Evaluation of segmental mobility in patients with lumbar spondylolisthesis : A comparison of images from standing flexion-extension and standing/supine slippage.
To evaluate segmental mobility with degenerative lumbar spondylolisthesis (DLS), upright lateral flexion-extension radiographs (FE) are widely used. However, some authors have described that a combination of lateral radiographs in the standing position and supine sagittal image (SS) reveal more segmental mobility than FE. The purpose of this study was to investigate the optimal method for evaluating segmental mobility with DLS. We included 92 consecutive Japanese patients diagnosed with DLS. Sagittal translation (ST) determined by FE and SS were compared. Pathological instability was defined as ST more than 8% of the upper vertebra. Patients were divided into those diagnosed with pathological instability in FE (PI-FE) and those diagnosed with SS (PI-SS), and lumbar lordosis (LL) in the standing position in each group were compared. ST in FE was significantly greater than in SS. Of 92 patients, 31 had pathological instability in FE or SS ; 17 patients had PI-FE, and 10 patients had PI-SS. LL in the standing position in PI-FE was significantly smaller than in PI-SS. ST in FE was greater than that in SS, contrary to previous studies' reports on Caucasians. Since Japanese individuals have smaller LL than Caucasians, FE tends to reveal more segmental mobility than SS. J. Med. Invest. 70 : 135-139, February, 2023.


The Effects of Prodrug Size and a Carbonyl Linker on l-Type Amino Acid Transporter 1-Targeted Cellular and Brain Uptake.
The l-type amino acid transporter 1 (LAT1, SLC7A5) imports dietary amino acids and amino acid drugs (e. g., l-DOPA) into the brain, and plays a role in cancer metabolism. Though there have been numerous reports of LAT1-targeted amino acid-drug conjugates (prodrugs), identifying the structural determinants to enhance substrate activity has been challenging. In this work, we investigated the position and orientation of a carbonyl group in linking hydrophobic moieties including the anti-inflammatory drug ketoprofen to l-tyrosine and l-phenylalanine. We found that esters of meta-carboxyl l-phenylalanine had better LAT1 transport rates than the corresponding acylated l-tyrosine analogues. However, as the size of the hydrophobic moiety increased, we observed a decrease in LAT1 transport rate with a concomitant increase in potency of inhibition. Our results have important implications for designing amino acid prodrugs that target LAT1 at the blood-brain barrier or on cancer cells.


Changes in Femoral Posterior Condylar Offset, Tibial Posterior Slope Angle, and Joint Line Height after Cruciate-Retaining Total Knee Arthroplasty.
Changes in the femoral posterior condylar offset (PCO), tibial posterior slope angle (PSA), and joint line height (JLH) after cruciate-retaining total knee arthroplasty (CR-TKA) were evaluated to determine their influence on the flexion angle. A total of 125 CR-TKAs performed on 110 patients were retrospectively reviewed. Pre- and postoperative PCO, PSA, and JLH were compared using correlation analysis. Independent factors affecting the postoperative flexion angle of the knee were analyzed. The PCO was 28.2±2.0 mm (range, 24.5 to 33.1 mm) preoperatively and 26.7±1.8 mm (range, 22.2 to 31.2 mm) postoperatively (r=0.807, p<0.001). The PSA was 10.4°±4.9° (range, 1.6° to 21.2°) preoperatively and decreased to 4.9°±2.0° (2.2° to 10.7°) postoperatively (r=-0.023, p=0.800). The JLH was 16.2±3.0 mm (range, 10.2 to 27.5 mm) preoperatively and 16.1±2.6 mm (range, 11.1 to 24.8 mm) postoperatively (r=0.505, p<0.001). None of the independent factors affected the flexion angle (p>0.291). Although the PCO and JLH did not change significantly after CR-TKA, the PSA decreased by 5.5° with a small range of variation. Restoration of the PCO and JLH could promote optimization of knee flexion in spite of the decreased PSA after CR-TKA.


Management of the COVID-19 pandemic in Rhineland-Palatinate hospitals of all levels of care : Results of the COVID-19 Registry RLP.
The COVID-19 pandemic placed a significant burden on the German healthcare system. Based on the experience of severe disease progression of the SARS-CoV‑2 infection from neighboring European countries in the early 2020s, with ICU overload and high mortality rates, efforts were made in Germany to increase the capacity of available ICU beds. Subsequently, all documentation and reporting focused on the ICU capacities for COVID-19 patients. It was hypothesized that mainly a few large hospitals provided care for the majority of COVID-19 patients. The COVID-19 Registry RLP of Rhineland-Palatinate documented SARS-CoV‑2 inpatients from daily mandatory queries of all hospitals throughout the pandemic from April 2020 to March 2023, distinguishing between patients in ICUs and normal wards. In its 18th Corona Ordinance, the state government required all hospitals to participate in the care of SARS-CoV‑2 inpatients. We investigated the participation of hospitals at different levels of care in Rhineland-Palatinate in the management of the COVID-19 pandemic. Nine pandemic waves were documented during the pandemic and exemplary data on the respective pandemic peaks were evaluated. A distinction was made between the burden on hospitals at different levels of care: primary care hospitals, standard care hospitals, specialty hospitals, and maximal care hospitals. Analysis of the data showed that all hospital types participated equally in the care of SARS-CoV-2 patients. The requirement of the Ministry of Health of Rhineland-Palatinate to provide at least 20% of the available capacity was met by all levels of care and there were no disparities between hospitals of different levels of care in the management of the pandemic.Hospitals at all levels of care participated equally in the care of SARS-CoV‑2 inpatients and thus contributed significantly to the management of the pandemic in Rhineland-Palatinate.


An immunochemical evaluation for the identification and typing of monoclonal proteins.
Using automated measurements of kappa (kappa) and lambda (lambda) light chain and IgG, IgA and IgM concentrations we assessed the ability of the kappa/lambda ratio and the heavy/light chain ratio to identify and type monoclonal components which had been previously identified by serum protein electrophoresis and immunoelectrophoresis. We examined 1151 samples, of which 277 contained monoclonal components; 90% of the monoclonal proteins could be identified by this approach, of which 95% were correctly typed. In addition 19 of 874 samples without monoclonal components showed an abnormal kappa/lambda ratio. We assessed the ability of the immunochemical evaluation to calculate monoclonal component concentration and then compared the results to the scanning densitometry of serum protein electrophoresis.


Platelet components associated with adverse reactions: predictive value of mitochondrial DNA relative to biological response modifiers.
Biological response modifiers (BRMs), secreted by platelets (PLTs) during storage, play a role in adverse events (AEs) associated with transfusion. Moreover, mitochondrial DNA (mtDNA) levels in PLT components (PCs) are associated with AEs. In this study we explore whether there is a correlation between pathogenic BRMs and mtDNA levels and whether these markers can be considered predictors of transfusion pathology. We investigated a series of reported AEs after PC transfusion, combining clinical observations and mathematical modeling systems. mtDNA was consistently released during the first days of PC storage; however, mtDNA release was earlier in "pathogenic" than in nonpathogenic PCs. PC supernatants with high levels of mtDNA along with soluble CD40 ligand (sCD40L) were significantly associated with occurrences of AEs. The fact that mtDNA did not associate with the 14 BRMs tested suggests the role of mtDNA in PC transfusion-linked inflammation is independent of that of BRMs, known to be associated with AEs. We present evidence that PLTs generate distinct pathogenic secretion profiles of BRMs and mtDNA. The calculated area under the curve for mtDNA was significantly associated with AEs, although less stringently predictive than those of sCD40L or interleukin-13, standard predictors of AE. The established model predicts that distinct subtypes of AEs can be distinguished, dependent on mtDNA levels and PC storage length. Further work should be considered to test the propensity of mtDNA in PLT concentrates to generate inflammation and cause an AE.


A probe for intracellular concentrations of drugs: delayed fluorescence from acridine orange.
The aim of this work is to develop fluorescent probes that will indicate effective concentrations of therapeutic agents, or endogenous protectors, at important cellular sites. Acridine orange associates with nucleic acids and emits a 'delayed' fluorescence signal. This signal is quenched by oxidants such as oxygen, nitroaryl radiosensitizers, adriamycin and mitomycin-c, and reductants such as thiols, ascorbate and other radioprotectors. The quenching of the acridine orange delayed fluorescence reflects the effective concentration of these therapeutically-important oxidants and reductants near DNA. The relative concentration of basic radiosensitizers such as pimonidazole (Ro 03-8799) near the DNA is greater than that of misonidazole. Thiols quench the delayed fluorescence signal according to the degree of ionization of the thiol function; this may model the reactivity of thiols with guanine radical sites in DNA. Ascorbate and aminopyrine do not quench the delayed fluorescence from cells stained with acridine orange as these compounds are taken up by cells very inefficiently.


Hyaluronate in healing of corneal alkali wound in the rabbit.
The effect of topically applied 1% and 2% sodium hyaluronate was studied on the healing of a standardized rabbit corneal alkali wound. The healing of the epithelium, the stroma, and the endothelium was evaluated separately by applying quantitative methods. The healing was followed for 8 weeks. Both 1% and 2% sodium hyaluronate have a statistically significant positive influence on the epithelial re-surfacing, especially during the late healing phase. Furthermore, sodium hyaluronate has a positive healing influence on the stromal healing at a certain time interval during the observation period. This was reflected as a better maintained stromal dry mass level compared to control. The stromal healing was parallel to a faster re-surfacing of the endothelium.


The Glu298Asp variant of the endothelial nitric oxide synthase gene is associated with an increased risk for abruptio placentae in pre-eclampsia.
Attempts to define a pre-eclampsia susceptibility profile have been hampered by the wide clinical spectrum of the condition and the complex genetics underlying it. Genes that modulate blood pressure, fluid homeostasis and placental vascular development have been considered plausible candidates. Among these are the angiotensinogen (AGT) gene variant Met235Threo, which has been associated with pre-eclampsia and the endothelial nitric oxide synthase (eNOS) polymorphism Glu298Asp, which has been associated with both pre-eclampsia and abruptio placentae, a condition that often co-exists with pre-eclampsia. The aim of this study was to investigate a potential association between these gene variants and pre-eclampsia with and without abruptio placentae in a South African patient group. Fifty primigravidas with early onset, severe pre-eclampsia, 50 women presenting primarily with abruptio placentae (whether associated with pre-eclampsia or not) and a control panel of 50 healthy pregnant women constituted the study groups. The Met235Threo and Glu298Asp variants were characterised by polymerase chain reaction and restriction enzyme analysis. No association was demonstrated between the M235T variant of the AGT gene and pre-eclampsia or abruptio placentae. In contrast, the combined frequency of the eNOS variant genotypes (GT and TT) was significantly higher in the abruptio placentae group (49%) than the control group (21%) (p=0.006). Furthermore, in the pre-eclampsia patients who subsequently developed abruptio placentae, the eNOS GT genotype emerged as a major risk factor for the development of abruptio placentae (p<0.0001). These data suggest that the presence of a Glu298Asp eNOS variant may pre-dispose a pre-eclamptic woman to develop abruptio placentae or that it is a marker for predisposition.


