Plasma concentrations during naltrexone implant treatment of opiate-dependent patients.
To evaluate individual variations in plasma concentrations over time in patients with naltrexone implants. Ten opioid-dependent patients received up to four implants. Plasma samples were collected regularly for the analyses of naltrexone and the metabolite beta-naltrexol. The median naltrexone C(max) was 12.3 (range 5.8-22.1) ng ml(-1), the median T(max) was 1 day (range 3 h to 35 days), and the median length of time that plasma concentrations were above 1 ng ml(-1) was 55 (range 30-80) days. Two patients reported heroin use without experiencing any effect. Tissue reactions were recorded in two patients after repeated implantation. Marked individual and intraindividual variations in naltrexone concentrations were observed. Further studies should be performed to evaluate the need for therapeutic drug monitoring during naltrexone implant treatment.


[Status of the pituitary-adrenal and cholinergic system of patients with a pain syndrome in spinal osteochondrosis before and after a course of reflexotherapy].
The pituitary-adrenal and cholinergic systems were studied in 57 patients with chronic pain related to vertebral osteochondrosis before and after an acupuncture course. The degree of the therapeutic effect of electroacupuncture (EAP) was found to correlate with the nature of changes in the level of the spontaneous secretion of aldosterone and intensity of the process of acetylcholine (AC) release. Most patients in whom the treatment was followed by the recovery of the physiologic level of the initially depressed secretion of aldosterone and a clear-cut decrease in the initially elevated AC concentrations showed good clinical response. In patients in whom the initially elevated levels of aldosterone and AC failed to decline or in whom there was an even greater increase in AC concentrations, the therapeutic effect of EAP procedures was insignificant and short-lived.


Mutations of the Epidermal Growth Factor Receptor Gene in Triple-Negative Breast Cancer.
Epidermal growth factor receptor (EGFR) is considered a potential therapeutic target for anti-EGFR therapy in triple-negative breast cancer (TNBC). However, the frequency of EGFR gene mutation in TNBC is low and varies with ethnicity. This study aimed to investigate the incidence of EGFR gene mutation in TNBC. EGFR protein expression was evaluated by immunohistochemistry in tissue microarrays of 493 TNBC cases using four different primary antibodies, which included mutation-specific antibodies. For cases with an immunoreactivity level ≥1+, we performed pyrosequencing analysis for EGFR gene mutation. A case was considered mutation-positive when its mutation frequency minus its limit of detection (LOD) was >10%. Cases with mutation frequency higher than LOD were assessed for EGFR gene mutation status using the Cobas assay and by peptide nucleic acid-mediated polymerase chain reaction (PNA-clamping). Among 493 TNBCs, 148 (30.0%) exhibited staining ≥1+ for EGFR, including 78 with 1+, 49 with 2+, and 21 with 3+. Positive EGFR expression (≥2+) was significantly associated with lymphovascular invasion (p=0.010), but not with overall survival (p=0.444) or disease-free survival (p=0.388). None of the 493 TNBCs harbored an EGFR gene mutation. Among 148 cases with an EGFR staining result ≥1+, five (3.4%) showed mutation frequencies (4.4%-10.9%) higher than LOD (2.6%-4.3%) in exons 19 (L747_P753>Q) or 21 (L858R and L861Q) as determined by pyrosequencing. However, Cobas and PNA-clamping failed to detect the presence of EGFR gene mutation in these five cases. No activating mutation of EGFR gene of clinical significance was observed in 148 TNBC cases using three commercially available methods. Thus, EGFR gene mutation appears to be an extremely rare event in patients with TNBC.


Ten years after Daubert: the status of the states.
This paper examines how many of the states have changed their respective scientific-evidence admissibility standards under the influence of the United States Supreme Court's 1993 Daubert decision. The authors offer a definition of what constitutes a Daubert state, and using this definition classify the fifty states into three categories. These are: Frye states (15 states, 10 with codified evidence rules patterned after the Federal Rules of Evidence (FRE)); Daubert states (26 states, 24 with FRE-based rules), and non-Frye/non-Daubert states (9 states, 7 with FRE-based rules). The authors discuss how the reliability requirement varies among the non-Frye states, and examine how particular types of evidence have fared in the Daubert era. Finally, the authors offer some predictions for the scientific evidence trends of the states.


Syntheses of alpha-arbutin-alpha-glycosides and their inhibitory effects on human tyrosinase.
Alpha-arbutin is a tyrosinase inhibitor. We synthesized alpha-arbutin-alpha-glycosides by the transglycosylation reaction of cyclomaltodextrin glucanotransferase from Bacillus macerans using alpha-arbutin and starch as acceptor and donor molecules, respectively. We isolated and characterized two major products from the reaction mixture. The structural analyses using 13C- and 1H-NMR spectroscopy proved that they were 4-hydroxyphenyl alpha-maltoside (alpha-Ab-alpha-G1) and 4-hydroxyphenyl alpha-maltotrioside (alpha-Ab-alpha-G2). Both alpha-Ab-alpha-G1 and alpha-Ab-alpha-G2 exhibited competitive-type inhibition on human tyrosinase as alpha-arbutin does. Their K(i) values were calculated to be 0.6 mM and 2.8 mM, respectively, which is slightly and significantly higher than that of alpha-arbutin (0.2 mM).


Synthesis and biophysical characterization of engineered topographic immunogenic determinants with alpha alpha topology.
Model peptides with predetermined secondary, tertiary, and quaternary conformation have been successfully designed, synthesized, and characterized in an attempt to mimic the three-dimensional structure of an antigenic determinant. This work is a continuing effort to map the antigenic structure of the protein antigen lactate dehydrogenase C4 (LDH-C4) to develop a contraceptive vaccine. A putative topographic determinant with alpha alpha topology which associates into four-helix bundles was designed on the basis of the framework model of protein folding. An idealized amphiphilic 18-residue sequence (alpha 1) and a 40-residue alpha alpha fold (alpha 3) have been shown to form stable 4-helix structures in solution with a free energy of association on the order of -20.8 kcal/mol (tetramerization of alpha 1) and -7.8 kcal/mol (dimerization of alpha 3). Both alpha 1 and alpha 3 form stable monolayers at the air-water interface. The CD spectra of Langmuir-Blodgett monolayers are characteristically alpha-helical. Both CD and FTIR spectroscopic studies reval a high degree of secondary structure. The SAXS data strongly suggest that the helices are arranged in a four-helix bundle since the radius of gyration of 17.2 A and the vector distribution function are indicative of a prolate ellipsoid of axial dimensions and molecular weight appropriate for the four-helix bundle. The major contribution to the formation and stabilization of alpha 1 and alpha 3 is believed to be hydrophobic interaction between the amphiphilic alpha-helices. The displayed heptad repeat, helix dipole, ion pairs, and the loop sequence may have also contributed to the overall stability and antiparallel packing of the helices. A detailed structural analysis of a relevant topographic immunogenic determinant will elucidate the nature of antigen-antibody interactions as well as provide insight into protein folding intermediates.


[Deaths attributable to alcohol use and its impact on life expectancy in China, 2013].
Objective: To analyze the deaths attributable to alcohol use and its impact on people's life expectancy in China in 2013. Methods: The mortality data from the Disease Surveillance Points System and alcohol use data from China Chronic Disease Surveillance (2013) were used. The deaths attributed to alcohol use and its impact on the life expectancy of Chinese residents were estimated based on the principle of comparative risk assessment by calculating population attributable fraction. Results: In 2013, alcohol use resulted in 381 200 deaths, including 97 100 hemorrhagic stroke deaths, 88 200 liver cancer deaths, 61 400 liver cirrhosis deaths and 48 700 esophageal cancer deaths, and prevented 76 500 deaths, including 68 500, 4 900 and 3 100 deaths which might be caused by ischemic heart disease, hemorrhagic stroke and diabetes respectively. If risk factor of alcohol use is removed, the people's life expectancy would rise by an average of 0.43 years, especially in western China by 0.52 years, which was 0.12 years higher than that in eastern and central China, and the life expectancy of the population in rural and urban areas would rise by 0.48 years and 0.31 years respectively. Conclusions: Although alcohol has a protective effect on reducing ischemic heart disease, stroke and diabetes deaths, alcohol use is still a risk factor influencing the mortality and life expectancy of residents in China. It is necessary to take targeted measures to reduce the health problems caused by harmful use of alcohol.


Floral scents induce recall of navigational and visual memories in honeybees.
During foraging flights, honeybees learn visual and chemical cues associated with a food source. We investigated whether learned olfactory cues can trigger visual and navigational memories in honeybees that assist them in navigating back to a known food source. In a series of experiments, marked bees were trained to forage at one or more sugar water feeders, placed at different outdoor locations and carrying different scents or colours. We then tested the ability of these bees to recall the locations (or colours) of these food sites and to fly to them, when the training scents were blown into the hive, and the scents and food at the feeders were removed. The results show that (1) bees, trained to a single-scented feeder at a given location, can be induced to fly to the same location by blowing the scent into the hive; (2) bees, trained to two feeders, each placed at a different location and carrying a different scent, can be induced to fly to either location by blowing the appropriate scent into the hive; and (3) bees, trained to two feeders, each decorated with a different colour and carrying a different scent, can be induced to find a feeder of either colour by blowing the appropriate scent into the hive. Thus, familiar scents can trigger navigational and visual memories in experienced bees. Our findings suggest that the odour and taste of the nectar samples that are distributed by successful foragers on returning to the hive, may trigger recall of navigational memories associated with the food site in experienced recruits and, thus, facilitate their navigation back to the site.


