Dendritic cells and the replication of HIV-1.
Dendritic cells (DCs) are a distinct lineage of white cells that arise from CD34+ progenitors in the bone marrow. DCs exhibit many specializations that lead to efficient antigen capture and presentation to T cells, both CD4+ helpers and CD8+ killers. In several human tissues, DCs express the CD4 receptor for HIV-1. Some early reports described the explosive infection of blood-derived DCs by HIV-1 and a severe compromise of their presenting function. In contrast, other studies described active HIV-1 replication when DCs were interacting with CD4+ T cells. This productive infection could begin with a low viral burden in DCs but required that the DCs retain their normal binding and stimulatory function for T cells. In this review we first summarize those features of the DC system that seem pertinent to HIV-1 infection. Then we consider the current literature on the interaction of HIV-1 with DCs, from several different tissues, in HIV-1-infected patients or following challenge with HIV-1 in vitro. The literature leads to the hypothesis that HIV-1 infection is a battleground in which DCs could be leading both of the armies, the aggressor that promotes HIV-1 replication from relatively small numbers of infected cells and the defender that mediates T cell-dependent resistance.


Responses of neurones in the medullary raphe nuclei to inputs from visceral nociceptors and the ventrolateral periaqueductal grey in the rat.
The ventrolateral periaqueductal grey matter (PAG) is believed to have a role in mediating cardiovascular responses to noxious visceral stimuli. The present study was carried out as a first stage in establishing whether the ventrolateral PAG may exert these influences after a relay in the caudal medullary raphe nuclei (nucleus raphe obscurus and nucleus raphe pallidus). Single unit extracellular recordings were made from neurones in the caudal raphe nuclei and, for comparison, in the more rostral nucleus raphe magnus in Saffan-anaesthetized and paralysed rats. Neurones in the mid-line medulla were tested for their responses to electrical stimulation at chemically identified depressor sites in the ventrolateral PAG and to noxious visceral stimuli (distensions of the urinary bladder and electrical stimulation of the greater splanchnic nerve). Fifty-two per cent of caudal and 74% of rostral mid-line neurones gave short latency excitatory responses to stimulation of depressor sites in the ventrolateral PAG. Of the neurones that were also tested with noxious visceral stimuli, 5% of the caudal and 47% of the rostral neurones responded to bladder distension, while 33 and 35%, respectively, of caudal and rostral neurones responded to splanchnic nerve stimulation. These results indicate that many mid-line medullary neurones receive inputs from both the ventrolateral PAG and visceral nociceptors and may, therefore, be part of the output pathway by which the ventrolateral PAG produces integrated physiological responses to noxious visceral stimuli.


Chronic comorbid conditions associated with risk of febrile neutropenia in breast cancer patients treated with chemotherapy.
Chemotherapy-induced febrile neutropenia (FN) is associated with increased patient mortality and health care costs. Comorbid conditions such as liver and renal dysfunction have been linked to increased risk of FN. However, the effects of other chronic comorbid conditions on risk of FN have not been well studied. To examine the association between chronic comorbid conditions and FN in breast cancer patients, we identified incident breast cancer patients from 2000 to 2009 treated with chemotherapy at Kaiser Permanente Southern California, a large managed care organization. Patients who received primary prophylactic granulocyte colony-stimulating factor (G-CSF) were excluded. We assessed history of comorbid conditions prior to cancer diagnosis using ICD-9 codes and disease registries. FN events were identified in the first chemotherapy cycle using a combination of ICD-9 codes and hospital discharge diagnoses. For each comorbid condition, propensity scores that included patient characteristics and other predisposing comorbid conditions were calculated and adjusted for in Cox models to determine associations between that comorbid condition and FN. We also evaluated secondary models that additionally adjusted for cancer stage, baseline absolute neutrophil count (ANC), chemotherapy regimen, and dose reductions. A total of 7,127 breast cancer patients were included; median age was 55 years, and the majority had localized (47 %) or regional (49 %) disease at diagnosis. In the first chemotherapy cycle, 335 (4.7 %) patients developed FN. Congestive heart failure (HR = 3.0; 95 % CI: 1.3-5.9), osteoarthritis (HR = 2.0; 95 % CI: 1.4-2.8), previous cancer (HR = 3.4; 95 % CI: 1.2-7.5), and thyroid disorder (HR = 1.6; 95 % CI: 1.1-2.3) were associated with increased risk of FN. These estimates were similar to those from secondary models that also adjusted for additional cancer and treatment-related covariates. Our findings suggest that several chronic comorbid conditions may be associated with risk of FN. This information, if confirmed by others, may aid clinical decision making with respect to use of prophylactic G-CSF during chemotherapy treatment.


[Isolation of NAD-kinase from pigeon heart].
A procedure of isolation of pigeon breast muscle NAD-kinase resulting in a 100--130-fold purification of the enzyme with a total yield of 30--35% is described. The enzyme is electrophoretically homogenous; its molecular weight as determined by SDS-electrophoresis is 45 000. The partially purified preparation contains multiple enzymic forms with molecular weights varying from 45 000 to 270 000, which represent an equilibrious system of structurally different oligomers. At the last purification step, i. e. ion-exchange chromatography, the enzyme loses its ability for oligomerization. Possible causes of disappearance of the enzyme multiple forms during purification are discussed.


A combination of ceftaroline and daptomycin has synergistic and bactericidal activity in vitro against daptomycin nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA).
There is an urgent need to optimize therapeutic options in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia who have failed conventional therapy. Two clinical isolates were obtained from a 68-year-old male with persistent MRSA bacteremia before and after the development of daptomycin nonsusceptibility. The pharmacodynamic activity of monotherapies and combinations of ceftaroline, daptomycin, cefoxitin, nafcillin and vancomycin were evaluated in time-kill experiments versus 108 CFU/mL of the pre- and post-daptomycin nonsusceptible MRSA isolates. Cefoxitin, nafcillin and vancomycin alone or in combination with ceftaroline failed to generate prolonged bactericidal activity against the post-daptomycin nonsusceptible isolate whereas a ceftaroline-daptomycin combination resulted in 6, 24 and 48 h log10(CFU/mL) reductions of 3.90, 4.40 and 6.32. Population analysis profiles revealed a daptomycin heteroresistant subpopulation of the pre-daptomycin nonsusceptible MRSA isolate that expanded by >10,000× on daptomycin agar containing 2-16 mg/L in the post-daptomycin nonsusceptible isolate. Daptomycin and ceftaroline combinations may be promising against persistent MRSA bacteremia.


Developing supportive care for family members of people with lung cancer: a feasibility study.
Families provide crucial support, yet their own needs often go unrecognised and, as a consequence, remain unmet. The purpose of this study was to evaluate a newly developed supportive intervention for family members of patients with lung cancer. A consecutive convenience sample of 25 family members of people with lung cancer received an individualised supportive intervention from a support nurse over a period of 12 weeks. This involved in-depth assessment followed up with a tailored plan of ongoing support to address informational, emotional, social and practical needs. A concurrent mixed method design explored perceptions and outcomes of those receiving the intervention and assess its appropriateness, acceptability and feasibility. Data were collected through a semi structured telephone interview with family members, and support nurses maintained a contact log. A questionnaire addressed emotional well-being [general health questionnaire (GHQ-12)], quality of life [quality of life family version (Family QoL)] and needs for care [family inventory of needs (FIN)]-at baseline and week 12. Family members perceived they had derived benefit from the intervention. Certain elements clearly emerged as important for participants, including being listened to by someone who could facilitate emotional expression, being provided with individually tailored information and receiving practical help and advice. Outcomes mapped to five main areas: information needs, communication between family members, emotional well-being, being supported and facilitating family member's role. There was a trend for more needs to be met and quality of life and emotional well-being to improve at week 12. This study has demonstrated that a supportive intervention for family members of patients with lung cancer can be delivered to good effect by experienced cancer nurses. The active components of the intervention have been distinguished and provide the basis for development of a larger sufficiently powered trial.


Characterization of a spotted fever group Rickettsia from Ixodes ricinus ticks in Sweden.
A spotted fever group rickettsia isolated from the common tick, Ixodes ricinus, was genetically characterized by PCR and genomic sequencing. This study was performed with nymphal and adult ticks collected in southern and central Sweden. I. ricinus is the only North European tick species of medical importance which is regularly collected from humans. No species of the genus Rickettsia has previously been found in Scandinavian ticks, nor has any case of domestic rickettsial infection in humans or animals been reported. According to the nucleotide sequencing, the present Rickettsia sp. belongs to the spotted fever group of rickettsiae. Ticks are the most common arthropod reservoirs and vectors of the rickettsiae of this group. Among 748 ticks investigated, 13 (1.7%) were positive for a Rickettsia sp. Borrelia burgdorferi was detected in 52 (7%) of the ticks, a prevalence similar to or somewhat lower than that previously been recorded in other Swedish studies. There was no evidence of ehrlichial or chlamydial DNA in these ticks. The Rickettsia sp. was further characterized by 16S ribosomal DNA (rDNA) sequencing and restriction fragment length polymorphism (RFLP). The 16S rDNA sequencing resulted in a sequence identical to that described for Rickettsia helvetica, but the pattern obtained with RFLP of the citrate synthetase gene diverged from previously known patterns. The rickettsial agent of one tick which was positive by PCR was confirmed by transmission electron microscopy. The morphology of this rickettsia was similar to that of the spotted fever and typhus group rickettsiae. This represents the first documented isolate of a Rickettsia sp. from Swedish ticks.


Evidence-based medicine and neurophysiology.
Evidence-based medicine (EBM) was introduced to meet the increasing need of clinicians to keep up-to-date with the research evidence. EBM integrates advances in information technology with those in clinical epidemiology (the study of the distribution and determinants of disease) to provide a coherent strategy for the timely acquisition of the best available evidence on which to base clinical practice. A fundamental component of EBM has been the development of the methodology of research synthesis. Although the main driver of the development of EBM has been to get existing research into practice, the same approach can be used to inform the development of treatments.


