Radiolabeling nanomaterials for multimodality imaging: New insights into nuclear medicine and cancer diagnosis.
Nuclear medicine imaging has been developed as a powerful diagnostic approach for cancers by detecting gamma rays directly or indirectly from radionuclides to construct images with beneficial characteristics of high sensitivity, infinite penetration depth and quantitative capability. Current nuclear medicine imaging modalities mainly include single-photon emission computed tomography (SPECT) and positron emission tomography (PET) that require administration of radioactive tracers. In recent years, a vast number of radioactive tracers have been designed and constructed to improve nuclear medicine imaging performance toward early and accurate diagnosis of cancers. This review will discuss recent progress of nuclear medicine imaging tracers and associated biomedical imaging applications. Radiolabeling nanomaterials for rational development of tracers will be comprehensively reviewed with highlights on radiolabeling approaches (surface coupling, inner incorporation and interface engineering), providing profound understanding on radiolabeling chemistry and the associated imaging functionalities. The applications of radiolabeled nanomaterials in nuclear medicine imaging-related multimodality imaging will also be summarized with typical paradigms described. Finally, key challenges and new directions for future research will be discussed to guide further advancement and practical use of radiolabeled nanomaterials for imaging of cancers.


Stable DNA-protein complexes in eukaryotic chromatin.
Demembranized sperm and somatic nuclei of mammalian origin were extracted with high salt/urea/2-mercaptoethanol, treated with detergents and purified in CsCl density gradients to isolate DNA. Under these conditions a protein component still remained bound to DNA. This stable DNA-protein complex could be reduced to an oligodeoxynucleotide-peptide complex by extensive sequential digestions with DNase I and Pronase E. Chemical and enzymatic treatments of this complex indicated the presence of a phosphoester bond between DNA and a hydroxyamino acid. Two-dimensional tryptic peptide mapping revealed a remarkable similarity among the covalently linked protein components in all types of chromatin studied. These maps differed from the maps of mammalian topoisomerases I and II.


Haptic feedback helps bipedal coordination.
The present study investigated whether special haptic or visual feedback would facilitate the coordination of in-phase, cyclical feet movements of different amplitudes. Seventeen healthy participants sat with their feet on sliding panels that were moved externally over the same or different amplitudes. The participants were asked to generate simultaneous knee flexion-extension movements, or to let their feet be dragged, resulting in reference foot displacements of 150 mm and experimental foot displacements of 150, 120, or 90 mm. Four types of feedback were given: (1) special haptic feedback, involving actively following the motions of the sliders manipulated by two confederates, (2) haptic feedback resulting from passive motion, (3) veridical visual feedback, and (4) enhanced visual feedback. Both with respect to amplitude assimilation effects, correlations and standard deviation of relative phase, the results showed that enhanced visual feedback did not facilitate bipedal independence, but haptic feedback with active movement did. Implications of the findings for movement rehabilitation contexts are discussed.


Design, synthesis, and biological evaluation of a series of benzofuran[3,2-d]pyrimidine-4(3H)-one derivatives containing thiosemicarbazone analogs as novel PARP-1 inhibitors.
Poly ADP ribose polymerase-1 (PARP-1), one of the most important members of the PARP protein family, plays a crucial role in DNA damage repair, gene transcription, and apoptosis of cancer cells. In this work, benzofuran[3,2-d]pyrimidine-4(3H)-one was used as a framework to design and synthesize a series of novel PARP-1 inhibitors by introducing thiosemicarbazone or its derivatives into the scafford. Among all the target compounds, 19b and 19c were found to exhibit more potent inhibitory activity and higher selectivity against PARP-1 than Olaparib, especially the latter had an IC50 value of 0.026 μM against PARP-1 enzyme and a PARP-2/PARP-1 selectivity of 85.19-fold over Olapanib. Apart from strong cytotoxicity against the tested cancer cell lines, 19c was most sensitive to SK-OV-3 cells, with an IC50 value of 4.98 μM superior to Olaparib. Anti-cancer mechanism studies revealed that 19c could inhibit DNA single-strand breakage repair and aggravate DNA double-strand breakage by inhibiting PARP-1 activity, and promote the apoptosis of cancer cells through the mitochondrial apoptosis pathway.


[Cryoglobulinemia and mesangio-capillary glomerulonephritis (comparison of the 2 histological types)].
Sera from 21 patients with mesangiocapillary glomerulonephritis were examined for the presence of cryoglobulins, for the complement levels and in 8 cases for the C3 splitting activity. Patients were divided, on the basis of histology, into two groups; the first of 10 patients with subendothelial deposits, the second of 11 patients with intramembranous dense deposits. The incidence of cryoglobulins and the cryoprecipitate components were similar in the two groups. As previously described, in the first group low levels the C3 was low without alterations in the C4 levels. There are no previous reports on this high incidence of cryoglobulins in dense deposits disease and these data add further support to the hypothesis that this disease is, at least partially immunecomplexes mediated.


Chemotherapy in Children with Head and Neck Cancers: Perspectives and Review of Current Therapies.
Cancers of the head and neck in children represent a heterogeneous group of malignancies requiring a variety of treatment modalities. In many instances of childhood head and neck cancers, chemotherapy will be required for treatment, often in conjunction with surgery and/or radiation therapy. Chemotherapy in children with head and neck cancers poses unique challenges in terms of immediate as well as long-term toxicities. This article focuses on the common chemotherapeutic agents, with a particular focus on early and late effects, used in the treatment of children with head and neck cancers.


School achievement of children with intellectual disability: the role of socioeconomic status, placement, and parents' engagement.
The objective of this study was to describe the selected conditions for school achievement of students with mild intellectual disabilities from Polish elementary schools. Participants were 605 students with mild disabilities from integrative, regular, and special schools, and their parents (N=429). It was found that socioeconomic status (SES) was positively associated with child placement in integrative and regular schools rather than special schools, as well as with higher parental engagement in their children's studies. Parental engagement mediated the positive effects of SES and placement in regular and integrative schools on school achievement. The results are discussed in the context of inclusive education theory.


Recovery of Equilibrium Free Energy from Nonequilibrium Thermodynamics with Mechanosensitive Ion Channels in E. coli.
In situ measurements of the free energy difference between the open and closed states of ion channels are challenging due to hysteresis effects and inactivation. Exploiting recent developments in statistical physics, we present a general formalism to extract the free energy difference ΔF between the closed and open states of mechanosensitive ion channels from nonequilibrium work distributions associated with the opening and closing of the channels (gating) in response to ramp stimulation protocols recorded in native patches. We show that the work distributions obtained from the gating of MscS channels in E. coli membrane satisfy the strong symmetry relation predicted by the Crooks fluctuation theorem. Our approach enables the determination of ΔF using patch-clamp experiments, which are often inherently restricted to the nonequilibrium regime.


Binding sites for horseradish peroxidase on the cell surface. Suppression of binding by gangliosides and effects of some bivalent cations.
The cytochemical reaction for surface-bound horseradish peroxidase (HRP) on cultured HeLa cells, GH3 cells, and isolated rat liver cells was suppressed by 30 microM monosialoganglioside, by 30 microM trisialoganglioside, or by 5 mM CMP-neuraminic acid. The reaction was also suppressed by 10 mM chitotriose or by 10 mM UDP-galactose, a galactose acceptor and donor, respectively, for galactosyl-transferase. The addition of 2 mM Mn2+ to the incubation medium with HRP suppressed the reaction for surface-bound HRP, and the addition of 10-20 mM Ca2+ intensified the reaction. The addition of 2 mM Zn2+ caused less inhibition than that of 2 mM Mn2+, and the addition of 2 mM Co2+ caused either a slight inhibition, or no inhibition. These observations support the hypothesis that HRP may be bound to a glycosyltransferase at the cell surface.


Heidelberg ETV score to assess success of ETV in patients with occlusive hydrocephalus: a retrospective single-center study.
In aqueduct stenosis, pressure difference below and above level of obstruction leads to bulging of third ventricular floor (TVF) and lamina terminalis (LT). Endoscopic third ventriculocisternostomy (ETV) is the standard treatment in these patients. We tried to assess success of ETV depending on those two radiological changes in aqueduct stenosis. We implemented "Heidelberg ETV score" retrospectively to assess the state of TVF as well as LT in same manner in midsagittal MR image. Every patient had a preoperative, direct, 3-months and one-year postoperative score from -2 to + 2. We correlated the scores to clinical course to decide whether the score is reliable in defining success of ETV. Between 2017-2021, 67 (mean age 25.6 ± 23.9y) patients treated with ETV were included. Success rate of primary and Re-ETVs was 91% over 46.8 ± 19.0 months. A marked shift of score to the left after surgery in success group was noticed through the distribution of score immediate postoperative, 3-months later; 70.2% showed (+ 2) before surgery, 38.9% scored (0) after surgery and 50.9% showed further score drop to (-1) 3 months later, p < 0.001. In cases of failure, there was initial decrease after surgery followed by increase with ETV-failure (mean time to failure: 7.2 ± 5.7 months) in 100%. Significant difference was noticed in Heidelberg score at postoperative 1-year- and failure-MRI follow-up between two groups, p < 0.001. Heidelberg score describes anatomical changes in third ventricle after ETV and can serve in assessment of MR images to define success of the procedure in patients with aqueduct stenosis.


[Celiac disease].
Celiac disease is a frequent auto-immune disease characterized by villous atrophy related to gluten intake in patients with genetic susceptiblity. Patients do not present symptoms in the majority of cases. Presence of the disease must be investigated in case of digestive symptoms or presence of auto-immune disease. Diagnosis is based on anti-transglutaminase antibody and dudodenal biospies. The only available treatment is gluten-free diet. Associated auto-immune diseases must be investigated, especially thyroiditis. Complications related to nutritional deficiency must be accounted for also.


