Parents' Perceived Barriers to Accessing Sports and Recreation Facilities in Ontario, Canada: Exploring the Relationships between Income, Neighbourhood Deprivation, and Community.
Sports and recreation facilities provide places where children can be physically active. Previous research has shown that availability is often worse in lower-socioeconomic status (SES) areas, yet others have found inverse relationships, no relationships, or mixed findings. Since children's health behaviours are influenced by their parents, it is important to understand parents' perceived barriers to accessing sports and recreation facilities. Data from computer assisted telephone interviews with parents living in Ontario, Canada were merged via postal codes with neighbourhood deprivation data. Multivariable logistic regression modeling was used to estimate the likelihood that parents reported barriers to accessing local sports and recreation facilities. Parents with lower household incomes were more likely to report barriers to access. For each unit increase in deprivation score (i.e., more deprived), the likelihood of reporting a barrier increased 16% (95% CI: 1.04, 1.28). For parents, the relationships between household income, neighbourhood-level deprivation, and barriers are complex. Understanding these relationships is important for research, policy and planning, as parental barriers to opportunities for physical activity have implications for child health behaviours, and ultimately childhood overweight and obesity.


Discriminant analysis of MRI measures as a method to determine the presence of dementia of the Alzheimer type.
Multivariate discriminant analysis of brain volumes obtained from semiautomated magnetic resonance image (MRI) quantification was used in an attempt to identify demented patients very early in the course of the disease. Temporal and posterior frontal brain volumes were quantified from MRIs in a cross-sectional study of 31 male and female patients with dementia of the Alzheimer type (DAT) and 29 age- and sex-matched healthy comparison subjects. Mean scores on the Folstein Mini-Mental State Examination (MMS) were in the mild range for the DAT group (20 +/- 6.6), but patients with moderate and severe dementia were also included (MMS range of entire DAT group = 4-28). Significant mean differences in frontal and temporal lobe brain volumes were found between the DAT group and the age- and sex-matched healthy comparison group, but the sensitivity of any single measure was limited to 87% with a specificity of 83%. Initial multivariate discriminant analysis revealed significant gender differences among the healthy subjects, but not the DAT patients. The large group size allowed for subsequent discriminant analyses to be performed by gender. All healthy subjects and DAT patients were correctly classified by gender-specific discriminant functions. The male discriminant variables included brain volume, age, and temporal lobe measures. Inclusion of age in the male discriminant function accounted for age-related brain atrophy, a finding that may have emerged as a consequence of the broad age range of the male DAT population (50-81 years). The male discriminant function was also successfully applied to an independent group of mildly demented subjects that included patients for whom the diagnosis of dementia was uncertain but verified by follow-up clinical evaluations. Measures of temporal lobe brain matter and temporal lobe cerebrospinal fluid volumes were the significant discriminator variables for the women. Quantitative MRI and multivariate discriminant analysis showed promise in distinguishing the dementing process from healthy aging in a group of 60 subjects. Moreover, while not diagnostic of DAT, the approach appeared to offer additional information about the probability of a diagnosis being later confirmed in patients with very mild dementia for whom the clinical identification of DAT is uncertain.


Household migration and the local public sector: evidence from Sweden, 1981-1984.
"In this paper, the relationship between public sector attributes and household characteristics, and Swedish household migration, 1981-4, is studied. We report results separately for metropolitan and nonmetropolitan areas because the per capita levels of the tax base and intergovernmental grants are theoretically important migration determinants where population is sparse, whilst the tax rate may be more important where population is dense. Because fiscal influences are likely to be stronger for short-distance migration, we apply multinomial logit to a three-way choice set: staying and migrating short and long distances. Empirical results support our fiscal hypotheses and are consistent with previous findings on household characteristics." (SUMMARY IN FRE AND GER)


Towards VO2 monitoring: Validation of a heart rate based algorithm.
This article presents and validates a novel algorithm for the continuous monitoring of the VO2 during exercise. The algorithm relies on instantaneous HR measurements to provide a continuous estimation, and can be integrated in a wearable device (e.g., smartwatch, sensor patch). It can be customized by user's main anthropomorphic parameters and automatically learns from newly incoming data recalibrating itself if needed. The system is evaluated against a database of 14 healthy subjects performing various maximal endurance tests. The proposed method provides a VO2 estimation with average RMSE of 4.63 ml/kg/min.


[The treatment of recent isolated tears of the anterior cruciate ligament (author's transl)].
The authors have observed that the systematic use of arthroscopy results in the discovery of a number of isolated ruptures of the anterior cruciate ligament which could not be diagnosed by clinical examination alone. Twelve such cases have been operated on. The authors believe that the initial trauma was not one of hyper-extension or of forced internal rotation of the tibia. They have shown by biomechanical studies that it was due to an excessive contraction of the quadriceps on the weight-bearing limb with the tibia in internal rotation. They recommend the early use of tendons such as the patellar tendon for the repair of the ligament.


Beneficial effects of dietary EGCG and voluntary exercise on behavior in an Alzheimer's disease mouse model.
Alzheimer's disease (AD) is a progressive, age-dependent neurodegenerative disorder affecting specific brain regions that control memory and cognitive functions. Epidemiological studies suggest that exercise and dietary antioxidants are beneficial in reducing AD risk. To date, botanical flavonoids are consistently associated with the prevention of age-related diseases. The present study investigated the effects of 4 months of wheel-running exercise, initiated at 2-months of age, in conjunction with the effects of the green tea catechin (-)-epigallocatechin-3-gallate (EGCG) administered orally in the drinking water (50 mg/kg daily) on: (1) behavioral measures: learning and memory performance in the Barnes maze, nest building, open-field, anxiety in the light-dark box; and (2) soluble amyloid-β (Aβ) levels in the cortex and hippocampus in TgCRND8 (Tg) mice. Untreated Tg mice showed hyperactivity, relatively poor nest building behaviors, and deficits in spatial learning in the Barnes maze. Both EGCG and voluntary exercise, separately and in combination, were able to attenuate nest building and Barnes maze performance deficits. Additionally, these interventions lowered soluble Aβ1-42 levels in the cortex and hippocampus. These results, together with epidemiological and clinical studies in humans, suggest that dietary polyphenols and exercise may have beneficial effects on brain health and slow the progression of AD.


Bullet markers--a simple technique to assist in the evaluation of penetrating trauma.
Radio-opaque markers in penetrating trauma are useful in both the clinical evaluation of the injuries and in the permanent record of the location of the wounds. The use of an unfolded paperclip taped over the wound as a marker is recommended as a valuable adjunct in the radiological evaluation of penetrating trauma.


Functional characterization of salt-tolerant microbial esterase WDEst17 and its use in the generation of optically pure ethyl (R)-3-hydroxybutyrate.
The two enantiomers of ethyl 3-hydroxybutyrate are important intermediates for the synthesis of a great variety of valuable chiral drugs. The preparation of chiral drug intermediates through kinetic resolution reactions catalyzed by esterases/lipases has been demonstrated to be an efficient and environmentally friendly method. We previously functionally characterized microbial esterase PHE21 and used PHE21 as a biocatalyst to generate optically pure ethyl (S)-3-hydroxybutyrate. Herein, we also functionally characterized one novel salt-tolerant microbial esterase WDEst17 from the genome of Dactylosporangium aurantiacum subsp. Hamdenensis NRRL 18085. Esterase WDEst17 was further developed as an efficient biocatalyst to generate (R)-3-hydroxybutyrate, an important chiral drug intermediate, with the enantiomeric excess being 99% and the conversion rate being 65.05%, respectively, after process optimization. Notably, the enantio-selectivity of esterase WDEst17 was opposite than that of esterase PHE21. The identification of esterases WDEst17 and PHE21 through genome mining of microorganisms provides useful biocatalysts for the preparation of valuable chiral drug intermediates.


The effect of the smoke-free workplace policy in the exposure to secondhand smoke in restaurants, pubs, and discos in San Juan, Puerto Rico.
Tobacco use and the involuntary exposition to secondhand smoke (SHS) is one of the leading causes of all cancers in the world. The objective of this study was to assess the effect of the smoke-free workplace policy implemented in March of 2007 in Puerto Rico on the exposition to secondhand smoke in restaurants, pubs, and discos of the metropolitan area of San Juan, Puerto Rico. The study used a pre-post comparison design on a random sample of 55 establishments (32 restaurants and 23 pubs and discos) in the metropolitan area of San Juan, Puerto Rico. Measurements of indoor concentrations of fine particulate matter (PM) (2.5 mm diameter, PM2.5) were taken before and after the introduction of the law banning smoking using a SidePak AM510 Personal Aerosol Monitor (TSI Company). Also, data on the number of smokers, number of customers, and establishment area was collected. Paired t-tests and linear regression analyses were used to test any statistically significant effect of the law. After the smoking ban was implemented, restaurants experienced an 83.6% (p = 0.013) reduction in the mean of PM 2.5 levels, from 0.169 to 0.028 mg/ m3, and pubs and discos experienced a 95.6% (p = 0.004) reduction, from 0.626 to .028 mg/m3. The implementation of the smoke-free workplace policy considerably reduced the exposition to SHS of workers and customers in the restaurants, pubs, and discos of the metropolitan area of San Juan, Puerto Rico.


Process of neovascularisation compared with pain intensity in tendinopathy of the long head of the biceps brachii tendon associated with concomitant shoulder disorders, after arthroscopic treatment. Microscopic evaluation supported by immunohistochemical.
Tendinopathy of the long head of the biceps brachii tendon (LHBT) is one of the most common, painful conditions of the anterior part of the shoulder and often coexists with rotator cuff tears. Multifactorial aetiopathology of tendi-nopathy is poorly understood; however, several studies indicated that it is seen predominantly in areas with decreased vascularity of the tissue; the pathology is also characterised by expansive and abundant neovascular in-growth. The aim of the study was to investigate the relationship between the neovascularisation of proximal part of the LHBT and pain along the bicipital groove. Tissue material was obtained from 28 patients who underwent a shoulder arthroscopy and experienced pain along the bicipital groove measured using Visual-Analog Scale (VAS) score. CD31 and CD34 molecules were visualised by immunohistochemical method to assess biceps tendon neovascula-risation and quantify it based on a Bonar scoring system. Although all patients reported pain prior to arthroscopy (mean VAS score was 7.5), microscopic examination did not reveal neovascularisation in all cases. Immunohistochemical staining for CD31 and CD34 allowed for very precise visualisation and quantification of neovascularisation; however there was also no correlation between vessels in-growth scores and pain. The obtained data suggest that neovascularisation process in tendino-pathy is not directly related to pain; however, further studies are needed to explain its significance in the LHBT tendinopathy. (Folia Morphol 2018; 77, 2: 378-385).