Training, credentialing and re-credentialing for the performance of a thyroid FNA: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference.
The National Cancer Institute (NCI) sponsored the NCI Thyroid Fine-Needle Aspiration (FNA) State of the Science Conference on October 22-23, 2007 in Bethesda, MD. The 2-day meeting was accompanied by a permanent informational website and several on-line discussion periods between May 1 and December 15, 2007 (http://thyroidfna.cancer.gov). This document summarizes matters regarding training for the performance of thyroid FNA via palpation; training for the performance of thyroid FNA via ultrasound imaging, and credentialing/re-credentialing for the performance of a thyroid FNA. (http://thyroidfna.cancer.gov/pages/info/agenda/)


[The effect of methylenum coeruleum in laparoscope cholecystectomy].
To help the operator correctly judge in operation the cystic gall duct and choledoch, and eliminate the operation wound. To divide laparoscope cholecystectomy patients with the same weight at the same period into two groups: development group (589 cases) using methylenum coeruleum and conducting cholecysto-puncture visualization during the operation in which colors of cholecyst, cystic gall duct and choledoch turn blue; comparative group (553 cases) using regular laparoscope cholecystectomy. The two groups differed remarkably in operation time, complication, and transferring rate (P < 0.01). Methylenum coeruleum development technology in operation is a kind of visualization to help the operator judge in operation Calot triangular anatomy construction correctly, reduce the operation time obviously, and increase the rate of success.


Does the Ring Work? Perceptions and Understanding of the Efficacy of a Dapivirine Vaginal Ring for HIV Prevention Amongst Women in a Placebo-Controlled Trial.
As demonstrated by the Phase III clinical trial, MTN-020/ASPIRE, the monthly dapivirine vaginal ring is well tolerated and reduces the risk of HIV-1 as a woman-initiated prevention option. This analysis uses data from the follow-on MTN-032/Assessment of ASPIRE and HOPE Adherence (AHA) qualitative study to understand how perceptions (or misperceptions) of ring efficacy may have influenced behavior during ASPIRE, and affected intention to use the ring in future ring projects, specifically HOPE, the planned open-label extension study. Single in-depth interviews (n = 98) and 12 focus group discussions (n = 89) were conducted with women at seven sites in Malawi, South Africa, Uganda and Zimbabwe. Eligibility included participation in the ASPIRE active arm, and ring use for ≥ 3 months or at least 1 month if seroconversion occurred. Interviews were audio-recorded, transcribed into English, coded in Dedoose and thematically analyzed. Demographic and behavioral questionnaire data were summarized in Stata. Most AHA participants perceived the ring to be effective, and described simply trusting it or having confidence in it because they, or other participants in risky situations, remained HIV-uninfected. Participants described ring efficacy after receiving ASPIRE results as a binary assessment: the ring worked or not. Many did not remember exact efficacy percentages because of lack of comprehension or memory but recalled key details about age differences. The majority expressed interest in future ring use. There is a need to investigate improved ways of explaining placebo-controlled trials and efficacy to women in Sub-Saharan Africa. Now that ring efficacy, is known, these benefits must be well communicated, and understood by end-users and key stakeholders. Engagement with end-users to construct effective messages and to develop tools to measure understanding of partial efficacy will be essential.


APPL endosomes are not obligatory endocytic intermediates but act as stable cargo-sorting compartments.
Endocytosis allows cargo to enter a series of specialized endosomal compartments, beginning with early endosomes harboring Rab5 and its effector EEA1. There are, however, additional structures labeled by the Rab5 effector APPL1 whose role in endocytic transport remains unclear. It has been proposed that APPL1 vesicles are transport intermediates that convert into EEA1 endosomes. Here, we tested this model by analyzing the ultrastructural morphology, kinetics of cargo transport, and stability of the APPL1 compartment over time. We found that APPL1 resides on a tubulo-vesicular compartment that is capable of sorting cargo for recycling or degradation and that displays long lifetimes, all features typical of early endosomes. Fitting mathematical models to experimental data rules out maturation of APPL1 vesicles into EEA1 endosomes as a primary mechanism for cargo transport. Our data suggest instead that APPL1 endosomes represent a distinct population of Rab5-positive sorting endosomes, thus providing important insights into the compartmental organization of the early endocytic pathway.


Cancer Recurrence and Omics: Metabolic Signatures of Cancer Dormancy Revealed by Transcriptome Mapping of Genome-Scale Networks.
A major problem in medicine and oncology is cancer recurrence through the activation of dormant cancer cells. A system scale examination of metabolic dysregulations associated with the cancer dormancy offers promise for the discovery of novel molecular targets for cancer precision medicine, and importantly, for the prevention of cancer recurrence. In this study, we mapped the total mRNA sequencing-based transcriptomic data from dormant cancer cell lines and nondormant cancer controls onto a human genome-scale metabolic network by using a graph-based approach, and two mass balance-based approaches with one based on reaction activity/inactivity and the other one on flux changes. The gene expression datasets were accessed from Gene Expression Omnibus (GSE83142 and GSE114012). This analysis included two diverse cancer types, a liquid and a solid cancer, namely, acute lymphoblastic leukemia and colorectal cancer. For the dormant cancer state, we observed changes in major adenosine triphosphate-producing pathways, including the citric acid cycle, oxidative phosphorylation, and glycolysis/gluconeogenesis, indicating a reprogramming in the metabolism of dormant cells away from Warburg-based energy metabolism. All three computational approaches unanimously predicted that folate metabolism, pyruvate metabolism, and glutamate metabolism, as well as valine/leucine/isoleucine metabolism are likely dysregulated in cancer dormancy. These findings provide new insights and molecular pathway targets on cancer dormancy, comprehensively catalog dormancy-associated metabolic pathways, and inform future research aimed at prevention of cancer recurrence in particular.


A role for an indoleamine other than 5-hydroxytryptamine in the hypothalamic thermoregulatory pathways of the rat.
1. Intrahypothalamic injection of either 5-hydroxytryptamine (5-HT) (20 mug) or tryptamine (1 mug) caused hypothermia and hyperthermia respectively in lightly restrained rats maintained at an ambient temperature of 20 +/- 1 degrees C.2. Both the 5-HT- and the tryptamine-sensitive sites were located within the same region of the preoptic area.3. When rats were tested at different ambient temperatures (4, 20 and 29 degrees C), intrahypothalamic injection of 5-HT caused a marked fall in core temperature (-1.3 degrees C) in rats maintained at 4 degrees C, but smaller responses were obtained at 20 and 29 degrees C (-0.9 and -0.5 degrees C respectively). Tryptamine caused a significant hyperthermia in rats kept at 20 degrees C, but had no significant effect in rats maintained at either 4 or 29 degrees C.4. The hypothermic effect of 5-HT was selectively antagonized by systemic pre-treatment with cyproheptadine (2.5 mg/kg), but not by methergoline (0.625 mg/kg) and methysergide (0.2 mg/kg). In contrast, the hyperthermic effect of tryptamine was blocked by methergoline and methysergide, but not by cyproheptadine.5. Cyproheptadine (2.5 mg/kg) reduced the ability of rats to cope with a heat load but had no effect on the response to cold. In contrast, methergoline (0.625 mg/kg) and methysergide (0.2 mg/kg) reduced the ability to cope with cold but the rats' ability to cope with a heat load remained intact.6. These results suggest the existence of two indoleamine pathways within the preoptic anterior hypothalamus involved in the control of body temperature: a serotonergic pathway mediating heat loss and a non-serotonergic pathway mediating heat gain. The non-serotonergic system may exert its effects by modulating the activity of a central serotonergic system.


Significance of collateral circulation in reversible left ventricular asynergy by nitroglycerin in patients with relatively recent myocardial infarction.
To evaluate the functional role of coronary collateral circulation in reversible asynergy of the left ventricle, cineventriculography was performed before and after the administration of sublingual nitroglycerin in 19 patients with complete occlusion of the proximal part of the left anterior descending coronary artery. In nine patients who had significant collateral circulation to the infarct-related coronary artery (group A), there was significant improvement in both the left ventricular ejection fraction (53% to 60%, p less than 0.05) and regional wall motion in the infarct zone (8% to 18%, p less than 0.01 in the anterolateral area) with administration of nitroglycerin. In contrast, in the remaining 10 patients without significant collateral perfusion (group B), there were no detectable changes in either global function (49% versus 50%) or regional wall motion (6% versus 8% in the anterolateral area) before and after nitroglycerin. Changes in heart rate and left ventricular peak systolic and end-diastolic pressures with nitroglycerin were comparable in both groups. These results suggest that angiographically demonstrable collaterals preserve viable myocardium, which can improve its contraction when the supply-demand relationship is favorably affected because of increased collateral flow and/or more favorable loading conditions produced by nitroglycerin.


The WHO safe community program for injury prevention: evaluation of the impact on injury severity.
Despite the fact that injuries consume a considerable amount of health care resources world-wide, 3.5 million people die from unintentional injuries each year. To handle this central public health problem, WHO has introduced the Safe Community accreditation for injury prevention programs. This study was to investigate the impact from a Safe Community program with regard to injury severity. Data were collected in Motala municipality (population = 41,000), Ostergötland county, Sweden, during one year before and one year after program intervention, from two sources: registration of trivial (AIS 1) and non-trivial (AIS 2-6) unintentional injuries from all acute care episodes in the area and recollection of hospital bed days from discharge registers. The incidence of non-trivial injuries treated in health care was found to have decreased by 41% (95% confidence interval, 37-45%), while the trivial injuries increased by 16% (9-22%). The larger decrease of non-trivial injuries was observed in all ages and injury event environments. The total number of bed days at emergency hospitals due to injuries decreased by 39% (37-41%) from 1983-84 to 1989, while the hospital bed utilization for other reasons decreased by 9% (8-9%). The study showed the implementation of a WHO Safe Community program led to the harm from unintentional injuries within the community being considerably more reduced than that of the injury incidence. In future assessments of injury prevention programs, classification of injury severity should be included to increase the validity of inter-program comparisons.