The m6A methyltransferase METTL3 controls epithelial-mesenchymal transition, migration and invasion of breast cancer through the MALAT1/miR-26b/HMGA2 axis.
Previous studies have revealed the key functions of N6-methyladenosine (m6A) modification in breast cancer (BC). MALAT1 as a highly m6A modified lncRNA associated with cancer development and metastasis, but the functional relevance of m6A methyltransferase and MALAT1 in BC is still unknown. Here, our study investigated the effects of the novel m6A methyltransferase METTL3 on epithelial-mesenchymal transition (EMT) in BC via the MALAT1/miR-26b/HMGA2 axis. Firstly, we collected clinical BC samples and cultured BC cells, and detected mRNA and protein levels in the human samples and human cell lines by RT-qPCR and Western blot, respectively. Then, the binding of MALAT1 and miR-26b and the targeting relationship between miR-26b and HMGA2 were examined by dual-luciferase assay. Moreover, the binding of MALAT1 and miR-26b was tested by RNA pull down and RNA immunoprecipitation (RIP) assays. Methylated-RNA immunoprecipitation (Me-RIP) was used to detect the m6A modification level of MALAT1. The interaction of METTL3 and MALAT1 was detected by photoactivatable ribonucleoside-crosslinking immunoprecipitation (PAR-CLIP). Finally, effects on invasion and migration were detected by Transwell. In BC, the level of miR-26b was consistently low, while the levels of METTL3, MALAT1 and HMGA2 were high. Further experiments showed that METTL3 up-regulated MALAT1 expression by modulating the m6A modification of MALAT1, and that MALAT1 could promote the expression of HMGA2 by sponging miR-26b. In BC cells, we found that silencing METTL3 could inhibit EMT and tumor cell invasion by suppressing MALAT1. Furthermore, MALAT1 mediated miR-26b to target HMGA2 and promote EMT, migration, and invasion. In summary, METTL3 promoted tumorigenesis of BC via the MALAT1/miR-26b/HMGA2 axis. Silencing METTL3 down-regulate MALAT1 and HMGA2 by sponging miR-26b, and finally inhibit EMT, migration and invasion in BC, providing a theoretical basis for clinical treatment of BC.


Meta-Analysis of the Ease of Care From the Nurses' Perspective Comparing Fentanyl Iontophoretic Transdermal System (ITS) Vs Morphine Intravenous Patient-Controlled Analgesia (IV PCA) in Postoperative Pain Management.
The aim of this meta-analysis was to compare the ease of care (EOC) of fentanyl iontophoretic transdermal system (ITS) vs the morphine intravenous patient-controlled analgesia (IV PCA) as assessed by the nurse. Meta-analysis of three phase 3B randomized active-comparator trials. This meta-analysis according to Cochrane's approach assessed EOC using a validated nurse questionnaire (22 items grouped into three subscales, which include time efficiency, convenience, and satisfaction) in adult patients treated with fentanyl ITS or morphine IV PCA for postoperative pain management. The weighted mean difference (WMD) between treatments was calculated. EOC analyses were based on responses to questionnaires from 848 (fentanyl ITS) and 761 (morphine IV PCA) nurses. Fentanyl ITS was reported to provide significant advantages compared with morphine IV PCA in terms of nurses' overall EOC (WMD = -0.57, P < .0001) and each of the subscales: time efficiency (WMD = -0.58, P < .0001), convenience (WMD = -0.57, P < .0001), and satisfaction (WMD = -0.47, P < .0001). In this meta-analysis, fentanyl ITS is associated with a superior EOC profile from the nurses' perspective than morphine IV PCA.


[Electrical infusion pump for patient-controlled analgesia].
Electrical infusion pumps (pump) were featured with the focus on patient-controlled analgesia (PCA). The specification and functional aspects of four types of PCA pumps were briefly summarized and listed in two tables. The clinical application of these PCA pumps should benefit both patients and medical staffs. For the successful introduction of PCA pumps into clinical practice, a medical team must be organized, where not only anesthesiologists but also nurses, pharmacists, medical electronic engineers and surgeons are expected to participate.


Risk of multiple myeloma in a case-spouse study.
This study examined lifestyle, occupation, medical history and medication use with multiple myeloma risk in a case-spouse study (481 patients, 351 spouses). Odds ratios (ORs) and 95% confidence intervals (CI) were calculated using logistic regression. Compared to spouse controls, cases were more likely to have a family history of multiple myeloma (OR = 2.8, 95% CI = 1.2-6.4) and smoked cigarettes (OR = 1.7, 95% CI = 1.2-2.5), but less likely to have consumed alcohol (OR = 0.6, 95% CI = 0.4-0.9). Nurse/health practitioners (OR = 2.8, 95% CI = 1.3-6.2) and production workers (OR = 3.7, 95% CI = 1.0-13.7) had significantly increased risks; and some occupations linked to diesel exhaust had elevated, but non-significant, risks. History of herpes simplex (OR = 1.7, 95% CI = 1.2-2.4), shingles (OR = 1.7, 95% CI = 1.1-2.7), sexually transmitted diseases (OR = 2.0, 95% CI = 1.0-3.7) and medication allergies (OR = 1.7, 95% CI = 1.2-2.4) were associated with higher risks. Use of angiotensin-converting enzyme inhibitors, anti-convulsants, antidepressants, statins and diuretics were associated with reduced risks. The results are consistent with previous population-based studies and support the utility of patient databanks and spouse controls as a resource in epidemiologic research.


Effect of a fish oil and arginine-fortified diet in thermally injured patients.
Burn injury induces a hypercatabolic inflammatory state, predisposing burn patients to malnutrition, poor wound healing, and infectious complications. We conducted this study to determine what effect a diet fortified with fish oil and arginine (FAD) would have on wound healing in a thermally injured population. Twenty-three thermally injured patients were enrolled in this randomized double blind enteral feeding study from July 2002 to August 2004. All study patients received isonitrogenous enteral intragastric feeding within 48 hours of admission. Patients were randomized to our standard diet (STD, ProBalance with Promix, Probalance from Nestlé, Glendale, CA; ProMix R.D., Navaco Laboratories, Phoenix, AZ) or a diet fortified with fish oil and arginine (FAD, Crucial, Nestlé Nutrition Glendale, CA) Diets were advanced as tolerated to meet 100% of estimated needs. The primary endpoint of the study was time to heal the first donor site. There were no statistical differences between the study groups with respect to baseline characteristics. Both diets were well tolerated, and there were no differences in the daily total kilocalories or protein intake per kilogram between the two diet groups throughout the study. Although nonsignificant, the patients in the FAD group showed a slightly faster healing time than those in the STD group (10.8 +/- 2.7 days vs 12.3 +/- 5.2 days, respectively). This trend was further accelerated when those with body surface area burns less than 30% were examined (patients with body surface area burns <30% in the FAD healed in 9.0 +/- 1.7 vs corresponding patients in the standard group who healed in 12.2 +/- 6.2, P = .63). Patients in the FAD group trended to more infections and more adverse complications. The adverse complications were predominantly associated with inhalation injuries. The role of fortified enteral diets in the outcomes of thermally injured patients deserves further study. Such a future study should be conducted in a multicenter trial and involve inhalation injury stratification systems to accurately score and randomize patients for inhalation injury. Finally, the frequency and pattern of infections in patients receiving fortified enteral diets deserves further evaluation.


Prediction of virus-host protein-protein interactions mediated by short linear motifs.
Short linear motifs in host organisms proteins can be mimicked by viruses to create protein-protein interactions that disable or control metabolic pathways. Given that viral linear motif instances of host motif regular expressions can be found by chance, it is necessary to develop filtering methods of functional linear motifs. We conduct a systematic comparison of linear motifs filtering methods to develop a computational approach for predicting motif-mediated protein-protein interactions between human and the human immunodeficiency virus 1 (HIV-1). We implemented three filtering methods to obtain linear motif sets: 1) conserved in viral proteins (C), 2) located in disordered regions (D) and 3) rare or scarce in a set of randomized viral sequences (R). The sets C,D,R are united and intersected. The resulting sets are compared by the number of protein-protein interactions correctly inferred with them - with experimental validation. The comparison is done with HIV-1 sequences and interactions from the National Institute of Allergy and Infectious Diseases (NIAID). The number of correctly inferred interactions allows to rank the interactions by the sets used to deduce them: D∪R and C. The ordering of the sets is descending on the probability of capturing functional interactions. With respect to HIV-1, the sets C∪R, D∪R, C∪D∪R infer all known interactions between HIV1 and human proteins mediated by linear motifs. We found that the majority of conserved linear motifs in the virus are located in disordered regions. We have developed a method for predicting protein-protein interactions mediated by linear motifs between HIV-1 and human proteins. The method only use protein sequences as inputs. We can extend the software developed to any other eukaryotic virus and host in order to find and rank candidate interactions. In future works we will use it to explore possible viral attack mechanisms based on linear motif mimicry.


Are leg ulcers in rheumatoid arthritis due to vasculitis?
Five patients with severe rheumatoid arthritis are reported in whom leg ulcers were not apparently associated with vasculitis. The conventional explanation for these ulcers deserves review. Patients with rheumatoid arthritis may develop 'gravitational' leg ulceration and pressure sores on their legs. In addition, they may develop ulcers on the lower aspects of the legs and around the ankles which are well demarcated, punched out, painful and slow to heal. These ulcers usually occur in patients with longstanding, severe, seropositive disease. They are presently considered to be due to a necrotising arteritis causing dermal infarction, since they are frequently associated with other clinical features of rheumatoid vasculitis. Wilkinson has commented that 'biopsies are seldom taken from leg ulcers'. In this paper we report five patients with severe rheumatoid arthritis who developed such leg ulcers in the absence of other clinical evidence of vasculitis and in whom biopsies of the ulcers failed to reveal vasculitis. A case is summarised as illustrative of the five patients, whose relevant histories, clinical findings, and laboratory investigations are summarised in Table 1.


The primary structure of Escherichia coli K12 2-deoxyribose 5-phosphate aldolase. Nucleotide sequence of the deoC gene and the amino acid sequence of the enzyme.
The sequence of the deoC gene of Escherichia coli K12 and the amino acid sequence of the corresponding protein, deoxyriboaldolase, has been established. The protein consists of 259 amino acids with a molecular weight of 27 737. The purified enzyme may exist both as a monomer and as a dimer. On the basis of amino acid composition, molecular weight and catalytic properties, the enzymes from E. coli and Salmonella typhimurium seem to be almost similar. They belong to the class I aldolases, which form Schiff base intermediates. Using data for the S. typhimurium enzyme, the lysine residue involved in the active site in the E. coli enzyme was tentatively identified.


Teprotumumab-related Cutaneous Hypersensitivity Reactions.
The authors report 4 cases of cutaneous hypersensitivity reactions developing in the course of teprotumumab treatment for thyroid eye disease. The onset of the cutaneous hypersensitivity reaction was also observed during the treatment course in all cases, between the second and fifth infusions. Teprotumumab-related cutaneous reactions suggest a possible immunogenic component of the monoclonal antibody and highlight the importance of close monitoring during treatment.


[Psychotropic substances and endocrine mechanisms: the effect on gonadal function].
Psychotropic drugs of different classes exhibit the ability to interfere in the sexual sphere. This is evidenced by clinical observations and the latest data concerning experimental research on pharmacological sensitivity of the central mechanisms controlling gonadal function. Both trend and stability of endocrine changes depend significantly on the profile of the neurotransmitter action of the drugs. Such changes can in turn influence the character of the specific activity and degree of side effects of the drugs. The above data prompt to pay more attention to the possibility of the sexual gland function disturbances during the course of psychopharmacotherapy.


