Effect of desmopressin acetate on bleeding times and plasma von Willebrand factor in Doberman pinscher dogs with von Willebrand's disease.
Effects of desmopressin acetate (1-desamino-8-D-arginine vasopressin [DDAVP]) on plasma von Willebrand factor (vWf) were studied in 12 purebred Doberman pinschers confirmed to have von Willebrand's disease (vWd) (plasma vWf antigen [vWf:Ag] concentrations, less than 30 U/dl). Twelve dogs had subnormal plasma botrocetin cofactor (BCf) activity and 11 dogs had prolonged buccal mucosa bleeding times. Tranquilization of three dogs with lenperone and three dogs with xylazine did not induce significant changes in mean plasma vWf:Ag concentrations or mean BCf activities. Thirty and 120 minutes after administration of DDAVP (1 micrograms/kg subcutaneously), there was significant shortening of the mean buccal mucosa bleeding time. Ten dogs responded to DDAVP with increases in BCf activity which exceeded 10 U/dl at 30 or 120 minutes, or both, after the drug was administered. At the same time, increases in plasma vWf:Ag concentrations were smaller than the increases in BCf activity. It was shown by multimeric analysis that primarily the higher molecular weight forms of vWf increased in plasma in response to DDAVP.


Effects of repeated long-term psychosocial stress and acute cannabinoid exposure on mouse corticostriatal circuitries: Implications for neuropsychiatric disorders.
Vulnerability to psychiatric manifestations is achieved by the influence of genetic and environment including stress and cannabis consumption. Here, we used a psychosocial stress model based on resident-intruder confrontations to study the brain corticostriatal-function, since deregulation of corticostriatal circuitries has been reported in many psychiatric disorders. CB1 receptors are widely expressed in the central nervous system and particularly, in both cortex and striatum brain structures. The investigation presented here is addressed to assess the impact of repeated stress following acute cannabinoid exposure on behavior and corticostriatal brain physiology by assessing mice behavior, the concentration of endocannabinoid and endocannabinoid-like molecules and changes in the transcriptome. Stressed animals urinated frequently; showed exacerbated scratching activity, lower striatal N-arachidonylethanolamine (AEA) levels and higher cortical expression of cholinergic receptor nicotinic alpha 6. The cannabinoid agonist WIN55212.2 diminished locomotor activity while the inverse agonist increased the distance travelled in the center of the open field. Upon CB1 activation, N-oleoylethanolamide and N-palmitoylethanolamide, two AEA congeners that do not interact directly with cannabinoid receptors, were enhanced in the striatum. The co-administration with both cannabinoids induced an up-regulation of striatal FK506 binding protein 5. The inverse agonist in controls reversed the effects of WIN55212.2 on motor activity. When Rimonabant was injected under stress, the cortical levels of 2-arachidonoylglycerol were maximum. The agonist and the antagonist influenced the cortical expression of cholinergic receptor nicotinic alpha 6 and serotonin transporter neurotransmitter type 4 in opposite directions, while their co-administration tended to produce a null effect under stress. The endocannabinoid system had a direct effect on serotoninergic neurotransmission and glucocorticoid signaling. Cholinergic receptor nicotinic alpha-6 was shown to be deregulated in response to stress and following synthetic cannabinoid drugs thus could confer vulnerability to cannabis addiction and psychosis. Targeting the receptors of endocannabinoids and endocannabinoid-like mediators might be a valuable option for treating stress-related neuropsychiatric symptoms.


Cyclooxygenase-2 inhibitory 1,4-naphthoquinones from Impatiens balsamina L.
Significant selective cyclooxygenase-2 (COX-2) inhibitory activities were observed for two new 1,4-naphthoquinone sodium salts, sodium 3-hydroxide-2[[sodium 3-hydroxide-1,4-dioxo(2-naphthyl)]ethyl]naphthalene-1,4-dione (impatienolate) (1) and sodium 2-hydroxide-3-(2-hydroxyethyl)naphthalene-1,4-dione (balsaminolate) (2), which were isolated from the corolla of Impatiens balsamina L. (Balsaminaceae). Their structures were elucidated by spectral techniques. Our results offer evidence supporting the use of I. balsamina L. to treat articular rheumatism, pain, and swelling.


Insertional mutation in the intron 1 of Unc5h3 gene induces ataxic, lean and hyperactive phenotype in mice.
Mice carrying a mutation in the first intron of Unc5h3 were accidentally produced by transgenic insertion and characterized for their homozygous mutant phenotypes. Morphological and histological analysis revealed cerebellar and midbrain abnormalities, which are similar to the previously reported phenotypes of the Unc5h3 mutant. Behavioral analysis showed higher ambulatory activity and circling, and defects in habituation in a novel environment. Their body weights were 10-30% less than wildtype mice from 2-3 weeks of age to 22 months possibly due to reduced accumulation of adipose tissues. The transgenic insertion site was identified and mapped to the intron 1 of Unc5h3 gene with approximately 50 kb deletion of the intron sequence. This intronic mutation interfered with the mRNA expression of the Unc5h3 gene not in testes, but in many tissues including the brain, implying that this intronic region may play a role in regulating tissue-specific transcription of Unc5h3.


Assessment of clinical and pathological features of patients who underwent thyroid surgery: A retrospective clinical study.
To evaluate whether there was any correlation between the clinical parameters and final pathological results among patients who underwent thyroid surgery. We retrospectively analyzed parameters, including age, sex, complete blood cell count parameters, nodule diameter, nodule localization, thyroid function testing, and pathology reports, in patients who underwent thyroid surgery. The patients were divided into malignant (n = 92) and benign (n = 413) groups depending on the final pathological results. Both groups were compared for demographic and clinical parameters. The Kolmogorov-Smirnov normality test was used to determine if the quantitative variables had a normal distribution. The nonparametric Mann-Whitney U test was used to compare quantitative data that were not normally distributed, and Pearson's chi-squared test was used to compare the qualitative data. The correlation between the final pathological results and fine-needle aspiration biopsy findings was calculated using the cross-tabulation method. This study included 406 women and 99 men aged between 15 and 85 years. No significant differences were found between the groups with respect to age, sex, white blood cell count, neutrophil count, lymphocyte count, thrombocyte count, red cell distribution width, platelet distribution width, mean platelet volume, platecrit, nodule localization, and thyroid function testing. On the other hand, there were significant differences between the groups with respect to nodule size (P = 0.001), cervical lymphadenopathy (P = 0.0001) and nodular calcification (P = 0.0001). Compared with the malignant group, the benign group had a significantly greater nodule size (35.4 mm vs 27.6 mm). The best cut-off point (≤ 28 mm) for nodule size, as determined by the receiver operating characteristic curve, had a sensitivity and specificity of 67.7% and 64.4%, respectively. The correlation between fine-needle aspiration biopsy and the final pathological results was assessed using the cross-table method. The sensitivity and specificity of fine-needle aspiration biopsy were 60% and 98%, respectively. This study showed that significant differences existed between the malignant and benign groups with regard to nodule size, cervical lymphadenopathy, and nodular calcification.


Post-Progression Survival Influences Overall Survival among Patients with Advanced Non-Small Cell Lung Cancer Undergoing First-Line Pembrolizumab Monotherapy.
Among patients with non-small cell lung cancer (NSCLC), the impact of first-line treatment on overall survival (OS) may be influenced by subsequent therapies. Thus, using patient-level data, we assessed the relationships of progression-free survival (PFS) and post-progression survival (PPS) with OS among patients with high-programmed death-ligand 1 (PD-L1) expression undergoing first-line pembrolizumab monotherapy for NSCLC. We reviewed data from 133 patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC at 6 Japanese centers between February 2017 and December 2018. The correlations of PFS and PPS with OS were evaluated at the patient level. Linear regression analyses and Spearman's rank correlation coefficient revealed that PPS was strongly correlated with OS (r = 0.76, p < 0.05, R2 = 0.65), while PFS was only moderately correlated with OS (r = 0.71, p < 0.05, and R2 = 0.4). Furthermore, PPS was significantly associated with performance status at the end of pembrolizumab monotherapy, as well as the use of platinum-based combination chemotherapy after pembrolizumab monotherapy (both p < 0.05). Among patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC, PPS was more strongly correlated with OS, relative to the relationship between PFS and OS. Therefore, subsequent treatment appears to significantly influence OS in patients with disease progression following first-line pembrolizumab monotherapy.


The Burden of Wildfire Smoke on Respiratory Health in California at the Zip Code Level: Uncovering the Disproportionate Impacts of Differential Fine Particle Composition.
Wildfires constitute a growing source of extremely high levels of particulate matter that is less than 2.5 microns in diameter (PM2.5). Recently, toxicologic and epidemiologic studies have shown that PM2.5 generated from wildfires may have a greater health burden than PM2.5 generated from other pollutant sources. This study examined the impact of PM2.5 on hospitalizations for respiratory diseases in California between 2006 and 2019 using a health impact assessment approach that considers differential concentration-response functions (CRF) for PM2.5 from wildfire and non-wildfire sources of emissions. We quantified the burden of respiratory hospitalizations related to PM2.5 exposure at the zip code level through two different approaches: (a) naïve (considering the same CRF for all PM2.5 emissions) and (b) nuanced (considering different CRFs for PM2.5 from wildfires and from other sources). We conducted a Geographically Weighted Regression to analyze spatially varying relationships between the delta (i.e., the difference between the naïve and nuanced approaches) and the Centers for Disease Control and Prevention's Social Vulnerability Index (SVI). A higher attributable number of respiratory hospitalizations was found when accounting for the larger health burden of wildfire PM2.5. We found that, between 2006 and 2019, the number of hospitalizations attributable to PM2.5 may have been underestimated by approximately 13% as a result of not accounting for the higher CRF of wildfire-related PM2.5 throughout California. This underestimation was higher in northern California and areas with higher SVI rankings. The relationship between delta and SVI varied spatially across California. These findings can be useful for updating future air pollution guideline recommendations.


