Thrombin signaling in the brain: the role of protease-activated receptors.
Signaling by the protease thrombin has started to be appreciated in cell biology, especially since the gene for protease-activated receptor-1 (PAR-1) has been cloned. Apart from the central role of thrombin in blood coagulation and wound healing, thrombin also regulates cellular functions in a large variety of cells through PAR-1, PAR-3 and PAR-4. Receptors are activated by a proteolytic cleavage mechanism via G protein-coupled signaling pathways. Accumulating evidence shows that thrombin changes the morphology of neurons and astrocytes, induces glial cell proliferation, and even exerts, depending on the concentration applied, either cytoprotective or cytotoxic effects on neural cells. These effects may be mediated, through either distinct or overlapping signal transduction cascades, by activation of PARs. This review focuses on the underlying signaling events initiated by thrombin in neuronal and glial cells, to summarize our understanding of the intracellular signaling machinery linking thrombin receptors to their potential physiological and pathological functions in the CNS.


Time-reversal symmetry breaking hidden order in Sr2(Ir,Rh)O4.
Layered 5d transition iridium oxides, Sr2(Ir,Rh)O4, are described as unconventional Mott insulators with strong spin-orbit coupling. The undoped compound, Sr2IrO4, is a nearly ideal two-dimensional pseudospin-1/2 Heisenberg antiferromagnet, similarly to the insulating parent compound of high-temperature superconducting copper oxides. Using polarized neutron diffraction, we here report a hidden magnetic order in pure and doped Sr2(Ir,Rh)O4, distinct from the usual antiferromagnetic pseudospin ordering. We find that time-reversal symmetry is broken while the lattice translation invariance is preserved in the hidden order phase. The onset temperature matches that of the odd-parity hidden order recently highlighted using optical second-harmonic generation experiments. The novel magnetic order and broken symmetries can be explained by the loop-current model, previously predicted for the copper oxide superconductors.


The biogeographic differentiation of algal microbiomes in the upper ocean from pole to pole.
Eukaryotic phytoplankton are responsible for at least 20% of annual global carbon fixation. Their diversity and activity are shaped by interactions with prokaryotes as part of complex microbiomes. Although differences in their local species diversity have been estimated, we still have a limited understanding of environmental conditions responsible for compositional differences between local species communities on a large scale from pole to pole. Here, we show, based on pole-to-pole phytoplankton metatranscriptomes and microbial rDNA sequencing, that environmental differences between polar and non-polar upper oceans most strongly impact the large-scale spatial pattern of biodiversity and gene activity in algal microbiomes. The geographic differentiation of co-occurring microbes in algal microbiomes can be well explained by the latitudinal temperature gradient and associated break points in their beta diversity, with an average breakpoint at 14 °C ± 4.3, separating cold and warm upper oceans. As global warming impacts upper ocean temperatures, we project that break points of beta diversity move markedly pole-wards. Hence, abrupt regime shifts in algal microbiomes could be caused by anthropogenic climate change.


Opportunistic Measurement of Skeletal Muscle Size and Muscle Attenuation on Computed Tomography Predicts 1-Year Mortality in Medicare Patients.
Opportunistic assessment of sarcopenia on CT examinations is becoming increasingly common. This study aimed to determine relationships between CT-measured skeletal muscle size and attenuation with 1-year risk of mortality in older adults enrolled in a Medicare Shared Savings Program (MSSP). Relationships between skeletal muscle metrics and all-cause mortality were determined in 436 participants (52% women, mean age 75 years) who had abdominopelvic CT examinations. On CT images, skeletal muscles were segmented at the level of L3 using two methods: (a) all muscles with a threshold of -29 to +150 Hounsfield units (HU), using a dedicated segmentation software, (b) left psoas muscle using a free-hand region of interest tool on a clinical workstation. Muscle cross-sectional area (CSA) and muscle attenuation were measured. Cox regression models were fit to determine the associations between muscle metrics and mortality, adjusting for age, sex, race, smoking status, cancer diagnosis, and Charlson comorbidity index. Within 1 year of follow-up, 20.6% (90/436) participants died. In the fully-adjusted model, higher muscle index and muscle attenuation were associated with lower risk of mortality. A one-unit standard deviation (SD) increase was associated with a HR = 0.69 (95% CI = 0.49, 0.96; p = .03) for total muscle index, HR = 0.67 (95% CI = 0.49, 0.90; p < .01) for psoas muscle index, HR = 0.54 (95% CI = 0.40, 0.74; p < .01) for total muscle attenuation, and HR = 0.79 (95% CI = 0.66, 0.95; p = .01) for psoas muscle attenuation. In older adults, higher skeletal muscle index and muscle attenuation on abdominopelvic CT examinations were associated with better survival, after adjusting for multiple risk factors.


Defective glycerolatocobalt(ii) for enhancing the oxygen evolution reaction.
Glycerolatocobalt(ii) (CoGly) was reported as an electrocatalyst for the first time. Ar plasma was adopted to create a defective CoGly with rich coordinatively unsaturated metal sites (CUMs) as an effective OER catalyst. This study expanded the family of metal-organic complexes for electrocatalysis and proved the critical role of CUMs in the OER directly.


Immunomodulatory agents for idiopathic pulmonary fibrosis.
Idiopathic Pulmonary Fibrosis (IPF) or Usual Interstitial Pneumonia (UIP) is a form of chronic fibrosing interstitial pneumonia of unknown aetiology, with progressively deteriorating respiratory function and ultimately death from respiratory failure. Most treatments are intended to suppress inflammation but none has been proven to alter this process. The most widespread approach uses oral corticosteroids; others use immunosuppressive, immunomodulatory or anti-fibrotic agents, alone or with corticosteroids. A Cochrane review of corticosteroids in IPF has found no evidence that they are of benefit. To determine the effect of non-corticosteroid immunosuppressive, anti-fibrotic and immunomodulatory agents in the treatment of IPF(UIP). We searched the Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library, Issue 2 2003), MEDLINE (January 1966 to April 2003), EMBASE (January 1985 to April 2003) and with additional handsearching. RCTs/CCTs utilising non-corticosteroid immunosuppressive, anti-fibrotic or immunomodulatory agents versus either placebo or corticosteroids alone in adult patients with histological evidence of IPF(UIP) or with a diagnosis consistent with published American Thoracic Society guidelines were included. We retrieved abstracts of identified articles and reviewed those possibly fulfilling inclusion criteria and included or excluded. Two reviewers assessed the studies for inclusion in the review. Where doubt existed a third reviewer re-assessed the article and consensus was obtained. Methodological quality was assessed using the Jadad scale and the Cochrane assessment of allocation of concealment. 59 studies were identified. Quality was generally poor. Only three RCT/CCTs were suitable for meta-analysis, two lesser quality RCTs were included in discussion only, 52 studies were excluded and two ongoing trials were identified. Each high quality trial used a different agent (azathioprine, colchicine, interferon-gamma 1b) and meaningful comparisons are not possible. Azathioprine and Interferon were studied as additional therapy, whilst colchicine was compared with oral corticosteroids. Only interferon was shown to produce any significant improvement in pulmonary function and arterial oxygenation. There may be a small (but undefined) long term survival advantage for azathioprine. One of the lower quality studies showed a marginal benefit for cyclophosphamide and prednisone over prednisone alone; the other showed no benefit for azathioprine and prednisone over prednisone alone. There are no high quality studies utilising cyclophosphamide. There is little good quality information regarding the efficacy of non-corticosteroid agents in IPF(UIP). The older agents have generally not been well evaluated. A number of new agents require further evaluation. Currently there is little to justify the routine use of any non-corticosteroid agent in the management of IPF(UIP).


[Glucuronate media for isolating tremelloid yeasts].
D-Glucuronate-containing agar is suggested for evaluation the population density and diversity of tremelloid yeasts in natural cenoses. This medium is superior to the commonly used wort agar on which many representatives of tremelloid yeasts cannot be revealed.


Voltage-Induced Rearrangements in Atomic-Size Contacts.
We study voltage-induced conductance changes of Pb, Au, Al, and Cu atomic contacts. The experiments are performed in vacuum at low temperature using mechanically controllable break junctions. We determine switching histograms, i.e., distribution functions of switching voltages and switching currents, as a function of the conductance. We observe a clear material dependence: Au reveals the highest and almost conductance-independent switching voltage, while Al has the lowest with a pronounced dependence on the conductance. The theoretical study uses density functional theory and a generalized Langevin equation considering the pumping of particular phonon modes. We identify a runaway voltage as the threshold at which the pumping destabilizes the atomic arrangement. We find qualitative agreement between the average switching voltage and the runaway voltage regarding the material and conductance dependence and contact-to-contact variation of the average characteristic voltages, suggesting that the phonon pumping is a relevant mechanism driving the rearrangements in the experimental contacts.


The role and mechanism of HIF-1α-mediated glypican-3 secretion in hypoxia-induced tumor progression in hepatocellular carcinoma.
To explore the expression and secretion mechanism of glypican-3 (GPC3) in hepatocellular carcinoma (HCC) cells under hypoxic conditions, and its role in tumor progression. Huh7 cells with and without the knockdown of hypoxia-inducible factor 1-alpha (HIF-1α) were cultured under 1% O2 for varying durations to induce hypoxia. The expression levels of GPC3, HSP70, CD63, STX11 and SYT7 in the cytoplasm and exosomes of Huh7 cells were evaluated by western blotting and immunofluorescence. GPC3 protein expression was further measured in cells treated with GW4869 under hypoxic conditions. Huh7 cells and human umbilical vein endothelial cells (HUVECs) were cultured with the exosomes extracted from the control and GPC3-knockdown cells, the cell proliferation, migration, epithelial-mesenchymal transition (EMT), invasion, and in vitro angiogenesis were analyzed. Tumor xenografts were established to assess the role of GPC3-deficient exosomes in tumor growth. Hypoxic culture conditions downregulated GPC3, STX11 and SYT7 protein levels in the Huh7 cells and upregulated GPC3 mRNA, and also increased GPC3 protein expression in the exosomes. HIF-1α knockdown, as well as treatment with GW4869, upregulated GPC3 protein in the Huh7 cells grown under 1% O2, but downregulated exosomal GPC3. Furthermore, exosomes derived from the GPC3-knockdown cells inhibited the proliferation and migration of Huh7 cells, decreased the expression of N-cadherin, vimentin, β-catenin, c-Myc and cyclin D1, and increased that of E-cadherin. Likewise, the GPC3-deficient exosomes also suppressed the invasion and tube formation ability of the HUVECs compared to that of control cells. Consistent with the in vitro results, the GPC3-deficient exosomes also repressed tumor growth in vivo. Hypoxia promoted secretion of exosomal GPC3 through the activation of HIF-1α. GPC3-deficient exosomes inhibited the proliferation, migration and EMT of HCC cells via the Wnt/β-catenin signaling pathway, and suppressed the angiogenic potential of HUVECs. This provided a novel understanding of the role of exosomal GPC3 in HCC progression.


