Intratarsal epidermal inclusion cyst.
To report 3 cases of epidermal inclusion cyst that arose within the tarsus, an unusual site of origin. A retrospective review of medical records of patients undergoing excision of eyelid epidermal inclusion cysts by one surgeon (MJL) over a decade revealed 3 cases of intratarsal epidermal inclusion cyst. Initially, these lesions resembled chalazia and were first addressed with incision and curettage. There was recurrence of the cyst in all the 3 cases from 1 to 4 months, and subsequent complete excision was necessary. At surgery in each of these cases a cyst arising within the tarsus was encountered. Eventually, the tarsus containing the base of the cyst was excised to ensure complete removal. The cysts were approximately 8 mm to 10 mm in greatest dimension and had yellowish-white gelatinous contents. Histopathologic evaluation revealed keratin-filled cysts arising from tarsus and lined by stratified keratinized epithelium. In one of the cases the tarsal tissue around the cyst wall showed epidermal elements presumably derived from sebaceous gland. There have been no recurrences after complete excision (follow-up range, 9-60 months). Intratarsal epidermal inclusion cysts share some clinical features with chalazia. Lack of inflammation, lack of fluctuation in size, gradual continued slow growth, and delayed onset of recurrence may help to differentiate tarsal cyst from recurrent chalazion. Incision and curettage, however, is not effective long-term treatment for this entity. Total excision of the cyst including full-thickness excision of tarsus at the cyst's base of origin is suggested for definitive treatment.


Cationic salt-responsive bottle-brush polymers.
A class of cationic bottle-brush polymers that show ionic strength-dependent stimuli responsiveness is prepared. Brush polymers with norbornene as backbone and quaternary ammonium (QA)-containing polycaprolactone copolymers as side chains are synthesized by a combination of ring-opening metathesis polymerization, ring-opening polymerization, and click reaction. In water with low ionic strength, brush polymers are soluble due to the strong electrostatic repulsion between cationic QA groups. As the addition of salt to increase ionic strength, single brush polymers undergo a transition from extended conformation to collapsed state and finally become insoluble in solution due to the screening effect of salts that yield the once-dominant electrostatic interactions among QA species to hydrophobic-hydrophobic interactions.


Understanding nonlinear vibration behaviours in high-power ultrasonic surgical devices.
Ultrasonic surgical devices are increasingly used in oral, craniofacial and maxillofacial surgery to cut mineralized tissue, offering the surgeon high accuracy with minimal risk to nerve and vessel tissue. Power ultrasonic devices operate in resonance, requiring their length to be a half-wavelength or multiple-half-wavelength. For bone surgery, devices based on a half-wavelength have seen considerable success, but longer multiple-half-wavelength endoscopic devices have recently been proposed to widen the range of surgeries. To provide context for these developments, some examples of surgical procedures and the associated designs of ultrasonic cutting tips are presented. However, multiple-half-wavelength components, typical of endoscopic devices, have greater potential to exhibit nonlinear dynamic behaviours that have a highly detrimental effect on device performance. Through experimental characterization of the dynamic behaviour of endoscopic devices, it is demonstrated how geometrical features influence nonlinear dynamic responses. Period doubling, a known route to chaotic behaviour, is shown to be significantly influenced by the cutting tip shape, whereas the cutting tip has only a limited effect on Duffing-like responses, particularly the shape of the hysteresis curve, which is important for device stability. These findings underpin design, aiming to pave the way for a new generation of ultrasonic endoscopic surgical devices.


Analysis of intact tetraether lipids in archaeal cell material and sediments by high performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry.
A method combining normal phase high performance liquid chromatography (HPLC) with positive ion atmospheric pressure chemical ionization mass spectrometry (APCI-MS) was developed for the analysis of intact glycerol dialkyl glycerol tetraethers (GDGTs) in archaeal cell material and sediments. All GDGTs previously reported to occur in the thermophilic archaeon Sulfolobus solfataricus could be identified based on their mass spectra and retention time. Positive ion mass spectra consisted of abundant protonated molecules and fragment ions corresponding to loss of water and the glycerol moiety. In addition, two novel GDGTs representing alternative combinations of biphytanyl moieties were observed. Using this method, the tetraethers present in the thermophilic archaeon Metallosphaera sedula and two sediment samples were characterized. This rapid method will greatly contribute to the establishment of the sedimentary record of these compounds and increase our understanding of archaea and their occurrence in widely different environments.


Prevalence of diverse complications and its association with karyotypes in Japanese adult women with Turner syndrome-a questionnaire survey by the Foundation for Growth Science.
The reported prevalence of complications in Turner Syndrome (TS) was highly variable because of the rarity and the limited numbers analyzed. Again, possible presence of other complications that are not described as specific for TS, is also speculated. To resolve these issues, a questionnaire survey was conducted in hGH treated 492 patients with adult TS (17-42 years). The possible association with these complications and karyotypes were also analyzed. The complications and their prevalence were as follows: chronic thyroiditis (25.2%), inflammatory bowel disease (1.8%), congenital cardiovascular anomaly (11.8%), urinary tract malformation (11.8%), low bone mineral density (BMD) (42.9%), scoliosis (8.4%), hearing loss (6.2%), epilepsy (2.8%) and schizophrenia (0.9%). The majority of prevalence of these diseases in TS was higher than in the general population. In distribution, the most frequent karyotype was 45,X monosomy (28.9%), followed by 45,X/46,X,Xi (16.9%), 46,X,Xi (9.1%), and 45,X/46,XX (6.3%), while other mosaic 45,X was noted in 29.9%. Regarding the karyotype, cardiovascular anomaly was more frequent in the 45,X group and less in the 46,X,Xi group. Urinary tract malformation and epilepsy were frequently associated with the chromosome 45,X. The prevalence of low BMD was noticed more in the chromosome 46,X,Xi and 45,X/46,X,Xi, and less in other mosaic 45,X. In conclusion, the more exact prevalence of diverse complications was clarified and it exceeded the prevalence of the majority of complications in general population. As novel findings, it was observed that the prevalence of epilepsy was significantly high, and epilepsy and low BMD were frequently associated with the specific karyotypes.


Psychometric properties of the English version of the Oral Health Literacy Adults Questionnaire - OHL-AQ.
To test the psychometric properties of the Oral Health Literacy Adult Questionnaire (OHL-AQ) in English. The OHL-AQ was designed to test functional oral health literacy in general populations and was initially validated in Iran. The instrument was administered to 405 adult subjects (mean age 45 (SD 16) years and 67% female) attending the 2014 Minnesota State Fair. The OHL-AQ is composed of 17 items measuring four conceptual dimensions: reading comprehension, numeracy, listening, and decision-making. Participants selected the best answer for written or verbally administered items and entered answers on an electronic tablet. Item responses for each individual were combined into a summary score (range 0-17) with higher scores indicating better oral health literacy. Score dimensionality, reliability, and validity were investigated. For dimensionality, both exploratory factor analysis and a parallel analysis yielded evidence for scale unidimensionality. Reliability was sufficient indicated by a Cronbach's alpha ⟩0.74. Validity of scores was supported by "small" and "medium" effect sizes for construct validity. "Small" effect sizes were observed for global oral health self-report, OHIP-5 scores, treatment urgency, and having a regular dentist. "Medium" effect sizes were seen for presence of dentures, number of natural teeth present, and educational level. Dimensionality, reliability and validity of the English version of the OHL-AQ in a general adult English-speaking population is supported, providing sufficient psychometric properties in an important target population of the instrument.


Selective killing of human cancer cells by polyunsaturated fatty acids.
Polyunsaturated fatty acids killed incubated human breast, lung and prostate cancer cells at concentrations which had no adverse effects on normal human fibroblasts or on normal animal cell lines. The most consistent and selective effects were obtained with fatty acids containing 3, 4 and 5 double bonds. When human cancer cells and normal human fibroblasts were co-cultured in the absence of polyunsaturated fatty acids, the malignant cells overgrew the normal ones. When eicosapentaenoic acid (EPA, 20:5n-3), gamma-linolenic acid (GLA, 18:3n-6) or arachidonic acid (AA, 20:4n-6) were added to the co-cultures, the normal cells outgrew the malignant ones. These observations suggest that treatment of malignancy with polyunsaturated fatty acids may have considerable potential while being associated with a high level of safety.


Intubation after cervical spinal cord injury: to be done selectively or routinely?
Patients with cervical spinal cord injuries (CSCIs) often develop acute respiratory failure and require intubation. It is unknown if intubation should be offered preemptively in all CSCI patients or selectively based on signs of acute respiratory failure. The purpose of this study was to evaluate the role of routine early intubation in CSCI patients. The medical records of 68 patients with CSCI were reviewed. Univariate and multivariate analyses were used to identify independent risk factors for the need of intubation. Statistical significance was considered at P < 0.05. Fifty patients (74%) required intubation and 27 (40%) developed pneumonia. Of patients with CSCI above C5, 87.5 per cent required intubation compared with 61 per cent of patients with CSCI at C5-C8 (P = 0.026). Similarly, of patients with complete quadriplegia, 90 per cent required intubation compared to 48.5 per cent of patients with incomplete quadriplegia or paraplegia (P < 0.001). Of 31 patients not presenting with overt signs of acute respiratory failure on admission, 13 (42%) decompensated later and were eventually intubated up to 53 hours after admission. Six of these 13 patients had emergent intubation due to acute desaturation and developed pulmonary complications associated with emergent intubation. There were 3 independent risk factors for the need of intubation: Injury Severity Score > 16, CSCI higher than C5, and complete quadriplegia. The combination of the 2 latter risk factors resulted in intubation in 21 of 22 patients (95%). The majority of patients with CSCI require intubation. In patients with CSCI above C5 and complete quadriplegia, intubation should be offered routinely and early because delays may cause preventable morbidity.


