With or without intent: how racial disparities prevent effective implementation of care.
The limited affects of translation within the United States remains a central issue for the medical profession. Racial disparities are noted as a significant factor contributing to this problem. This pilot study sought to explore how racial barriers limit the effective implementation of health care by examining the barriers that affect health care among African-Americans in Dayton, Ohio through their expression of experiences on the subject. This qualitative study relied on the focus group method to accomplish its objective. Both African-American (Black) and White (non-Hispanic White) individuals were invited to participate in the focus group to facilitate comparison between the experiences of the two groups and identify experiences that are uniquely African-American. Of the 18 individuals who participated in the study, 16 were African-American and 2 were White. Participants were selected using the purposive sampling method which drew participants from a list of individuals who had received health services from a public health clinic in Dayton, Ohio, and who had not returned for care during a 12-18 month period prior to their participation in the study. These participants represent some of the most vulnerable members of US society when it comes to access to health care. The focus group conversation was audio taped, recorded on flip charts, and transcribed by an observer to ensure data accuracy. Focus group participants had immediate access to the flip chart notes and were asked to correct inaccurate recordings. The data was analyzed using the grounded theory approach. According to participants, the key barriers they experienced to effective health care were economic factors; the quality of care they received and the disrespect of medical practitioners; accessibility to health services based on location, cost, and decentralized services; lower literacy and education levels; and cultural differences and the related factors of discrimination and racism embedded in the health system. This study suggests that without addressing racial, cultural and ethnic disparities in health care, efforts at translation will continue to be thwarted. Moreover, physicians' efforts at translation must be matched by changes to the institutional arrangements within health care systems.


Sleep Hygiene and Sleep Outcomes in a Sample of Urban Children With and Without Asthma.
To assess sleep hygiene and the sleep environment of urban children with and without asthma, and examine the associations among urban stressors, sleep hygiene, and sleep outcomes. Urban children, 7-9 years old, with (N = 216) and without (N = 130) asthma from African American, Latino, or non-Latino White backgrounds were included. Level of neighborhood risk was used to describe urban stress. Parent-reported sleep hygiene and daytime sleepiness data were collected using questionnaires. Sleep duration and efficiency were assessed via actigraphy. Higher neighborhood risk, not asthma status, was associated with poorer sleep hygiene. Controlling for neighborhood risk, sleep hygiene was related to daytime sleepiness. Asthma status, not sleep hygiene, was related to sleep efficiency. In children with asthma, poorer sleep hygiene was associated with shorter sleep duration. Considering urban stressors when treating pediatric populations is important, as factors related to urban stress may influence sleep hygiene practices and sleep outcomes.


CD27low CD4 T lymphocytes that accumulate in the mouse lungs during mycobacterial infection differentiate from CD27high precursors in situ, produce IFN-gamma, and protect the host against tuberculosis infection.
The generation of effector, IFN-gamma producing T lymphocytes and their accumulation at sites of infection are critical for host protection against various infectious diseases. The activation and differentiation of naive T lymphocytes into effector memory cells starts in lymphoid tissues, but it is not clear whether the Ag-experienced cells that leave lymph nodes (LN) are mature or if they undergo further changes in the periphery. We have previously shown that CD44(high)CD62L(low) effector CD4 T lymphocytes generated during the course of mycobacterial infection can be segregated into two subsets on the basis of CD27 receptor expression. Only the CD27(low) subset exhibited a high capacity for IFN-gamma secretion, indicating that low CD27 expression is characteristic of fully differentiated effector CD4 T lymphocytes. We demonstrate now that CD27(low) IFN-gamma-producing CD4 T lymphocytes accumulate in the lungs but are rare in LNs. Several factors contribute to their preferential accumulation. First, CD27(low) CD4 T lymphocytes present in the LN are highly susceptible to apoptosis. Second, circulating CD27(low) CD4 T cells do not enter the LN but efficiently migrate to the lungs. Third, CD27(high) effector CD4 T cells that enter the lungs down-regulate CD27 expression in situ. In genetically heterogeneous mice that exhibit varying susceptibility to tuberculosis, the accumulation of mature CD27(low) CD4 T cells in the lungs correlates with the degree of protection against infection. Thus, we propose that terminal maturation of effector CD4 T lymphocytes in the periphery provides the host with efficient local defense and avoids potentially harmful actions of inflammatory cytokines in lymphoid organs.


Polycystic ovary syndrome is associated with severe platelet and endothelial dysfunction in both obese and lean subjects.
Platelet hyporesponsiveness to the anti-aggregatory effects of nitric oxide (NO) occurs commonly in association with myocardial ischemia and coronary risk factors, often co-exists with endothelial dysfunction and represents an independent marker of long-term cardiovascular risk. We sought to determine whether polycystic ovary syndrome (PCOS), which has been postulated as a cardiovascular risk factor in women, is independently associated with this phenomenon. Twenty-four young women with PCOS (mean age 32.1+/-1.3) were evaluated in lean (n=12) and obese (n=12) subgroups, and compared with age-matched lean normals (n=12). Platelet aggregation and its inhibition by the nitric oxide donor sodium nitroprusside (SNP) were assessed and compared with vascular endothelial function. Plasma concentrations of malondialdehyde (MDA), N(G),N(G)-dimethyl-L-arginine (ADMA) and hs-CRP were measured as markers of oxidative stress, endothelial dysfunction and inflammation, respectively. Circulating endothelial progenitor cell (EPC) counts were also documented. In both PCOS subgroups, which demonstrated hyperaggregability to ADP, responses to SNP inhibition of aggregation (the principal end-point of the study) were significantly impaired (P<0.01 for both), as were their endothelium-dependent vascular responses to salbutamol (P<0.05 for both). However, vasomotor responses to nitroglycerin and circulating EPC counts did not vary between groups. PCOS subjects also had significantly elevated ADMA, MDA and hs-CRP levels relative to normals (all P<0.05). Impairment of SNP response remained unaltered after mean 30+/-2.4 months follow-up in PCOS subjects. We conclude that in PCOS subjects, independent of obesity and associated insulin resistance, profound and reproducible impairment of platelet responsiveness to NO is an additional component of cardiovascular homeostatic disturbance.


Basal ganglia T1 hyperintensity in LGI1-autoantibody faciobrachial dystonic seizures.
To characterize the clinical features and MRI abnormalities of leucine-rich glioma-inactivated 1 (LGI1)-autoantibody (Ab) faciobrachial dystonic seizures (FBDS). Forty-eight patients with LGI1-Ab encephalopathy were retrospectively identified by searching our clinical and serologic database from January 1, 2002, to June 1, 2015. Of these, 26 met inclusion criteria for this case series: LGI1-Ab seropositivity and FBDS. In a separate analysis of all 48 patients initially identified, the MRIs of patients with (n = 26) and without (n = 22) FBDS were compared by 2 neuroradiologists blinded to the clinical details. The median age of the 26 included patients was 62.5 years (range 37-78); 65% were men. FBDS involved arm (26), face (22), and leg (12). Ten were previously diagnosed as psychogenic. Ictal EEGs were normal in 20 of 23 assessed. Basal ganglia T1 and T2 signal abnormalities were detected in 11 patients (42%), with excellent agreement between neuroradiologists (κ scores of 0.86 and 0.93, respectively), and included T1 hyperintensity alone (2), T2 hyperintensity alone (1), or both (8). The T1 hyperintensities persisted longer than the T2 hyperintensities (median 11 weeks vs 1 week, p = 0.02). Improvement with immunotherapy (18/18) was more frequent than with antiepileptic medications (10/24). A separate analysis of all 48 patients initially identified with LGI1-Ab encephalopathy showed that basal ganglia MRI abnormalities were present in 11 of 26 with FBDS but not present in those without FBDS (0/22) (p < 0.001). In contrast, mesial temporal MRI abnormalities were less common among those with FBDS (42%) than those without (91%) (p < 0.001). Basal ganglia T1 hyperintensity is a clinically useful MRI biomarker of LGI1-Ab FBDS and suggests a basal ganglia localization.


Rapidly progressive osteoarthrosis of the hip.
A retrospective review of 991 primary total hip arthroplasties was performed to determine the incidence of rapidly progressive osteoarthrosis of the hip joint. Thirty-four patients (35 hips) were identified (3.5%). Females were predominantly affected (85%). A history of hypertension and regular non-steroidal anti-inflammatory drug use was significantly more common in those with rapid progression as compared to the normally progressive group. Transfusion requirements were also significantly greater for the rapidly progressive group. Patient age and operating time were both greater in those with rapid progression, but neither proved statistically significant. No significant difference was noted when comparing the affected side, body mass index or the pre-operative range of hip movements, ESR or Oxford Hip Score. From the radiographs, twenty cases were classified as type I (rapid), 11 type II (moderate) and 3 type III (delayed). Wear distribution was predominantly superolateral (85%) and anterosuperior (97%). All patients were treated by total hip arthroplasty. At latest follow-up (average, 18 months; range, 13-36 months) there was no significant difference in the Oxford Hip Score between the normally progressive and rapidly progressive groups. All radiographs were satisfactory. Total hip arthroplasty in these cases is technically challenging. When identified, such individuals should be given priority treatment due to the potentially rapid and extensive loss of bone stock that can occur. (Hip International 2004; 14: 217-22).


Novel Insights into Somatic Comorbidities in Children and Adolescents Across Psychiatric Diagnoses: An Explorative Study.
Many children with psychiatric disorders display somatic symptoms, although these are frequently overlooked. As somatic morbidity early in life negatively influences long-term outcomes, it is relevant to assess comorbidity. However, studies of simultaneous psychiatric and somatic assessment in children are lacking. The aim of this study was to assess the prevalence of somatic comorbidities in a clinical sample of children and adolescents with psychiatric disorders in a naturalistic design. Data were assessed from 276 children with various psychiatric disorders (neurodevelopmental disorders, affective disorders, eating disorders and psychosis) aged 6-18 years. These data were collected as part of routine clinical assessment, including physical examination and retrospectively analyzed. For a subsample (n = 97), blood testing on vitamin D3, lipid spectrum, glucose and prolactin was available. Results of this cross-sectional study revealed that food intake problems (43%) and insomnia (66%) were common. On physical examination, 20% of the children were overweight, 12% displayed obesity and 38% had minor physical anomalies. Blood testing (n = 97) highlighted vitamin D3 deficiency (< 50 nmol/L) in 73% of the children. None of the predefined variables (gender, age, medication and socioeconomic factors) contributed significantly to the prevalence of somatic comorbidities. The main somatic comorbidities in this broad child- and adolescent psychiatric population consisted of (1) problems associated with food intake, including obesity and vitamin D3 deficiency and (2) sleeping problems, mainly insomnia. Child and adolescent psychiatrists need to be aware of potential somatic comorbidities and may promote a healthy lifestyle.


