Phosphorylation of purified rat brain Na+ channel reconstituted into phospholipid vesicles by protein kinase C.
Phosphorylation of voltage-sensitive Na+ channels in neurons by protein kinase C slows Na+ channel inactivation and reduces peak Na+ currents. Na+ channels purified from rat brain and reconstituted into phospholipid vesicles under conditions that restore Na+ channel function were rapidly phosphorylated by protein kinase C on their 260-kDa alpha subunit. The phosphorylation reaction required Ca2+, diolein, and phosphatidylserine for activation of protein kinase C, and the rate of phosphorylation of reconstituted Na+ channels was 3- to 4-fold faster than for Na+ channels in detergent solution. Phosphorylation was on serine residues in three distinct tryptic phosphopeptides designated A, B, and C. Up to 2.5 mol of phosphate were incorporated per mol of Na+ channel. Following maximum phosphorylation by protein kinase C, cAMP-dependent protein kinase was able to incorporate more than 2.25 mol of phosphate per mol of Na+ channel indicating that these two kinases phosphorylate distinct sites. However, prior phosphorylation by cAMP-dependent protein kinase prevented phosphorylation of phosphopeptide B indicating that both kinases phosphorylate the site in this peptide. Phosphopeptide B shown here to be phosphorylated by protein kinase C and phosphopeptide 7 previously shown to be phosphorylated by cAMP-dependent protein kinase co-migrate on two-dimensional phosphopeptide maps and evidently are identical. The reduction in peak Na+ currents caused by both protein kinase C and cAMP-dependent protein kinase may result from phosphorylation of this single common site.


Oral Immunotherapy for Hazelnut Allergy: A Single-Center Retrospective Study on 100 Patients.
Oral immunotherapy (OIT) protects patients with IgE-mediated food allergies from food-induced allergic reactions due to accidental exposure and may improve their quality of life. This approach has never been evaluated for hazelnut, a major cause of food allergy in Europe. To determine the proportion of hazelnut-desensitized patients after 6 months of OIT and to identify predictors of successful desensitization. In a retrospective single-center study, we included patients younger than 18 years who underwent at least 6 months of hazelnut OIT for IgE-mediated allergy, defined by history of hypersensitivity reaction after hazelnut ingestion, positive hazelnut skin prick test result or specific IgE, and positive double-blind, placebo-controlled food challenge. Patients able to tolerate 1635 mg of hazelnut protein (∼8 hazelnuts) were considered to be hazelnut desensitized. We determined the proportion of desensitized patients after 6 months of OIT, searched for associations between baseline variables and successful desensitization, and estimated the frequency and severity of OIT-related adverse reactions. One hundred patients were included (64% males; median age, 5 years). History of severe reactions was noted in 7% of cases. At 6 months, the proportion of desensitized patients was 34% (95% CI, 25-44). The median eliciting dose (defined as the amount of hazelnut protein provoking a hypersensitivity reaction during the double-blind, placebo-controlled food challenge) increased from 106 mg (interquartile range, 51-249) at baseline to 523 mg (interquartile range, 190-1635) after 6 months of OIT (P < .0001). With longer therapy, the proportion of desensitized patients increased. Using multivariate analysis, successful desensitization was associated with older age (odds ratio [OR], 1.5; 95% CI, 1.2-2.2), smaller hazelnut skin prick test wheal diameter (OR, 0.61; 95% CI, 0.4-0.8), lower hazelnut specific IgE level (OR, 0.86; 95% CI, 0.72-0.98), and absence of cashew allergy (OR, 0.42; 95% CI, 0.12-0.64). Adverse reactions occurred in 30% of patients; none were severe. In a cohort of 100 patients aged 3 to 9 years, our results show for the first time that hazelnut OIT is associated with hazelnut desensitization and may be safe in most patients undergoing this therapy.


Effects of bromodeoxyuridine substitution on metaphase chromosome structures examined by scanning electron microscopy.
Chinese hamster chromosomes were differentially substituted with 50 microM 5-bromodeoxyuridine (BrdU) to obtain chromosomes with bifilarly and unifilarly substituted (BB-TB) and unifilarly and non-substituted (TB-TT) chromatid constitutions. To avoid the effect of Giemsa staining on the ultrastructure of chromosomes, unstained preparations were exclusively used. When TB-TT chromosomes were prepared with the conventional air-drying method followed by the osmium tetroxide-thiocarbohydrazide (OsO4-TCH) technique and examined by scanning electron microscopy (SEM), the TB-chromatid appeared somewhat more slender and showed more conspicuous spiral structures, thereby appearing more loosened compared to the TT-chromatid. At higher magnifications, however, 30 nm chromatin fibres which were seen to constitute both chromatids showed no discernible differences in dimension between the TT- and TB-chromatids. On the other hand, TB-TT chromosomes specially prepared for SEM without the process of air-drying appeared in their entirety less extended and no spiral configuration was observed even in the TB-chromatid. The TB-chromatid instead appeared rather less loosened than the TT-chromatid whereas thick fibre-like structures which in turn seemed to consist of 30 nm fibres were more easily discernible in the TT-chromatid compared to the TB. Such seemingly contradictory results obtained from the two different preparatory procedures were tentatively explained on the basis of our multiple coiling model (Taniguchi and Takayama 1986).


The complete nucleotide sequence of cell fusing agent (CFA): homology between the nonstructural proteins encoded by CFA and the nonstructural proteins encoded by arthropod-borne flaviviruses.
Cell fusing agent (CFA) is an RNA virus originally isolated from a line of Aedes aegypti mosquito cells. Although our characterization of the virus many years ago showed that it resembled the flaviviruses, there was no detectable serological cross-reaction with members of the genus flavivirus. Furthermore, unlike the well-studied members of the genus flavivirus, CFA did not replicate in any of several vertebrate cell lines tested. We have now determined the nucleotide sequence of the CFA genome. Comparison of the predicted amino acid sequence of the CFA polyprotein with viral protein sequences in Genbank, has made it apparent that CFA should now be assigned to the family Flaviviridae, genus flavivirus. The homology between CFA proteins and those of other flaviviruses was highest for NS5 (45%) and NS3 (34%). Little homology was found for the structural proteins. Thus, CFA is only distantly related to the other flaviviruses for which there is sequence information; nevertheless, with respect to their hydrophobicity plots, the CFA polyprotein and the polyproteins of other flaviviruses are remarkably similar. We suggest that CFA is an insect virus, which was present in the embryos from which the Ae. aegypti cell line was established. Thus, CFA seems to be the first member of the family Flaviviridae, genus flavivirus, to be identified as an insect virus.


Opportunities and challenges in CO2 utilization.
CO2 utilizations are essential to curbing the greenhouse gas effect and managing the environmental pollutant in an energy-efficient and economically-sound manner. This paper seeks to critically analyze these technologies in the context of each other and highlight the most important utilization avenues available thus far. This review will introduce and analyze each major pathway, and discuss the overall applicability, potential extent, and major limitations of each of these pathways to utilizing CO2. This will include the analysis of some previously underreported utilization avenues, including CO2 utilization in industrial filtration and the processing of raw industrial materials such as iron and alumina. The core theme of this paper is to seek to treat CO2 as a commodity instead of a liability.


TH2 activated cells prevent experimental autoimmune uveoretinitis, a TH1-dependent autoimmune disease.
Mercuric chloride (HgCl2) injections protect (Lewis x Brown-Norway) F1 (F1) rats against experimental autoimmune uveoretinitis (EAU) induced by immunization with the retinal S antigen (S-Ag); in contrast HgCl2-injected F1 rats develop EAU following transfer of lymph node (LN) cells from rats immunized with S-Ag alone. In the present study we demonstrate that the ability of LN cells from rats protected against EAU to transfer the disease into naive F1 rats was considerably reduced. These LN cells neither produced interleukin (IL)-2 nor (interferon (IFN)-gamma but exhibited mRNA for IL-4. In contrast, LN cells from diseased rats easily transferred EAU into naive F1 rats, produced significant IL-2 and IFN-gamma levels but barely exhibited mRNA for IL-4. Furthermore protected rats predominantly produced IgG1 anti-S-Ag antibodies, while diseased rats produced IgG2b anti-S-Ag antibodies and the increase in expression of MHC class II molecules on B cells was higher in protected rats than in diseased rats. These data suggest that (1) to exert a protective effect, HgCl2 must act at an early stage of differentiation of precursors of S-Ag specific T cells, and (2) this effect is related to the preferential activation of TH2 cells to the detriment of uveitogenic TH1 cells. Finally, these results indicate that activation of TH2 cells protect from a TH1-dependent autoimmune disease.


Effects of spatially oriented attention on the facilitation of the H reflex by a cutaneous stimulus.
The effects of spatially oriented attention on the facilitation of the H reflex induced by a mild electrical stimulation of the sural nerve was investigated in 11 human subjects. The H reflex facilitation produced by the cutaneous stimulus was smaller when attention was focused on this stimulus than when it was directed to the same cutaneous field on the opposite leg. This demonstrates that selective attention involves specific descending controls on the spinal circuits mediating the segmental effects of cutaneous afferents.


Hoxc12 expression pattern in developing and cycling murine hair follicles.
We examine the Hoxc12 RNA expression pattern during both hair follicle morphogenesis and cycling in direct comparison to its only upstream neighbor, Hoxc13. Expression of both genes is restricted to the epidermal part of the follicle excluding the outer root sheath and interfollicular epidermis in a distinct stage-dependent and cyclical manner. During the progressive growth phase (anagen) of developing and cycling follicles, the distinct proximo-distal expression domain of Hoxc12 overlaps only proximally, at the upper-most region of the bulb, with the more proximally restricted Hoxc13 domain. This arrangement of the expression domains of the two genes along the proximal-toward-distal axis of increasing follicular differentiation correlates with the sequential expression of first Hoxc13 and then Hoxc12. This indicates a reversal of the typical temporal colinearity of Hox gene activation otherwise observed along the anterior-posterior morphogenetic axis of the embryo (review: Cell 78 (1994) 191).