Effect of Bidispersity on Structure and Entanglement of Confined Polymer Films.
Using Monte Carlo simulations combined with a geometric primitive path analysis method (Z1 algorithm), we investigate the effect of bidispersity on the structure and entanglement of polymer films which consist of short (the molecular length is below the characteristic entanglement molecular length) and long (the molecular length is above the characteristic entanglement molecular length) chains between two neutral walls. Our results demonstrate the length-based migrations of chains in bidisperse films (the longer chains reside away from the walls and the shorter chains are close to the walls), which becomes more obvious with the decrease in the weight fraction of long chains. With decreasing the weight fraction of long chains, the number of short-long entanglements exhibits a dramatic increase, whereas the number of long-long entanglements exhibits a slight decrease, which indicates that short chains can significantly affect the local situations of entanglements of bidisperse polymer films. On the basis of the constraint release mechanism, our simulations imply that for the lower weight fraction of long chains, the local degree of confinement instead of the long-long entanglements has a marked effect on the relaxation of long chains, due to the fast relaxation of short chains dilating the tube diameter of long chains. However, for the higher weight fraction of long chains, after the relaxation of short chains, the long-long entanglements are in sufficient quantities to restrict long chains within a tube, which implies that the relaxation of long chains is hardly affected by the number of short-long entanglements. Our work can be helpful for understanding the microscopic structure and entanglement of bidisperse polymer films, which can provide computational support for their various technological applications.


Correlations between immunoglobulin- and antibody-synthesizing cells during primary and secondary immune responses of rats immunized with peroxidase.
The development of cells synthesizing immunoglobulins without detectable antibody activity and of antibody-synthesizing cells was studied during primary and secondary immune responses of rats immunized with horseradish peroxidase. After primary immunization with peroxidase emulsified in Freund's complete or incomplete adjuvant, the first antibody-producing cells appeared 4 days after injection. They were preceded by cells synthesizing IgG and IgM without antibody function, appearing 3 days after giving antigen. The ratio between the latter and the former population of cells regularly decreased during the primary response. Seventy to 100 per cent of cells synthesizing immunoglobulins without antibody activity were induced by the antigen, the remainder being induced by the adjuvant. In both populations, the positive cells were always immature or mature plasmocytes. At various times after primary injection, animals received a booster inoculation of soluble peroxidase or of peroxidase emulsified in Freund's adjuvant. Antibody-producing cells, in early stages of differentiation, appeared between 2 and 3 days after challenge and were not preceded by cells synthesizing immunoglobulins without antibody function. These latter cells were reduced or absent after secondary challenge. Increasing the sensitivity of detection of active sites of antibodies, by using direct methods of staining with fixed or unfixed cells gave no increase of antibody-producing cells.


Effect of dietary β-glucan on growth, survival and regulation of immune processes in rainbow trout (Oncorhynchus mykiss) infected by Aeromonas salmonicida.
The present study evaluated the effects of dietary β-glucan (0, 0.05%, 0.1%, and 0.2%) on growth performance after 42 days of feeding. Thereafter, rainbow trout (Oncorhynchus mykiss) were infected with Aeromonas salmonicida, and survival rates as well as the regulating processes of stress- and immune-related factors were analyzed. In general, higher dietary β-glucan levels obviously improved specific growth rate (SGR), weight gain (WG) and feed efficiency (FE) (P ≤ 0.05). Survival rates in β-glucan groups increased significantly compared with the control group after A. salmonicida infection (P ≤ 0.05). Serum total superoxide dimutase (T-SOD), peroxidase (POD) as well as catalase (CAT) activities, and their mRNA expressions in the head kidney of fish in the β-glucan groups generally increased to higher levels after infection, and more quickly, compared with in the control group. Serum lysozyme (LSZ) and its expression in the head kidney in β-glucan groups reached a higher peak earlier than in the control group. Serum glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels in the β-glucan groups were significantly lower than in the control group (P ≤ 0.05). The peak of heat shock protein 70 (HSP70) expression in the 0.2% β-glucan group was higher and occurred earlier than in other groups (P ≤ 0.05). These results confirm that 0.1% and 0.2% dietary β-glucan are beneficial for promoting growth in rainbow trout and enhancing resistance against A. salmonicida. Furthermore, β-glucan could play an important role in regulating stress- and immune-related factors in rainbow trout to more quickly fight against bacterial infection.


Fixed-point quantum search.
The quantum search algorithm consists of an iterative sequence of selective inversions and diffusion type operations, as a result of which it is able to find a state with desired properties (target state) in an unsorted database of size N in only sqrt[N] queries. This is achieved by designing the iterative transformations in a way that each iteration results in a small rotation of the state vector in a two-dimensional Hilbert space that includes the target state; if we choose the right number of iterative steps, we will stop just at the target state. This Letter shows that by replacing the selective inversions by selective phase shifts of pi/3, the algorithm preferentially converges to the target state irrespective of the step size or number of iterations. This feature leads to robust search algorithms and also to new schemes for quantum control and error correction.


Identification of a major PAF acetylhydrolase in human serum/plasma as a 43 kDa glycoprotein containing about 9 kDa asparagine-conjugated sugar chain(s).
Platelet-activating factor (PAF) acetylhydrolase from human serum/plasma was identified on a polyvinylidene difluoride (PVDF) membrane by electroblotting proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme activity was detected in the 43 kDa region on the membrane as a decrease in the beta-radioluminescence of [3H]acetyl-PAF or by the convenient method for determining PAF acetylhydrolase activity (the TCA precipitation method). The enzyme activity on treatment with N-glycosidase F shifted to the 34 kDa region on the PVDF membrane. On the other hand, only one band was observed, corresponding to a molecular mass of 53 kDa, on analysis by SDS-PAGE with silver staining. Treatment of the 53 kDa protein with N-glycosidase F changed its molecular mass to 43 kDa (protein A). The NH2-terminal 32 amino acid sequence of protein A completely corresponds to that of the heterogenous enzyme with 54 amino acids deleted from the NH2 terminus reported by Tjoelker et al. (Nature 374, 549-553, 1995). Even after trypsin treatment of the N-glycosidase F-digested enzyme, its PAF-AH activity remained in the 34 kDa region, but the contaminating protein A disappeared, on the PVDF membrane. In addition, the majority of serum PAF-AH was retained on a Sambucus sieboldiana agglutinin (SSA)-agarose column and was eluted with the hapten sugar, lactose. These results indicate that PAF acetylhydrolase consisting of a 34 kDa protein and about 9 kDa asparagine-conjugated sugar chain(s) is a major enzyme in human serum/plasma.


Influenza vaccine hesitancy in a low-income community in central New York State.
Influenza vaccine (IV) coverage rates remain suboptimal among US adults. Socioeconomic disparities exist in IV coverage. We describe influenza vaccine attitudes among a low-income community in central New York. Adults attending a Salvation Army function during December 2012 were surveyed regarding IV including their intention to be immunized. On-site IV was offered to eligible participants. The 1041 participants included Whites (non-Hispanics), African Americans, Hispanics, Native Americans, and multi-racial ethnicities. At time of enrollment, 386 (37%) participants had already received 2012-13 IV. Of the 655 unimmunized participants, 299 (46%) stated intent to receive IV, evenly distributed by age, gender, and ethnicity. Of the 312 participants who declined IV, 46% did so because of IV misperceptions. Of the 299 participants who intended to receive vaccine but had not yet done so, 284 (95%) stated the reason for delay was difficult access to vaccine. Intent to receive vaccine was strongly associated with the belief that IV is safe and/or effective (P < 0.05). IV misperceptions regarding IV efficacy and safety result in suboptimal vaccine uptake in this low-income community, regardless of age, gender, or ethnicity.


[Drug treatment of anxiety disorders].
Current customary medication with anxiolytic potential has different main-points of impact and individual potentials of risk, which influence strategies of therapy in a limiting way. Benzodiazepines--which are very effective in various anxiety-disorders--can therefore only be applied under well controllable conditions within a limited period of time, in order to reduce the risks of dependency. Also administration of low-doses neuroleptica--which within these doses also show a high potential of anxiety-impact beside a high tolerance--must be limited to a period of two or three months to prevent late development of dyskinesias. Main indications for the application of antidepressive drugs are panic-conditions, cases of phobia and depressive anxiety. In the following a therapy-pattern for management of panic-conditions with Clomipramin will be gone into more detailed. Complementary anxiolytic characteristics of Buspiron and beta-blockers with their specific indication-fields will be brought up.


Mutations of KRAS, NRAS, BRAF, EGFR, and PIK3CA genes in urachal carcinoma: Occurence and prognostic significance.
Targeted therapy represents an attractive alternative for rare tumors such as urachal carcinoma (UrC). The aim of this study was to assess the mutations of the most commonly affected 5 genes in the targetable EGFR-pathway in UrC and comapre their frequencies to those of found in urothelial and colorectal cancer. Mutational hot-spots of selected genes were tested in 22 UrC samples by pyrosequencing. Mutational patterns were compared to those published for colorectal and urothelial cancers. Furthermore, we sought correlations between mutations and clinicopathological and follow-up data. We found 11 mutations in 10 of 22 (45%) patients. The most frequently mutated gene was KRAS (27%) followed by BRAF (18%) and NRAS (5%), while no mutations were detected in the EGFR and PIK3CA genes. No correlation was found between the mutation status and clinicopathological parameters (Sheldon/Mayo stage, tumor grade, metastases). Furthermore, none of the mutations correlated with progression-free or overall survival. The mutation pattern of UrC is more similar to colorectal than to urothelial cancer. However, the mutation characteristics of UrC seems to be unique suggesting that clinical decision-making for UrC cannot be simply adopted from urothelial or colorectal carcinoma. The high occurence of EGFR-pathway mutations warrants the testing for KRAS and BRAF mutations when considering anti-EGFR therapy in UrC.


Pediatric resuscitation guidelines in the new millennium.
In year 2000, American Heart Association published the new guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. The new guidelines are the consensus of American Heart Association & International Liaison Committee on Resuscitation. There are a number of new changes concerning the knowledge and skills for the performance of basic and advanced cardiopulmonary resuscitation in adults, pediatric and neonatal patients based on evidence-based medicine principle. The new guidelines re-emphasize the importance of sequential ABCD approach during cardiopulmonary resuscitation and include many new changes resulting from the growing knowledge and skills concerning pediatric and neonatal cardiopulmonary resuscitation in recent years. As with previous editions of Pediatric Advanced Life Support & Neonatal Resuscitation Program textbooks, the pediatric and neonatal parts of the new guidelines were the collaborative efforts of subcommittees with members from American Heart Association, American Academy of pediatrics and the International Liaison Committee on Resuscitation. For each step, the new advances in the past few years were considered and discussed and were included in the new guidelines if scientific merit existed. The new changes are discussed and summarized within the text of the article, and in the end there is a table briefly listing all the major changes of cardiopulmonary resuscitation in the pediatric and neonatal aspects. The readers may find the latest editions of Pediatric Advanced Life Support & Neonatal Resuscitation Program textbook and correlate the specific steps mentioned in this article with the original previous edition of textbook so a full scale of the new way to conduct cardiopulmonary resuscitation in pediatric patients may be undertaken.