Characterization of an unusual sex steroid binding component from the chicken oviduct.
In addition to the classical estrogen receptor, chick oviduct cytosol contains a sex steroid binding component (SSB) with specificity for steroidal estrogens, androgens and progestins. We have optimized the measurement of SSB and have further characterized this protein. It was possible to quantitate [3H]estradiol binding to SSB by performing the measurements in the presence of excess diethylstilbestrol, which saturates the estrogen receptor and does not bind to SSB, and by using excess progesterone to determine nonspecific binding. Since SSB appears to be quite unstable with rapid hormone dissociation kinetics, we determined that short incubation times (usually 2 h) at 0 degrees C with 20-30% glycerol in the buffer gave optimal SSB measurements. The affinity of SSB for estradiol (Kd = 20 nM) is about 5% that of the estrogen receptor. In addition to estradiol, several androgens and progestins bind to SSB. However, the nonsteroidal antiestrogen, H1285 does not bind to SSB even though it binds well to the avian estrogen receptor. The tissue content of SSB is about 15-fold greater than for estrogen receptor and is stimulated by estrogen treatment. Whereas labeled SSB cannot be readily resolved by ion-exchange chromatography due to rapid dissociation of hormone from SSB, post-labeling experiments yield binding activity eluting with 0.2 M KCl indicating that SSB is an acidic protein having a chromatography behavior similar to that of estrogen receptor. SSB binding was dramatically reduced by the chaotropic salt, NaSCN, whereas binding to the estrogen receptor was not disrupted. SSB is stabilized by sodium molybdate, a property which is characteristic of steroid receptors. Although the role of SSB in the chick oviduct is yet to be determined, an understanding of its properties is essential for accurate determinations of the estrogen receptor.


Topiramate-induced angle closure with acute myopia, macular striae.
Topiramate is a sulfamate-substituted monosaccharide used in the treatment of seizures, and prophylaxis of migraine. A number of ocular side-effects have been described with use of topiramate, like bilateral angle closure, acute myopia and macular striae. Ultrasound biomicroscopy (UBM) clinches the diagnosis after ruling out other causes of shallow anterior chamber. Previous studies have not demonstrated internal limiting membrane folds presenting as macular striae. We report a case of topiramate-induced acute myopia with angle closure and macular striae in a young adult. This is the first report wherein striae formation after low doses of topiramate and their resolution have been documented by Optical Coherence Tomography (OCT).


Strategies in a metallophyte species to cope with manganese excess.
The effect of exposure to high Mn concentration was studied in a metallophyte species, Erica andevalensis, using hydroponic cultures with a range of Mn concentrations (0.06, 100, 300, 500, and 700 mg L-1). At harvest, biomass production, element uptake, and biochemical indicators of metal stress (leaf pigments, organic acids, amino acids, phenols, and activities of catalase, peroxidase, superoxide dismutase) were determined in leaves and roots. Increasing Mn concentrations led to a decrease in biomass accumulation, and tip leaves chlorosis was the only toxicity symptom detected. In a similar way, photosynthetic pigments (chlorophylls a and b, and carotenoids) were affected by high Mn levels. Among organic acids, malate and oxalate contents in roots showed a significant increase at the highest Mn concentration, while in leaves, Mn led to an increasing trend in citrate and malate contents. An increase of Mn also induced an increase in superoxide dismutase activity in roots and catalase activity in leaves. As well, significant changes in free amino acids were induced by Mn concentrations higher than 300 mg L-1, especially in roots. No significant changes in phenolic compounds were observed in the leaves, but root phenolics were significantly increased by increasing Mn concentrations in treatments. When Fe supply was increased 10 and 20 times (7-14 mg Fe L-1 as Fe-EDDHA) in the nutrient solutions at the highest Mn concentration (700 mg Mn L-1), it led to significant increases in photosynthetic pigments and biomass accumulation. Manganese was mostly accumulated in the roots, and the species was essentially a Mn excluder. However, considering the high leaf Mn concentration recorded without toxicity symptoms, E. andevalensis might be rated as a Mn-tolerant species.


Subjective General Health and the Social Regulation of Hypothalamic Activity.
Social support is associated with better health. This association may be partly mediated through the social regulation of adrenomedullary activity related to poor cardiovascular health and glucocorticoid activity known to inhibit immune functioning. These physiological cascades originate in the hypothalamic areas that are involved in the neural response to threat. The aim of the study investigated whether the down regulation, by social support, of hypothalamic responses to threat is associated with better subjective health. A diverse community sample of seventy-five individuals, aged 23 to 26 years, were recruited from an ongoing longitudinal study. Participants completed the Short Form Health Survey, a well-validated self-report measure used to assess subjective general health. They were scanned, using functional magnetic resonance imaging, during a threat of shock paradigm involving various levels of social support, which was manipulated using handholding from a close relational partner, a stranger, and an alone condition. We focused on a hypothalamic region of interest derived from an independent sample to examine the association between hypothalamic activity and subjective general health. Results revealed a significant interaction between handholding condition and self-reported general health (F(2,72) = 3.53, p = .032, partial η = 0.05). Down regulation of the hypothalamic region of interest during partner handholding corresponded with higher self-ratings of general health (ß = -0.31, p = .007). Higher self-ratings of general health correspond with decreased hypothalamic activity during a task that blends threat with supportive handholding. These results suggest that associations between social support and health are partly mediated through the social regulation of hypothalamic sensitivity to threat.


Towards Assisted Moderation in Online Healthcare Social Networks: Improving Trust in YouTube Searches.
Moderation of content in online Health Social Networks (HSN) is critical because information is not only published and produced by experts or health professionals, but also by users of that information. The objective of this paper is to propose a semi-automatic moderation Web Service for assessing the quality (trustworthiness) of health-related videos published on the YouTube social network. The service is relevant for moderators or community managers, who get enabled to control the quality of videos published on their online HSN sites. The HealthTrust metric was selected as the metric to be implemented in the service in order to support the assessment of trustworthiness of videos in Online HSN. The service is a RESTful service which can be integrated into open source Virtual Social Network Platforms, therefore improving trust in the process of searching and publishing content extracted from YouTube. A preliminary pilot evaluation in a simple use case demonstrated that the relevance of videos retrieved using the moderation service was higher compared to the relevance of the videos retrieved using the YouTube search engine.


TNF-alpha bifunctionally induces proliferation in primary hepatocytes: role of cell anchorage and spreading.
In the absence of a growth factor or an appropriate extracellular matrix (ECM), cells are arrested in the G0/G1 phase. In this report, we demonstrate the evidence that TNF-alpha induced DNA synthesis of primary mouse hepatocytes in vitro by activating two distinct pathways. TNF-alpha induced drastic spreading of hepatocytes on hydrophobic plastic, while the adhesion was not influenced. The effect was time and dose dependent. The cell spreading was accompanied by the phosphorylation of paxillin, indicating the stimulation of focal adhesion molecules. TNF-alpha-induced spreading of hepatocytes was not transient, and kinetic analysis and morphologic observation suggest that the effect was different from epidermal growth factor- or hepatocyte growth factor-induced transient hepatocyte spreading. TNF-alpha-induced hepatocyte spreading was blocked by cytochalasin D, Arg-Gly-Asp peptides, cycloheximide, or anti-integrin beta1 Ab. Results of competitive PCR for ECM proteins demonstrated that TNF-alpha increased the expression of laminin alpha3 and gamma1 chains in hepatocytes. These data suggested that TNF-alpha induced cell anchorage for hepatocytes by up-regulating ECM production. More importantly, TNF-alpha, but neither epidermal growth factor nor hepatocyte growth factor, induced DNA synthesis following the spreading in primary hepatocytes on hydrophobic plastic, while mere cell spreading on collagen did not induce DNA synthesis. The DNA synthesis was blocked by the inhibition of either cell spreading or DNA polymerase, demonstrating that TNF-alpha induced DNA synthesis in primary hepatocytes by activating two distinct pathways, i.e., forming the scaffold and inducing growth signals. Taken together, TNF-alpha bifunctionally regulates the proliferation of primary hepatocytes, serving as both an ECM inducer and a growth factor.


Application of Cold Storage and Short In Vitro Germination for Somatic Embryos of Pinus radiata and P. sylvestris.
Somatic embryogenesis (SE) is an advanced vegetative propagation technology that, when used in combination with breeding and cryopreservation, offers the forest industry a powerful tool for the deployment of elite genotypes. Germination and acclimatization are critical and cost-intensive phases in the production of somatic plants. The efficient conversion of somatic embryos into robust plants is a necessity if a propagation protocol is to be successfully adopted by the industry. In this work, these late phases of the SE protocol of two pine species were investigated. A shortened germination protocol and more controlled acclimatization were investigated for Pinus radiata, testing embryos from 18 embryogenic cell lines. A more simplified protocol, including a cold storage phase, was also compared among 10 of these cell lines. A shortened germination period and more controlled protocols significantly improved the acclimatization of somatic embryos directly from the lab to the glasshouse. When results for all cell lines were pooled, there were significant improvements in all growth characteristics (shoot height, root length, root collar diameter, and root quadrant score). When the more simplified protocol involving cold storage was tested, improvements were seen in the root architecture. For Pinus sylvestris, the late phases of somatic embryogenesis were investigated on seven cell lines in a set of two trials (four to seven cell lines per trial). During the germination phase, a shortened and simplified in vitro period, a cold storage option and basal media were explored. Viable plants were obtained from all treatments. However, there is still the need to improve germination and related protocols together with growing regimes for Pinus sylvestris. The improvements to protocols presented here, particularly for Pinus radiata, result in greater survival and quality of somatic emblings, leading to reduced costs and increased confidence in the technology. Simplified protocols using a cold storage option show great promise and, with some further research, could lead to reductions in the cost of the technology.