Near-infrared spectroscopic imaging of the whole hand: A new tool to assess tissue perfusion and peripheral microcirculation in scleroderma.
Systemic sclerosis (SSc) causes functional and structural microcirculatory dysfunction, affecting also distal extremities. Optical Near-InfraRed Spectroscopy (NIRS) of blood HbO2 saturation (stO2) is able to evaluate O2 delivery/consumption balance in the explored tissue. The NIRS-sensitive camera non-invasively detects stO2 values in superficial tissues, automatically generating 2D-imaging maps in real time. We aimed at testing whether NIRS hand imaging may evaluate peripheral microcirculatory dysfunction and its spatial heterogeneity in SSc patients compared to controls. Forty SSc patients (aged 55.1 ± 15.6 years) and twenty-one healthy controls (aged 54.3 ± 14.5years, p = 0.89) were studied by palmar hand NIRS-2D imaging. A blood pressure cuff was applied to the forearm and 3 min ischemia was induced. Images were acquired at basal conditions and every 10 seconds during 3 minutes of ischemia and 5 minutes of reperfusion. Five regions of interest were positioned on each fingertip, from the second to the fifth finger and one on the thenar eminence. A significant difference was found between controls and SSc patients in basal stO2 (84.3 ± 7.5 vs. 75.4 ± 10.9%, p < 0.001), minimum stO2 (65.2 ± 8.0 vs. 53.4 ± 10.1%, p < 0.001) and time to maximum stO2 during hyperemia (63 ± 38 vs. 85 ± 49 s, p < 0.05). Among clinical characteristics, anti-Scl70 antibody positivity, digital ulcers history and smoke exposure affected NIRS parameters, as well as sildenafil and statins therapy. Conversely, no significant differences were found in NIRS-2D values between different nailfold-videocapillaroscopy patterns. NIRS-2D imaging is a simple, automated tool to non-invasively detect regional microcirculatory impairment in SSc, which seems to add significant functional information to the morphological picture of nailfold-videocapillaroscopy.


Superior Capsular Reconstruction: A Systematic Review of Surgical Techniques and Clinical Outcomes.
To evaluate surgical techniques and clinical outcomes of arthroscopic superior capsular reconstruction (SCR) for the treatment of massive irreparable rotator cuff tears. A systematic review was registered with PROSPERO and performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. The PubMed, Scopus, and Cochrane databases were searched. Studies investigating SCR with reported surgical techniques were included. Animal studies, cadaveric studies, review studies, and letters to the editor were excluded. The technical aspects of the surgical techniques for SCR were analyzed in each article, which included graft type, glenoid fixation method, greater tuberosity fixation method, graft passage technique, suture management, margin convergence, concomitant procedures, and postoperative rehabilitation protocol. Clinical outcomes, when available, were also analyzed. We screened 365 articles, of which 29 described surgical techniques for SCR. According to the Modified Coleman Methodology Score, 24 articles were rated as poor (score < 55), 4 were rated as fair (score between 55 and 69), and 1 was rated as good (score between 70 and 84), with an average score of 25.8 ± 20.9. The most commonly performed technique for SCR used the following: an acellular dermal allograft, 2 biocomposite suture anchors for glenoid fixation, transosseous-equivalent double-row suture anchor fixation for greater tuberosity fixation with 2 biocomposite medial-row anchors and 2 biocomposite lateral-row anchors, the double-pulley technique combined with an arthroscopic grasper and/or pull suture to pass the graft into the shoulder, the performance of both anterior and posterior margin convergence, and a native rotator cuff repair when possible. Only 8 studies reported clinical outcomes, and they showed that SCR provides significant improvement in patient-reported outcomes, significant improvement in shoulder range of motion, variable graft failure rates, low complication rates, and variable reoperation rates. There were no studies comparing outcomes among the various surgical techniques. Many surgical techniques exist for arthroscopic SCR. However, no superior technique was shown because there were no studies comparing clinical outcomes among these various techniques. Level V, systematic review of Level III, IV, and V studies.


Enhancement of fermentable sugar yields by α-xylosidase supplementation of commercial cellulases.
Although α-linked xylose is a major constituent of the hemicelluloses of land plants, few secreted α-xylosidases have been described from fungi or bacteria. AxlA of Aspergillus niger is a secreted α-xylosidase that was earlier shown to promote the release of free glucose (Glc) and xylose (Xyl) from substrates containing α-linked xylose, including isoprimeverose (IP), the heptasaccharide subunit of pea xyloglucan (XG), and tamarind XG. The utility of AxlA for enhancing release of free Glc and Xyl in combination with commercial enzyme cocktails from dicotyledonous and monocotyledonous plants was examined. Without AxlA supplementation, a mixture of CTec2 and HTec2 (both of which are derived from T. reesei) did not release significant levels of Glc from pea XG or tamarind XG. This is consistent with their lack of detectable α-xylosidase activity using model substrates. On alkaline hydrogen peroxide-pretreated corn stover, supplementation of CTec2/HTec2 (at a loading of 2.5 mg/g glucan) with AxlA (at a loading of 8 mg/g glucan) increased Glc yields from 82% to 88% of the total available Glc and increased Xyl yields from 55% to 60%. AxlA supplementation also improved Glc yields from corn stover treated with the commercial cellulase Accellerase 1000. The AxlA enhancement was not a general protein effect because bovine serum albumin or bovine gamma-globulin at similar concentrations did not enhance Glc yields from corn stover in response to CTec2/HTec2. Supplementation of CTec2/HTec2 with AxlA did not enhance Glc release from pretreated green or etiolated pea tissue. However, AxlA did enhance Glc and Xyl yields compared to CTec2/HTec2 alone from another dicotyledonous herbaceous plant, Chenopodium album (lamb's quarters). Supplementation of commercial cellulase cocktails with AxlA enhances yields of Glc and Xyl from some biomass substrates under some conditions, and may prove useful in industrial lignocellulose conversion.


Cyclist's palsy: clinical and electrodiagnostic findings.
Electrodiagnostic findings in cyclist's palsy have rarely been reported. The purpose of this paper is to report a case and discuss clinical and electrodiagnostic findings. Possible aetiologies are presented and preventive measures emphasised.


Frequency and significance of immunoglobulin M antibody to hepatitis B core antigen in corticosteroid-treated severe chronic active hepatitis B.
To assess the frequency and significance of immunoglobulin M (IgM) antibody to hepatitis B core antigen (anti-HBc) in corticosteroid-treated severe chronic active hepatitis B, we tested 96 serum samples from 16 patients who were seropositive for hepatitis B surface antigen (HBsAg) (group 1) and 8 HBsAg-negative, anti-HBc-positive patients (group 2) by enzyme-linked immunoassay. Samples obtained in the presence and absence of disease activity before, during, and after long-term corticosteroid therapy (mean duration, 42 +/- 7 months) were evaluated. Seropositivity for IgM antibody was demonstrated in 12 group 1 patients, including 9 tested before corticosteroid therapy; no group 2 patients were seropositive. Seropositivity was more common in serum samples obtained during active than during inactive disease (51% versus 22%; P less than 0.05) and more frequent in serum samples that contained hepatitis B e antigen (46% versus 11%; P less than 0.02) and hepatitis B virus deoxyribonucleic acid (50% versus 24%; P less than 0.05) than in those without these markers. In some patients, seropositivity persisted or recurred intermittently during corticosteroid therapy for up to 57 months. We conclude that seropositivity for IgM antibody can be demonstrated frequently by enzyme-linked immunoassay in corticosteroid-treated patients with severe disease. Seropositivity reflects active virus replication, and it is commonly associated with inflammatory activity. The duration of seropositivity may be protracted during long-term corticosteroid therapy.


Combination of Mustardè cheek advancement flap and paramedian forehead flap as a reconstructive option in orbital exenteration.
To describe a combinatory technique made of Mustardè cheek advancement flap and paramedian forehead flap as a reconstructive option after orbital exenteration. We retrospectively reviewed all patients who underwent orbital exenteration and subsequent reconstruction with this technique at our Head and Neck Department, Divisions of Ophthalmology and Otolaryngology, at San Raffaele Hospital, Milan, Italy. Three patients were treated with the aforementioned technique, following orbital exenteration due to malignancies. All of them were affected by recurrent diseases arising from the ocular components or periorbital structures: one basal cell carcinoma and two squamous cell carcinomas. Excellent result was achieved considering skin texture and colour match, aesthetic results and intra and post-operative complications (only minor, surgically controlled haemorrhage and minimal dehiscence subsequent to defective healing occurred). The proposed technique can be considered by the head and neck reconstructive surgeon as a good option in extended orbital exenteration.


Hollow cathode plasma nitriding of medical grade Ti6Al4V: A comprehensive study.
Ti6Al4V used in biomedical applications still has several surface-related problems, such as poor bone compatibility and low wear resistance. In this work, the formation of a protective layer of titanium nitride obtained by plasma treatment in hollow cathode was studied, and the best experimental conditions were verified by a statistical factorial design of experiments. The samples were characterized in terms of their physical and chemical properties, correlating the effects of time (min) and temperature (°C). An achieved ideal condition was further analysed in terms of in vitro cytotoxicity, micro-abrasion, and electrochemical properties. The carried-out assessment has shown that nitrided condition has an improvement in wettability, microhardness, along with TixNy formation and roughness increment, when compared to pristine condition.


Standard laparoscopic versus robotic retromuscular ventral hernia repair.
Laparoscopic ventral hernia repair (LVHR) demonstrates comparable recurrence rates, but lower incidence of surgical site infection (SSI) than open repair. Delayed complications can occur with intraperitoneal mesh, particularly if a subsequent abdominal operation is required, potentially resulting in bowel injury. Robotic retromuscular ventral hernia repair (RRVHR) allows abdominal wall reconstruction (AWR) and extraperitoneal mesh placement previously only possible with open repair, with the wound morbidity of LVHR. All LVHR and RRVHR performed in our institution between June 2013 and May 2015 contained in the Americas Hernia Society Quality Collaborative database were analyzed. Continuous bivariate analysis was performed with Student's t test. Continuous nonparametric data were compared with Chi-squared test, or Fisher's exact for small sample sizes. p values <0.05 were considered significant. We compared 103 LVHR with 53 RRVHR. LVHR patients were older (60.2 vs. 52.9 years; p = 0.001), but demographics were otherwise similar between groups. Hernia width was similar (6.9 vs. 6.5 cm, p = 0.508). Fascial closure was achieved more often with RRVHR (96.2 vs. 50.5 %; p < 0.001) and aided by myofascial release in 43.4 %. Mesh was placed in an intraperitoneal position in 90.3 % of LVHR and extraperitoneal in 96.2 % of RRVHR. RRVHR operative time was longer (245 vs. 122 min, p < 0.001). Narcotic requirement was similar between LVHR and RRVHR (1.8 vs. 1.4 morphine equivalents/h; p = 0.176). Seroma was more common after RRVHR (47.2 vs. 16.5 %, p < 0.001), but SSI was similar (3.8 vs. 1 %, p = 0.592). Median length of stay was shorter after RRVHR (1 vs. 2 days, p = 0.004). Direct hospital cost was similar (LVHR $13,943 vs. RRVHR $19,532; p = 0.07). RRVHR enables true AWR, with myofascial release to offset tension for midline fascial closure, and obviates the need for intraperitoneal mesh. Perioperative morbidity of RRVHR is comparable to LVHR, with shorter length of stay despite a longer operative time and extensive tissue dissection.