Attitudes toward hysterectomy in women undergoing evaluation for uterovaginal prolapse.
To investigate attitudes toward hysterectomy in women seeking care for pelvic organ prolapse. Two hundred twenty women referred for evaluation of prolapse without evidence of previous hysterectomy were surveyed with the Pelvic Organ Prolapse Distress Inventory; the Control Preferences Scale; and questions regarding patients' perception of the impact of hysterectomy on health, social life, and emotional well-being. Additional items presented hypothetical scenarios. Surveys were distributed in small batches until 100 responses were obtained from patients who met inclusion criteria. One hundred women with an intact uterus responded. Sixty percent indicated they would decline hysterectomy if presented with an equally efficacious alternative to a hysterectomy-based prolapse repair. The doctor's opinion, risk of surgical complications, and risk of malignancy were the most important factors in surgical decision making. Many women with prolapse prefer to retain their uterus at the time of surgery in the absence of a substantial benefit to hysterectomy. These findings should provide further impetus to investigate the efficacy of uterine-sparing procedures to help women make informed decisions regarding prolapse surgery.


Toxicity Testing of Pristine and Aged Silver Nanoparticles in Real Wastewaters Using Bioluminescent Pseudomonas putida.
Impact of aging on nanoparticle toxicity in real matrices is scarcely investigated due to a lack of suitable methodologies. Herein, the toxicity of pristine and aged silver nanoparticles (Ag NPs) to a bioluminescent Pseudomonas putida bioreporter was measured in spiked crude and final wastewater samples (CWs and FWs, respectively) collected from four wastewater treatment plants (WWTPs). Results showed lower toxicity of pristine Ag NPs in CWs than in FWs. The effect of the matrix on the eventual Ag NP toxicity was related to multiple physico-chemical parameters (biological oxygen demand (BOD), chemical oxygen demand (COD), total suspended solids (TSS) pH, ammonia, sulfide and chloride) based on a multivariate analysis. However, no collection site effect was concluded. Aged Ag NPs (up to eight weeks) were found less toxic than pristine Ag NPs in CWs; evident increased aggregation and decreased dissolution were associated with aging. However, Ag NPs exhibited consistent toxicity in FWs despite aging; comparable results were obtained in artificial wastewater (AW) simulating effluent. The study demonstrates the potency of performing nanoparticle acute toxicity testing in real and complex matrices such as wastewaters using relevant bacterial bioreporters.


Phony doc walks into ED--could it happen to you?
Don't wait until you are victimized to tighten your security procedures. Take these actions today. Provide photo ID badges for all ED employees, and require they be able to present them upon demand. Hold an inservice to remind staff to spread the word to be wary of all visitors. Increase security presence to monitor and direct family, patient access to the ED.


A descriptive study of nurse-reported missed care in neonatal intensive care units.
The aims of this study are to describe: (1) the frequency of nurse-reported missed care in neonatal intensive care units; and (2) nurses' reports of factors contributing to missed care on their last shift worked. Missed nursing care, or necessary care that is not delivered, is increasingly cited as a contributor to adverse patient outcomes. Previous studies highlight the frequency of missed nursing care in adult settings; the occurrence of missed nursing care in neonatal intensive care units is unknown. A descriptive analysis of neonatal nurses' self-reports of missed care using data collected through a cross-sectional web-based survey. A random sample of certified neonatal intensive care nurses in seven states was invited to participate in the survey in April 2012. Data were collected from nurses who provide direct patient care in a neonatal intensive care unit (n = 230). Descriptive statistics constituted the primary analytic approach. Nurses reported missing a range of patient care activities on their last shift worked. Nurses most frequently missed rounds, oral care for ventilated infants, educating and involving parents in care and oral feedings. Hand hygiene, safety and physical assessment and medication administration were missed least often. The most common reasons for missed care included frequent interruptions, urgent patient situations and an unexpected rise in patient volume and/or acuity on the unit. We find that basic nursing care in the neonatal intensive care unit is missed and that system factors may contribute to missed care in this setting.


Enhancing Clients' Communication Regarding Goals for Using Psychiatric Medications.
Discordance between psychiatric care providers' and clients' goals for medication treatment is prevalent and is a barrier to person-centered care. Power statements-short self-advocacy statements prepared by clients in response to a two-part template-offer a novel approach to help clients clarify and communicate their personal goals for using psychiatric medications. This study described the power statement method and examined a sample of power statements to understand clients' goals for medication treatment. More than 17,000 adults with serious mental illness at 69 public mental health clinics had the option to develop power statements by using a Web application located in the clinic waiting areas. A database query determined the percentage of clients who entered power statements into the Web application. The authors examined textual data from a random sample of 300 power statements by using content analysis. Nearly 14,000 (79%) clients developed power statements. Of the 277 statements in the sample deemed appropriate for content analysis, 272 statements had responses to the first part of the template and 230 had responses to the second part. Clients wanted psychiatric medications to help control symptoms in the service of improving functioning. Common goals for taking psychiatric medications (N=230 statements) were to enhance relationships (51%), well-being (32%), self-sufficiency (23%), employment (19%), hobbies (15%), and self-improvement (10%). People with serious mental illness typically viewed medications as a means to pursue meaningful life goals. Power statements appear to be a simple and scalable technique to enhance clients' communication of their goals for psychiatric medication treatment.


Facial palsy and atrial fibrillation: a special case of Ramsay Hunt syndrome.
Ramsay Hunt syndrome (herpes zoster oticus) is a rare complication of latent Varicella Zoster virus infection. It can be complicated by permanent hearing loss, loss of taste and postherpetic neuralgia. Although Ramsay Hunt syndrome most prominently involves the facial nerve, a number of other cranial nerves can be involved such as the vestibulocochlear, glossopharyngeal and the vagus nerve. We report on a case of Ramsay Hunt syndrome with cranial polyneuritis complicated by atrial fibrillation. Vagal involvement as evidenced by physical examination and MRI findings was present in our patient. We hypothesise that viral vagal neuritis likely contributed to the development of atrial fibrillation in our patient through involvement of the autonomic components of the vagus nerve.


Development of a Deep-Learning-Based Artificial Intelligence Tool for Differential Diagnosis between Dry and Neovascular Age-Related Macular Degeneration.
The use of deep-learning-based artificial intelligence (AI) is emerging in ophthalmology, with AI-mediated differential diagnosis of neovascular age-related macular degeneration (AMD) and dry AMD a promising methodology for precise treatment strategies and prognosis. Here, we developed deep learning algorithms and predicted diseases using 399 images of fundus. Based on feature extraction and classification with fully connected layers, we applied the Visual Geometry Group with 16 layers (VGG16) model of convolutional neural networks to classify new images. Image-data augmentation in our model was performed using Keras ImageDataGenerator, and the leave-one-out procedure was used for model cross-validation. The prediction and validation results obtained using the AI AMD diagnosis model showed relevant performance and suitability as well as better diagnostic accuracy than manual review by first-year residents. These results suggest the efficacy of this tool for early differential diagnosis of AMD in situations involving shortages of ophthalmology specialists and other medical devices.


Molecular analysis of the RET proto-oncogene in patients with sporadic medullary thyroid carcinoma: a novel point mutation in the extracellular cysteine-rich domain.
Germline point mutations in the RET proto-oncogene are associated with multiple endocrine neoplasia type 2 (2A and 2B) and familial medullary thyroid carcinoma. On the other hand, somatic point mutations of RET have been described in a subset of sporadic medullary thyroid carcinomas (MTCs). We examined tumor and blood DNA of thirteen apparently sporadic MTC patients for mutations in RET exons 10, 11, 13, 15 and 16 to determine whether they had true sporadic tumors or either de novo or occult germline mutations. Three different somatic missense mutations were documented in seven patients. In five patients a mutation in exon 16, codon 918, (ATG-->ACG) causing a Met-->Thr substitution was found. In the remaining two patients the mutation affected exon 11: codon 630 in one case and codon 634 in the other. In both cases a T-->C transversion was identified causing a Cys-->Arg substitution. In conclusion, absence of a germline mutation in RET exons 10, 11, 13 or 16 is evidence against an inherited form in all cases. In seven patients, identification of a somatic mutation supported the previous clinical diagnosis of sporadic medullary thyroid carcinoma; in one of them we identified a hitherto undescribed somatic point mutation at codon 630.


Sterile endophthalmitis following intravitreal injection of triamcinolone acetonide.
To investigate clinical findings and ocular characteristics of sterile endophthalmitis following intravitreal injection (IVI) of triamcinolone for the treatment of macular edema. IVI is an institutional practice at our hospital. From March 2002 to January 2003, a total of 21 IVIs of triamcinolone acetonide were performed on 19 patients with macular edema secondary to various retinal disorders. Cases diagnosed as sterile endophthalmitis after IVI of triamcinolone were selected for the study. Fisher's discriminant linear analysis was used to determine whether a significant correlation existed between specific ocular features and the occurrence of post-injection sterile endophthalmitis. Five of 21 eyes (23.8%) had sterile endophthalmitis with hypopyon formation after the injection. Of the five sterile endophthalmitis patients, three were pseudophakic with impaired posterior capsule and four had a diagnosis of Irvine-Gass syndrome. The rate of sterile endophthalmitis was significantly higher in pseudophakic patients with impaired posterior capsule (p = 0.0075) and in patients with Irvine-Gass syndrome (p = 0.0008). The best-corrected visual acuity (BCVA) in these patients remained unchanged or even improved when the inflammation subsided. Pseudophakia with impaired posterior capsule and the diagnosis of cystoid macular edema due to Irvine-Gass syndrome are two risk factors of sterile endophthalmitis following IVI triamcinolone. No loss of BCVA was noted in the patients with post-injection sterile endophthalmitis.


Lewis Base/Copper Cooperatively Catalyzed Asymmetric α-Amination of Esters with Diaziridinone.
An enantioselective α-amination of esters by a Lewis base/copper(I) cooperative catalysis strategy has been developed. The transient chiral C1-ammonium enolate generated from pentafluorophenyl ester and nucleophilic Lewis base is nicely compatible with the copper intermediate formed from N, N-di- t-butyldiaziridinone and Cu(I) to allow for high levels of stereochemical control. The cooperative catalytic reaction leads to a diverse set of highly enantioenriched hydantoins in good yields with excellent enantioselectivities (90-99% ee).