Comparison of Antibiotic Therapy and Appendectomy for Acute Uncomplicated Appendicitis in Children: A Meta-analysis.
Antibiotic therapy for acute uncomplicated appendicitis is effective in adult patients, but its application in pediatric patients remains controversial. To compare the safety and efficacy of antibiotic treatment vs appendectomy as the primary therapy for acute uncomplicated appendicitis in pediatric patients. The PubMed, MEDLINE, EMBASE, and Cochrane Library databases and the Cochrane Controlled Trials Register for randomized clinical trials were searched through April 17, 2016. The search was limited to studies published in English. Search terms included appendicitis, antibiotics, appendectomy, randomized controlled trial, controlled clinical trial, randomized, placebo, drug therapy, randomly, and trial. Randomized clinical trials and prospective clinical controlled trials comparing antibiotic therapy with appendectomy for acute uncomplicated appendicitis in pediatric patients (aged 5-18 years) were included in the meta-analysis. The outcomes included at least 2 of the following terms: success rate of antibiotic treatment and appendectomy, complications, readmissions, length of stay, total cost, and disability days. Data were independently extracted by 2 reviewers. The quality of the included studies was examined in accordance with the Cochrane guidelines and the Newcastle-Ottawa criteria. Data were pooled using a logistic fixed-effects model, and the subgroup pooled risk ratio with or without appendicolith was estimated. The primary outcome was the success rate of treatment. The hypothesis was formulated before data collection. A total of 527 articles were screened. In 5 unique studies, 404 unique patients with uncomplicated appendicitis (aged 5-15 years) were enrolled. Nonoperative treatment was successful in 152 of 168 patients (90.5%), with a Mantel-Haenszel fixed-effects risk ratio of 8.92 (95% CI, 2.67-29.79; heterogeneity, P = .99; I2 = 0%). Subgroup analysis showed that the risk for treatment failure in patients with appendicolith increased, with a Mantel-Haenszel fixed-effects risk ratio of 10.43 (95% CI, 1.46-74.26; heterogeneity, P = .91; I2 = 0%). This meta-analysis shows that antibiotics as the initial treatment for pediatric patients with uncomplicated appendicitis may be feasible and effective without increasing the risk for complications. However, the failure rate, mainly caused by the presence of appendicolith, is higher than for appendectomy. Surgery is preferably suggested for uncomplicated appendicitis with appendicolith.


hetC, a gene coding for a protein similar to bacterial ABC protein exporters, is involved in early regulation of heterocyst differentiation in Anabaena sp. strain PCC 7120.
Transposon-generated mutant C3 of Anabaena sp. strain PCC 7120 is unable to form heterocysts upon deprivation of combined nitrogen but forms a pattern of spaced, weakly fluorescent cells after 2 days of deprivation. Sequence analysis of chromosomal DNA adjacent to the ends of transposon Tn5-1058 in mutant C3 showed a 1,044-amino-acid open reading frame, designated hetC, whose predicted protein product throughout its C-terminal two-thirds has extensive similarity to the HlyB family of bacterial protein exporters. Its N-terminal third is unique and does not resemble any known protein. hetC lies 1,165 bp 5' from the previously described gene hetP. Reconstruction of the C3 mutation and its complementation in trans with a wild-type copy of hetC confirmed that hetC has an essential regulatory role early in heterocyst development. hetC is induced ca. 4 h after nitrogen stepdown, hours after induction of hetR. Expression of hetC depends on HetR and may depend on HetC. Highly similar sequences are present 5' from the initiation codons and in the 3' untranslated regions of hetC and of two heterocyst-specific genes, devA and hetP.


Heat shock-mediated regulation of MKP-1.
Heat shock modulates cellular proinflammatory responses, and we have been interested in elucidating the mechanisms that govern this modulation. The dual specific phosphatase, MAP kinase phosphatase-1 (MKP-1), is an important modulator of cellular inflammatory responses, and we recently reported that heat shock increases expression of MKP-1. Herein we sought to elucidate the mechanisms by which heat shock modulates MKP-1 gene expression. Subjecting RAW264.7 macrophages to heat shock increased MKP-1 gene expression in a time-dependent manner. Transfection with a wild-type murine MKP-1 promoter luciferase reporter plasmid demonstrated that heat shock activates the MKP-1 promoter. When the reporter plasmid was transfected into heat shock factor-1 (HSF-1)-null fibroblasts, the MKP-1 promoter was activated in response to heat shock in a manner similar to that of wild-type fibroblasts with intact HSF-1. Site-directed mutagenesis of two potential heat shock elements in the MKP-1 promoter demonstrated that both sites are required for basal promoter activity. mRNA stability assays demonstrated that heat shock increased MKP-1 mRNA stability compared with cells maintained at 37 degrees C. Inhibition of p38 MAP kinase activity inhibited heat shock-mediated expression of MKP-1. These data demonstrate that heat shock regulates MKP-1 gene expression at both the transcriptional and posttranscriptional levels. Transcriptional mechanisms are HSF-1 independent but are dependent on putative heat shock elements in the MKP-1 promoter. Posttranscriptional mechanisms involve increased stability of MKP-1 mRNA that is partially dependent on p38 MAP kinase activity. These data demonstrate another potential mechanism by which heat shock can modulate inflammation-related signal transduction.


Neutralizing antibodies to Escherichia coli Vero cytotoxin 1 and antibodies to O157 lipopolysaccharide in healthy farm family members and urban residents.
An enzyme-linked immunosorbent assay (ELISA) to detect antibodies to Escherichia coli O157 lipopolysaccharide (LPS) was developed with sera from 63 children with confirmed recent E. coli O157 infection and from 256 age-stratified urban controls. The median ELISA values for control and case sera were 0.05 (interquartile range, 0 to 0.20; mean +/- standard deviation [SD], 0.15 +/- 0.22) and 1.41 (interquartile range, 1.11 to 1.59; mean +/- SD, 1.41 +/- 0.53), respectively (P < 0.001). With a breakpoint of 0.59 (mean ELISA value of the control sera + 2 SDs), the assay had a sensitivity, specificity, and positive and negative predictive values of 95, 94, 80, and 98%, respectively, for recent E. coli O157 infection. The O157 LPS assay and Vero cytotoxin (VT) 1-neutralizing-antibody (NAb) assay were used to compare the relative frequencies of O157 LPS antibodies and VT1-NAbs in an age-stratified urban population from Toronto, Ontario, Canada, and in 216 healthy family members from dairy farm in southern Ontario. The frequency of O157 LPS antibodies was about threefold higher in dairy farm residents (12.5%) than in urban residents (4.7%) (P < 0.01). Similarly, the frequency of VT1-NAbs was about sixfold higher in dairy farm residents (42.0%) than in urban residents (7.7%) (P < 0.001). These findings are consistent with a greater level of exposure of dairy farm residents to VT-producing E. coli (VTEC) strains. The high rate of seropositivity to VT1 in farm residents probably reflects the booster effect of repeated VTEC exposures and argues against a sustained generalized immunosuppressive effect of VT1. Seroepidemiological studies may help in assessing the level of exposure of different populations to VTEC strains.


Global Mean Sea Level Variations from TOPEX/POSEIDON Altimeter Data.
The TOPEX/POSEIDON satellite altimeter mission has measured global mean sea level every 10 days over the last 2 years with a precision of 4 millimeters, which approaches the requirements for climate change research. The estimated rate of sea level change is +3.9 +/- 0.8 millimeters per year. A substantial portion of this trend may represent a short-term variation unrelated to the long-term signal expected from global warming. For this reason, and because the long-term measurement accuracy requires additional monitoring, a longer time series is necessary before climate change signals can be unequivocally detected.


Effects of dietary antioxidants on human DNA ex vivo.
The protective effect of fruits and vegetables against cancer is well established. It is believed that this effect is mediated by antioxidants and decreased oxidative damage to DNA. However, the identity of the antioxidant(s) responsible is not clear. Moreover, a potentially damaging pro-oxidant effect of some antioxidants has been reported. In this study the ex vivo effects of several dietary antioxidants, including quercetin, various catechins, ascorbic acid and alpha-tocopherol, were investigated, at concentrations up to 200 microM, using the single cell gel electrophoresis (comet) assay for DNA damage. Lymphocytes from three healthy subjects were pre-incubated with these antioxidants, and the comet assay was performed on treated, untreated, challenged and unchallenged cells in parallel, oxidant challenge being induced by 5 min exposure to hydrogen peroxide (final concentrations H2O2: 30, 45, or 60 microM). Results using this ex vivo cellular assay showed protection by some antioxidants (quercetin, caffeic acid), no effect by some (catechin, epicatechin, catechin gallate, epicatechin gallate) and an apparently damaging effect by others (epigallocatechin, epigallocatechin gallate). Damage may have been caused by production of H2O2 from these polyphenolics. Neither ascorbic acid nor alpha-tocopherol protected or damaged DNA. Further study of the role of quercetin and caffeic acid in DNA protection is needed.


Doppler-free spectroscopy with a terahertz quantum-cascade laser.
We report on the Doppler-free saturation spectroscopy of a molecular transition at 3.3 THz based on a quantum-cascade laser and an absorption cell in a collinear pump-probe configuration. A Lamb dip with a sub-Doppler linewidth of 170 kHz is observed for a rotational transition of HDO. We found that a certain level of external optical feedback is tolerable as long as the free spectral range of the external cavity is large compared to the width of the absorption line.


Association Between Prostate Magnetic Resonance Imaging and Observation for Low-risk Prostate Cancer.
To evaluate the association between prostate magnetic resonance imaging (MRI) and the use of observation for men with low-risk prostate cancer (PCa). We used the Surveillance, Epidemiology, and End Results-Medicare database to identify men diagnosed with low-risk PCa during 2010-2013. We assessed the use of prostate MRI and management using claims in period surrounding PCa diagnosis. The relation of clinical and demographic factors to receipt of MRI was evaluated with multivariable logistic regression analysis. Following propensity score matching, we fit conditional logistic regression models to examine the association between prostate MRI and initial management, ie, observation or definitive treatment. Of 8144 patients with low-risk PCa, 495 (6.1%) received MRI. Use of MRI increased from 3.4% in 2010 to 10.5% in 2013. A total of 3060 (37.6%) patients received observation. MRI was performed in 265 (8.7%) of patients receiving observation, and 230 (4.5%) who were treated (P < .0001). In multivariable analysis, measures of socioeconomic status were significantly associated with the use of prostate MRI. Following propensity score matching, receipt of prostate MRI surrounding the diagnosis of PCa was associated with a significantly higher likelihood of observation (odds ratio = 1.90, 95% confidence interval: 1.56-2.32). This effect persisted in sensitivity analyses attempting to exclude treatment-planning MRIs. Receipt of prostate MRI surrounding PCa diagnosis was associated with a nearly 2-fold greater odds of receiving observation vs definitive treatment.


[Expression of the restriction fragment of phage T7 DNA in a cell-free transcription-translation system from E. coli].
The matrix activity of phage T7 DNA and the restriction fragment of phage T7 DNA containing gene 0,3 with a promoter was studied with respect to RNA and protein syntheses in a cell-free transcription-translation system from E. coli. A comparison of the protein products of cell-free synthesis was carried out, using polyacrylamide gel electrophoresis and a subsequent radiofluorography. Data from PAAG suggest that the restriction fragment codes the synthesis of a polypeptide, whose size is identical to that of a polypeptide synthesized on a corresponding gene in phage T7 DNA. A possible use of the cell-free system of coupled transcription-translation for the functional mapping of the genome DNA is discussed.


