Inducible forebrain-specific ablation of the transcription factor Creb during adulthood induces anxiety but no spatial/contextual learning deficits.
The cyclic AMP (cAMP)-response element binding protein (CREB) is an activity-dependent transcription factor playing a role in synaptic plasticity, learning and memory, and emotional behavior. However, the impact of Creb ablation on rodent behavior is vague as e.g., memory performance of different Creb mutant mice depends on the specific type of mutation per se but additionally on the background and learning protocol differences. Here we present the first targeted ablation of CREB induced during adulthood selectively in principal forebrain neurons in a pure background strain of C57BL/6 mice. All hippocampal principal neurons exhibited lack of CREB expression. Mutant mice showed a severe anxiety phenotype in the openfield and novel object exploration test as well as in the Dark-Light Box Test, but unaltered hippocampus-dependent long-term memory in the Morris water maze and in context dependent fear conditioning. On the molecular level, CREB ablation led to CREM up regulation in the hippocampus and frontal cortex which may at least in part compensate for the loss of CREB. BDNF, a postulated CREB target gene, was down regulated in the frontal lobe but not in the hippocampus; neurogenesis remained unaltered. Our data indicate that in the adult mouse forebrain the late onset of CREB ablation can, in case of memory functionality, be compensated for and is not essential for memory consolidation and retrieval during adulthood. In contrast, the presence of CREB protein during adulthood seems to be pivotal for the regulation of emotional behavior.


Structural flexibility of the periplasmic protein, FlgA, regulates flagellar P-ring assembly in Salmonella enterica.
A periplasmic flagellar chaperone protein, FlgA, is required for P-ring assembly in bacterial flagella of taxa such as Salmonella enterica or Escherichia coli. The mechanism of chaperone-mediated P-ring formation is poorly understood. Here we present the open and closed crystal structures of FlgA from Salmonella enterica serovar Typhimurium, grown under different crystallization conditions. An intramolecular disulfide cross-linked form of FlgA caused a dominant negative effect on motility of the wild-type strain. Pull-down experiments support a specific protein-protein interaction between FlgI, the P-ring component protein, and the C-terminal domain of FlgA. Surface plasmon resonance and limited-proteolysis indicate that flexibility of the domain is reduced in the covalently closed form. These results show that the structural flexibility of the C-terminal domain of FlgA, which is related to the structural difference between the two crystal forms, is intrinsically associated with its molecular chaperone function in P-ring assembly.


Treatment of Swedish Patients with Graves' Hyperthyroidism Is Associated with Changes in Acylcarnitine Levels.
Hyperthyroidism is associated with alterations in metabolism that are currently only partially understood. The objective of the study was to investigate changes in metabolism associated with reinstatement of euthyroidism in Swedish patients. Eighty metabolites in plasma were profiled from 10 subjects with Graves' disease (GD) at baseline and after 9 and 15 months of treatment to reinstate euthyroidism. Thyroid parameters, thyrotropin (TSH), TSH receptor antibodies, free triiodothyronine, and free thyroxine were followed. Main findings were validated in plasma from 20 subjects with GD at baseline and at three, six, and nine months. The study was conducted at the endocrinology clinic in Malmö, Sweden. Euthyroidism was reinstated at three months, and thyroid status did not change further during the 15-month follow-up. This was paralleled by altered levels of 9/19 detected acylcarnitines (p < 0.05 after adjustment for multiple testing). Levels of short-chain acylcarnitines were decreased, intermediate-chain acylcarnitines elevated, and long-chain acylcarnitines unaltered. GD and treatment of the disease is associated with pronounced acyl chain length-dependent alterations in acylcarnitine levels. These changes may be impacted by ethnicity and or dietary differences.


Mapping of rRNA genes with integrable plasmids in Bacillus subtilis.
Integrable plasmids pGR102 and pWR103 containing ribosomal sequences from within the transcriptional units for 16S and 23S were used to transform Bacillus subtilis. To date, these plasmids integrated into 7 of 10 known rrn operons. Two such events occurred at unassigned operons, revealing a close linkage of the CAT gene of the plasmid to pha-1 situated between dal-1 and purB33 for rrnE and to thiA78 situated between glyB133 and re-12 for rrnD. All seven integration events that led to the loss of unique ribosomal BclI fragments can now be assigned to known rrn operons.


Debye series analysis of scattering of a plane wave by a spherical Bragg grating.
The Debye series decomposition of the partial-wave scattering amplitudes of a multilayer sphere is derived. The partial-wave transmission and reflection terms appearing in the Debye series are multiple-scattering amplitudes written in terms of four basic quantities and combined together layer by layer in an identical way. The resulting expressions are then used to calculate the scattered intensity of a spherical Bragg grating covering a dielectric core particle and to analyze a number of new structures appearing in the scattered intensity.


High-flow nasal cannula therapies for respiratory management in pediatric patients.
High-flow nasal cannula (HFNC) oxygen therapy is a non-invasive form of respiratory support that is rapidly being taken up in pediatric intensive care units (PICU). For infants with bronchiolitis, who are the largest non-elective source of admissions to a PICU, there is some evidence that using HFNC therapy reduces the need for intubation and mechanical ventilation. The aim of this review article is to explore, describe, critique and add to the evidence surrounding the use of HFNC therapy in the pediatric population for the management of respiratory distress.


[One hundred years after the Geminal law, Rene Cerbelaud publishes secret remedies].
Our colleague René Cerbelaud was an original character. He played an important part in the pharmaceutical history of the 20th century when published recipes of countless medicines and cosmetic products, incurring the hostility of their manufacturers. As a matter of fact, he contributed to the disappearance of secret remedies and therefore to the enforcement of the Germinal law more than a century after it was promulgated. In a sense he may be looked on as the inventor of generic drugs and the promoter of what has become "parapharmacie".


[Pathology of Meckel's diverticulum. Apropos of a case. Notes on surgical anatomy and surgical technic].
Remembering an observed case of intestinal invagination from Meckel's diverticle the A. describe the most important anatomical and anatomo-surgical characteristics of the diverticle of Meckel, laying particular stress on the variation in form; position and size with reference to the part they have in surgical operations. The operation tecnique of transportation of the diverticle in its various pathologic cases is also a point treated in this work; the principle methods of ablation are brought up to date with synthetic iconography.


Hereditary nonpolyposis colorectal cancer family members' perceptions about the duty to inform and health professionals' role in disseminating genetic information.
This study's aim was to ascertain hereditary nonpolyposis colorectal cancer (HNPCC) families' views on the duty to inform with particular focus on the role of health professionals in disseminating familial genetic information. Eighty members of 16 families with a clinical or molecular diagnosis of HNPCC completed qualitative interviews regarding views on family members' right to know and who should disseminate familial genetic information. Most indicated that everyone in the family should know about the presence of a mutation in the family, with family members themselves being the preferable informant, supported by health professionals who were seen as helpful in overcoming barriers. All but one respondent indicated that if a parent did not test and presumably did not inform his/her child about the family mutation, the child should be informed by other family members or by a health professional. Many were attuned to confidentiality concerns, but judged them to be outweighed by the importance of family members knowing about the mutation and undertaking proper surveillance. Respondents were more private about the disclosure of individual results to other family members, clearly distinguishing personal results from familial genetic information. These families with a hereditary colon cancer syndrome favor open sharing of genetic information within the family, and desire the supportive involvement of health care professionals in disseminating genetic information.


Antioxidant and anti-osteoporotic effects of anthraquinones and related constituents from the aqueous dissolved Aloe exudates.
In this study, 25 known anthraquinones and related compounds were isolated from aqueous dissolved Aloe exudates. The antioxidant and anti-osteoporotic activities of the isolated compounds were then investigated. Compounds 8, 11, 20, and 23 showed good antioxidant activity based on peroxyl radical-scavenging and reducing capacity assays at a concentration of 10.0 μM. Additionally, compounds 7, 9, 15-16, 18, 21-22 and 24-25 showed potent peroxyl radical-scavenging activities with values ranging from 5.28 to 14.60 at 10.0 μM. Moreover, compounds 8, 11, 15, 20 and 22 exhibited significantly suppressed tartrate-resistant acid phosphatase (TRAP) activity in nuclear factor-κB ligand-activated osteoclastic RAW 264.7 cells, with values of 125.67, 118.54, 127.64, 125.82 and 124.98%, respectively. These results indicate that Aloe is an excellent source of antioxidant and anti-osteoporotic phytochemicals.


Programmed death-ligand 1 expression and CD8+ tumor-infiltrating lymphocytes in advanced non-small cell lung cancer treated with microwave ablation and chemotherapy.
Programmed death-ligand 1 (PD-L1) and CD8+ tumor-infiltrating lymphocytes (TILs) were associated with non-small cell lung cancer (NSCLC). We conducted this study to evaluate the correlation between PD-L1 or CD8+ TILs expression and MWA or survival in advanced NSCLC patients treated with microwave ablation (MWA) plus chemotherapy. Previously untreated, pathologically verified advanced NSCLC patients with adequate tissues for the analysis of PD-L1 expression and the presence of CD8+ TILs were retrospectively enrolled. None of the patients had sensitive mutations, and therefore, they were treated with MWA of the primary tumors followed by chemotherapy. A total of 51 patients were enrolled. PD-L1 expression and the presence of CD8+ TILs were identified in 31 (60.8%) and 9 (17.6%) patients, respectively. PD-L1 expression and CD8+ TILs had no correlation with baseline characteristics, the response to chemotherapy or MWA. Patients with PD-L1 expression had similar progression-free survival (PFS: 7.9 months for PD-L1-positive vs. 5.8 months for PD-L1-negative; p = .660) and overall survival (OS: 18.7 months for PD-L1-positive vs. 15.2 months for PD-L1-negative; p = .901). Patients with CD8+ TIL expression did not show superior PFS (CD8+ TIL vs. CD8- TIL, 8.0 vs. 6.2 months, p = .435) or OS (CD8+ TIL vs. CD8- TIL, 20.5 vs. 16.9 months, p = .653). PD-L1 expression and the presence of CD8+ TILs could predict neither the patients' response to chemotherapy or MWA nor survival in advanced NSCLC patients treated with MWA plus chemotherapy.