Regulation of ERK1/2 activity by ghrelin-activated growth hormone secretagogue receptor 1A involves a PLC/PKCvarepsilon pathway.
1. The growth hormone secretagogue receptor 1a (GHSR-1a) is a G-protein coupled receptor, involved in the biological actions of ghrelin by triggering inositol phosphates and calcium intracellular second messengers. It has also been reported that ghrelin could activate the 44- and 42-kDa extracellular signal-regulated protein kinases (ERK1/2) in different cell lines, but it is not clear whether this regulation is GHSR-1a dependent or not. 2. To provide direct evidence for the coupling of GHSR-1a to ERK1/2 activation, this pathway has been studied in a heterologous expression system. 3. Thus, in Chinese hamster ovary (CHO) cells we showed that ghrelin induced, via the human GHSR-1a, a transient and dose-dependent activation of ERK1/2 leading to activation of the transcriptional factor Elk1. 4. We then investigated the precise mechanisms involved in GHSR-1a-mediated ERK1/2 activation using various specific inhibitors and dominant-negative mutants and found that internalization of GHSR-1a was not necessary. Our results also indicate that phospholipase C (PLC) was involved in GHSR-1a-mediated ERK1/2 activation, however, pathways like tyrosine kinases, including Src, and phosphoinositide 3-kinases were not found to be involved. GHSR-1a-mediated ERK1/2 activation was abolished both by a general protein kinase C (PKC) inhibitor, Gö6983, and by PKC depletion using overnight pretreatment with phorbol ester. Moreover, the calcium chelator, BAPTA-AM, and the inhibitor of conventional PKCs, Gö6976, had no effect on the GHSR-1a-mediated ERK1/2 activation, suggesting the involvement of novel PKC isoforms (epsilon, delta), but not conventional or atypical PKCs. Further analyses suggest that PKCepsilon is required for the activation of ERK1/2. 5. Taken together, these data suggest that ghrelin, through GHSR-1a, activates the Elk1 transcriptional factor and ERK1/2 by a PLC- and PKCepsilon-dependent pathway.


Fabrication of lipid tubules with embedded quantum dots by membrane tubulation protein.
The first one-dimensional (1D) assembly of low-toxicity CuInS(2) /ZnS quantum dots (QDs) embedded in lipid nanotubules, formed from liposomes using the Amphiphysin-BAR (Bin-Amphiphysin-Rvs domain of human amphiphysin) protein to elongate the structure, is reported. The QD-containing lipid nanotubules display a high aspect ratio of ≈500:1 (≈40 nm diameter and 20 μm length) and are stable for more than 20 h. Furthermore, this methodology is extended to the assembly of various nanoparticle species within 1D lipid nanotubules, and includes materials such as CdSe and Au. Encapsulation within the hydrophobic core of the bilayer makes these materials highly biocompatible. The developed methodology and materials with these unique characteristics could be useful for various applications in nanobiotechnology and nanomedicine.


Gait and function after intra-articular arthrodesis of the hip in adolescents.
Patients who have had a hip arthrodesis have been reported to have pain in the back and the knee due to an altered gait. There is little information about the specific compensatory mechanisms that are adopted when walking. The purpose of this study was to objectively define gait adaptations after an arthrodesis of the hip and to correlate the kinematic findings with pain and other patient outcomes. Nine patients who had had an arthrodesis of the hip at an average age of thirteen years and five months (range, ten years and nine months to sixteen years and eleven months) were evaluated with gait analysis and muscle strength-testing and completed a questionnaire related to pain and function. The average duration of follow-up was eight years and ten months (range, two years and one month to thirteen years and ten months). The frequency of the postoperative visits varied. Seven patients were adults at the time of the study and were called back specifically for the study. All patients had decreased cadence and step lengths. The kinematic findings included decreased dorsiflexion of the ipsilateral ankle, hyperextension of the ipsilateral knee during the stance phase, and a tendency toward increased genu valgum during gait. In normal gait, there is no genu varum or valgum during the stance phase. The patients had an average (and standard deviation) of 7 +/- 4 degrees of genu valgum. Pelvic and lumbar motion in the sagittal plane was excessive in all patients. Strength-testing revealed clinically relevant weakness in the ipsilateral quadriceps in all patients, with a difference of more than 20 percent between the two extremities in six patients. The gastrocnemius. soleus muscle was stronger on the side with the fused hip in six patients. The questionnaire, designed by Harris in 1969 and completed by the patients at the time of the gait analysis, revealed back pain in seven patients. The questionnaire was administered only once. The functional outcome as measured with use of the same questionnaire worsened as the duration of follow-up increased. The gait analysis showed excessive motion in the lumbar spine and the ipsilateral knee in all nine patients. This abnormal motion led to pain as the duration of follow-up increased, and all patients who had been followed for four or more years after the arthrodesis complained of back pain. We hypothesized that excessive motion for an extended duration can lead to back pain. The preferred position of the hip for the arthrodesis was 20 to 25 degrees of flexion, neutral abduction-adduction, and neutral rotation.


Estimating Risk of Postsurgical General and Geriatric Complications Using the VESPA Preoperative Tool.
As greater numbers of older patients seek elective surgery, one approach to preventing postoperative complications is enhanced assessment of risks during preoperative evaluation. To determine whether a geriatric assessment tool can be implemented in a preoperative clinic and can estimate risk of postoperative complications. In this prospective cohort study, patients 70 years of age or older were assessed in a preoperative clinic for elective surgery from July 9, 2008, to January 5, 2011. Patients were screened using the Vulnerable Elders Surgical Pathways and Outcomes Assessment (VESPA) tool developed for this study. Patients were assessed on 5 preoperative activities of daily living recommended by the American College of Surgeons (bathing, transferring, dressing, shopping, and meals), history of falling or gait impairment, and depressive symptoms (2-item Patient Health Questionnaire). Patients also underwent a brief cognitive examination (Mini-Cog) and gait and balance assessment (Timed Up and Go test). A novel question was also asked as to whether patients expected they could manage themselves alone after discharge. Comorbidities and work-related relative value units (categorized into low, moderate, and high tertiles) were also collected. Multivariable logistic regression was performed to estimate risk of postoperative complications. Sustainability of VESPA over time was also evaluated. Medical record review was performed from December 11, 2012, to October 2, 2015, and data analysis was performed from November 15, 2015, to May 18, 2016. Postoperative surgical and geriatric complications. Of the 770 patients evaluated, 736 (384 women and 352 men; mean [SD] age, 77.7 [5.7] years) underwent 740 operative procedures; of these patients, 711 had complete data for multivariable analysis. In our sample, 105 patients (14.3%) reported 1 or more difficulties with the 5 activities of daily living, and 270 of 707 patients (38.2%) foresaw themselves unable to manage self-care alone. A total of 131 of 740 patients had geriatric complications, and 114 of 740 patients had surgical complications; 187 of 740 patients (25.3%) had either geriatric or surgical complications. On multivariable analysis, the number of difficulties with activities of daily living (odds ratio [OR], 1.3; 95% CI, 1.0-1.6), anticipated difficulty with postoperative self-care (OR, 1.6; 95% CI, 1.0-2.2), Charlson Comorbidity score of 2 or more vs less than 2 (OR, 1.5; 95% CI, 1.0-2.3), male sex (OR, 1.6; 95% CI, 1.1-2.3), and work-related relative value units (moderate vs low: OR, 1.9; 95% CI, 1.1-3.3; high vs low: OR, 8.8; 95% CI, 5.3-14.5) were independently associated with postoperative complications (overall model area under the receiver operating characteristic curve, 0.77). With these results, a whole-point VESPA score used alone to estimate risk of complications also demonstrated excellent fit (area under the curve, 0.76). Preoperative assessment of older geriatric patients is feasible in the general preoperative clinic and can help identify patients at higher risk of postoperative complications.


The extremely halophilic archaeon Haloferax volcanii has two very different dihydrofolate reductases.
The gene encoding dihydrofolate reductase, hdrA, from the extremely halophilic archaeon Haloferax volcanii was previously isolated from a spontaneous trimethoprim-resistant mutant in a DNA sequence that had undergone amplification. Here, we show that deletion of hdrA did not affect growth in minimal medium and that the strain carrying the deletion remained sensitive to trimethoprim. A spontaneous trimethoprim-resistant colony was isolated in the hdrA deletion strain and found to possess a new DNA amplification. Sequencing of the amplification revealed a second, substantially different, dihydrofolate reductase gene, hdrB, which was found to be located immediately downstream of the thymidylate synthase gene, hts. The physiological role of hDHFR-1 and hDHFR-2 was determined by generating Haloferax volcanii strains in which each gene, hdrA or hdrB, or both genes were deleted. It was found that hdrB alone can support growth of Haloferax volcanii in minimal medium, whereas hdrA alone can support growth of Haloferax volcanii in minimal medium only when the medium is supplemented with thymidine. It was also shown that, in contrast to Escherichia coli, the DeltahdrA, DeltahdrB double deletion mutant is viable in the presence of a functional thymidylate synthase gene. The hdrB gene was overexpressed in Escherichia coli and the enzyme purified to homogeneity. The biochemical properties of the new enzyme (hDHFR-2) are markedly different from those of hDHFR-1. The use of the dihydrofolate reductase and thymidylate synthase genes as stable selectable markers is described.


Low-intensity pulsed ultrasound for bone healing: an overview.
Low-intensity ultrasound is a biophysical form of intervention in the fracture-repair process, which through several mechanisms accelerates healing of fresh fractures and enhances callus formation in delayed unions and nonunions. The goal of this review is to present the current knowledge obtained from basic science and animal studies, as well as existing evidence from clinical trials and case series with the different applications of ultrasound in the management of fractures, delayed unions, nonunions and distraction osteogenesis. Low-intensity pulsed ultrasound is currently applied transcutaneously, although recent experimental studies have proven the efficacy of a trans-osseous application for both enhancement and monitoring of the bone healing process with modern smart implant technologies.


Investigating the genetic basis of fever-associated syndromic epilepsies using copy number variation analysis.
Fever-associated syndromic epilepsies ranging from febrile seizures plus (FS+) to Dravet syndrome have a significant genetic component. However, apart from SCN1A mutations in >80% of patients with Dravet syndrome, the genetic underpinnings of these epilepsies remain largely unknown. Therefore, we performed a genome-wide screening for copy number variations (CNVs) in 36 patients with SCN1A-negative fever-associated syndromic epilepsies. Phenotypes included Dravet syndrome (n = 23; 64%), genetic epilepsy with febrile seizures plus (GEFS+) and febrile seizures plus (FS+) (n = 11; 31%) and unclassified fever-associated epilepsies (n = 2; 6%). Array comparative genomic hybridization (CGH) was performed using Agilent 4 × 180K arrays. We identified 13 rare CNVs in 8 (22%) of 36 individuals. These included known pathogenic CNVs in 4 (11%) of 36 patients: a 1q21.1 duplication in a proband with Dravet syndrome, a 14q23.3 deletion in a proband with FS+, and two deletions at 16p11.2 and 1q44 in two individuals with fever-associated epilepsy with concomitant autism and/or intellectual disability. In addition, a 3q13.11 duplication in a patient with FS+ and two de novo duplications at 7p14.2 and 18q12.2 in a patient with atypical Dravet syndrome were classified as likely pathogenic. Six CNVs were of unknown significance. The identified genomic aberrations overlap with known neurodevelopmental disorders, suggesting that fever-associated epilepsy syndromes may be a recurrent clinical presentation of known microdeletion syndromes.