[Iatrogenic esophagus perforation in newborn infants].
Two cases of an iatrogenic oesophageal perforation in new-born are presented. Incidence and main sources of risk are discussed. Attention is drawn to early recognition and urgent surgical treatment.


[Association study of sleep apnea syndrome and polymorphisms in the serotonin transporter gene].
To identify polymorphisms of the serotonin transporter(5-HTT) gene and to find out whether there was relationship between any such polymorphisms and sleep apnea syndrome (SAS). For two polymorphisms of 5-HTT target DNA gene was amplified using polymerase chain reaction (PCR) and 6% non-denaturing polyacrylamide gels electrophoresis. The frequencies of the different forms of the genotypes and alleles of 5-HTT gene were analyzed in 104 patients with SAS and 150 healthy controls. The frequencies of the S or L alleles and the S/S, S/L or L/L genotypes in promoter region of 5-HTT gene in SAS group were not significantly different to those in healthy controls (P > 0.05). However, the frequencies of 10/10, 12/10 genotypes of 5-HTT-VNTR in SAS patients were significantly higher than those in healthy control subjects (P < 0.05). Moreover, the frequency of the allele 10 of 5-HTT-VNTR in SAS patients was significantly higher than that in healthy controls (P<0.01). The allele 10 of 5-HTT-VNTR might be a susceptible factor in the pathogenesis of SAS.


Pitfalls in surveillance for hepatocellular carcinoma: How successful is it in the real world?
Surveillance for hepatocellular carcinoma (HCC) with ultrasound in high-risk populations is generally believed to improve opportunities for treatment. However, tumors are still missed due to various factors. This study explores success versus failure of HCC surveillance. This is a retrospective study of 1,125 HCC cases. Categories considered for successful detection were largest tumor ≤3.0 cm, single tumors ≤3.0 cm and ≤2.0 cm, and adherence to Milan criteria. Examined factors were age <60 years, gender, rural residence, body-mass index (BMI), hepatitis infection, smoking, diabetes, hyperlipidemia, cirrhosis, ascites, and Model for End-Stage Liver Disease <10. HCC was found on surveillance in 257 patients with a mean tumor size of 3.17 cm; multiple tumors were seen in 28% of cases, bilateral tumors in 7.4%, and vascular invasion in 3.7%. Surveillance was successful in 61.5% of cases involving a largest tumor ≤3.0 cm, with BMI ≥35 negatively affecting detection (odds ratio [OR] 0.28, P=0.014) and cirrhosis positively affecting detection (OR 2.31, P=0.036). Ultrasound detected 19.1% of single tumors ≤2.0 cm with ascites improving the detection rate (OR 3.89, P=0.001). Finally, adherence to Milan criteria occurred in 75.1% of cases, revealing negative associations with diabetes (OR 0.48, P=0.044 and male gender (OR 0.49, P=0.08). Although surveillance is recommended for HCC, not all surveillance ultrasound are ideal. Tumor detection can depend on gender, BMI, diabetes, cirrhosis, and ascites and is achieved in 19.1-75% of cases depending on the definition of success. Closer follow-up or additional imaging might be necessary for some patient subgroups.


Prognosis value of Chinese Ocular Fundus Diseases Society classification for proliferative diabetic retinopathy on postoperative visual acuity after pars plana vitrectomy in type 2 diabetes.
To compare the postoperative visual acuity among eyes with proliferative diabetic retinopathy (PDR) of different stages after pars plana vitrectomy (PPV) in type 2 diabetic patients. A retrospective study was conducted for PDR eyes undergoing PPV in type 2 diabetic patients. All patients were divided into three groups based on Chinese Ocular Fundus Diseases Society (COFDS) classification for PDR: Group A (primary vitreous hemorrhage), Group B (primary fibrovascular proliferation) and Group C (primary vitreous hemorrhage and/or fibrovascular proliferative combined with retinal detachment). The postoperative visual acuity and the change between postoperative and preoperative visual acuity were compared among three groups. The associated risk factors for postoperative visual acuity were analyzed in the univariate and multiple linear aggression. In total, 195 eyes of 195 patients were collected in this study, including 71 eyes of 71 patients in Group A, 75 eyes of 75 patients in Group B and 49 eyes of 49 patients in Group C. The eyes in Group A got better postoperative best-corrected visual acuity (BCVA) compared to the eyes in Group B and C (0.48±0.48 vs 0.89±0.63, P<0.001; 0.48±0.48 vs 1.04±0.67, P<0.001; respectively). The eyes in Group A got more improvement of BCVA compared to the eyes in Group B and C (1.07±0.70 vs 0.73±0.68, P=0.004; 1.07±0.70 vs 0.77±0.78, P=0.024; respectively). In the multiple linear regression analysis, primary fibro-proliferative type (β=0.194, 95%CI=0.060-0.447, P=0.01), retinal detachment type (β=0.244, 95%CI=0.132-0.579, P=0.02), baseline logMAR BCVA (β=0.192, 95%CI=0.068-0.345, P=0.004), silicone oil tamponade (β=0.272, 95%CI=0.173-0.528, P<0.001) was positively correlated with postoperative logMAR BCVA. Eyes undergoing phacovitrectomy had better postoperative BCVA (β=-0.144, 95%CI=-0.389 to -0.027, P=0.025). PDR eyes of primary vitreous hemorrhage type usually have better visual acuity prognosis compared to primary fibrovascular proliferation type and retinal detachment type. COFDS classification for PDR may have a high prognostic value for postoperative visual outcome and surgical management indications.


Welfare and Management of Civets in Civet Coffee Tourism Plantations.
Civet coffee is produced with coffee beans that have passed through the digestive tract of civets which are then processed for drinking. Outlets, known as civet coffee tourism plantations are popular tourist attractions in Bali, Indonesia. These outlets keep caged civets for public viewing and sell civet coffee. We assessed civet welfare in 29 civet coffee tourism plantations to assess husbandry factors, the five freedoms and body condition scores. We also assessed civet welfare in eight wildlife markets where civets are sourced for civet coffee tourism and calculated turnover of civets. We found 99 civets in civet coffee tourism plantations and 136 in markets, where. Annually between 400 and 800 civets are sold. Welfare standards do not meet the Indonesian laws and regulations. Diet, hygiene, presence of water and mobility affected body condition scores and no civet met all of the five freedoms. Enforcement of welfare and trade laws is needed to improve civet welfare, and to curb the illegal civet trade. Tourists frequenting civet coffee tourism plantations should be made aware of the low welfare standards to inform their choice about supporting this industry.


Structure and High Performance of Lead-Free (K0.5Na0.5)NbO3 Piezoelectric Nanofibers with Surface-Induced Crystallization at Lowered Temperature.
Lead-free potassium and sodium niobate (KNN) nanofiber webs with random and aligned configurations were prepared by the electrospinning process from polymer-modified chemical solution. The crystallization process, structure, composition, dielectric, ferroelectric, and piezoelectric properties of the nanofibers and nanofiber webs were investigated. Theoretical analysis and experimental results showed that the surface-induced heterogeneous nucleation resulted in the remarkable lower crystallization temperature for the KNN nanofibers with the {100} orientation of the perovskite phase in contrast to the bulk KNN gel and thus well-controlled chemical stoichiometry. Low dielectric loss, large electric polarization, and high piezoelectric performance were obtained in the nanofiber webs. In particular, the aligned nanofiber web exhibited further improved piezoelectric strain and voltage coefficients and higher FOM than their thin film counterparts and is promising for high-performance electromechanical sensor and transducer applications.


Protein kinase C inhibitor generates stable human tolerogenic dendritic cells.
Tolerogenic dendritic cells (DCs) are a promising tool for a specific form of cellular therapy whereby immunological tolerance can be induced in the context of transplantation and autoimmunity. From libraries of bioactive lipids, nuclear receptor ligands, and kinase inhibitors, we screened conventional protein kinase C inhibitors (PKCIs) bisindolylmaleimide I, Gö6983, and Ro32-0432 with strong tolerogenic potential. PKCI-treated human DCs were generated by subjecting them to a maturation process after differentiation of immature DCs. The PKCI-treated DCs had a semimature phenotype, showing high production of IL-10, and efficiently induced IL-10-producing T cells and functional Foxp3(+) regulatory T cells from naive CD4(+) T cells, thus eliciting a strong immunosuppressive function. They also showed CCR7 expression and sufficient capacity for migration toward CCR7 ligands. Additionally, PKCI-treated DCs were highly stable when exposed to inflammatory stimuli such as proinflammatory cytokines or LPS. Conventional PKCIs inhibited NF-κB activation of both the canonical and noncanonical pathways of DC maturation, thus suppressing the expression of costimulatory molecules and IL-12 production. High production of IL-10 in PKCI-treated DCs was due to not only an increase of intracellular cAMP, but also a synergistic effect of increased cAMP and NF-κB inhibition. Moreover, PKCI-treated mouse DCs that had properties similar to PKCI-treated human DCs prevented graft-versus-host disease in a murine model of acute graft-versus-host disease. Conventional PKCI-treated DCs may be useful for tolerance-inducing therapy, as they satisfy the required functional characteristics for clinical-grade tolerogenic DCs.


[Evaluation of the cefoxitin 30 microg disk diffusion method for detection of methicillin-resistance in selected Staphylococcus aureus isolates].
Oxacillin tests may fail to detect some methicillinresistant S. aureus populations. The objective of this study is to evaluate the discriminative capacity of the Clinical and Laboratory Standards Institute (CLSI) disk diffusion method with a cefoxitin 30 microg disk on S. aureus isolates with unusual phenotypic characteristics of antimicrobial resistance. We studied 53 clinical S. aureus isolates. The antimicrobial susceptibility of all isolates was routinely studied by the VITEK 2 System (bioMérieux). Methicillin resistance was also studied by CLSI oxacillin method and confirmed by a previously described multiplex polymerase chain reaction (PCR) method which permits S. aureus identification and simultaneous detection of methicillin resistance. MecA positive isolates presenting a diffuse growth within the zone of inhibition when exposed to oxacillin were considered heteroresistant; mecA negative, oxacillin intermediate or resistant isolates were considered borderline. All the isolates were tested with a cefoxitin 30 microg disk, according to the CLSI guidelines (susceptibility: > 22 mm; resistance: < 21 mm). Control strains for all assays included MRSA ATCC 43300 and MSSA ATCC 25923. The isolates formed four groups. Group I: 20 multiresistant, oxacillin susceptible and mecA negative isolates; group II: 16 resistant or with intermediate oxacillin susceptibility and mecA negative isolates; group III: 11 heteroresistant and mecA positive isolates; group IV: six mecA positive isolates with atypical resistance profiles (penicillin and oxacillin, or ciprofloxacin and erythromycin resistance). Thirty-five mecA negative isolates included in groups I and II showed inhibition zones > 22 mm; one isolate from group II showed 20 mm. The 17 mecA positive isolates from groups III and IV showed resistance to cefoxitin disk. The 30 microg cefoxitin disk diffusion method is proposed as an efficient method for the detection of methicillin resistance and permits a clear determination set S. aureus isolates, even those with atypical antimicrobial characteristics.


