An Evaluation of the Youth Quitline Service Young Hong Kong Smokers.
The psychological and social factors associated with smoking initiation and continuation are different for young and adult smokers. Before 2005, there were no population-based smoking cessation interventions targeting young smokers in Hong Kong, China. This study describes the processes and outcomes of an individualized "Youth Quitline" service for young Hong Kong Chinese smokers over a 10-year period. A retrospective population-based study was conducted to evaluate the effectiveness of the Quitline and identify the predictors of quitting. Telephone records were used to obtain information of each call. Young smokers of the Quitline completed a questionnaire at baseline and 6-month follow-up. Data were collected between August 2005 and August 2015. Over the 10-year period, the Youth Quitline received 7,720 telephone inquiries and provided smoking cessation counseling to 1,684 young smokers. At the 6-month follow-up, 16.9% had reduced cigarette consumption by more than 50%, 33.8% had tried quitting, and 23.6% had successfully quit smoking. Logistic regression analyses indicated that 7 factors, including (1) age; (2) daily cigarette consumption; (3) level of nicotine dependence; (4) intention to quit; (5) having made at least one quit attempt; (6) level of self-efficacy; and (7) adherence to telephone counseling, significantly predicted smoking cessation at 6 months. During the first 10 years of the Youth Quitline, we trained many youths to become smoking cessation peer counselors. The Youth Quitline successfully increased youths' awareness of the risks of smoking and smoking cessation services and provided individualized smoking cessation counseling services to young smokers.


Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism.
To characterize the nature and dynamics of the neutralizing antibody (NAb) response and escape in chronically HIV-2 infected patients. Twenty-eight chronically infected adults were studied over a period of 1-4 years. The neutralizing activity of plasma immunoglobulin G (IgG) antibodies against autologous and heterologous primary isolates was analyzed using a standard assay in TZM-bl cells. Coreceptor usage was determined in ghost cells. The sequence and predicted three-dimensional structure of the C2V3C3 Env region were determined for all isolates. Only 50% of the patients consistently produced IgG NAbs to autologous and contemporaneous virus isolates. In contrast, 96% of the patients produced IgG antibodies that neutralized at least two isolates of a panel of six heterologous R5 isolates. Breadth and potency of the neutralizing antibodies were positively associated with the number of CD4(+) T cells and with the titer and avidity of C2V3C3-specific binding IgG antibodies. X4 isolates were obtained only from late stage disease patients and were fully resistant to neutralization. The V3 loop of X4 viruses was longer, had a higher net charge, and differed markedly in secondary structure compared to R5 viruses. Most HIV-2 patients infected with R5 isolates produce C2V3C3-specific neutralizing antibodies whose potency and breadth decreases as the disease progresses. Resistance to antibody neutralization occurs in late stage disease and is usually associated with X4 viral tropism and major changes in V3 sequence and conformation. Our studies support a model of HIV-2 pathogenesis in which the neutralizing antibodies play a central role and have clear implications for the vaccine field.


NTP technical report on the toxicity studies of Butanal oxime (CAS No. 110-69-0) administered in drinking water and by gavage to F344/N rats and B6C3F1 mice.
Butanal oxime is used as a volatile antiskinning agent in paints, inks, and similar products. Butanal oxime was chosen for toxicology testing as a representative of the aldoxime class. Male and female F344/N rats and B6C3F1 mice received butanal oxime (99 percent pure) in drinking water for 15 days or by gavage in 0.5 percent methylcellulose for 14 weeks. Animals were evaluated for clinical pathology, reproductive system effects, and histopathology. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse peripheral blood erythrocytes. In the 15-day studies, groups of five male and five female rats and mice received 0, 312, 625, 1,250, 2,500, or 5,000 ppm butanal oxime in drinking water, resulting in average daily doses of approximately 40, 70, or 100 mg butanal oxime/kg body weight to male and female rats; 45, 90, 130, 200, or 300 mg/kg to male mice; and 45, 85, 100, 130, or 170 mg/kg to female mice. Due to body weight loss and lack of water consumption, all male and female rats receiving 2,500 or 5,000 ppm were removed from the study on day 9; average daily doses were not calculated for these groups. All other rats and mice survived until the end of the studies. Mean body weights of 1,250 ppm male and female rats and 2,500 and 5,000 ppm male and female mice were significantly less than those of the controls. Male mice receiving 5,000 ppm and females receiving 2,500 or 5,000 ppm lost weight during the study. Water consumption by rats and mice receiving 1,250 ppm or greater was less than that by the controls. Thinness in 2,500 and 5,000 ppm rats and mice was the only clinical finding of toxicity. Spleen weights were significantly decreased in 2,500 and 5,000 ppm female mice. No chemical-related lesions were observed grossly; histologic examinations were not performed. In the 14-week studies, groups of 10 male and 10 female rats and mice received butanal oxime by gavage at doses of 0, 25, 50, 100, 200, or 600 mg/kg, 5 days per week for 14 weeks. All 600 mg/kg rats died or were killed moribund during the first week of the study; in the 600 mg/kg mouse groups, seven males and nine females died, were killed moribund, or were killed accidentally before the end of the study. Mean body weights of 100 and 200 mg/kg male rats, 600 mg/kg male mice, and female mice administered 50 mg/kg or greater were less than those of the controls. Clinical findings of toxicity in 600 mg/kg rats included loss of coordination, wobbly gait, shaking, blinking, constant grooming and scratching of the face, head weaving, burying of the face in bedding, lethargy, and prostration; in 600 mg/kg mice, clinical findings included ataxia, loss of balance after rearing, squinting, and burying of the face in the bedding. Hematology results of the 14-week gavage studies indicate that butanal oxime induces a methemoglobinemia and a responsive anemia in rats and mice. Spleen weights of 100 and 200 mg/kg male rats, female rats administered 50 mg/kg or greater, and 200 and 600 mg/kg male mice were increased, as were the liver weights of 200 mg/kg female rats and mice. In animals that died early due to butanal oxime administration, hepatocellular necrosis was the primary pathologic finding. Degeneration of the nasal olfactory epithelium was observed in dosed rats and mice that died early as well as in animals that survived to the end of the studies. Additional chemical-related nasal findings were respiratory epithelial changes in male rats and suppurative exudate in male and female mice. Increased incidences and/or severities of splenic hematopoietic cell proliferation and pigmentation (hemosiderin) as well as bone marrow hyperplasia were also observed in dosed groups, particularly in the 200 and 600 mg/kg groups, and were indicative of erythrocyte damage. Butanal oxime (3 to 10,000 ug/plate) was mutagenic in S. typhimurium strain TA1535 in the presence of 5 percent or 10 percent rat liver S9; an equivocal response was seen in TA100 with 30 percent rat S9, and no mutagenic activity was seen in TA98, with or without rat or hamster liver S9. Butanal oxime induced chromosomal aberrations in cultured Chinese hamster ovary cells, with and without S9. Significant increases in the frequencies of micronucleated normochromatic erythrocytes were observed in vivo in peripheral blood of male and female mice administered 25 to 600 mg/kg butanal oxime for 14 weeks by gavage. Synonyms: Butanaloxime; butylaldoxime; butyraldehyde oxime; n-butyraldehyde oxime; butyraldoxime; n-butyraldoxime Trade names: Exkin 1, Exkin No. 1 Anti-Skinning Agent, Skino #1, Troykyd Anti-Skin BTO


[Subcutaneous implantation type central venous port management in patients with malignant tumors effect of different antiseptic agents on central venous port-related infection].
Subcutaneous implantation type central venous ports(CV ports)are used in chemotherapy. Here, we prospectively examined the frequency of CV port-related infections when the disinfectant was changed from 10% povidone iodine to 1% chlorhexidine ethanol or 70% ethanol. The subjects were patients with malignant tumors, who had newly been implanted with CV ports. We examined CV port-related infections at 1 week after CV port implantation and every 2 weeks thereafter, following sterilization upon insertion of a Huber needle to the CV port. CV port evulsion due to CV port-related infection was noted in 3 patients(4.8%)in whom 15%chlorhexidine ethanol was used(n=62)and in 2 patients(3.3%)in whom 70% ethanol was used(n=60). Infection rates per 1,000 days of CV port use were 1.48% and 1.01%, respectively. Thus, the outcomes of sterilization using 1% chlorhexidine ethanol and 70% ethanol did not differ significantly from those on using 10% povidone iodine for sterilization, based on preliminary results at our institution(3 of 59 patients[5.1%]had port evulsion due to CV port-related infection and the infection rate per 1,000 days of CV port use was 1.47%, Akahane et al, 2012). Chlorhexidine ethanol and ethanol are very convenient to use because they dry quickly and do not need discoloration. Accordingly, chlorhexidine ethanol and ethanol might be useful in CV port management.


Differential binding properties of [3H]dextrorphan and [3H]MK-801 in heterologously expressed NMDA receptors.
The N-methyl-D-aspartate receptor (NMDAR) antagonists: MK-801, phencyclidine and ketamine are open-channel blockers with limited clinical value due to psychotomimetic effects. Similarly, the psychotomimetic effects of the dextrorotatory opioids, dextromethorphan and its metabolite dextrorphan, derive from their NMDAR antagonist actions. Differences in the use dependency of blockade, however, suggest that the binding sites for MK-801 and dextrorphan are distinct. In the absence of exogenous glutamate and glycine, the rate of association of [3H]MK-801 with wild-type NR1-1a/NR2A receptors was considerably slower than that for [3H]dextrorphan. Glutamate individually, and in the presence of the co-agonist glycine, had substantial effects on the specific binding of [3H]MK-801, while the binding of [3H]dextrorphan was not affected. Mutation of residues N616 and A627 in the NR1 subunit had a profound effect on [3H]MK-801 binding affinity, while that of [3H]dextrorphan was unaltered. In contrast, NR1 residues, W611 and N812, were critical for specific binding of [3H]dextrorphan to NR1-1a/NR2A complexes with no corresponding influence on that of [3H]MK-801. Thus, [3H]dextrorphan and [3H]MK-801 have distinct molecular determinants for high-affinity binding. The ability of [3H]dextrorphan to bind to a closed channel, moreover, indicates that its recognition site is shallower in the ion channel domain than that of MK-801 and may be associated with the extracellular vestibule of the NMDAR.