Cerebellar Development in Preterm Infants at Term-Equivalent Age Is Impaired after Low-Grade Intraventricular Hemorrhage.
To investigate cerebellar development in preterm infants at term-equivalent age compared with healthy full-term infants and to examine the effect of a low-grade intraventricular hemorrhage (IVH) on cerebellar development. This study used 3T magnetic resonance and diffusion tensor imaging (DTI) at 36-41 weeks' postmenstrual age (PMA) in 72 preterm infants without severe brain injury and 16 full-term infants. Cerebellar volumes and DTI parameters of the cerebellar peduncles including fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity, and radial diffusivities were measured. Clinical variables that may affect brain development were collected. Compared with full-term infants, preterm infants showed smaller cerebellar volumes and a lower FA, greater ADC, and increased radial diffusivities in the cerebellar peduncles (all P < .05). This cerebellar impairment was associated significantly with PMA and IVH grade 2 but was independent of gestational age at birth. When we adjusted for clinical variables, an IVH grade 2 was related with 1.73 cm(3) reduction in cerebellar volumes and altered DTI parameters in the cerebellar peduncles, including decreased FA and increased radial diffusivities in the superior cerebellar peduncle and increases in ADC, axial diffusivity, and radial diffusivities of the middle cerebellar peduncle (all P < .05). Cerebellar hemispheric volumes were associated with both ipsilateral and contralateral IVH grade 2. Preterm infants without severe brain abnormalities showed impaired cerebellar development at term-equivalent age after we controlled for PMA at the time of the scan, and this is associated with IVH grade 2. These findings suggest that even a low-grade IVH has potential harmful effects on cerebellar development.


Parieto-motor functional connectivity is impaired in Parkinson's disease.
Bradykinesia in Parkinson's disease is associated with a difficulty in selecting and executing motor actions, likely due to alterations in the functional connectivity of cortico-cortical circuits. Our aims were to analyse the functional interplay between the posterior parietal cortex and the ipsilateral primary motor area in Parkinson's disease using bifocal transcranial magnetic stimulation, to evaluate its modulation by dopaminergic treatment and its relationship to a simple choice reaction task. We studied 12 Parkinson's disease patients with and without dopaminergic treatment and 12 healthy controls. A paired-pulse transcranial magnetic stimulation protocol was applied over the right posterior parietal cortex and the right primary motor area using different conditioning stimulus intensities and interstimulus intervals. Reaction and movement times were studied by a simple choice reaction task. In controls, we observed a significant facilitation of motor evoked potential amplitudes at 4 ms interstimulus interval when conditioning stimulus intensity was set to 90% of resting motor threshold. This functional interaction was not observed in Parkinson's disease patients without dopaminergic treatment and was not restored with treatment. Moreover, correlation analyses revealed that Parkinson's disease patients with less impaired parieto-motor interaction were faster in executing reaching movements in a choice reaction time task, suggesting that the functional parieto-motor impairment described here could be related to bradykinesia observed in Parkinson's disease patients. Parieto-motor functional connectivity is impaired in Parkinson's disease. The reduced efficacy of this connection could be related to presence of bradykinesia previously observed in Parkinson's disease.


Treatment of juxtafusional degeneration with artificial disc replacement (ADR): preliminary results of an ongoing prospective study.
Eleven patients with juxtafusional degeneration syndrome underwent artificial disc replacement (ADR). Of these, five patients followed up for >6 months were analyzed for the current report. Surgery for juxtafusional degeneration was performed mean 4.9 years from their initial operation. The presenting features were neurologic compromise in four and severe back pain in one, with a mean Oswestry Disability Index (ODI) score of 64%. The replaced levels were L1-L2 in one, L3-L4 in three, L4-L5 in one, and L5-S1 in one. L1-L2 replacement was performed through a left flank approach. At 6 months, all patients had complete resolution of neurologic symptoms, and ODI decreased to 24%. ADR shows promising early results in juxtafusional degeneration in well-selected patients.


A comprehensive evaluation of regression-based drug responsiveness prediction models, using cell viability inhibitory concentrations (IC50 values).
Predicting drug response is critical for precision medicine. Diverse methods have predicted drug responsiveness, as measured by the half-maximal drug inhibitory concentration (IC50), in cultured cells. Although IC50s are continuous, traditional prediction models have dealt mainly with binary classification of responsiveness. However, since there are few regression-based IC50 predictions, comprehensive evaluations of regression-based IC50 prediction models, including machine learning (ML) and deep learning (DL), for diverse data types and dataset sizes, have not been addressed. Here, we constructed 11 input data settings, including multi-omics settings, with varying dataset sizes, then evaluated the performance of regression-based ML and DL models to predict IC50s. DL models considered two convolutional neural network architectures: CDRScan and residual neural network (ResNet). ResNet was introduced in regression-based DL models for predicting drug response for the first time. As a result, DL models performed better than ML models in all the settings. Also, ResNet performed better than or comparable to CDRScan and ML models in all settings. The data underlying this article are available in GitHub at https://github.com/labnams/IC50evaluation. Supplementary data are available at Bioinformatics online.


The role of the clinical psychologist within a cleft service.
Clinical psychologists are core members of UK cleft services. This paper outlines the variety of ways in which clinical psychologists work across the lifespan to promote the psychological wellbeing of those born with a cleft and their families. In the context of dental or orthodontic treatment, this involves a combination of early intervention and advice, psychological assessment or specialist psychological therapy for individuals experiencing dental anxiety or anxiety regarding the appearance of their teeth. This paper therefore aims to highlight the varying roles which clinical psychologists play in the provision of cleft-related dental care, often alongside multidisciplinary colleagues.


[National consensus statement by the Austrian Societies for Rheumatology, Pulmonology, Infectiology, Dermatology and Gastroenterology regarding the management of latent tuberculosis and the associated utilization of biologic and targeted synthetic DMARDS (disease modifying antirheumatic drugs)].
This nationwide Austrian consensus statement summarizes the recommendations on the management of latent tuberculosis by treatment with biologic and targeted synthetic DMARDs. The essential questions with respect to screening and preventive treatment were discussed by experts from the disciplines of rheumatology, pneumology, infectious diseases, dermatology and gastroenterology, based on the available data, and then a joint consensus was formed by agreement. This involved a differentiated discussion on the various forms of treatment, and clear recommendations were formulated.


An alternative surgical technique for advanced tongue/tongue base cancer without free flap reconstruction.
Locally advanced tongue or tongue base cancer is recommended to be treated by radical resection that is usually detrimental to physiological functions. This study reports the efficacy and treatment outcome of the patients who had received total glossectomy and laryngeal suspension without lip-split mandibulotomy and free flap reconstruction to preserve laryngopharyngeal function. From 2010 to 2018, 37 consecutive patients who had received the surgery were retrospectively recruited. The overall five-year survival is 72%. The postoperative dependent rate of feeding tube and tracheostomy largely decreases within 1-year follow-up. Treated by this surgical method, these patients are free from facial disfiguration, donor site morbidity, and destructive mastication and occlusion. It is also feasible to perform this surgical technique in the recurrent cases previously treated by chemoradiation. Total glossectomy with laryngeal suspension can be successfully applied to locally advanced tongue or tongue base cancer, and benefits the patients with improved survival and preserved physiological function. Especially surgeons for free flap reconstruction are understaffed at some regional or district hospitals.


Thermally trainable dual network hydrogels.
Inspired by biological systems, trainable responsive materials have received burgeoning research interests for future adaptive and intelligent material systems. However, the trainable materials to date typically cannot perform active work, and the training allows only one direction of functionality change. Here, we demonstrate thermally trainable hydrogel systems consisting of two thermoresponsive polymers, where the volumetric response of the system upon phase transitions enhances or decreases through a training process above certain threshold temperature. Positive or negative training of the thermally induced deformations can be achieved, depending on the network design. Importantly, softening, stiffening, or toughening of the hydrogel can be achieved by the training process. We demonstrate trainable hydrogel actuators capable of performing increased active work or implementing an initially impossible task. The reported dual network hydrogels provide a new training strategy that can be leveraged for bio-inspired soft systems such as adaptive artificial muscles or soft robotics.


Characterization and bacteriostatic effects of β-cyclodextrin/quercetin inclusion compound nanofilms prepared by electrospinning.
Quercetin has various biological activities, but its poor water solubility and stability limit its applications. In this study, β-cyclodextrin was used as the host and quercetin was encapsulated in its cavity to prepare an inclusion compound. Then, a nanofilm was formed using electrospinning. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and thermogravimetric differential scanning calorimetry (TG-DSC) were used to characterize the properties of the inclusion compound nanofilms. SEM images showed that the nanofilm prepared by optimizing the electrospinning process parameters had a good nanofiber structure. XRD, FTIR and TG/DSC characterization of the nanofilm showed that quercetin was encapsulated in the cavity of β-cyclodextrin and was present in the nanofilm. The quercetin was slowly released from the nanofilm and still had good bacteriostatic effects on Staphylococcus aureus and Escherichia coli, indicating that the process of embedding and electrospinning did not affect the antibacterial activity of quercetin.


The many roles of PTK7: a versatile regulator of cell-cell communication.
PTK7 (protein tyrosine kinase 7) is an evolutionarily conserved transmembrane receptor with functions in various processes ranging from embryonic morphogenesis to epidermal wound repair. Here, we review recent findings indicating that PTK7 is a versatile co-receptor that functions as a molecular switch in Wnt, Semaphorin/Plexin and VEGF signaling pathways. We focus in particular on the role of PTK7 in Wnt signaling, as recent data indicate that PTK7 acts as a Wnt co-receptor, which activates the planar cell polarity pathway, but inhibits canonical Wnt signaling.