Mood and cognition after electrical injury: a follow-up study.
Individuals who have experienced an electrical injury have been reported to demonstrate both acute and delayed cognitive and psychiatric symptoms. The present study assessed 20 electrically injured patients who underwent neuropsychological evaluations twice following their injury. Time since injury, time between assessments, and longitudinal mood changes were evaluated for their potential impact on simple and complex attention outcomes. As an overall group, there was little change over time from low average to average baseline attention/concentration performance. However, results indicated that longitudinal increases in depressive symptoms were consistently associated with poorer performance on a measure of simple and complex attention. Loss of consciousness, litigation status, baseline injury status (acute vs. post-acute), and time between evaluations were not significant predictors of changes in cognitive performance. Implications for the treatment of comorbid psychiatric issues and for future research on victims of electrical trauma are discussed.


What is your diagnosis? Ventral neck mass in a dog.
: A 14-year-old male Labrador Retriever was presented for lethargy and collapse. On physical examination, numerous abnormalities were found, including a large ventral neck mass (100 cm(3)) in the area of the thyroid gland. Fine-needle aspirates revealed 2 apparent populations of cells: one suspected to be a well-differentiated thyroid carcinoma, and the other consisting of large pleomorphic to spindloid cells suggestive of sarcoma. Two days later, the dog died at home. A full necropsy was not performed, but examination of the head and neck revealed a well-encapsulated mass adjacent to the cranial trachea and larynx. A section of the mass was evaluated histologically and a diagnosis of anaplastic thyroid carcinoma was made. Immunohistochemical evaluation with antibodies to thyroglobulin, cytokeratin, and vimentin confirmed distinct populations of malignant epithelial and malignant mesenchymal cells, and the diagnosis was amended to thyroid carcinosarcoma. Thyroid carcinosarcoma is a rare neoplasm in dogs in which the cell type comprising the mesenchymal component can vary. Immunochemistry to demonstrate the 2 cell types may be necessary to differentiate thyroid carcinosarcoma from anaplastic thyroid carcinoma.


The Internet and Computer User Profile: a questionnaire for determining intervention targets in occupational therapy at mental health vocational centers.
In this study, the assessment tool "Internet and Computer User Profile" questionnaire (ICUP) is presented and validated. It was developed in order to gather information for setting intervention goals to meet current demands. Sixty-eight subjects aged 23-68 participated in the study. The study group (n = 28) was sampled from two vocational centers. The control group consisted of 40 participants from the general population that were sampled by convenience sampling based on the demographics of the study group. Subjects from both groups answered the ICUP questionnaire. Subjects of the study group answered the General Self- Efficacy (GSE) questionnaire and performed the Assessment of Computer Task Performance (ACTP) test in order to examine the convergent validity of the ICUP. Twenty subjects from both groups retook the ICUP questionnaire in order to obtain test-retest results. Differences between groups were tested using multiple analysis of variance (MANOVA) tests. Pearson and Spearman's tests were used for calculating correlations. Cronbach's alpha coefficient and k equivalent were used to assess internal consistency. The results indicate that the questionnaire is valid and reliable. They emphasize that the layout of the ICUP items facilitates in making a comprehensive examination of the client's perception regarding his participation in computer and internet activities. Implications for Rehabiliation The assessment tool "Internet and Computer User Profile" (ICUP) questionnaire is a novel assessment tool that evaluates operative use and individual perception of computer activities. The questionnaire is valid and reliable for use with participants of vocational centers dealing with mental illness. It is essential to facilitate access to computers for people with mental illnesses, seeing that they express similar interest in computers and internet as people from the general population of the same age. Early intervention will be particularly effective for young adults dealing with mental illness, since the digital gap between them and young people in general is relatively small.


[MTP inhibitors and ACAT inhibitors. An update].
Currently, statin therapy is the first-line treatment for patients with hypercholesterolemia, although their effects on plasma triglyceride(TG) levels are modest and variable. Inhibition of microsomal triglyceride transfer protein(MTP), a key protein involved in the assembly of the apoB-containing lipoproteins, is an attractive lipid-lowering strategy. In animal models, MTP inhibitors have dramatic effects not only on plasma cholesterol and LDL levels but on TG levels as well, offering the potential for greater efficacy and plasma lipid control in both hypertriglyceridemia and mixed hyperlipidemia. Inhibitors of acyl-CoA: cholesterol acyltransferase(ACAT) present another strategy in treating atherosclerosis through direct inhibition of ACAT in macrophages of the arterial wall. Recent studies in mouse models of atherosclerosis lacking ACAT1, however, may argue against the selective inhibition of macrophage ACAT1.


Gold nanoparticle photosensitized radical photopolymerization.
We report the photopolymerization of an acrylic monomer using thiol-stabilized gold nanoparticles (AuNPs) and [4-[(octyloxy)phenyl] phenyl] iodonium hexafluoroantimonate (OPPI) as photoinitiator and coinitiator, respectively. Polymerization occurred only when the AuNPs, in the presence of the iodonium salt, were irradiated at the particle plasmonic absorption region (lambda>450 nm). The AuNPs activate the coinitiator by intermolecular electron transfer since OPPI has no absorption in the visible region. Fourier transform infrared spectroscopy was used to monitor polymerization. UV-Vis spectroscopy and transmission electron microscopy measurements were used to characterize the NPs.


Effects of temperature and fish oil supplementation on ovarian development and foxl2 mRNA expression in spotted scat Scatophagus argus.
In this study, the complete foxl2 complementary (c)DNA sequence was isolated by simple modular-architecture research tool (SMART)er rapid amplification of cDNA ends (RACE). Two year-old female spotted scat, Scatophagus argus, were reared at different temperatures (23, 26 and 29° C) for 6 weeks, or fed with different concentrations of dietary fish oil (0, 2 or 6%) for 8 weeks. Ovarian development, serum oestradiol-17β (E2 ) levels, as well as ovarian foxl2 expression were measured. At the end of experiment, ovarian foxl2 messenger (m)RNA expression in fish reared at 23 and 26° C was significantly higher than that in fish reared at 29° C, and that in 2 and 6% fish oil groups was also significantly higher than that in control group (P < 0·05). Serum E2 levels exhibited the same trend with foxl2 mRNA expression in temperature treatment groups and fish oil fed groups. There was a significant positive correlation between stage of oocytes and foxl2 expressions. Results showed that from 23 to 29° C, the optimal temperature for ovarian development in S. argus was 23-26° C, and 6% fish oil supplementation could effectively promote ovarian development. Optimal temperature and fish oil supplement might increase ovarian foxl2 mRNA expressions to promote ovarian development in S. argus.


Syndecan-4 proteoglycan cytoplasmic domain and phosphatidylinositol 4,5-bisphosphate coordinately regulate protein kinase C activity.
Phosphatidylinositol 4,5-bisphosphate (PIP2) is involved in the organization of the actin cytoskeleton by regulating actin-associated proteins. The transmembrane heparan sulfate proteoglycan syndecan-4 also plays a critical role in protein kinase C (PKC) signaling in the formation of focal adhesions and actin stress fibers. The cytoplasmic domain of syndecan-4 core protein directly interacts with and potentiates PKCalpha activity, and it can directly interact with the phos- phoinositide PIP2. We, therefore, investigated whether the interaction of inositol phosphates and inositol phospholipids with syndecan-4 could regulate PKC activity. Data from in vitro kinase assays using purified PKCalpha beta gamma show that in the absence of phosphatidylserine and diolein, PIP2 increased the extent of autophosphorylation of PKCalpha beta gamma and partially activated it to phosphorylate both histone III-S and an epidermal growth factor receptor peptide. This activity was dose-dependent, and its calcium dependence varied with PKC isotype/source. Addition of the cytoplasmic syndecan-4 peptide, but not equivalent syndecan-1 or syndecan-2 peptides, potentiated the partial activation of PKCalpha beta gamma by PIP2, resulting in activity greater than that observed with phosphatidylserine, diolein, and calcium. This study indicates that syndecan-4 cytoplasmic domain may bind both PIP2 and PKCalpha, localize them to forming focal adhesions, and potentiate PKCalpha activity there.


Participants' Perspectives of a Primary Exercise-Based Prevention Program for Cardiac Patients: A Prepost Intervention Qualitative Case Study.
Perseverance in exercise-based, cardiovascular disease prevention programs is generally very low. The purpose of this case study is to understand the experience of participants enrolled in a 6-month primary and secondary exercise-focused, cardiovascular disease prevention out of hospital program. Ten participants were interviewed about their experiences at entry and after it ended 6 months later to understand the facilitators and difficulties encountered by participants in such exercise programs. Four out of ten participants completed the 6-month program. The six participants who left the program accepted to contribute to the postprogram interview. The results showed that the four participants who persevered in the program became aware of cardiac risk factors and their conditions were willing to make changes in their lifestyles to reach their objectives, felt a strong perception of self-efficacy, and felt like they belonged in the program. Both persevering and nonpersevering participants experienced many episodes of discouragement during the program and faced many barriers that interfered with their progress. Suggestions to help coping with these barriers while reinforcing self-efficacy and the sentiment of belonging are discussed.


Analytical prospect of compact disk technology in immunosensing.
A sensitive and versatile methodology involving recordable compact disks as molecular screening surfaces and a standard optical CD/DVD drive as detector, is reported. Quantitative immunoanalysis, in microarray format, of a cancer marker (alpha-fetoprotein, AFP) and a selective herbicide (atrazine) on four types of audio-video disc was conducted. Enzyme or gold nanoparticle-labeled antibodies were used as tracers, forming a precipitate on the sensing disk surface. The principle of disk reading is based on capture of analog signals with the disk drive that were proportional to the darkness of the immunoreaction product. Detection limits for AFP (8.0 microg L(-1)) and for atrazine (0.04 microg L(-1)) were under the threshold needed to detect nonseminomatous testicular cancer, and below the maximum E.U. residue limit for drinking water, respectively. The described methodology improves the previous developments using CDs and highlights the enormous potential of immunoassay methods using standard audio-video disk surfaces in combination with the CD/DVD drive for clinical analysis, drug discovery, or high-throughput multiresidue screening applications.