Caloric restriction improves thermotolerance and reduces hyperthermia-induced cellular damage in old rats.
Adult-onset, long-term caloric restriction (CR) prolongs maximum life span in laboratory rodents. However, the effect of this intervention on an organism's ability to cope with a physical challenge has not been explored. We investigated the influence of CR and aging on stress tolerance in old rats exposed to an environmental heating protocol on two consecutive days. We hypothesized that CR would increase heat tolerance by reducing cellular stress and subsequent accrual of oxidative injury. All calorically restricted rats survived both heat exposures compared with only 50% of their control-fed counterparts. CR also decreased heat-induced radical generation, stress protein accumulation, and cellular injury in the liver. In addition, heat stress stimulated marked induction of the antioxidant enzymes manganese-containing superoxide dismutase and catalase, along with strong nuclear catalase expression in liver samples from rats subjected to CR. In contrast, stress-related induction of antioxidant enzymes was blunted, and nuclear catalase expression was unchanged from euthermic conditions in the control-fed group. These data suggest that CR reduces cellular injury and improves heat tolerance of old animals by lowering radical production and preserving cellular ability to adapt to stress through antioxidant enzyme induction and translocation of these proteins to the nucleus.


Role of thrombomodulin in cancer biology.
Effects of malignancy on haemostasis have long been recognized. The role of coagulation factors, anticoagulants and fibrinolytic agents in cancer biology have emerged more recently. Thrombomodulin is a naturally occurring anticoagulant, expressed by numerous epithelial and lymphovascular tumour cells. It may have a role in tumour metastasis.


[Lymphaticovenous communication in the mammary gland of the female dog].
Lymphaticovenous Communications were searched in the mammary glands of 24 bitches. Injections of indian ink into the interstice of living animals were followed after death by the filling of the veins with latex and barium sulphate. Afterwards, the used techniques were: microdissection, angiography, clarification and histological section. The results obtained would seem to prove the existence of Lymphovenous Anastomoses. The roles of these communications in the canine mammary gland neoplasia are discussed.


Photoregulation of Phosphoenolpyruvate Carboxylase in Salsola soda L. and Other C(4) Plants.
Photoactivation of phosphoenolpyruvate carboxylase was found to occur in several, though not all, C(4) species examined; Salsola soda L. was used for a detailed study of this effect of light.Activity differences between light and darkness are maximized when glycerol (25% v/v) is included in the extraction medium and in the absence of mercaptoethanol. In plants grown in the growth chamber, the night-form of the enzyme, in addition to low activity, shows a positive cooperativity (with phosphoenolpyruvate), which is gradually abolished by light of increasing intensities. This allosteric behavior is absent in plants adapted to a high light environment. Activation and deactivation, under light and darkness respectively, are quite fast, suggesting post-translational regulation. The photoactivation appears to depend on photosynthetic electron flow, since it is saturated at high photon fluxes (around 1000 microeinsteins per square meter per second) and inhibited by 3-(3,4-dichlorophenyl)-1,1-dimethylurea.


Investigations on Green Blends Comprising Biodegradable Polymer and Ionic Liquid.
The green blends of an ionic liquid, 1-ethyl-3-propylimidazolium bis(trifluoromethanesulfonyl)imide {[EPrI][TFSI]}, and a biodegradable polymer, poly(3-hydroxybutyrate) (PHB), were investigated in this study. The influence of an ionic liquid on the crystallization behaviors of a biodegradable polymer was explored. In the blends, the presence of [EPrI][TFSI] decreased the Tg and Tm of PHB. Incorporating [EPrI][TFSI] in the blends reduced the degree of crystallinity of PHB, inferring that the [EPrI][TFSI] weakened the crystallization of PHB. It further showed retarded isothermal and non-isothermal crystallization for PHB with the presence of [EPrI][TFSI]. The smaller K and 1/t0.5 estimated by the Avrami equation for the blends indicated that [EPrI][TFSI] weakened the isothermal crystallization of PHB with exhibiting the slower crystallization rate. The present study also discussed non-isothermal crystallization of the blends. We found that the Mo model, which is generally used to discuss the non-isothermal crystallization, adequately described the non-isothermal behaviors of the [EPrI][TFSI]/PHB blends. By increasing the [EPrI][TFSI] content, the rate-related parameter F(T) systematically increased, inferring a decreased crystallization rate of PHB with the addition of [EPrI][TFSI] in the blends. The FTIR results suggested an ion⁻dipole interaction between [EPrI][TFSI] and PHB. This proposes the occurrence of possible complexation between [EPrI][TFSI] and PHB.


Non-invasive imaging through scattering medium and around corners beyond 3D memory effect.
The three-dimensional (3D) memory effect (ME) has been shown to exist in a variety of scattering scenes. Limited by the scope of ME, speckle correlation technology only can be applied in a small imaging field of view (FOV) with a small depth of field (DOF). In this Letter, an untrained neural network is constructed and used as an optimization tool to restore the targets beyond the 3D ME range. The autocorrelation consistency relationship and the generative adversarial strategy are combined. Only single frame speckle and unaligned real targets are needed for online optimization; therefore, the neural network does not need to train in advance. Furthermore, the proposed method does not need to conduct additional modulation for the system. This method can reconstruct not only hidden targets behind the scattering medium, but also targets around corners. The combination strategy of the generative adversarial framework with physical priors used to decouple the aliasing information and reconstruct the target will provide inspiration for the field of computational imaging.


Apoptosis induction in MDA-MB-435S, Hep3B and PC-3 cell lines by Rheum emodi rhizome extracts.
The study was aimed at evaluating apoptosis induction potentials of methanolic and aqueous extracts of Rheum emodi Wall. ex Meissn. rhizome. The ability of the extracts to induce apoptosis in MDA-MB-435S (human breast carcinoma), Hep3B (human hepatocellular carcinoma) and PC-3 (human prostate cancer) cell lines were tested by ELISA to detect cellular DNA fragmentation. Results obtained from the present study confirm that the extracts target the cancerous cells towards apoptosis. The study concludes that R. emodi possess anticancer metabolites that can be isolated and used as precursors in development of anticancer drugs. Suppression of apoptosis might contribute to tumor development by means of accumulation of continuously proliferating cells. The strategy employed in this study, to induce apoptosis in the tumor cells, could be a potential target of therapeutic intervention of cancers.


Acoustic and long-term average spectrum measures to detect vocal aging in women.
Along the normal aging process, voice tends to become weak, breathy, and loses projection, which may interfere in the communication process. One reliable way to evaluate voice quality is through acoustical analysis using, for instance, the long-term average spectrum (LTAS). The aim of this study was to identify acoustic measures, particularly LTAS's, which characterize vocal aging in women without vocal complaints. For this purpose, 30 elderly and 30 young women were included in this study. All spoke standard Portuguese and none had a history of vocal and laryngeal alterations or respiratory diseases. On the basis of the reading task, in habitual and loud levels, the following parameters were assessed: the equivalent sound level (L(eq)), the speaking fundamental frequency (SFF) and, at the LTAS window, the difference between the levels of the regions of the first formant and fundamental frequency F(0) (L(1) - L(0)), alpha ratio, and the amplitude levels obtained at equal intervals of 160 Hz, ranging from 0 to 8 kHz. There were significant differences between young and old voices for SFF and L(eq) in both levels. In the LTAS window, amplitude levels were higher for young voices, comprising all frequencies except those in the regions between 4.6-6.7 and 4.8-6.5 kHz, in habitual and loud levels, respectively. There were also significant differences regarding L(1) - L(0) and alpha ratio between groups, in both levels.The observed differences in LTAS's slopes, L(1) - L(0) measures, and even L(eq) and SFF measures, may be attributed, to some extent, to lower subglottal pressure or a glottal setting providing a slower glottal closing speed for the elderly group.


Evaluation of treatment-resistant schizophrenia.
A systematic approach to the evaluation and characterization of treatment resistance in schizophrenia has become increasingly important since the introduction of clozapine, risperidone, and olanzapine. The need for accurate evaluation will increase with the introduction of the next generation of antipsychotic medications. People with schizophrenia may manifest a poor response to therapy secondary to intolerance of medication, poor compliance, or inappropriate dosing, as well as true resistance of their illness to antipsychotic drug therapy. Clinicians facing the decision of when to change from one antipsychotic to another must clearly understand the appropriate length of a trial and what target symptoms respond to antipsychotics in order to maximize the response in patients with treatment-resistant schizophrenia.


[Influence of the Parameter "The Rate of Administration" During the Test "Abnormal Toxicity" on Quality Control of Ceftriaxone an Antibiotic of the Cephalosporin Group].
The influence of the rate of administration was examined during the test "Abnormal toxicity" on the quality control of ceftriaxone in a comparative experimental study on the basis of the methodologies Rus. Ph. XII and Eur. Ph. Recommendations are issued for conducting study entitled "Abnormal toxicity" for the formulations of ceftriaxone.


Evaluation of shear bond strength with different enamel pretreatments: an in vitro study.
Bonding procedures are time consuming and debonding of brackets is a common problem encountered in orthodontics. The purpose of this in vitro study was to evaluate the shear bond strength (SBS) with different enamel pretreatment (acid etching, air abrasion, and bur abrasion) to enhance the bonding performance. A total of 60 extracted premolars for orthodontic purposes were randomly assigned to three groups based on conditioning method: Group I - conventional etching with 37% phosphoric acid; Group II - air abrasion with 50 μm aluminum oxide; and Group III - bur abrasion with diamond fissure (#330, MANI, Dia-Burs, New Jersey, USA). After storing the specimens for 24 h in distilled water at 37°C, SBS was measured with Universal testing machine (Lloyd Universal testing machine-Model No. L.R 100K, UK). The shear force at a crosshead speed of 1 mm/min was transmitted to brackets. The adhesive remnant index (ARIs) scores were recorded after bracket failure. Descriptive statistics, multiple comparisons of the SBS of different groups, were performed by analysis of variance. The Tukey's test was used to evaluate differences in ARI scores between groups. All statistical evaluations were calculated using the Statistical Package for Social Sciences Windows, release 10.0.0 (SPSS Inc., Chicago, Illinois, USA). The analysis of SBS variance (P < 0.01) and Chi-square test of ARIs scores (P < 0.01) revealed significant differences among three groups tested. The SBS in Group I (mean: 8.822 ± 0.92 MPa) and Group III (mean: 6.015 ± 0.87 MPa) was significantly higher than Group II (mean: 3.824 ± 0.57 MPa). The ARI was used to evaluate the residual adhesive on the enamel after bracket removal. The Tukey's test was used to evaluate differences in the ARI scores among the groups. The current findings indicate that enamel surface preparation using bur abrasion results in a significant higher than air abrasion; within the limitations of this study recommend bur abrasion as a viable alternative to acid etching.


