Effect of urbanisation on the relationship between total serum IgE and asthma.
It is unclear if the relationship of total serum IgE with asthma varies with degree of urbanisation. We hypothesised that the relationship of total serum IgE to asthma is more pronounced in an urban versus a rural environment. We enrolled 1441 children aged 13-15 years in a peri-urban shanty town in Lima, Peru (n=725) and 23 villages in rural Tumbes, Peru (n=716). We asked participants about asthma and allergy symptoms, environmental exposures and sociodemographics; and performed spirometry, and exhaled nitric oxide and allergy skin testing. We obtained blood for total serum IgE in 1143 (79%) participants. Geometric means for total serum IgE were higher in Lima versus Tumbes (262 versus 192 kU·L(-1); p<0.001). The odds of asthma increased by factors of 1.6 (95% CI 1.3-2.0) versus 1.4 (95% CI 0.9-2.1) per log unit increase in total serum IgE in Lima versus Tumbes, respectively. Atopy was an effect modifier of the relationship of total serum IgE on asthma. Among atopics and non-atopics, the odds of asthma increased by a factor of 2.0 (95% CI 1.5-2.7) and 1.0 (95% CI 0.7-1.4) per log unit increase in total serum IgE, respectively. Total serum IgE was associated with atopic asthma but not with non-atopic asthma. Urbanisation did not appear to be an effect modifier of this relationship.


A cluster of neuropeptide S neurons regulates breathing and arousal.
Neuropeptide S (NPS) is a highly conserved peptide found in all tetrapods that functions in the brain to promote heightened arousal; however, the subpopulations mediating these phenomena remain unknown. We generated mice expressing Cre recombinase from the Nps gene locus (NpsCre) and examined populations of NPS+ neurons in the lateral parabrachial area (LPBA), the peri-locus coeruleus (peri-LC) region of the pons, and the dorsomedial thalamus (DMT). We performed brain-wide mapping of input and output regions of NPS+ clusters and characterized expression patterns of the NPS receptor 1 (NPSR1). While the activity of all three NPS+ subpopulations tracked with vigilance state, only NPS+ neurons of the LPBA exhibited both increased activity prior to wakefulness and decreased activity during REM sleep, similar to the behavioral phenotype observed upon NPSR1 activation. Accordingly, we found that activation of the LPBA but not the peri-LC NPS+ neurons increased wake and reduced REM sleep. Furthermore, given the extended role of the LPBA in respiration and the link between behavioral arousal and breathing rate, we demonstrated that the LPBA but not the peri-LC NPS+ neuronal activation increased respiratory rate. Together, our data suggest that NPS+ neurons of the LPBA represent an unexplored subpopulation regulating breathing, and they are sufficient to recapitulate the sleep/wake phenotypes observed with broad NPS system activation.


How are overweight and obesity associated with reinforcement learning deficits? A systematic review.
Reinforcement learning (RL) refers to the ability to learn stimulus-response or response-outcome associations relevant to the acquisition of behavioral repertoire and adaptation to the environment. Research data from correlational and case-control studies have shown that obesity is associated with impairments in RL. The aim of the present study was to systematically review how obesity and overweight are associated with RL performance. More specifically, the relationship between high body mass index (BMI) and task performance was explored through the analysis of specific RL processes associated with different physiological, computational, and behavioral manifestations. Our systematic analyses indicate that obesity might be associated with impairments in the use of aversive outcomes to change ongoing behavior, as revealed by results involving instrumental negative reinforcement and extinction/reversal learning, but further research needs to be conducted to confirm this association. Hypotheses regarding how obesity might be associated with altered RL were discussed.


Empathic Neural Responses Predict Group Allegiance.
Watching another person in pain activates brain areas involved in the sensation of our own pain. Importantly, this neural mirroring is not constant; rather, it is modulated by our beliefs about their intentions, circumstances, and group allegiances. We investigated if the neural empathic response is modulated by minimally-differentiating information (e.g., a simple text label indicating another's religious belief), and if neural activity changes predict ingroups and outgroups across independent paradigms. We found that the empathic response was larger when participants viewed a painful event occurring to a hand labeled with their own religion (ingroup) than to a hand labeled with a different religion (outgroup). Counterintuitively, the magnitude of this bias correlated positively with the magnitude of participants' self-reported empathy. A multivariate classifier, using mean activity in empathy-related brain regions as features, discriminated ingroup from outgroup with 72% accuracy; the classifier's confidence correlated with belief certainty. This classifier generalized successfully to validation experiments in which the ingroup condition was based on an arbitrary group assignment. Empathy networks thus allow for the classification of long-held, newly-modified and arbitrarily-formed ingroups and outgroups. This is the first report of a single machine learning model on neural activation that generalizes to multiple representations of ingroup and outgroup. The current findings may prove useful as an objective diagnostic tool to measure the magnitude of one's group affiliations, and the effectiveness of interventions to reduce ingroup biases.


Serial CT features of pulmonary leptospirosis in 10 dogs.
Leptospirosis pulmonary haemorrhage syndrome (LPHS) is a frequent manifestation of Leptospira infection in dogs and is associated with a high morbidity and mortality. Three helical 16-slice thoracic CT scans were performed in 10 dogs naturally infected with Leptospira, within 24 hours of admission, and three and seven days later. Patients were sedated and scanned without breathhold, with a protocol adapted for rapid scanning. One dog died of respiratory failure on the morning following the first scan. On the initial scan, imaging features of LPHS included ground-glass nodules (10/10), peribronchovascular interstitial thickening (10/10), diffuse or patchy ground-glass opacity (9/10), solid nodules (8/10) and consolidation (7/10). Temporary bronchiolar dilation was observed in all dogs in association with peribronchovascular interstitial thickening, which had completely resolved at day 7. Nodules were with few exceptions assigned to the centrilobular region. Regression of lesion severity was observed after each subsequent scan. Consolidation and solid nodules changed over time into lesions of ground-glass attenuation. Pleural effusion (3/10) and mediastinal effusion (2/10) were mild and transient. Lesion severity appeared unassociated with survival to discharge.


5,6-trans-16-ene-vitamin D3: a new class of potent inhibitors of proliferation of prostate, breast, and myeloid leukemic cells.
The 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] is the physiologically active form of vitamin D3 that inhibits proliferation and induces differentiation of a variety of malignant cells. We evaluated a newly synthesized vitamin D3 analogue [1,25(OH)2-16-ene-5,6-trans-D3 (Ro 25-4020)] that has a novel 5,6-trans motif. Dose-response studies showed that 1,25(OH)2-16-ene-5,6-trans-D3 had 10-100-fold greater antiproliferative activities than 1,25(OH)2D3 when measuring clonal growth of breast (MCF-7) and prostate (LNCaP) cancer cell lines as well as a myeloid leukemia cell line (HL-60). Because the chief toxicity of vitamin D3 is hypercalcemia, we examined the calcemic activity of 1,25(OH)2-16-ene-5,6-trans-D3 in mice. Remarkably, 1,25(OH)2-16-ene-5,6-trans-D3 was at least 40-fold less calcemic as compared with 1,25(OH)2D3 and 1,25(OH)2-16-ene-D3 (Ro 24-2637). To explore the mechanism by which the 1,25(OH)2-16-ene-5,6-trans-D3 analogue mediated its antiproliferative activity, several studies were performed. Pulse-exposure studies showed that a 4-day pulse exposure to 1,25(OH)2-16-ene-5,6-trans-D3 (10(-7) M) in liquid culture was adequate to achieve a 40% inhibition of MCF-7 clonal growth in the absence of the analogue, suggesting that the growth inhibition mediated by 1,25(OH)2-16-ene-5,6-trans-D3 was at least in part irreversible. Cell cycle studies showed that 1,25(OH)2-16-ene-5,6-trans-D3 increased the proportion of MCF-7 cells in the G0-G1 phase and decreased those in the S phase. Furthermore, 1,25(OH)2-16-ene-5,6-trans-D3 induced an elevated expression of the cyclin-dependent kinase inhibitors, p21waf1 and p27kip1. In addition, 1,25(OH)2-16-ene-5,6-trans-D3 almost completely inhibited telomerase activity, as measured by telomeric repeat amplification protocol assay and human telomerase reverse transcriptase mRNA. For each of the growth-related parameters that were examined, the vitamin D3 analogue was more active than 1,25(OH)2D3. In contrast, 1,25(OH)2D3 was more calcemic than 1,25(OH)2-16-ene-5,6-trans-D3. In summary, 1,25(OH)2-16-ene-5,6-trans-D3, having a novel 5,6-trans motif, strongly inhibited clonal proliferation and reduced telomerase activity with low calcemic activity, suggesting further testing in in vivo cancer models. This analogue may gain a therapeutic niche for selected malignancies.


Evaluation of hospital readmissions in surgical patients: do administrative data tell the real story?
The Centers for Medicare & Medicaid Services has developed an all-cause readmission measure that uses administrative data to measure readmission rates and financially penalize hospitals with higher-than-expected readmission rates. To examine the accuracy of administrative codes in determining the cause of readmission as determined by medical record review, to evaluate the readmission measure's ability to accurately identify a readmission as planned, and to document the frequency of readmissions for reasons clinically unrelated to the original hospital stay. Retrospective review of all consecutive patients discharged from general surgery services at a tertiary care, university-affiliated teaching hospital during 8 consecutive quarters (quarter 4 [October through December] of 2009 through quarter 3 [July through September] of 2011). Clinical readmission diagnosis determined from direct medical record review was compared with the administrative diagnosis recorded in a claims database. The number of planned hospital readmissions defined by the readmission measure was compared with the number identified using clinical data. Readmissions unrelated to the original hospital stay were identified using clinical data. Discordance rate between administrative and clinical diagnoses for all hospital readmissions, discrepancy between planned readmissions defined by the readmission measure and identified by clinical medical record review, and fraction of hospital readmissions unrelated to the original hospital stay. Of the 315 hospital readmissions, the readmission diagnosis listed in the administrative claims data differed from the clinical diagnosis in 97 readmissions (30.8%). The readmission measure identified 15 readmissions (4.8%) as planned, whereas clinical data identified 43 readmissions (13.7%) as planned. Unrelated readmissions comprised 70 of the 258 unplanned readmissions (27.1%). Administrative billing data, as used by the readmission measure, do not reliably describe the reason for readmission. The readmission measure accounts for less than half of the planned readmissions and does not account for the nearly one-third of readmissions unrelated to the original hospital stay. Implementation of this readmission measure may result in unwarranted financial penalties for hospitals.