Reading achievement declines during the COVID-19 pandemic: evidence from 5 million U.S. students in grades 3-8.
The COVID-19 pandemic has been an unprecedented disruption in students' academic development. Using reading test scores from 5 million U.S. students in grades 3-8, we tracked changes in achievement across the first two years of the pandemic. Average fall 2021 reading test scores in grades 3-8 were .09 to .17 standard deviations lower relative to same-grade peers in fall 2019, with the largest impacts in grades 3-5. Students of color attending high-poverty elementary schools saw the largest test score declines in reading. Our results suggest that many upper elementary students are at-risk for reading difficulties and will need targeted supports to build and strengthen foundational reading skills. The online version contains supplementary material available at 10.1007/s11145-022-10345-8.


Crystal structure of N-hy-droxy-picolinamide monohydrate.
The crystal structure of the title compound, C6H6N2O2·H2O, consists of N-hy-droxy-picolinamide and water mol-ecules connected through O-H⋯O and N-H⋯N hydrogen bonds. The O-H⋯O inter-actions and π-π stacking inter-actions between the pyridine rings [centroid-centroid distance = 3.427 (1) Å] organize the components into columns extending along the b axis and the N-H⋯N hydrogen bonds link these columns into a two-dimensional framework parallel to (100). The N-hy-droxy-picolinamide mol-ecule adopts a strongly flattened conformation and only the O-H group H atom deviates significantly from the mol-ecule best plane. The dihedral angle between the hydroxamic group and the pyridine ring is 5.6 (2)°. The conformation about the hydroxamic group C-N bond is Z and that about the C-C bond between the pyridine and hydroxamic groups is E.


Effects of furazolidone, PCB77, PCB126, Aroclor 1248, paraquat and p,p'-DDE on transketolase activity in embryonal chicken brain.
The effect of in ovo exposure to PCBs, DDE and paraquat on transketolase activity was measured in 19-day-old chicken embryos. Furazolidone was used as a positive control for decreased activity of the enzyme. The potency of contaminants to interact with transketolase was also tested in an in vitro system, using control brain 7000xg supernatants containing the enzyme. No effects were found on transketolase activity after in ovo or in vitro exposure to PCB126, Aroclor, DDE or paraquat. PCB77 decreased transketolase activity in vitro, but only at concentrations that, extrapolated to in ovo exposure, would be lethal to the embryo. Furazolidone decreased transketolase activity both in ovo and in vitro. For this contaminant, thiamine residues were analysed in the yolk sacs, but no differences were found between exposed and non-exposed eggs. Transketolase is dependent on thiamine pyrophosphate as a cofactor, and therefore, the decreased enzyme activity could be the result of an interaction between furazolidone and thiamine metabolism. Since thiamine residues were not affected by furazolidone and transketolase inhibition in vitro was similar to the inhibition after in ovo exposure, it was concluded that furazolidone interacted with transketolase on the enzymatic level rather than by a depletion of thiamine.


Encounter Complexes Between the N-terminal of Neurotensin with the Extracellular Loop 2 of the Neurotensin Receptor 1 Steer Neurotensin to the Orthosteric Binding Pocket.
Neurotensin (NT) is a linear disordered peptide that activates two different class A GPCRs, neurotensin receptor 1 (NTS1) and NTS2. Resolved structures of the complex of the C-terminal fragment of NT, NT8-13, with NTS1 shows the peptide takes a well-defined structure in the bound state. However, the mechanisms underlying NT recognition of NTS1, and the conformational transition of NT upon binding NTS1 is an open question that if answered may aid discovery of highly selective drugs and reveal potential secondary binding sites on the surface of the receptor. Herein we investigated the interactions guiding NT to the orthosteric binding pocket of NTS1 by combining NMR experiments with kinetic analysis of the binding pathway using stopped-flow fluorescence and mutagenesis on both NT and NTS1. We show the presence of transient structures in the middle part of NT that kinetically regulate the binding of NT to NTS1. Moreover, our results indicate that the binding pathway of NT onto NTS1 is mediated via electrostatic interactions between the N-terminal region of NT with the extracellular loop 2 of NTS1. These interactions induce backbone conformational changes in neurotensin similar to the bound-state neurotensin, suggesting that the N-terminal region of NT and these interactions should be considered for development of selective drugs against NTS1.


Eating attitudes and temperament attributes of normal and overweight college students.
The aim of the present investigation was to compare temperament and eating attitudes in overweight versus "normal" weight samples of college students. In Study 1, the responses of women of normal and overweight status on measures of temperament and eating attitudes were analyzed. Overweight women were shown lower on self-rated "activity" and "oral control." Given the suggestive nature of the results, a larger sample including both women and men was obtained for Study 2. The results of the first study were replicated for the women, and overweight men were additionally found lower in "emotional distress" and "fear," with weight status related to all three aspects of eating behavior. That is, differences by weight status were discerned for both women and men on oral control, with overweight men also higher in "dieting" and "bulimia-food preoccupation." Further research on overweight men versus women, their perceptions of their own temperaments, and their attitudes toward eating, may be beneficial in understanding more about risk factors for the development of obesity.


Thallium (I) interactions in biological fluids: a potentiometric investigation of thallium(I) complex equilibria with some sulphur-containing amino acids.
Formation constants for thallium(I) complexes of L-cysteine (CysH2), DL-penicillamine (PenH2), N-acetyl-L-cysteine (AcyH2), and N-acetyl-DL-penicillamine (ApeH2) in aqueous solution have been determined in 150 mmol dm-3 NaCl medium at 37 degrees C by potentiometric titrations using a glass electrode. Glycine has been used as a model for simple amino acids. The experimental data may be explained by the formation of the complexes T1(Cys)-, T1(Cys)H, T1(Pen)-, T1(Pen)H, T1(Acy)-, and T1(Ape)- with log formation constants 3.26, 11.28, 3.60, 12.05, 2.27, and 2.45, respectively. Analysis of the results obtained and comparison of thallium(I) complexing ability with that of dimethyl-thallium(III) seem to indicate that thallium(I) toxicity does not directly stem from its interference with the metabolism of sulphur-containing compounds.


[A study of genetic stability of male sterile mutant of maize obtained from space flighted seeds].
To select a male sterile mutant of maize through space flight for production application. Air dried seeds of maize (Chuan Dan No. 9) were carried to space for 15 d. After returned to the earth, a male sterile mutant was selected and a sterile line was obtained through direction breeding. It was found that the sterile material was thoroughly abortive. The sterile was trail stable and expressed a genetic feature of single recessive gene controlled nucleus sterility. The appearance of male sterile mutant was due to gene mutation caused by space conditions.


Oscillopsia after lateral wall orbital decompression.
To assess the incidence, duration, and severity of oscillopsia after lateral wall orbital decompression for thyroid eye disease. Retrospective telephone interview. A consecutive group of patients who had undergone lateral wall orbital decompression for thyroid eye disease performed by 2 consultants at Moorfields Eye Hospital between January 2008 and December 2010. Patients were telephoned and a standardized interview related to postoperative oscillopsia was performed. The degree of preoperative and late postoperative exophthalmometry was assessed from clinical records. The presence, severity, and duration of postoperative oscillopsia and its impact on daily activities. Ninety-eight patients were interviewed successfully, of which 34 (35%) had noted postoperative oscillopsia that occurred upon chewing in 29 of 34 patients (85%) and upon walking in 8 of 34 patients (24%). The oscillopsia resolved within 1 year in 15 of 34 patients (44%), and 16 of 34 (47%) still had mild symptoms at 2 years or more after surgery. Fourteen patients (41% of affected patients; 14% of the entire group) initially were troubled by the symptom, but at the time of interview, only 1 person found it troublesome and 7 reported it as a minimal problem. The reduction in proptosis was similar among those with and without oscillopsia. The incidence of oscillopsia after lateral wall orbital decompression was 35% when patients were questioned directly, and was much higher than anticipated from extensive clinical experience (where very few patients mention the symptom). In almost all cases, the oscillopsia resolved or was not troublesome, and only 1 patient found it bothersome more than 2 years after surgery. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Self-threading of a poly(ethylene glycol) chain in a cyclodextrin-ring: control of the exchange dynamics by chain length.
Poly(ethylene glycol) (PEG)-substituted cyclodextrins (CDs) with different chain lengths have been synthesized. PEG-substituted CDs formed self-threading complexes in aqueous solutions, and the conformational exchange dynamics between self-threading and dethreading could be regulated by its chain length.


A reagentless electrochemical sensor for aflatoxin B1 with sensitive signal-on responses using aptamer with methylene blue label at specific internal thymine.
Aptamer electrochemical sensors using immobilized aptamers with redox tag rely on the target binding-induced changes of current signal on electrode, offering advantages in operation convenience, no separation, rapidity, and sensitivity. Usually, the redox tag is placed on aptamer terminal, however, sometimes the terminal label may be insensitive to target-binding and fail to generate sensitive responses. The redox tag methylene blue (MB) labeled on different sites of aptamer may experience distinct changes in local environment, distance to electrode, or interactions with aptamer bases during affinity binding, which affect the current signal. Thus, it is possible to construct aptamer electrochemical sensors with sensitive and significant responses to targets by screening a series of sites (e.g., internal thymine T) of the aptamer and placing MB tag on a specific site of the aptamer. With this strategy, we successfully fabricated an electrochemical sensor on gold electrode for rapid, reagentless, and sensitive detection of aflatoxin B1 (AFB1), an important mycotoxin causing great health risks, by using a 26-mer DNA aptamer with MB on an internal T site (e.g., 18th T) and a thiol moiety at 5' terminal. This sensor generated remarkable signal-on responses to AFB1, allowed a detection limit of 6 pM, and enabled detection of AFB1 in wine, milk and corn flour samples. This sensor can be well regenerated by rinsing with deionized water and reused, and shows good stability. This sensor and the demonstrated strategy are promising in wide applications.


Expression of steroidogenic enzymes and sex-steroid receptors in human prostate.
Identification of the cell types expressing the steroidogenic enzymes and sex steroid receptors in the human prostate has recently been performed using immunocytochemistry and in-situ hybridization. The enzymes 3beta-hydroxysteroid dehydrogenase (3beta-HSD), which converts dehydroepiandrosterone (DHEA) into androstenedione, and type 5 17beta-HSD, which catalyzes the reduction of androstenedione to testosterone, have been localized in basal cells of alveoli as well as in stromal cells and endothelial cells of blood vessels. On the other hand, type-2 5alpha-reductase, which converts testosterone into the most potent androgen dihydrotestosterone (DHT), has been mostly observed in the luminal cells in alveoli. Aromatase, which converts testosterone into estradiol, has also been found to be expressed in the luminal cells of the alveoli as well as in stromal cells. Androgen receptor (AR) has been localized in luminal cell nuclei of alveoli and a large number of stromal cells, while estrogen receptor beta has been detected in both basal and luminal cells in alveoli and also in stromal cells.