Renin gene expression, biosynthesis, and cellular pathways of secretion.
The molecular biology of the human renin gene is reviewed. This 12.5 kb gene contains 10 exons and 9 introns. In its 5' flanking region, major control elements are present. These include promoters and enhancers as well as regulatory elements. The combined action of these elements would result in tissue specific expression and regulation of the gene. In addition to the control at the gene expression level, renin is also regulated at the posttranslational and secretory levels. The translational product of renin mRNA is preprorenin, which is cotranslationally cleaved to prorenin, an inactive precursor of renin. The majority of new synthesized human prorenin is constitutively secreted. However, prorenin is also processed intracellularly to the mature single chain active renin which is stored in secretory granules. Active renin is released by a regulated mechanism which can be stimulated by cAMP and other secretagogues. Studies are under way to examine the responses of renin gene expression, biosynthesis and secretion to various physiological conditions.


Functional brain network and trail making test changes following major surgery and postoperative delirium: a prospective, multicentre, observational cohort study.
Delirium is a frequent complication after surgery in older adults and is associated with an increased risk of long-term cognitive impairment and dementia. Disturbances in functional brain networks were previously reported during delirium. We hypothesised that alterations in functional brain networks persist after remission of postoperative delirium and that functional brain network alterations are associated with long-term cognitive impairment. In this prospective, multicentre, observational cohort study, we included older patients who underwent clinical assessments (including the Trail Making Test B [TMT-B]) and resting-state functional MRI (rs-fMRI) before and 3 months after elective surgery. Delirium was assessed on the first seven postoperative days. Of the 554 enrolled patients, 246 remained after strict motion correction, of whom 38 (16%) developed postoperative delirium. The rs-fMRI functional connectivity strength increased 3 months after surgery in the total study population (β=0.006; 95% confidence interval [CI]: 0.001-0.011; P=0.013), but it decreased after postoperative delirium (β=-0.015; 95% CI: -0.028 to 0.002; P=0.023). No difference in TMT-B scores was found at follow-up between patients with and without postoperative delirium. Patients with decreased functional connectivity strength declined in TMT-B scores compared with those who did not (β=11.04; 95% CI: 0.85-21.2; P=0.034). Postoperative delirium was associated with decreased brain functional connectivity strength after 3 months, suggesting that delirium has a long-lasting impact on brain networks. The decreased connectivity strength was associated with significant cognitive deterioration after major surgery. NCT02265263.


Knockdown of GLP-1 Receptors in Vagal Afferents Affects Normal Food Intake and Glycemia.
Nutrient stimulation of enteroendocrine L cells induces the release of the incretin and satiating peptide glucagon-like peptide 1 (GLP-1). The vagus nerve innervates visceral organs and may contribute to the mediation of gut-derived GLP-1's effects on food intake, energy homeostasis, and glycemic control. To test the hypothesis that vagal afferent neuron (VAN) GLP-1 receptors (GLP-1Rs) are necessary for these effects of endogenous GLP-1, we established a novel bilateral nodose ganglia injection technique to deliver a lentiviral vector and to knock down VAN GLP-1Rs in male Sprague Dawley rats. We found that a full expression of VAN GLP-1Rs is not necessary for the maintenance of long-term energy balance in normal eating conditions. VAN GLP-1R knockdown (kd) did, however, increase meal size and accelerated gastric emptying. Moreover, postmeal glycemia was elevated and insulin release was blunted in GLP-1R kd rats, suggesting that VAN GLP-1Rs are physiological contributors to the neuroincretin effect after a meal. Collectively, our results highlight a crucial role for the VANs in mediating the effects of endogenous GLP-1 on food intake and glycemia and may promote the further development of GLP-1-based therapies.


Biochemical evaluation of antidiabetogenic properties of some commonly used Indian plants on streptozotocin-induced diabetes in experimental rats.
1. Diabetes mellitus is a serious metabolic disorder with micro- and macrovascular complications that results in significant morbidity and mortality. 2. The aim of the present study was to evaluate the hypoglycaemic efficacy of commonly used traditional Indian plants, such as Murraya koenigii, Mentha piperitae, Ocimum sanctum and Aegle marmelos, in streptozotocin (STZ)-induced experimental rats. 3. Oral administration of the ethanolic extract of these plants resulted in a significant decrease in the levels of blood glucose, glycosylated haemoglobin and urea, with a concomitant increase in glycogen, haemoglobin and protein, in diabetic rats. Treatment with these plant extracts also resulted in an increase in insulin and C-peptide levels and glucose tolerance. 4. The decreased activities of carbohydrate-metabolising enzymes, such as hexokinase, glucose-6-phosphate dehydrogenase and glycogen synthase, in diabetic rats were significantly elevated towards near normal in rats treated with extracts of M. koenigii, O. sanctum and A. marmelos; the increased activities of lactate dehydrogenase, fructose-1,6-bisphosphatase, glucose-6-phosphatase and glycogen phosphorylase in STZ diabetic rats were significantly reduced following treatment with the plant extracts. 5. Elevated specific binding of [(125)I]-labelled insulin to the receptor found in diabetic rats was markedly decreased in extract-treated groups. However, treatment of diabetic rats with M. piperitae did not result in any significant modification in all parameters. 6. Phytochemical screening conducted by us revealed the presence of biologically active ingredients in the ethanolic extracts of M. koenigii, O. sanctum and A. marmelos, which may readily account for the observed hypoglycaemic activity.


Theoretical reassessment of Whelk-O1 as an enantioselective receptor for 1-(4-halogeno-phenyl)-1-ethylamine derivatives.
A combination of molecular mechanics and first principles calculations was used to explore the enantioselectivity of receptors, taking into account experimental data from the CHIRBASE database. Interactions between the Whelk-O1 HPLC chiral stationary phase with the complete series of 1-(4-halogeno-phenyl)-1-ethylamine derivative racemates were studied. The objective was to extract information from the interactions between the chiral Whelk-O1 stationary phase and the enantiomers, hence probing the origin of the enantioselective behavior. Calculations correctly reproduce the elution orders and reasonably describe the experimental enantioselectivities and retention factors. Different binding modes were observed for the first eluted enantiomer complexes, whereas the second eluted show only one prevalent diastereomeric binding fashion. Natural bond orbital (NBO) analysis was used on the global minima bound-complexes to quantify donor-acceptor interactions among chiral stationary phase and ligand moieties. Intermolecular hydrogen bonding was found to be the essential energetic interaction for all systems studied. CH-pi, aromatic stacking and various charge transfer interactions were found to be smaller in magnitude but still important for the global enantioselective behavior. The three-point interaction model is discussed, pointing out the difficulty of its application for the qualitative prediction of elution orders (absolute configurations).


Educating African pastors on mother-to-child transmission of HIV/AIDS.
To educate pastors of the Assemblies of God in Burkina Faso concerning HIV/AIDS and mother-to-child transmission (MTCT). A pretest-posttest design was used with a convenience sample of 102 pastors attending the educational program on HIV/AIDS and MTCT in January, February, and March of 2005. The educational program was implemented in local Bible colleges in Ouagadougou, Burkina Faso. Participants attended an 18-hour program on HIV/AIDS and MTCT. A picture booklet was designed and used to help explain the prevention of MTCT of HIV The pretest-posttest examination and follow-up evaluation were designed for this project. Results of the pretest showed minimal knowledge of pastors regarding HIV/AIDS. The median composite scores on the knowledge questions increased from 16% on the pretest to 92% on the posttest. Within the 3-month follow-up period, 34 follow-up evaluations were received. Although all the responding pastors had recommended testing for expectant mothers, only 13 had discussed MTCT in their churches or communities. The educational program was effective in increasing the pastors' knowledge of HIV/AIDS and MTCT. Further research is needed to identify barriers to full utilization of that knowledge.


Orbital metastasis as the initial presentation of lung adenocarcinoma: a case report.
Orbital metastasis as the initial presentation of lung adenocarcinoma is very rare, and so the lack of knowledge about this phenomenon can easily result in misdiagnosis, either as a orbital primary tumor or benign lesion. Here, we report a rare case in which the orbital symptom appeared first without any pulmonary manifestations. Our patient developed decreasing vision in his right eye over a 3-month duration. He then presented with proptosis and multiple aches from head to back. After systemic evaluation, our patient was diagnosed with Stage IV non-small-cell lung cancer and was managed with palliative chemoradiotherapy. The final result of treatment suggests that the therapeutic efficacy of chemotherapy on orbital metastasis is uncertain, and only some orbital metastatic masses may have a favorable response to radiation. Furthermore, we review the recent data and provide an in-depth discussion on the clinical features and course of ocular pulmonary metastases, and explain a new type of non-small-cell lung cancer metastatic pattern for ophthalmologists and oncologists to help them distinguish the orbital metastasis as the first manifestation.


Dealing with femtorisks in international relations.
The contemporary global community is increasingly interdependent and confronted with systemic risks posed by the actions and interactions of actors existing beneath the level of formal institutions, often operating outside effective governance structures. Frequently, these actors are human agents, such as rogue traders or aggressive financial innovators, terrorists, groups of dissidents, or unauthorized sources of sensitive or secret information about government or private sector activities. In other instances, influential "actors" take the form of climate change, communications technologies, or socioeconomic globalization. Although these individual forces may be small relative to state governments or international institutions, or may operate on long time scales, the changes they catalyze can pose significant challenges to the analysis and practice of international relations through the operation of complex feedbacks and interactions of individual agents and interconnected systems. We call these challenges "femtorisks," and emphasize their importance for two reasons. First, in isolation, they may be inconsequential and semiautonomous; but when embedded in complex adaptive systems, characterized by individual agents able to change, learn from experience, and pursue their own agendas, the strategic interaction between actors can propel systems down paths of increasing, even global, instability. Second, because their influence stems from complex interactions at interfaces of multiple systems (e.g., social, financial, political, technological, ecological, etc.), femtorisks challenge standard approaches to risk assessment, as higher-order consequences cascade across the boundaries of socially constructed complex systems. We argue that new approaches to assessing and managing systemic risk in international relations are required, inspired by principles of evolutionary theory and development of resilient ecological systems.


Effect of hemagglutinin glycosylation on influenza virus susceptibility to neuraminidase inhibitors.
Inhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA). Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication. With the use of reverse genetics technique, we investigated the effect of glycans attached at Asn 94a, 129, and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activity.