Hepatocellular Carcinoma (HCC) in Egypt: A comprehensive overview.
Worldwide, hepatocellular carcinoma (HCC) is a universal problem and its epidemiological data showed variation from place to place. Hepatocellular carcinoma (HCC) is the sixth and fourth common cancer in worldwide and Egypt, respectively. Egypt ranks the third and 15th most populous country in Africa and worldwide, respectively. The aim of this review is to compare the status of HCC in Egypt to that in the worldwide from different issues; risk factors, screening and surveillance, diagnosis and treatment, prevention, as well as research strategy. The risk factors for HCC in Egypt are of great importance to be reported. The risk factor for HCC are either environmental- or host/genetic-related risk factors. In the last years, there is a tangible improvement of both screening and surveillance strategies of HCC in Egypt. The unprecedented national screening campaign launched by the end of 2018 is a mirror image of this improvement. While the improvement of the HCC prevention requires the governmental health administration to implement health policies. Although the diagnosis of Egyptian HCC patients follows the international guidelines but HCC treatment options are limited in terms of cost. In addition, there are limited Egyptian reports about HCC survival and relapse. Both basic and clinical HCC research in Egypt are still limited compared to worldwide. Deep analysis and understanding of factors affecting HCC burden variation worldwide help in customization of efforts exerted to face HCC in different countries especially large country like Egypt. Overall, the presence of a research strategy to fight HCC in Egyptian patients will help in the optimum allocation of available resources to reduce the numbers of HCC cases and deaths and to improve the quality of life.


Administration of imatinib after allogeneic hematopoietic stem cell transplantation may improve disease-free survival for patients with Philadelphia chromosome-positive acute lymphobla stic leukemia.
Maintenance therapy with imatinib during the post-transplant period has been used for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL); however, its efficacy has not been demonstrated. A study was designed to investigate the safety of imatinib and its efficacy in preventing hematological relapse and improving disease-free survival (DFS) when administered after allogeneic hematopoietic stem cell transplantation (allo-HCT). Patients with Ph + ALL that received allo-HCT were enrolled in the study. Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect BCR-ABL transcript levels. Imatinib therapy was initiated if patient neutrophil counts were > 1.0 × 10(9)/L and platelet counts were > 50.0 × 10(9)/L, or if they displayed either elevated BCR-ABL transcript levels in two consecutive tests, or a BCR-ABL transcript level ≥ 10(-2) after initial engraftment. Patients receiving imatinib after relapse were assigned to the non-imatinib group. The imatinib treatment was scheduled for 3-12 months, until BCR-ABL transcript levels were negative at least for three consecutive tests or complete molecular remission was sustained for at least 3 months. A total of 82 patients were enrolled. Sixty-two patients initiated imatinib therapy post-HCT. Imatinib therapy was initiated at a median time of 70 days post-HCT. Grade 3-4 adverse events (AEs) occurred in 17.7% of patients. Ten patients (16.1%) terminated imatinib therapy owing to AEs. Among the patients in imatinib and non-imatinib groups, the estimated 5-year relapse rate was 10.2% and 33.1% (p = 0.016), and the 5-year probability of DFS was 81.5% and 33.5% (p = 0.000) with the median follow-up of 31 months (range, 2.5-76 months) and 24.5 months (range, 4-72 months), respectively. Multivariate analysis identified imatinib maintenance therapy post-HCT as an independent prognostic factor for DFS (p = 0.000, hazard ratio [HR] =4.8) and OS (p = 0.000, HR = 6.2). These results indicate that relapse rate can be reduced and DFS may be improved in Ph + ALL patients with imatinib maintenance therapy after HCT. BCR-ABLmonitoring by qRT-PCR can guide maintenance therapy with imatinib including initiation time and treatment duration after allo-HCT.


Identification and functional characterization of AMVp33, a novel homolog of the baculovirus caspase inhibitor p35 found in Amsacta moorei entomopoxvirus.
Members of the baculovirus p35 gene family encode proteins that specifically inhibit caspases, cysteine proteases that are involved in apoptosis. To date, p35 homologs have only been found in baculoviruses. We have identified AMVp33, a gene from Amsacta moorei entomopoxvirus with low but significant homology to baculovirus p35 genes. Expression of AMVp33 blocked apoptosis in several different insect and human cell lines. Purified recombinant P33 protein was an efficient inhibitor of insect and human effector caspases, but not initiator caspases. P33 was cleaved by effector caspases, and the resulting cleavage fragments stably associated with the caspases. Mutation of the predicted caspase cleavage site in P33 eliminated cleavage, caspase inhibition and anti-apoptotic function. Thus, AMVp33 encodes a caspase inhibitor similar to baculovirus P35 with a preference for effector caspases. This is the first report of a p35 homolog from any viral or cellular genome outside of the baculovirus family.


Diagnostic characteristics of clozapine-induced myocarditis identified by an analysis of 38 cases and 47 controls.
To analyze cases of clozapine-induced myocarditis for clinical and diagnostic trends. A case definition was developed by a multidisciplinary group using reports of myocarditis with clozapine submitted to the Australian Therapeutic Goods Administration. The definition uses for diagnosis either histology or the combination of new signs of cardiac dysfunction combined with a cardiac-specific diagnostic parameter occurring within 45 days of starting clozapine. Potential cases of clozapine-related myocarditis occurring between January 1993 and September 2008 and a comparative group of long-term clozapine users were documented from the patients' medical records. Thirty-eight of 59 reviewed cases met the case definition. Three patients died, and the diagnosis for these was confirmed on cardiac histology. Nearly all of the remaining patients had persistent tachycardia and elevated troponin level. The time to onset was 14-22 days in all except 2 patients. Of the patients who survived, 66% (23 cases) had eosinophilia occurring 0-7 days (mean, 4.0) after the peak in troponin. C-reactive protein (CRP) level was elevated to above 100 mg/L (952 nmol/L) in 79% (23 cases), and some had elevated levels of CRP when troponin level was still normal. None of the control group (47 patients) met the case definition. Eosinophil counts should not be relied on for diagnosis of clozapine-related myocarditis, but elevated CRP may be an early indicator of developing myocarditis. Patients starting clozapine should be actively monitored for myocarditis during the first 4 weeks, with extra care taken during week 3.


Rate-limiting proton-transfer in the sigma-adduct forming reactions of 1,3,5-trinitrobenzene and 4-nitrobenzofuroxan with substituted anilines in dimethyl sulfoxide.
Kinetic and equilibrium results are compared for the reactions in dimethyl sulfoxide of 1,3,5-trinitrobenzene, 1, and 4-nitrobenzofuroxan, 4, with a series of substituted anilines in the presence of Dabco or in, some cases, quinuclidine. pKa values for the corresponding anilinium ions are reported. The reactions of 1and 4 are likely to proceed through nucleophilic attack by the aniline to yield zwitterionic intermediates which may transfer an acidic proton to the bases present to yield the anionic adducts 9 or 12 respectively. In the formation of 9 from 1 the proton transfer step is rate-limiting; however, the slower interconversion of 4 and its zwitterion leads to only partial rate-limiting proton transfer in the formation of 12. Results with substituted anilines including 2-substituted and N-methyl aniline indicate that steric effects are not a major factor in determining rates of proton-transfer in these systems. Contrary to previous reports no evidence was found for a strong interaction between 1 and Dabco in DMSO.


Comparison of Habitual Versus Recurrent Patellar Dislocation in Children and Adolescents: Differences in Radiological Features.
Recurrent patellar dislocation (RPD) and habitual patellar dislocation (HPD) in flexion are frequently encountered in children and adolescents. To compare the radiological features of RPD and HPD in children and adolescents. Cross-sectional study; Level of evidence, 3. Imaging data were collected from patients aged 9 to 15 years who received surgical treatment for HPD or RPD at a single institution between June 2015 and September 2020. The prevalence of trochlear dysplasia, tibial tubercle lateralization, and lower limb rotational deformity was assessed through hip/knee/ankle computed tomography (CT) using the following quantitative indicators: trochlear depth index, lateral trochlear inclination, sulcus angle, tibial tubercle-trochlear groove (TT-TG) distance, ratio of TT-TG distance to femoral width, TT-TG angle, femoral anteversion angle, and tibial external rotation angle. The morphology of trochlea and patella were graded on knee CT using the Dejour and Wiberg classification. The Insall-Salvati index and Caton-Deschamps index were used to evaluate the height of the patella on lateral view radiographs. To evaluate lower limbs malalignment, the mechanical lateral distal femoral angle and medial proximal tibial angle were measured on weightbearing full-length radiographs. The collected data were analyzed and compared between the HPD and RPD groups. Enrolled were 15 patients (21 knees) diagnosed with HPD and 18 patients (22 knees) diagnosed with RPD. The age of first dislocation was significantly younger in the HPD group (7.6 ± 3.4 vs 11.2 ± 1.4 years; P = 0.003). Knees in the HPD group had a significantly higher proportion of Dejour type C dysplasia (57.1% vs 4.5%; P < .005) and Wiberg type 3 patella (66.7% vs 9.1%; P < .001). There were statistically significant differences between the groups in the trochlear depth index (HPD vs RPD: 1.1 ± 1.7 vs 2.2 ± 1.5 mm; P = .039), sulcus angle (170.3° ± 13.7° vs 157.3° ± 16.0°; P = .007), Insall-Salvati index (1.1 ± 0.2 vs 1.3 ± 0.2; P = .034), and tibial external rotation angle (31.3° ± 7.8° vs 38.4° ± 8.5°; P = .009). Patients in the HPD group presented with poorer trochlear and patellar development, lower patellar height, and less tibial external rotation compared with patients in the RPG group.


Endogenous Retroviruses Transcriptional Modulation After Severe Infection, Trauma and Burn.
Although human endogenous retroviruses (HERVs) expression is a growing subject of interest, no study focused before on specific endogenous retroviruses loci activation in severely injured patients. Yet, HERV reactivation is observed in immunity compromised settings like some cancers and auto-immune diseases. Our objective was to assess the transcriptional modulation of HERVs in burn, trauma and septic shock patients. We analyzed HERV transcriptome with microarray data from whole blood samples of a burn cohort (n = 30), a trauma cohort (n = 105) and 2 septic shock cohorts (n = 28, n = 51), and healthy volunteers (HV, n = 60). We described expression of the 337 probesets targeting HERV from U133 plus 2.0 microarray in each dataset and then we compared HERVs transcriptional modulation of patients compared to healthy volunteers. Although all 4 cohorts contained critically ill patients, the majority of the 337 HERVs was not expressed (around 74% in mean). Each cohort had differentially expressed probesets in patients compared to HV (from 19 to 46). Strikingly, 5 HERVs were in common in all types of severely injured patients, with 4 being up-modulated in patients. We highlighted co-expressed profiles between HERV and nearby CD55 and CD300LF genes as well as autonomous HERV expression. We suggest an inflammatory-specific HERV transcriptional response, and importantly, we introduce that the HERVs close to immunity-related genes might have a role on its expression.