Self-perception and oral health in pregnant adolescents.
To evaluate the oral health indicators by determining the experience of dental caries and periodontal disease and identification of self-perceived oral health status of pregnant adolescents and to assess the association between the studied variables. A transversal study, survey type and survey of the oral health status of 127 adolescents, 10-19 years of age, pregnant, accompanied by the Unified Health System of Araçatuba-SP was performed. The self-perceived oral health and socio-demographic data were recorded using an adapted questionnaire. The oral health statuses were analyzed using the DMFT and CPI indices in accordance with the criteria established by the WHO for epidemiological survey. Descriptive statistical analyzes and the Fisher's exact test with a significance level of 5% was performed, as well as a logistic regression analysis to verify the association between the variables. Of the total, 41.0% reported having satisfactory oral health, while 63.0% believed they had problems with their teeth and gums. The DMFT index was 12.51 (SD = 4.21). The percentage of caries-free was 6.3%, and 91.3% had periodontal problems. A statistically significant association was found between the variables: self-perceived oral health and periodontal disease p = 0.0166 and self-reported gum disease and periodontal disease p = 0.0039. Most patients considered their oral health as poor and reported having dental and gum problems, which can also be observed in the clinical examination since the caries experience of the pregnant women examined was considered high and the symptoms of periodontal disease were observed in most of the volunteers.


Genes in the terminal regions of orthopoxvirus genomes experience adaptive molecular evolution.
Orthopoxviruses are dsDNA viruses with large genomes, some encoding over 200 genes. Genes essential for viral replication are located in the center of the linear genome and genes encoding host response modifiers and other host interacting proteins are located in the terminal regions. The central portion of the genome is highly conserved, both in gene content and sequence, while the terminal regions are more diverse. In this study, we investigated the role of adaptive molecular evolution in poxvirus genes and the selective pressures that act on the different regions of the genome. The relative fixation rates of synonymous and non-synonymous mutations (the d(N)/d(S) ratio) are an indicator of the mechanism of evolution of sequences, and can be used to identify purifying, neutral, or diversifying selection acting on a gene. Like highly conserved residues, amino acids under diversifying selection may be functionally important. Many genes experiencing diversifying selection are involved in host-pathogen interactions, such as antigen-antibody interactions, or the "host-pathogen arms race." We analyzed 175 gene families from orthopoxviruses for evidence of diversifying selection. 79 genes were identified as experiencing diversifying selection, 25 with high confidence. Many of these genes are located in the terminal regions of the genome and function to modify the host response to infection or are virion-associated, indicating a greater role for diversifying selection in host-interacting genes. Of the 79 genes, 20 are of unknown function, and implicating diversifying selection as an important mechanism in their evolution may help characterize their function or identify important functional residues. We conclude that diversifying selection is an important mechanism of orthopoxvirus evolution. Diversifying selection in poxviruses may be the result of interaction with host defense mechanisms.


Physical oncology: New targets for nanomedicine.
Physical oncology is an emerging paradigm which recognizes tissue mechanics, per se, as an active modulator of tumorigenesis, treatment resistance and clinical outcome, mediated by mechanosignaling pathways, matrix remodeling and physical barriers to drugs. The tumor microenvironment displays abnormal physical properties in comparison to healthy tissue which contribute to cancer progression and resistance to current treatments. Physical aberrancies comprise the chaotic organization of tumor vasculature, an increased interstitial pressure, an increased solid stress, hypoxia, an abundant extracellular matrix and a progressive stiffening of solid tumors. The physical barriers in tumors are of critical importance, as tissue mechanics compromises drug delivery, reduces immune cell infiltration and promotes disease aggressiveness. All these physical hallmarks of cancer, although not fully understood, are inspiring new anticancer strategies aiming to target and normalize the physical anomalies of solid tumors, particularly in the field of nanomedicine. Here we summarize the recent paradigm shift of physical oncology and review some of the proposed strategies using nanomaterials to tackle the tumor microenvironment and its aberrant physical properties. Nanomedicine might harness the features of the tumor microenvironment in order to improve nanoparticle and drug delivery, or propose nano-agents that can be activated on demand to achieve a tailored spatio-temporal modulation of the tumor microenvironment, reduce tumor pressure and stiffness and alleviate the resistance to current treatments.


Calcium sensitivity of glutamate release in a calyx-type terminal.
Synaptic efficacy critically depends on the presynaptic intracellular calcium concentration ([Ca2+]i). We measured the calcium sensitivity of glutamate release in a rat auditory brainstem synapse by laser photolysis of caged calcium. A rise in [Ca2+]i to 1 micromolar readily evoked release. An increase to >30 micromolar depleted the releasable vesicle pool in <0.5 millisecond. A comparison with action potential-evoked release suggested that a brief increase of [Ca2+]i to approximately 10 micromolar would be sufficient to reproduce the physiological release pattern. Thus, the calcium sensitivity of release at this synapse is high, and the distinction between phasic and delayed release is less pronounced than previously thought.


Asthma self-management programmes in a population of Italian children: a multicentric study. Italian Study Group on Asthma Self-Management Programmes.
This study was designed to answer three main questions: 1) Does asthma self-management education reduce asthma morbidity? 2) Are the two programmes "Living With Asthma" and "Open Airways" equally effective in doing so? 3) Is a shortened version of these programmes (4 weeks) as effective as the longer original programme (8 weeks)? Twelve Italian centres of paediatric bronchopneumology selected 312 children with asthma, who were stratified by disease severity, gender and age, and then randomly assigned to an Experimental group which received an educational programme or to a Comparison group, which did not. Of the 312 children selected, 209 (114 Experimental and 95 Comparison) completed the educational protocol and a 1 year follow-up. Data recorded during the last 2 months of follow-up, 10 months after the educational intervention, showed that the Experimental group required significantly fewer emergency treatments: this reduction was more evident in the more severe asthma cases. In the Experimental, but not in the Comparison group, patients with more severe asthma consumed more medications than patients with milder asthma "Open Airways" yielded, in some cases, better results than "Living with Asthma": but a type 2 error is possible. The standard and the shortened programmes proved equally effective. In conclusion, following education, regardless of receiving a short or long educational programme, asthma patients use emergency care services less and use medications more appropriately in comparison with standard care without education. This suggests that short educational programmes can be highly cost-effective in children with asthma.


Exogenous PP2A inhibitor exacerbates the progression of nonalcoholic fatty liver disease via NOX2-dependent activation of miR21.
Nonalcoholic fatty liver disease (NAFLD) is an emerging global pandemic. Though significant progress has been made in unraveling the pathophysiology of the disease, the role of protein phosphatase 2A (PP2A) and its subsequent inhibition by environmental and genetic factors in NAFLD pathophysiology remains unclear. The present report tests the hypothesis that an exogenous PP2A inhibitor leads to hepatic inflammation and fibrogenesis via an NADPH oxidase 2 (NOX2)-dependent pathway in NAFLD. Results showed that microcystin (MC) administration, a potent PP2A inhibitor found in environmental exposure, led to an exacerbation of NAFLD pathology with increased CD68 immunoreactivity, the release of proinflammatory cytokines, and stellate cell activation, a process that was attenuated in mice that lacked the p47phox gene and miR21 knockout mice. Mechanistically, leptin-primed immortalized Kupffer cells (a mimicked model for an NAFLD condition) treated with apocynin or nitrone spin trap 5,5 dimethyl-1- pyrroline N-oxide (DMPO) had significantly decreased CD68 and decreased miR21 and α-smooth muscle actin levels, suggesting the role of NOX2-dependent reactive oxygen species in miR21-induced Kupffer cell activation and stellate cell pathology. Furthermore, NOX2-dependent peroxynitrite generation was primarily responsible for cellular events observed following MC exposure since incubation with phenylboronic acid attenuated miR21 levels, Kupffer cell activation, and inflammatory cytokine release. Furthermore, blocking of the AKT pathway attenuated PP2A inhibitor-induced NOX2 activation and miR21 upregulation. Taken together, we show that PP2A may have protective roles, and its inhibition exacerbates NAFLD pathology via activating NOX2-dependent peroxynitrite generation, thus increasing miR21-induced pathology.NEW & NOTEWORTHY Protein phosphatase 2A inhibition causes nonalcoholic steatohepatitis (NASH) progression via NADPH oxidase 2. In addition to a novel emchanism of action, we describe a new tool to describe NASH histopathology.


Validation of the Subjective Global Nutrition Assessment (SGNA) and Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP) to Identify Malnutrition in Hospitalized Malaysian Children.
Early detection of malnutrition in hospitalized children helps reduce length of hospital stay and morbidity. A validated nutrition tool is essential to correctly identify children at risk of malnutrition or who are already malnourished. This study compared the use of the Subjective Global Nutrition Assessment (SGNA, nutrition assessment tool) and Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP, nutrition screening tool) with objective nutritional parameters to identify malnutrition in hospitalized children. A cross-sectional study was carried out in two general paediatric wards in a public hospital. SGNA and STAMP were performed on 82 children (52 boys and 30 girls) of age 1-7 years. The scores from both methods were compared against Academy of Nutrition and Dietetics/American Society of Parental and Enteral Nutrition Consensus Statement for identification of paediatric malnutrition. The objective measurements include anthropometry (weight, height and mid-arm circumference), dietary intake and biochemical markers (C-reactive protein, total lymphocytes and serum albumin). Kappa agreement between methods, sensitivity, specificity and cross-classification were computed. SGNA and STAMP identified 45% and 79% of the children to be at risk of malnutrition, respectively. Using a compendium of objective parameters, 46% of the children were confirmed to be malnourished. The agreement between SGNA and objective measurements (k = 0.337) was stronger than between STAMP and objective measurements (k = 0.052) in evaluating the nutritional status of hospitalized children. SGNA also has a 4-fold higher specificity (70.45%) than STAMP (18.18%) in detecting children who are malnourished. SGNA is a valid nutrition assessment tool in diagnosing malnutrition status among hospitalized children in Malaysia. The discrepancy in specificity values between the two methods explains the distinguished roles between SGNA and STAMP. The use of STAMP will have to be followed up with a more valid tool such as SGNA to verify the actual nutrition status of the paediatric population.


