Early malnutrition predicts parent reports of externalizing behaviors at ages 9-17.
To determine whether externalizing behaviors are more prevalent in youth who have experienced an episode of malnutrition in the first year of life than in healthy comparison youth. Parents of previously malnourished youth and a matched healthy comparison group completed a behavior rating scale when the youth were 9-15 years of age and again, 2 years later, when they were 11-17 years of age. Longitudinal multiple regression analysis was applied to evaluate group differences adjusted for baseline age, sex, household standard of living, and maternal depressive symptoms. Early childhood malnutrition was associated with problems in executive functioning at both occasions. Malnutrition also predicted discernibly higher parent-reported levels of aggression toward peers at 9-15 years than at 11-17 years. These findings were independent of baseline age, sex, household standard of living, and maternal depressive symptoms. Problem behaviors in general decreased during follow-up. Parents report persisting problems with executive functioning through adolescence in youth who suffered an episode of moderate-to-severe protein-energy malnutrition in the first year of life, while reports of aggression, although more common when this cohort were younger, did not persist at follow-up.


Perillaldehyde mitigates virulence factors and biofilm formation of Pseudomonas aeruginosa clinical isolates, by acting on the quorum sensing mechanism in vitro.
The incidence of biofilm linked catheter-associated urinary tract infections is increasing worldwide and Pseudomonas aeruginosa is one of the major causes. Perillaldehyde (PLD): as a natural, widely used flavouring agent, has been reported to possess various pharmacological properties. We hypothesized that PLD can inhibit biofilm formation and virulence factor (VF) production by P. aeruginosa by hampering the quorum sensing (QS) system(s). Minimum inhibitory concentration (MIC) of PLD was assessed for standard strain and two multi-drug resistant catheter isolates of P. aeruginosa utilizing the microdilution method. Microtiter plate assay, crystal violet staining and scanning electron microscopy were used to evaluate the biofilm inhibition property. CFU was utilized to assess the antifouling property of PLD. Detection of VFs and expression analysis of virulence determinants were applied to investigate the anti-virulence activity. Gene expression and molecular docking studies were also executed to explore the QS inhibition and binding of PLD with QS receptors. In the present study, PLD has significantly inhibited biofilm formation and antivirulence activity at sub-MIC levels (2.5 and 3.5 mM) in all the tested strains. In addition, molecular docking studies revealed a significant affinity towards QS receptors. Perillaldehyde, being a non-toxic food flavouring agent, significantly inhibited biofilm formation and exhibited antifouling property. PLD exhibited significantly reduced levels of VFs (p < 0.001) and their respective genetic determinants (p < 0.001). Gene expression analysis and molecular docking studies confirmed the interactions of PLD to the QS receptors, indicating the plausible mechanism for the anti-virulence property. This study identified the anti-virulence potential of PLD and provided mechanistic insights. PLD can be a suitable, non-toxic candidate for countering biofilms and associated pathogens, contributing to the prevention of biofilm-associated nosocomial infections.


Clinical indications for cervical spine radiographs in the traumatized patient.
During a 4 1/2 year period, 4,941 trauma patients were admitted to a hospital, and details of their injuries and treatment were entered in a computerized trauma registry. Using that database, patients with cervical spine injury were studied. Of the 4,941 patients, 1,823 (38 percent) had radiographs of the cervical spine. Ninety-four patients (5 percent) of these patients had injuries of the cervical spine or spinal cord. Sixty five of the 94 patients with cervical spine injury were alert. All had either neck pain or neck tenderness. We do not recommend screening cervical spine radiographs for the alert trauma patient without neck pain; however, we do recommend screening for all patients with decreased levels of consciousness and an injury that could have conceivably injured the cervical spine, for all patients with neurologic deficits compatible with a cervical origin, and for all patients with neck pain or tenderness. Lateral cervical spine radiographs were obtained in all injured patients. They demonstrated cervical spine injury in 70 patients (74 percent) and missed the injury in the remaining 24, which resulted in an unacceptable false-negative rate of 26 percent. We believe that all patients at risk for cervical spine injuries must have complete radiographic examinations of the cervical spine. Computerized axial tomography was the most useful modality to confirm a cervical spine injury in those patients whose lateral cervical spines appeared normal radiographically, especially in patients with associated head injury requiring computerized axial tomography of the brain. Computerized axial tomography diagnosed the injury in 14 of the 24 patients requiring study beyond initial screening. Also presented herein is a radiologic screening algorithm for cervical spine injuries in trauma patients.


History of benign breast disease and risk of breast cancer among women in China: a case-control study.
Data from the Shanghai Breast Cancer Study were analyzed to evaluate the relationship between benign breast disease (BBD) and breast cancer among Chinese women with a self-report of physician-diagnosed BBD. Study participants consisted of 3,452 breast cancer cases and 3,474 population controls recruited by the Shanghai Breast Cancer Study. In-person interviews were conducted to collect information on demographics and suspected risk factors for breast cancer, including a detailed history of BBD. Unconditional logistic regression was used to derive adjusted odds ratios (OR(adj)) and 95% confidence intervals (CI) for the association between self-reported BBD and breast cancer. Women with breast cancer were significantly more likely to have a self-reported history of BBD including lobular proliferation (OR(adj) = 1.6; 95% CI 1.4-1.8), fibroadenoma (OR(adj) = 1.9; 95% CI 1.6-2.3), and other BBD (OR(adj) = 1.6; 95% CI 1.3-2.1). Breast cancer risk was lower for surgically treated fibroadenoma as compared to non-surgically treated and higher for other BBDs that were surgically treated versus non-surgically treated. Our results suggest that personal history of BBD is associated with an increased risk of future breast cancer among women in China. Surgical intervention for fibroadenoma may reduce the risk.


Better prognosis in females with severe COVID-19 pneumonia: possible role of inflammation as potential mediator.
Sex differences in COVID-19 severity and mortality have been described. Key aims of this analysis were to compare the risk of invasive mechanical ventilation (IMV) and mortality by sex and to explore whether variation in specific biomarkers could mediate this difference. This was a retrospective, observational cohort study among patients with severe COVID-19 pneumonia. A survival analysis was conducted to compare time to the composite endpoint of IMV or death according to sex. Interaction was formally tested to compare the risk difference by sex in sub-populations. Mediation analysis with a binary endpoint IMV or death (yes/no) by day 28 of follow-up for a number of inflammation/coagulation biomarkers in the context of counterfactual prediction was also conducted. Among 415 patients, 134 were females (32%) and 281 males (67%), median age 66 years (IQR 54-77). At admission, females showed a significantly less severe clinical and respiratory profiles with a higher PaO2/FiO2 (254 mmHg vs. 191 mmHg; p 0.023). By 28 days from admission, 49.2% (95% CI 39.6-58.9%) of males vs. 31.7% (17.9-45.4%) of females underwent IMV or death (log-rank p < 0.0001) and this amounted to a difference in terms of HR of 0.40 (0.26-0.63, p 0.0001). The area under the curve in C-reactive protein (CRP) over the study period appeared to explain 85% of this difference in risk by sex. Our analysis confirms a difference in the risk of COVID-19 clinical progression by sex and provides a hypothesis for potential mechanisms leading to this. Specifically, CRP showed a predominant role to mediate the difference in risk by sex.


How to kill an ERKsome target: PROTACs deliver the deathblow.
In this issue of Cell Chemical Biology, You et al. demonstrate that selective degradation of ERK5 exhibits neither anti-proliferative nor anti-inflammatory activities previously attributed to ERK5 inactivation. This settles a longstanding debate in the field and highlights the power of PROTACs to investigate non-enzymatic activities of target proteins.


Flavonoid composition and antimicrobial activity of Cirsium rivulare (Jacq.) All. flowers.
A new flavonoid compound isokaempferide 7-O-beta-d-(6''-methylglucuronide) (1) was isolated from flowers of Cirsium rivulare (Jacq.) All. Its structure was elucidated on the basis of spectroscopic studies (UV, (1)H and (13)C NMR, FABMS). Moreover, five known flavonoid compounds: apigenin 7-(6''-methylglucuronide) (2), hispidulin 7-glucoside (3), isokaempferide 7-glucuronide (4), kaempferol 3-galactoside (5), pectolinarin (6) were isolated from this source for the first time. The antimicrobial activity of aqueous, methanolic and 70% ethanolic extracts of Cirsium rivulare flowers and leaves was also evaluated.


Characterization of tyrosine hydroxylase from Manduca sexta.
In insects, 3,4-dihydroxyphenylalanine (DOPA) is required for tanning of newly formed cuticle and the production of melanin during some types of immune responses. DOPA is produced by the hydroxylation of tyrosine, and this reaction can be catalyzed by two types of enzymes: tyrosine hydroxylase (TH) and phenoloxidase (PO). TH is required for cuticle tanning in Drosophila melanogaster and for cuticle pigmentation in other insect species, but additional functions of TH have been uncertain. In contrast, an immune function for PO has been well documented. The goal of this study was to characterize TH from Manduca sexta with a focus on its possible contribution to cuticle tanning and immune-associated melanization. We cloned a full-length TH cDNA, purified recombinant TH, and confirmed that MsTH and MsPO have tyrosine hydroxylating activity. To determine possible functions, we analyzed TH expression profiles. TH mRNA and protein were present in eggs at the stage when the pharate larval cuticle begins to tan and also in the integument of molting larvae. The amount of TH in the integument was correlated with the degree of cuticle tanning. Unlike PO, which was found to be constitutively expressed by hemocytes and was present in plasma, TH was upregulated in hemocytes and the fat body in response to an immune challenge and remained intracellular. These data suggest that TH is required for cuticle tanning and immunity in M. sexta. Based on the collective information from many studies, we propose a model in which TH is a major producer of the DOPA required for both cuticle tanning and immune-associated melanization.


Navigation by parallax in three-dimensional space during fluoroscopy: application in guide wire-directed axillary/subclavian vein puncture.
Fluoroscopy is range ambiguous--the relative positions in three-dimensional space of two structures with superimposed silhouettes cannot be ascertained. The parallax effect can be used to overcome this problem, and was used to develop a technique of axillary/subclavian vein puncture. Patients requiring axillary/subclavian vein puncture were considered for the new technique. The vein was marked by a guide wire placed inside. In the postero-anterior (P-A) caudal projection, the needle was advanced dorsally from medial to the coracoid process at an arbitrary angle until its tip overlay the guide wire over the first intercostal space. Depending on whether the needle tip appeared caudad or cephalad of the guide wire in the P-A projection, the needle was advanced farther into or withdrawn back from the body, with its tip maintained over the guide wire in the P-A caudal projection at all times. Maneuvering of the needle stopped when the needle tip overlay the guide wire in both the P-A caudal and P-A projections or blood was aspirated. Forty-one separate successful punctures were performed in 20 patients. No complications were recorded. Each puncture took no more than 1 minute, and the image intensifier needed to swing between the P-A caudal and the P-A projections only twice. The new technique was effective, efficient, and safe when implemented in clinical practice, justifying the parallax principles on which it is based. The parallax principles may be applied to other invasive medical procedures with due modifications.