Isolated arthroscopic biceps tenotomy or tenodesis improves symptoms in patients with massive irreparable rotator cuff tears.
Lesions of the long head of the biceps tendon are often associated with massive rotator cuff tears and may be responsible for shoulder pain and dysfunction. The purpose of this study was to evaluate the clinical and radiographic outcomes of isolated arthroscopic biceps tenotomy or tenodesis as treatment for persistent shoulder pain and dysfunction due to an irreparable rotator cuff tear associated with a biceps lesion. We conducted a retrospective study of sixty-eight consecutive patients (mean age [and standard deviation], 68 +/- 6 years) in whom a total of seventy-two irreparable rotator cuff tears had been treated arthroscopically with biceps tenotomy or tenodesis. A simple tenotomy was performed in thirty-nine cases, and a tenodesis was performed in thirty-three. No associated acromioplasty was performed. All patients were evaluated clinically and radiographically by an independent observer at a mean of thirty-five months postoperatively. Fifty-three patients (78%) were satisfied with the result. The mean Constant score improved from 46.3 +/- 11.9 points preoperatively to 66.5 +/- 16.3 points postoperatively (p < 0.001). A healthy-appearing teres minor on preoperative imaging was associated with significantly increased postoperative external rotation (40.4 degrees +/- 19.8 degrees compared with 18.1 degrees +/- 18.4 degrees ) and a significantly higher Constant score (p < 0.05 for both) compared with the values for the patients with an absent or atrophic teres minor preoperatively. Three patients with pseudoparalysis of the shoulder did not benefit from the procedure and did not regain active elevation above the horizontal level. In contrast, the fifteen patients with painful loss of active elevation recovered active elevation. The acromiohumeral distance decreased 1.1 +/- 1.9 mm on the average, and glenohumeral osteoarthritis developed in only one patient. The results did not differ between the tenotomy and tenodesis groups (mean Constant score, 61.2 +/- 18 points and 72.8 +/- 12 points, respectively). The "Popeye" sign was clinically apparent in twenty-four (62%) of the shoulders that had been treated with a tenotomy; of the sixteen patients who noticed it, none were bothered by it. Both arthroscopic biceps tenotomy and arthroscopic biceps tenodesis can effectively treat severe pain or dysfunction caused by an irreparable rotator cuff tear associated with a biceps lesion. Shoulder function is significantly inferior if the teres minor is atrophic or absent. Pseudoparalysis of the shoulder and severe rotator cuff arthropathy are contraindications to this procedure. Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.


Analysis of the effect of a 60 Hz AC field on histamine release by rat peritoneal mast cells.
Reports have indicated effects of electromagnetic fields on inflammatory processes in vivo. To begin a systematic approach toward separating and examining the many components of such responses, we created and tested a temperature-controlled device to develop 5 mT 60 Hz magnetic fields for studies of the effects of fields on mast cells, a key component in acute inflammatory responses. Such fields have been reported to modulate cell activity, including changes in membrane function, in various systems. The magnetic field was generated using a solenoid and calibrated with an induction probe. Tests of mast cell function were determined by histamine release response to stimulation by compound 48/80, using both an "expose then test" and a "test during exposure" protocol. Aliquots not treated with 48/80 were used to evaluate field treatment effects on spontaneous histamine release. Freshly harvested rat peritoneal mast cells were exposed to the magnetic field for periods of 30 min to 2 h at 37 degrees C. They showed no significant degranulation during treatment, nor did they show reduced sensitivity to the degranulating agent 48/80. These observations are consistent with a model in which such processes are exclusively reflexive by the cells using field-independent membrane systems. This observation is very useful and was needed before examining longer term exposures in which gene expression in the cells might be influenced; this is the first such report of in vitro exposure of purified mast cells under these conditions and will further the study of the effects of electromagnetic fields on cell types active in acute inflammation.


Are pesticide residues in honey related to oilseed rape treatments?
Pesticide treatments before and during the flowering of honey bee forage crops may lead to residues in honey. In northern regions oilseed rape belongs to the main forage crops that is mostly cultivated by means of intensive agriculture, including several pesticide treatments. However, in addition to the focal forage crops, pesticides from non-forage crops can spread to wild flowers around fields, and thus the residues in honey would reflect the whole range of pesticides used in the agricultural landscape. The aim of our study was to clarify which currently used pesticides are present in honey gathered from heterogeneous agricultural landscapes after the end of flowering of oilseed crops. Honey samples (N = 33) were collected from beehives of Estonia during 2013 and 2014, and analysed for residues of 47 currently used agricultural pesticides using the multiresidue method with HPLC-MS/MS and GC-MS and a single residue method for glyphosate, aminopyralid and clopyralid. Residues of eight different active ingredients with representatives from all three basic pesticide classes were determined. Although no correlation was detected between the cumulative amount of pesticide residues and percent of oilseed crops in the foraging territory, most of the residues are those allowed for oilseed rape treatments. Among all pesticides, herbicide residues prevailed in 2013 but not in 2014. Despite the relatively small agricultural impact of Estonia, the detected levels of pesticide residues sometimes exceeded maximum residue level; however, these concentrations do not pose a health risk to consumers, also acute toxicity to honey bees would be very unlikely.


Effects of pH on maximal power output and fatigue during short-term dynamic exercise.
Six healthy subjects performed four exercise studies in random order on separate days: a control study, metabolic acidosis induced by ammonium chloride, metabolic alkalosis induced by sodium bicarbonate, and respiratory acidosis induced by 5% CO2 inhalation. The subjects exerted maximal force on the pedals of a constant-velocity cycle ergometer at 100 rpm for 30 s; torque was measured and power calculated. Arterialized venous blood was sampled, and plasma lactate concentrations was measured immediately after and at 2-min intervals for 10 min following exercise. Although maximal peak power and total work, for the 30-s test, were lower in the two acidosis conditions, this effect was not statistically significant. Plasma lactate 30-s postexercise was lower in metabolic acidosis (2.8 +/- 1.6 mmol X 1(-1) (mean +/- SD) and respiratory acidosis (1.5 +/- 0.8 mmol X 1(-1) than in placebo conditions (5.9 +/- 3.3 mmol X 1(-1) and metabolic alkalosis 7.8 +/- 4.2 mmol X 1(-1). These differences were maintained but lessened during 10 min of recovery. In contrast to previous studies, which showed a marked reduction in endurance time during sustained heavy exercise, reductions in blood pH are associated with only small reductions in the total work performed in 30 s of maximal exercise. A delayed and smaller accumulation of lactate in plasma was observed following exercise during acidosis.


Intrapleural streptokinase in the management of malignant multiloculated pleural effusions.
Pleural effusions are a frequent complication of malignancy and cause considerable morbidity from dyspnea. The drainage and control of malignant effusions relieve symptoms and maintain quality of life but these are difficult in patients with multiloculated effusions in whom drainage usually fails. This observational series reports the use of intrapleural streptokinase (IPSK) in the management of malignant multiloculated pleural effusions resistant to standard chest tube drainage. Ten consecutive patients with malignant multiloculated pleural effusions, aged 39 to 89 years, were given 250,000-IU doses of IPSK twice daily after failure to drain the effusions with a standard chest tube because of multiloculation and multiseptation, as demonstrated by CT or ultrasound scanning. Outcome was assessed by radiographic improvement and symptom control. All 10 patients responded to between 500,000 and 1,500,000 IU of streptokinase. There was an increase in pleural fluid drained (mean volume+/-SD; pre-IPSK, 843+/-690 mL; post-IPSK, 2,368+/-1,051 mL; p < 0.001, paired t test), and radiographic improvement was seen in all 10 patients. All subjects tolerated the instillation of streptokinase well. One subject required opiate analgesia for transient chest pain, and there were no hemorrhagic or allergic complications. One patient died of unrelated septicemia. This series suggests that IPSK may be useful in the drainage of malignant multiloculated pleural effusions in patients who fail to drain adequately with a standard chest tube. Malignant pleural effusions should not be considered a contraindication to IPSK.


Genetic variation and susceptibility to infection: the red cell and malaria.
There is now convincing evidence that the extremely high frequencies of certain genetic disorders of the red cell involving haemoglobin, the red-cell membrane, or its metabolic pathways reflect relative resistance to malaria over thousands of years. At least some progress has been made towards an understanding of the cellular mechanisms involved, although much remains to be learnt. As well as the extremely valuable information that this field is providing about how exposure to infection has moulded the current structure of the human genome, recent research in this field is starting to provide some valuable new approaches to the better control of parasitic and other infections that remain a major global health problem.


Spectral transmission of the human crystalline lens in adult and elderly persons: color and total transmission of visible light.
To experimentally measure the spectral transmission of human crystalline lenses belonging to adult and elderly persons, and to determine the color and total transmission of visible light of such crystalline lenses. The spectral transmission curve of 32 human crystalline lenses was measured using a PerkinElmer 800UV/VIS spectrometer. Total transmission of visible light and the chromatic coordinates of these crystalline lenses were determined from these curves for solar illumination. The crystalline lens that filters UV and its transmission in the visible spectrum decreases with age; such a decrease is greater for short wavelengths. The total transmission of visible light decreases, especially after the age of 70 years, and the crystalline color becomes yellower and saturated. The great variability existing in the spectral transmission of the human crystalline lens is lesser between the ages of 40 and 59 years, but greater from the age of 60 and older. The decrement in transmittance between these two age groups varies from 40% for 420 nm to 18% for 580 nm. Nevertheless, it is proven that age is not the only parameter affecting crystalline transmission. In the range of 40 to 59 years, age does not bear an influence on total transmission of light, but from 60 years and older it does. Moreover, the light transmitted decreases with age. This total transmission of light is similar to or lower than the amount that the different intraocular lenses transmit, even with a yellow or orange filter. The color of the human lens becomes yellowish and saturated with age.


