A high-throughput, precipitating colorimetric sandwich ELISA microarray for Shiga toxins.
Shiga toxins 1 and 2 (Stx1 and Stx2) from Shiga toxin-producing E. coli (STEC) bacteria were simultaneously detected with a newly developed, high-throughput antibody microarray platform. The proteinaceous toxins were immobilized and sandwiched between biorecognition elements (monoclonal antibodies) and pooled horseradish peroxidase (HRP)-conjugated monoclonal antibodies. Following the reaction of HRP with the precipitating chromogenic substrate (metal enhanced 3,3-diaminobenzidine tetrahydrochloride or DAB), the formation of a colored product was quantitatively measured with an inexpensive flatbed page scanner. The colorimetric ELISA microarray was demonstrated to detect Stx1 and Stx2 at levels as low as ~4.5 ng/mL within ~2 h of total assay time with a narrow linear dynamic range of ~1-2 orders of magnitude and saturation levels well above background. Stx1 and/or Stx2 produced by various strains of STEC were also detected following the treatment of cultured cells with mitomycin C (a toxin-inducing antibiotic) and/or B-PER (a cell-disrupting, protein extraction reagent). Semi-quantitative detection of Shiga toxins was demonstrated to be sporadic among various STEC strains following incubation with mitomycin C; however, further reaction with B-PER generally resulted in the detection of or increased detection of Stx1, relative to Stx2, produced by STECs inoculated into either axenic broth culture or culture broth containing ground beef.


Pulmonary cryptococcosis in patients without HIV infection.
To further elucidate the diagnostic and therapeutic approaches to patients with pulmonary cryptococcosis who are not HIV-infected. All of the patients without HIV infection who received care at two Midwest hospitals between January 1986 and February 1996 and had a respiratory isolate of Cryptococcus neoformans. The medical records of the study patients were reviewed for demographic data, host immune status, respiratory symptoms, diagnostic studies, treatment, and follow-up. Forty-two patient presentations comprised the overall study group. Thirty-six patients (85.7%) had no evidence of dissemination, and six patients (14.3%) had disseminated disease. Seven of the 36 patient presentations were definitive pulmonary cryptococcosis, 15 were presumptive disease, and 14 were colonization with C neoformans. Neither the baseline demographic parameters nor the immune status appeared to discriminate the patients with disease from the patients with colonization. A serum cryptococcal antigen (sCRAG) was positive for 7 of 18 patients, 3 of whom were proven by culture to have a disseminated infection. A negative sCRAG was observed in 11 patients, one of whom had proven dissemination. Fifteen patients underwent a lumbar puncture as part of their evaluation, and cryptococcal meningitis was diagnosed in three of these patients, all of whom had positive blood cultures for C neoformans. The majority of the patients did not receive antifungal therapy. In the majority of the patients, the lung appeared to be the sole organ involved, and a workup for systemic infection was rarely helpful. A positive sCRAG was not specific for dissemination. Antifungal therapy should be reserved for symptomatic patients, for patients with a positive sCRAG, and for patients with underlying immunosuppression.


Sedentary behaviour among general practitioners: a systematic review.
Sedentary behaviour is when someone is awake, in a sitting, lying or reclining posture and is an independent risk factor for multiple causes of morbidity and mortality. A dose-response relationship has been demonstrated, whereby increasing sedentary time corresponds with increasing mortality rate. This study aimed to identify current levels of sedentary behaviour among General Practitioners (GPs), by examining and synthesising how sedentary behaviour has been measured in the primary care literature. A systematic review was conducted to identify studies relating to levels of sedentary behaviour among GPs. Searches were performed using Medline®, Embase®, PscycINFO, Web of Science and the Cochrane Library, from inception of databases until January 2020, with a subsequent search of grey literature. Articles were assessed for quality and bias, with extraction of relevant data. The search criteria returned 1707 studies. Thirty four full texts were reviewed and 2 studies included in the final review. Both were cross-sectional surveys using self-reported estimation of sedentary time within the International Physical Activity Questionnaire (IPAQ). Keohane et al. examined GP trainees and GP trainers in Ireland. 60% reported spending in excess of 7 h sitting each day, 24% between 4 and 7 h, and 16% less than or equal to 4 h. Suija et al. examined female GPs in Estonia. The mean reported daily sitting time was 6 h and 36 min, with 56% sitting for over 6 h per day. Both studies were of satisfactory methodological quality but had a high risk of bias. There is a paucity of research examining current levels of sedentary behaviour among GPs. Objective data is needed to determine GPs' current levels of sedentary behaviour, particularly in light of the increase in remote consulting as a result of the COVID-19 pandemic.