Cell-type-specific regulation of nerve growth factor (NGF) synthesis in non-neuronal cells: comparison of Schwann cells with other cell types.
We have previously shown that after peripheral nerve lesion the synthesis of NGF is induced in cells of the nerve sheath (Heumann et al., 1987a). Further analysis led to the identification of growth factors and intracellular mechanisms responsible for this induction in sciatic fibroblasts (Lindholm et al., 1988; Hengerer et al., 1990). The present work aimed at the elucidation of the regulation of NGF synthesis in Schwann cells. A variety of cytokines and peptide growth factors, including interleukin-1 (IL-1) and platelet-derived growth factor (PDGF), which are known to increase NGF-mRNA in fibroblasts and astrocytes, failed to do so in Schwann cell cultures. Forskolin (FK), an activator of adenylate cyclase, increased the level of NGF-mRNA eightfold within 3 hr of incubation. The effect of FK on NGF-mRNA was mimicked by analogs of cAMP but not by dideoxyforskolin, an FK derivative not activating adenylate cyclase. Application of norepinephrine and isoproterenol also augmented the NGF-mRNA content. Pretreatment of Schwann cells with N-[2-(methylamino)ethyl]-5-isoquinoline sulfonamide dihydrochloride (H-8), an inhibitor of cyclic-nucleotide-dependent protein kinases, decreased both basal and elevated levels of NGF-mRNA. Ionomycin, a Ca2+ ionophore, and phorbol 12-myristate 13-acetate (TPA), an activator of protein kinase C, potentiated the effect of FK in an H-8-sensitive manner. We show that the action of FK is independent of changes in mRNA stability and of protein synthesis. Thus, in cultured Schwann cells upregulation of NGF-mRNA expression seems to be mainly achieved by a cAMP-triggered transcriptional activation of the NGF gene. Another striking difference between various glial cell types was revealed by application of transforming growth factor beta-1 (TGF-beta 1), which is the strongest inducer of NGF-mRNA in cultured astrocytes (Lindholm et al., 1990). Schwann cells responded to TGF-beta 1 by decreasing basal as well as FK-induced NGF-mRNA levels. Together with previously published work, our results show that cell-type-specific mechanisms not only account for the different control of NGF expression in neurons as compared to glial cells, but also reveal a surprising specificity of regulatory mechanisms in different non-neuronal cell types, even those derived from the same tissue such as fibroblasts and Schwann cells of peripheral nerves.


Lost and changed meaning in life of people with Long Covid: a qualitative study.
Long Covid (LC) has been called the greatest mass-disabling event in human history. For patients, LC not only has implications for quality of life but also for meaning in life: how one's life and the world are understood and what is seen as valuable in one's life. This qualitative empirical study used a Constructivist Grounded Theory approach to investigate the meaning in life of people struggling with LC through ten patient interviews. This study shows that patients lose their prior understanding of life and come to a changed meaning in life, in part due to the experienced (social) isolation and loss of (both physical and cognitive) abilities caused by LC. Moreover, patients struggled with acceptance, uncertainty, and the inherent incomprehensibility and uncontrollability that living with LC entails, though this simultaneously co-existed with hope, optimism and acceptance. Additionally, dimensions of meaning intersect; a patient having some understanding of their illness (dimension of meaning: comprehension) required an understanding Other (dimension of meaning: connection). Emerging from lockdown brought the challenge and isolation of adjusting to chronic illness in society as usual (albeit divided about COVID-19 measures). This study thus offers novel insights regarding changed, present, and sought meaning in life for LC patients.


Trans-oral robotic submandibular gland removal.
Submandibular gland excision is traditionally performed via a trans-cervical approach. While generally regarded as a relatively simple surgical procedure, several complications are possible, including injury to the marginal mandibular branch of the facial nerve, lingual nerve, hypoglossal nerve, facial artery and a visible unsightly neck scar or keloid. The trans-oral route has the ability to eliminate a cervical scar and decrease risk of injury to several structures. Coincident with the development of the trans-oral approach, robotic surgery has been gaining popularity in the operative management of early oral cavity, tonsil, and tongue base malignancies. A 51-year-old female presented to our institution with a 15-year history of recurrent left submandibular gland sialoadenitis. She previously underwent a rhytidectomy with cervicoplasty and was interested in a trans-oral approach to avoid a neck incision. Here we present a novel application of the da Vinci Surgical Robot for trans-oral removal of the submandibular gland.


The development of The Society of Thoracic Surgeons voluntary national database system: genesis, issues, growth, and status.
The purpose of this communication is to demonstrate the feasibility of a voluntary national cardiac surgical database. The genesis of the Society of Thoracic Surgeons (STS) National Cardiac and General Thoracic Surgery Databases in the interval of 1986 to 1990 is described. The issues facing the Committee in the initial decision making processes are discussed choosing a society-based, in-house activity versus using an outside vendor, private practice needs versus academic ones; open versus closed membership and vendors, risk stratification; data quality; audit; and access to data. In the 6 years of operation the STS cardiac surgical database has grown from 41,000 to 706,000 patients. The number of practice groups, hospitals, and surgeons has increased from 26 to 624, 32 to 750, and 120 to 1850, respectively. All but one state is represented, as are more than 400 teaching hospitals, including 28 Veterans Administration hospitals and 60 university centers. The STS database system has become firmly established and is a model for other societies and associations. The data placed yearly in the public domain have become a national standard.


[Dissociative stupor--differential diagnosis of coma following injury].
Two cases are described in which a dissociative stupor originating from conversion neurosis simulated a coma following a sustained trauma. At first both patients showed no response to being addressed or to pain stimuli. They presented an upward eye gaze deviation, cardiorespiratory functions were stable. Following extensive diagnostic procedures revealing no organic cause for the clinical symptoms, the diagnosis of a hysterical consciousness disorder was stated. Symptoms of conversion neuroses include lacking call response, gait disorder, seizure-like conditions and strength diminution in one or more extremities. In these cases suspicious facts are the absence of injuries (for example by falling down or tongue bite during a dissociative attack), eye gaze deviation and the phenomenon that, when the patient's arm is raised above the head and let fall, it never hits the face but glides down beside the body.


Inaccurate ascertainment of morbidity and mortality due to influenza in administrative databases: a population-based record linkage study.
Historically, counting influenza recorded in administrative health outcome databases has been considered insufficient to estimate influenza attributable morbidity and mortality in populations. We used database record linkage to evaluate whether modern databases have similar limitations. Person-level records were linked across databases of laboratory notified influenza, emergency department (ED) presentations, hospital admissions and death registrations, from the population (∼6.9 million) of New South Wales (NSW), Australia, 2005 to 2008. There were 2568 virologically diagnosed influenza infections notified. Among those, 25% of 40 who died, 49% of 1451 with a hospital admission and 7% of 1742 with an ED presentation had influenza recorded on the respective database record. Compared with persons aged ≥65 years and residents of regional and remote areas, respectively, children and residents of major cities were more likely to have influenza coded on their admission record. Compared with older persons and admitted patients, respectively, working age persons and non-admitted persons were more likely to have influenza coded on their ED record. On both ED and admission records, persons with influenza type A infection were more likely than those with type B infection to have influenza coded. Among death registrations, hospital admissions and ED presentations with influenza recorded as a cause of illness, 15%, 28% and 1.4%, respectively, also had laboratory notified influenza. Time trends in counts of influenza recorded on the ED, admission and death databases reflected the trend in counts of virologically diagnosed influenza. A minority of the death, hospital admission and ED records for persons with a virologically diagnosed influenza infection identified influenza as a cause of illness. Few database records with influenza recorded as a cause had laboratory confirmation. The databases have limited value for estimating incidence of influenza outcomes, but can be used for monitoring variation in incidence over time.


Induction of spermidine N1-acetyltransferase by sodium n-butyrate and phytohemagglutinin in bovine lymphocytes.
An increased activity of spermidine N1-acetyltransferase was induced in bovine lymphocytes by stimulation with either sodium n-butyrate or phytohemagglutinin (PHA). The acetylase activity was elevated by 2- to 3-fold 24 h after the addition of butyrate, whereas a similar increase of the enzyme activity was found 48 h after stimulation with PHA. When butyrate and PHA were added to the lymphocyte suspensions simultaneously, the peak of enzyme induction was observed at 24 h after the addition and the increase (9-fold) was found to be more than additive. Since the increases in acetylase activity by both butyrate and PHA were markedly inhibited by actinomycin D or cycloheximide, they appear to have resulted from the synthesis of new protein rather than the release of the enzyme from a cryptic inactive form. The enzyme induced by the two agents was most active with spermidine as a substrate, but spermine was also acetylated to a smaller extent (25% of spermidine). Virtually no acetylation was observed with putrescine. Also, the product formed from spermidine and acetyl CoA was more than 90% N1-acetylspermidine. These results indicate that the acetylases induced by the two agents are similar. Although the addition of indomethacin or 8-bromocyclic AMP to PHA-stimulated lymphocytes caused an inhibition of the enzyme induction, no such inhibitory effect was found in the case of enzyme induction by butyrate. These results indicate that both sodium n-butyrate and PHA induce spermidine N1-acetyltransferase in bovine lymphocytes, but the induction mechanisms are different from each other.