The role of trainees as clinical teachers of medical students in psychiatry.
To consider the role of specialty trainees as clinical teachers of medical students in psychiatry. We discuss the role of specialty trainees as teachers and approaches to improving their skills and capacity, giving examples from the local and international literature and our own experience as psychiatry medical educators. Good clinical teaching is crucial for medical students' learning but sharp increases in numbers combined with economic and workforce pressures have stretched capacity. Specialty trainees do much of the medical student teaching during their clinical placements but infrequently receive instruction on how to teach. The two common approaches to increasing capacity are, first, establishing education rotations for individual trainees and, second, providing workshops to improve trainees' confidence and skill. Psychiatry trainees surveyed in New South Wales welcomed the role of teacher and the opportunity to improve their teaching capacity. Further support from supervisors, health services and medical schools is needed to assist trainees in their teaching role. The role that trainees play as clinical teachers should be acknowledged and supported. Further development of research and scholarship in medical education is needed to determine how best to teach trainees to teach.


[Lupus anticoagulant and ischemic strokes: about two case reports].
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic clinical manifestations, including ischemic stroke. Testing for lupus anticoagulant (LA) among antiphospholipid antibodies is key to the diagnosis of antiphospholipid syndrome (APS). Given the impact on patient management, close clinician-pathologist collaboration is crucial for the presence of LA in a thrombotic setting. Testing for LA must be carried out using specific and appropriate clotting assays and the pathologist should be aware of interferences. We report here two cases of stroke associated with the presence of LA, and recall the strategy for screening for LA.


Results of endoscopic cartilage tympanoplasty procedure with limited tympanomeatal flap incision.
The aim of this study was to evaluate the outcomes of this minimally invasive tympanomeatal incision technique performed during endoscopic transcanal cartilage tympanoplasty. Prospective clinical study. Eighty-seven patients (87 ears) who had TM perforation with noncomplicated COM were included. All of the patients were operated with the endoscopic transcanal cartilage tympanoplasty technique. All of the data were prospectively collected. These included demographic data, date of the surgery, preoperative and postoperative pure-tone audiometry (PTA), localization of TM perforation and graft healing success. Mean follow-up time was 14.76 ± 4.32 months. Graft-healing rate was 100%. Mean air bone gap level improvement (dB HL) at 0.5, 1, 2 and 4 kHz were 13.87 ± 7.30 dB HL, 9.09 ± 7.59 dB HL, 9.74 ± 6.40 dB HL and 7.46 ± 6.37 dB HL, respectively. At all frequencies, there was significant difference between pre and postoperative mean air bone gap levels (p < .05). There was no significant correlation between the postoperative mean air bone gap level improvement and the localization of the perforation (p > .05). Endoscopic ear surgery has successful surgical outcomes with low complication rates. In this study, the outcomes of limited tympanomeatal flap incision was discussed. It is suggested that this technique is reliable with good hearing results with low postoperative complications rates.


High-quality reference genomes of swallowtail butterflies provide insights into their coloration evolution.
Swallowtail butterflies (Papilionidae) are a historically significant butterfly group due to their colorful wing patterns, extensive morphological diversity, and phylogenetically important position as a sister group to all other butterflies and have been widely studied regarding ecological adaption, phylogeny, genetics, and evolution. Notably, they contain a unique class of pigments, i.e., papiliochromes, which contribute to their color diversity and various biological functions such as predator avoidance and mate preference. To date, however, the genomic and genetic basis of their color diversity and papiliochrome origin in a phylogenetic and evolutionary context remain largely unknown. Here, we obtained high-quality reference genomes of 11 swallowtail butterfly species covering all tribes of Papilioninae and Parnassiinae using long-read sequencing technology. Combined with previously published butterfly genomes, we obtained robust phylogenetic relationships among tribes, overcoming the challenges of incomplete lineage sorting (ILS) and gene flow. Comprehensive genomic analyses indicated that the evolution of Papilionidae-specific conserved non-exonic elements (PSCNEs) and transcription factor binding sites (TFBSs) of patterning and transporter/cofactor genes, together with the rapid evolution of transporters/cofactors, likely promoted the origin and evolution of papiliochromes. These findings not only provide novel insights into the genomic basis of color diversity, especially papiliochrome origin in swallowtail butterflies, but also provide important data resources for exploring the evolution, ecology, and conservation of butterflies.


Head and eyes: Looking behavior in 12- to 24-month-old infants.
This study demonstrates evidence for a foundational process underlying active vision in older infants during object play. Using head-mounted eye-tracking and motion capture, looks to an object are shown to be tightly linked to and synchronous with a stilled head, regardless of the duration of gaze, for infants 12 to 24 months of age. Despite being a developmental period of rapid and marked changes in motor abilities, the dynamic coordination of head stabilization and sustained gaze to a visual target is developmentally invariant during the examined age range. The findings indicate that looking with an aligned head and eyes is a fundamental property of human vision and highlights the importance of studying looking behavior in freely moving perceivers in everyday contexts, opening new questions about the role of body movement in both typical and atypical development of visual attention.


Atomic force microscopy in biomaterials surface science.
Recent progress in surface science, nanotechnology and biophysics has cast new light on the correlation between the physicochemical properties of biomaterials and the resulting biological response. One experimental tool that promises to generate an increasingly more sophisticated knowledge of how proteins, cells and bacteria interact with nanostructured surfaces is the atomic force microscope (AFM). This unique instrument permits to close in on interfacial events at the scale at which they occur, the nanoscale. This perspective covers recent developments in the exploitation of the AFM, and suggests insights on future opportunities that can arise from the exploitation of this powerful technique.


Localization and quantification of alpha-1-proteinase inhibitor in the human cornea.
alpha-1-Proteinase inhibitor, formerly called alpha-1-antitrypsin, was detected in human corneal epithelium, stroma, Descemet's membrane and endothelium using an indirect immunolocalization technique. The average alpha-1-proteinase inhibitor levels detected by an immunodot blot assay in the epithelium, stroma and Descemet's membrane-endothelium extracts per total human cornea were 29.5 micrograms, 54.3 micrograms and 3.5 micrograms, respectively. Immunolocalization on Western blots of SDS polyacrylamide electrophoresis gels revealed that all three layers contained a molecule with a molecular weight equal to the native alpha-1-proteinase inhibitor. Additionally, in the epithelial and stromal extracts minor bands at 75 kD and 110 kD were noted which are possibly due to complexes with proteases. The 110 kD band alternatively may be a dimer of the inhibitor. The epithelial extract contained bands at 40 kd and less than 30 kD indicating the presence of proteolysis products. alpha-1-Proteinase inhibitor probably plays a major role in the protection of the cornea from proteases released by inflammatory cells.


LIF- and IL-6-induced acetylation of STAT3 at Lys-685 through PI3K/Akt activation.
Signal transducer and activator of transcription 3 (STAT3), which mediates biological actions in many physiological processes, is activated by cytokines and growth factors via specific tyrosine or serine phosphorylation, dimerization and nuclear translocation. A recent study has demonstrated, by using antibody to acetylated lysine, and a STAT3 mutant with Lys-685-to-Arg substitution, that STAT3 is acetylated at Lys-685 by histone acetyltransferase p300, and that acetylation at Lys-685 is critical for STAT3 activation. In the present study, we created an acetyl-specific antibody against STAT3 acetylated at Lys-685, and found that leukemia inhibitory factor (LIF) or interleukin (IL)-6 induced acetylation of STAT3 at Lys-685 in 293T and Hep3B cells. Moreover, acetylation of STAT3 at Lys-685 was suppressed by PI3K inhibitor LY294002, or a dominant negative Akt. Taken together, our findings demonstrate that endogenous STAT3 is acetylated at Lys-685 by LIF or IL-6 through PI3K/Akt activation.


Asymmetric insertion of membrane proteins in lipid bilayers by solid-state NMR paramagnetic relaxation enhancement: a cell-penetrating Peptide example.
A novel solid-state NMR technique for identifying the asymmetric insertion depths of membrane proteins in lipid bilayers is introduced. By applying Mn (2+) ions on the outer but not the inner leaflet of lipid bilayers, the sidedness of protein residues in the lipid bilayer can be determined through paramagnetic relaxation enhancement (PRE) effects. Protein-free lipid membranes with one-side Mn (2+)-bound surfaces exhibit significant residual (31)P and lipid headgroup (13)C intensities, in contrast to two-side Mn (2+)-bound membranes, where lipid headgroup signals are mostly suppressed. Applying this method to a cell-penetrating peptide, penetratin, we found that at low peptide concentrations, penetratin is distributed in both leaflets of the bilayer, in contrast to the prediction of the electroporation model, which predicts that penetratin binds to only the outer lipid leaflet at low peptide concentrations to cause an electric field that drives subsequent peptide translocation. The invalidation of the electroporation model suggests an alternative mechanism for intracellular import of penetratin, which may involve guanidinium-phosphate complexation between the peptide and the lipids.


Definition of glomerular antigens by monoclonal antibodies produced against a human glomerular membrane fraction.
Experimental animal models of glomerulonephritis (GN) produced by direct antibody binding to non-basement membrane glomerular capillary wall antigens do not to date have human parallels. To examine the potential for this form of humoral glomerular injury in man, we sought to define discrete human non-GBM glomerular antigenic targets using hybridoma technology. Mice were immunised intraperitoneally with 20-100 micrograms of a human glomerular membrane fraction (HGMF). Six fusions have yielded 12 stable reagents defined by positive glomerular indirect immunofluorescence (IF) and microELISA using HGMF as the screening antigen. Subclass analysis of ascitic McAbs indicated several IgG1, one IgG2b, and three IgM reagents. Distinctive IF patterns of reactivity with epithelial, endothelial or mesangial structures have been observed, with or without peritubular capillary, tubular basement membrane and vessel wall reactivity. Seven normal non-renal human organs and the kidneys of rat, rabbit and sheep have shown patterns characteristic of each individual McAb, restricted to human or with species cross reactivity. To partially characterise McAb-reactive antigens, detergent-solubilised renal cortex and collagenase-solubilised GBM (CS-GBM) extracts have been probed by immunoblot. A unique McAb 7-5Q, reactive with glomerular and tubular epithelial structures, binds major bands of approximately 107 KD and 93 KD in detergent solubilised cortex and a single band of similar size by immunoprecipitation (110 KD). 5-3A (a human-restricted linear-reacting McAb) binds bands of 20-200 KD (major band 58 KD) in CS-GBM. In conclusion, distinct species-restricted and more broadly disposed glomerular epitopes are definable in man by McAbs and are potential targets for humoral injury. Purification of these antigens will allow assay for circulating putative nephritogenic auto-antibody and potentially, McAbs may be useful in screening urine for evidence of occult structural renal disease.


