cases. EV was detected in 50.8% (119/234), HPeV in 29.9% (70/234), HCoSV in 27.3% (64/234), and AiV/SalV in 2.1% (5/234) of the specimens tested by RT-qPCR. Using nested PCR and/or snPCR techniques, the positivity rates were 94.11% (112/119) for EV, 72.85% (51/70) for HPeV, and 20.31% (13/64) for HCoSV. It was not possible to amplify the samples that were positive for AiV/SalV. Sequencing revealed 67.2% (80/119) EV, 51.4% (36/70) HPeV, and 20.31% (13/64) HCoSV. Forty-five different types of EV were found among species A, B, and C; HCoSV identified five species, including a possible recombinant strain; all HPeV were identified as belonging to species A, in two samples a possible recombination involving three different strains was verified. This study demonstrated the high circulation and diversity of different types of picornaviruses in fecal samples, including those collected more than 30 years ago. This endorsed the evaluation of important points in the epidemiology of these viruses, such as the presence of co-infection and the possibility of knowing more about these agents, considering that some were recently described; therefore, their detection in older samples can provide more data about their ancestry.


Surgeons' mental distress and risks after severe complications following radical gastrectomy in China: a nationwide cross-sectional questionnaire.
This study was designed to investigate incidences of surgeons' mental distress following severe complications after radical gastrectomy. A cross-sectional survey was conducted between 1 June 2021 and 30 September 2021 among Chinese general and/or gastrointestinal surgeons who experienced severe complications after radical gastrectomy. The clinical features collected in the questionnaire included: (i) feeling burnout, anxiety, or depression; (ii) avoiding radical gastrectomy or feeling stress, slowing down the process during radical gastrectomy operations; (iii) having physical reactions, including heart pounding, trouble breathing, or sweating while recalling; (iv) having urges to quit being a surgeon; (v) taking psychiatric medications; and (vi) seeking psychological counselling. Analyses were performed to identify risk factors of severe mental distress, which was defined as meeting three or more of the above-mentioned clinical features. A total of 1062 valid questionnaires were received. The survey showed that most of the participating surgeons (69.02%) had at least one clinical feature of mental distress following severe complications after radical gastrectomy, and more than 25% of the surgeons suffered from severe mental distress. Surgeons from non-university affiliated hospitals, the junior surgeons, and existing violent doctor-patient conflicts were recognized as independent risk factors for surgeons' severe mental distress related to the severe complications after radical gastrectomy. About 70% of surgeons had mental health problems following severe complications after radical gastrectomy, and more than 25% of the surgeons suffered from severe mental distress. More strategies and policies are needed to improve the mental well-being of these surgeons after such incidences.


Transition metal oxide nanoparticles are effective in inhibiting lung cancer cell survival in the hypoxic tumor microenvironment.
The transition metal oxide nanoparticles are in focus for their anti-cancer potential. In this study we have synthesized and characterized CuO, NiO and Fe2O3 nanoparticles and, investigated their cytotoxic potential in the heterogeneous tumour microenvironment. Nanoparticles were synthesized by aqueous precipitation method and characterized with UV-Visible spectrophotometer, Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) and X-ray diffraction (XRD). Cell viability of lung cancer cells (A549) grown in normoxia (18%O2) and hypoxia (1%O2) was determined for all nanoparticles. The mechanism of cell death was assessed by nuclear morphological analysis, flow cytometry analysis and western blotting. Generation of intracellular ROS in treated cells and its contribution to cell viability was determined. The synthesized metal oxide nanoparticles were successfully characterized with SEM, spectroscopy and X-ray diffraction patterns. Cell viability of lung cancer cells was compromised in both normoxia and hypoxia. ROS generation was shown to contribute to cellular toxicity in CuO, but not NiO and Fe2O3. We have shown the therapeutic potential of CuO, NiO and Fe2O3 nanoparticles in non small cell lung cancer cells cultured in hypoxia, a relevant feature of solid tumors along with normoxia. The newly synthesized nanoparticles showed efficacy in both conditions. Hypoxia drives metabolic alterations and epigenetic modifications in the tumor microenvironment. By using conditions that mimic tumour microenvironment, this study expands the possibility of using metal oxide nanoparticles as a therapeutic agent for lung cancer treatment.


Conformational Preferences of π-π Stacking Between Ligand and Protein, Analysis Derived from Crystal Structure Data Geometric Preference of π-π Interaction.
π-π Interaction is a direct attractive non-covalent interaction between aromatic moieties, playing an important role in DNA stabilization, drug intercalation, etc. Aromatic rings interact through several different conformations including face-to-face, T-shaped, and offset stacked conformation. Previous quantum calculations indicated that T-shaped and offset stacked conformations are preferred for their smaller electron repulsions. However, substitution group on aromatic ring could have a great impact on π-π interaction by changing electron repulsion force between two rings. To investigate π-π interaction between ligand and aromatic side chain of protein, Brookhaven Protein Data Bank was analyzed. We extracted isolated dimer pairs with the aim of excluding multiple π-π stacking effects and found that T-shaped conformation is prevalent among aromatic interaction between phenyl ring of ligand and protein, which corresponds with the phenomenon of Phe-Phe interactions in small peptide. Specifically, for the non-substitution model, both Phe-Phe and Phenyl-Phe exhibit a favored T-shaped conformation whose dihedral angle is around 50°-70° and centroid distance is between 5.0 and 5.6 Å. However, it could be changed by substituent effect. The hydroxyl group could contact in the case of Tyr-Tyr pairs, while they point away from phenyl plane in Phe-Tyr pairs.


Complementary Ca2+ Activity of Sensory Activated and Suppressed Layer 6 Corticothalamic Neurons Reflects Behavioral State.
Layer 6 (L6) corticothalamic neurons project to thalamus, where they are thought to regulate sensory information transmission to cortex. However, the activity of these neurons during different behavioral states has not been described. Here, we imaged calcium changes in visual cortex L6 primary corticothalamic neurons with two-photon microscopy in head-fixed mice in response to passive viewing during a range of behavioral states, from locomotion to sleep. In addition to a substantial fraction of quiet neurons, we found sensory-activated and suppressed neurons, comprising two functionally distinct L6 feedback channels. Quiet neurons could be dynamically recruited to one or another functional channel, and the opposite, functional neurons could become quiet under different stimulation conditions or behavior states. The state dependence of neuronal activity was heterogeneous with respect to locomotion or level of alertness, although the average activity was largest during highest vigilance within populations of functional neurons. Interestingly, complementary activity of these distinct populations kept the overall corticothalamic feedback relatively constant during any given behavioral state. Thereby, in addition to sensory and non-sensory information, a constant activity level characteristic of behavioral state is conveyed to thalamus, where it can regulate signal transmission from the periphery to cortex.