A history of continuous glucose monitors (CGMs) in self-monitoring of diabetes mellitus.
Self-monitoring of glucose for individuals afflicted with diabetes mellitus has allowed patients to take control of their disease and thus directly affect the outcomes related to it. It has been almost a century since the first test to monitor one's sugar was developed; that being a urine test. The most well-known and prominent medical device for monitor blood glucose for individuals with diabetes are the finger-prick devices. This itself is an approximately 50year old technology. More recently has been the introduction of continuous glucose monitors (CGMs) which entered the market place in the last year of the 20th century. As this technology has been further refined and improved, limitations associated with it have decreased. The scope of this review is to present a brief history of CGMs, both with the development of these medical devices and the challenges/limitations that they have shown.


Influence of colored face masks on judgments of facial attractiveness and gaze patterns.
Facial aesthetics are of great importance in social interaction. With the widespread adoption of face masks in response to the Covid-19 pandemic, there is growing interest in understanding how wearing masks might impact perceptions of attractiveness, as they partially or completely conceal facial features that are typically associated with attractiveness. This study aimed to explore the impact of mask wearing on attractiveness and to investigate whether the color (red or blue) of the mask has any effect on the perception of a person's attractiveness, while also considering gender and age as contributing factors. Additionally, the study intended to evaluate gaze patterns, initial focus, and dwell time in response to masked and unmasked faces. 30 AI-generated images of 15 female and 15 male faces were presented to 71 participants (35 male, 36 female) in 3 conditions: not wearing any mask, wearing a red surgical mask, and wearing a blue surgical mask. The perceived attractiveness was rated on an ordinal scale of 1-10 (10 being most attractive). Gaze behavior, dwell time and initial focus were recorded using a stationary eye-tracking system. The study found that wearing masks had no significant effect on the attractiveness ratings of female faces (p = .084), but it did benefit the perceived attractiveness of male faces which were initially rated lower (p = .16). Gender and age also played a significant role, as both male and female participants rated female stimuli higher than male stimuli (p < .001), and younger participants rated both genders as less attractive than older participants (p < .01). However, there was no significant influence of the mask's color on attractiveness. During the eye-tracking analysis, the periorbital region was of greater interest while masked, with the time to first fixation for the eyes being lower than the non-masked stimulus (p < .001) and showed a longer dwell time (p < .001). The lower face was shown less interest while masked as the time to first fixation was higher (p < .001) and the fixation count was less (p < .001). Mask color did not influence the scan path and there was no difference in revisits to the mask area between red or blue masks (p = .202), nor was there a difference in time to first fixation (p = .660). The study findings indicate that there is an interplay between the gender and age of the participant and the facial stimuli. The color red did have an effect on the perception attractiveness, however not in female faces. The results suggest that masks, especially red ones, might be more beneficial for male faces, which were perceived as less attractive without a mask. However, wearing a mask did not significantly impact already attractive faces. The eye-tracking results revealed that the periorbital region attracted more attention and was fixated on more quickly while wearing a mask, indicating the importance of eyes in social interaction and aesthetic perception.


Identification of enterococcal, streptococcal and Weissella species in the faecal flora of individually owned dogs.
To improve the limited information on the composition of the faecal Gram-positive coccal flora of healthy dogs by the use of a molecular identification method. Faecal swabs were collected for the selective isolation of Gram-positive coccal strains. Colonies with enterococcal- and streptococcal-like morphology were identified by tRNA intergenic length polymorphism analysis (tDNA-PCR). Fourteen known species belonging to three genera (Enterococcus, Streptococcus and Weissella) and one alleged new enterococcal species were found. The faecal flora of dogs comprises an unusually broad diversity of culturable Gram-positive coccal species with Enterococcus faecalis being most frequently present followed by not less than six other species of about equal importance. Many human- and animal-associated enterococci and streptococci are also present in dog faeces together with the largely uncharacterized Weissella cibaria and a group of strains resembling Enterococcus dispar, but representing a distinct and hitherto unknown species. Phenotypic characteristics of the latter two species were determined and the test results were compared with the species descriptions of W. cibaria and E. dispar respectively.


Relationships among resilience, depressive symptoms, self-esteem, and quality of life in children with cancer.
To examine the interrelationships among resilience, self-esteem, and depressive symptoms and determine whether resilience was a factor associated with quality of life for Hong Kong Chinese children with cancer. We used a cross-sectional study design. Participants were 138 Hong Kong Chinese children (aged 7-14 years) who were admitted to the pediatric oncology units of an acute public hospital. The resilience, depressive symptoms, self-esteem, and quality of life of participating children were assessed. The primary outcome was the association between resilience and quality of life in children with cancer. In total, 72 boys and 66 girls were recruited for this study (mean age 10.6 years). The mean levels of resilience, depressive symptoms, self-esteem, and quality of life were 23.4, 30.0, 23.0, and 63.6, respectively. There was a statistically significant strong positive correlation between resilience and quality of life (r = 0.60, p < 0.01), indicating that greater resilience was associated with better quality of life. Children with cancer from single-parent families, those diagnosed with a brain tumor, and those who received multiple treatments reported significantly lower levels of resilience, self-esteem, and quality of life, and greater depressive symptoms than other children (all p's < 0.001). Results of a multiple regression analysis revealed that resilience (p < 0.001) was a strong factor associated with quality of life among children with cancer. It is essential that healthcare professionals implement interventions to boost the resilience of children with cancer, thereby enhancing their quality of life.


After the mandates: Massachusetts employers continue to support health reform as more firms offer coverage.
Based on a spring 2008 survey of 1,003 randomly selected Massachusetts firms, this paper examines views and responses of employers to health care reform after employer and individual mandates went into effect. A majority of firms view reform as "good for Massachusetts." The percentage of firms with three or more workers offering coverage increased from 73 percent to 79 percent. Massachusetts employers are less likely than employers nationally to indicate plans to terminate coverage or restrict eligibility for health benefits, which suggests that crowd-out is not occurring.


Surgical correction of ankylosed TMJ in a child: case report.
The temporomandibular joint (TMJ) ankylosis describes the bone or fibrous adhesion of the TMJ components, with functional impairment. The present report shows the surgical correction the TMJ ankylosis due to a condyle fracture in a child. A 12-year-old patient, female, attended to the Oral and Maxillofacial Surgery Department of the Clinical Hospital/Federal University of Uberlândia, showing severe mouth opening limitation (9 mm) and history of bilateral condyle fracture and symphysis fracture. The right TMJ ankylosis was diagnosed, removed, reshaped, and repositioned to form the reshaped condyle, by the sliding reconstruction of the condyle using posterior border of mandibular ramus and myofascial interposition of the temporal fascia. Five months of follow-up showed mouth opening of 44 mm maintained after 2 years, without complaints. The surgical treatment of the TMJ ankylosis is needed for the reestablishment of the immediate function; however, the patient must be watched until the end of development.


Performance of the 1 mg dexamethasone suppression test in patients with severe obesity.
To analyze the performance of the 1 mg dexamethasone suppression test (DST) in patients with obesity. Special attention was paid to the influence of interfering medication on DST. In this prospective cohort study (Mannheim Obesity Study), patients with obesity were evaluated before bariatric surgery. For evaluation of hypercortisolism, a 1 mg dexamethasone-suppression test (DST) in all subjects was performed. Medication was assessed for possible interference. Two hundred seventy-eight patients with a mean age of 42.3 years (68.8% women) and a mean BMI of 47.9 ± 8.4 kg/m(2) were screened. Insufficient suppression of cortisol after DST was found in 24 patients (8.6%). In two patients hypercortisolism was confirmed. The specificity for DST was calculated at 92.0%. Only CYP3A4 inducers (n = 22, 7.9%) and estrogen therapy (n = 17, 6.1%) were significantly associated with falsely elevated cortisol after DST. Regression analysis excluded any interrelation between DST and anthropometry. Low prevalence of hypercortisolism (0.7 or <1.8%) was found. Specificity of DST in this cohort typically screened for hypercortisolism was 92.0% (≤ 50 nmol/L). DST should be avoided in patients taking CYP3A4 inducers or estrogen therapy, due to their significant interaction. In summary, the 1 mg DST is an adequate test for screening for hypercortisolism even in patients with extreme obesity.


Photothermal-Triggered Sulfur Oxide Gas Therapy Augments Type I Photodynamic Therapy for Potentiating Cancer Stem Cell Ablation and Inhibiting Radioresistant Tumor Recurrence.
Despite advances in cancer therapy, the existence of self-renewing cancer stem cells (CSC) can lead to tumor recurrence and radiation resistance, resulting in treatment failure and high mortality in patients. To address this issue, a near-infrared (NIR) laser-induced synergistic therapeutic platform has been developed by incorporating aggregation-induced emission (AIE)-active phototheranostic agents and sulfur dioxide (SO2 ) prodrug into a biocompatible hydrogel, namely TBH, to suppress malignant CSC growth. Outstanding hydroxyl radical (·OH) generation and photothermal effect of the AIE phototheranostic agent actualizes Type I photodynamic therapy (PDT) and photothermal therapy through 660 nm NIR laser irradiation. Meanwhile, a large amount of SO2 is released from the SO2 prodrug in thermo-sensitive TBH gel, which depletes upregulated glutathione in CSC and consequentially promotes ·OH generation for PDT enhancement. Thus, the resulting TBH hydrogel can diminish CSC under 660 nm laser irradiation and finally restrain tumor recurrence after radiotherapy (RT). In comparison, the tumor in the mice that were only treated with RT relapsed rapidly. These findings reveal a double-boosting ·OH generation protocol, and the synergistic combination of AIE-mediated PDT and gas therapy provides a novel strategy for inhibiting CSC growth and cancer recurrence after RT, which presents great potential for clinical treatment.