Clozapine-loaded nanocapsules improve antipsychotic activity in rats: building a sequential PopPK/PD model to discriminate nanocarriers in the preformulation step.
We investigated the impact of nanoformulations on the dose-exposure-response relationship of clozapine (CZP), a low-solubility antipsychotic with serious adverse effects, using a popPK/PD approach. We evaluated the pharmacokinetics and PK/PD profiles of three coated polymeric CZP-loaded nanocapsules functionalized with polysorbate 80 (NCP80), polyethylene glycol (NCPEG), and chitosan (NCCS). Data on in vitro CZP release by dialysis bag, plasma pharmacokinetic profiles in male Wistar rats (n = 7/group, 5 mg kg-1, i.v.), and percentage of head movements in a stereotyped model (n = 7/group, 5 mg kg-1, i.p.) were integrated using a sequential model building approach (MonolixSuiteTM-2020R1-Simulation Plus). A base popPK model developed with CZP solution data collected after the i.v. administration of CZP was expanded to describe the changes in drug distribution caused by nanoencapsulation. Two additional compartments were inserted into the NCP80 and NCPEG models, and a third compartment was included in the NCCS model. The nanoencapsulation showed a decrease in the central volume of distribution for NCCS (V1NCpop = 0.21 mL), while for FCZP, NCP80, and NCPEG, it was ~1 mL. The peripheral distribution volume was higher for the nanoencapsulated groups (19.1 and 129.45 mL for NCCS and NCP80, respectively) than for FCZP. The popPK/PD model showed a formulation-dependent plasma IC50, with 20-, 50-, and 80-fold reductions compared to the CZP solution (NCP80, NCPEG, and NCCS, respectively). Our model discriminates the coatings and describes the peculiar PK and PD behavior of nanoencapsulated CZP, especially NCCS, making it an exciting tool for evaluating the preclinical performance of nanoparticles.


High-potential states of blue and purple copper proteins.
Electrochemical measurements show that there are high-potential states of two copper proteins, Pseudomonas aeruginosa azurin and Thermus thermophilus CuA domain; these perturbed states are formed in guanidine hydrochloride (GuHCl) solution in which the proteins are still blue (azurin) and purple (CuA). In each case, the high-potential state forms reversibly. Absorption (azurin, CuA), visible circular dichroism (azurin, CuA), resonance-Raman (CuA), and EPR (CuA) spectra indicate that the structure of the oxidized copper site of each high-potential form is very similar to that of the native protein. It is proposed that GuHCl perturbs one or more H-bonds in the blue or purple copper active site, thereby allowing Cu(I) to adopt a more favorable coordination structure than that in the rigid cavity of the native protein.


The effect of obesity-related allostatic changes on cardio-metabolic risk in euthyroid children.
The hormonal thyroid changes related to obesity, even when in the euthyroid state, may contribute to the unfavorable cardio-metabolic profile of obese patients. In this retrospective study, we aim to investigate the biochemical thyroid changes and the association between serum TSH, FT4, FT3 and cardio-metabolic risk factors in euthyroid obese youths. Four hundred ninety-one Caucasian euthyroid obese children and adolescents aged 9.93 ± 2.90 years were recruited. Each patient underwent clinical and auxological examination and laboratory workup including an OGTT and the measurement of thyroid function and lipid profile. Homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride to high-density lipoprotein cholesterol ratio, total cholesterol to HDL ratio, atherogenic index of plasma, insulinogenic index, area under the glucose and insulin curves were calculated. We found that TSH was positively correlated with BMI-SDS values and significantly associated with hypercholesterolemia and hyperinsulinemia; FT4 resulted negatively correlated with BMI-SDS; FT3 was positively correlated with BMI-SDS and the area under the curve of insulin and negatively correlated with HDL. FT3 and FT4 resulted significantly associated with severe obesity. In addition, children with high-normal TSH values showed higher triglyceride to high-density lipoprotein cholesterol ratio values than those with normal TSH levels. Our data showed that thyroid hormones could influence obesity, lipid and glycemic parameters in euthyroid youths. These findings could carry implications regarding optimal TSH levels in obese children and confirm the importance of evaluating the thyroid function as possible adjunctive cardio-metabolic risk factor related to obesity.


[Exercise testing in respiratory medicine].
This document replaces the DGP recommendations published in 1998. Based on recent studies and a consensus conference, the indications, choice and performance of the adequate exercise testing method in its necessary technical and staffing setting are discussed. Detailed recommendations are provided: for arterial blood gas analysis and right heart catherterization during exercise, 6-minute walk test, spiroergometry, and stress echocardiography. The correct use of different exercise tests is discussed for specific situations in respiratory medicine: exercise induced asthma, monitoring of physical training or therapeutical interventions, preoperative risk stratification, and evaluation in occupational medicine.


Comparative multi-methodological measurement of ERBB2 status in breast cancer.
The ERBB2 transmembrane tyrosine kinase receptor is both a prognostic marker and a therapeutic target in breast cancer. Accurate determination of ERBB2 status is a prerequisite for the establishment of prognostic significance and for the selection of ERBB2-overexpressing breast tumours for specific treatment. Unfortunately, there is no complete agreement on how this determination should be performed. This study has compared four methods of assessment of ERBB2 status. Two global, extraction-based methods using real-time quantitative PCR on DNA (Q-PCR) or RNA (RQ-PCR) and two non-global, tissue-based methods, ie fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), were used. The 94 breast cancers tested were enriched in cases scoring 2+ using the IHC scoring system currently in use and for which the actual ERBB2 status remains ill defined. To determine the best parameters and reagents for assessment, two protocols for FISH and five anti-ERBB2 antibodies were used, and both FISH and IHC were carried out on the same tissue microarrays (TMAs). It is shown that the combination of the two tissue-based methods gives the best results. The use of either PCR-based method did not improve the results significantly. A new combined IHC score based on the association of two selected anti-ERBB2 antibodies (HercepTest trade mark and TAB250) and a dual scale for improved assessment of ERBB2 protein expression, particularly in 2+ cases, are proposed.


A novel approach to iron oxide separation from e-waste and bisphenol A detection in thermal paper receipts using recovered nanocomposites.
To promote sustainability, the effective reutilization of electronic waste and profitable recovery of valuable materials from e-scrap are essential. A recent report showed that 500 million printer cartridges enter landfill annually, creating immense interest in establishing a facile recovery method for transforming waste toner into a ferrous resource. Furthermore, the European Union and US Food and Drug Administration have published guidelines concerning bisphenol A (BPA) use in the manufacture of thermal paper receipts. Accordingly, in this study, BPA levels in thermal receipts collected from various stores in Taiwan were detected by glassy carbon electrodes fabricated using graphene oxide-recovered Fe3O4 nanocomposites.


Accuracy of custom temporomandibular joint replacement surgery using a virtual surgical planning protocol.
Accurate placement of TMJ implant components may be facilitated by virtual surgical planning (VSP) technologies. The aim of this study was to assess the accuracy of a typical VSP protocol and describe the pattern of surgical error associated with total alloplastic TMJ replacement. A retrospective analysis was undertaken on 40 adult patients who were implanted with a fully customised, 3D printed TMJ prosthesis due to end-stage TMJ disease. Planned TMJ implant position based on preoperative CBCT images was compared with final position on postoperative OPGs using a previously validated linear rescaling method. Translational discrepancy was described in the anterior-posterior direction and superior-inferior direction. Rotational discrepancy was described as anterior or posterior. Lin's concordance between preoperative and postoperative position was 0.97, with no significant differences (p > 0.05). The Bland-Altman analysis showed a 95% limit of agreement between planned and final position of - 5.9 to 5.4 mm. Overall, final implant position was more anterior (0.4 mm), superior (0.4 mm) and posteriorly rotated (2.4°) compared with planned position. The use of VSP in TMJ replacement surgery results in accurate implant placement with good agreement between planned and final implant position. Discrepancies in planned and final implant position tended to result in the mandibular component of the implant being translated anterior superiorly and rotated posteriorly, with potential implications for the biomechanical performance of the implant and overall device longevity. These results should be used to assist TMJ surgeons pre- and intraoperatively to facilitating accurate implant positioning and optimal surgical rehabilitation.


Lack of Medicaid Coverage of Routine Newborn Circumcision Leads to Increased Operative Circumcisions, Chordee Procedures, and Balanitis.
To compare proportions of newborn circumcisions, operative circumcisions, chordee procedures, and cases of balanitis in states where Medicaid covers newborn circumcision (covered states) versus states that do not (noncovered states) using the pediatric health information system database. A retrospective review of pediatric health information system data was conducted from 2011 to 2020. The proportions and median ages of newborn circumcision current procedural terminology (CPT 54,150, 54,160), operative circumcision (CPT 54,161), chordee (CPT 54,360), and balanitis (ICD-9 607.1, ICD-10 N48.1, N47.6) were compared in covered versus noncovered states. A total of 118,530 circumcisions were reviewed. Covered states had significantly higher proportions of circumcision overall (9.7% vs 7.1%, P < 0.0001). Noncovered states had significantly higher proportions of Medicaid-covered operative circumcisions (54.9% vs 47.7%, P < 0.0001). Compared to covered states, noncovered states had significantly higher median ages of all types of circumcisions. Noncovered states also had higher numbers of balanitis cases and double the incidence of balanitis compared with covered states. The median age of chordee (1.07 vs 0.79 years, P < 0.0001) and proportion of chordee repairs (15.2% vs 12.9%, P < 0.0001) were also significantly higher in noncovered states. The lack of Medicaid coverage of circumcision increases the number of foreskin procedures done in the operating room. In addition, in states without Medicaid coverage of circumcision, there is an increased burden of disease related to the foreskin. These findings represent a need to further investigate the costs of healthcare associated with Medicaid coverage of circumcision or the lack thereof.


Patients' attitudes towards sharing their health information.
The current policies of the governments of Australia and New Zealand encourage the use of electronic information systems to exchange patient information between various stakeholders. This research investigated (1) the attitudes of patients toward sharing their medical information and (2) whether patients considered themselves to be well-informed about the uses that are made of their information. A questionnaire survey of adult primary-care patients was conducted in five clinics within a medium sized New Zealand city. Outcome measures were the proportions of respondents willing to share different categories of their information with different classes of recipients. Patients' evaluations of their knowledge about the uses made of their information were also collected. Over 200 responses were collected from five clinics. Respondents' attitudes toward sharing their information were found to be influenced by three factors. (1) Identity of recipient: whilst respondents were generally willing to have their information shared between health professionals, they were increasingly unwilling for it to be distributed to other stakeholders, such as administrators, researchers or other government departments. (2) Level of anonymity: respondents were more prepared to share anonymous information. (3) Type of information: respondents were increasingly unwilling to share their information as it takes on a more personal nature. Respondents were also found to be very poorly informed about the use of their information, 90% of respondents indicated that they had either incomplete or no knowledge of how their information was shared and 79% had no knowledge of the uses of their National Health Index (NHI) number. The findings also indicate that respondents would prefer to be consulted about the distribution of their information. These findings indicate that many respondents were unwilling to have their personal information distributed other than for purposes of clinical care and a sizeable proportion of the respondents would like to be consulted before their information is released. The high level of interest and concern that this research revealed among respondents, suggests that more attention should be directed towards ensuring that patients are fully informed about current information sharing practices. The findings also imply that the design and development of future systems should also incorporate sophisticated and flexible access control policies that can be adapted to meet the preferences of individual patients.