Long-Term Outcome Up To 40 Years after Single Patch Repair of Complete Atrioventricular Septal Defect in Infancy or Childhood.
Patients with repaired complete atrioventricular septal defect (CAVSD) represent an increasing portion of grown-ups with congenital heart disease. For repair of CAVSD, the single-patch technique has been employed first. This technique requires division of the bridging leaflets, thus, among other issues, long-term function of the atrioventricular valves is of particular concern. Between 1978 and 2001, 100 consecutive patients with isolated CAVSD underwent single-patch repair in our institution. Hospital mortality was 11%. Primary endpoints were clinical status, atrioventricular valve function, and freedom from reoperation in long term. Follow-up was obtained contacting the patient and/or caregiver, and the referring cardiologist. Eighty-three patients were eligible for long-term follow-up (21.0 ± 8.7, mean ± standard deviation [21.5; 2.1-40.0, median; min-max] years after surgical repair). Actual long-term mortality was 3.4%. Quality of life (QoL; self- or caregiver-reported in patients with Down syndrome) was excellent or good in 81%, mild congestive heart failure was present in 16%, moderate in 3.6% as estimated by New York Heart Association classification. Echocardiography revealed normal systolic left ventricular function in all cases. Regurgitation of the right atrioventricular valve was mild in 48%, mild-moderate in 3.6%, and moderate in 1.2%. The left atrioventricular valve was mildly stenotic in 15% and mild to moderately stenotic in 2%; regurgitation was mild in 54%, mild to moderate in 13%, and moderate in 15% of patients. Freedom from left atrioventricular-valve-related reoperation was 95.3, 92.7, and 89.3% after 5, 10, and 30 years, respectively. Permanent pacemaker therapy, as an immediate result of CAVSD repair (n = 7) or as a result of late-onset sick sinus syndrome (n = 5), required up to six reoperations in single patients. Freedom from pacemaker-related reoperation was 91.4, 84.4, and 51.5% after 5, 10, and 30 years, respectively. Up to 40 years after single-patch repair of CAVSD, clinical status and functional results are promising, particularly, in terms of atrioventricular valve function. Permanent pacemaker therapy results in a life-long need for surgical reinterventions.


Leukocytes in the regulation of pain and analgesia.
When tissue is destroyed or invaded by leukocytes in inflammation, numerous mediators are delivered by the circulation and/or liberated from resident and immigrated cells at the site. Proalgesic mediators include proinflammatory cytokines, chemokines, protons, nerve growth factor, and prostaglandins, which are produced by invading leukocytes or by resident cells. Less well known is that analgesic mediators, which counteract pain, are also produced in inflamed tissues. These include anti-inflammatory cytokines and opioid peptides. Interactions between leukocyte-derived opioid peptides and opioid receptors can lead to potent, clinically relevant inhibition of pain (analgesia). Opioid receptors are present on peripheral endings of sensory neurons. Opioid peptides are synthesized in circulating leukocytes, which migrate to inflamed tissues directed by chemokines and adhesion molecules. Under stressful conditions or in response to releasing agents (e.g., corticotropin-releasing factor, cytokines, noradrenaline), leukocytes can secrete opioids. They activate peripheral opioid receptors and produce analgesia by inhibiting the excitability of sensory nerves and/or the release of excitatory neuropeptides. This review presents discoveries that led to the concepts of pain generation by mediators secreted from leukocytes and of analgesia by immune-derived opioids.


The Chemistry of Gut Microbial Metabolism of Polyphenols.
Gut microbiota contribute to the metabolism of dietary polyphenols and affect the bioavailability of both the parent polyphenols and their metabolites. Although there is a large number of reports of specific polyphenol metabolites, relatively little is known regarding the chemistry and enzymology of the metabolic pathways utilized by specific microbial species and taxa, which is the focus of this review. Major classes of dietary polyphenols include monomeric and oligomeric catechins (proanthocyanidins), flavonols, flavanones, ellagitannins, and isoflavones. Gut microbial metabolism of representatives of these polyphenol classes can be classified as A- and C-ring cleavage (retro Claisen reactions), C-ring cleavage mediated by dioxygenases, dehydroxylations (decarboxylation or reduction reactions followed by release of H2O molecules), and hydrogenations of alkene moieties in polyphenols, such as resveratrol, curcumin, and isoflavones (mediated by NADPH-dependent reductases). The qualitative and quantitative metabolic output of the gut microbiota depends to a large extent on the metabolic capacity of individual taxa, which emphasizes the need for assessment of functional analysis in conjunction with determinations of gut microbiota compositions.


Pathology of sinoatrial node. Correlations with electrocardiographic findings in 111 patients.
Histological study of the sinoatrial node (SAN) was performed in 111 patients in order to estabilsh correlations between the ECG findings and the anatomical lesions. This series includes both patients with sinus rhythm and patients with atrial arrhythmias. The results are as fololows: (a) the amount of nodal cells in the SAN was found to be inversely proportional to the age of the patients (p less than 0.001); (b) normal sinus rhythm was present in some cases with severe fibrosis of the SAN; (c) the present study does not support lesions of the SAN as responsible for atrial fibrillation; (d) chronic sinoatrial block was associated with extensive lesions of the approaches of the AV node or the AV node itself; (e) the auricular tachycardia-bradycardia syndrome was associated in most cases with both lesions of the main feature of the SAN lesion. The pathogenesis of these fibrotic lesions are discussed.


A novel approach to studying transformation of human stem cells into cardiac cells in vivo.
Stem cell transplantation has been proposed as a novel means of regenerating new myocardium following cardiac damage. Many laboratories have demonstrated that stem cells from different sources have the potential to transform into cardiomyocytes. Human peripheral blood CD34+ cells were transplanted into the hearts of mice with severe combined immune deficiency syndrome, and it was demonstrated that human stem cells could transform into cardiomyocytes, endothelial cells and smooth muscle cells. Using single cell preparation, cell sorting and fluorescent in situ hybridization, human peripheral blood CD34+ cells were transformed into cardiomyocytes mainly through cell fusion, whereas endothelial cells were derived through direct differentiation of the transplanted stem cells. This analytical method should provide a novel approach to identifying the mechanisms of stem cell transformation into cardiomyocytes in vivo.


Four new compounds from the basidiomycete Craterellus odoratus.
Four new compounds, craterellin D (1), 5-hydroxymethyl-2-hydroxy-4-methoxy-phenylethanone (2), 5-carboxyl-2-[2-(1,2-dihydroxyisopropyl)]-benzofuran (3), and 6α-hydroxy-3-methoxy-4α-methyl-2-cyclohexen-1-one (4), were isolated from cultures of the basidiomycete Craterellus odoratus, together with three known compounds craterellins A-C (5-7). Structures of 1-4 were elucidated on the basis of extensive spectroscopic analysis. Selected compounds were evaluated for their inhibitory activities against one isozyme of 11β-hydroxysteroid dehydrogenase (11β-HSD1) and cytotoxic activities on five tumor cell lines. Compound 2 was found to exhibit inhibitory activity against human 11β-HSD1 with an IC₅₀ value of 16.4 μg/ml.