Skin Dosimetry with EBT3 Radiochromic Film in Radiotherapy of Parotid Cancer.
Skin is a sensitive organ and should be spared in radiotherapy and irradiation of skin in radiotherapy can cause to acute and late skin effects such as erythema, desquamation, epilation, color change, or even necrosis. The aim of the present study is to do skin dosimetry in radiotherapy of parotid cancer using Gafchromic EBT3 radiochromic film. EBT3 radiochromic films were calibrated in 0.2-5 Gy dose range. This is an experimental study in the field of radiotherapy physics. Treatment planning was performed on a RANDO phantom for treatment of parotid cancer by a clinical oncologist. Based on the treatment planning, the skin dose at various points in the overlapping region of right anterior-oblique and right posterior-oblique fields were measured using EBT3 radiochromic film. The minimum and maximum skin doses in a fraction (with 2.0 Gy prescribed dose) were 0.50 Gy and 0.97 Gy, respectively. Based on these values, the total skin dose in 30 treatment fractions (for removed tumor) or in 35 treatment fractions (for unremoved tumor) was in the range of 15-33 Gy. Based on the skin dosimetry results of parotid cancer radiotherapy using EBT3 films, it is predicted that there will occur mild skin reactions and these reactions can be neglected due to being mild.


Performance of a recirculating aquaculture system using biofloc biofilters with convertible water-treatment efficiencies.
To achieve high water-treatment efficiencies and simplify the setup of recirculating aquaculture systems (RAS), this study examined the use of suspended growth reactors (R1 and R2) based on biofloc technology (BFT) as water-treatment biofilters. Moreover, the conversion of the heterotrophic R1 biofilter to a nitrifying role was investigated. During RAS operation using heterotrophic BFT biofilters, R1 and R2 simultaneously controlled total ammonium nitrogen, nitrite (NO2--N), nitrate (NO3--N), soluble reactive phosphate (SRP), and alkalinity, with relevant functional microbes including denitrifying bacteria (DNB), phosphorus accumulating organisms (PAOs), denitrifying PAOs (DNPAOs), glycogen accumulating organisms, ammonia oxidizing bacteria, and nitrite oxidizing bacteria. To achieve low concentrations of nitrogen, phosphorus, and save carbon sources, we were able to quickly convert R1 into a nitrifying BFT biofilter by stopping carbohydrate addition. Although there were dominant relative abundances of DNB, PAOs, and DNPAOs in the converted R1, the lack of carbon sources resulted in continuous rise of NO3--N in the effluent, stable NO2--N removal efficiency, and absence of SRP removal after 40 h. However, R2 retained the previous NO3--N and SRP removal efficiencies with carbohydrate addition. This indicated that this novel RAS using BFT biofilters achieved simultaneous nitrogen and phosphate removal, and that the convertible water-treatment efficiencies of BFT biofilters could be controlled by carbohydrate addition. This approach could simplify the RAS setup and meet real-time water quality demands.


Live cell imaging to understand monocyte, macrophage, and dendritic cell function in atherosclerosis.
Intravital imaging is an invaluable tool for understanding the function of cells in healthy and diseased tissues. It provides a window into dynamic processes that cannot be studied by other techniques. This review will cover the benefits and limitations of various techniques for labeling and imaging myeloid cells, with a special focus on imaging cells in atherosclerotic arteries. Although intravital imaging is a powerful tool for understanding cell function, it alone does not provide a complete picture of the cell. Other techniques, such as flow cytometry and transcriptomics, must be combined with intravital imaging to fully understand a cell's phenotype, lineage, and function.


COVID-19 Vaccination Rates and Attitudes Among Young Adults With Recent Experiences of Homelessness.
This study provides information on COVID-19 vaccination and attitudes among young adults with recent experiences of homelessness. Participants (n = 134) from a clinical trial of a risk reduction program for youth experiencing homelessness in Los Angeles completed survey items about COVID-19 vaccinations between March and October 2021. A total of 29% of respondents were vaccinated, and 50% were not interested in getting vaccinated. Among the unvaccinated, 58% had not been offered the vaccine; furthermore, 38%-45% had strong distrust of the vaccine and were worried about its harmfulness. Vaccination status was generally unrelated to demographics, housing instability, service use, substance use, or mental health. Our data suggest that vaccination rates are lower among young adults with recent experiences of homelessness than those in the general US population. The results suggest a need for greater direct outreach that includes both offering the vaccine and addressing misconceptions about its safety to increase vaccination rates in this population.


[Lengthening of QT interval by antipsychotic drugs].
Prolongation of myocardial repolarisation, i.e. lengthening of the QT interval on surface electrocardiogram, has been recognised as a side effect of many drugs, including antipsychotics. In predisposed individuals, abnormal excessive QT prolongation and severe ventricular arrhythmias (the ventricular tachycardia type 'torsade de pointes', or TdP) may occur. In almost all cases, additional factors are present that increase the propensity of patients to develop TdP, such as serum hypokalemia, the combination of drugs prolonging repolarisation, overdosing, intoxication, and factors interfering with drug metabolism and excretion. Serum hypokalemia and/or bradycardia may induce TdP alone, in the absence of drugs prolonging the QT interval. Experimental studies demonstrate that prolongation of myocardial repolarisation is a class effect of neuroleptics. Clinically, the extent to which individual drugs prolong the QT interval varies. Among the antipsychotics, thioridazine has the greatest propensity to induce abnormal QT prolongations and TdP. Case reports of TdP with other antipsychotics have been published. Physicians prescribing physicians these drugs must be aware that they can induce proarrhythmia in individual cases. They should also be aware of the circumstances which are necessary for abnormal QT prolongation and TdP to develop. Patients should be monitored with regard to these risk factors before and during drug treatment.


An unusual neoplasm of the pancreas: Pancreatic metastasis of a Merkel cell carcinoma. Case report and review of the literature.
Isolated pancreatic metastases are rare. The differential diagnosis of pancreatic neoplasms can be difficult, especially it can be troublesome to obtain tissue diagnosis. However, pancreatic lesions in patients with a history of a malignancy must be considered to be metastases. We present a case of a patient with a history of a Merkel cell carcinoma (MCC) in the neck. Twelve months after this diagnosis a follow-up CT shows a large isolated tumor in the head of the pancreas. Histological and immunohistochemical studies of specimen obtained through ultrasound-guided transabdominal biopsy, show similar characteristics as the primary MCC. To our knowledge twelve cases of a pancreatic metastasis of a MCC have been reported in English literature. A review of the literature was performed.


Active behavioural physiotherapy intervention for acute non-specific neck pain: a cluster randomised double-blind pilot and feasibility clinical trial.
To evaluate the feasibility of an active behavioural physiotherapy intervention (ABPI) and procedures to prevent the transition to chronicity in patients with acute non-specific neck pain (ANSNP). A cluster-randomised double-blind (assessors and participants), parallel 2-arm (ABPI versus standard physiotherapy intervention [SPI]) pilot and feasibility clinical trial was conducted owing to a pre-specified published protocol. Six public hospitals were recruited and cluster-randomised (computer-generated randomisation with block sampling). Sixty participants (30 in each arm, 10 per hospital) were assessed at baseline and 3 months following baseline for neck disability index, numerical pain rating scale, cervical range-of-motion, fear-avoidance beliefs questionnaire and EuroQol 5-dimension 5-level. All procedures worked well. The participants' median age was 36.5 (range 21-59, interquartile range: 20.75) years. Participants in the ABPI demonstrated better improvement in all outcomes compared to SPI. Furthermore, the number of fully recovered participants following ABPI (27/30, 90.00%) was higher than SPI (16/30, 53.33%) with fewer treatment sessions and lower costs of management. The findings suggest that the ABPI is feasible and valuable (e.g. a high number of fully recovered participants, fewer treatment sessions and reduced management costs compared to the SPI) in conducting a future definitive trial to evaluate the effectiveness of the ANSNP management. TCTR20180607001Implications for RehabilitationAn active behavioural physiotherapy intervention (ABPI) is feasible to manage acute non-specific neck pain.The ABPI demonstrated a high number of fully recovered participants, fewer treatment sessions and reduced management costs compared to the standard physiotherapy intervention.The ABPI is valuable to conduct a future definitive trial to evaluate the effectiveness of acute non-specific neck pain management.


Downregulation of MicroRNA-222 Reduces Insulin Resistance in Rats with PCOS by Inhibiting Activation of the MAPK/ERK Pathway via Pten.
Polycystic ovary syndrome (PCOS), characterized by the dysfunction of endocrine metabolism, is a common disease among women. Insulin (INS) resistance (IR) is considered as an obstruction to effective PCOS treatment. Here, we aimed to explore the mechanism by which microRNA-222 (miR-222) affects IR in PCOS via Pten. Quantitative reverse transcription-polymerase chain reaction and western blot assays indicated that miR-222 expression was higher in the peripheral blood of PCOS patients with IR than in PCOS patients without IR, while Pten expression was lower. Further mechanistic analysis identified Pten as a target gene of miR-222. Moreover, PCOS rat models were established through the administration of dehydroepiandrosterone and were subsequently treated with miR-222 agomir, miR-222 antagomir, or Pten overexpression plasmid. The inhibition of miR-222 improved ovarian morphology, enhanced the production of serum sex hormones (follicle-stimulating hormone [FSH], luteotropic hormone [LH], estradiol 2 [E2], prolactin [PRL], and testosterone [T]), increased the levels of glucose metabolism indicators (homeostasis model of assessment for IR [HOMA-IR], blood glucose [BG]120min, and INS120min), and reduced the production of progesterone in the PCOS rats. Notably, miR-222 downregulation resulted in the inactivation of the mitogen-activated protein kinase (MAPK)/ERK pathway by upregulating Pten. Collectively, miR-222 inhibition might reduce IR in PCOS by inactivating the MAPK/ERK pathway and elevating Pten expression, which indicates miR-222 as a promising target for PCOS treatment.


Intra-abdominal desmoid tumor and chronic inflammatory bowel disease. An uncommon scenario.
We present the case of a patient with an inflammatory bowel disease to whom a pelvic desmoid tumor is discovered during an infertility study.


The chemical synthesis and preliminary biological studies of phosphodiester and phosphorothioate analogues of 2-methoxy-lysophosphatidylethanolamine.
The chemical synthesis of phosphorothioate/phosphodiester analogues of 2-methoxy-lysophosphatidylethanolamine has been described. For the preparation of phosphorothioate derivatives oxathiaphospholane approach has been employed. The phosphodiester compounds were prepared by OXONE® oxidation of corresponding phosphorothioates. Each lysophospholipid analogue was synthesized as a series of four compounds, bearing different fatty acid residues both saturated (14:0, 16:0, 18:0) and unsaturated (18:1). The methylation of glycerol 2-hydroxyl function was applied in order to increase the stability of prepared analogues by preventing 1→2 acyl migration. The cytotoxicity of newly synthesized 2-methoxy-lysophosphatidylethanolamine derivatives was evaluated with resazurin-based method in prostate cancer PC3 cell line. The highest reduction of cell viability was noted for LPE analogues containing myristoyl acyl chain.