[Comparison of different methods for attenuation correction in brain PET: effect on the calculation of the metabolic rate of glucose].
There are several approaches for correcting the effects of photon scatter or absorption by body tissues on positron emission tomography (PET). We examined the influence of cold, hot and segmented transmission as well as of a mathematical procedure on attenuation correction using regional cerebral glucose metabolism (rMRGlu). 6 patients with different cerebral diseases were examined under resting conditions using an ECAT Exact 922/47. The attenuation-corrected data (corrected by means of cold, hot and segmented transmission as well as a mathematical procedure) were then quantified absolutely for assessment of regional glucose metabolism in 16 regions of interest (ROIs). Using absolutely quantified glucose metabolism in 16 ROIs, no significant differences were found between cold transmission and the mathematical procedure except for three regions (left and right temporal occipital and right parietal occipital). Unlike the mathematical procedure, both hot and segmented transmission showed a significantly lower value for regional glucose utilization in all 16 ROIs than did cold transmission. The left and the right hemisphere both showed metabolic values (rMRGlu) in the same decreasing order: cold transmission, the mathematical procedure, hot or segmented transmission. There was no significant difference between global cerebral glucose metabolism values for cold transmission and the mathematical procedure (p = 0.25) while those for hot (p = 0.03) and segmented transmission (p = 0.03) did show a significant difference. Except for 3 regions (temporo-occipital left, temporo-occipital right and parieto-occipital right) attenuation correction procedures used for brain PET studies on patients show no significant quantitative differences between cold transmission and the mathematical procedure. rMRGlu of images corrected for attenuation using hot and segmented transmission is significantly lower than of attenuation corrected images where cold transmission was employed. For clinical routine examinations, the mathematical procedure seems the best alternative to cold transmission for a faster brain PET acquisition.


Monkeypox: EpiMPX Surveillance System and Open Data with a Special Focus on European and Italian Epidemic.
The current out-of-Africa 2022 outbreak of Monkeypox requires a coordinated, international response through the rapid sharing of data and research results, as we have seen with COVID-19 and the previous Ebola and Zika outbreaks, which demonstrated how important real-world data are to inform public health, to create surveillance systems, to determine policy decisions and to improve clinical trials. To support global response efforts by providing public access to real-time Monkeypox-related data for effective use of open data that could accelerate scientific knowledge and discoveries in terms of understanding, preventing, and treating the disease. In practice, to create a new surveillance system easy to consult and utilize. This work aims to build a surveillance system, namely EpiMPX, that allows researchers and policymakers to monitor the impact of Monkeypox in Europe, with a special focus on the epidemic trends in the Italian regions, based on an open-access database containing information on the laboratory confirmed Monkeypox cases reported by EU/EEA countries and updated once a week. In addition, users will be provided open-access R codes to estimate key epidemiological parameters such as the reproduction number (updating the Serial Interval distribution when new estimates will be published) and produce real-time results on their devices. EpiMPX monitors the space-time distribution of cases and their characteristics, such as age, gender, symptoms, clinical status, and sexual orientation, when available. Even if it is currently too early for reliable calculation of epidemiological parameters, we estimated reproduction number R t in European countries with more than 28 days of observed incidence, assuming that the Serial Interval (SI) early estimate in Italy is valid for other countries too. This provides a direct visual assessment of the geographic distribution of risk areas as well as insights into the evolution of the outbreak over time. Italian data were evaluated concerning gender, region prevalence and cumulative data. The proposed EpiMPX surveillance system provides an overview of the European and Italian Monkeypox epidemiological situation with an open-access database to support epidemiological understanding of the origins and transmission dynamics of the disease with informative graphical outputs. These data confirmed the prevalent expression of Monkeypox within males, both in Europe and Italy. European MSM patients were affected by Monkeypox in a high percentage, confirming close sexual contact and possible sexual transmission. For the first time, Italian data on the regional distribution of cases and gender distribution were graphically evaluated. The data and research results are freely available and can be easily enriched to provide a prompt response to the scientific community and accelerate global efforts to contain the Monkeypox virus.


[Tramal in the treatment of acute and chronic pain syndromes in cancer patients].
The study of 65 cancer patients has demonstrated the advantages and disadvantages of tramal as an agent used for the relief of acute and chronic pain syndrome. In 18 patients tramal was used in postoperative analgesia, in 17 patients it was used for the treatment of chronic pain syndrome. It has been shown that in the postoperative period tramal has no noticeable advantages over promedol. However, tramal had definite advantages over other opiate agonists when used for the treatment of chronic pain syndrome in incurable cancer patients. Thus, the data obtained show that tramal, a synthetic analgesic of a new generation, has no dangerous side effects, is effective in a convenient, non-invasive drug form, interacts well with non-narcotic and supplementary agents and causes no clinical signs of drug tolerance or addiction in prolonged application.


Human ocular effects from self-reported exposures to Roundup herbicides.
We evaluated ocular effects from reported human exposures to Roundup herbicides based on 1513 calls to an American Association of Poison Control Centers (AAPCC) certified regional poison center during the years 1993 through 1997. The preponderance of reported exposures were judged by poison center specialists to result in either no injury (21%) or transient minor symptoms (70%). There was some temporary injury in 2% of cases; one injury took more than 2 weeks to resolve. In no instance did exposure result in permanent change to the structure or function of the eye. Since the representativeness of calls to poison control centers is unknown, several interpretations of these findings are possible. The most conservative interpretation is that there were no serious ocular effects from exposure to Roundup herbicides during a 5 year period among callers to a single regional poison center. A less conservative interpretation would be that severe ocular effects from Roundup exposures are rare among users of these products.


The novel Rac effector RIN-1 regulates neuronal cell migration and axon pathfinding in C. elegans.
Cell migration and axon guidance require proper regulation of the actin cytoskeleton in response to extracellular guidance cues. Rho/Rac small GTPases are essential regulators of actin remodeling. Caenorhabditis elegans CED-10 is a Rac1 homolog that is required for various cellular morphological changes and migration events and is under the control of several guidance signaling pathways. There is still considerable uncertainty regarding events following the activation of guidance receptors by extracellular signals and the regulation of actin dynamics based on spatiotemporally restricted Rac activity. Here we show that the VPS9 domain protein RIN-1 acts as a novel effector for CED-10 in C. elegans. The orthologous mammalian Rin1 protein has previously been identified as an effector for Ras GTPase and is now known to function as a guanine nucleotide exchange factor for Rab5 GTPase. We found that RIN-1 specifically binds to the GTP-bound form of CED-10 and that mutations in rin-1 cause significant defects in migration and axon guidance of restricted neuronal cell types including AVM and HSN neurons, in contrast to the various defects observed in ced-10 mutants. Our analyses place RIN-1 in the Slit-Robo genetic pathway that regulates repulsive signaling for dorsoventral axon guidance. In rin-1 mutants, actin accumulated on both the ventral and dorsal sides of the developing HSN neuron, in contrast to its ventral accumulation in wild type. These results strongly suggest that RIN-1 acts as an effector for CED-10/Rac1 and regulates actin remodeling in response to restricted guidance cues.


Recurrent respiratory papillomatosis.
Juvenile-onset recurrent respiratory papillomatosis is a vertically transmitted disease caused by members of the human papilloma virus family. Characterized by the relentless growth of papillomatous lesions of the larynx, recurrent respiratory papillomatosis imposes significant morbidity on patients and strain on their families. Surgical excision of the papillomata remains the mainstay of therapy, but human papilloma virus DNA persists in adjacent, normal-appearing mucosa and likely serves as a reservoir for viral reseeding. Despite multiple adjuvant treatment modalities, a cure for recurrent respiratory papillomatosis remains elusive. Most afflicted patients eventually enter spontaneous remission, but some endure several hundred surgical procedures before this welcome respite.


American Association of Clinical Endocrinologists and American College of Endocrinology Protocol for Standardized Production of Clinical Practice Guidelines, Algorithms, and Checklists--2014 Update and the AACe G4G Program.
In 2010, the American Association of Clinical Endocrinologists (AACE) published an update to the original 2004 guidelines. This update hybridized strict evidence-based medicine methods with subjective factors and improved the efficiency of clinical practice guidelines (CPG) production, clinical applicability, and usefulness. Current and persistent shortcomings involving suboptimal implementation and protracted development timelines are addressed in the current 2014 update. The major advances include 1) formulation of an organizational educational strategy, represented by the AACE Council on Education, to address relevant teaching and decision-making tools for clinical endocrinologists, and to generate specific clinical questions to drive CPG, clinical algorithm (CA), and clinical checklist (CC) development; 2) creation and prioritization of printed and online CAs and CCs with a supporting evidence base; 3) focus on clinically relevant and question-oriented topics; 4) utilization of "cascades," where there can be more than 1 recommendation for 1 clinical question; and 5) incorporation of performance metrics to validate, optimize, and effectively update CPG, CAs, and CCs. Efforts continue to translate these clinical tools to electronic formats that can be integrated into a paperless healthcare delivery system, as well as applying them to diverse clinical settings by incorporating transcultural factors.


Combined mucormycosis and aspergillosis of the oro-sinonasal region in a patient affected by Castleman disease.
One case of aspergillosis and mucormycosis occurring in a patient with stage-IV Castleman disease was investigated. The patient, who had undergone polychemotherapy and was in otherwise good general condition, without lymphadenopathies or imbalance of the immune system, presented with a palatal ulceration that progressively involved the palatal mucosa and bone, the paranasal sinuses and the orbit. Repeated cultural examinations were always negative. He had undergone multiple cytological smears of the inflammatory infiltration and biopsies of both the oral and nasal mucosa, which resulted in extensive necrotic debris and suppurative inflammation, and, on the very last biopsy, fungal hyphae, spores and conidia were also detected. These were large, branching, mostly non-septate hyphae, associated with conidiophores and conidia, the latter appearing dark brown to black in the histological preparations. Following the diagnosis of combined mucormycosis and aspergillosis, the patient underwent prolonged topic and systemic antibiotic treatment that resulted curative. Mucormycosis usually is a fatal complication of head and neck or systemic disorders, leading to severe immune suppression. Nevertheless, early diagnosis may be achieved using a combination of special stains and may lead to effective antibiotic treatment and cure of the patient, even if associated with other opportunistic infections, such as aspergillosis.


[Use of enterosorption in correction of immune changes during the acute period of mild craniocerebral trauma].
The immune system indexes were studied in 30 injured persons with craniocerebral trauma. In 15 patients (1st group) the conventional methods of treatment were applied and in 15 (2nd group)--the enterosorption using polysorb MP was included in the complex of treatment. Rapid regression of neurological symptoms was promoted by the enterosorption application.