Potential impact of accelerating the primary dose of rotavirus vaccine in infants.
We estimated the potential impact of administering the first dose of rotavirus vaccine at 6 weeks (42 days of life) instead of 2 months of age, which is permissible for all U.S. vaccines recommended at 2 months of age, on rotavirus hospitalization rates. We used published data for hospitalization rates, vaccine coverage, and vaccine efficacy after one dose and assumed a two-week delay in seroconversion after vaccine administration in the United States. Administering the first dose of rotavirus vaccine at 6 weeks instead of 8 weeks of age should have prevented 1110, 1660, and 2210 rotavirus hospitalizations among U.S. infants <3 months of age in 2006 when the vaccine was first introduced. This estimated benefit represents a 2-4% reduction in rotavirus hospitalizations among children <5 years of age.


Dialogue on Peace and Power.
An analysis of how Peace and Power have evolved over time is described in this dialogue between Pamela Clarke and Peggy Chinn.


Influence of affective and cognitive judgments on autonomic parameters during inhalation of pleasant and unpleasant odors in humans.
Hedonic tone is so salient in odor perception that several authors have used odors to induce affective states. Various studies have shown that the electrophysiological and psychophysiological response patterns induced by olfactory stimuli are different for pleasant and unpleasant odors, and that these types of odor activate brain structures differentially. These results suggest that odors are first categorized according to pleasantness. The objective of the present work was to study the possible existence of an involuntary affective categorization in olfaction. Given that certain variations in the autonomic system, such as skin conductance amplitude and heart rate, are not under the voluntary control of human subjects, we used such psychophysiological methods for this investigation. Our results indicate that unpleasant odors provoke heart-rate acceleration during both a smelling task (control condition: a task in which subjects had only to inhale odors) and a pleasantness judgment, but not during a familiarity judgment. These results suggest that subjects involuntarily categorize odors by their pleasantness.


Red cell adenosine deaminase (ADA) polymorphism in Southern Africa, with special reference to ADA deficiency among the !Kung.
Studies have been carried out on polymorphism of adenosine deaminase in 36 Southern African populations comprising more than 3000 individuals. The common variant allele ADA2 has been found to attain polymorphic frequencies only in those populations descended from non-indigenous (i.e. non-Negro and non-Khoisan) groups. Its presence in certain other populations at low frequencies could be ascribed to small-scale Caucasoid admixture. A deficiency of the enzyme is found in certain members of the !Kung division of the San ('Bushman'). The low levels of enzyme activity are not associated with severe combined immunodeficiency and the gene which determines them appears to be polymorphic in the !Kung and possibly in some other San populations as well as possibly in Negro populations which have received substantial contributions of San genes.


Cytoreductive surgery (peritonectomy procedures) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of diffuse peritoneal carcinomatosis from ovarian cancer.
Because of scarce data from larger series and nonhomogeneous selection criteria, further information is needed on peritonectomy with hyperthermic intraperitoneal chemotherapy (HIPEC) in managing patients with ovarian peritoneal carcinomatosis. In an open, prospective, single-center nonrandomized phase 2 study conducted from November 2000 to April 2007, 47 patients with primary advanced or recurrent ovarian cancer and diffuse peritoneal carcinomatosis were enrolled; 22 underwent primary and 25 secondary cytoreduction plus immediate HIPEC followed by systemic chemotherapy. The overall mean Sugarbaker peritoneal cancer index was 14.9 (range, 6-28). A mean of 6 surgical procedures were required per patient (range, 4-10). In 87.3% of the patients debulking achieved optimal cytoreduction (Sugarbaker completeness of cytoreduction [CC] score 0-1), whereas in 12.7% it left macroscopic residual disease (CC-2 or CC-3). Major complications developed in 21.3% of the patients and the in-hospital mortality rate was 4.2%. The mean overall survival was 30.4 months, median survival was 24 months, and mean disease-free survival was 27.4 months. Five-year survival was 16.7%. Univariate (log-rank test and analysis of variance) and multivariate analyses (Cox proportional-hazard model) identified the CC score as the main factor capable of independently influencing survival. Peritonectomy procedures combined with HIPEC offer promising long-term survival in patients with diffuse peritoneal ovarian carcinomatosis. They achieve high adequate primary and secondary surgical cytoreduction rates with acceptable morbidity and mortality.


The effect of charged lipids on bacteriorhodopsin membrane reconstitution and its photochemical activities.
Bacteriorhodopsin (BR) was reconstituted into artificial lipid membrane containing various charged lipid compositions. The proton pumping activity of BR under flash and continuous illumination, proton permeability across membrane, as well as the decay kinetics of the photocycle intermediate M(412) were studied. The results showed that lipid charges would significantly affect the orientation of BR inserted into lipid membranes. In liposomes containing anionic lipids, BRs were more likely to take natural orientation as in living cells. In neutral or positively charged liposomes, most BRs were reversely assembled, assuming an inside out orientation. Moreover, the lipids charges also affect BR's M intermediate kinetics, especially the slow component in M intermediate decay. The half-life M(412s) increased significantly in BRs in liposomes containing cationic lipids, while decreased in those in anionic liposomes.


A Tomato Spotted Wilt Virus S RNA-based Replicon System in Yeast.
Tomato spotted wilt virus (TSWV) is a negative-strand RNA virus of the order Bunyavirales, family Tospoviridae, genus Orthotospovirus. TSWV infects a broad range of plant species, causing serious economic losses. Despite its agronomic importance, molecular biological understanding of TSWV has been limited, partly due to the lack of a reverse genetics system, which would enable genetic manipulation of the virus. Here, we report that RNA synthesis by TSWV RNA polymerase occurs in the yeast Saccharomyces cerevisiae using a segment of the TSWV genome, S RNA expressed from cloned cDNA, as a template. Viral nucleocapsid protein was required for RNA synthesis. Replacement of the protein-coding and intergenic regions of TSWV S RNA by a yellow fluorescent protein (YFP)-coding sequence drastically increased the accumulation of both sense and antisense strands of the RNA, showing that this RNA was replicated. Using this system, we revealed that efficient RNA synthesis by TSWV RNA polymerase in yeast requires the 5'-terminal 17-nt and 3'-terminal ~50-nt regions of the TSWV S cRNA (complementary RNA to the genomic RNA) template.


Effects of continuous nicotine infusion on nicotine self-administration in rats: relationship between continuously infused and self-administered nicotine doses and serum concentrations.
The efficacy of nicotine replacement therapy (NRT) for smoking cessation is limited. One reason for this limited efficacy may be that typical serum nicotine concentrations provided by NRT do not match the peak arterial nicotine concentrations achieved from smoking. The purpose of the present study was to determine whether continuous nicotine infusion at a rate producing serum nicotine concentrations that match the estimated peak arterial nicotine concentrations associated with nicotine self-administration (NSA) in rats produces greater suppression of NSA than lower infusion rates. The effects of continuous nicotine infusion were studied by intravenously administering nicotine at various rates (1.0, 3.0, and 8.0 mg/kg per day) to rats concurrently self-administering nicotine (0.03 mg/kg per infusion) during 23-h sessions or cocaine (0.17 mg/kg per infusion) during 2-h sessions. Continuous nicotine infusion suppressed NSA in a rate-related fashion. NSA was suppressed by 17, 50, and 73% at infusion rates of 1.0, 3.0 and 8.0 mg/kg per day, respectively. The 8.0-mg/kg per day infusion rate, which provided venous serum nicotine concentrations equaling the peak arterial concentrations associated with NSA, suppressed NSA to a greater extent than lower infusion rates. The 8.0-mg/kg per day nicotine infusion rate had no effect on cocaine-maintained responding, demonstrating that its effects were specific for suppression of NSA. This infusion rate provided a mean percentage replacement of nicotine from NSA of more than 700%. Reacquisition of NSA after suppression by the two highest infusion rates was delayed compared with reacquisition after saline extinction. Continuous nicotine infusion produced an infusion rate-related suppression of NSA that was greatest when the infusion provided nicotine doses and venous serum concentrations substantially higher than those typically associated with NRT in humans.