Cudraflavone C Induces Apoptosis of A375.S2 Melanoma Cells through Mitochondrial ROS Production and MAPK Activation.
Melanoma is the most malignant form of skin cancer and is associated with a very poor prognosis. The aim of this study was to evaluate the apoptotic effects of cudraflavone C on A375.S2 melanoma cells and to determine the underlying mechanisms involved in apoptosis. Cell viability was determined using the MTT and real-time cytotoxicity assays. Flow cytometric evaluation of apoptosis was performed after staining the cells with Annexin V-FITC and propidium iodide. The mitochondrial membrane potential was evaluated using the JC-1 assay. Cellular ROS production was measured using the CellROX assay, while mitochondrial ROS production was evaluated using the MitoSOX assay. It was observed that cudraflavone C inhibited growth in A375.S2 melanoma cells, and promoted apoptosis via the mitochondrial pathway mediated by increased mitochondrial ROS production. In addition, cudraflavone C induced phosphorylation of MAPKs (p38, ERK, and JNK) and up-regulated the expression of apoptotic proteins (Puma, Bax, Bad, Bid, Apaf-1, cytochrome C, caspase-9, and caspase-3/7) in A375.S2 cells. Pretreatment of A375.S2 cells with MitoTEMPOL (a mitochondria-targeted antioxidant) attenuated the phosphorylation of MAPKs, expression of apoptotic proteins, and the overall progression of apoptosis. In summary, cudraflavone C induced apoptosis in A375.S2 melanoma cells by increasing mitochondrial ROS production; thus, activating p38, ERK, and JNK; and increasing the expression of apoptotic proteins. Therefore, cudraflavone C may be regarded as a potential form of treatment for malignant melanoma.


Sensorineural hearing loss associated with systemic lupus erythematosus.
Because our recent clinical experiences suggested a possible association between hearing loss and systemic lupus erythematosus (SLE), we prospectively studied the hearing of 30 patients hospitalized because of exacerbation of SLE. Twenty-nine of the 30 patients were receiving immunosuppressive therapy at the time of testing. We found an 8% incidence of substantial, previously undetected hearing loss without attributable cause. Hearing loss could not be correlated to age, sex, disease activity, organ-system involvement, laboratory test abnormalities, or duration of symptoms of SLE. Otolaryngologists treating patients with unexplainable hearing loss--particularly if it is sudden, fluctuating, or rapidly progressive--are alerted to the possibility of underlying systemic autoimmunity. We advise physicians who frequently treat patients with SLE to include questions on hearing in the review of systems and to refer the patient with hearing complaints for thorough otologic evaluation.


Cyclic changes in the concentrations of peripheral blood immune cells during the normal menstrual cycle.
The optimal availability of immune cells in the peripheral blood streams of women may play a critical role in their response to disease and therapeutic interventions. This study was designed to examine concentrations of circulating white blood cells (WBC) including lymphocyte subsets, during the 24-hr daily and 28-day menstrual cycles. Venous blood (20 ml) from five healthy young women was obtained at 0, 6, 12, and 18 hr on the 6th and 22nd day of the normal menstrual cycle. Cortisol, progesterone (P4), estradiol (E2), total WBC, granulocyte, monocyte, and total lymphocyte levels were measured. Using fluorescent activated cell scanning, levels of T, B, Helper (H), Suppressor (S) and Natural Killer (NK) cells were also determined. Significant differences in the diurnal and Day 6 and 22 means were identified using analysis of variance and the Student's t test. Mean WBC counts differed significantly between individuals and ranged from 3.63 +/- 0.33 to 8.60 +/- 1.00 on Day 6 and 3.75 +/- 0.56 to 9.45 +/- 0.98 on Day 22 (P < 0.05). Fluctuations in the concentrations of peripheral blood immune cells followed a similar pattern for the time points selected. They were lowest in the morning at 6 hr and reached peak concentrations in the evening at 17 hr or at midnight at 24:00 hr. Total WBC and granulocyte levels were consistently highest in the evening at 18 hr while lymphocyte levels either peaked in the evening or at midnight. Between midnight and early morning, levels of WBC, lymphocytes, T, B, H, and S cells all decreased significantly (P < 0.01) and subsequently increased significantly, between 6 hr and noon or noon and 18 hr (P < 0.01). When compared every 12 hr, the levels of WBC, granulocytes, lymphocytes, T, B, H, and S cells showed a significant day time rise between 6 and 18 hr (P < 0.02). NK cells revealed no significant fluctuations for any of the diurnal time point comparisons examined in this study. The WBC means for all subjects on Day 6 was 6.15 +/- 1.96 and on Day 22 was 6.39 +/- 2.14, evidence that the total number of white blood cells was not significantly altered between the 2 days. However when comparing specific time points during the day for the follicular (Day 6) and luteal (Day 22) phases of the menstrual cycle, significant differences were found. Most striking were the monocyte patterns, which revealed a nadir at 12:00 noon on Day 6 and a peak at the same time on Day 22.(ABSTRACT TRUNCATED AT 400 WORDS)


Interventional radiology for the non-surgical removal of sialoliths.
To clarify the usefulness and limitations of interventional radiology for sialolithiasis. Sixteen patients (5 with parotid and 11 with submandibular sialolithiasis) were treated with a stone retrieval catheter (Dormia basket) under fluoroscopy. Digital subtraction sialography (DSS) and direct digital dental imaging (RVG) were performed in addition for 11 of the cases (DSS for 7 and RVG for 4 cases). The sialolith was successfully removed in 10 cases. DSS and RVG were useful. Four cases failed because the stone was adherent to the ductal wall and two because the catheter could not reach the stone because of the ductal anatomy. Interventional radiology is less invasive than surgical treatment and is the recommended first choice for treatment in the majority of cases of sialolithiasis.


Reduction of HbA1c and diabetes-related distress after intervention in a diabetes day care clinic in people with type 2 diabetes but not with type 1 diabetes.
The aim of this prospective, longitudinal study was to assess diabetes-related distress in people with diabetes mellitus type 1 (DM1) and type 2 (DM2) treated for diabetes-related problems and to evaluate, whether distress by diabetes are reduced after intervention in a diabetes day care clinic (DDC). Diabetes-related burden was assessed with the "Problem Area In Diabetes" (PAID) questionnaire before (T0), directly after (T1) and 6 months after intervention (T2) in the DDC in 72 people (18 DM1, 54 DM2) admitted with a diabetes-specific problem to a DDC in a University department for metabolic diseases. A PAID score of ≥40 was considered as high diabetes-related distress. The PAID score in people with DM1 was not significantly different between T0, T1 and T2. Furthermore, neither HbA1c nor insulin dose did change at T2. In participants with DM2, the PAID score decreased significantly from T0 to T1 (18.4±15.9 vs. 15.4+± 13.0, p=0.042) and preserved the benefit at T2 (15.0±13.3). In addition, there was a significant reduction in HbA1c (-1.2%, p<0.001) and body weight (-1.3 kg, p=0.038) between T0 and T2. Insulin dose per day was 15.0 IU/day lower at T1 (p=0.006) and 9.0 IU/day lower at T2 (p=0.212) in comparison to T0. Diabetes-related distress was reduced after a problem-oriented intervention in a DDC in people with DM2 but not with DM1. Although, all participants at tertiary care level had serious diabetes-specific problems before intervention, mean PAID score was far under the threshold of 40 points thus distress was low.


Significance of infectious agents in colorectal cancer development.
Colorectal cancer (CRC) is a major burden to healthcare systems worldwide accounting for approximately one million of new cancer cases worldwide. Even though, CRC mortality has decreased over the last 20 years, it remains the third most common cause of cancer-related mortality, accounting for approximately 600,000 deaths in 2008 worldwide. A multitude of risk factors have been linked to CRC, including hereditary factors, environmental factors and inflammatory syndromes affecting the gastrointestinal tract. Recently, various pathogens were added to the growing list of risk factors for a number of common epithelial cancers, but despite the multitude of correlative studies, only suggestions remain about the possible relationship between selected viruses and bacteria of interest and the CRC risk. United States military service members are exposed to various risk factors impacting the incidence of cancer development. These exposures are often different from that of many sectors of the civilian population. Thereby, cancer risk identification, screening and early detection are imperative for both the military health care beneficiaries and the population as a whole. In this review, we will focus on several pathogens and their potential roles in development of CRC, highlighting the clinical trials evaluating this correlation and provide our personal opinion about the importance of risk reduction, health promotion and disease prevention for military health care beneficiaries.


Cross metathesis assisted solid-phase synthesis of glycopeptoids.
A solid-phase synthesis of glycopeptoids was explored through olefin cross metathesis (CM). Peptoids and sugar derivatives with appropriate olefin moieties were coupled in the presence of an olefin metathesis catalyst to afford glycopeptoids in good yields. This systematic solid-phase CM study can provide facile access to the molecular sources of glycopeptidomimetics and postchemical modifications on various molecular scaffolds.


Coordinated Action of Nap1 and RSC in Disassembly of Tandem Nucleosomes.
The SWI/SNF and RSC family of ATP-dependent chromatin remodelers disassembles nucleosomes by moving nucleosomes into the vicinity of adjoining nucleosomes. We found that the histone chaperone Nap1 efficiently promotes disassembly of adjacent nucleosomes with which RSC collides and not the disassembly of nucleosomes mobilized by RSC. Nap1 is specific to RSC, as it does not target SWI/SNF, its paralog in Saccharomyces cerevisiae Extensive mutational analysis of Nap1 has revealed that Nap1 affinity for histones H2A-H2B and H3-H4 and its ability to displace histones from DNA are required for Nap1 to enhance RSC-mediated disassembly. Other histone chaperones, such as Vps75, that also bind histones are not able to enhance RSC-mediated disassembly. Our study suggests a mechanism by which Nap1 is recruited to actively transcribed regions and assists in the passage of the transcription complex through chromatin, and it provides a novel mechanism for the coordinated action of RSC and Nap1.


Telephone clinic follow-up following carpal tunnel decompression.
This paper investigates the feasibility of a telephone clinic follow-up service for patients undergoing carpal tunnel decompression. Six hundred and thirty patients were recruited over a 2-year period and we assessed their outcome and satisfaction level in the service, using a pre-determined questionnaire 6 weeks following surgery. The telephone clinic was overseen by a surgical care practitioner. We followed up 598 patients (93%) in total, and found 42 patients to be dissatisfied with the service (7%). These patients were referred for outpatient consultation and investigation. Most patients were satisfied with their surgical outcome and found the telephone clinic service to be convenient and effective. Cost analysis calculations estimated a potential saving of pound 45,958 over the 2-year period when compared to standard outpatient consultation. This model has been developed in our trust to follow up patients undergoing similar minor hand surgery.