[Mutation analysis of LITAF, RAB7, LMNA and MTMR2 genes in Chinese Charcot-Marie-Tooth disease.].
The purpose of this study was to understand the mutation features of lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF), ras-associated protein RAB7 (RAB7), lamin A/C (LMNA) and myotubularin-related protein 2 (MTMR2) genes in Chinese Charcot-Marie-Tooth disease (CMT) patients. Mutation analysis of LITAF gene was carried out using PCR combined with DNA sequencing, and mutation analysis of RAB7 gene by PCR-single strand conformation polymorphism (PCR-SSCP) combined with DNA sequencing in 33 CMT patients including 6 probands of autosomal domi-nated CMT families and 27 sporadic patients; mutation analysis of LMNA and MTMR2 genes was observed using PCR-SSCP combined with DNA sequencing in 41 CMT patients, including 14 probands of autosomal recessive CMT fami-lies and 27 sporadic patients. Two sequence variations c.269G-->A and c.274A-->G were detected in LITAF gene and two sequence variations c.1243G-->A and c.1910C-->T were detected in LMNA gene. No sequence variation was found in RAB7 and MTMR2 gene. Variations of c.269G-->A in LITAF gene and c.1243G-->A, c.1910C-->T in LMNA gene are newly found SNPs in this study. Variation of c.274A-->G in LITAF gene is known SNP reported in SNP database. Mutations in LITAF, RAB7, LMNA, and MTMR2 genes are rare in Chinese CMT patients.


[Acute pyelonephritis. Role of diagnostic imaging].
To asses the role of imaging in acute pyelonephritis by retrospectively evaluating a number of cases observed with special care to US and CT signs that may be useful for an early and correct diagnostic assessment. From 1994 to the first quarter of 2000 we observed 95 patients clinically suspected of having acute pyelonephritis (81 females and 14 males, age range 2-80 years; 75% were under 40 years old). Sonography was performed as an emergency in 78 patients. CT scan with contrast media was performed in acute phase in 78 patients acquiring the images in the pre-contrastographic phase, 60 s after the administration of contrast media (portal phase), after 5 to 10 min (excretory phase), and after 3 to 6 hours (very late phase). In 47 patients, diagnosed as having acute pyelonephritis, a follow-up CT scan was performed at 30 days, 45 days, 3 months and 6 months from the acute episode. In 78 of the patients clinically suspected of having acute pyelonephritis, the CT examination allowed to assess the presence or lack of the inflammatory focus. In 17 cases US discovered causes other than acute pyelonephritis on admission; in 25 out of 61 patients it allowed assessment of a pyelonephritic focus that was confirmed with CT. The CT examination with contrast media proved to be a reliable and fondaments method in the diagnosis of pyelonephritic focus especially as it revealed the lack of concentration of contrast media in the flogistic foci, in the very late fase. This method furthermore allows to discover alterations in peri and pararenal regions and to rule out abscesses and renal infarcts. US had a sensitivity of 50% and a specificity of 70% in the diagnosis of acute pyelonephritis, but those may be improved by power Doppler. In suspected acute pyelonephritis US offers useful indications for a quick and correct diagnostic assessment, but CT examination with contrast media proved to be more reliable than US. In our experience US and above all CT examination rapidly identified patients affected by acute pyelonephritis, thereby allowing us institute a timely antibiotic therapy and obtain a brilliant therapeutic response.


The origin of electrochemical activity in Li2MnO3.
The electrochemical activity of Li2MnO3 in non-aqueous media has been investigated and found to involve neither Mn(4+)-Mn5+ oxidation nor simultaneous O2- removal but exchange of Li+ by H+, the latter being generated in the electrolyte.


Frequency Of Non-Diabetic Renal Disease In Type 2 Diabetes Mellitus Patients Undergoing Renal Biopsy.
Diabetes mellitus has become a major emerging health concern. Its burden, estimated to be 451 million in 2017, has been projected to rise to 693 million by 2045. This will bring a rise in the prevalence of its associated complications. There is a wide spectrum of non-diabetic renal disease (NDRD) known to be present in diabetic patients with variable prevalence. However, the majority of diabetes mellitus (DM) patients with renal disease are yet not biopsied and the diagnosis of diabetic nephropathy (DN) is presumed on clinical grounds. It is a retrospective cross-sectional study. We selected a total of 126 cases of renal biopsies with a history of type 2 diabetes mellitus. Demographic data was collected from the medical records and pathology reports while all cases were evaluated by reviewing the archived slides. Patients were categorized into group 1 with isolated NDRD, group 2 showing NDRD mixed with DN and group 3 with isolated DN. Thirty-four (27%) cases had isolated NDRD (group 1), 14 (11%) had NDRD mixed with DN and 78 (62%) patients had isolated DN. NDRD, either alone or in combination with DN, was found to be present in 48 patients with an overall prevalence of 38%. Our study concludes that NDRD is frequent in type 2 diabetes mellitus patients. Renal biopsy remains the key diagnostic tool in such cases, providing crucial information for proper management of the underlying pathology.


Ticagrelor versus prasugrel in diabetic patients with an acute coronary syndrome. A pharmacodynamic randomised study.
Optimal P2Y12 receptor blockade is critical to prevent ischaemic recurrence in patients undergoing percutaneous coronary intervention (PCI). We aimed to compare the level of platelet reactivity (PR) inhibition achieved by prasugrel and ticagrelor loading dose (LD) in diabetic acute coronary syndrome (ACS) patients undergoing PCI. We performed a single-center prospective open-label randomised trial. Patients with diabetes mellitus undergoing PCI for an ACS were randomised to receive prasugrel 60 mg or ticagrelor 180 mg. The primary endpoint of the study was the level of platelet reactivity (PR) assessed between 6 and 18 hours post-LD using the VASP index. We randomised 100 diabetic patients undergoing PCI for an ACS. No difference was observed in baseline characteristics between the two groups. In particular, the rate of patient receiving insulin therapy was identical (25 vs 28.6%; p =0.7). Ticagrelor achieved a significantly lower PR compared to prasugrel loading dose (17.3 ± 14.2 vs 27.7 ± 23.3%; p=0.009). In addition the rate of high on-treatment platelet reactivity, defined by a VASP ≥50%, tend to be lower in the ticagrelor group although the difference did not reach statistical significance (6 vs 16%; p=0.2). The rate of low on treatment PR was identical (60 vs 54%; p=0.8). The present study demonstrates that ticagrelor LD is superior to prasugrel LD to reduce PR in ACS patients with diabetes mellitus. Whether the higher potency of ticagrelor could translate into a clinical benefit should be investigated.


User adoption issues in renal telemedicine.
We carried out a longitudinal survey to evaluate the users' attitudes to the introduction of telemedicine into the dialysis units of a renal ward in South Australia. The first questionnaire was distributed to all members of staff involved with the introduction of the system. There were 44 responses (80%). Staff were fairly positive about the telemedicine system, and felt that it was easy to use and reliable. They also clearly felt that the confidentiality and privacy offered by the system in an open ward were unsatisfactory. A second questionnaire was distributed to all staff about six months later and there were 40 responses (66%). Of these, 22 could be matched with the responses from the first survey (a response rate of 50% from the first sample). There were no significant differences in the staff members' feelings between the two surveys, except in two cases: there were significant changes in staff opinion about the degree of confidentiality (P < 0.05) and privacy (P < 0.01) offered by the system, with attitudes becoming more positive in each case. The results indicate the need for dialogue with users, in order to address their concerns regarding the system and practical difficulties. This study highlights the importance of planning, effort, cooperation and an appropriate culture within a renal unit in order for telemedicine to be accepted.


[Genetic testing in cardiologic diagnostics].
Gene tests may be beneficial in cases of suspected hereditary heart disease or hyperlipidemia. A gene defect can be found in approx. 20% of those with hypertrophic cardiomyopathy in Finland. In the long QT syndrome, four major mutations account for almost three fourths of the Finnish cases. The gene defect causing familial hypercholesterolemia is found in approx. 90% of cases. If the familial gene defect is revealed, DNA testing can be applied to find the symptomless carriers of the mutation who require follow-up, and to liberate those not carrying the mutation from the follow-up.


Basic needs, stress and the effects of tailored health communication in vulnerable populations.
This study examined whether unmet basic needs (food, housing, personal and neighborhood safety, money for necessities) and perceived stress affect recall of and response to a tailored print intervention one month later. Participants (N = 372) were adults who had called 2-1-1 Missouri between June 2010 and June 2012. A series of path analyses using Mplus were conducted to explore the relationships among basic needs, perceived stress, number of health referrals received in a tailored intervention, recalling the intervention and contacting a health referral. Participants were mainly women (85%) and African-American (59%) with a mean age of 42.2 years (SD = 13.3; range 19-86); 41% had annual household income <$10 000. Unmet basic needs were positively associated with increased levels of perceived stress, which, in turn, were negatively associated with recalling the intervention and calling any of the health referrals provided. Tailored printed interventions may be less effective in populations with acute unmet basic needs. More broadly, the effectiveness of minimal contact behavioral interventions might be enhanced by simultaneous efforts to address unmet basic needs.


mTORC1 Signaling Promotes Limb Bud Cell Growth and Chondrogenesis.
mTORC1 signaling has been shown to promote limb skeletal growth through stimulation of protein synthesis in chondrocytes. However, potential roles of mTORC1 in prechondrogenic mesenchyme have not been explored. In this study, we first deleted Raptor, a unique and essential component of mTORC1, in prechondrogenic limb mesenchymal cells. Deletion of Raptor reduced the size of limb bud cells, resulting in overall diminution of the limb bud without affecting skeletal patterning. We then examined the potential role of mTORC1 in chondrogenic differentiation in vitro. Both pharmacological and genetic disruption of mTORC1 significantly suppressed the number and size of cartilage nodules in micromass cultures of limb bud mesenchymal cells. Similarly, inhibition of mTORC1 signaling in chondrogenic ATDC5 cells greatly impaired cartilage nodule formation, and decreased the expression of the master transcriptional factor Sox9, along with the cartilage matrix genes Acan and Col2a1. Thus, we have identified an important role for mTORC1 signaling in promoting limb mesenchymal cell growth and chondrogenesis during embryonic development. J. Cell. Biochem. 118: 748-753, 2017. © 2016 Wiley Periodicals, Inc.