Optic neuropathy in vitamin B12 deficiency.
There are many neurological manifestations of vitamin B(12) deficiency. Optic neuropathy is a rare, but important, manifestation of vitamin B(12) deficiency that should be suspected in patients with risk factors for malnutrition. We present a case of a 68-year-old male who presented with bilateral decreased central vision for months and was found to have a low vitamin B(12) level. After a few months, his vision improved with parenteral vitamin B(12) supplementation. Vitamin B(12) optic neuropathy is a reversible, treatable cause of vision loss and may be a harbinger for other manifestations of the disease.


Receptor binding and conformational properties of bovine and ovine prolactins after chemical modification of the two tryptophan residues.
The two tryptophan residues in ovine and bovine prolactins were modified by reaction with 2-nitrophenylsulfenyl chloride in 75% formic acid. These derivatives exhibited an important loss of receptor affinity (less than 1% of the native hormones) to a rabbit mammary gland preparation. To a lesser degree, they also lost their binding affinity to specific guinea pig antibodies as detected by radioimmunoassay. The chemical modifications induced a change in the folding of the polypeptide chain, which in itself could be partly or totally responsible for the loss of biological or binding activities. This conformational change has been analyzed by circular dichroism and by prediction of secondary structures from the amino acid sequence using the method of Garnier et al. (Garnier, J., Osguthorpe, D.J. and Robson, B. (1978) J. Mol. Biol. 120, 97--120). The comparison of predicted prolactin and somatotropin structures revealed almost identical alpha-helix, turns and coil regions with an overall content of 67% alpha-helix, 5% beta-sheet, 17% turn and 11% of aperiodic structures. These values were close to those obtained from circular dichroism. The conformational change of the chemically modified hormones as compared to native folding, can be described as a partial loss of alpha-helical structure and an increase in beta-sheet content.


Direct imaging of paracrystalline phospholipid structure in the electron microscope.
A long chain amphiphilic molecule--the phospholipid 1,2-dihexadecyl sn glycerophosphoethanolamine--has been crystallized epitaxially so that the interlamellar molecular periodicity is parallel to the substrate and hence normal to the electron beam in the electron microscope. This has permitted the direct resolution of the 55.6 A lamellae in unstained crystals at room temperature. The lattice images have shown the presence of line dislocations and lenticular cracks in the crystals. Of significance to their biological properties is that the lattice is undulating with a periodicity of 0.1-0.5 micron. This would also account for the difficulties encountered by X-ray and electron diffraction techniques when examining these crystals.


Initial management of the trauma patient.
The early management of the multiply injured patient is discussed. Emphasis is placed on recognizing life-threatening injuries early, intervening with appropriate treatments, performing a complete initial assessment, and establishing definitive care. Specific organ systems and injuries are stressed.


Induction of mutation and chromosome damage by excess bases and nucleosides.
The studies reported in this communication were conducted to determine if naturally occurring cell constituents could themselves cause mutation. All the bases and their corresponding nucleosides have been shown in culture to produce chromosome damage in P388 mouse lymphoma and Chinese hamster ovary cells (CHO) and adenosine has produced an increased incidence of sister chromatid exchanges in CHO cells. In addition thymidine has produced an increase in V79 cells resistant to 8-azaguanine and ouabain, although no effects were seen in six strains of Salmonella typhimurium. Such damage probably arises as a result of imbalanced DNA-precursor pools. Thus mutagenic events may arise by mechanisms unrelated to direct alterations of DNA.


Interobserver reliability of a recently proposed semiological classification in psychogenic nonepileptic seizures in children.
The aim of this study is to examine the semiological features of Psychogenic Nonepileptic Seizures (PNES) in children and to evaluate interobserver reliability (IR) of two different classifications. to identify the sources of any variance in agreement and to estimate the IR of the classification systems METHODS: Semiological features of 137 pediatric patients with PNES with and without epilepsy were analyzed. Two different, blinded observers evaluated these semiological features according to A. Asadi-Pooya and Seneviratne et al. classifications. The interobserver reliability was measured using a kappa (κ) coefficient for each PNES classification. The mean age of patients with PNES was 14.3 (SD: 2.9) years. Ninety five patients were female (69.3 %), 42 were male (30.6 %). Ictal eye closure (n:109, 79.5 %), was the most common seizure semiology. Asymmetric limb movements (n: 71, 51.8 %), motor phenomenon lasting> two minutes (n:69, 50.3 %), and closed mouth (n:53, 38.6 %) were other common seizure semiologies of PNES. Kappa value was higher in A. Asadi-Pooya classification than Seneviratne classification (k = 0.697 and k = 0.433; p < 0.05). Kappa values were higher in the motor and non-motor categories of A. Asadi-Pooya classification than in the mixed category (k = 0.713, k = 0.799 and k = 0.455; p < 0.05). The added value of the new classification scheme with respect to uniform application by experienced pediatric neurologists seems to be reliable and influential, as interobserver reliability of the new classification system was higher than the early classification. Our findings suggest that a simple but comprehensive classification would be useful in the management of PNES.


Design and fabrication of a 40-MHz annular array transducer.
This paper investigates the feasibility of fabricating a five-ring, focused annular array transducer operating at 40 MHz. The active piezoelectric material of the transducer was a 9-microm thick polyvinylidene fluoride (PVDF) film. One side of the PVDF was metallized with gold and forms the ground plane of the transducer. The array pattern of the transducer and electrical traces to each annulus were formed on a copper-clad polyimide film. The PVDF and polyimide were bonded with a thin layer of epoxy, pressed into a spherically curved shape, then back filled with epoxy. A five-ring transducer with equal area elements and 100-microm kerfs between annuli was fabricated and tested. The transducer had a total aperture of 6 mm and a geometric focus of 12 mm. The pulse/echo response from a quartz plate located at the geometric focus, two-way insertion loss (IL), complex impedance, electrical crosstalk, and lateral beamwidth all were measured for each annulus. The complex impedance data from each element were used to perform electrical matching, and the measurements were repeated. After impedance matching; fc approximately equal to 36 MHz and -6-dB bandwidths ranged from 31 to 39%. The ILs for the matched annuli ranged from -28 to -38 dB.


Morphofunctional state of the adrenal glands in albino rats under conditions of toxic stress caused by cadmium salt in winter and summer periods.
We studied the morphology and function of the adrenal glands in male and female albino rats in cadmium intoxication during winter and summer periods (January and July). In animals of the control group, sex-related differences in the total area of the adrenal glands and in the size of their zones were revealed. In females, zones of adrenal gland were larger than in males. In winter months, these differences were most pronounced. Analysis of seasonal differences in the area of the adrenal glands in males revealed no significant differences in winter and summer months. Irrespective of the season and gender, cadmium chloride treatment led to an increase in the size of the adrenal glands. Cadmium salts caused more pronounced functional strain in males in winter months and in females in summer.


Blocking PD-L1-PD-1 improves senescence surveillance and ageing phenotypes.
The accumulation of senescent cells is a major cause of age-related inflammation and predisposes to a variety of age-related diseases1. However, little is known about the molecular basis underlying this accumulation and its potential as a target to ameliorate the ageing process. Here we show that senescent cells heterogeneously express the immune checkpoint protein programmed death-ligand 1 (PD-L1) and that PD-L1+ senescent cells accumulate with age in vivo. PD-L1- cells are sensitive to T cell surveillance, whereas PD-L1+ cells are resistant, even in the presence of senescence-associated secretory phenotypes (SASP). Single-cell analysis of p16+ cells in vivo revealed that PD-L1 expression correlated with higher levels of SASP. Consistent with this, administration of programmed cell death protein 1 (PD-1) antibody to naturally ageing mice or a mouse model with normal livers or induced nonalcoholic steatohepatitis reduces the total number of p16+ cells in vivo as well as the PD-L1+ population in an activated CD8+ T cell-dependent manner, ameliorating various ageing-related phenotypes. These results suggest that the heterogeneous expression of PD-L1 has an important role in the accumulation of senescent cells and inflammation associated with ageing, and the elimination of PD-L1+ senescent cells by immune checkpoint blockade may be a promising strategy for anti-ageing therapy.


Assessment of effects of pre- and post-training programme for healthcare professionals about breastfeeding.
This retrospective study assessed the effects of pre- and post-training programme for healthcare professionals about breastfeeding. The study included 3,114 mothers who had children aged 1-72 month(s). Their knowledge and behaviours relating to breastfeeding were evaluated. The mothers were randomly divided into two groups: the 'before' group included 2,000 women who were not informed about breastfeeding, and the 'after' group comprised 1,114 women who had been informed about breastfeeding. 56.2% and 66.1% of the mothers started breastfeeding within 30 minutes after delivery, respectively, in the before and the after group (chi2 = 29.31, p < 0.001). 16.7% and 36.5% gave exclusive breastfeeding for six months (chi2 = 72.85, p < 0.001), and 28.5% and 23.7% stopped breastfeeding within the first five months (chi2 = 17.20, p = 0.002). Ninety-four percent delivered in a hospital or in a primary healthcare centre. Therefore, prenatal and postnatal breastfeeding education and support courses may improve a woman's chance of starting and continuing to breastfeed her baby. In terms of the number of antenatal check-ups, since the differences between the two groups were significant (chi2 = 390.67, p = 0.000), the importance of the training programme about breastfeeding was highlighted. Follow-up interventions after training are suggested.


Liquid lithium as divertor material to mitigate severe damage of nearby components during plasma transients.
The successful operation of thermonuclear fusion reactors such as ITER, DEMO, and future commercial plants is mainly determined by the optimum choice of materials for various components. The objective of this work is to accurately and comprehensively simulate the entire device in 3D to predict pros and cons of various materials, e.g., liquid lithium in comparison to tungsten and carbon to predict future ITER-like and DEMO divertor performances. We used our comprehensive HEIGHTS simulation package to investigate ITER-like components response during transient events in exact 3D geometry. Starting from the lost hot core plasma particles through SOL, deposition on the divertor surface, and the generation of secondary plasma of divertor materials. Our simulations predicted significant reduction in the heat loading and damage to the divertor nearby and internal components in the case when lithium is used on the divertor plates. While if tungsten or carbon are used on the divertor plate, significant melting areas and vaporization spots can occur (less for carbon) on the reflector, dome, and stainless steel tubes, and even parts of the first walls can melt due to the high radiation power of the secondary divertor plasma. Lithium photon radiation deposition into the divertor and nearby surfaces was decreased by two orders of magnitude compared to tungsten and by one order of magnitude compared to carbon. This analysis showed that using liquid lithium for ITER-like surfaces and future DEMO can lead to significant enhancement in components lifetime.