A Pilot Study of an In-Home Multicomponent Exergame Training for Older Adults: Feasibility, Usability and Pre-Post Evaluation.
Aging is associated with sensory, motor and cognitive impairments that may lead to reduced daily life functioning including gait disturbances, falls, injuries and mobility restrictions. A strong need exists for implementing effective evidence-based interventions for healthy aging. Therefore, the aim of this study was to (i) evaluate the feasibility and usability of an in-home multicomponent exergame training and (ii) explore its effects on physical functions, cognition and cortical activity. Twenty-one healthy and independently living older adults were included (11 female, 74.4 ± 7.0 years, range: 65-92 years) and performed 24 trainings sessions (each 40 min) over eight weeks. The first part was conducted in a living lab (home-like laboratory environment), the second part at participants' home. The multicomponent exergame included Tai Chi-inspired exercises, dance movements and step-based cognitive games to train strength, balance and cognition. Attendance and attrition rates were calculated and safety during training was evaluated to determine feasibility. Participants rated the usability of the exergame (System Usability Scale) and reported on their game experience (Game Experience Questionnaire). Physical and cognitive functions and cortical activity (resting state electroencephalopathy) were assessed pre and post intervention. Results showed a high training attendance rate for the living lab and the home-based setting (91.7 and 91.0%, respectively) with a rather high attrition rate (28.6%, six drop-outs). Half of the drop-out reasons were related to personal or health issues. System usability was rated acceptable with a mean score of 70.6/100. Affective game experience was rated favorable. Significant improvements were found for minimal toe clearance, short-term attentional span, and information processing speed (p < 0.05). No significant pre-post differences were found for cortical activity. To summarize, the exergame is generally feasible and usable for healthy older adults applied in an in-home setting and provides an overall positive emotional game experience. Nevertheless, flawless technical functionality should be a mandatory consideration. Additionally, the training might have potential positive influence on specific functions in older adults. However, the efficacy has to be evaluated in a future randomized controlled trial assessing the behavioral and neuroplastic changes in a larger population after a longer training period.


Macronutrient intake and frailty: the Rotterdam Study.
To investigate the longitudinal association between the macronutrient composition of the diet and frailty. Data were obtained from 5205 Dutch middle-aged and older adults participating in the Rotterdam Study. Frailty was measured using a frailty index based on the accumulation of 38 health-related deficits, score between 0 and 100, and a higher score indicating more frailty. Frailty was assessed at baseline and 11 years later (range of 23 years). Macronutrient intake was assessed using food-frequency questionnaires. The association between macronutrients and frailty over time was evaluated using multivariable linear regression, adjusted for the frailty index at baseline, energy intake, and other relevant confounders. All analyses were performed in strata of BMI. Median frailty index score was 13.8 points (IQR 9.6; 19.1) at baseline and increased by a median of 2.3 points (IQR - 2.0; 7.6) after 11 years. Overall, we found no significant associations between intake of carbohydrates or fat and frailty over time. We did observe a significant positive association between an iso-energetic intake of 10 g protein and frailty over time (β 0.31 (95% CI 0.06; 0.55)) which was mainly driven by animal protein (β 0.31 (95% CI 0.07; 0.56)). It did not depend on whether it was substituted fat or carbohydrates. Our findings suggest that a reduction in the intake of animal protein may improve the overall health status over time in a relatively healthy population. More research is needed on the optimal macronutrient composition of the diet and frailty in more vulnerable populations.


The possible roles of solar ultraviolet-B radiation and vitamin D in reducing case-fatality rates from the 1918-1919 influenza pandemic in the United States.
Deaths during the 1918-1919 influenza pandemic have been linked to both the influenza virus and secondary bacterial lung infections. Case fatality rates and percentage of influenza cases complicated by pneumonia were available from survey data for twelve United States locations in the 1918-1919 pandemic. This study analyzes case fatality rates and cases complicated by pneumonia with respect to estimated summertime and wintertime solar ultraviolet-B (UVB) doses as indicators of population mean vitamin D status. Substantial correlations were found for associations of July UVB dose with case fatality rates (r = -0.72, p = 0.009) and rates of pneumonia as a complication of influenza (r = -0.77, p = 0.005). Similar results were found for wintertime UVB. Vitamin D upregulates production of human cathelicidin, LL-37, which has both antimicrobial and antiendotoxin activities. Vitamin D also reduces the production of proinflammatory cytokines, which could also explain some of the benefit of vitamin D since H1N1 infection gives rise to a cytokine storm. The potential role of vitamin D status in reducing secondary bacterial infections and loss of life in pandemic influence requires further evaluation.


The effects of multiple daily applications of ice to the hamstrings on biochemical measures, signs, and symptoms associated with exercise-induced muscle damage.
There is inconclusive evidence for the effectiveness of cryotherapy for the treatment of exercised-induced muscle damage (EIMD). Small sample sizes and treatment applications that did not correspond to evidence-based practice are limitations in previous studies that may have contributed to these equivocal findings. The purpose of this study was to examine the effectiveness of daily multiple applications of ice on EIMD throughout the 72-hour recovery period, an icing protocol that more closely resembles current clinical practice. Thirty-three subjects were assigned to either the cryotherapy group (n = 23) or control group (n = 10). The EIMD was induced through repeated isokinetic eccentric contractions of the right hamstring muscle group. The experimental group received ice immediately after induction of EIMD and continued to ice thrice a day for 20 minutes throughout the 72 hours; the control group received no intervention. Isometric torque, hamstring length, pain, and biochemical markers (creatine kinase [CK], alanine aminotransferase, and aspartate aminotransferase [AST]) were assessed at baseline, 24, 48, and 72 hours. Both groups demonstrated a significant change (p < 0.05) in all dependent variables compared with that at baseline, but there was no difference between groups except for pain. The cryotherapy group had significantly (p = 0.048) less pain (3.0 ± 2.1 cm) compared with the control (5.35 ± 2.5 cm) at 48 hours. Although not statistically significant, the cryotherapy group had a greater range of motion and lower CK and AST means at 72 hours compared with that of the control group. Repeated applications of ice can decrease the pain associated with EIMD significantly at 48 hours post EIMD. Although the results may not be unique, the methodology in this study was distinctive in that we used a larger sample size and an icing protocol similar to current recommended treatment practice.


Comparative Studies on Phenolic Composition, Antioxidant, Wound Healing and Cytotoxic Activities of Selected Achillea L. Species Growing in Turkey.
Turkey is one of the most important centers of diversity for the genus Achillea L. in the world. Keeping in mind the immense medicinal importance of phenols, in this study, three species growing in Turkey, A. coarctata Poir. (AC), A. kotschyi Boiss. subsp. kotschyi (AK) and A. lycaonica Boiss. & Heldr. (AL) were evaluated for their phenolic compositions, total phenolic contents (TPC), antioxidant properties, wound healing potencies on NIH-3T3 fibroblasts and cytotoxic effects on MCF-7 human breast cancer cells. Comprehensive LC-MS/MS analysis revealed that AK was distinctively rich in chlorogenic acid, hyperoside, apigenin, hesperidin, rutin, kaempferol and luteolin (2890.6, 987.3, 797.0, 422.5, 188.1, 159.4 and 121.2 µg analyte/g extract, respectively). The findings exhibited a strong correlation between TPC and both free radical scavenging activity and total antioxidant capacity (TAC). Among studied species, the highest TPC (148.00 mg GAE/g extract) and TAC (2.080 UAE), the strongest radical scavenging (EC50 = 32.63 μg/mL), the most prominent wound healing and most abundant cytotoxic activities were observed with AK. The results suggested that AK is a valuable source of flavonoids and chlorogenic acid with important antioxidant, wound healing and cytotoxic activities. These findings warrant further studies to assess the potential of AK as a bioactive source that could be exploited in pharmaceutical, cosmetics and food industries.


Failure modes of Y-TZP crowns at different cusp inclines.
To compare the reliability of the disto-facial (DF) and mesio-lingual (ML) cusps of an anatomically correct zirconia (Y-TZP) crown system. The research hypotheses tested were: (1) fatigue reliability and failure mode are similar for the ML and DF cusps; (2) failure mode of one cusp does not affect the failure of the other. The average dimensions of a mandibular first molar crown were imported into CAD software; a tooth preparation was modelled by 1.5 mm marginal high reduction of proximal walls and occlusal surface by 2.0 mm. The CAD-based tooth preparation was milled and used as a die to fabricate crowns (n=14) with porcelain veneer on a 0.5 mm Y-TZP core. Crowns were cemented on composite reproductions of the tooth preparation. The crowns were step-stress mouth motion fatigued with sliding (0.7 mm) a tungsten-carbide indenter of 6.25 mm diameter down on the inclines of either the DF or ML cusps. Use level probability Weibull curve with use stress of 200 N and the reliability for completion of a mission of 50,000 cycles at 200 N load were calculated. Reliability for a 200 N at 50,000 cycles mission was not different between tested cusps. SEM imaging showed large cohesive failures within the veneer for the ML and smaller for the DF. Fractures originated from the contact area regardless of the cusp loaded. No significant difference on fatigue reliability was observed between the DF compared to the ML cusp. Fracture of one cusp did not affect the other.


Coculture model of blood-brain barrier on electrospun nanofibers.
The blood-brain barrier (BBB) is a control mechanism that limits the diffusion of many substances to the central nervous system (CNS). In this study, we designed an in-vitro 3-dimensional BBB system to obtain a fast and reliable model to mimic drug delivery characteristics of the CNS. A support membrane of polycaprolactone nanofiber surfaces was prepared using electrospinning. After confirming the fiber morphology and size, endothelial cells (HUVEC) and glial cells were cultured on either side of this membrane. The model's similarity to in vivo physiology was tested with a home-designed transmembrane resistance (TR) device, with positive and negative control molecules. Finally, 2 doses of methotrexate (MTX), a chemotherapy agent, were applied to the model, and its permeability through the model was determined indirectly by a vitality test on the MCF-7 cell line. Nicotine, the positive control, completed its penetration through the model almost instantly, while albumin, the negative control, was blocked significantly even after 2 days. MTX reached a deadly threshold 24 h after application. The TR value of the model was promising, being around 260 ohm.cm2. The provided model proposes a disposable and reliable tool for investigating drug permeability through the BBB and has the potential to reduce the number of animal experiments.