Emerging Roles for Glycogen in the CNS.
The ability of glycogen, the depot into which excess glucose is stored in mammals, to act as a source of rapidly available energy substrate, has been exploited by several organs for both general and local advantage. The liver, expressing the highest concentration of glycogen maintains systemic normoglycemia ensuring the brain receives a supply of glucose in excess of demand. However the brain also contains glycogen, although its role is more specialized. Brain glycogen is located exclusively in astrocytes in the adult, with the exception of pathological conditions, thus in order to benefit neurons, and energy conduit (lactate) is trafficked inter-cellularly. Such a complex scheme requires cell type specific expression of a variety of metabolic enzymes and transporters. Glycogen supports neural elements during withdrawal of glucose, but once the limited buffer of glycogen is exhausted neural function fails and irreversible injury ensues. Under physiological conditions glycogen acts to provide supplemental substrates when ambient glucose is unable to support function during increased energy demand. Glycogen also supports learning and memory where it provides lactate to neurons during the conditioning phase of in vitro long-term potentiation (LTP), an experimental correlate of learning. Inhibiting the breakdown of glycogen or intercellular transport of lactate in in vivo rat models inhibits the retention of memory. Our current understanding of the importance of brain glycogen is expanding to encompass roles that are fundamental to higher brain function.


Cell-cell adhesion by homophilic interaction of the neuronal recognition molecule axonin-1.
The axonal surface glycoprotein axonin-1, which occurs both as a glycosyl-phosphatidylinositol-anchored membrane-bound form and a secreted form, promotes neurite outgrowth and is thought to be involved in axon-guidance mechanisms in the developing nervous system. Recently, we have demonstrated that the neurite-outgrowth-promoting activity of axonin-1, presented as a substratum for cultured neurons, is mediated by a heterophilic interaction with the axonal glycoprotein neuronglia cell-adhesion molecule (Ng-CAM). Here we present evidence for homophilic (like-like) binding among axonin-1 molecules. Axonin-1 was heterologously expressed in myeloma cells. Clonal cell lines, with exposed membrane-bound axonin-1 at their surface, formed large multicellular aggregates. Incubations of transfected and parental myeloma cells, under a series of different conditions, revealed homophilic axonin-1/axonin-1 interactions across the intermembrane space as the molecular mechanism promoting stable cell-cell contacts. Using structural and functional characterisation, recombinant axonin-1 was very similar to native axonin-1, suggesting that homophilic axonin-1 interactions are also established in neurons. The capability of axonin-1 to interact with both Ng-CAM and other axonin-1 molecules might contribute to the formation of macromolecular networks at contact sites of growth cones and axons, comprising molecules of both membranes, and thus represent a mechanism for regulating neurite outgrowth and pathfinding.


Role of craniotomy in the management of pituitary adenomas and sellar/parasellar tumors.
The transphenoidal procedure has become the preferred approach in the surgical management of sellar/parasellar tumors. Nevertheless, specific indications remain for the transcranial approach and the objective of this review is to evaluate the available data on outcomes following transcranial or transphenoidal approaches to sellar/parasellar tumors. We assess the indications used for each approach and parameters that favor one over the other. Factors such as tumor size, consistency and configuration are important variables in choosing the transcranial approach. Other important considerations include persistent visual loss after incomplete decompression via the transphenoidal route, ectatic midline carotid arteries, co-existent intracranial aneurysms and sphenoid sinusitis. We review the data on visual and endocrinological outcomes following the transcranial or transphenoidal approach and provide an argument that, while there appears to be a trend towards greater visual improvement after transcranial surgery for large-to-giant pituitary adenomas, this benefit is offset by a greater risk of postoperative pituitary dysfunction. There is no difference in the rate of recurrence between the two procedures in the published literature. Overall, craniotomies will continue to play a role in the management of patients with sellar/parasellar tumors, although patient selection and careful preoperative evaluation are key elements in choosing the most appropriate approach.


Developing and Evaluating an Educational Program for Respiratory Infection Prevention among Rural Elderly Residents in South Korea.
Based on social cognitive theory (SCT), an educational program was developed to prevent rural elderly residents from respiratory infections in South Korea. The effectiveness of the program was investigated in terms of knowledge, attitudes, and practices about respiratory infection prevention, as well as social capital. A pretest-posttest nonequivalent control group quasi-experimental design was used to test the short-term effect of this program. In addition, 1- and 6-month follow-up surveys were administered to evaluate the long-term effects. A total of 69 subjects (37 in the experimental group and 32 in the control group) participated in the experiment. The results showed that knowledge about respiratory infection prevention, respiratory infection prevention practices, and social capital were enhanced among the elderly residents who participated in the educational program. The educational effects differed significantly across time periods (pretest, posttest, 1- and 6-month follow up) in all the above variables. In particular, the program remained effective 1 month after the intervention, but a reinforcement session extended the program's effects up to 6 months later. This educational program would be used as an effective intervention to help rural elderly residents prevent respiratory infections.


Influence of Mn doping on structural and vibrational properties of self-assembled Mn doped ZnO nanocrystals.
Nanocrystallites (15-25 nm) of Mn doped ZnO prepared by refluxing their acetate precursors in the presence of diethylene glycol, self-assemble into polydisperse spheres of broad size distributation (100-400 nm). The center of X-ray diffraction peaks shifts towards lower angle and the line gets broadened on increasing Mn concentration. Compared to the vibration modes of wurtzite ZnO, one additional vibration mode is observed in the range of 522-518 cm(-1) in Raman spectra of Mn doped ZnO whose intensity increases on increasing the Mn concentration. The origin of this peak could be related to the incorporation of Mn2+ in Zn2+ lattice site. Further, on increasing Mn concentration, infrared band red shifted and surface phonon mode absorption get pronounced due to the incorporation of Mn2+ in Zn2+ lattice site resulting changes in the local structure parameters (effective mass, force constant, bond length).


Proteomics in the investigation of HIV-1 interactions with host proteins.
Productive HIV-1 infection depends on host machinery, including a broad array of cellular proteins. Proteomics has played a significant role in the discovery of HIV-1 host proteins. In this review, after a brief survey of the HIV-1 host proteins that were discovered by proteomic analyses, I focus on analyzing the interactions between the virion and host proteins, as well as the technologies and strategies used in those proteomic studies. With the help of proteomics, the identification and characterization of HIV-1 host proteins can be translated into novel antiretroviral therapeutics.


Technology-delivered cognitive-behavioral therapy for pediatric anxiety disorders: a meta-analysis of remission, posttreatment anxiety, and functioning.
The efficacy of technology-delivered cognitive-behavioral therapy (tCBT) for pediatric anxiety disorders (ADs) is uncertain as no meta-analysis has examined outcomes in trials that used structured diagnostic assessments at pre- and posttreatment. We carried out a systematic review and meta-analysis of randomized controlled trials (RCTs) of tCBT for pediatric ADs that included participants <18 years of age with a confirmed primary AD according to a structured diagnostic interview. Nine studies with 711 participants were included. tCBT outperformed control conditions for remission for primary AD (37.9% vs. 10.2%; k = 9; OR = 4.73; p < .0001; I2 = 0%; moderate certainty), remission for all ADs (19.5% vs. 5.3%; k = 8; OR = 3.32; p < .0001; I2 = 0%; moderate certainty), clinician-rated functioning (k = 7; MD = -4.38; p < .001; I2 = 56.9%; low certainty), and caregiver-reported anxiety (k = 7; SMD = 0.27; p = .02; I2 = 41.4%; low certainty), but not for youth-reported anxiety (k = 9; SMD = 0.13; p = .12; I2 = 0%; low certainty). More severe pretreatment anxiety, a lower proportion of completed sessions, no face-to-face sessions, media recruitment, and a larger proportion of females were associated with lower remission rates for primary AD. tCBT has a moderate effect on remission for pediatric ADs and clinician-rated functioning, a small effect on caregiver-reported anxiety, and no statistically significant effect on youth-reported anxiety. The certainty of these estimates is low to moderate. Remission rates vary substantially across trials and several factors that may influence remission were identified. Future research should examine for whom tCBT is most appropriate and what care to offer the large proportion that does not remit. Future RCTs should consider contrasting tCBT with partial tCBT (e.g., including therapist-led exposure) and/or face-to-face CBT.


A stereoselective intramolecular 1,3-dipolar nitrone cycloaddition for the synthesis of substituted chromanes.
A stereoselective intramolecular 1,3-dipolar nitrone cycloaddition useful in the synthesis of chromanes is described. The reaction relies on the use of a chiral auxiliary on the nitrone partner. Key to the success of the reaction is the choice of auxiliary and the choice of Lewis acid catalyst. Utilizing an auxiliary with a pendant coordinating group, and Zn(OTf)(2) as the Lewis acid, diastereoselectivities up to 22:1 could be achieved.


The natural course of allergic rhinitis during 12 years of follow-up.
As symptoms of allergic rhinitis are generally thought to disappear with increasing age, we decided to follow up our allergic rhinitis patients to ascertain whether their disease had regressed or progressed, and whether they had developed respiratory symptoms. At our department, between 1979 and 1982, allergic rhinitis was diagnosed in 108 patients. In 1993, 82 of the patients (40 women, 42 men; mean age 36 years), none of whom had received immunotherapy, answered a questionnaire concerning the status of their allergic rhinitis, and any development of the disease during the interim. Of the 82 patients, one was free of allergic symptoms and 39% had become better; symptoms were unchanged in 39% of cases, and worse in 21%. Six percent had suffered from asthma at presentation, 6% had developed asthma in the interim, and 34% reported other lower airways symptoms. Neither sex nor age at diagnosis was a determinant of the course of allergic rhinitis. Thus, in contrast to findings in other studies, the severity of allergic rhinitis seems to have increased among our patients.