The role of automatic and controlled processes in the positivity effect for older adults.
The positivity effect can be defined as an age-related attentional preference for positive information. The age differences are due to an attentional bias in which the young focused more intently on the negative stimuli, whereas the older attend to capture positive stimuli. There are two cognitive-emotional models that can explain the positivity effect: the socio-emotional selectivity theory (SST) and the dynamic integration theory (DIT). The SST states that in the older the positivity effect is related to controlled attentional processes, on the opposite, the DIT states that the positivity effect is related to automatic processes. The main aim of the present study was to examine automatic and controlled attentional orienting of young and older adults in the positivity effect. To reach these goals and to verify the generalization of the previous results, we used two experimental paradigms: the dot-probe task and the visual discrimination task with facial stimuli with positive (happy and surprise), negative (fair and angry) and neutral emotional expressions. 50 older and 35 young adults participated in this study. The older adults reacted faster to positive emotions than neutral or negative ones. They had similar RTs for the three types of emotions in both automatic and controlled attention. The findings are discussed in light of SST and DIT theories. This study confirms the positivity effect for the older subjects and support the idea that both automatic and controlled processes play a key role in this effect.


Topical growth factors and home-based microneedling for facial skin rejuvenation.
Cosmeceutical products are an important therapeutic option for facial rejuvenation. Of these, topical application of growth factors has been shown to increase dermal collagen synthesis, improve skin texture, and reduce fine lines and wrinkles. Limited data exist for the use of growth factors in combination with microneedling. This prospective, single-center, uncontrolled study evaluated the efficacy of topical growth factor treatment in conjunction with transdermal delivery of growth factors via home-based microneedling for facial skin rejuvenation. Eleven healthy female individuals aged 33-61 years, with mild-moderate facial wrinkling were included in the study. Over 3 months, participants received twice-daily application of a topical recombinant human growth factor preparation (SkinGenuity® Regenerative and Reparative Serums) along with twice-weekly transdermal delivery of growth factors using a home-based microneedling (0.2 mm) device. Objective skin analysis (VISIA® ) and a subjective patient-reported outcome (FACE-Q® ) assessment measuring satisfaction with appearance were performed at baseline and after 3 months. Objective skin analysis showed a significant improvement in skin texture (17.6%, p < 0.001), wrinkles (17.3%, p < 0.001), red areas (12.4%, p =0.004), and brown spots (6.0%, p =0.03) at 3 months follow-up. FACE-Q scales showed a significant improvement from baseline, including satisfaction with skin, facial appearance, nasolabial folds, cheeks, and lower face/jawline (all p ≤ 0.02). Numerical improvement in adverse effects related to skin was also observed (p = 0.07). No serious adverse effects were reported. Three months of twice-daily topical growth factor treatment in conjunction with transdermal delivery of growth factors via microneedling improved skin analysis parameters and participant-reported outcome measures, indicative of facial skin rejuvenation.


A model of local-minima distribution on conformational space and its application to protein structure prediction.
A quantitative two-parameter model is developed to describe local energy minima distribution. On a conformational space measured by least-square-fitting root-mean-squared distance (RMSD), the number of local minima in a r RMSD region is proposed to be proportional to exp(-1/r). As part of the model derivations, the minimum RMSD of decoys from the largest cluster, the number of decoys in the largest cluster, and the RMSD distribution of the decoys have inner connections with each other. The model is successfully verified on a 49 helix-packing decoy set and a 30 loop-prediction decoy set, as well as both knowledge-based potential (DFIRE) and physical force-fields (OPLS and CHARMM). One of the model's applications is predicting behaviors of a large amount of decoys (e.g., minimum RMSD of 40,000 decoys) by generating only a small number of decoys (e.g., 500). It may be applied to structure predictions guided by any Lennard-Jones-like potential functions and can be extended to other sampling methods guided by simple energy terms.


Use of novel artificial intelligence computer-assisted detection (AI-CAD) for screening mammography: an analysis of 17,884 consecutive two-view full-field digital mammography screening exams.
Novel artificial intelligence computer-assisted detection (AI-CAD) systems based on deep learning (DL) promise to support screen reading. To test a DL-AI-CAD system compared to human reading on consecutive screening mammograms. In this retrospective study, 17,884 consecutive anonymized screening mammograms, double-read from January to November 2018, were processed by the DL-AI-CAD system. AI-CAD reading was considered positive if the AI-CAD case scores exceeded 30 (range = 1-100) and the lesion was correctly marked. Likewise, human reading (R1 or R2, respectively) was considered positive if the lesion was correctly identified and called. Receiver operating characteristic (ROC) analysis was performed and accuracy data were calculated. Ground truth for benign lesions: absence of malignancy after cancer registry matching (2022); for malignancy: histopathologic proof; evaluation was patient-based. In total, 114 screen-detected and 17 interval cancers (ICA) occurred. ROC analysis of screen-detected cancers yielded an AUC of 89% for AI-CAD. Sensitivity/specificity was 81.7%/80.2% for AI-CAD; 77.1%/91.7% for R1; 78.6/91.6% for R2. Combining each human reading with AI-CAD was as sensitive as human double-reading (all approximately 88%), but less specific (approximately 75%) compared to human double-reading (approximately 87%). These AI-CAD combinations required consensus readings for twice as many cases as the human combination. Four of 17 ICA exceeded a case score of 30; two of four CAD correctly marked the quadrant of the subsequent ICA. Including ICA cases, this AI-CAD achieved comparable sensitivity to human reading at lower specificity. Combining human reading and AI-CAD allows increasing sensitivity compared to single-reading.


A novel tool to assess the risk of urinary incontinence after nerve-sparing radical prostatectomy.
WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Urinary incontinence is one of the most important morbidities after radical prostatectomy that has detrimental effect on the postoperative quality of life. The present study provides an accurate and dynamic multivariable risk stratification tool that predicts the postoperative urinary incontinence risk after radical prostatectomy based on patient-related as well as surgeon-related variables. To develop a multivariable risk classification tool to estimate postoperative urinary incontinence (UI) risk as UI represents one of the most disabling surgical sequelae after radical prostatectomy (RP). We evaluated 1311 patients treated with nerve-sparing RP between 2006 and 2010 at our institution. Regression tree analysis was used to stratify patients according to their postoperative UI risk. Kaplan-Meier curve estimates were used to assess the UI rate in the novel UI-risk groups. The discrimination of the novel tool was measured with the area under the curve method. At 3, 6 and 12 months, the UI rates were 44%, 26% and 12%, respectively. Regression tree analysis stratified patients into high risk (International Index of Erectile Function - Erectile Function domain [IIEF-EF] = 1-10), intermediate risk (IIEF-EF > 10 and age ≥ 65 years), low risk (IIEF-EF > 10, age < 65 years and body mass index [BMI] ≥ 25 kg/m(2) ) and very low risk (IIEF-EF > 10, age < 65 years and BMI < 25 kg/m(2) ) groups. The 3-month UI rates in these groups were 37%, 43%, 45% and 48%, respectively. The 6-month UI rates were 19%, 23%, 29% and 34%, respectively. The 12-month UI rates were 7%, 13%, 14% and 15%, respectively (log-rank P < 0.001). The area under the curve was 71%, 70% and 68% at 3, 6 and 12 months, respectively. We developed the first risk classification tool that predicts patients at high risk of UI after RP. These consisted mainly of individuals who were impotent before RP, elderly and/or overweight. This tool can be used for patient counselling.


Presence of viral and bacterial pathogens in the nasopharynx of otitis-prone children. A prospective study.
The purpose of the present study was to examine and follow up the presence of respiratory viral and bacterial pathogens in the nasopharynx of otitis-prone children during the cold season and compare the findings with the child's respiratory symptoms. We enrolled 121 otitis-prone children, aged 10 months to 4 years for a prospective study. The nasopharyngeal swab (NPS) were studied at the baseline and after 12 and 24 weeks for respiratory viruses and at the baseline and after 24 weeks for bacteria. Presence of picorna(rhino-entero-parecho)-, influenza-, adenoviruses and Mycoplasma pneumoniae was detected by PCR. NPS specimens were cultured for Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Clinical data (the rate of respiratory symptom days, otitis media, tympanometry findings, day-care attendance and the number of siblings) were compared with microbiological data. Rhinovirus was found in 30% of the samples at the baseline, in 8% and in 19% of the samples after 12 and 24 weeks, respectively. Enterovirus was detected in 19% of the samples, in 21% and in 12% of samples after 12 and 24 weeks, respectively. Picornavirus positivity correlated with the respiratory symptoms but not with the number of otitis media or with abnormal tympanometry. Two samples were adeno- and three samples influenzavirus positive. Parechovirus and M. pneumoniae were negative in all samples. Rhinovirus positivity correlated with that of M. catarrhalis and S. pneumonia but not with H. influenzae. Microbiological positivity was not significantly associated with the type of day-care. Picornaviruses as well as bacteria were commonly found in the nasopharynx of otitis-prone children during the cold season, even in the absence of clinical symptoms.


Amino acid sequence around the serine phosphorylated by casein kinase II in brain myosin heavy chain.
Casein kinase II from bovine brain transfers about one mole of phosphate to a serine residue near the COOH terminus of the heavy chain of myosin isolated from bovine brain. We have purified and characterized a peptide that contains this phosphoserine. The peptide was generated by chymotryptic and thermolytic digestion and was isolated by gel filtration, Fe3+ affinity chromatography, and reverse-phase high pressure liquid chromatography. Its sequence, Leu-Glu-Leu-Ser(PO4)-Asp-Asp-Asp-Asp-Glu-Ser-Lys-Ala-Ser-(Xaa)-Ile-Asn-Glu-Thr- Gln-Pro-Pro-Gln, shows that the Ser(PO4) is in an acidic environment, as is typical for casein kinase II phosphorylation sites. The "hydrophobic repeat" typical of alpha-helical coiled-coils is absent, suggesting that the sequence is part of a non-helical "tail piece" of the heavy chain. A synthetic peptide corresponding to residues 1-9 is shown to be an effective substrate for casein kinase II.