Epstein-Barr virus serology in the control of nasopharyngeal carcinoma.
Epstein-Barr virus (EBV) is suspected as being etiologically related to nasopharyngeal carcinoma (NPC). Antibodies to EBV antigens have been used in the early detection of NPC and serologic assays are being utilized in the mass screening of high risk populations. While areas of potential application to disease control, such as therapy, are still in the developmental phase, EBV serology has been reported to be of value in the detection of early relapse. Since the data from a series of studies provide conflicting results, however, in this report we review the current information regarding detection of early relapse and describe specific areas that require particular attention if the role of EBV serology in this aspect of NPC control is to be well defined.


PEG-Hemoglobin as a resuscitation solution in the treatment of hypovolemic shock in the anesthetized rat.
This study was designed to determine the advantages of using the hemoglobin-based oxygen carrier, polyethylene glycol conjugated bovine hemoglobin (PEG-Hb), as an additive to Ringer's lactate solution (RLS) for the treatment of acute hemorrhage in anesthetized female rats. Different compositions of PEG-Hb and RLS were administered intravenously in a paradigm that provided 30 ml/kg of resuscitation fluid following an episode of 15 min of hypotension. Hypotension was achieved by the removal of blood (1 ml/min) from the femoral vein until the mean arterial pressure was lowered to or below 50 mmHg and subsequently maintained until resuscitation. Short-term cardiovascular assessment showed that resuscitation fluids containing PEG-Hb resulted in higher mean arterial pressure, aortic blood flow, renal blood flow, and less dramatic shifts in arterial base excess and respiratory blood gases than plain RLS. The long-term survival experiment showed lower lactate dehydrogenase, alkaline phosphatase, and serum glutamic pyruvic transaminase levels in most groups resuscitated with solutions containing PEG-Hb, but no differences in survival (100%) were observed. The data suggest that the addition of PEG-Hb to RLS improves its resuscitative effects. Specifically, a solution of 50% RLS:50% PEG-Hb appeared to have the most favorable cardiovascular and metabolic effects in this anesthetized rat hypovolemic shock resuscitation model. Presumably, the improved effects seen with the addition of PEG-Hb were due to its innate plasma expansion and oxygen-delivery capabilities.


Precocious and premature puberty associated with treatment of acute lymphoblastic leukaemia.
Early puberty in 28 children (23 girls, five boys) treated for acute lymphoblastic leukaemia (ALL) at a mean age of 4.0 years (range 1.4-7.8) is described. All but one had received prophylactic cranial irradiation (1800-2400 cGy) and three children had received additional cranial or craniospinal irradiation as treatment for relapse of their leukaemia. Mean age for the onset of puberty was 8.8 (SD 0.8) years in the girls and 9.3 (0.8) years in the boys; this is greater than two standard deviations from the mean for normal girls and boys. Five children (three girls, two boys) had precocious puberty. The onset of puberty occurred at greater than two standard deviations from the mean for normal girls and boys in 14(13%) girls and 4(3%) boys treated at less than eight years of age between 1970 and 1985. In a group of 55 girls treated for ALL who had survived in first remission for six years or more from diagnosis, there was a relation between young age at onset of treatment and early menarche. We suggest that premature activation of the hypothalamic-pituitary-gonadal axis occurs as a consequence of hypothalamic dysfunction due to cranial irradiation. Precocious and premature puberty in children treated for ALL may be an important factor in contributing to short stature.


The value of genomic sequencing in complex pediatric neurological disorders: a discrete choice experiment.
To estimate the value of genomic sequencing for complex pediatric neurological disorders of suspected genetic origin. A discrete choice experiment (DCE) was undertaken to elicit societal preferences and values. A Bayesian D-efficient and explicit partial profile design was used. The design included 72 choice tasks, split across six blocks, with eight attributes (three overlapping per choice task) and three alternatives. Choice data were analyzed using a panel error component mixed logit model and a latent class model. Preference heterogeneity according to personal socioeconomic, demographic, and attitudinal characteristics was explored using linear and fractional logistic regressions. In total, 820 members of the Australian public were recruited. Statistically significant preferences were identified across all eight DCE attributes. We estimated that society on average would be willing to pay AU$5650 more (95% confidence interval [CI]: AU$5500 to $5800) (US$3955 [95% CI: US$3850 to $4060]) for genomic sequencing relative to standard care. Preference heterogeneity was identified for some personal characteristics. On average, society highly values all diagnostic, process, clinical, and nonclinical components of personal utility. To ensure fair prioritization of genomics, decision makers need to consider the wide range of risks and benefits associated with genomic information.


Gut Microbiota and Oral Contraceptive Use in Overweight and Obese Patients with Polycystic Ovary Syndrome.
Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder. Emerging animal and human data point to various changes in microbiota that could be linked with the syndrome. However, the effects of therapeutic approaches on gut microbial composition in women with PCOS remain unknown. We aimed to assess whether gut microbial composition is altered in PCOS and to determine the potential impact of oral contraceptive (OC) use on gut microbiota. Prospective observational study. Tertiary referral hospital. The study included 17 overweight/obese patients with PCOS and 15 age- and body mass index-matched healthy control women. At baseline, clinical, hormonal, and metabolic evaluations and gut microbial composition assessment by 16S rRNA gene amplicon sequencing were performed for both groups. All measurements were repeated in patients after receiving an OC along with general lifestyle advice for 3 months. Alpha and beta diversity did not show a difference between patients with PCOS and healthy controls at baseline and remained unaltered after 3 months of OC use in the PCOS group. Relative abundance of Ruminococcaceae was higher in PCOS (P = 0.006) and did not show a significant change after treatment. Women with PCOS have an increased abundance of Ruminococcaceae, whereas short-term OC use does not alter compositional features of gut microbiota in the syndrome.


Annotating significant pairs of transcription factor binding sites in regulatory DNA.
In the presented work we search for transcription factor binding sites (BS) by including additional information about typical BS patterns. The new proposed score combines the ordinary profile score based on TRANSFAC-matrices together with a score based on pairs of BS. The latter score positively weights pairs of BS that tend to occur together in many regulatory DNA-sequences, in contrast to a random background model. The empirical BS pair frequencies result from our evaluation of a large dataset of orthologous genes.


Towards high sensitivity gas detection with hollow-core photonic bandgap fibers.
This paper investigates the effect of modal interference on the performance of hollow-core photonic bandgap fiber (HC-PBF) gas sensors. By optimizing mode launch, using proper length of sensing HC-PBF, and applying proper wavelength modulation in combination with lock-in detection, as well as appropriate digital signal processing, an estimated lower detection limit of less than 1 part-per-million by volume (ppmv) acetylene is achieved.


Gametogenesis in Chlamydomonas eugametos: I. Light Requirements.
Male and female mating types of Chlamydomonas eugametos Moewus show an absolute light requirement for gametogenesis. Increasing light intensity from 0.3 to 1.2 mw cm(-2) during nitrogen starvation (a precondition for gametogenesis) caused an increase in gametogenesis throughout a 28-hour period. Gametogenesis was measured by determining the percentage of paired cells after a 1-hour mixing period. Light requirements for the male and female differed. There was a 9-hour lag period in gametogenesis in the male, but no lag in the female. Gametogenesis was reduced 50% in the female and 90% in the male when 6.0 mum 3-(3,4-dichlorophenyl)-1, 1-dimethyl-urea was in the N-starvation medium. Sodium acetate, 1.8 mm, in the N-starvation medium increased gametogenesis in both mating types and eliminated the 9-hour lag in the male for cells irradiated for 3, 6, 9, 12, 15, 18, or 23 hours during the last part of a 23-hour N-starvation period. Sodium acetate concentrations higher than 1.8 mm inhibited the mating process. 3-(3,4-Dichlorophenyl)-1, 1-dimethylurea inhibition of gametogenesis was decreased in the male but increased in the female, when sodium acetate was added to the N-starvation medium. These results indicate a nonphotosynthetic as well as a photosynthetic role for light in the gametogenesis of both mating types. Also, the male will not undergo gametogenesis unless a required amount of energy is provided either in the medium or through photosynthesis.


Evaluation of the porcine ameroid constrictor model of myocardial ischemia for therapeutic angiogenesis studies.
The porcine ameroid model of chronic myocardial ischemia has been widely used for the evaluation of coronary collateralization development. The impact of target vessel occlusion on the presence of myocardial ischemia, and the relationship between morphological, functional, and hemodynamic measurements in the context of therapeutic angiogenesis studies, however, has not been studied thus far. The authors therefore performed a systematic analysis of 94 animals undergoing ameroid constrictor placement around the left circumflex coronary artery (LCX) and, furthermore, a comprehensive evaluation including echocardiography and coronary angiography 26 +/- 1 (mean +/- SEM) days after ameroid placement. Complete LCX occlusion was observed in 34/94 animals (36%) and identified those with myocardial ischemia of the lateral wall, both at rest and under pharmacological stress. By applying a set of angiographic criteria (TIMI <or= 2 flow in LCX and/or collateral flow Rentrop class >or= 1), another 27/94 animals with myocardial ischemia under conditions of pharmacological stress conditions could be identified. Interestingly, echocardiographic parameters of regional and global myocardial function were not correlated with myocardial blood flow or the degree of ischemia. There was no relationship between the extent of coronary collateralization, as assessed by angiography, echocardiographic parameters, or myocardial blood flow. The authors therefore conclude that complete occlusion of the ameroid instrumented coronary artery is not a prerequisite for successfully establishing the pathophysiology of myocardial ischemia. Defined angiographic criteria are important in identifying ischemic animals, thus reducing total animal numbers. Angiographic assessment of the degree of coronary collateralization, however, is not associated with myocardial blood flow or function and should not be used as a primary outcome measure of therapeutic angiogenesis studies in this model.