Rural Family Medicine Outcomes at the University of Minnesota Medical School Duluth.
The University of Minnesota Medical School Duluth (MSD) opened in 1972 with a mission to train physicians serving rural Minnesota, emphasizing family medicine and American Indian (AI) communities. Nationwide there are shortages in family medicine and AI physicians, and MSD is a leader in these outcomes. This is a longitudinal, retrospective cohort analysis of 1972-2009 MSD graduates using descriptive statistics and multivariate regression to determine relationships between gender, race, age, and hometown and outcomes of family medicine specialty, rural practice, and rural family medicine practice. MSD graduate outcomes are significantly higher than other US medical schools but declining, 47% chose family medicine and 37% chose a rural first practice location. Selection of rural and family medicine declined more rapidly for men than women, but there was no overall gender difference. AI graduates had rates of rural family medicine similar to their white classmates and older AI students were more likely to select rural family medicine. Graduates from rural hometowns were more likely to select rural practice but not to practice family medicine. MSD culture and curricula produce AI, family medicine, and rural physicians, but the school is experiencing a downward trend. Understanding the relationship between demographics and outcomes over time will assist policy makers and educators in optimizing strategies to develop the rural family medicine workforce.


Pilot Study of Return of Genetic Results to Patients in Adult Nephrology.
Actionable genetic findings have implications for care of patients with kidney disease, and genetic testing is an emerging tool in nephrology practice. However, there are scarce data regarding best practices for return of results and clinical application of actionable genetic findings for kidney patients. We developed a return of results workflow in collaborations with clinicians for the retrospective recontact of adult nephrology patients who had been recruited into a biobank research study for exome sequencing and were identified to have medically actionable genetic findings. Using this workflow, we attempted to recontact a diverse pilot cohort of 104 nephrology research participants with actionable genetic findings, encompassing 34 different monogenic etiologies of nephropathy and five single-gene disorders recommended by the American College of Medical Genetics and Genomics for return as medically actionable secondary findings. We successfully recontacted 64 (62%) participants and returned results to 41 (39%) individuals. In each case, the genetic diagnosis had meaningful implications for the patients' nephrology care. Through implementation efforts and qualitative interviews with providers, we identified over 20 key challenges associated with returning results to study participants, and found that physician knowledge gaps in genomics was a recurrent theme. We iteratively addressed these challenges to yield an optimized workflow, which included standardized consultation notes with tailored management recommendations, monthly educational conferences on core topics in genomics, and a curated list of expert clinicians for patients requiring extranephrologic referrals. Developing the infrastructure to support return of genetic results in nephrology was resource-intensive, but presented potential opportunities for improving patient care. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_04_16_12481019.mp3.


Resting brain activity in disorders of consciousness: a systematic review and meta-analysis.
To quantitatively synthesize results from neuroimaging studies that evaluated patterns of resting functional activity in patients with disorders of consciousness (DOC). We performed a systematic review and coordinate-based meta-analysis of studies published up to May 2014. Studies were included if they compared resting-state functional neuroimaging data acquired in patients with DOC (coma, minimally conscious state, emergence from minimally conscious state, or vegetative state) with a group of healthy controls. Coordinate-based meta-analysis was performed in studies that included voxel-based comparisons at the whole-brain level and if analysis was accomplished with data-driven approaches. A total of 36 studies (687 patients, 637 healthy controls) were included in the systematic review. Reported DOC were vegetative state (43.2%), coma (23.4%), minimally conscious state (22.8%), and emergence from minimally conscious state (1.6%); the most common etiologies of DOC were traumatic brain injury (37.7%) and anoxic brain injury (36.9%). Functional neuroimaging was accomplished using fMRI (16 studies), PET (15 studies), SPECT (4 studies), and both PET and SPECT in one study. Meta-analysis in 13 studies (272 patients, 259 healthy controls) revealed consistently reduced activity in patients with DOC in bilateral medial dorsal nucleus of the thalamus, left cingulate, posterior cingulate, precuneus, and middle frontal and medial temporal gyri. In patients with DOC evaluated in the resting state, functional neuroimaging indicates markedly reduced activity within midline cortical and subcortical sites, anatomical structures that have been linked to the default-mode network. Studies are needed to determine the relation between activation (and coherence) within these structures and the emergence of conscious awareness.


Communication and language challenges experienced by Chinese and South Asian immigrant parents of children with cancer in Canada: implications for health services delivery.
Language is an important aspect of health literacy and plays a vital role in families' ability to access and use health information and resources. Our study explored the role of communication and language in the healthcare experiences of immigrant parents of children with cancer living in Canada. We used a grounded theory approach. Chinese and South Asian parents of children 6 months post-diagnosis were recruited from six Canadian pediatric oncology centers. Semi-structured interviews were conducted in Cantonese, Mandarin, Hindi, Punjabi, Urdu, or English. Questions relevant to communication included: how parents navigated the healthcare system; nature of interpreter services and translated materials; and suggestions about how to improve services. Analysis involved line-by-line, focused and theoretical coding, and constant comparison. Thirty-one (62%) parents reported no difficulty communicating with healthcare providers in English, while 13 (26%) parents struggled with English, and six (12%) parents could not communicate in English. Communication challenges influenced parents' role in caring for their child and made it difficult to learn complex medical terminology. Interpreting services were sometimes inadequate or not accessible. Parents occasionally missed out on services and resources, reported limited availability of linguistically and culturally appropriate information, and experienced a lack of social integration in the healthcare process. Language ability played an essential role in parents' healthcare experiences for pragmatic and social purposes. Language challenges can heighten systemic and socio-cultural barriers to accessing health information and resources. The provision of enhanced culturally and linguistically sensitive services may support immigrant families in their caregiving role.


BCL11A enhancer haplotypes and fetal hemoglobin in sickle cell anemia.
Fetal hemoglobin (HbF) levels in sickle cell anemia patients vary. We genotyped polymorphisms in the erythroid-specific enhancer of BCL11A to see if they might account for the very high HbF associated with the Arab-Indian (AI) haplotype and Benin haplotype of sickle cell anemia. Six BCL112A enhancer SNPs and their haplotypes were studied in Saudi Arabs from the Eastern Province and Indian patients with AI haplotype (HbF ~20%), African Americans (HbF ~7%), and Saudi Arabs from the Southwestern Province (HbF ~12%). Four SNPs (rs1427407, rs6706648, rs6738440, and rs7606173) and their haplotypes were consistently associated with HbF levels. The distributions of haplotypes differ in the 3 cohorts but not their genetic effects: the haplotype TCAG was associated with the lowest HbF level and the haplotype GTAC was associated with the highest HbF level and differences in HbF levels between carriers of these haplotypes in all cohorts were approximately 6%. Common HbF BCL11A enhancer haplotypes in patients with African origin and AI sickle cell anemia have similar effects on HbF but they do not explain their differences in HbF.


Helicobacter pylori in peptic ulcer disease in Kenya.
Sixty six patients with dyspeptic symptoms underwent upper gastrointestinal endoscopy and biopsies for Helicobacter pylori culture. The number of H. pylori isolated increased with age reaching a peak at 51 to 60 years of age. Antral gastritis closely followed by duodenitis accounted for the highest number of H. pylori isolated, (87.5% and 85.7% respectively). In patients with duodenal ulceration only, 57% had H. pylori isolated from their antral biopsies, a result that was just slightly higher than that where no endoscopic diagnosis was made (50%).


Value of fourth and subsequent post-therapy follow-up 18F-FDG PET/CT scans in patients with breast cancer.
To evaluate the accuracy and value of the fourth and subsequent post-therapy follow-up fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) scans in the clinical assessment of breast cancer patients. Ninety-two female patients, with a total of 426 fourth and subsequent follow-up PET/CT scans, were retrospectively included. Patients were followed for a median of 23.7 months (range, 0.7-124.4) from the fourth follow-up PET/CT. The diagnostic accuracy of PET/CT, its impact on clinical assessment, patients' management, and survival outcome were established. Of the 426 follow-up PET/CT scans, 264 (62%) were interpreted as positive and 162 (38%) were interpreted as negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the fourth and subsequent follow-up PET/CT scans were 97.7, 98.1, 98.8, 96.3, and 97.9%, respectively. Fourth and subsequent follow-up PET/CT were useful in excluding a tumor in 13.4% (39/292) of patients with a clinical suspicion of recurrence and identifying suspected recurrence in 10.5% (14/134) of patients without previous clinical suspicion. A change in management was noted in 6.7% (9/134) of scan times when the scans were performed without previous clinical suspicion of recurrence or therapy response and was 27.7% (81/292) when the scans were performed with clinical suspicion. Overall survival differed significantly between patients with all negative follow-up scans (n=23) and those who had at least one positive follow-up scan (n=69) (hazard ratio of 4.65, P<0.001). The fourth and subsequent PET/CT scans performed after the completion of primary treatment led to a change in management in 27.7% of patients when the scans were performed with clinical suspicion and only in 6.7% of patients when performed without clinical suspicion or context.


Ultrathin Aerogel Micro/Nanofiber Membranes with Hierarchical Cellular Architecture for High-Performance Warmth Retention.
A low temperature environment poses significant challenges to the global economy and public health. However, the existing cold-protective materials still struggle with the trade-off between thickness and thermal resistance, resulting in poor thermal-wet comfort and limited personal cold protection performance. Here, a scalable strategy, based on electrospinning and solution casting, is developed to create aerogel micro/nanofiber membranes with a hierarchical cellular architecture by manipulating the phase separation of the charged jets and of the spreading casting solution. The integration of interconnected nanopores (30-60 nm), ultrafine fiber diameter, and high porosity, enables the aerogel micro/nanofiber membranes with lightweight, ultrathin thickness (∼0.5 mm), and superior warmth retention performance with ultralow thermal conductivity of 14.01 mW m-1 K-1. And the resultant membrane with customized semiclosed walls exhibits both striking wind resistance and satisfactory thermal-wet comfort (3.4 °C warmer than the cutting-edge thermal underwear). This work will inspire the design and development of high-performance fibrous materials for thermal management applications.


Asparagine-344 is a key residue for ligand binding in keratinocyte growth factor receptor.
The membrane proximal, immunoglobulin- (Ig-) like domain 3 of KGFR shows significant sequence similarity to the Ig light chain variable (V) domain. According to our model, based on this similarity, the F-G loop in KGFR corresponds to the complementarity determining region (CDR) 3 of the Ig V domain. The F-G loop in the membrane proximal domain of the keratinocyte growth factor receptor has previously been shown to participate in determining the FGF ligand binding specificity of KGFR [Gray, T. E., Eisenstein, M., Shimon, T., Givol, D., & Yayon, A. (1995) Biochemistry 34, 10325-10333]. Here, we report the effects of additional mutations in this F-G loop. Both a single mutant KGFR Q348-->I and a double mutant KGFR Q348-->I, Q351-->H are found to have relatively mild effects on ligand binding, as was previously found for three other F-G loop mutant receptors. In contrast, a single mutation N344-->A in the F-G loop of KGFR is sufficient to abolish essentially all affinity of this receptor for its primary ligand KGF, while some affinity for aFGF is retained. Asparagine-344 is, therefore, essential for ligand binding by KGFR. We discuss the likelihood of this effect being due to global or local structural changes or to the removal of a specific interaction with the ligand, in relation to various known and model structures. Taking into account the mild effects of other mutations in the region and various other considerations, we tend to favor the idea that asparagine-344 is a key residue in determining the local conformation of the F-G loop.