Sagnac interferometer based flat-top birefringent interleaver.
We propose and demonstrate a novel Sagnac interferometer based flat-top birefringent optical interleaver employing a ring-cavity as a phase-shift element. The Sagnac interferometer with birefringent crystals provides the optical path difference for interference between the two orthogonal polarization components and the ring-cavity provides the phase shifts needed to achieve a flat-top spectral passband at the output. Fresnel reflections at the prism-air interface of the ring cavity are employed to obtain the desired phase shifts so that highly accurate thin-film coatings are not needed. The Sagnac interferometer based interleaver in a 25-GHz channel spacing (0.2 nm) application exhibits a 0.5-dB passband larger than 0.145 nm, a 25-dB stop band greater than 0.145 nm, and a channel isolation higher than 36 dB over the entire C-band. The superior performance is accompanied with a group velocity dispersion and ripples that can be compensated by using dispersion compensators. (c)2006 Optical Society of America.


[The combination of neoadjuvant chemoradiotherapy and epidermal growth factor receptor inhibitors in the treatment of rectal adenocarcinoma].
Rectal adenocarcinoma, in contrast to colorectal carcinoma, is typical of its high local reccurence rate. Radiotherapy is proved to reduce the incidence of recurrences. Neoadjuvant chemoradiotherapy demonstrated better treatment results than adjuvant chemoradiotherapy. Standard cytotoxic agents involved in combination therapy are 5- flurouracil or capecitabin. Epidermal growth factor receptor (EGFR) is supposed to play an important role in cell- cycle regulation, proliferation, differentiation, and surviving of normal epithelial tissues. EGFR overexpression in patients with rectal adenocarcinoma is associated with radioresistance of malignant tissues, lower rates of patological complete response after neoadjuvant chemoradiation and generally poor survival. There are many clinical studies describing combination of neoadjuvant chemoradiotherapy with EGFR inhibitors, however, this regimen has not gained an acceptance as a standard of treatmentment.


The zebrafish young mutation acts non-cell-autonomously to uncouple differentiation from specification for all retinal cells.
Embryos from mutagenized zebrafish were screened for disruptions in retinal lamination to identify factors involved in vertebrate retinal cell specification and differentiation. Two alleles of a recessive mutation, young, were isolated in which final differentiation and normal lamination of retinal cells were blocked. Early aspects of retinogenesis including the specification of cells along the inner optic cup as retinal tissue, polarity of the retinal neuroepithelium, and confinement of cell divisions to the apical pigmented epithelial boarder were normal in young mutants. BrdU incorporation experiments showed that the initiation and pattern of cell cycle withdrawal across the retina was comparable to wild-type siblings; however, this process took longer in the mutant. Analysis of early markers for cell type differentiation revealed that each of the major classes of retinal neurons, as well as non-neural Müller glial cells, are specified in young embryos. However, the retinal cells fail to elaborate morphological specializations, and analysis of late cell-type-specific markers suggests that the retinal cells were inhibited from fully differentiating. Other regions of the nervous system showed no obvious defects in young mutants. Mosaic analysis demonstrated that the young mutation acts non-cell-autonomously within the retina, as final morphological and molecular differentiation was rescued when genetically mutant cells were transplanted into wild-type hosts. Conversely, differentiation was prevented in wild-type cells when placed in young mutant retinas. Mosaic experiments also suggest that young functions at or near the cell surface and is not freely diffusible. We conclude that the young mutation disrupts the post-specification development of all retinal neurons and glia cells.