Calibration with confidence: a principled method for panel assessment.
Frequently, a set of objects has to be evaluated by a panel of assessors, but not every object is assessed by every assessor. A problem facing such panels is how to take into account different standards among panel members and varying levels of confidence in their scores. Here, a mathematically based algorithm is developed to calibrate the scores of such assessors, addressing both of these issues. The algorithm is based on the connectivity of the graph of assessors and objects evaluated, incorporating declared confidences as weights on its edges. If the graph is sufficiently well connected, relative standards can be inferred by comparing how assessors rate objects they assess in common, weighted by the levels of confidence of each assessment. By removing these biases, 'true' values are inferred for all the objects. Reliability estimates for the resulting values are obtained. The algorithm is tested in two case studies: one by computer simulation and another based on realistic evaluation data. The process is compared to the simple averaging procedure in widespread use, and to Fisher's additive incomplete block analysis. It is anticipated that the algorithm will prove useful in a wide variety of situations such as evaluation of the quality of research submitted to national assessment exercises; appraisal of grant proposals submitted to funding panels; ranking of job applicants; and judgement of performances on degree courses wherein candidates can choose from lists of options.


[The development of polymer immunoglobulin preparations to identify different serovars legionella pneumophilia in reaction of slide-agglutination].
The article deals with the results of study targeted to develop polymer diagnostic preparation to identify epidemically significant serogroups Legionella pneumophilia. The preparation combines rate of record (1-5 min) of reaction of paragglutinining preparations with color visualization and demonstrative of reaction of volume agglomeration with polymer diagnosticums. The specially synthesized polymer microspheres were sensibilized with serums enriched with antibodies to lipopolysaccharide of corresponding serovar L. pneumophilia. The derived immunoglobulin diagnostic preparations detect agent of legionellesis in the reaction of slide-agglutination on glass during 1-5 min. The polymer diagnostic preparations provide positive reaction with culture of corresponding serovar and no reaction with other gomologic and geterologic agents of infectious diseases.


Effects of simple and disposable chicken cages for experimental Eimeria infections.
During experimental Eimeria infections in chickens, facilities are often contaminated by fecal oocysts known to be highly resistant to both chemical and enzymatic treatments. Thus, studies using experimental Eimeria infections have been limited due to the difficulty of complete elimination of residual oocysts from both cages and facilities. To overcome this limitation, simple, inexpensive, and disposable cages were constructed from cardboard boxes and tested during experimental Eimeria maxima infections. The cages were used in animal rooms with only a 1.7% evidence of coccidia contamination between adjacent cages. No significant differences in fecal oocyst output and body weight gain were noted between animals housed in disposable cages and animals housed in wire control cages. This cage design is a useful means for preventing oocyst contamination during experimental conditions, suggesting that this disposable cage design could be used for other avian infectious disease studies.


Molecular mechanisms of pore formation and membrane disruption by the antimicrobial lantibiotic peptide Mutacin 1140.
The emergence of antibiotic-resistance is a major concern to global human health and identification of novel antibiotics is critical to mitigate the threat. Mutacin 1140 (MU1140) is a promising antimicrobial lanthipeptide and is effective against Gram-positive bacteria. Like nisin, MU1140 targets and sequesters lipid II and interferes with its function, which results in the inhibition of bacterial cell wall synthesis, and leads to bacteria cell lysis. MU1140 contains a structurally similar thioether cage for binding the lipid II pyrophosphate as for nisin. In addition to lipid II binding, nisin is known to form membrane pores. Membrane pore formation and membrane disruption is a common mode of action for many antimicrobial peptides, including gallidermin, a lantibiotic peptide with similar structural features as MU1140. However, whether and how MU1140 and its variants can form permeable membrane pores remains to be demonstrated. In this work, we explored the potential mechanisms of membrane pore formation by performing molecular simulations of the MU1140-lipid II complex in the bacterial membrane. Our results suggest that MU1140-lipid II complexes are able to form water permeating membrane pores. We find that a single chain of MU1140 complexed with lipid II in the transmembrane region can permeate water molecules across the membrane via a single-file water transport mechanism. The ordering of the water molecules in the single-file chain region as well as the diffusion behavior is similar to those observed in other biological water channels. Multiple complexes of MU1140-lipid II in the membrane showed enhanced permeability for the water molecules, as well as a noticeable membrane distortion and lipid relocation, suggesting that a higher concentration of MU1140 assembly in the membrane can cause significant disruption of the bacterial membrane. These investigations provide an atomistic level insight into a novel mode of action for MU1140 that can be exploited to develop optimized peptide variants with improved antimicrobial properties.


[Diagnostic features of newly diagnosed tuberculosis on different accounts of consulting with a physician].
The specific features of diagnosis were studied in 209 patients with tuberculosis at 9 phthisiological stations of the Yaroslavl Region in 1998-2002. In 96.2% of the patients, tuberculosis was found to have been newly diagnosed in general polyclinics and polyclinics. Only in 3.8% of the patients, the diagnosis of tuberculosis was made at prophylactic fluorography performed on the patients' initiative. A retrospective assessment of outpatient records indicated a significant delay in establishing tuberculosis, by using adequate diagnostic criteria if a physician had professional skills. The authors arrive at the conclusion that dispensary should assume the functions of phthisiopulmonological centers that will secure the continuity of early diagnosis of tuberculosis and its early treatment.


A hypergeometric probability model for protein identification and validation using tandem mass spectral data and protein sequence databases.
We present a new probability-based method for protein identification using tandem mass spectra and protein databases. The method employs a hypergeometric distribution to model frequencies of matches between fragment ions predicted for peptide sequences with a specific (M + H)+ value (at some mass tolerance) in a protein sequence database and an experimental tandem mass spectrum. The hypergeometric distribution constitutes null hypothesis-all peptide matches to a tandem mass spectrum are random. It is used to generate a score characterizing the randomness of a database sequence match to an experimental tandem mass spectrum and to determine the level of significance of the null hypothesis. For each tandem mass spectrum and database search, a peptide is identified that has the least probability of being a random match to the spectrum and the corresponding level of significance of the null hypothesis is determined. To check the validity of the hypergeometric model in describing fragment ion matches, we used chi2 test. The distribution of frequencies and corresponding hypergeometric probabilities are generated for each tandem mass spectrum. No proteolytic cleavage specificity is used to create the peptide sequences from the database. We do not use any empirical probabilities in this method. The scores generated by the hypergeometric model do not have a significant molecular weight bias and are reasonably independent of database size. The approach has been implemented in a database search algorithm, PEP_PROBE. By using a large set of tandem mass spectra derived from a set of peptides created by digestion of a collection of known proteins using four different proteases, a false positive rate of 5% is demonstrated.


The well-being of children impacted by a parent with cancer: an integrative review.
This paper reviewed the peer-reviewed scientific literature on well-being of children impacted by a parent with cancer. An integrative review of peer-reviewed literature between 2000 and 2015 regarding parental cancer and its impact on families was conducted by searching relevant databases using predefined key search terms. A thematic analysis was undertaken on literature that met inclusion criteria. Forty-nine studies met the criteria for this review, and five major themes were established: impact of cancer, communication, coping strategies, parenting factors mediating impact, and support services. There was considerable variability in study design, methodological approaches, and findings. In the majority of studies, children were significantly impacted by the parent's cancer diagnosis and exhibited distress. Daughters appeared to experience worsened mental health, and sons experienced a greater totality of internalizing and externalizing problems. Children of all ages were impacted by their parent's cancer diagnosis and initiated a number of coping strategies in response. Despite this, a significant number of studies revealed that parents underestimated the impact that their cancer had on their children. Family functioning, as well as the ill parents' gender, coping strategies, cancer severity, and mental and physical health mediated their children's well-being. Parent-child communication was a key element in supporting children. Parental cancer may impact children's long-term well-being. Further investigations are needed in this area. Additionally, review of support programs and interventions are warranted in terms of their uptake and impact on families affected by a parent's cancer.


Complication rate of endosonography (endobronchial and endoscopic ultrasound): a systematic review.
Endosonography [endoscopic ultrasound (EUS)-guided fine needle aspiration and endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration] is increasingly used for lung cancer staging and the assessment of sarcoidosis. Serious adverse events (SAE) have been reported in case reports, but the true incidence of complications is yet unknown. To assess the rate of SAE related to endosonography and to investigate associated risk factors. PubMed, EMBASE and Cochrane libraries were searched for eligible references up to April 2012 and these included studies reporting on linear EUS or EBUS for the analysis of mediastinal/hilar nodal or central intrapulmonary lesions. Case series describing complications were excluded. Reported complications were classified into SAE or minor adverse events (AE). 190 studies met the inclusion criteria. Information on follow-up was missing in half of the studies. In 16,181 patients, 23 SAE (0.14%) and 35 AE (0.22%) were reported. No mortality was observed. SAE were more frequent in patients investigated with EUS (0.30%) than in those investigated with EBUS (0.05%). Infectious SAE were most prevalent (0.07%) and predominantly occurred in patients with cystic lesions and sarcoidosis. In lung cancer patients, complications were rare. Endosonography for intrathoracic nodal assessment seems safe for lung cancer patients and mortality has not been reported. For cystic lesions and sarcoidosis, there may be a small, but nonnegligible risk of infectious complications. The true incidence of SAE might be higher as accurate documentation of complications is missing in most studies.


[Elderly patients with chronic pain].
Chronic pain is a serious and frequent health problem in elderly people. We have assessed main characteristics of chronic pain in elderly patients referred to a Norwegian multidisciplinary pain clinic. Medical records were assessed for patients with chronic pain who were at least 60 years old (n = 48) and treated at the Pain clinic, Haukeland University hospital in 2004. Pain was assessed in relation to sociodemographic, somatic and psychosocial factors. Pain in the lower extremities and various types of back pain were most frequently reported. Somatic and psychiatric comorbidity (including sleep disturbances) was prevalent. The results confirm findings from a number of studies on main characteristics of chronic pain conditions in the elderly. It is important that regular general practitioners emphasize psychosocial factors when assessing and treating chronic pain in the elderly.