Intimate partner violence, employment,and the workplace: consequences and future directions.
The purpose of this article is to examine the literature on violence against women and employment. After a brief discussion of the definition and consequences of intimate partner violence, the article reviews the research and related literatures to describe the (a) types of job interference tactics used by abusers, (b) employee-level consequences of partner violence, (c) victimized employee responses to intimate partner violence, (d) organizational-level consequences of partner violence, and (e) employer responses to intimate partner violence. Future research directions and workplace implications are discussed.


Elastosonography in the diagnosis of the nodular breast lesions: preliminary report.
To assess the diagnostic accuracy of elastography in characterising nodular breast lesions. A total of 82 patients who received mammographic, ultrasonographic and elastographic evaluation in a single session at two Italian centres (Dept of Radiology, Az. Ospedali Riuniti, Ancona, and Ospedale Valduce, Como, Italy) between January and August 2004 according to identical protocols exhibited 91 nodules that were subjected to cytological/histological examination. Lesions were classified and scored and the sensitivity and specificity of elastography calculated. Overall sensitivity and specificity were 79% and 89%, respectively. However, sensitivity was 86% and 65% and specificity 100% and 62% for lesions < 2 cm and > 2 cm in diameter, respectively. Despite the small sample and the fact that it does not include the full range of cell types, tumour cell composition seemed to affect accuracy. Elastography is easy and rapid to perform. Larger studies are needed to establish semiological patterns; despite the small patient sample, these data provide an interesting contribution.


Primary structure of locust opsins: a speculative model which may account for ultraviolet wavelength light detection.
The sequences of two locust opsins have been determined by dideoxy nucleotide sequencing of PCR products from cDNA derived from eyecup tissue. The opsins (Lo1 and Lo2) are encoded by 381 and 380 amino acid residues, respectively, with hydropathy profiles and placement of key amino acid residues suggestive of a typical seven-transmembrane rhodopsin structure. The sequence alignment of Lo1 reveals significant homology to mantid opsin. These opsins contain retinal as their visual chromophore and have similarity to the Rh1 type sequences from Drosophila and Calliphora which use 3-hydroxy retinal. Lo2 is most closely related to the Rh3/4 type of visual pigments from Drosophila. The retinal-based opsins show reduced numbers of charged amino acids in the loop region connecting transmembrane segments V and VI compared to the 3-hydroxy retinal opsins. Sequence alignment of all the known insect visual pigments has shown that only those with maximal sensitivity in the blue/UV spectral range, Lo2 and the Rh3/4 opsins of Drosophila, have three charged amino acids in transmembrane segments II, IV and VII. The charged residue in transmembrane VII is two helical turns away from the positively charged Schiff base and could act directly as a counterion to it. From the secondary structure analysis of opsin, the two charged residues in transmembrane II and IV would be in close proximity to form a dipole. These polar motifs in Lo2 and Rh3/Rh4 could act in wavelength modulation of short wavelength sensitive pigments and substantiate the proposed external two-point charge model which accounts for the spectral sensitivity of visual pigments [Honig, B., Dinur, U., Nakanishi, K., Balogh-Nair, V., Gawinowicz, M.A. and Motto, M. (1979). Journal of the American Chemical Society, 101, 7084-7086].


Ceftolozane-tazobactam and ceftazidime-avibactam activity against β-lactam-resistant Pseudomonas aeruginosa and extended-spectrum β-lactamase-producing Enterobacterales clinical isolates from U.S. medical centres.
Despite availability of ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (CZA) for several years, the individual spectrum of activity of each agent may not be widely known. We compared the activity of C/T and CZA against convenience samples of 119 extended-spectrum β-lactamase (ESBL)-producing Enterobacterales and 60 β-lactam-resistant Pseudomonas aeruginosa clinical isolates collected from three U.S. institutions. Minimal inhibitory concentrations (MICs) for C/T and CZA were determined by broth microdilution. Molecular identification of nine β-lactamase gene targets was conducted for Enterobacterales and P. aeruginosa isolates with increased MICs to C/T or CZA. More than 90% of Enterobacterales isolates demonstrated susceptibility to both C/T and CZA, in contrast to the other traditional β-lactam agents tested, which were much less active. The MIC50/90 values were nearly equivalent between agents. The most common β-lactamase genes identified in Enterobacterales isolates with MIC values ≥2 mg/L were the CTX-M-1 group (85%) and CMY-2-like (23%) β-lactamases. Both agents were active against >80% of β-lactam-resistant P. aeruginosa isolates tested, most of which had oprD mutations identified. One P. aeruginosa isolate was positive for a Klebsiella pneumoniae carbapenemase-type gene but remained meropenem-susceptible. The MIC50 values were four-fold lower in favour of C/T (1 mg/L vs. 4 mg/L) against P. aeruginosa. Our data suggest that either agent may be a reasonable choice for centres with a high proportion of ESBL producers; however, C/T may have improved activity against P. aeruginosa and may be preferred in institutions with a higher frequency of resistant pseudomonal isolates.


Thyroidectomy With or Without Nerve Identification: A Personal Experience and Technique.
Careful and precise dissection of the gland, away from the typical trajectory of the recurrent and external laryngeal nerves, poses a minimal or similar risk of nerve injuries compared to directly visualizing and identifying the nerves. In a randomized controlled study involving 150 patients with various thyroid disorders who underwent different surgical procedures (total, near total, and hemi thyroidectomy), the patients were randomly assigned into two groups using a coin toss. The first group (G1) consisted of 75 patients who underwent thyroidectomy with nerve visual identification, while the second group (G2) comprised 75 patients without the requirement of nerve visualization. The aim was to determine the method with a lower risk of complications. The incidence of external laryngeal nerve palsy (ELNP) was found to be higher in G1 patients compared to G2 patients (5.3% vs 2%), while no cases of permanent recurrent laryngeal nerve (RLN) palsy were observed in either group. The frequency of total nerve injury was higher in G1, with 14 patients (10.2%), compared to G2, with eight patients (5.3%). However, there was no significant association between nerve identification and the rate of nerve injury (P value = 0.452). Among the different surgical procedures, total thyroidectomy for toxic goiter was the most common operation associated with transient external laryngeal nerve (TELN) injury and permanent external laryngeal nerve (PELN) injury. By employing meticulous dissection techniques in proximity to the thyroid capsule, experienced surgeons can effectively reduce the risk of nerve injury, even in the absence of direct nerve visualization.


[Characteristics of the extracellular matrix in the formation of sclerosis of the chorionic villi (immunofluorescence studies)].
Distribution of the eight components of extracellular matrix in small villi of human placenta was studied with indirect immunofluorescence. Normal full-term pregnancy was found to present rough fibers and type I collagen conglomerates accumulated in the stromal center, while type III and V collagens occurred all over the villous surface. Stromal localization of type IV collagen was recorded as well as its presence in basal membranes of the epithelium and vessels. Fibronectin showed diffuse distribution concentrating along the vessels. Laminin, entactin and in lesser degree heparan sulphate proteoglycan were registered in epithelial and vascular basal membranes. Isolated sclerosis of the villi in pathological pregnancy involved stromal accumulation of type I, III collagens, small fragments of collagens type IV, V and fibronectin. Multiple sclerosis of adherent villi demonstrated hyalin-like conglomerates of various collagens and fibronectin filling up the stroma. Laminin, heparan sulphate proteoglycan and entactin were not observed at these sites.


Pineal Gland Agenesis: Review and Case Illustration.
Agenesis of the pineal gland has rarely been reported in the medical literature. Herein, we report a cadaveric specimen found to have agenesis of the pineal gland. The remaining gross examination of the brain was normal. A review of the literature was performed on this unusual finding.


Gallium arsenide selectively up-regulates inflammatory cytokine expression at exposure site.
Gallium arsenide (GaAs), a technologically and economically important semiconductor, is widely utilized in both military and commercial applications. This chemical is a potential health hazard as a carcinogen and immunotoxicant. We previously reported that macrophages at the exposure site exhibit characteristics of activation. In vitro culture of macrophages with GaAs fails to recapitulate the in vivo phenotype, suggesting that complete GaAs-mediated activation in vivo may require other cells or components found in the body's microenvironment. Our present study examined the role of cytokines upon GaAs-mediated macrophage activation. Intraperitoneal administration of GaAs elicited rapid specific recruitment of blood monocytes to the exposure site. This recruitment occurred concomitant with up-regulation of 17 chemokine and inflammatory cytokine mRNAs, while transcripts of three inhibitory cytokines diminished. Administration of latex beads caused less cytokine induction than GaAs, indicating that changes in mRNA levels could not be attributed to phagocytosis. Four representative chemokines and cytokines were selected for further analysis. Increased cytokine mRNA expression was paralleled by similar increases in cytokine protein levels, and secreted protein products were detected in peritoneal fluid. Cytokine protein expression was constrained to myeloid cells, and to a lesser extent to B cells. Alterations in patterns of cytokine gene expression elucidate mechanisms for increased cellular activation and antigen processing, and modulation of the inflammatory response. Our findings indicate that in vivo GaAs exposure alters cytokine gene expression, which may lead to an inflammatory reaction and contribute to pathological tissue damage.


Life satisfaction, positive affect, depression and anxiety symptoms, and their relationship with sociodemographic, psychosocial, and clinical variables in a general elderly population sample from Chile.
This study aims to describe the relationship between life satisfaction, positive affect, depression and anxiety symptoms with sociodemographic, psychosocial and clinical variables, and to identify the relative importance of these predictor groups. We evaluated life satisfaction (SWLS), positive affect (PANAS), depressive (PHQ-9), and anxiety (GAI) symptoms and their association with sociodemographic, psychosocial and clinical variables in a multistage, random general population sample of fully functioning individuals aged 60-80 years from the Concepción province and Gran Santiago, Chile (n = 396). We performed weighted multiple regression analysis, considering the complex sample structure with age group, sex, and geographical area, complemented with general and conditional dominance analyses to estimate the relevance of the predictor groups. We found significant associations with the geographical area, sex, age, education level, household members, having a partner, employment status, caregiver status, economic satisfaction, presence of chronic diseases, medication use, and alcohol use. Satisfaction with health was the most important predictor for positive affect (p < 0.001), depressive (p < 0.001), and anxiety (p < 0.001) symptoms, while alcohol use was the most significant predictor for life satisfaction (p < 0.001). Simultaneously studying the positive and negative dimensions of wellbeing and mental health in older adults allows for a more comprehensive perspective on the challenges faced during this stage of life. This study accounts for previously unknown associations and contributes to the identification of common and specific predictors in both dimensions.


