Frontoamygdalar Effective Connectivity in Youth Depression and Treatment Response.
Emotion regulation deficits are characteristic of youth depression and are underpinned by altered frontoamygdalar function. However, the causal dynamics of frontoamygdalar pathways in depression and how these dynamics relate to treatment prognosis remain unexplored. This study aimed to assess frontoamygdalar effective connectivity during cognitive reappraisal in youths with depression and to test whether pathway dynamics are predictive of individual response to combined cognitive behavioral therapy plus treatment with fluoxetine or placebo. One hundred seven young people with moderate to severe depression and 94 healthy control participants completed a functional magnetic resonance imaging cognitive reappraisal task. After the task, 87 participants with depression were randomized and received 12 weeks of cognitive behavioral therapy plus either fluoxetine or placebo. Dynamic causal modeling was used to map frontoamygdalar effective connectivity during reappraisal and to assess the predictive capacity of baseline frontoamygdalar effective connectivity on depression diagnosis and posttreatment depression remission. Young people with depression showed weaker inhibitory modulation of ventrolateral prefrontal cortex to amygdala connectivity during reappraisal (0.29 Hz, posterior probability = 1.00). Leave-one-out cross-validation demonstrated that this effect was sufficiently large to predict individual diagnostic status (r = 0.20, p = .003). Posttreatment depression remission was associated with weaker excitatory ventromedial prefrontal cortex to amygdala connectivity (-0.56 Hz, posterior probability = 1.00) during reappraisal at baseline, though this effect did not predict individual remission status (r = -0.02, p = .561). Frontoamygdalar effective connectivity shows promise in identifying youth depression diagnosis, and circuits responsible for negative affect regulation are implicated in responsiveness to first-line depression treatments.


Continuous transcutaneous gas monitoring in adults on regular dialysis treatment.
We tested a transcutaneous (tc) oxygen (O2) and carbon dioxide (CO2) sensor in 15 normal adults and in 20 patients on regular dialysis treatment (RDT). We compared the tc gas values (ptcO2, PtcCO2) with the gas tension values in arterial blood samples (PaO2, PaCO2), in normal adults and in RDT-patients at the end of a 30-min test and six times during RDT. During the test, PtcO2 correlated with PaO2 both in normal adults (r 0.72 p less than 0.01) and in RDT patients (r 0.41 p less than 0.05). PtcCO2 correlated with PaCO2 (r 0.59 in normal adults and r 0.76 in RDT). During 14 acetate dialyses the changes were expressed as % delta from time 0. % delta PaO2 was -12.7 at 60 min, + 4.8 at 240 min; % delta PtcO2 -6.0 at 60 min, + 9.7 at 240 min; % delta PaO2 -17.7 at 240 min, -1.8 1 h later; % delta PtcCO2 was -15.8 at 240 min, -3.2 1 h later. Both in normal adults and in RDT, patients there was a good relationship between PtcCO2 and PaCO2 values. In normal adults the absolute PtcO2 values were always lower than PaO2 (-14.4 +/- 10 mmHg); in RDT-patients this difference was more pronounced (-27.6 +/- 15.1) and is probably attributable to the lower Hb levels (6.7 +/- 1.1 vs 12.4 +/- 1.2). During RDT the pattern was the same between tc and gas tension values.(ABSTRACT TRUNCATED AT 250 WORDS)


Upregulation of Homer1a Promoted Retinal Ganglion Cell Survival After Retinal Ischemia and Reperfusion via Interacting with Erk Pathway.
Retinal ischemia and reperfusion (I/R) is extensively involved in ocular diseases, causing retinal ganglion cell (RGCs) death resulting in visual impairment and blindness. Homer1a is considered as an endogenous neuroprotective protein in traumatic brain injury. However, the roles of Homer1a in RGCs I/R injury have not been elucidated. The present study investigated the changes in expression and effect of Homer1a in RGCs both in vitro and in vivo after I/R injury using Western blot, TUNEL assay, gene interference and overexpression, and gene knockout procedures. The levels of Homer1a and phosphorylated Erk (p-Erk) increased in RGCs and retinas after I/R injury. Upregulation of Homer1a in RGCs after I/R injury decreased the level of p-Erk, and mitigated RGCs apoptosis. Conversely, downregulation of Homer1a increased the level of p-Erk, and augmented RGCs apoptosis. Furthermore, inhibition of the p-ERK reduced RGCs apoptosis, and increased the expression of Homer 1a after I/R injury. Finally, the retinas of Homer1a KO mice treated with I/R injury had significantly less dendrites and RGCs, compared with Homer1a WT mice. These findings demonstrated that Homer1a may contribute to RGCs survival after I/R injury by interacting with Erk pathway.


GABA metabolism in cultured glial cells.
GABA-transaminase has been characterized in cultured astrocytes. It is identical to the synaptosomal and perikaryal enzyme in terms of charge, molecular weight, and stability, but it differs in its affinity for GABA, which is much higher in the glial compartment. GABA-transaminase has been shown to be inducible by high GABA concentrations, which suggests that astrocytes have the possibility not only to transport GABA but also to metabolize the amino acid which is taken up.


Nox4 oxidase overexpression specifically decreases endogenous Nox4 mRNA and inhibits angiotensin II-induced adventitial myofibroblast migration.
The vascular adventitia is emerging as an important modulator of vessel remodeling. Adventitial myofibroblasts migrate to the neointima after balloon angioplasty, contributing to restenosis. We postulated that angiotensin II (Ang II) enhances adventitial myofibroblast migration in vitro via reduced nicotinamide-adenine dinucleotide phosphate oxidase-derived H(2)O(2) and that Nox4-based oxidase promotes migration. Ang II increased myofibroblast migration in a concentration-dependent manner, with a peak increase of 1023+/-83%. Rat adventitial myofibroblasts were cotransfected with human Nox4 and human p22-phox plasmids or an empty vector. PCR showed an 8-fold increase in human Nox4 and human p22-phox plasmid expression. Using RT-PCR with primers specifically designed for rat reduced nicotinamide-adenine dinucleotide phosphate oxidases, endogenous Nox levels were determined. Ang II decreased endogenous Nox4 and Nox1 mRNA to 41% and 27% of control, respectively, but had no effect on Nox2. Cotransfection with human Nox4 and human p22-phox plasmids combined with Ang II reduced endogenous Nox4 mRNA levels (37+/-5% of control; P<0.05), whereas it had no significant effect on Nox1 or Nox2. In empty vector-transfected cells, Ang II increased myofibroblast migration by 192+/-32% versus vehicle (P<0.01) while increasing H(2)O(2) (473+/-22% versus control; P<0.001). Cotransfection with human Nox4 and human p22-phox plasmids decreased Ang II-induced migration (46+/-6%; P<0.001) in parallel with attenuation of H(2)O(2) production (23+/-8% versus empty vector; P<0.05). Our data suggest that Nox4 promotes Ang II-induced myofibroblast migration via an H(2)O(2)-dependent pathway. The data also suggest that Nox4 causes feedback inhibition of its own expression in adventitial myofibroblasts.


Mental illness and social integration among suicide attempters in Copenhagen. Comparison with the general population and a four-year follow-up study of 100 patients.
In order to describe a population of suicide attempters in an affluent suburb of Copenhagen, 100 patients were interviewed, randomly chosen from a group of 246 patients referred to psychiatric consultation after a suicide attempt. The group consisted of 71 women and 29 men. Single status, abuse, and previous suicide attempts occurred frequently as did suicide among first-degree relatives. The most frequent reason for a suicide attempt was conflict with partners. In comparison with the normal population in the same catchment area, the patients were alone and felt lonely, but no difference was found in the group's relation to the labor market. After a four-year follow-up period, 9 persons had died by suicide. Borderline personality disorder and affective psychosis, no employment, 2 or more previous attempts, violent method and potential lethal attempt proved to be predictors of suicide later on. Alcohol and drug abuse, lack of social support and loneliness did not influence the risk.


The optimal diagnostic criteria of endogenous hyperinsulinemic hypoglycemia based on a large cohort of Chinese patients.
An end-of-fast insulin level ≥ 3 µIU/ml, C-peptide level ≥ 0.6 ng/ml, and proinsulin level ≥ 5 pmol/l with end-of-fast glucose level ≤ 3.0 mmol/l have been established as the criteria for endogenous hyperinsulinemic hypoglycemia. However, all these criteria have been proposed based on patients in Western populations. This study aimed to determine the optimal criteria using a large series of Chinese patients. This retrospective study comprised 144 patients with surgically proven insulinoma and 40 controls who underwent a 72-h fasting test at the Peking Union Medical College Hospital(PUMCH) from 2000 to 2020. Receiver operating characteristic curves were used for analysis. In this series of patients, the optimal diagnostic criteria for endogenous hyperinsulinemic hypoglycemia were insulin ≥ 5.5 μIU/ml, C-peptide ≥ 0.7 ng/ml, and proinsulin ≥ 12 pmol/l with end-of-fast glucose ≤ 2.8 mmol/l; the sensitivity and specificity were 99% and 100% for insulin, 100% and 100% for C-peptide, and 93% and 100% for proinsulin, respectively. The diagnostic efficacy of the criteria based on Western populations was then tested. The sensitivity and specificity of end-of-fast insulin ≥ 3 μIU/ml, C-peptide ≥ 0.6 ng/ml, and proinsulin ≥ 5 pmol/l with end-of-fast glucose ≤ 3.0 mmol/l were 100% and 83%, 100% and 80%, and 97% and 78%, respectively. New and optimized diagnostic criteria for endogenous hyperinsulinemic hypoglycemia in Chinese populations have been proposed, and these criteria yield satisfactory accuracy.


Synthesis and aggregation properties of a novel enzymatically resistant nucleoamino acid.
In this work, we describe the synthesis, evaluation of some biological properties, such as DNA- and RNA-binding ability and in sero stability, as well as the supramolecular assembly of a novel nucleoamino acid based on L-spinacine. More particularly, a thymine-containing L-spinacine derivative was synthesized in liquid phase by a simple peptide-coupling procedure. Subsequently, nucleic acid and Cu(2+)-binding ability, as well as self-assembly properties of the novel nucleoamino acid, were investigated by spectroscopy (CD and UV) and laser light scattering which furnished interesting information on the assembly of supramolecular networks based on the peptidyl nucleoside analog. Finally, nucleoamino acid enzymatic stability was studied and a half life of about 7 days was found in the presence of fresh human serum.