Collagen fibrils in the human corneal stroma: structure and aging.
Transparency and biomechanical properties of the cornea depend on the structure and organization of collagen fibrils. The authors determined diameter, axial period, and lateral molecular spacing of collagen fibrils in human corneal stroma as a function of age. Seventeen normal human corneas were investigated in their native state by means of small-angle and wide-angle x-ray scattering. The mean radius of collagen fibrils, the axial period of collagen fibrils, and the lateral intermolecular Bragg spacing were found to be age dependent. The authors determined fibril radii of 16.1 +/- 0.5 nm in persons older than 65 years of age (n = 10) and 15.4 +/- 0.5 nm (mean +/- SD) in persons younger than 65 years (n = 7) (P < 0.022). The related age-dependent values were 66.4 +/- 0.7 nm (> 65 years) and 65.2 +/- 0.8 nm (< 65 years) for the axial period (P < 0.006) and 1.515 +/- 0.010 nm (> 65 years) and 1.499 +/- 0.013 nm (< 65 years) for the intermolecular Bragg spacing (P < 0.022). Aging is related to a three-dimensional growth of collagen fibrils in the human corneal stroma. The age-related growth of the fibril diameter was mostly a result of an increased number of collagen molecules and, in addition, to some expansion of the intermolecular Bragg spacing probably resulting from glycation-induced cross-linking. The observed expansion of the fibrils in an axial direction may result from reduction of the molecular tilting angle within collagen fibrils. The observed alterations of the collagen framework may have implications for refractive surgery and ocular tonometry achieved through related changes in the biomechanical properties of the cornea.


Combinatorial effect of Bacillus thuringiensis kurstaki and Photorhabdus luminescens against Spodoptera littoralis (Lepidoptera: Noctuidae).
Spodoptera littoralis, one of the major pests of many important crop plants, is more susceptible to Bacillus thuringiensis aizawai delta-endotoxins than to those of Bacillus thuringiensis kurstaki. Within the framework of the development of efficient bioinsecticides and the prevention against insect resistance, we tested the effect of mixing B. thuringiensis kurstaki delta-endotoxins and Photorhabdus luminescens cells on S. littoralis growth. The obtained results showed that the growth inhibition of this insect was more effective when B. thuringiensis kurstaki spore-crystal mixture and Photorhabdus luminescens cells were used in combination. Furthermore, this synergism is mainly due to the presence of Cry1Ac, which is one of the three delta-endotoxins that form the crystal of B. thuringiensis kurstaki strain BNS3 in addition to Cry1Aa and Cry2Aa. This work shows a possibility to use B. thuringiensis as a delivery means for Photorhabdus bacteria in order to infect the insect hemocoel and to reduce the risk of developing resistance in the target organism.


Habitat structure and the evolution of diffusible siderophores in bacteria.
Bacteria typically rely on secreted metabolites, potentially shareable at the community level, to scavenge resources from the environment. The evolution of diffusible, shareable metabolites is, however, difficult to explain because molecules can get lost, or be exploited by cheating mutants. A key question is whether natural selection can act on molecule structure to control loss and shareability. We tested this possibility by collating information on diffusivity properties of 189 secreted iron-scavenging siderophores and the natural habitats occupied by the siderophore-producing species. In line with evolutionary theory, we found that highly diffusible siderophores have preferentially evolved in species living in structured habitats, such as soil and hosts, because structuring can keep producers and their shareable goods together. Poorly diffusible siderophores, meanwhile, have preferentially evolved in species living in unstructured habitats, such as seawater, indicating that these metabolites are less shareable and more likely provide direct benefits to the producers.


Metoidioplasty as a single stage sex reassignment surgery in female transsexuals: Belgrade experience.
Metoidioplasty represents one of the variants of phalloplasty in female transsexuals. Its main characteristic is that it is a one-stage procedure. It involves lengthening and straightening of hypertrophied clitoris to create a neophallus, urethral lengthening to enable voiding while standing, and scrotal reconstruction with insertion of testicle prostheses. Our aim is to describe our technique and highlight its advantages. Between September 2002 and April 2007, 82 female transsexuals, aged 18-54 years (mean age 31) underwent one-stage metoidioplasty. Clitoris is lengthened and straightened by division of clitoral ligaments and short urethral plate. Urethroplasty is done with combined buccal mucosa graft and genital skin flaps. Scrotum is created from labia majora in which two testicle prostheses are inserted. Simultaneously, female genitalia are removed. Patients' personal satisfaction about sensitivity and length of neophallus, possibility to void in standing position, real length of reconstructed urethra as well as complication rate comparing to other published data. The median follow-up was 32 months (range 14-69). The mean neophallic length was 5.7 cm (range 4-10). Voiding in standing position was reported in all patients, while dribbling and spraying were noticed in 23 cases and solved spontaneously. There were two urethral strictures and seven fistulas that required secondary minor revision. All patients reported preserved sensation and normal postoperative erection. Testicle prostheses rejection was not observed in any of the patients. Metoidioplasty is a single-stage and time-saving procedure. It could be an alternative to total phalloplasty in female transsexuals who do not wish to have sexual intercourse. Also, it represents a first step in cases where additional augmentation phalloplasty is required.


Bayesian Spatiotemporal Modeling of Routinely Collected Data to Assess the Effect of Health Programs in Malaria Incidence During Pregnancy in Burkina Faso.
Control of malaria in pregnancy (MiP) remains a major challenge in Burkina Faso. Surveillance of the burden due to MiP based on routinely collected data at a fine-scale level, followed by an appropriate analysis and interpretation, may be crucial for evaluating and improving the effectiveness of existing control measures. We described the spatio-temporal dynamics of MiP at the community-level and assessed health program effects, mainly community-based health promotion, results-based financing, and intermittent-preventive-treatment with sulphadoxine-pyrimethamine (IPTp-SP). Community-aggregated monthly MiP cases were downloaded from Health Management Information System and combined with covariates from other sources. The MiP spatio-temporal pattern was decomposed into three components: overall spatial and temporal trends and space-time interaction. Bayesian hierarchical spatio-temporal Poisson models were used to fit the MiP incidence rate and assess health program effects. The overall annual incidence increased between 2015 and 2017. The findings reveal spatio-temporal heterogenicity throughout the year, which peaked during rainy season. From the model without covariates, 96 communities located mainly in the Cascades, South-West, Center-West, Center-East, and Eastern regions, exhibited significant relative-risk levels. The combined effect (significant reducing effect) of RBF, health promotion and IPTp-SP strategies was greatest in 17.7% (17/96) of high burden malaria communities. Despite intensification of control efforts, MiP remains high at the community-scale. The provided risk maps are useful tools for highlighting areas where interventions should be optimized, particularly in high-risk communities.


Evidence of interlipidic ion-pairing in anion-induced DNA release from cationic amphiphile-DNA complexes. Mechanistic implications in transfection.
Complex formation of DNA with a number of cationic amphiphiles has been examined using fluorescence, gel electrophoresis, and chemical nuclease digestion. Here we have addressed the status of both DNA and lipid upon complexation with each other. DNA upon binding with cationic amphiphiles changes its structure in such a way that it loses the ability to intercalate and becomes resistant to nuclease digestion. Fluorescence anisotropy measurements due to 1, 6-diphenylhexatriene (DPH) doped in cationic liposomes demonstrated that upon complexation with DNA, the resulting complexes still retain lamellar organizations with modest enhancement in thermal stabilities. The lipid-DNA complexation is most effective only when the complexation was carried out at or around the phase transition temperatures of the cationic lipid employed in the complexation with DNA. The release of DNA from cationic lipid-DNA complexes could be induced by several anionic additives. Determination of fluorescence anisotropies (due to DPH) as a function of temperature clearly demonstrates that the addition of equivalent amounts of anionic amphiphile into cationic lipid-DNA complexes leads to the ion-pairing of the amphiphiles, the melting profiles of which are virtually the same as those obtained in the absence of DNA. In this process DNA gets released from its complexes with cationic lipids and regains its natural intercalation ability, movement, and staining ability on agarose gel and also the sensitivities toward nuclease digestion. This clearly suggests that combination of ion-pairing and hydrophobic interactions between cationic and anionic amphiphiles is stronger than the electrostatic forces involved in the cationic lipid-DNA complexation. It is further revealed that the DNA release by anions is most efficient from the cationic lipid-DNA complexes at or around the Tm of the cationic lipid used in DNA complexation. This explains why more effective DNA delivery is achieved with cationic lipids that bear unsaturated hydrocarbon chains than with their saturated hydrocarbon counterparts.


The evolution of bat pollination: a phylogenetic perspective.
Most tropical and subtropical plants are biotically pollinated, and insects are the major pollinators. A small but ecologically and economically important group of plants classified in 28 orders, 67 families and about 528 species of angiosperms are pollinated by nectar-feeding bats. From a phylogenetic perspective this is a derived pollination mode involving a relatively large and energetically expensive pollinator. Here its ecological and evolutionary consequences are explored. This review summarizes adaptations in bats and plants that facilitate this interaction and discusses the evolution of bat pollination from a plant phylogenetic perspective. Two families of bats contain specialized flower visitors, one in the Old World and one in the New World. Adaptation to pollination by bats has evolved independently many times from a variety of ancestral conditions, including insect-, bird- and non-volant mammal-pollination. Bat pollination predominates in very few families but is relatively common in certain angiosperm subfamilies and tribes. We propose that flower-visiting bats provide two important benefits to plants: they deposit large amounts of pollen and a variety of pollen genotypes on plant stigmas and, compared with many other pollinators, they are long-distance pollen dispersers. Bat pollination tends to occur in plants that occur in low densities and in lineages producing large flowers. In highly fragmented tropical habitats, nectar bats play an important role in maintaining the genetic continuity of plant populations and thus have considerable conservation value.