Communication and management of incidental pathology in 1,214 consecutive appendicectomies; a cohort study.
Important incidental pathology requiring further action is commonly found during appendicectomy, macro- and microscopically. We aimed to determine whether the acute surgical unit (ASU) model improved the management and disclosure of these findings. An ASU model was introduced at our institution on 01/08/2012. In this retrospective cohort study, all patients undergoing appendicectomy 2.5 years before (Traditional group) or after (ASU group) this date were compared. The primary outcomes were rates of appropriate management of the incidental findings, and communication of the findings to the patient and to their general practitioner (GP). 1,214 patients underwent emergency appendicectomy; 465 in the Traditional group and 749 in the ASU group. 80 (6.6%) patients (25 and 55 in each respective period) had important incidental findings. There were 24 patients with benign polyps, 15 with neuro-endocrine tumour, 11 with endometriosis, 8 with pelvic inflammatory disease, 8 Enterobius vermicularis infection, 7 with low grade mucinous cystadenoma, 3 with inflammatory bowel disease, 2 with diverticulitis, 2 with tubo-ovarian mass, 1 with secondary appendiceal malignancy and none with primary appendiceal adenocarcinoma. One patient had dual pathologies. There was no difference between the Traditional and ASU group with regards to communication of the findings to the patient (p = 0.44) and their GP (p = 0.27), and there was no difference in the rates of appropriate management (p = 0.21). The introduction of an ASU model did not change rates of surgeon-to-patient and surgeon-to-GP communication nor affect rates of appropriate management of important incidental pathology during appendectomy.


Cord blood prolidase activity correlates with gestational age and birth weight.
Prolidase, a specific iminopeptidase involved in collagen turnover, is especially active in growing tissues. To investigate the relationship between cord blood prolidase activity and both birth weight and gestational age. Cord blood was collected consecutively from 50 healthy newborns (35 term, 15 preterm). Prolidase activity was measured in the samples using standard methods. Themean +/- SD cord blood prolidase activity was 41.4 +/- 6.9 U/l in term infants and 35.2 +/- 8.0 U/l in preterm infants and these were significantly different (p < 0.01). There were positive correlations between cord blood prolidase and both birth weight (r = 0.533, p < 0.01) and gestational age (r = 0.806, p < 0.01). Cord blood prolidase activity may be a good indicator of fetal maturation and gestational age.


Pancreatoscopy-guided retrieval of a migrated pancreatic duct stent.
Video 1The case report is presented in the video, with a description of the patient's clinical presentation and course along with a set of endoscopic interventions, including different stent retrieval devices and the ultimate use of pancreatoscopy with a Spyglass Retrieval Snare (Boston Scientific, Marlborough, Mass, USA) to remove the migrated pancreatic duct stent after serial dilations of the pancreatic duct.


Interaction of DNA-binding proteins with the 5'-flanking region of a cytokinin-responsive cucumber hydroxypyruvate reductase gene.
Transcription of the cucumber hpr-A gene is responsive to cytokinin and light. To investigate the molecular basis for transcriptional regulation by cytokinin, we have identified DNA sequences and proteins that may be involved in the regulation of hpr-A gene expression. Transient expression assays in etiolated cucumber cotyledons indicate that the 315 bp fragment (-382 to -67) contains sequences necessary for cytokinin responsiveness of the luciferase reporter gene. Band shift assays detected cytokinin-enhanced and -reduced protein binding sites in a 97 bp fragment (-382 to -285) upstream of the hpr-A gene. DNase I footprinting identified two protein-protected sites, a 15 bp sequence, 5'-AAATGACGAAAATGC-3', that contains an as-1 TGACG motif found in other plant promoters, and a 13 bp sequence, 5'-AAGATTGATTGAG-3', of unknown function. Two-dimensional band shift analysis of the cytokinin-responsive DNA protein complex revealed the presence of six DNA protein interactions. Band shift assays showed that cytokinin and light have different effects on the interaction of nuclear proteins to the 97 bp fragment of the hpr-A gene. These data suggest that cytokinin and light do not share identical signal transduction pathways in regulating hpr-A gene expression.


Expression of transforming growth factor-β1 and autophagy markers in the bladder of rats with neurogenic lower urinary tract injury.
This study was conducted to explore the expression of transforming growth factor-beta 1 (TGF-β1) and its correlation with autophagy markers in the bladder of rats with neurogenic lower urinary tract dysfunction (NLUTD) post spinal cord injury (SCI). A total of 36 male Wistar rats were randomly divided into the SCI group and control group. Rats in the SCI group were subjected to T10-T11 spinal cord transection. At day 1, 4, and 7, 6 rats were euthanized daily and the Basso, Beattie and Bresnahan score (BBB score), post-void residual (PVR), urinary bladder function score (UBFS) and bladder weight were assessed. The expression TGF-β1 and autophagy markers were evaluated by immunofluorescence staining, Western bolt, and qRT-PCR. A total of 36 male Wistar rats were randomly divided into the SCI group and control group, with three time points in each group. Not applicable. SCI modeling impaired the motor function of the hind limbs and the bladder function of rats. NLUTD muscle exhibited a punctated immunostaining pattern for LC3, suggesting the accumulation of autophagosomes. Our results further indicated that compared with the control group, the expression levels of TGF-β1 and LC3 were increased, while the level of P62 was decreased after SCI modeling. TGF-β1 was significantly increased in SCI rats with NLUTD and was correlated with autophagy markers LC3 and p62.


Ontogeny and sexual dimorphism of estradiol-2-hydroxylase activity in rat liver microsomes.
A radio-enzymatic method was used to measure the activity of estradiol-2-hydroxylase in liver microsomes of male and female Wistar rats, ranging in age from 10 to 63 days. In pre-pubertal rats (10-30 days) the Vmax increased, but revealed no sex differences. After 30 days of age, however, it decreased in females. In males, on the other hand, it increased still further, reaching a maximum in adulthood. The apparent Km showed no significant sex differences in pre-pubertal rats, but appeared to decline after puberty in females. In females puberty was also associated with the appearance of important changes in the kinetic properties of estradiol-2-hydroxylase. These changes were reflected in hyperbolic Lineweaver-Burk plots. Hill plots of this data gave straight lines with slopes significantly less than one--indicating negative cooperativity. Alternatively the hyperbolic Lineweaver-Burk plots could mean that the enzyme consists of more than one form, which act on the same substrate, but with different affinities. It is concluded that development in female Wistar rats is associated with important qualitative changes in the kinetic properties of estradiol-2-hydroxylase and that factors which become operative during puberty play a key role in initiating these changes.


[Influence of exogenous supplementation with luteinizing hormone during controlled ovarian hyperstimulation on the results of IVF cycle].
To evaluate the effect of exogenous luteinizing hormone in in vitro fertilization cycles with depot GnRH agonist and low residual LH levels. Prospective randomized clinical trial. 2nd Department of Gynecology and Obstetrics, Medical Faculty and L. Pasteur University Hospital Kosice In the prospective randomized clinical trial the effect of exogenous LH on outcomes of assisted reproduction was evaluated. The total number of 68 in vitro fertilization cycles in normogonadotrophic women undergoing assisted reproduction with GnRH agonist down-regulation and recombinant FSH controlled ovarian stimulation were included. In all cycles the low residual LH level in the middle of stimulation was detected. The cycles were randomized into three groups. The first group was stimulated with pure recombinant FSH. In the second group the exogenous LH activity in the form of human menotrophin was added. And in the third group the human recombinant LH was added. Better outcomes of assisted reproduction were detected in both groups with exogenous LH activity. But these results, except the dosage of FSH, were not statistically significant. The increase of pregnancy rate by more than one fifth in these both groups can be considered as clinically relevant. It can not be positively proved at the base of our results that exogenous LH activity in cycles with low residual LH level can improve outcomes of assisted reproduction. It could be appropriate in the future to select women that can profit from exogenous LH activity according to other parameters not only to the LH serum level.


Critically ill cancer patients are not consistently hypercoagulable after craniotomy.
Recent reports using thrombelastography have suggested that neurosurgical patients develop a hypercoagulable state in the postoperative period. Since venous thromboembolism is a potentially life threatening complication in these patients, we studied a similar population in our institution. We conducted a prospective pilot study to evaluate postoperative coagulation changes in critically ill cancer patients after craniotomy. Data collected included demographics, diagnoses, severity of illness, all hematological information (coagulation tests included conventional and TEG), therapies, and complications. Analysis included descriptive statistics, and multivariate regression analysis. Eleven patients were included in the study. Mean age was 52 +/- 17 years, BMI 28 +/- 6.5, APACHE II and SOFA scores were 11.18 +/- 5.0 and 3.82 +/- 1.6 respectively. The Coagulation Index (CI), which is derived from the measured values of R, K, MA, and alpha angle was 1.22 +/- 3.5, R 4.2 +/- 1.6, K 2.0 +/- 2.1, MA 60.78 +/- 5.97, and alpha angle 66.88 +/- 14.9; while the Thrombodynamic Potential Index (TPI), which is derived from the measured values of K and MA only was 32.48 +/- 21. The CI correlated significantly with R, K, alpha angle, MA, TMA, TPI, PMA, E, A30 and A60 but not with the PTT, INR, or SOFA and APACHE II scores. One patient was hypocoagulable by CI and TPI values; in contrast, nine patients were hypercoagulable by TPI but only one by CI. There were no cases of VTE. Hypercoagulability as defined by the CI was not a common finding in this study. Although the TPI indicated hypercoagulability in a large number of patients, we do not believe it is a good tool to assess the patient's clotting status or predictor of thrombosis because in contrast to the CI, it does not take into account the enzymatic portions of the clotting cascade. A larger TEG study is warranted to determine the clinical significance of these changes in this and other populations.


Oncogenic K-Ras requires activation for enhanced activity.
Oncogenic Ras mutations are widely considered to be locked in a permanent 'On' state and 'constitutively active'. Yet, many healthy people have cells possessing mutant Ras without apparent harm, and in animal models mutant Ras causes transformation only after upregulation of Ras activity. Here, we demonstrate that oncogenic K-Ras is not constitutively active but can be readily activated by upstream stimulants to lead to prolonged strong Ras activity. These data indicate that in addition to targeting K-Ras downstream effectors, interventions to reduce K-Ras activation may have important cancer-preventive value, especially in patients with oncogenic Ras mutations. As other small G proteins are regulated in a similar manner, this concept is likely to apply broadly to the entire Ras family of molecules.


Tissue tolerance of normal and surgically manipulated canine liver to intraoperative radiation therapy (IORT).
The purpose of the study is to obtain dose guidelines for the delivery of intraoperative radiotherapy to the liver of patients with colorectal liver metastases. Following partial resection of the liver, a single high dose of 10, 20, 25, and 30 Gy intraoperative radiotherapy was applied to both the resection plane as well as a nonsurgically manipulated part of the liver of 25 beagles. The temporal sequence of histological and ultrastructural changes of these irradiated parts of the liver tissue was investigated. The feasibility of delivering single large dose of intraoperative electron beam radiotherapy to the normal and partially hepatectomized liver was experimentally investigated in a canine study. There were no postoperative complications, no morbidity or mortality with a minimal follow-up of 1 year. Autopsy performed 3 months following irradiation showed only mild histopathological changes. One year following intraoperative radiotherapy more distinct histopathological changes consisting of capsular thickening, diffuse parenchymal fibrosis and subcapsular hepatocellular atrophy were found. The liver function remained intact. This study demonstrated that intraoperative radiotherapy to part of the liver in the canine model can be safely applied and doses up to 30 Gy are well tolerated.