Role of androgen signaling in androgen receptor-positive extramammary Paget's disease: Establishment of organoids and their biological analysis as a novel therapeutic target.
Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma that mainly affects the anogenital and axillary regions. Although its etiology has not been fully elucidated, there is evidence that androgen receptors (AR) are expressed in most cases of EMPD. However, the role of androgen signaling in the pathogenesis of EMPD remains unclear. To evaluate the role of androgen signaling in tumor growth of AR-positive EMPD. Patient-derived organoids were established and cultured from two AR-positive EMPD patients: one man and one woman. Cultured organoids were treated with androgen agonists and/or antagonists, then subjected to analysis of changes in organoid proliferation, as well as changes in androgen signaling pathway-specific genes. Organoid cultures were established from each EMPD sample. These organoids were immunohistologically and genetically identical to the original tumor. For each organoid sample, viable cell number increased in response to androgen exposure. The mRNA level of Fkbp5, a known AR target gene, increased in a concentration-dependent manner in organoids exposed to the synthetic androgen R1881. Conversely, the AR inhibitor darolutamide suppressed the viable cell number in a concentration-dependent manner. The mRNA expression levels of MKI67 and Fkbp5 were also suppressed by darolutamide. Our results indicate that androgen signaling is a key pathway involved in the growth of AR-positive EMPD. Therefore, androgen signaling inhibition may be a novel treatment option for EMPD patients who require systemic therapy.


Loss of pyruvate kinase M2 limits growth and triggers innate immune signaling in endothelial cells.
Despite their inherent proximity to circulating oxygen and nutrients, endothelial cells (ECs) oxidize only a minor fraction of glucose in mitochondria, a metabolic specialization that is poorly understood. Here we show that the glycolytic enzyme pyruvate kinase M2 (PKM2) limits glucose oxidation, and maintains the growth and epigenetic state of ECs. We find that loss of PKM2 alters mitochondrial substrate utilization and impairs EC proliferation and migration in vivo. Mechanistically, we show that the NF-κB transcription factor RELB is responsive to PKM2 loss, limiting EC growth through the regulation of P53. Furthermore, S-adenosylmethionine synthesis is impaired in the absence of PKM2, resulting in DNA hypomethylation, de-repression of endogenous retroviral elements (ERVs) and activation of antiviral innate immune signalling. This work reveals the metabolic and functional consequences of glucose oxidation in the endothelium, highlights the importance of PKM2 for endothelial growth and links metabolic dysfunction with autoimmune activation in ECs.


Association between IL28B Polymorphisms and Outcomes of Hepatitis B Virus Infection: A meta-analysis.
Interleukin (IL) 28B polymorphisms encoding pro-inflammatory and anti-inflammatory cytokines trigger diverse clinical outcome of hepatitis virus infection. However, there is controversy concerning the association of IL28B polymorphisms with the outcome of hepatitis B virus (HBV) infection, with several studies obtaining inconsistent results. We performed a meta-analysis to evaluate the role of 3 single nucleotide polymorphisms (SNPs) rs12979860, rs12980275 and rs8099917 in the progression of HBV infection, overall and by ethnicity. Searched PubMed, Embase and Wiley Online Library electronic databases using 'interleukin 28B', 'IL 28B', 'IL 28B polymorphism', 'hepatitis B virus', 'HBV', and performed meta- analysis for rs12979860, rs12980275 and rs8099917 in Asian and Caucasian populations under the dominant recessive and allele model. Eighteen studies were found in total and used for this meta-analysis, including 5587 cases and 4295 controls. The IL28B polymorphism rs12979860 had no association with HBV persistence (CC vs CT + TT: OR = 0.86, 95% CI = 0.76-1.00; TT vs CT + CC: OR = 1.14, 95% CI = 0.76-1.70; T vs C: OR = 1.03, 95% CI = 0.94-1.13). Similarly, neither rs12980275 nor rs8099917 had associations with HBV persistence (rs12980275 in AA vs AG + AA: OR = 1.15, 95% CI = 0.96-1.38; rs8099917 in TT vs GT + GG: OR = 1.15, 95% CI = 0.96-1.39). There was also no significant association of IL28B polymorphisms with persistent HBV infection in Asians or Chinese. There was no evidence of an association of rs12979860 with the HBV-related hepatocellular carcinoma susceptibility (T vs C: OR = 1.53, 95% CI = 0.96-2.43). IL28B polymorphisms had no association with the outcome of HBV infection overall, nor in the Asians and the Chinese. These 3 SNPs might not be relevant to the development of HBV infection.


Evaluation of a new collagen-based medical device (ElastiCo®) for the treatment of acute Achilles tendon injury and prevention of peritendinous adhesions: An in vitro biocompatibility and in vivo investigation.
Tendon healing still represents a challenge for clinicians because it is slow and incomplete. The most injured is the Achilles tendon, and surgery is the therapeutic strategy often adopted because it provides a quicker functional recovery. Peritendinous adhesions are the main complication of surgery with hyperplasia and chemotaxis of fibroblasts. A biomaterial that blocks fibroblast migration, without interfering with the passage of cytokines and growth factors, might be useful. The present study evaluated the biocompatibility of a new Type I collagen-based scaffold (ElastiCo®) and its ability to promote Achilles tendon healing, inhibiting adhesion formation. After verifying in vitro biocompatibility, physical, and mechanical properties of the scaffold, an in vivo study was performed in 28 rats, operated to induce an acute lesion in both Achilles tendons. One tendon was treated with the suture only and the contralateral one with suture wrapped with ElastiCo® film. After 8 and 16 weeks, it was observed that ElastiCo® reduced internal and external peritendinous adhesions and Collagen III content and increased Collagen I. Elastic modulus increased with both treatments over time. Current results highlighted the clinical translationality of ElastiCo® that could improve the quality of life in patients affected by Achilles tendon lesions surgically treated.


Antiangiogenic activity of thalidomide in combination with fludarabine, carboplatin, and topotecan for high-risk acute myelogenous leukemia.
Forty-two patients with poor prognosis AML were enrolled in a phase II study combining fludarabine, carboplatin, and topotecan (FCT) with thalidomide. Laboratory correlates included serum vascular endothelial growth factor levels (VEGF) and bone marrow microvascular density (MVD). Ten of 42 (24%) patients achieved a complete remission (CR or CRp). Serious thrombotic adverse events were observed in 5 patients suggesting that the combination of cytotoxic chemotherapy and thalidomide may be thrombogenic despite significant thrombocytopenia. VEGF did not correlate with response to therapy, while a trend towards decreased MVD was noted in patients who achieved CR. The addition of thalidomide did not significantly influence angiogenic markers. It is not clear that thalidomide adds any efficacy to the FCT regimen.


Association of Preoperative Rehabilitation With Postoperative Length of Hospital Stay for Elderly Lung Cancer Patients.
This study aimed to evaluate the effect of preoperative rehabilitation on postoperative hospital stay in elderly lung cancer patients following lung resection. This was a retrospective observational study using the Japanese Diagnosis Procedure Combination database. Data of patients diagnosed between April 2016 and March 2020 were collected. Patients were identified using the International Statistical Classification of Disease and Related Health Problems Version 10-10 codes, C34.0-C34.3 and C34.8. Multilevel linear regression analysis was performed to evaluate the effect of preoperative rehabilitation on the length of hospital stay. A total of 9,393 patients were included in the study. Univariate analysis showed that preoperative rehabilitation was significantly associated with postoperative length of hospital stay (coefficient: -1.61; 95% confidence interval: -2.42, -0.81; P <0.001). In addition, multivariate analysis showed preoperative rehabilitation to be associated with a significant decrease in postoperative length of hospital stay (coefficient=-1.38; 95% confidence interval: -2.19, -0.58; P =0.001). Preoperative rehabilitation may shorten length of hospital stay in elderly patients with lung cancer.


The eyes of Johann Sebastian Bach.
Johann Sebastian Bach's only physical problem seems to have been his vision. Myopia seems most likely, and it is probable that he developed cataracts at an older age. In addition to the cataracts, his worsening vision may have been due in part to some other eye problem. During the last year of his life, Bach's vision became so poor that he decided to have his eyes operated on. Two operations were performed in 1750 by the traveling English eye surgeon John Taylor. Most likely the first operation was Taylor's standard couching procedure. About 1 week after the first operation, Bach had to be operated on again because of a reappearance of the cataract. Many painful and/or vision-reducing complications could have been induced by these intraocular operations: uveitis or endophthalmitis, secondary glaucoma, hemorrhage, retinal detachment, and even sympathetic ophthalmia. Bach was "completely blind" after the operations, and he died less than 4 months after the final operation.


Vitamin B6 status of breast-fed infants in relation to pyridoxine HCl supplementation of mothers.
The vitamin B6 nutritue of breast-fed infants was evaluated by vitamin B6 intake, plasma pyridoxal 5'-phosphate (PLP) concentration, and growth patterns during the infants' first 6 mo of age. Vitamin B6 intakes of 47 healthy, term infants were significantly correlated with four levels of maternal vitamin B6 supplements: 2.5, 4.0, 7.5, or 10.0 mg pyridoxine (PN) HCl/d and met the B6 Adequate Intake (AI, 1998) of 0.1 mg/d for infants 0 to 6 mo. Only infants whose mothers received 10.0 mg PN x HCl/d exceeded or met the Recommended Dietary Allowances (RDA, 1989) of 0.3 mg vitamin B6/d from 4 to 6 mo of age. Plasma PLP concentrations of infants, measured at 1, 4, and 6 mo of age paralleled their mother's vitamin B6 intake. Most infants showed normal growth. The findings indicated that a maternal PN x HCl supplement of 2.5 mg/d provided an adequate amount of vitamin B6 in breast milk (0.15 mg/d) for the vitamin B6 status parameters and the growth of breast-fed infants.