Use of Machine Learning for Predicting Escitalopram Treatment Outcome From Electroencephalography Recordings in Adult Patients With Depression.
Social and economic costs of depression are exacerbated by prolonged periods spent identifying treatments that would be effective for a particular patient. Thus, a tool that reliably predicts an individual patient's response to treatment could significantly reduce the burden of depression. To estimate how accurately an outcome of escitalopram treatment can be predicted from electroencephalographic (EEG) data on patients with depression. This prognostic study used a support vector machine classifier to predict treatment outcome using data from the first Canadian Biomarker Integration Network in Depression (CAN-BIND-1) study. The CAN-BIND-1 study comprised 180 patients (aged 18-60 years) diagnosed with major depressive disorder who had completed 8 weeks of treatment. Of this group, 122 patients had EEG data recorded before the treatment; 115 also had EEG data recorded after the first 2 weeks of treatment. All participants completed 8 weeks of open-label escitalopram (10-20 mg) treatment. The ability of EEG data to predict treatment outcome, measured as accuracy, specificity, and sensitivity of the classifier at baseline and after the first 2 weeks of treatment. The treatment outcome was defined in terms of change in symptom severity, measured by the Montgomery-Åsberg Depression Rating Scale, before and after 8 weeks of treatment. A patient was designated as a responder if the Montgomery-Åsberg Depression Rating Scale score decreased by at least 50% during the 8 weeks and as a nonresponder if the score decrease was less than 50%. Of the 122 participants who completed a baseline EEG recording (mean [SD] age, 36.3 [12.7] years; 76 [62.3%] female), the classifier was able to identify responders with an estimated accuracy of 79.2% (sensitivity, 67.3%; specificity, 91.0%) when using only the baseline EEG data. For a subset of 115 participants who had additional EEG data recorded after the first 2 weeks of treatment, use of these data increased the accuracy to 82.4% (sensitivity, 79.2%; specificity, 85.5%). These findings demonstrate the potential utility of EEG as a treatment planning tool for escitalopram therapy. Further development of the classification tools presented in this study holds the promise of expediting the search for optimal treatment for each patient.


Efficient Genome-Wide Sequencing and Low-Coverage Pedigree Analysis from Noninvasively Collected Samples.
Research on the genetics of natural populations was revolutionized in the 1990s by methods for genotyping noninvasively collected samples. However, these methods have remained largely unchanged for the past 20 years and lag far behind the genomics era. To close this gap, here we report an optimized laboratory protocol for genome-wide capture of endogenous DNA from noninvasively collected samples, coupled with a novel computational approach to reconstruct pedigree links from the resulting low-coverage data. We validated both methods using fecal samples from 62 wild baboons, including 48 from an independently constructed extended pedigree. We enriched fecal-derived DNA samples up to 40-fold for endogenous baboon DNA and reconstructed near-perfect pedigree relationships even with extremely low-coverage sequencing. We anticipate that these methods will be broadly applicable to the many research systems for which only noninvasive samples are available. The lab protocol and software ("WHODAD") are freely available at www.tung-lab.org/protocols-and-software.html and www.xzlab.org/software.html, respectively.


Development and applications of a model for cellular response to multiple chemotactic cues.
The chemotactic response of a cell population to a single chemical species has been characterized experimentally for many cell types and has been extensively studied from a theoretical standpoint. However, cells frequently have multiple receptor types and can detect and respond chemotactically to more than one chemical. How these signals are integrated within the cell is not known. and we therefore adopt a macroscopic phenomenological approach to this problem. In this paper we derive and analyze chemotactic models based on partial differential (chemotaxis) equations for cell movement in response to multiple chemotactic cues. Our derivation generalizes the approach of Othmer and Stevens [29], who have recently developed a modeling framework for studying different chemotactic responses to a single chemical species. The importance of such a generalization is illustrated by the effect of multiple chemical cues on the chemotactic sensitivity and the spatial pattern of cell densities in several examples. We demonstrate that the model can generate the complex patterns observed on the skin of certain animal species and we indicate how the chemotactic response can be viewed as a form of positional indicator.


Premature and severe cardiovascular disease in a Mexican male with markedly low high-density-lipoprotein-cholesterol levels and a mutation in the lecithin:cholesterol acyltransferase gene: a family study.
Epidemiological and clinical studies have shown that a low plasma high‑density lipoprotein cholesterol (HDL-C) level is a strong predictor of cardiovascular disease (CVD). Lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the formation, maturation and function of HDL. Therefore impaired LCAT function may enhance atherosclerosis because of defective cholesterol transport. In this study, we examined a 34-year old LCAT‑deficient patient and eight first-degree family members. There was a strong family history for CVD and type 2 diabetes mellitus (DM2). The proband was found homozygous for a previously reported LCAT gene mutation (Thr37Met). A sister and two sons of the proband were heterozygous for the same mutation. The proband had DM2 and showed severe multivessel coronary artery disease, corneal opacification and extremely low HDL-C levels. Large HDL particles were absent while small HDL particles were increased. The HDL of the patient had a reduced ability to promote cell cholesterol efflux, and the low‑density lipoproteins (LDL) were more susceptible to oxidation. Among his family members, two heterozygotes and one non-carrier had early carotid or coronary atherosclerosis. In conclusion, as the increased LDL oxidability and structural and functional abnormalities of HDL particles have been reported in patients with obesity and diabetes, the results suggested that the adverse coronary risk profile, and not being LCAT deficient, may be responsible for the CVD found in our proband, and for the early atherosclerosis observed in the two heterozygotes and in the wild‑type family members.


Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia.
Data regarding the outcome of cord-blood transplantation in adults are scant, despite the fact that these grafts are increasingly used in adults. We compared the outcomes of the transplantation of hematopoietic stem cells from unrelated donors in adults with leukemia who had received cord blood that was mismatched for one HLA antigen (34 patients) or two antigens (116 patients), bone marrow that had one HLA mismatch (83 patients), and HLA-matched bone marrow (367 patients). We used Cox proportional-hazards models to analyze the data. Cord-blood recipients were younger and more likely to have advanced leukemia than were bone marrow recipients, and they received lower doses of nucleated cells. Hematopoietic recovery was slower with transplantation of mismatched bone marrow and cord blood than with matched marrow transplantations. Acute graft-versus-host disease (GVHD) was more likely to occur after mismatched marrow transplantation, and chronic GVHD was more likely to occur after cord-blood transplantation. The rates of treatment-related mortality, treatment failure, and overall mortality were lowest among patients who received matched marrow transplants. Patients who received mismatched bone marrow transplants and those who received mismatched cord-blood transplants had similar rates of treatment-related mortality (P=0.96), treatment failure (P=0.69), and overall mortality (P=0.62). There were no differences in the rate of recurrence of leukemia among the groups. There were no differences in outcome after cord-blood transplantation between patients with one HLA mismatch and those with two HLA mismatches. HLA-mismatched cord blood should be considered an acceptable source of hematopoietic stem-cell grafts for adults in the absence of an HLA-matched adult donor.


Cellular resolution volumetric in vivo retinal imaging with adaptive optics-optical coherence tomography.
Ultrahigh-resolution adaptive optics-optical coherence tomography (UHR-AO-OCT) instrumentation allowing monochromatic and chromatic aberration correction was used for volumetric in vivo retinal imaging of various retinal structures including the macula and optic nerve head (ONH). Novel visualization methods that simplify AO-OCT data viewing are presented, and include co-registration of AO-OCT volumes with fundus photography and stitching of multiple AO-OCT sub-volumes to create a large field of view (FOV) high-resolution volume. Additionally, we explored the utility of Interactive Science Publishing by linking all presented AO-OCT datasets with the OSA ISP software.


Genomics-based prognosis and therapeutic prediction in breast cancer.
Breast cancer is a heterogeneous disease. DNA microarray technology is being applied to breast cancer to identify new prognostic biomarkers, to predict response to therapy, and to discover targets for the development of novel therapies. New diagnostic assays based on global gene expression are being introduced into clinical practice or tested in large-scale clinical trials. This review focuses on translational studies using microarray analyses and discusses best practice features and pitfalls. We note that factors that predict metastatic disease are not necessarily the same factors that predict therapeutic response. We believe that the characterization and discernment of different systems among breast cancers is crucial for understanding drug sensitivity and resistance mechanisms and for guiding therapy.


Antagonism of serotonergic 5-HT2A/2C receptors: mutual improvement of sleep, cognition and mood?
Serotonin [5-hydroxytryptamine (5-HT)] and 5-HT receptors are involved in sleep and in waking functions such as cognition and mood. Animal and human studies support a particular role for the 5-HT(2A) receptor in sleep, which has led to renewed interest in this receptor subtype as a target for the development of novel pharmacological agents to treat insomnia. Focusing primarily on findings in healthy human volunteers, a review of the available data suggests that antagonistic interaction with 5-HT(2A) receptors (and possibly also 5-HT(2C) receptors) prolongs the duration of slow wave sleep and enhances low-frequency (< 7 Hz) activity in the sleep electroencephalogram (EEG), a widely accepted marker of sleep intensity. Despite certain differences, the changes in sleep and the sleep EEG appear to be remarkably similar to those of physiologically more intense sleep after sleep deprivation. It is currently unclear whether these changes in sleep are associated with improved vigilance, cognition and mood during wakefulness. While drug-induced interaction with sleep must be interpreted cautiously, too few studies are available to provide a clear answer to this question. Moreover, functional relationships between sleep and waking functions may differ between healthy controls and patients with sleep disorders. A multimodal approach investigating subjective and objective aspects of sleep and wakefulness provides a promising research avenue for shedding light on the complex relationships among 5-HT(2A/2C) receptor-mediated effects on sleep, the sleep EEG, cognition and mood in health and various diseases associated with disturbed sleep and waking functions.


Hippocampal structural and functional changes associated with electroconvulsive therapy response.
Previous animal models and structural imaging investigations have linked hippocampal neuroplasticity to electroconvulsive therapy (ECT) response, but the relationship between changes in hippocampal volume and temporal coherence in the context of ECT response is unknown. We hypothesized that ECT response would increase both hippocampal resting-state functional magnetic resonance imaging connectivity and hippocampal volumes. Patients with major depressive disorder (n=19) were scanned before and after the ECT series. Healthy, demographically matched comparisons (n=20) were scanned at one-time interval. Longitudinal changes in functional connectivity of hippocampal regions and volumes of hippocampal subfields were compared with reductions in ratings of depressive symptoms. Right hippocampal connectivity increased (normalized) after the ECT series and correlated with depressive symptom reduction. Similarly, the volumes of the right hippocampal cornu ammonis (CA2/3), dentate gyrus and subiculum regions increased, but the hippocampal subfields were unchanged relative to the comparison group. Connectivity changes were not evident in the left hippocampus, and volume changes were limited to the left CA2/3 subfields. The laterality of the right hippocampal functional connectivity and volume increases may be related to stimulus delivery method, which was predominately right unilateral in this investigation. The findings suggested that increased hippocampal functional connectivity and volumes may be biomarkers for ECT response.