Carbon-Ion Radiotherapy Combined with Concurrent Chemotherapy for Locally Advanced Pancreatic Cancer: A Retrospective Case Series Analysis.
Systemic chemotherapy has significantly improved in recent years. In this study. the clinical impact of carbon-ion radiotherapy (CIRT) with concurrent chemotherapy for locally advanced unresectable pancreatic cancer (URPC) was evaluated. Patients with URPC who were treated with CIRT between January 2016 and December 2020 were prospectively registered and analyzed. The major criteria for registration were (1) diagnosed as URPC on imaging; (2) pathologically diagnosed adenocarcinoma; (3) no distant metastasis; (4) Eastern Cooperative Oncology Group performance status of 0-2; (5) tumors without gastrointestinal tract invasion; and (6) available for concurrent chemotherapy. Patients who received neoadjuvant chemotherapy (NAC) for more than one year prior to CIRT were excluded. Forty-four patients met the inclusion criteria, and thirty-seven received NAC before CIRT. The median follow-up period of living patients was 26.0 (6.0-68.6) months after CIRT. The estimated two-year overall survival, local control, and progression-free survival rates after CIRT were 56.6%, 76.1%, and 29.0%, respectively. The median survival time of all patients was 29.6 months after CIRT and 34.5 months after the initial NAC. CIRT showed survival benefits for URPC even in the multiagent chemotherapy era.


Prey handling using whole-body fluid dynamics in batoids.
Fluid flow generated by body movements is a foraging tactic that has been exploited by many benthic species. In this study, the kinematics and hydrodynamics of prey handling behavior in little skates, Leucoraja erinacea, and round stingrays, Urobatis halleri, are compared using kinematics and particle image velocimetry. Both species use the body to form a tent to constrain the prey with the pectoral fin edges pressed against the substrate. Stingrays then elevate the head, which increases the volume between the body and the substrate to generate suction, while maintaining pectoral fin contact with the substrate. Meanwhile, the tip of the rostrum is curled upwards to create an opening where fluid is drawn under the body, functionally analogous to suction-feeding fishes. Skates also rotate the rostrum upwards although with the open rostral sides and the smaller fin area weaker fluid flow is generated. However, skates also use a rostral strike behavior in which the rostrum is rapidly rotated downwards pushing fluid towards the substrate to potentially stun or uncover prey. Thus, both species use the anterior portion of the body to direct fluid flow to handle prey albeit in different ways, which may be explained by differences in morphology. Rostral stiffness and pectoral fin insertion onto the rostrum differ between skates and rays and this corresponds to behavioral differences in prey handling resulting in distinct fluid flow patterns. The flexible muscular rostrum and greater fin area of stingrays allow more extensive use of suction to handle prey while the stiff cartilaginous rostrum of skates lacking extensive fin insertion is used as a paddle to strike prey as well as to clear away sand cover.


Using protein motion to read, write, and erase ubiquitin signals.
Eukaryotes use a tiny protein called ubiquitin to send a variety of signals, most often by post-translationally attaching ubiquitins to substrate proteins and to each other, thereby forming polyubiquitin chains. A combination of biophysical, biochemical, and biological studies has shown that complex macromolecular dynamics are central to many aspects of ubiquitin signaling. This review focuses on how equilibrium fluctuations and coordinated motions of ubiquitin itself, the ubiquitin conjugation machinery, and deubiquitinating enzymes enable activity and regulation on many levels, with implications for how such a tiny protein can send so many signals.


Challenges facing seed banks and agriculture in relation to seed quality.
Seeds form a convenient vehicle for storage of germplasm, both for agricultural purposes and conservation of wild species. When required, seeds can be taken from storage and germinated, and plants can be propagated for the desired purpose, e.g., crop production or biome restoration. However, seed dormancy often interferes with stand establishment or industrial utilization in crops and germination of wild species. An anticipated termination of dormancy (i.e., before crop harvest) also occurs, with preharvest sprouting as a consequence. In order to overcome these problems, a better understanding of dormancy is required. This chapter is devoted to discuss the achievement of such understanding in problematic species.


Morphological evidence for pancreatic polarity of beta-cell within islets of Langerhans.
Reconstructions from serial paraffin sections were used to define the relationships of the pancreatic endocrine cells and the microvasculature of the islets of Langerhans of the rat. We have reported that the afferent vessel to an islet, an arteriole, enters the islet directly in the beta-cell core. Immediately after entering the islet, this arteriole branches into capillaries. Herein, we report that beta-cells have two capillary faces. When viewed in cross section, 8-10 beta-cells form a tubelike structure around a central capillary. The outer side of each beta-cell also abuts a capillary. A clear polarity of secretory granules was seen on the ultrastructural level when the beta-cells were partially degranulated by prior in vivo treatment with glyburide. Of the remaining granules, 75.7 +/- 1.7% were accumulated in the apical portion of the cell, even though this portion was only 50.4 +/- 3.2% of the cytoplasm. beta-Cells around a particular cross-sectioned capillary shared the same orientation of granular accumulation. These findings provide morphological evidence of in situ beta-cell polarity that could be an anatomical basis for functional compartmentalization.


Interfering effect of Isospora suis infection on Salmonella typhimurium infection in swine.
Piglets were each orally inoculated daily for 4 consecutive days, with 10(4)-10(5) nalidixic acid-resistant Salmonella typhimurium and, starting 1 day after inoculation, with 50 000 Isospora suis sporulated oocysts. Control pigs were given S. typhimurium alone following the same inoculation schedule. Fecal samples were taken 5, 7 and 10 days after the coccidial inoculation, and all the pigs were necropsied 13 days after inoculation. S. typhimurium counts in the feces and in the cecal contents and the numbers of pigs positive for presence of S. typhimurium in the mesenteric lymph nodes of the dual-infected pigs were significantly (P less than 0.05) smaller than in those infected with S. typhimurium alone.