Endothelial cell toxicity of solid-organ preservation solutions.
Endothelial cell damage caused by myocardial cardioplegic solutions (Bretschneider HTK and St. Thomas' Hospital No. 2) or renal and hepatic cold storage solutions (modified Collins and University of Wisconsin solution) was assessed in monolayer cultures of adult human venous endothelial cells at 4 degrees to 10 degrees C with phase-contrast microscopy. St. Thomas' Hospital solution caused the cells to contract, resulting in disruption of monolayer integrity and opening of intercellular gaps, and resulted in a 24-hour postexposure survival of 51.0% +/- 2.4%. Bretschneider HTK solution altered cellular morphology less and produced the best postexposure survival (80.2% +/- 2.6%; p less than 0.001). Although morphology was altered the least with University of Wisconsin solution, postexposure survival with this solution, which was similar to that with modified Collins solution, was superior to that with St. Thomas' (p less than 0.01) but inferior to that with Bretschneider HTK (p less than 0.05). The superior protection provided by Bretschneider HTK was due to its additives histidine, tryptophan, and KH-2-oxygluterate (p less than 0.005), and to its low chloride content (p less than 0.005). Furthermore, modifying St. Thomas' solution by decreasing its chloride content improved cell survival to 71.2% +/- 2.3% (p less than 0.001). Normothermic (37 degrees C) exposure to Bretschneider HTK, modified Collins, and University of Wisconsin solution was cytotoxic, whereas normothermic exposure to St. Thomas' cardioplegia was not. In conclusion, the preservation solution that is the least harmful to endothelial cells at hypothermia is Bretschneider HTK cardioplegic solution.


Coactivation of the PI3K/Akt and ERK signaling pathways in PCB153-induced NF-κB activation and caspase inhibition.
Polychlorinated biphenyls (PCBs) are a group of persistent and widely distributed environmental pollutants that have various deleterious effects, e.g., neurotoxicity, endocrine disruption and reproductive abnormalities. In order to verify the hypothesis that the PI3K/Akt and MAPK pathways play important roles in hepatotoxicity induced by PCBs, Sprague-Dawley (SD) rats were dosed with PCB153 intraperitoneally at 0, 4, 16 and 32mg/kg for five consecutive days; BRL cells (rat liver cell line) were treated with PCB153 (0, 1, 5, and 10μM) for 24h. Results indicated that the PI3K/Akt and ERK pathways were activated in vivo and in vitro after exposure to PCB153, and protein levels of phospho-Akt and phospho-ERK were significantly increased. Nuclear factor-κB (NF-κB) activation and caspase-3, -8 and -9 inhibition caused by PCB153 were also observed. Inhibiting the ERK pathway significantly attenuated PCB153-induced NF-κB activation, whereas inhibiting the PI3K/Akt pathway hardly influenced phospho-NF-κB level. However, inhibiting the PI3K/Akt pathway significantly elevated caspase-3, -8 and -9 activities, while the ERK pathway only synergistically regulated caspase-9. Proliferating cell nuclear antigen (PCNA), a reliable indicator of cell proliferation, was also induced. Moreover, PCB153 led to hepatocellular hypertrophy and elevated liver weight. Taken together, PCB153 leads to aberrant proliferation and apoptosis of hepatocytes through NF-κB activation and caspase inhibition, and coactivated PI3K/Akt and ERK pathways play critical roles in PCB153-induced hepatotoxicity.


Neospora caninum infection in stray and farm dogs: seroepidemiological study and oocyst shedding.
In a previous study, farm and stray dogs were considered potential high risk populations of Neospora caninum infection in Spain. Consequently, we decided to investigate the significance of N. caninum infection in these populations. Specific antibodies were detected in 120 out of 275 dog sera (43.6%), with titres ranging from 1:50 to 1:800. Differences in seroprevalence between farm (47.5%, 67/141) and stray (39.5%, 53/134) dogs were not significant (P>0.05; χ(2) test), but farm dogs showed significantly higher titres (P<0.01; Student's t-test). N. caninum seroprevalence in farm dogs was associated with increasing age (P<0.01; χ(2) test) and dogs with free access to the farm were more likely to be seropositive than controlled-dogs (P<0.05; χ(2) test). The presence of anti-N. caninum antibodies was more often detected in dogs from farms with 5-20% N. caninum within-herd seroprevalence (56.9%, 37/65) than those from farms with 0-5% seroprevalence (38%, 23/60) (P<0.05; χ(2) test). We microscopically observed N. caninum-like oocysts in the faeces from one farm dog, but the number of oocysts was very low, and the aetiology could not be confirmed. Also, parasite isolation was attempted from fresh neural tissue from stray dogs but was unsuccessful.


Effects of off-pump versus on-pump coronary artery bypass grafting on function and viability of circulating endothelial progenitor cells.
Off-pump coronary artery bypass grafting may result in fewer myocardial and vascular complications than on-pump. Although differences in aortic manipulations likely play a role, the systemic responses of endothelial progenitor cells to both types of operations have not been examined. We sought to examine endothelial progenitor cell characteristics after off-pump versus on-pump coronary artery bypass grafting. Twenty patients undergoing off-pump or on-pump coronary artery bypass grafting were prospectively enrolled and had endothelial progenitor cells isolated and cultured from their peripheral blood before and 24 hours after surgery. Endothelial progenitor cells were identified by fluorescent dual lectin/low-density lipoprotein binding. Their number, phenotype characteristics, proliferation, migratory function, and viability were determined in a blinded fashion. Patient characteristics and numbers of grafts were equivalent. Endothelial progenitor cells had similar phenotypes between groups before and after surgery. Off-pump and on-pump coronary artery bypass grafting resulted in similar increases in endothelial progenitor cell numbers and showed equivalent proliferation activity. However, endothelial progenitor cell migratory function was higher in off-pump patients (25.3 +/- 5.0 vs 5.0 +/- 1.0 cells per high-powered field for off-pump vs on-pump coronary artery bypass grafting, respectively; P = .04). Postoperative endothelial progenitor cell viability adjusted for preoperative baseline was also higher after off-pump than on-pump coronary artery bypass grafting by 72.4% +/- 14.6% (P = .01). Endothelial progenitor cells of on-pump patients were less viable after surgery than before surgery, whereas the reverse was observed in off-pump patients. Both on-pump and off-pump coronary artery bypass grafting elicit mobilization of endothelial progenitor cells into the peripheral blood. On-pump coronary artery bypass grafting, however, impairs the migratory function and viability of these vascular repair cells, which are conversely preserved after off-pump surgery. Further work is necessary to determine whether the function and viability of endothelial progenitor cells correlate with vascular outcomes and whether their therapeutic modulation may one day benefit coronary artery bypass grafting patients.


Contemporary Management of Parapharyngeal Tumors.
Management of parapharyngeal tumors is challenging due to the complex anatomic nature of the space and the wide range of pathologies encountered. This article will review the anatomy, common pathologies, and management of parapharyngeal masses. Surgical strategies are also reviewed. Masses of the parapharyngeal space are most commonly benign (80%). More recent longitudinal studies have shown that observation and non-surgical therapy are indicated in many cases. When surgery is indicated, innovative endoscopic and robotic-assisted techniques allow for improved visualization and complete tumor removal while avoiding significant blood loss, tumor spillage, and injury to surrounding nerves and vessels. Management of parapharyngeal masses should consider morbidity of surgical resection versus the natural course of the disease. Surgical strategy is determined by location, size, and pathology. Adequate access is needed surgically to ensure complete resection and avoid tumor rupture.


Anti-inflammatory effects of doxepin hydrochloride against LPS-induced C6-glioma cell inflammatory reaction by PI3K-mediated Akt signaling.
Recent studies have shown that tricyclic antidepressants (TCAs) may have anti-inflammatory and anticonvulsant effects in addition to its antidepressant effects. So far, the nonantidepressant effects of TCAs and their molecular pharmacological mechanisms remain completely unclear. Chronic inflammation in the brain parenchyma may be related to the pathogenesis and progression of various neurodegenerative diseases. As a common antidepressant and anti-insomnia drug, doxepin also may be a potential anti-inflammatory and anticonvulsant drug, so the study on the anti-inflammatory protective effect of doxepin and its molecular mechanism has become a very important issue in pharmacology and clinical medicine. Further elucidating the anti-inflammatory and neuroprotective effects of doxepin and its molecular mechanism may provide the important theoretical and clinical basis for the prevention and treatment of neurodegenerative disease. This study was designed to understand the glio-protective mechanism of doxepin against the inflammatory damage induced by lipopolysaccharide (LPS) exposure in C6-glioma cells. We found the treatment of C6-glioma cells with LPS results in deleterious effects, including the augmentation of inflammatory cytokine levels (tumor necrosis factor-α, interleukin-1β), and suppresses the Akt phosphorylation. Furthermore, our outcomes demonstrated that doxepin was able to suppress these effects induced by LPS, through activation of the phosphatidylinositol-3-kinase-mediated protein kinase B (Akt) pathway. To sum up, these results highlight the potential role of doxepin against neuroinflammatory-related disease in the brain.


The perception of expressive timing in music.
This paper is concerned with the perception of small-scale timing changes in musical sequences. The control and expressive function of these have been studied quite extensively from a production perspective, but not much is known about listeners' ability to detect them. A pilot study and two experiments are reported which investigate the detectability of different amounts of timing change in different sequential positions, different pitch contexts, and against the background of both metronomic and expressive comparisons. The results show that listeners are able to perceive as little as 20 ms lengthening in the context of notes lasting between 100 and 400 ms, and that this threshold appears not to be a function of base duration in this range. Sequential position and pitch structure influence the detectability of timing changes to a limited extent, for which some possible explanations are offered. A case is made for regarding timing in music as both a medium to convey structure and an object in its own right, suggesting that it may be perceptually organized in two different ways--as the consequence of a structural interpretation and as a directly registered quantity.


Problematic online behaviors and psychopathology in Australia.
This study aimed to ascertain frequency rates and predictors of six problematic online behaviors (POBs) in an Australian sample. Participants (N = 1626) completed instruments measuring problematic online gaming, cyberchondria, problematic cybersex, problematic online shopping, problematic use of social networking sites, problematic online gambling, anxiety, depression and attention deficit/hyperactivity disorder (ADHD). Each POB was presumed to be present based on the cut-off score on the corresponding instrument and at least one indicator of interference with functioning. Generalized linear model analyses were used to determine socio-demographic and psychopathological predictors of each POB. The most common POB was problematic online shopping (12.2%), followed by problematic online gambling (11.4%), problematic use of social networking sites (6.0%), problematic cybersex (5.3%), problematic online gaming (5.2%) and cyberchondria (4.6%). Age group 27-36 had the highest rates of POBs. The intensity of ADHD symptoms predicted all POBs, whereas younger age predicted all POBs except for problematic cybersex and online gambling. Female gender predicted lower scores on the measures of problematic online gaming and cybersex. These findings have implications for age- and gender-adapted education, prevention and treatment efforts and suggest that specific POBs should be investigated separately instead of lumping them together under the umbrella terms such as "Internet addiction".