Accelerated triacylglycerol turnover kinetics in hearts of diabetic rats include evidence for compartmented lipid storage.
Triacylglycerol (TAG) storage and turnover rates in the intact, beating rat heart were determined for the first time using dynamic mode (13)C- NMR spectroscopy to elucidate profound differences between hearts from diabetic rats (DR, streptozotocin treatment) and normal rats (NR). The incorporation of [2,4,6,8,10,12,14,16-(13)C(8)]palmitate into the TAG pool was monitored in isolated hearts perfused with physiological (0.5 mM palmitate, 5 mM glucose) and elevated substrate levels (1.2 mM palmitate, 11 mM glucose) characteristic of the diabetic condition. Surprisingly, although the normal hearts were enriched at a near-linear profile for >or=2 h before exponential characterization, exponential enrichment of TAG in diabetic hearts reached steady state after only 45 min. Consequently, TAG turnover rate was determined by fitting an exponential model to enrichment data rather than conventional two-point linear analysis. In the high-substrate group, both turnover rate (DR 820+/- 330, NR 190 +/-150 nmol.min(-1).g(-1) dry wt; P< 0.001) and [TAG] content (DR 78 +/-10, NR 32+/- 4 micromol/g dry wt; P< 0.001) were greater in the diabetic group. At lower substrate concentrations, turnover was greater in diabetics (DR 530+/-300, NR 160+/- 30; P<0.05). However, this could not be explained by simple mass action, because [TAG] content was similar between groups [DR 34+/- 7, NR 39+/- 9 micromol/g dry wt; not significant (NS)]. Consistent with exponential enrichment data, (13)C fractional enrichment of TAG was lower in diabetics (low- substrate groups: DR 4+/-1%, NR 10+/- 4%, P<0.05; high-substrate groups: DR 8+/- 3%, NR 14+/- 9%, NS), thereby supporting earlier speculation that TAG is compartmentalized in the diabetic heart.


Granulomatous pyoderma gangrenosum in a patient with ulcerative colitis.
A 34-year-old woman with a past history of inflammatory bowel disease developed a painful elevated edematous swelling with ulcerations on the dorsum of her left foot. Histopathological examination revealed dense infiltration of neutrophils and mononuclear cells in the lower dermis and subcutaneous tissue. Tumor necrosis factor (TNF) was strongly detected in giant cells. To date, only a few cases of pyoderma gangrenosum with granulomatous changes have been reported. Tumor necrosis factor may have played a role in the granulomatous reaction in our case.


[Cloning and antimicrobial activity of pigeon avian beta-defensin 5].
The objective of the study was to clone avian beta-defensin (AvBD) 5 gene from pigeon bone marrow tissues and liver tissues, to express the recombinant AvBD5 protein in E. coli, and to determine its antimicrobial activity. The mRNA of duck AvBD5 was cloned from pigeon bone marrow tissues and liver tissues by RT-PCR. In addition, phylogenetic relationships between amino acid sequence of the pigeon AvBD5, AvBDs from other avian species, and some mammalian beta-defensin-5 were analyzed. The cDNA of pigeon AvBD5 was sub-cloned into pGEX-6p-1 vector to construct recombinant plasmid pGEX-pigeon AvBD5. The recombinant protein was expressed into E. coli and purified. Antimicrobial activity and physical-chemical stability of the recombinant fusion protein were measured in vitro. The complete nucleotide sequence of both cDNAs contained 201 bp nucleotides, encoding a polypeptide of 66 amino acids. Both beta-defensins have six conserved cysteines. Phylogenetic relationships were analyzed. Both pigeon AvBDs shared the highest amino acid homology (87.9% and 78.8%) with duck AvBD5. So it was named as pigeon AvBD5alpha (bone marrow) and AvBD5beta (liver). Both recombinant plasmids were transformed into E. coli BL21 and the bacteria were induced with Isopropyl beta-D-1-Thiogalactopyranoside (IPTG). After purification, antibacterial activity of the purified was investigated. In addition, effect of ionic strength on the antibacterial activity, and hemolytic recombinant protein activity of the purified recombinant protein were investigated. A 32 kDa protein was highly expressed. Both purified recombinant pigeon AvBD5alpha and AvBD5beta exhibited extensive antimicrobial activities against 12 bacteria, including Gram-positive and Gram-negative. In high salt ions concentrations, antibacterial activity of both recombinant proteins was decreased. In addition, the hemolysis activity of recombinant protein was extremely low.


Dosimetry of 175Ytterbium-poly (amidoamine) Therapy for Humans' Organs.
This investigation focuses on biodistribution of irradiated dendrimer encapsulated ytterbium-175 (175Yb) and to estimate the absorbed dose from intravenous injection of PAMAM encapsulated 175Yb to human organs. A dendrimer compound containing an average of 55 Yb+3 ions per dendrimer was prepared and irradiated with neutrons for 2h at 3×1011 n.cm-2s-1 neutron flux. The resulting mixture was injected into a group of tumor bearing mice and the mice were excised, weighed and counted at certain times to study the biodistribution. The human organs absorbed dose was assessed by MIRD schema and MCNP simulation. The specific activity and radiochemical purity of the irradiated nano-composite were 7MBq/mg and >99% respectively. The rapid up take of dendrimer was in liver, lung, and, spleen. MIRD and MCNPX were applied for dose estimation. The human absorbed dose in liver, lung, spleen, kidney and bone that simulated by MCNP are 1.266, 0.8081, 0.8347, 0.03979 and 0.01706 mGy/MBq respectively and these values for MIRD schema are 1.351, 0.73, 1.03, 0.039, and 0.0097 mGy/MBq respectively. The results showed that 175Yb-PAMAM nano-radiopharmaceutical has potential of application for liver and lung tumors.


Sirevirus LTR retrotransposons: phylogenetic misconceptions in the plant world.
Sireviruses are an ancient and plant-specific LTR retrotransposon genus. They possess a unique genome structure that is characterized by a plethora of highly conserved sequence motifs in key domains of the non-coding genome, and often, by the presence of an envelope-like gene. Recently, their crucial role in the organization of the maize genome, where Sireviruses occupy approximately 21% of its nuclear content, was revealed, followed by an analysis of their distribution across the plant kingdom. It is now suggested that Sireviruses have been a major mediator of the evolution of many plant genomes. However, the name 'Sirevirus' has caused confusion in the scientific community in regards to their classification within the LTR retrotransposon order and their relationship with viruses - a situation that is not unique to Sireviruses, but also affects other LTR retrotransposon genera. Here, we clarify the phylogenetic position of Sireviruses as typical LTR retrotransposons of the Copia superfamily and explain that the confusion stems from the discrepancy in the categorization of LTR retrotransposons by the two main classification systems: the International Committee on the Taxonomy of Viruses (ICTV) system and the unified classification system for eukaryotic transposable elements. While the name 'Sirevirus' has been given by ICTV, we show that the transposable element system, which is more suitable for eukaryotic genome studies, lacks an appropriate taxonomic level for describing them. We urge for this inconsistency to be addressed. Finally, we provide data suggesting that of the three ICTV-proposed genera of the Pseudoviridae (that is, Copia) family, only Sireviruses form a monophyletic group, while the phylogenetic distinction between Pseudoviruses and Hemiviruses is unclear. We conclude that because of their ongoing important contribution to the classification of transposable elements, these schemes need to be frequently revisited and revised - as shown by the example of the Sirevirus LTR retrotransposon genus.


Rotational Atherectomy and Stent Implantation for Calcified Left Main Lesions.
Left main coronary artery (LMCA) bifurcation and heavily calcified lesions are common and challenging to treat percutaneously. Rotational atherectomy (RA) may be beneficial in this setting to facilitate stent placement though direct supporting evidence is lacking. This study sought to analyze patients who underwent RA of the LMCA. Consecutive cases involving RA of the LMCA between 1/1/2004 and 12/31/2009 at a private, tertiary referral hospital were reviewed retrospectively. Medical records, angiograms and clinically driven follow-up were reviewed. Thirty-one cases were identified (20 protected, 11 unprotected), including 23 with stent implantation (21 drug-eluting, 2 bare metal). All 31 lesions had moderate to severe calcification, 84% involved the distal segment. Mean burr-to-vessel ratio was 0.43. Overall angiographic success was 90% (28/31) and was higher with a drug-eluting stent versus no stent (100% vs. 62%; P = 0.0153). In-hospital major adverse cardiovascular events (MACE) occurred in 1 patient (3%). Mid-term MACE occurred in 6 patients (26%) and tended to occur less frequently in patients with protected LMCAs (P = 0.0697). At final follow-up, patients were more likely to be alive and free from angina with a protected LMCA (94% vs. 57% unprotected; P = 0.0564) and with a drug-eluting stent (89% vs. 50% with no stent; P = 0.0281). RA of the LMCA to facilitate stent implantation appears to be safe and effective with favorable mid-term outcomes. In the setting of severe calcification and distal LMCA involvement RA and drug-eluting stent implantation should be considered.


Verification of the Crooks fluctuation theorem and recovery of RNA folding free energies.
Atomic force microscopes and optical tweezers are widely used to probe the mechanical properties of individual molecules and molecular interactions, by exerting mechanical forces that induce transitions such as unfolding or dissociation. These transitions often occur under nonequilibrium conditions and are associated with hysteresis effects-features usually taken to preclude the extraction of equilibrium information from the experimental data. But fluctuation theorems allow us to relate the work along nonequilibrium trajectories to thermodynamic free-energy differences. They have been shown to be applicable to single-molecule force measurements and have already provided information on the folding free energy of a RNA hairpin. Here we show that the Crooks fluctuation theorem can be used to determine folding free energies for folding and unfolding processes occurring in weak as well as strong nonequilibrium regimes, thereby providing a test of its validity under such conditions. We use optical tweezers to measure repeatedly the mechanical work associated with the unfolding and refolding of a small RNA hairpin and an RNA three-helix junction. The resultant work distributions are then analysed according to the theorem and allow us to determine the difference in folding free energy between an RNA molecule and a mutant differing only by one base pair, and the thermodynamic stabilizing effect of magnesium ions on the RNA structure.


Assessment of Drug-Induced QTc Prolongation in Mental Health Practice: Validation of an Evidence-Based Algorithm.
Drug-induced QTc interval prolongation (QTcIP) can lead to serious consequences and is often a concern for mental health practitioners, as access to experts such as cardiologists, for consultation is time-limiting and can delay treatment decisions. This research aimed at validating the content of an algorithm for the assessment, management and monitoring of drug-induced QTcIP in mental health practice. Following an initial face validity by content experts, a cross-sectional survey of mental health care practitioners with a 4-point Likert-type scale was used to assess the validity of the decision steps on the QTcIP algorithm (QTcIPA) by estimating the content validity index (CVI) and the modified kappa statistic (κ*). Participants' open-ended comments were also thematically analyzed. Mental health practitioners found the QTcIPA to be appropriate, safe, and evidence-based, as indicated by the high individual item CVI scores ranging from 0.89 to 1 for all of the steps/decision statements in the three domains assessed: appropriateness, safety and reliability of the references used. Five themes emerged from the qualitative analysis of the open-ended comments, of which three were identified as strengths, including practical usability, reliable references and beneficial for pharmacists. Two themes were recognized as limitations, namely, the need for additional clinical content and application barriers. These results suggest that the QTcIPA may be a useful tool for mental health clinicians at the time of prescribing medications with potential risk of QTcIP. Future research will explore the implementation of the QTcIPA into clinical practice using computerized decision support tools through web-based and mobile applications.