Biodistribution of p-borophenylalanine (BPA) in dogs with spontaneous undifferentiated thyroid carcinoma (UTC).
Human undifferentiated thyroid carcinoma (UTC) is a very aggressive tumor which lacks an adequate treatment. The UTC human cell line ARO has a selective uptake of BPA in vitro and after transplanting into nude mice. Applications of boron neutron capture therapy (BNCT) to mice showed a 100% control of growth and a 50% histological cure of tumors with an initial volume of 50 mm(3) or less. As a further step towards the potential application in humans we have performed the present studies. Four dogs with diagnosis of spontaneous UTC were studied. A BPA-fructose solution was infused during 60 min and dogs were submitted to thyroidectomy. Samples of blood and from different areas of the tumors (and in one dog from normal thyroid) were obtained and the boron was determined by ICP-OES. Selective BPA uptake by the tumor was found in all animals, the tumor/blood ratios ranged between 2.02 and 3.76, while the tumor/normal thyroid ratio was 6.78. Individual samples had tumor/blood ratios between 8.36 and 0.33. These ratios were related to the two histological patterns observed: homogeneous and heterogeneous tumors. We confirm the selective uptake of BPA by spontaneous UTC in dogs and plan to apply BNCT in the future.


Cost-Effectiveness of Hearing Screening in Older Adults: A Scoping Review.
Age is the most common predictor of hearing loss; however, many older adults are not screened. Hearing screening could improve healthcare access, participation, and outcomes. Establishing whether hearing screening in older adults is cost-effective could improve the availability and utilization of screening. We searched nine databases in January 2020. Studies with populations aged 50+ and provided data on the cost-effectiveness of hearing screening were included in the review. Five studies met the inclusion criteria and all found hearing screening programs to be cost-effective compared to no hearing screening, regardless of screening method (i.e., instrument or strategy). The maximum number of repeated screenings, coupled with younger ages, was most cost-effective. This review suggests that hearing screening in older adults is cost-effective, however, the evidence is limited. There is pressing need for research focused on economic impacts of hearing healthcare in older adults to inform research, policy and practice.


A prospective study of hepatic imaging in the detection of metastatic disease.
This prospective study of 80 patients compared the results of liver scintiscan, ultrasound, and CT scan to the objective findings recorded at laparotomy. Analysis of these data revealed no significant differences in sensitivity, specificity, or accuracy among these three imaging procedures, although a trend toward increased accuracy of the CT scan was noted. In a composite analysis, the accuracy was not improved by combining two or all three of these examinations. A lesion by lesion analysis revealed the inability of any of the three currently used techniques to accurately detect lesions less than 3 cm in diameter.


[The modulating action of serotonin on single calcium channels in the neurons of the snail Helix pomatia].
The influence of a neurotransmitter serotonin (5-hydroxytriptamine, 5-HT) on single Ca2+ channel activity was studied on unidentified neurons of the snail Helix pomatia. Our findings showed that 5-HT influences the channel molecule in indirect manner, as it appeared effective at its application by adding to the bath solution, that had no contact with the tested membrane fragment. This finding excludes the possibility of direct binding of 5-HT to the channel molecule and shows that the effect is really mediated through a cytoplasmic messenger, cAMP-dependent cascade of phosphorylation. Also our investigations shows, that only one type of Ca2+ channel with the unitary conductance of 5 pS was identified in this kind of neurons.


Identification and application of bacterial volatiles to attract a generalist aphid parasitoid: from laboratory to greenhouse assays.
Recent studies have shown that microorganisms emit volatile compounds that affect insect behaviour. However, it remains largely unclear whether microbes can be exploited as a source of attractants to improve biological control of insect pests. In this study, we used a combination of coupled gas chromatography-electroantennography (GC-EAG) and Y-tube olfactometer bioassays to identify attractive compounds in the volatile extracts of three bacterial strains that are associated with the habitat of the generalist aphid parasitoid Aphidius colemani, and to create mixtures of synthetic compounds to find attractive blends for A. colemani. Subsequently, the most attractive blend was evaluated in two-choice cage experiments under greenhouse conditions. GC-EAG analysis revealed 20 compounds that were linked to behaviourally attractive bacterial strains. A mixture of two EAG-active compounds, styrene and benzaldehyde applied at a respective dose of 1 μg and 10 ng, was more attractive than the single compounds or the culture medium of the bacteria in Y-tube olfactometer bioassays. Application of this synthetic mixture under greenhouse conditions resulted in significant attraction of the parasitoids, and outperformed application of the bacterial culture medium. Compounds isolated from bacterial blends were capable of attracting parasitoids both in laboratory and greenhouse assays, indicating that microbial cultures are an effective source of insect attractants. This opens new opportunities to attract and retain natural enemies of pest species and to enhance biological pest control.


The business case for pediatric asthma quality improvement in low-income populations: examining a provider-based pay-for-reporting intervention.
To measure the return on investment (ROI) for a pediatric asthma pay-for-reporting intervention initiated by a Medicaid managed care plan in New York State. Practice-level, randomized prospective evaluation. Twenty-five primary care practices providing care to children enrolled in the Monroe Plan for Medical Care (the Monroe Plan). Practices were randomized to either treatment (13 practices, 11 participated) or control (12 practices). For each of its eligible members assigned to a treatment group practice, the Monroe plan paid a low monthly incentive fee to the practice. To receive the incentive, treatment group practices were required to conduct, and report to the Monroe Plan, the results of chart audits on eligible members. Chart audits were conducted by practices every 6 months. After each chart audit, the Monroe Plan provided performance feedback to each practice comparing its adherence to asthma care guidelines with averages from all other treatment group practices. Control practices continued with usual care. Intervention implementation and operating costs and per member, per month claims costs. ROI was measured by net present value (discounted cash flow analysis). The ROI to the Monroe Plan was negative, primarily due to high intervention costs and lack of reductions in spending on emergency department and hospital utilization for children in treatment relative to control practices. A pay-for-reporting, chart audit intervention is unlikely to achieve the meaningful reductions in utilization of high-cost services that would be necessary to produce a financial ROI in 2.5 years.


Effect of stimulus and recording parameters on spatial spread of excitation and masking patterns obtained with the electrically evoked compound action potential in cochlear implants.
Spread of excitation within the cochlea in response to electrical stimulation can be measured with the electrically evoked compound action potential (ECAP). Different spread of excitation measurement techniques have been reported in the literature. One method uses a fixed stimulus location while varying the recording electrode along the length of the implanted array. This results in a relatively coarse estimate of spatial spread (SS) along the cochlea. Another method uses a forward-masking paradigm to evaluate the relative overlap of stimulated neural populations between electrodes. Both the probe and recording electrodes are fixed in location while a masker stimulus is systematically applied across electrodes. This method, which yields a more precise estimate of spatial excitation patterns, is termed spatial masking (SM). Five experiments were conducted to examine potential effects of stimulus and/or recording parameters on SS and SM patterns. Experiment 1 examined whether SS patterns were systematically broader than SM patterns across electrodes and subjects. Experiments 2 and 3 evaluated the effects of stimulus level on SS and SM patterns, respectively, to determine whether increased stimulus level systematically resulted in broader patterns. Experiment 4 evaluated whether recording electrode location affected SM patterns, and Experiment 5 evaluated whether SM patterns varied significantly across repeated trials within a test session. Data were collected for 27 ears in 26 adult and teenage subjects (N = 6 ears with Advanced Bionics CII, N = 8 ears with Advanced Bionics HiRes 90K, N = 10 ears with Nucleus 24R[CS], N = 3 ears with Nucleus 24RE[CA] Freedom). A standard forward-masking subtraction paradigm was used for all ECAP measures. For SS patterns, the masker and probe were fixed on the same electrode at the same level while the recording electrode varied across the remaining electrodes in the array. For SM patterns, the probe and recording locations were fixed while the masker location varied across all electrodes except the recording electrode. In experiment 1, SS patterns were broader than SM patterns. Subjects with Advanced Bionics devices exhibited relatively broad patterns for both measures, whereas Nucleus subjects typically exhibited narrower SM functions relative to SS functions. In experiments 2 and 3, there was a significant effect of stimulus level on the spread of both SS and SM patterns in roughly one-third of measures in each experiment. In experiment 4, there was a significant effect of recording electrode location on the width/spread of SM patterns for only 11.5% of comparisons. In experiment 5, there were no significant differences in SM amplitudes across repeated trials for 94% of comparisons, which suggests that ECAP measures are highly robust within a test session. Results showed that SS functions were generally broader than SM functions, which suggests that SS measures reflect volume conduction of the ECAP response along the length of the cochlea. Differences in the spread of SM functions across devices are likely due to differences in modiolar proximity between the respective electrode array designs. Stimulus level had a more significant effect on the spread of SM functions than recording electrode location. Finally, ECAP measures were shown to be highly stable across repeated measurements within a test session; however, repeatability was not assessed across sessions or over extended time intervals.


Unlocking same-sign CPL: solvent effects on spectral form and racemisation kinetics in nine-coordinate chiral europium(III) complexes.
Understanding the factors that shape the circularly polarised luminescence (CPL) emission profiles of europium(III)-based CPL emitters to have specific sign properties, e.g. monosignate individual CPL transitions, is key to design novel complexes for applications ranging from advanced security inks to bio-probes for live cell imaging. In order to correlate structure and spectral characteristics, a photophysical and kinetic investigation has been conducted on a series of coordinatively saturated nine-coordinate europium(III) systems based on 1,4,7-triazacyclononane. We highlight that lanthanide emission is sensitive to changes in the ligand field by showing the linear dependence of total emission intensity ratios as a function of solvent polarity, for europium(III) complexes displaying an internal charge transfer (ICT) excited state. This sensitivity increases by a factor of 20 when studying changes in CPL spectra, rendering these complexes accurate probes of local polarity. Solvent polarity, solvent-specific effects, and the nature of the chromophores' coordinating donor atoms strongly influence the kinetic stability of europium(III) complexes with respect to enantiomer interconversion. Notably, we show that the choice of donor groups to coordinating to europium(III) and the nature and polarity of the solvent affects the rate of racemisation, leading to very long half-lives at room temperature in non-polar media.