Current Surgical Therapy of Locally Advanced cSCC: From Patient Selection to Microsurgical Tissue Transplant. Review.
Among the non-melanoma skin cancers (NMSC) the squamous cell carcinoma (SCC) is one of the most challenging for the surgeon. Local aggressiveness and a tendency to metastasize to regional lymph nodes characterize the biologic behavior. The variants locally advanced and metastatic require wide excision and node dissection. Such procedures can be extremely detrimental for patients. The limit of the surgery can be safely pushed forward with a multidisciplinary approach. The concept of skin oncoplastic surgery, the ablative procedures and the reconstructive options (skin graft, pedicled flap, microsurgical free flap) are discussed together with a literature review.


Atypical Memory and Regulatory B Cell Subsets in Tumor Draining Lymph Nodes of Head and Neck Squamous Cell Carcinoma Correlate with Good Prognostic Factors.
Research on the role of B cells in the development and modulation of antitumor immunity has increased in recent years; however, knowledge about B cell phenotype and function in tumor draining lymph nodes (TDLNs) is still incomplete. This study aimed to investigate changes in the phenotypic profile of B cells in TDLNs of head and neck squamous cell carcinoma (HNSCC) during disease progression. Mononuclear cells were isolated from TDLNs and stained with antibodies for CD19 and other B cell-related markers and analyzed by flow cytometry. CD19+ B cells comprised 38.6 ± 8.9% of lymphocytes in TDLNs of HNSCC. Comparison of metastatic and non-metastatic LNs disclosed no significant differences in the frequencies of B cell subsets including antigen-experienced, naïve, switched, unswitched, atypical memory, marginal zone-like B cells, and B cells with regulatory phenotypes. The percentage of atypical memory (CD27-IgM-IgD-) B cells was significantly higher in patients with tongue SCC with no involved LNs (p = 0.033) and correlated inversely with the number of involved LNs. The frequency of CD24hiCD38hi B cells was significantly higher in non-metastatic LNs of patients with grade I compared to grade II (p = 0.016), and the percentage of CD5+ B cells decreased as tumors progressed from stage III to IV (p = 0.008). Our data show that in TDLNs of HNSCC, the frequency of B cells with atypical memory and regulatory phenotypes was significantly associated with good prognostic factors; however, their function remains to be investigated.


Karl Kleist and his refusal of an appointment at Leipzig in 1923.
Further to the study of Newmärker and Bartsch (2003) of Karl Kleist (1879-1960), this short contribution based on archive material, cited for the first time, looks into Kleist's motives for refusing an appointment as Professor of Psychiatry and Neurology at Leipzig University. This study comes to the conclusion that Kleist thought seriously of moving to Leipzig. However, the Saxony Ministry of People's Education refused to make a definite financial commitment to the reconstruction and building work that Kleist considered essential. On the other hand, the authorities in Frankfurt am Main, where Kleist had been appointed 3 years earlier, evidently agreed to the funding he required if he was to remain there. This finally prompted him to turn down the Leipzig offer.


Application of a novel Mass Bio System to remove low-concentration ammonia nitrogen from water bodies.
Water pollution due to ammonia is one of the most serious problems faced by the human beings and other life forms worldwide. With the rapid development of economy, pollution of water resources by ammonium (NH4 +) pollutants has increased severely. The water supply system has exceeded its capacity with regard to both quantity and quality of water. Many countries have already established a standard for strict limitation of ammonium nitrogen (NH4 +-N) or NH3 content in drinking water. In this study, a novel Mass Bio System (MBS), a suspended biologically activated carbon granular carrier cubic particle with 2-5 mm side length and a specific gravity of 1.02-1.08, was used for water treatment. In order to find a suitable method for ammonium removal from water resources, synthetic water containing NH4 +-N at a concentration of about 10 ppm was treated by MBS. NH4 +-N was nitrified to nitrate nitrogen (NO3 --N) by MBS in an inner-circulated fluidized bed reactor continuously. MBS showed an efficient and stable NH4 +-N nitrifying performance at temperature of 20-30 °C and DO of 3-4 mg L-1. With an influent concentration of NH4 +-N at 10-15 mg L-1, the concentration of effluent NH4 +-N and nitrite nitrogen (NO2 --N) was below 0.25 mg L-1, showing an average removal efficiency of above 90% within a hydraulic retention time (HRT) of 30 min. The pH value of effluent water remained at 7.2-7.3 automatically. Removal of load could reach 256.1 mg-N per (L-pellet h) and oxygen uptake rate increased to 1170.9 mg-O2 per (L-pellet h). The nitrifying process fits to zero-order degradation kinetics. High biomass retention was observed by scanning electron microscopy (SEM).


Correlation between serum prostate-specific antigen and cancer volume in prostate glands of different sizes.
To further evaluate the relationship of prostate-specific antigen (PSA) with prostate size and tumor volume in a contemporary surgical series. Although early studies showed a strong correlation between PSA and tumor volume, it has been suggested that PSA is no longer a valid marker for prostate cancer and only correlates with prostate size. From 2003 to 2009, 1234 men with data on prostate weight and total tumor volume underwent radical prostatectomy by a single surgeon. Prostate size was classified into tertiles: small (≤ 41.2 g), medium (41.3-54.5 g), and large (≥ 54.6 g). Pearson correlation coefficients were used to examine the relationship of PSA with prostate size and tumor volume across different prostate sizes. Median preoperative PSA was 4.9 ng/mL (standard deviation ± 4.6), mean prostate size was 51.7 g, and mean tumor volume was 5.6 cm(3). PSA had a significant correlation with prostate size only at a prostate weight ≥ 54.6 g (P = .02). Regardless of prostate size, PSA had a more robust significant correlation with tumor volume than with prostate size (all P < .0001). PSA was significantly correlated with prostate size only in the largest prostate glands, but was significantly associated with tumor volume in small, medium, or large prostates. Thus, PSA continues to be a better marker for tumor volume than for prostate size.


The roles of AMPK-mediated autophagy and mitochondrial autophagy in a mouse model of imiquimod-induced psoriasis.
Psoriasis is a systemic inflammatory disease characterized by epidermal hyperplasia and skin inflammatory infiltrates. Inactivation of AMPK has been shown to decrease autophagy, thereby inhibiting elimination of inflammatory factors and harmful substances, and aggravating psoriasis. However, the molecular mechanism through which AMPK affects psoriasis remains to be further explored. In this study, we investigated whether AMPK regulates autophagy through the ULK1/Atg7 signaling pathway and regulates mitochondrial autophagy through the PINK1/Parkin signaling pathway, thereby affecting a mouse model of psoriasis. Imiquimod was used to induce psoriasis-like lesions on the backs of mice. The severity of skin lesions in psoriatic mice was evaluated with the skin inflammation severity score, and epidermal thickness was measured on the basis of H&E staining. RT-PCR, western blotting and immunofluorescence staining were used to detect indicators of autophagy and mitochondrial autophagy. AMPK activity was inhibited in the psoriasis mouse model, the autophagy-associated proteins ULK1/Atg7 were inhibited, and the mitochondrial autophagy proteins PINK1/Parkin were also decreased. Results indicated that autophagy and mitochondrial autophagy were inhibited in the mouse model. When AMPK signaling was upregulated, ULK1/Atg7 and PINK1/Parkin were upregulated, autophagy and mitochondrial autophagy increased, and skin lesions in the mouse model were alleviated. ULK1/Atg7 and PINK1/Parkin were down-regulated when AMPK signaling was downregulated, and psoriasis-like skin lesions were aggravated in mice. These results indicated that AMPK regulates autophagy through the ULK1/Atg7 signaling pathway and regulates mitochondrial autophagy through the PINK1/Parkin signaling pathway, thus affecting the prognosis of psoriasis in the mouse model. AMPK affects the prognosis of psoriasis in a mouse model by regulating autophagy and mitochondrial autophagy.


The versatility of temporalis myofascial flap in maxillo-facial reconstruction: a clinical study.
This clinical study was conducted in the department of Oral & Maxillofacial Surgery, at our institute, to study the versatility of temporalis myofascial flap in maxillofacial reconstruction. The study group comprised of 20 patients, both male and female patients between the age group of 6 years and 60 years underwent surgery under general anesthesia and temporalis myofascial flap was used for reconstruction of various types of maxillofacial defects including maxillectomy defects arising as a result of ablative surgery for tumors and treatment of aggressive cysts, as an interposing material in TMJ ankylosis surgery and facial reanimation in cases of long standing facial nerve paralysis. Following surgery the cases were evaluated for clinical parameters weekly for first post-operative month followed by monthly review for a minimum period of one and maximum of three years from January 2003 to June 2006. Temporalis myofascial flap fared well in 16 out of 20 cases (80%), in remaining four cases (20%) three reported back with reankylosis, and in one case of facial reanimation flap breakdown occurred due to infection leading to failure of the procedure. The temporalis myofascial flap is a versatile option for reconstruction of moderate to large sized maxillofacial defects, the muscle can provide abundant viable and vascular tissue, with minimal to no functional morbidity or esthetic deformity at the donor site.


Hepatitis B surface antigenemia in a chronic hemodialysis program: lack of influence on morbidity and mortality.
One hundred one patients established on chronic hemodialysis on January 1, 1978, were retrospectively evaluated over the ensuing 8-year period to determine the effect of hepatitis B surface antigenemia on morbidity and mortality. Sixty-four patients remained HBsAg-negative after reaching end-stage renal disease; 30 were transiently or persistently HBsAg-positive; seven patients were excluded from study because of insufficient data. The HBsAg-positive and HBsAg-negative patients did not differ with respect to age, sex, race, or etiology of renal disease. There were no differences between the positive and negative groups in terms of death rates (50% v 34.4%, P = not significant), causes of death, hospitalizations (1.5 v 1.2/patient/yr), or hospitalized days (18.0 v 11.8 patient/yr). Only mild liver enzyme elevation (SGOT) was observed at the time of conversion in 13 patients with enzyme abnormalities who seroconverted after beginning hemodialysis (mean SGOT 255 micron/mL). No patient had persistent liver enzyme elevation over the 8-year period. These data suggest that chronic hepatitis B surface antigenemia is not, in itself, associated with increased morbidity or mortality in a chronic hemodialysis population.