Pattern of breast diseases in Accra: review of mammography reports.
To document the mammographic patterns in females seeking medical attention in Accra. An analytic retrospective study was conducted using data extracted from mammography request forms and corresponding radiological reports of 180 females. The radiology departments of Korle-Bu Teaching Hospital the Trust Hospital and Medical Imaging Ghana all located in Accra. One hundred and eighty radiologic request forms for mammographic evaluations and their corresponding reports from the study period were reviewed. The mean age of the study population was 48.7 years (SD=10.0), and the median age group was the 41-50 group. There were more screening mammography evaluations (115 examinations) than diagnostic mammography evaluations (65 examinations). Most of the cases diagnosed as breast cancer were in the age group 41-50 years. Benign lesions were commoner than cancer (55 and 16 cases respectively). The commonest presenting complaint was of pain. The larger number of screening mammographic evaluations conducted for asymptomatic females during the study period, as compared to diagnostic mammographic evaluations for symptomatic females, suggests that educational programs on early breast cancer detection are having a positive impact on the target population. The observation that 22.8% of lesions had features suggestive of breast cancer in the study is significantly high to also warrant intensification of the existing awareness programs. As non-specific masses were the most common radiographically observed lesions, hospitals equipped with sonography and biopsy facilities that compliment their mammography are better suited for thorough breast disease evaluation.


Revealing bacterial targets of growth inhibitors encoded by bacteriophage T7.
Today's arsenal of antibiotics is ineffective against some emerging strains of antibiotic-resistant pathogens. Novel inhibitors of bacterial growth therefore need to be found. The target of such bacterial-growth inhibitors must be identified, and one way to achieve this is by locating mutations that suppress their inhibitory effect. Here, we identified five growth inhibitors encoded by T7 bacteriophage. High-throughput sequencing of genomic DNA of resistant bacterial mutants evolving against three of these inhibitors revealed unique mutations in three specific genes. We found that a nonessential host gene, ppiB, is required for growth inhibition by one bacteriophage inhibitor and another nonessential gene, pcnB, is required for growth inhibition by a different inhibitor. Notably, we found a previously unidentified growth inhibitor, gene product (Gp) 0.6, that interacts with the essential cytoskeleton protein MreB and inhibits its function. We further identified mutations in two distinct regions in the mreB gene that overcome this inhibition. Bacterial two-hybrid assay and accumulation of Gp0.6 only in MreB-expressing bacteria confirmed interaction of MreB and Gp0.6. Expression of Gp0.6 resulted in lemon-shaped bacteria followed by cell lysis, as previously reported for MreB inhibitors. The described approach may be extended for the identification of new growth inhibitors and their targets across bacterial species and in higher organisms.


Effects of Classroom Practices on Reading Comprehension, Engagement, and Motivations for Adolescents.
We investigated the roles of classroom supports for multiple motivations and engagement in students' informational text comprehension, motivation, and engagement. A composite of classroom contextual variables consisting of instructional support for choice, importance, collaboration, and competence, accompanied by cognitive scaffolding for informational text comprehension, was provided in four-week instructional units for 615 grade 7 students. These classroom motivational-engagement supports were implemented within integrated literacy/history instruction in the Concept-Oriented Reading Instruction (CORI) framework. CORI increased informational text comprehension compared with traditional instruction (TI) in a switching replications experimental design. Students' perceptions of the motivational-engagement supports were associated with increases in students' intrinsic motivation, value, perceived competence, and increased positive engagement (dedication) more markedly in CORI than in TI, according to multiple regression analyses. Results extended the evidence for the effectiveness of CORI to literacy/history subject matter and informational text comprehension among middle school students. The experimental effects in classroom contexts confirmed effects from task-specific, situated experimental studies in the literature.


Analysis of diffusion of plant metabolites from polyethylene glycol hydrogels using free volume theory.
The present work aims to comprehensively analyze the diffusion of plant metabolites from the polyethylene glycol (PEG) hydrogels for controlled release applications. For this study, a mathematical model based on free volume theory has been utilized to simulate the diffusion of low molecular weight plant metabolites. The results demonstrate that the mesh size of the crosslinked network, thereby the diffusion coefficient of the natural compound can be computed using the current framework. The proposed model has also been validated using the experimental data. The diffusion period has been observed to vary within a wide range of 3.42 h for Cinnamaldehyde to 49.25 h for Grandinin. An empirical parametric relationship between the diffusion time and molecular weight of both the hydrogels and natural compounds is established. It appears that the reported modeling approach will be clinically useful for improving the design of the sustained drug delivery systems.


Cerebral sinus thrombosis in patients with inflammatory bowel disease: a case report.
Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease of the gastrointestinal tract. The pathophysiology of IBD is probably the result of the complex interaction of genetic susceptibility and environmental influences. There is a well-known risk of thrombosis in patients with IBD. We present the case of a 53-year-old man with ulcerative colitis, who spontaneously developed intracranial sinus thrombosis that was treated with low molecular weight heparin. Literature was searched to assess the frequency and characteristics of cerebral sinus thrombosis in IBD and the role of certain etiopathological factors in such thrombotic patients.


Functional Disabilities and Food Insufficiency During Pregnancy: Results from the Pregnancy Risk Assessment Monitoring System.
Background: Disability is a well-documented risk factor for food insecurity. However, prior literature has overlooked the possible connection between disability and food insecurity during the antenatal period. This study extends previous research by examining the relationship between those with any functional disabilities and food insufficiency during pregnancy among a sample of mothers. Methods: Data are from the Pregnancy Risk Assessment Monitoring System, 2019-2020 (N = 9084). The relationship between the number of self-reported functional disabilities and food insufficiency is examined using modified multivariable Poisson regression. Results: After adjusting for control variables, the results reveal that those with any functional disability have a significantly higher risk of food insufficiency during pregnancy (risk ratio [RR] = 1.464, 95% confidence interval [CI] = 1.201-1.785). Findings reveal that all types of functional disability are associated with a higher risk of food insufficiency, including difficulty seeing, difficulty hearing, difficulty walking, difficulty remembering, difficulty with self-care, and difficulty communicating. Finally, the findings revealed that respondents with two functional disabilities (RR = 1.473, 95% CI = 1.153-1.882) and three or more functional disabilities (RR = 1.974, 95% CI = 1.534-2.541) are significantly more likely to report food insufficiency compared with respondents with no disabilities. Conclusions: There is a significant positive association between reporting functional disabilities and food insufficiency. Expanding current public health programs, educating health care professionals, and implementing effective screening guidelines directed at pregnant women with disabilities may reduce the prevalence of food insufficiency and promote greater health equity.


Structure of the beta subunit of translational initiation factor eIF-2.
A human liver cDNA encoding the beta subunit of protein synthesis initiation factor 2 (eIF-2) was isolated and sequenced. The 1416 bp cDNA encodes a protein of 333 amino acids (38,404 daltons) with characteristics that resemble authentic purified eIF-2 beta. De novo synthesized eIF-2 beta from cDNA transcripts incorporates into endogenous rabbit eIF-2 complexes. The protein possesses putative GTP-binding sites, a zinc finger motif, and a highly charged N-terminal region composed of three basic polylysine blocks separated by acidic domains. The polylysine blocks and the zinc finger motif suggest that eIF-2 beta interacts with RNA. A yeast protein, Sui3, isolated as an extragenic suppressor of his4 initiation codon mutations, exhibits extensive sequence identity with human eIF-2 beta, especially in the polylysine and zinc finger domains, thereby reinforcing the view that these elements are important for function.


Neuroestradiol in the Stalk Median Eminence of Female Rhesus Macaques Decreases in Association With Puberty Onset.
In primates, despite the fact that GnRH neurons are mature at birth, a gonadal steroid independent central inhibition restrains the initiation of puberty. The neural substrates responsible for this central inhibition, however, are unclear. In this study, we tested the hypothesis that neuroestradiol release in the hypothalamus decreases prior to the pubertal increase in GnRH release. We found that in female monkeys at the prepubertal stage, when GnRH release was low, estradiol (E2) levels in the stalk-median eminence of the hypothalamus were higher than those in older, early pubertal females in which nocturnal GnRH release begins to increase. Furthermore, estrone (E1) levels were higher in the stalk-median eminence of prepubertal and early pubertal monkeys compared with midpubertal monkeys, which have the highest GnRH release. The elevated E2 and E1 levels at the prepubertal stage are likely hypothalamic in origin because circulating E2 and E1 levels in prepubertal and early pubertal monkeys were much lower than those in midpubertal monkeys. Heightened synthesis and release of neuroestradiol during the prepubertal period and subsequent reduction at puberty onset indicate possible roles for neuroestradiol in central inhibition of GnRH release. The mechanism governing the reduction in neuroestradiol synthesis at puberty onset remains to be determined.


An empirical time-intensity relationship for thermal bioelectromagnetic effects.
Published experimental data for three thermal/harmful bioelectromagnetic effects (lethality, cataractogenesis, and threshold pain sensation) are examined in an effort to develop a generally consistent empirical expression relating the time of irradiation necessary to induce an effect to the intensity of the radiation. A critical organ is assigned to each effect and the SAR's in these organs are estimated, when necessary, from the incident power density. It is found that all the data can be satisfactorily described by a single power function expression which gives the exposure duration as a function of the SAR in the critical organ and an experiment-specific constant.


Human nesidioblastosis tissue as an immunogen for generation of islet cell specific monoclonal antibodies.
Nesidioblastosis pancreas was used as an immunogen in BALB/c-mice to generate monoclonal antibodies against structures of human islet cells. Seven clones were selected by screening 311 growing hybridomas for reactivity with the rat insulinoma cell line, RIN m5F, and with cryostat sections from human pancreas. None of the selected clones reacted with pancreatic hormones or endocrine-specific peptides. Monoclonal antibodies cross-reacting with the RIN-cell line also bound to different endocrine organs or cell lines, while some RIN-cell-negative clones bound only to Langerhans islets from human pancreas.