Meet the authors: Tomoyuki Fukuda, Kentaro Furukawa, and Tomotake Kanki.
We talk to corresponding author Tomotake Kanki and co-first authors Tomoyuki Fukuda and Kentaro Furukawa about their paper "The mitochondrial intermembrane space protein mitofissin drives mitochondrial fission required for mitophagy" (this issue of Molecular Cell), their career paths, interests outside of their fields, and how they strike a work-life balance.


A 1D sensitivity-enhanced 1H spin diffusion experiment for determining membrane protein topology.
A sensitivity-enhanced 1D (1)H spin diffusion experiment, CHH, for determining membrane protein topology is introduced. By transferring the magnetization of the labeled protein (13)C to lipid and water protons for detection, the CHH experiment reduces the time of the original 2D (13)C-detected experiment by two orders of magnitude. The sensitivity enhancement results from (1)H detection and the elimination of the (13)C dimension. Consideration of the spin statistics of the membrane sample indicates that the CHH sensitivity depends on the (13)C labeling level and the number of protein protons relative to the mobile protons. 5-35% of the theoretical sensitivity was achieved on two extensively (13)C labeled proteins. The experimental uncertainties arise from incomplete suppression of the equilibrium (1)H magnetization and the magnetization of lipid protons directly bonded to natural-abundance carbons. The technique, demonstrated on colicin Ia channel domain, confirms the presence of a transmembrane domain and the predominance of surface-bound helices.


A novel fully enzymatic method for determining glucose and 1,5-anhydro-D-glucitol in serum of one cuvette.
The aim of the study was to set up a novel fully enzymatic method for screening glucose and 1,5-anhydro-D-glucitol (1,5-AG) in one cuvette. We have determined glucose and 1,5-AG, based on glucokinase (GK) converting glucose to G6P, a compound that can be catalyzed ultimately into 6-PGA by G-6PD and its coenzyme NADP(+), and then calculated glucose concentration according to absorbance variety. Furthermore, pyranose oxidase was used to oxidize 1,5-AG with the formation of 1, 5-anhydro-fructose and H(2)O(2). Measurement was done according to Trinder's reaction principle. The mean within-run and day-to-day precision (CV) of this method for glucose was 0.88% and 1.4%, and also that for 1,5-AG was 1.05% and 1.94%, respectively. The mean recovery rate of two targets was 100.2% and 101.6%, respectively. The correlation (R(2)) between the results of 1,5-AG obtained with our proposed method (y) and those obtained with LanaAG method (x) was 0.999 (y=1.002x-0.675 micromol/l; n=86), and the correlation (R(2)) of glucose between the results obtained with our GK method (y) and those obtained with recommendatory hexokinase method (x) was 0.9999 (y=1.0043x+0.1229 mmol/l; n=86). The reference range (95%) of serological glucose and 1,5-AG was 3.7 to 5.7 mmol/l (4.70+/-0.51 mmol/l) and 83.1 to 240.7 micromol/l (161.9+/-40.2 micromol/l), respectively; and there was no difference with age and sex (P>0.05). This newly developed method was dependable and steady-going, with analysis automatization, and allows quicker and easier measurement of serum glucose and 1,5-AG in one identical reaction cuvette in-phase than previously described methods.


Alcohol-induced rash caused by topical tacrolimus.
Topical treatment with tacrolimus may be complicated by ingestion-related flushing caused by consuming small amounts of alcohol, a reaction that can be mistaken for food allergy. To increase awareness of a drug interaction with alcohol that can mimic food allergy. We describe 3 patients who used topical tacrolimus, 2 with an atopic history and 1 without, who presented with a flushing reaction after ingesting alcohol. Cessation of topical tacrolimus use resolves the alcohol-related skin reaction. A careful history, including consideration of alcohol use, should be obtained in patients who use topical tacrolimus and present with new skin complaints, because these factors may be evidence of an avoidable drug interaction and not worsening of atopic disease or a food allergy.


Sleep function: Toward elucidating an enigma.
Sleep function remains controversial. Individual perspectives frame the issue of sleep function differently. We briefly illustrate how sleep measurement and the evolution, tissue organization levels, molecular mechanisms, and regulation of sleep could influence one's view of sleep function. Then we discuss six viable theories of sleep function. Sleep serves host-defense mechanisms and conserves caloric expenditures, but these functions likely are opportunistic functions evolving later in evolution. That sleep replenishes brain energy stores and that sleep serves a glymphatic function by removing toxic byproducts of waking activity are attractive ideas, but lack extensive supporting experimental evidence. That sleep restores performance is experimentally demonstrated and has obvious evolutionary value. However, this hypothesis lacks experimentally verified mechanisms although ideas relating to this issue are presented. Finally, the ideas surrounding the broad hypothesis that sleep serves a connectivity/plasticity function are many and attractive. There is experimental evidence that connectivity changes with sleep, sleep loss, and with changing afferent input, and that those changes are linked to sleep regulatory mechanisms. In our view, this is the leading contender for the primordial function of sleep. However, much refinement of ideas and innovative experimental approaches are needed to clarify the sleep-connectivity relationship.


Draw-fill batch culture mode for production of xylanases by Cellulomonas flavigena on sugar cane bagasse.
Draw-fill culture was evaluated as a method for xylanase production by Cellulomonas flavigena on sugar cane bagasse. Specific xylanase activity and volumetric xylanase activities were measured by harvesting 50%, 55%, 60% and 70% of fermented broth at the end of each subculture. Maximum specific (64 IU mg(-1) protein) and volumetric (166 IU ml(-1)) xylanase activities were obtained by harvesting 50-55% of broth. Values were 3.4 and 3.8 times greater than those obtained in batch cultures carried out under the same conditions. Enzyme productivity of 4.2 IU ml(-1) h(-1) was significantly greater than that obtained in continuous cultures (2.4 IU ml(-1) h(-1)) (P<0.05).


Differentiation of non-aureus staphylococci species isolated from bovine mastitis by PCR-RFLP of groEL and gap genes in comparison to MALDI-TOF mass spectrometry.
Intramammary infections (IMI) cause serious economic losses for farmers and the dairy industry. Cases of subclinical mastitis are commonly the result of infection by minor pathogens such as non-aureus staphylococci (NAS), so their correct identification is important for appropriate therapeutic intervention and management. The aim of this study was to assess the reliability of PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) of the groEL and gap genes to discriminate between bovine-associated NAS species, using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) as the reference method. MALDI-TOF MS was able to correctly identify 112 NAS isolates from bovine IMI at species level out of a total of 115 (97.4%). These results were considered definitive and thus compared with those from the PCR-RFLP analyses. Only 50% (56/112) of the samples classified through groEL PCR-RFLP matched the molecular identity determined by MALDI-TOF MS, whereas coincidence rose to 96.4% (108/112) when comparing results from gap PCR-RFLP and the spectral analysis. This study demonstrates that gap PCR-RFLP is a useful and reliable tool for the identification of NAS species isolated from bovine mastitis.


Female bone physiology resilience in a past Polynesian Outlier community.
Remodelling is a fundamental biological process involved in the maintenance of bone physiology and function. We know that a range of health and lifestyle factors can impact this process in living and past societies, but there is a notable gap in bone remodelling data for populations from the Pacific Islands. We conducted the first examination of femoral cortical histology in 69 individuals from ca. 440-150 BP Taumako in Solomon Islands, a remote 'Polynesian Outlier' island in Melanesia. We tested whether bone remodelling indicators differed between age groups, and biological sex validated using ancient DNA. Bone vascular canal and osteon size, vascular porosity, and localised osteon densities, corrected by femoral robusticity indices were examined. Females had statistically significantly higher vascular porosities when compared to males, but osteon densities and ratios of canal-osteon (~ 8%) did not differ between the sexes. Our results indicate that, compared to males, localised femoral bone tissue of the Taumako females did not drastically decline with age, contrary to what is often observed in modern populations. However, our results match findings in other archaeological samples-a testament to past female bone physiology resilience, also now observed in the Pacific region.


Identification of positive parenting practices among parents of young children living in low-income and racially, ethnically, and culturally diverse households.
Using the positive deviance approach, the purpose of this study was to identify parent feeding practices that might be protective against early childhood obesity among children with lower weight status (BMI percentile ≥5th-<85th) relative to higher weight status (BMI percentile ≥85th). Qualitative interviews were conducted with 71 parents of children aged 2-5 years old (48% girls) enrolled in the Minnesota Special Supplemental Nutrition Program for Women Infants and Children (WIC). Children were identified as having lower weight status (defined as 'positive deviants') (n = 36) or 'higher weight status' (n = 35), and were African American [n = 22], Hispanic [n = 23], or Hmong [n = 26]). Parents were asked about approaches to child feeding and health- and weight-related practices. Findings indicated that relative to caregivers of children with higher weight status, parents of children identified as positive deviant were more likely to report having a consistent routine for providing meals, using a guided choices approach, serving small portions of food during mealtimes, and trusting their child hunger and satiety cues. Moreover, parents of children identified as positive deviant were more likely to promote healthful eating and physical activity engagement and implement clear rules and limits for screen time than parents of children with higher weight status. Results suggest specific parent feeding behaviors and health-related practices that may influence child weight status among children living in low-income and racialized households. The findings of this study also provide research evidence and support the tenets of the Satter Division of Responsibility in Feeding framework. Parenting practices and strategies among parents of children identified as positive deviant are expected to be feasible and should be explored and communicated in future interventions to support age- and sex-recommended weight and health-related outcomes among young children to promote health equity.


Stigmatizing attitudes toward obesity in a representative population-based sample.
The aim of this study was to determine stigmatizing attitudes toward obesity in the population, and its related psychological and sociodemographic determinants. In a representative population-based survey (N=1,000), computer-assisted telephone interviewing was used to assess stigmatizing attitudes toward obesity, causal attributions of obesity, the labeling of obesity as an illness, perceptions about prevalence, severity, and chronicity of obesity, support of obesity prevention, and sociodemographic characteristics. Of the 1,000 participants, 23.5% (n=235) had stigmatizing attitudes toward obesity, 21.5% (n=215) did not have stigmatizing attitudes toward obesity, and 55.0% (n=550) had attitudes that were undetermined with respect to stigmatization. Predictors of greater stigmatization were more causal attributions of obesity to individual behavior, less education, and older age, while causal attributions of obesity to heredity and labeling obesity as an illness predicted less stigmatization. Stigmatizing attitudes were significantly associated with stronger overall support of obesity prevention, but less readiness to support prevention financially. Our results indicate that stigmatizing attitudes toward obesity are prevalent in the population. Information about the etiology of obesity and the clinical relevance of this condition could prove useful for destigmatization efforts.