Matching segments of images.
This correspondence describes research in the development of symbolic registration techniques directed toward the comparison of pairs of images of the same scene to ultimately generate descriptions of the changes in the scene. Unlike most earlier work in image registration, all the matching and analysis will be performed at a symbolic level rather than a signal level. We have applied this registration procedure on several different types of scenes and the system appears to work well both on pairs of images which may be analyzed in part by signal based systems and those which cannot be so analyzed.


Pilot Randomized Controlled Trial of a Syndemics Intervention with HIV-Positive, Cocaine-Using Women.
This pilot randomized controlled trial examined the feasibility and acceptability of a Syndemics intervention targeting the intersection of stimulant use, trauma, and difficulties with HIV disease management in cocaine-using women. All participants received contingency management (CM) for 3 months with financial incentives for stimulant abstinence during thrice-weekly urine screening and refilling antiretroviral medications monthly. Sixteen participants were randomized to complete four expressive writing (n = 9) or four neutral writing (n = 7) sessions delivered during the CM intervention period. Completion rates for writing sessions were high (15 of 16 women completed all four sessions) and engagement in CM urine screening was moderate with women randomized to expressive writing providing a median of 11 non-reactive urine samples for stimulants. There were non-significant trends for those randomized to expressive writing to provide more CM urine samples that were non-reactive for stimulants, report greater decreases in severity of cocaine use, and display reductions in log10 HIV viral load at 6 months. Although the Syndemics intervention was feasible and acceptable to many women, qualitative interviews with eligible participants who were not randomized identified structural and psychological barriers to engagement. Further clinical research is needed to test the efficacy of Syndemics interventions with HIV-positive, cocaine-using women.


Nongenomic vascular action of aldosterone in the glomerular microcirculation.
Aldosterone (Aldo) accelerates hypertension, proteinuria, and glomerulosclerosis in animal models of malignant hypertension or chronic renal failure. Aldo may exert these deleterious renal effects by elevating renal vascular resistance and glomerular capillary pressure. To test this possibility, directly examined were the action of Aldo on the afferent (Af) and efferent (Ef) arterioles (Arts). Examined were the effect of Aldo added to both the bath and lumen on the intraluminal diameter (measured at the most responsive point) of rabbits. Aldo caused dose-dependent constriction in both arterioles with a higher sensitivity in Ef-Arts. Vasoconstrictor action of Aldo was not affected by a mineralocorticoid receptor antagonist spironolactone and was reproduced by membrane-impermeable albumin-conjugated Aldo, suggesting that the vasoconstrictor actions are nongenomic. Pretreatment with neomycin (a specific inhibitor of phospholipase C) abolished the vasoconstrictor action of Aldo in both arterioles. In addition, the vasoconstrictor action of Aldo on Af-Arts was inhibited by both nifedipine and efonidipine, whereas that on Ef-Arts was inhibited by efonidipine but not nifedipine. The results demonstrate that Aldo causes nongenomic vasoconstriction by activating phospholipase C with a subsequent calcium mobilization thorough L- or T-type voltage-dependent calcium channels in Af- or Ef-Arts, respectively. These vasoconstrictor actions on the glomerular microcirculation may play an important role in the pathophysiology and progression of renal diseases by elevating renal vascular resistance and glomerular capillary pressure.


Sexual partners for the stressed: facultative outcrossing in the self-fertilizing nematode Caenorhabditis elegans.
Sexual reproduction shuffles genetic variation, potentially enhancing the evolutionary response to environmental change. Many asexual organisms respond to stress by generating facultative sexual reproduction, presumably as a means of escaping the trap of low genetic diversity. Self-fertilizing organisms are subject to similar genetic limitations: the consistent loss of genetic diversity within lineages restricts the production of variation through recombination. Selfing organisms may therefore benefit from a similar shift in mating strategy during periods of stress. We determined the effects of environmental stress via starvation and passage through the stress-resistant dauer stage on mating system dynamics of Caenorhabditis elegans, which reproduces predominantly through self-fertilization but is capable of outcrossing in the presence of males. Starvation elevated male frequencies in a strain-specific manner through differential male survival during dauer exposure and increased outcrossing rates after dauer exposure. In the most responsive strain, the mating system changed from predominantly selfing to almost exclusively outcrossing. Like facultative sex in asexual organisms, facultative outcrossing in C. elegans may periodically facilitate adaptation under stress. Such a shift in reproductive strategy should have a major impact on evolutionary change within these populations and may be a previously unrecognized feature of other highly selfing organisms.


Affective learning in medical education.
The purpose of this study was to test a theory of affective learning and to develop a data-gathering instrument for evaluation of affective learning. Two primary areas of affective learning were conceptualized for study: coping with feelings about professional knowledge and coping with feelings about the necessity for development of professional attitudes toward illness and disability and toward death and dying. This two-year study project (1977-1979) involved a total of 70 first-year medical students. Data were obtained by means of observing students in small group discussions. The observation instrument consisted of a checklist of behaviors. Observer reliability was tested. Study results suggested that students progress through phases of affective learning as described in the theory. Implications of the findings are discussed.


Antiangiogenic therapy for glioma.
Currently, antiangiogenic agents are routinely used for the treatment of patients with glioma. However, despite advances in pharmacological and surgical therapy, glioma remains an incurable disease. Indeed, the formation of an abnormal tumor vasculature and the invasion of glioma cells along neuronal tracts are proposed to comprise the major factors that are attributed to the therapeutic resistance of these tumors. The development of curative therapeutic modalities for the treatment of glioma requires further investigation of the molecular mechanisms regulating angiogenesis and invasion. In this review, we discuss the molecular characteristics of angiogenesis and invasion in human malignant glioma, we present several available drugs that are used or can potentially be utilized for the inhibition of angiogenesis in glioma, and we focus our attention on the key mediators of the molecular mechanisms underlying the resistance of glioma to antiangiogenic therapy.


Cell cycle-regulated proteolysis of mitotic target proteins.
The ubiquitin-dependent proteolysis of mitotic cyclin B, which is catalyzed by the anaphase-promoting complex/cyclosome (APC/C) and ubiquitin-conjugating enzyme H10 (UbcH10), begins around the time of the metaphase-anaphase transition and continues through G1 phase of the next cell cycle. We have used cell-free systems from mammalian somatic cells collected at different cell cycle stages (G0, G1, S, G2, and M) to investigate the regulated degradation of four targets of the mitotic destruction machinery: cyclins A and B, geminin H (an inhibitor of S phase identified in Xenopus), and Cut2p (an inhibitor of anaphase onset identified in fission yeast). All four are degraded by G1 extracts but not by extracts of S phase cells. Maintenance of destruction during G1 requires the activity of a PP2A-like phosphatase. Destruction of each target is dependent on the presence of an N-terminal destruction box motif, is accelerated by additional wild-type UbcH10 and is blocked by dominant negative UbcH10. Destruction of each is terminated by a dominant activity that appears in nuclei near the start of S phase. Previous work indicates that the APC/C-dependent destruction of anaphase inhibitors is activated after chromosome alignment at the metaphase plate. In support of this, we show that addition of dominant negative UbcH10 to G1 extracts blocks destruction of the yeast anaphase inhibitor Cut2p in vitro, and injection of dominant negative UbcH10 blocks anaphase onset in vivo. Finally, we report that injection of dominant negative Ubc3/Cdc34, whose role in G1-S control is well established and has been implicated in kinetochore function during mitosis in yeast, dramatically interferes with congression of chromosomes to the metaphase plate. These results demonstrate that the regulated ubiquitination and destruction of critical mitotic proteins is highly conserved from yeast to humans.


Chemopreventive effects of hydatid disease on experimental breast cancer.
Breast cancer is one of the most common and letal cancers in all over the world. Since there have been significant improvements in treatment of breast cancer, there is still a big need for alternative approaches. In this study, we aimed to investigate protective role of hydatid disease against breast cancer. Twenty Wistar rats were divided into two groups of 10 rats each Group I (control) and Group II. In Group II intraperitoneal hydatidosis was performed. Then DMBA was applied to mammary tissues of all rats. Immunohistochemistry studies for Ki-67 and S-100 in the tumoral tissue sections of DMBA induced mammary tumor in rats were performed. TUNEL Assay was used to detect apoptotic cells of tumoral tissue. In vivo anticancer activity testing was carried out by preventing the tumorigenesis by DMBA in mammary tissue of rats. The expressions of the Ki-67 and S-100 protein decreased in rats who had Hydatid Disease (HD) (Group II), compared with the control rats (Group I). TUNEL positive cells were higher in rats with HD (Group II), compared with the control rats (Group I). In vivo studies showed that HD prevented the tumorigenesis by DMBA in mammary tissue of rats with 50 percent.In the light of the evidence the present study showed that HD may have chemopreventive effects on DMBA induced breast cancer.


Glioblastoma Primary Cells Retain the Most Copy Number Alterations That Predict Poor Survival in Glioma Patients.
Gliomas are solid tumors that originate from glial cells in the brain or spine and account for 74.6% of malignant primary central nervous system tumors worldwide. As patient-derived primary cells are important tools for drug screening and new therapy development in glioma, we aim to understand the genomic similarity of the primary cells to their parental tumors by comparing their whole-genome copy number variations and expression profile of glioma clinicopathologic factors. We found that the primary cells from grade II/III gliomas lost most of the gene copy number alterations (CNAs), which were mainly located on chromosome 1p and 19q in their parental tumors. The glioblastoma (GBM) primary cells preserved 83.7% of the gene CNAs in the parental GBM tumors, including chromosome 7 gain and 10q loss. The CNA gains of LINC00226 and ADAM6 and the chromosome 16p11 loss were reconstituted in primary cells from both grade II/III gliomas and GBMs. Interestingly, we found these CNAs were correlated to overall survival (OS) in glioma patients using the Merged Cohort LGG and GBM dataset from cBioPortal. The gene CNAs preserved in glioma primary cells often predicted poor survival, whereas the gene CNAs lost in grade II/III primary cells were mainly associated to better prognosis in glioma patients. Glioma prognostic factors that predict better survival, such as IDH mutations and 1p/19q codeletion in grade II/III gliomas, were lost in their primary cells, whereas methylated MGMT promoters as well as TERT promoter mutations were preserved in GBM primary cells while lost in grade II/III primary cells. Our results suggest that GBM primary cells tend to preserve CNAs in their parental tumors, and these CNAs are correlated to poor OS and predict worse prognosis in glioma patients.