Glomerular size and charge selectivity in insulin-dependent diabetes mellitus.
The pathogenesis of clinical nephropathy in Type 1 (insulin-dependent) diabetes was investigated by measuring renal fractional clearances of albumin, total IgG, IgG4 and beta 2-microglobulin, four plasma proteins which differ in size and charge. Seventy patients and eleven control subjects were studied. In diabetic patients with normal urinary albumin excretion (less than 30 mg/24 hr), fractional IgG clearance was two to three times higher than in control subjects, whereas fractional clearance of the anionic plasma proteins IgG4 and albumin was similar to that of control subjects. These alterations indicate an increase in anionic pore charge within the glomerular basement membrane concomitant with an increase in either pore size or impairment of tubular reabsorption. Diabetic patients, whose urinary albumin excretion has started to rise (30 to 100 mg/24 hr), had unchanged fractional IgG compared to patients with normal albumin excretion, while fractional IgG4 and albumin clearances were increased three- to fourfold; indicating unchanged glomerular pore size, but a decrease in anionic pore charge. In patients demonstrating urinary albumin excretion of greater than 100 mg/24 hr fractional IgG clearance increased to the same extent as fractional albumin clearance, indicating an increase in large pore area. Fractional beta 2-microglobulin clearances were similar to that of control subjects in the different patient groups indicating unchanged tubular reabsorption of proteins. Thus, the increase in large pore area seen in patients with clinical nephropathy is preceded by loss of anionic charge in the glomerular basement membrane. It is likely that this loss of anionic charge is due to loss of heparan sulphate-proteoglycan.


Abnormal expression of epilepsy-related gene ERG1/NSF in the spontaneous recurrent seizure rats with spatial learning memory deficits induced by kainic acid.
Previous epilepsy-related gene screen identified a spontaneous recurrent seizure (SRS)-related gene named epilepsy-related gene (ERG1) that encodes N-ethylmaleimide-sensitive fusion protein (NSF). To explore whether spatial learning memory deficits are relevant to SRS and whether hippocampal NSF expression is altered by SRS, we used the kainic acid (KA)-induced epilepsy animal model. SRS was monitored for 3 weeks after injection of a single convulsive dose of KA. KA-treated rats with SRS, KA-treated rats without SRS, and saline-treated rats were then measured in Morris water maze. In this spatial learning task, KA-treated rats with SRS performed poorer compared to those without SRS and those treated with saline. During the subsequent probe trials, KA-treated rats with SRS spent less swim path and time in the target quadrant but more swim path and time in the opposite quadrant, and showed fewer platform crossings. Moreover, in situ hybridization and immunohistochemistry showed that both ERG1/NSF mRNA and NSF immunoreactive expression were down-regulated in the CA1 and dorsal dentate gyrus cells (dDGCs) of the hippocampus, and interestingly, tyrosine hydroxylase (TH) immunoreactive dopamine (DA) neurons were lost in ventral tegmental area (VTA) in the KA rats with SRS. These data demonstrate that SRS impairs spatial learning memory and suggest that the down-regulation of NSF expression pattern in the hippocampus and the loss of DA neurons in VTA might contribute to the spatial learning memory deficits induced by SRS.


Two smart coumarin-based fluorescent probes with AIE effect for sensing ClO- and imaging in living cells.
It's worth noting that detect effective methods for tracking ClO- could help us uncover the function of ClO- in living systems. Here, two coumarin-based probes, named (E)-3-(1-hydrazonoethyl)-2H-chromen-2-one (1A) and 3-((E)-1-(((E)-(2,3-dihydro-1H-imidazol-4-yl)methylene)-hydrazono)ethyl)- 2H-chromen-2-one (1B) with aggregation-induced emission (AIE) effect in Tris-HCl (pH = 7.2) buffer solution were synthesized and used for sensing ClO- selectivity. 1A and 1B responded to ClO- through the oxidation hydrolysis effect. The mechanism was further verified by HR-MS and DFT calculation. Cell imaging indicated that 1A and 1B were good membrane permeability with low toxicity to HEK293T, and expected to be used to detect ClO- in cells.


Sertraline, chlorprothixene, and chlorpromazine characteristically interact with the REST-binding site of the corepressor mSin3, showing medulloblastoma cell growth inhibitory activities.
Dysregulation of repressor-element 1 silencing transcription factor REST/NRSF is related to several neuropathies, including medulloblastoma, glioblastoma, Huntington's disease, and neuropathic pain. Inhibitors of the interaction between the N-terminal repressor domain of REST/NRSF and the PAH1 domain of its corepressor mSin3 may ameliorate such neuropathies. In-silico screening based on the complex structure of REST/NRSF and mSin3 PAH1 yielded 52 active compounds, including approved neuropathic drugs. We investigated their binding affinity to PAH1 by NMR, and their inhibitory activity toward medulloblastoma cell growth. Interestingly, three antidepressant and antipsychotic medicines, sertraline, chlorprothixene, and chlorpromazine, were found to strongly bind to PAH1. Multivariate analysis based on NMR chemical shift changes in PAH1 residues induced by ligand binding was used to identify compound characteristics associated with cell growth inhibition. Active compounds showed a new chemo-type for inhibitors of the REST/NRSF-mSin3 interaction, raising the possibility of new therapies for neuropathies caused by dysregulation of REST/NRSF.


Personalized Psychological Interventions in Children: Harnessing Advancements in Genetic and Epigenetic Research.
Advancements in genetic and epigenetic research have opened new avenues for personalized psychological intervention in children [...].


Scaling characteristics in ozone concentration time series (OCTS).
One-year series of hourly average ozone observations, which were obtained from urban and national park air monitoring stations at Taipei (Taiwan), were analyzed by means of descriptive statistics and fractal methods to examine the scaling structures of ozone concentrations. It was found that all ozone measurements exhibited the characteristic right-skewed frequency distribution, cyclic pattern, and long-term memory. A mono-fractal analysis was performed by transferring the ozone concentration time series (OCTS) into a useful compact form, namely, the box-dimension (D(B))-threshold (T(h)) and critical scale (C(S))-threshold (T(h)) plots. Scale invariance was found in these time series and the box dimension was shown to be a decreasing function of the threshold ozone level, implying the existence of multifractal characteristics. To test this hypothesis, the OCTS were transferred into the multifractal spectra, namely, the tau(q)-q plots. The analysis confirmed the existence of multifractal characteristics in the investigated OCTS. A simple two-scale Cantor set with unequal scales and weights was then used to fit the calculated tau(q)-q plots. This model fitted remarkably well the entire spectrum of scaling exponents for the examined OCTS. Because the existence of chaos behavior in OCTS has been reported in the literature, the possibility of a chaotic multifractal approach for OCTS characterization was discussed.


High-dose vaginal misoprostol versus concentrated oxytocin plus low-dose vaginal misoprostol for midtrimester labor induction: a randomized trial.
This study was undertaken to compare the efficacy and side effects of a high-dose vaginal misoprostol regimen to concentrated intravenous oxytocin plus low-dose vaginal misoprostol for midtrimester labor induction. Women at 14 to 24 weeks, with obstetric or fetal indications for delivery and no prior cesarean, were randomly assigned to receive either vaginal misoprostol 600 microg x 1, then 400 microg every 4 hours x 5 (group 1) or escalating dose-concentrated oxytocin infusions (277-1667 mU/min) plus vaginal misoprostol 400 microg x 1, then 200 microg every 6 hours x 2, then 100 microg x 1 (group 2). Analysis was by intent to treat. Primary outcomes were live birth rate and induction-to-delivery interval. The intended sample size was 70 women per group; however, the trial was terminated at the initial interim analysis because of a highly significant difference in 1 of the primary study outcomes. Twenty women were assigned to group 1 and 18 were assigned to group 2. Median induction-to-delivery interval was significantly shorter in group 1 (12 hours, range 4-44 hours) versus group 2 (18 hours, range 7-36 hours; P = .01). Induction success rate at 12 hours was significantly higher in group 1 (60%) compared with group 2 (22%, P = .02). No significant difference was noted in the live birth rate between groups 1 and 2 (13%, 0%, P = .16). The incidence of retained placenta requiring curettage, chorioamnionitis, intrapartum fever, nausea, emesis, and diarrhea were similar between both groups. Compared with concentrated oxytocin plus low-dose vaginal misoprostol, high-dose vaginal misoprostol significantly shortens midtrimester labor inductions.


Cholesteryl ester distribution in lecithin bilayer membranes.
The saturated cholesteryl ester, cholesteryl 16-doxylstearate, is shown to incorporate into hydrated egg yolk lecithin multilayers in two distinct forms as visualized by electron spin resonance (ESR) spectroscopy. At concentrations less than 1 mole%, the ester is uniformly distributed in the membrane while at higher concentrations, patches of solid ester are formed.


Spatial-temporal variability of methane fluxes in lakes varying in latitude, area, and depth.
Many previous studies have found spatial and seasonal variabilities in CH4 fluxes, which could significantly affect lake-wide CH4 budgets. However, the ways in which the spatial and seasonal patterns of CH4 fluxes vary among lakes on a global scale is largely unknown. We compiled literature on CH4 flux data from global lakes and analyzed the spatial and seasonal variabilities for lakes varying in latitude, maximum depth, and area. Spatially, we found a significant linear relationship between the ratio of littoral to profundal fluxes and lake morphology (more related to area than depth), while globally, half of the lakes would have within 5% error of CH4 emission estimation under single-zone sampling. Seasonally, mid-latitude lakes showed higher CH4 fluxes in the summer and autumn, indicating the influence of temperature and autumn overturn, and the latter being largely related to maximum depth. Globally, due to abundant shallow lakes in the mid-latitude zone, approximately 99% of lakes had higher fluxes in the summer, while 75% of lakes showed errors in CH4 emission estimation within 20% when only the summer flux was investigated. In the high-latitude lakes, CH4 evasion during the spring ice-off period was significantly correlated with lake maximum depth, while lake area was also important when analyzing the CH4 diffusive flux. Our study yields preliminary conclusions about spatial and seasonal patterns of CH4 flux in different lake types, which are fundamental to building an effective sampling strategy and to determining an accurate CH4 budget from global lakes.