Mimicking human bipolar ion dysregulation models mania in rats.
Psychiatric diseases in general, and bipolar illness in particular, are difficult to model in animals since the subjective nature of the core symptoms appears to preclude objective observation of behavioral changes. An adequate animal model of a psychiatric condition must fulfill three core criteria: share pathophysiological characteristics of the human condition (face validity), have similar behavioral manifestations as the human disease (construct validity), and improve with medications that improve the symptoms seen in afflicted humans (predictive validity). The ouabain model for bipolar illness mimics a widely reproduced biologic abnormality in mania: reduced sodium pump activity. An intracerebroventricular (ICV) administration of 5microL 10(-3)M ouabain induces motoric hyperactivity preventable by lithium, carbamazepine, and haloperidol. ICV ouabain may also produce environmentally dependent hypoactivity. The model, however, has not yet been examined for other potential manic behavior in rats such as reduced need for sleep, increased sexual activity, or increased irritability. While additional characterization of the model is required, the ouabain model for bipolar illness is the only available animal model that fulfills the three criteria for an adequate animal model for bipolar illness.


Tunable dual-wavelength continuous-wave diode laser operated at 830 nm.
An external grating cavity semiconductor diode laser is made to operate simultaneously at two separately adjustable wavelengths. Lasing is restricted to the vicinity of the solitary laser 6talon resonances.


Precision medicine advances in idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a highly heterogeneous, unpredictable and ultimately lethal chronic lung disease. Over the last decade, two anti-fibrotic agents have been shown to slow disease progression, however, both drugs are administered uniformly with minimal consideration of disease severity and inter-individual molecular, genetic, and genomic differences. Advances in biological understanding of disease endotyping and the emergence of precision medicine have shown that "a one-size-fits-all approach" to the management of chronic lung diseases is no longer appropriate. While precision medicine approaches have revolutionized the management of other diseases such as lung cancer and asthma, the implementation of precision medicine in IPF clinical practice remains an unmet need despite several reports demonstrating a large number of diagnostic, prognostic and theragnostic biomarker candidates in IPF. This review article aims to summarize our current knowledge of precision medicine in IPF and highlight barriers to translate these research findings into clinical practice.


Inverse problem beyond two-body interaction: The cubic mean-field Ising model.
In this paper, we solve the inverse problem for the cubic mean-field Ising model. Starting from configuration data generated according to the distribution of the model, we reconstruct the free parameters of the system. We test the robustness of this inversion procedure both in the region of uniqueness of the solutions and in the region where multiple thermodynamics phases are present.


An investigation of a passive opened top-end pipe as an alternative solution for passive soil depressurisation systems for indoor radon mitigation.
This study carried out a series of large-scale experimental tests and numerical simulations to investigate the performance of a passive opened top-end pipe as an alternative solution for passive soil depressurisation systems for indoor radon mitigation. Measurements were conducted in terms of wind velocity, extracted air velocity and negative pressure at the sump-end inside the pipe. Investigations were performed with controlled and natural wind conditions. Test results confirmed that the passive opened top-end pipe can be used as an alternative solution for indoor radon concentration mitigation at low additional construction cost. However, the extracted air velocity and negative pressure were found to fluctuate when tested under natural wind conditions. This fluctuation would reduce the effectiveness of the performance of the passive pipe. To reduce this fluctuation, a novel static ventilator has been developed and can be added on the top-end of the pipe.


Real time ultrasound scanning of the head in neonates and infants, including a correlation between ultrasound and computed tomography.
The results of ultrasound (US) head scans performed in a children's hospital over a 6 month period have been reviewed and correlated with the results of computed tomography (CT). Two hundred and twenty-four scans were performed on 141 children ranging in age from a few days to 18 months. The clinical indications with which these children were referred were: abnormal neurological symptoms or signs, screening for hydrocephalus in neural tube defects (NTD), enlarging heads, suspected intra-cranial haemorrhage (ICH) and its sequelae, suspected complications of meningitis, investigations of suspected syndromes and following trauma. Twenty-nine of these children also had CT scans. There was good correlation between the two examinations and in only one case (a subdural collection) was a serious abnormality missed by US. US head scanning has been found to be a very reliable technique. It is the initial investigation of choice for imaging the brain of neonates and infants and in many instances it is the only investigation necessary.


Ethnic divergence and linkage disequilibrium of novel SNPs in the human NLI-IF gene: evidence of human origin and lack of association with tuberculosis susceptibility.
Sequence variation in the human genome has been used as a tool in studying human diseases and the evolutionary history of man. A human inherited predisposition to tuberculosis has been suggested and studied; however. genetic mechanisms are still ambiguous. In the present study, we scanned the regulatory and coding region of Nuclear LIM Interactor-Interacting Factor gene (NLI-IF), which is physically close to the tuberculosis-associated gene NRAMP1. Thirteen biallelic single-nucleotide polymorphisms (SNPs) were identified from four ethnic populations (African-American, Caucasian, Hispanic, and Asian) with population-specific distribution of alleles. The extent of linkage disequilibrium (LD) between 402T > C, and 472-42G > A varied distinctly from complete LD in the non-African-American groups to strong but incomplete LD in African-Americans. Both SNPs were in significant LD with the polymorphism 3' UTR in NRAMP1 among these ethnic groups (P < 0.02), except 402T > C in African-Americans. In a case-control study with a Caucasian population, three cosmopolitan SNPs (204C > A, 402T > C and 472 - 42G > A) in NLI-IF showed no significant association with human susceptibility to tuberculosis. Our results support the "out-of-Africa" model of human origin, and suggest the time for the common ancestor dispersing from Africa could not have been more than approximately 385,620 years ago.


Detection of distinct Epstein-Barr virus genotypes in NPC biopsies from southern Chinese and Caucasians.
Using the polymerase chain reaction (PCR) to analyze paraffin sections from 12 Caucasian patients, we detected only the prototype F Epstein-Barr virus (EBV) in 10 specimens from patients with nasopharyngeal carcinoma (NPC). This is in contrast to the higher frequency of association of "f" variants in NPC biopsies from Southern Chinese. The results of EBV genotyping support evidence that the EBV strains associated with NPC in the Southern Chinese population differ from those found in Caucasians. DNA sequencing confirmed that a simple point mutation is responsible for the restriction-fragment-length polymorphism which distinguishes the prototype F virus from the "f" variant.


Working towards a new psychiatry - neuroscience, technology and the DSM-5.
This Editorial introduces the thematic series on 'Toward a New Psychiatry: Philosophical and Ethical Issues in Classification, Diagnosis and Care' http://www.biomedcentral.com/series/newpsychiatry.


A rhesus macaque model of Streptococcus pneumoniae carriage.
Nasopharyngeal colonization by Streptococcus pneumoniae precedes pneumococcal disease. Elucidation of procedures to prevent or eradicate nasopharyngeal carriage in a model akin to the human would help to diminish the incidence of both pneumonia and invasive pneumococcal disease. We conducted a survey of the nasopharynx of infant rhesus macaques from our breeding colony, in search of natural carriers of S. pneumoniae. We also attempted experimental induction of colonization, by nasopharyngeal instillation of a human S. pneumoniae strain (19F). None of 158 colony animals surveyed carried S. pneumoniae in the nasopharynx. Colonization was induced in eight of eight infant rhesus by nasopharyngeal instillation and lasted 2weeks in 100% of the animals and 7weeks in more than 60%. Rhesus macaques are probably not natural carriers of S. pneumoniae. The high rate and duration of colonization obtained in our experiments indicates that the rhesus macaque will serve as a human-like carriage model.