Histologic Changes Following Continuous Wave and Micropulse Transscleral Cyclophotocoagulation: A Randomized Comparative Study.
To compare the macroscopic and microscopic histologic changes in eyes treated with micropulse transscleral cyclophotocoagulation (MP-TCP) versus continuous wave transscleral cyclophotocoagulation (CW-TCP). Twelve halves of globes from three pairs of adult cadaveric eyes were randomly assigned to nontreated control, CW-TCP, single MP-TCP treatment, or double MP-TCP treatments, and then sectioned for histologic analysis. Presence or absence of the following four unique histologic changes was recorded: splitting within the ciliary process epithelium (splitting), separation of the pigmented ciliary process epithelium from the stroma (separation), coagulation of collagen and destruction of ciliary process stroma (coagulation), and full-thickness destruction of ciliary process epithelium (destruction). A total of 498 slides were analyzed, and laser scars in all treated specimens were located in the pars plana. Logistic regression analysis showed that compared with controls, CW-TCP-treated specimens were significantly more likely to experience separation (odds ratio [OR] = 11.1, P = 0.02), coagulation (OR = 24.3, P = 0.002), and destruction (OR = 11.1, P = 0.03). Destruction of the ciliary process epithelium was observed exclusively in CW-TCP-treated sections. No significant differences in histologic features were observed between controls and MP-TCP. MP-TCP does not produce significant histologic changes in cadaveric eyes, whereas CW-TCP treatment does. These findings improve understanding of the mechanism of MP-TCP, help explain the increased rates of adverse effects following CW-TCP treatment compared with MP-TCP, and describe effects of MP-TCP at various doses.


Photosensitizer-loaded magnetic nanoemulsion for use in synergic photodynamic and magnetohyperthermia therapies of neoplastic cells.
In this study a magnetic nanoemulsion (MNE) was developed from a mixture of two components, namely biodegradable surfactants and biocompatible citrate-coated cobalt ferrite-based magnetic fluid, for entrapment of Zn(II)-Phthalocyanine (ZnPc), the latter a classical photosensitizer (PS) species used in photodynamic therapy (PDT) procedures. The sample's stability was evaluated as a function of time using photocorrelation spectroscopy (PCS) for determination of the average hydrodynamic diameter, diameter dispersion and zeta potential. The ZnPc-loaded magneto nanoemulstion (ZnPc/MNE) formulation was evaluated in vitro assays to access the phototoxicity and the effect of application of AC magnetic fields (magnetohyperthermia damage) after incubation with J774-A1 macrophages cells. Darkness toxicity, phototoxicity and AC magnetic field exposures revealed an enhancement response for combined photodynamic and magnetohyperthermia (MHT) processes, indicating the presence of the synergic effect.


Racial Disparities in Avoidable Hospitalizations in Traditional Medicare and Medicare Advantage.
Compared with traditional Medicare (TM), Medicare Advantage (MA) has the potential to reduce racial disparities in hospitalizations for ambulatory care sensitive conditions (ACSC). As racial disparities may be partly attributable to unequal treatment based on where people live, this suggests the need of examining geographic variations in racial disparities. The aim of this study was to examine differences in ACSC hospitalizations between White and Black beneficiaries in TM and MA and examine geographic variations in racial differences in ACSC hospitalizations in TM and MA. We analyzed the 2015-2016 Medicare Provider Analysis and Review files. We used propensity score matching to account for differences in characteristics between TM and MA beneficiaries. Then, we conducted linear regression and estimated adjusted outcomes for TM and MA beneficiaries by race. Also, we estimated racial differences in adjusted outcomes by insurance and hospital referral region (HRR). While White beneficiaries in TM and MA had similar rates of ACSC hospitalizations (163.7 vs. 162.2/10,000 beneficiaries), Black beneficiaries in MA had higher rates of ACSC hospitalizations than Black beneficiaries in TM (221.2 vs. 209.3/10,000 beneficiaries). However, the racial differences were greater in MA than TM (59.0 vs. 45.6/10,000 beneficiaries). Racial differences in ACSC hospitalizations in MA were prevalent across almost all HRRs. 95.5% of HRRs had higher rates of ACSC hospitalizations among Black beneficiaries than White beneficiaries in MA relative to just 54.2% of HRRs in TM. Our findings provide evidence of racial disparities in access to high-quality primary care, especially in MA.


Increased p53 phosphorylation after microtubule disruption is mediated in a microtubule inhibitor- and cell-specific manner.
p53 is present at low levels in unstressed cells. Numerous cellular insults, including DNA damage and microtubule disruption, elevate p53 protein levels. Phosphorylation of p53 is proposed to be important for p53 stabilization and activation after genotoxic stress; however, p53 phosphorylation after microtubule disruption has not been analysed. The goal of the current study was to determine if p53 phosphorylation increases after microtubule disruption, and if so, to identify specific p53 residues necessary for microtubule inhibitor-induced phosphorylation. Two dimensional gel analyses demonstrated that the number of p53 phospho-forms in cells increased after treatment with microtubule inhibitors (MTIs) and that the pattern of p53 phosphorylation was distinct from that observed after DNA damage. p53 phosphorylation also varied in a MTI-dependent manner, as Taxol and Vincristine induced more p53 phospho-forms than nocodazole. Further, MTI treatment increased phosphorylation of p53 on serine-15 in epithelial tumor cells. In contrast, serine-15 phosphorylation of p53 did not increase in MTI-treated primary cultures of human fibroblasts. Analysis of ectopically expressed p53 phospho-mutant proteins from Taxol- and nocodazole-treated cells indicated that multiple p53 amino terminal residues, including serine-15 and threonine-18, were required for Taxol-mediated phosphorylation of p53. Taken together, the results of this study demonstrate that distinct p53 phospho-forms are induced by MTI treatment as compared to DNA damage and that p53 phosphorylation is mediated in a MTI- and cell-specific manner. Oncogene (2001) 20, 113 - 124.


Nanometric dispersion of a Mg/Al layered double hydroxide into a chemically modified polycaprolactone.
Polycaprolactone (PCL) was chemically modified by grafting maleic anhydride on it, through a radical reaction induced by benzoyl peroxide as initiator. To improve the grafting degree, a second unsaturated comonomer such as glycidyl methacrylate (GMA) has been added, demonstrating a good reactivity in melt grafting without leading to long grafted chains. The quantitative determination of grafted maleic anhydride, performed by FTIR analysis, revealed a grafting weight percentage of 9.5 +/- 0.9, and the NMR characterization made it possible to propose a structure for the grafted polymer (PCLgMA). The modified polymer was analyzed by DSC and X-ray diffraction, showing a structural organization even better than that of the pristine polymer. An exchange reaction with a layered double hydroxide (LDH), hydrotalcite-like solid in the nitrate form, led to the disappearance of the crystalline basal peak of LDH in the X-ray diffractograms, suggesting a possible exfoliation of the inorganic sample. An oxidative etching on the composite surface followed by atomic force microscopy analysis made it possible to enlighten the lamellar structure in the pristine sample. In the composite sample, the well identifiable narrow fissures homogeneously distributed on the surface demonstrate that nanometer stacks of LDH sheets, embedded in a highly textured PCLgMA matrix, are present in the composite sample. The comparison of X-ray diffractograms and AFM analysis suggests either a partial exfoliation or an intercalation of the polymer in a lamellar texture with a basal spacing higher than 5 nm. In any case, the process of ionic exchange between nitrate LDH and PCLgMA led to the formation of nanocomposites, in which no large hydrotalcite aggregates are present. This is an interesting method to obtain a direct intercalation of the modified polymer into the inorganic solid with a simple ionic exchange reaction.


Fast axonally transported proteins in regenerating goldfish optic axons.
Fast axonal transport of protein was examined in regenerating goldfish optic axons after a lesion of either the optic tract or optic nerve, which revealed changes in the original intact optic axon segments or in the newly regenerated axon segments, respectively. In animals killed either 6 or 24 hr after injection of 3H-proline into the eye, labeling of total fast-transported protein in the original axon segments was increased by 2 d after the lesion, reached a peak of nearly 20 X normal at 2 weeks, and then declined to a level somewhat above normal at 12 weeks. When the labeling of individual transported proteins was examined by 2-dimensional gel electrophoresis, it was found that no new labeled proteins appeared during regeneration, but all proteins examined showed an increase in labeling. Among the various proteins, there was great variation in the magnitude and time course of the labeling increase. The largest increase, to nearly 200 X normal with 6 hr labeling, was seen in a protein with a molecular weight of 45 kDa and a pl of about 4.5, resembling a protein that has previously been designated a "growth-associated protein" (GAP-43; Skene and Willard, 1981a). The proteins showing increased labeling included a small fraction of cytoskeletal proteins (alpha-tubulin, beta-tubulin, and actin) that was apparently transported at a much faster rate than is usually expected of these constituents. In the new axon segments, the total protein labeling was increased by 1 week after the lesion, remained elevated at a nearly constant level of about 7 X normal from about 2 to 5 weeks, and then declined to levels somewhat above normal by 12 weeks. The 45 kDa protein again showed the largest increase, and became the single most prominently labeled constituent in the new axons. On the basis of the time course of labeling in both original and new axon segments during regeneration, the fast-transported proteins were tentatively separated into 5 classes that may represent groups of proteins that are coregulated during regeneration. They may conceivably correspond to different functional or structural entities within the neuron.