Epstein-Barr virus in AIDS-related primary central nervous system lymphoma.
Primary central nervous system lymphoma occurs more often in patients with AIDS. Epstein-Barr virus (EBV) has been detected in these tumours, but the degree of association has not been defined because of both the highly restricted expression of EBV in malignant tissue and the lack of a technique that is reliable in formalin-fixed paraffin-embedded specimens. EBV-transformed lymphocytes contain short non-protein coding EBV transcripts (EBERs), which are expressed in much higher quantity than other EBV-latency transcripts. We describe a new strategy for detection of latent EBV with these transcripts as targets for in-situ hybridisation. 18 cases of AIDS-related primary CNS lymphoma from a consecutive necropsy series together with specimens from 3 further cases were studied. In each case, a strong positive signal over tumour cells indicated abundant expression of the EBV-EBER1 transcript. This 100% association suggests that the pathogenesis of these AIDS-associated lymphomas may differ from the systemic disease in which only 30-50% of tumours are associated with EBV. A pathogenetic role for EBV was further supported by showing expression of a viral protein (the latent membrane protein) that is implicated as an effector for EBV-associated lymphomagenesis. EBV might have a role as a tumour marker in the diagnosis and management of AIDS-related primary CNS lymphoma.


A theoretical comparison of Lewis acid vs bronsted acid catalysis for n-hexane --> propane + propene.
Cracking of an all-trans n-alkane, via idealized Lewis acid and Bronsted acid catalysis, was examined using density functional theory. Optimized geometries and transitions states were determined for catalyst-reactant complexes, using AlCl3 and HCl.AlCl3 as the Lewis and Bronsted acids. For the Lewis acid cycle, hydride-transfer steps are seen to have large barriers in both forward and reverse directions, and an unstable physisorbed carbenium ion (lying 20 kcal mol(-1) above the chemisorbed intermediate) is the launching point for the beta-scission that leads to products. For the Bronsted acid cycle, proton-transfer steps have smaller barriers in both forward and reverse directions, and a semistable physisorbed alkanium ion is the launching point for the alkanium alpha-scission that leads to products. In the idealized Lewis cycle, formation of HCl units (and hence Bronsted acids) was found to be a common side reaction. A recent ionic-liquid catalysis study is mentioned as motivation, although our study is not a computational modeling study; we are more interested in the fundamental differences between Brosnted and Lewis mechanisms rather than merely mimicking a particular system. However, results of exploratory optimizations of various intermediates with Al2Cl7- as the catalyst are presented to provide the first step for future modeling studies on the ionic liquid system.


[Pneumology. Treatment of obstructive sleep apnea by continuous positive airway pressure: new options].
Continuous Positive Airway Pressure (CPAP) is accepted as first line therapy for Sleep Obstructive Apnea-Hypopnea Syndrome. Over the past few years, several new devices have been made available, aiming to improve patient comfort and compliance. In 25 years, major changes in technology have occurred, and CPAP has evolved from fixed pressure devices to auto-adjusting bi-level positive airway pressure. The algorithms and software of the newly commercialized devices are sometimes difficult to apprehend. In spite of impressive changes in technology, an obvious benefit in terms of compliance or comfort is yet to be demonstrated, and independent validations of these new devices are necessary.


Acute Effects of Moderate Alcohol Consumption on Postural Stability in Older Adults.
This study involved healthy community-living older adults in an investigation of the association between moderate alcohol consumption (AC) and acute changes in postural stability and whether the association differed according to pre-AC balance skills. Thirty-nine moderate drinkers aged ≥ 65 years (62% women; mean age: 73.9 ± 6.1 years) consumed a moderate dose of alcohol (0.4 g/kg; administered as two drinks). Breath alcohol concentration and postural stability were measured at five time points (pre-AC and 40, 80, 120, and 160 minutes post-AC) using unipedal stance time (UPST) and center of pressure (CoP) displacement. Pre-AC UPST was used to categorize participants into good-balance (≥30 seconds) and poor-balance (<30 seconds) groups. Peak breath alcohol concentration was 30 mg/dL at 40 minutes post-AC. For all participants, postural stability declined significantly at 80 minutes post-AC (UPST, p = .005; anterior-posterior CoP displacement, p = .029). While the poor-balance group did not show a significant decrease in UPST duration over the course of the study, the good-balance group experienced significant decline at 80 minutes compared with baseline ( p < .001) and remained above the 30-second UPST cutoff. Both groups experienced similar worsening in anterior-posterior CoP displacement at 80 minutes post-AC. Thus, moderate AC was associated with acute decline in postural stability in older adults. The worsened anterior-posterior CoP displacement post-AC in the poor-balance group was of particular concern because these participants were already at lower balance functioning pre-AC. Larger, more representative studies of varying groups of participants are needed to further explore how this change relates to fall incidents and fall risk.


Myosin phosphorylation and contraction of feline esophageal smooth muscle.
We tested the hypothesis that phosphorylation of the 20,000-Da light chain of myosin (LC 20) is related to mechanical activation of esophageal smooth muscle. Circular muscle layer strips of cat esophagus were taken from the lower esophageal sphincter (LES) and the distal esophageal body (EB). The LES strips developed tone spontaneously, and the EB strips were tonically contracted with carbachol. Both tissues relaxed in response to electrical-field stimulation. Phosphorylation of the LC 20 was determined in tissues quick-frozen during relaxation and during stress redevelopment after cessation of field stimulation. Stress and phosphorylation levels were low after 30 s of field stimulation, and a rapid contraction followed field stimulation. Phosphorylation in the LES increased from 0.043 +/- 0.029 to 0.328 +/- 0.043 mol Pi/mol LC 20 within 10 s after stimulation of the inhibitory nerves was terminated, while stress was still rising rapidly. Phosphorylation in the LES then declined to a steady-state value of 0.162 +/- 0.034 mol Pi/mol LC 20 after 10 min. Isotonic shortening velocities at a constant afterload following a quick release showed changes with time that were proportional to the level of phosphorylation. This was also true for values of maximal shortening velocity estimated for zero external load and for the rate of stress redevelopment after a step shortening. Comparable measurements were made in the carbachol-contracted EB. These results indicate that visceral smooth muscles, which normally function tonically (LES) or phasically (EB), exhibit an initial rapid mechanical activation associated with myosin phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)


The pharmacokinetics of silymarin is altered in patients with hepatitis C virus and nonalcoholic Fatty liver disease and correlates with plasma caspase-3/7 activity.
Silymarin, used by 30 to 40% of liver disease patients, is composed of six major flavonolignans, each of which may contribute to silymarin's hepatoprotective properties. Previous studies have only described the pharmacokinetics for two flavonolignans, silybin A and silybin B, in healthy volunteers. The aim of this study was to determine the pharmacokinetics of the major silymarin flavonolignans in liver disease patients. Healthy volunteers and three patient cohorts were administered a single, 600-mg p.o. dose of milk thistle extract, and 14 blood samples were obtained over 24 h. Silybin A and B accounted for 43% of the exposure to the sum of total silymarin flavonolignans in healthy volunteers and only 31 to 38% in liver disease cohorts as a result of accumulation of silychristin (20-36%). Area under the curve (AUC(0-24h)) for the sum of total silymarin flavonolignans was 2.4-, 3.3-, and 4.7-fold higher for hepatitis C virus (HCV) noncirrhosis, nonalcoholic fatty liver disease (p <or= 0.03), and HCV cirrhosis cohorts (p <or= 0.03), respectively, compared with healthy volunteers (AUC(0-24h) = 2021 ng . h/ml). Caspase-3/7 activity correlated with the AUC(0-24h) for the sum of all silymarin conjugates among all subjects (R(2) = 0.52) and was 5-fold higher in the HCV cirrhosis cohort (p <or= 0.005 versus healthy). No correlation was observed with other measures of disease activity, including plasma alanine aminotransferase, interleukin 6, and 8-isoprostane F(2alpha), a measure of oxidative stress. These findings suggest that the pharmacokinetics of silymarin is altered in patients with liver disease. Patients with cirrhosis had the highest plasma caspase-3/7 activity and also achieved the highest exposures for the major silymarin flavonolignans.


Inclusive Teaching.
Over the past two decades, science, technology, engineering, and mathematics (STEM) faculty have been striving to make their teaching practices more inclusive and welcoming to the variety of students who enter college. However, many STEM faculty, even those at teaching-focused institutions, have been educated in a traditional environment that emphasizes research and may not include classroom teaching. This can produce a deficit in training that leaves many STEM faculty feeling uncertain about inclusive teaching practices and their essential undergirding principles. This essay describes an online, evidence-based teaching guide ( https://lse.ascb.org/evidence-based-teaching-guides/inclusive-teaching ) intended to help fill this gap, serving as a resource for science faculty as they work to become more inclusive, particular with regard to differences in race, ethnicity, and gender. The guide describes the importance of developing self-awareness and empathy for students as a precursor to considering classroom practices. It also explores the role of classroom climate before turning to pedagogical choices that can support students' sense of belonging, competence, and interest in the course. Finally, the guide suggests that true inclusivity is a community effort and that instructors should leverage local and national networks to maximize student learning and inclusion. Each of these essential points is supported by summaries of and links to articles that can inform these choices. The guide also includes an instructor checklist that offers a concise summary of key points with actionable steps that can guide instructors as they work toward a more inclusive practice. We hope that the guide will provide value for both faculty who are just beginning to consider how to change their teaching practices and faculty seeking to enrich their current efforts.