Rare long-range cortical connections enhance human information processing.
What are the key topological features of connectivity critically relevant for generating the dynamics underlying efficient cortical function? A candidate feature that has recently emerged is that the connectivity of the mammalian cortex follows an exponential distance rule, which includes a small proportion of long-range high-weight anatomical exceptions to this rule. Whole-brain modeling of large-scale human neuroimaging data in 1,003 participants offers the unique opportunity to create two models, with and without long-range exceptions, and explicitly study their functional consequences. We found that rare long-range exceptions are crucial for significantly improving information processing. Furthermore, modeling in a simplified ring architecture shows that this improvement is greatly enhanced by the turbulent regime found in empirical neuroimaging data. Overall, the results provide strong empirical evidence for the immense functional benefits of long-range exceptions combined with turbulence for information processing.


Expression of c-Fos, Fos B, Jun B, and Zif268 transcription factor proteins in rat barrel cortex following apomorphine-evoked whisking behavior.
Apomorphine-evoked expression of transcription factor proteins: c-Fos, Fos B, Jun B, and Zif268 (also named Krox-24, NGFI-A, Egr-1), was investigated in rat somatosensory (barrel) cortex. The effect of the N-methyl-D-aspartate receptor antagonist MK-801 on their expression was also analyzed. Apomorphine is a dopamine receptor agonist, eliciting motor activity, including enhanced whisking leading to the activation of vibrissae representation in the barrel cortex. Rats had their whiskers clipped on one side of the snout. The Zif268 levels were markedly reduced by this procedure alone. In contrast, apomorphine (5.0 mg/kg) evoked marked c-Fos elevation, less pronounced changes in Jun B and Zif268 and no change in Fos B. The greatest apomorphine-evoked c-Fos accumulation was observed in layers IV and V/VI of non-deprived barrel cortex and was not significantly influenced by MK-801 injection at 0.1 mg/kg. A higher dose of MK-801 (1.0 mg/kg) produced abnormalities in locomotor behavior and diminished c-Fos levels on the non-deprived side to the ones observed in the sensory stimulus-deprived cortex. We conclude that the response of the somatosensory cortex is selective with respect to both the gene activated and its cortical layer localization. Furthermore, sensory stimulation provides a major but not the only component to apomorphine-evoked barrel cortex gene activation.


Refrigeration of donor cells in preparation for bovine somatic nuclear transfer.
In mammals, preparation of donor cells for somatic nuclear transfer is very important because the character of the donor cell directly affects the efficiency and outcome of transfer. The protocols used most commonly for donor preparation are (i) disaggregating cells from fresh tissue 1-2 h before micromanipulation or (ii) trypsinizing cultured cells temporarily, after special treatments for 3-8 days (for example, serum starvation). In this study, a new simple protocol was designed, whereby the donor cells (cumulus cells) used in bovine somatic nuclear transfer were refrigerated. In brief, cultured cells at 80-100% confluency were detached using trypsin, washed by centrifugation, aliquoted into different vials and refrigerated at 4 degrees C. The density of viable cells was decreased after day 1 of refrigeration; however, the rate of decrease tended to slow down with increasing duration of refrigeration. Cells refrigerated for 15 days were seeded at a density of 5 x 10(4) ml(-1) and reached 70% confluency after day 2 of culture. Most cells had the normal number of chromosomes (2n = 60). Cells chilled at 4 degrees C for different durations were removed from refrigeration and immediately subjected to micromanipulation. The in vitro development of reconstructed embryos (fusion rates, cleavage rates, morula and blastocyst rates) indicated that there were no significant differences among treatment groups regardless of the duration of refrigeration (0-2 weeks) of the donor cells. Reconstructed embryos were transferred into the uteri of recipient cows. No significant differences were observed in established early pregnancies between embryos derived from the non-refrigerated donor cells and those derived from refrigerated donor cells. This study indicates that refrigeration of donor cells for 1-2 weeks is a feasible protocol for preparing donor cells for bovine somatic nuclear transfer, and does not compromise development in vitro and early development in vivo.


Effectiveness of therapeutic lumbar transforaminal epidural steroid injections in managing lumbar spinal pain.
Among the multiple interventions used in managing chronic spinal pain, lumbar epidural injections have been used extensively to treat lumbar radicular pain. Among caudal, interlaminar, and transforaminal, transforaminal epidural injections have gained rapid and widespread acceptance for the treatment of lumbar and lower extremity pain. The potential advantages of transforaminal over interlaminar and caudal, include targeted delivery of a steroid to the site of pathology, presumably onto an inflamed nerve root. However, there are only a few well-designed, randomized, controlled studies on the effectiveness of steroid injections. Consequently, multiple systematic reviews with diverse opinions have been published. A systematic review of therapeutic transforaminal epidural injection therapy for low back and lower extremity pain. To evaluate the effect of therapeutic transforaminal lumbar epidural steroid injections in managing low back and lower extremity pain. The available literature on lumbar transforaminal epidural injections in managing chronic low back and lower extremity pain was reviewed. The quality assessment and clinical relevance criteria utilized were the Cochrane Musculoskeletal Review Group criteria as utilized for interventional techniques for randomized trials and by the Newcastle-Ottawa Scale criteria for observational studies. Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to December 2011, and manual searches of the bibliographies of known primary and review articles. The level of evidence was classified as good, fair, or poor based on the quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF). The primary outcome measure was pain relief (short-term relief = up to 6 months and long-term > 6 months). Secondary outcome measures were improvement in functional status, psychological status, return to work, and reduction in opioid intake. For this systematic review, 70 studies were identified. Of these, 43 studies were excluded and a total of 27 studies met inclusion criteria for methodological quality assessment with 15 randomized trials (with 2 duplicate publications) and 10 non-randomized studies. For lumbar disc herniation, the evidence is good for transforaminal epidural with local anesthetic and steroids, whereas it was fair for local anesthetics alone and the ability of transforaminal epidural injections to prevent surgery. For spinal stenosis, the available evidence is fair for local anesthetic and steroids. The evidence for axial low back pain and post lumbar surgery syndrome is poor, inadequate, limited, or unavailable. The limitations of this systematic review include the paucity of literature. In summary, the evidence is good for radiculitis secondary to disc herniation with local anesthetics and steroids and fair with local anesthetic only; it is fair for radiculitis secondary to spinal stenosis with local anesthetic and steroids; and limited for axial pain and post surgery syndrome using local anesthetic with or without steroids.


Adaptational changes of fatty acid composition and the physical state of membrane lipids following the change of growth temperature in Yersinia enterocolitica.
Yersinia enterocolitica is capable of growing in a broad range of temperatures from 4 to 45 C. How this organism alters its membrane lipids in response to the change of growth temperature is very interesting. The fatty acids of membrane lipids of cells cultured at 5, 15, 25 and 37 C were analyzed and the physical states of these membrane lipids were characterized. The major phospholipids of this bacterium were phosphatidylethanolamine, phosphatidylglycerol, cardiolipin, lysophosphatidylglycerol and lysophosphatidylethanolamine. No significant difference in phospholipid composition in response to culture temperatures was observed. It was reported in our previous paper that the major fatty acids of membrane phospholipids of Y. enterocolitica were C15:0, C16:0, C16:1, cyclopropane C17:0 and C18:0. Some differences in the fatty acid composition were, however, observed with the change of culture temperature. When the culture temperature was raised, the saturated and cyclopropane fatty acids substantially increased and the unsaturated ones decreased. A reverse phenomenon was observed when culture temperature was lowered. From the viewpoints of membrane physical state, adaptational changes were analyzed using a nylon microcapsule method. Phase transition in membrane lipids of cells grown at each culture temperature took place in the range of about 5 C below and about 10 C above the culture temperature. It is, therefore, considered that Y. enterocolitica maintains its membrane rigidity and fluidity in response to growth temperature by changing the membrane fatty acid composition.


Is neonatal circumcision judicious?
Circumcision is the most frequently performed procedure in male children. The aim of the study was to compare the outcome of circumcision performed in the early neonatal period and circumcision performed at 5 months of age. Setting of the study was the King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia. The study was performed as a prospective cohort study. A total of 350 infants were enrolled. 250 neonates were circumcised at the age of 1 to 4 days (early group) and 100 infants underwent circumcision at the age of 5 months (late group). A bone cutter was used for 50 neonates, a Gomco clamp in another 50 neonates, and a Plastibell in the remaining 250 cases (150 in the early group and 100 in the late group). Complications including meatal deformities, meatal stenosis, adhesions and infection were more frequent and more significant in the neonatal circumcision group. From our study, circumcision at 5 months results in significantly fewer serious complications than circumcision in the neonatal period, irrespective of the method used. Therefore, neonatal circumcision should not be recommended.


Lower thoracic disc herniation mimicking lower lumbar disk disease: A case report.
Thoracic disk herniation comprises 0.15% of all disk herniation and has various and confusing manifestations. Among them, radicular pain down the leg could be the rarest presentation, especially if it is the only complaint. On the other hand, finding the relationship between clinical and paraclinical needs require high index of suspension and it is demanding. A 34-year-old patient, who had a history of intermittent back pain, with lower thoracic disk herniation presented by acute leg sciatica-like pain, is reported. He suffered 3 weeks of acute back pain prior to admission, which radiated down to buttock and leg, with a vague left abdominal pain, whose clinical examination indicated a distal lumbar problem. MRI showed T-12 L-1 disk herniation. Lower thoracic disc herniation can compress lumbosacral roots immediately after exiting from cord thickening in the lower thoracic area, so they can incite lower lumbar radiculopathy and cause discordance between MRI findings and clinical presentation, suggesting a lumbar problem, and this can lead to delayed diagnosis. However, the acute pain was completely improved after open discectomy.