Characterization of dolichol and dolichyl phosphate phosphatase from soya beans (Glycine max).
A series of polyprenols, ranging in length from 15 to 22 isoprene units, has been isolated from soya beans (Glycine max) and purified by high-pressure liquid chromatography. N.m.r., i.r. and mass spectra of the compounds indicated that they are alpha-saturated polyprenols of the dolichol type. The amount present in dry seeds was about 9 mg/100 g, whereas dolichyl phosphate (Dol-P) was present only in trace amounts. Dol-P phosphatase activity was detected in the microsomal fraction of 5-day-old germinating soya-bean cotyledons. The Dol-P phosphatase activity was linear with respect to time and protein concentration and exhibited a broad pH optimum (pH 7-9). Triton X-100 was necessary for significant enzyme activity. Enzyme activity was slightly enhanced by EDTA, whereas dithiothreitol was without effect. An apparent Km of 5 microM was determined for Dol-P. Bivalent metal ions were not required for enzyme activity. A number of phosphorylated compounds tested as enzyme substrates (including a number of nucleoside phosphates, glucose 6-phosphate, sodium beta-glycerophosphate and Na4P2O7) did not compete with [1-3H]Dol-P as substrate. A number of phospholipids were also tested for their ability to act as Dol-P phosphatase substrates. At 1 mM concentration, phosphatidylcholine, phosphatidylethanolamine, phosphatidic acid and lysophosphatidic acid each inhibited enzymic activity. However, at 0.1 mM concentration, phosphatidylcholine and phosphatidylethanolamine were slightly stimulatory, whereas phosphatidic acid and lysophosphatidic acid were still inhibitory. Phosphatidic acid showed competitive inhibition.


Properties of the P-type ATPases encoded by the copAP operons of Helicobacter pylori and Helicobacter felis.
The cop operons of Helicobacter pylori and Helicobacter felis were cloned by gene library screening. Both operons contain open reading frames for a P-type ion pump (CopA) with homology to Cd2+ and Cu2+ ATPases and a putative ion binding protein (CopP), the latter representing a CopZ homolog of the copYZAB operon of Enterococcus hirae. The predicted CopA ATPases contained an N-terminal GMXCXXC ion binding motif and a membrane-associated CPC sequence. A synthetic N-terminal peptide of the H. pylori CopA ATPase bound to Cu2+ specifically, and gene disruption mutagenesis of CopA resulted in an enhanced growth sensitivity of H. pylori to Cu2+ but not to other divalent cations. As determined experimentally, H. pylori CopA contains four pairs of transmembrane segments (H1 to H8), with the ATP binding and phosphorylation domains lying between H6 and H7, as found for another putative transition metal pump of H. pylori (K. Melchers, T. Weitzenegger, A. Buhmann, W. Steinhilber, G. Sachs, and K. P. Schäfer, J. Biol. Chem. 271:446-457, 1996). The corresponding transmembrane segments of the H. felis CopA pump were identified by hydrophobicity analysis and via sequence similarity. To define functional domains, similarly oriented regions of the two enzymes were examined for sequence identity. Regions with high degrees of identity included the N-terminal Cu2+ binding domain, the regions of ATP binding and phosphorylation in the energy transduction domain, and a transport domain consisting of the last six transmembrane segments with conserved cysteines in H4, H6, and H7. The data suggest that H. pylori and H. felis employ conserved mechanisms of ATPase-dependent copper resistance.


[A study of the burnout syndrome in medical personnel of a general hospital].
We studied the existence of the burnout syndrome, the state of general health and their relation with sociodemographic and work factors in the sanitary personnel of a Spanish general hospital. We established three professional categories A: physicians, B: nurses and technicians of a similar level, C: nurses' aides. The sample studied includes a total of 363 individuals, both male and female. Of them 102 of category A, 168 of category B and 93 of category C. The instruments used for evaluation were a sociodemographic questionnaire, the Maslach Burnout Inventory (M.B.I.) and the Goldberg's General Health Questionnaire-28 (G.H.G. -28). The results showed the existence of a middle degree of burnout in the sample studied not related neither with the profesional category nor with the sociodemographic factors studied. Some correlations were found between the burnout degree and general health with seniority, daily leisure time, smoking habits and use of analgesics and tranquillizers. 29.25% of the total sample presented bad general health (23% of group A, 30.7% of group B and 33.3% of group C).


Workers' perceptions of workplace safety: an African perspective.
This study investigated workers' perceptions of workplace safety in an African work environment, specifically in Ghanaian work places. Workers' safety perceptions were examined with Hayes et al.'s. (1998) Work Safety Scale. Comparative analyses were done between high- and low-accident groups, and t tests were employed to test for differences of statistical significance. Relative to their colleagues in the low-accident category, workers in the high-accident category exhibited negative perceptions on safety. They had negative perceptions regarding work safety, safety programmes, supervisors, and co-workers' contributions. Besides, they expressed less job satisfaction and were less committed to safety management policies. Perceptions regarding management's attitude towards safety between the 2 groups were not of statistical significance. The analyses provided an explanation for the cause of a substantial portion of the high rate of industrial accidents in Ghana's work environment. Implications for safety management are discussed.


US Perspectives in the Management of Psoriasis and Psoriatic Arthritis: Patient and Physician Results from the Population-Based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) Survey.
The Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP), a population-based survey of patients, dermatologists, and rheumatologists, was conducted for better understanding of the unmet needs of psoriasis and psoriatic arthritis (PsA) patients. To report results from US physicians and patients. Adults were contacted by household telephone, using random digit dialing, and asked to participate if they had ever been diagnosed with psoriasis or PsA. Physicians were identified through national databases and contacted through random sampling methods. In the USA, 1005 patients, 101 dermatologists, and 100 rheumatologists were surveyed. PsA had been diagnosed in 270 patients (26.9%). Of those with psoriasis alone, fewer than 60% (versus 85.6% of PsA patients) had seen a healthcare provider within 12 months. Joint pain was reported by 51.8% of psoriasis patients without a diagnosis of PsA, and 37.6% of dermatologists cited their greatest challenge in managing PsA patients as being differentiating PsA from other arthritic diseases. Itching was reported by 36% of psoriasis patients versus 12% of dermatologists as the most important factor contributing to disease severity. Patients reported lower rates of current treatment than did dermatologists and rheumatologists. Conventional oral and biologic therapies were used by 24.9 and 17.7% of patients, respectively. Among patients who had received injectable biologics, treatment dissatisfaction was related to long-term safety/tolerability, injection-related anxiety/fear, and cost. This large, population-based survey identified unmet needs in the management of psoriasis and PsA patients in the USA, including assessment of disease severity, PsA diagnosis, undertreatment, and satisfaction with therapy.


Contralateral acupuncture versus ipsilateral acupuncture in the rehabilitation of post-stroke hemiplegic patients: a systematic review.
Contralateral acupuncture (CAT) involves inserting needles in the meridian on the side opposite the disease location and is often used in post-stroke rehabilitation. The aim of this systematic review is to summarize and critically evaluate the evidence for and against the effectiveness of CAT for post-stroke rehabilitation as compared to ipsilateral acupuncture (IAT). Seventeen databases were searched from their inceptions through June 2010. Prospective clinical trials were included if CAT was tested as the sole treatment or as an adjunct to other treatments for post-stroke rehabilitation and compared to IAT. Eight randomized clinical trials (RCTs) met our inclusion criteria. Four of them reported favorable effects of CAT compared to IAT for at least one outcome. A meta-analysis showed superior effects of CAT compared to IAT on recovery rate (n = 361; risk ratio (RR), 1.12; 95% confidence intervals (CIs), 1.04 to 1.22, P = 0.005). Subgroup analysis also showed favorable effects of using CAT on patients with cerebral infarction (n = 261; RR, 1.15; 95% CIs, 1.04 to 1.27, P = 0.006). Further analysis including patients with cerebral infarction and intracranial hemorrhage, however, failed to show these advantages (n = 100; RR, 1.11; 95% CIs, 0.85 to 1.46, P = 0.43). The results of our systematic review and meta-analysis suggest that there is limited evidence for CAT being superior to IAT in the treatment of cerebral infarction. The total number of RCTs included in our analysis was low, however, and the RCTs included had a high risk of bias. Future RCTs appear to be warranted.


Impact of smoking on mortality in 80-year-old Japanese from the general population.
It is well known that cigarette smoking is the main health hazard in middle-aged people.However, data regarding smoking and health in old-aged people are limited, especially in the Japanese population. The present study aimed to investigate the influence of smoking on mortality in the elderly Japanese population. A cohort of 690 individuals of 80 years of age were categorized into 3 groups: non-smokers, ex-smokers and current smokers. The adjusted mortality after 4 years was compared among the 3 groups. The possible influence of smoking status on the cause of death was also investigated. The overall mortality was significantly higher in males [relative risk (RR): 2.3, 95% confidence interval (CI): 1.0-5.2] and females (RR: 4.2, 95% CI: 1.9-9.5) in the current-smoker group than in the non-smoker group. The risk of any-cause mortality in the ex-smoker group was not statistically different from that in the non-smoker group. In males, current smokers died of cancer more frequently than non-smokers (RR: 10.7, 95% CI: 1.3-90.8). Cardiovascular disease was a significant cause of death in female current smokers (RR: 5.2, 95% CI: 1.6-16.9). This difference in mortality was not observed between groups of non-smokers and ex-smokers of both genders. In male smokers, there was a positive relationship between the daily amount of consumed cigarettes and overall mortality. Smokers should be encouraged to stop smoking, since habitual smoking increases the risk of mortality even in old age.


Impact of a quality improvement intervention on neonatal mortality in a regional hospital in Burkina Faso.
The neonatal period is the most vulnerable time in terms of a child's survival, with mortality during this period accounting for approximately half of the deaths before the age of 5 years. The Neonatal Essential Survival Technology (NEST) project is a program aiming to reduce mortality by improving the quality of neonatal care in sub-Saharan Africa. This study presents the evaluation of the first phase of the NEST intervention program at Saint Camille Hospital Ouagadougou (HOSCO), Burkina Faso, in terms of the reduction in neonatal mortality. This is a retrospective analysis, based on "pre-intervention" data collected in 2015, and "post-intervention" data collected in 2018, including all infants admitted to the neonatal unit of HOSCO. The intervention period (2016 and 2017) comprised a structured quality improvement process conducted by a multidisciplinary working group that focused on improving infrastructure, equipment, training and use of clinical protocols, team working within the neonatal unit and with other hospital departments, and communication with referring healthcare facilities. Mortality data were compared pre- vs. post-intervention using a logistic regression model. The analysis included 1427 infants in the pre-intervention period, and 819 post-intervention. In both time periods, more than 75% of admissions were infants with low birth weight, and nearly 50% were very low birth weight. Post-intervention, while there was a decrease in overall admission, the proportion of multiple births increased from 20% to 24% (p = .01). The overall mortality rate was 44.9% (641/1427) pre-intervention, and 42.2% (346/819) post-intervention (OR 0.90, 95% confidence interval (CI) 0.76-1.07; p = .23). Adjusting for clinically relevant factors, the intervention was not associated with a change in overall mortality (OR 1.39, 95% CI 0.91-2.12; p = .13), but was associated with a reduced likelihood of mortality in outborn infants compared to inborn infants (OR 0.57, 95% CI 0.36-0.92; p = .02). The first phase of the NEST quality improvement program was associated with a decrease in mortality in outborn infants admitted to the neonatal unit at HOSCO. Long-term assessment is expected to provide a more comprehensive evaluation of the program in a low-income setting.