Intense red photoluminescence from Mn2+-doped (Na+; Zn2+) sulfophosphate glasses and glass ceramics as LED converters.
We report on intense red fluorescence from Mn(2+)-doped sulfophosphate glasses and glass ceramics of the type ZnO-Na(2)O-SO(3)-P(2)O(5). As a hypothesis, controlled internal crystallization of as-melted glasses is achieved on the basis of thermally-induced bimodal separation of an SO(3)-rich phase. Crystal formation is then confined to the relict structure of phase separation. The whole synthesis procedure is performed in air at <or= 800 degrees C. Electron spin resonance and Raman spectroscopy indicate that Mn(2+) species are incorporated on Zn(2+) sites with increasingly ionic character for increasing concentration. Correspondingly, in the glasses, increasing MnO content results in decreasing network polymerization. Stable glasses and continuously increasing emission intensity are observed for relatively high dopant concentration of up to 3 mol.%. Recrystallization of the glass results in strongly increasing emission intensity. Dynamic emission spectroscopy reveals only on type of emission centers in the glassy material, whereas three different centers are observed in the glass ceramic. These are attributed to octahedrally coordinated Mn(2+) in the residual glass phase and in crystalline phosphate and sulfate lattices, respectively. Relatively low crystal field strength results in almost ideal red emission, peaking around 625 nm. Excitation bands lie in the blue-to-green spectral range and exhibit strong overlap. The optimum excitation range matches the emission properties of GaN- and InGaN-based light emitting devices.


A WC/WO star exploding within an expanding carbon-oxygen-neon nebula.
The final fate of massive stars, and the nature of the compact remnants they leave behind (black holes and neutron stars), are open questions in astrophysics. Many massive stars are stripped of their outer hydrogen envelopes as they evolve. Such Wolf-Rayet stars1 emit strong and rapidly expanding winds with speeds greater than 1,000 kilometres per second. A fraction of this population is also helium-depleted, with spectra dominated by highly ionized emission lines of carbon and oxygen (types WC/WO). Evidence indicates that the most commonly observed supernova explosions that lack hydrogen and helium (types Ib/Ic) cannot result from massive WC/WO stars2,3, leading some to suggest that most such stars collapse directly into black holes without a visible supernova explosion4. Here we report observations of SN 2019hgp, beginning about a day after the explosion. Its short rise time and rapid decline place it among an emerging population of rapidly evolving transients5-8. Spectroscopy reveals a rich set of emission lines indicating that the explosion occurred within a nebula composed of carbon, oxygen and neon. Narrow absorption features show that this material is expanding at high velocities (greater than 1,500 kilometres per second), requiring a compact progenitor. Our observations are consistent with an explosion of a massive WC/WO star, and suggest that massive Wolf-Rayet stars may be the progenitors of some rapidly evolving transients.


Episiotomy wound healing by Commiphora myrrha (Nees) Engl. and Boswellia carteri Birdw. in primiparous women: A randomized controlled trial.
Traditional Persian medicine manuscripts refer to plants such as Commiphora myrrha (Nees) Engl. (myrrh) and Boswellia carteri Birdw. (frankincense), which could be used to improve wound healing process. Since that time, local midwives in Iran continue to provide these herbs to precipitate episiotomy wound healing. To investigate the efficacy and safety of myrrh- and frankincense-based sitz-baths on episiotomy wound healing in primiparous women. This randomized controlled trial was conducted on 90 primiparous women with singleton pregnancies after normal vaginal delivery at Hafez hospital affiliated to Shiraz University of Medical Sciences from July to October 2019. Study participants were randomly allocated in three groups (2 intervention groups and 1 control group). Women in intervention groups were assigned to receive either 10-min sitz-bath of myrrh extract or frankincense extract twice a day for 1 week. While the women in control group received the betadine sitz-bath for the same period of time. The main outcome was the episiotomy wound healing, which was measured using the REEDA scale before intervention, on 2nd and 7th postpartum days. An improvement in the episiotomy wound healing was significantly greater in patients receiving myrrh than those receiving the frankincense or betadine on 2nd (p = 0.003 and p < 0.001) and 7th (p = 0.043 and p = 0.015) postpartum days. However, the total REEDA score was not statistically different between the frankincense and betadine groups on 2nd and 7th postpartum days (p > 0.05). The present results suggest that myrrh was more efficient than frankincense and betadine in healing of the episiotomy wound and could be recommended as a safe natural therapy.


Neoadjuvant Chemotherapy Shifts Breast Tumor Microbiota Populations to Regulate Drug Responsiveness and the Development of Metastasis.
Breast tumors have their own specific microbiota, distinct from normal mammary gland tissue. Patients with breast cancer that present with locally advanced disease often undergo neoadjuvant chemotherapy to reduce tumor size prior to surgery to allow breast conservation or limit axillary lymph node dissection. The purpose of our study was to evaluate whether neoadjuvant chemotherapy modulates the tumor microbiome and the potential impact of microbes on breast cancer signaling. Using snap-frozen aseptically collected breast tumor tissue from women who underwent neoadjuvant chemotherapy (n = 15) or women with no prior therapy at time of surgery (n = 18), we performed 16S rRNA-sequencing to identify tumoral bacterial populations. We also stained breast tumor microarrays to confirm presence of identified microbiota. Using bacteria-conditioned media, we determined the effect of bacterial metabolites on breast cancer cell proliferation and doxorubicin therapy responsiveness. We show chemotherapy administration significantly increased breast tumor Pseudomonas spp. Primary breast tumors from patients who developed distant metastases displayed increased tumoral abundance of Brevundimonas and Staphylococcus. We confirmed presence of Pseudomonas in breast tumor tissue by IHC staining. Treatment of breast cancer cells with Pseudomonas aeruginosa conditioned media differentially effected proliferation in a dose-dependent manner and modulated doxorubicin-mediated cell death. Our results indicate chemotherapy shifts the breast tumor microbiome and specific microbes correlate with tumor recurrence. Further studies with a larger patient cohort may provide greater insights into the role of microbiota in therapeutic outcome and develop novel bacterial biomarkers that could predict distant metastases. IMPLICATIONS: Breast tumor microbiota are modified by therapy and affects molecular signaling.


Sonic hedgehog inhibitors prevent colitis-associated cancer via orchestrated mechanisms of IL-6/gp130 inhibition, 15-PGDH induction, Bcl-2 abrogation, and tumorsphere inhibition.
Sonic hedgehog (SHH) signaling is essential in normal development of the gastrointestinal (GI) tract, whereas aberrantly activated SHH is implicated in GI cancers because it facilitates carcinogenesis by redirecting stem cells. Since colitis-associated cancer (CAC) is associated with inflammatory bowel diseases, in which SHH and IL-6 signaling, inflammation propagation, and cancer stem cell (CSC) activation have been implicated, we hypothesized that SHH inhibitors may prevent CAC by blocking the above SHH-related carcinogenic pathways. In the intestinal epithelial cells IEC-6 and colon cancer cells HCT-116, IL-6 expression and its signaling were assessed with SHH inhibitors and levels of other inflammatory mediators, proliferation, apoptosis, tumorsphere formation, and tumorigenesis were also measured. CAC was induced in C57BL/6 mice by administration of azoxymethane followed by dextran sodium sulfate administration. SHH inhibitors were administered by oral gavage and the mice were sacrificed at 16 weeks. TNF-α-stimulated IEC-6 cells exhibited increased levels of proinflammatory cytokines and enzymes, whereas SHH inhibitors suppressed TNF-α-induced inflammatory signaling, especially IL-6/IL-6R/gp130 signaling. SHH inhibitors significantly induced apoptosis, inhibited cell proliferation, suppressed tumorsphere formation, and reduced stemness factors. In the mouse model, SHH inhibitors significantly reduced tumor incidence and multiplicity, decreased the expression of IL-6, TNF-α, COX-2, STAT3, and NF-κB, and significantly induced apoptosis. In colosphere xenografts, SHH inhibitor significantly suppressed tumorigenesis by inhibiting tumorsphere formation. Taken together, our data suggest that administration of SHH inhibitors could be an effective strategy to prevent colitis-induced colorectal carcinogenesis, mainly by targeting IL-6 signaling, ablating CSCs, and suppressing oncogenic inflammation, achieving chemoquiescence ultimately.


Ten years of liver transplantation: an evolving understanding of late graft loss.
We undertook this study to understand the causes of late graft loss and long-term outcome in orthotopic liver transplantation (OLT) recipients. Prospectively collected data of 1174 consecutive OLT in 1045 adult patients who received liver grafts between April 1985 and August 1995 were reviewed. The causes of graft loss, pretransplant patient characteristics, and posttransplant events were analyzed in patients who survived at least 1 year after OLT, in an attempt to establish a link between these factors and graft loss. One hundred fifty-nine (17.9%) grafts were lost after the first year. Of these, 132 grafts were lost by death and 27 by retransplantation. Recipients who survived the first year (n=884) had 5- and 10-year survivals of 81.4% and 67.2%, respectively. Death with a functioning graft occurred in 97 (61%) patients. The main causes of late graft loss were recurrent disease (n=48), cardiovascular and cerebral vascular accidents (n=28), infections (n=24), and chronic rejection (n = 15). Pretransplant heart disease and diabetes were found to be significant risk factors for late graft loss due to cardiovascular diseases and cerebral vascular accidents. Survival of OLT patients who live beyond the first posttransplant year is excellent. Some patient characteristics may be associated with late graft loss. Compared with previous reports, this study shows an increased incidence of late graft loss secondary to recurrent diseases, de novo malignancies, cardiovascular diseases, and cerebral vascular accidents. Chronic rejection seems to be a less frequent cause of late graft loss. The prevention of recurrent disease and better immunosuppression may further improve these results.


The relationship between childhood parental loss and metabolic syndrome in obese subjects.
The increasing global trend of obesity is a fundamental contributor to the growing prevalence of metabolic syndrome, a cluster of medical abnormalities including impaired glucose and lipid metabolism, obesity and hypertension. Results from animal and human investigations have shown that early life stress can result in weight gain and metabolic changes. Our aim is to investigate whether a particular type of an early adverse event, i.e. parental loss during childhood, is associated with the development of metabolic syndrome in severely obese subjects. One hundred thirty-five consecutive obese patients who were seeking bariatric surgery were assessed for metabolic syndrome according to the Adult Treatment Panel (ATP) III criteria. Information regarding the experience of parental separation or bereavement before the age of 17 was collected with the use of a semi-structured interview. In our population, 31.1% of the subjects met the criteria for metabolic syndrome. No significant differences in demographic factors, health habits or psychiatric diagnosis were found between patients with and without coexisting metabolic syndrome. After adjusting for age and gender, multivariate logistic regression analysis revealed that both childhood loss of a parent and a body mass index (BMI) value greater than 50 were significant predictors of metabolic syndrome. This study provides preliminary evidence linking childhood parental loss to risk factors for the development of metabolic syndrome.