[Community home healthcare in 6-year pharmacy education].
As we enter more and more into a super-aging society, the requirement for home healthcare will increase. Pharmacists must work along with doctors and nurses in the field of home healthcare. Within the 6-year pharmacy curriculum, we must educate students as medicinal professionals who will join a medical team to serve the community. The Good Practice (GP) program, which has been supported by the Ministry of Education, Culture, Sports, Science & Technology, continues to be offered in our university. As a part of this program, students learn home healthcare in the community in cooperation with Yubari Medical Center. In addition, our students (pharmacy) can study community medicine together with students from Tenshi College (nursing and nutrition) in an optional class made available in Yubari during their summer vacation. According to the results of our survey after these programs, students have achieved a deep recognition of the importance of community medicine and cooperation with other medical staff in contributing to community home healthcare. We carry out these programs under agreements of collaboration with Yubari Medical Center and Tenshi College. We will talk today about training for pharmaceutical care in the community and the effect of training through this class on pharmacy education.


Self-assembling endohedrally doped CdS nanoclusters: new porous solid phases of CdS.
Hollow CdS nanoclusters were predicted to trap alkali metals and halogen atoms inside their cavity. Furthermore, electron affinities (EA) of endohedrally halogen doped clusters and ionization potentials (IE) of endohedrally alkali doped clusters were predicted to be very similar. This makes them suitable to build cluster-assembled materials, in the same vein as do related ZnO, ZnS and MgO nanoclusters, which yield porous solid materials. With this aim in mind, we have focused on the assembly of bare Cd(i)S(i) and endohedral K@Cd(i)S(i)-X@Cd(i)S(i) (i = 12, 16, X = Cl, Br) clusters in order to obtain solids with tailored semiconducting and structural properties. Since these hollow nanoclusters possess square and hexagonal faces, three different orientations have to be considered, namely, edge-to-edge (E-E), square-to-square (S-S) and hexagon-to-hexagon (H-H). These three orientations lead to distinct zeolite-like nanoporous bulk CdS solid phases denoted as SOD, LTA and FAU. These solids are low-density crystalline nanoporous materials that might be useful in a wide range of applications ranging from molecular sieves for heterogeneous catalysis to gas storage templates.


The influence of reinforcement schedule on experience-dependent changes in motivation.
The progressive ratio procedure is used across fields to assess motivation for different reinforcers, define the effects of experimental interventions on motivation, and determine experience-dependent changes in motivation. However, less is known about how operant training schedules affect performance on this widely utilized task. Here we designed an experiment to examine the effect of variable ratio versus fixed ratio training schedules of reinforcement on progressive ratio performance while holding other performance variables constant between groups. We found a robust increase in maximum ratio completed between the pretest and posttraining test highlighting a robust training effect on progressive ratio performance. However, it did not matter if the training was under a fixed or variable ratio schedule. Additionally, we show that neither individual rates during training nor extinction responding correlated with maximum ratio achieved during the sessions. Finally, we show that rates during the training sessions do correlate with extinction performance, suggesting that these variables measure a different aspect of performance that does not predict motivation.


Inherent force-dependent properties of β-cardiac myosin contribute to the force-velocity relationship of cardiac muscle.
The heart adjusts its power output to meet specific physiological needs through the coordination of several mechanisms, including force-induced changes in contractility of the molecular motor, the β-cardiac myosin (βCM). Despite its importance in driving and regulating cardiac power output, the effect of force on the contractility of a single βCM has not been measured. Using single molecule optical-trapping techniques, we found that βCM has a two-step working stroke. Forces that resist the power stroke slow the myosin-driven contraction by slowing the rate of ADP release, which is the kinetic step that limits fiber shortening. The kinetic properties of βCM are affected by load, suggesting that the properties of myosin contribute to the force-velocity relationship in intact muscle and play an important role in the regulation of cardiac power output.


Caffeine ingestion impairs insulin sensitivity in a dose-dependent manner in both men and women.
The effects of alkaloid caffeine on insulin sensitivity have been investigated primarily in men, and with a single caffeine dose most commonly of 5-6 mg·kg(-1) of body weight (BW). It is unknown if the effects of caffeine on glucose homeostasis are sex-specific and (or) dose-dependent. This study examined whether caffeine ingestion would disrupt glucose homeostasis in a dose-dependent or threshold manner. It also examined whether sex-specific responses to caffeine exist. It was hypothesized that women would have an exaggerated response to caffeine, and that caffeine would only impair glucose metabolism once a threshold was reached. Twenty-four healthy volunteers (12 males, 12 females) participated in 4 trials, in a crossover, randomized, and double-blind fashion. They ingested caffeine (1, 3, or 5 mg·kg(-1) of BW) or placebo followed, 1 h later, by a 2-h oral glucose tolerance test. Glucose, insulin, C-peptide area under the curve (AUC), and insulin sensitivity index data were fitted to a segmented linear model to determine dose-responses. There were no differences between sexes for any endpoints. Regression slopes were significantly different from zero (p < 0.05) for glucose, insulin, and C-peptide AUCs, with thresholds being no different from zero. Increasing caffeine consumption by 1 mg·kg(-1) of BW increased insulin and C-peptide AUCs by 5.8% and 8.7%, respectively. Despite this exaggerated insulin response, glucose AUC increased by 11.2 mmol per 120 min·L(-1) for each mg·kg(-1) BW consumed. These results showed that caffeine ingestion disrupted insulin sensitivity in a dose-dependent fashion beginning at very low doses (0-1 mg·kg(-1) BW) in both healthy men and women.


Current Insight into the Therapeutic Potential of Phytocompounds and their Nanoparticle-Based Systems for Effective Management of Lung Cancer.
Lung cancer is the second most common cancer and the primary cause of cancer-related death in both men and women worldwide. Due to diagnosis at an advanced stage, it is associated with high mortality in the majority of patients. At present, various treatment approaches are available, such as chemotherapy, surgery, and radiotherapy, but all these approaches usually cause serious side effects like degeneration of normal cells, bone marrow depression, alopecia, extensive vomiting, etc. To overcome the aforementioned problems, researchers have focused on the alternative therapeutic approach in which various natural compounds are reported, which possessed anti-lung cancer activity. Phytocompounds exhibit their anti lung cancer activity via targeting various cell-signaling pathways, apoptosis and cell cycle arrest, and by regulating antioxidant status and detoxification. Apart from the excellent anti-cancer activity, clinical administration of phytocompounds is confined because of their high lipophilicity and low bioavailability. Therefore, researchers show their concern in the development of a stable, safe and effective approach of treatment with minimal side effects by the development of nanoparticle-based delivery of these phytocompounds to the target site. Targeted delivery of phytocompound through nanoparticles overcomes the aforementioned problems. In this article, the molecular mechanism of phytocompounds, their emerging combination therapy, and their nanoparticles-based delivery systems in the treatment of lung cancer have been discussed.


Laparoscopy-assisted total gastrectomy for a case of MALT lymphoma: a case report.
A case of laparoscopy-assisted total gastrectomy with regional lymph node dissection for MALT (mucosa-associated lymphoid tissue) lymphoma is reported. The patient was a 45-year-old male with MALT lymphoma. Eradication of Helicobacter pylori as the initial therapy had failed to halt progression of the tumor. Considering certainty of the second therapy, he was transferred to surgical treatment. Total gastrectomy was required and this was performed by the laparoscopy-assisted approach. The postoperative course was satisfactory and the patient has been disease-free for 5 years after the operation. Laparoscopic operation could be a useful option in the second-line treatment for MALT lymphoma after failure to eradicate H. pylori.


Evaluation of estimated genetic values and their application to genome-wide investigation of systolic blood pressure.
The concept of breeding values, an individual's phenotypic deviation from the population mean as a result of the sum of the average effects of the genes they carry, is of great importance in livestock, aquaculture, and cash crop industries where emphasis is placed on an individual's potential to pass desirable phenotypes on to the next generation. As breeding or genetic values (as referred to here) cannot be measured directly, estimated genetic values (EGVs) are based on an individual's own phenotype, phenotype information from relatives, and, increasingly, genetic data. Because EGVs represent additive genetic variation, calculating EGVs in an extended human pedigree is expected to provide a more refined phenotype for genetic analyses. To test the utility of EGVs in genome-wide association, EGVs were calculated for 847 members of 20 extended Mexican American families based on 100 replicates of simulated systolic blood pressure. Calculations were performed in GAUSS to solve a variation on the standard Best Linear Unbiased Predictor (BLUP) mixed model equation with age, sex, and the first 3 principal components of sample-wide genetic variability as fixed effects and the EGV as a random effect distributed around the relationship matrix. Three methods of calculating kinship were considered: expected kinship from pedigree relationships, empirical kinship from common variants, and empirical kinship from both rare and common variants. Genome-wide association analysis was conducted on simulated phenotypes and EGVs using the additive measured genotype approach in the SOLAR software package. The EGV-based approach showed only minimal improvement in power to detect causative loci.


In-hospital ischaemic stroke treated with intravenous thrombolysis or mechanical thrombectomy.
Patients with in-hospital strokes (IHS) may be eligible for recanalization therapies. The objective of this study is to compare outcomes in patients with IHS and community-onset strokes (COS) treated by recanalization therapy. We analysed data prospectively collected in consecutive patients treated by thrombolysis, thrombectomy, or both for cerebral ischemia at the Lille University Hospital. We compared four outcomes measures at 3 months in patients with IHS and COS: (1) modified Rankin scale (mRS) 0-1, (2) mRS 0-2, (3) death, and (4) symptomatic intracranial haemorrhage (ECASS 2 definition). Of 1209 patients, 64 (5.3%) had IHS, with an increasing proportion over time (p = 0.001). Their median onset-to-needle time was 128 min vs. 145 in COS (p < 0.001). They were more likely to have had a recent TIA [odds ratio (OR) 30.1; 95% confidence interval (CI) 11.5-78.7], to have been treated by vitamin K antagonist before (OR 4.2; 95% CI 1.4-12.0) and to undergo mechanical thrombectomy (45 vs. 10%, p < 0.001). They were less likely to have a pre-stroke mRS 0-1 (OR 0.22; 95% CI 0.09-0.50). After adjustment, IHS was not associated with any of the four outcome measures. Patients with IHS are treated 17 min earlier than patients with COS, but, taking into account that they were already in the hospital, delays are still too long. Their outcome does not differ from that of patients with COS, suggesting room for improvement if delays can be reduced. IHS being frequent, pre-specified pathways should be organised.