Building codes: An often overlooked determinant of health.
Although the vast majority of the world's population spends most of their time in buildings, building codes are not often thought of as 'determinants of health'. The standards that govern the design, construction, and use of buildings affect our health, security, safety, and well-being. This is true for dwellings, schools, and universities, shopping centers, places of recreation, places of worship, health-care facilities, and workplaces. We urge proactive engagement by the global public health community in developing these codes, and in the design and implementation of health protection and health promotion activities intended to reduce the risk of injury, disability, and death, particularly when due to poor building code adoption/adaption, application, and enforcement.


Rhegmatogenous retinal detachment complicating cytomegalovirus retinitis.
Six eyes in four patients with cytomegalovirus retinitis developed retinal holes and retinal detachment. Holes appeared in areas of necrosis and were typically large and round with shaggy edges. Differentiation from exudative detachment was sometimes difficult because of obscuration of the fundus by vitreous haze. Cryotherapy was successful in closing open breaks without detachment; cryotherapy and exoplant surgery were used effectively to treat the initial detachments. The occurrence of massive periretinal proliferation and late development of new areas of hole formation or retinitis complicated therapy for these detachments.


The pattern of presentation of carcinoma of the uterine cervix in East Anglia 1960 to 1975.
Changes in the pattern of presentation of carcinoma of the uterine cervix between 1960 and 1975 were studied using the records of 3193 patients registered with the East Anglian Cancer Registration Bureau. Between 1963 and 1968, an increased registration rate for invasive tumours was largely attributable to increased registrations of Stage I and II lesions in the 35 to 49 age group. After 1970 the registration rate for lesions of all stages in this age group declined. Over the same period the 50 to 64 age group showed a tendency for an increased proportion of registrations to be of Stage I or II lesions. There was little change in pattern in the over-65 age group. The possible relation of these changes to the introduction of a cervical cytology screening programme and the implications for future screening policies are discussed.


Zidovudine antagonizes the action of pyrimethamine in experimental infection with Toxoplasma gondii.
The effect of zidovudine (azidothymidine; AZT) on the action of pyrimethamine against Toxoplasma gondii was investigated. Zidovudine was found to antagonize the toxoplasmacidal effect of low concentrations of pyrimethamine in vitro, and in vitro synergism of pyrimethamine and sulfadiazine against T. gondii was reversed by zidovudine. Zidovudine also antagonized the therapeutic effect of pyrimethamine in mice acutely infected with T. gondii.


Structure-activity relationship (SAR) between some natural flavonoids and ocular blood flow in the rabbit.
Flavonoids with two to five hydroxy groups, with or without sugar, and/or methoxy groups were studied on their effects to affect ocular blood flow. Colored microsphere technique was used to determine the ocular blood flow in rabbit eyes. Flavonoids with three free hydroxy (OH) groups seemed to produce the optimal effects in increasing ocular blood flow (naringenin and hesperitin, Pfalts and Bauer, Waterbury, CT). Whether the OH groups are below three (naringenin, hesperitin, Pfalts and Bauer, Waterbury, CT) or above four (Quercetin, Pfalts and Bauer, Waterbury, CT), they produced no effects on the ocular blood flow. When OH groups are four (rutin, Aldrich, Milwaukee, WI), it produced mixed effects on ocular blood flow. The attachment of rutinose and/or methoxy group in the structure did not affect the ocular blood flow one way or the other. The ocular blood flow is increased significantly by the number of OH group in the molecule, with three the best to increase the ocular blood flow.


Permanent cardiac pacing after open-heart surgery: acquired heart disease.
Retrospective review of 5,942 patients who underwent open-heart surgery for acquired heart disease revealed that 123 patients (2.1%) required permanent cardiac pacing postoperatively; 4.6% of these underwent predominantly valvular surgery and 0.6% had coronary bypass. The most important factors appeared to be: 1) preoperative evidence of a conduction disorder; 2) advanced patient age; 3) dense calcium in the aortic annulus; 4) valvular surgery and, especially, tricuspid valve surgery; and 5) poor myocardial protection. Postoperative permanent pacing had a considerable impact on patient morbidity from maintenance operations; most complications were lead-related problems.


Low serum total cholesterol level is a surrogate marker, but not a risk factor, for poor outcome in patients hospitalized with acute heart failure: a report from the Korean Heart Failure Registry.
Hypercholesterolemia is a major risk factor for incident coronary artery disease and the prevalence of heart failure (HF). The causal relationship between low total cholesterol (TC) levels and poor clinical outcome in patients with acute HF has not been investigated. This study evaluated the effect of cholesterol levels on the long-term outcome in patients hospitalized due to acute HF. We analyzed a cohort of 2,797 HF patients who were eligible for analysis in 3,200 patients of the Korean Heart Failure Registry. Patients were stratified into quartiles of TC (Q1 <133, Q2 133-158, Q3 159-190, and Q4 >190 mg/dL). Propensity score matching was performed with the patients in Q1 and Q4. Patients with lower serum TC had lower blood pressure, lower hemoglobin, lower serum sodium, and higher natriuretic peptide levels than patients with higher TC levels. Low TC was associated with increased risks for death and readmission due to HF; the adjusted hazard ratio (HR) of Q1 compared with Q4 was 1.57 (95% confidence interval [CI] 1.30-1.90). However, propensity score matching analysis revealed that low cholesterol itself did not affect outcome (HR 1.12, 95% CI 0.85-1.48). Low TC is strongly associated with mortality and morbidity in patients with HF. However, low TC seemed to be a secondary result of the patient's state rather than an independent risk factor for poor outcome.


Hospitals collaborate to reduce surgical infections.
Quality improvement organization (QIO) trains other QlOs and participating QI professionals. Initiative emphasizes rapid testing, then spread of small changes. Teams typically include QI managers, nurses, and physicians.


Reaction of an alkyne with dinickel-diphenylsilyl complexes. An emissive disilane formed via the consecutive Si-C and Si-Si bond-making processes.
[{Ni(dmpe)}(2)(μ-SiHPh(2))(2)] (dmpe = 1,2-bis(dimethylphosphino)ethane) reacted with PhC≡CPh to yield fluorescent 1,2-bis{(E)-1,2-diphenylethenyl}-1,1,2,2-tetraphenyldisilane via addition of the Si-H bond of the ligand to the alkyne and subsequent coupling of the tertiary silyl ligands forming the Si-Si bond.


Comparison of Staphylococcus aureus surface protein extraction methods and immunogenicity.
Staphylococcus aureus is the major contagious bovine mastitis pathogen and has no effective vaccine. Strain variation and limited knowledge of common immunogenic antigen/s are among major constraints for developing effective vaccines. S. aureus cell surface proteins that are exposed to the host immune system constitute good vaccine candidates. The objective of this study was to compare two novel S. aureus surface protein extraction methods with biotinylation method and evaluate immune-reactivity of extracted proteins. Surface proteins were extracted from nine genetically distinct S. aureus strains from cases of bovine mastitis. After extraction, bacterial cell integrity was examined by Gram staining and electron microscopy to determine if extraction methods caused damage to cells that may release non-surface proteins. The extracted proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and evaluated for immune-reactivity using western blot. Results showed that all three extraction methods provided multiple protein bands on SDS-PAGE. Western blot result showed several immunoreactive surface proteins, in which some proteins strongly (well-resolved, thick, dark, and intense band) reacted across the nine strains tested. The three methods are valid for the extraction of surface proteins and hexadecane, and cholic acid methods are more feasible than biotinylation since both are easier, cheaper, and have minor effects on the bacterial cell. Strongly immune-reactive surface proteins may serve as potential candidates for a vaccine to control S. aureus mastitis in dairy cows.


pH-triggered "PEG" sheddable and folic acid-targeted nanoparticles for docetaxel delivery in breast cancer treatment.
Multifunctional nanoparticles have attracted significant attentions for oncology and cancer treatment. In fact, they could address critical point for tumour treatment by creating a stimuli-responsive targeted drug delivery system that can exist stably in the systemic circulation, efficiently penetrate the tumour tissue, and then accumulate in tumour cells in large quantities. A novel stepwise pH-responsive multifunctional nanoparticles (FPDPCNPs/DTX) for targeted delivery of the antitumour drug docetaxel (DTX) is prepared by coating a tumour acidity-sensitive "sheddable" FA modified β-carboxylic amide functionalized PEG layer (folic acid-polyethylene glycol-2,3-dimethylmaleic anhydride, FA-PEG-DA) on the cationic drug-loaded core (poly(β-amino ester-cholesterol, PAE-Chol) through electrostatic interaction in this study. The charge shielding behaviour of the FPDPCNPs/DTX was confirmed by zeta potential assay. The surface charges of the nanoparticles can change from positive to negative after PEG coating. The IC50 values of FPDPCNPs/DTX was 3.04 times higher than that of PEG "unsheddable" nanoparticles in cytotoxicity experiments. The results of in vivo experiment further showed that FPDPCNPs/DTX had enhanced tumour targeting effect, the tumour inhibition rate of FPDPCNPs/DTX was as high as 81.99%, which was 1.51 times that of free DTX. Under a micro acidic environment and folate receptor (FR)-mediated targeting, FPDPCNPs/DTX contributed to more uptake of DTX by MCF-7 cells. In summary, FPDPCNPs/DTX as a multifunctional nano-drug delivery system provides a promising strategy for efficiently delivering antitumour drugs.


Laser suture lysis for non-valved aqueous drainage implants.
To describe a technique for laser suture lysis with non-valved aqueous drainage implants. The surgical juxtaposition of the aqueous drainage tube and notched scleral graft allows the ligature to be placed in a predictable position aiding laser suture lysis. After drainage device encapsulation limits the possibility of hypotony, this technique allows easy postoperative lysis of drainage tube ligatures. This simple modification of surgical technique aids surgeons in finding and releasing aqueous drainage device ligature sutures.


Prevalence and Treatment Outcomes of Marine-Lenhart Syndrome in Japan.
Marine-Lenhart syndrome (MLS) is now understood to be a combination of Graves' disease and autonomously functioning thyroid nodule(s) (AFTNs). The prevalence of the syndrome and suitable treatments for those living in iodine-sufficient areas are uncertain. We aimed to investigate the prevalence, treatment, and prognosis of MLS in Japan, an iodine-sufficient area. This study involved patients who visited our hospital between February 2005 and August 2019. Among patients with both thyrotoxicosis and thyroid nodule(s) larger than 10 mm, MLS and isolated AFTNs were diagnosed based on serum thyroid-stimulating hormone receptor antibody levels and scintigraphy using radioiodine or technetium-99m and thyroid uptake. Twenty-two patients were found to have MLS, compared to 372 with isolated AFTNs and 8,343 with Graves' disease, during the period. Therefore, the rate of MLS cases was 0.26% among all patients with Graves' disease (22/8,343). Treatments and outcomes were assessed for cases of MLS (n = 18) and isolated AFTNs (n = 269). Antithyroid drugs (ATDs) were withdrawn in 27.8% of cases in the MLS group and 10.3% in the isolated AFTN group. There was no significant difference in the clinical outcome after ATD withdrawal between the 2 groups. However, the rate of hypothyroidism after radioactive iodine (RAI) administration was significantly higher in the MLS group than in the isolated AFTN group (42.9 vs. 9.0%, p = 0.005) despite similar doses of RAI. The prevalence of MLS among patients with Graves' disease was 0.26% in Japan. RAI therapy induces hypothyroidism more frequently than in those with AFTNs probably because RAI is taken up in the surrounding Graves' tissues.