Evidence of complement dysregulation in outer retina of Stargardt disease donor eyes.
Stargardt macular degeneration (STGD) is a central blinding disease caused by loss of or dysfunctional ABCA4 transporter in both photoreceptors and retinal pigment epithelial (RPE) cells. Toxic bisretinoid-lipofuscin buildup in the RPE cells is a pathological hallmark of STGD patients and its mouse model, the Abca4-/-. These vitamin A-derived fluorophores have been shown to induce oxidative stress, stimulate complement activity, and cause chronic inflammation of the RPE. In vivo modulation of complement regulatory pathway in the STGD mouse model has partially rescued the STGD phenotype suggesting that complement attack on the RPE is an important etiologic factor in disease pathogenesis. While bisretinoid-dependent complement activation was further evidenced in cultured RPE cells, this pathway has never been investigated directly in the context of RPE from STGD donor eyes. In the current study, we evaluate the complement reactivity in postmortem donor eyes of clinically diagnosed STGD patients. All three STGD donor eyes RPE displayed strong immunoreactivity for an antibody specific to 4-Hydroxynonenal, a lipid peroxidation byproduct. Also, unlike the control eyes, all three STGD donor eyes showed significantly increased membrane attack complex deposition on the RPE cells. In STGD eyes, increased MAC accumulation was mirrored by elevated C3 fragments internalized by the RPE and inversely correlated with the levels of complement factor H, a major complement regulatory protein. Here, we report the first direct evidence of RPE complement dysregulation as a causative factor in developing Stargardt phenotype.


What impact could DMPA use have had in South Africa and how might its continued use affect the future of the HIV epidemic?
Some studies suggest that use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) may increase susceptibility to HIV infection. We aim to determine the influence that such an association could have had on the HIV epidemic in South Africa. We simulate the heterosexual adult HIV epidemic in South Africa using a compartmental model stratified by age, behavioural risk group, sex, male circumcision status and contraceptive use. We model two possible scenarios: (1) The "With Effect" scenario assumes that DMPA increases susceptibility to HIV infection by 1.20-fold (95% confidence interval 1.06 to 1.36) based on a combination of the results of a recent randomised controlled trial (ECHO trial) and a number of observational studies. (2) The "No Effect" scenario assumes that DMPA has no effect on HIV acquisition risk. We calculate the difference in HIV-related outcomes between the With Effect and No Effect scenarios to determine the potential impact that DMPA use could have had on the HIV epidemic. A causal association between DMPA and HIV acquisition could have caused 430,000 (90% of model runs 160,000 to 960,000) excess HIV infections and 230,000 (90,000 to 470,000) AIDS deaths in South Africa from 1980 to 2017. These figures represent 4.3% (1.6% to 9.6%) and 6.9% (2.6% to 15.2%) of the total modelled estimates of HIV infections and AIDS deaths respectively in South Africa in that period. Of the additional infections, 36% (25% to 48%) would have occurred among men. If DMPA use continues at current levels, a potential causal association could cause an additional 130,000 (50,000 to 270,000) infections between 2018 and 2037. The excess infections would have required an additional 640,000 (190,000 to 1,660,000) years of ART from 1980 to 2017, and a further 2,870,000 (890,000 to 7,270,000) years of ART from 2018 to 2037. If there is a causal association between DMPA use and HIV risk, it could have substantially increased the scale of the HIV epidemic in South Africa, affecting not only the users of DMPA, but also their partners and the wider population. The magnitude of this potential effect demands careful data collection and a careful consideration of policy choices for contraception in settings with large HIV epidemics.


Surgical Treatment of Prosthetic Joint Infections of the Hip and Knee: Changing Paradigms?
Prosthetic joint infection (PJI) of the hip and knee remains one of the most common and feared arthroplasty complications. The impact and cost of PJI is significant, both to the patient and to the health care system. Recent reports of results of different treatment strategies have led many surgeons to modify their approach to management of PJI. This paper will explore apparent paradigm shifts, both to indications and technique, including the importance of waiting for bacterial identification, the decreasing role for irrigation and debridement (I&D) with retention of components, the increased utilization of single stage revision, and conversely a decreasing role for two-stage exchange. Strategies for treating drug-resistant organisms and management of failed treatment will also be examined.


Mode of action of the xylan-degrading enzymes from Aspergillus awamori on alkali-extractable cereal arabinoxylans.
Alkali-extractable cereal arabinoxylan and oligosaccharides of known structure derived from it by enzymic hydrolysis were treated with endo-(1-->4)-beta-D-xylanases I and III from Aspergillus awamori CMI 142717 and the digests subjected to analysis by high performance anion-exchange chromatography. Clear differences in the mode of action of the two endo-(1-->4)-beta-D-xylanases were observed. When counting from the reducing end, at least one unsubstituted xylopyranosyl residue adjacent to singly substituted xylopyranosyl residues or two unsubstituted xylopyranosyl residues adjacent to doubly substituted xylopyranosyl residues cannot be removed by endo-(1-->4)-beta-D-xylanase I. At least two unsubstituted xylopyranosyl residues adjacent to singly or doubly substituted xylopyranosyl residues cannot be removed by endo-(1-->4)-beta-D-xylanase III. beta-D-Xylosidase from the same xylanolytic system was able to remove terminal xylopyranosyl residues from the nonreducing end of branched oligosaccharides only when two contiguous unsubstituted xylopyranosyl residues were present adjacent to singly or doubly substituted xylopyranosyl residues.


Development of a high-speed bioaerosol elimination system for treatment of indoor air.
We developed a high-speed filterless airflow multistage photocatalytic elbow aerosol removal system for the treatment of bioaerosols such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human-generated bioaerosols that diffuse into indoor spaces are 1-10 μm in size, and their selective and rapid treatment can reduce the risk of SARS-CoV-2 infection. A high-speed airflow is necessary to treat large volumes of indoor air over a short period. The proposed system can be used to eliminate viruses in aerosols by forcibly depositing aerosols in a high-speed airflow onto a photocatalyst placed inside the system through inertial force and turbulent diffusion. Because the main component of the deposited bioaerosol is water, it evaporates after colliding with the photocatalyst, and the nonvolatile virus remains on the photocatalytic channel wall. The residual virus on the photocatalytic channel wall is mineralized via photocatalytic oxidation with UVA-LED irradiation in the channel. When this system was operated in a 4.5 m3 aerosol chamber, over 99.8% aerosols in the size range of 1-10 μm were removed within 15 min. The system continued delivering such performance with the continuous introduction of aerosols. Because this system exhibits excellent aerosol removal ability at a flow velocity of 5 m/s or higher, it is more suitable than other reactive air purification systems for treating large-volume spaces.


Resveratrol and curcumin ameliorate di-(2-ethylhexyl) phthalate induced testicular injury in rats.
The present study aimed to evaluate the protective role of resveratrol and curcumin on oxidative testicular damage induced by di-(2-ethylhexyl) phthalate (DEHP). Male Wistar rats were divided into six groups; three groups received oral daily doses of DEHP (2g/kgBW) for 45days to induce testicular injury. Two of these groups received either resveratrol (80mg/kgBW) or curcumin (200mg/kgBW) orally for 30days before and 45days after DEHP administration. A vehicle-treated control group was also included. Another two groups of rats received either resveratrol or curcumin alone. Oxidative damage was observed by decreased levels of total antioxidant capacity (TAC) and glutathione (GSH) and increased malondialdehyde (MDA) level in the testes of DEHP-administered rats. Serum testosterone level as well as testicular marker enzymes activities; acid and alkaline phosphatases (ACP and ALP) and lactate dehydrogenase (LDH) showed severe declines. DEHP administration caused significant increases in the testicular gene expression levels of Nrf2, HO-1, HSP60, HSP70 and HSP90 as well as a significant decrease in c-Kit protein when compared with the control group. Histopathological observations provided evidence for the biochemical and molecular analysis. These DEHP-induced pathological alterations were attenuated by pretreatment with resveratrol and curcumin. We conclude that DEHP-induced injuries in biochemical, molecular and histological structure of testis were recovered by pretreatment with resveratrol and curcumin. The chemoprotective effects of these compounds may be due to their intrinsic antioxidant properties along with boosting Nrf2, HSP 60, HSP 70 and HSP 90 gene expression levels and as such may be useful potential tools in combating DEHP-induced testicular dysfunction.


A tailored intervention does not reduce low value MRI's and arthroscopies in degenerative knee disease when the secular time trend is taken into account: a difference-in-difference analysis.
To evaluate the effectiveness of a tailored intervention to reduce low value MRIs and arthroscopies among patients ≥ 50 years with degenerative knee disease in 13 Dutch orthopaedic centers (intervention group) compared with all other Dutch orthopaedic centers (control group). All patients with degenerative knee disease ≥ 50 years admitted to Dutch orthopaedic centers from January 2016 to December 2018 were included. The tailored intervention included participation of clinical champions, education on the Dutch Choosing Wisely recommendation for MRI's and arthroscopies in degenerative knee disease, training of orthopaedic surgeons to manage patient expectations, performance feedback, and provision of a patient brochure. A difference-in-difference analysis was used to compare the time trend before (admitted January 2016-June 2017) and after introduction of the intervention (July 2017-December 2018) between intervention and control hospitals. Primary outcome was the monthly percentage of patients receiving a MRI or knee arthroscopy, weighted by type of hospital. 136,446 patients were included, of whom 32,163 were treated in the intervention hospitals. The weighted percentage of patients receiving a MRI on average declined by 0.15% per month (β = - 0.15, P < 0.001) and by 0.19% per month for arthroscopy (β = - 0.19, P < 0.001). However, these changes over time did not differ between intervention and control hospitals, neither for MRI (β = - 0.74, P = 0.228) nor arthroscopy (β = 0.13, P = 0.688). The extent to which patients ≥ 50 years with degenerative knee disease received a MRI or arthroscopy declined significantly over time, but could not be attributed to the tailored intervention. This secular downward time trend may reflect anoverall focus of reducing low value care in The Netherlands. III.


Rho-kinase mediates spinal nitric oxide formation by prostaglandin E2 via EP3 subtype.
Prostaglandin E2 (PGE2), the principal pro-inflammatory prostanoid, is known to play versatile roles in pain transmission via four PGE receptor subtypes, EP1-EP4. We recently demonstrated that continuous production of nitric oxide (NO) by neuronal NO synthase (nNOS) following phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS) and NMDA receptor NR2B subunits is essential for neuropathic pain. These phosphorylation and nNOS activity visualized by NADPH-diaphorase histochemistry were blocked by indomethacin, a PG synthesis inhibitor. To clarify the interaction between cyclooxygenase and nNOS pathways in the spinal cord, we examined the effect of EP subtype-selective agonists on NO production. NO formation was stimulated in the spinal superficial layer by EP1, EP3, and EP4 agonists. While the EP1- and the EP4-stimulated NO formation was markedly blocked by MK-801, an NMDA receptor antagonist, the EP3-stimulated one was completely inhibited by H-1152, a Rho-kinase inhibitor. Phosphorylation of MARCKS and NADPH-diaphorase activity stimulated by the EP3 agonist were also blocked by H-1152. These results suggest that PGE2 stimulates NO formation by Rho-kinase via EP3, a mechanism(s) different from EP1 and EP4.