Role of Nedd4 and ubiquitination of Rous sarcoma virus Gag in budding of virus-like particles from cells.
Rous sarcoma virus (RSV) budding requires an interaction of the L domain within the p2b region of Gag with cellular Nedd4-family E3 ubiquitin protein ligases. Members of our laboratories previously demonstrated that overexpression of a fragment of the chicken Nedd4-like protein (LDI-1 WW) inhibits Gag release in a dominant-negative manner (A. Kikonyogo, F. Bouamr, M. L. Vana, Y. Xiang, A. Aiyar, C. Carter, and J. Leis, Proc. Natl. Acad. Sci. USA 98:11199-11204, 2001). We have now identified the complete 3' end of LDI-1 and determined that it has a C-terminal ubiquitin ligase HECT domain, similar to other Nedd4 family members. While overexpression of the full-length LDI-1 clone (LDI-1 FL) had little effect on Gag budding, an LDI-1 FL mutant with a substitution in the HECT domain catalytic site blocked Gag release, similar to LDI-1 WW. The coexpression of Gag and hemagglutinin-tagged ubiquitin (HA-Ub) resulted in the detection of mono- and polyubiquitinated forms of Gag in cells and mostly monoubiquitinated Gag in virus-like particles (VLPs). When the Nedd4-binding site (L domain) was deleted, ubiquitinated Gag was not detected. Interestingly, the release of Gag with ubiquitin covalently linked to the C terminus (Gag-Ub) was still blocked by LDI-1 WW. To understand the mechanism of this inhibition, we examined cells expressing Gag and LDI-1 WW by electron microscopy. In the presence of LDI-1 WW, VLPs were found in electron-dense inclusion bodies in the cytoplasm of transfected cells. In contrast, when cells that coexpressed Gag-Ub and LDI-1 WW were examined, inclusion bodies were detected but did not contain VLPs. These results indicate that the ubiquitination of Gag is dependent upon Nedd4 binding to the L domain and suggest that Nedd4 has additional functions during RSV release besides the ubiquitination of Gag.


Intranasal interferon alpha 2 for prevention of rhinovirus infection and illness.
In two placebo-controlled, double-blind studies, the prophylactic efficacy of recombinant DNA-produced interferon alpha 2 (IFN-alpha 2) against induced rhinovirus (RV) type 39 infection in susceptible volunteers was assessed. IFN-alpha 2 was given by intranasal drops in either multiple treatments (11.4 X 10(6) IU four times per day for four days) or one treatment daily (42.8 X 10(6) IU once per day for five days) starting before RV type 39 challenge. The efficacy rates of multiple-dose IFN-alpha 2 for preventing infection, virus shedding, and RV type 39-specific colds were 78%, 78%, and 100%, respectively. The corresponding rates for one daily treatment were 45%, 64%, and 75%, respectively. Both dosage regimens were associated with significant reductions in days of virus shedding and nasal mucus production. In the second study, three IFN-alpha 2 recipients developed transient leukopenia (less than 4,000 leukocytes/mm3). The results suggest that intranasal IFN-alpha 2 may prove to be a safe and effective method of preventing rhinovirus infection and illness.


Toward a Unified Description of the Electrostatic Assembly of Microgels and Nanoparticles.
The interplay of soft responsive particles, such as microgels, with nanoparticles (NPs) yields highly versatile complexes that show great potential for applications, ranging from plasmonic sensing to catalysis and drug delivery. However, the microgel-NP assembly process has not been investigated so far at the microscopic level, thus hindering the possibility of designing such hybrid systems a priori. In this work, we combine state-of-the-art numerical simulations with experiments to elucidate the fundamental mechanisms taking place when microgel-NP assembly is controlled by electrostatic interactions and the associated effects on the structure of the resulting complexes. We find a general behavior where, by increasing the number of interacting NPs, the microgel deswells up to a minimum size after which a plateau behavior occurs. This occurs either when NPs are mainly adsorbed to the microgel corona via the folding of the more external chains or when NPs penetrate inside the microgel, thereby inducing a collective reorganization of the polymer network. By varying microgel properties, such as fraction of cross-linkers or charge, as well as NP size and charge, we further show that the microgel deswelling curves can be rescaled onto a single master curve, for both experiments and simulations, demonstrating that the process is entirely controlled by the charge of the whole microgel-NP complex. Our results thus have a direct relevance in fundamental materials science and offer novel tools to tailor the nanofabrication of hybrid devices of technological interest.


Representations of eating and of a nutrition program among female caregivers of children under 5 years old in Tizimin, Yucatan, Mexico.
This study was carried out between January and April 2008 with 14 caregivers of children younger than 5 years residing in Tizimín city, Mexico. It aimed to understand the social representations of eating and the Programa Oportunidades [Opportunity Program] held by caregivers taking into account their social and cultural context. This qualitative investigation with an ethnographic approach was based on participant observation and semi-structured interviews. Two empirical categories emerged: 1) feeding and 2) an aid. The first refers to the caregivers' representation of eating patterns of children younger than 5 years and the second reveals that the program is considered an aid, which favors and helps caregivers to meet part of their needs. The study achieved the proposed objectives since it enabled us to understand caregivers in the complex task of feeding these children and also to propose strategies in several spheres to improve infant nutrition.


It's Getting Hot in Here: Targeting Cancer Stem-like Cells with Hyperthermia.
Cancer stem-like cells (CSCs) are a subset of cancer cells that are resistant to conventional radiotherapy and chemotherapy. As such, CSCs have been recognized as playing a large role in tumor initiation and recurrence. Although hyperthermia is broadly used in cancer treatment either alone or in combination with radio- or chemo-therapy, its potential to target CSCs is not well understood. In this review, we discuss different types of hyperthermia and potential mechanisms of action in cancer treatment, particularly in regards to killing CSCs.


Longitudinal changes of SARA scale in Friedreich ataxia: Strong influence of baseline score and age at onset.
The Scale for Assessment and Rating of Ataxia (SARA) is widely used in different types of ataxias and has been chosen as the primary outcome measure in the European natural history study for Friedreich ataxia (FA). To assess distribution and longitudinal changes of SARA scores and its single items, we analyzed SARA scores of 502 patients with typical-onset FA (<25 years) participating in the 4-year prospective European FA Consortium for Translational Studies (EFACTS). Pattern of disease progression was determined using linear mixed-effects regression models. The chosen statistical model was re-fitted in order to estimate parameters and predict disease progression. Median time-to-change and rate of score progression were estimated using the Kaplan-Meier method and weighted linear regression models, respectively. SARA score at study enrollment and age at onset were the major predictive factors of total score progression during the 4-year follow-up. To a less extent, age at evaluation also influenced the speed of SARA progression, while disease duration did not improve the prediction of the statistical model. Temporal dynamics of total SARA and items showed a great variability in the speed of score increase during disease progression. Gait item had the highest annual progression rate, with median time for one-point score increase of 1 to 2 years. Analyses of statistical properties of SARA suggest a variable sensitivity of the scale at different disease stages, and provide important information for population selection and result interpretation in future clinical trials.


Simultaneous Quantification of Protein Binding Kinetics in Whole Cells with Surface Plasmon Resonance Imaging and Edge Deformation Tracking.
Most drugs work by binding to receptors on the cell surface. Quantification of binding kinetics between drug and membrane protein is an essential step in drug discovery. Current methods for measuring binding kinetics involve extracting the membrane protein and labeling, and both have issues. Surface plasmon resonance (SPR) imaging has been demonstrated for quantification of protein binding to cells with single-cell resolution, but it only senses the bottom of the cell and the signal diminishes with the molecule size. We have discovered that ligand binding to the cell surface is accompanied by a small cell membrane deformation, which can be used to measure the binding kinetics by tracking the cell edge deformation. Here, we report the first integration of SPR imaging and cell edge tracking methods in a single device, and we use lectin interaction as a model system to demonstrate the capability of the device. The integration enables the simultaneous collection of complementary information provided by both methods. Edge tracking provides the advantage of small molecule binding detection capability, while the SPR signal scales with the ligand mass and can quantify membrane protein density. The kinetic constants from the two methods were cross-validated and found to be in agreement at the single-cell level. The variation of observed rate constant between the two methods is about 0.009 s-1, which is about the same level as the cell-to-cell variations. This result confirms that both methods can be used to measure whole-cell binding kinetics, and the integration improves the reliability and capability of the measurement.


Latino men's sexual behavior with transgender persons.
Male-to-female transgender persons are thought to be "vectors" for HIV/STI transmission, yet little quantitative information exists about the risk behavior of their male sexual partners who may serve as a "bridge" for HIV transmission into the general population. As part of an online survey examining the sexual risk behavior of Latino men who have sex with men (N = 1,026), we identified 44 (4%) participants who reported having had sex with a transgender partner. Compared with a randomly selected sub-sample of 200 men who did not report sex with a transgender person, sexual partners of transgender persons were almost three times more likely to have had unprotected sexual intercourse in the last three months. In addition, men who had sex with transgender persons were more likely to be HIV-positive; married, separated, or divorced; identify as bisexual or straight; have sex with women; and live in rural or small town communities. Regression analysis revealed that community size, sexual compulsivity, and having had a transgender partner were independent predictors of unprotected sex. Among Latino men who have sex with men, men with a history of sex with a transgender person appear more likely to be sexually compulsive and at greater risk for HIV and other sexually transmitted infections. These men may, therefore, also serve as a "bridge" for HIV transmission to (as opposed to from) the transgender population.