Neurodynamics of mind: the arrow illusion of conscious intentionality as downward causation.
In cognitive neuroscience, the reissue of the notion of emergence and downward causation has been used as an interlevel model of mind-brain interactions from different perspectives. Within this perspective, intentionality has been interpreted as global to local determination (downward causation) on the neurophysiological level. Consciousness would act as the large-scale, global activity of the system that governs or constrains local interactions of neurons. This argument seems to solve several difficulties with regard to descriptions of consciousness on a neurophysiological and mental level. Nevertheless, the inconsistencies of this argument are shown, and a contextual and pragmatic explanation of the downward causation of consciousness is given.


Analyzing histone ChIP-seq data with a bin-based probability of being signal.
Histone ChIP-seq is one of the primary methods for charting the cellular epigenomic landscape, the components of which play a critical regulatory role in gene expression. Analyzing the activity of regulatory elements across datasets and cell types can be challenging due to shifting peak positions and normalization artifacts resulting from, for example, differing read depths, ChIP efficiencies, and target sizes. Moreover, broad regions of enrichment seen in repressive histone marks often evade detection by commonly used peak callers. Here, we present a simple and versatile method for identifying enriched regions in ChIP-seq data that relies on estimating a gamma distribution fit to non-overlapping 5kB genomic bins to establish a global background. We use this distribution to assign a probability of being signal (PBS) between zero and one to each 5 kB bin. This approach, while lower in resolution than typical peak-calling methods, provides a straightforward way to identify enriched regions and compare enrichments among multiple datasets, by transforming the data to values that are universally normalized and can be readily visualized and integrated with downstream analysis methods. We demonstrate applications of PBS for both broad and narrow histone marks, and provide several illustrations of biological insights which can be gleaned by integrating PBS scores with downstream data types.


On the Ethics of Mandatory Reporting of Positive Drug Tests in Newborns and Pregnant Parents at the Time of Delivery.
The opioid epidemic has renewed debate about how to structure laws, agency policies and hospital protocols for mandatory reporting of illicit substances during pregnancy. This paper analyzes the ethics of Rhode Island's approach to mandatory reporting - in particular, reporting of positive maternal and newborn drug tests at time of delivery. Given that state intervention is generally perceived by pregnant people as punitive and threatening to their family, we consider how four elements often used to justify punitive action by the state - retribution, deterrence, rehabilitation, and incapacitation (societal protection) - apply to Rhode Island's policy and approach to prenatal substance use. In addition, the paper considers the equity implications of Rhode Island's approach. It concludes that, given the potential for the policy to do more harm than good, investment of resources would be better spent on clinical and community services that support substance using parents and their newborns.


18F-Fluoromisonidazole Kinetic Modeling for Characterization of Tumor Perfusion and Hypoxia in Response to Antiangiogenic Therapy.
Multiparametric imaging of tumor perfusion and hypoxia with dynamic 18F-fluoromisonidazole (18F-FMISO) PET may allow for an improved response assessment to antiangiogenic therapies. Cediranib (AZD2171) is a potent inhibitor of tyrosine kinase activity associated with vascular endothelial growth factor receptors 1, 2, and 3, currently in phase II/III clinical trials. Serial dynamic 18F-FMISO PET was performed to investigate changes in tumor biomarkers of perfusion and hypoxia after cediranib treatment. Methods: Twenty-one rats bearing HT29 colorectal xenograft tumors were randomized into a vehicle-treated control group (0.5% methylcellulose daily for 2 d [5 rats] or 7 d [4 rats]) and a cediranib-treated test group (3 mg/kg daily for 2 or 7 d; 6 rats in both groups). All rats were imaged before and after treatment, using a 90-min dynamic PET acquisition after administration of 42.1 ± 3.9 MBq of 18F-FMISO by tail vein injection. Tumor volumes were delineated manually, and the input function was image-derived (abdominal aorta). Kinetic modeling was performed using an irreversible 1-plasma 2-tissue compartmental model to estimate the kinetic rate constants K1, K1/k2, and k3-surrogates for perfusion, 18F-FMISO distribution volume, and hypoxia-mediated entrapment, respectively. Tumor-to-blood ratios (TBRs) were calculated on the last dynamic frame (80-90 min). Tumors were assessed ex vivo by digital autoradiography and immunofluorescence for microscopic visualization of perfusion (pimonidazole) and hypoxia (Hoechst 33342). Results: Cediranib treatment resulted in significant reduction of mean voxelwise 18F-FMISO TBR, K1, and K1/k2 in both the 2-d and the 7-d groups (P < 0.05). The k3 parameter was increased in both groups but reached significance only in the 2-d group. In the vehicle-treated groups, no significant change in TBR, K1, K1/k2, or k3 was observed (P > 0.2). Ex vivo tumor analysis confirmed the presence of hypoxic tumor regions that nevertheless exhibited relatively lower 18F-FMISO uptake. Conclusion:18F-FMISO kinetic modeling reveals a more detailed response to antiangiogenic treatment than a single static image is able to reveal. The reduced mean K1 reflects a reduction in tumor vascular perfusion, whereas the increased k3 reflects a rise in hypoxia-mediated entrapment of the radiotracer. However, if only late static images are analyzed, the observed reduction in 18F-FMISO uptake after treatment with cediranib may be mistakenly interpreted as a global decrease, rather than an increase, in tumor hypoxia. These findings support the use of 18F-FMISO kinetic modeling to more accurately characterize the response to treatments that have a direct effect on tumor vascularization and perfusion.


Biology, ecology, and control of the vampire bat.
The importance of the vampire bat as a vector of rabies and its taxonomy, anatomic characteristics, distribution, feeding habits, behavior, and habitat are described. Also described are studies of methods of reducing vampire bat populations. Anticoagulants such as diphenadione and warfarin were shown to be effective in reducing vampire bat populations. These substances were used in different ways: application of the compound to the skin of captured vampires and then the release of the animals to contaminate the rest of the colony; treatment of vampire niches; topical treatment of vampire bites; and systemic treatment of cattle by administration of the anticoagulant intraruminally or intramuscularly. All these methods were shown to be effective and can be used to reduce vampire populations and to decrease the risk of transmission of rabies in enzootic areas.


Predicting accident frequency in children.
The concept of "accident proneness" is frequently discussed and rarely documented. We predicted that children who take more risks as judged by their behavior in gym class, or who have more stressful life changes as determined by their score on a Social Readjustment Rating Questionnaire (SRRQ), would be more likely to injure themselves. 103 junior high school boys were rated for these factors, and then followed for injuries by weekly telephone calls for five months. Boys having high SRRQ scores had significantly more accidents than those with low scores; risk-taking levels were not predictive. In this study, children undergoing stressful changes in their lives were more susceptible to accidents.


Bindin is essential for fertilization in the sea urchin.
Species-specific sperm-egg interactions are essential for sexual reproduction. Broadcast spawning of marine organisms is under particularly stringent conditions, since eggs released into the water column can be exposed to multiple different sperm. Bindin isolated from the sperm acrosome results in insoluble particles that cause homospecific eggs to aggregate, whereas no aggregation occurs with heterospecific eggs. Therefore, Bindin is concluded to play a critical role in fertilization, yet its function has never been tested. Here we report that Cas9-mediated inactivation of the bindin gene in a sea urchin results in perfectly normal-looking embryos, larvae, adults, and gametes in both males and females. What differed between the genotypes was that the bindin-/- sperm never fertilized an egg, functionally validating Bindin as an essential gamete interaction protein at the level of sperm-egg cell surface binding.


Properties and distribution of pure GA-sequences of mammalian genomes.
The article describes DNA sequences of mammalian genomes that are longer than 50 bases, but consist exclusively of G's and A's ('pure GA-sequences'). Although their frequency of incidence should be 10(-16) or smaller, the chromosomes of human, chimpanzee, dog, cat, rat, and mouse contained many tens of thousands of them ubiquitously located along the chromosomes with a species-dependent density, reaching sizes of up to 1300 [b]. With the exception of a small number of poly-A-, poly-G-, poly-GA-, and poly-GAAA-sequences (combined <0.5%), all pure GA-sequences of the mammals tested were unique individuals, contained several repeated short GA-containing motifs, and shared a common hexa-nucleotide spectrum. At most 2% of the human GA-sequences were transcribed into mRNAs; all others were not coding for proteins. Although this could have made them less subject to natural selection, they contained many [corrected] times fewer point mutations than one should expect from the genome at large. As to the presence of other sequences with similarly restricted base contents, there were approximately as many pure TC-sequences as pure GA-sequences, but many fewer pure AC-, TA, and TG-sequences. There were practically no pure GC-sequences. The functions of pure GA-sequences are not known. Supported by a number of observations related to heat shock phenomena, the article speculates that they serve as genomic sign posts which may help guide polymerases and transcription factors to their proper targets, and/or as spatial linkers that help generate the 3-dimensional organization of chromatin.


Integrating ultrasound into modern medical curricula.
Ultrasonography is widely practiced in many disciplines. It is becoming increasingly important to design well-structured curricula to introduce imaging to students during medical school. This review aims to analyze the literature for evidence of how ultrasonography has been incorporated into anatomy education in medical school curricula worldwide. A literature search was conducted using multiple databases with the keywords: "Ultrasound OR Ultrasonographic examination*" and "Medical student* OR Undergraduate teaching* OR Medical education*" and "Anatomy* OR Living anatomy* OR Real-time anatomy.*" This review found that ultrasound curricula vary in stage of implementation, course length, number of sessions offered to students as well as staffing and additional course components. Most courses consisted of didactic lectures supplemented with demonstration sessions and/or hands-on ultrasound scanning sessions. The stage of course implementation tended to depend on the aim of the course; introductory courses were offered earlier in a student's career. Most courses improved student confidence and exam performance, and more junior students tended to benefit more from learning anatomy with ultrasound guidance rather than learning clinical examination skills. Students tended to prefer smaller groups when learning ultrasound to get more access to using the machines themselves. Ultrasonography is an important skill, which should be taught to medical students early in their careers as it facilitates anatomical education and is clinically relevant, though further objective research required to support the use of ultrasound education as a tool to improve clinical examination skills in medical students. Clin. Anat. 30:452-460, 2017. © 2017 Wiley Periodicals, Inc.