Abnormalities of endogenous glucagon and insulin in unstable diabetes.
The responses of glucagon, growth hormone, and insulin secretion to the oral administration of glucose and to the intravenous infusion of saline, arginine, and insulin were measured in seven patients who had stable diabetes, eight who had unstable diabetes, and seven healthy volunteers. Hyperglycemia suppressed secretion of glucagon in normal subjects but not in diabetics. The oral glucose and arginine infusion tests demonstrated partial preservation of insulin-secretory ability in stable diabetics and its virxual absence in unstable diabetics. Glucagon responses to arginine infusion were similar in all three groups. In response to hypoglycemia induced by insulin infusion, the concentrations of plasma glucagon increased in normal subjects and, to a lesser extent, in stable diabetics but increased in only two of the unstable diabetics. The impairment in glucagon response during hypoglycemia in diabetics correlated positively with the degree of diabetic instability and insulin deficiency during glucose and arginine testing. The severity of the insulin deficiency also correlated with the degree of diabetic instability. These findings support the hypothesis that inherent abnormalities of insulin and glucagon secretion may account for many of the clinical characteristics of unstable and stable diabetic patients.


Kinetic analysis of segmentation gene interactions in Drosophila embryos.
A major challenge for developmental biologists in coming years will be to place the vast number of newly identified genes into precisely ordered genetic and molecular pathways. This will require efficient methods to determine which genes interact directly and indirectly. One of the most comprehensive pathways currently under study is the genetic hierarchy that controls Drosophila segmentation. Yet, many of the potential interactions within this pathway remain untested or unverified. Here, we look at one of the best-characterized components of this pathway, the homeodomain-containing transcription factor Fushi tarazu (Ftz), and analyze the response kinetics of known and putative target genes. This is achieved by providing a brief pulse of Ftz expression and measuring the time required for genes to respond. The time required for Ftz to bind and regulate its own enhancer, a well-documented interaction, is used as a standard for other direct interactions. Surprisingly, we find that both positively and negatively regulated target genes respond to Ftz with the same kinetics as autoregulation. The rate-limiting step between successive interactions (<10 minutes) is the time required for regulatory proteins to either enter or be cleared from the nucleus, indicating that protein synthesis and degradation rates are closely matched for all of the proteins studied. The matching of these two processes is likely important for the rapid and synchronous progression from one class of segmentation genes to the next. In total, 11 putative Ftz target genes are analyzed, and the data provide a substantially revised view of Ftz roles and activities within the segmentation hierarchy.


Frac-seq reveals isoform-specific recruitment to polyribosomes.
Pre-mRNA splicing is required for the accurate expression of virtually all human protein coding genes. However, splicing also plays important roles in coordinating subsequent steps of pre-mRNA processing such as polyadenylation and mRNA export. Here, we test the hypothesis that nuclear pre-mRNA processing influences the polyribosome association of alternative mRNA isoforms. By comparing isoform ratios in cytoplasmic and polyribosomal extracts, we determined that the alternative products of ∼30% (597/1954) of mRNA processing events are differentially partitioned between these subcellular fractions. Many of the events exhibiting isoform-specific polyribosome association are highly conserved across mammalian genomes, underscoring their possible biological importance. We find that differences in polyribosome association may be explained, at least in part by the observation that alternative splicing alters the cis-regulatory landscape of mRNAs isoforms. For example, inclusion or exclusion of upstream open reading frames (uORFs) in the 5'UTR as well as Alu-elements and microRNA target sites in the 3'UTR have a strong influence on polyribosome association of alternative mRNA isoforms. Taken together, our data demonstrate for the first time the potential link between alternative splicing and translational control of the resultant mRNA isoforms.