Structural modulation study of inhibitory compounds for ribonuclease H activity of human immunodeficiency virus type 1 reverse transcriptase.
Reverse transcriptase of human immunodeficiency virus type 1 (HIV-1) has two enzymatic functions. One of the functions is ribonuclease (RNase) H activity concerning the digestion of only RNA of RNA/DNA hybrid. The RNase H activity is an attractive target for a new class of anti-HIV drugs because no approved inhibitor is available now. In our previous studies, an agent bearing 5-nitro-furan-2-carboxylic acid ester core was found from chemical screening and dozens of the derivatives were synthesized to improve compound potency. In this work, some parts of the chemical structure were modulated to deepen our understanding of the structure-activity relationship of the analogous compounds. Several derivatives having nitro-furan-phenyl-ester skeleton were shown to be potent RNase H inhibitors. Attaching methoxy-carbonyl and methoxy groups to the phenyl ring increased the inhibitory potency. No significant cytotoxicity was observed for these active derivatives. In contrast, the derivatives having nitro-furan-benzyl-ester skeleton showed modest inhibitory activities regardless of attaching diverse kinds of functional groups to the benzyl ring. Both the modulation of the 5-nitro-furan-2-carboxylic moiety and the conversion of the ester linkage resulted in a drastic decrease in inhibitory potency. These findings are informative for designing potent inhibitors of RNase H enzymatic activity of HIV-1.


Alterations in circulatory and renal angiotensin-converting enzyme and angiotensin-converting enzyme 2 in fetal programmed hypertension.
Antenatal betamethasone treatment is a widely accepted therapy to accelerate lung development and improve survival in preterm infants. However, there are reports that infants who receive antenatal glucocorticoids exhibit higher systolic blood pressure in their early adolescent years. We have developed an experimental model of programming whereby the offspring of pregnant sheep administered clinically relevant doses of betamethasone exhibit elevated blood pressure. We tested the hypothesis as to whether alterations in angiotensin-converting enzyme (ACE), ACE2, and neprilysin in serum, urine, and proximal tubules are associated with this increase in mean arterial pressure. Male sheep were administered betamethasone (2 doses of 0.17 mg/kg, 24 hours apart) or vehicle at the 80th day of gestation and delivered at term. Sheep were instrumented at adulthood (1.8 years) for direct conscious recording of mean arterial pressure. Serum and urine were collected and proximal tubules isolated from the renal cortex. Betamethasone-treated animals had elevated mean arterial pressure (97+/-3 versus 83+/-2 mm Hg; P<0.05) and a 25% increase in serum ACE activity (48.4+/-7.0 versus 36.0+/-2.7 fmol/mL per minute) but a 40% reduction in serum ACE2 activity (18.8+/-1.2 versus 31.4+/-4.4 fmol/mL per minute). In isolated proximal tubules, ACE2 activity and expression were 50% lower in the treated sheep with no significant change in ACE or neprilysin activities. We conclude that antenatal steroid treatment results in the chronic alteration of ACE and ACE2 in the circulatory and tubular compartments, which may contribute to the higher blood pressure in this model of fetal programming-induced hypertension.


Machine learning methods to predict child posttraumatic stress: a proof of concept study.
The care of traumatized children would benefit significantly from accurate predictive models for Posttraumatic Stress Disorder (PTSD), using information available around the time of trauma. Machine Learning (ML) computational methods have yielded strong results in recent applications across many diseases and data types, yet they have not been previously applied to childhood PTSD. Since these methods have not been applied to this complex and debilitating disorder, there is a great deal that remains to be learned about their application. The first step is to prove the concept: Can ML methods - as applied in other fields - produce predictive classification models for childhood PTSD? Additionally, we seek to determine if specific variables can be identified - from the aforementioned predictive classification models - with putative causal relations to PTSD. ML predictive classification methods - with causal discovery feature selection - were applied to a data set of 163 children hospitalized with an injury and PTSD was determined three months after hospital discharge. At the time of hospitalization, 105 risk factor variables were collected spanning a range of biopsychosocial domains. Seven percent of subjects had a high level of PTSD symptoms. A predictive classification model was discovered with significant predictive accuracy. A predictive model constructed based on subsets of potentially causally relevant features achieves similar predictivity compared to the best predictive model constructed with all variables. Causal Discovery feature selection methods identified 58 variables of which 10 were identified as most stable. In this first proof-of-concept application of ML methods to predict childhood Posttraumatic Stress we were able to determine both predictive classification models for childhood PTSD and identify several causal variables. This set of techniques has great potential for enhancing the methodological toolkit in the field and future studies should seek to replicate, refine, and extend the results produced in this study.


Dextran sulfate sodium-induced chronic colitis attenuates Ca2+-activated Cl- secretion in murine colon by downregulating TMEM16A.
Attenuated Ca2+-activated Cl- secretion has previously been observed in the model of dextran sulfate sodium (DSS)-induced colitis. Prior studies have implicated dysfunctional muscarinic signaling from basolateral membranes as the potential perpetrator leading to decreased Ca2+-activated Cl- secretion. However, in our chronic model of DSS-colitis, cholinergic receptor muscarinic 3 ( Chrm3) transcript (1.028 ± 0.12 vs. 1.029 ± 0.27, P > 0.05) and CHRM3 protein expression (1.021 ± 0.24 vs. 0.928 ± 0.09, P > 0.05) were unchanged. Therefore, we hypothesized that decreased carbachol (CCH)-stimulated Cl- secretion in DSS-induced colitis could be attributed to a loss of Ca2+-activated Cl- channels (CaCC) in apical membranes of colonic epithelium. To establish this chemically-induced colitis, Balb/C mice were exposed to 4% DSS for five alternating weeks to stimulate a more moderate, chronic colitis. Upon completion of the protocol, whole thickness sections of colon were mounted in an Ussing chamber under voltage-clamp conditions. DSS-induced colitis demonstrated a complete inhibition of basolateral administration of CCH-stimulated Cl- secretion that actually displayed a reversal in polarity (15.40 ± 2.22 μA/cm2 vs. -2.47 ± 0.25 μA/cm2). Western blotting of potential CaCCs, quantified by densitometric analysis, demonstrated no change in bestrophin-2 and cystic fibrosis transmembrane regulator, whereas anoctamin-1 [ANO1, transmembrane protein 16A (TMEM16A)] was significantly downregulated (1.001 ± 0.13 vs. 0.510 ± 0.12, P < 0.05). Our findings indicate that decreased expression of TMEM16A in DSS-induced colitis contributes to the decreased Ca2+-activated Cl- secretion in murine colon.


Parametric Optimization of Laser Additive Manufacturing of Inconel 625 Using Taguchi Method and Grey Relational Analysis.
In order to improve the forming quality of the Inconel 625 cladding layer and make it to be more widely used. This paper addresses an experimental investigation on the influence of major process parameters like laser power, scanning speed, powder feed rate, and overlapping rate along with their interactions on surface roughness and width error of laser additive manufacturing process for forming Inconel 625 samples. Taguchi method and grey relational analysis were used to optimize the selected parameters, and the verification tests were carried out. The change of microhardness and microstructure in the overlapping zone and nonoverlapping zone of the cladding layer were studied by microhardness tester and scanning electron microscopy (SEM). The results show that the most significant effect in processing parameters on surface roughness and width error are both overlapping rate, and the optimal levels of laser power, scanning speed, powder feeder rate, and overlapping rate are 1800 W, 8 mm/s, 10 g/min, and 30%, respectively. Analysis of microstructure and composition showed that the content of Cr was high both in the Laves phase and matrix, the content of Nb in the Laves phase increased significantly and reached up to 24.48 wt%, and the Laves in the nonoverlapping zone was more compact than the overlapping zone.


Symptoms and signs of acromegaly: an ongoing need to raise awareness among healthcare practitioners.
INTRODUCTION Chronic excess growth hormone production results in acromegaly, a condition associated with widespread physical changes, including soft tissue and bony overgrowth. When untreated, acromegaly reduces life expectancy. Patients usually remain undiagnosed for years after the onset of symptoms, by which stage irreversible physical changes have often occurred. METHOD A cross-sectional questionnaire study involving patients with acromegaly from the Waikato Endocrine Unit and the New Zealand Acromegaly Society evaluated features of acromegaly that were present before diagnosis. The aim of this study was to identify acromegaly features that were most prevalent to promote increased awareness about the disease by healthcare providers. RESULTS 81 participants were included. The main pre-diagnosis physical changes participants reported were acral changes, alterations in facial features and oral symptoms. For some, these features were present for more than 10 years before the acromegaly diagnosis. Multiple co-morbidities associated with acromegaly were reported. Two-thirds of the participants felt that an earlier diagnosis was possible. Most participants were in contact with General Practitioners (GPs) and/or dentists before diagnosis. Endocrinologists had the highest diagnosis rate, followed by GPs. Dentists had a low diagnosis rate despite a high prevalence of oral symptoms among study participants. CONCLUSION Increased awareness of acromegaly among primary care clinicians is important as they are the first-point-of-contact with the healthcare system for most patients. Health professionals' early recognition of symptoms and signs of acromegaly would reduce delays in time-to-diagnosis, enable earlier treatment and may improve outcomes for patients with acromegaly. MESH KEYWORDS Acromegaly; symptoms; delayed diagnosis; clinicians; primary healthcare.


Impact of antiretroviral therapy duration and intensification on isolated shedding of HIV-1 RNA in semen.
Effective antiretroviral therapy (ART) dramatically reduces human immunodeficiency virus (HIV) transmission. However, isolated shedding of HIV type 1 (HIV-1) in semen (IHS) can occur in the absence of detectable viremia or genital infections. We hypothesized that ART intensification with medications active in semen might prevent IHS. Paired blood and semen samples were collected monthly for 6 months from HIV-infected men starting ART that was intensified (iART) with maraviroc and raltegravir in an open-label fashion. Semen parameters were compared to those of historical controls starting standard ART (sART). Compared with 25 controls who started sART, the semen HIV-1 load in 13 subjects who started iART was more rapidly suppressed (P = .043). IHS was detected at >1 visit in 2 participants (15%) receiving iART and in 12 controls (48%) receiving sART (P = .040). Among iART recipients, IHS was associated with lower raltegravir concentrations in blood and semen, compared with complete HIV-1 suppression (P = .03). Prolonged, high-level IHS (ie, shedding of >5000 RNA copies/mL) was observed in 1 iART recipient (8%), despite rapid viremia suppression and therapeutic drug levels; for 10 months, this virus remained R5 tropic, drug susceptible, and similar in sequence to virus recovered from blood. IHS was not seen after >3 years of effective ART in a parallel, prospective cohort study. iART transiently reduced the occurrence of IHS early after ART initiation but did not prevent high-level IHS. IHS was not seen after more prolonged sART.