Copper, zinc-superoxide dismutase enhances the mutagenicity in Salmonella typhimurium induced by 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole.
The mutagenicities of various carcinogens induced by liver microsomes are increased in the presence of liver cytosol in rodents. It still remains, however, to be clarified which factor or factors in the cytosol enhance(s) the microsome-mediated mutagenicities. In the present study, we sought to identify the enhancing factor in liver cytosol prepared from rats using the microsome-mediated Salmonella mutagenicity induced by 2-amino-6-methyldipyrido [1,2-a:3',2'-d] imidazole (Glu-P-1). By a series of chromatographic steps, we purified a 16-kDa protein on SDS-PAGE from the cytosol of rat livers. Partial amino acid sequences of this protein revealed that the 16-kDa protein was copper, zinc-superoxide dismutase (CuZn-SOD). The purified CuZn-SOD enhanced the microsome-mediated mutagenicities of several heterocyclic amines and aromatic amines. Furthermore, bovine and human CuZn-SOD also enhanced the microsome-mediated mutagenicity of Glu-P-1. The CuZn-SOD caused an increase in the mutagenicity of N-hydroxylated Glu-P-1 formed from Glu-P-1 by the microsomes, although CuZn-SOD did not affect either the formation or the stability of the N-hydroxylated derivative. These findings suggest that the enhancing cytosol factor for the mutagenicity of Glu-P-1 is CuZn-SOD, which stimulates the mutagenicity of N-hydroxylated Glu-P-1 without changing its metabolism.


The site of cutaneous infection influences the immunological response and clinical outcome of hamsters infected with Leishmania panamensis.
We determined that the site of inoculation (foot or snout) influences the clinical evolution and immune responses of hamsters infected with Leishmania (Viannia) panamensis. Hamsters infected in the snout showed (i) a more rapid and severe lesion evolution at multiple time points (P < 0.05), (ii) a more extensive inflammatory infiltrate and tissue necrosis, (iii) a higher tissue parasite burden, (iv) a higher antibody titre (P < 0.01), but lower antigen-specific spleen cell proliferative response (P = 0.02), and (v) a slower response to anti-leishmanial drug treatment (P < 0.002). In both inoculation groups there was co-expression of type 1 (IFN-gamma and IL-12) and some type 2 (IL-10 and TGF-beta, but not IL-4) cytokines in the cutaneous lesions and spleen. Early in the course of infection, hamsters infected in the snout showed higher expression of splenic IL-10 (P = 0.04) and intra-lesional IFN-gamma (P = 0.02) than foot infections. No expression of IL-12p40 or IL-4 was detected. During the chronic phase, snout lesions expressed more IFN-gamma (P = 0.001), IL-12p40 (P = 0.01), IL-10 (P = 0.009) and TGF-beta (P = 0.001), and the level of expression of each of these cytokines correlated with lesion size (P < or = 0.01). These results suggest that the site of infection influences the clinical outcome in experimental cutaneous leishmaniasis, and that the expression of macrophage-deactivating type 2 cytokines and/or an exaggerated type 1 proinflammatory cytokine response may contribute to lesion severity.


Biochar reduces bioavailability of phosphorus during swine manure composting: Roles of phoD-harboring bacterial community.
The bioavailability of phosphorus is a vital index for evaluating the quality of compost products. This study examined the effects of adding wheat straw biochar (WSB) and bamboo charcoal (BC) on the transformation of various phosphorus fractions during composting, as well as analyzing the roles of the phoD-harboring bacterial community in the transformation of phosphorus fractions. Adding WSB and BC reduced the available phosphorus content in the compost products by 35.2 % and 38.5 %, respectively. Redundancy analysis showed that the alkaline phosphatase content and pH were the most important factors that affected the transformation of phosphorus fractions. The addition of biochar resulted in changes in the composition and structures of the phoD-harboring bacteria communities during composting. In addition, the key bacterial genera that secreted alkaline phosphatase and decomposed different forms of phosphorus under WSB and BC were different compared with those under control. Network and correlation analysis demonstrated that the activities of phoD-harboring bacteria could have been enhanced by biochar to accelerate the consumption of available phosphorus, and the activities of key phosphorus-solubilizing bacteria (Lysobacter, Methylobacterium, and Saccharothrix) might be inhibited when the pH increased, thereby increasing the insoluble phosphorus content.


Hematogenous spread as a mechanism for the generation of abdominal wound metastases following laparoscopy.
We designed this study to determine whether hematogenous spread has a role in the etiology of port site metastases following laparoscopic surgery. The study design had two parts. In experiment 1, two groups (n = 30) of male Dark Agouti rats were studied. Under general anesthesia, the first group (20 rats) underwent 15 mins of laparoscopic insufflation, followed by an injection of a suspension of 105 Dark Agouti mammary adenocarcinoma (DAMA) cells into the internal jugular vein and a further 15-mins period of insufflation. The laparoscopic ports were then removed, and the wounds were closed and marked. In the second group (n = 10), the procedure was identical except that a 2.5-cm midline laparotomy was performed 15 mins after the commencement of anesthesia and insufflation was not used. The laparotomy was closed in two layers. In experiment 2, one group (n = 4) was studied. The study protocol was identical to the first laparoscopic group except that a larger number of 106 DAMA cells were injected. All rats in both experiments were killed 15 days later, and the injection site, laparoscopy wounds, and laparotomy wound were examined histologically by a blinded histopathologist. In experiment 1, one port site tumor was detected in the laparoscopic group and no wound metastases were found in the laparotomy group. Postoperative weight loss was significantly less in the laparoscopic group (p < 0.001). In experiment 2, no port site metastases were detected. Although hematogenous spread is a possible mechanism in the development of port site metastases, judging from the low number of port site metastases in this study as compared to previous reports using this tumor model, this mechanism is unlikely to be a major contributor to the problem of wound metastasis following laparoscopy.