(+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate (SNI-2011, cevimeline hydrochloride) induces saliva and tear secretions in rats and mice: the role of muscarinic acetylcholine receptors.
We investigated effects of (+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate (SNI-2011, cevimeline hydrochloride), a rigid analogue of acetylcholine, on saliva and tear secretions in rats and mice to evaluate its therapeutical efficacy for xerostomia and xerophthalmia in patients with Sjogren's syndrome and X-ray exposure in the head and neck. Intraduodenal administrations of SNI-2011 increased saliva secretion in a dose-dependent manner at doses ranging from 3 to 30 mg/kg in normal rats and mice, two strains of autoimmune disease mice and X-irradiated saliva secretion defective rats. The salivation elicited by SNI-2011 was completely inhibited by atropine. A similar atropine-sensitive response was observed in tear secretion. In rat submandibular/sublingual gland membranes, [3H]quinuclidinyl benzilate (QNB) binding was saturable, and Scatchard plot analysis revealed a single population of binding sites with a Kd of 22 pM and a maximal binding capacity of 60 fmol/mg protein. The competitive inhibition curve of the [3H]QNB binding by SNI-2011 was obtained, and its dissociation constant value calculated from IC50 was 1-2 microM. These results suggest that SNI-2011 increases saliva and tear secretions through a direct stimulation to muscarinic receptors in salivary and lacrimal glands, and they suggest that SNI-2011 should be beneficial to patients with Sjögren's syndrome and X-ray exposure in the head and neck.


Impact of soyasaponin I on TLR2 and TLR4 induced inflammation in the MUTZ-3-cell model.
Previous studies have demonstrated that soyasaponin (SoSa) possesses anti-inflammatory properties in lipopolysaccharide (LPS)-stimulated immune cells by influencing the immune sensing of toll-like receptor (TLR) 4. The aim of this study was to investigate the immune modulatory effect of SoSa I on TLR2- and TLR4-induced inflammation within the monocytic MUTZ-3-cell model. MUTZ-3 cells were stimulated with gram-negative (Escherichia coli) or gram-positive (Staphylococcus aureus) bacteria or bacterial pathogen-associated molecular patterns (PAMPs) such as LPS or peptidoglycans (PGN) alone or in combination with SoSa I. Cell morphology was characterized by raster scanning and light microscopy. Cytokine production (IL-1β, IL-6, TNF-α, IP-10, RANTES and IL-8) was measured by cytometric bead array and the expression of surface markers was assessed by flow cytometry. MUTZ-3 cells revealed a cell maturation-like alteration in morphology and increased expression of CD80, CD86, TLR2 and TLR4 after stimulation with either gram-negative and gram-positive bacteria or bacterial PAMPs. The addition of SoSa I suppressed pro-inflammatory cytokine and chemokine secretions in a dose-dependent manner regardless of TLR2 or TLR4 stimulation. Interestingly, E. coli- and S. aureus-induced inflammation was always inhibited better by SoSa I than that induced by LPS and PGN. Additionally, SoSa I reduced the expression of CD86 in PGN- or LPS-stimulated cells. This study demonstrated that the anti-inflammatory capacity of SoSa I is based on influencing both monocytic TLR2 and TLR4 and that SoSa I inhibits more effectively whole bacteria compared to solely LPS or PGN what points to a broader role of SoSa I in the down-regulation of inflammation.


Raman-based diagnostics of drought, heat and light-induced stresses in three different varieties of hemp.
Hand-held Raman spectroscopy can be used for highly accurate differentiation between drought, heat and light-triggered stresses in hemp. The differentiation is based on the changes in the biochemistry of plants caused by such stresses. Hemp farming is a rapidly growing industry. This dioecious plant is primarily cultivated for its fibers, seeds, and cannabinoid-rich oils. The yield of these materials can be drastically lowered by many abiotic stresses, such as drought, heat and light. It becomes critically important to develop robust and reliable approaches that can be used to diagnose such abiotic stresses in hemp. In this study, we investigate the accuracy of Raman spectroscopy, an emerging tool within crop monitoring, in the confirmatory identification of drought, heat, and light-induced stresses in three varieties of hemp. Our results showed that mono, double and triple stresses uniquely alter plant biochemistry that results in small spectroscopic changes detected in the Raman spectra acquired from the hemp leaves. These changes could be used for the 80-100% accurate identification of individual abiotic stresses and their combinations in plants. These results demonstrate that a hand-held Raman spectrometer can be used for highly accurate, non-invasive, non-destructive, and label-free diagnostics of hemp stresses directly in the greenhouse or in the field.


Short communication: serum-based assay accurately detects single nucleotide polymorphisms of IL28B and SOCS3 in HIV/hepatitis C virus-coinfected subjects.
Single nucleotide polymorphisms (SNPs) have become important in predicting treatment response to interferon containing anti-hepatitis C virus (HCV) therapy in HCV and HIV/HCV-infected patients. A reliable method for extracting host DNA from serum for genotyping assays would present a practical alternative for clinicians and investigators seeking to perform SNP analyses in HCV-infected patients, particularly in resource-limited settings. Human genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) and serum of 51 HIV/HCV coinfected patients using the QIAamp DNA Blood Mini Kit and QIAamp Min Elute Virus Spin Kit, respectively. Genotyping assays for the IL28B SNP (rs12979860) and SOCS3 SNP (rs4969170) were performed using the commercially available ABI Taqman allelic discrimination kit and reverse transcriptase-polymerase chain reaction (RT-PCR) was performed using 50 cycles. Results of the genotyping assays using DNA from both PBMCs and cell-free serum were determined separately and then analyzed for concurrence. Genotype analyses performed using DNA isolated from PBMCs or cell-free serum showed a 100% agreement between the IL28B genotyping results from the serum and PBMC isolates and 98% agreement for SOCS3 SNP. This novel serum-based assay to isolate DNA fragments from the serum of HIV/HCV-coinfected subjects can accurately determine a subject's genotype for IL28B (rs12979860) and SOCS3 (rs4969170). This assay could be immediately valuable for detecting clinically relevant SNPs from serum in cases in which PBMCs are not available.


The influence of different cements on the fracture resistance and marginal adaptation of all-ceramic and fiber-reinforced crowns.
This in vitro study investigated the marginal adaptation and fracture resistance of heat-pressed glass-ceramic and fiber-reinforced composite molar crowns luted with resin, resin-modified glass-ionomer, or zinc-oxide-eugenol-free cements. A total of 24 heat-pressed all-ceramic and 24 glass fiber-reinforced composite crowns were constructed and cemented using the above-mentioned luting agents (eight crowns per cement). The restorations were thermocycled and mechanically stressed, and fracture resistance was determined. Marginal adaptation was evaluated before and after stress application using semiquantitative analysis in a scanning electron microscope. All-ceramic and fiber-reinforced composite crowns reached the highest fracture resistance after stress application in combination with the resin cement. When luted with resin-modified glass-ionomer or zinc-oxide-eugenol-free cements, the fracture resistance of all-ceramics decreased significantly, while the fiber-reinforced composite crowns maintained their fracture resistance level; the lowest values were found for zinc-oxide-eugenol-free cements. The marginal adaptation remained unchanged after stress for all-ceramics and fiber-reinforced composite restorations if they were luted with resin cements. Luting with resin-modified glass-ionomers significantly deteriorated the marginal adaptation after stress application, with the exception of the crown-cement interface of all-ceramics. The highest fracture resistance and marginal adaptation were found for all-ceramic and glass fiber-reinforced composite molar crowns if they were luted with resin cement.


Factors underlying taking a child to HIV care: implications for reducing loss to follow-up among HIV-infected and -exposed children.
With the aim of reducing pediatric loss to follow-up (LTFU) from HIV clinical care programs in sub-Saharan Africa, we sought to understand the personal and socio-cultural factors associated with the behavior of caregivers taking HIV-infected and -exposed children for care in western Kenya. Between May and August, 2010, in-depth interviews were conducted with 26 purposively sampled caregivers caring for HIV-infected (7), HIV-exposed (17) and HIV-unknown status (2) children, documented as LTFU from an urban and rural HIV care clinic. All were women with a majority (77%) being biological parents. Interviews were audio-recorded, transcribed and content analyzed. Thematic content analysis of the women's perceptions revealed that their decision about routinely taking their children to HIV care involved multiple levels of factors including: (1) intrapersonal: transport costs, food availability, time constraints due to work commitment, disclosure of HIV status for both mother and child, perception that child is healthy and religious beliefs; (2) interpersonal: unsupportive male partner, stigma by the family and family conflicts; (3) community: cultural norms, changing community dynamics and perceived stigma; (4) health care system: clinic location, lack of patient-centered care, delays at the clinic and different appointment schedules (mother and child). Furthermore, the factors across these different levels interacted with each other in a complex way, illustrating the challenges women face in taking their children to HIV care. The complexity and interconnectedness of the factors underlying retention of children in HIV care perceived by these women caregivers suggests that interventions to reduce pediatric LTFU need to be holistic and address multiple socio-ecological levels. Patient-centered care that integrates a family-centered approach to HIV pediatric care is recommended.


Deprotonation in Mixed-Valent Diiron(II,III) Complexes with Aniline or Benzimidazole Ligands.
We have previously investigated cis/trans isomerization processes in phenoxido-bridged mixed-valent Fe(II)Fe(III) complexes that contain either one aniline or one anilide ligand. In this work, we compare the properties of similar complexes bearing one terminal protic ligand, either aniline or 1H-benzimidazole. Whatever the ligand, (1)H NMR spectroscopy clearly evidences that the complexes are present in CH3CN as a mixture of cis- and trans-isomers in a close to 1:1 ratio. We show here that addition of NEt3 indeed allows the deprotonation of these ligands, the resulting complexes bearing either anilide or benzimidazolide that are coordinated to the ferric site. The latter are singular examples of a high-spin ferric ion coordinated to a benzimidazolide ligand. Whereas the trans-isomer of the anilide complex is the overwhelming species, benzimidazolide species are mixtures of cis- and trans-isomers in equal proportions. Moreover, cyclic voltammametry studies show that Fe(III)Fe(III) complexes with 1H-benzimidazole are more stable than their aniline counterparts, whereas the reverse is observed for the deprotonated species.