FT-IR and FT-Raman, NMR and UV spectroscopic investigation and hybrid computational (HF and DFT) analysis on the molecular structure of mesitylene.
The spectroscopic properties of mesitylene were investigated by FT-IR, FT-Raman, UV, (1)H and (13)C NMR techniques. The geometrical parameters and energies have been obtained from density functional theory (DFT) B3LYP method and Hartree-Fock (HF) method with 6-311++G(d,p) and 6-311G(d,p) basis sets calculations. The geometry of the molecule was fully optimized, vibrational spectra were calculated and fundamental vibrations were assigned on the basis of the total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM) method and PQS program. Total and partial density of state (TDOS and PDOS) and also overlap population density of state (OPDOS) diagrams analysis were presented. (13)C and (1)H NMR chemical shifts were calculated by using the gauge-invariant atomic orbital (GIAO) method. The electronic properties, such as excitation energies, oscillator strength, wavelengths, HOMO and LUMO energies, were performed by time-dependent density functional theory (TD-DFT) results complements with the experimental findings. The results of the calculations were applied to simulate spectra of the title compound, which show excellent agreement with observed spectra. Besides, frontier molecular orbitals (FMO), molecular electrostatic potential (MEP) and thermodynamic properties were performed. Reduced density gradient (RDG) of the mesitylene was also given to investigate interactions of the molecule.


From galactorrhea to osteopenia: rethinking serotonin-prolactin interactions.
The widespread use of the selective serotonin reuptake inhibitors (SSRIs) has been accompanied by numerous reports describing a potential association with hyperprolactinemia. Antipsychotics are commonly known to elevate serum prolactin (PRL) through blockade of dopamine receptors in the pituitary. However, there is little awareness of the mechanisms by which SSRIs stimulate PRL release. Hyperprolactinemia may result in overt symptoms such as galactorrhea, which may be accompanied by impaired fertility. Long-term clinical sequelae include decreased bone density and the possibility of an increased risk of breast cancer. Through literature review, we explore the possible pathways involved in serotonin-induced PRL release. While the classic mechanism of antipsychotic-induced hyperprolactinemia directly involves dopamine cells in the tuberoinfundibular pathway, SSRIs may act on this system indirectly through GABAergic neurons. Alternate pathways involve serotonin stimulation of vasoactive intestinal peptide (VIP) and oxytocin (OT) release. We conclude with a comprehensive review of clinical sequelae associated with hyperprolactinemia, and the potential role of SSRIs in this phenomenon.


Project Y: The search for clues explaining phenotype variability in MS.
To study phenotypic variability in MS patients, well-defined unbiased cohort studies are necessary. The most common and probably most important confounding factor when studying disease phenotype in MS is age. To describe study design and subject characteristics of a unique birth cohort (Project Y). The overall aim of Project Y is to identify determinants associated with phenotypic variability in MS, eliminating the possibility of confounding by age. Project Y is a population-based cross-sectional study of all people with MS born in the Netherlands in 1966. Patients and healthy controls were subjected to comprehensive examinations: functional and static imaging, physical and cognitive measurements, and lifestyle factors early and later in life. In addition body fluids were collected and stored for future biomarker research. 452 eligible MS patients were identified. Between December 2017 and January 2021, 367 MS patients and 125 healthy controls participated. The total number of identified cases results in a current prevalence of at least 189/100.000 for people born in the year 1966 in The Netherlands. Project Y is a unique cohort designed to identify factors associated with phenotypic variability in MS patients without the confounding effects of age. This first description of the Project Y cohort indicates that the prevalence of MS in the Netherlands might be higher than previously presumed. Various studies using Project Y data are ongoing and results will be published in upcoming years.


Inflammatory arthritis: case review and primary care perspectives.
Inflammatory arthritis (IA) has significant physical, psychosocial and economic consequences. Delays in diagnosis and initiation of treatment significantly impact on prognosis. The infrequent, variable, non-specific and, sometimes, indolent presentation make recognition of IA by primary care physicians (PCPs) challenging. To undertake an in-depth case review assessing the diagnostic trajectory of patients diagnosed with IA to inform development of practical recommendations to facilitate timely recognition and referral of suspected IA to specialist services, a case review was undertaken in one UK general practice using a proforma to collect information on patient demographics, diagnostic activities (presentation to PCP, specialist referral and final diagnosis) and documentation of disease-specific features for all patients diagnosed with IA between January 2000 and February 2011. Cases were excluded if consultation notes, a definitive diagnosis or evidence of specialist assessment were absent. Twenty-four cases were included in the final analysis. Duration from first primary care presentation to specialist rheumatological referral ranged from 4 to 2,165 days. Undertaking radiographs significantly lengthened delays from presentation to referral. Patients with IA attended between 2 and 41 primary care appointments before being referred. None of the cases identified had a comprehensive record of symptoms documented in the medical record. Once patients present to primary care, specialist referral is not always in accordance with the urgency necessitated in current guidelines. Improving PCPs' knowledge and awareness of IA, development of screening tools and improvement in record keeping are proposed to facilitate early recognition and referral of IA and subsequently reduce the disease burden of IA.


Evaluation of the Food and Nutrient Database for Dietary Studies for use with a mobile telephone food record.
The development of a mobile telephone food record (mpFR) in which image analysis and volume estimation data can be indexed with the Food and Nutrient Database for Dietary Studies (FNDDS) has the potential to improve the accuracy of dietary assessment. To validate the mpFR for use with adolescents, a convenience sample of adolescents, aged 11-18 years, was recruited to eat all meals and snacks in a controlled feeding environment over a 24-hour period. Each food item matched a food code in the FNDDS 3.0. The objective of this analysis was to compare the measured energy and protein content of foods to the published values in the FNDDS. Duplicate plates of all meals and snacks were prepared, and samples of 20 foods were individually weighed, homogenized, freeze dried, and analyzed for energy with a bomb calorimeter and for protein with a Dumas nitrogen analyzer. Eleven of the twenty food items had energy values in the FNDDS within ±10% of the measured energy value. The measured energy and protein values from all foods correlated significantly with the energy (r=0.981, P<0.01) and protein (r= 0.911, P<0.01) values in the FNDDS. These results support the use of the FNDDS with the mpFR.


Isolation of Renewable Phenolics by Adsorption on Ultrastable Hydrophobic MIL-140 Metal-Organic Frameworks.
The isolation and separation of phenolic compounds from aqueous backgrounds is challenging and will gain in importance as we become more dependent on phenolics from lignocellulose-derived bio-oil to meet our needs for aromatic compounds. Herein, we show that highly stable and hydrophobic Zr metal-organic frameworks of the MIL-140 type are effective adsorbent materials for the separation of different phenolics and far outperform other classes of porous solids (silica, zeolites, carbons). The mechanism of the hydroquinone-catechol separation on MIL-140C was studied in detail by combining experimental results with computational techniques. Although the differences in adsorption enthalpy between catechol and hydroquinone are negligible, the selective uptake of catechol in MIL-140C is explained by its dense π-π stacking in the pores. The interplay of enthalpic and entropic effects allowed separation of a complex, five-compound phenol mixture through breakthrough over a MIL-140C column. Unlike many other metal-organic frameworks, MIL-140C is remarkably stable and maintained structure, porosity and performance after five adsorption-desorption cycles.


Absolute structure of the chiral pyrrolidine derivative (2S)-methyl (Z)-5-(2-tert-butoxy-1-cyano-2-oxoethylidene)pyrrolidine-2-carboxylate, a compound with low resonant scattering.
The enantiopure monopyrrolidine derivative (2S)-methyl (Z)-5-(2-tert-butoxy-1-cyano-2-oxoethylidene)pyrrolidine-2-carboxylate, C13H18N2O4, (1), represents a potential ligand and an attractive intermediate for the synthesis of chiral metal complexes. At the molecular level, the compound features an intramolecular N-H...O hydrogen bond; neighbouring molecules interact via N-H...N contacts to form chains along [100]. Due to its elemental composition, resonant scattering of the target compound is entirely insignificant for diffraction experiments with Mo Kα and small even for Cu Kα radiation. A preliminary study with the harder radiation type confirmed the chiral space group and the suitability of the single crystal chosen; as expected, the results concerning the absolute structure remained completely inconclusive. A second data collection with the longer wavelength gave satisfactory quality indicators for the correct handedness of the molecule, albeit with high standard uncertainties. The absolute configuration has been assessed independently: CD spectra for both enantiomers of the target molecule were calculated and the spectrum for the S-configured stereoisomer was in agreement with the experiment. The Cotton effect of (1) may be ascribed to π-π* transitions from HOMO to LUMO and from HOMO to LUMO+1. As both independent techniques agree with respect to the handedness of the target molecule, the absolute structure may be assigned with a high degree of confidence.


Using an anterior chamber maintainer to control intraocular pressure during phacoemulsification.
We describe a phacoemulsification technique that uses an anterior chamber maintainer (ACM) to control intraocular pressure. Continuous irrigation through the ACM maintains pressurized intraocular conditions throughout surgery and when the automated system is not activated. Intraocular pressure is stabilized at predetermined levels with minor fluctuations. Viscoelastics can be used in conjunction with the ACM.


Cephaloceles: classification, pathology, and management.
A cephalocele is defined as a herniation of cranial contents through a defect in the skull. Cephaloceles are classified according to their contents and location. We have reviewed a total of 112 patients with cephaloceles, 51 of whom had sincipital meningoencephaloceles (fronto-ethmoidal meningoencephaloceles). This group is distinctive in its demographic distribution, in the effect on growth of other facial structures, and in the combined craniofacial approach needed to treat them. This review is based on the sincipital encephaloceles with the other cephaloceles included for completeness. Despite many theories, the cause of congenital cephalocele is not known. Preoperative work-up includes 3-dimensional computed tomography scan of the facial skeleton, and surgical management is multidisciplinary in nature. The aim is to remove the lesion before the deformity has time to greatly distort facial growth, which appears to realign itself after surgery. The 50 patients who underwent surgery for fronto-ethmoidal encephalocele all survived with minimal complications.