Presteady-state analysis of avian sarcoma virus integrase. I. A splicing activity and structure-function implications for cognate site recognition.
Integrase catalyzes insertion of a retroviral genome into the host chromosome. After reverse transcription, integrase binds specifically to the ends of the duplex retroviral DNA, endonucleolytically cleaves two nucleotides from each 3'-end (the processing activity), and inserts these ends into the host DNA (the joining activity) in a concerted manner. In first-turnover experiments with synapsed DNA substrates, we observed a novel splicing activity that resembles an integrase joining reaction but uses unprocessed ends. This splicing reaction showed an initial exponential phase (k(splicing) = 0.02 s(-1)) of product formation and generated products macroscopically indistinguishable from those created by the processing and joining activities, thus bringing into question methods previously used to quantitate these reactions in a time regime where multiple turnovers of the enzyme have occurred. With a presteady-state assay, however, we were able to distinguish between different pathways that led to formation of identical products. Furthermore, the splicing reaction allowed characterization of substrate binding and specificity. Although integrase requires only a 3' hydroxyl with respect to nucleophiles derived from DNA, it specifically favors the cognate sequence CATT as the electrophile. These experimental results support a two-site "switching" model for binding and catalysis of all three integrase activities.


Coronary angiography in the setting of acute infective endocarditis requiring surgical treatment.
International guidelines recommend that preoperative coronary angiography is performed on patients at risk of coronary disease who have infective endocarditis requiring surgical treatment. However, the risks of contrast-induced nephropathy or vegetation embolization in case of aortic endocarditis should be considered. To assess the safety, therapeutic implications and prognostic impact of coronary angiography in patients requiring surgical treatment for active infective endocarditis. This retrospective monocentric study was conducted in patients referred to a tertiary care centre for active endocarditis management with a theoretical indication for surgery between January 2013 and February 2017. One hundred and ninety-three patients were included; 73.1% were men, the mean age was 61.9±16.3 years and the median EuroSCORE II was 5.8%. One hundred and nineteen patients (61.7%) had aortic endocarditis, which was associated with aortic vegetation in 74 cases (38.3%). Invasive coronary angiography was performed in 142 patients (73.6%) - 130 (91.6%) by radial approach - and 14 patients were evaluated by coronary multislice computed tomography (one patient had exploration with both techniques). Acute renal failure after coronary angiography was observed in 15 patients (10.6%), two patients (1.4%) presented a stroke within 24h after coronary angiography, but none had aortic endocarditis. Among the 178 patients (92.2%) who underwent surgery, 35 (19.7%) had significant coronary lesion(s) and 25 (14.0%) underwent an associated coronary artery bypass graft. Preoperative coronary angiography in patients affected by infective endocarditis provides relevant information in a significant proportion of patients and can be performed safely.


Nursing care resources for individuals with intellectual and developmental disabilities across the life span.
This article provides resources that can be used by nurses working with individuals with intellectual and developmental disabilities (I/DD) across the life span and in a variety of settings. Resources include books, articles, videos, disability-related organizations, professional organizations, and agencies providing disability-related services. Additionally, resources are provided on a range of topics, including advocacy, issues across the lifespan for individuals with I/DD, health promotion, and legislation.


Gene expression of factors related to the immune reaction in response to intramammary Escherichia coli lipopolysaccharide challenge.
Pathogenic microorganisms invading the mammary gland induce an inflammatory reaction which includes an increase of somatic cells in milk and activation of bacteriostatic enzymes and proteins in milk. During spontaneously occurring subclinical mastitis the somatic milk cells, mainly macrophages, secrete cytokines, eicosanoids, acute phase proteins and other immunomediators. In contrast, the bacteriostatic protein lactoferrin is mainly secreted by mammary epithelial tissue, while major milk proteins like alpha-lactalbumin and kappa-casein are down-regulated already during subclinical infection. Changes of the mRNA expression of various immunomediators in the mammary tissue of cows during 12 h after induction of mastitis via intramammary administration of lipopolysaccharide (LPS) in several studies are reported. Six healthy lactating cows were injected in one quarter with 100 microg Escherichia coli-LPS (O26: B6) and the contralateral quarter with saline (9 g/l) serving as control. mRNA expression in mammary biopsy samples of various inflammatory factors and milk proteins at 0, 3, 6, 9 and 12 h after LPS administration was quantified by real-time reverse transcription-PCR. In LPS-challenged quarters tumour necrosis factor alpha and cyclooxygenase-2 mRNA expression increased to their highest values (P<0.05) at 3 h after LPS-challenge. Expression of lactoferrin, lysozyme, inducible nitric oxide synthase, and of the apoptotic factors caspase-3, caspase-7 and FAS was elevated (P<0.05) and peaked at 6 h after challenge. No significant increase in mRNA expression of platelet-activating factor acethylhydrolase, 5-lipoxygenase, and insulin-like growth factor 1 was found. None of the parameters tested did change significantly in the control quarters. mRNA expression of major milk proteins did not change significantly in response to the LPS challenge (alphaS1-casein, alphaS2-CN, beta-CN and beta-lactoglobulin) except for alpha-lactalbumin which decreased (P<0.05) in LPS-treated and control quarters and for kappa-CN which decreased in the LPS-treated quarters. In conclusion, mRNA expression of the majority albeit not all inflammatory factors changed within hours of LPS challenge. Decreased gene expression of alpha-lactalbumin and kappa-CN may reduce milk yield and suitability for cheese production.


Free radicals quenching potential, protective properties against oxidative mediated ion toxicity and HPLC phenolic profile of a Cameroonian spice: Piper guineensis.
Considerations on antioxidants derived from plants have continuously increased during this decade because of their beneficial effects on human health. In the present study we investigated the free radical scavenging properties of extracts from Piper guineense (P. guineense) and their inhibitory potentials against oxidative mediated ion toxicity. The free radical quenching properties of the extracts against [1,1-diphenyl-2-picrylhydrazyl (DPPH•), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS•), hydroxyl radical (HO•), nitric oxide (NO•)] radical and their antioxidant potentials by FRAP and phosphomolybdenum were determined as well as their protective properties on liver enzymes. The phenolic profile was also investigated by HPLC. The results obtained, revealed that the extracts significantly inhibited the DPPH, NO, HO and ABTS radicals in a concentration depending manner. They also showed a significant ferrous ion chelating ability through FRAP and phosphomolybdenum antioxidant potential. Their polyphenol contents varied depending on the type of extracts and the solvent used. The hydroethanolic extracts (FFH) and the ethanolic extracts (FFE) of P. guineense leaves showed the higher level of phenolic compounds respectively of 21.62 ± 0.06 mg caffeic acid/g dried extract (CAE/g DE) and 19.01 ± 0.03 CAE/g DE. The HPLC phenolic compounds profile revealed a higher quantity of Eugenol, quercetin, rutin and catechin in the stem than in the leaves. The presence of these molecules could be responsible of the protective potentials of P. guineense extracts against lipid peroxidation and SOD, catalase and peroxidase. In conclusion, P. guineense extracts demonstrated significant antioxidant property and may be used as a prospective protector against metal related toxicity.


Lateral plate evolution in the threespine stickleback: getting nowhere fast.
Gasterosteus aculeatus is a small Holarctic fish with marine, anadromous, and freshwater populations. Marine and anadromous populations apparently have changed little in the past 10 million years and exhibit limited geographical variation. In contrast, freshwater isolates have been founded repeatedly by marine and anadromous populations, and post-glacial isolates have undergone extraordinary adaptive radiation. Stickleback traits that have diversified during post-glacial radiation, including the 'lateral plates' (LP), can evolve substantially within decades after colonization of fresh water or when the environment (particularly predation regime) changes. Although highly divergent freshwater isolates of G. aculeatus have existed for at least 10 million years, they have rarely experienced sustained evolutionary divergence leading to formation of widespread, phenotypically distinct species. The paradox of rapid LP evolution without sustained divergence has resulted from selective extinction of highly divergent populations, because they are specialized for conditions in small, isolated habitats that tend to dry up within limited periods. Biological species of G. aculeatus may also evolve within decades, and are also prone to extinction because they are endemic to and specialized for small, ephemeral habitats. The high rate of evolution observed in contemporary threespine stickleback populations may not be unique to this species complex and has important implications for use of post-glacial populations in comparative studies, speciation rate, and discrimination of sympatric and allopatric speciation.


Multifactorial interplay controls the splicing profile of Alu-derived exons.
Exonization of Alu elements creates primate-specific genomic diversity. Here we combine bioinformatic and experimental methodologies to reconstruct the molecular changes leading to exon selection. Our analyses revealed an intricate network involved in Alu exonization. A typical Alu element contains multiple sites with the potential to serve as 5' splice sites (5'ss). First, we demonstrated the role of 5'ss strength in controlling exonization events. Second, we found that a cryptic 5'ss enhances the selection of a more upstream site and demonstrate that this is mediated by binding of U1 snRNA to the cryptic splice site, challenging the traditional role attributed to U1 snRNA of binding the 5'ss only. Third, we used a simple algorithm to identify specific sequences that determine splice site selection within specific Alu exons. Finally, by inserting identical exons within different sequences, we demonstrated the importance of flanking genomic sequences in determining whether an Alu exon will undergo exonization. Overall, our results demonstrate the complex interplay between at least four interacting layers that affect Alu exonization. These results shed light on the mechanism through which Alu elements enrich the primate transcriptome and allow a better understanding of the exonization process in general.


A sexually dimorphic hypothalamic circuit controls maternal care and oxytocin secretion.
It is commonly assumed, but has rarely been demonstrated, that sex differences in behaviour arise from sexual dimorphism in the underlying neural circuits. Parental care is a complex stereotypic behaviour towards offspring that is shared by numerous species. Mice display profound sex differences in offspring-directed behaviours. At their first encounter, virgin females behave maternally towards alien pups while males will usually ignore the pups or attack them. Here we show that tyrosine hydroxylase (TH)-expressing neurons in the anteroventral periventricular nucleus (AVPV) of the mouse hypothalamus are more numerous in mothers than in virgin females and males, and govern parental behaviours in a sex-specific manner. In females, ablating the AVPV TH(+) neurons impairs maternal behaviour whereas optogenetic stimulation or increased TH expression in these cells enhance maternal care. In males, however, this same neuronal cluster has no effect on parental care but rather suppresses inter-male aggression. Furthermore, optogenetic activation or increased TH expression in the AVPV TH(+) neurons of female mice increases circulating oxytocin, whereas their ablation reduces oxytocin levels. Finally, we show that AVPV TH(+) neurons relay a monosynaptic input to oxytocin-expressing neurons in the paraventricular nucleus. Our findings uncover a previously unknown role for this neuronal population in the control of maternal care and oxytocin secretion, and provide evidence for a causal relationship between sexual dimorphism in the adult brain and sex differences in parental behaviour.