[Australia antigen in rheumatoid arthritis].
Australian antigen (Au Ag) was first described by Blumberg in the serum of an Australian aborigen. Its main clinical significance is based on the fact of its association with the presence of hepatitis B (Okochi, Nurakami, 1968; Prince, 1968) (9). Almeida (1969) outlines the intervention of immune complexes on the production of the referred illness. Later works show the importance of the type of immunologic response created by Au Ag (2). Alpert et al. (1) (1970) state the possibility that immune complexes developed by Au Ag and anti Au Ag antibodies may produce in patients with hepatitis B other allied manifestations including arthritis. On the basis of similar immunopathological findings (illnesses including immunocomplexes on their production), Au Ag investigation in rheumatoid arthritis (RA) has been the object of several works, whose results reveal certain discrepancies. We have investigated the presence of Au Ag on 70 patients whose diagnostic was RA "classical (according to the judgement of the American Rheumatism Association). We used immunoelectrophoresis (counter immunoelectrophoresis-CIEP-) and radioimmunoassay (RIA) techniques. We prepared individual records including clinical, epidemic, biochemical and personal data. Au Ag investigation both through different techniques gave negative results in 70 cases, of which only four referred a possible previous hepatitis B clinic history, not showing during the investigation suggestive clinical data of hepatitis or biochemical alterations. Panus et al. (1970) (5), Desche-Labarte et al. (1972), Trempo (1972), Burrel (1973) (6), Serré et al. (1973) (8), obtained negative results in the matter, with similar or lower casuistics than ours. Notwithstanding Roqués et al. (1975) (7), in 300 cases of RA showed the presence of Au Ag in a significant number of cases (5%) as compared to Au Ag incidence in the French population (estimated in about 0.22%) (6). However, Roqués did not find in their Au Ag positive cases any evidence which enables to think that this antigen has played an important role on the origin and development of the rheumatic illness. These important discrepancies may be due to different reasons: a) Use of different techniques for Au Ag detection. b) The transitory character of the presence of Au Ag in the serum. c) Important differences in the antigen geographic distribution. d) Previous hepatitis B. There are som other factors which have attained importance recently, as a consequence of the broad epidemiological studies carried out. So, Au Ag increased incidence has been found--statistically significant--on groups of persons who have been submitted to several surgical interventions and/or have needed repeated hospitalizations or reiterated blood transfusions (6). These three conditions--especially the first two--are accomplished in an illness with chronic and invalidating characteristics as RA...


Incidence of intracranial tumors following hospitalization for head injuries (Denmark).
The incidence of brain and other intracranial tumors following head trauma was evaluated in a cohort of 228,055 Danish residents hospitalized because of concussion, fractured skull, or other head injury between 1977 and 1992 and followed for an average of eight years (maximum, 17 years). Traffic accidents, falls, and sports-related incidents were the usual causes of the injury. Malignant and benign neoplasms were identified by linking the study roster with records of the Danish Cancer Registry for the years 1977 to 1993. This approach precludes differential reporting of injuries by study participants as an explanation for any associations seen. Intracranial tumors of the nervous system occurred more often than expected based on incidence rates for the Danish population; however, most of the excess occurred during the first year after the injury and likely was due to the detection of tumors that were present before the injury occurred. Excluding the first year of follow-up, the standardized incidence ratio (SIR) was 1.15 (95 percent confidence interval [CI] = 0.99-1.32). The same general temporal pattern was seen for the major subtypes of brain tumor as for all types combined. SIRs after the first year were 1.0 for glioma (CI = 0.8-1.2), 1.2 for meningioma (CI = 0.8-1.7), and 0.8 for neurilemmoma (CI = 0.4-1.7). However, hemangioblastoma and hemangioma were more frequent than expected, based on 15 cases (SIR = 2.6, CI = 1.4-4.2). Results indicate that head trauma causes, at most, a small increase in the overall risk of brain tumors during the ensuing 15 years; however, a possible association with intracranial vascular tumors warrants further evaluation.


The importance of phylogeny to the study of phenological response to global climate change.
Climate change has resulted in major changes in the phenology--i.e. the timing of seasonal activities, such as flowering and bird migration--of some species but not others. These differential responses have been shown to result in ecological mismatches that can have negative fitness consequences. However, the ways in which climate change has shaped changes in biodiversity within and across communities are not well understood. Here, we build on our previous results that established a link between plant species' phenological response to climate change and a phylogenetic bias in species' decline in the eastern United States. We extend a similar approach to plant and bird communities in the United States and the UK that further demonstrates that climate change has differentially impacted species based on their phylogenetic relatedness and shared phenological responses. In plants, phenological responses to climate change are often shared among closely related species (i.e. clades), even between geographically disjunct communities. And in some cases, this has resulted in a phylogenetically biased pattern of non-native species success. In birds, the pattern of decline is phylogenetically biased but is not solely explained by phenological response, which suggests that other traits may better explain this pattern. These results illustrate the ways in which phylogenetic thinking can aid in making generalizations of practical importance and enhance efforts to predict species' responses to future climate change.


Polaronic transport and current blockades in epitaxial silicide nanowires and nanowire arrays.
Crystalline micrometer-long YSi2 nanowires with cross sections as small as 1 × 0.5 nm(2) can be grown on the Si(001) surface. Their extreme aspect ratios make electron conduction within these nanowires almost ideally one-dimensional, while their compatibility with the silicon platform suggests application as metallic interconnect in Si-based nanoelectronic devices. Here we combine bottom-up epitaxial wire synthesis in ultrahigh vacuum with top-down miniaturization of the electrical measurement probes to elucidate the electronic conduction mechanism of both individual wires and arrays of nanowires. Temperature-dependent transport through individual nanowires is indicative of thermally assisted tunneling of small polarons between atomic-scale defect centers. In-depth analysis of complex wire networks emphasize significant electronic crosstalk between the nanowires due to the long-range Coulomb fields associated with polaronic charge fluctuations. This work establishes a semiquantitative correlation between the density and distributions of atomic-scale defects and resulting current-voltage characteristics of nanoscale network devices.


Isolation and characterization of the RAD3 gene of Saccharomyces cerevisiae and inviability of rad3 deletion mutants.
The RAD3 gene of Saccharomyces cerevisiae is required for nicking of DNA containing pyrimidine dimers or interstrand crosslinks. We have cloned the RAD3 gene and physically mapped it to 2.6 kilobase of DNA. A DNA segment of the cloned RAD3 insert was ligated into plasmid YIp5, which transforms yeast by homologous integration, and shown to integrate at the RAD3 site in chromosome V, thus verifying the cloned DNA segment to be the RAD3 gene and not a suppressor. The RAD3 gene encodes a 2.5-kilobase mRNA, extending between the Kpn I site and the Sau3A1/BamHI fusion junction in plasmid pSP10, and the direction of transcription has been determined. The 2.5-kilobase transcript could encode a protein of about 90,000 daltons. We also show the deletions of the RAD3 gene to be recessive lethals, indicating that the RAD3 gene plays an important role in other cellular processes in addition to incision of damaged DNA.


Integrative transcriptome and metabolome analysis reveals the mechanisms of light-induced pigmentation in purple waxy maize.
Waxy maize, mainly consumed at the immature stage, is a staple and vegetable food in Asia. The pigmentation in the kernel of purple waxy maize enhances its nutritional and market values. Light, a critical environmental factor, affects anthocyanin biosynthesis and results in pigmentation in different parts of plants, including in the kernel. SWL502 is a light-sensitive waxy maize inbred line with purple kernel color, but the regulatory mechanism of pigmentation in the kernel resulting in purple color is still unknown. In this study, cyanidin, peonidin, and pelargonidin were identified as the main anthocyanin components in SWL502, evaluated by the ultra-performance liquid chromatography (UPLC) method. Investigation of pigment accumulation in the kernel of SWL502 was performed at 12, 17, and 22 days after pollination (DAP) under both dark and light treatment conditions via transcriptome and metabolome analyses. Dark treatment affected genes and metabolites associated with metabolic pathways of amino acid, carbohydrate, lipid, and galactose, biosynthesis of phenylpropanoid and terpenoid backbone, and ABC transporters. The expression of anthocyanin biosynthesis genes, such as 4CL2, CHS, F3H, and UGT, was reduced under dark treatment. Dynamic changes were identified in genes and metabolites by time-series analysis. The genes and metabolites involved in photosynthesis and purine metabolism were altered in light treatment, and the expression of genes and metabolites associated with carotenoid biosynthesis, sphingolipid metabolism, MAPK signaling pathway, and plant hormone signal transduction pathway were induced by dark treatment. Light treatment increased the expression level of major transcription factors such as LRL1, myc7, bHLH125, PIF1, BH093, PIL5, MYBS1, and BH074 in purple waxy maize kernels, while dark treatment greatly promoted the expression level of transcription factors RVE6, MYB4, MY1R1, and MYB145. This study is the first report to investigate the effects of light on waxy maize kernel pigmentation and the underlying mechanism at both transcriptome and metabolome levels, and the results from this study are valuable for future research to better understand the effects of light on the regulation of plant growth.


History, Rats, Fleas, and Opossums: The Ascendency of Flea-Borne Typhus in the United States, 1910-1944.
Flea-borne typhus, due to Rickettsia typhi and Rickettsia felis, is an infection causing fever, headache, rash, hepatitis, thrombocytopenia, and diverse organ manifestations. Although most cases are self-limited, 26%-28% have complications and up to one-third require intensive care. Flea-borne typhus was recognized as an illness similar to epidemic typhus, but having a milder course, in the Southeastern United States and TX from 1913 into the 1920s. Kenneth Maxcy of the US Public Health Service (USPHS) first described the illness in detail and proposed a rodent reservoir and an arthropod vector. Other investigators of the USPHS (Eugene Dyer, Adolph Rumreich, Lucius Badger, Elmer Ceder, William Workman, and George Brigham) determined that the brown and black rats were reservoirs and various species of fleas, especially the Oriental rat flea, were the vectors. The disease was recognized as a health concern in the Southern United States in the 1920s and an increasing number of cases were observed in the 1930s and 1940s, with about 42,000 cases reported between 1931-1946. Attempts to control the disease in the 1930s by fumigation and rat proofing and extermination were unsuccessful. The dramatic increase in the number of cases from 1930 through 1944 was due to: the diversification of Southern agriculture away from cotton; the displacement of the smaller black rat by the larger brown rat in many areas; poor housing conditions during the Great Depression and World War II; and shortages of effective rodenticides and insecticides during World War II.