Regenerative potential of chitosan-coated poly-3-hydroxybutyrate conduits seeded with mesenchymal stem cells in a rat sciatic nerve injury model.
A number of chemical and biological factors, including mesenchymal stem cells (MSCs), have been developed to enhance nerve regeneration by introduction through a variety of nerve conduits. This study was designed to assess the efficacy of using chitosan-coated poly-3-hydroxybutyrate (PHB) nerve conduits seeded with human bone marrow-derived MSCs (hMSC-bm) to augment repair in an experimental rat model of sciatic nerve injury. A total of 30 rats were randomly assigned to one of three groups (n = 10). In each rat, a 10 mm segment of the sciatic nerve was removed and was replaced by a chitosan-coated PHB conduit seeded with hMSC-bm (PHB/chitosan-hMSC-bm group), a chitosan-coated PHB conduit (PHB/chitosan group), or an autograft (autograft group) as the control. The results were evaluated 8 weeks postoperatively by observation, electromyography and histologic examination with light microscopy and immunostaining. Histologic examination showed that both PHB/chitosan-hMSC-bm conduits and PHB/chitosan conduits led the damaged axons through the injured area. When the effects were compared, the results with the PHB/chitosan-hMSC-bm conduits were superior to those with the PHB/chitosan conduits (p < 0.05) but not as successful as with the autologous nerve grafts (p < 0.05). PHB/chitosan-hMSC-bm nerve conduits may be a useful artificial guide for nerve regeneration.


Arrayed primer extension technology simplifies mutation detection in Bardet-Biedl and Alström syndrome.
Bardet-Biedl syndrome (BBS; OMIM no. 209 900) and Alström syndrome (ALMS; OMIM no. 203 800) are rare, multisystem genetic disorders showing both a highly variable phenotype and considerable phenotypic overlap; they are included in the emerging group of diseases called ciliopathies. The genetic heterogeneity of BBS with 14 causal genes described to date, serves to further complicate mutational analysis. The development of the BBS-ALMS array which detects known mutations in these genes has allowed us to detect at least one mutation in 40.5% of BBS families and in 26.7% of ALMS families validating this as an efficient and cost-effective first pass screening modality. Furthermore, using this method, we found two BBS families segregating three BBS alleles further supporting oligogenicity or modifier roles for additional mutations. We did not observe more than two mutations in any ALMS family.


Glucose Monitoring Dermopathy.
A 75-year-old man had been monitoring his glucose using a blood glucose monitoring system at the same body site for at least 20 years (>7300 needlesticks). The asymptomatic skin lesion had been present for many years. He used the same site because it hurt less than the fingers and bled well. His medical history was remarkable for diabetes mellitus, hypertension, coronary artery disease, and a pacemaker. His medications included glipizide, metformin, carvedilol, furosemide, lisinopril, amlodipine, clopidogrel, and aspirin. Physical examination revealed a brown, slightly raised, rough plaque with focal, punctate hemorrhagic crusts, on the distal area of the right thigh (Figure 1). The clinical differential diagnosis was more likely to be lichen simplex chronicus than pigmented Bowen's disease. A skin biopsy demonstrated an acanthotic epidermis with coarse collagen bundles in a thickened papillary dermis with extravasated erythrocytes, consistent with a dermal reparative reaction (Figure 2).


Pruritus in Patients Under Targeted Anticancer Therapy: A Multidimensional Analysis Using the 5-D Itch Scale.
Pruritus is a very common symptom in patients, undergoing targeted anticancer therapy. However, the characteristics of pruritus, according to the targeted anticancer agents, are still unclear. The objective of this study was to determine the characteristics of pruritus, induced by targeted anticancer agents, using a questionnaire-based survey. The survey was administered to cancer patients currently receiving anticancer agents. Medical records were also reviewed. A total of 374 cancer patients completed the survey, of which 108 were treated with the targeted therapy. A total of 205 patients had pruritus, of which 66 were under the targeted therapy. Epidermal growth factor receptor inhibitor (EGFRI) users showed the highest prevalence rate of itching and numeric rating scale score for itching. The 5-D itch score was also highest among users of EGFRIs. In conclusion, patients receiving EGFRIs suffer from severe pruritus frequently. They not only experienced long lasting and intense itching, causing sleep discomfort, but also developed itching at specific body sites.


Characterization of NLRP3-like gene from Apostichopus japonicus provides new evidence on inflammation response in invertebrates.
Inflammatory/defensive response after pathogen invasion is considered a local defense reaction in vertebrates. Inflammation response in Apostichopus japonicus was hardly determined due to scarce information available for nucleotide binding domain-like receptor family, pyrin domain-containing (NLRP) family. In the present study, invertebrate NLRP homologue was identified from A. japonicus (designated as AjNLRP3-like) by rapid amplification of cDNA ends. Full-length cDNA of AjNLRP3-like measured 2970 bp with 2265 bp open reading frame encoding a 754-amino acid (aa) residue protein. Structural analysis revealed that AjNLRP3-like processed characteristic domains of pyrin (32-102aa) and NACHT (183-339aa). Multiple sequence alignment and phylogenetic analysis supported that AjNLRP3-like belongs to a new member of NLRP3 protein subfamily. Spatial expression analysis revealed that AjNLRP3-like was ubiquitously expressed in all examined tissues with larger magnitude in coelomocytes. Both Vibrio splendidus challenge in vivo and lipopolysaccharide stimulation in vitro significantly upregulated mRNA expression of AjNLRP3-like when compared with the control group. NLRP3-mediated inflammation response depended on release of lysosomal cathepsin B (CTSB) and subsequent activation of high-mobility group box (HMGB) in vertebrates. We investigated expression profiles of AjNLRP3-like and AjHMGB after AjCTSB knock-down and discovered that AjNLRP3-like was depressed by 0.66-fold and 0.47-fold, whereas AjHMGB was depressed by 0.70-fold and 0.50-fold at 24 and 48 h in AjCTSB-silenced group, respectively. Similarly, down-regulation of AjHMGB was also observed after AjNLRP3-like knock-down. This study therefore suggests that A. japonicus feature similar inflammatory events as those in vertebrates, and activation of AjNLRP3-like depends on AjCTSB expression and release of AjHMGB.


Neural correlates of the Pythagorean ratio rules.
Millennia ago Pythagoras noted a simple but remarkably powerful rule for the aesthetics of tone combinations: pairs of tones--intervals--with simple ratios such as an octave (ratio 2 : 1) or a fifth (ratio 3 : 2) were pleasant sounding (consonant), whereas intervals with complex ratios such as the major seventh (ratio 243 : 128) were harsh (dissonant). These Pythagorean ratio rules are the building blocks of Western classical music; however, their neurophysiologic basis is not known. Using functional MRI we have found the neurophysiologic correlates of the ratio rules. In musicians, the inferior frontal gyrus, superior temporal gyrus, medial frontal gyrus, inferior parietal lobule and anterior cingulate respond with progressively more activation to perfect consonances, imperfect consonances and dissonances. In nonmusicians only the right inferior frontal gyrus follows this pattern.


V-shaped double-row distal triceps tendon repair: a novel technique using unicortical button fixation.
This report was designed to present a novel technique combining suture anchor and unicortical button fixation for distal triceps tendon repair. For anatomical reinsertion of an acute distal triceps tendon rupture, two suture anchors and one unicortical button forming a V-shaped configuration were used. The operative approach is described in detail. Excellent clinical and functional results were achieved in the early postoperative phase. The patient reached full elbow range of motion and extension muscle strength (5/5) compared to the uninjured arm 12 weeks after surgery. Complications did not occur. This is the first report using unicortical button fixation in distal triceps tendon repair with promising preliminary results. Technical description, case report, Level V.


Antipsychotics-induced metabolic alterations: focus on adipose tissue and molecular mechanisms.
The use of antipsychotic drugs for the treatment of mood disorders and psychosis has increased dramatically over the last decade. Despite its consumption being associated with beneficial neuropsychiatric effects in patients, atypical antipsychotics (which are the most frequently prescribed antipsychotics) use is accompanied by some secondary adverse metabolic effects such as weight gain, dyslipidemia and glucose intolerance. The molecular mechanisms underlying these adverse effects are not fully understood but have been suggested to involve a dysregulation of adipose tissue homeostasis. As such, the aim of this paper is to review and discuss the role of adipose tissue in the development of secondary adverse metabolic effects induced by atypical antipsychotics. Data analyzed in this article suggest that atypical antipsychotics may increase adipose tissue (particularly visceral adipose tissue) lipogenesis, differentiation/hyperplasia, pro-inflammatory mediator secretion and insulin resistance and decrease adipose tissue lipolysis. Consequently, patients receiving antipsychotic medication could be at risk of developing obesity, type 2 diabetes and cardiovascular disease. A better knowledge of the impact of these drugs on adipose tissue homeostasis may unveil strategies to develop novel antipsychotic drugs with less adverse metabolic effects and to develop adjuvant therapies (e.g. behavioral and nutritional therapies) to neuropsychiatric patients receiving antipsychotic medication.


Dysautonomia with acute sensory motor neuropathy. A new classification of acute autonomic neuropathy.
To characterize the dysautonomia associated with acute sensory motor neuropathy and to discuss the classification of acute autonomic neuropathy. Case series. Sympathetic skin response. Local sweat response to acetylcholine. Norepinephrine infusion test and acetylcholinesterase histochemistry of sural nerve biopsy specimens in addition to making conventional analyses of myelinated and unmyelinated fibers. In 12 patients with chronic neuropathy, acetylcholinesterase-positive fiber density and plantar sympathetic skin response size were well correlated, but in the two patients with acute autonomic sensory and motor neuropathy, there were discrepancies, acetylcholinesterase-positive fiber density being well preserved and sympathetic skin responses being absent. Histologic and electrophysiologic results indicated primary demyelination of the myelinated fibers. In contrast, previous studies of acute autonomic sensory and motor neuropathy reported dysfunction of the sympathetic postganglionic fibers and axonopathic change in myelinated fibers, poor recovery from dysautonomia. Dysautonomia with acute idiopathic neuropathy can be divided into two categories--postganglionic axonopathic and preganglionic demyelinating types of the sympathetic efferent pathways. The recovery from dysautonomia produced by the former lesion is poor, but recovery is better for that produced by the latter lesion.