Development of prospective hospital-based venous thromboembolism registry across India: a study protocol.
Indian Council of Medical Research (ICMR), New Delhi has established a nationwide registry 'Indian Registry for Venous Thromoembolism Disorder (i-RegVeD)' for real-time analytics of sociodemographic profile of patients, disease patterns, management strategies, treatment choices and outcomes of patients with venous thromboemobolism (VTE). The purpose is to generate evidence on VTE in order to fill the gaps in the knowledge of the disease across various demographic regions. This prospective hospital-based registry will be a continuous data collection process on the occurrence and characteristics of VTE from the 16 hospital sites pan India. This process would include obtaining clinical profiles, risk factors, diagnostic tests, treatment and outcome information of patients collected from medical records through an active method of data abstraction and data capture mechanism guided by an online web-based tool. At centralised programme management unit, the study protocol was approved by the Institutional Ethics Committees (IEC) named ICMR-Central Ethics Committee on Human Research and similarly each of the participating site has obtained the ethical approval by their respective IECs. The results from this study will be disseminated publicly on the study website (https://iregved.icmr.org.in) as well as through scientific meetings and publications.


Toward next-generation primate neuroscience: A collaboration-based strategic plan for integrative neuroimaging.
Open science initiatives are creating opportunities to increase research coordination and impact in nonhuman primate (NHP) imaging. The PRIMatE Data and Resource Exchange community recently developed a collaboration-based strategic plan to advance NHP imaging as an integrative approach for multiscale neuroscience.


Ten years experience with paravariceal injection sclerotherapy of esophageal varices in children.
Esophageal varices in 59 consecutive children with portal hypertension were treated by paravariceal injection sclerotherapy. Repeated injections were performed using a special rigid instrument under general anesthesia. In children older than 10 a flexible endoscope was used without general anesthesia. Using 0.5% Polidocanol, a fibrous layer protecting varices against the further bleeding was produced in 59 children. Complications during treatment included hemorrhage, esophageal ulceration and stricture, each in two children. 55 children have been followed for 6 months to 10 years after two phases of paravariceal injection following the first phase of treatment. Three rebleeds have occurred in this group. Sclerotherapy was repeated. Thereafter, using a regular endoscopic control every year, no rebleeding occurred. Four children with liver cirrhosis died of liver failure. All other children except four foreign ones could be followed. 51 of them (86%) are alive.


Stapled side-to-side anastomosis for ileostomy reversal: a simple and reproducible technique with video.
Protective diverting ileostomy is commonly performed in rectal surgery to avoid septic complications of low colorectal anastomosis. Ileostomy closure usually occurs three months after the surgery and can be realized in two ways: hand sewn or stapled. Existing randomized studies comparing the two techniques showed no difference in terms of complications. Our study describes the standard technique of ileostomy reversal as done in Bordeaux University Hospital in 10 steps individually illustrated and with an explicative video. We also collected data concerning the 50 last patients who underwent an ileostomy reversal in our center from June 2021 to June 2022. Mean duration of the ileostomy closure was 46.8 minutes, and the mean total hospital stay was 4.66 days. Five of 50 (10%) patients had a post-operative bowel obstruction, 2/50 (4%) patients had a post-operative bleeding, 1/50 (2%) patient had a wound infection, and there was no anastomotic leakage observed. Stapled side-to-side anastomosis is a rapid, simple, and reproducible technique for ileostomy reversal. There are no more complications compared to hand-sewn anastomosis. It engenders an additional cost compensated by the gain in operating time which altogether saves money.


Compartment Syndrome of the Leg after Intraosseous (IO) Needle Insertion.
Intraosseous (IO) needles are used in patients who are critically ill when it is not possible to obtain venous access. While IO allows for immediate access, IO infusions are associated with complications including fractures, infections, and compartment syndrome. We present a case of an 87-year-old man who developed lower extremity compartment syndrome after receiving an IO needle insertion and had to be treated surgically with fasciotomy to correct the problem.


Antiretroviral therapy voluntarily taken at half-dosage, but fully effective after 6-10 years: a provocative issue for adherence requirements: case report.
Aim of our report is to discuss some key adherence features in the real world, by reporting two exceptional patients, who deliberately took all antiretroviral medications at half-dosage compared with standard prescriptions, and maintained a fully stable and sustained virological and immunological response after 6-10 consecutive years. The potential causes and consequences of this apparent misconduct of our patients on drug tolerability, resistance development, compliance monitoring, direct drug delivery, and health care providers behavior, are discussed.


Parathyroid hormone-like peptide in pancreatic endocrine carcinoma and adenocarcinoma associated with hypercalcemia.
Parathyroid hormone-like peptide (PLP) is produced by a number of tumors commonly associated with hypercalcemia as well as by nontumorous tissue, including some endocrine organs. We applied immunohistochemistry using the avidin-biotin-peroxidase technique to localize PLP in formalin-fixed, paraffin-embedded tissues of two human pancreatic carcinomas associated with hypercalcemia and normal blood parathyroid hormone levels. One tumor was endocrine and one was exocrine in differentiation. There was no evidence of bone metastasis in either case. We documented normalization of serum calcium level after removal of the pancreatic endocrine tumor. These observations support the suggestion that PLP production by pancreatic carcinoma may play a role in the development of hypercalcemia. However, the presence of PLP in tumors not associated with hypercalcemia indicates that other factors in addition to PLP are necessary for the manifestation of hypercalcemia. Hypercalcemia associated with exocrine pancreatic tumor has rarely been reported. Our exocrine pancreatic tumor appears to be the first reported case in which immunohistochemistry localized PLP. Since PLP has been localized to cells of exocrine ducts and ductules of normal pancreas, our results provide insight into the cell of origin of this tumor type.


Characterization of particulate and soluble guanylate cyclases from rat lung.
Rat lung homogenates contained significant amounts of guanylate cyclase activity in both 100,000 times g (60 min) particulate and supernatant fractions. In the presence of detergent, the particulate fraction contained 40% as much activity as did the supernatant fraction. Detergent-dispersed particulate and partially purified soluble guanylate cyclase preparations were characterized with respect to divalent cation requirements, divalent cation interactions, kinetic behavior, and gel filtration profiles. Both soluble and particulate guanylate cyclases required divalent cation for activity. The soluble preparation was 10 times more active in the presence of Mn-2plus than in the presence of Mg-2plus or Ca-2plus and no detectable activity was seen with Ba-2plus or Sr-2plus. Particulate guanylate cyclase activity was detectable only in the presence of Mn-2plus. Both enzyme preparations required Mn-2plus in excess of GTP for optimal activity at subsaturating amounts of GTP. At near-saturating GTP, the soluble enzyme required excess Mn-2plus, but the particulate enzyme did not. For kinetic analyses the enzymes were considered to require two substrates: metal-GTP and Me-2plus. Apparent negative cooperative behavior was seen with the soluble enzyme when excess Mn-2plus (in excess of GTP) was varied from 0.01 to 0.2 mM; above 0.2 mM excess Mn-2plus classical kinetic behavior was seen with an apparent KMn-2plus of 0.2 mM at near-saturating MnGTP. Similar studies using the particulate preparation yielded only classical kinetic behavior, but the apparent KMn-2plus decreased to near zero when MnGTP was near-saturating. Kinetic patterns for the particulate and soluble enzymes also differed when reciprocal initial velocities were plotted as a function of reciprocal MnGTP concentrations; classical kinetic behavior was seen with the soluble enzyme with an apparent KMnGTP of about 12 muM (at near-saturating excess Mn-2plus), whereas apparent positive cooperative behavior was seen with the particulate preparation (Hill coefficient equals 1.6, S0.5 EQUALS 70 MUM. Ca-2plus "activation" of soluble guanylate cyclase was related to the Mn-2plus:GTP ratio. Activation was most apparent when saturating amounts of Mn-2plus and MnGTP. At relatively high concentrations of Ca-2plus (0.1 to 4 mM), the addition of 10 muM Mn-2plus resulted in a 3- to 5-fold increase in soluble guanylate cyclase activity. In contrast, Ca-2plus sharply inhibited particulate guanylate cyclase activity. Gel filtration profiles of particulate and soluble preparations indicated differences in physical properties of the enzymes. As estimated by gel filtration, particulate (detergent-dispersed)evels. Here, removal of renal tissue is contraindicated. In all renal hy


The ground of ground, essence, and explanation.
This paper is about the so-called meta-grounding question, i.e. the question of what grounds grounding facts of the sort 'ϕ is grounded in Γ'. An answer to this question is pressing since some plausible assumptions about grounding and fundamentality entail that grounding facts must be grounded. There are three different accounts on the market which each answer the meta-grounding question differently: Bennett's and deRosset's "Straight Forward Account" (SFA), Litland's "Zero-Grounding Account" (ZGA), and "Grounding Essentialism" (GE). I argue that if grounding is to be regarded as metaphysical explanation (i.e. if unionism is true), (GE) is to be preferred over (ZGA) and (SFA) as only (GE) is compatible with a crucial consequence of the thought that grounding is metaphysical explanation. In this manner the paper contributes not only to discussions about the ground of ground but also to the ongoing debate concerning the relationship between ground, essence, and explanation.


Alcohol consumption and risk for congestive heart failure in the Framingham Heart Study.
Although excessive alcohol consumption can promote cardiomyopathy, little is known about the association between alcohol consumption and risk for congestive heart failure in the community. To determine the relation between alcohol consumption and risk for congestive heart failure in the community. Community-based, prospective observational study. Framingham, Massachusetts. Participants in the Framingham Heart Study who were free of congestive heart failure and coronary heart disease. Self-reported alcohol consumption; sex-specific rates of congestive heart failure per 1000 person-years of follow-up by level of alcohol consumption. In men, 99 cases of congestive heart failure occurred during 26 035 person-years of follow-up. In women, 120 cases of congestive heart failure occurred during 35 563 person-years of follow-up. After adjustment for multiple confounders, risk for congestive heart failure was lower among men at all levels of alcohol consumption compared with men who consumed less than 1 drink/wk. The hazard ratio for congestive heart failure was lowest among men who consumed 8 to 14 drinks/wk (0.41 [95% CI, 0.21 to 0.81]) compared with those who consumed less than 1 drink/wk. In women, the age-adjusted hazard ratio for congestive heart failure was lowest among those who consumed 3 to 7 drinks/wk (0.49 [CI, 0.25 to 0.96]) compared with those who consumed less than 1 drink/wk. However, after adjustment for multiple predictors of congestive heart failure, this association was no longer statistically significant. In the community, alcohol consumption is not associated with increased risk for congestive heart failure, even among heavy drinkers (> or = 15 drinks/wk in men and > or = 8 drinks/wk in women). To the contrary, when consumed in moderation, alcohol appears to protect against congestive heart failure.