Childhood health in Jamaica: changing patterns in health conditions of children 0-14 years.
The new thrust by WHO is healthy life expectancy. Therefore, health must be more than morbidity. It is within this framework that a study on childhood health in Jamaica is of vital importance. This study 1) expands the health literature in Jamaica and by extension the Caribbean, 2) will aid public health practitioners with research findings upon which they are able to further improve the quality of life of children, 3) investigates the age at with children in Jamaica become influenced by particular chronic diseases and 4) assesses the subjective wellbeing of children. The current study extracted a sample of 8,373 and 2,104 children 0-14 years from two surveys collected jointly by the Planning Institute of Jamaica and the Statistics Institute of Jamaica for 2002 and 2007 respectively. A self-administered questionnaire was used to collect the data. Ninety-one percent of children in Jamaica, for 2007, reported good health. The number of children who had diarrhea fell by 84.2% in 2007 over 2002, and a similar reduction was observed for those with asthma (42.1% in 2002 and 19.7% in 2007). Another critical finding was that 1.2% of children, in 2007, had diabetes mellitus compared to none in 2002. Public health now has an epidemiological profile of health conditions of children and the demographic shifts which are occurring and this can be used for effective management and planning of the new health reality of the Jamaican child.


Heterogeneous variances and genetics by environment interactions in genetic evaluation of crossbred lambs.
Accounting for environmental heteroscedasticity and genetics by environment interaction (G×E) in genetic evaluation is important because animals may not perform predictably across environments. The objectives of this study were to evaluate the presence and consequences of heteroscedasticity and G×E on genetic evaluation. The population considered was crossbred lambs sired by terminal sires and reared under commercial conditions in the UK. Data on 6325 lambs sired by Charollais, Suffolk and Texel rams were obtained. The experiment was conducted between 1999 and 2002 on three farms located in England, Scotland and Wales. There were 2322, 2137 and 1866 lambs in England, Scotland and Wales, respectively. A total of 89 sires were mated to 1984 ewes of two types (Welsh and Scottish Mules). Most rams were used for two breeding seasons with some rotated among farms to create genetic links. Lambs were reared on pasture and had their parentage, birth, 5 week, 10 week, and slaughter weights recorded. Lambs were slaughtered at a constant fatness, at which they were ultrasonically scanned for fat and muscle depth. Heteroscedasticity was evaluated in two ways. First, data were separated into three subsets by farm. Within-farm variance component estimates were then compared with those derived from the complete data (Model 1). Second, the combined data were fitted, but with a heterogeneous (by farm) environmental variance structure (Model 2). To investigate G×E, a model with a random farm by sire (F×S) interaction was used (Model 3). The ratio of the F×S variance to total variance was a measure of the level of G×E in the population. Heterogeneity in environmental variability across farm was identified for all traits (P<0.01). Rank correlations of sire estimated breeding value between farms differed for Model 1 for all traits. However, sires ranked similarly (rank correlation of 0.99) for weight traits with Model 2, but less so for ultrasonic measures. Including the F×S interaction (Model 3) improved model fit for all traits. However, the F×S term explained a small proportion of variation in weights (<2%) although more in ultrasonic traits (at least 10%). In conclusion, heteroscedasticity and G×E were not large for these data, and can be ignored in genetic evaluation of weight but, perhaps, not ultrasonic traits. Still, before incorporating heteroscedasticity and G×E into routine evaluations of even ultrasonic traits, their consequences on selection response in the breeding goal should be evaluated.


An extended mathematical model of tumor growth and its interaction with the immune system, to be used for developing an optimized immunotherapy treatment protocol.
Chemotherapy is usually known as the main modality for cancer treatment. Nevertheless, most of chronic cancers could not be treated with chemotherapy alone. Immunotherapy is a new modality for cancer treatment that is effective for early stages of cancer and it has fewer side effects compared to chemotherapy, specifically for those types of cancer that are resistant to it. This work presents an extended mathematical model to depict interactions between cancerous and adaptive immune system in mouse. We called the model an extended model, because we embedded all those compartments that have important roles in response to tumor in one model. The model includes tumor cells, natural killers, naïve and mature cytotoxic T cells, naïve and mature helper T cells, regulatory T cells, dendritic cells and interleukin 2 cytokine. Whole cycle of cell division program of immune cells is also considered in the model. We also optimized protocol of immunotherapy with DC vaccine based on the proposed mathematical model. Simulation results of the proposed model are in conformity with the experimental data recorded from mouse in immunology department of Tehran University of Medical Science as well as what has been explained in the literature. Our results explain dynamics of the immune cells from the first day of cancer growth and progression. Simulation result shows that reducing intervals between immunotherapy injections, efficacy of the treatment will be increased because CD8+ cells are boosted more rapidly. Optimized protocol for immunotherapy suggests that if the effect of DC vaccines on increasing number of anti-tumor immune cells be just before the maximum number of CD8+ cells, the effect of treatment will be maximized.


Evidence for platelet-activating factor as a late-phase mediator of chronic pancreatitis in the rat.
The role of platelet-activating factor (PAF) as a mediator of pancreatic inflammation was examined in the rat pancreatic duct ligation model of obstructive pancreatitis. Pancreatic generation of PAF, as measured by bioassay (ie, platelet [3H]serotonin secretion), was determined at various times after induction of inflammation. Tissue levels of PAF in the normal pancreas averaged 600 +/- 49 pg/g, but PAF was not detectable during the initial 24 hours of pancreatitis, a time when the inflammatory reaction would be considered acute, that is, during the period of maximal serum amylase release and the development of interstitial edema. However a substantial increase in pancreatic PAF levels (12 times control levels) was observed 7 to 14 days after duct ligation during the late-phase response interval similar to the situation characteristic of chronic pancreatitis in which parenchymal atrophy, fibrosis, and pancreatic insufficiency evolve. One week after duct ligation when PAF levels peaked, an evaluation was made of the effects of PAF antagonists (BN52021 and WEB2170) on pancreatic lesions using Evan's blue extravasation, pancreatic myeloperoxidase (MPO) activity, and acid phosphatase activity in peritoneal lavage fluid. BN52021 or WEB2170 treatment was shown to reduce pancreatic damage and inflammation significantly. Long-term in vivo administration of exogenous PAF (20 micrograms/kg/hr for 7 days) exhibited a reduction of [3H]thymidine uptake into and amylase release from pancreatic acini in vitro. Our observations 1) that pancreatic PAF levels increased significantly during the chronic phase of obstructive pancreatitis induced by duct ligation; 2) that inhibition of the action of PAF, through specific receptor antagonism, caused an attenuation of pancreatic lesions; and 3) that chronic administration of PAF resulted in decreased pancreatic regeneration and exocrine function are consistent with a pivotal role for PAF as a late-phase inflammatory mediator in chronic pancreatitis in rats.


Association of polymorphism in cytochrome P450 2D6 and N-acetyltransferase-2 with Parkinson's disease.
The present case-control study was carried out to investigate the association of polymorphism in cytochrome P450 2D6 (CYP2D6) and N-acteyltransferase-2 (NAT2}, that are involved in the metabolism and detoxification of chemicals causing Parkinson disease (PD) like symptoms, with PD. Our data demonstrated increased frequency of CYP2D6*2 (1749G/C and 2938C/T), CYP2D6*4 (1934G/A) and CYP2D6*10A (188C/T) polymorphisms in PD cases when compared to the controls. Statistical analysis revealed the significant association of CYP2D6*4 (1934G/A) and CYP2D6*10A (188C/T) polymorphism with PD. Likewise, increased frequency of NAT2*7 polymorphism that leads to the slow acetylator phenotype was observed in PD patients with more than fivefold increased risk (OR: 5.55; 95% CI: 0.56-54). No change was observed in the frequency of NAT*5 or NAT*6 alleles in the cases. Further, cases carrying combination of heterozygous genotypes of CYP2D6*4 or CYP2D6*10A(188C > T) and NAT2*5 were found to be at significantly higher risk for PD demonstrating the importance of gene-gene interactions in determining susceptibility to PD.


Current Patterns of Training in Personality Assessment During Internship.
Training in broad-based objective and projective personality assessments has been a mainstay of applied psychology. Stedman (2007) and Piotrowski (2015) have documented a decline in projective training during internship. This study investigated internship directors' current expectations regarding graduate school training with objective and projective instruments, their ratings of the importance of that training, and current training patterns with objective and projective instruments during internship. Participants were 355 psychology internship programs, representing 46.1% of the Association of Psychology Postdoctoral and Internship Centers. Results indicated the following current internship training patterns: Minnesota Multiphasic Personality Inventory (68% to 51%), Personality Assessment Inventory (59% to 25%), Millon Clinical Multiaxial Inventory (51% to 34%), Rorschach (35 to 26%), story telling (41% to 19%), sentence completion (41% to 18%), and drawings (36% to 9%). Adult program directors reported higher percentages for objective tests; child program directors reported higher percentages for projective tests. A decreased valuation of projective techniques is now typical of current internship training programs.