Root extract of Angelica reflexa B.Y.Lee reduces allergic lung inflammation by regulating Th2 cell activation.
Traditionally, the roots of Angelica reflexa B.Y.Lee (AR) have been used to treat cough, phlegm, neuralgia, and arthralgia in Northeast Asia. The anti-asthmatic effect of AR root extract (ARE) was determined using a murine airway allergic inflammation model and the primary T cell polarization assay. To evaluate the anti-asthmatic effect of ARE, inflammatory cell infiltration was determined histologically and inflammatory mediators were measured in bronchoalveolar lavage fluid (BALF). Furthermore, the effects of AREs on Th2 cell differentiation and activation were determined by western blotting and flow cytometry. Asthmatic phenotypes were alleviated by ARE treatment, which reduced mucus production, inflammatory cell infiltration (especially eosinophilia), and type 2 cytokine levels in BALF. ARE administration to mice reduced the number of activated Th2 (CD4+CD25+) cells and level of GATA3 in the lungs. Furthermore, ARE treatment inhibited the differentiation of Th2 cells in primary cell culture systems via interferon regulatory factor 4 (IRF4) signaling. Our findings indicate that the anti-asthmatic effect of AREs is mediated by the reduction in Th2 cell activation by regulating IRF4.


Global Seasonal Influenza Mortality Estimates: A Comparison of 3 Different Approaches.
Prior to updating global influenza-associated mortality estimates, the World Health Organization convened a consultation in July 2017 to understand differences in methodology and implications for results of 3 influenza mortality projects from the US Centers for Disease Control and Prevention (CDC), the Netherlands Institute for Health Service Research's Global Pandemic Mortality Project II (GLaMOR), and the Institute for Health Metrics and Evaluation (IHME). The expert panel reviewed estimates and discussed differences in data sources, analysis, and modeling assumptions. We performed a comparison analysis of the estimates. Influenza-associated respiratory death counts were comparable between CDC and GLaMOR; the IHME estimate was considerably lower. The greatest country-specific influenza-associated fold differences in mortality rate between CDC and IHME estimates and between GLaMOR and IHME estimates were among countries in Southeast Asia and the Eastern Mediterranean region. The data envelope used for the calculation was one of the major differences (CDC and GLaMOR: all respiratory deaths; IHME: lower-respiratory infection deaths). With the assumption that there is only one cause of death for each death, IHME estimates a fraction of the full influenza-associated respiratory mortality that is measured by the other 2 groups. Wide variability of parameters was observed. Continued coordination between groups could assist with better understanding of methodological differences and new approaches to estimating influenza deaths globally.


Postoperative estradiol levels associate with development of primary graft dysfunction in lung transplantation patients.
Primary graft dysfunction (PGD) frequently complicates lung transplantation in the immediate postoperative period. Both female gender and estradiol modulate the body's response to injury and can influence the rate of alveolar fluid clearance. We hypothesized that female gender and higher estradiol levels would be associated with a lower risk of PGD after lung transplantation. We measured plasma estradiol levels preoperatively, 6 hours postoperatively, and 24 hours postoperatively in a cohort of 111 lung transplant recipients at 2 institutions. Mean age was 57 years (12.5) and 52% were female. Median postoperative estradiol level was 63.9 pg/mL (interquartile range, 28.8-154.3 pg/mL) in male and 65.1 pg/mL (interquartile range, 28.4-217.2 pg/mL) in female patients. Contrary to our hypothesis, higher estradiol levels at 24 hours were associated with an increased risk of PGD at 72 hours in male patients (P = 0.001). This association was preserved when accounting for other factors known to be associated with PGD. However, there was no relationship between gender and risk of PGD or between estradiol levels and PGD in females. These findings suggest that there might be different biologic effects of estrogens in males and females, and highlight the importance of considering gender differences in future studies of PGD.


Lighting the Patient Room of the Future: Evaluating Different Lighting Conditions for Performing Typical Nursing Tasks.
This study explores how aspects of lighting in patient rooms are experienced and evaluated by nurses while performing simulated work under various lighting conditions. The lighting conditions studied represent design standards consistent with different environments of care-traditional, contemporary, and future. Recent advances in lighting research and technology create opportunities to use lighting in hospital rooms to improve everyday experience and provide researchers with opportunities to explore a new set of research questions about the effects of lighting on patients, guests, and staff. This study focuses on the experience of nurses delivering simulated patient care. Perceptions of each of the 13 lighting conditions were evaluated by nurses using rating scales for difficulty of task completion, comfort, intensity, appropriateness of the lighting color, and naturalness of the lighting during the task. The nurses' ratings were analyzed alongside qualitative reflections to provide insight into their responses. Significant differences were found for several a priori hypotheses. Interesting findings provide insight into lighting to support circadian synchronization, lighting at night, the distribution of light in the patient room and the use of multiple lighting zones, and the use of colored lighting. The results of this study provide insight into potential benefits and concerns of these new features for patient room lighting systems and reveal gaps in the existing evidence base that can inform future investigations.


Murine Embryonic Stem Cell Culture, Self-Renewal, and Differentiation.
Embryonic stem cells (ESCs), derived from the inner cell mass of the blastocyst, can proliferate indefinitely in vitro (self-renewal) and can differentiate into cells of all three germ layers (pluripotency). These unique properties make them exceptionally valuable in basic science and clinical researches, including cell replacement therapies, drug discovery, and regenerative medicine. Mouse ESCs represent an important model system for studying gene function during development and disease.ESCs culture is time-consuming, laborious, and costly. Suboptimal ESCs culture conditions can alter their identity, pluripotency, and their compatibility with downstream differentiation protocols. In this chapter, we provide a general guideline for murine ESCs culture on murine fibroblast feeder layers. Moreover, we describe protocols for maintenance of ESCs pluripotency and induction of ESCs differentiation.


Is it safe to initiate selective cerebral perfusion with normothermia?
Preceding selective cerebral perfusion (P-SCP) is a method whereby SCP and systemic perfusion start simultaneously, and the arch vessels are clamped. Cerebral circulation is isolated from systemic circulation to avoid cerebral embolization due to detachment of atherosclerotic material from the aorta, caused by the "sandblasting" effect of high-velocity jets of blood exiting the aortic cannula. However, neither the safety of SCP at normothermia nor the influence of extended SCP time has been sufficiently clarified. To clarify the safety of P-SCP, the comparison study of P-SCP and conventional SCP (C-SCP) was performed retrospectively. Fifty-seven patients (C-SCP group: 29 patients; P-SCP: 28 patients) underwent surgery between 1992 and 2002. Nine (15.8%) in-hospital death occurred; 4 in the C-SCP group (13.8%) and 5 in the P-SCP group (17.9%) (NS). The SCP time was 136.6 +/- 68.5 minutes in the C-SCP group and 195.8 +/- 30.7 minutes in the P-SCP group (p < 0.05). One patient in each group exhibited postoperative neurological dysfunction. It may be little dangerous to initiate the SCP with normothermia. P-SCP may be useful in cases in which there is pedunculated atherosclerotic material, or mural thrombus in the ascending and arch aorta.


Molecular basis of neonatal cholestasis.
At present, specific evidence regarding the molecular mechanisms of neonatal cholestasis is limited. The recent explosion in the understanding of the molecular physiology of bile formation has been fueled by the discovery of several genes that are involved in familial cholestasis. The ever-growing understanding of the functional immaturity of the neonatal liver is sure to be enhanced by the study of the ontogeny of important hepatobiliary transporters as they are discovered. The understanding of the functional differences between the immature and mature liver is key to the understanding of neonatal cholestasis.


Whole-exome sequencing enhances prognostic classification of myeloid malignancies.
To date the standard nosology and prognostic schemes for myeloid neoplasms have been based on morphologic and cytogenetic criteria. We sought to test the hypothesis that a comprehensive, unbiased analysis of somatic mutations may allow for an improved classification of these diseases to predict outcome (overall survival). We performed whole-exome sequencing (WES) of 274 myeloid neoplasms, including myelodysplastic syndrome (MDS, N=75), myelodysplastic/myeloproliferative neoplasia (MDS/MPN, N=33), and acute myeloid leukemia (AML, N=22), augmenting the resulting mutational data with public WES results from AML (N=144). We fit random survival forests (RSFs) to the patient survival and clinical/cytogenetic data, with and without gene mutation information, to build prognostic classifiers. A targeted sequencing assay was used to sequence predictor genes in an independent cohort of 507 patients, whose accompanying data were used to evaluate performance of the risk classifiers. We show that gene mutations modify the impact of standard clinical variables on patient outcome, and therefore their incorporation hones the accuracy of prediction. The mutation-based classification scheme robustly predicted patient outcome in the validation set (log rank P=6.77 × 10(-21); poor prognosis vs. good prognosis categories HR 10.4, 95% CI 3.21-33.6). The RSF-based approach also compares favorably with recently-published efforts to incorporate mutational information for MDS prognosis. The results presented here support the inclusion of mutational information in prognostic classification of myeloid malignancies. Our classification scheme is implemented in a publicly available web-based tool (http://myeloid-risk. edu/).


Integrins and vascular development in differentiated embryonic stem cells in vitro.
The development of techniques for the in vitro differentiation of mouse embryonic stem (ES) cells has provided researchers with the tools to investigate vascular development as would occur in an early embryo. Mice lacking the vascular integrins have various defects in the vasculature, including defects in vessel architecture and hemorrhage: some animals die before birth. Using homozygous null ES cells for these integrins and in vitro differentiation of vascular networks in embryoid bodies, we can recapitulate the defects that give rise to embryonic lethality in mice. This allows the investigation of the molecular and cellular mechanisms responsible for the vascular defects that arise in the embryo.