Cold ischemia contributes to the development of chronic rejection and mitochondrial injury after cardiac transplantation.
Chronic rejection (CR) remains an unsolved hurdle for long-term heart transplant survival. The effect of cold ischemia (CI) on progression of CR and the mechanisms resulting in functional deficit were investigated by studying gene expression, mitochondrial function, and enzymatic activity. Allogeneic (Lew→F344) and syngeneic (Lew→Lew) heart transplantations were performed with or without 10 h of CI. After evaluation of myocardial contraction, hearts were excised at 2, 10, 40, and 60 days for investigation of vasculopathy, gene expression, enzymatic activities, and mitochondrial respiration. Gene expression studies identified a gene cluster coding for subunits of the mitochondrial electron transport chain regulated in response to CI and CR. Myocardial performance, mitochondrial function, and mitochondrial marker enzyme activities declined in all allografts with time after transplantation. These declines were more rapid and severe in CI allografts (CR-CI) and correlated well with progression of vasculopathy and fibrosis. Mitochondria related gene expression and mitochondrial function are substantially compromised with the progression of CR and show that CI impacts on progression, gene profile, and mitochondrial function of CR. Monitoring mitochondrial function and enzyme activity might allow for earlier detection of CR and cardiac allograft dysfunction.


Adaptive reorientation of endothelial collectives in response to strain.
Mature epithelial monolayers share the ability to coherently respond to external mechanical stimuli. Tissue remodeling requires cell shape changes and coordinated movements. Human endothelia provide an exquisite example of such emerging collective activities. As part of their function in maintaining body homeostasis under variable hemodynamic loadings, endothelial ensembles must dynamically adapt to wall shear stress and cyclic deformation. While the alignment of several types of cells, including fibroblasts, osteoblasts and epithelial tissues, in response to various flow conditions or wall shear stress levels has been described in detail, less is known about collective endothelial remodeling under pure wall deformation. Here, using a custom-developed bioreactor, we exposed mature human endothelia to two distinct physiological levels of cyclic loading, generating overlapping gradients of strain. Endothelial cells remodeled depending on the level of imposed strain yielding local variations of cell density. In particular, a collective cell orientation orthogonal to the main direction of strain was observed at low levels of wall deformation, while cells reoriented parallel to the main direction of strain at high levels of wall deformation. The tissue adaptation depended on the establishment of mature adherens junctions, which were reinforced by the polarized recruitment of the adaptor protein vinculin. The pivotal role of cell-to-cell junctions was confirmed by the biochemical inhibition of vascular endothelial cadherin homotypic contacts, which impaired the collective remodeling. Together, our data establish wall deformation as an independent determinant of endothelial architecture with direct implications in vascular physiopathology.


A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction.
The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function.The full extent of the genetic basis for hearing impairment is unknown. Here, as part of the International Mouse Phenotyping Consortium, the authors perform a hearing loss screen in 3006 mouse knockout strains and identify 52 new candidate genes for genetic hearing loss.


Variability of angular measurements of head posture within a session, within a day, and over a 7-day period in healthy participants.
Head posture (HP) is used as part of the clinical examination of patients with neck pain to inform diagnosis, plan treatment, and monitor progress. For related information to be interpreted correctly, clinicians need to know how much of the variation in HP between measurements can be attributed to a change in the patient condition and how much is due to measurement error and/or biological variation. The aim of this study was to investigate the variability of angular measurements indicative of forward HP, head extension, and side flexion within a session, within a day, and over a 7-day period. Angles were calculated from 27 participants in three sessions over a period of 7 days through digitization of video images. Intraclass correlation coefficients (ICC) and standard error of measurement (SEM) showed that forward HP (ICC between 0.82 and 0.91; SEM between 1.42° and 1.70°) and side flexion (ICC between 0.63 and 0.85; SEM between 0.83° and 1.27°) were stable within a session, within a day, and over a 7-day period. Head extension was found to be less stable (ICC between 0.71 and 0.83; SEM between 2.69° and 3.72°). Time of day did not appear to influence forward HP, side flexion, or head extension.


A comparison of two techniques for the synchronisation of oestrus in dairy heifers.
Seventy-four heifers in four separate breeding groups were allocated into two treatment groups for oestrus synchronisation. Group 1 was given a combination of an initial injection of norgestomet and oestradiol valerate together with a norgestomet ear implant left in place for nine days. Group 2 was given two injections of the synthetic prostaglandin luprostiol 10 days apart. The animals in group 1 were artificially inseminated once 48 hours after the removal of the implant and those in group 2 were inseminated once 72 hours after the second injection of luprostiol. Subsequently any returns were rebred by either AI or natural service. There was no significant difference between the numbers of animals in the two treatment groups which were diagnosed pregnant 33 to 35 days after insemination, although the implant treatment gave a higher overall proportion of pregnancies (70 per cent, 51 per cent). It also gave significantly smaller numbers of 'open' days over the whole of the breeding period. A study of individual animals by progesterone assay and investigation of ovarian structures by real-time ultrasound showed that some of them had unusual progesterone profiles but nevertheless became pregnant. It would appear that a corpus luteum may be responsive to prostaglandins even though it is secreting only a low level of progesterone.


Lumbar intradural paragangliomas: report of two cases.
Paraganglioma (PG) is a rare tumor of the dispersed neuroendocrine system. PG derives from the embryonic sympathetic and parasympathetic nervous system. Paraganglioma is a neoplasm of the dispersed neuroendocrine system that affects a variety of anatomic sites, mainly the head and neck. It occurs commonly in the carotid body, glomus jugulare, mediastinum and retroperitoneum. Primary spinal paragangliomas are quite rare tumors. They are commonly located in the cauda equina region, and manifest their own clinical and radiological features. In this study, two cases of lumbar intradural paragangliomas are presented. Both of the tumors were totally resected with surgery and there was no evidence of recurrence or metastases during follow-up period. It was concluded that paragangliomas should be taken into consideration during the preoperative workup studies of lumbar intradural tumors.


A novel p64-related Cl- channel: subcellular distribution and nephron segment-specific expression.
Several closely related proteins that have been implicated as chloride channels of intracellular membranes have recently been described. We report here the molecular cloning and characterization of a new member of this family from human cells. On the basis of sequence similarity, we conclude that this new protein represents the human version of a previously described protein from rat brain named p64H1. The human version of p64H1 (huH1) is a 28.7-kDa protein that shows an apparent molecular mass of 31 kDa by SDS-PAGE. A single 4.5-kb message is detected on Northern blots and is present in all tissues probed. The protein is expressed in an intracellular vesicular pattern in Panc-1 cells that is distinct from the endoplasmic reticulum, fluid-phase endocytic, and transferrin-recycling compartments, but which does colocalize with caveolin. In human kidney, huH1 is highly expressed in a diffuse pattern in the apical domain of proximal tubule cells. huH1 is expressed less abundantly in a vesicular pattern in glomeruli and distal nephron.


First principles determination of the effects of phosphorus and boron on iron grain boundary cohesion.
Toward an electronic level understanding of intergranular embrittlement and its control in steels, the effects of phosphorus and boron impurities on the energy and electronic properties of both an iron grain boundary and its corresponding intergranular fracture surface are investigated by the local density full potential augmented plane wave method. When structural relaxations are taken into account, the calculated energy difference of phosphorus in the two environments is consistent with its measured embrittlement potency. In contrast to the nonhybridized interaction of iron and phosphorus, iron-boron hybridization permits covalent bonding normal to the boundary contributing to cohesion enhancement. Insights into bonding behavior offer the potential for new directions in alloy composition for improvement of grain boundary-sensitive properties.


Charge transfer and current fluctuations in single layer graphene transistors modified by self-assembled C60 adlayers.
Flicker noise in a "fullerene + graphene" hybrid transistor is investigated to reveal the electrical coupling between the graphene channel and C60 adsorbates. The charge trapping and detrapping events at the C60 /graphene interface induce current fluctuations in the devices. The evolution of noise characteristics at varying temperatures indicates the different contributions related to Coulomb scattering and charge exchange kinetics.


[Spinal mechanism of the inhibitory effect of somatic input on the cardiac ischemia induced by hypothalamus stimulation].
Experiments were carried out on 58 urethane-chloralose anaesthetized, gallamine triethiodide immobilized and vagotomized rabbits under artificial ventilation. Median nerve (MN) or deep peroneal nerve(DPN) stimulation could inhibit completely or partially the deflection of ischemic ECG ST segment due to stimulation of dorsomedial hypothalamic nucleus (DMH). The inhibitory effect of MN stimulation was more marked than that of DPN stimulation. Intrathecal injection (ith) of morphine (40 micrograms) could also inhibit these ischemic ECG ST segment changes. After ith naloxone (20 micrograms), the inhibitory effect of MN stimulation on DMH stimulation-induced ischemic ECG ST segment changes was abolished. In intact rabbits, it was demonstrated that L-enkephalin (LENK) immunoreactive material was increased in the left or right intermediolateral cell column (IML) of T2-5 spinal cord after stimulation of left MN or DPN for five minutes. In the Cl transected rabbits, stimulation of MN only increased ipsilateral LENK immunoreactive material content in the thoracic IML, while stimulation of DPN produced no such an effect. These results indicate that stimulation of MN or DPN can inhibit cardiac ischemia induced by DMH stimulation and that the effect of MN stimulation is more potent. The inhibitory effects may be mediated by an increase of LENK immunoreactive material in the bilateral IML produced through some supraspinal mechanisms; whereas the effect of MN stimulation may also be mediated by an increase of ipsilateral spinal LENK immunoreactive material in the thoracic IML through segmental mechanism to inhibit the sympathetic activity.


The Utility of Urine-Based Sampling for Cervical Cancer Screening in Low-Resource Settings.
Background: WHO has recommended Visual Inspection with Acetic acid (VIA) or Human Papillomavirus (HPV) DNA testing if feasible, for cervical cancer screening in low income countries. However, the number of women undergoing screening is very low as a result of limited information, inadequate infrastructure and invasive nature of sampling. Methods: A cross sectional study was carried out comparing HPV DNA detection by Polymerase Chain Reaction (PCR) in paired cervical and urine samples procured from histologically confirmed cervical cancer cases. Results: Amongst the samples collected from 114 cervical cancer cases, HPV DNA was tested positive in cervical samples of 89 (78.1%) and urine samples of 55 (48.2%) patients. The agreement between the two sampling methods was 66.7% and the kappa value was 0.35 indicating a fair agreement. The sensitivity of HPV detection using urine samples was 59.6% (95% confidence interval 49.16%-69.15%) and the specificity was 92% (95% confidence interval 75.0%-97.8%). Conclusion: Even though not acceptable as an HPV DNA screening tool due to low sensitivity, the urine sampling method is inexpensive and more socially acceptable for large epidemiological surveys in developing countries to estimate the burden.