The Structures and Functions of VZV Glycoproteins.
The virions of all enveloped viruses, including those of the Herpesviridae, must bind to the cell surface then undergo a process of membrane fusion between the cell plasma membrane and the virus particle envelope. As for all herpesviruses, glycoproteins in the virion envelope are the modus operandi of these events.


Two-port approach for fully thoracoscopic right upper lobe sleeve lobectomy.
This report describes a case report of a minimally invasive technique for VATS right upper sleeve lobectomy with a two-port approach. To our knowledge it is the first report of this kind. A 50-year-old man with a pulmonary nodule occluding the orifice of the right upper lobe bronchus was referred to our department. Dissection, stapling the right upper lobe pulmonary vessels and anastomosis between the right intermediate and the right main bronchus were performed via the two port. To deal with blocking of pulmonary artery and obtain a satisfactory exposure and manipulating space in the course of bronchial anastomosis were the key points. Intraoperative blood loss was 150 ml and total operative time was 220 minutes. The postoperative course was uneventful. Chest X-rays showed no sign of atelectasis. Postoperative histopathological examination revealed that the tumor was T3N0M0 squamous cell carcinoma. The patient was discharged from hospital on postoperative day 9 without any complications. We conclude that video-assisted thoracoscopic sleeve lobectomy with mediastinal dissection by two-port approach is feasible and convenient.


Outcomes of emergency surgery for acute type A aortic dissection complicated by malperfusion syndrome.
The study objective was to determine the impact of malperfusion syndrome on in-hospital mortality and midterm survival after emergency aortic arch reconstruction for acute type A aortic dissection. This was an observational study of aortic surgeries from 2010 to 2018. All patients with acute type A aortic dissection undergoing open aortic arch reconstruction were included. Patients were dichotomized by the presence or absence of malperfusion syndrome and were analyzed for differences in short-term postoperative outcomes, including morbidity and in-hospital mortality. Kaplan-Meier survival estimation and multivariable Cox analysis were performed to identify variables associated with survival. A total of 467 patients undergoing aortic arch reconstruction for acute type A aortic dissection were identified, of whom 332 (71.1%) presented without malperfusion syndrome and 135 (28.9%) presented with malperfusion syndrome. Patients with malperfusion syndrome had higher in-hospital mortality (21.5% vs 5.7%) than patients without malperfusion syndrome. After multivariable adjustment, malperfusion syndrome was associated with worse survival (hazard ratio, 2.43, 95% confidence interval, 1.61-3.66, P < .001) compared with patients without malperfusion syndrome. The predicted risk of mortality increased as the number of malperfused vascular beds increased. Patients with coronary malperfusion syndrome and neuro-malperfusion syndrome had reduced survival compared with the rest of the cohort (P < .05). Malperfusion syndrome is associated with higher in-hospital mortality and reduced survival for patients with acute type A aortic dissection, with the risk of mortality increasing as the number of malperfused vascular beds increases. Coronary malperfusion syndrome and neuro-malperfusion syndrome may represent a high-risk subgroup of patients presenting with acute type A aortic dissection complicated by malperfusion syndrome. Finally, malperfusion syndrome may benefit from immediate surgical intervention to restore true lumen perfusion, as opposed to operative delay.


Trauma-focused treatment in a state system of care: is it worth the cost?
The efficacy of Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) in treating child traumatic stress inspires nationwide dissemination, yet widespread adoption by state systems of care is lagging. A significant barrier is the cost of implementation and maintenance of evidence-based services. Thus, the current study examined the annual costs of mental health services accrued for 90 publiclyinsured, trauma-exposed children from the time they began participation in a TF-CBT implementation project to 1 year after their admission. These costs were compared to those accrued over that same time period by 90 trauma-exposed control children that were matched by demographics and prior mental health services utilization using a propensity score matching algorithm and provided outpatient treatment as usual. Results indicated that (a) 27.5 % of the total cost was attributed to high-end services utilized by only 1.67 % of children; (b) two times more money was spent on low-end mental health services received by the TF-CBT group than the control group, and (c) five times more money was spent on high-end mental health services received by the control group than the TF-CBT group in that year. These data suggest that providing evidence-based trauma-focused outpatient treatment to children with trauma-related problems may offset the eventual need for services that are more restrictive and costly.


Inducible nitric oxide synthase: from cloning to therapeutic applications.
Elucidation of the many roles of nitric oxide (NO) in homeostasis and disease states has uncovered many areas where manipulation of NO production would be of therapeutic benefit. Recent advances in gene transfer technology and the cloning of the inducible nitric oxide synthase (iNOS) gene have led to the development of strategies for gene therapy to increase NO production for the treatment of disorders ranging from vascular restenosis to impaired wound healing. This review summarizes the current status of iNOS gene therapy research.


[Adiana(®) hysteroscopic tubal occlusion device for the treatment of hydrosalpinx prior to in vitro fertilization: a case report].
This case report outlines a successful pregnancy after proximal occlusion of a fallopian tube with Adiana(®) micro-insert in a patient with hydrosalpinx. A 32-year-old nulligravid patient with pelvic adhesive disease and unilateral hydrosalpinx underwent a successful occlusion of the hydrosalpinx by Adiana(®) matrix with a pregnancy after IVF cycle. Adiana(®) hysteroscopic tubal occlusion device can be used prior to IVF and seems to be an alternative to Essure(®) procedure. The theoretical advantage of Adiana(®) is the ability to maintain a uterine cavity free of all foreign matter.


Building an extended inverse crown motif via alkali-metal-mediated alpha-magnesiation of furan.
deprotonated selectively at the -position by the mixed-metal alkyl-amido base [(TMEDA) x Na(Bun)(TMP)Mg(TMP)] to generate a transient intermediate which undergoes disproportionation to the disodium dimagnesium hexafuryl tri(thf) complex [{{(thf)3 x Na2}{(TMEDA) x Mg2}(2-C4H3O)6}infinity], a new type of inverse crown structure with triply-stabilized (through Mg-C , Na-O and Na...C-C interactions) furyl guest anions, and the tris(amide) [(TMEDA)x.NaMg(TMP)3].


Nephropathy induced in rats by repeated intravenous injections of rabbit anti-FX1A antibody.
Repeated intravenous injections of small amounts of rabbit anti-rat FXIA antibodies (RAFA) induced a renal damage with the morphological features of epimembranous glomerulonephritis with significant and persistent proteinuria. These findings indicated that repeatedly injected RAFA accumulated in glomeruli and that there seems to be a threshold in quantity of RAFA localized in glomeruli to induce renal damage with proteinuria.


Clinical and ethical aspects of financial capacity in dementia: a commentary.
In contrast to issues such as treatment and research consent capacity, financial capacity has received relatively little clinical and ethical attention in the dementia literature. Yet issues of financial capacity emerge frequently in patients with Alzheimer disease, Parkinson disease, and related dementias, and commonly present ethical and clinical challenges for clinicians treating these patients. These issues include whether a patient with possible dementia has sufficient capacity to manage independently their financial affairs, needs referral for financial capacity assessment, and/or is being financially exploited or abused by others. The accurate identification, assessment and successful handling of such financial capacity issues can have a substantial impact on the financial and psychological well-being of patients and their family members. This commentary presents an overview of financial capacity and associated clinical and ethical issues in dementia and describes a set of possible clinician roles regarding these issues as they arise in clinical practice. The commentary concludes with a section describing educational resources available to clinicians and bioethicists seeking additional guidance in handling financial capacity issues. The ultimate goal of the article is to focus clinical and ethical attention on a neglected capacity that is of fundamental importance for patients, families, and healthcare and legal professionals.


Iron-oxidation-state-dependent O-O bond cleavage of meta-chloroperbenzoic acid to form an iron(IV)-oxo complex.
The mechanism of formation of [Fe(IV)(O)(N4Py)](2+) (2, N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine) from the reaction of [Fe(II)(N4Py)(CH(3)CN)](2+) (1) with m-chloroperbenzoic acid (mCPBA) in CH(2)Cl(2) at -30 °C has been studied on the basis of the visible spectral changes observed and the reaction stoichiometry. It is shown that the conversion of 1 to 2 in 90% yield requires 1.5 equiv peracid and takes place in two successive one-electron steps via an [Fe(III)(N4Py)OH](2+)(3) intermediate. The first oxidation step uses 0.5 equiv peracid and produces 0.5 equiv 3-chlorobenzoic acid, while the second step uses 1 equiv peracid and affords byproducts derived from chlorophenyl radical. We conclude that the Fe(II)(N4Py) center promotes O-O bond heterolysis, while the Fe(III)(N4Py) center favors O-O bond homolysis, so the nature of O-O bond cleavage is dependent on the iron oxidation state.


A cognitive task, deep breathing, and static stretching reduce variability of motor evoked potentials during subsequent transcranial magnetic stimulation.
Motor evoked potentials (MEPs) induced via transcranial magnetic stimulation (TMS) demonstrate trial-to-trial variability limiting detection and interpretation of changes in corticomotor excitability. This study examined whether performing a cognitive task, voluntary breathing, or static stretching before TMS could reduce MEP variability. 20 healthy young adults performed no-task, a cognitive task (Stroop test), deep breathing, and static stretching before TMS in a randomized order. MEPs were collected in the non-dominant tibialis anterior muscle at 130% active motor threshold. Variability of MEP amplitude was quantified as coefficient of variation (CV). MEP CV was greater after no-task (25.4 ± 7.0) than after cognitive task (23.3 ± 7.2; p < 0.05), deep breathing (20.1 ± 6.3; p < 0.001), and static stretching (20.9 ± 6.0; p = 0.004). MEP CV was greater after cognitive task than after deep breathing (p = 0.007) and static stretching (p = 0.01). There was no effect of condition on MEP amplitude. Performing brief cognitive, voluntary breathing, and stretching tasks before TMS can reduce MEP variability with no effect on MEP amplitude in the tibialis anterior of healthy, young adults. Similar tasks could be incorporated into research and clinical settings to improve detection of changes, normative data, and clinical predictions.