Interleukin-6 and cardiovascular diseases.
Inflammatory cytokines are important for both cardiovascular scientists and practicing clinicians. Interleukin-6 (IL-6) has been emphasized by reports of elevated circulating as well as intracardiac IL-6 levels in patients with congestive heart failure (CHF). IL-6 may contribute to the progression of myocardial damage and dysfunction in chronic heart failure syndrome resulting from different causes. As the cause of CHF in cardiomyopathy, myocarditis, allograft rejection, and left ventricular assist device (LVADs) conditions, circulating IL-6 levels are associated with the severity of left ventricular dysfunction, and are also strong predictors of subsequent clinical outcomes. Continuous and excessive production of IL-6 promotes myocardial injury by breaking down both cytokine networks and viral clearance under viral myocarditis. Although IL-6 is likely important in the process of viral antigen presentation, early activation of immune responses and attenuation of viral replication also appear to be significant in an animal model of viral myocarditis. IL-6 can cause cardiac hypertrophy through the IL-6 signal transducing receptor component, glycoprotein 130. There are several interesting cases of cardiac myxoma complicated with mediastinal lymphadenopathy or left ventricular hypertrophy. Increased expression of IL-6 is observed in the myocardium of all donor hearts showing marked dysfunction. Myocardial IL-6 concentrations are also significantly higher in LVAD candidates compared with advanced heart failure patients. Although the IL-6 family plays a central role in the pathophysiology of cardiovascular diseases, it remains to be determined whether the IL-6 family is beneficial or detrimental. Future study will be needed to resolve this question.


Mechanism of Zn stabilization in hydroxyapatite and hydrated (0 0 1) surfaces of hydroxyapatite.
A basic understanding of Zn incorporation on bulk and hydrated (0 0 1) surfaces of hydroxyapatite (HA) is attained through electronic structure calculations which use a combined first principles density functional (DFT) and extended Hückel tight binding (EHTB) methodology. A Zn substituted hydroxyapatite relaxed structure is obtained through a periodic cell DFT geometry optimization method. Electronic structure properties are calculated by using both cluster DFT and periodic cell EHTB methods. Bond order calculations show that Zn preference for the Ca2 vacancy, near the OH channel and with greater structural flexibility, is associated with the formation of a four-fold (bulk) and nearly four-fold (surface) coordination, as in ZnO. When occupying the octahedral Ca1 vacancy, Zn remains six-fold in the bulk, but coordination decreases to five-fold in the surface. In the bulk and surface, Zn2 is found to be more covalent than Zn1, due to a decrease in bond lengths at the four-fold site, which approach the 1.99 Å ZnO value. Zn is however considerably less bound in the biomaterial than in the oxide, where calculated bond orders are twice as large as in HA. Surface phosphate groups (PO(4)) and hydroxide ions behave as compact individual units as in the bulk; no evidence is found for the presence of HPO(4). Ca-O bond orders decrease at the surface, with a consequent increase in ionicity. Comparison between DFT and EHTB results show that the latter method gives a good qualitative account of charge and bonding in these systems.


Are preferences over health states informed?
The use of preference-elicitation tasks for valuing health states is well established, but little is known about whether these preferences are informed. Preferences may not be informed because individuals with little experience of ill health are asked to value health states. The use of uninformed preferences in cost-effectiveness can result in sub-optimal resource allocation. The aim of this study was to pilot a novel method to assess whether members of the public are informed about health states they value in preference-elicitation tasks. The general public was said to be informed if the expectations of the public about the effect of ill health on people's lives were in agreement with the experience of patients. Sixty-two members of the public provided their expectations of the consequences of ill health on five life domains (activities, enjoyment, independence, relationships, and avoiding being a burden). A secondary dataset was used to measure patient experience on those five consequences. There were differences between the expectations of the public and the experience of patients. For example, for all five life consequences the public underestimated the effects of problems in usual activities compared to problems in mobility. They also underestimated the effect of 'anxiety or depression' compared to physical problems on enjoyment of life and on the quality of personal relationships. This proof-of-concept study showed that it is possible to test whether preferences are informed. This study should be replicated using a larger sample. The findings suggest that preferences over health states in this sample are not fully informed because the participants do not have accurate expectations about the consequences of ill health. These uninformed preferences may not be adequate for allocation of public resources, and research is needed into methods to make them better informed.


MicroRNAs Dysregulation and Mitochondrial Dysfunction in Neurodegenerative Diseases.
Neurodegenerative diseases are debilitating and currently incurable conditions causing severe cognitive and motor impairments, defined by the progressive deterioration of neuronal structure and function, eventually causing neuronal loss. Understand the molecular and cellular mechanisms underlying these disorders are essential to develop therapeutic approaches. MicroRNAs (miRNAs) are short non-coding RNAs implicated in gene expression regulation at the post-transcriptional level. Moreover, miRNAs are crucial for different processes, including cell growth, signal transmission, apoptosis, cancer and aging-related neurodegenerative diseases. Altered miRNAs levels have been associated with the formation of reactive oxygen species (ROS) and mitochondrial dysfunction. Mitochondrial dysfunction and ROS formation occur in many neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases. The crosstalk existing among oxidative stress, mitochondrial dysfunction and miRNAs dysregulation plays a pivotal role in the onset and progression of neurodegenerative diseases. Based on this evidence, in this review, with a focus on miRNAs and their role in mitochondrial dysfunction in aging-related neurodegenerative diseases, with a focus on their potential as diagnostic biomarkers and therapeutic targets.


[Peripheral T-cell lymphoma: diagnosis and treatment].
Peripheral T/NK-cell lymphomas (PTCL) comprise a heterogeneous group of rare diseases accounting for approximately 10-15% of all non-Hodgkin"s lymphomas. Compared to B-cell lymphomas, PTCL more frequently involve extranodal sites and have a worse prognosis. Because of their usually indolent course, primary cutaneous T/NK-cell lymphomas should be distinguished from the other PTCL. Staging of PTCL is done according to the Ann Arbor staging system. The International Prognostic Index, established for aggressive B-cell lymphomas, has also proved relevant for PTCL. Standard therapy for PTCL has not been defined, yet. First line anthracycline-based chemotherapy brings about long-term remissions in 15 to 42% of patients. Apart from (ALK-positive) anaplastic large cell lymphoma it thus gives poorer results than those obtained in patients with aggressive B-cell lymphomas. Data for high-dosage therapy with autologous stem cell transplantation (autoSCT) for relapsing and refractory PTCL are similar to those reported for aggressive B-cell lymphomas. Thus this treatment seems to constitute a sensible salvage strategy. Allogeneic stem cell transplantation following reduced conditioning regimens has also given promising results in patients with relapse. However, the impact of high-dosage strategies and the implementation of newer agents, such as alemtuzumab, in first-line treatment are still uncertain. Hence patients with PTCL should be treated within clinical trials.


Therapies for symptomatic primary osteoporosis.
There is no universally accepted pharmacologic treatment for primary symptomatic osteoporosis. However, three agents discussed in this review show varying degrees of promise. Calcitonin increases bone density and has the added benefit of analgesic properties. Etidronate disodium, a diphosphonate approved for symptomatic Paget's disease, has been shown to increase bone density and decrease fractures in osteoporosis. Sodium fluoride, although an effective stimulator of bone growth in low turnover osteoporosis, has been associated with toxicity and increased fractures.


Clinical Humanities in Primary Care for Year 2 Medical Students: A Student perspective.
This article was migrated. The article was marked as recommended. As part of a new MBBS Curriculum at GKT Medical School, King's College London, second year medical students undertook a clinical humanities assignment during their longitudinal GP placement. Groups of students all produced a humanities output relating to medicine and patient care in the community. This article explores the experiences from the student perspective and key learning points for subsequent cohorts, identifying four themes from the feedback obtained in a student evaluation: Broadening horizons; teamworking and leadership, wider community care involvement and seeing patients through different eyes.


The effect of cigarette smoking on asthma control during exacerbations in pregnant women.
Smoking and severe asthma exacerbations in pregnancy are risk factors for low birth weight babies. No studies have assessed the clinical implications of smoking on asthma exacerbations in pregnancy. Pregnant women with current asthma (n=80) were prospectively assessed at clinic visits (18, 30, 36 weeks), during exacerbations and with fortnightly phone calls. The asthma control questionnaire was administered at each contact and exacerbations classified as severe (requiring medical intervention) or mild (self-managed). Medications, self-management skills, smoking history, fractional exhaled nitric oxide (FENO), exhaled carbon monoxide (ECO) and lung function were assessed. Pregnant women without asthma (controls, n=46) were assessed prospectively at clinic visits. Women with asthma were more likely to smoke (34% current smokers) than women without asthma (15% current smokers). In women with asthma, the median (IQR) exacerbation rate during pregnancy was 2.0 (1.0-3.0) in current smokers, 2.0 (1.0-3.0) in ex-smokers and 1.5 (1.0-2.0) in never smokers. The asthma control score during exacerbations was higher in current smokers (median (IQR) 2.17 (1.17-2.7)) compared with never smokers (1.17 (0.8-2.17), p=0.056). An adjusted linear regression model found that smoking was significantly associated with higher asthma control score during exacerbation (P=0.04). birth weights were lower among children of smokers than non-smokers (p=0.023 control group, p=0.086 asthma group). During pregnancy, asthma exacerbations are more common and more severe in current smokers than never smokers. The risk of effects of maternal asthma on the fetus may be greater among smokers.