Saturated fat consumption and the Theory of Planned Behaviour: exploring additive and interactive effects of habit strength.
The additive and interactive effects of habit strength in the explanation of saturated fat intake were explored within the framework of the Theory of Planned Behaviour (TPB). Cross-sectional data were gathered in a Dutch adult sample (n=764) using self-administered questionnaires and analyzed using hierarchical regression analyses and simple slope analyses. Results showed that habit strength was a significant correlate of fat intake (beta=-0.11) and significantly increased the amount of explained variance in fat intake (R(2-change)=0.01). Furthermore, based on a significant interaction effect (beta=0.11), simple slope analyses revealed that intention was a significant correlate of fat intake for low levels (beta=-0.29) and medium levels (beta=-0.19) of habit strength, but a weaker and non-significant correlate for high levels (beta=-0.07) of habit strength. Higher habit strength may thus make limiting fat intake a non-intentional behaviour. Implications for information and motivation-based interventions are discussed.


Mediating Role of Depression Between Diabetes Management Self-Efficacy and Diabetes Self-Care Behavior Among Elderly Type 2 Diabetes Mellitus Patients in China.
To investigate the current status of diabetes self-care behavior and the association between depression, self-efficacy and self-care in a sample of Chinese elderly type 2 diabetes mellitus (T2DM) patients. A cross-sectional study with a convenient sample including 240 elderly T2DM patients collected the data of demographic characteristics, diabetes self-care behavior, self-efficacy and depression status. The difference of self-care behavior in different sample characteristics was compared by independent t-test. The Personal correlation analysis was employed to examine the correlation of study variables. The method of bootstrap was used to analyze mediating role of depression. Only 22.5% of patients reported better diabetes self-care behavior and depression partly mediated the association between self-efficacy and self-care behavior. The significant coefficient of path a (B = -0.052, p < 0.001) and path b (B = -0.423, p < 0.05) indicated negative associations of self-efficacy on depression, and depression on self-care behavior. The indirect effect (Path a × b) between self-efficacy and self-care behavior through depression was significant (B = 0.022, p < 0.05), the 95% bias-corrected bootstrap confidence interval was 0.004 to 0.006. Meanwhile, the mediating role of depression was not found significant among the participants reported 60-74 years old (B = 0.104, p < 0.001). But depression completely mediated this association among the participants reported 75-89 years old (B = 0.034, p > 0.05). The level of diabetes self-care behavior among the elderly T2DM patients in Dahu community of Anqing city was hardly optimistic. The self-efficacy focused intervention could be encouraged for community and clinicians to improve diabetes self-care behavior. Moreover, the prevalence of depression and T2DM is increasing in younger population. More work is needed to confirm these findings, especially conducting cohort studies on different populations.


Inner ear function in children with Fabry disease.
The prevalence of hearing loss in patients with Fabry disease is still uncertain. This paper examines hearing loss in a group of young patients with Fabry disease. A clinical ear nose and throat examination, pure-tone air and bone conduction audiometry, speech audiometry and middle ear testing (tympanometry and acoustic reflex testing) were carried out in four girls and two boys with Fabry disease (age, 7-17 years), receiving enzyme replacement therapy (ERT). None of the patients complained of a hearing disorder or suffered from hearing loss. Three female patients reported tinnitus; however, this was not reported as being a problem. One boy reported tinnitus for the first time during 6 months of ERT. Based on this small sample of patients, it appears that the hearing disorders associated with Fabry disease develop mainly in adulthood. Tinnitus may be an earlier symptom than previously thought in Fabry disease.


Evaluation of setting properties and retention characteristics of mineral trioxide aggregate when used as a furcation perforation repair material.
Furcation perforations were created in 32 extracted maxillary and mandibular molars. The perforations were prepared in the center of the pulp chamber floor parallel to the long axis of each tooth and a saline-moistened Gelfoam matrix was placed below the perforation to simulate a clinical condition. The teeth were randomly divided into four groups, and the perforations were all repaired with mineral trioxide aggregate (MTA) and then covered with either a wet or dry cotton pellet for 24 or 72 h. Instron testing was used to measure the force required to displace the material from the perforation. The force measurements showed that MTA resisted displacement at 72 h to a significantly greater level than at 24 h (p < 0.05). When slight displacement occurred at 24 h the material demonstrated the ability to re-establish resistance to dislodgement from the dentin wall. The presence of some moisture in the perforation during placement was advantageous in aiding adaptation of MTA to the walls of the perforation, but there was no significant difference in MTA retention when a wet or dry cotton pellet was placed in the pulp chamber during the setting time (p > 0.05).


High frequency jet ventilation at the distal end of tracheostenosis during flexible bronchoscopic resection of large intratracheal tumor: Case series.
Resection of a large intratracheal tumor with severe obstruction via flexible bronchoscope remains a formidable challenge to anesthesiologists. Many artificial airways positioned proximal to tracheal obstruction can not ensure adequate oxygen supply. How to ensure effective gas exchange is crucial to the anesthetic management. Five patients of intratracheal tumor occupying 70% to 85% of the tracheal lumen were scheduled for tumor resection via flexible bronchoscope. The patients were diagnosed with intratracheal tumor based on their symptoms, radiographic findings and tracheoscopy. We describe a technique of high frequency jet ventilation (HFJV) using an endobronchial suction catheter distal to tracheostenosis during the surgery, which ensured the good supply of oxygen. We applied general anesthesia with preserved spontaneous breathing. A comprehensive anesthesia protocol that emphasizes bilateral superior laryngeal nerve (SLN) block and sufficient topical anesthesia. An endobronchial suction catheter was introduced transnasally into the trachea and then advanced through the tracheostenosis with the tip proximal to the carina under direct vision with the aid of fiber bronchoscope. HFJV was then performed through the suction catheter. The SPO2 maintained above 97% during the surgery. Carbon dioxide retention was alleviated obviously when adequate patency of the trachea lumen achieved about 30 min after the beginning of surgery. HFJV was ceased and all patients had satisfactory spontaneous breathing at the end of the procedure. HFJV at the distal end of tracheostenosis is a suitable ventilation strategy during flexible bronchoscopic resection of a large intratracheal tumor.


Disparities in detection of suspected child abuse.
Child abuse is a significant cause of injury and death among children, but accurate identification is often challenging. This study aims to assess whether racial disparities exist in the identification of child abuse. The 2010-2014 and 2016-2017 National Trauma Data Bank was queried for trauma patients ages 1-17. Using ICD-9CM and ICD-10CM codes, children with injuries consistent with child abuse were identified and analyzed by race. Between 2010-2014 and 2016-2017, 798,353 patients were included in NTDB. Suspected child abuse victims (SCA) accounted for 7903 (1%) patients. Of these, 51% were White, 33% Black, 1% Asian, 0.3% Native Hawaiian/Other Pacific Islander, 2% American Indian, and 12% other race. Black patients were disproportionately overrepresented, composing 12% of the US population, but 33% of SCA patients (p < 0.001). Although White SCA patients were more severely injured (ISS 16-24: 20% vs 16%, p < 0.01) and had higher in-hospital mortality (9% vs. 6%, p = 0.01), Black SCA patients were hospitalized longer (7.2 ± 31.4 vs. 6.2 ± 9.9 days, p < 0.01) despite controlling for ISS (1-15: 4. 5.7 ± 35.7 vs. 4.2 ± 6.2 days, p < 0.01). In multivariate regression, Black children continued to have longer lengths of stay despite controlling for ISS and insurance type. Utilizing a nationally representative dataset, Black children were disproportionately identified as potential victims of abuse. They were also subjected to longer hospitalizations, despite milder injuries. Further studies are needed to better understand the etiology of the observed trends and whether they reflect potential underlying unconscious or conscious biases of mandated reporters. Treatment study. III.


Transcranial Doppler quantification of residual shunt after percutaneous patent foramen ovale closure: correlation of device efficacy with intracardiac anatomic measures.
Percutaneous, mechanical closure of defects of the atrial septum fails to completely resolve shunting in up to 20% of cases. Little is known about the factors associated with device failure. We measured the left atrial opening (X), right atrial opening (Z), tunnel length (Y), septum secundum, device-septum primum separation, and tunnel compressibility of the patent foramen ovale (PFO) in 301 patients with cryptogenic neurological events, PFO anatomy, and severe Valsalva shunting (Spencer Grade 5-5+). All patients then underwent percutaneous closure with the GORE®HELEX Septal Occluder device and were evaluated at 3 months for residual shunt by transcranial Doppler (TCD). Severe residual Valsalva shunt (TCD Grade 5-5+) was found at 3 months in 21 of 301 (7%) patients. X, Y, and Z were associated with failure with a high degree of statistical significance, whereas the width of the septum secundum, device-septum primum separation, and tunnel compressibility were not. An unanticipated finding was that 14 of 35 (40%) patients sized with a large balloon failed compared with 9 of 280 (3%) sized with a small balloon (P < 0.0001). In the multivariate logistic regression model, X (P = < 0.0001) and balloon size (P < 0.0001) were both strong predictors of failure. In an intracardiac echocardiography-defined PFO population, characterized by severe baseline Valsalva shunt and a high incidence of persistent (rest) shunting, association of six intracardiac measurements to closure device failure by multivariate logistic regression showed that the width of the left atrial opening was a strong predictor of residual shunting. An unanticipated finding was that use of a large sizing balloon was also strongly associated with failure.


Antibiotic-associated diarrhea: Clinical characteristics and the presence of Clostridium difficile.
Evidence in Colombia and Latin America has been insufficient for establishing the clinical characteristics of patients with antibiotic-associated diarrhea (AAD). The present study attempts to describe the clinical characteristics of patients with AAD and to determine the presence of Clostridium difficile, utilizing the polymerase chain reaction (PCR) technique. Forty-three patients with AAD, managed at the Hospital Universitario San Ignacio in Bogotá, Colombia, were evaluated. Prospective patient information was collected, with respect to demographic characteristics, profile of the antibiotic management received, clinical manifestations, risk factors, and paraclinical reports. In addition, the real time PCR test for Clostridium difficile (Cepheid Xpert®, Sunnyvale, CA, United States) was performed. Patient mean age was 58 years (19.31 SD). The majority of the patients received 2 or more antibiotics (62.9%) and the beta-lactams were the most frequently used. Hospital stay ranged from 2 to 104 days with a median of 10 days. The most frequent clinical manifestations were abdominal pain and bloating, followed by fever and tachycardia. At the time of diagnosis, 23 patients had noninflammatory results in the stool sample analyses and 18 had kidney failure. The mean level of albumin was 2.4mg/dl (0.7 SD). The presence of Clostridium difficile was documented through PCR in 6 patients (13.95% of the cases). AAD patients were characterized by a high frequency of severe comorbidities and prolonged hospital stay. The presence of Clostridium difficile in only 13.9% of the cases suggests that other causes of diarrhea in the hospitalized patient should be considered.