Effects of airborne pollen on allergic rhinitis and asthma across different age groups in Beijing, China.
In the context of global warming and rapid urbanization, pollen has become a significant public health concern for Chinese citizens. However, there is a paucity of epidemiological research on the impact of pollen on allergen-linked diseases, such as allergic rhinitis and asthma, in China. Using data from the Beijing Chaoyang Hospital between 2013 and 2019, which included allergic rhinitis and asthma incidence, meteorological records, and air pollution data, we employed a Generalized Additive Model (GAM) to examine the relationship between overall and type-specific pollen concentrations in relation to varying population exposures. We found that increased overall pollen concentrations significantly increased the risks of allergic rhinitis and asthma in diverse populations. Notably, the risk of allergic rhinitis was higher than that of asthma at equivalent pollen concentrations. Seasonal trends indicated that spring pollen peaks, primarily from trees, were associated with a lower risk of both allergic rhinitis and asthma than autumn peaks, predominantly from weeds. This study underscores the importance of identifying pollen species that pose heightened risks to different demographic groups across seasons, thereby providing targeted interventions for public health agencies.


The superficial anulus fibrosus ligament. An incipient description of a separate ligament between the lumbar anterior longitudinal ligament and the intervertebral disc.
A previously unknown ligament, the superficial anulus fibrosus ligament (SAFL), situated on the ventral part of the L5 intervertebral disc (ID) was observed and described from autopsy material. Twenty-eight cadaveric specimens from 12 black and 16 white persons aged 17-30 years were studied during routine forensic autopsies. The anterior longitudinal ligament was separated from the ID and the ventral part of the SAFL was visualized. The SAFL samples were removed, measured and studied with both conventional histology and examination by transmission electron microscopy. The SAFL was a completely separate ligament at the level of the L5-S1 ID situated between the anterior longitudinal ligament and the anulus fibrosus of the ID. The fibers of the ligament were vertically oriented. A difference in distance between the L5-S1 vertebral bodies ventrally was noted in the two groups studied (18.7 +/- 1.2 mm in the black vs. 15.2 +/- 1.0 mm in the white, p < 0.001), indicating a difference in the ventral thickness of the intervertebral disc. Also, there was a difference in the length (black: 17.7 +/- 1.6 mm vs. white: 14.1 +/- 1.1), thickness (black: 3.3 +/- 0.3 mm vs. white: 2.1 +/- 1.9), and the cross-sectional area (black: 58.2 +/- 6.7 mm(2) vs. white: 26.5 +/- 2.7 mm(2), p < 0.001) of the SAFL. Conventional light microscopy revealed no obvious differences. However, transmission electron microscopy revealed notably larger collagen fibril diameter in black than white subjects. In conclusion, the interbody distances were greater in the black group, indicating a greater intervertebral disc thickness, compared to that of the white. Furthermore, the SAFL was significantly longer and thicker in the black than in the white group. Albeit unsubstantiated, these race-specific macroscopic findings may have implications for understanding the etiology of various low back stress problems.


Improved function and myocardial repair of infarcted heart by intracoronary injection of mesenchymal stem cell-derived growth factors.
Transplantation of mesenchymal stem cells (MSC) improves repair and function recovery following myocardial infarction (MI), but underlying mechanisms remain to be elucidated. We hypothesize that MSC could achieve protection by paracrine effects through released mediators rather than direct cardiac regeneration. We sought to characterize the effects of MSC-secreted growth factors on extent of early recovery from MI. Swine subjected to acute MI by temporary balloon occlusion of the left anterior descending coronary artery using percutaneous techniques received intracoronary injection of either concentrated MSC-derived growth factors or control medium. Animals were killed at 7 days to evaluate early effects. Treatment with MSC-derived factors significantly reduced cardiac troponin-T elevation and improved echocardiographic parameters, including fractional area shortening, stroke volume, cardiac output, and wall motion score index. Quantitative evaluation of fibrosis by Verhoff staining revealed a reduction of the fibrotic area in the infarcted zone. Similarly, Masson's trichrome staining revealed reduced myocardial damage as demonstrated by areas of relatively preserved myocardium in the infarcted area. TUNEL assay demonstrated less cardiomyocyte apoptosis. Protein array detected the presence of angiogenic (vascular endothelial growth factor, endothelin, and epiregulin), anti-apoptotic (Galectin-3, Smad-5, sRFP-1, and sRFP-4) and anti-remodeling factors. Reverse transcription polymerase chain reaction confirmed the expression of these factors. In summary, a single intracoronary injection of concentrated biologically active factors secreted by MSC could achieve early protection of ischemic myocardium and improve cardiac repair and contractility. MSC-derived growth factors injection (rather than MSC themselves) should be evaluated as a novel therapy to treat ischemic heart disease, avoiding many practical and technical issues of cell therapy.


[The role of sex steroids in the regulation of carbohydrate metabolism in rat lungs after a single whole-body cooling].
A single total body cooling was found to cause a more distinct alteration in carbohydrate metabolism in lung tissue of male rats as compared with female rats. These metabolic alterations were less distinct in castrated males. Preadministration of one of the sex hormones (testosterone, estradiol or progesterone) into the castrated males led to normalisation of carbohydrate metabolism in cooling; among the sex steroids estrogen was the most effective.


A checklist of the bats of Peninsular Malaysia and progress towards a DNA barcode reference library.
Several published checklists of bat species have covered Peninsular Malaysia as part of a broader region and/or in combination with other mammal groups. Other researchers have produced comprehensive checklists for specific localities within the peninsula. To our knowledge, a comprehensive checklist of bats specifically for the entire geopolitical region of Peninsular Malaysia has never been published, yet knowing which species are present in Peninsular Malaysia and their distributions across the region are crucial in developing suitable conservation plans. Our literature search revealed that 110 bat species have been documented in Peninsular Malaysia; 105 species have precise locality records while five species lack recent and/or precise locality records. We retrieved 18 species from records dated before the year 2000 and seven species have only ever been recorded once. Our search of Barcode of Life Datasystems (BOLD) found that 86 (of the 110) species have public records of which 48 species have public DNA barcodes available from bats sampled in Peninsular Malaysia. Based on Neighbour-Joining tree analyses and the allocation of DNA barcodes to Barcode Index Number system (BINs) by BOLD, several DNA barcodes recorded under the same species name are likely to represent distinct taxa. We discuss these cases in detail and highlight the importance of further surveys to determine the occurences and resolve the taxonomy of particular bat species in Peninsular Malaysia, with implications for conservation priorities.


Topography of simian virus 40 A protein-DNA complexes: arrangement of pentanucleotide interaction sites at the origin of replication.
Investigation of the DNA binding properties of the simian virus 40 (SV40) A protein (large T antigen) and the hybrid adenovirus-SV40 D2 protein revealed that both viral proteins protect similar regions of SV40 DNA from digestion by DNase I or methylation by dimethyl sulfate. However, the interaction of D2 protein with DNA was more sensitive to increases of NaCl concentration than was the interaction of wild-type SV40 A protein. Dimethylsulfate footprinting identified 13 DNA pentanucleotide contact sites at the viral origin of replication. The sequences of these sites corresponded to the consensus family 5'-(G greater than T) (A greater than G)GGC-3'. The pentanucleotides were distributed in three regions of origin DNA. Region I contained three pentanucleotide contact sites arranged as direct repetitions encompassing a span of 23 base pairs. In region II, four pentanucleotides were oriented as inverted repetitions that also spanned a total of 23 base pairs. Region III had six recognition pentanucleotides arranged as direct repetitions in a space of 59 base pairs. These fundamental variations in DNA arrangement are likely to determine different patterns of protein binding in each region.


Ciprofloxacin-induced glutathione redox status alterations in rat tissues.
The possible oxidative stress inducing effect of a fluoroquinolone (FQ) antibiotic, ciprofloxacin (CPFX), was investigated in rats measuring glutathione redox status. For this purpose, the drug was administered to rats as two different single doses (100 and 150 mg/kg, ip) or a repeated dose (500 mg/kg/d, ig, for 5d). Then, total and oxidized glutathione levels were determined in hepatic and cerebral tissues of the rats by an enzymatic cycling assay, and the glutathione redox status was calculated. The possible protective effects of vitamin E or allopurinol against CPFX-induced alterations on glutathione system have also been examined. Following both routes of administration of CPFX, the total glutathione content of the liver, but not of brain decreased significantly. The oxidized glutathione (GSSG) in the brain increased after single or repeated dose treatments, but only with repeated doses of CPFX in the liver. CPFX induced dose-dependent alterations in the glutathione redox status in both tissues. With single doses the effect was more pronounced in cerebral tissue, and with repeated ig doses it was significant in both tissues. Pretreatment of rats with vitamin E or allopurinol before the administration of CPFX provided marked protection against glutathione redox status alterations in both tissues. Our results, thus, indicate that CPFX treatment introduces an oxidative stress in cerebral and hepatic tissues of rat.


Evaluation of a web-based portal to improve resident education by neonatology fellows.
Integration of web-based educational tools into medical training has been shown to increase accessibility of resources and optimize teaching. We developed a web-based educational portal (WBEP) to support teaching of pediatric residents about newborn medicine by neonatology fellows. 1) To compare residents' attitudes about their fellow-led education in the NICU pre- and post-WBEP; including assessment of factors that impact their education and usefulness of teaching tools. 2) To compare fellow utilization of various teaching modalities pre- and post-WBEP. We queried residents about their attitudes regarding fellow-led education efforts and various teaching modalities in the NICU and logistics potentially impacting effectiveness. Based on these data, we introduced the WBEP - a repository of teaching tools (e.g., mock code cases, board review questions, journal articles, case-based discussion scenarios) for use by fellows to supplement didactic sessions in a faculty-based curriculum. We surveyed residents about the effectiveness of fellow teaching pre- and post-WBEP implementation and the type of fellow-led teaching modalities that were used. After analysis of survey responses, we identified that residents cited fellow level of interest as the most important factor impacting their education. Post-implementation, residents described greater utilization of various teaching modalities by fellows, including an increase in use of mock codes (14% to 76%, p<0.0001) and journal articles (33% to 59%, p=0.02). A web-based resource that supplements traditional curricula led to greater utilization of various teaching modalities by fellows and may encourage fellow involvement in resident teaching.