Transgenic B7-H3 therapy induces tumor-specific immune response in human oral squamous cell cancer: an in vitro study.
Tumors may present antigens to T cells but lack costimulatory signals which are necessary to initialize an effective immunologic response. This study aimed to develop a tumor cell-based cancer vaccine by genetically modifying oral squamous cell cancer (OSCC) cell line Tca8113 with human B7-H3 immunoglobulin, and to evaluate its efficacy in enhancing the tumor-specific immune response. Human B7-H3 gene was extracted from isolated T lymphocytes of healthy volunteers. Tumor cell vaccine TCV-hB7-H3 and mock control were prepared by transfecting Tca8113 cells with B7-H3 or mock vector. After being stimulated with TCV-hB7-H3 or mock control, the proliferation, IFN-mu expression, and cytotoxicity of the T cells were assessed. The Tca8113 cells transfected with human B7-H3 significantly enhanced the proliferation, IFN-mu expression, and cytotoxicity of the T cells. Genetically modified OSCC cells encoding B7-H3 enhance the induction of tumor specific immune response.


Spontaneous dyadic behavior predicts the emergence of interpersonal neural synchrony.
Synchronization of neural activity across brains - Interpersonal Neural Synchrony (INS) - is emerging as a powerful marker of social interaction that predicts success of multi-person coordination, communication, and cooperation. As the origins of INS are poorly understood, we tested whether and how INS might emerge from spontaneous dyadic behavior. We recorded neural activity (EEG) and human behavior (full-body kinematics, eye movements, and facial expressions) while dyads of participants were instructed to look at each other without speaking or making co-verbal gestures. We made four fundamental observations. First, despite the absence of a structured social task, INS emerged spontaneously only when participants were able to see each other. Second, we show that such spontaneous INS, comprising specific spectral and topographic profiles, did not merely reflect intra-personal modulations of neural activity, but it rather reflected real-time and dyad-specific coupling of neural activities. Third, using state-of-art video-image processing and deep learning, we extracted the temporal unfolding of three notable social behavioral cues - body movement, eye contact, and smiling - and demonstrated that these behaviors also spontaneously synchronized within dyads. Fourth, we probed the correlates of INS in such synchronized social behaviors. Using cross-correlation and Granger causality analyses, we show that synchronized social behaviors anticipate and in fact Granger cause INS. These results provide proof-of-concept evidence for studying interpersonal neural and behavioral synchrony under natural and unconstrained conditions. Most importantly, the results suggest that INS could be conceptualized as an emergent property of two coupled neural systems: an entrainment phenomenon, promoted by real-time dyadic behavior.


Experimental hybridization within the genus Triturus (Urodela: Salamandridae). I. Spermatogenesis of F1 species hybrids, Triturus cristatus carnifex female x T. vulgaris meridionalis male.
The spermatogenesis of 9 F1 hybrids of Triturus cristatus carnifex female x T. vulgaris meridionalis male was studied in squash preparations of testicular fragments, treated by the C-staining method. The chromosome number of these hybrids was examined in spermatogonial metaphases and found to be diploid. The two parental sets were always recognized, which means that a regular, although heterospecific, amphimixis occurred (2n = nfemale + nmale). Meiotic prophase I is greatly altered owing to a failure of typical chromosome pairing and chiasma formation. At metaphase I and/or meta-anaphase I, the effects of the hybrid combination of the 2 specific parental sets are clearly visable. Most primary spermatocytes contain only univalents. A few show chromosome associations (bivalents, trivalents and, more rarely, quadrivalent chains) besides univalents. Such associations are of 2 types: (a) intragenomal associations = associations of 2 chromosomes by a terminal (a1) or subterminal chiasma (a2); (b) intergenomal associations = associations of 2 chromosomes by a terminal (b1) or subterminal chiasma (b2). Univalents segregate at random while the associations often lag on the equatorial plane or migrate entire to a spindle pole. Primary spermatocytes with chromosome multivalents can encounter greater difficulties in accomplishing the first cytokinesis. Secondary spermatocytes are numerically and qualitatively unbalanced; however, some of them undergo spermiogenesis and can give rise to a small number of sperms, generally abnormal and never united in bundles. --Problems related to the occurrence of "anomalous" chiasmata and of intra- and inter-genomal homologies are discussed.


Sequence-based typing of a novel HLA-DRB1*14 allele, DRB1*1475, in a Caucasian woman.
The sequence of the human leukocyte antigen (HLA)-DRB1*1475 differs from the closest aligned sequence HLA-DRB1*140102 by a single-nucleotide substitution at codon 81 (CAC-->TAC) resulting in an amino acid change from Leu to Gln.


Voriconazole activity against clinical yeast isolates: a multicentre Italian study.
The activity of voriconazole was tested in vitro against 1996 clinical yeast isolates collected in 20 Italian microbiology laboratories. Voriconazole susceptibility testing was carried out with the broth microdilution (NCCLS M27-A2), Etest and disk diffusion methods. The minimum inhibitory concentrations at which 90% of the isolates were inhibited (MIC90) obtained with the NCCLS method were 0.03 mg/L for Candida albicans, 0.5 mg/L for Candida non-albicans and 0.25 mg/L for other genera; those obtained with Etesting were, respectively, 0.032 mg/L, 0.125 mg/L and 0.125 mg/L. With the disk diffusion method, the majority of isolates (92.3%) showed inhibition zone diameters between 21 mm and 40 mm. Using a tentative MIC cut-off of 1mg/L as indicative of in vitro susceptibility, 98.1% of the isolates tested in our study would be classified as susceptible, and only 28 (1.4%) of the isolates, with MICs higher than 2mg/L, would be classified as resistant to the drug. Our findings confirm the broad-spectrum in vitro activity of voriconazole against yeasts, including Candida species that are generally less susceptible to other azoles.


Histochemical studies on Raillietina (Raillietina) johri (Cestoda: Davaineidae). II. Nucleoside diphosphatase and thiamine pyrophosphatase.
Thiamine pyrophosphatase and nucleoside diphosphatase have been studied histochemically in Raillietina (Raillietina) johri. Thiamine pyrophosphatase activity has been observed in the tegument, subtegumental muscle, subtegumental cells, medullary parenchyma, excretory canal and various reproductive structures like testes, ovary, vas deferens, spermatozoa and vitellaria. Eggs exhibit moderate enzyme activity. Various nucleoside diphosphates have been found to be hydrolyzed by thiamine pyrophosphatase. CaCl2, MgCl2 and MnCl2 each activated the enzyme at a final concentration of 6 mM whereas cysteine, reduced glutathione and PCMB inhibited the enzyme activity at a final concentration of 10 mM, 10 mM and 20 mM, respectively. KCN and NaF had no effect on the enzyme staining at concentration as high as 50 mM and 30 mM, respectively. Possible roles of the enzyme in the parasite have been discussed.


Life at High Latitudes Does Not Require Circadian Behavioral Rhythmicity under Constant Darkness.
Nearly all organisms evolved endogenous self-sustained timekeeping mechanisms to track and anticipate cyclic changes in the environment. Circadian clocks, with a periodicity of about 24 h, allow animals to adapt to day-night cycles. Biological clocks are highly adaptive, but strong behavioral rhythms might be a disadvantage for adaptation to weakly rhythmic environments such as polar areas [1, 2]. Several high-latitude species, including Drosophila species, were found to be highly arrhythmic under constant conditions [3-6]. Furthermore, Drosophila species from subarctic regions can extend evening activity until dusk under long days. These traits depend on the clock network neurochemistry, and we previously proposed that high-latitude Drosophila species evolved specific clock adaptations to colonize polar regions [5, 7, 8]. We broadened our analysis to 3 species of the Chymomyza genus, which diverged circa 5 million years before the Drosophila radiation [9] and colonized both low and high latitudes [10, 11]. C. costata, pararufithorax, and procnemis, independently of their latitude of origin, possess the clock neuronal network of low-latitude Drosophila species, and their locomotor activity does not track dusk under long photoperiods. Nevertheless, the high-latitude C. costata becomes arrhythmic under constant darkness (DD), whereas the two low-latitude species remain rhythmic. Different mechanisms are behind the arrhythmicity in DD of C. costata and the high-latitude Drosophila ezoana, suggesting that the ability to maintain behavioral rhythms has been lost more than once during drosophilids' evolution and that it might indeed be an evolutionary adaptation for life at high latitudes.


Neuropsychological predictors of conversion from mild cognitive impairment to dementia at different timepoints.
Impairment of episodic memory is largely considered the main cognitive marker of prodromic Alzheimer's disease (AD). Nevertheless, the neuropathological process in AD starts several years before and, apart from biomarkers well defined in the Amyloid (A), Tauopathy (T), Neurodegeneration (N) framework, early clinical and neuropsychological markers able to detect mild cognitive impairment (MCI) due to AD before the appearance of memory disorders are lacking in clinical practice. Investigations on semantic memory have shown promising results in providing an earlier marker of dementia in MCI patients. A total of 253 MCI subjects were followed up every 6 months for 6 years-186 converted to dementia and 67 remained stable at the sixth year of follow-up. Twenty-seven patients progressed in the first 2 years (fast converters), 107 in the third to fourth year (intermediate converters), and 51 after the fourth year of follow-up (slow converters). Stable MCI subjects performed better than fast decliners in Mini-Mental State Examination (MMSE), several long-term memory scores, and category verbal fluency test (CFT); stable and intermediate converters differ only in MMSE and CFT tests; and stable and slow converters differ only in MMSE and phonological/semantic discrepancy score. Early impairment of semantic memory could predict the evolution to AD before the onset of episodic memory disorders, and the discrepancy between phonological and semantic verbal fluency could be able to detect this impairment in advance in respect of simple CFT tests. The assessment of different aspects of semantic memory and its degradation could represent an early cognitive marker to intercept MCI due to AD in clinical practice.


Efficacy of Percutaneous Intraarterial Facial/Supratrochlear Arterial Hyaluronidase Injection for Treatment of Vascular Embolism Resulting From Hyaluronic Acid Filler Cosmetic Injection.
Vascular embolism is a serious complication of hyaluronic acid (HA) filler cosmetic injection, and hyaluronidase injection has been proposed as the treatment. Until now, there has been a lack of adequate clinical evidence regarding the benefits of treatment for HA filler-induced vascular embolism by percutaneous facial or supratrochlear arterial hyaluronidase injection. The authors sough to evaluate the efficacy of percutaneous facial or supratrochlear arterial hyaluronidase injection as a rescue treatment for HA filler-induced vascular embolism. We included 17 patients with vascular embolism after facial HA filler injection. Intraarterial injection of 1500 units hyaluronidase was performed via facial artery for 13 cases with skin necrosis and via supratrochlear arterial for 4 cases with severe ptosis and skin necrosis but no visual impairment. Simultaneously, general symptomatic treatment and nutritional therapy were performed. After hyaluronidase injection, facial skin necrosis in all cases was restored and ptosis in the 4 cases was also significantly relieved. Patients were subsequently followed-up for 1 month to 1 year. The skin necrosis in 16 patients completely healed, and only 1 patient had small superficial scars. It is effective to alleviate skin necrosis and ptosis resulting from HA filler embolism via percutaneous facial or supratrochlear arterial hyaluronidase injection.