[Congenital cystic duplication of the stomach--a rare surgical disease].
Duplication of the stomach is a rare congenital disease of the childhood. We report the exceptional manifestation in two adults. The clinical presentation and developmental theory is discussed by reviewing the literature. Today the therapy of choice is resection of the duplication with removal of the adjacent wall of the stomach.


Narcolepsy-cataplexy: how does recent understanding help in evaluation and treatment.
Narcolepsy is a substantially disabling disease with profound physical, mental, and social effects. The burden on patients is compounded by delayed and missed diagnoses and by the subsequent undertreatment of narcolepsy and associated symptoms such as cataplexy. The recent advances in the elucidation of the genetics of canine narcolepsy and the pathophysiologic role of hypocretin, in animals and humans, enhances current diagnostic capability and will provide better treatment modalities in the future. The varied symptoms of narcolepsy are challenging to manage and may require treatment with a combination of agents. The recent development of a markedly enhanced characterization of sodium oxybate in the treatment of the excessive daytime sleepiness, nocturnal sleep fragmentation, and cataplexy of narcolepsy offers the potential of treating multiple symptoms simultaneously and marks a dramatic advance in the treatment of narcolepsy.


Prognostic value of exercise echocardiography in 5,798 patients: is there a gender difference?
This study was designed to determine the effect of gender on the prognostic value of exercise echocardiography. Limited information exists regarding gender differences in prognostic value of exercise echocardiography. We obtained follow-up (3.2 +/- 1.7 years) in 5,798 consecutive patients who underwent exercise echocardiography for evaluation of known or suspected coronary artery disease. There were 3,322 men (mean age 62 +/- 12 years) and 2,476 women (mean age 62 +/- 12 years) (p = 0.7). New or worsening wall motion abnormalities developed with exercise in 35% of men and 25% of women (p = 0.001). Cardiac events, including cardiac death (107 patients) and nonfatal myocardial infarction (148 patients), occurred in 5.3% of men and 3.1% of women (p = 0.001). Addition of the percentage of ischemic segments to the clinical and rest echocardiographic model provided incremental information in predicting cardiac events for both men (chi(2) = 137 to 143, p = 0.014) and women (chi(2) = 72 to 76, p = 0.046). By multivariate analysis, exercise electrocardiographic and exercise echocardiographic predictors of cardiac events in both men and women were workload and exercise wall motion score index. There was no significant interaction effect of rest echocardiography (p = 0.79), exercise electrocardiography (p = 0.38) or exercise echocardiography (p = 0.67) with gender. Although cardiac events occurred more frequently in men, the incremental value of exercise echocardiography was comparable in both genders. Of all exercise electrocardiographic and exercise echocardiographic variables, workload and exercise wall motion score index had the strongest association with outcome. The results of exercise echocardiography have comparable implications in both men and women.


Differential effects of erythrocyte lysates on spectra of potential-sensing carbocyanine dyes.
A recent report by Hladky, S.B. and Rink, T.J. ((1976) J. Physiol. 263, 287--319) demonstrates the binding of a thiocarbocyanine dye (di-S-C3 (5)) to an intracellular constituent from human erythrocytes. Evidence presented below shows that the binding of carbocyanine dyes depends on the particular type of dye used and on the species of erythrocyte from which cellular constituents are prepared. It is recommended that dyes which show minimal binding to intracellular components be used for investigations where carbocyanine dyes are employed as probes of membrane potential.


Changes of total content of serum magnesium in elderly Chinese women with osteoporosis.
To explore whether the serum levels of magnesium (Mg) and calcium (Ca) differ between osteoporotic and nonosteoporotic elderly Chinese women. Using WHO classification criteria based on bone mineral density (BMD), general healthy Chinese women older than 65 yr were classified as osteoporosis (OP), osteopenia, and normal group according to the T-score of the femur neck. Then their physical characteristics, serum levels of magnesium (sMg), calcium (sCa), and other biochemical measurements were analyzed. Altogether, 324 subjects were included in the final analysis with 77 in OP, 137 in osteopenia, 110 in normal group. The level of sMg in women with OP is significantly higher (0.91+/-0.11 mmol/L) than both the osteopenia (0.88 +/- 0.09 mmol/L) and the normal (0.877+/-0.08 mmol/L) even after being adjusted for both age and body mass index (BMI), which might result from potentially low levels of sCa. sMg inversely related to sCa in subjects with OP (r=-0.240, p=0.038), whereas the total levels of sCa and sMg kept relatively steady. High content of sMg and potentially low content of sCa could be a feature of the serum profile of elderly Chinese women with OP, the clinical significance of which needs further elucidation. Supplementation of Mg for elderly Chinese women with OP did not appear to be necessary.


Spermatogenesis in Anthozoa: differentiation of the spermatid.
The fine structure of spermatids has been examined in Calliactis, Protanthea, Gonactinia and Parazoanthus (Cnidaria, Anthozoa). The sperm cells are relatively simple and lack distinct acrosomes. Their nuclei, spherical in the zoanthid, in the actinians are slendertipped cones. Condensation of the chromatin is interpreted in terms of progressive coiling of densely-stained filaments and the elimination of nucleoplasm. Nuclear elongation occurs in the absence of microtubules. A well-developed centriolar complex is attached to the nuclear envelope by fibres and in this area (that of a shallow fossa in actinian spern) the nuclear membranes seem to be thickened. The centrioles are surrounded by a mitochondrial collar, especially pronounced in Calliactis. In contact with the mitochondria and nucleus is a ring of lipid-containing vesicles 300-700 nm in diameter. A system of densely-staining vesicles 150-300 nm in size corresponds to the "pro-acrosomal vesicles" described for other coelenterates. They are scattered in the peripheral cytoplasm and are regarded as derivatives of the endoplasmic reticulum. Problems of organelle function and of differentiation during spermiogenesis are discussed.


Leukocyte myeloperoxidase deficiency and diabetes mellitus associated with Candida albicans liver abscess.
Reported here is a case of hereditary myeloperoxidase deficinecy in a diabetic patient suffering from a Candida albicans liver abscess. Peroxidase activity is completely absent from the neutrophils and monocytes although it is present in the eosinophils. The different forms of myeloperoxidase deficiency are discussed.


A murine model of Nijmegen breakage syndrome.
Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by microcephaly, immunodeficiency, and predisposition to hematopoietic malignancy. The clinical and cellular phenotypes of NBS substantially overlap those of ataxia-telangiectasia (A-T). NBS is caused by mutation of the NBS1 gene, which encodes a member of the Mre11 complex, a trimeric protein complex also containing Mre11 and Rad50. Several lines of evidence indicate that the ataxia-telangiectasia mutated (ATM) kinase and the Mre11 complex functionally interact. Both NBS and A-T cells exhibit ionizing radiation (IR) sensitivity and defects in the intra S phase checkpoint, resulting in radioresistant DNA synthesis (RDS)-the failure to suppress DNA replication origin firing after IR exposure. NBS1 is phosphorylated by ATM in response to IR, and this event is required for activation of the intra S phase checkpoint (the RDS checkpoint). We derived a murine model of NBS, the Nbs1(DeltaB/DeltaB) mouse. Nbs1(DeltaB/DeltaB) cells are phenotypically identical to those established from NBS patients. The Nbs1(DeltaB) allele was synthetically lethal with ATM deficiency. We propose that the ATM-Mre11 complex DNA damage response pathway is essential and that ATM or the Mre11 complex serves as a nexus to additional components of the pathway.


Arthroscopic treatment of ulnar impaction syndrome.
Ulnar impaction syndrome occurs in the setting of a central traumatic or degenerative defect in the triangular fibrocartilage complex in patients with ulnar positive variance. Chondral and subchondral edema, mechanical impingement of the articular disc, and chondromalacia of the distal ulna, proximal lunate, and proximal triquetrum produce symptoms with activity that do not improve with rest. Decreasing ulnocarpal load-sharing across the wrist with recession of the distal ulna is necessary to relieve symptoms in the majority of patients. Arthroscopic treatment with triangular fibrocartilage complex debridement and arthroscopic ulnar wafer resection is an effective treatment for ulnar impaction syndrome. It affords a single-stage, minimally invasive approach, with similar efficacy and fewer complications than open wafer resection or ulnar shortening osteotomy.


Comparison of Aseptic Partial- and Full-Component Revision Total Knee Arthroplasty.
Revision total knee arthroplasty (rTKA) can be performed with isolated tibial, isolated femoral, and combined tibial and femoral component exchange for different indications. Replacement of only 1 fixed component in rTKA leads to shorter operative times and decreased complexity. We sought to compare functional outcomes and rates of rerevision in patients undergoing partial and full rTKA. This retrospective study examined all aseptic rTKA patients with a minimum follow-up of 2 years in a single center between September 2011 and December 2019. Patients were divided into two groups: full rTKA (F-rTKA) if both components (femoral and tibial) were revised and partial rTKA (P-rTKA) if only 1 component was revised. A total of 293 patients (P-rTKA = 76, F-rTKA = 217) were included. P-rTKA patients had significantly shorter surgical time (109 ± 37 Versus. 141 ± 44 minutes, P < .001). At mean follow-up of 4.2 (range 2.2-6.2) years, rerevision rates did not significantly differ between groups (11.8 Versus. 16.1%, P = .358). Improvements in postoperative Visual Analogue Scale (VAS) pain and Knee Injury and Osteoarthritis Scale (KOOS), Joint Replacement scores were similar as well (P = .100 and P = .140, respectively). For patients undergoing rTKA due to aseptic loosening, freedom from rerevision due to aseptic loosening was similar between groups (100 Versus. 97.8%, P = .321). For patients undergoing rTKA due to instability, freedom from rerevision due to instability did not significantly differ as well (100 Versus. 98.1%, P = .683). In the P-rTKA cohort, freedom from all-cause and aseptic revision of preserved components was 96.1% and 98.7% at the 2-year follow-up. Compared to F-rTKA, P-rTKA yielded similar functional outcomes and implant survivorship with shorter surgical time. When indications and component compatibility allow for such a procedure, surgeons can expect good outcomes when performing P-rTKA.