Prevention of striae gravidarum and quality of life among pregnant Japanese women.
striae gravidarum affects the quality of life (QOL) of Japanese pregnant women. Many pregnant women use skin moisturisers to prevent striae gravidarum. However, the relationship between these preventive steps and QOL remains unclear. to evaluate the moisturising effect and QOL of pregnant women in an urban prefecture in central Japan with preventive steps against striae gravidarum. cross-sectional study. Pregnant women at 36 weeks of gestation were recruited at antenatal examinations. four private clinics in an urban prefecture in central Japan. 156 pregnant women consisting of 83 primiparae and 73 multiparae were analysed. a self-administered questionnaire, the severity of striae gravidarum assessed by Davey's score and the dermatology-specific QOL were assessed by Skindex29. The water content in the stratum corneum of each woman's abdomen was measured with a Moisture checker. The Ethical Committee of Osaka University Medical School approved the study. the prevalence of striae gravidarum was 37.8% and 121 (77.6%), including 76 (91.6%) primiparae and 45 (61.6%) multiparae, said they used a cream and/or lotion in an attempt to prevent striae gravidarum. The water content in the stratum corneum of the abdominal wall increased significantly after using cream and/or lotion (p=0.001). The severity and presence of striae gravidarum were not correlated with the preventive steps or water content in the stratum corneum of the abdominal wall (p=0.330 and p=0.835). Pregnant women who took the preventive steps showed higher scores for emotion on Skindex29 than those who did not (p=0.002). Although pregnant women with striae gravidarum showed a lower QOL for emotion than those without striae gravidarum (p=0.045), those who took the preventive steps maintained a similar level of QOL for emotion regardless of striae gravidarum. There have been few trials evaluating the QOL of pregnant women with striae gravidarum so a comparison of results among studies and determination of an appropriate sample size could not be conducted. preventive steps increase the amount of water content in the stratum corneum but this does not prevent striae gravidarum. Although pregnant women with striae gravidarum showed a lower QOL for emotion, the preventive steps were correlated with the level of QOL for emotion in pregnant women with striae gravidarum. Midwives need to absorb such information and recommend moisturising skin care for pregnant women.


Predictors of treatment failure among patients with gunshot wounds and post-traumatic stress disorder.
The 82.1% treatment failure of post-traumatic stress disorder (PTSD), associated with gunshot wounds, is related to high incidence of chronic pain syndrome as well as resistance to the PTSD treatment. Defining treatment failure predictors among the PTSD patients with gunshot extremity wounds and the following therapy would improve treatment outcomes. A total of 218 patients completed the study. The Mississippi Scale for Combat-Related PTSD (M-PTSD) was used for assessment of the treatment outcome rate. The risk relation between treatment failure and factors was assessed by a univariate or multivariate logistic regression method, with the model accuracy measured by the AUC - Area under the ROC curve. The odds ratio (OR) was considered for the qualitative factor assessment. The predictors of the PTSD treatment failure among the patients with gunshot wounds to the extremities are: 1) anesthesia type: the risk of failure is higher with the general anesthesia compared to the regional (p = 0.002), OR = 0.30 (95% CI 0.13-0.69) and the regional one with sedation (p = 0.004), OR = 0.30 (95% CI 0,14-0.65); 2) severe postoperative pain: the risk of treatment failure rises with increased pain intensity assessed by the visual analogue scale (p = 0.02), OR = 3.2 (95% CI 1.2-8.3). The analysis showed that administration of general anesthesia compared to the regional one (regardless of the sedation) and high postoperative pain intensity are associated with higher risk of the PTSD treatment failure among patients with gunshot wounds to the extremities. The preference of regional anesthesia and postoperative pain control may potentially improve the treatment outcomes. ClinicalTrials.gov: Retrospectively registered on December 30, 2020, NCT04689022 .


Early prediction of response to neoadjuvant chemotherapy in breast cancer patients: comparison of single-voxel (1)H-magnetic resonance spectroscopy and (18)F-fluorodeoxyglucose positron emission tomography.
To prospectively compare performances of single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting pathologic response to neoadjuvant chemotherapy (NAC) in breast cancer patients. Thirty-five breast cancer patients who received NAC and subsequent surgery were prospectively enrolled. MRS and FDG-PET were performed before and after the 1st NAC cycle. Percentage changes of total choline-containing compounds (tCho) via MRS, and maximum and peak standardized uptake values (SUVmax, SUVpeak) and total lesion glycolysis (TLG) via FDG-PET were measured, and their performances in predicting pathologic complete response (pCR) were compared. Of the 35 patients, 6 showed pCR and 29 showed non-pCR. Mean % reductions of tCho, SUVmax, SUVpeak, and TLG of the pCR group were larger than those of the non-pCR group (-80.3 ± 13.9 % vs. -32.1 ± 49.4 %, P = 0.025; -54.7 ± 22.1 % vs. -26.3 ± 33.7 %, P = 0.058; -60.7 ± 18.3 % vs. -32.3 ± 23.3 %, P = 0.009; -89.5 ± 8.5 % vs. -52.6 ± 36.2 %, P = 0.020). Diagnostic accuracy (area under ROC curve; Az, 0.911) of the % reduction of tCho was comparable to those of %SUVmax (0.822), SUVpeak (0.862), and TLG (0.879) in distinguishing pCR from non-pCR (all P > 0.05). MRS showed comparable performance to FDG-PET in early prediction of pCR in breast cancer patients. • MRS can predict response to NAC in breast cancer post-1 (st) cycle. • Changes in tCho and SUV after NAC reflect tumour cellularity changes. • MRS can be an alternative to FDG-PET in predicting response to NAC.


Intimate details of the most poisonous poison.
Crystal structures of type B botulinum neurotoxin, determined under conditions relevant to the extracellular binding and intracellular substrate cleavage steps of its toxic action, reveal that minimal structural changes occur upon binding a ganglioside or after substrate cleavage. The unique structure of this toxin provides information for developing preventive measures against botulism.


Subacute measles encephalitis complicating Hodgkin's disease in an adult.
A progressive neurological illness characterized by myoclonus, motor and sensory deficits, and lethargy occurred in a patient with Hodgkin's disease and was fatal within two months. A focal inclusion cell encephalitis was demonstrated by immunohistological means to be due to measles virus. Measles encephalitis must be considered a potential opportunistic agent in the immune-compromised host.


Biological evaluation and molecular docking studies of new curcuminoid derivatives: Synthesis and characterization.
In the present study, three series of dimethylamino curcuminoids viz. 4-phenylaminomethyl curcumin (3a-d), arylidene curcumin (3e) and pyrazole curcumin (3f-i) derivatives have been synthesized and studied for their in vitro anti-inflammatory, antioxidant and antibacterial activities. Synthesized dimethylamino curcuminoid derivatives namely 3d, 3e, 3h and 3i have shown potent anti-inflammatory properties than parent curcumin. Molecular docking interactions of dimethylamino curcuminoids derivatives against cyclooxygenase enzymes (COX-1 and COX-2) were studied.


Investigation of glucocorticoid-induced apoptotic pathway: processing of caspase-6 but not caspase-3.
Glucocorticoids (GCs) are essential therapeutic reagents for the treatment of lymphomas and leukemias. GCs cause cell death in certain types of lymphoid cells mediated by the process known as apoptosis. This cell death is completely inhibited by Bcl-2. Here we report that Bcl-2 and benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk), a broad spectrum caspase inhibitor, prevent loss of mitochondrial membrane potential (delta psi m) and the production of reactive oxygen species (ROS) caused by GC, while acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO), an inhibitor of the caspase-3 family proteases, does not. This suggests that the inhibition by Bcl-2 and activation of some initiator caspases are upstream events of mitochondrial damage, whereas the activation of caspase-3 family proteases occurs downstream of mitochondrial changes. We also demonstrate that caspase-6 but not caspase-3 is cleaved and activated during GC-mediated apoptosis and that poly(ADP-ribose) polymerase (PARP), a substrate of caspases, also undergoes proteolysis. In addition, we provide the evidence that DNA fragmentation is markedly inhibited by Ac-DEVD-CHO, while cell death, assessed by the damage of the plasma membrane, is marginally inhibited or merely delayed.


Laying the foundation: a residency curriculum that supports informed advocacy by family physicians.
This is one of six short papers that describe additional innovations to help integrate public health into medical education; these were featured in the "Patients and Populations: Public Health in Medical Education" conference. They represent relatively new endeavors or curricular components that had not been explored in prior publications. Although evaluation data are lacking, it was felt that sharing a description of a longitudinal curriculum focused on the development of basic advocacy skills through practical activities in community assessment and engagement combined with legislative advocacy at the University of New Mexico would be of value to medical educators.


Intracortical termination of the retino-geniculo-striate pathway studied with transsynaptic tracer (wheat germ agglutinin-horseradish peroxidase) and cytochrome oxidase staining in the macaque monkey.
The tracer, wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), was used as a transneuronal marker in the macaque monkey to study retino-geniculo-striate pathway terminals in area 17. Concomitantly, we stained matching sections for metabolic capacity using the cytochrome oxidase staining technique. Terminal labeling by WGA-HRP and cytochrome oxidase activity staining revealed duplicate patterns in layers II and III, IVA, IVC alpha, IVC beta, and VI. The absence of WGA-HRP-labeled neuronal cell bodies in area 17 supports the conclusion that WGA-HRP is a transsynaptic marker in the macaque visual pathways.


Complement C5a inhibition improves late hemodynamic and inflammatory changes in a rat model of nonocclusive mesenteric ischemia.
Nonocclusive mesenteric ischemia (NOMI) can evolve in a variety of low-flow states. Although the mechanisms leading to NOMI-related intestinal necrosis are largely unknown, circumstantial evidence suggests that excessive vasoconstriction and complement activation both play important roles in this process. Because targeting of the circulatory malfunction of the splanchnic area could be of therapeutic relevance, we set out to investigate the long-term effects of treatment with a complement C5a antagonist in a rat model of partial aortic occlusion (PAO)-induced transient mesenteric hypoperfusion. The mean arterial pressure of the splanchnic area was kept between 30 and 40 mm Hg by 60 minutes of PAO in anesthetized male Sprague-Dawley rats. C5a inhibitor acetyl-peptide-A (AcPepA; 4 mg kg(-1) intravenously) or vehicle administration was initiated at the 45th minute of PAO. After 24 hours, the animals were reanesthetized to record the macrohemodynamics and ileal microcirculation, and plasma and tissue samples were taken for determination of high-mobility group box protein-1 (HMGB-1), endothelin-1, tumor necrosis factor (TNF)-α levels, and small intestinal leukocyte infiltration. Epithelial structural changes were visualized by in vivo confocal laser scanning endomicroscopy. At 24 hours after PAO, mean arterial pressure, heart rate, and cardiac output were significantly greater, the intestinal intramural microcirculation was significantly impaired, and plasma HMGB-1, endothelin-1, TNF-α levels, the degree of epithelial damage and leukocyte infiltration was increased. The AcPepA treatment moderated the hemodynamic and microcirculatory changes, and decreased inflammatory activation and histologic signs of mucosal damage. C5a inhibition ameliorated the potentially harmful local mesenteric hypoperfusion and global long-term inflammatory consequences of PAO. This approach is of promise for use in NOMI-associated situations.