Epidemiology of Ebola Virus Disease in the Western Area Region of Sierra Leone, 2014-2015.
Western Area (WA) of Sierra Leone including the capital, Freetown, experienced an unprecedented outbreak of Ebola from 2014 to 2015. At the onset of the epidemic, there was little information about the epidemiology, transmission dynamics, and risk factors in urban settings as previous outbreaks were limited to rural/semi-rural settings. This study, therefore, aimed to describe the epidemiology of the outbreak and the factors which had most impact on the transmission of the epidemic and whether there were different drivers from those previously described in rural settings. We conducted a descriptive epidemiology study in WA, Sierra Leone using secondary data from the National Ebola outbreak database. We also reviewed the Ebola situation reports, response strategy documents, and other useful documents. A total of 4,955 Ebola cases were identified between June 2014 and November 2015, although there were reports of cases occurring in WA toward end of May. All wards were affected, and Waterloo Area I (Ward 330), the capital city of Western Area Rural District, recorded the highest numbers of cases (580) and deaths (236). Majority of cases (63.4%) and deaths (66.8%) were in WA Urban District (WAU); 44 cases were imported from other provinces. Only 20% of cases had a history of contact with an Ebola case, and more than 30% were death alerts. Equal numbers of males and females were infected, and very few cases (3.2%) were health workers. Overall, transmission was through contact with infected individuals, and intense transmission occurred at the community level. In WAU, transmission was mostly between neighbors and among inhabitants of shared accommodations. The drivers of transmission included high population movement to and from WA, overcrowding, fear and lack of trust in the response, and negative community behaviors. Transmission was mostly through contact and with limited transmission through sex and breast milk. The unprecedented outbreak in WA was attributed to delayed detection, inadequate preparedness and response, intense population movements, overcrowding, and unresponsive communities. Anticipation, strengthening preparedness for early detection, and swift and effective response remains critical in mitigating a potential urban explosion of similar future outbreaks.


Assessment of Sotalol and Dofetilide Dosing at a Large Academic Medical Center.
Patients initiated on sotalol and dofetilide require inpatient monitoring and dose adjustments due to risks of corrected QT (QTc) prolongation and Torsades de pointes (TdP). Patients may receive higher initial doses than recommended due to close monitoring by specialized practitioners. The objective of this study was to describe prescribing practices of sotalol and dofetilide and to compare safety outcomes between standard and nonstandard dosing strategies. This was a single-center retrospective analysis of adult inpatients who underwent sotalol or dofetilide initiation between June 1, 2015, and August 1, 2018. The end points of this study included the percentage of patients who received standard and nonstandard dosing, incidence of QTc prolongation (≥500 milliseconds or ≥15% from baseline), incidence of TdP, and dose reduction or medication discontinuation. A total of 379 patients (195 sotalol and 184 dofetilide) were included in this analysis. There were 110 (56.4%) patients in the sotalol group and 111 (58.4%) patients in the dofetilide group that received nonstandard initial dosing. Nonstandard dosing was associated with a greater incidence of QTc prolongation compared to standard dosing (57.5% vs 43.0%, P = .005). Only one patient in the nonstandard dosing group experienced TdP. Patients initiated on nonstandard dosing required dose reduction or therapy discontinuation (37.6% vs 23.4%, P = .003) more frequently. Higher than recommended initial doses of sotalol or dofetilide were associated with higher incidence of QTc prolongation and more frequent therapy modification.


First Report of Meloidogyne enterolobii Yang & Eisenback, 1983 (Guava Root-knot Nematode) Infecting Guava (Psidium guajava) in Egypt.
Meloidogyne enterolobii Yang & Eisenback, 1983 (guava root-knot nematode) is an important disease in subtropical to tropical climate in several areas of the world (Subbotin et al., 2021). It is a highly polyphagous root-knot nematode species causing major damage to a range of economically important crops. The expansion of this species is increasing worldwide creating a potential problem to the maintenance of resistance genes to other major Meloidogyne species (Castagnone-Sereno and Castillo, 2020). Additionally, the diagnosis of M. enterolobii can be challenging due to morphological similarities with other root-knot nematode species (Castagnone-Sereno, 2012). In the African continent, it has been cited in several countries of Equatorial and South Africa (Subbotin et al., 2021), but not in North Africa. Two guava groves (at Bany Salama, Natrn vally, El Beheira governorate, 30.322043N, 30.518529E; and Izbat Al Halawijah, Monshaah Alaweyah, Abu El Matamir, El Beheira governorate 30.9398050N, 30.1484430E), in Egypt, were found with significant symptoms of tree decline and root galling damage. The presence of egg masses and females of root-knot nematodes were found inside the galls (Figure 1A, B). Nematodes were extracted from soil samples with levels of 12300 and 12600 second-stage juveniles (J2s)/250 g of soil using a modified Baerman method (Hooper, 1986), respectively. Nematode root density was 24367 eggs/g of root, using the protocol described in Hussey and Barker (1973) for Izbat Al Halawijah population. For morphological and morphometrical identification, J2s and females were fixed using a hot formalin solution (4% v/v). DNA was isolated from single J2s specimen for: i) testing multiplex specific-PCR assay for M. incognita, M. javanica and M. arenaria (Kiewnick et al., 2013), and ii) amplifying and sequencing of cytochrome oxidase subunit II (COII) and the 16S rRNA mitochondrial region using the primer pair C2F3 (5'-GGTCAATGTTCAGAAATTTGTGG-3') (Powers and Harris, 1993) and MRH106 (5'- AATTTCTAAAGACTTTTCTTAGT-3') (Stanton et al., 1997). Perineal patterns of females for Izbat Al Halawijah population were typical of the species (Fig. 1D), body size (L: 520-774 µm; W: 214-487 µm), stylet length (12.5-13.7 µm) and ratio from distance from anterior end to excretory pore and stylet length (4.2) in females (n = 18), fitting with original description and others (Subbotin et al., 2021). J2s from Izbat Al Halawijah population (n=13) (Fig. 1C, E-H) showed: body length (393.5-475 µm), stylet length (11.5-13.5), excretory pore to anterior end (89-95.5 µm), tail length (50.0-60.0 µm), tail hyaline region (12.0-21.0 µm), a ratio (24.2-32.5), b ratio (4.9-6.5), c ratio (7.3-8.6) and c' (5.0-6.4), also fitting with original description and others (Subbotin et al., 2021). Specific PCR did not amplify any band (Kiewnick et al., 2013). Four J2s individuals were sequenced for COII-16S rRNA region for each population showing M. enterolobii as unique species and without intraspecific variability. Two identical DNA fragments of 814 bp obtained for both populations (OP434400 and OP434401) were compared with those in GenBank. A BLAST search indicated the sequences were 100% identical to several sequences of M. enterolobii (MF467278 and KX823371). On the basis of these results, the root-knot nematodes isolated from these two guava groves in Egypt were confirmed as M. enterolobii. This is a well-known pathogen of guava, causing important losses in this crop (Castagnone-Sereno and Castillo, 2020) and it is regulated as quarantine nematode in the Mediterranean region (EPPO).


Stereochemistry of 1,2-dichloroethane adsorbed on Pt(111).
The rotational isomerism of 1,2-dichloroethane (DCE, CH2ClCH2Cl) adsorbed on Pt(111) was studied in the temperature range of 35-100 K using high-resolution electron energy loss spectroscopy and metastable atom electron spectroscopy. In the coverage below monolayer the physisorbed and chemisorbed species coexist at 35 K in the gauche and slightly distorted trans form, respectively. Owing to the direct Pt-Cl interactions, the nonbonding Cl 3p states of the chemisorbed DCE are split off, giving rise to degradation in symmetry from the pure trans form (C2h). The physisorbed gauche conformers are arranged with the C2 axis parallel (or heavily tilted) to the substrate and converted irreversibly to the pseudo-trans form by heating at 70 K. In the multilayer, the trans and gauche conformers exist at 35 K, where the former population is increased with increasing layer thickness. Upon annealing the bilayer at 80 K, the irreversible conversion takes place to yield a higher population of the gauche conformer in the topmost layer. The conformational stabilities and mutual changes of DCE adsorbed on a metal surface are discussed in terms of intramolecular rotational potential.


Basal Cell Carcinoma and Eccrine Porocarcinoma of the Eyelid.
An 81-year-old woman presented with a progressively enlarging indurated, firm lesion encompassing one-third of the left upper eyelid. Four years prior, a similar lesion at that same site had been excised and diagnosed as a basal cell carcinoma. The patient underwent a full-thickness excision of the lesion with frozen section, cryotherapy, and reconstruction. A free tarsal graft and hard palate composite graft was used to reconstruct the posterior lamella. A Mustarde myocutaneous rotational flap was used to reconstruct the anterior lamella. Histopathology illustrated nests of pleomorphic basophilic cells with varying mitotic activity and immunohistochemical staining consistent with eccrine porocarcinoma. This case highlights similarities in the presentation and appearance of basal cell carcinoma and periorbital eccrine porocarcinoma. It is possible that there was de novo development of the 2 tumors on the eyelid or recurrence of a misdiagnosed eccrine porocarcinoma. Eccrine porocarcinomas are rare malignant sweat gland tumors associated with a risk of recurrence after excision and metastasis.


Involvement of the cytoskeleton in early grey crescent formation in axolotl oocytes.
Maturing axolotl oocytes which are treated with protein synthesis inhibitors or which are heat-shocked can be induced to reorganize their cytoplasm and to form an early grey crescent. The maturing axolotl oocyte has been used as a model system to study the role of the cytoskeleton in dorsoventral polarization as visualized by grey crescent formation. Results presented here provide evidence for the involvement of microtubules in the formation of the early grey crescent. Whereas inhibitors of microtubule polymerization and antibodies against tubulin both elicit early grey crescent formation, the effect of taxol shows that microtubule polymerization is required at a late stage in this event. The nucleus furnishes important factors required for early grey crescent formation and might play a role in microtubule polymerization.


Class-Incremental Learning on Video-Based Action Recognition by Distillation of Various Knowledge.
Recognition of activities in the video is an important field in computer vision. Many successful works have been done on activity recognition and they achieved acceptable results in recent years. However, their training is completely static, meaning that all classes are taught to the system in one training step. The system is only able to recognize the equivalent classes. The main disadvantage of this type of training is that if new classes need to be taught to the system, the system must be retrained from scratch and all classes retaught to the system. This specification has many challenges, such as storing and retaining data and respending training costs. We propose an approach for training the action recognition system in video data which can teach new classes to the system without the need for previous data. We will provide an incremental learning algorithm for class recognition tasks in video data. Two different approaches are combined to prevent catastrophic forgetting in the proposed algorithm. In the proposed incremental learning algorithm, two approaches are introduced and used to maintain network information in combination. These two approaches are network sharing and network knowledge distillation. We introduce a neural network architecture for action recognition to understand and represent the video data. We propose the distillation of network knowledge at the classification and feature level, which can be divided into spatial and temporal parts at the feature level. We also suggest initializing new classifiers using previous classifiers. The proposed algorithm is evaluated on the USCF101, HMDB51, and Kinetics-400 datasets. We will consider various factors such as the amount of distillation knowledge, the number of new classes and the incremental learnings stages, and their impact on the final recognition system. Finally, we will show that the proposed algorithm can teach new classes to the recognition system without forgetting the previous classes and does not need the previous data or exemplar data.