Different localization of inositol 1,4,5-trisphosphate and ryanodine binding sites in rat liver.
The distribution of inositol 1,4,5-trisphosphate and ryanodine binding sites between plasma membrane, microsomal, and mitochondrial fractions of rat liver were compared. IP3 bound mostly to the plasma membrane fraction (Kd = 6 nM; Bmax = 802 fmol/mg protein). Some IP3 binding sites were also present in the microsomal and mitochondrial fractions (Kd = 2.5 and 2.9 nM; Bmax = 35 and 23 fmol/mg protein respectively). The possibility that these binding sites are due to contamination of the fractions with plasma membrane cannot be excluded. Binding of IP3 to the plasma membrane was inhibited by heparin but not by either caffeine or tetracaine. High-affinity ryanodine binding sites were present mostly in the microsomal fraction (Kd = 13 nM; Bmax = 301 fmol/mg protein). Lower affinity binding sites were also found to be present in the mitochondrial and plasma membrane fractions. Binding of ryanodine to the microsomal fraction was inhibited by both caffeine and tetracaine but not by heparin. These data demonstrate that IP3 and ryanodine binding sites are present in different cellular compartments in the liver. These differences in the localization of the binding sites might be indicative of their functional differences.


Measurement of renal volumes with contrast-enhanced MRI.
To determine the accuracy of in vivo magnetic resonance imaging (MRI) measurement of total renal parenchymal volume and medullary fraction. Sixteen kidneys in eight pigs were imaged with a multiphasic contrast-enhanced fast three-dimensional sequence on a 1.5-T imager. Kidney segmentation, followed by a process of signal intensity thresholding for cortical and nephrographic phase datasets, allowed for MRI measurements of parenchymal volume and medullary fraction. Autopsy provided reference standards of renal volume, weight, and medullary fraction. An excellent correlation was found between MRI measurement of total renal parenchymal volume and autopsy volume (R2 = 0.86) and weight (R2 = 0.90). Medullary fraction (mean +/- SD) measured with MRI was 0.120 +/- 0.067, and with autopsy was 0.116 +/- 0.025 (t-test P = 0.84, F-test P = 0.001). MRI measurements of total renal volume are accurate. MRI measurements of medullary fraction show promise, but precision is limited when using a simple signal intensity thresholding algorithm.


Acute Stress Disorder Among Frontline Health Professionals During the COVID-19 Outbreak: A Structural Equation Modeling Investigation.
The outbreak of COVID-19 that commenced in December 2019 in Wuhan, China, has caused extensive public health concerns and posed substantial challenges to health professionals, especially for those in the center of the epidemic. The current study aimed to assess the prevalence, related factors, and mechanism of acute stress disorder (ASD) among health professionals in Wuhan during this critical period. The study used a cross-sectional design. Self-administered questionnaires were distributed to the frontline health professionals in Wuhan hospitals from January 28 to February 1, 2020. Mental health-related measurements included ASD, depression, anxiety, conflict experiences, hostility, and psychosomatic symptoms. Structural equation modeling was used to analyze the factors associated with ASD among health professionals. A total of 332 frontline health professionals were included in the analysis (mean [standard deviation] age = 32.21 [8.77] years; 78.0% women). ASD was a prominent mental health problem in the health professionals surveyed, with a prevalence of 38.3%. Anxiety (24.7%) and depression (20.2%) were also common. Structural equation modeling analyses revealed that emotional distress (i.e., anxiety and depressive symptoms) fully mediated the association between conflicts with ASD (the standardized indirect coefficient β = 0.47, p = .016). The most common reported symptom was chest pain (51.2%). ASD was significantly associated with psychosomatic symptoms. The majority (67.8%) reported being easily annoyed or irritated, and ASD was associated with hostility. During the COVID-19 outbreak, a substantial number of health professionals in Wuhan suffered from ASD. Furthermore, ASD was found to be associated with psychosomatic symptoms as well as the hostility. The poor mental health of health professionals has detrimental impacts both on the well-being of staff in health care systems and may adversely affect the quality of patient care. We call for interventions that aim to relieve the psychological and occupational stress. Considering that most of our participants were young, female frontline health professionals, the results may not be generalized to more heterogenous samples.


Repeated phlebographic examination during and after fibrinolytic therapy with streptokinase and urokinase.
Forty-three patients with deep vein thrombosis were given fibrinolytic therapy with streptokinase and/or urokinase. In all patients the diagnosis was made phlebographically, and repeat phlebography was performed after termination of therapy. Sixty-four of 104 vein segments initially occluded (62%) were partially or completely recanalized. No vein segments particularly suitable for fibrinolytic therapy could be defined. The therapy was as successful in cases in which the thrombosis extended over several segments as in those in which the occlusions involved only one or two segments. Similarly, there was no difference in the success rate for thrombi that were still freely floating and for thrombi that occluded the veins completely. It is recommended that fibrinolytic therapy be given in suitable cases in which clinical symptoms have persisted up to two weeks; in some cases this limit may even be extended up to one month.


Prospective Longitudinal Evaluation of the Peripheral Choroidal Thickness in High-Risk Infants with Retinopathy of Prematurity: A Pilot Study.
The purpose of this study was to prospectively follow up the peripheral choroidal development and thickness for retinopathy of prematurity (ROP) in high-risk premature infants using optic coherence tomography. All infants included in the analysis had an optical coherence tomography (OCT) evaluation, serially over 6 weeks, starting at the first ROP screening exam and at each follow-up screening exam. We included infants born at or earlier than 25 weeks of gestation, weighing less than 700 grams, and those who developed interventricular hemorrhage. We evaluated the choroidal thickness and development, centrally and at the extreme nasal and temporal periphery, for each eye with each ROP screening exam. Changes in the choroidal thickness and the choroidal thickness to retinal thickness ratio (C/R ratio) were evaluated over time not only for each individual infant, but between the infants as well. Six infants met our inclusion criteria. Infants with severe ROP had a mean choroidal thickness that was significantly thinner in the extreme temporal periphery than infants that did not develop significant ROP (P=0.02). The mean value of the C/R ratio was smaller in infants with severe ROP compared to those that did not develop any significant ROP at any of the evaluated locations (P < 0.001). The peripheral choroid appears to be significantly thinner relative to the retinal thickness in infants with severe ROP.


Ophthalmic manifestations of maxillary sinus mucoceles.
Mucoceles involving any of the paranasal sinuses may present with ophthalmic disturbances. Maxillary antral mucoceles can encroach on the inferior orbit with ocular displacement and compression, proptosis or enophthalmos, lower lid distortion, tethering of extraocular muscles, and ptosis. Periocular pain, erosion of the inferior orbital rim, infraorbital nerve compression, epiphora, and inner canthal swellings are other important presentations. Postoperative mucoceles may involve only a portion of the antrum. Five illustrative cases are presented.


Erratum: Application of systematic nursing in patients with maniac access of bipolar disorder and its impact on treatment compliance and quality of life.
[This corrects the article on p. 6929 in vol. 13, PMID: 34306445.].


Histopathological evidence in support of the association of elevated proton spin-lattice relaxation times with the malignant state.
The pulsed nuclear magnetic resonance technique was explored for its potential diagnostic value in human cancer. Measurements of proton spin-lattice relaxation times (T1) of cellular water protons of normal and malignant esophageal tissues showed elevated T1 values in the latter. In some cases, tissues which appeared normal on gross examination assumed as uninvolved tissues had T1 values higher than the other grossly uninvolved tissues and often closer to the T1 of the corresponding tumor tissue. A histopathological study of the assumed uninvolved areas also studied for the T1 values was therefore undertaken. A preliminary study demonstrated the presence of malignant cell groups or clusters in some of the uninvolved samples with higher T1 compared to the true uninvolved tissues, which had a normal histological picture and low T1 values. This observation has brought out the importance of histopathological studies in addition to relaxation studies to comprehend contributory factors to relaxation. Secondly, it lends support to the thesis of elevated T1 values being characteristics of the malignant state.


The impact of early thromboelastography directed therapy in trauma resuscitation.
Conventional coagulation tests do not provide an accurate representation of the complex nature of trauma induced coagulopathy. Thrombelastography provides a prompt global overview of all dynamic sequential aspects of trauma induced coagulopathy. The objective of this study was to evaluate the impact of using thrombelastography on blood products utilization, crystalloids utilization, hospital, and intensive care using length of stay, and cost savings. We retrospectively reviewed 134 patients (May of 2012 to February of 2015) meeting Class I trauma activation. Outcome data was compared between two groups: patients prior to thrombelastography implementation (n = 87) and patients with thrombelastography guided trauma resuscitation (n = 47). Blood product usage was compared for three time periods: first 4 h, the next 20 h, and first 24 h. For the first 24 h of treatment, patients with thrombelastography guided trauma resuscitation had lower packed red blood cells (p = 0.0022) and fresh frozen plasma (p = 0.0474), but higher jumbo pack platelets (p = 0.0476) utilization when compared to the patients prior to thrombelastography implementation. There was no statistical significant difference in the utilization of crystalloids for any of the three time intervals. Patients with thrombelastography guided trauma resuscitation had a shorter hospital length of stay (p = 0.0011) and intensive care unit length of stay (p = 0.0059) than the patients prior to thrombelastography implementation. Cost savings in blood products transfusion were most pronounced in patients with penetrating injuries. Using visco-elastic tests to guide blood transfusion was first used for liver transplant patients and then applied to cardiovascular surgery and trauma. Similar to other studies, this study showed using visco-elastic tests for trauma patietns corresponded to an overall reduction in the use of packed red blood cells and fresh frozen plasma during the first 24 hours of resuscitation. In addition, this study showed using visco-elastic tests corresponded to a significant reduction in both hospital and intensive care unit length of stay. This study demonstrates that Thrombelastography guided trauma resuscitation decreases the overall transfusion requirements of packed red blood cells and fresh frozen plasma. However, given the nature of under-recognized jumbo pack platelets dysfunction in the conventional laboratory parameters, jumbo pack platelets utilization is higher when following Thrombelastography directed resuscitation. The utilization of Thrombelastography corresponded to a reduction in hospital length of stay, intensive care unit length of stay and cost of transfused blood products.


Generation of immune memory by haptenated derivatives of thymus-independent antigens in C57BL/6 mice. I. The differentiation of memory B lymphocytes into antibody-secreting cells depends on the nature of the thymus-independent carrier used for memory induction and/or revelation.
It has been previously reported that trinitrophenylated lipopolysaccharide (TNP-LPS), a thymus-independent (TI)-1 antigen, elicits an anamnestic response to TNP in C57BL/6 mice. The ability of these mice to mount a secondary response to TI-2 antigens was analyzed. Priming with DNP-Ficoll or DNP-Dextran, both TI-2 antigens, resulted in an increased frequency of TNP-binding B lymphocytes. Evidence is presented that memory cell-induction by DNP-Ficoll does not require functional T cells. The differentiation into antibody-forming cells (AFC) of memory cells generated by DNP-Dextran or DNP-Ficoll cannot be obtained by a challenge with either antigen. There was no indication that the lack of a secondary response to TI-2 antigens was related to suppressive T cells interfering with memory expression. Memory cells induced by DNP-Dextran or DNP-Ficoll can nevertheless be activated by TNP-LPS. In contrast to the restricted sensitivity of TNP-memory cells generated by TI-2 antigens, TNP-LPS-induced memory cells are indifferently susceptible to TI-1 or TI-2 antigenic stimulation. These results are discussed in terms of memory B-cell subpopulations.