The link between flowering time and stress tolerance.
Evolutionary success in plants is largely dependent on the successful transition from vegetative to reproductive growth. In the lifetime of a plant, flowering is not only an essential part of the reproductive process but also a critical developmental stage that can be vulnerable to environmental stresses. Exposure to stress during this period can cause substantial yield losses in seed-producing plants. However, it is becoming increasingly evident that altering flowering time is an evolutionary strategy adopted by plants to maximize the chances of reproduction under diverse stress conditions, ranging from pathogen infection to heat, salinity, and drought. Here, recent studies that have revealed new insights into how biotic and abiotic stress signals can be integrated into floral pathways are reviewed. A better understanding of how complex environmental variables affect plant phenology is important for future genetic manipulation of crops to increase productivity under the changing climate.


Obesity and the reproductive system disorders: epigenetics as a potential bridge.
Obesity and overweight are significantly involved in several reproductive pathologies contributing to infertility in men and women. In addition, several cancers of the reproductive system, such as endometrial, ovarian, breast, testicular and prostate cancers, are strongly influenced by obesity. However, the molecular mechanisms involved in the association between obesity and reproductive disorders remain unclear. Our proposal is to review the current scientific evidence regarding the effect of obesity-related factors as the core of the collective mechanisms directly and indirectly involved in the relationship between obesity and reproductive disorders, with a special and original focus on the effect of the obesity state microenvironment on the epigenetic profile as a reversible mechanistic link between obesity and the reproductive disorders. A PubMed search was performed using keywords related to obesity and adipose-related factors and epigenetics and associated with keywords related to reproduction. Full-text articles and abstracts in the English language published prior to 31 December 2013 were reviewed. The obesity state notably contributes to a reproductive dysfunction in both men and women, ranging from infertility to oncological outcomes. Several epidemiological and experimental studies demonstrate that factors secreted by the adipose tissue and gut in an obesity state can directly induce reproductive disturbances. Relevantly, these same factors are able to alter the epigenetic regulation of genes, a dynamic and reversible mechanism by which the organism responds to environmental pressures critical to the reproductive function. This review outlines the evidence showing that the association between the reproductive pathologies and obesity is not inevitable but is potentially preventable and reversible. The epigenetic marks related to obesity could constitute a therapeutic target for the reproductive disorders associated with obesity.


Ca and S K-edge XANES of CaS calculated by different methods: influence of full potential, core hole and Eu doping.
Ca and S K-edge spectra of CaS are calculated by the full-potential Green's function multiple-scattering method, by the FLAPW method and by the finite-difference method. All three techniques lead to similar spectra. Some differences remain close to the edge, both when comparing different calculations with each other and when comparing the calculations with earlier experimental data. Here it is found that using the full potential does not lead to significant improvement over the atomic spheres approximation and that the effect of the core hole can be limited to the photoabsorbing atom alone. Doping CaS with Eu will not affect the Ca and S K-edge XANES of CaS significantly but may give rise to a pre-edge structure not present for clean CaS.


Creating an Ethnodrama to Catalyze Dialogue in Home-Based Dementia Care.
This article describes the development of a theater script derived from a critical ethnographic study that followed people living with dementia--and their family and professional caregivers--over an 18-month period. Analysis of the ethnographic data yielded four themes that characterized home-based dementia care relationships: managing care resources, making care decisions, evaluating care practices, and reifying care norms. The research team expanded to include a colleague with playwright experience, who used these themes to write a script. A theater director was included to cast and direct the play, and finally, a videography company filmed the actors on a realistic set. To contribute to the qualitative health research and the research-based theater knowledge translation literatures, this article describes and explains the creative decisions taken as part of our effort to disseminate research focused on home-based dementia care in a way that catalyzes and fosters critical (actionable) dialogue.


Single-Center Retrospective Analysis of Neutrophil, Monocyte, and Platelet to Lymphocyte Ratios as Predictors of Complicated Appendicitis.
Aim We look at the ability of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) to differentiate between uncomplicated and complicated appendicitis. Methods and materials This was a retrospective, single-center study of 234 individuals diagnosed with acute appendicitis between January 1, 2020, and December 31, 2020. Patients were grouped into uncomplicated and complicated appendicitis subgroups. Patients with histologically or radiologically proven gangrenous or perforated appendicitis, as well as those with peritonitis or peri-appendiceal abscess development, comprise the complicated subgroup. Independent Mann-Whitney samples The U test was used to predict lab values of complicated appendicitis. Furthermore, the receiver operating characteristic (ROC) curve and area under the curve (AUC) were utilized to predict the sensitivity and specificity of laboratory results reported to have a significant connection with complex appendicitis Results The criteria were met by 186 patients, with a male-to-female proportion of 1.06:1, an average age of 36.4 years, and an average stay of 2.73 days. There were 95 individuals with complicated appendicitis. With 66.3%, perforated appendicitis was the most prevalent condition. The ratios of neutrophils to lymphocytes, monocytes to lymphocytes, and platelets to lymphocytes were linked with complicated appendicitis with a p-value of < 0.0001, and p-values = 0.015, and 0.015, respectively. Conclusion NLR, MLR, and PLR are valid, less onerous surrogate biomarkers for measuring the severity of acute complicated appendicitis and differentiating it from uncomplicated appendicitis.


Safety assessment of gamma-cyclodextrin.
Gamma-cyclodextrin (gamma-CD) is a cyclic alpha-(1,4)-linked oligosaccharide consisting of eight glucose molecules. Like other cyclodextrins, gamma-CD can form inclusion complexes with a variety of organic molecules because the inner side of the torus-like molecule is less polar than the outer side. In foods, gamma-CD may be used as a carrier for flavors, vitamins, polyunsaturated fatty acids, and other ingredients. It also has useful properties as a stabilizer in different food systems. The daily intake from all its intended uses in food at highest feasible concentrations has been estimated at 4.1g/person/day for consumers of gamma-CD containing foods. The present review summarizes the safety data of gamma-CD. The toxicity studies consist of standard genotoxicity tests, subchronic rat studies with oral and intravenous administration of gamma-CD for up to 3 months, a subchronic (3-month) toxicity study in dogs, a (1-year) oral toxicity study in rats, and embryotoxicity/teratogenicity studies in rats and rabbits. In the studies with oral administration, gamma-CD was given at dietary concentrations of up to 20%. All these studies demonstrated that gamma-CD is well tolerated and elicits no toxicological effects. Metabolic studies in rats showed that gamma-CD is rapidly and essentially completely digested by salivary and pancreatic amylase. Therefore, the metabolism of gamma-CD closely resembles that of starch and linear dextrins. A human study with ingestion of single doses of 8 g gamma-CD or 8 g maltodextrin did not reveal a difference in gastrointestinal tolerance of these two products. An interaction of ingested gamma-CD with the absorption of fat-soluble vitamins or other lipophilic nutrients is not to be expected because the formation of inclusion complexes is a reversible process, gamma-CD is readily digested in the small intestine, and studies with beta-CD, a non-digestible cyclodextrin, have shown that the bioavailability of vitamins (A, D, and E) is not impaired. On basis of these studies it is concluded that gamma-CD is generally recognized as safe (GRAS) for its intended uses in food.


N-methyl-1-deoxynojirimycin (MOR-14), an alpha-glucosidase inhibitor, markedly reduced infarct size in rabbit hearts.
N-methyl-1-deoxynojirimycin (MOR-14), an alpha-glucosidase inhibitor, reduces the glycogenolytic rate by inhibiting the alpha-1,6-glucosidase of glycogen-debranching enzyme in the liver, in addition to possessing an antihyperglycemic action by blocking alpha-1,4-glucosidase in the intestine. Because the reduction of the glycogenolytic rate may be one of the mechanisms of myocardial protection in ischemic preconditioning, the compounds inhibiting myocardial alpha-1,6-glucosidase may be protective against ischemic damage. Thus, we investigated whether MOR-14 could inhibit alpha-1,6-glucosidase and reduce the infarct size in rabbit hearts without collateral circulation. MOR-14 dose-dependently decreased the alpha-1,6-glucosidase activity in rabbit heart extract. A tracer study demonstrated the myocardial uptake of a considerable amount of MOR-14 sufficient to fully inhibit alpha-1,6-glucosidase. To assess the infarct size-reducing effect of MOR-14, 54 rabbits were subjected to 30-minute coronary occlusion followed by 48-hour reperfusion. Preischemic treatment with 25, 50, and 100 mg/kg of MOR-14 dose-dependently reduced the infarct size (to 26+/-4%, 19+/-3%, and 14+/-2% of the area at risk, respectively), compared with the saline control (45+/-5%) without altering the blood pressure or heart rate. Another 40 rabbits given 100 mg of MOR-14 or saline 10 minutes before ischemia were euthanized at 10 or 30 minutes of ischemia for biochemical analysis. MOR-14 decreased the alpha-1,6-glucosidase activity to approximately 20% in vivo, reduced the glycogen breakdown, and attenuated the lactate accumulation at both 10 and 30 minutes of ischemia. Preischemic treatment with MOR-14 preserved glycogen, attenuated the accumulation of lactate, and reduced the myocardial infarct size by 69%. This cardioprotective effect was independent of changes of blood pressure and heart rate or regional blood flow. It may be associated with alpha-1,6-glucosidase inhibition, because MOR-14 markedly decreased the alpha-1,6-glucosidase activity in the heart.


K-channel blocking drugs induce histamine release and 45Ca uptake in isolated mast cells.
Histamine secretion and 45Ca uptake processes were studied in mast cells treated with four K+ channel blocking drugs in physiological saline and in media containing different ionic concentrations. Quinine, 4-aminopyridine and sparteine were effective as histamine-releasing agents when mast cells were incubated in physiologic saline solution. The dose-response profile obtained was in the range of 0.1-0.5 mM for quinine, 1-10 for 4-aminopyridine and 0.5-5 mM for sparteine and did not show significant differences between purified and unpurified mast cells. By contrast, tetraethylammonium (1-100 mM) did not induce histamine release. The presence of high K+ or Rb+ concentrations in the medium (Tris-K+ or Tris-Rb+, both at 150 mM) displaced the profile obtained to the right in cells stimulated with 4-aminopyridine or sparteine, but abolished histamine release induced by quinine. Additionally, all three K+ channel blockers increased 45Ca uptake in mast cells. The exact mechanism of the action of K+ channel blockers on mast cells is unknown. However, the fact that the drugs used were effective as histamine-releasing and 45Ca uptake promoters suggests both that mast cells might be endowed with a K+ channel activity and that the blockade of this should open certain calcium channels, leading to elevated intracellular Ca2+ levels which in turn activate mast cell secretion.