Unnecessary thyroid surgery rate for suspicious nodule in the absence of molecular testing.
Molecular tests for suspicious thyroid nodules decrease rates of unnecessary surgeries but are not widely used due to reimbursement issues. The aim of this study was to assess the rate of unnecessary surgery performed in real-life setting for Bethesda III, IV and V nodules in the absence of molecular testing. This is a single-center retrospective study of consecutive patients undergoing fine needle aspiration cytology (FNAC) with rapid on-site evaluation between January 2017 and December 2021. Unnecessary surgery was defined as surgery performed because of Bethesda III, IV, or V results in the absence of local compressive symptoms with final benign pathology and as second surgery for completion thyroidectomy. In the 862 patients (640 females, mean age: 54.2 years), 1010 nodules (median size: 24.4 mm) underwent 1189 FNAC. Nodules were EU-TIRADS 2, 3, 4, and 5 in 3%, 34%, 42%, and 22% of cases, respectively. FNAC was Bethesda I, II, III, IV, V, and VI in 8%, 48%, 17%, 17%, 3%, and 6%, respectively. Surgery was performed in 36% of Bethesda III nodules (benign on pathology: 81%), in 74% of Bethesda IV nodules (benign on pathology: 76%) and in 97% of Bethesda V nodules (benign on pathology: 21%). Surgery was considered unnecessary in 56%, 68%, and 21% of patients with Bethesda III, IV, and V nodules, respectively. In this real data cohort surgery was unnecessary in more than half of patients with Bethesda III and IV nodules and in 21% of patients with Bethesda V nodules.


Retinol-binding protein and beta 2-microglobulin in urine of cadmium-fed rhesus monkeys.
Retinol-binding protein (RBP) in the Rhesus monkey had the same electrophoretic mobility, molecular weight, and common antigens as human RBP; beta 2-microglobulin protein (MG) had similar electrophoretic mobility and partial common antigens to human MG. After a prolonged oral administration of cadmium chloride to 10 monkeys over a period of 55 weeks, one monkey of the 30 mg Cd/day group indicated RBPuria and MGuria with the use of anti-human RBP and MG sera when proteinuria appeared. The immunological assay of low-molecular-weight proteins in urine was not applicable for the early detection of cadmium health effects in monkeys.


Decrease in and polarization of dental caries occurrence among child and youth populations, 1976-1993.
With data on children's dental state from 1976 to 1993, we evaluated how the size of the high-caries group has changed concurrently with simultaneously decreasing mean numbers of teeth with past or current caries. Information related to all dental check-ups done for 5- and 15-year-olds in Helsinki, some 4,000 subjects of each age by year, consisted of numbers of teeth with caries experience (dmft or DMFT) and of all decayed teeth (dt + DT). Polarization of dental caries was described as the proportion of high-caries groups in each year, both in terms of caries experience and current untreated caries, diagnosed at subjects' annual clinical dental check-ups. For 5-year-olds, the high-caries group by caries experience included patients with their dmft > or = 3. For 15-year-olds the limits were set at DMFT > or = 6 and DMFT > or = 15. The high-caries group in terms of untreated caries was similar for both age groups: dt + DT > or = 3. Furthermore, polarization of caries was calculated as the share of numbers of both dmf or DMF teeth and dt + DT in each high-caries group of the total number of such teeth in the entire age cohort. During the 17 years, mean dmft for 5-year-olds decreased from 4.6 to 0.8 and mean dt + DT from 0.9 to 0.6. In 1993, 78% had their dmft = 0, whereas only 8% of the patients accounted for 76% of all decayed teeth. For 15-year-olds the decrease was even greater: their DMFT fell from 12.1 to 3.0 and their dt + DT from 3.1 to 0.8. However, only 26% had their DMFT = 0 in 1993, with 55% of all dt + DT occurring in 10% of the patients. The present results confirmed a strong polarization in caries for both age cohorts, showing the need for renewed strategies in preventive caries treatment.


Onset of clinical effects and plasma concentration of fluvoxamine in Japanese patients.
It is widely accepted that selective serotonin reuptake inhibitors (SSRIs) require 2 to 4 weeks of administration before improvements in emotional symptoms of depression are seen. We evaluated whether early monitoring of Hamilton Rating Scale for Depression (HAMD) scores in patients treated with the SSRI fluvoxamine could predict antidepressant response, and also assessed the relationship between the onset of clinical response following the start of fluvoxamine administration and its plasma concentration. Twelve depressed patients (baseline HAMD score ≥15) received an initial dose of fluvoxamine (50 mg/d) followed by an optimized maintenance dose according to their clinical symptoms after 7 d. HAMD scores and plasma drug concentrations were determined at 7 and 28 d after the first administration. There were 7 responders and 5 non-responders on day 28, as evaluated by HAMD scores. The HAMD score for the responders was significantly lower than that for the non-responders on day 7 (mean±S.D., 11.6±6.1 vs. 26.6±6.5, p=0.006). Thus, the reduction in HAMD score on day 7 was clearly divided between responders and non-responders. On day 28, the plasma concentration of fluvoxamine in responders was lower than that in non-responders (14.2±10.5 ng/ml vs. 44.2±28.1 ng/ml, p=0.051). Furthermore, receiver operating characteristic curve analysis conducted on day 28 revealed an upper concentration threshold of 28.2 ng/ml (p=0.042), with none in the responder group above that level. Our results suggest that HAMD score after the first week of treatment with fluvoxamine and the upper threshold of plasma drug concentration could predict whether a patient is a non-responder.


[Quantification of dry matter accumulation and distribution among different organs of winter wheat].
Based on the field experimental data, dry matter accumulation and distribution among different organs of winter wheat were studied to modify the dry matter distribution of the winter wheat growth model. The calculating method of distribution and transition coefficient was introduced, and a function table between distribution coefficient and relative development stage was established. Meanwhile, the model was verified based on the experimental data, and the result was reasonable.


Electromagnetic Fields Ameliorate Insulin Resistance and Hepatic Steatosis by Modulating Redox Homeostasis and SREBP-1c Expression in db/db Mice.
The prevalence of nonalcoholic fatty liver disease (NAFLD), which has recently become known as metabolic-associated fatty liver disease (MAFLD), has risen. However, pharmacotherapies for this disease have not been approved. Electromagnetic fields (EMFs) have excellent bioeffects on multiple diseases. However, the effects of EMFs on NAFLD are unknown. This study investigated the bioeffects of EMF exposure on insulin resistance, liver redox homeostasis and hepatic steatosis in db/db mice. Animals were sacrificed after EMF exposure for 8 weeks. The fasting blood glucose and insulin levels in the serum were tested. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated by a formula. The levels of MDA, GSSG and GSH, biomarkers of redox, were assessed. The activities of CAT, SOD and GSH-Px were assessed. The body and liver weights were measured. Hepatic lipid accumulation was observed by Oil Red O staining. Hepatic CAT, GR, GSH-Px, SOD1, SOD2 and SREBP-1 expression was determined by Western blotting. EMF exposure ameliorated insulin resistance and oxidative stress in the liver by downregulating the MDA and GSSG levels, increasing the reduced GSH levels, and promoting the GSH-Px levels in db/db mice. In addition, liver weight and triglyceride (TG) levels were reduced by EMF exposure. Simultaneously, EMF exposure improved hepatic steatosis by downregulating the protein expression of SREBP-1c. The present findings suggest that EMF exposure has positive effects in the treatment of NAFLD.


Long-term results and complications of proximal interphalangeal arthrodesis in horses.
A retrospective study was made of 21 horses in which proximal interphalangeal arthrodesis had been performed. The right hindlimb was the most often affected (52%). Acute trauma was the most common reason for performing the surgery (62%). Follow-up data were obtained from the owners regarding return to serviceability . When available, follow-up radiographs and clinical examinations were reviewed. Of the 20 horses on which follow-up information was available, 16 were serviceable . Of the horses in which a hindlimb was arthrodesed , 86% were serviceable , whereas 67% of the horses affected in the forelimb were serviceable . An average of 1 year was required for return to serviceability . Follow-up radiography of forelimb cases revealed radiographic changes consistent with navicular disease, distal interphalangeal degenerative joint disease, and a bony exostosis off the dorsal surface of the third phalanx; however, these radiographic changes did not correlate well with the owner's assessment of serviceability . Follow-up clinical examination of forelimb cases revealed 2 horses in which the toe came off the ground during weight bearing.


Lifting, Loading, and Buckling in Conical Shells.
Liquid crystal elastomer films that morph into cones are strikingly capable lifters. Thus motivated, we combine theory, numerics, and experiments to reexamine the load-bearing capacity of conical shells. We show that a cone squashed between frictionless surfaces buckles at a smaller load, even in scaling, than the classical Seide-Koiter result. Such buckling begins in a region of greatly amplified azimuthal compression generated in an outer boundary layer with oscillatory bend. Experimentally and numerically, buckling then grows subcritically over the full cone. We derive a new thin-limit formula for the critical load, ∝t^{5/2}, and validate it numerically. We also investigate deep postbuckling, finding further instabilities producing intricate states with multiple Pogorelov-type curved ridges arranged in concentric circles or Archimedean spirals. Finally, we investigate the forces exerted by such states, which limit lifting performance in active cones.


Detection of the disease-associated isoform of the prion protein in formalin-fixed tissues by Western blot.
Clinical signs of prion disease are not specific and include a variety of differential diagnoses. Serological tests and nucleic acid-based detection methods are not applicable to prion-disease-agent detection because of the unusual nature of the infectious agent. Prion-disease diagnosis is primarily conducted by means of immunodetection of the infectious agent, typically by at least 2 distinct procedures with immunohistochemistry and Western blot being the most informative. These approaches differ in the need for formalin-fixed and frozen or fresh tissue respectively. This work describes a method for the detection of the disease-associated isoform of the prion protein by Western blot using formalin-fixed tissues. The approach requires only minimal modification of existing Western-blot procedures and could readily be incorporated into existing detection schemes for confirmatory purposes when fresh or frozen tissues are unavailable.


Precise and Efficient In-Frame Integration of an Exogenous GFP Tag in Aspergillus fumigatus by a CRISPR System.
As one of the most common airborne fungal pathogenic species, Aspergillus fumigatus infection is the increasingly fatal threat to immunocompromised patients worldwide. Setting up an efficient live-cell pathogen-labeling system will give insight into the dynamic process of the pathogen invasion in host, which offers us opportunities to explore the pathogenesis of A. fumigatus. In this chapter, we have described an efficient CRISPR-Cas9 system, which enables a precise in situ tag-insertion of an exogenous GFP tag at the predicted site with or without marker insertion in A. fumigatus. According to the detectable proportional fluorescence intensity, it is possible to in vivo track the A. fumigatus infection and to assess the fungal burden in relative organs.