Reconstruction of wound defects in the perineum.
Surgical procedures in the perineum can cause major soft-tissue defects that require reconstruction with plastic surgery. In this article we present plastic surgery principles for the reconstruction of wound defects and common methods used to reconstruct wound defects in the perineum.


From children's toy to versatile sensor: One-step doping of Play-Doh with primary amino group for explosive detection both on surfaces and in solution.
2,4,6-trinitrotoluene (TNT) sensing on surfaces and in solution is an important issue in sensor fabrication for homeland security and environmental protection. Herein, Play-Doh, a modeling material popular for kids, was proposed as a versatile sensor for on-site fluorescent (FL), visual FL (VFL), and colorimetric detection of TNT both on surfaces and in solution after being doped with -NH2 through a one-step approach. Play-Doh exhibits FL emission due to the main ingredient of flour. After -NH2 doping, amino-Play-Doh (APD) was utilized to construct a FL sensor based on FL resonance energy transfer and inner filter effect for TNT detection. The advantage of APD was that no additional fluorophore was needed compared with the traditional sensors for FL and VFL analysis. The orange complex visible to the naked eye was also recorded for smartphone-based colorimetric detection of TNT. In both cases, the APD demonstrated good analytical performance for TNT. Finally, APD was successfully utilized for TNT sensing on fingerprints, luggage, and in environmental water samples, respectively. Play-Doh might be a potential sensor for future on-site detection of TNT owing to the merits of being cost-effective and versatile.


A new method of lower extremity immobilization in radiotherapy.
We developed a new method for immobilization of the fix lower extremities by using a thermoplastic mask, a carbon fiber base plate, a customized headrest, and an adjustable angle holder. The lower extremities of 11 patients with lower extremity tumors were immobilized by this method. CT simulation was performed for each patient. For all 11 patients, the device fit was suitable and comfortable and had good reproducibility, which was proven in daily radiotherapy.


The antimicrobial efficacy of plasma-activated water against Listeria and E. coli is modulated by reactor design and water composition.
This study aimed to compare the efficacy of plasma-activated water (PAW) generated by two novel plasma reactors against pathogenic foodborne illness organisms. The antimicrobial efficacy of PAW produced by a bubble spark discharge (BSD) reactor and a dielectric barrier discharge-diffuser (DBDD) reactor operating at atmospheric conditions with air, multiple discharge frequencies and Milli-Q and tap water, was investigated with model organisms Listeria innocua and Escherichia coli in situ. Optimal conditions were subsequently employed for pathogenic bacteria Listeria monocytogenes, E. coli and Salmonella enterica. DBDD-PAW reduced more than 6-log of bacteria within 1 min. The BSD-PAW, while attaining high log reduction, was less effective. Analysis of physicochemical properties revealed that BSD-PAW had a greater variety of reactive species than DBDD-PAW. Scavenger assays designed to specifically sequester reactive species demonstrated a critical role of superoxide, particularly in DBDD-PAW. DBDD-PAW demonstrated rapid antimicrobial activity against pathogenic bacteria, with superoxide the critical reactive species. This study demonstrates the potential of DBDD-PAW produced using tap water and air as a feasible and cost-effective option for antimicrobial applications, including food safety.


Cost and Effectiveness of Percutaneous Endoscopic Interlaminar Discectomy versus Microscope-Assisted Tubular Discectomy for L5-S1 Lumbar Disc Herniation.
To assess the cost and effectiveness of percutaneous endoscopic interlaminar discectomy (PEID) and microscope-assisted tubular discectomy (MATD) for patients with L5/S1 lumbar disc herniation (LDH). The medical and financial records of patients diagnosed with L5/S1 LDH and who underwent either PEID or MATD from April 2021 to April 2022 were retrospectively collected. Demographic and baseline information, perioperative observational index, clinical outcomes, and inpatient costs were analyzed. Sixty patients were included, with 30 patients in the PEID group and 30 patients in the MATD group. No significant difference was found in demographic and baseline information between the 2 groups (P > 0.05). The PEID group showed significantly shorter incision length, less intraoperative blood loss, shorter hospital stays, and higher intraoperative fluoroscopy frequency compared with the MATD group (P < 0.05). There were no significant differences in visual analog scale back/leg score, Oswestry Disability Index, and 36-Item Short-Form Survey score between PEID and MATD groups before the surgery and at any follow-up time points (P > 0.05). The total cost, surgery cost, and surgical instruments/materials cost were significantly higher in the PEID group compared with the MATD group (P < 0.05). In contrast, the drug and nursing costs were significantly higher in the MATD group than in the PEID group (P < 0.05). PEID and MATD provide equivalent clinical efficacy and safety in treating LDH at L5/S1 segment within a 1-year follow-up. However, PEID is less invasive and MATD is less costly. No one surgical technique is superior in all aspects and patients should make decisions according to their top concern.


Brief Visual Deprivation Effects on Brain Oscillations During Kinesthetic and Visual-motor Imagery.
It is widely recognized that opening and closing the eyes can direct attention to external or internal stimuli processing. This has been confirmed by studies showing the effects of changes in visual stimulation changes on cerebral activity during different tasks, e.g., motor imagery and execution. However, an essential aspect of creating a mental representation of motion, such as imagery perspective, has not yet been investigated in the present context. Our study aimed to verify the effect of brief visual deprivation (under eyes open [EO] and eyes closed [EC] conditions) on brain wave oscillations and behavioral performance during kinesthetic imagery (KMI) and visual-motor imagery (VMI) tasks. We focused on the alpha and beta rhythms from visual- and motor-related EEG activity sources. Additionally, we used machine learning algorithms to establish whether the registered differences in brain oscillations might affect motor imagery brain-computer interface (MI-BCI) performance. The results showed that the occipital areas in the EC condition presented significantly stronger desynchronization during VMI tasks, which is typical for enhanced visual stimuli processing. Furthermore, the stronger desynchronization of alpha rhythms from motor areas in the EO, than EC condition confirmed previous effects obtained during real movements. It was also found that simulating movement under EC/EO conditions affected signal classification accuracy, which has practical implications for MI-BCI effectiveness. These findings suggest that shifting processing toward external or internal stimuli modulates brain rhythm oscillations associated with different perspectives on the mental representation of movement.


Noninvasive measurement of molar concentrations of 31P metabolites in vivo, using surface coil NMR spectroscopy.
The measurement of absolute concentration of 31P metabolites is described, using water 1H as an internal concentration standard. An analysis of the effect of variations in coil Q on flip angle and sensitivity is presented and verified experimentally. Concentrations of nucleoside triphosphate in rat brain and muscle have been measured.


Preparation of PS/TiO2/UF multilayer core-shell hybrid microspheres with high stability.
In this paper, we report a facile method for preparation of polystyrene/titania/urea-formaldehyde resin (PS/TiO(2)/UF) multilayer core-shell hybrid microspheres with high stability through in situ condensation polymerization. The TEM images show that the thickness of UF shells is about 10 nm. The Zeta potential is close to zero. The density of PS/TiO(2)/UF could be controlled to 1.85 g/cm(3), which matches well with the non-polar dispersant (tetrachloroethylene). They are well dispersed and remain non-agglomerated even over several months, so they could be potential building blocks to fabricate electrophoretic display. Some parameters such as the ratio of urea-formaldehyde prepolymer (UFP) to PS/TiO(2), the pH value, and the temperature are also investigated.


Ornithine decarboxylase induction and polyamine biosynthesis by phorone (diisopropylidene acetone), a glutathione depletor, in rats.
The administration of Phorone (diisopropylidene acetone, 250 mg/kg, ip.), a glutathione (GSH) depletor, markedly induced (400-fold of the control at 12 hr) ornithine decarboxylase (ODC) in the liver of rats. Parallel to ODC induction there was a marked increase in hepatic putrescine content. Phorone also produced an increase in spermidine content and a decrease in spermine content. The effects of phorone on ODC and putrescine content occurred dose-dependently with more than a 1000-fold increase in ODC activity over the controls at a dose of 500 mg/kg. Pretreatment of rats with buthionine sulfoximine, a GSH depletor by inhibition of biosynthesis, failed to inhibit phorone-mediated induction of ODC. In contrast, pretreatment with GSH, but not post-treatment, blocked the induction of ODC by phorone.


Prolactin: a hormonal regulator of the neonatal tissue water reservoir.
Groups of newborn rabbits were treated with exogenous prolactin, with fluphenazine (a stimulant of endogenous prolactin secretion) with bromocriptine (a blocker of endogenous prolactin secretion), or with bromocriptine plus exogenous prolactin, and lean body hydration in these animals was compared with that of untreated controls. Animals treated with prolactin or fluphenazine retained more water than did the controls. Bromocriptine-treated animals retained less water than did the controls. Exogenous prolactin abolished the effect of bromocriptine.


Comparison of functional and total capillary densities in fast and slow muscles of the chicken.
The anterior latissimus dorsi (ALD) and posterior latissimus dorsi (PLD) of the domestic chicken were used to study the possible differences in functional capillary density of slow and fast skeletal muscle. Frozen sections of each muscle were prepared for histochemical determination of fiber homogeneity, capillary/fiber ratios, and capillary densities. The functional capillary bed (percent open capillaries) was determined by comparing the number of ink-filled capillaries, after a systemic injection of india ink (for 90-120 s), with the total number of capillaries/mm2. ALD is a slow-tonic muscle consisting of two fiber types, with an average of 1.34 +/- 0.03 capillaries/fiber, a density of 699 +/- 20 capillaries/mm2, and a functional capillary bed representing 29% (ratio of open to total number of capillaries/mm2 was 0.286 +/- 0.022) of the total bed. PLD is a fast-twitch muscle also having two fiber types, with an average of 1.08 +/- 0.04 capillaries/fiber, a density of 561 +/- 26 capillaries/mm2, and a functional bed representing 11% (ratio of open capillaries to total is 0.111 +/- 0.014) of the total. These findings of increased capillarity (24% more capillaries/fiber and 25% more capillaries/mm2) and higher functional capillary density in an avian pure slow muscle (ALD), corroborate previous findings of increased capillarity around slow fibers in mixed muscles of several mammalian species. The values given represent the means +/- SEM.