In vitro model for the study of the dissociation of increasing antigenemia and decreasing DNAemia and viremia during treatment of human cytomegalovirus infection with ganciclovir in transplant recipients.
The paradox phenomenon (i.e., the dissociation of increasing antigenemia and decreasing DNAemia and viremia) that occurs during treatment of human cytomegalovirus (HCMV) infections with ganciclovir (Gcv), in transplant recipients, was investigated by use of an in vitro model for the study of interactions between polymorphonuclear leukocytes and endothelial cells. The paradox phenomenon was reproduced in vitro in the presence of Gcv and, to a much lesser extent, in the presence of cidofovir, but not in the presence of foscarnet. The pathogenetic basis for such a paradox response was found, by use of drug concentrations in the range of 90%-99% of the inhibitory dose, to rely on the partial synthesis of HCMV phosphoprotein 65. The opposite situation (i.e., the simultaneous increase of antigenemia, viremia, and DNAemia), which is observed in clinical conditions associated with inefficacy of treatment due to drug-resistant strains, was also reproduced in vitro by use of drug-resistant HCMV strains. The conclusion for clinicians is that antiviral therapy must be changed only in the latter case.


Pregnancy after treatment of breast cancer--a population-based study on behalf of Danish Breast Cancer Cooperative Group.
Estrogen is an established growth factor in breast cancer and it has been hypothesized that pregnancy associated estrogens may increase the risk of recurrence of breast cancer. In 1997 we published a population-based Danish study indicating no negative prognostic effect of pregnancy after breast cancer treatment. The present study is a ten-year update. Danish Breast Cancer Cooperative Group has since 1977 collected population-based data on tumour characteristics, treatment regimes, and follow-up status on Danish women with breast cancer. Pregnancy history was added from the Danish Civil Registration System, the National Birth Registry, and the National Induced Abortion registry. Cox regression was used to estimate the risk ratio of dying among women with a pregnancy after breast cancer treatment compared with women without such experience. In all, 10 236 women with primary breast cancer aged 45 years or less at the time of diagnosis were followed for 95 616 person years. Among these, 371 women experienced pregnancy after treatment of breast cancer. In a multivariate analysis that included age at diagnosis, stage of disease, and pregnancy history prior to diagnosis, women who had a full-term pregnancy subsequent to breast cancer treatment were found to have a reduced risk of dying (relative risk: 0.73; 95% confidence interval: 0.54-0.99) compared with other women with breast cancer. The effect was not significantly modified by age at diagnosis, tumour size, nodal status, or pregnancy history before diagnosis of breast cancer. Neither spontaneous abortions nor induced abortions subsequent to breast cancer treatment had a negative impact on prognosis. In line with our previous study, but based on more than twice the patient material, we found no evidence that a pregnancy after treatment of breast cancer has a negative influence the prognosis.


Complications leading to surgery after breast implantation.
Local complications that require additional surgical procedures are an important problem for women with breast implants. We studied 749 women who lived in Olmsted County, Minnesota, and received a first breast implant at the Mayo Clinic between 1964 and 1991. We identified complications that occurred after the initial procedure and after any subsequent implantation. A complication was defined as a surgical procedure performed for any of the following reasons: capsular contracture; rupture of the implant; hematoma or bleeding; infection or seroma of the wound; chronic pain; extrusion, leakage, or sweating of the implant; necrosis of the nipple, areola, or flap; malfunction of the filler port of a tissue expander; and wound dehiscence. During follow-up (mean, 7.8 years; range, 0 to 25.8), 208 (27.8 percent) of the women underwent 450 additional implant-related surgical procedures. Ninety-one (20.2 percent) were anticipated, staged procedures or were done because the patient requested a size change or aesthetic improvement, and 359 procedures (79.8 percent) had at least one clinical indication (thus constituting a complication). Complications occurred in 178 (23.8 percent) of the 749 women and involved 274 (18.8 percent) of the 1454 breasts with implants and 321 (18.8 percent) of the 1703 implants. The most frequent problem was capsular contraction (272 cases), followed by rupture of the implant (60), hematoma (55), and wound infection (23). The rate of complications was significantly lower (P<0.001) among women with cosmetic implants (6.5 percent at one year, 12 percent at five years) than among women who underwent implantation after mastectomy for breast cancer (21.8 percent at one year, 34 percent at five years) or prophylactic mastectomy (17.3 percent at one year, 30.4 percent at five years). Women who have had breast implantation frequently experience local complications during the subsequent five years. Complications were significantly less frequent among patients who received implants for cosmetic reasons than among those who received implants after mastectomy for cancer or for cancer prophylaxis.