Cardiac deficiency of P21-activated kinase 1 promotes atrial arrhythmogenesis in mice following adrenergic challenge.
P21-activated kinase 1 (Pak1) signalling plays a vital and overall protective role in the heart. However, the phenotypes of Pak1 deficiency in the cardiac atria have not been well explored. In this study, Pak1 cardiac-conditional knock-out (cKO) mice were studied under baseline and adrenergic challenge conditions. Pak1 cKO mice show atrial arrhythmias including atrial fibrillation (AF) in vivo, detected during anaesthetized electrocardiography without evidence of interstitial fibrosis upon Masson's trichrome staining. Optical mapping of left atrial preparations from Pak1 cKO mice revealed a higher incidence of Ca2+ and action potential alternans under isoprenaline challenge and differences in baseline action potential and calcium transient characteristics. Type-2 ryanodine receptor (RyR2) channels from Pak1 cKO hearts had a higher open probability than those from wild-type. Reverse transcription-quantitative polymerase chain reaction and Western blotting indicated that pCamkIIδ and RyR2 are highly phosphorylated at baseline in the atria of Pak1 cKO mice, while the expression of Slc8a2 and Slc8a3 as a Na+-Ca2+ exchanger, controlling the influx of Ca2+ from outside of the cell and efflux of Na+ from the cytoplasm, are augmented. Chromatin immunoprecipitation study showed that pCreb1 interacts with Slc8a2 and Slc8a3. Our study thus demonstrates that deficiency of Pak1 promotes atrial arrhythmogenesis under adrenergic stress, probably through post-translational and transcriptional modifications of key molecules that are critical to Ca2+ homeostasis. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.


International Legal Approaches to Neurosurgery for Psychiatric Disorders.
Neurosurgery for psychiatric disorders (NPD), also sometimes referred to as psychosurgery, is rapidly evolving, with new techniques and indications being investigated actively. Many within the field have suggested that some form of guidelines or regulations are needed to help ensure that a promising field develops safely. Multiple countries have enacted specific laws regulating NPD. This article reviews NPD-specific laws drawn from North and South America, Asia and Europe, in order to identify the typical form and contents of these laws and to set the groundwork for the design of an optimal regulation for the field. Key challenges for this design that are revealed by the review are how to define the scope of the law (what should be regulated), what types of regulations are required (eligibility criteria, approval procedures, data collection, and oversight mechanisms), and how to approach international harmonization given the potential migration of researchers and patients.


Natural world physical, brain operational, and mind phenomenal space-time.
Concepts of space and time are widely developed in physics. However, there is a considerable lack of biologically plausible theoretical frameworks that can demonstrate how space and time dimensions are implemented in the activity of the most complex life-system - the brain with a mind. Brain activity is organized both temporally and spatially, thus representing space-time in the brain. Critical analysis of recent research on the space-time organization of the brain's activity pointed to the existence of so-called operational space-time in the brain. This space-time is limited to the execution of brain operations of differing complexity. During each such brain operation a particular short-term spatio-temporal pattern of integrated activity of different brain areas emerges within related operational space-time. At the same time, to have a fully functional human brain one needs to have a subjective mental experience. Current research on the subjective mental experience offers detailed analysis of space-time organization of the mind. According to this research, subjective mental experience (subjective virtual world) has definitive spatial and temporal properties similar to many physical phenomena. Based on systematic review of the propositions and tenets of brain and mind space-time descriptions, our aim in this review essay is to explore the relations between the two. To be precise, we would like to discuss the hypothesis that via the brain operational space-time the mind subjective space-time is connected to otherwise distant physical space-time reality.


Factors contributing to health disparities in liver transplantation in a Hispanic population.
Among the challenges that Puerto Rico transplant patients face are a lack of social support that would enable them to move away from Puerto Rico, the difficulty of obtaining insurance coverage, and limitations imposed by language barriers. These factors may lead to reduced access to liver transplantation, which is a form of healthcare disparity. The objective of the study is to describe a group of Puerto Rican liver transplant candidates for the first time and to determine whether the above-named factors limit the possibilities of these candidates to be listed for transplant. Using non-public databases from the referral and the transplant center, we performed a retrospective analysis of the medical records of patients who had been evaluated for liver transplant candidacy. Candidates (137) from the Liver Transplant Clinic at the University of Puerto Rico School of Medicine pre-evaluated for transplant candidacy during the period of 2002 to 2008 were selected. Records from 86 men and 51 women were reviewed. The most predominant etiologies of liver disease were hepatitis C virus (36%), a combination of etiologies (26%), alcoholic liver disease (16%), and cryptogenic cirrhosis (10%). While social support and history of psychiatric disorders did not affect listing, private insurance increased the odds of being enlisted for liver transplant (OR = 2.97) 195%CI: 1.067-8.242) (p<0.05). Access to private insurance increases the possibility of patient's being enlisted for liver transplantation. Recommendations for overcoming the gap in access to transplants by patients without private insurance are discussed.


Binocular cross-correlation analyses of the effects of high-order aberrations on the stereoacuity of eyes with keratoconus.
Stereoacuity losses are induced by increased magnitudes and interocular differences in high-order aberrations (HOAs). This study used keratoconus as a model to investigate the impact of HOAs on disparity processing and stereoacuity. HOAs and stereoacuity were quantified in subjects with keratoconus (n = 21) with HOAs uncorrected (wearing spectacles) or minimized (wearing rigid gas-permeable contact lenses) and in control subjects without keratoconus (n = 5) for 6-mm pupil diameters. Disparity signal quality was estimated using metrics derived from binocular cross-correlation functions of stereo pairs convolved with point-spread functions from these HOAs. Metrics computed for all subjects were compared with stereoacuities. The effects of contrast losses and phase shifts on disparity signal quality were studied independently by manipulating the amplitude and phase components of optical transfer functions. The magnitudes, orientations, interocular relationships in magnitude, and shape of the point-spread function affected the cross-correlation metrics that determine disparity signal quality. Stereoacuity covaries strongly with cross-correlation metrics and moderately with image-quality metrics. Both phase distortions and contrast losses due to HOAs significantly influence computations of binocular disparity. HOA-induced stereoacuity reductions are attributable to disparity blur and noise from image properties that reduce the height and kurtosis of the peak stimulus disparity match of the cross-correlation. Phase distortions and contrast losses due to HOAs are both partly responsible for the greater stereoacuity losses seen with spectacles compared to rigid gas-permeable contact lenses in keratoconus.


Accrual of Older Patients With Breast Cancer to Alliance Systemic Therapy Trials Over Time: Protocol A151527.
Purpose Despite increasing awareness of accrual challenges, it is unknown if accrual of older patients to breast cancer treatment trials is improving. Methods We examined accrual of older patients to Alliance for Clinical Trials in Oncology systemic therapy breast cancer trials during 1985-2012 and compared disease characteristics and reasons for therapy cessation for older (age ≥ 65 years and ≥ 70 years) versus younger (age < 65 years and < 70 years) participants. To examine accrual trends, we modeled age as a function of time, using logistic regression. Results Overall, 17% of study participants were ≥ 65 years of age. Approximately 15%, 24%, and 24% of participants in adjuvant, neoadjuvant, and metastatic trials were age ≥ 65 years, and 7%, 15%, and 13% were age ≥ 70 years, respectively. The odds of a patient age ≥ 65 years enrolling significantly increased over time for adjuvant trials (odds ratio [OR] per year, 1.04; 95% CI, 1.04 to 1.05) but decreased significantly for neoadjuvant and metastatic trials (OR, 0.62; 95% CI, 0.58 to 0.67 and OR, 0.98, 95% CI, 0.97 to 1.00). Similar trends were seen for those age ≥ 70 years but these were statistically significant for adjuvant and neoadjuvant trials only (OR, 1.05, 95% CI, 1.04 to 1.07; and OR, 0.57, 95% CI, 0.52 to 0.62). In general, those age ≥ 65 years ( v those < 65 years) in adjuvant studies had a higher mean number of lymph nodes involved and more hormone receptor-negative tumors, although tumor sizes were similar. Early protocol treatment cessation was also more frequent in those age ≥ 65 years (50%) versus < 65 years (35.9%) across trials. Conclusion Older patients with breast cancer remain largely underrepresented in cooperative group therapeutic trials. We observed some improvement in accrual to adjuvant trials but worsening of accrual for neoadjuvant/metastatic trials. Novel strategies to increase accrual of older patients are critical to meaningfully change the evidence base for this growing patient population.


Nanoscale spectroscopic and mechanical characterization of individual aerosol particles using peak force infrared microscopy.
Atmospheric aerosol particles of sizes less than 2.5 microns affect public health in cities. Understanding the fine structures of aerosol particles is important to decipher their source. Here, we use a novel spectroscopic and mechanical microscopy technique of 10 nm spatial resolution to reveal the nanoscale structures of individual aerosol particles.


Role of subcutaneous adipose tissue in the pathogenesis of insulin resistance.
Burden of obesity has increased significantly in the United States over last few decades. Association of obesity with insulin resistance and related cardiometabolic problems is well established. Traditionally, adipose tissue in visceral fat depot has been considered a major culprit in development of insulin resistance. However, growing body of the literature has suggested that adipose tissue in subcutaneous fat depot, not only due to larger volume but also due to inherent functional characteristics, can have significant impact on development of insulin resistance. There are significant differences in functional characteristics of subcutaneous abdominal/truncal versus gluteofemoral depots. Decreased capacity for adipocyte differentiation and angiogenesis along with adipocyte hypertrophy can trigger vicious cycle of inflammation in subcutaneous adipose tissue and subsequent ectopic fat deposition. It is important to shift focus from fat content to functional heterogeneity in adipose tissue depots to better understand the relative role of subcutaneous adipose tissue in metabolic complications of obesity. Therapeutic lifestyle change continues to be the most important intervention in clinical practice at any level of increased adiposity. Future pharmaceutical interventions aimed at improving adipose tissue function in various subcutaneous depots have potential to help maintain adequate insulin sensitivity and reduce risk for development of insulin resistance complications.