Identifying Barriers and Facilitators of Success for Female Radiology Researchers: An Analysis of In-Depth Interviews With Nationally Recognized Leaders of the Field.
Women are highly underrepresented among leadership positions within radiology research, disproportionate to their underrepresentation in radiology overall. We sought to identify the causes and solutions of such disparity at the personal, organizational, and institutional levels among female radiology researchers who are leaders in the field. We used purposive sampling to identify nationally recognized female leaders in radiology research. We developed a semistructured interview guide and conducted in-depth one-on-one telephone interviews with participants (n = 16) that ranged from 36 to 65 min. All interviews were recorded and transcribed. Data were analyzed by two researchers trained in qualitative methods using Saldana's first- and second-cycle coding method. Themes were identified using a grounded theory approach to identify meaningful patterns that addressed the research question. Participants identified barriers to their professional development and success, including personal and professional obstacles often associated with work-life balance and the nonlinear nature of women's careers because of caregiving responsibilities. Participants also identified facilitators of success that operated at the individual, organizational, and institutional level, such as purposeful networking, having an advocate, and participating in leadership events. This study represents the first effort to qualitatively capture the facilitators of success for nationally recognized female radiology researchers. Findings suggest that synergistic efforts can be undertaken by early-career female radiologists and their colleagues, national radiology organizations, and academic institutions to systematically enable the inclusion and participation of women. The field of radiology should consider how to work dynamically at multiple levels to implement the identified potential changes.


Interplay Between Amphetamine and Activity Level in Gene Networks of the Mouse Striatum.
The psychostimulant amphetamine can be prescribed to ameliorate the symptoms of narcolepsy, attention-deficit hyperactivity disorder and to facilitate weight loss. This stimulant can also have negative effects including toxicity and addiction risk. The impact of amphetamine on gene networks is partially understood and this study addresses this gap in consideration of the physical activity. The striata of mice exposed to either amphetamine or saline treatment were compared in a mouse line selected for home cage physical overactivity, a phenotype that can be mitigated with amphetamine, and in a contemporary control line using RNA-seq. Genes presenting opposite expression patterns between treatments across lines included a pseudogene of coiled-coil-helix-coiled-coil-helix domain containing 2 gene (Chchd2), ribonuclease P RNA component H1 (Rpph1), short stature homeobox 2 (Shox2), transient receptor potential melastatin 6 (Trpm6), and tumor necrosis factor receptor superfamily, member 9 (Tnfrsf9). Genes presenting consistent treatment patterns across lines, albeit at different levels of significance included cholecystokinin (Cck), vasoactive intestinal polypeptide (Vip), arginine vasopressin (Avp), oxytocin/neurophysin (Oxt), thyrotropin releasing hormone (Trh), neurotensin (Nts), angiotensinogen (Agt), galanin (Gal), prolactin receptor (Prlr), and calcitonin receptor (Calcr). Potassium inwardly rectifying channel, subfamily J, member 6 (Kcnj6), and retinoic acid-related (RAR)-related orphan receptor alpha (Rora) were similarly differentially expressed between treatments across lines. Functional categories enriched among the genes presenting line-dependent amphetamine effect included genes coding for neuropeptides and associated with memory and neuroplasticity and synaptic signaling, energy, and redox processes. A line-dependent association between amphetamine exposure and the synaptic signaling genes neurogranin (Nrgn) and synaptic membrane exocytosis 1(Rims1) was highlighted in the gene networks. Our findings advance the understanding of molecular players and networks affected by amphetamine in support of the development of activity-targeted therapies that may capitalize on the benefits of this psychostimulant.


Cytokines of Cervical Mucosa and Human Papilloma Virus Infection of the Cervix: A Descriptive Study.
The production of cytokines by various cervical cells can be triggered by antigenic stimuli, including human papilloma virus (HPV) infection. The aim of the present study was to evaluate differences in cytokine levels between various intraepithelial cervical lesions. A total of 97 women participated in this descriptive study. Within our study population, 27 subjects presented with high-grade squamous intraepithelial lesions (HSIL), 48 with low-grade squamous intraepithelial lesion (LSIL) and 22 with a normal smear. Colposcopy and directed biopsy were performed as needed. To confirm the presence of HPV, an HPV-DNA test was performed using polymerase chain reaction. Using flow cytometry to ThinPrep cervical samples, we assessed the family of interleukins (ILs), including IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor (TNF)-α and TNF-β and transforming growth factor-β1. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS for Windows; version 20.0). Significantly lower levels of IL-1α, IL-2, IL-4 and TNF-α were detected in cervical samples obtained from the LSIL group when compared to samples obtained from the HSIL group. Significant differences in tissue cytokine levels exist between intraepithelial cervical lesions obtained from patients presenting with HSIL versus LSIL.


Human sulfotransferases SULT1C1 and SULT1C2: cDNA characterization, gene cloning, and chromosomal localization.
Sulfate conjugation catalyzed by sulfotransferase (SULT) enzymes is an important pathway in the biotransformation of many drugs, other xenobiotics, neurotransmitters, and hormones. We previously described a human cDNA, SULT1C1, that encoded a protein similar in sequence to that of rat ST1C1. Subsequently, a related human cDNA, SULT1C2, was reported. In the present study, we set out to characterize further the human SULT1C1 cDNA and then to clone, structurally characterize, and map its gene. As an initial step, we performed 5'- and 3'-RACE with SULT1C1 cDNA. Those experiments demonstrated that a small number of SULT1C1 transcripts contained an "insert," which we later showed resulted from alternative splicing that involved an Alu sequence in intron 3 of SULT1C1. We then cloned and structurally characterized the SULT1C1 gene from a human genomic BAC library. Because the sequence of SULT1C2 was closely related to that of SULT1C1 and because the genes for other human SULT paralogues occur in clusters, we screened the BAC clones that had been positive for SULT1C1 to search for SULT1C2 and discovered a clone that contained both genes. That BAC was used to sequence and structurally characterize SULT1C2. SULT1C1 and SULT1C2 were approximately 21 and 10 kb in length, respectively. Both genes contained seven exons that encoded protein, and both had structures that were similar to those of other genes that encode members of the SULT1 family. Finally, human SULT1C1 and SULT1C2 mapped to 2q11.2 by fluorescence in situ hybridization. The cloning and structural characterization of SULT1C1 and SULT1C2 will now make it possible to perform molecular genetic and pharmacogenomic studies of these sulfate-conjugating enzymes in humans.


Anion-Dependent Potential Precycling Effects on Lithium Deposition/Dissolution Reaction Studied by an Electrochemical Quartz Crystal Microbalance.
The electrochemical quartz crystal microbalance technique was employed to study the initial stage of the electrodeposition and dissolution of lithium utilizing three kinds of electrolyte solutions such as LiPF6, LiTFSI, or LiFSI in tetraglyme. The native-SEI (solid-electrolyte interphase) formed by a potential prescan before lithium deposition/dissolution in all three solutions. Simultaneous additional SEI (add-SEI) deposition and its dissolution with lithium deposition and dissolution, respectively, were observed in LiPF6 and LiTFSI. Conversely, the add-SEI dissolution with lithium deposition and its deposition with lithium dissolution were observed in LiFSI. Additional potential precycling resulted in the accumulation of a "pre-SEI" layer over the native-SEI layer in all of the solutions. With the pre-SEI, only lithium deposition/dissolution were significantly observed in LiTFSI and LiFSI. On the basis of the potential dependences of the mass and resistance changes, the anion-dependent effects of such a pre-SEI layer presence/absence on the lithium deposition/dissolution processes were discussed.


Meralgia paresthetica after aortic valve surgery.
We report a case of meralgia paresthetica, a rare neurological complication, following aortic valvuloplasty. Although this complication was previously described after coronary artery bypass surgery, we believe this is the first case described after a valve procedure and hypothesize on its etiology.


[Percutaneous transhepatic disintegration of gallstones and fragment extraction].
Attempts at percutaneous removal have been made in 13 patients with solitary and multiple intra- and extra-hepatic biliary duct stones measuring 5 to 30 mm. The stones were fragmented with a Dormia basket and the fragments removed transhepatically. In ten patients the procedure was successful, including one patient with multiple intra-hepatic stones. The procedure can be recommended for cases of calculous obstruction of biliary anastomoses or of stones which could not be removed by endoscopy, or where there is already biliary drainage being carried out, or in patients with a high operative risk. In two patients, dilatation of the papilla was also carried out, in four patients a stenosis was dilated and in a further two patients, dilated and in a further two patients, electro-incision of a stenosis was performed.


Functional movement screening: predicting injuries in officer candidates.
Functional movement screening (FMS) is a musculoskeletal assessment method that incorporates seven movements and yields an overall score based on movement quality. The objectives of this study were to document the distribution of scores and to determine whether FMS scores could predict injury in a large military cohort. A cohort of 874 Marine officer candidates were recruited, consented, completed demographic questionnaires, and had FMS performed during medical in-processing. Candidates were enrolled in either long-cycle (LC: 68 d; n = 427) or short-cycle (SC: 38 d; n = 447) training and followed up for injuries occurring in training. The mean FMS score (score range = 0-21) among all candidates was 16.6 ± 1.7; approximately 10% of candidates had FMS scores ≤14. A score of ≤14 on the FMS predicted any injury with a sensitivity of 0.45 and a specificity of 0.71 and serious injury with a sensitivity of 0.12 and a specificity of 0.94. Both LC and SC cohorts demonstrated higher injury risk among candidates who had scores ≤14 compared with those with scores >14 (LC: risk ratio (RR) = 1.65, 95% confidence interval = 1.05-2.59, P = 0.03; SC: RR = 1.91, 95% confidence interval = 1.21-3.01, P < 0.01). Overall, 79.8% of persons with scores ≤14 were in the group with fitness scores <280 (/300), whereas only 6.6% of candidates in the group with fitness scores ≥280 had scores ≤14. This was the first large-scale study performed in an active-duty military cohort to examine the utility of FMS during medical in-processing. Further work is warranted to evaluate FMS and the potential for injury prediction and prevention.