Prenatal and Peripartum Management of Patients with Hypofibrinogenemia Resulted in Two Successful Deliveries.
Fibrinogen is an essential agent involved in maintaining pregnancy and coagulation. Since inherited fibrinogen disorders introduce greater risks for conditions such as placental abruption and postpartum hemorrhage, careful prenatal and perinatal management is essential for this patient population. We report two cases of successful deliveries in patients with hypofibrinogenemia. Case 1 is of a 26-year-old (gravida 1, para 1) woman. The patient's fibrinogen level increased spontaneously to higher than 300 mg/dL during pregnancy, without treatment. She delivered at week 38 of gestation, with no complications. Case 2 is of a 30-year-old (gravida 3, para 1) woman. We performed repeated infusions of fibrinogen to maintain the level higher than 100 mg/dL during pregnancy and at least 200 mg/dL in the perioperative period; the patient delivered a healthy infant. We identified a new mutation, Hiroshima I (γ278Tyr→His). It is important to maintain appropriate fibrinogen levels in cases of inherited fibrinogen disorders for successful prenatal and peripartum management.


Inhibition of cell elongation in Avena coleoptile by hydroxyproline.
A study has been made of the hydroxyproline-induced inhibition of elongation of Avena coleoptile tissues. The isomers of 4-hydroxyproline differ in their effectiveness; only the L isomers are growth inhibitors with the cis form (allohydroxyproline) being more effective than the trans form (hydroxyproline). Hydroxyproline differs from other amino acid antagonists and protein synthesis inhibitors in respect to 2 characteristics of the growth inhibition. First, a certain increment of auxin-induced elongation must take place following addition of hydroxyproline before the growth is inhibited. In contrast, pretreatment with other amino acid antagonists or protein synthesis inhibitors completely eliminates the ability of Avena coleoptile sections to respond to auxin. Secondly, sucrose markedly increases the magnitude of the hydroxyproline inhibition; i.e., sucrose acts to inhibit rather than promote growth when in the presence of hydroxyproline. It appears that hydroxyproline is a specific inhibitor for the synthesis of some factor which is utilized in elongation. Following addition of hydroxyproline, auxin-induced elongation continues until the pool of this factor is exhausted; then elongation is inhibited.


Epithelial-Mesenchymal Transition Markers in HCVAssociated Hepatocellular Carcinoma: A Multivariate Follow Up Study.
Validated markers to predict recurrence after surgical resection of hepatocellular carcinoma (HCC) are needed. Little data is available regarding epithelial-mesenchymal transition (EMT) markers in HCC. The objective of this study was to investigate the expression of EMT markers and their correlation with clinicopathological variables and survival in hepatitis C virus (HCV)-associated HCC. This longitudinal study included 109 cases of HCV-associated HCC treated with surgical resection. Nine different EMT markers (vimentin, E-cadherin, N-cadherin, Stat3, Snail1, Slug, Twist1, Zeb1 and integrin α5) were evaluated on liver tissue from HCC cases. Twenty fresh HCC samples from the studied cases were used for gene expression of EMT markers by quantitative real time polymerase chain reaction (PCR). EMT markers expression was 71%, 25%, 26%, 27%, 9%, 4%, 72%, 47%, 87% for vimentin, E-cadherin, N-cadherin, Stat3 snail1, slug, twist1, Zeb1 and integrin α5 respectively. EMT mRNA in HCC tissues correlated with protein expression by 50-70%. Vimentin was independent predictor of large tumor size (P=0.001), high risk of recurrence (HRR) (P=0.006) and shorter disease free survival (P=0.03) in multivariate analysis. Reduced E-cadherin was a predictor of HRR (P=0.002). Vimentin and E-cadherin were the most powerful prognostic EMT markers in HCV-associated HCC in prediction of recurrence.


The basolateral amygdala modulates specific sensory memory representations in the cerebral cortex.
Stress hormones released by an experience can modulate memory strength via the basolateral amygdala, which in turn acts on sites of memory storage such as the cerebral cortex [McGaugh, J. L. (2004). The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annual Review of Neuroscience, 27, 1-28]. Stimuli that acquire behavioral importance gain increased representation in the cortex. For example, learning shifts the tuning of neurons in the primary auditory cortex (A1) to the frequency of a conditioned stimulus (CS), and the greater the level of CS importance, the larger the area of representational gain [Weinberger, N. M. (2007). Associative representational plasticity in the auditory cortex: A synthesis of two disciplines. Learning & Memory, 14(1-2), 1-16]. The two lines of research suggest that BLA strengthening of memory might be accomplished in part by increasing the representation of an environmental stimulus. The present study investigated whether stimulation of the BLA can affect cortical memory representations. In male Sprague-Dawley rats studied under urethane general anesthesia, frequency receptive fields were obtained from A1 before and up to 75min after the pairing of a tone with BLA stimulation (BLAstm: 100 trials, 400ms, 100Hz, 400microA [+/-16.54]). Tone started before and continued after BLAstm. Group BLA/1.0 (n=16) had a 1s CS-BLAstm interval while Group BLA/1.6 (n=5) has a 1.6s interval. The BLA/1.0 group did develop specific tuning shifts toward and to the CS, which could change frequency tuning by as much as two octaves. Moreover, its shifts increased over time and were enduring, lasting 75min. However, group BLA/1.6 did not develop tuning shifts, indicating that precise CS-BLAstm timing is important in the anesthetized animal. Further, training in the BLA/1.0 paradigm but stimulating outside of the BLA did not produce tuning shifts. These findings demonstrate that the BLA is capable of exerting highly specific, enduring, learning-related modifications of stimulus representation in the cerebral cortex. These findings suggest that the ability of the BLA to alter specific cortical representations may underlie, at least in part, the modulatory influence of BLA activity on strengthening long-term memory.


Differences in platelet growth factor release and leucocyte kinetics during autologous platelet gel formation.
Three commercial systems for whole blood separation were compared to obtain the buffy coat composed of platelet-rich plasma (BC-PRP) and leucocytes . These samples of the buffy coat were used to make a platelet gel (PG), which was used to measure platelet growth factor (PGF) release, to perform a white blood cell (WBC) count and to measure myeloperoxidase (MPO) release from WBCs. Aliquots of whole blood obtained from ten volunteers were distributed either to a blood cell separator (The Electa Cell-Separator, E-CS) or to a tabletop centrifuge (Gravitational Platelet Sequestration System, GPS) to prepare the BC-PRP. The third system combines the BC-PRP production by E-CS with a micro porous filter (Autologous Growth Factor filter, AGF) to enrich for the BC-PRP. Autologous thrombin was used to activate the BC-PRP and to prepare the PG and subsequently to degranulate the platelet concentrate. Platelet-derived growth factor-AB and transforming growth factor-beta1 were present in high levels after thrombin activation of the E-CS or GPS prepared samples. However, the AGF prepared samples released their growth factors before thrombin activation. The WBCs were significantly increased with each of the three systems. Contrary to the AGF, no leucocyte degranulation occurred with the E-CS or GPS prepared samples, based upon the low MPO concentrations in the BC-PRP. The three types of apparatus had different harvesting capacities for collecting the enriched platelets and the release of high concentrations of PGF. When the E-CS and GPS, but not the AGF, were used, low levels of MPO were maintained in the PG, which potentially contributes to antimicrobial properties of platelet gel at the site of application.


Physical Performance Impairments and Limitations Among Hospitalized Frail Older Adults.
Early rehabilitation is important for frail older adults due to reduced reserve capacity and physical fitness. To facilitate individualized rehabilitation programs, we need tools to make it possible to assess physical fitness in relation to frailty, instead of chronological age. The purpose of this study was, in a Swedish context, to describe measures of physical fitness in hospitalized frail older adults in relation to their degree of frailty. This was a cross-sectional study. A total of 408 frail older adults, mean age 86.6 years (75-99 years), in need of emergency medical inpatient care, were included in the NÄL-Uddevalla (NU) hospital group in Sweden. During the hospital stay, physical fitness was assessed using 4 different tests: hand-grip strength, the Timed Up and Go Test, 5-time sit-to-stand test, and 6-minute walk test. In the analyses, the physical fitness outcomes were related to the degree of frailty using the FRail Elderly Support ResearcH group screening instrument and previously used cutoffs or age-related reference values for older adults. This study showed that most hospitalized frail older adults perform far lower than previously described age-related reference values relating to physical fitness. An increased degree of frailty contributes to reduced physical fitness in tests assessing strength and endurance. A frail-related screening instrument may be useful in the evaluation of physical fitness in hospitalized frail older adults and may facilitate the development of realistic, individualized rehabilitation programs beneficial to an early start on the emergency medical ward.


Self-paced resistance training and walking exercise in community-dwelling older adults: effects on neuromotor performance.
Resistance-training intervention studies have demonstrated meaningful health benefits in older adults; however, most have used exercises performed at specific intensities on expensive equipment, which limit their widespread applicability. We tested whether two self-paced, less expensive exercise protocols could be effective and safe for modifying neuromotor performance and functional capacity in community-dwelling adults 65-95 years of age. One hundred and thirty-one subjects were randomized to a novel resistance training, walking, or control group. Subjects determined their level of resistance or walking intensity (self-paced) on a session-by-session basis. Muscle strength, balance, reaction time, stair climbing speed, and a timed pen pickup task were measured before and after the intervention period. Exercisers met three times per week for 10 months. Significant improvements in tandem stance and single-legged stance with eyes open times and stair climbing speed were seen in both exercise groups. In addition, resistance trainers improved their muscle strength and ability to pick up an object from the floor and reduced the number of missteps taken during tandem walking, and walkers reduced tandem walking time. Controls showed no significant improvement in any variable. The two self-paced exercise protocols were effective at improving neuromotor performance and functional capacity in the study sample and show promise as a safe, effective, cost-efficient, acceptable exercise model for primary and secondary prevention in the general population of community-dwelling older adults.


Comparing indices of median nerve among diabetic patients with or without metabolic syndrome.
Metabolic syndrome is highly prevalent among patients with type II diabetes and is reported as a strong risk factor for cardiovascular diseases as well as carpal tunnel syndrome (CTS). The aim of the current study was to compare median nerve indices among diabetic patients with and without metabolic syndrome. This cross-sectional study was conducted on 105 patients with type II diabetes whom participated in the coronary artery disease risk factor study in Kerman, Iran (KERCARDS). Patients with type II diabetes were called and those with clinical symptoms of CTS were included in the study, and median nerve indices were measured according to standard electro diagnosis tests. GEE statistical model was used to compare median nerve indices among diabetic patients with and without metabolic syndrome. All statistical analysis was done using SPSS 20.0. The mean age of participants was 57.57±9.53. There was no significant difference between the left and right hand regarding median nerve indices except median nerve motor amplitude (MA). Furthermore, components of metabolic syndrome including BMI and LDL were determined as risk factors for CTS according to several indices. Components of metabolic syndrome had more influence on sensory indices than motor indices and primary control of these components might prevent dysfunction of sensory neurons and also motor neurons in advanced stages among diabetic patients.