Alert signals enhance animal communication in "noisy" environments.
Environmental noise that reduces the probability that animals will detect communicative signals poses a special challenge for long-range communication. The application of signal-detection theory to animal communication lead to the prediction that signals directed at distant receivers in noisy environments will begin with conspicuous "alerting" components to attract the attention of receivers, before delivery of the information-rich portion of the signal. Whether animals actually adopt this strategy is not clear, despite suggestions that alerts might exist in a variety of taxa. By using a combination of behavioral observations and experimental manipulations with robotic lizard "playbacks," we show that free-living territorial Anolis lizards add an "alert" to visual displays when communicating to distant receivers in situations of poor visibility, and that these introductory alerts in turn enhance signal detection in adverse signaling conditions. Our results show that Anolis lizards are able to evaluate environmental conditions that affect the degradation of long-distance signals and adjust their behavior accordingly. This study demonstrates that free-living animals enhance the efficiency of long-range communication through the modulation of signal design and the facultative addition of an alert. Our findings confirm that alert signals are an important strategy for communicating in "noisy" conditions and suggest a reexamination of the existence of alerts in other animals relying on long-range communication.


Maternal toxemia and neonatal germinal matrix hemorrhage in intubated infants less than 1751 g.
Two hundred seventy-two intubated infants who weighed less than 1751 g were enrolled in a clinical trial of phenobarbital prophylaxis of postnatal germinal matrix hemorrhage. The incidence of germinal matrix hemorrhage was 3.1% (one of 32) among infants born to women with toxemia, and 23% (55 of 240) among those born to women without toxemia. The apparent protective effect of toxemia could not be explained by intrauterine growth retardation, mode of delivery, or maternal receipt of any medication. Infants born to toxemic women were less likely than their peers to develop pneumothorax, become acidotic, and to require extensive respiratory assistance. This apparently protective effect of maternal toxemia was not seen in infants born to nontoxemic, hypertensive women. Thus, maternal toxemia, but not hypertension, might reduce the risk of germinal matrix hemorrhage by reducing the occurrence and/or severity of pulmonary and related problems that place infants at high risk of germinal matrix hemorrhage.


Hyperglycemia requiring insulin during acute lymphoblastic leukemia induction chemotherapy is associated with increased adverse outcomes and healthcare costs.
Hyperglycemia is a complication of induction chemotherapy in 10%-50% of pediatric patients with acute lymphoblastic leukemia (ALL). Though hyperglycemia in ALL patients is usually transient, it may be associated with adverse health outcomes. However, the risk factors for and consequences of hyperglycemia are poorly understood. We hypothesized that hyperglycemia significant enough to require insulin therapy during induction chemotherapy would be associated with increased morbidity and mortality in pediatric ALL patients during induction chemotherapy and in subsequent care. We abstracted clinical and resource utilization data from the Pediatric Health Information System (PHIS) database utilizing ICD-9 codes and medication charges. We used logistic regression analysis to predict the development of hyperglycemia. The effects of hyperglycemia on binary and count adverse outcomes following induction chemotherapy were modeled using mixed-effect regression models. An increased risk of hyperglycemia requiring insulin was associated with older age, female sex, higher risk group and trisomy 21. Patients on insulin for hyperglycemia had increased mortality following induction chemotherapy. These patients were more likely to have subsequent infectious complications, need for bone marrow transplant, and risk of disease relapse. They also had greater length of inpatient stay, higher cost of care, and were more likely to require intensive care unit admission during induction chemotherapy. Hyperglycemia requiring insulin during induction chemotherapy in pediatric ALL is associated with an increased risk of short-term and long-term complications. Prospective studies are needed to analyze formal screening, preventive measures, and optimal management practices for hyperglycemia during ALL induction chemotherapy.


Crystallization and preliminary crystallographic analysis of D-aspartate oxidase from porcine kidney.
D-Aspartate oxidase (DDO) from porcine kidney was crystallized by the sitting-drop vapour-diffusion method using PEG 8000 as a precipitant. The crystal belonged to space group P2(1), with unit-cell parameters a = 79.38, b = 144.0, c = 80.46 Å, β = 101.1°, and diffracted to 1.80 Å resolution. Molecular-replacement trials using the structure of human D-amino-acid oxidase, which is 42% identical in sequence to DDO, as a search model provided a satisfactory solution.


Rate of skill acquisition in the use of a robotic laparoscope holder (FreeHand(®)).
Robotic equipment can greatly add to the ergonomics of a surgical procedure and pre-operative simulation can provide risk-free training of the surgeon leading to precision surgery and less trauma to the patient. Freehand(®) is a second-generation robotic camera-holding device, which has recently become available to laparoscopic surgeons. It is controlled by the operator selecting a direction using head movement followed by activation with a foot pedal. The purpose of this study was to assess the rate of skill acquisition in the use of the FreeHand(®) robotic laparoscope holder by a group of laparoscopic surgeons by enrolling them into a programme of training modules at The ICENI Centre, Colchester Hospital University, UK. Twenty surgical registrars performed a series of exercises, escalating in difficulty, to test their skill in controlling the FreeHand(®) robot. Subjective and objective assessments were evaluated by an observer and by tracking analysis software created for this trial. The observed number of head movements showed a Percentage Performance Score (PPS) of 98% by the end of the third repetition of all exercises, the mean Total Head Movements Score (HMS) reached a plateau of performance at 72%. Fifty per cent of the participants selected 'Effective control of movements without difficulty' in the subjective evaluation by the end of the third repetition of exercises, while 35% selected 'competent intuitive movements'. The FreeHand(®) robotic laparoscope holder is a useful device, which is easy to operate and requires a very short course of training to achieve competence in its use.


Ambulance staff awareness of vitamin D and risk of deficiency in a UK ambulance service: a survey-based evaluation.
The aim of this service evaluation was to explore staff awareness of vitamin D and the risks associated with deficiency in the ambulance setting, to inform the need for appropriate well-being support and resources. An online, anonymous 20-question survey was purpose-designed, based on a validated vitamin D questionnaire. It was made available to staff for completion in one UK ambulance service between 16 June and 12 July 2020, resulting in a convenience sample of 354 responses. These were analysed using quantitative (descriptive) and qualitative (thematic) approaches. The cohort age range was 20 to 65+ years; 41% (n = 156) were male. Over half of respondents worked within emergency operational service delivery (57%; n = 219), but all key service roles were represented. Respondents reported to be predominantly 'White British' (92%; n = 352), but nine ethnic groups were included. According to the Fitzpatrick Scale, most staff described themselves as having a 'Medium, between white to moderate brown: sometimes mild burns, gradual tan' complexion (47%; n = 182) or 'White, Fair: usually burns, tans with difficulty' (32%; n = 124). The majority felt they got sufficient sunlight exposure when at home (66%; n = 253), but not at work (58%; n = 222). Typically, respondents stated they were 'neither unconcerned or concerned' about having vitamin D deficiency (35%; n = 135), although almost a fifth (17%; n = 66) reported to have been told they had vitamin D deficiency by a medical professional. Forty percent of respondents took vitamin D supplements: 12% (n = 45) as advised by a medical professional, and 28% (n = 107) self-directed to prevent vitamin D deficiency. Of the remaining, many (35%; n = 136) had not considered taking such dietary supplements. The ability of respondents to recognise known factors that affect vitamin D production in the skin, good vitamin D food sources and individuals at risk of vitamin D deficiency was variable. Additional comments raised by respondents related to lack of vitamin D awareness, the risk factors and impact of deficiency, vitamin supplementation, COVID-19, work arrangements and sunlight exposure, self-learning and general well-being. There is scope for improved awareness of vitamin D and the risks for deficiency in the ambulance setting. It appears service staff are at risk of vitamin D deficiency irrespective of their role: access to sunlight and use of vitamin D supplements are variable. The physical and mental impacts of deficiency can be significant, requiring absence from work. The development of appropriate vitamin D and well-being resources appears to be warranted.


A new endogean, anophthalmous species of Parazuphium Jeannel from Northern Morocco (Coleoptera, Carabidae), with new molecular data for the tribe Zuphiini.
A new species of the genus Parazuphium (Coleoptera, Carabidae, Zuphiini), Parazuphium aguileraisp. n., is described from the Tingitan peninsula in North Morocco. The only known specimen was found under a large deeply buried boulder, and belongs to an anophthalmous, depigmented and flattened species. This is the second species of blind Parazuphium known so far, the other being Parazuphium feloi Machado 1998 from a lava tube in the Canary Islands. Molecular data of the only known Parazuphium aguilerai sp. n. specimen are provided, and a reconstructed phylogeny based on these molecular data confirms its inclusion inside Zuphiini within Harpalinae. Identification keys to the Mediterranean and Macaronesian species of Parazuphium are provided.


Low-dose oral methotrexate for maintaining Crohn's disease remission: where we stand.
Methotrexate has been considered a second-line immunomodulating therapy, behind azathioprine (AZA) or its metabolite 6-mercaptopurine (6-MP), for the treatment of Crohn's disease (CD). Approximately 27% to 50% of patients with refractory CD are intolerant or resistant to AZA or 6-MP. Two well-designed randomized double-blind placebo-controlled trials have demonstrated that low-dose methotrexate (<25 mg/wk), given intramuscularly (IM), is effective in inducing and maintaining remission in CD. In clinical practice, IM injection involves an inconvenience for patients and higher costs. Furthermore, frequent IM injections increase the risk of complications such as peripheral nerve injury, local irritation, pain, bleeding, fibrosis, abscess formation, gangrene, and contractures. Alternatively, subcutaneous (SQ) injection has been advocated because it has been shown to have similar pharmacokinetics to IM injection. However, because of a recent and ongoing national shortage of parenteral methotrexate, patients who were receiving IM methotrexate had to switch to the oral form until the parenteral formulation becomes available. Oral methotrexate has been used with great success in treatment of rheumatoid arthritis and psoriasis for the past 50 years. However, the data on the usage of low-dose oral methotrexate in maintaining CD remission are scanty and controversial. The purpose of this article is to review the mechanism of action, absorption, and the objective evidence in supporting the use of oral methotrexate in maintaining CD remission.