Cerebral Amyloidoma Accompanied by Sjögren's Syndrome: A Case Report and Literature Review.
We present a 69-year-old woman with colorectal cancer and a left frontal lobe tumor that was diagnosed as a cerebral amyloidoma after surgical resection. Further postoperative systemic evaluation revealed another amyloidoma in her hip as well as Sjögren's syndrome. Systemic amyloidosis was not present. To the best of our knowledge, this is the first case of cerebral amyloidoma presenting as one of the multiple localized amyloidomas accompanied by Sjögren's syndrome. We also present a systematic review of 65 cerebral amyloidoma cases reported in the literature over the past 40 years and discuss patient characteristics and pathological and imaging findings associated with prognosis.


Exercise-Induced Extracellular Vesicles Delay the Progression of Prostate Cancer.
Increasing evidence suggests that regular physical exercise not only reduces the risk of cancer but also improves functional capacity, treatment efficacy and disease outcome in cancer patients. At least partially, these effects are mediated by the secretome of the tissues responding to exercise. The secreted molecules can be released in a carrier-free form or enclosed into extracellular vesicles (EVs). Several recent studies have shown that EVs are actively released into circulation during physical exercise. Here, we for the first time investigated the effects of exercise-induced EVs on the progression of cancer in an F344 rat model of metastatic prostate cancer. Although we did not observe a consistent increase in the circulating EV levels, RNA sequencing analysis demonstrated substantial changes in the RNA content of EVs collected before and immediately after forced wheel running exercise as well as differences between EVs from runners at resting state and sedentary rats. The major RNA biotype in EVs was mRNA, followed by miRNA and rRNA. Molecular functions of differentially expressed RNAs reflected various physiological processes including protein folding, metabolism and regulation of immune responses triggered by the exercise in the parental cells. Intravenous administration of exercise-induced EVs into F344 rats with orthotopically injected syngeneic prostate cancer cells PLS10, demonstrated reduction of the primary tumor volume by 35% and possibly-attenuation of lung metastases. Hence, our data provide the first evidence that exercise-induced EVs may modulate tumor physiology and delay the progression of cancer.


Voluntary Exercise Prevents Hypertensive Response Sensitization Induced by Angiotensin II.
Exercise training has profound effects on the renin-angiotensin system, inflammatory cytokines and oxidative stress, all of which affect autonomic nervous system activity and regulate blood pressure (BP) in both physiological and pathophysiological states. Using the Induction-Delay-Expression paradigm, our previous studies demonstrated that various challenges (stressors) during Induction resulted in hypertensive response sensitization (HTRS) during Expression. The present study tested whether voluntary exercise would protect against subpressor angiotensin (ANG) II-induced HTRS in rats. Adult male rats were given access to either "blocked" (sedentary rats) or functional running (exercise rats) wheels for 12 weeks, and the Induction-Delay-Expression paradigm was applied for the rats during the last 4 weeks. A subpressor dose of ANG II given during Induction produced an enhanced hypertensive response to a pressor dose of ANG II given during Expression in sedentary rats in comparison to sedentary animals that received saline (vehicle control) during Induction. Voluntary exercise did not attenuate the pressor dose of ANG II-induced hypertension but prevented the expression of HTRS seen in sedentary animals. Moreover, voluntary exercise reduced body weight gain and feed efficiency, abolished the augmented BP reduction after ganglionic blockade, reversed the increased mRNA expression of pro-hypertensive components, and upregulated mRNA expression of antihypertensive components in the lamina terminalis and hypothalamic paraventricular nucleus, two key brain nuclei involved in the control of sympathetic activity and BP regulation. These results indicate that exercise training plays a beneficial role in preventing HTRS and that this is associated with shifting the balance of the brain prohypertensive and antihypertensive pathways in favor of attenuated central activity driving sympathetic outflow and reduced BP.


Sub-Phenotypes of Acute Kidney Injury: Do We Have Progress for Personalizing Care?
Acute kidney injury (AKI) is the most common form of organ dysfunction occurring in patients admitted to the intensive care unit and contributes significantly to poor long-term outcomes. Despite this public health impact, no effective pharmacotherapy exists for AKI. One reason may be that heterogeneity is present within AKI as currently defined, thereby concealing unique pathophysiologic processes specific to certain AKI populations. Supporting this notion, we and others have shown that diversity within the AKI clinical syndrome exists, and the "one-size-fits-all" approach by current diagnostic guidelines may not be ideal. A "precision medicine" approach that exploits an individual's genetic, biologic, and clinical characteristics to identify AKI sub-phenotypes may overcome such limitations. Identification of AKI sub-phenotypes may address a critical unmet clinical need in AKI by (1) improving risk prognostication, (2) identifying novel pathophysiology, and (3) informing a patient's likelihood of responding to current therapeutics or establishing new therapeutic targets to prevent and treat AKI. This review discusses the current state of phenotyping AKI and future directions.


Electrodeformation of Vesicles Suspended in a Liquid Medium.
Deformation of flexible vesicles suspended in a fluid medium due to an applied electric field can provide valuable insight into deformation dynamics at a very small scale. In an electric field, the response of the vesicle membrane is strongly influenced by the conductivity of surrounding fluid, vesicle size and shape, and the magnitude of applied field. We studied the electrodeformation of vesicles immersed in a fluid media under a DC electric field. An immersed interface method is used to solve the electric field over the domain with conductive or non-conductive vesicles while an immersed boundary method is employed to solve fluid flow, fluid-solid interaction, membrane mechanics and vesicle deformation. Initial force analysis on the membrane surface reveals almost linear influence of vesicle size, but the vesicle size does not affect the long-term deformation which is consistent with experimental evidence. Highly nonlinear effect of the applied field as well as the conductivity ratios inside and outside of the vesicle are observed. Results also point towards an early linear deformation regime followed by an equilibrium stage for the membranes. Modeling results suggest that electrodeforming vesicles can create unique external flows for different conductivity ratios. Moreover, significant influence of the initial aspect ratio of the vesicle on the force distribution is observed across a range of conductivity ratios.


[Prognosis in delusional psychoses: comparison of prognostic value of schizophrenia by six diagnostic criteria].
A group of 107 patients with diagnosis of syndromological dilusional psychosis underwent a catamnestic examination after 11.2 years from contracting the disease (8.7 years after the first hospitalization). During the first hospitalization with application of different criteria, the dependence of the early (clinical improvement after the first hospitalization) and late stages of the disease, qualified on the basis of catamnesis (intensification of the residual complex, life functioning, hospitalization intensity) on nosological qualification of disorders (schizophrenia vs no-schizophrenia) was analysed. It was concluded that the prognostisity of the course of illness depended in negligible degree on the kind of applied criteria. Of greater prognostic value, however, were the criteria in case of which diagnosis of schizophrenia depended, from the very beginning, on meeting the conditions formulated either directly (DSM-III-R) or indirectly (AS, VRC) of illness chronisity.


The pharmacological management of depression.
Antidepressants, given in the correct dosage and for an adequate period of time, are very effective in the treatment of the majority of cases of primary depressive illness. In this review, a rational approach to the pharmacological management of depression is discussed. The relative advantages and problems associated with the various types of antidepressants are reviewed. The role of benzodiazepines in the management of depression is considered.


The butanol fraction of guava (Psidium cattleianum Sabine) leaf extract suppresses MMP-2 and MMP-9 expression and activity through the suppression of the ERK1/2 MAPK signaling pathway.
The leaf extract of guava (Psidium cattleianum Sabine) has traditionally been used for the treatment of diarrhea and diabetes in East Asia and other countries. Recently, the leaf extract has been employed in the therapy of cancer, bacterial infections, and inflammation in experimental models. However, the exact mechanisms of how guava leaf extract inhibits tumor metastasis and invasion are still unknown. In the present study, we investigated in detail the molecular mechanism(s) responsible for the potential antimetastatic and antiinvasive effects of the butanol fraction of guava leaf extract (GBF). Interestingly, we observed for the first time that GBF suppressed both matrix metalloproteinases (MMP)-9 and MMP-2 expression and activity in part through the downregulation of the ERK1/2 activation in lung cancer cells. Also, importantly, the major components of the GBF were identified as d-glucuronic acid, quercetin 3-glucuronide, loganin, and xanthyletin by LC-ESI-MS/MS. Collectively, our data indicate that the guava leaf could reduce the metastasis of lung cancer cells and therefore suggest that it could be advantageously used to control the metastatic process.


Review of readmissions due to complications from uterine fibroid embolization.
To determine the frequency, nature and outcome of complications resulting in readmission to hospital following uterine artery embolization (UAE). A retrospective review of the medical notes and available imaging of 42 consecutive patients who had undergone elective uterine artery embolization for the treatment of fibroid disease was performed. The mean age of the patients was 42 years (range 31--54 years) and seven patients (17%) were readmitted to hospital. The median time to readmission was 3 weeks (range 1-29 weeks). All seven patients were admitted with signs and symptoms of infection. In four patients an organism was isolated from high vaginal swabs, and in one patient the midstream urine sample was confirmed as the source of infection. In the other two patients no definite source of infection was identified. All patients were treated with intravenous antibiotics. Six of the seven patients responded to treatment. The remaining patient required hysterectomy for uncontrolled uterine sepsis. Readmission following UAE is common and arises secondary to infection. Infection can occur several months after the procedure.


Assessing and managing the risks of COVID-19 in the workplace: Applying industrial hygiene (IH)/occupational and environmental health and safety (OEHS) frameworks.
As businesses attempt to reopen to varying degrees amid the current coronavirus disease (COVID-19) pandemic, industrial hygiene (IH) and occupational and environmental health and safety (OEHS) professionals have been challenged with assessing and managing the risks of COVID-19 in the workplace. In general, the available IH/OEHS tools were designed to control hazards originating in the workplace; however, attempts to tailor them specifically to the control of infectious disease outbreaks have been limited. This analysis evaluated the IH decision-making framework (Anticipate, Recognize, Evaluate, Control, and Confirm ("ARECC")) as it relates to biological hazards, in general, and to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), specifically. Available IH/OEHS risk assessment and risk management tools (e.g. control banding and the hierarchy of controls) are important components of the ARECC framework. These conceptual models, however, were primarily developed for controlling chemical hazards and must be adapted to the unique characteristics of highly infectious and virulent pathogens, such as SARS-CoV-2. This assessment provides an overview of the key considerations for developing occupational infection control plans, selecting the best available controls, and applying other emerging tools (e.g. quantitative microbial risk assessment), with the ultimate goal of facilitating risk management decisions during the current global pandemic.