Treatment Options for Persistent Coagulase Negative Staphylococcal Bacteremia in Neonates.
Coagulase-negative staphylococci (CoNS) are the leading cause of late-onset sepsis in neonatal intensive-care units (NICUs). Despite adequate therapeutic levels and in vivo susceptibility, vancomycin is not always adequate in clearing CoNS bacteremias and other theurapeutic regimens are warranted especially when dealing with persistent CoNS bacteremias. Retrospective analysis of neonates with persistent CoNS bacteremias in a tertiary NICU in two study periods (January 2006 to December 2007 and January 2011 to December 2012). Demographics, clinical characteristics and antibiotics used were recorded. We also performed a literature review on the treatment options for persistent CoNS bacteremia. Out of the 1485 admissions during the 4 years, 121 (8,1%) neonates developed CoNS bacteremia and 42 of them (34.7%) were persistent. The most common CoNS species was S.epidermidis (91%). Apart from the shorter mean duration of bacteremia (p = 0.003), during the second part of the study, no other differences were observed between the two study periods. Ten (23.8%) neonates were treated with vancomycin monotherapy. In 23 (54.7%) neonates, rifampicin was added to vancomycin. Linezolid was given to seven neonates (16.6%), whereas daptomycin was given to two neonates (4.7%). No differences were found when we compared the characteristics of neonates treated with different antibiotics. All neonates tolerated treatment well. Our literature review revealed 16 relevant studies, the majority of which are small case series. The addition of rifampicin, linezolid and daptomycin in neonates with persistent CoNS bacteremia can provide useful therapeutic alternatives. Further studies are required to bring more insight into the field.


Do Naturally Modified Nucleotides Contribute to Stabilizing Complexes between Ribosomes and Small Molecules? A Case Study with the Antitumor Drug Homoharringtonine.
Modified nucleotides are ubiquitous with RNAs, also in contact with drugs that target the ribosome. Whether this represents a stabilization of the drug-ribosome complex, thus affecting the drug's affinity and possibly also intrinsic efficacy, remains an open question, however. The challenge of answering this question has been taken here with the only human-ribosome-targeting small-molecule currently in clinical use, the antitumor plant alkaloid homoharringtonine (HHT). The approach consisted in dissecting HHT-nucleotide interaction energies from QM-MM simulations in explicit water. What emerged is a network of mostly weak interactions of the large, branched HHT with standard nucleotides and a single modified nucleotide, out of the four ones present at PCT's A site. This is unlike the case of the small, compact marine antitumor alkaloid agelastatin A, which displays only a few, albeit strong, interactions with site-A ribosome nucleotides. This should aid tailoring drugs targeting the ribosome.


[The imprint cytology: a tool diagnosis in the operating room].
since 1929, the imprint cytology has a great value in the transoperatory as a diagnostic tool and in some cases as an alternate method. during two years period, 416 transoperatory specimens and 384 frozen sections were performed in the Pathology and Cytopathology Department of the University Hospital, "Dr. José E. Gonzalez." Diagnoses were recorded and compared both methods with the final diagnosis given at definitive histological sections. The results were evaluated and p statistics were performed. nine of 416 patients (2.2 %) were incorrectly diagnosed by cytology, and 8 of 384 (2.1 %) by frozen section. The diagnostic accuracy for the imprint cytology was 97.8 % and 97.9 % for frozen section. Six of the 416 cases (1.4 %) were misdiagnosed by imprints and frozen sections; the percentage success was 98.5 % using both methods together. The p was statistically significant (0.0005). the transoperatory cytology is a fast, easy and inexpensive. It provides morphological detail on intact cells and without the freezing artifacts, so its use as an adjunct to the frozen method is of great value.


New pathogen, same disparities: why COVID-19 and HIV remain prevalent in U.S. communities of colour and implications for ending the HIV epidemic.
The U.S. Ending the HIV Epidemic (EHE) Initiative was launched nationally in February 2019. With a target of ending the HIV epidemic by 2030, EHE initially scales up effective HIV prevention and care in 57 localities that comprise the greatest proportion of annual HIV diagnoses in the United States (US). However, the EHE effort has been eclipsed by another infectious disease 11 months into the Initiative's implementation. SARS-COV-2, a novel coronavirus, has infected more than eight million Americans and at least 223 000 (as of 23 October 2020) have succumbed to the disease. This commentary explores the social conditions that place communities of colour at greater risk for COVID-19 and HIV, and assesses challenges to EHE in a post-COVID-19 universe. One of the many common threads between HIV and COVID-19 is the disproportionate impact of each disease among communities of colour. A recent report by the National Academy of Sciences surmised that as much as 70% of health outcomes are due to health access, socio-economic factors and environmental conditions. Social determinants of health associated with greater HIV burden in Black and Brown communities have re-emerged in epidemiological studies of disproportionate COVID-19 cases, hospitalizations and deaths in communities of colour. Using data from the scientific literature, this commentary makes direct comparisons between HIV and COVID-19 racial disparities across the social determinants of health. Furthermore, I examine three sets of challenges facing EHE: (1) Challenges that hamper both the EHE and COVID-19 response (i.e. insufficiently addressing the social determinants of health; amplification of disparities as new health technologies are introduced) (2) Challenges posed by COVID-19 (i.e. diverting HIV resources to address COVID-19 and tapering of EHE funding generally); and (3) Challenges unrelated to COVID-19 (i.e. emergence of new and related health disparities; repeal of the Affordable Care Act and long-term viability of EHE). Racism and discrimination place communities of colour at greater risk for COVID-19 as well as HIV. Achieving and sustaining an end to the U.S. HIV epidemic will require structural change to eliminate conditions that give rise to and maintain disparities.


In Vivo three-dimensional kinematics of normal knees during sitting sideways on the floor.
The normal knee kinematics during asymmetrical kneeling such as the sitting sideways remains unknown. This study aimed to clarify in vivo kinematics during sitting sideways of normal knees. Twelve knees from six volunteers were examined. Under fluoroscopy, each volunteer performed a sitting sideways. A two-dimensional/three-dimensional registration technique was used. The rotation angle, varus-valgus angle, anteroposterior translation of the medial and lateral sides of the femur relative to the tibia, and kinematic pathway in each flexion angle was evaluated. Bilateral knees during sitting sideways showed a femoral external rotation relative to the tibia with flexion (ipsilateral: 13.7 ± 3.5°, contralateral: 5.8 ± 6.8°). Whereas the ipsilateral knees showed valgus movement of 4.6 ± 2.5° from 130° to 150° of flexion, and the contralateral knees showed varus movement of -3.1 ± 4.4° from 110° to 150° of flexion. The medial side of the contralateral knees was more posteriorly located than that of the ipsilateral knees beyond 110° of flexion. The lateral side of the contralateral knees was more anteriorly located than that of the ipsilateral knees from 120° to 150° of flexion. In the ipsilateral knees, a medial pivot pattern followed by a bicondylar rollback was observed. In the contralateral knees, no significant movement followed by a bicondylar rollback was observed. Even though the asymmetrical kneeling such as sitting sideways, the knees did not display asymmetrical movement.


Immunostaining of skeletal and cardiac muscle surface membrane with antibody against Duchenne muscular dystrophy peptide.
Duchenne muscular dystrophy (DMD) is a debilitating X-linked muscle disease. We have used sequence information from complementary DNA clones, derived from the gene that is deleted in DMD patients, to generate an antiserum that stains the surface membrane of intact human and mouse skeletal muscle, but not that of DMD patients and mdx mice. Here we identify the protein reacting with this antiserum as a single component of relative molecular mass 210,000 (Mr = 210K) that fractionates with a low-ionic strength extract of intact human and mouse skeletal muscle. It is therefore distinct from the 400 K protein found in the heavy microsomal fraction of normal muscle and identified as a putative product of the DMD gene. We also analyse further the disease specificity of the antiserum. Positive staining is seen in normal controls, and in samples from patients with a wide range of muscular dystrophies other than DMD. Becker muscular dystrophy, which is allelically related to DMD, was the only other exception, and gave a sporadic staining pattern. The demonstration of a specific defect in the surface membrane of DMD muscle fibres substantiates the hypothesis that membrane lesions may initiate muscle degradation in DMD.


Prostacyclin (PGI2) decreases the cyclic AMP level in coronary arteries.
The effects of prostacyclin (PGI2) on vascular tension and cAMP content were measured in isolated bovine coronary artery strips. 3 nM PGI2 did not alter the tension but diminished the cAMP content by 56% of the control level (P less than 0.005). 30 and 300 nM PGI2 diminished the tension and further reduced the cAMP content, which amounted to only 5% of the control at 300 nM PGI2. These results are in contrast to the increase in cAMP level by PGI2 in blood platelets and might indicate a different mechanism of action of PGI2 in platelets and vascular tissue.


Fluoride release and absorption at different pH from glass-ionomer cements.
The aim of this study was to evaluate the fluoride release (release-tests) from two glass-ionomer cements (GIC), before and after NaF solution treatment (fluoride treatment) in different pH environments. After 21 days, every second sample was submitted to fluoride treatment to simulate a fluoride recharge. After fluoride treatment every second sample was submitted to a further three days of long release-tests. Sample surfaces were analyzed by SEM before and after the release-tests in all pH solutions studied. The present study showed that GICs released fluoride ions for the duration of the examination period. For both materials the amount of F(-) released at low pH was considerably greater than at higher pH. The massive superficial breaking up observed by SEM probably promoted the releasing processes. Recharge is possible at different pH levels using NaF solution. Fluoride release may depend on GICs surface degradation caused by pH in the solution. The use of this kind of material may be an important issue in patients with with low pH saliva and with a high risks caries.


RET oncoproteins induce tyrosine phosphorylation changes of proteins involved in RNA metabolism.
We report the identification of proteins induced in response to RET/PTC2, an oncogene implicated in thyroid cancers. Anti-phosphotyrosine antibody affinity resin was used to purify Tyr(P)-containing and interacting proteins from 293T and NIH3T3 cells which were transfected with kinase active or inactive RET/PTC and RETMEN2 oncogenes. Proteins were separated by one-dimensional SDS-PAGE, extracted by in-gel digestion, and identified by MALDI-TOF peptide mass fingerprinting. The expression and tyrosine phosphorylation of Sam68, a protein implicated in mRNA nucleocytoplasmic translocation and splicing, were further examined in RET-transfected cells and thyroid tumors. Of relevance, cells transfected with RETMEN2B examined for anti-phosphotyrosine bound proteins, showed other proteins implicated in splicing: DEAD-box p68 RNA helicase, SYNCRIP, and hnRNP K. Western blotting analysis suggested that these proteins are singularly tyrosine phosphorylated in RETMEN2B-transfected cells, and that they constitutively bind with Sam68. The study concludes that regulation of splicing factors is likely to be important in RET-mediated thyroid carcinogenesis.