Epidemiology of anaphylaxis in Olmsted County: A population-based study.
Awareness of the clinical features of anaphylaxis and its causative triggers is important if recurrent episodes are to be avoided. The incidence of anaphylaxis in the general population is often underreported, and epidemiologic studies are few. Because an accurate profile of anaphylaxis could heighten awareness of this problem, we investigated the epidemiology of anaphylaxis in the general population of Olmsted County, Minn. The purpose of this study was to describe the epidemiology of anaphylaxis in Olmsted County residents from 1983 through 1987. This was a retrospective population-based cohort study. The medical records of 1255 Olmsted County residents identified by computer-linked, medical diagnostic indices (the Rochester Epidemiology Study) were reviewed retrospectively to identify residents whose clinical episodes met the criteria for anaphylaxis. We determined the incidence and rate of occurrence of anaphylaxis, rate of recurrence, prevalence of atopy, cause of anaphylaxis, frequency of referral to an allergy specialist, hospital admission rate, and case-fatality rate. There were 133 residents who experienced 154 anaphylactic episodes during the 5-year period: 116 residents had 1 episode of anaphylaxis, 13 residents had 2 episodes, and 4 residents had 3 episodes. The anaphylaxis occurrence rate was 30 per 100,000 person-years (95% confidence interval, 25-35). There were 110 residents who had a first lifetime episode of anaphylaxis (that was medically evaluated) during the years 1983 to 1987. The average annual incidence rate of anaphylaxis was 21 per 100,000 person-years (95% confidence interval, 17-25). Atopy was present in 53% of the cohort, and allergy consultation was obtained in 52%. A suspect allergen was identified in 68% of the cohort, most frequently a food, medication, or insect sting. The hospitalization rate was 7%, and 1 patient died. The incidence of anaphylaxis is less than 1%, and death rarely occurs. People with atopy experience anaphylaxis more frequently than people without atopy. Anaphylaxis frequently is not recognized by patients and physicians.


Patients with schizophrenia at risk for excessive antipsychotic dosing.
Patient Outcomes Research Team treatment recommendations were used to investigate the relationship between patient characteristics and higher-than-recommended dosages (> 1000 chlorpromazine equivalents [CPZe]) at discharge. Inpatients who met the DSM-IV criteria for schizophrenia or schizoaffective disorder were recruited from 4 general hospitals. For those patients (N = 293) prescribed antipsychotics at discharge, chi-square tests and multiple regression analyses were used to assess the relationship between demographics, admission characteristics, comorbid diagnoses, and antipsychotic dosages. The relationship between clinical symptoms and antipsychotic dosage at discharge was also examined. Antipsychotic dosages conformed to treatment guidelines for approximately 65% of patients; 21% received doses in excess of recommended levels. African American patients and those with a history of psychiatric hospitalization were more likely to be prescribed discharge antipsychotic doses greater than 1000 CPZe. Hospital differences in antipsychotic management were also observed. Regression analyses indicated that higher-than-recommended dosages found among African American patients could not be explained by differences in symptom levels at discharge. Patients with more thought disorder were also more likely to be prescribed antipsychotic dosages in excess of the recommended range. Compared with oral administration, depot administration increased the risk of excess dosage by a factor of 30. Controlling for method of administration reduced the impact of race to nonsignificance. These results replicate earlier findings that minority individuals are more likely to be prescribed dosages in excess of the recommended range and suggest that this pattern is due to higher use of depot injection in African American patients. Further research should examine how patient characteristics and institutional factors influence medication use.


[Use of transcatheter high-frequency artificial ventilation of the lungs in surgical treatment of obturating papillomatosis of the larynx and trachea in children].
Investigations of transcatheter high-frequency artificial ventilation of the lungs (THFAVL) in surgical treatment of obturating papillomatosis in children led the authors to the conclusion that this method is optimal in assisting breathing in operative intervention on the larynx. THFAVL is not feasible unless adequate expiration is provided. Hence, the high-frequency regimen must be acquired gradually under control of blood gases in parallel with reopening of rima glottidis with consideration of individual clinical situation. The most effective parameters of the above surgery are: P-1 kgs/cm 2; heart rate under 80 per minute; inhalation/expiration ratio 1:3, 1:4. The emergence of side effects can be prevented in coordinated actions of the surgeon and anesthesiologist.


Quantitative Analysis of Immunohistochemistry in Melanoma Tumors.
Identification of positive staining is often qualitative and subjective. This is particularly troublesome in pigmented melanoma lesions, because melanin is difficult to distinguish from the brown stain resulting from immunohistochemistry (IHC) using horse radish peroxidase developed with 3,3'-Diaminobenzidine (HRP-DAB). We sought to identify and quantify positive staining, particularly in melanoma lesions. We visualized G-protein coupled estrogen receptor (GPER) expression developed with HRP-DAB and counterstained with Azure B (stains melanin) in melanoma tissue sections (n = 3). Matched sections (n = 3), along with 22 unmatched sections, were stained only with Azure B as a control. Breast tissue (n = 1) was used as a positive HRP-DAB control. Images of the stained tissues were generated using a Nuance Spectral Imaging Camera. Analysis of the images was performed using the Nuance Spectral Imaging software and SlideBook. Data was analyzed using a Kruskal-Wallis one way analysis of variance (ANOVA). We showed that a pigmented melanoma tissue doubly stained with anti-GPER HRP-DAB and Azure B can be unmixed using spectra derived from a matched, Azure B-only section, and an anti-GPER HRP-DAB control. We unmixed each of the melanoma lesions using each of the Azure B spectra, evaluated the mean intensity of positive staining, and examined the distribution of the mean intensities (P = .73; Kruskal-Wallis). These results suggest that this method does not require a matched Azure B-only stained control tissue for every melanoma lesion, allowing precious tissues to be conserved for other studies. Importantly, this quantification method reduces the subjectivity of protein expression analysis, and provides a valuable tool for accurate evaluation, particularly for pigmented tissues.


Ultrasonographic screening for abdominal aortic aneurysm in an urban community.
As part of the Birmingham Community Aneurysm Screening Project, 3500 men aged 65-75 years from 20 urban general practices were invited for aortic ultrasonographic screening at their own general practitioner's surgery; 2669 (76.3 per cent) attended. Compliance rates varied between catchment areas, from 52.1 per cent for inner-city areas to 89.6 per cent for suburbs. Successful aortic imaging was achieved in 97.3 per cent of scans. Aortic diameter > 29 mm occurred in 219 patients (8.4 per cent) and 79 (3.0 per cent) with a diameter > 40 mm were referred for vascular surgical assessment; 140 patients with an aortic diameter of 29-40 mm are currently undergoing follow-up by serial ultrasonographic examinations at intervals of 3 months at their doctor's surgery. Risk factor analysis revealed ischaemic heart disease in 21.9 per cent of men with aneurysm, compared with 11.6 per cent in those without (P < 0.001); 18.3 per cent of men with aneurysm had had a previous myocardial infarction and 13.2 per cent had peripheral vascular disease, compared with 7.4 per cent (P < 0.001) and 8.0 per cent (P < 0.01) respectively of those without. No association was found between aneurysm and hypertension or diabetes. Community-based aortic screening is an inexpensive, effective method of diagnosis of aneurysm, with high compliance from the at-risk cohort of an urban population. Such screening programmes may help to reduce the mortality rate from aortic aneurysm rupture.


[Effect of quaterin and S-methylmethionine on the intensity of chromatin protein methylation].
It is known that 3-(2,2,2-trimethylhydrazinium) propionate (quaterin) synthetized at the Institute of Organic Synthesis of the Latvian SSR Academy of Sciences has a stimulating effect on cell proliferation in the process of healing wounds and burns. In this connection the above preparation is studied for its effect on the methylation intensity of histones and nonhistone proteins of rat tissues possessing different proliferative activity. For comparison S-methylmethionine (vitamin U), a known stimulator of the methylation reactions, was studied. The experiments conducted have shown that the methylation processes in all the studied tissues (heart, liver, small intestine mucosa, thymus and spleen) depend on the quaterin and the S-methylmethionine effect. On the whole, quaterin 1-6 h after its administration increases, as a rule, the methylation levels of histones and nonhistone proteins. This effect is the least in the thymus and the highest in the liver and spleen. When quaterin is applied daily for 5-15 days considerable changes occur in the levels of chromatin proteins methylation. The data obtained indicate that the processes of chromatin proteins methylation are an important link in the realization of quaterin action on transcription and replication which underlie the proliferative cell response.


Effect of penicillin or cefprozil therapy on tonsillar flora.
The effect on the tonsillar bacterial flora of antimicrobial therapy with penicillin or a second-generation cephalosporin (cefprozil) was studied. Sixty children scheduled for elective tonsillectomy because of recurrent group A beta-haemolytic streptococcal tonsillitis participated in a prospective randomized study that divided them into three groups. One group received no therapy, and the others were given either penicillin or cefprozil for 10 days prior to surgery. The core of the patients' tonsils was cultured for aerobic bacteria. Group A beta-haemolytic streptococci (GABHS) were isolated from 15/20 (75%) of untreated, 11/20 (55%) of penicillin, and 2/20 (10%) of the cefprozil group (P < 0.001). Thirty-two beta-lactamase-producing bacteria were recovered from 19/20 (95%) of untreated, 33 from 17/20 (85%) treated with penicillin and six from 4/20 (20%) treated with cefprozil (P < 0.01). Alpha-haemolytic streptococci (AHS) inhibiting GABHS were less often isolated from patients treated with penicillin. These data illustrate the ability of a second-generation cephalosporin to eradicate GABHs, as well as beta-lactamase-producing bacteria, while preserving AHS.