Analytical computation of the derivative of PSF for the optimization of phase mask in wavefront coding system.
Wavefront coding system can realize defocus invariance of PSF/OTF with a phase mask inserting in the pupil plane. Ideally, the derivative of the PSF/OTF with respect to defocus error should be close to zero as much as possible over the extended depth of field/focus for the wavefront coding system. In this paper, we propose an analytical expression for the computation of the derivative of PSF. With this expression, the derivative of PSF based merit function can be used in the optimization of the wavefront coding system with any type of phase mask and aberrations. Computation of the derivative of PSF using the proposed expression and FFT respectively are compared and discussed. We also demonstrate the optimization of a generic polynomial phase mask in wavefront coding system as an example.


Entropy of network ensembles.
In this paper we generalize the concept of random networks to describe network ensembles with nontrivial features by a statistical mechanics approach. This framework is able to describe undirected and directed network ensembles as well as weighted network ensembles. These networks might have nontrivial community structure or, in the case of networks embedded in a given space, they might have a link probability with a nontrivial dependence on the distance between the nodes. These ensembles are characterized by their entropy, which evaluates the cardinality of networks in the ensemble. In particular, in this paper we define and evaluate the structural entropy, i.e., the entropy of the ensembles of undirected uncorrelated simple networks with given degree sequence. We stress the apparent paradox that scale-free degree distributions are characterized by having small structural entropy while they are so widely encountered in natural, social, and technological complex systems. We propose a solution to the paradox by proving that scale-free degree distributions are the most likely degree distribution with the corresponding value of the structural entropy. Finally, the general framework we present in this paper is able to describe microcanonical ensembles of networks as well as canonical or hidden-variable network ensembles with significant implications for the formulation of network-constructing algorithms.


Adverse Interaction between Capecitabine and Warfarin Resulting in Altered Coagulation Parameters: A Review of the Literature Starting from a Case Report.
Capecitabine is an orally active prodrug of fluorouracil and is extensively used as an antineoplastic agent. It is converted to 5-Fluorouracil in the liver and tumor tissues. Warfarin is an anticoagulant agent for preventing and treating venous and arterial thrombosis and embolism and is metabolized by cytochrome P450 isoenzymes in the liver. Preclinical in vitro studies using human liver microsomes report no inhibitory effects between capecitabine and substrates of cytochrome P. However, the concomitant administration of capecitabine and warfarin resulted in INR elevation in the cases previously reported in the literature. The exact mechanism of this interaction is unknown but may be related to downregulation of cytochrome P450 2C9 by capecitabine or its metabolites. We report on the possible adverse interaction between capecitabine and warfarin in a patient with metastatic breast cancer and critically review the existing literature on this topic. Physicians should be aware of adverse reactions arising from the combined use of capecitabine and warfarin. In the light of the current data, INR levels should be closely monitored in patients using these drugs together.


Closed Rupture of the Flexor Tendon Secondary to Sclerosis of the Hook of the Hamate: A Report of Two Cases.
Closed flexor tendon ruptures in the little finger can be caused by fracture or nonunion of the hook of the hamate, but no case of the disorder secondary to the sclerosis and thinning of the hamate hook has been reported. We report two rare cases with this complication due to rough surface of the hamate hook. Carpal tunnel view radiographs and computed tomography showed the sclerosis and thinning of the hook.


Romanowsky-Giemsa as a counterstain for immunohistochemistry: optimizing a traditional reagent.
We describe a detailed protocol for using Romanowsky-Giemsa (RG) counterstaining on formalin fixed, paraffin embedded tissue sections that are stained immunohistochemically (IHC) after antigen retrieval using hot acidic citrate buffer. RG staining is easy to perform and provides consistent results that are similar to hematoxylin and eosin (HE) staining. The counterstaining was applied after a variety of antibodies that used the DAB chromogen and the intensity of IHC stained structures was preserved. Moreover, RG counterstaining provided finer cell detail than HE, methyl green or nuclear fast red. A detailed troubleshooting guide is provided for the RG staining protocol.


[Some real problems of human opisthorchiasis].
Forty six sera from residents of the Novosibirsk Region in whom the diagnosis of chronic opisthorchiasis had been helminthoovoscopically verified were examined. In the thin layer immunoassay, of them 14 (30.4%) sera were responsive to excretory O. felineus antigens, 3 (7.9%) were to M. bilis antigens, and 29 (63.2%) were to the above antigens simultaneously. The results of these studies determine it possible to regard M. bilis methorchiasis as a zooanthroponous disease and a human being as a final host of this helminth.


Outcome of coronary endarterectomy: a case-control study.
Despite early reports showing a high incidence of postoperative morbidity and mortality, coronary endarterectomy continues to be used as an adjunct to coronary artery bypass grafting, particularly in diffusely diseased coronary arteries. The changing nature of patients and improvements in modern cardiac surgery call for a reevaluation of the role of coronary endarterectomy. Data from the 56 patients, who underwent coronary endarterectomy in our institution between January 1993 and August 1996, were reviewed retrospectively and compared with a control group of 56 patients matched for age, sex, LV function, and angina class. In the endarterectomy group, there were 47 men and nine women, with a mean age of 59.6 years. The mean follow-up time was 21 months. Indications for operation were angina in 45 (80.3%), angina with signs or symptoms of cardiac failure in 3 (5.4%), and prognosis in 8 (14.3%) asymptomatic patients. Fifty (89%) patients had one, four (7.2%) had two, and 2 (3.6%) patients had three coronary arteries endarterectomized. Of these 64 endarterectomies, 33 (51.5%) involved the right coronary artery, 20 (31.3%) the left anterior descending artery, and 11 (17.2%) branches of the circumflex artery. There were three (5.4%) nonfatal myocardial infarctions in the endarterectomy group, but none in the control group (p>0.05). Two patients (3.6%) in the endarterectomy group, but none in the control group, died within the first 30 days (p>0.05). Actuarial survival and incidence of recurrent angina were similar in the two groups. In current cardiac surgical practice, coronary endarterectomy displays satisfactory rates of postoperative morbidity and medium term results in selected groups of patients.


Water molecules insert into N-H...Cl-M hydrogen bonds while M-Cl...X-C halogen bonds remain intact in dihydrates of halopyridinium hexachloroplatinates.
The crystal structures of the 3-halopyridinium hexachloroplatinate(IV) dihydrates (HPyX-3)(2)[PtCl(6)]x2H(2)O [(1), X = Br; (2a), (2b), X = I] comprise networks in which the molecular components are linked via N-H...O and O-H...Cl-Pt hydrogen bonds and Pt-Cl...X-C halogen bonds (X = Br, I). The iodo derivative has been isolated in two polymorphic forms. Of particular interest to the understanding of the utility of the hydrogen bonds and M-X...X'-C halogen bonds that propagate the networks in anhydrous salts of this type is that the water molecules insert exclusively into the putative N-H...Cl-Pt hydrogen bonds, while the Pt-Cl...X'-C halogen bonds remain undisrupted by the presence of water molecules.


Parotid duct carcinoma arising in bilateral chronic sialadenitis.
It is well recognized that, in general, chronic inflammation can predispose to malignant change. There is however, to our knowledge, no previously reported association between chronic obstructive sialadenitis and salivary gland epithelial malignancy. We describe here the first reported example in the English literature of a salivary duct carcinoma arising in a parotid gland with a long history of chronic obstructive sialadenitis. It is possible that a causal relationship exists between the two conditions. If this were the case then non-surgically treated chronic obstructive sialadenitis patients may well warrant careful clinical follow-up.


Diameter modulation by fast temperature control in laser-assisted chemical vapor deposition of single-walled carbon nanotubes.
Diameter modulation by fast temperature control in laser-assisted chemical vapor deposition (LCVD) was successfully achieved to tune the diameters of single-walled carbon nanotubes (SWNTs) in different segments. Due to the inverse relationship between the SWNT diameter and the growth temperature, SWNTs with ascending diameters were obtained by reducing the LCVD temperature from high to low. The diameter-modulated SWNTs were integrated in electrodes to form field-effect transistors (FETs) and to investigate their electronic transport properties. The SWNTs in the FET structures have electronic properties similar to Schottky diodes, indicating clear evidence of different bandgap structures at the two ends of the SWNTs. Raman spectroscopy, transmission electron microscopy, and electronic transport characteristics were studied to investigate the influence of temperature variation on the structural and electronic characteristics of the SWNTs.


Chronic lymphocytic leukemia: diagnosis and treatment.
Traditionally, the goal of therapy in chronic lymphocytic leukemia (CLL) has been palliative, with first-line therapy using alkylating agents and/or involved field radiotherapy (depending on the stage of disease and sites of involvement) because of the older age of affected patients and the low rate of complete remissions (CRs) with no improvement in overall survival despite treatment. With increasing knowledge about the biology, molecular genetics, and prognostic factors of the disease, the philosophy of care for patients with CLL has evolved from palliation to aiming for a potential cure, especially in younger patients. Furthermore, multiple treatment options have emerged, including purine analogues, monoclonal antibodies, and potentially stem cell transplantation. These have been associated with higher frequencies of CRs and longer durations of responses compared to conventional chemotherapy. In addition, a subset of patients treated with chemoimmunotherapy can achieve durable CRs and molecular remissions. This may translate into improved disease-free survival and potentially a "cure." Because of the heterogeneous nature of CLL, new prognostic markers are currently being incorporated into clinical trials to determine their role in routine clinical practice. This review summarizes current therapeutic regimens that are being evaluated in patients with CLL and management of disease-related complications.


Acute effects of fine particulate matter constituents on cardiopulmonary function in a panel of COPD patients.
Exposure to fine particulate matter (PM2.5) has been linked with adverse cardiorespiratory health conditions. However, evidence for PM2.5 constituents is still scarce, especially among patients with chronic obstructive pulmonary disease (COPD). To investigate the associations of short-term exposure to different chemical constituents of PM2.5 with measures of cardiac and lung function in COPD patients. We conducted a retrospective panel study among 100 COPD patients who received repeated measures of left ventricular ejection fraction (LVEF), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF) in Shanghai, China from August 2014 to September 2019. Daily PM2.5 and PM2.5 constituents were obtained from fixed-site monitoring station. Linear mixed-effects models were used to estimate the associations of PM2.5. We found water-soluble ions of PM2.5, mainly NO3-, SO42-, and NH4+ were robustly associated with reduced LVEF, and the reductions in LVEF associated with an IQR increase of them ranged from 1.8% to 2.0% (lag 1 d). Metal constituents such as Cu and As were associated with FEV1, FVC and PEF. The corresponding reductions in lung function parameters for an IQR increase of them ranged from 1.4% to 2.3% (lag 0 or 1 d). These associations remained relatively robust after adjusting for total PM2.5 mass and gaseous pollutants. Our results suggest that water-soluble ions and several metal/metalloid elements might be important constituents in PM2.5 that were associated with reduced cardiorespiratory function among COPD patients.