Energy Transfer between Tm-Doped Upconverting Nanoparticles and a Small Organic Dye with Large Stokes Shift.
Lanthanide-doped upconverting nanoparticles (UCNP) are being extensively studied for bioapplications due to their unique photoluminescence properties and low toxicity. Interest in RET applications involving UCNP is also increasing, but due to factors such as large sizes, ion emission distributions within the particles, and complicated energy transfer processes within the UCNP, there are still many questions to be answered. In this study, four types of core and core-shell NaYF₄-based UCNP co-doped with Yb3+ and Tm3+ as sensitizer and activator, respectively, were investigated as donors for the Methyl 5-(8-decanoylbenzo[1,2-d:4,5-d']bis([1,3]dioxole)-4-yl)-5-oxopentanoate (DBD-6) dye. The possibility of resonance energy transfer (RET) between UCNP and the DBD-6 attached to their surface was demonstrated based on the comparison of luminescence intensities, band ratios, and decay kinetics. The architecture of UCNP influenced both the luminescence properties and the energy transfer to the dye: UCNP with an inert shell were the brightest, but their RET efficiency was the lowest (17%). Nanoparticles with Tm3+ only in the shell have revealed the highest RET efficiencies (up to 51%) despite the compromised luminescence due to surface quenching.


[Iron, copper and molybdenum metabolism under different conditions of ultraviolet irradiation].
The paper carries information on the influence exerted by different conditions of ultraviolet radiation on the metabolism of copper, molibdenum and iron. The results made available showed that prophylactic doses of UV-irradiation (100-400 microerg/cm2 per day) reduced elimination of copper and iron from the organism; made for their mobilization from the repository (liver), led to their higher level in hemopoietic and other organs and improved blood formation. The UV-deficit and UV-excess led to a poorer utilization of copper and iron by the organism. Under corresponding climatic conditions it is necessary, therefore, to raise the iron and copper content in the diurnal food ration.


Clinical Characteristics Associated with Return Visits to the Emergency Department after COVID-19 Diagnosis.
Patients diagnosed with coronavirus disease 2019 (COVID-19) require significant healthcare resources. While published research has shown clinical characteristics associated with severe illness from COVID-19, there is limited data focused on the emergency department (ED) discharge population. We performed a retrospective chart review of all ED-discharged patients from Wake Forest Baptist Health and Wake Forest Baptist Health Davie Medical Center between April 25-August 9, 2020, who tested positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) from a nasopharyngeal swab using real-time reverse transcription polymerase chain reaction (rRT-PCR) tests. We compared the clinical characteristics of patients who were discharged and had return visits within 30 days to those patients who did not return to the ED within 30 days. Our study included 235 adult patients who had an ED-performed SARS-CoV-2 rRT-PCR positive test and were subsequently discharged on their first ED visit. Of these patients, 57 (24.3%) had return visits to the ED within 30 days for symptoms related to COVID-19. Of these 57 patients, on return ED visits 27 were admitted to the hospital and 30 were not admitted. Of the 235 adult patients who were discharged, 11.5% (27) eventually required admission for COVID-19-related symptoms. With 24.3% patients having a return ED visit after a positive SARS-CoV-2 test and 11.5% requiring eventual admission, it is important to understand clinical characteristics associated with return ED visits. We performed multivariate logistic regression analysis of the clinical characteristics with independent association resulting in a return ED visit, which demonstrated the following: diabetes (odds ratio [OR] 2.990, 95% confidence interval [CI, 1.21-7.40, P = 0.0179); transaminitis (OR 8.973, 95% CI, 2.65-30.33, P = 0.004); increased pulse at triage (OR 1.04, 95% CI, 1.02-1.07, P = 0.0002); and myalgia (OR 4.43, 95% CI, 2.03-9.66, P = 0.0002). As EDs across the country continue to treat COVID-19 patients, it is important to understand the clinical factors associated with ED return visits related to SARS-CoV-2 infection. We identified key clinical characteristics associated with return ED visits for patients initially diagnosed with SARS-CoV-2 infection: diabetes mellitus; increased pulse at triage; transaminitis; and complaint of myalgias.