A clinical trial to evaluate the measurement properties of 2 direct preference instruments administered with and without hypothetical marker states.
Health economists recommend that when patients provide preference ratings of their own health state using utility and health state preference measures such as the feeling thermometer (FT) and standard gamble (SG), they first rate hypothetical health states (clinical marker states [CMS]). However, there is no evidence to support improvement in measurement properties with the use of CMS. The authors evaluated validity and responsiveness of the SG and FT with and without administration of the CMS. Respiratory rehabilitation improves health-related quality of life in patients with chronic airflow limitation. The authors randomized 84 patients undergoing pulmonary rehabilitation to administration of the FTand SG with (FT+ or SG+) or without (FT- or SG-) CMS before and after a standard 12-week respiratory rehabilitation program. Patients also completed the Health Utilities Index 3 (HUI3), the Chronic Respiratory Questionnaire (CRQ), and the St. George Respiratory Questionnaire (SGRQ) to evaluate longitudinal validity. Marker state status did not significantly affect baseline scores on either FT or SG (FT+ 0.54, FT- 0.60, SG+ 0.68, SG- 0.66, on a scale from 0 [dead] to 1.0 [full health]). The improvement after the rehabilitation program was 0.14 (P < 0.001) in the FT+ group and 0.08 (P = 0.02) in the FT- group (difference between FT+ and FT- = 0.06; 95% confidence interval [CI] = -0.03 to 0.15, P = 0.17). The corresponding improvement was 0.12 (P = 0.009) in the SG+ group and 0.07 in the SG- group (P = 0.11) (difference between SG+ and SG- = 0.05; 95% CI= -0.07 to 0.17, P = 0.39). Correlations between change in the FT+ with the CRQ and SGRQ were slightly but not significantly lower than between the change in FT- and these 2 specific instruments. The correlations between change in the SG with the CRQ and the SGRQ were weaker in patients randomized to SG+ (from 0.00 to 0.17) compared to the SG- group (from 0.21 to 0.58). These differences were statistically significant for the CRQ domains of dyspnea and fatigue. The authors found nonsignificant trends toward superior responsiveness when patients rated hypothetical health states before rating their own health state. Although including hypothetical health states did not significantly influence the validity of the FT, it decreased the longitudinal validity of the SG. This study fails to show convincing advantage for use of marker states. Theoretical arguments in favor of marker states cannot stand alone without empirical support.


Complementary deoxyribonucleic acid cloning and enzymatic characterization of a novel 17beta/3alpha-hydroxysteroid/retinoid short chain dehydrogenase/reductase.
17Beta-hydroxysteroid dehydrogenases (17betaHSDs) convert androgens and estrogens between their active and inactive forms, whereas retinol dehydrogenases catalyze the conversion between retinol and retinal. Retinol dehydrogenases function in the visual cycle, in the generation of the hormone retinoic acid, and some also act on androgens. Here we report cloning and expression of a complementary DNA that encodes a new mouse liver microsomal member of the short chain dehydrogenase/reductase (SDR) superfamily and its enzymatic characterization, i.e. 17betaHSD9. Although 17betaHSD9 shares 88% amino acid identity with rat 17betaHSD6, its closest homolog, the two differ in substrate specificity. In contrast to other 17betaHSD, 17betaHSD9 has nearly equivalent activities as a 17betaHSD (with estradiol approximately = adiol) and as a 3alphaHSD (with adiol approximately = androsterone). It also recognizes retinol as substrate and represents in part the NAD+-dependent liver microsomal dehydrogenase that uses unbound retinol, but not retinol complexed with cellular retinol-binding protein. Thus, this enzyme has catalytic properties that overlap with two subgroups of SDR, 17betaHSD and retinol dehydrogenases. Inactivation of estrogen and a variety of androgens seems to be its most probable function. Because of its apparent inability to access retinol bound with cellular retinol-binding protein, a function in the pathway of retinoic acid biosynthesis seems less obvious. These data provide additional insight into the enzymology of estrogen, androgen, and retinoid metabolism and illustrate how closely related members of the SDR superfamily can have strikingly different substrate specificities.


The yvyD gene of Bacillus subtilis is under dual control of sigmaB and sigmaH.
During a search by computer-aided inspection of two-dimensional (2D) protein gels for sigmaB-dependent general stress proteins exhibiting atypical induction profiles, a protein initially called Hst23 was identified as a product of the yvyD gene of Bacillus subtilis. In addition to the typical sigmaB-dependent, stress- and starvation-inducible pattern, yvyD is also induced in response to amino acid depletion. By primer extension of RNA isolated from the wild-type strain and appropriate mutants carrying mutations in the sigB and/or spo0H gene, two promoters were mapped upstream of the yvyD gene. The sigmaB-dependent promoter drives expression of yvyD under stress conditions and after glucose starvation, whereas a sigmaH-dependent promoter is responsible for yvyD transcription following amino acid limitation. Analysis of Northern blots revealed that yvyD is transcribed monocistronically and confirmed the conclusions drawn from the primer extension experiments. The analysis of the protein synthesis pattern in amino acid-starved wild-type and relA mutant cells showed that the YvyD protein is not synthesized in the relA mutant background. It was concluded that the stringent response plays a role in the activation of sigmaH. The yvyD gene product is homologous to a protein which might modify the activity of sigma54 in gram-negative bacteria. The expression of a sigmaL-dependent (sigmaL is the equivalent of sigma54 in B. subtilis) levD-lacZ fusion is upregulated twofold in a yvyD mutant. This indicates that the yvyD gene product, being a member of both the sigmaB and sigmaH regulons, might negatively regulate the activity of the sigmaL regulon. We conclude that (i) systematic, computer-aided analysis of 2D protein gels is appropriate for the identification of genes regulated by multiple transcription factors and that (ii) YvyD might form a junction between the sigmaB and sigmaH regulons on one side and the sigmaL regulon on the other.


Medical ozone therapy reduces shock wave therapy-induced renal injury.
Extracorporeal shock wave (ESW) lithotripsy is the preferred treatment modality for uncomplicated kidney stones. More recently free oxygen radical production following ESW application has been considered to be crucial in shock wave-induced renal damage. It has been shown that ozone therapy (OT) has ameliorative and preventive effects against various pathological conditions due to increased nitro-oxidative stress. In current study, we aimed to evaluate the efficacy of OT against ESW-induced renal injury. Twenty-four male Sprague-Dawley rats were divided into three groups: sham-operated, ESW, and ESW + OT groups. All groups except sham-operated group were subjected to ESW procedure. ESW + OT group received 1 mg/kg/day of oxygen/ozone mixture intraperitoneally at 2 h before ESW, and OT was continued once a day for consecutive three days. The animals were killed at the 4th day, and kidney tissue and blood samples were harvested for biochemical and histopathologic analysis. Serum ALT and AST levels, serum neopterin, tissue nitrite/nitrate levels, and tissue oxidative stress parameters were increased in the ESW group and almost came close to control values in the treatment group (p < 0.05, ESW vs. ESW + OT). Histopathological injury scores were significantly lower in treatment group than the ESW group (p < 0.05, ESW vs. ESW + OT). Immunohistochemical iNOS staining scores in ESW group were higher than those of sham-operated group (p < 0.05, ESW vs. sham-operated), iNOS staining scores in OT group were significantly lower than the ESW group (p < 0.05, ESW + OT vs. ESW). OT ameliorates nitro-oxidative stress and reduces the severity of pathological changes in the experimental ESW-induced renal injury of rat model.


Clinical and Short-Term Radiographic Outcomes of Minimally Invasive Transforaminal Lumbar Interbody Fusion With Expandable Lordotic Devices.
Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is a well-accepted procedure for the treatment of degenerative lumbar disease. However, its ability to restore lumbar lordosis has been limited. Development of expandable lordotic interbody devices has challenged this limitation, furthering the scope of minimally invasive surgery. To evaluate the radiographic and clinical effects of expandable lordotic interbody devices placed through an MIS-TLIF approach. We conducted a retrospective review of 32 1-level and 18 2-level MIS-TLIFs performed using lordotic expandable interbody devices. Lumbar radiographic measurements, Oswestry Disability Index scores (ODI), and Visual Analogue Scale scores (VAS) were obtained at preoperative, 6 wk follow up, and last follow up time points. Last follow up occurred at a mean of 11.5 ± 7.6 mo (mean ± SD). At 6-wk follow-up, segmental lordosis, disc height, and foraminal height increased by an average of 3.4°, 6.4 mm, and 4.4 mm, respectively. Only the 2-level group showed a significant increase in lumbar lordosis of 5.8°. No significant changes occurred in sacral slope, pelvic tilt, or pelvic incidence. Average ODI and VAS decreased by -12.0 and -4.5, respectively. Postoperative lumbar lordosis inversely correlated with preoperative lordosis in patients with an initial Pelvic Incidence to Lumbar Lordosis mismatch (PI-LL) of >10°, (r = -0.5, P = .009). When applied across 2-levels, MIS-TLIF using expandable lordotic interbody devices produced a significant increase in lumbar lordosis. Preoperative lumbar lordosis was found to be a predictor of postoperative lumbar lordotic change in patients with sagittal imbalance.


Mechanisms of HIV-1 neurotropism.
Human immunodeficiency virus type 1 (HIV) infects macrophages and microglia in the CNS and frequently causes neurocognitive impairment. Although antiviral therapy generally reduces the viral load in the CNS and improves HIV-associated neurological dysfunction, most current antiviral drugs have poor CNS penetrance and cannot completely suppress viral replication. Furthermore, drug-resistance mutations can evolve independently in the CNS. Thus, a long-lived viral reservoir persists in macrophages and microglia in the brain despite antiviral therapy. This review discusses mechanisms underlying the neurotropism of HIV, focusing on the role of the HIV envelope glycoproteins and their interactions with CD4 and the chemokine receptors CCR5 and CXCR4. We review data from studies of neurotropic HIV derived from the brains of patients with HIV-associated neurocognitive impairment as well as studies of nonhuman primate models. Understanding mechanisms that underlie HIV neurotropism and neurovirulence is critical for development of therapeutics to inhibit CNS infection and preventing neurological injury in HIV-infected individuals.


Multiple birth defects in a newborn exposed to Mycoplasma pneumoniae in utero.
A newborn baby girl with progressive hydrocephalus and congenital defects of the skin and eyes was born to a mother who experienced bilateral bronchopneumonia in her first trimester. At the time of her infection, the mother's serum cold agglutinin titer was 1:128 and at delivery the mother's and baby's serum samples had complement-fixation titers to Mycoplasma pneumoniae of 1:1,024 and 1:256, respectively. At 1 week of age the baby's serum IgM value was 44 mg/100 ml (98% of cord IgM values in normal newborns range from 0 to 20 mg/100 ml). The baby died of progressive hydrocephalus, which may have had an inflammatory basis in view of the cerebrospinal fluid (CSF) protein level of 192 mg/100 ml. We realize that the significance of this association is questionable, but we believe that it is worthwhile to call the coincidence of events to the attention of others.


Adaptive neural coding: from biological to behavioral decision-making.
Empirical decision-making in diverse species deviates from the predictions of normative choice theory, but why such suboptimal behavior occurs is unknown. Here, we propose that deviations from optimality arise from biological decision mechanisms that have evolved to maximize choice performance within intrinsic biophysical constraints. Sensory processing utilizes specific computations such as divisive normalization to maximize information coding in constrained neural circuits, and recent evidence suggests that analogous computations operate in decision-related brain areas. These adaptive computations implement a relative value code that may explain the characteristic context-dependent nature of behavioral violations of classical normative theory. Examining decision-making at the computational level thus provides a crucial link between the architecture of biological decision circuits and the form of empirical choice behavior.