[Molecular immunology of Japanese cedar pollen allergens: analysis of T cell epitopes].
Recent studies demonstrated that partial alteration of the amino acid sequence of T cell epitopes induced a stimulatory signal that was qualitatively different. Therefore, it is conceivable that immunotherapy using peptides representing dominant T cell epitopes could modulate the T cell response of allergic patients and prevent the production of IgE antibodies. Accordingly, a number of allergens have been molecularly cloned to determine their amino acid sequences. In Japan, the number of patients suffering from Japanese cedar pollinosis is steadily increasing and it has become a serious social problem. In this paper, we review the recent advances on T cell epitope mapping of Japanese cedar pollen, Cry j 1 and Cry j 2 and immunomodulating trials based on the mechanisms of T cell antigen-recognition.


A novel GATA6 mutation leading to congenital heart defects and permanent neonatal diabetes: a case report.
Permanent neonatal diabetes mellitus is a rare condition mostly due to heterozygous mutations in the KCNJ11, ABCC8 and INS genes. Neonatal diabetes due to pancreatic agenesis is extremely rare. Mutations in PDX1, PTF1A, HNF1B, EIF2AK3, RFX6 and GATA6 genes have been shown to result in pancreatic agenesis or hypoplasia. This report describes a 40-day-old male infant diagnosed with permanent neonatal diabetes associated with atrial septal defect, pulmonary stenosis, patent ductus arteriosus and a novel de novo heterozygous missense mutation (p.N466S) in the GATA6 gene with no evidence of exocrine pancreas insufficiency. In addition to permanent neonatal diabetes, the patient had transient idiopathic neonatal cholestasis and hypoglycaemic episodes unrelated to insulin treatment, features that are rarely described in children with permanent neonatal diabetes.


Efficacy and tolerability of adjunctive lamotrigine for refractory epilepsy in institutional or community residents with mental retardation.
To determine whether the efficacy and tolerability of adjunctive lamotrigine differ as a function of whether persons with mental retardation and refractory epilepsy resided in institutions or the community. The analysis was retrospective and employed data from a previously published, open-label study. To be eligible for enrollment, patients needed to be receiving stable regimens of up to three antiepileptic medications at enrollment and to have experienced at least two seizures per month in the 3 months prior to enrollment. The study included an Escalation Phase during which lamotrigine was titrated to a target dose, an 8-week Maintenance Phase during which doses of lamotrigine and concomitant antiepileptic drugs were maintained, and a 12-week Optimization Phase during which doses of antiepileptic drugs could be adjusted. Outcomes of interest included baseline characteristics; the percentage of persons with 25%, 50%, and 75% reductions in seizure frequency and with zero seizures; investigator-rated clinical status; and mean scores on the Habilitative Improvement Scale and the Aberrant Behavior Checklist. The small sample size did not allow for sufficient power for statistical comparisons between groups. Demographics and baseline clinical characteristics were similar between groups (31 institutional and 36 community residents) except institutional residents were more likely to have severe or profound mental retardation and complex partial and partial secondarily generalized seizures. The percentages of persons with 25%, 50%, and 75% reductions in seizure frequency and zero seizures were 64%, 50%, 29%, and 18% respectively, for community residents and 42%, 38%, 23%, and 12% for institutional residents. Investigator-rated clinical status at the end of the Maintenance Phase was improved versus baseline in 68% of community residents and 62% of institutional residents. Most individuals (81% of institutionalized persons, 69% of community-dwelling persons) were considered to have experienced no change in adverse events with the addition of lamotrigine. The mean Habilitative Improvement Scale score was significantly improved (p < or = 0.05) versus baseline at the end of the Escalation, Maintenance, and Optimization Phases in both groups. The efficacy and tolerability of lamotrigine were similar between institutional residents and community residents despite the numerically higher prevalence of severe or profound mental retardation among institutional residents.


Skin-on-a-Chip Technology for Testing Transdermal Drug Delivery-Starting Points and Recent Developments.
During the last decades, several technologies were developed for testing drug delivery through the dermal barrier. Investigation of drug penetration across the skin can be important in topical pharmaceutical formulations and also in cosmeto-science. The state-of- the-art in the field of skin diffusion measurements, different devices, and diffusion platforms used, are summarized in the introductory part of this review. Then the methodologies applied at Pázmány Péter Catholic University are shown in detail. The main testing platforms (Franz diffusion cells, skin-on-a-chip devices) and the major scientific projects (P-glycoprotein interaction in the skin; new skin equivalents for diffusion purposes) are also presented in one section. The main achievements of our research are briefly summarized: (1) new skin-on-a-chip microfluidic devices were validated as tools for drug penetration studies for the skin; (2) P-glycoprotein transport has an absorptive orientation in the skin; (3) skin samples cannot be used for transporter interaction studies after freezing and thawing; (4) penetration of hydrophilic model drugs is lower in aged than in young skin; (5) mechanical sensitization is needed for excised rodent and pig skins for drug absorption measurements. Our validated skin-on-a-chip platform is available for other research groups to use for testing and for utilizing it for different purposes.


The 22K variant of rat prolactin: evidence for identity to prolactin-(1-173), storage in secretory granules, and regulated release.
Western blot analyses of the rat pituitary have detected a 22K PRL variant distinct from intact PRL (25K). We recently reported that glandular kallikrein (GK), an estrogen-induced lactotroph protease, can process PRL in vitro from a 25K form to a 22K form in a thiol-dependent cleavage at Arg174-Arg175 to remove 23 amino acids. We also detected an estrogen- and thiol-induced 22K PRL variant in the rat pituitary comigrating with a PRL product generated by in vitro processing with GK and carboxypeptidase-B. This study addressed whether the in vivo 22K PRL variant originates through a GK-like cleavage and is a regulated secretory product of the rat pituitary. A polyclonal antipeptide antiserum was raised against a synthetic peptide [PRL-(163-173)] representing the new C-terminus after GK and carboxypeptidase-B processing. In slot and Western blots, this antiserum (CT-antiserum) specifically recognized PRL processed in vitro by GK and carboxypeptidase-B and did not recognize intact PRL or PRL cleaved by GK alone. Western blot analysis of rat pituitary extracts with CT-antiserum specifically detected an estrogen- and thiol-induced 22K band that comigrated with a PRL product generated by in vitro processing with GK and carboxypeptidase-B. This 22K band was concentrated in subcellular fractions of the pituitary enriched in secretory granules. During short term incubations in medium 199, pituitaries from normal adult female rats released substantial amounts of 22K PRL; in contrast, male pituitaries did not release detectable 22K PRL. The release of 22K PRL from female pituitaries was powerfully blocked by bromocriptine, a dopaminergic agonist. GK was also released from pituitaries of female, but not male, rats, and GK release was inhibited by bromocriptine. The results identify the 22K PRL variant as PRL-(1-173), which is consistent with GK-like processing at Arg174-Arg175, followed by carboxypeptidase-B-like processing. The results also show that 22K PRL is a natural female-specific secretory product of the rat pituitary under inhibitory dopaminergic control.


Dendrimer Anion-Exchange Stationary Phase for Separation of Oligonucleotides.
Oligonucleotides are used in many research areas. Thus, there is a need for their successful separation methods. Ion-exchange chromatography is the most popular separation technique, but it has limitations for these compounds. For this reason, new stationary phases are developed in order to increase separation selectivity. This study aimed to apply a series of dendrimer anion exchangers with various bonded layers to separate oligonucleotides by using different mobile phases to find conditions that allow sufficient separation. The number of anion-exchange layers, type of salt, and pH significantly impacted the oligonucleotide analysis. The developed chromatographic method was characterized by adequate selectivity for oligonucleotides differing in sequence length. It is essential to underline that the number of bonded layers appeared to have a significant influence, and the three layers appeared optimal. Based on our results, it may be concluded that the dendrimer stationary phases can be successfully used as an alternative to commonly applied packing materials in ion-exchange chromatography.


Targeting Oxidative Stress, NLRP3 Inflammasome, and Autophagy by Fraxetin to Combat Doxorubicin-Induced Cardiotoxicity.
Doxorubicin belongs to the class of anthracycline antibiotics that is widely used in the treatment protocols of a wide range of malignancies. The major deleterious effect of doxorubicin use is the possible occurrence of cardiotoxicity. This study aimed to delineate the possible effects of targeting oxidative stress, NLRP3 inflammasome, and autophagy by fraxetin on doxorubicin-induced cardiac dysfunction in rats. In a model of doxorubicin-induced cardiotoxicity, the effects of different doses of fraxetin were assessed by determination of biochemical, histopathological, immunohistochemical, and electron microscopic changes. Fraxetin, in a dose-dependent manner, was found to have the ability to mitigate the harmful effects of oxidative stress and inflammation on myocardial muscles with significant decrease in NLRP3 inflammasome, augmentation of autophagy, and amelioration of the apoptotic signaling pathways. In addition, fraxetin, in a dose-dependent manner, had the ability to combat the echocardiographic, histopathological, immunohistochemical, and electron microscopic changes induced by doxorubicin in cardiomyocytes. As a result, fraxetin may be put into consideration as a new adjuvant line of therapy on the way to mitigate doxorubicin-induced cardiotoxicity.


Acoustic duration changes associated with two types of treatment for children who stutter.
The purpose of this study was (a) to examine in young children the effects of Speech Motor Training (SMT) on selected temporal acoustic durations considered to be related to speech motor programming, (b) to compare the speech motor effects of that treatment with those of a treatment of childhood stuttering that did not directly incorporate speech motor control training (Extended Length of Utterance [ELU]), and (c) to examine the relation of acoustic duration changes to reduction of stuttering. Twelve children who stutter were recorded while repeating syllable sets /see text/ and /see text/ before and after SMT (n = 6) or ELU treatment (n = 6). Children who did not stutter served as matched reference groups. The syllables beginning with /p/ and /t/ were used as tokens for the acoustic measurement. Five measures served as indicators of temporal aspects of speech motor performance: vowel duration, stop gap duration, voice onset time, stop gap/vowel duration ratio, and total token duration. Results indicated that following SMT there was a significant increase in vowel duration and some reduction in stop gap duration that resulted in significantly reduced stop gap/vowel duration ratios. These acoustic effects were consistent across most participants. The ELU treatment reduced stuttering more than the SMT, but was not accompanied by significant effects on the selected temporal acoustic measures. These findings are compared with previous findings of increased vowel durations associated with fluency enhancement and stuttering treatment. We speculate that the increased vowel durations allow more time for speech motor planning and that stuttering is reduced moderately as a by-product of longer vowel durations. The mechanism(s) by which ELU treatment reduces stuttering did not appear to be captured by the dependent variables measured in this study.