Autocatalytic Sets and RNA Secondary Structure.
The dominant paradigm in origin of life research is that of an RNA world. However, despite experimental progress towards the spontaneous formation of RNA, the RNA world hypothesis still has its problems. Here, we introduce a novel computational model of chemical reaction networks based on RNA secondary structure and analyze the existence of autocatalytic sub-networks in random instances of this model, by combining two well-established computational tools. Our main results are that (i) autocatalytic sets are highly likely to exist, even for very small reaction networks and short RNA sequences, and (ii) sequence diversity seems to be a more important factor in the formation of autocatalytic sets than sequence length. These findings could shed new light on the probability of the spontaneous emergence of an RNA world as a network of mutually collaborative ribozymes.


Mutations in the holocarboxylase synthetase gene HLCS.
Holocarboxylase synthetase (HLCS) deficiency is an autosomal recessive disorder. HLCS is an enzyme that catalyzes biotin incorporation into carboxylases and histones. Since the first report of the cDNA sequence, 30 mutations in the HLCS gene have been reported. Mutations occur throughout the entire coding region except exons 6 and 10. The types of mutations are one single amino acid deletion, five single nucleotide insertions/deletions, 22 missense mutations, and two nonsense mutations. The only intronic mutation identified thus far is c.1519+5G>A (also designated IVS10+5G>A), which causes a splice error. Several lines of evidence suggest that c.1519+5G>A is a founder mutation in Scandinavian patients. Prevalence of this mutation is about 10 times higher in the Faroe Islands than in the rest of the world. The mutations p.L237P and c.780delG are predominant only in Japanese patients. These are probably founder mutations in this population. Mutations p.R508W and p.V550M are identified in several ethic groups and accompanied with various haplotypes, suggesting that these are recurrent mutations. There is a good relationship between clinical biotin responsiveness and the residual activity of HLCS. A combination of a null mutation and a point mutation that shows less than a few percent of the normal activity results in neonatal onset. Patients who have mutant HLCS with higher residual activity develop symptom after the neonatal period and show a good clinical response to biotin therapy.


Assessment of neutralizing antibodies elicited by a vaccine (Nakayama) strain of Japanese encephalitis virus in Taiwan.
A total of 368 blood specimens were resampled from a serum collection containing 2914 blood samples which were collected by a random sampling in Taiwan in 1991. The plaque reduction neutralization test was applied to evaluate the neutralizing ability to two strains of Japanese encephalitis viruses, i.e. Nakayama (the present vaccine strain) and JE5 (a Taiwan isolate). The result revealed that antibodies against JE virus were present in each stratified age group. Antibody positive rates were both highest in the group older than 70 years although the lowest rates were located in different groups. In addition, the result showed that the immunogenicity potency of the antibody induced by the vaccine strain did not have a good coverage against JE5. The rate of neutralizing antibodies above the level of protective efficacy of the present vaccine was limited as low as 37.93%. Efficacy of the vaccine used at present was apparently not efficient. Consideration of a more promising vaccine may be necessary.