Setting ambitious targets for surveillance and treatment rates among patients with hepatitis C related cirrhosis impacts the cost-effectiveness of hepatocellular cancer surveillance and substantially increases life expectancy: A modeling study.
Hepatocelluar cancer (HCC) is the leading cause of death among people with hepatitis C virus (HCV)-related cirrhosis. Our aim was to determine the optimal surveillance frequency for patients with HCV-related compensated cirrhosis. We developed a decision analytic Markov model and validated it against data from the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) study group and published epidemiologic studies. Four strategies of different surveillance intervals were compared: no surveillance and ultrasound surveillance every 12, 6, and 3 months. We estimated lifetime survival, life expectancy, quality adjusted life years (QALY), total costs associated with each strategy, and incremental cost effectiveness ratios. We applied a willingness to pay threshold of $100,000. Analysis was conducted for two scenarios: a scenario reflecting current HCV and HCC surveillance compliance rates and treatment use and an aspirational scenario. In the current scenario the preferred strategy was 3-month surveillance with an incremental cost-effectiveness ratio (ICER) of $7,159/QALY. In the aspirational scenario, 6-month surveillance was preferred with an ICER of $82,807/QALY because treating more people with HCV led to a lower incidence of HCC. Sensitivity analyses suggested that surveillance every 12 months would suffice in the particular circumstance when patients are very likely to return regularly for testing and when appropriate HCV and HCC treatment is readily available. Compared with the current scenario, the aspirational scenario resulted in a 1.87 year gain in life expectancy for the cohort because of large reductions in decompensated cirrhosis and HCC incidence. HCC surveillance has good value for money for patients with HCV-related compensated cirrhosis. Investments to improve adherence to surveillance should be made when rates are suboptimal. Surveillance every 12 months will suffice when patients are very likely to return regularly for testing and when appropriate HCV and HCC treatment is readily available.


Influence of spring phenology on seasonal and annual carbon balance in two contrasting New England forests.
Spring phenology is thought to exert a major influence on the carbon (C) balance of temperate and boreal ecosystems. We investigated this hypothesis using four spring onset phenological indicators in conjunction with surface-atmosphere CO(2) exchange data from the conifer-dominated Howland Forest and deciduous-dominated Harvard Forest AmeriFlux sites. All phenological measures, including CO(2) source-sink transition dates, could be well predicted on the basis of a simple two-parameter spring warming model, indicating good potential for improving the representation of phenological transitions and their dynamic responsiveness to climate variability in land surface models. The date at which canopy-scale photosynthetic capacity reached a threshold value of 12 micromol m(-2) s(-1) was better correlated with spring and annual flux integrals than were either deciduous or coniferous bud burst dates. For all phenological indicators, earlier spring onset consistently, but not always significantly, resulted in higher gross primary productivity (GPP) and ecosystem respiration (RE) for both seasonal (spring months, April-June) and annual flux integrals. The increase in RE was less than that in GPP; depending on the phenological indicator used, a one-day advance in spring onset increased springtime net ecosystem productivity (NEP) by 2-4 g C m(-2) day(-1). In general, we could not detect significant differences between the two forest types in response to earlier spring, although the response to earlier spring was generally more pronounced for Harvard Forest than for Howland Forest, suggesting that future climate warming may favor deciduous species over coniferous species, at least in this region. The effect of earlier spring tended to be about twice as large when annual rather than springtime flux integrals were considered. This result is suggestive of both immediate and lagged effects of earlier spring onset on ecosystem C cycling, perhaps as a result of accelerated N cycling rates and cascading effects on N uptake, foliar N concentrations and photosynthetic capacity.


Comparison of sweet white lupin seeds with soybean meal as a protein supplement for lactating dairy cows.
Data were from 45 Holstein cows (23 multiparous, 22 primiparous) assigned by calving date and parity within groups to one of two isonitrogenous (16% crude protein) diets. The diets were 50% forages (corn silage, alfalfa silage) and 50% concentrate, dry basis. In diet A, soybean meal supplied 34.2% of total crude protein; in diet B, ground sweet white lupin seeds provided 37.9% of total crude protein. Cows were fed once daily during the experimental period (d 4 to 116 postpartum). Cows fed lupins consumed significantly less dry matter, produced 1.8 kg/d less milk (but not significantly different), and had lower milk protein percent. Milk fat and total solids percents were similar. Reasons for reduced intake of cows fed lupins were not evident. Traces of alkaloids (.005% dry basis) were present in diet B. Combined results of in vitro continuous culture fermentation and in situ degradation measurements indicated that crude protein from lupins was more degradable than that of soybean meal. Poor performances of cows fed lupins could be partly due to a reduced true protein supply to the small intestine.


The Prenatal Microbiome: A New Player for Human Health.
The last few years have featured an increasing interest in the study of the human microbiome and its correlations with health status. Indeed, technological advances have allowed the study of microbial communities to reach a previously unthinkable sensitivity, showing the presence of microbes also in environments usually considered as sterile. In this scenario, microbial communities have been described in the amniotic fluid, the umbilical blood cord, and the placenta, denying a dogma of reproductive medicine that considers the uterus like a sterile womb. This prenatal microbiome may play a role not only in fetal development but also in the predisposition to diseases that may develop later in life, and also in adulthood. Thus, the aim of this review is to report the current knowledge regarding the prenatal microbiome composition, its association with pathological processes, and the future perspectives regarding its manipulation for healthy status promotion and maintenance.


Genetic basis of dentigerous cysts associated with supernumerary teeth: A narrative review.
In the present study, we sought to: (a) analyze the p53 gene status in dentigerous cysts (DC) associated with supernumerary teeth (ST) in a pair of siblings with ST, of whom one developed a DC; and (b) conduct a narrative review of the literature on ST associated with DC. Blood samples were obtained, and the isolated DNA was used to amplify exons 4-8 of the p53 gene using specific primers, and subsequently sequenced. No mutations were identified in the coding regions of the p53 gene. A review of the literature revealed a prevalence of DC associated with ST to be as high as 13.6%, and that 83% of the case reports performed enucleation of DC and removal of ST. Dentigerous cysts associated with ST in one sibling demonstrated that variations in phenotypes exist, and the absence of mutations cannot eliminate the potential influence of genetic risk factors.


Ethical evaluation of informed consent forms used in cardiology clinics and the importance of institutional standardized approach.
This study aimed to evaluate the content of informed consent forms (ICFs) used during cardiology interventions by the university, research and training (R-T), and private hospitals with regard to ethical standards and compare them with the Turkish Society of Cardiology (TSC) templates and among various institutions. A total of 185 forms from the university, R-T, and private hospitals and 19 TSC templates were selected and analyzed for 26 criteria. Compliance with TSC templates was also evaluated. Data were presented as the percentage of ICFs satisfying the criteria and compared using the Fisher exact test, and 95% confidence intervals were calculated. TSC templates were more compatible and included more information to comply with ethical standards than ICFs of all 3 types of healthcare institutions. The areas of improvement for these templates were prospects of treatment and alternative treatments, quality of life, explanation for third-party consent, duration of hospitalization, and time to return to normal life. Among the 3 types of hospitals, R-T-ICFs were more compatible with templates. Private hospital ICFs had the poorest compliance with TSC templates. Separate anesthesia ICFs and detailed information about exposure to radioactivity were lacking. The current ICFs for cardiology interventions have major ethical deficiencies and need urgent improvement. Professional societies such as TSC are essential institutions to develop and provide guidance and templates for ICFs to meet the ethical standards during the informed consent process and standardization of the process among various institutions.


Mathematical modeling of respiratory viral infection and applications to SARS-CoV-2 progression.
Viral infection in cell culture and tissue is modeled with delay reaction-diffusion equations. It is shown that progression of viral infection can be characterized by the viral replication number, time-dependent viral load, and the speed of infection spreading. These three characteristics are determined through the original model parameters including the rates of cell infection and of virus production in the infected cells. The clinical manifestations of viral infection, depending on tissue damage, correlate with the speed of infection spreading, while the infectivity of a respiratory infection depends on the viral load in the upper respiratory tract. Parameter determination from the experiments on Delta and Omicron variants allows the estimation of the infection spreading speed and viral load. Different variants of the SARS-CoV-2 infection are compared confirming that Omicron is more infectious and has less severe symptoms than Delta variant. Within the same variant, spreading speed (symptoms) correlates with viral load allowing prognosis of disease progression.


The effects of citric acid on phytate-phosphorus utilization in young chicks and pigs.
Several bioassays were conducted with young chicks and pigs fed phosphorus (P)-deficient corn-soybean meal diets. With diets for chicks containing .62% Ca and .42% P (.10% available P), graded doses of a citric acid + sodium citrate (1:1, wt:wt) mixture (0, 1, 2, 4, or 6% of diet) resulted in linear (P < .01) increases in both weight gain and tibia ash. Relative to chicks fed no citric acid, tibia ash (%) and weight gain (g/d) were increased by 43 and 22%, respectively, in chicks fed 6% citric acid. Additional chick trials showed that 6% citric acid alone or sodium citrate alone was as efficacious as the citric acid + sodium citrate mixture and that 1,450 U/kg of phytase produced a positive response in bone ash and weight gain in chicks fed a diet containing 6% citrate. Varying the Ca:available P ratio with and without citrate supplementation indicated that citric acid primarily affected phytate-P utilization, not Ca, in chicks. Moreover, chicks did not respond to citrate supplementation when fed a P-deficient (.13% available P), phytate-free casein-dextrose diet. Young pigs averaging 10 to 11 kg also were used to evaluate citric acid efficacy in two experiments. A P-deficient corn-soybean meal basal diet was used to construct five treatment diets that contained 1) no additive, 2) 3% citric acid, 3) 6% citric acid, 4) 1,450 U/kg phytase, and 5) 6% citric acid + 1,450 U/kg phytase. Phytase supplementation increased (P < .01) weight gain, gain:feed, and metatarsal ash, whereas citric acid addition increased only gain:feed (P < .05) and metatarsal ash (P < .08). A subsequent 22-d pig experiment was conducted to evaluate the effect of lower levels of citric acid (0, 1, 2, or 3%) or 1,450 U/kg phytase addition to a P-deficient corn-soybean meal diet. Phytase supplementation improved (P < .01) all criteria measured. Weight gain and gain:feed data suggested a response to citric acid addition, but this was not supported by fibula ash results (P > .10). The positive responses to phytase were much greater than those to citric acid in both pig experiments. Thus, dietary citric acid effectively improved phytate P utilization in chicks but had a much smaller effect in pigs.