Test-retest reliability of the College of Optometrists in Vision Development Quality of Life Outcomes Assessment.
Medical diagnoses such as headaches, diplopia, nausea, and asthenopia are conditions that are often treated with optometric vision therapy. Improvement of such subjective conditions after a regimen of therapy is often difficult to objectively quantify. The goal of this study was to verify the test-re-test reliability of a new clinical survey instrument, the College of Optometrists in Vision Development (COVD) Quality of Life Outcomes Assessment, which allows the analysis of symptoms data. The first-year class of optometry students at the Oklahoma College of Optometry at Northeastern State University were administered the instrument in a group setting on two different occasions, two weeks apart. Nineteen students completed both test and re-test. Statistical analysis by the Wilcoxon Signed Rank Test and paired t test were performed. Each subject reported some of the 30 symptoms on both test and re-test. The instrument was found to be reliable. Wilcoxon Signed Rank Analysis showed no significant differences in test-retest scores, either pooled or item-by-item. A paired t-test group and item analysis were insignificantly different between scores. Spearman's rho correlation for test-retest of each subject was 0.878. Eighty-nine percent (17 of 19) scored insignificantly different between administrations. Ninety percent of the items (27 of 30) were found to vary insignificantly between the two administrations. The COVD Quality of Life Outcomes Assessment is a reliable tool to measure changes in symptoms on the basis of optometric intervention--specifically, vision therapy.


Gender differences in mutual-help attendance one year after treatment: Swedish and U.S. samples.
In the United States, many people turn to Alcoholics Anonymous (AA) and other mutual-help groups as a first source of help for an alcohol or drug problem, whereas others are introduced to AA while in treatment. Because AA and similar groups in the United States add to the treatment system and function without governmental funds, they represent an important element in ongoing care for individuals with substance-use disorders in the health care system. In countries with free (or more affordable) and more comprehensive systems of care, their role is less clearly defined. In this study, we compared men and women from representative treatment samples from studies with parallel designs, one Swedish (n = 1,525) and the other American (n = 926), to explore whether rates and correlates of attendance at 1-year follow- up (63% and 78% followed) differ by gender. We explore individual characteristics (demographic, severity, motivational) and formal and informal influences (treatment, mutual help, coercive, social) as possible help-seeking correlates of attendance. In both countries, similar proportions of men and women attended mutual-help groups. However, twice as many U.S. clients reported attendance. Moreover, twice as many U.S. clients set abstinence as a treatment goal. In multivariate models, having an abstinence goal, a perceived need for treatment, suggestions from one's employment environment, and prior mutual-help attendance predicted posttreatment attendance for men and women in both countries. Gender differences were also found. Given the stages in which individuals seek care and the cyclical nature of relapse and recovery, mutual-help groups are an efficient resource in the continuum of services.


Feline salmonellosis. A nosocomial outbreak and experimental studies.
An outbreak of S. typhimurium gastroenteritis and septicemia is described in young cats admitted to a veterinary hospital for routine medical and surgical reasons. A morbidity of 32% and a mortality of 61% was observed in the outbreak. Affected cats exhibited oral shedding of the organism and contaminated feed and water dishes may have been the vehicle of spread of infection. Possible detrimental effects of incorrect choice of antibiotic therapy are discussed. Attempts to reproduce the disease in a group of laboratory cats were unsuccessful. Antibody production was poorly correlated with infection in these cats.


Effects of bovine SMO gene polymorphisms on the body measurement and meat quality traits of Qinchuan cattle.
Beef cattle breeding programs focus on improving important economic traits, including growth rates, and meat quantity and quality. Molecular marker-assisted selection based on genetic variation represents a potential method for breeding genetically improved livestock with better economic traits. Smoothened (SMO) protein is a signal transducer that contributes to the regulation of both osteogenesis and adipogenesis through the hedgehog pathway. In this study, we detected polymorphisms in the bovine SMO gene of Qinchuan cattle, and we analyzed their associations with body measurement traits (BMTs) and meat quality traits (MQTs). Using DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism, 3 novel single nucleotide polymorphisms were identified in the SMO gene of 562 cattle: 1 G > C mutation on exon 9 (G21234C) and 2 C > T mutations on exon 11 (C22424T and C22481T). Association analysis showed that polymorphisms on both the G21234C and C22424T loci significantly affected certain BMTs and MQTs (P < 0.05 or P < 0.01), whereas those on the C22481T locus did not (P > 0.05). Therefore, the SMO gene could be used as a candidate gene to alter BMTs and MQTs in Qinchuan cattle or for marker-assisted selection to breed cattle with superior BMTs and MQTs.


[Extraction and characterization of soluble protein fractions from Phaseolus lunatus L seeds].
Legume proteins as a potential source of valuable nutrients, are the object of several studies in order to obtain the best use. A basic knowledge becomes more important for those proteins from species not wholly utilized, before using them as food ingredients. The objective of this work was to determine several structural and nutritional characteristics of the protein fractions from Phaseolus lunatus, separated in different solvents. The relative amount of extraction for the albumins (ALB), globulins (GLB), prolamines (PRL), and glutelins (GLT) was 62.3, 34.8, 1.4 and 1.5%, respectively. The SDS-PAGE electrophoretic profile of both ALB and GLB, showed seven common bands in intervals from 10 to 95 kDa, and 14 to 99 kDa, respectively; the amino acids profile showed that PRL was the rich fraction in sulfurated amino acids (11.5 g/100 g protein); the content of lysine in the fraction of ALB was smaller than expected but the requirement of the FAO in the fractions of GLB and GLT was covered. In general, the fraction of GLB had the best balance of amino acids and digestibility (80%); however, it had a relationship of calculated protein efficiency ratio (C-PER) of 0.11, smaller than the ratio in ALB (0.97). The calorimetric analysis showed denatured temperatures around 90 degrees C for the ALB, GLB, and GLU fractions. The PRL fraction probably did not present a thermal transition because the proteins were denaturalized by the extraction conditions.


[Management of periprosthetic infection].
Periprosthetic infection is a permanent risk and severe complication in joint arthroplasty. Systematic diagnostics under optimal conditions are necessary for a successful therapy. Patient history, clinical examination and an elevated CRP-level is the basis for suspicion of infection. The diagnosis is confirmed by identification of the pathogen from a sample collected through joint aspiration under sterile conditions. The microbiological examination is done in a laboratory specialized in the diagnosis of foreign body infections. The pattern of resistance of the identified pathogen determines the topical and systemic course of antibiotics. Surgical treatment is characterized by exchange of the prosthesis and radical debridement. The exchange can be carried out in one or two stages. The one-stage exchange offers several advantages compared to two or more stage procedures for all those involved - patient, surgeon and health care system - while providing the same chance of successful elimination of infection, with even better functional results.


Herpes simplex virus type 2: a possible interaction with human papillomavirus types 16/18 in the development of invasive cervical cancer.
A case-control study of 766 histologically confirmed incident cases of invasive cervical cancer and 1,532 hospital and community controls was conducted in Latin America to evaluate the etiologic role of herpes simplex virus type 2 (HSV-2) and to examine whether HSV-2 interacts with other risk factors. In addition to a personal interview, all subjects were asked to donate blood samples and cervical swabs for assessment of exposure to HSV-2 and human papillomaviruses (HPVs) respectively. Ninety-eight percent of cases and 91% of controls agreed to the interview and blood collection. Women testing positive for HSV-2 antibodies were found to have a 60% increased risk of cervical cancer compared with seronegative women (95% CI = 1.3, 1.9). Control for education, sexual and reproductive behavior, prior Pap-smear screening, smoking, oral contraceptive use, HPV-6/11 DNA, or HPV-16/18 DNA detection did not materially affect this estimate. No effect modification of HSV-2 by age, HPV-6/11 DNA, pregnancies, oral contraceptive use or cigarette smoking was observed. However, a significant interaction was detected between HSV-2 and HPV-16/18. Compared with women testing negative to both virus types, those positive for HSV-2 alone had a RR of 1.2 (95% CI = 0.9, 1.6), those positive for HPV-16/18 DNA alone had a RR of 4.3 (95% CI = 3.0, 6.0), and those positive for both viruses had a RR of 8.8 (95% CI = 5.9, 13.0). These findings corroborate recent laboratory evidence of a possible biological interaction between HSV-2 and HPV-16/18 in the development of cervical cancer. Further confirmatory studies are needed, given concerns with potential misclassification of exposure by the laboratory assays utilized.


Integrated molecular and behavioural data reveal deep circadian disruption in response to artificial light at night in male Great tits (Parus major).
Globally increasing levels of artificial light at night (ALAN) are associated with shifting rhythms of behaviour in many wild species. However, it is unclear whether changes in behavioural timing are paralleled by consistent shifts in the molecular clock and its associated physiological pathways. Inconsistent shifts between behavioural and molecular rhythms, and between different tissues and physiological systems, disrupt the circadian system, which coordinates all major body functions. We therefore compared behavioural, transcriptional and metabolomic responses of captive great tits (Parus major) to three ALAN intensities or to dark nights, recording activity and sampling brain, liver, spleen and blood at mid-day and midnight. ALAN advanced wake-up time, and this shift was paralleled by advanced expression of the clock gene BMAL1 in all tissues, suggesting close links between behaviour and clock gene expression across tissues. However, further analysis of gene expression and metabolites revealed that clock shifts were inconsistent across physiological systems. Untargeted metabolomic profiling showed that only 9.7% of the 755 analysed metabolites followed the behavioural shift. This high level of desynchronization indicates that ALAN disrupted the circadian system on a deep, easily overlooked level. Thus, circadian disruption could be a key mediator of health impacts of ALAN on wild animals.


pH-Responsive Polypropylene Sulfide Magnetic Nanocarrier-Mediated Chemo-Hyperthermia Kills Breast Cancer Stem Cells by Long-Term Reversal of Multidrug Resistance and Chemotherapy Resensitization.
Cancer stem cells (CSCs) present a formidable challenge in cancer treatment due to their inherent resistance to chemotherapy, primarily driven by the overexpression of ABC transporters and multidrug resistance (MDR). Despite extensive research on pharmacological small-molecule inhibitors, effectively managing MDR and improving chemotherapeutic outcomes remain elusive. On the other hand, magnetic hyperthermia (MHT) holds great promise as a cancer therapeutic, but there is limited research on its potential to reverse MDR in breast CSCs and effectively eliminate CSCs through combined chemo-hyperthermia. To address these gaps, we developed tumor microenvironment-sensitive, drug-loaded poly(propylene sulfide) (PPS)-coated magnetic nanoparticles (PPS-MnFe). These nanoparticles were employed to investigate hyperthermia sensitivity and MDR reversion in breast CSCs, comparing their performance to that of small-molecule inhibitors. Additionally, we explored the efficacy of combined chemo-hyperthermia in killing CSCs. CSC-enriched breast cancer cells were subjected to low-dose MHT at 42 °C for 30 min and then treated with the chemical MDR inhibitor salinomycin (SAL). The effectiveness of each treatment in inhibiting MDR was assessed by measuring the efflux of the MDR substrate, rhodamine 123 (R123) dye. Notably, MHT induced a prolonged reversal of MDR activity compared with SAL treatment alone. After successfully inhibiting MDR, the breast CSCs were exposed to chemotherapy using paclitaxel to trigger synergistic cell death. The combination of MHT and chemotherapy demonstrated remarkable reductions in stemness properties, MDR reversal, and the effective eradication of breast CSCs in this innovative dual-modality approach.