Synthesis and structure-activity relationship study of novel quinazolinone-based inhibitors of MurA.
MurA is an intracellular bacterial enzyme that is essential for peptidoglycan biosynthesis, and is therefore an important target for antibacterial drug discovery. We report the synthesis, in silico studies and extensive structure-activity relationships of a series of quinazolinone-based inhibitors of MurA from Escherichia coli. 3-Benzyloxyphenylquinazolinones showed promising inhibitory potencies against MurA, in the low micromolar range, with an IC50 of 8µM for the most potent derivative (58). Furthermore, furan-substituted quinazolinones (38, 46) showed promising antibacterial activities, with MICs from 1µg/mL to 8µg/mL, concomitant with their MurA inhibitory potencies. These data represent an important step towards the development of novel antimicrobial agents to combat increasing bacterial resistance.


Adolescent homicide--Fulton County, Georgia, 1988-1992.
In Fulton County, Georgia (1990 population: 648,951), during 1988-1992, 12% of homicides occurred among persons aged < or = 18 years, of whom 75% were adolescents aged 13-18 years. Recognition of homicide as the leading cause of death among adolescents in Fulton County has prompted planning of local surveillance, prevention, intervention, advocacy, and mentoring programs and antiviolence media campaigns. This report summarizes descriptive information for homicides of adolescents in Fulton County during 1988-1992 and addresses the use of this information for local prevention and intervention programs.


[Malignant thymoma. Apropos of 10 cases].
The current article proposes a review of the literature on the malignant thymoma, from 10 cases treated in the Henri Becquerel's Centre in Rouen. The middle age varies between 45 and 55 years, the sex ratio is 1/1. The principal histological type is the lympho-epithelial, then épithelial and lymphocytic. The 5-year survival varies between 45 and 75%. The most important factor of prognosis is the invading's degree. The initial treatment is surgical with an excision as complete as possible, then X-ray treatment. The utilization of the chemotherapy is still undecided, the cisplatin is the most effective product.


The Reproductive Capacities of the Calanoid Copepods Parvocalanus crassirostis and Acartia pacifica under Different pH and Temperature Conditions.
The increasing atmospheric CO2 concentrations and warming of marine waters have encouraged experiments on multi-stressor interactions in marine organisms. We conducted a multigenerational experiment to assess reproductive capacities regarding egg production in calanoid copepods Parvocalanus crassirostis and Acartia pacifica under different pH and temperature conditions. The experimental set-up allowed assessing the tandem effect of warming and acidification on the number of eggs produced by healthy copepod pairs under two pH conditions of 8.20 and 7.50 (hard selection) as well as with a gradual reduction of 0.05 pH units at each generation (soft selection). The results are quite interesting, with very diverse performance across temperatures. The number of eggs produced under hard selection was higher at pH 8.20 compared to pH 7.50 for both species, with the maximum number of eggs produced at 24-28 °C, whereas under soft selection, there was no significant difference in the egg production rate at 24-28 °C across generations and there was an improvement in the number of eggs produced at 8-16 °C. The results provide evidence that in a future ocean scenario of lower pH and higher temperature, the two species, and possibly the copepod population at large, might not decrease. Copepod populations might be resilient, and the transcriptomic evidence of adaptation to increased temperature and lower pH is a ray of hope. We believe further studies are needed to provide more robust datasets to underpin the hypothesis of adaptation to climate change.


Nursing Assessment Tool for People With Liver Cirrhosis.
The aim of this study was to describe the process of developing a nursing assessment tool for hospitalized adult patients with liver cirrhosis. A descriptive study was carried out in three stages. First, we conducted a literature review to develop a data collection tool on the basis of the Conceptual Model of Wanda Horta. Second, the data collection tool was assessed through an expert panel. Third, we conducted the pilot testing in hospitalized patients. Most of the comments offered by the panel members were accepted to improve the tool. The final version was in the form of a questionnaire with open-closed questions. The panel members concluded that the tool was useful for accurate nursing diagnosis. Horta's Conceptual Model assisted with the development of this data collection tool to help nurses identify accurate nursing diagnosis in hospitalized patients with liver cirrhosis. We hope that the tool can be used by all nurses in clinical practice.


Ecological tracers can quantify food web structure and change.
Disruption of natural food webs is becoming a commonplace occurrence as a result of human activities. Considering this, there is a need to improve our ability to define food web structure as well as to detect and understand the implications of trophodynamic change. This requires the development, validation, and application of ecologicaltracers that can provide insights into the movement of energy, nutrients, and contaminants through food webs. In this study, we examine the utility of two groups of naturally occurring intrinsic tracers (stable nitrogen isotopes and fatty acids) to provide such information in a predatory seabird, the herring gull (Larus argentatus). Spatial and temporal patterns in gull trophic position (inferred from egg stable nitrogen isotope values) were related to gull diet composition (inferred from egg fatty acid concentrations). These two independent groups of ecological tracers provided corroborating evidence that gull trophic position was related to the degree to which aquatic foods, namely fish, were consumed. The use of these tracers in concert led to a better understanding of routes of energy flow and contaminant transfer in food webs and how these pathways may be affected by ecosystem change.


Ovarian needle aspiration in the diagnosis and management of ovarian masses.
Ovarian needle aspiration and biopsy (ONAB) may be employed for pretreatment diagnosis of ovarian malignancies or intraoperatively to facilitate removal of ovarian masses. However, there is reluctance to utilize this procedure due to potential cyst rupture or seeding of malignant cells. The objective of this study was to examine the efficacy of ONAB over a 13-year period at our institution. Between 2000 and 2013, all ONAB specimens were identified from the Queen's Medical Center Pathology Department database. All cytologic specimens were reviewed and correlated with histopathologic findings. A retrospective chart review was conducted to retrieve data on clinical course and treatment. This study identified 144 cases of ovarian masses sampled by aspiration or needle biopsy between 2000 and 2013. Ninety-two (64%) cases had corresponding histopathology, 84 (91%) of which were obtained concomitantly. On histology, 12 (13%) cases were malignant and 80 (87%) benign. Three false negative cases were noted; 2 serous borderline tumors and 1 mucinous cystadenocarcinoma. These were sampling errors; no diagnostic tumor cells were present in the aspirates. Sensitivity and specificity of ONAB in the detection of malignancy were 75% and 100%, respectively. The positive and negative predictive values were 100% and 96%, respectively. ONAB represents a valuable tool in the diagnosis of malignancy and treatment of ovarian masses. In our study, it was highly specific, with excellent positive and negative predictive value.


Nutritional supplementation in adult patients on hemodialysis.
At the beginning of the 1980s, nutritional status appeared as a key element of quality of life, health care requirements, and survival during chronic renal failure. In patients on dialysis, malnutrition is a major determinant of survival, and its management appears to be a key element in terms of outcome. Recommendations for the nutritional management of patients on hemodialysis have been elaborated by the National Kidney Foundation (NKF) and the European Society of Parenteral and Enteral Nutrition (ESPEN).


Exploring the Communication of the SASP: Dynamic, Interactive, and Adaptive Effects on the Microenvironment.
Cellular senescence is a complex cell state that can occur during physiological ageing or after exposure to stress signals, regardless of age. It is a dynamic process that continuously evolves in a context-dependent manner. Senescent cells interact with their microenvironment by producing a heterogenous and plastic secretome referred to as the senescence-associated secretory phenotype (SASP). Hence, understanding the cross-talk between SASP and the microenvironment can be challenging due to the complexity of signal exchanges. In this review, we first aim to update the definition of senescence and its associated biomarkers from its discovery to the present day. We detail the regulatory mechanisms involved in the expression of SASP at multiple levels and develop how SASP can orchestrate microenvironment modifications, by focusing on extracellular matrix modifications, neighboring cells' fate, and intercellular communications. We present hypotheses on how these microenvironmental events may affect dynamic changes in SASP composition in return. Finally, we discuss the various existing approaches to targeting SASP and clarify what is currently known about the biological effects of these modified SASPs on the cellular environment.


Analogical reasoning and prefrontal cortex: evidence for separable retrieval and integration mechanisms.
The present study examined the contributions of prefrontal cortex (PFC) subregions to two component processes underlying verbal analogical reasoning: semantic retrieval and integration. Event-related functional magnetic resonance imaging data were acquired while subjects performed propositional analogy and semantic decision tasks. On each trial, subjects viewed a pair of words (pair 1), followed by an instructional cue and a second word pair (pair 2). On analogy trials, subjects evaluated whether pair 2 was semantically analogous to pair 1. On semantic trials, subjects indicated whether the pair 2 words were semantically related to each other. Thus, analogy--but not semantic--trials required integration across multiple retrieved relations. To identify regions involved in semantic retrieval, we manipulated the associative strength of pair 1 words in both tasks. Anterior left inferior PFC (aLIPC) was modulated by associative strength, consistent with a role in controlled semantic retrieval. Left frontopolar cortex was insensitive to associative strength, but was more sensitive to integration demands than was aLIPC, consistent with a role in integrating the products of semantic retrieval to evaluate whether distinct representations are analogous. Right dorsolateral PFC exhibited a profile consistent with a role in response selection rather than retrieval or integration. These findings indicate that verbal analogical reasoning depends on multiple, PFC-mediated computations.


[Critical reflexion on quality improvement and networking].
Qualitiy-control and networking are two issues of debate in modern medicine. The origin of these terms is not to be found in medicine, but rather in industry. However their naive transfer to the field of medicine causes damage. It is relatively easy to test industrial products for their quality. Dealing with meaningful medical problems is far too complex. Simple data such as blood pressure, HbA1c, etc. may be assessed. The only means of quality-control of complex medical situations and actions are ward rounds by attending physicians, case presentations at staff meetings, etc. Issues of clinical quality-control are discussed on the basis of the history of an aged couple. Furthermore a personal clinical experience illustrates how doctors create a useful network with other physicians and how they eliminate "useless" colleagues from their network. Economists should have no influence or impact whatsoever on the quality-control and networking of physicians.