Outcomes after bilateral implantation of AcrySof IQ PanOptix trifocal intraocular lens: a prospective interventional study.
Implantation of multifocal intraocular lenses (IOLs) is becoming increasingly popular for the treatment of visual demands at various distances in patients undergoing phacoemulsification cataract surgery. We aimed to assess the visual performance and rates of photic phenomena, posterior capsule opacification (PCO), and spectacle independence in patients with bilateral implantation of the AcrySof® IQ PanOptix® multifocal IOL model TFNT00 at one and six months postoperatively. This prospective interventional cohort study included adult patients who underwent uneventful phacoemulsification cataract surgery with bilateral implantation of AcrySof® IQ PanOptix® IOL. Uncorrected and corrected visual acuities at far, intermediate, and near distances were measured preoperatively and at the one- and six-month postoperative follow-up examinations. The rates of photic phenomena, postoperative need for near and distance spectacles, and PCO were also recorded. We included 164 eyes of 82 patients with a male-to-female ratio of 38 (46.3%) to 44 (53.7%) and a mean (standard deviation [SD]) age of 52.37 (7.62) years. There were statistically significant improvements in the visual acuities of both eyes across all distances at the one- and six-month follow-up examinations compared to the preoperative values (all P < 0.001), except for corrected near visual acuity in the right eye (P > 0.05) at six-month. We also detected significant postoperative improvements in visual acuities of both eyes across all distances at the six-month follow-up compared to values at the one-month follow-up (all P < 0.05), except for corrected near visual acuity in the right eye (P > 0.05). The photic phenomenon was reported by 12 (14.6%) of the 82 patients at the six-month postoperative follow-up. Five (6.1%) and eight (9.8%) of the 82 patients reported using spectacles for distance and near, respectively. Additionally, PCO developed in 19 (11.6%) of the 164 included eyes, although it was not clinically significant at six months. The AcrySof® IQ PanOptix® IOL model TFNT00 is recommended for use, given its excellent performance in all ranges of vision, a high rate of spectacle independence, and a good safety profile. Future comparative studies with longer follow-up periods are warranted to verify superiority of its performance over that of other available multifocal IOLs.


Particulate matter speciation profiles for light-duty gasoline vehicles in the United States.
Representative profiles for particulate matter particles less than or equal to 2.5 microm (PM2.5) are developed from the Kansas City Light-Duty Vehicle Emissions Study for use in the US. Environmental Protection Agency (EPA) vehicle emission model, the Motor Vehicle Emission Simulator (MOVES), and for inclusion in the EPA SPECIATE database for speciation profiles. The profiles are compatible with the inputs of current photochemical air quality models, including the Community Multiscale Air Quality Aerosol Module Version 6 (AE6). The composition of light-duty gasoline PM2.5 emissions differs significantly between cold start and hot stabilized running emissions, and between older and newer vehicles, reflecting both impacts of aging/deterioration and changes in vehicle technology. Fleet-average PM2.5 profiles are estimated for cold start and hot stabilized running emission processes. Fleet-average profiles are calculated to include emissions from deteriorated high-emitting vehicles that are expected to continue to contribute disproportionately to the fleet-wide PM2.5 emissions into the future. The profiles are calculated using a weighted average of the PM2.5 composition according to the contribution of PM2.5 emissions from each class of vehicles in the on-road gasoline fleet in the Kansas City Metropolitan Statistical Area. The paper introduces methods to exclude insignificant measurements, correct for organic carbon positive artifact, and control for contamination from the testing infrastructure in developing speciation profiles. The uncertainty of the PM2.5 species fraction in each profile is quantified using sampling survey analysis methods. The primary use of the profiles is to develop PM2.5 emissions inventories for the United States, but the profiles may also be used in source apportionment, atmospheric modeling, and exposure assessment, and as a basis for light-duty gasoline emission profiles for countries with limited data. PM2.5 speciation profiles were developed from a large sample of light-duty gasoline vehicles tested in the Kansas City area. Separate PM2.5 profiles represent cold start and hot stabilized running emission processes to distinguish important differences in chemical composition. Statistical analysis was used to construct profiles that represent PM2.5 emissions from the U.S. vehicle fleet based on vehicles tested from the 2005 calendar year Kansas City metropolitan area. The profiles have been incorporated into the EPA MOVES emissions model, as well as the EPA SPECIATE database, to improve emission inventories and provide the PM2.5 chemical characterization needed by CMAQv5.0 for atmospheric chemistry modeling.


Venous Thromboembolism in Patients with Liver Cirrhosis: Findings from the RIETE (Registro Informatizado de la Enfermedad TromboEmbolica) Registry.
Patients with cirrhosis are not only at an increased risk of bleeding but also at risk of venous thromboembolism (VTE). We sought to determine the clinical characteristics, management, and outcomes after VTE in patients with cirrhosis. We used the data from RIETE (Registro Informatizado de la Enfermedad TromboEmbolica), an international registry of patients with VTE, to compare the outcomes in patients with and without cirrhosis. Main outcomes included all-cause mortality, pulmonary embolism (PE)-related mortality, recurrent VTE, and bleeding. Among 43,611 patients with acute VTE, 187 (0.4%) had cirrhosis. Of these, 184 (98.4%) received anticoagulation for a median of 109 days (interquartile range [IQR]: 43-201 days), most commonly with enoxaparin (median dose: 1.77 [IQR: 1.38-2.00] mg/kg/day). Compared with patients without cirrhosis, those with cirrhosis had a higher rate of all-cause mortality (10.7 vs. 3.4%; odds ratio [OR]: 3.41; 95% confidence interval [CI]: 2.03-5.46) and fatal bleeding (2.1 vs. 0.2%; OR: 13.94; 95% CI: 3.65-37.90) but similar rates of fatal PE (0.5 vs. 0.5%; OR: 1.17; 95% CI: 0.03-6.70). Patients with cirrhosis had a higher rate of all-cause mortality per 100 patient-years of follow-up (58.9 vs. 16.0; hazard ratio [HR]: 3.70; 95% CI: 2.69-4.91). One-year hazard ratio of clinically relevant bleeding (HR: 2.86; 95% CI: 1.91-4.27), fatal bleeding (HR: 8.51; 95% CI: 3.5-20.7), or recurrent VTE (HR: 2.08; 95% CI: 1.00-4.36) was higher in patients with cirrhosis. Cirrhosis is a challenging comorbidity in patients with VTE. Most patients were treated with anticoagulation and had an elevated risk of recurrence, similar risk of fatal PE, and a very high risk of bleeding including fatal bleeds.


Engineering and characterisation of chimeric monoclonal antibody 806 (ch806) for targeted immunotherapy of tumours expressing de2-7 EGFR or amplified EGFR.
We report the generation of a chimeric monoclonal antibody (ch806) with specificity for an epitope on the epidermal growth factor receptor (EGFR) that is different from that targeted by all other anti-EGFR therapies. Ch806 antibody is reactive to both de2-7 and overexpressed wild-type (wt) EGFR but not native EGFR expressed in normal tissues at physiological levels. Ch806 was stably expressed in CHO (DHFR -/-) cells and purified for subsequent characterisation and validated for use in preliminary immunotherapy investigations. Ch806 retained the antigen binding specificity and affinity of the murine parental antibody. Furthermore, ch806 displayed enhanced antibody-dependent cellular cytotoxicity against target cells expressing the 806 antigen in the presence of human effector cells. Ch806 was successfully radiolabelled with both iodine-125 and indium-111 without loss of antigen binding affinity or specificity. The radioimmunoconjugates were stable in the presence of human serum at 37 degrees C for up to 9 days and displayed a terminal half-life (T(1/2beta)) of approximately 78 h in nude mice. Biodistribution studies undertaken in BALB/c nude mice bearing de2-7 EGFR-expressing or amplified EGFR-expressing xenografts revealed that (125)I-labelled ch806 failed to display any significant tumour retention. However, specific and prolonged tumour localisation of (111)In-labelled ch806 was demonstrated with uptake of 31%ID g(-1) and a tumour to blood ratio of 5 : 1 observed at 7 days postinjection. In vivo therapy studies with ch806 demonstrated significant antitumour effects on established de2-7 EGFR xenografts in BALB/c nude mice compared to control, and both murine 806 and the anti-EGFR 528 antibodies. These results support a potential therapeutic role of ch806 in the treatment of suitable EGFR-expressing tumours, and warrants further investigation of the potential of ch806 as a therapeutic agent.


Cardiovascular ultrafast computed tomographic angiography.
Ultrafast computed tomography can substitute for angiography and provide answers to clinical and therapeutic questions. Because of superior definition of vessels and myocardium, current applications include imaging the aorta, carotids, vena cava, and other venous structures, congenital and acquired pulmonary artery abnormalities, coronary arteries, coronary artery saphenous, and internal mammary artery bypass grafts, right and left ventricles, cardiac tumors and thrombi, cardiomyopathies (ischemic, dilated, hypertrophic, and restrictive), congenital heart disease, and a variety of other acquired abnormalities. Parallel contiguous tomographic levels provide excellent structural definition including inner vessel wall and endocardium.


[Secondary Standard Dosimetry Laboratory at the Ruder Bosković Institute, Zagreb].
The Secondary Standard Dosimetry Laboratory at the Ruder Bosković Institute (SSDL), Zagreb, Croatia, was set up over the last few years with a strong support by the International Atomic Energy Agency (IAEA) through the Technical Cooperation Project CRO/1/004, Establishing Calibration Services. The SSDL occupies two calibration rooms, each 9.6 m long and 6 m wide and each with proper air conditioning. Their walls are concrete and 1 m thick, and the entrance doors are plated with lead to protect the control rooms and the surroundings against radiation. In the first calibration room in the basement, there are two sealed sources which share the same, 6 m long calibration bench. A 30 TBq 60Co source on one side of the bench is used for calibrating ionising chambers and other high-dose radiation equipment. The irradiation unit on the other side of the bench combines two sealed sources, that is, a 740 MBq 137Cs source and a 185 MBq 60Co source, and is used for radiation protection purposes. It has three attenuators with nominal attenuations of x10, x100, and x1000. The second calibration room, which is just above the first, accommodates an X-ray unit (ISOVOLT 420, 40 kV to 300 kV, 1 mA to 20 mA) with a 5 m long calibration bench, aperture wheel assembly designed to modify the X-ray beam diameter to meet various configuration requirements for calibration instruments, a set of filter assemblies to control beam definition according to ISO 4037-3, and a half-value layer kit.


Association between nonmedical prescription drug use and health status among young Swiss men.
To examine the relationship between the nonmedical prescription drug use (NMPDU) of six drug classes and health. Data on young adults males (mean age, 19.96 years) from the baseline and follow-up of the Cohort Study on Substance Use Risk Factors (C-SURF) were used (n = 4,958). Two sets of logistic regression models were fitted to examine the associations between NMPDU of opioid analgesics, sedatives or sleeping pills, anxiolytics, antidepressants, beta blockers and stimulants, and health status (assessed using the Medical Outcomes Study 12-Item Short Form Survey Instrument [SF-12 v2]). We first computed odds ratios between NMPDU at baseline and poor mental and physical health at follow-up, adjusting for poor mental or physical health at baseline. We then computed odds ratios between poor mental and physical health at baseline and NMPDU at follow-up, adjusting for NMPDU at baseline. Three key findings regarding mental health were (1) there was a reciprocal risk between poor mental health and sedatives and anxiolytics; (2) poor mental health increased NMPDU of opioid analgesics and antidepressants but not vice versa; and (3) there were no associations with stimulants. Three key findings regarding physical health were (1) poor physical health increased the risk of NMPDU of anxiolytics; (2) the only reciprocal risk was between physical health and NMPDU of opioid analgesics; and (3) there were no associations with stimulants. These results, among the first ever on reciprocal effects between NMPDU and mental and physical health status, give unique information concerning the adverse effects of NMPDU on health and vice versa. The study shows that NMPDU is not only a sign of self-medication but may induce health problems.


Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism.
Experimental studies and indirect clinical evidence suggest that low molecular weight heparins may have antineoplastic effects. We investigated the influence of a low molecular weight heparin dalteparin on the survival of patients with active cancer and acute venous thromboembolism. Survival data were examined in a posthoc analysis in patients with solid tumors and venous thromboembolism who were randomly assigned to dalteparin or a coumarin derivative for 6 months in a multicenter, open-label, randomized, controlled trial. All-cause mortality at 12 months was compared between treatment groups in patients with and without metastatic malignancy. The effect of dalteparin on survival was compared between the two patient subgroups. During the 12-month follow-up period, 356 of 602 patients with solid tumors and acute venous thromboembolism died. Among patients without metastatic disease, the probability of death at 12 months was 20% in the dalteparin group, as compared with 36% in the oral anticoagulant group (hazard ratio, 0.50; 95% CI, 0.27 to 0.95; P = .03). In patients with metastatic cancer, no difference in mortality between the treatment groups was observed (72% and 69%, respectively; hazard ratio, 1.1; 95% CI, 0.87 to 1.4; P = .46). The observed effects of dalteparin on survival were statistically significantly different between patients with and without metastatic disease (P = .02). The use of dalteparin relative to coumarin derivatives was associated with improved survival in patients with solid tumors who did not have metastatic disease at the time of an acute venous thromboembolic event. Additional studies are warranted to investigate these findings.


Fetal and neonatal exposure to nicotine disrupts ovarian function and fertility in adult female rats.
Women born to mothers who smoked during pregnancy have been shown to have impaired fertility, although the mechanisms underlying this association are unknown. Nicotine administration in adult animals has adverse effects on the ovary and uterus; however, the effects of fetal exposure to nicotine on postnatal ovarian function have not been determined. The goal of this study was to assess the effect of fetal and neonatal exposure to nicotine on ovarian function and fertility of the offspring. Nulliparous female Wistar rats were given 1 mg.kg-1.d-1 nicotine bitartrate, subcutaneously for 14 d prior to mating, during pregnancy and throughout lactation until weaning. Measures of fertility, breeding success, and serum levels of ovarian steroid hormones in offspring were assessed at 4 and 6 mo of age. Fetal and neonatal exposure to nicotine significantly increased the time to pregnancy as the animals aged. Similarly, evidence of altered ovarian steroidogenesis including increased serum progesterone concentrations and a decreased estrogen:progesterone ratio was observed in 6-mo-old animals. We conclude that fetal and neonatal exposure to nicotine results in delayed ovarian dysfunction in adult female offspring.


Phosphorylation state defines discrete roles for monopolin in chromosome attachment and spindle elongation.
It is unknown how oscillations in Cdk1 activity drive the dramatic changes in chromosome and spindle dynamics that occur at the metaphase/anaphase transition. We show that the Schizosaccharomyces pombe monopolin complex has distinct functions in metaphase and anaphase that are determined by the phosphorylation state of its Mde4 subunit. When Cdk1 activity is high in metaphase, Mde4 is hyperphosphorylated on Cdk1 phosphorylation sites and localizes to kinetochores. A nonphosphorylatable mutant of Mde4 does not localize to kinetochores, appears prematurely on the metaphase spindle, and interferes with spindle dynamics and chromosome segregation, illustrating the importance of Cdk1 phosphorylation in regulating metaphase monopolin activity. When Cdk1 activity drops in anaphase, dephosphorylation of Mde4 triggers monopolin localization to the mitotic spindle, where it promotes spindle elongation and integrity, coupling the late mitotic loss of Cdk1 activity to anaphase spindle dynamics. Together, these findings illustrate how the sequential phosphorylation and dephosphorylation of monopolin helps ensure the orderly execution of discrete steps in mitosis.


Patient-reported Outcome Measures of Revision Total Hip Arthroplasty for Prosthetic Joint Infection is not Inferior to Aseptic Revision Total Hip Arthroplasty.
This study aims to investigate whether patients undergoing two-stage revision total hip arthroplasty (THA) for prosthetic joint infection (PJI) and one-stage revision THA for aseptic reasons have similar clinical outcomes and patient satisfaction during their post-operative follow-up. We hypothesise that the two-stage revision THA for PJI is associated with poorer outcomes as compared to aseptic revision THA. We reviewed prospectively collected data in our tertiary hospital arthroplasty registry and identified patients who underwent revision THA between 2001 and 2014, with a minimum of two years follow-up. The study group (two-stage revision THA for PJI) consists of 23 patients and the control group (one-stage revision THA for aseptic reasons) consists of 231 patients. Patient demographics, Western Ontario and McMaster Universities Arthritis Index (WOMAC), Oxford Hip Score (OHS), Short Form-36 (SF-36) scores and patient reported satisfaction were evaluated. Student's t-test was used to compare continuous variables between the two groups. Statistical significance was defined as p <0.05. The pre-operative demographics and clinical scores were relatively similar between the two groups of patients. At two years, patients who underwent revision THA for PJI reported a better WOMAC Pain Score and OHS as compared to aseptic revision THA. A similar proportion of patients were satisfied with their results of surgery in both groups (p=0.093). Although patients who underwent revision THA for PJI had poorer pre-operative functional scores (WOMAC function and SF-36 PF), at two years follow-up, these two groups of patients have comparable post-operative outcomes. Interestingly, patients who had revision THA for PJI reported a better clinical outcome in terms of OHS and WOMAC Pain score as compared to the aseptic group. We conclude that the revision THA for PJI is not inferior to aseptic revision THA in terms of patient satisfaction and clinical outcomes.


A feature-enriched completely blind image quality evaluator.
Existing blind image quality assessment (BIQA) methods are mostly opinion-aware. They learn regression models from training images with associated human subjective scores to predict the perceptual quality of test images. Such opinion-aware methods, however, require a large amount of training samples with associated human subjective scores and of a variety of distortion types. The BIQA models learned by opinion-aware methods often have weak generalization capability, hereby limiting their usability in practice. By comparison, opinion-unaware methods do not need human subjective scores for training, and thus have greater potential for good generalization capability. Unfortunately, thus far no opinion-unaware BIQA method has shown consistently better quality prediction accuracy than the opinion-aware methods. Here, we aim to develop an opinion-unaware BIQA method that can compete with, and perhaps outperform, the existing opinion-aware methods. By integrating the features of natural image statistics derived from multiple cues, we learn a multivariate Gaussian model of image patches from a collection of pristine natural images. Using the learned multivariate Gaussian model, a Bhattacharyya-like distance is used to measure the quality of each image patch, and then an overall quality score is obtained by average pooling. The proposed BIQA method does not need any distorted sample images nor subjective quality scores for training, yet extensive experiments demonstrate its superior quality-prediction performance to the state-of-the-art opinion-aware BIQA methods. The MATLAB source code of our algorithm is publicly available at www.comp.polyu.edu.hk/~cslzhang/IQA/ILNIQE/ILNIQE.htm.


Ontogeny of clenched-hand development in trisomy 18 fetuses: A serial transabdominal fetoscopic observation.
Malpositioning of the fingers is a characteristic anomaly in fetuses with trisomy 18. The defect results in part from muscle variations along the radial margin of forearm and hand, absence of the thenar muscles, anomalous tendons and attachments among the forearm groups, and fusions among the arm flexor group. These variations result in radial or ulnar displacement of the tendons of extensor digitorum and digiti minimi, with overlapping of the fourth and fifth fingers radially and second finger in an ulnar direction. The ontogeny of these changes is unknown. We performed serial transabdominal thin-gauge fetoscopy in a patient with increased nuchal thickening at 12 weeks of pregnancy at the time of genetic testing and again at 14 weeks at the time of termination of pregnancy. Changes in the positioning of the fingers were not apparent at 12 weeks, but were evident at 14 weeks. The findings were beyond the resolution of ultrasound. We conclude that malpositioning of the fingers in trisomy 18 occurs some time between 12 and 14 weeks of gestation. Noninvasive confirmation of these findings may be possible with new and improved ultrasound imaging capabilities or perhaps with three-dimensional ultrasound.


Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays.
Several high-sensitivity cardiac troponin (hs-cTn) assays have recently been developed. It is unknown which hs-cTn provides the most accurate prognostic information and to what extent early changes in hs-cTn predict mortality. In a prospective, international multicentre study, cTn was simultaneously measured with three novel [high-sensitivity cardiac Troponin T (hs-cTnT), Roche Diagnostics; hs-cTnI, Beckman-Coulter; hs-cTnI, Siemens] and a conventional assay (cTnT, Roche Diagnostics) in a blinded fashion in 1117 unselected patients with acute chest pain. Patients were followed up 2 years regarding mortality. Eighty-two (7.3%) patients died during the follow-up. The 2-year prognostic accuracy of hs-cTn was most accurate for hs-cTnT [area under the receivers operating characteristic curve (AUC) 0.78 (95% CI: 0.73-0.83) and outperformed both hs-cTnI (Beckman-Coulter, 0.71 (95% CI: 0.65-0.77; P = 0.001 for comparison), hs-cTnI (Siemens) 0.70 (95% CI: 0.64-0.76; P < 0.001 for comparison)] and cTnT 0.67 (95% CI: 0.61-0.74; P < 0.001 for comparison). Absolute changes of hs-cTnT were more accurate than relative changes in predicting mortality, but inferior to presentation values of hs-cTnT. Combining changes of hs-cTnT within the first 6 h with their presentation values did not further improve prognostic accuracy. Similar results were obtained for both hs-cTnI assays regarding the incremental value of changes. Hs-cTn concentrations remained predictors of death in clinically challenging subgroups such as patients with pre-existing coronary artery disease, impaired renal function, and patients older than 75 years. High-sensitivity cardiac Troponin T is more accurate than hs-cTnI in the prediction of long-term mortality. Changes of hs-cTn do not seem to further improve risk stratification beyond initial presentation values.