A Risk Score to Diagnose Cardiac Involvement and Provide Prognosis Information in Patients at Risk of Cardiac Light-Chain Amyloidosis.
Cardiac light-chain amyloidosis (AL CA) portends poor prognosis. Contrast cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) imaging is an important tool in recognizing AL CA. But contraindications to contrast CMR would significantly restrict its clinical application value. Our study aims to construct a convenient risk score to help identify cardiac involvement in patients at risk of AL CA. Moreover, we also investigate whether this risk score could provide prognosis information. Sixty-three patients at risk of AL CA were retrospectively included in our study. Basic clinical characters, lab results, 12-lead electrocardiogram data, and cardiac magnetic resonance image data were collected. AL CA was diagnosed according to typical CA LGE pattern. Logistic analysis was used to figure out predictive parameters of AL CA and their β coefficients, further constructing the risk score. Receiver operating characteristics (ROC) curve was used to find the cut-off point best distinguishing AL CA+ from AL CA-patients. Bootstrapping was used for internal validation. All patients were divided into high-risk and low-risk group according to the diagnostic cut-off point, and followed up for survival information. Kaplan-Meier plots and log-rank test were performed to analyze if this score had prognostic value. The risk score finally consisted of 4 parameters: pericardial effusion (PE) (1 point), low electrocardiographic QRS voltages (LQRSV) (1 point), CMR-derived impaired global radial strain (GRS) (<15.14%) (1 point) and increased left ventricular maximum wall thickness (LVMWT) (>13 mm) (2 points). Total score ranged from 0 to 5 points. A cut-off point of 1.5 showed highest accuracy in diagnosing AL CA with an AUC of 0.961 (95% CI: 0.924-0.997, sensitivity: 90.6%, specificity: 83.9%). Kaplan-Meier plots and log-rank test showed that the high-risk group had significantly poor overall survival rates. In patients at risk of AL CA, a risk score incorporating the presence of PE, LQRSV, and CMR-derived impaired GRS and increased LVMWT is predictive of a diagnosis of AL CA by LGE criteria. This risk score may be helpful especially when contrast CMR is not available or contraindicated, and further studies should be considered to validate this score.


Parental manual ventilation in resource-limited settings: an ethical controversy.
Lower respiratory tract infections are a leading cause of paediatric morbidity and mortality worldwide. Children in low-income countries are disproportionately affected. This is in large part due to limitations in healthcare resources and medical technologies. Mechanical ventilation can be a life-saving therapy for many children with acute respiratory failure. The scarcity of functioning ventilators in low-income countries results in countless preventable deaths. Some hospitals have attempted to adapt to this scarcity by using hand-bag ventilation, as either a bridge to a mechanical ventilator, or until clinical improvement occurs rendering mechanical ventilation no longer necessary. In instances of hand-bag ventilation, an endotracheal tube is first placed. Family members are then asked to play the role of a ventilator, manually compressing a bag repeatedly to inflate the child's lungs. This approach is fraught with numerous ethical challenges. A careful examination of the data and a nuanced approach to the ethical considerations are imperative. Ethical arguments in support of and in opposition to allowing parental hand-bag ventilation are explored, including the best interests of the child, the child's right to an open future, beneficence and parental protection, legitimising substandard care, and finally, contextual concerns. An algorithmic, potentially ethically permissible approach to parental participation in manual ventilation is proposed.


A novel bidirectional clustering algorithm based on local density.
With the widely application of cluster analysis, the number of clusters is gradually increasing, as is the difficulty in selecting the judgment indicators of cluster numbers. Also, small clusters are crucial to discovering the extreme characteristics of data samples, but current clustering algorithms focus mainly on analyzing large clusters. In this paper, a bidirectional clustering algorithm based on local density (BCALoD) is proposed. BCALoD establishes the connection between data points based on local density, can automatically determine the number of clusters, is more sensitive to small clusters, and can reduce the adjusted parameters to a minimum. On the basis of the robustness of cluster number to noise, a denoising method suitable for BCALoD is proposed. Different cutoff distance and cutoff density are assigned to each data cluster, which results in improved clustering performance. Clustering ability of BCALoD is verified by randomly generated datasets and city light satellite images.


B cell response to T helper cell subsets. II. Both the stage of T cell differentiation and the cytokines secreted determine the extent and nature of helper activity.
Helper activity of several murine CD4+ T cell subsets was examined. Effector Th, derived from naive cells after 4 days of in vitro stimulation with alloantigen, when generated in the presence of IL-4, secreted high levels of IL-4, IL-5, and IL-6, and low levels of IL-2 and IFN-gamma, and induced the secretion of all Ig isotypes particularly IgM, IgG1, IgA, and IgE from resting allogeneic B cells. Effectors generated with IL-6 secreted IL-2, IL-4, IL-5, IL-6, and IFN-gamma, and induced similar levels of total Ig, 25 to 35 micrograms/ml, but with IgM, IgG3, IgG1, and IgG2a isotypes predominating. Helper activity of these Th was significantly greater than that of effectors generated with IL-2 (10-15 micrograms/ml Ig) and of 24-h-activated naive and memory cells (2-4 micrograms/ml), both of which induced mainly IgM. Unlike other isotypes, IgE was induced only by effector Th generated with IL-4. Blocking studies showed that secretion of all isotypes in response to IL-6-primed effectors was dependent on IL-2, IL-5, and IL-6. IL-4 was required for optimal IgM, IgG1, and IgA secretion, but limited secretion of IgG2a, whereas IFN-gamma was required for optimal IgG2a secretion, and limited IgM, IgG1, and IgA. In contrast, secretion of all isotypes in response to IL-4-primed effectors was dependent on IL-5, although IL-4 and IFN-gamma were also essential for IgE and IgG2a, respectively. Addition of exogenous IL-5 to B cell cultures driven by IL-6-primed effectors did not obviate the requirement for IL-2, IL-4, and IL-6, suggesting that interaction of IL-4-primed effectors with B cells was qualitatively different from that of IL-6-primed effectors, driving B cells to a stage requiring only IL-5 for differentiation. Addition of exogenous factors to IL-2-primed effector Th, particularly IL-4 in the presence of anti-IFN-gamma, resulted in levels of Ig, including IgE, comparable to those induced with other effectors. These results show that functionally distinct Th cell subsets can be generated rapidly in vitro, under the influence of distinct cytokines, which vary dramatically in their levels of help for resting B cells. The cytokines involved in responses to distinct Th cells differ depending on the quality of interaction with the B cell, and the extent of help is strongly determined by the quantity and nature of cytokines secreted by the T cells.


Cardiac stress MRI evaluation of anomalous aortic origin of a coronary artery.
Myocardial ischemia is an insult that is primarily thought of in an adult population. However, there are several congenital and acquired cardiac lesions that may lead to myocardial ischemia in a pediatric population. One of the prominent congenital lesions is anomalous aortic origin of a coronary artery (AAOCA). Anomalous aortic origin of a coronary artery is one of the leading causes sudden cardiac death in pediatric and young adult patients, and thus the assessment of myocardial perfusion is of the utmost importance. Over the past decade, pharmacologic stress MRI has proven to be a highly sensitive and accurate diagnostic examination for qualifying myocardial perfusion in adults with coronary artery disease. This noninvasive imaging modality may be a useful tool in assessing the function impact of AAOCA on myocardial perfusion.


Delayed hypersensitivity to crude and partially purified murine tumor-specific transplantation antigens and alloantigens utilizing the footpad swelling assay.
Antigen preparations extracted from C3H/HeJ methylcholanthrene-induced fibrosarcomas by the 3M KCl extraction procedure were assessed for tumor-specific and allospecific antigenicity. Specificity of crude tumor antigen preparations and of fractions from preparative isoelectric focusing was investigated by evocation of footpad swelling (FPS) in syngeneic mice immunized with irradiated fibrosarcoma cells. Tumor immune mice displayed delayed hypersensitivity as positive FPS responses to challenge with 3M KCl extract and with fraction (Fr) 15 (pH 5.7 to 6.0) from preparative isoelectrically focused 3M KCl extract. Crude extracts and Fr 15 exhibited immunoprotective activity in vivo. Immune mice demonstrated a specific FPS response only to crude antigen preparations of Fr 15 from immunizing tumors, not to materials from a noncross-reactive neoplasm. DBA/2J mice immunized with C3H/HeJ spleen cells displayed FPS to challenge with crude antigen preparations, but not with the tumor-specific Fr 15. Alloantigen activity, however, was detected by a positive FPS response in C3H-immune DBA mice in fractions from the pH range 5.1 to 5.5. These experiments demonstrated that the FPS assay provides the setting for detection of specific delayed hypersensitivity responses to crude and fractionated tumor antigen preparations and for delineation of tumor-specific and histocompatibility antigen activities in fractions from crude extracts.


AIDS-related non-Hodgkin lymphoma: imaging feature analysis of 27 cases and correlation with pathologic findings.
Some tumor types are related to HIV, including non-Hodgkin lymphoma (NHL). The morbidity and mortality of NHL has remained high, even after highly active antiretroviral therapy (HAART) was introduced. We collected cases of AIDS with NHL, and evaluated the imaging features and strategies for diagnosis. There were 27 patients with AIDS and tumors confirmed by pathology. There were 9 patients with Burkitt lymphoma, 16 with diffuse large B cell lymphomas (DLBCLs), and 2 with primary central nervous system (PCNS) lymphomas. All of the patients underwent a series of imaging studies. Three radiologists analyzed the images, and any disagreement was discussed until consensus was reached. The radiologic manifestations of AIDS with NHL were mainly masses and lymphadenopathy, 3 patients having one mass and 12 two or more masses. 7 patients had lymphadenopathy in one site and 3patients had lymphadenopathy in two or more sites. Coarse mucosal folds, thickening of the gastrointestinal wall, and lumen narrowing were typical manifestations of NHL within the gastrointestinal tract. There were 4 patients with masses and 5 with lymphadenopathy inthe 9 with Burkitt lymphoma, and 11 patients with masses 5 with lymphadenopathy in the 16 with DLBCLs. NHL is a malignancy that usually occurs in patients with AIDS. Imaging is an important method by which to evaluate lesions, masses, and lymphadenopathy. Fine needle aspiration biopsy and stereotaxis biopsy are useful methods by which to diagnose NHL.