Kynurenine Pathway in Psoriasis-a Promising Link?
Psoriasis is a common dermatosis which affects the patient's skin and general well-being because of its link to diseases such as depression, kidney disease and metabolic syndrome. Pathogenesis remains unknown; however, genetic, environmental and immunological factors seem to play a role in the development of the disease. Due to a lack of complete understanding of the psoriasis pathology, effective treatment is yet to be developed. The kynurenine pathway is one of the ways amino acid tryptophan is metabolised. In comorbidities typical for psoriasis such as chronic kidney disease, depression and atherosclerotic alterations in the activation of the kynurenine pathway were observed, which were mainly characterised by higher activity compared to that in healthy individuals. However, the kynurenine pathway has not been thoroughly studied among patients with psoriasis even though increased levels of L-kynurenine, one of the enzymes in the kynurenine pathway, were found in psoriatic skin lesions. Given the unknown pathogenesis of the disease, this finding seems to be a potential new field of study and shows a possible link between psoriasis and its comorbidities that could also lead to novel effective treatment for this chronic condition.


Controversial association between polycystic ovary syndrome and breast cancer.
Polycystic ovary syndrome (PCOS) risk factors overlap with breast cancer, and the hormonal profile may be implicated in breast cancer pathogenesis. This study aims to report a literature review considering epidemiological and molecular mechanisms that correlate PCOS and breast cancer, as well as the influence of PCOS treatment on the incidence of breast cancer. Epidemiological studies failed to adjust potential variables that affect the risk and have thus provided inconclusive results. Molecular effects of androgenic pathways in breast cancer have been studied and androgens seem to have an inhibitory effect on mammary epithelial proliferation. However, increased bioavailable androgens were associated with recurrence of breast cancer due to conversion to oestrogens. Sex hormone-binding globulin has a role in hormone-dependent cancers and can be considered a marker for PCOS; a gene profile has already been linked to breast cancer risk in these patients. PCOS medical treatment is a promising tool for stratifying breast cancer risk due to the metabolic influence and hormonal environment. Clinical reports are inconsistent, emphasizing the need for further studies with a prospective design. In the future, the role of pharmacological interventions in PCOS will increase knowledge and awareness of breast cancer pathogenesis and will help to refine breast cancer risk stratification.


Suicide mortality in the city of São Paulo: epidemiological characteristics and their social factors in a temporal trend between 2000 and 2017. Retrospective study.
Suicide is one of the leading causes of death worldwide, accounting for one million deaths annually. Greater understanding of the causal risk factors is needed, especially in large urban centers. To ascertain the epidemiological profile and temporal trend of suicides over two decades and correlate prevalence with social indicators. Descriptive population-based longitudinal retrospective study conducted in the city of São Paulo, Brazil. A temporal trend series for suicide mortality in this city was constructed based on data from the Ministry of Health's mortality notification system, covering 2000-2017. It was analyzed using classic demographic variables relating to social factors. Suicide rates were high throughout this period, increasing from 4.6/100,000 inhabitants in the 2000s to 4.9/100,000 in 2017 (mean: 4.7/100,000). The increase in mortality was mainly due to increased male suicide, which went from 6.0/100,000 to the current 8.0/100,000. Other higher coefficients corresponded to social risk factors, such as being a young adult (25-44 years old), being more educated (eight years of schooling) and having white ethnicity (67.2%). Suicide was also twice as likely to occur at home (47.8%). High suicide rates were seen over the period 2000-2017, especially among young adults and males. High schooling levels and white ethnicity were risk factors. The home environment is the crucial arena for preventive action. One special aspect of primary prevention is the internet and especially social media, which provides a multitude of information for suicide prevention.


Transperineal prostate biopsy with ECHO-MRI fusion. Biopsee system. Initial experience.
The aim of this study is to present our initial experience with the stereotactic echo-MRI fusion system for diagnosing prostate cancer. Between September 2014 and January 2015, we performed 50 prostate biopsies using the stereotactic echo-MRI fusion system. The 3-Tesla multiparameter MR images were superimposed using this image fusion system on 3D echo images obtained with the Biopsee system for the exact locating of areas suspected of prostate cancer. The lesions were classified using the Prostate Imaging Report and Date System. We assessed a total of 50 patients, with a mean age of 63 years (range, 45-79), a mean prostate-specific antigen level of 8 ng/mL (range, 1.9-20) and a mean prostate volume of 52mL (range, 12-118). Prostate cancer was diagnosed in 69% of the patients and intraepithelial neoplasia in 6%. The results of the biopsy were negative for 24% of the patients. The results of the biopsy and MRI were in agreement for 62% of the patients; however, 46% also had a tumour outside of the suspicious lesion. We diagnosed 46% anterior tumours and 33% apical tumours. One patient had a haematuria, another had a haematoma and a third had acute urine retention. Multiparametric prostatic MRI helps identify prostate lesions suggestive of cancer. The Biopsee echo-MRI fusion system provides for guided biopsy and increases the diagnostic performance, reducing the false negatives of classical biopsies and increasing the diagnosis of anterior tumours. Transperineal access minimises the risk of prostatic infection and sepsis.


Engineering the pre-metastatic niche.
The pre-metastatic niche - the accumulation of aberrant immune cells and extracellular matrix proteins in target organs - primes the initially healthy organ microenvironment and renders it amenable for subsequent metastatic cell colonization. By attracting metastatic cancer cells, mimics of the pre-metastatic niche offer both diagnostic and therapeutic potential. However, deconstructing the complexity of the niche by identifying the interactions between cell populations and the mediatory roles of the immune system, soluble factors, extracellular matrix proteins, and stromal cells has proved challenging. Experimental models need to recapitulate niche-population biology in situ and mediate in vivo tumour-cell homing, colonization and proliferation. In this Review, we outline the biology of the pre-metastatic niche and discuss advances in engineered niche-mimicking biomaterials that regulate the behaviour of tumour cells at an implant site. Such oncomaterials offer strategies for early detection of metastatic events, inhibiting the formation of the pre-metastatic niche, and attenuating metastatic progression.


Certain Hermite-Hadamard type inequalities via generalized k-fractional integrals.
Some Hermite-Hadamard type inequalities for generalized k-fractional integrals (which are also named [Formula: see text]-Riemann-Liouville fractional integrals) are obtained for a fractional integral, and an important identity is established. Also, by using the obtained identity, we get a Hermite-Hadamard type inequality.


Super-resolution imaging visualizes the eightfold symmetry of gp210 proteins around the nuclear pore complex and resolves the central channel with nanometer resolution.
One of the most complex molecular machines of cells is the nuclear pore complex (NPC), which controls all trafficking of molecules in and out of the nucleus. Because of their importance for cellular processes such as gene expression and cytoskeleton organization, the structure of NPCs has been studied extensively during the last few decades, mainly by electron microscopy. We have used super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) to investigate the structure of NPCs in isolated Xenopus laevis oocyte nuclear envelopes, with a lateral resolution of ~15 nm. By generating accumulated super-resolved images of hundreds of NPCs we determined the diameter of the central NPC channel to be 41 ± 7 nm and demonstrate that the integral membrane protein gp210 is distributed in an eightfold radial symmetry. Two-color dSTORM experiments emphasize the highly symmetric NPCs as ideal model structures to control the quality of corrections to chromatic aberration and to test the capability and reliability of super-resolution imaging methods.


Genotypes of esterase II determined from frass of Anthonomus grandis Boh. (Coleoptera, Curculionidae).
Esterase II was separated, using gel electrophoresis, from the frass of the cotton boll weevil, allowing genotyping of the individual weevil. The method and its application are discussed.


Changes in hydrocarbon groups, soil ecotoxicity and microbiology along horizontal and vertical contamination gradients in an old landfarming field for oil refinery waste.
Horizontal and vertical contaminant gradients in an old landfarming field for oil refinery waste were characterised with the aim to assess parallel changes in hydrocarbon groups and general, microbiological and ecotoxicological soil characteristics. In the surface soil polar compounds were the most prevalent fraction of heptane-extractable hydrocarbons, superseding GC-FID-resolvable and high-molar-mass aliphatics and aromatics, but there was no indication of their relatively higher mobility or toxicity. The size of the polar fraction correlated poorly with soil physical, chemical and microbiological properties, which were better explained by the total heptane-extractable and total petroleum hydrocarbons (TPH). Deleterious effects on soil microbiology in situ were observed at surprisingly low TPH concentrations (0.3%). Due to the accumulation of polar and complexed degradation products, TPH seems an insufficient measure to assess the quality and monitor the remediation of soil with weathered hydrocarbon contamination.


Trained lay coaches and self-care cognitive-behavioral tools improve depression outcomes.
Identify the key effective components of a depression self-care intervention. Secondary analysis of data from 3 studies that demonstrated effectiveness of a similar depression self-care intervention (n = 275): 2 studies among patients with chronic physical conditions and 1 among cancer survivors. The studies used similar tools, and telephone-based lay coaching. Depression remission and reduction at 6 months were assessed with either PHQ-9 (chronic condition cohorts) or CES-D (cancer survivor cohort). Multiple logistic regression was used to analyze data when the interaction p-value with cohort was < 0.10. The 3 coached cohorts achieved better depression outcomes than usual care. The combination of coaching and joint use of 2 tools based on cognitive-behavioral therapy (CBT) was associated with depression remission and reduction among chronic condition cohorts but not among cancer survivors. Neither the number nor the length of coach calls were associated with outcomes in pooled data. Trained lay coaching and use of CBT-based self-care tools were associated with improved depression outcomes in patients with chronic conditions but not among cancer survivors. Trained lay coaching and CBT tools are key components of depression self-care interventions. Further research is needed on the effective components in cancer survivors.


R-848 triggers the expression of TLR7/8 and suppresses HIV replication in monocytes.
Toll-like receptors (TLR) 7 and 8 are important in single-stranded viral RNA recognition and may play a role in HIV infection and disease progression. We analyzed TLR7/8 expression and signaling in monocytes from HIV-infected and uninfected subjects to investigate a pathway with new potential for the suppression of HIV replication. Eighty-one HIV-infected and uninfected subjects from Liaoning and Henan provinces in China participated in this study. Monocytes were isolated from subjects' peripheral blood mononuclear cells by magnetic bead selection. TLR7 and TLR8 mRNA was measured using quantitative real-time reverse transcriptase PCR. R-848 (resiquimod) was used as a ligand for TLR7 and TLR8 in order to 1) assess TLR7/8-mediated monocyte responsiveness as indicated by IL-12 p40 and TNF-α secretion and 2) to examine HIV replication in cultured monocytes in the presence of R-848. We found that expression of TLR7/8 mRNA in peripheral blood monocytes decreased with disease progression. TLR7 expression was decreased with stimulation with the TLR7/8 agonist, R-848, in vitro, whereas TLR8 expression was unaffected. Following R-848 stimulation, monocytes from HIV-infected subjects produced significantly less TNF-α than those from uninfected subjects, but trended towards greater production of IL-12 than stimulated monocytes from uninfected subjects. R-848 stimulation also suppressed HIV replication in cultured monocytes. Our study provides evidence that the TLR7 and TLR8 triggering can suppress HIV replication in monocytes and lead to postpone HIV disease progression, thereby offering novel targets for immunomodulatory therapy.