What's at Stake in U.S. Health Reform: A Guide to the Affordable Care Act and Value-Based Care.
The U.S. presidential election of 2016 accentuated the divided perspectives on the Patient Protection and Affordable Care Act of 2010, commonly known as Obamacare. The perspectives included a pledge from then candidate Donald J. Trump to "repeal and replace on day one"; Republican congressional leaders' more temperate suggestions in the first weeks of the Trump administration to "repair" the Affordable Care Act (ACA); and President Trump's February 5, 2017 statement-16 days after inauguration-that a Republican replacement for the ACA may not be ready until late 2017 or 2018. The swirling rhetoric, media attention, and the dizzying rate of U.S. health and payment reforms both within and outside of the ACA makes it difficult for nurses, both United States and globally, to discern which health policy issues are grounded in the ACA and which aspects reflect payer-driven "volume to value" reimbursement changes. Moreover, popular and controversial elements of the ACA-for example, the clause that prohibits insurance carriers to deny coverage to those with preexisting health conditions and the more controversial individual mandate that bears Supreme Court support as a constitutional provision-are paired in ways that might be unclear to those unfamiliar with nuances of insurance rate determination. To support nurses' capacity to maximize their impact on health policy, this overview distills the 906-page ACA into major themes and describes payment reform legislation and initiatives that are external to the ACA. Understanding the political and societal forces that affect health care policy and delivery is necessary for nurses to effectively lead and advocate for the best interests of their patients.


Superior parietal lobule approach for choroid plexus papillomas without preoperative embolization in very young children.
OBJECT Choroid plexus papillomas (CPPs) are rare neoplasms, often found in the atrium of the lateral ventricle of infants, and cause overproduction hydrocephalus. The extensive vascularity and medially located blood supply of these tumors, coupled with the young age of the patients, can make prevention of blood loss challenging. Preoperative embolization has been advocated to reduce blood loss and prevent the need for transfusion, but this mandates radiation exposure and the additional risks of vessel injury and stroke. For these reasons, the authors present their experience using the superior parietal lobule approach to CPPs of the atrium without adjunct therapy. METHODS A retrospective review was conducted of all children who presented to Columbia University/Morgan Stanley Children's Hospital of New York with a CPP in the atrium of the lateral ventricle and who underwent surgery using a superior parietal lobule approach without preoperative embolization. RESULTS Nine children were included, with a median age of 7 months. There were no perioperative complications or new neurological deficits. All patients had intraoperative blood loss of less than 100 ml, with a mean minimum hematocrit of 26.9% (range 19.6%-36.2%). No patients required a blood transfusion. The median follow-up was 39 months, during which time no patient demonstrated residual or recurrent tumor on MRI, nor did any have an increase in ventricular size or require CSF diversion. CONCLUSIONS The superior parietal lobule approach is safe and effective for very young children with CPPs in the atrium of the lateral ventricle. The results suggest that preoperative embolization is not essential to avoid transfusion or achieve overall good outcomes in these patients. This management strategy avoids radiation exposure and the additional risks associated with embolization.


Ultrastructural and physiological responses of potato (Solanum tuberosum L.) plantlets to gradient saline stress.
Salinity is one of the major abiotic stresses that impacts plant growth and reduces the productivity of field crops. Compared to field plants, test tube plantlets offer a direct and fast approach to investigate the mechanism of salt tolerance. Here we examined the ultrastructural and physiological responses of potato (Solanum tuberosum L. c.v. "Longshu No. 3") plantlets to gradient saline stress (0, 25, 50, 100, and 200 mM NaCl) with two consequent observations (2 and 6 weeks, respectively). The results showed that, with the increase of external NaCl concentration and the duration of treatments, (1) the number of chloroplasts and cell intercellular spaces markedly decreased, (2) cell walls were thickened and even ruptured, (3) mesophyll cells and chloroplasts were gradually damaged to a complete disorganization containing more starch, (4) leaf Na and Cl contents increased while leaf K content decreased, (5) leaf proline content and the activities of catalase (CAT) and superoxide dismutase (SOD) increased significantly, and (6) leaf malondialdehyde (MDA) content increased significantly and stomatal area and chlorophyll content decline were also detected. Severe salt stress (200 mM NaCl) inhibited plantlet growth. These results indicated that potato plantlets adapt to salt stress to some extent through accumulating osmoprotectants, such as proline, increasing the activities of antioxidant enzymes, such as CAT and SOD. The outcomes of this study provide ultrastructural and physiological insights into characterizing potential damages induced by salt stress for selecting salt-tolerant potato cultivars.