Right hemisphere partial complex seizures: mania, hallucinations, and speech disturbances during ictal events.
A patient with right hemisphere complex partial seizures exhibited extreme emotional lability resembling mania, neologisms resembling those found in fluent aphasia, and hallucinations during ictal periods. The electroencephalographic and clinical findings in this case suggest that cortical and subcortical structures of the right hemisphere may play a role in mediating the expression of language content.


Hormonal regulation of the System A amino acid transport adaptive response mechanism in a kidney epithelial cell line (MDCK).
When mammalian cells are starved for amino acids, the activity of the A amino acid transport system increases, a phenomenon called adaptive regulation. We have examined the effects of those factors which support Madin-Darby canine kidney (MDCK) cell growth in a defined medium on the derepression of System A activity. Of the five factors which supported MDCK cell growth, insulin was found to be an absolute requirement for derepression. In contrast, PGE1 was a negative controlling factor for the transport system. Growth of MDCK cells in the absence of PGE1 resulted in elevated System A activity which derepressed poorly upon amino acid starvation. Kinetic analysis of alpha-(methylamino) isobutyric acid (mAIB) uptake as a function of substrate concentration showed that the elevated A activity observed when cells were grown in the absence of PGE1 was kinetically similar to the activity induced by starvation for amino acids. Transport of mAIB by amino-acid-fed cells grown in the presence of PGE1 was characterized by a linear Eadie-Hofstee graph and by a relatively low Vmax. Transport by cells starved for amino acids or by cells grown in the absence of PGE1 was characterized by biphasic kinetics for mAIB transport and by elevated Vmax values. An influence of growth factors on the inactivation of derepressed A activity was also observed. In the presence of cycloheximide the rate of loss of A activity in amino-acid-starved cells was 1/4-1/2 that of amino-acid-fed cells. Insulin slowed inactivation in the absence of most amino acids in a protein-synthesis-independent manner, but insulin did not influence the more rapid inactivation observed in amino-acid-fed cells. These results indicate that the level of System A activity observed in response to regulation by amino acids represents a balance between carrier synthesis and inactivation, which can be positively or negatively influenced by growth factors.


Visualisation and characterisation of ageing induced changes of polymeric surfaces by spectroscopic imaging methods.
A polymeric resin material was chosen as the model system to visualise the ageing-induced chemical surface changes with molecular spectroscopic imaging techniques and correlate these results to physical properties such as colour changes. The influence of light radiation, temperature and humidity on the polymeric surfaces was analysed by means of attenuated total reflection infrared imaging, Raman imaging spectroscopy and scanning electron microscopy. Samples were analysed before, during and after the weathering/ageing tests. From these combined data, the mechanisms for the damaging of the resin surface under the various environmental conditions (as applied in the accelerated ageing tests) were deduced. Photo-oxidative decay of the resin leading to a degradation of the uppermost surface layers as well as hydrolysis of the aged surface was identified. The combination of the spectral and spatial data as obtained from spectroscopic imaging with the morphological and elemental information of scanning electron microscopic mapping experiments turned out to be highly advantageous for the elucidation of ageing processes. A correlation between the molecular spectroscopic data and the results from the macroscopic colour difference measurements was found.


Complications of Roux-en-Y gastric bypass and sleeve gastrectomy.
Roux-en-Y gastric bypass and sleeve gastrectomy are two of the most common bariatric procedures performed in 2011. Although the complication rates associated with these procedures are low, the consequences of these complications are significant and can be associated with high morbidity and mortality. Timely diagnosis and proper management of these complications are extremely important. The most commonly used radiologic studies in bariatric surgery are the upper GI contrast study and the CT scan, which are used to rule out leak, obstruction, perforation, anastomotic stricture, or pouch dilatation. As with all imaging studies, a negative result should not override strong clinical suspicion of a complication.


Evaluation of efficacy of oral pregabalin in reducing postoperative pain in patients undergoing total knee arthroplasty.
Optimal pain treatment with minimal side effects is essential for early mobility and recovery in patients undergoing total knee arthroplasty (TKA). We investigated the effect of pregabalin as an adjuvant for postoperative analgesia provided by opioid-based patient-controlled epidural analgesia (PCEA) in such patients. Forty patients undergoing unilateral primary TKA were randomly assigned to two equal groups, to receive either placebo or pregabalin 75 mg twice a day. The drug was administered orally starting before surgery and was continued for 2 days after surgery. Anesthetic technique was standardized. Postoperatively, static and dynamic pain was assessed by verbal rating score. Mean morphine consumption, PCEA usage, rescue analgesic requirement, and overall patient satisfaction were also assessed. Treatment emergent adverse drug reactions were recorded. Mean morphine consumption was significantly reduced by pregabalin. Postoperative pain (both static and dynamic) and PCEA consumption too was significantly reduced in the pregabalin group during the first 48 h after surgery. This group needed fewer rescue analgesics and recorded higher overall patient satisfaction. Pregabalin-treated patients had fewer opioid-related adverse reactions like nausea, vomiting, and constipation. Dizziness was noted in two of the patients receiving pregabalin. There was no statically significant difference in the incidence of sedation in the two groups. Oral pregabalin 75 mg started preoperatively is a useful adjunct to epidural analgesia following TKA. It reduces opioid consumption, improves postoperative analgesia, and yields higher patient satisfaction levels.


One-pot regioselective synthesis and X-ray crystal structure of a stable [60]fullerene trisadduct with the e(edge),e(face),trans-1 addition pattern.
The Bingel functionalisation of C(60) with a structurally novel tether equipped with three reactive malonate groups afforded a C(2v)-symmetrical e(edge),e(face),trans-1 trisadduct in a complete regioselective manner and in an excellent yield of 65%. The [60]fullerene trisadduct showed pronounced ability to crystallise and gave X-ray quality single crystals for analysis.


Obesity and perioperative adverse events in patients undergoing complex revision surgery for the thoracolumbar spine.
There are no previous studies that evaluate the effect of obesity on patients undergoing complex revision thoracolumbar spine surgery. The primary objective was to determine the relationship between obesity and perioperative adverse events (AEs) with patients undergoing complex revision thoracolumbar spine surgery while controlling for psoas muscle index (PMI) as a confounding variable. The secondary objective was to determine the relationship between obesity and 30-day readmission rates, 30-day re-operation rates, rate of discharge to a facility, and post-operative length of stay (LOS). Between May 2016 and February 2020, a retrospective analysis of individuals undergoing complex revision surgery of the thoracolumbar spine was performed at a single institution. Obesity was defined as BMI ≥ 30.0 kg/m2. PMI < 500 mm2/m2 for males and < 412 mm2/m2 for females were used to define low muscle mass. A Spine Surgical Invasiveness Index (SSII) > 10 was used to define complex revision surgery. A multivariable logistic regression model was used to ascertain the effects of low muscle mass, obesity, age, and gender on the likelihood of the occurrence of any AE. A total of 114 consecutive patients were included in the study. Fifty-four patients were in the obese cohort and 60 patients in the non-obese cohort. There was not a significant difference in perioperative outcomes of both the obese and non-obese patients. There were 22 obese patients (40.7%) and 33 non-obese patients (55.0%) that experienced any AE (p = 0.130). Multivariable analysis demonstrated that individuals with low muscle mass had a significantly higher likelihood for an AE than individuals with normal or high muscle mass (OR: 7.53, 95% CI: 3.05-18.60). Obesity did not have a significant effect in predicting AEs. Obesity is not associated with perioperative AEs, 30-day readmission rates, 30-day re-operation rates, rate of discharge to a facility, or post-operative length of stay (LOS) among patients undergoing complex revision thoracolumbar spine surgery. III.


Detection and Quantification of Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus in Coastal Waters of Guinea-Bissau (West Africa).
V. cholerae, V. parahaemolyticus, and V. vulnificus are recognized human pathogens. Although several studies are available worldwide, both on environmental and clinical contexts, little is known about the ecology of these vibrios in African coastal waters. In this study, their co-occurrence and relationships to key environmental constraints in the coastal waters of Guinea-Bissau were examined using the most probable number-polymerase chain reaction (MPN-PCR) approach. All Vibrio species were universally detected showing higher concentrations by the end of the wet season. The abundance of V. cholerae (ISR 16S-23S rRNA) ranged 0-1.2 × 10(4) MPN/L, whereas V. parahaemolyticus (toxR) varied from 47.9 to 1.2 × 10(5) MPN/L. Although the presence of genotypes associated with virulence was found in environmental V. cholerae isolates, ctxA+ V. cholerae was detected, by MPN-PCR, only on two occasions. Enteropathogenic (tdh+ and trh+) V. parahaemolyticus were detected at concentrations up to 1.2 × 10(3) MPN/L. V. vulnificus (vvhA) was detected simultaneously in all surveyed sites only at the end of the wet season, with maximum concentrations of 1.2 × 10(5) MPN/L. Our results suggest that sea surface water temperature and salinity were the major environmental controls to all Vibrio species. This study represents the first detection and quantification of co-occurring Vibrio species in West African coastal waters, highlighting the potential health risk associated with the persistence of human pathogenic Vibrio species.


The top 100 articles in the radiology of trauma: a bibliometric analysis.
The purpose of this study was to identify the 100 top-cited articles in the radiology of trauma, analyze the resulting database to understand factors resulting in highly cited works, and establish trends in trauma imaging. An initial database was created via a Web of Science (WOS) search of all scientific journals using the search terms "trauma" and either "radiology" or a diagnostic modality. Articles were ranked by citation count and screened by two attending radiologists plus a tiebreaker for appropriateness. The following information was collected from each article: WOS all database citations, year, journal, authors, department affiliation, study type and design, sample size, imaging modality, subspecialty, organ, and topic. Citations for the top 100 articles ranged from 82-252, and citations per year ranged from 2.6-37.2. A plurality of articles were published in the 1990s (n = 45) and 1980s (n = 31). Articles were published across 24 journals, most commonly Radiology (n = 31) and Journal of Trauma-Injury, Infection, and Critical Care (n = 28). Articles had an average of five authors and 35 % of first authors were affiliated with a department other than radiology. Forty-six articles had sample sizes of 100 or fewer. Computed tomography (CT) was the most common modality (n = 67), followed by magnetic resonance (MR; n = 22), and X-ray (XR; n = 11). Neuroradiology (n = 48) and abdominal radiology (n = 36) were the most common subspecialties. The 100 top-cited articles in the radiology of trauma are diverse. Subspecialty bibliometric analyses identify the most influential articles of a particular field, providing more implications to clinical radiologists, trainees, researchers, editors, and reviewers than radiology-wide lists.