Correlation of genotype and in vitro susceptibilities of Cryptococcus gattii strains from the Pacific Northwest of the United States.
Cryptococcus gattii emerged in North America in 1999 as a human and veterinary pathogen on Vancouver Island, British Columbia. The emergent subtype, VGIIa, and the closely related subtype VGIIb can now be found in the United States in Washington, Oregon, and California. We performed multilocus sequence typing and antifungal susceptibility testing on 43 isolates of C. gattii from human patients in Oregon, Washington, California, and Idaho. In contrast to Vancouver Island, VGIIa was the most frequent but not the predominant subtype in the northwest United States. Antifungal susceptibility testing showed statistically significant differences in MICs between the subtypes. This is the first study to apply antifungal susceptibility testing to C. gattii isolates from the Pacific Northwest and the first to make direct comparisons between subtypes.


Mitigation of scattering defect and absorption of DKDP crystals by laser conditioning.
The variation of scattering and absorption in DKDP crystals by laser conditioning was investigated by combining light scattering technique and on-site transmittance measurement technique. Laser-induced disappearance of scattering defects was observed, and variation of transmittance was achieved. Using Mie theory, a kind of absorbing defects, aside from scattering defect, was discovered. Moreover, the experimental results demonstrated that the absorption of crystal could be mitigated by laser conditioning.


[The anatomy Lesson of Dr. Nicolaes Tulp: The beginning of a medical utopia].
The Anatomy Lesson of Dr. Nicolaes Tulp was painted by Rembrandt Harmen-szoon van Rijn at the early age of 26 years. In the XVII century these paintings were very popular in the Netherlands, and in this country the cities flourished as cultural centers searching the anatomy knowledge. Nicolaes Tulp was one of the persons in the center of Amsterdam's scene during XVII century. In 1632 Tulp was 39 years old, and he was an anatomist and a surgeon. Rembrandt masterly shows an autopsy performed by Dr. Tulp. This picture is the description of the beginning of a medical intellectual utopia: the absolute visibility of the disease. Unfortunately this utopia is blind to the complete visibility of the psycho-socio-cultural dimensions of the ill.


Reflow into a thrombosed giant middle cerebral artery aneurysm after extracranial-intracranial bypass.
This report graphically illustrates the consequences of flow augmentation through extracranial-intracranial bypass grafts. Propagation of clot from a thrombosed middle cerebral artery aneurysm into the middle cerebral artery produced transient ischemic attacks. Superficial temporal artery-middle cerebral artery bypass was performed to augment cerebral blood flow. Postoperative angiography demonstrated filling of the aneurysm through improved collateral channels. The role of bypass operation in the presence of an aneurysm and its contribution to collateral blood flow and clot lysis are discussed.


FIP200 is required for the cell-autonomous maintenance of fetal hematopoietic stem cells.
Little is known about whether autophagic mechanisms are active in hematopoietic stem cells (HSCs) or how they are regulated. FIP200 (200-kDa FAK-family interacting protein) plays important roles in mammalian autophagy and other cellular functions, but its role in hematopoietic cells has not been examined. Here we show that conditional deletion of FIP200 in hematopoietic cells leads to perinatal lethality and severe anemia. FIP200 was cell-autonomously required for the maintenance and function of fetal HSCs. FIP200-deficient HSC were unable to reconstitute lethally irradiated recipients. FIP200 ablation did not result in increased HSC apoptosis, but it did increase the rate of HSC proliferation. Consistent with an essential role for FIP200 in autophagy, FIP200-null fetal HSCs exhibited both increased mitochondrial mass and reactive oxygen species. These data identify FIP200 as a key intrinsic regulator of fetal HSCs and implicate a potential role for autophagy in the maintenance of fetal hematopoiesis and HSCs.


Phase 2 safety trial targeting amyloid beta production with a gamma-secretase inhibitor in Alzheimer disease.
To evaluate the safety, tolerability, and amyloid beta (Abeta) response to the gamma-secretase inhibitor LY450139 in Alzheimer disease. Multicenter, randomized, double-blind, dose-escalation, placebo-controlled trial. Community-based clinical research centers. Patients Fifty-one individuals with mild to moderate Alzheimer disease were randomized to receive placebo (n=15) or LY450139 (100 mg [n=22] or 140 mg [n=14]), with 43 completing the treatment phase. Intervention The LY450139 groups received 60 mg/d for 2 weeks, then 100 mg/d for 6 weeks, and then either 100 or 140 mg/d for 6 additional weeks. Primary outcome measures were adverse events, plasma and cerebrospinal fluid Abeta levels, vital signs, electrocardiographic data, and laboratory safety test results. Secondary outcome measures included the Alzheimer's Disease Assessment Scale cognitive subscale and the Alzheimer's Disease Cooperative Study Activities of Daily Living Scale. Group differences were seen in skin and subcutaneous tissue concerns (P=.05), including 3 possible drug rashes and 3 reports of hair color change in the treatment groups. There were 3 adverse event-related discontinuations, including 1 transient bowel obstruction. The plasma Abeta(40) concentration was reduced by 58.2% for the 100-mg group and 64.6% for the 140-mg group (P<.001). No significant reduction was seen in cerebrospinal fluid Abeta levels. No group differences were seen in cognitive or functional measures. LY450139 was generally well tolerated at doses of up to 140 mg/d for 14 weeks, with several findings indicating the need for close clinical monitoring in future studies. Decreases in plasma Abeta concentrations were consistent with inhibition of gamma-secretase. Trial Registration clinicaltrials.gov Identifier: NCT00244322.


Prevention of cardiovascular and renal pathology of aging by the advanced glycation inhibitor aminoguanidine.
Human aging is impacted severely by cardiovascular disease and significantly but less overtly by renal dysfunction. Advanced glycation endproducts (AGEs) have been linked to tissue damage in diabetes and aging, and the AGE inhibitor aminoguanidine (AG) has been shown to inhibit renal and vascular pathology in diabetic animals. In the present study, the effects of AG on aging-related renal and vascular changes and AGE accumulation were studied in nondiabetic female Sprague-Dawley (S-D) and Fischer 344 (F344) rats treated with AG (0.1% in drinking water) for 18 mo. Significant increases in the AGE content in aged cardiac (P < 0.05), aortic (P < 0.005), and renal (P < 0.05) tissues were prevented by AG treatment (P < 0.05 for each tissue). A marked age-linked vasodilatory impairment in response to acetylcholine and nitroglycerine was prevented by AG treatment (P < 0.005), as was an age-related cardiac hypertrophy evident in both strains (P < 0.05). While creatinine clearance was unaffected by aging in these studies, the AGE/ creatinine clearance ratio declined 3-fold in old rats vs. young rats (S-D, P < 0.05; F344, P < 0.01), while it declined significantly less in AG-treated old rats (P < 0.05). In S-D but not in F344 rats, a significant (P < 0.05) age-linked 24% nephron loss was completely prevented by AG treatment, and glomerular sclerosis was markedly suppressed (P < 0.01). Age-related albuminuria and proteinuria were markedly inhibited by AG in both strains (S-D, P < 0.01; F344, P < 0.01). These data suggest that early interference with AGE accumulation by AG treatment may impart significant protection against the progressive cardiovascular and renal decline afflicting the last decades of life.


Expression of hepatic pyruvate carboxylase mRNA in C57BL/6J Ah(b/b) and congenic Ah((d/d)) mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
The activity and level of hepatic pyruvate carboxylase (PC) has been reported to be altered by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment in mice. If alteration in PC level/activity by TCDD influences TCDD toxicity, one would expect to observe an early post-exposure reduction in PC mRNA. To examine the molecular events responsible for the alteration of PC activity in livers of TCDD-treated mice, we designed a synthetic DNA oligonucleotide probe specific for PC mRNA. Northern blot analysis on RNA extracts from hepatic tissue at various times and doses post-TCDD exposure were done. Furthermore, to elucidate the role of the dioxin Ah locus on alterations of PC activity by TCDD, we utilized C57BL/6J (Ahb/b, Ah high TCDD affinity) mice and a congenic (Ahd/d, AH low TCDD affinity) mouse strain. At 8 days post TCDD treatment, a dose-dependent reduction of hepatic PC mRNA levels was observed in Ahb/b mice. The response, reduction in PC mRNA levels, in the Ahb/b strain was about 10-fold greater than that of comparably exposed congenic Ahd/d mice. These results indicate that previously reported reductions in PC activity/level by TCDD treatment of mice is a consequence of a reduction in PC mRNA levels and that the effect requires a competent Ah receptor.


Plant-Based Colloidal Delivery Systems for Bioactives.
The supplementation of plant-based foods and beverages with bioactive agents may be an important strategy for increasing human healthiness. Numerous kinds of colloidal delivery systems have been developed to encapsulate bioactives with the goal of improving their water dispersibility, chemical stability, and bioavailability. In this review, we focus on colloidal delivery systems assembled entirely from plant-based ingredients, such as lipids, proteins, polysaccharides, phospholipids, and surfactants isolated from botanical sources. In particular, the utilization of these ingredients to create plant-based nanoemulsions, nanoliposomes, nanoparticles, and microgels is covered. The utilization of these delivery systems to encapsulate, protect, and release various kinds of bioactives is highlighted, including oil-soluble vitamins (like vitamin D), ω-3 oils, carotenoids (vitamin A precursors), curcuminoids, and polyphenols. The functionality of these delivery systems can be tailored to specific applications by careful selection of ingredients and processing operations, as this enables the composition, size, shape, internal structure, surface chemistry, and electrical characteristics of the colloidal particles to be controlled. The plant-based delivery systems discussed in this article may be useful for introducing active ingredients into the next generation of plant-based foods, meat, seafood, milk, and egg analogs. Nevertheless, there is still a need to systematically compare the functional performance of different delivery systems for specific applications to establish the most appropriate one. In addition, there is a need to test their efficacy at delivering bioavailable forms of bioactives using in vivo studies.