Herpes Simplex Virus Esophagitis in Immunocompetent Children: A Harbinger of Eosinophilic Esophagitis?
Herpes simplex virus (HSV) is a common cause of infectious esophagitis. The aim of this retrospective study is to identify comorbid and predisposing conditions and sequelae of HSV esophagitis in immunocompetent children. We reviewed 16 cases of HSV esophagitis diagnosed from January 1982 to March 2016. Five patients were immunosuppressed, 11 were immunocompetent and included in the study. Three (27%) had no other significant medical history. Five patients (45%) had repeat biopsies following their HSV infection, which showed eosinophilic infiltrate consistent with current diagnostic criteria of eosinophilic esophagitis (EoE), one of whom had known EoE. Environmental allergies and/or asthma were present in 4 of 5 of these patients. Among the immunocompetent patients, EoE was a comorbidity in almost half, although biopsies at the time of HSV esophagitis did not show diagnostic features of EoE. Clinical follow-up is therefore warranted for immunocompetent children presenting with HSV esophagitis, particularly those with atopic conditions.


The role of dietary fats in plant-based diets.
In the United States, the notion that low-fat, high-carbohydrate diets are essential for health has grown into an obsession, driven largely by an effort to reduce heart disease and, more recently, certain types of cancer. We know that saturated fatty acids are more closely associated with risk factors for heart disease than are unsaturated fatty acids. Many people believe that plant-based diets are healthy because they are low in fat. However, plant-based diets are not necessarily low-fat. In true plant-based diets, unsaturated fatty acids predominate, whereas saturated fatty acids come largely from animal sources such as dairy products and eggs. Plant-based diets include foods that contain fats, such as nuts and seeds and oils from grains and seeds. The fats in these foods are not associated with increased risk for heart disease. In addition, for people with insulin resistance, higher-fat diets protect against the heart disease risk factors of low HDL-cholesterol concentration, hypertriglyceridemia, hyperglycemia, and hyperinsulinemia. Because humans can synthesize fat from dietary carbohydrate, and because our adipose stores and circulating fatty acids reflect dietary intake, scientists understand the relations between the amounts and types of dietary fats and the types of fats found in body fat depots. Consuming dietary fats that are not associated with increased risk of disease can be a part of a healthful diet.


Dermatoses in newborns.
Benign dermatoses in newborns must be distinguished from more serious disorders with cutaneous manifestations. Erythema toxicum neonatorum, transient neonatal pustular melanosis, sucking blister, miliaria and mongolian spots are among the many benign skin conditions that can occur in newborns. Recognition of these dermatoses allows the physician to proceed appropriately, reassure the parents and initiate further evaluation or treatment as necessary. To avoid adverse sequelae, special attention must be given to more persistent conditions and those with the potential for complications or malignant transformation. Consultation with a pediatric dermatologist, a plastic surgeon or a neurosurgeon may be necessary.


Plasma and Peritoneal Fluid Fibronectin and Collagen IV Levels as Potential Biomarkers of Endometriosis.
Laparoscopy as a diagnostic tool for patients with suspected endometriosis is associated with several potentially life-threatening complications. Therefore, it is imperative to identify reliable, non-invasive biomarkers of the disease. The aim of this study was to analyse the concentrations of fibronectin and type IV collagen in peritoneal fluid and plasma to assess their role as potential biomarkers in the diagnosis of endometriosis. Fibronectin and collagen IV protein levels were assessed by surface plasmon resonance imaging (SPRi) biosensors with the usage of monoclonal antibodies. All patients enrolled in the study were referred for laparoscopy for the diagnosis of infertility or chronic pelvic pain (n = 84). The study group included patients with endometriosis confirmed during surgery (n = 49). The concentration of fibronectin in the plasma (329.3 ± 98.5 mg/L) and peritoneal fluid (26.8 ± 11.1 μg/L) in women with endometriosis was significantly higher than in the control group (251.2 ± 84.0 mg/L, 7.0 ± 5.9 μg/L). Fibronectin levels were independent of endometriosis stage (p = 0.874, p = 0.469). No significant differences were observed in collagen IV levels (p = 0.385, p = 0.465). The presence of elevated levels of fibronectin may indicate abnormalities in cell-ECM signalling during the course of endometriosis, and may be a potential biomarker for early detection.


[Musculoskeletal manifestations as the onset of acute leukemias in childhood].
To study the frequency, the clinical features and laboratory exams of patients with musculoskeletal symptoms at the onset of acute leukemia. Retrospective, descriptive study including patients diagnosed with acute leukemia, and treated at the Institute of Pediatric Oncology of UNIFESP, carried out from November 1999 to February 2000. The data on musculoskeletal complaints were obtained from a questionnaire. The medical records were revised in order to get data on the clinical examination and laboratory tests at the beginning of the illness. Sixty-one children were included in this trial, 93% with acute lymphoid leukemia, and 7% with acute myeloid leukemia. Thirty-eight patients (62%) had musculoskeletal pain at the onset. Arthritis was observed in eight patients. The mean number of involved joints was 2.5 (1-6). The most frequently involved joints were the knees, ankles and elbows. Three patients (4.9%) had normal blood count. Low hemoglobin was reported in 54 patients (88%) (in six patients it was the only hematological abnormality), leukopenia in 14 (22%), leukocytosis in 26 (42%) and low platelet count in 46 (75%). The musculoskeletal symptoms are common at the onset of acute leukemia so, malignancy should always be ruled out in patients presenting chronic or acute arthritis or benign limb pain. The laboratory tests may be normal at the onset of the illness, making differential diagnosis more difficult.


Giant clam growth in the Gulf of Aqaba is accelerated compared to fossil populations.
The health of reef-building corals has declined due to climate change and pollution. However, less is known about whether giant clams, reef-dwelling bivalves with a photosymbiotic partnership similar to that found in reef-building corals, are also threatened by environmental degradation. To compare giant clam health against a prehistoric baseline, we collected fossil and modern Tridacna shells from the Gulf of Aqaba, Northern Red Sea. After calibrating daily/twice-daily growth lines from the outer shell layer, we determined that modern individuals of all three species (Tridacna maxima, T. squamosa and T. squamosina) grew faster than Holocene and Pleistocene specimens. Modern specimens also show median shell organic δ15N values 4.2‰ lower than fossil specimens, which we propose is most likely due to increased deposition of isotopically light nitrate aerosols in the modern era. Nitrate fertilization accelerates growth in cultured Tridacna, so nitrate aerosol deposition may contribute to faster growth in modern wild populations. Furthermore, colder winter temperatures and past summer monsoons may have depressed fossil giant clam growth. Giant clams can serve as sentinels of reef environmental change, both to determine their individual health and the health of the reefs they inhabit.


Comparison of methods for detecting specific IgM antibody in infants with congenital rubella.
Serum specimens from 14 infants with congenital rubella were examined for specific IgM antibody by six different methods. IgM-containing fractions were separated either by sucrose density-gradient centrifugation or by gel filtration through Sephadex G-200, and were then tested by the indirect immunofluorescence technique and by the haemagglutination-inhibition (HI) test (long-and short-incubation methods). Immunofluorescence staining of density-gradient fractions detected specific IgM in all 14 infants. The HI test (long method), applied to density-gradient fractions, was almost as sensitive, detecting antibody in 13 infants; the short method was less sensitive. The gel-filtration technique proved to be generally less satisfactory than sucrose density-gradient centrifugation. Evidence was obtained for the occurrence of as yet unclassified non-specific inhibitors in the serum of some infants. These inhibitors were deposited with the IgM on sucrose-density gradients and they could have been mistaken for rubella-specific IgM antibody, particularly in the HI test (long method).


Prehospital rapid sequence induction following trauma in the era of regional networks for major trauma.
Rapid sequence induction (RSI) provides prompt airway control during emergency evacuation of trauma patients. Physicians may be tasked to travel with paramedic ambulance crews to the scene of injury when RSI is more likely to be required. This study investigates whether there are any differences in the practice of prehospital RSI during emergency retrievals for trauma since the establishment of the regional Major Trauma Network (MTN) in March 2012. A retrospective observational study examined prehospital records for all trauma patients from September 2010 to January 2015 at a Major Trauma Centre in Birmingham, UK. Prehospital physician availability increased from 12 to 24 h after March 2012, and tasking became centralized. Data included demographics, mechanism of injury, crew personnel, and details of RSI. The periods before and after the establishment of the regional MTN were compared. There were 5244 patients: 1432 (27.3%) before and 3812 (72.7%) after March 2012. Of the patients, 67.2% were male. The most common injuries were road traffic collisions (45.0%). Physicians were more likely to be present after (2345 missions, 61.5%) than before (529 missions, 36.9%) March 2012 (P<0.01). RSI was performed 434 (8.3%) times and was more likely during the latter than the former period [359 (9.4%) vs. 75 (5.2%), P<0.01]. Successful tracheal intubation was achieved in 99% of occasions. The establishment of regional MTNs enables centrally tasked, 24-h physician availability for emergency trauma patients. There has been an increase in physician presence on emergency missions and increased frequency of RSI for at-risk trauma patients at times when there may previously have been an unmet requirement.