High-intensity interval training versus moderate-intensity continuous training on patient quality of life in cardiovascular disease: a systematic review and meta-analysis.
This systematic review and meta-analysis aimed to compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on the quality of life (QOL) and mental health (MH) of patients with cardiovascular disease (CVDs). Web of Science, Medline, Embase, Cochrane (CENTRAL), CINAHL, China National Knowledge Infrastructure, Wanfang, and China Science and Technology Journal databases were searched from their date of establishment to July, 2023. A total of 5798 articles were screened, of which 25 were included according to the eligibility criteria. The weighted mean difference (WMD) and standardized mean difference (SMD) were used to analyze data from the same and different indicator categories, respectively. The fixed-effects model (FE) or random-effects model (RE) combined data based on the between-study heterogeneity. There were no statistically significant differences regarding QOL, physical component summary (PCS), mental component summary (MCS), and MH, including depression and anxiety levels, between the HIIT and MICT groups [SMD = 0.21, 95% confidence interval (CI) - 0.18-0.61, Z = 1.06, P = 0.290; SMD = 0.10, 95% CI - 0.03-0.23, Z = 1.52, P = 0.128; SMD = 0.07, 95% CI - 0.05-0.20, Z = 1.13, P = 0.25; SMD = - 0.08, 95% CI - 0.40-0.25, Z = - 0.46, P = 0.646; WMD = 0.14. 95% CI - 0.56-0.84, Z = 0.39, P = 0.694, respectively]. HIIT significantly improved PCS in the coronary artery disease (CAD) population subgroup relative to MICT. HIIT was also significantly superior to MICT for physical role, vitality, and social function. We conclude that HIIT and MICT have similar effects on QOL and MH in patients with CVD, while HIIT is favorable for improving patients' self-perceived physiological functioning based on their status and social adjustment, and this effect is more significant in patients with CAD.


One-step totally robotic Hartmann reversal and complex abdominal wall reconstruction with bilateral posterior component separation: a technical note.
This paper describes a robotic approach to combined gastrointestinal continuity restoration and complex abdominal wall reconstruction after Hartmann's procedure complicated by large midline and parastomal hernias. A robotic Hartmann reversal is performed, followed by robotic retromuscular abdominal wall reconstruction of all ventral defects with bilateral posterior component separation using the double-docking approach. Surgical steps are thoroughly described, and the accompanying video highlights critical steps of the procedure, anatomical landmarks and technical details relevant to successful completion. Complete restoration of the anatomy was achieved with an operative time of 6.5 h. Mobilization occured on day 1, and bowels were opened on day 3. Surgical discharge was possible on day 5. No intra-operative surgical complication occurred and follow-up at 6 months showed no recurrence or mid-term complication. Combined minimally invasive reconstruction of the gastrointestinal tract and abdominal wall was feasible using a robotic system. In addition, potential advantages of postoperative rehabilitation and reduced surgical site complications are suggested. Prospective evaluation of the technique is ongoing.


Kainate-induced currents in rat cortical neurons in culture are modulated by riluzole.
The action of the neuroprotective and anticonvulsant agent riluzole on kainate-induced currents was studied in rat cortical neurons in primary culture by using the whole-cell configuration of the patch-clamp technique. Kainate elicited macroscopic, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive inward currents in all the patched cells and the amplitude of the current was concentration-dependent (EC50= 106 microM). Riluzole decreased the inward currents induced by 100 microM kainate at all holding potentials and the reduction was dose-dependent (IC50= 101 microM). The maximal response to kainate decreased in the presence of 50 microM riluzole, without changing its EC50, indicating a noncompetitive mechanism of inhibition. The amplitude of the responses induced by kainate under control conditions and during riluzole was a linear function of the membrane potential and the reversal potential of the currents was not significantly different in the two experimental conditions. Instead, the total conductance of the cell membrane for the currents induced by 100 microM kainate was significantly reduced in the presence of 50 microM riluzole (P < 0.05). The analysis of the kainate membrane current noise performed under control conditions and during perfusion of 100 microM riluzole revealed that riluzole reduced the probability of kainate-activated ionic channels to be in the open state. Conversely, the unitary conductance of channels, as well as their characteristic time constant, seemed to be unchanged. These results reveal an additional mechanism by which riluzole can interact with glutamatergic neurotransmission and provides further support for the idea that riluzole may prove beneficial in the treatment of central nervous system injuries involving the excitotoxic actions of glutamate.


Microglia activation in the hippocampus mediates retinal degeneration-induced depressive-like behaviors via the NLRP3/IL-1β pathway.
Epidemiological studies have shown that patients with glaucoma are more prone to depression, but the mechanism of comorbid depression in patients with glaucoma remains unknown. Excessive neuroinflammation has been shown to participate in glaucoma-induced retinal degeneration and hippocampal neural apoptosis in depression. However, little research has been conducted to determine whether neuroinflammation contributes to glaucoma-induced depression. Since the degeneration of retinal ganglion cells is a hallmark of glaucoma, we investigated the role of microglia-induced neuroinflammation in retinal degeneration-induced depression and its potential mechanism. An N-methyl-D-aspartate (NMDA)-induced retinal degeneration model was established, and behavioral tests were conducted at 3, 7, 14, and 21 days after retinal degeneration. After tissue collection, we used immunohistochemistry to assess the activation of microglia and real-time polymerase chain reaction to measure the levels of pro-inflammatory cytokines and the NOD-, LRR-, and pyrin-domain containing protein 3 (NLRP3) inflammasome. The mice exhibited depressive-like behaviors 14 and 21 days after retinal degeneration, based on the open field test, tail suspension test, and forced swimming test. Mice also displayed a lower body weight gain than the control group. In addition, microglial activation was observed in the hippocampus. Microglial proliferation was first observed in the dentate gyrus on day 3, while the number of microglia in cornu ammonis 1 grew the most. Moreover, not only was the expression of pro-inflammatory cytokines, including interleukin-1β, interleukin-18, and interleukin-6 promoted, but the messenger ribonucleic acid levels of the NLRP3 inflammasome were also increased. In conclusion, our research shows that NMDA-induced retinal degeneration can induce depressive-like behaviors, which may be attributed to hippocampal neuroinflammation.


Actions of gamma-aminobutyric acid on rat supraoptic nucleus neurosecretory neurones in vitro.
1. Intracellular recordings were obtained from thirty-eight rat supraoptic nucleus (s.o.n.) neurosecretory neurones in perfused hypothalamic explants. Changes in membrane potential and conductance were monitored following application of gamma-aminobutyric acid (GABA), and related agonists and antagonists. 2. GABA depressed action potential discharge of all of thirty-five s.o.n. neurones tested and induced either membrane hyperpolarization or depolarization. Neurones that displayed membrane hyperpolarization in response to lower GABA concentrations (30-300 microM) demonstrated a biphasic membrane voltage change with a later depolarizing phase as a response to higher concentrations (up to 3000 microM). 3. GABA (10-3000 microM) induced a prominent concentration-dependent increase in membrane conductance in all neurones. The critical slope for the log-log plot of [GABA] vs. GABA-induced membrane conductance was 1.7, indicating co-operativity in the GABA receptor-induced conductance change. 4. Muscimol (0.3-30 microM) potently mimicked all the effects of GABA. Bicuculline (1-100 microM) antagonized the effects of GABA and muscimol in a competitive manner. 5. Glycine and taurine (1-10 mM) had weak effects, although comparatively similar to those of GABA. These actions were blocked both by bicuculline (100 microM) and by strychnine (1 microM). At higher concentrations (greater than 10 microM), strychnine also antagonized the actions of GABA. 6. In recordings with potassium-acetate-filled micropipettes, the reversal potential of hyperpolarizing membrane voltage responses to GABA was -72.5 +/- 1.5 mV in close agreement (+/- 5 mV) with the reversal potential of inhibitory post-synaptic potentials (i.p.s.p.s) recorded in the same neurones. Depolarizing responses to GABA reversed polarity at -50 +/- 1.6 mV. In recordings with KCl-filled micropipettes, voltage responses to GABA were always depolarizing and reversed near -40.0 +/- 4.3 mV. Similarly, reduction of the concentration of chloride ions in the perfusion medium from 134 to 10.4 mM induced a positive shift of the GABA reversal potential by 40-50 mV. 7. From measurements of input resistance (Rin) and cell time constant (tau O), input capacitance (Cin; representing total membrane capacitance) was calculated as 78.9 +/- 2.1 pF. During responses to GABA or muscimol, decreased Rin was accompanied by a linearly related decrease in tau o indicating that these substances had no effect on the membrane capacitance of s.o.n. neurones.(ABSTRACT TRUNCATED AT 400 WORDS)