Infection and labor. IV. Cachectin-tumor necrosis factor in the amniotic fluid of women with intraamniotic infection and preterm labor.
A growing body of evidence supports a causal link between subclinical intrauterine infection and preterm labor. The mechanisms responsible for the onset of parturition in this setting have not been elucidated. The conventional view has been that bacterial products increase prostaglandin biosynthesis by intrauterine tissues and this, in turn, leads to the onset of labor. An alternative or complementary mechanism is that microbial products activate the host monocyte-macrophage system and that cytokines released during this process signal the initiation of parturition by stimulating prostaglandin biosynthesis by intrauterine tissues. This study was conducted to determine if cachectin-tumor necrosis factor is present in the amniotic fluid of women with intraamniotic infection and whether this cytokine can alter the rate of prostaglandin biosynthesis by intrauterine tissues. Amniotic fluid from 54 women was assayed for tumor necrosis factor. Tumor necrosis factor was not detectable in the amniotic fluid of women without intraamniotic infection regardless of the presence or absence of term or preterm labor. On the other hand, the amniotic fluid of 11 of 15 women with preterm labor and intraamniotic infection had measurable tumor necrosis factor. This cytokine stimulated prostaglandin E2 biosynthesis by amnion cells in monolayer culture in a dose-dependent fashion. These data support the concept that macrophage activation is involved in the onset of human parturition in the setting of infection. We propose that the host (fetus and/or mother) signals the onset of parturition through the secretion of inflammatory cytokines released in response to bacterial invasion.


Heavy Metal Soil Contamination Detection Using Combined Geochemistry and Field Spectroradiometry in the United Kingdom.
Technological advances in hyperspectral remote sensing have been widely applied in heavy metal soil contamination studies, as they are able to provide assessments in a rapid and cost-effective way. The present work investigates the potential role of combining field and laboratory spectroradiometry with geochemical data of lead (Pb), zinc (Zn), copper (Cu) and cadmium (Cd) in quantifying and modelling heavy metal soil contamination (HMSC) for a floodplain site located in Wales, United Kingdom. The study objectives were to: (i) collect field- and lab-based spectra from contaminated soils by using ASD FieldSpec® 3, where the spectrum varies between 350 and 2500 nm; (ii) build field- and lab-based spectral libraries; (iii) conduct geochemical analyses of Pb, Zn, Cu and Cd using atomic absorption spectrometer; (iv) identify the specific spectral regions associated to the modelling of HMSC; and (v) develop and validate heavy metal prediction models (HMPM) for the aforementioned contaminants, by considering their spectral features and concentrations in the soil. Herein, the field- and lab-based spectral features derived from 85 soil samples were used successfully to develop two spectral libraries, which along with the concentrations of Pb, Zn, Cu and Cd were combined to build eight HMPMs using stepwise multiple linear regression. The results showed, for the first time, the feasibility to predict HMSC in a highly contaminated floodplain site by combining soil geochemistry analyses and field spectroradiometry. The generated models help for mapping heavy metal concentrations over a huge area by using space-borne hyperspectral sensors. The results further demonstrated the feasibility of combining geochemistry analyses with filed spectroradiometric data to generate models that can predict heavy metal concentrations.


Zn transporter levels and localization change throughout lactation in rat mammary gland and are regulated by Zn in mammary cells.
Mechanisms regulating the decrease in milk zinc (Zn) concentration that occurs during the course of lactation are currently unknown. We demonstrated Zn transporter expression (Zip3, ZnT-1, ZnT-2 and ZnT-4) in rat mammary gland during mid-lactation and we hypothesize that changes in the levels and localization of these transporters play a role in the longitudinal decrease in milk Zn concentration. Furthermore, we suggest that cellular Zn levels can mediate these responses and determined the effects of Zn exposure on Zn transporter expression and localization in cultured mouse mammary epithelial (HC11) cells. Although the milk Zn level declined, mammary gland Zn, ZnT-1 and ZnT-2 mRNA levels increased through mid-lactation; ZnT-4 was unaltered and ZIP3 decreased. Zip3 protein decreased through lactation and localized to the basolateral membrane of rat mammary cells. Although ZnT-1 and ZnT-4 protein increased, data indicate that these proteins are members of larger complexes whose levels change throughout lactation. ZnT-2 protein decreased, whereas apical membrane staining of ZnT-1, ZnT-2 and ZnT-4 was low by the end of lactation. Zn-treated HC11 cells had lower 65Zn uptake and ZIP3 mRNA levels and higher 65Zn export, ZnT-1 and ZnT-2 mRNA levels than untreated cells. Zn treatment resulted in relocalization from the plasma membrane (Zip3) or Golgi apparatus (ZnT-4) to an intracellular compartment, from an intracellular compartment toward the plasma membrane (ZnT-2) or from a perinuclear to an intracellular compartment (ZnT-1). The results from this study indicate that the decrease in milk Zn concentration that occurs throughout lactation is in part a result of changing Zn transporter protein levels and cellular localization, possibly as a consequence of increasing mammary gland Zn concentration.


Goal striving strategies and effort mobilization: When implementation intentions reduce effort-related cardiac activity during task performance.
Two experiments investigate the influence of goal and implementation intentions on effort mobilization during task performance. Although numerous studies have demonstrated the beneficial effects of setting goals and making plans on performance, the effects of goals and plans on effort-related cardiac activity and especially the cardiac preejection period (PEP) during goal striving have not yet been addressed. According to the Motivational Intensity Theory, participants should increase effort mobilization proportionally to task difficulty as long as success is possible and justified. Forming goals and making plans should allow for reduced effort mobilization when participants perform an easy task. However, when the task is difficult, goals and plans should differ in their effect on effort mobilization. Participants who set goals should disengage, whereas participants who made if-then plans should stay in the field showing high effort mobilization during task performance. As expected, using an easy task in Experiment 1, we observed a lower cardiac PEP in both the implementation intention and the goal intention condition than in the control condition. In Experiment 2, we varied task difficulty and demonstrated that while participants with a mere goal intention disengaged from difficult tasks, participants with an implementation intention increased effort mobilization proportionally with task difficulty. These findings demonstrate the influence of goal striving strategies (i.e., mere goals vs. if-then plans) on effort mobilization during task performance.


COMPARISON BETWEEN INCIDENCE OF INCISIONAL HERNIA IN LAPAROSCOPIC CHOLECYSTECTOMY AND BY SINGLE PORT.
Surgeries with single port access have been gaining ground among surgeons who seek minimally invasive procedures. Although this technique uses only one access, the incision is larger when compared to laparoscopic cholecystectomy and this fact can lead to a higher incidence of incisional hernias. To compare the incidence of incisional hernia after laparoscopic cholecystectomy and by single port. A total of 57 patients were randomly divided into two groups and submitted to conventional laparoscopic cholecystectomy (n=29) and laparoscopic cholecystectomy by single access (n=28). The patients were followed up and reviewed in a 40.4 month follow-up for identification of incisional hernias. Follow-up showed 21,4% of incisional hernia in single port group and 3.57% in conventional technique. There was a higher incidence of late incisional hernia in patients submitted to single port access cholecystectomy compared to conventional laparoscopic cholecystectomy.


Design and expression of a QconCAT protein to validate Hi3 protein quantification of influenza vaccine antigens.
Quantification of the antigens hemagglutinin and neuraminidase in influenza vaccines has been reported using an antibody-free liquid chromatography-mass spectrometry (LC-MS) based method known as MS(E) "Hi3". This approach is based on the average signal intensity of the three most intense tryptic peptides relative to a primary standard. This strategy assumes that the Hi3 signal responses are consistent for all proteins, and therefore comparable to a spiked reference for absolute quantification. This method is much faster than the current standard methods; however, the results can vary significantly which brought the method's accuracy into question. To address this question we generated synthetic proteins comprising a concatenation of the peptides used to quantify the proteins of interest (QconCAT). Complete tryptic digestion of a QconCAT protein produces equal molar peptide amounts, allowing verification of equal signal response of Hi3 peptides for the proteins of interest. The generation of an intact, stable, QconCAT protein that digest completely is challenging. We have designed and analyzed five QconCAT proteins with unique design elements to address these challenges. We conclude that a suitable QconCAT protein can be produced and that the results obtained reinforce the validity of the Hi3 approach for quantifying proteins in annual influenza vaccine formulations. The advances in quantitative proteomics have allowed the adaptation and application of these methods to numerous fields. In this paper we have validated a Hi3 approach to augment the antigen quantification for influenza vaccines injected into many millions annually. This methodology allows analysis of multiple antigens simultaneously without the need to generate antibodies. Key circumstances where this is advantageous are for quantitation of very similar antigens, such as the new quadravalent products and when time is critical such as in a flu pandemic.


Citrate synthase gene comparison, a new tool for phylogenetic analysis, and its application for the rickettsiae.
Using PCR and an automated laser fluorescent DNA sequencer, we amplified and sequenced a 1,234-bp fragment of the citrate synthase-encoding gene (gltA) of 28 bacteria belonging to the genus Rickettsia. Comparative sequence analysis showed that most of the spotted fever group (SFG) rickettsiae belonged to one of two subgroups. The first subgroup included Rickettsia massiliae, strain Bar 29, Rickettsia rhipicephali, "Rickettsia aeschlimanni," and Rickettsia montana, which have been isolated only from ticks. The second subgroup was larger and included the majority of the human pathogens and also rickettsiae isolated only from ticks; the members of this subgroup were strain S, Rickettsia africae, "Rickettsia monglotimonae," Rickettsia sibirica, Rickettsia parkeri, Rickettsia conorii, Rickettsia rickettsii, the Thai tick typhus rickettsia, the Israeli tick typhus rickettsia, the Astrakhan fever rickettsia, "Rickettsia slovaca," and Rickettsia japonica. The sequence analysis also showed that the tick-borne organisms Rickettsia helvetica and Rickettsia australis and the mite-borne organism Rickettsia akari were associated with the SFG cluster, that Rickettsia prowazekii and Rickettsia typhi, two representatives of the typhus group, clustered together, and that Rickettsia canada; Rickettsia bellii, and the AB bacterium probably represent three new groups. We compared the phylogenetic trees inferred from citrate synthase gene sequences and from 16S ribosomal DNA (rDNA) sequences. For rickettsial phylogeny, the citrate synthase approach was more suitable, as demonstrated by significant bootstrap values for all of the nodes except those in the larger subgroup defined above. We also compared phylogenetic analysis results obtained in a comparison of the sequences of both genes for all of the representatives of the domain Bacteria for which the gltA sequence was determined. We believe that comparison of gltA sequences could be a complementary approach to 16S rDNA sequencing for inferring bacterial evolution, especially when unstable phylogenetic models are obtained from ribosomal sequences because of high levels of sequence similarity between the bacteria studied.