Developmental differences in myocardial ATP metabolism.
Little is known about postnatal changes in myocardial purine metabolism. We therefore studied how ATP catabolism was affected by hypothermia and ischaemia in neonatal and adult hearts. Hypothermia during ischaemia protected isolated adult and newborn hearts against ATP decline. Reperfusion after normothermic ischaemia resulted in higher ATP levels in newborn hearts with less release of ATP-catabolites. During normoxia adult hearts released mainly urate (80% of total purine release), while newborns released mainly hypoxanthine (64%). During early reperfusion adult and newborn hearts released mainly inosine (50-60%). The very low xanthine oxidase activity in the neonatal heart could be an important factor in the observed ATP preservation during reperfusion.


Influence of physicochemical parameters on PPCP occurrences in the wetlands.
There have been many global studies on the occurrence and distribution of pharmaceuticals and personal care products (PPCPs) in the aquatic resources, but reports on the effects of physicochemical properties of water on their concentrations are very scarce. The amounts and removal of these contaminants in various environmental media are dependent on these physicochemical properties, which include pH, temperature, electrical conductivity, salinity, turbidity, and dissolved oxygen. Here, we reviewed the influence of these properties on determination of PPCPs. Reports showed that increase in turbidity, electrical conductivity, and salinity gives increase in concentrations of PPCPs. Also, neutral pH gives higher PPCP concentrations, while decrease in temperature and dissolved oxygen gives low concentration of PPCPs. Nevertheless, it is quite challenging to ascertain the influence of water quality parameters on the PPCP concentration, as other factors like climate change, type of water, source of pollution, persistence, and dilution factor may have great influence on the concentration of PPCPs. Therefore, routine monitoring is suggested as most water quality parameters vary because of effects of climate change.


At what level of unconsciousness is mild therapeutic hypothermia indicated for out-of-hospital cardiac arrest: a retrospective, historical cohort study.
Appropriate patient selection is very important when initiating mild therapeutic hypothermia (MTH) for patients following out-of-hospital cardiac arrest, and the extent of unconsciousness at implementation must be defined in such cases. However, there are no clear standards regarding the level of unconsciousness at which MTH would be beneficial. The effects of MTH in patients with different degrees of unconsciousness according to the motor response score of the Glasgow Coma Scale (GCS) were investigated. The subjects consisted of witnessed non-traumatic adult out-of-hospital cardiac arrest patients admitted to our institute from April 2002 to August 2011. The patients were divided into six groups according to the GCS motor response score: 1 (GCS M1), 2 (GCS M2), 3 (GCS M3), 4 (GCS M4), 5 (GCS M5), and 6 (GCS M6). The neurological outcome was evaluated at 30 days after hospital admission using the Cerebral Performance Category. Chi-squared Automatic Interaction Detection (CHAID) analysis was performed to estimate the threshold GCS M level where therapeutic hypothermia is indicated. Odds ratios were then calculated by multiple logistic-regression analysis using factors including GCS M5-6 and MTH. A total of 289 patients were enrolled in this study. CHAID analysis demonstrated two points of significant increase in percentage of good recovery at 30 days after admission, dividing the GCS M categories into three groups. Patients classified with a GCS motor response score of 5 or higher had the highest percentage of good recovery. The odds ratio for good recovery (CPC1-2) was 2.901 (95 % CI 1.460-5.763, P = 0.002) for MTH, and that for GCS M5-6 was 159.835 (95 % CI 33.592-760.513, P < 0.001). MTH may be unnecessary in patients with a GCS motor response score of 5 or higher. Consequently, because there are post cardiac arrest patients with a GCS motor response score of 4 or lower who benefit from MTH, MTH may be limited to patients with a GCS motor response score of 4 or lower.


Coconut Oil Alleviates the Oxidative Stress-Mediated Inflammatory Response via Regulating the MAPK Pathway in Particulate Matter-Stimulated Alveolar Macrophages.
Exposure to particulate matter (PM) is related to various respiratory diseases, and this affects the respiratory immune system. Alveolar macrophages (AMs), which are defenders against pathogens, play a key role in respiratory inflammation through cytokine production and cellular interactions. Coconut oil demonstrates antioxidant and anti-inflammatory properties, and it is consumed worldwide for improved health. However, reports on the protective effects of coconut oil on the PM-induced respiratory immune system, especially in AMs, are limited. In this study, we generated artificial PM (APM) with a diameter approximately of 30 nm by controlling the temperature, and compared its cytotoxicity with diesel exhaust particles (DEP). We also investigated the antioxidant and anti-inflammatory effects of coconut oil in APM− and DEP−stimulated AMs, and the underlying molecular mechanisms. Our results showed that APM and DEP had high cytotoxicity in a dose-dependent manner in AMs. In particular, APM or DEP at 100 μg/mL significantly decreased cell viability (p < 0.05) and significantly increased oxidative stress markers such as reactive oxygen species (p < 0.01); the GSSH/GSH ratio (p < 0.01); and cytokine production, such as tumor necrosis factor-α (p < 0.001), interleukin (IL)-1β (p < 0.001), and IL-6 (p < 0.001). The expression of the genes for chemokine (C-X-C motif) ligand-1 (p < 0.05) and monocyte chemoattractant protein-1 (p < 0.001); and the proteins toll-like receptor (TLR) 4 (p < 0.01), mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (p < 0.001), p38 (p < 0.001); and extracellular receptor-activated kinase (p < 0.001), were also upregulated by PM. These parameters were reversed upon treatment with coconut oil in APM− or DEP−stimulated AMs. In conclusion, coconut oil can reduce APM− or DEP−induced inflammation by regulating the TLR4/MAPK pathway in AMs, and it may protect against adverse respiratory effects caused by PM exposure.


Axillary reverse mapping: a prospective study in women with clinically node negative and node positive breast cancer.
The primary aim of axillary reverse mapping (ARM) is to prevent lymphedema by preserving arm versus breast axillary lymphatics. Concerns regarding feasibility and oncologic safety have limited the adoption of the technique. This prospective study was undertaken to investigate ARM in clinically node negative and node positive breast cancer patients. A total of 184 patients underwent 212 ARM procedures: 155 sentinel lymph node biopsies (SLNB) without axillary lymph node dissection (ALND) (group 1) and 57 ALNDs with/without SLNB (group 2). ARM lymphatics were not preserved if they were a SLN, directly entered a SLN, or were within ALND boundaries during ALND. SLN with radioisotope alone was successful in 92 % of procedures (181 of 197). ARM identification was 47 % (73 of 155) in group 1. Criteria were met in 30 % (47 of 155) for preservation, and 25 % (38 of 155) were preserved. Of those who met preservation criteria, 81 % (38 of 47) were preserved. In group 2, ARM identification was 72 % (41 of 57); 7 met criteria for preservation and were preserved. Of the ARM nodes, 10 % (22 of 212) were SLNs (crossover). ARM nodes contained metastatic disease in one crossover and two nonsentinel ARM nodes in clinically node positive patients with N2/N3 disease. ARM is a feasible technique for identification and preservation of axillary arm lymphatics with an acceptable incidence of SLN crossover. A larger sample size is needed to determine if ARM can reduce the incidence of lymphedema in patients undergoing SLNB alone and to confirm the absence of ARM metastases in clinically node negative patients undergoing ALND.


Chronic kidney disease and vaccinations-A practical guide for primary care providers.
Patients with chronic kidney disease (CKD) are susceptible to infectious organisms in part due to the many facets of uremia-associated immune deficiency. Vaccination plays a crucial role in curbing vaccine preventable infection in patients with CKD and Kidney transplant recipients. Vaccination should be done early in the course of CKD or prior to kidney transplantation when possible. It is incumbent upon all healthcare providers to not only stay abreast of the rapidly evolving evidence and recommendations regarding this area but to also continue to update clinical practice regarding vaccines for long-recognized infectious threats, such as pneumococcal disease and chronic hepatitis B infection, to mitigate the burden of infectious diseases on this particularly vulnerable patient population.


Fertilization potential in golden hamster eggs consists of recurring hyperpolarizations.
The fertilization potential, or activation potential, has been demonstrated in the eggs of various species, and it has been shown to block polyspermy in echinoderm, echiuran and frog eggs, but no studies have been reported of electrical phenomena occurring when mammalian eggs are fertilized. We report here the fertilization potential of golden hamster eggs in vitro. To correlate the change of potential with the interaction between sperm and egg, only one sperm was attached to each egg. We found that a sperm induces recurring hyperpolarizations, constituting a fertilization potential which differs from that in the eggs of other species.


Automatic detection of drowsiness in EEG records based on multimodal analysis.
Drowsiness is one of the main causal factors in many traffic accidents due to the clear decline in the attention and recognition of danger drivers, diminishing vehicle-handling abilities. The aim of this research is to develop an automatic method to detect the drowsiness stage in EEG records using time, spectral and wavelet analysis. A total of 19 features were computed from only one EEG channel to differentiate the alertness and drowsiness stages. After a selection process based on lambda of Wilks criterion, 7 parameters were chosen to feed a Neural Network classifier. Eighteen EEG records were analyzed. The method gets 87.4% and 83.6% of alertness and drowsiness correct detections rates, respectively. The results obtained indicate that the parameters can differentiate both stages. The features are easy to calculate and can be obtained in real time. Those variables could be used in an automatic drowsiness detection system in vehicles, thereby decreasing the rate of accidents caused by sleepiness of the driver.


Therapeutic wisdom in traditional Chinese medicine: a perspective from modern science.
The reasons why the standards of evaluating Western medicine are not suitable for testing traditional Chinese medicine (TCM) are explicit in the therapeutic objective and principles of TCM. TCM aims to correct maladjustments and restore the self-regulatory ability of the body, and not to antagonize specific pathogenetic targets. Maladjustments in a disease can be classified into several 'patterns' according to TCM theory. Multiple diseases might share one 'pattern' and be treated by the same herbal formula whereas one disease might display several different 'patterns' and be treated by multiple formulae. These principles are supported by evidence that multi-system changes in one pattern can be modulated by a herbal formula. The approaches used in systems biology and pharmacogenetics are similar to the practices of TCM. I propose that a combined approach using specific parameters associated with modern medicine, the general condition of individuals, as outlined by TCM, and pattern stratification of diseases should be employed to re-evaluate herbal formulae.