Multidomain proteins under force.
Advancements in single-molecule force spectroscopy techniques such as atomic force microscopy and magnetic tweezers allow investigation of how domain folding under force can play a physiological role. Combining these techniques with protein engineering and HaloTag covalent attachment, we investigate similarities and differences between four model proteins: I10 and I91-two immunoglobulin-like domains from the muscle protein titin, and two α + β fold proteins-ubiquitin and protein L. These proteins show a different mechanical response and have unique extensions under force. Remarkably, when normalized to their contour length, the size of the unfolding and refolding steps as a function of force reduces to a single master curve. This curve can be described using standard models of polymer elasticity, explaining the entropic nature of the measured steps. We further validate our measurements with a simple energy landscape model, which combines protein folding with polymer physics and accounts for the complex nature of tandem domains under force. This model can become a useful tool to help in deciphering the complexity of multidomain proteins operating under force.


Impact of 68Ga-DOTATATE PET/CT on the management of neuroendocrine tumors: the referring physician's perspective.
Somatostatin receptor imaging with (68)Ga-DOTATATE PET/CT (DOTATATE) is increasingly used for managing patients with neuroendocrine tumors. The objective of this study was to determine referring physicians' perspectives on the impact of DOTATATE on the management of neuroendocrine tumors. A set of 2 questionnaires (pre-PET and post-PET) was sent to the referring physicians of 100 consecutive patients with known or suspected neuroendocrine tumors, who were evaluated with DOTATATE. Questionnaires on 88 patients were returned (response rate, 88%). Referring physicians categorized the DOTATATE findings on the basis of the written PET reports as negative, positive, or equivocal for disease. The likelihood for metastatic disease was scored as low, moderate, or high. The intended management before and changes as a consequence of the PET study were indicated. The indications for PET/CT were initial and subsequent treatment strategy assessments in 14% and 86% of patients, respectively. Referring physicians reported that DOTATATE led to a change in suspicion for metastatic disease in 21 patients (24%; increased and decreased suspicion in 9 [10%] and 12 [14%] patients, respectively). Intended management changes were reported in 53 of 88 (60%) patients. Twenty patients (23%) scheduled to undergo chemotherapy were switched to treatments without chemotherapy, and 6 (7%) were switched from watch-and-wait to other treatment strategies. Conversely, 5 patients (6%) were switched from their initial treatment strategy to watch-and-wait. This survey of referring physicians demonstrates a substantial impact of DOTATATE on the intended management of patients with neuroendocrine tumors.


Determination of seven pyrethroids biocides and their synergist in indoor air by thermal-desorption gas chromatography/mass spectrometry after sampling on Tenax TA ® passive tubes.
A method coupling thermal desorption and gas chromatography/mass spectrometry (GC/MS) was developed for the simultaneous determination of 7 pyrethroids (allethrin, bifenthrin, cyphenothrin, imiprothrin, permethrin, prallethrin and tetramethrin) and piperonyl butoxide adsorbed on Tenax TA(®) passive samplers after exposure in indoor air. Thermal desorption was selected as it permits efficient and rapid extraction without solvent used together with a good sensitivity. Detection (S/N>3) and quantification (S/N>10) limits varied between 0.001 ng and 2.5 ng and between 0.005 and 10 ng respectively with a reproducibility varied between 14% (bifenthrin) and 39% (permethrin). The method was used for the comparison indoor air contamination after low-pressure spraying and fumigation application in a rubbish chute situated in the basement of a building.


3GPP NR V2X Mode 2: Overview, Models and System-Level Evaluation.
Following the successful use of sidelink in Long Term Evolution (LTE) for Proximity Services (ProSe) and Cellular Vehicular-to-everything (C-V2X), the 3rd Generation Partnership Project (3GPP) is working towards its evolution in New Radio (NR) systems in the context of the so-called NR V2X. This new technology is expected to complement LTE C-V2X for advanced services by offering low latency, high reliability, and high throughput V2X services for advanced driving use cases. To do this, NR V2X is equipped with new features, such as the support for groupcast and unicast communication, a novel feedback channel, and a new control channel design. In this paper, we provide a complete history of sidelink technology in 3GPP followed by a detailed overview of NR V2X technology, with special emphasis on Mode 2 for out of coverage operation and autonomous resource selection. Furthermore, this paper presents a system-level NR V2X standard-compliant simulator, as an extension of the popular and open-source NR network simulator 5G-LENA, based on ns-3. In particular, we focus on the design, implementation, and evaluation of the sensing-based resource selection in NR V2X Mode 2, in a highway scenario. Through several and extensive simulation campaigns, we test the impact of different NR V2X parameters, such as the numerology, the resource selection window size, the number of retransmissions, the maximum number of resources per reservation, and the probability of keeping the same resources during reselection, in a sensing-based resource selection. Finally, we provide a comparison campaign that shows the gains attained by the sensing-based resource selection, proposed during 3GPP Release 16, over the random selection strategy, considered in 3GPP Release 17 for power saving purposes.


IFN-γ and IgG responses to Mycobacterium tuberculosis latency antigen Rv2626c differentiate remote from recent tuberculosis infection.
Tuberculin skin test (TST) and IFN-γ release assays are currently used to detect Mycobacterium tuberculosis (Mtb) infection but none of them differentiate active from latent infection (LTBI). Since improved tests to diagnose Mtb infection are required, we studied the immune response to Mtb latency antigen Rv2626c in individuals exposed to the bacteria during different periods. Tuberculosis patients (TB), TB close contacts (CC: subjects exposed to Mtb for less than three months) and healthcare workers (HW: individuals exposed to Mtb at least two years) were recruited and QuantiFERON (QFT) assay, TST and IFN-γ secretion to Rv2626c were analyzed. Twenty-two percent of the individuals assessed had discordant results between QFT and TST tests. Furthermore, QFT negative and QFT positive individuals produced differential levels of IFN-γ against Rv2626c, in direct association with their exposure period to Mtb. Actually, 91% of CC QFT negative subjects secreted low levels of IFN-γ to Rv2626c, whereas 43% of HW QFT negative people produced elevated IFN-γ amounts against Rv2626c. Conversely, 69% of CC QFT positive subjects didn´t produce IFN-γ to Rv2626c. Interestingly, a similar pattern of IgG anti-Rv2626c plasma levels was observed. Therefore, determination of IFN-γ and IgG levels against the dormancy antigen Rv2626c allows to identify established LTBI.


Arachidonate and renal function.
Basic and clinical investigations into the roles of arachidonate-derived compounds in regulating renal function under normal and pathophysiological conditions continued to expand over the past year. Exciting new insights regarding the pathobiology of thromboxane A2 revealed new roles for this potent cyclooxygenase-derived vasoconstrictor in the glomerular dysfunction that accompanies inflammatory disorders and insulin-dependent diabetes. Major advances have extended our understanding of the proinflammatory actions of leukotriene B4 and other 5-lipoxygenase compounds in mediating glomerular injury during experimental glomerulonephritis. Intriguingly, emerging evidence suggests the presence of an anti-inflammatory arm in the lipoxygenase pathway, ie, 15-lipoxygenase, products of which may act as endogenous leukotriene antagonists. New information has also become available about the renal biology of cytochrome P-450 metabolites of arachidonic acid as well as about nonenzymatically generated biologically potent eicosanoids, the F2-isoprostanes.


Developing and implementing a pain management benchmark.
For most patients, pain is an inevitable part of the cancer journey. Pain may be acute or chronic, it may be related to the disease process or to treatments such as surgery, radiotherapy or chemotherapy. For 80-90 per cent of patients with cancer, effective pain relief could be attained using the analgesic guidelines outlined by the World Health Organization (1996). However, in routine practice this is not achieved (Portenoy and Lesage, 1999), which highlights the need to review and improve practice continuously.


The step-wise pathway of septin hetero-octamer assembly in budding yeast.
Septin proteins bind guanine nucleotides and form rod-shaped hetero-oligomers. Cells choose from a variety of available septins to assemble distinct hetero-oligomers, but the underlying mechanism was unknown. Using a new in vivo assay, we find that a stepwise assembly pathway produces the two species of budding yeast septin hetero-octamers: Cdc11/Shs1-Cdc12-Cdc3-Cdc10-Cdc10-Cdc3-Cdc12-Cdc11/Shs1. Rapid GTP hydrolysis by monomeric Cdc10 drives assembly of the core Cdc10 homodimer. The extended Cdc3 N terminus autoinhibits Cdc3 association with Cdc10 homodimers until prior Cdc3-Cdc12 interaction. Slow hydrolysis by monomeric Cdc12 and specific affinity of Cdc11 for transient Cdc12•GTP drive assembly of distinct trimers, Cdc11-Cdc12-Cdc3 or Shs1-Cdc12-Cdc3. Decreasing the cytosolic GTP:GDP ratio increases the incorporation of Shs1 vs Cdc11, which alters the curvature of filamentous septin rings. Our findings explain how GTP hydrolysis controls septin assembly, and uncover mechanisms by which cells construct defined septin complexes.


Initial empiric antimicrobial treatment of Chlamydia pneumoniae: a study of 54 cases in the Republic of Macedonia.
Analysis of the adequacy of the initial empiric antimicrobial treatment of patients with acute Chlamydia pneumoniae (CP) infection, admitted to the Infectious Diseases Clinic, Clinical Centre, Medical Faculty, Skopje, Republic of Macedonia, for community-acquired pneumonia. A total number of 407 patients with community-acquired pneumonia (CAP) hospitalized at the Clinic between September 1997 and June 2002, with an average age of x=46.44 years, of whom 53.56% were male. Acute Chlamydia pneumoniae infection was proven serologically with MIF assay in 54 (13.27%) patients. Initial empiric treatment with antibiotics in patients with CP pneumonia was provided with antimicrobial agents with intracellular activity in 26 (48.15%) patients; with fluoroquinolones in 19 (35.19%); macrolides in 5 (9.26%) and tetracyclines in 2 (3.7%). The treatment was conducted as monotherapy in 6 patients (11.11%) and in 20 patients (37.04%) in combination with betalactams. For 28 (51.85%) patients who were treated only with betalactams, empiric treatment was re-evaluated and new therapy with fluoroquinolon was conducted in 16 (29.63%), with macrolides in 8 (14.81%) and with tetracyclines in 4 (7.41%) patients. Adequate empiric treatment with antimicrobial agents with intracellular activity was performed in only 48.15% of the patients with acute CP infection. Therefore, when designing the initial empiric treatment of patients hospitalized with pneumonia, attention should be paid to this atypical pathogen of CAP.