Characterization of new β-galactosidase from acidophilic fungus, Teratosphaeria acidotherma AIU BGA-1.
The β-galactosidase exhibiting high activity from an extremely acidic pH region to neutral pH region was efficiently purified from an acidophilic fungus, Teratosphaeria acidotherma AIU BGA-1, using affinity chromatography with Toyopearl resins immobilized 4-aminophenyl-β-d-galactopyranoside. The enzyme was stable in the pH range from 1.5 to 7.0, and exhibited optimal activity at pH 2.5-4.0 and 70°C. 2-Nitrophenyl-β-d-galactopyranoside, 4-nitrophenyl-β-d-galactopyranoside and lactose were rapidly hydrolyzed, and the apparent Km values were estimated to be 0.19 mM, 1.2 mM and 170 mM, respectively. Thus, the enzyme can be used in the wide pH range for hydrolysis of lactose. The molecular mass of the enzyme was estimated to be 140 kDa with two hetero subunits of 86 kDa and 50 kDa. The N-terminal amino acid sequence of the small subunit was found to be NTRMIIFNDK. These enzymatic and physicochemical characteristics are remarkably different from those of the previously known β-galactosidases.


Utility of intrathoracic impedance monitoring in pediatric and congenital heart disease.
The utility of cardiac device-based intrathoracic monitoring (OptiVol, Medtronic Inc., Minneapolis, MN, USA) for congestive heart failure (CHF) exacerbation has not been evaluated in pediatric or congenital heart disease patients. This was a retrospective study of all patients at a single center with an endocardial OptiVol capable device. OptiVol index values were collected in 2-week bins from January 2007 to December 2010. The clinical outcomes were CHF exacerbation defined as hospitalization or medication change for CHF and device-treated ventricular arrhythmia based on remote or in-office device interrogation. Clinical and OptiVol data were collected by separate investigators blinded to the other parameter. OptiVol data were correlated to the clinical outcomes to determine sensitivity and predictability for multiple threshold values in the entire cohort and pediatric and congenital subgroups. Forty-seven patients were included. A total of 1,106 months of OptiVol data were collected. Median age of the cohort was 18 years (range 6-58 years). There were 23 pediatric, median age 13 years (range 6-16), at device implant, and 18 patients, median age 31 years (range 13-58), considered at risk for heart failure at implant. There were three heart failure exacerbations and 17 treated ventricular arrhythmias. The study population-specific positive predictive value (PPV) of OptiVol was low (sensitivity 33% and PPV ≤4.4%) for both CHF exacerbation and arrhythmias in all analyzed groups. The sensitivity and positive predictive value of intrathoracic impedance monitoring was low in this population of adult congenital and pediatric patients. Recent improvements to the OptiVol algorithm may decrease these deficiencies.


Deleterious mutations in exon 1 of MECP2 in Rett syndrome.
The MECP2 gene is responsible for 80-85% of typical cases of Rett syndrome with deleterious mutations affecting exons 3 and 4. Recently, an alternate transcript including exon 1 was discovered with a new protein isoform (MeCP2_e1) much more abundant in brain. We screened exon 1 of MECP2 for mutations and for large rearrangements in a panel of 212 typical cases of Rett syndrome and one family case with atypical Rett syndrome. We identified two deleterious mutations (c.48_55dup and c.62+2_62+3del) and four large rearrangements encompassing exon 1 of MECP2. We also identified the c.16_21dup alteration formerly reported as c.3_4insGCCGCC and give additional support to classify this sequence variation as polymorphic. In our large panel of typical Rett, mutations affecting exon 1 of MECP2 represent 1% of the deleterious alleles. This study confirms that mutations in exon 1 of MECP2 are a rare cause of Rett syndrome.


Tuning of photoreceptor function in three mantis shrimp species that inhabit a range of depths. II. Filter pigments.
Within single species of stomatopod crustaceans, visual pigment classes of homologous photoreceptors throughout the retina are identical in all individuals and do not vary with the spectral characteristics of local habitats. We examined whether spectral sensitivities of stomatopod photoreceptors are differentially tuned through variations in the filter pigments associated with particular receptor classes. All classes of intrarhabdomal filters were characterized using microspectrophotometry in retinas of three stomatopod species, Haptosquilla trispinosa, Gonodactylellus affinis, and Gonodactylopsis spongicola, comparing individuals of each species collected from shallow or deep water. Depending on the depth of collection, filters varied among individuals both in optical density and in spectral shape, and the variation that was observed was similar in all three species. The changes in filter density and spectrum increased absolute sensitivity in retinas of animals living at greater depths, and tuned their long-wavelength photoreceptors for improved function in the bluer light available in deep water. Plasticity in retinal spectral function may be common in mantis shrimp species that occupy a range of habitat depths.


Controlled electrophoretic deposition of multifunctional nanomodules for bioelectrochemical applications.
The design of an electrochemical glucose sensing device formed by the electrodeposition of multifunctional Au nanoparticles is reported here as a novel concept for an enhanced generic sensing platform. Initially gold nanoparticles (Au) were alternatively coated with a layer of positively charged redox polymer (ORP) and a negatively charged glucose oxidase (GOX) layer alternatively using layer-by-layer methodology to form multifunctional Au/ORP/GOX/ORP particles. The modification and stability of the Au nanoparticles was monitored by using UV-vis spectroscopy and zeta-potential measurements. The modified Au nanoparticles were electrophoretically deposited onto an electrode to produce an electrochemical glucose sensing device. A considerable influence of electrophoretic deposition time and potential was found on the sensing platform response. Preliminary responses to glucose addition showed an enhanced performance by applying an electrophoretic deposition potential of +1.2V vs. Ag/AgCl for 30 min. The observed response in the case of microelectrode geometry was in the range of mAcm(2). This work also shows that the presence of a second outer ORP layer on the functionalised Au nanoparticles improved the response.


Community-Engaged Approaches to Address the Ethical Concerns of Maternal Mental Health Disparities Research.
Participatory research approaches have brought to the forefront the ethical obligations that researchers have towards underserved communities. We describe how a community-academic partnership used community-based participatory research principles and structure to develop a human subjects research protocol and to address the ethical concerns community stakeholders had regarding maternal mental health research with Black women.


Loss of parkin promotes lipid rafts-dependent endocytosis through accumulating caveolin-1: implications for Parkinson's disease.
Parkinson's disease (PD) is characterized by progressive loss of midbrain dopaminergic neurons, resulting in motor dysfunctions. While most PD is sporadic in nature, a significant subset can be linked to either autosomal dominant or recessive mutations. PARK2, encoding the E3 ubiquitin ligase, parkin, is the most frequently mutated gene in autosomal recessive early onset PD. It has recently been reported that PD-associated gene products such as PINK1, α-synuclein, LRRK2, and DJ-1, as well as parkin associate with lipid rafts, suggesting that the dysfunction of these proteins in lipid rafts may be a causal factor of PD. Therefore here, we examined the relationship between lipid rafts-related proteins and parkin. We identified caveolin-1 (cav-1), which is one of the major constituents of lipid rafts at the plasma membrane, as a substrate of parkin. Loss of parkin function was found to disrupt the ubiquitination and degradation of cav-1, resulting in elevated cav-1 protein level in cells. Moreover, the total cholesterol level and membrane fluidity was altered by parkin deficiency, causing dysregulation of lipid rafts-dependent endocytosis. Further, cell-to-cell transmission of α-synuclein was facilitated by parkin deficiency. Our results demonstrate that alterations in lipid rafts by the loss of parkin via cav-1 may be a causal factor of PD, and cav-1 may be a novel therapeutic target for PD.


The burden of primary headache disorders in Zambia: national estimates from a population-based door-to-door survey.
Three headache disorders - migraine, tension-type headache (TTH) and medication-overuse headache (MOH) - are major contributors to population ill-health. Policy-makers need local knowledge of these to guide priority-setting. Earlier we reported the prevalence of these disorders in Zambia; here we describe the burdens attributable to them. This was a cross-sectional population-based survey of adults aged 18-65 years, selected by cluster-randomized sampling in the mostly urban Lusaka Province and mostly rural Southern Province. Interviewers visiting households used a structured questionnaire. Diagnoses made algorithmically applied ICHD-II criteria. Burden enquiry focused on the previous 3 months and the day before interview. Disability was estimated by applying disability weights (DWs) from the Global Burden of Disease Survey 2010. From 1,134 households, 1,085 unrelated adults (450 male, 635 female) were interviewed (refusal rate 4.3%). The gender- and habitation-adjusted 1-year prevalence of migraine was 22.9%, of TTH 22.8%, of headache on ≥15 days/month 11.5%, of probable MOH (pMOH) 7.1%. Reported mean intensity of migraine attacks was 2.7, representing severe pain. People with migraine spent 10.0% of their time in the ictal state (DW: 0.433); they were therefore 4.3% disabled overall. Disability from TTH was much lower. People with pMOH (time with headache: 37.5%; DW: 0.220) were 8.3% disabled overall. Average lost productive time in the preceding 3 months for migraine was 4.1 days from work (6.3% loss) and 4.2 days (4.7% loss) from household work. Losses for pMOH were 4.8 days (7.4% loss) from work and 4.5 days (5.0% loss) from household work. In the population aged 18-65 years (effectively the working population), estimated disability from migraine was 0.98%, with 1.4% of workdays lost, and from pMOH was 0.59%, with 0.53% of workdays lost. Headache yesterday was reported by 28.3% of participants, whose average productivity yesterday was 55.9% of expectation. Zambia loses 1.93% of GDP to headache, and action is required to mitigate this loss and the associated suffering. Structured headache services with their basis in primary care are the most efficient, effective, affordable and equitable solution. They could be implemented within the existing health-care infrastructure of Zambia. These matters require urgent political attention.


Retrograde dissection of the left main coronary artery after endarterectomy: a rare complication.
The case of a 72-year-old woman who died after bypass grafting and endarterectomy of the left anterior descending coronary artery is described. At autopsy a large intramural dissection of the left anterior descending artery that extended proximally to the left main ostium from the endarterectomy site was found. The dissection was associated with clotting of the false lumen and of the graft, and with a myocardial infarct that precipitated this woman's intraoperative death.