International consensus recommendations for outcome measurement in post-stroke arm rehabilitation trials.
Existing randomized controlled trials (RCTs) of arm rehabilitation interventions after stroke use a wide range of outcome measures, limiting ability to pool data to determine efficacy. Published recommendations also lack stroke survivor, carer and clinician involvement specifically about perceived relevance and importance of outcomes and measures. To generate international consensus recommendations for selection of outcome measures for use in future stroke RCTs in arm rehabilitation, considering outcomes important to stroke survivors, carers and clinicians. The recommendations are the Standardizing Measurement in Arm Rehabilitation Trials (SMART) Toolbox. Two-round international e-Delphi Survey and consensus meeting. Online and University. Fifty-five researchers and clinicians with expertise in stroke upper limb rehabilitation from 18 countries (e-Delphi); N.=13 researchers and clinicians, N.=2 stroke survivors, N.=1 carer (consensus meeting). Using systematically identified outcome measures from published RCTs, we conducted a two-round international e-Delphi Survey with researchers and clinicians to identify the most important measures for inclusion in the toolbox. Measures that achieved ≥60% consensus were categorized using the International Classification of Functioning, Disability and Health Framework (ICF); psychometric properties were ascertained from literature and research resources. At a final consensus meeting, expert stakeholders selected measures for inclusion in the toolbox. e-Delphi participants recommended 28/170 measures for discussion at the final consensus meeting. Expert stakeholders (N.=16) selected the Visual Analogue Scale for pain/0-10 Numeric Pain Rating Scale, dynamometry, Action Research Arm Test, Wolf Motor Function Test, Barthel Index, Motricity Index and Fugl-Meyer Assessment (upper limb section of each), Box and Block Test, Motor Activity Log 14, Nine Hole Peg Test, Functional Independence Measure, EQ-5D, Canadian Occupational Performance Measure and Modified Rankin Scale for inclusion in the toolbox. The SMART Toolbox provides a refined selection of measures that capture outcomes considered important by stakeholders for each ICF domain. The toolbox will facilitate data aggregation for efficacy analyses thereby strengthening evidence to inform clinical practice. Clinicians can also use the toolbox to guide selection of measures ensuring a patient-centered focus.


Florid periosteal reaction and focal fibrocartilaginous dysplasia.
Focal fibrocartilaginous dysplasia (FFCD) is a rare condition causing tibia vara in childhood. It is characterized by progressive tibia vara in young children with a characteristic radiographic lesion. This paper is thought to be the first to describe FFCD exhibiting florid periosteal reaction at the time of presentation with a subtle faint osteolytic lesion in the diametaphysis of the proximal tibia.


A taste of what to expect: top-down modulation of neural coding in rodent gustatory cortex.
A central aspect of sensory perception is the anticipation of forthcoming stimuli, allowing for a faster and more accurate assessment of the surrounding environment. A new study by Samuelsen et al. (2012) in this issue of Neuron highlights the neural mechanisms underlying the expectation of an imminent taste.


Sodium outflux and influx within nerve terminals from chronic epileptogenic foci.
The Na+-pump (oMpNa) or maximal sodium outflux inhibited by ouabain was studied in nerve terminals isolated from the primary and mirror epileptogenic foci of freezing lesions. In addition, the Na+ for Na+ exchange diffusion that is sensitive to ethacrynic acid and furosemide was also analyzed. oMpNa in control and epileptogenic states had similar and indistinguishable activation curves for K0 (extracellular K) in a sodium medium except for a two-fold difference in magnitude. However, the apparent affinity of the Na+-pump for K0 as measured by K1/2 was shifted to the right or decreased in epileptogenic foci (2 mM K0 compared to 0.5 mM in controls) when measured in a magnesium medium. A decrease in the apparent affinity for internal sodium was also observed. Of the total sodium outflux (67.7 nmol/mg/min), Na+ movements which are insensitive to ouabain and external K+ but stimulated by external Na+ and inhibited by furosemide and ethacrynic acid (20 nmol/mg/min or 32% of sodium outflux) represented the Na+ for Na+ exchange diffusion in nerve terminals. Na+ influx rising with increasing internal sodium in the presence of ouabain and blocked by furosemide represent the corresponding inward Na+ movement. No differences were observed between controls and epileptogenic states.


Experimental immunological intrahepatic cholestasis model.
Heat-killed Propionibacterium acnes (P. acnes) was intravenously injected into tuberculin-sensitized guinea pigs, and 7 days later, purified protein derivative (PPD) was also injected intravenously resulting in marked reductions in bile flow and bile acid excretion. Serum levels of bile acids and cholesterol were increased, and the activities of alkaline phosphatase (ALK-p) and leucine aminopeptidase (LAP) were also elevated. Histological examination revealed dilatation of bile canaliculi and diminution of microvilli. These results indicated that intrahepatic cholestasis was induced. These pathological changes were not detected in guinea pigs in which PPD was not injected. In this experimental model, the tuberculin-sensitized lymphocytes were infiltrated into the liver by P. acnes injection and the cholestatic factor was produced by PPD injection, resulting in the induction of intrahepatic cholestasis.


Electrophoretic analysis of phosphorylation of the yeast 20S proteasome.
The 26S proteasome complex, consisting of two multisubunit complexes, a 20S proteasome and a pair of 19S regulatory particles, plays a major role in the nonlysosomal degradation of intracellular proteins. The 20S proteasome was purified from yeast and separated by two-dimensional gel electrophoresis (2-DE). A total of 18 spots separated by 2-DE were identified as the 20S proteasome subunits by peptide mass fingerprinting with matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). The alpha2-, alpha4- and alpha7-subunits gave multiple spots, which converged into one spot for each subunit when treated with alkaline phosphatase. The difference of pI between phosphorylated and dephosphorylated spots and their reaction against anti-phosphotyrosine antibody suggested that the alpha2- and alpha4-subunits are phosphorylated either at Ser or at Thr residue, and the alpha7-subunit is phosphorylated at Tyr residue(s). These phosphorylated subunits were analyzed by electrospray ionization-quadrupole time of flight-tandem MS (ESI-QTOF-MS/MS) to deduce the phosphorylation sites. The 20S proteasome has three different protease activities: chymotrypsin-like, trypsin-like and peptidylglutamyl peptide-hydrolyzing activities. The phosphatase treatment increased K(m) value for chymotrypsin-like activity of the 20S proteasome, indicating that phosphorylation may play an important role in regulating the proteasome activity.


Analysis of protein kinase C delta (PKC delta) expression in endometrial tumors.
Endometrial cancer is the most common gynecologic malignancy in the United States. However, its underlying molecular mechanisms are poorly understood; and few prognostic indicators have been identified. The protein kinase C (PKC) family has been shown to regulate pathways critical to malignant transformation; and in endometrial tumors, changes in PKC expression and activity have been linked to a more aggressive phenotype and poor prognosis. We have recently shown that PKC delta is a critical regulator of apoptosis and cell survival in endometrial cancer cells; however, PKC delta levels in endometrial tumors had not been determined. We used immunohistochemistry to examine PKC delta protein levels in normal endometrium and endometrioid carcinomas of increasing grade. Normal endometrium exhibited abundant nuclear and cytoplasmic staining of PKC delta confined to glandular epithelium. In endometrial tumors, decreased PKC delta expression, both in intensity and fraction of epithelial cells stained, was observed with increasing tumor grade, with PKC delta being preferentially lost from the nucleus. Consistent with these observations, endometrial cancer cell lines derived from poorly differentiated tumors exhibited reduced PKC delta levels relative to well-differentiated lines. Treatment of endometrial cancer cells with etoposide resulted in a translocation of PKC delta from cytoplasm to nucleus concomitant with induction of apoptosis. Decreased PKC delta expression, particularly in the nucleus, may compromise the ability of cells to undergo apoptosis, perhaps conferring resistance to chemotherapy. Our results indicate that loss of PKC delta is an indicator of endometrial malignancy and increasing grade of cancer. Thus, PKC delta may function as a tumor suppressor in endometrial cancer.


Improvement of informed consent and the quality of consent documents.
Guidelines on informed consent intend to protect patients and promote ethical research conduct. To give informed consent, individuals should understand the purpose, process, risks, benefits, and alternatives to research (or a proposed clinical intervention) and make a free, voluntary decision about whether to participate. Many participants have incomplete understanding of various features of clinical trials. Issues associated with the length, format, and language of documents for written informed consent are common. Here, we analyse the written consent form, particularly in the context of clinical research, and the discussions that take place between clinician or investigator and patient. We review strategies to improve consent forms, particularly the use of plain language. Recommendations are made on discussions between investigator and patient to improve participant comprehension and satisfaction with the informed-consent process.


Implementing team-based learning in a nurse practitioner curriculum.
Team-based learning (TBL) is an innovative, learner-centered teaching strategy that promotes active learning. The authors describe their experience with implementing TBL in an adult-gerontology acute and primary care course for nurse practitioners as well as their evaluation of student outcomes.


COVID-19 experiences predicting high anxiety and depression among a sample of BRCA1/BRCA2-positive women in the US.
During the COVID-19 pandemic, breast and ovarian cancer survivors experienced more anxiety and depression than before the pandemic. Studies have not investigated the similarities of this trend among BRCA1/2-positive women who are considered high risk for these cancers. The current study examines the impact of COVID-19 experiences on anxiety and depression in a sample of BRCA1/2-positive women in the U.S. 211 BRCA1/2-positive women from medically underserved backgrounds completed an online survey. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression for associations between COVID-19 experiences and self-reported anxiety and depression stratified by demographic factors. Overall, women who reported COVID-19 stigma or discrimination (aOR, 5.14, 95% CI [1.55, 17.0]) experienced significantly more depressive symptoms than women who did not report this experience. Racial/ethnic minority women caring for someone at home during COVID-19 were 3.70 times more likely (95% CI [1.01, 13.5]) to report high anxiety while non-Hispanic white women were less likely (aOR, 0.34, 95% CI [0.09, 1.30], p interaction = 0.011). To date, this is the first study to analyze anxiety and depression considering several COVID-19 predictors among BRCA1/2-positive women. Our findings can be used to inform future research and advise COVID-19-related mental health resources specific to these women.