A new scheme for biomonitoring heavy metal concentrations in semi-natural wetlands.
This work introduces a semi-natural wetland biomonitoring framework for heavy metal concentrations based on a robust dynamic integration between biological assemblages and relevant biosensors. The cooperative/synergistic scheme developed minimizes uncertainty and monitoring costs and increases reliability of pollution control and abatement. Attention is given to establishing a fully functioning and reliable network approach for monitoring inflows and achieving dose-response relations and calibration of biomonitoring species. The biomonitoring network initially consists of both, biosensors and species, as a validation phase in each wetland of the surveillance area; once the species monitoring efficiency is verified by the biosensors, the biosensor network moves to the next wetland and so on, following a circular pattern until all area wetlands have a fully functional natural monitoring scheme. By means of species recalibration with periodic revisiting of the biosensors, the scheme progressively reaches a quasi steady-state (including seasonality), thus ensuring reliability and robustness. This framework, currently pilot-tested in Voiotia, Greece, for assessing chromium levels, has been built to cover short-, medium- and long-term monitoring requirements. The results gathered so far, support the employment of the proposed scheme in heavy metal monitoring, and, further, arise the need for volunteer involvement to achieve long-term viability.


Oligonucleotides bearing 5-formyl-2'-O-methyluridine: preference in binding affinity to the NF-kappa B (p50)2 homo- and p50/p65 heterodimers.
5-Formyl-2'-O-methyluridine was incorporated into the various positions of oligonucleotide 26-mers containing the NF-kappa B binding sequence. Some of them showed binding selectivity toward the homo- and heterodimers of subunits of NF-kappa B.


Analysis of tissue lipidomics and computed tomography pulmonary fat attenuation volume (CTPFAV ) in idiopathic pulmonary fibrosis.
There is increasing interest in the role of lipids in processes that modulate lung fibrosis with evidence of lipid deposition in idiopathic pulmonary fibrosis (IPF) histological specimens. The aim of this study was to identify measurable markers of pulmonary lipid that may have utility as IPF biomarkers. IPF and control lung biopsy specimens were analysed using a unbiased lipidomic approach. Pulmonary fat attenuation volume (PFAV) was assessed on chest CT images (CTPFAV ) with 3D semi-automated lung density software. Aerated lung was semi-automatically segmented and CTPFAV calculated using a Hounsfield-unit (-40 to -200HU) threshold range expressed as a percentage of total lung volume. CTPFAV was compared to pulmonary function, serum lipids and qualitative CT fibrosis scores. There was a significant increase in total lipid content on histological analysis of IPF lung tissue (23.16 nmol/mg) compared to controls (18.66 mol/mg, p = 0.0317). The median CTPFAV in IPF was higher than controls (1.34% vs. 0.72%, p < 0.001) and CTPFAV correlated significantly with DLCO% predicted (R2 = 0.356, p < 0.0001) and FVC% predicted (R2 = 0.407, p < 0.0001) in patients with IPF. CTPFAV correlated with CT features of fibrosis; higher CTPFAV was associated with >10% reticulation (1.6% vs. 0.94%, p = 0.0017) and >10% honeycombing (1.87% vs. 1.12%, p = 0.0003). CTPFAV showed no correlation with serum lipids. CTPFAV is an easily quantifiable non-invasive measure of pulmonary lipids. In this pilot study, CTPFAV correlates with pulmonary function and radiological features of IPF and could function as a potential biomarker for IPF disease severity assessment.


Influence of contralateral acoustic stimulation on the quadratic distortion product f2-f1 in humans.
Contralateral acoustic stimulation is known to activate the medial olivocochlear system which is capable of modulating the amplification process in the outer hair cells of the inner ear. We investigated the influence of different levels of contralateral broadband noise on distortion product otoacoustic emissions in humans, with a particular focus on the quadratic distortion product at f2-f1. The primary stimulus frequency ratio was optimized to yield maximum f2-f1 level. While the cubic distortion product at 2f1-f2 was not significantly affected during contralateral noise stimulation, the level of f2-f1 was reduced by up to 4.8dB on average (maximum: 10.1dB), with significant suppression occurring for noise levels as low as 40dB SPL. In addition, a significant phase lead was observed. Quadratic distortions are minimal at a symmetrical position of the transfer function of the cochlear amplifier. The observed sensitivity of f2-f1 to contralateral noise stimulation could hence be resulting from a shift of the operating state and/or a change in the gain of the cochlear amplification due to contralateral induced efferent modulation of the outer hair cell properties.


The efficacy of training of stress-coping strategies on marital satisfaction of spouses of veterans with post-traumatic stress disorder.
Marital satisfaction is an important factor in people's quality of life. It has become increasingly crucial in healthcare and health research and is dependent on coping styles of people exposed to traumatic events. The aim of this study was to assess the effectiveness of coping-style training on increasing the marital satisfaction of wives of veterans with post-traumatic stress disorder (PTSD). In this experimental study, 60 subjects were selected from the spouses of veterans with PTSD. The veterans were chosen from the Veterans Foundation of Northern Khorasan Province (Iran) in 2014. In this study, we used the Enrich questionnaire to determine the marital satisfaction of the aforementioned spouses. Subjects were assigned randomly to study and control groups. We used the training package of a Practical Guide for Stress Management according to cognitive behavioral approaches. Cognitive-behavioral group therapy was administered in 90-minute sessions over a 12-week period. We used the paired-samples t-test and ANCOVA to determine the effect of Cognitive Behavior Therapy (CBT) between the two groups. The mean and the standard deviation of age in the study and control groups were 36.8 ± 4.33 years and 35.3 ± 4.7 years, respectively. According to p < 0.005, a significant difference was observed between the subjects in the two groups. Therefore, treatment with cognitive behavioral group therapy showed evidence of clinical improvements in marital satisfaction of the study group. The results of our study showed that methods of coping with stress based on CBT are effective in increasing the marital satisfaction of wives of veterans with PTSD.


Lack of anticonvulsant tolerance with RU 32698 and Ro 17-1812.
Possible development of anticonvulsant tolerance to three benzodiazepine receptor ligands was assessed in mice using an i.v. infusion of pentylenetetrazol as the convulsive stimulus. Extensive tolerance developed rapidly in the case of diazepam (0.35 mg/kg b.d. or 1.5 mg/kg b.d.). No significant tolerance was seen with the imidazopyrimidine derivative RU 32698 (9 mg/kg b.d.) or the partial agonist benzodiazepine Ro 17-1812 (1 mg/kg b.d.) These results provide further support for the hypothesis that partial agonists at the benzodiazepine receptor induce less tolerance than full agonists.


The epigenetic silencing of the estrogen receptor (ER) by hypermethylation of the ESR1 promoter is seen predominantly in triple-negative breast cancers in Indian women.
The proportion of estrogen receptor (ER)-negative and triple-negative (TN) breast cancer in Indian women is higher than that reported in the West, and this difference persists even after their migration to the West. The causes for this significant difference are not entirely clear. Hypermethylation of the ER promoter, an epigenetic alteration, is known to be one of the mechanisms by which the expression of ER is suppressed. Two thirds of breast cancer specimens from an Indian center tested, using the highly sensitive, methylation-specific polymerase chain reaction (MSP) technique, were reported positive. We have used a quantitative assay, the MethyLight, to better assess the extent of methylation in the ESR1 promoter region in 98 breast cancer tumor specimens from Indian women. In addition, the amount of ER transcripts was determined by quantitative reverse transcriptase polymerase chain reaction. Using the stringent cutoff of at least 4% of the target sequence being methylated, 27% of TN tumors were methylated. In addition they demonstrated the highest levels of methylation. In contrast less than 2% ER-positive tumors were hypermethylated. While the proportion of hypermethylated tumors are lower in this study than that estimated using MSP, our results support the notion of increased epigenetic deregulations in ER-negative tumors in general and TN tumors in particular. The development of this assay also permits a rational approach to the selection of patients for clinical trials examining the efficacy of demethylating agents in the treatment of ER-negative breast cancer.


Type II endoleaks after endovascular repair of abdominal aortic aneurysms: fate of the aneurysm sac and neck changes during long-term follow-up.
To evaluate the frequency of type II endoleaks after endovascular aneurysm repair (EVAR) and to compare sac diameter and neck changes in patients with type II endoleak to endoleak-free patients with at least 3-year imaging follow-up. Among 407 consecutive EVAR patients, 109 patients (101 men; mean age 72.1 years, range 55-86) had at least 3-year computed tomography (CT) data and no type I or III endoleak. In this cohort, 49 patients presented with a type II endoleak at some time and 60 patients had no endoleak. Patients with type II endoleaks were further divided into subgroups based on the vessel origin and the perfusion status (persistent or transient). The course of the perfusion status of type II endoleaks and changes in the aneurysm sac diameters, neck diameters, and renal to stent-graft distances (RSD) were evaluated in the defined groups. Reintervention and death rates were also reported. The mean follow-up was 68.1 ± 23.8 months. Compared to the no endoleak group, overall sac diameter increased significantly in the type II endoleak group (p = 0.007), but vessel origin did not have any influence. With regard to the perfusion status of type II endoleaks, aneurysm sac changes were significantly higher (p = 0.002) in the persistent endoleak group. During the study period, the increase in the proximal neck diameter was significantly higher in the no endoleak group compared to the type II endoleak group (p = 0.025). No significant difference was found in RSD changes between the defined groups. Reinterventions were performed in 20 (18.3%) patients (13 for type II endoleak); 2 (1.8%) patients without type II endoleak died of ruptured aneurysm. Persistent type II endoleaks led to significant aneurysm sac enlargement, but without increased mortality or rupture rates.