Further validation of the Chinese (Mandarin) Tinnitus Handicap Inventory: comparison between patient-reported and clinician-interviewed outcomes.
The objective of this study was to evaluate the feasibility of the Chinese (Mandarin) Tinnitus Handicap Inventory (THI-C) by comparing patient-reported and clinician-interviewed outcomes and to raise awareness of the difficulties in using adapted international test measures. All patients were required to first complete the THI-C independently. Then, clinicians conducted a face-to-face interview, explained the exact meaning of each item and re-evaluated every item based on the patient's descriptions. During this process, patients were encouraged to make comments about each item. Both the self-administered and clinician-interviewed scores were recorded and compared. A total of 178 patients who reported tinnitus as a primary complaint were included. Among these patients, 88 (49.4%) completed the questionnaire independently, while 79 (44.4%) patients experienced difficulty in understanding at least one item. The difference between the self-administered and clinician-interviewed scores was statistically significant (p < 0.01). The feasibility of the THI-C is limited unless a revision is made. Follow-up studies are needed for validation when a newly translated self-administered questionnaire is put into use. In addition to semantic equivalence and idiomatic equivalence, experiential equivalence and conceptual equivalence should also be fully considered during the translation process.


Development and Testing of SPIDER-NET: An Interactive Tool for Brain Connectogram Visualization, Sub-Network Exploration and Graph Metrics Quantification.
Brain connectomics consists in the modeling of human brain as networks, mathematically represented as numerical connectivity matrices. However, this representation may result in difficult interpretation of the data. To overcome this limitation, graphical representation by connectograms is currently used via open-source tools, which, however, lack user-friendly interfaces and options to explore specific sub-networks. In this context, we developed SPIDER-NET (Software Package Ideal for Deriving Enhanced Representations of brain NETworks), an easy-to-use, flexible, and interactive tool for connectograms generation and sub-network exploration. This study aims to present SPIDER-NET and to test its potential impact on pilot cases. As a working example, structural connectivity (SC) was investigated with SPIDER-NET in a group of 17 healthy controls (HCs) and in two subjects with stroke injury (Case 1 and Case 2, both with a focal lesion affecting part of the right frontal lobe, insular cortex and subcortical structures). 165 parcels were determined from individual structural magnetic resonance imaging data by using the Destrieux atlas, and defined as nodes. SC matrices were derived with Diffusion Tensor Imaging tractography. SC matrices of HCs were averaged to obtain a single group matrix. SC matrices were then used as input for SPIDER-NET. First, SPIDER-NET was used to derive the connectogram of the right hemisphere of Case 1 and Case 2. Then, a sub-network of interest (i.e., including gray matter regions affected by the stroke lesions) was interactively selected and the associated connectograms were derived for Case 1, Case 2 and HCs. Finally, graph-based metrics were derived for whole-brain SC matrices of Case 1, Case 2 and HCs. The software resulted effective in representing the expected (dis) connectivity pattern in the hemisphere affected by the stroke lesion in Cases 1 and 2. Furthermore, SPIDER-NET allowed to test an a priori hypothesis by interactively extracting a sub-network of interest: Case 1 showed a sub-network connectivity pattern different from Case 2, reflecting the different clinical severity. Global and local graph-based metrics derived with SPIDER-NET were different between cases with stroke injury and HCs. The tool proved to be accessible, intuitive, and interactive in brain connectivity investigation and provided both qualitative and quantitative evidence.


Optical phase fluctuations thermally induced in a single-mode optical fiber.
Mathematical expressions have been derived on fluctuations of optical phase and frequency of a light wave which are thermally caused in a single-mode optical fiber in terms of fiber length, thermal coherence length, and fluctuation frequency. Fluctuations of optical phase and temperature were measured at a wavelength of 0.6328 microm by Mach-Zehnder interferometry, and the results are compared with theoretical predictions. A minimum detectable temperature change through optical phase shift depends on frequency stability of a source laser. It is 10(-5) K with a fractional frequency fluctuation of 10(-9).


Clinical features of community acquired adenovirus pneumonia during the 2011 community outbreak in Southern Taiwan: role of host immune response.
Human adenovirus 7 (HAdV-7) was responsible for a significant number of fatalities during the 2011 community outbreak in Taiwan. The mechanisms underlying the pathogenesis of severe adenovirus infections in non-immunocompromised individuals remain unclear. Adenovirus pneumonia was associated with pleural effusion in a number of patients from the 2011 outbreak suggesting that similar to bacterial pneumonia, patients diagnosed with adenovirus pneumonia who have pleural effusion are more severely and systemically infected, and may have a more protracted disease course. We hypothesized that the host immunological response determines the severity of adenoviral infection. This retrospective case series study included patients diagnosed with severe lower respiratory tract infections at the National Cheng Kung University Hospital in southern Taiwan between December 2010 and October 2011. The main inclusion criteria were 1) presence of multifocal patchy infiltrates, lobar consolidation or reticular interstitial opacities in chest X-rays, and 2) presence of adenovirus isolated from respiratory specimens. All patients had adenovirus isolated from respiratory specimens, and were negative for other viruses. Pleural effusion was confirmed in all patients using chest echography. Clinical features and laboratory data were compared in patients with (n = 12) and without (n = 15) parapneumonic effusion. Presence of parapneumonic effusion was significantly associated with a longer febrile duration, more complicated clinical management, and a greater risk of extrapulmonary involvement, notably hepatitis. Patients without pleural effusion had significantly higher numbers of WBCs, platelets, and absolute segment cell counts (ASCs) compared to patients with pleural effusion (all p < 0.05). Patients without pleural effusion had significantly higher counts of CD4+, CD8+, and CD20+ T cells (all p < 0.05) compared to patients with pleural effusion. Our data indicated that presence of parapneumonic effusion in adenoviral pneumonia was associated with longer febrile duration, more complicated clinical management, a greater risk of hepatitis, and suppression of host cellular immunity. Further prospective, large-scale studies are needed to validate our results.


The presumed ginkgophyte Umaltolepis has seed-bearing structures resembling those of Peltaspermales and Umkomasiales.
The origins of the five groups of living seed plants, including the single relictual species Ginkgo biloba, are poorly understood, in large part because of very imperfect knowledge of extinct seed plant diversity. Here we describe well-preserved material from the Early Cretaceous of Mongolia of the previously enigmatic Mesozoic seed plant reproductive structure Umaltolepis, which has been presumed to be a ginkgophyte. Abundant new material shows that Umaltolepis is a seed-bearing cupule that was borne on a stalk at the tip of a short shoot. Each cupule is umbrella-like with a central column that bears a thick, resinous, four-lobed outer covering, which opens from below. Four, pendulous, winged seeds are attached to the upper part of the column and are enclosed by the cupule. Evidence from morphology, anatomy, and field association suggests that the short shoots bore simple, elongate Pseudotorellia leaves that have similar venation and resin ducts to leaves of living GinkgoUmaltolepis seed-bearing structures are very different from those of Ginkgo but very similar to fossils described previously as Vladimaria. Umaltolepis and Vladimaria do not closely resemble the seed-bearing structures of any living or extinct plant, but are comparable in some respects to those of certain Peltaspermales and Umkomasiales (corystosperms). Vegetative similarities of the Umaltolepis plant to Ginkgo, and reproductive similarities to extinct peltasperms and corystosperms, support previous ideas that Ginkgo may be the last survivor of a once highly diverse group of extinct plants, several of which exhibited various degrees of ovule enclosure.


The effect of light intensity, temperature, and diet on growth in red-legged partridge.
Three hundred Red-legged partridge chicks ( Alectoris graeca) were divided into two groups and fed starter diets calculated to contain 24.5 and 24.9% crude protein and 2646 and 2662 kcal/kg metabolizable energy, respectively. One diet consisted of 5% fish meal while the other contained all vegetable protein. One-half of the birds on each diet were grown under fluorescent light intensity of 300 lx; the remainder received 5 lx. The results indicated that neither the source of protein nor intensity of light had an effect on the rate of growth to 8 weeks of age. At 8 weeks of age, the birds were randomly divided among three climatic chambers and kept under a constant temperature of either 18.3, 23.9, or 29.5 C. At 12 weeks of age, one-half of the birds in each chamber were fed a 20% turkey grower diet; the remainder received equal parts by weight of the turkey grower diet and whole milo . Individual body weights and feed consumption were measured biweekly. Best growth was obtained in birds kept at 29.5 C and fed equal parts of turkey grower and milo from 12 to 30 weeks of age.


Adaptive Mechanisms of Somatostatin-Positive Interneurons after Traumatic Brain Injury through a Switch of α Subunits in L-Type Voltage-Gated Calcium Channels.
Unilateral traumatic brain injury (TBI) causes cortical dysfunctions spreading to the primarily undamaged hemisphere. This phenomenon, called transhemispheric diaschisis, is mediated by an imbalance of glutamatergic versus GABAergic neurotransmission. This study investigated the role of GABAergic, somatostatin-positive (SST) interneurons in the contralateral hemisphere 72 h after unilateral TBI. The brain injury was induced to the primary motor/somatosensory cortex of glutamate decarboxylase 67-green fluorescent protein (GAD67-GFP) knock-in mice at postnatal days 19-21 under anesthesia in vivo. Single GFP+ interneurons of the undamaged, contralateral cortex were isolated by fluorescence-activated cell sorting and analyzed by mass spectrometry. TBI caused a switch of 2 α subunits of pore-forming L-type voltage-gated calcium channels (VGCC) in GABAergic interneurons, an increased expression of CaV1.3, and simultaneous ablation of CaV1.2. This switch was associated with 1) increased excitability of single SST interneurons in patch-clamp recordings and (2) a recovery from early network hyperactivity in the contralateral hemisphere in microelectrode array recordings of acute slices. The electrophysiological changes were sensitive to pharmacological blockade of CaV1.3 (isradipine, 100 nM). These data identify a switch of 2 α subunits of VGCCs in SST interneurons early after TBI as a mechanism to counterbalance post-traumatic hyperexcitability.


[The past, present and future of arterial infection].
Today, the pathology of large and medium-sized arteries is in most part considered as degenerative or inflammatory. The role of infection has been preponderant (syphilis) but has become quite modest now, restricted to infectious aneurysms. According to certain observations, infections may participate in initiating arterial inflammation, whether it be specific (Kawasaki's disease, Takayasu's arteritis, coronary artery disease of cardiac grafts) or less so ("plain" atherosclerosis). Suspected microbes (herpes viruses, Chlamydia pneumoniae, etc.) would damage the arterial wall either directly by infecting it, or indirectly by provoking an autoimmune reaction against some of its components (e.g. heat shock proteins). These hypotheses are worth serious consideration because, if established as correct, they would modify radically our etiologic, therapeutic and prophylactic conceptions of arterial diseases, including of course the main one, atherosclerosis.