Differential urinary proteins to diagnose coronary heart disease based on iTRAQ quantitative proteomics.
Coronary artery disease (CAD) is a manifestation of systemic atherosclerotic disease. It is assessed by intervention or traditional scoring risk factors. Diagnosis is limited by inaccurate and invasive methods. Developing noninvasive methods to screen for the risk of CAD is a major challenge. We aimed to identify urinary proteins associated with CAD. We utilized iTRAQ labeling followed by 2D LC-MS/MS to compare the urinary proteome of CAD patients to healthy cohorts. The multiple reaction monitoring (MRM) was used to verify the differential proteins. ROC analysis based on MRM data was used to evaluate the diagnostic application. A total of 876 proteins were quantified, and 100 differential proteins were found. Functional analysis revealed that the differential proteins were mainly associated with Liver X Receptor/Retinoid X Receptor (LXR/RXR) pathway activation, atherosclerosis signaling, production of nitric oxide and reactive oxygen species, and the top upstream regulator of the differential proteins by IPA analysis indicated to the APOE. Nineteen differential proteins were verified by MRM analysis. ROC based on MRM data revealed that the combination of two proteins (APOD and TFF1) could diagnose CAD with 85% sensitivity and 99% specificity (AUC 0.95). The urinary proteome might reflect the pathophysiological changes in CAD and be used for the clinical study of CAD.


A sanguine experience: Case Report.
A 68-year-old man presents at A&E with breathlessness but no chest pain, haemoptysis or sputum production http://ow.ly/R029n.


HSF1-dependent and -independent regulation of the mammalian in vivo heat shock response and its impairment in Huntington's disease mouse models.
The heat shock response (HSR) is a mechanism to cope with proteotoxic stress by inducing the expression of molecular chaperones and other heat shock response genes. The HSR is evolutionarily well conserved and has been widely studied in bacteria, cell lines and lower eukaryotic model organisms. However, mechanistic insights into the HSR in higher eukaryotes, in particular in mammals, are limited. We have developed an in vivo heat shock protocol to analyze the HSR in mice and dissected heat shock factor 1 (HSF1)-dependent and -independent pathways. Whilst the induction of proteostasis-related genes was dependent on HSF1, the regulation of circadian function related genes, indicating that the circadian clock oscillators have been reset, was independent of its presence. Furthermore, we demonstrate that the in vivo HSR is impaired in mouse models of Huntington's disease but we were unable to corroborate the general repression of transcription that follows a heat shock in lower eukaryotes.


Efficacy and safety of 0.5% levobupivacaine versus 0.5% bupivacaine for peribulbar anesthesia.
This randomized double-blind study examined the use of a new anesthetic agent, levobupivacaine 0.5%, which is the S(-)-enantiomer of a racemic mixture of bupivacaine, for peribulbar anesthesia and compared it with racemic bupivacaine 0.5% alone or in combination with hyaluronidase 10 IU/mL. A total of 160 patients undergoing ophthalmic surgery were randomized into four groups (n = 40 each) to receive inferotemporal peribulbar injection of levobupivacaine 0.5% (group L), racemic bupivacaine 0.5% (group B), levobupivacaine + hyaluronidase 10 IU/mL (group LH), or racemic bupivacaine + hyaluronidase 10 IU/mL (group BH) by two anesthetists and two ophthalmologists in a ratio of 25% each. Ocular akinesia and orbicularis oculi function were evaluated using a three-point scale; a value < 5 points was considered as requiring surgery, and movements were re-evaluated the day following surgery to confirm regression of the block. The time to onset (12 ± 2.6 minutes versus 13 ± 2.8 minutes) and duration of anesthesia (185 ± 33.2 minutes versus 188 ± 35.7 minutes) were similar between groups L and B. Complete akinesia (score 0) was obtained more frequently when hyaluronidase was used in addition to the anesthetic, with occurrences of 72.5% versus 57.5% in group LH versus L, respectively, and 67.5% versus 45% in group BH versus B. Moderate hypotension (<30% of baseline) was observed in four patients (10%) in group L, two (5.0%) in group B, one (2.5%) in group LH, and three (7.5%) in group BH. The time to onset was significantly different between groups L and BH, B and BH, and LH and BH, and the duration of anesthesia differed significantly between groups B and LH, B and BH, and L and LH. The akinesia score differed significantly between groups L and LH and between groups B and LH (P = 0.043 and P = 0.018, respectively), and the number of patients with a score of 0 differed significantly between groups B and LH and between groups B and BH (P = 0.004 and P = 0.017, respectively). Levobupivacaine is a long-lasting local anesthetic with limited cardiotoxicity and neurotoxicity, and may be considered the landmark for vitreoretinal surgery in elderly patients.


Age-related morphological and functional changes in the small intestine of senescence-accelerated mouse.
The ability of the small intestine to perform various functions, such as digestion/absorption of nutrients, gradually declines with age. However, the mechanism that causes intestinal senescence remains unclear. Therefore, age-related changes in the jejunum and ileum were evaluated using senescence-accelerated mouse (SAM) strains that possess characteristic phenotypes of aging. In particular, to understand how senescence affects the small intestine, we investigated whether age-related changes in the morphology of the intestinal villi and its capability to digest/absorb nutrients are associated with the senescence phenotypes identified in specific SAM strains. Four SAM strains were selected (SAMP1, SAMP6, SAMP10, and SAMR1; of which SAMR1 served as a control of SAMP strain) and age-related changes in the small intestine were evaluated for each strain. A villus morphological analysis, mRNA expression level analysis of the small intestine-specific molecules, and disaccharidase activity measurement were performed. We observed that the mRNA expression levels of the genes involved in the differentiation of intestinal epithelial cells and in the digestion/absorption of nutrients were markedly decreased in all the SAM strains, especially in the SAMP10 strain. Our results revealed that all the SAM strains spontaneously induced senescence of the small intestine, which occurred due to the disorders affecting the differentiation/maturation system of intestinal epithelial cells. In addition, it was evident that senile phenotypes, such as brain dysfunction, enhanced intestinal senescence in the SAMP10 strain. The results of this study suggest that the brain-intestinal nervous system may play role in maintenance of villous morphology and nutrients uptake via the GLP-2 and IGF-2 signaling pathway.