The effect of angiotensin converting enzyme inhibition of coronary blood flow and hemodynamics in patients without coronary artery disease.
We examined the role of the renin-angiotensin system in the regulation of systemic and coronary vascular tone by studying the effect of converting enzyme inhibition by teprotide on systemic and coronary hemodynamic parameters in 14 normal patients undergoing routine cardiac catheterization. Serial hemodynamic measurements were made before and up to 30 minutes after 1 mg/kg of intravenous teprotide. A significant rise in cardiac index and stroke volume index occurred with a fall in systemic vascular resistance. The increase in cardiac index was related to the level of resting plasma renin activity. Blood pressure, pulmonary artery and left ventricular end-diastolic pressures remained unchanged. Coronary sinus thermodilution blood flow also showed no significant change; however, some patients demonstrated dramatic increase in flow. The change in blood flow was highly correlated with the resting plasma renin activity (r = 0.939 P less than 0.001). The change in coronary vascular resistance and myocardial oxygen consumption were likewise related to the resting plasma renin level. Converting enzyme inhibition produces significant systemic hemodynamic changes in normal patients which implies that the renin-angiotensin system is important in normal cardiovascular homeostasis. The direct relationship between plasma renin activity and coronary blood flow suggests that the renin-angiotensin system may play an important role in coronary vasomotor regulation.


Intrapulmonary pharmacokinetics and pharmacodynamics of high-dose levofloxacin in healthy volunteer subjects.
The objective of this study was to determine the plasma and intrapulmonary pharmacokinetic parameters of intravenously administered levofloxacin in healthy volunteers. Three doses of either 750 mg or 1000 mg levofloxacin were administered intravenously to 4 healthy adult subjects (750 mg) to 20 healthy adult subjects divided into five groups of 4 subjects (1000 mg). Standardised bronchoscopy and timed bronchoalveolar lavage (BAL) were performed following administration of the last dose. Blood was obtained for drug assay prior to drug administration and at the time of BAL. Levofloxacin was measured in plasma, BAL fluid and alveolar cells (ACs) using a sensitive and specific combined high-performance liquid chromatographic tandem mass spectrometric technique (HPLC/MS/MS). Plasma, epithelial lining fluid (ELF) and AC pharmacokinetics were derived using non-compartmental methods. The maximum plasma drug concentration to minimum inhibitory concentration ratio (C(max)/MIC(90)) and the area under the drug concentration curve to minimum inhibitory concentration ratio (AUC/MIC(90)) during the dosing interval were calculated for potential respiratory pathogens with MIC(90) values from 0.03 microg/mL to 2 microg/mL. In the 1000 mg dose group, the C(max) (mean+/-standard deviation (S.D.)), AUC(0-8h) and half-life were: for plasma, 9.2+/-1.9 microg/mL, 103.6 microg h/mL and 7.45 h; for ELF, 25.8+/-7.9 microg/mL, 279.1 microg h/mL and 8.10h; and for ACs, 51.8+/-26.2 microg/mL, 507.5 microg h/mL and 14.32 h. In the 750 mg dose group, the C(max) values in plasma, ELF and ACs were 5.7+/-0.4, 28.0+/-23.6 and 34.2+/-18.7 microg/mL, respectively. Levofloxacin concentrations were significantly higher in ELF and ACs than in plasma at all time points. For pathogens commonly associated with community-acquired pneumonia, C(max)/MIC(90) ratios in ELF ranged from 12.9 for Mycoplasma pneumoniae to 859 for Haemophilus influenzae, and AUC/MIC(90) ratios ranged from 139 to 9303, respectively. The C(max)/MIC(90) ratios in ACs ranged from 25.9 for M. pneumoniae to 1727 for H. influenzae, and AUC/MIC(90) ratios ranged from 254 to 16917, respectively. The C(max)/MIC(90) and AUC/MIC(90) ratios provide a pharmacokinetic rationale for once-daily administration of a 1000 mg dose of levofloxacin and are favourable for the treatment of community-acquired respiratory pathogens.


High-quality reduced graphene oxide by a dual-function chemical reduction and healing process.
A new chemical dual-functional reducing agent, thiophene, was used to produce high-quality reduced graphene oxide (rGO) as a result of a chemical reduction of graphene oxide (GO) and the healing of rGO. Thiophene reduced GO by donation of electrons with acceptance of oxygen while it was converted into an intermediate oxidised polymerised thiophene that was eventually transformed into polyhydrocarbon by loss of sulphur atoms. Surprisingly, the polyhydrocarbon template helped to produce good-quality rGOC (chemically reduced) and high-quality rGOCT after thermal treatment. The resulting rGOCT nanosheets did not contain any nitrogen or sulphur impurities, were highly deoxygenated and showed a healing effect. Thus the electrical properties of the as-prepared rGOCT were superior to those of conventional hydrazine-produced rGO that require harsh reaction conditions. Our novel dual reduction and healing method with thiophene could potentially save energy and facilitate the commercial mass production of high-quality graphene.


Evaluation of discordance measures in oncology studies with blinded independent central review of progression-free survival using an observational error model.
To confirm results obtained from local evaluation at investigational centers, many oncology studies utilize blinded independent central review (BICR) to make assessments of the primary endpoint, progression-free survival (PFS). The comparison of data often leads to large discordances between these observations, casting doubt on the reliability of the estimated treatment effects from these trials. Here we propose new statistics to measure discordance and evaluate their utility to detect bias in the local evaluation of progression relative to the standard measures of discordance. A new observational error model is proposed that can be used to describe the discordance in patient assessments between multiple readers.


Prostatic acid phosphatase and sperm in the post-coital vagina.
Sperm and prostatic acid phosphatase identified in vaginal fluid after an alleged sexual assault constitute important physical evidence useful in courts of law during rape trials. The purpose of this study was to define a normal and abnormal range for acid phosphatase in the post-coital vagina for our emergency department and to compare the sensitivity of acid phosphatase versus sperm in determining recent coitus. Vaginal swabs obtained from 90 patients were analyzed for acid phosphatase activity by the Sigma p-nitrophenyl phosphate technique. Swabs were stored in a bovine albumin preservative broth. Pap smears for sperm identification were also performed. Acid phosphatase values greater than 50, especially those greater than 138 Sigma units/cc, correlated with intercourse within the preceding 24 hours (P .005). Values greater than 20 but less than 50 correlated with intercourse within 48 hours (P .005). The presence or absence of sperm was found to be less sensitive, and correlated poorly with the time since intercourse [of 12 cases less than or equal to 24 hours, 11 were acid phosphatase-positive (91.7%) while seven were sperm-positive (58.4%)].


Bone marrow chimerism breaks the barrier to pancreatic islet transplantation.
In their recent Cell Reports paper, Chang and colleagues report on a successful strategy to achieve durable mixed hematopoietic chimerism that promotes the engraftment and long-term function of pancreatic islet allotransplants in fully immunocompetent mice without immunosuppression.


CD5-induced apoptosis of B cells in some patients with chronic lymphocytic leukemia.
Although B chronic lymphocytic leukemia (B-CLL) is characterized by prolonged survival of CD5(+) B cells in vivo, these cells apoptose spontaneously in vitro. The effect of CD5 ligation on apoptosis was studied in 27 newly diagnosed patients with B-CLL, in relation to the expression of surface IgM (sIgM), CD79b, CD38, CD72 and CD19. B cells from 15 patients (group I) were resistant to anti-CD5-induced apoptosis, whereas apoptosis above spontaneous levels was seen in the remaining 12 studied (group II). Group II was then subdivided on the basis of differences in the time required to reach maximum apoptosis: whilst B cells from seven patients underwent apoptosis by 18 h, those from the remaining five needed 36 h to apoptose. The expression of sIgM, CD5, CD79b and CD38 was higher in group II than group I, suggesting that signaling for apoptosis might operate via CD79, and that CD38 expression was required. As shown by flow cytometry and confirmed by Western blotting, apoptosis was associated with a decrease in the ratios of Bcl-2/Bax and Bcl(XL)/Bax, due to an increase in the level of Bax, but no change in that of Bcl-2. This heterogeneous apoptotic response to CD5 ligation offers an explanation for the incomplete success of anti-CD5 monoclonal therapy, and might help identify patients who would respond to such treatment.


Muscle from grass- and grain-fed cattle differs energetically.
Insufficient acidification results in dark, firm, and dry beef. While this defect is often indicative of a stress event antemortem, muscle tissue may change in response to feeding regime. Longissimus dorsi muscle samples from 10 grain-fed and 10 grass-fed market weight, angus-crossbred beef cattle were collected postmortem. Lower (P < .05) L* and a* values were recorded for steaks from grass-fed cattle. Higher (P < .05) ultimate pH values were noted in lean of grass-fed cattle compared to grain-fed cattle, yet differences in lactate, glycogen and glucose were not detected. Further, increased (P < .05) ultimate pH values and lower (P < .05) lactate accumulations were noted when samples from grass-fed cattle were subjected to an in vitro glycolysis system. Muscle from grass-fed beef possessed nearly two-fold more (P < .05) succinate dehydrogenase and (P < .001) myoglobin than that of grain-fed cattle. These data show lean from grass-fed beef has greater enzymes reflective of oxidative metabolism and suggest dark lean from grass-fed cattle may be a function of more oxidative metabolism rather than a stress-related event antemortem.


Characterization of two divergent adenovirus 31 strains.
Two divergent strains of adenovirus type 31 were analyzed by neutralization test and restriction endonuclease (RE) patterns in an effort to find the basis for their genetic variability. One strain, isolated from the throat of a child in Maryland during an upper respiratory illness in 1968, was partially neutralized by Ad 31 antisera (to 16-fold lower than homologous titer) while its own antiserum fully neutralized prototype Ad 31 virus, but shared only 9% of comigrating RE fragments with Ad 31 prototype (vs. 30% with Ad 18 prototype); however, PCR tests specific for the inverted terminal repeat (ITR) sequence of Ads 12 and 18 were negative. The other strain, recovered from a stool sample from an infant with diarrhea in Georgia in 1979, was inhibited by Ad 31 antiserum to within 4-fold homologous titer, but shared only 15% of comigrating fragments with Ad 31 prototype (vs. 91% with Ad 18 prototype); ITR-specific PCR tests with this virus were positive for Ad 12/Ad 18. These data suggest that both strains are from separate evolutionary lines of Ad 31 unrelated to all other isolates studied to date by RE analysis, and that the partial neutralization by prototype Ad 31 antisera might represent small mutations in the hexon gene.


How can genipin assist gelatin/carbohydrate chitosan scaffolds to act as replacements of load-bearing soft tissues?
In the engineering of soft tissues, designing the scaffolds with adequate strength and controllable biodegradation properties are essential. To fulfill such design criteria gelatin/carbohydrate chitosan (G/CC) scaffolds have gained much attention in engineering replacement of soft tissues. In this research, the influence of different cross-linking methods and parameters with genipin on the physico-chemical properties of G/CC scaffolds was investigated in detail. The scaffolds with different concentrations of G and CC were prepared and cross-linked trough two different methods, and the impact of cross-linker concentration beside of cross-linking time and temperature were fully analyzed. The obtained results suggested that the 1% genipin-cross-linked G60/CC40 scaffolds, prepared at room temperature for 24h through scaffold cross-linking method, could be a promising replacement in missing segments of load-bearing soft tissues. This article describes a systematic study of genipin cross-linking effects on G/CC scaffolds.