Diversity, Dynamics, and Distribution of Bdellovibrio and Like Organisms in Perialpine Lakes.
Microbes drive a variety of ecosystem processes and services, but many of them remain largely unexplored because of a lack of knowledge on both the diversity and functionality of some potentially crucial microbiological compartments. This is the case with and within the group of bacterial predators collectively known as Bdellovibrio and like organisms (BALOs). Here, we report the abundance, distribution, and diversity of three families of these obligate predatory Gram-negative bacteria in three perialpine lakes (Lakes Annecy, Bourget, and Geneva). The study was conducted at different depths (near-surface versus 45 or 50 m) from August 2015 to January 2016. Using PCR-denaturing gradient gel electrophoresis (PCR-DGGE) and cloning-sequencing approaches, we show that the diversity of BALOs is relatively low and very specific to freshwaters or even the lakes themselves. While the Peredibacteraceae family was represented mainly by a single species (Peredibacter starrii), it could represent up to 7% of the total bacterial cell abundances. Comparatively, the abundances of the two other families (Bdellovibrionaceae and Bacteriovoracaceae) were significantly lower. In addition, the distributions in the water column were very different between the three groups, suggesting various life strategies/niches, as follows: Peredibacteraceae dominated near the surface, while Bdellovibrionaceae and Bacteriovoracaceae were more abundant at greater depths. Statistical analyses revealed that BALOs seem mainly to be driven by depth and temperature. Finally, this original study was also the opportunity to design new quantitative PCR (qPCR) primers for Peredibacteraceae quantification.IMPORTANCE This study highlights the abundance, distribution, and diversity of a poorly known microbial compartment in natural aquatic ecosystems, the Bdellovibrio and like organisms (BALOs). These obligate bacterial predators of other bacteria may have an important functional role. This study shows the relative quantitative importance of the three main families of this group, with the design of a new primer pair, and their diversity. While both the diversity and the abundances of these BALOs were globally low, it is noteworthy that the abundance of the Peredibacteraceae could reach important values.


Multiple congenital oral granular cell tumours in a newborn black female: a case report.
Congenital oral granular cell tumour of the newborn is an uncommon benign tumour of uncertain origin. The typical clinical appearance is of a single nodule occurring on the anterior maxillary ridge. In 10% of cases there are multiple lesions. The occurrence of congenital epulis in non-Caucasians is rare. Two firm pedunculated nodular lesions were noticed in the mouth of a 3-day-old black female: one on the anterior maxillary ridge and the other further posteriorly in the midline of the palate. Both lesions were excised when the baby was nine days old. Microscopic examination of the lesions showed densely packed round to oval cells with abundant granular eosinophilic cytoplasm and uniform nuclei. The diagnosis was congenital granular cell tumour. Congenital oral granular cell tumour occurs almost exclusively in Caucasian newborns but also rarely in black infants. The parents should be assured of the benign nature and the simple treatment of the condition.


Decisional stage distribution for colorectal cancer screening among diverse, low-income study participants.
Colorectal cancer (CRC) screening uptake among minorities and those with lower incomes is suboptimal. Behavioral interventions specifically tailored to these populations can increase screening rates and save lives. The Precaution Adoption Process Model (PAPM) allows assignment of a decisional stage for adoption of a behavior such as CRC screening. Here, we characterize the PAPM decisional stage distribution among 470 low income, racially and ethnically diverse study participants at intake into a behavioral intervention study designed to increase CRC screening uptake. We staged participants for stool blood test (SBT) and colonoscopy separately and used the highest stage for the two tests as the 'overall' stage for CRC screening. For SBT, sex, language (English versus Spanish) and doctor recommendation were significantly related to PAPM stage for CRC screening. For colonoscopy, language, education level, doctor recommendation and self-efficacy were related to stage. For overall CRC screening stage, all the variables associated with either SBT or colonoscopy, with the exception of language were significant. This study suggests attending to these key variables in designing interventions to promote CRC screening, particularly with respect to medically underserved populations.


Azasugar-based MMP/ADAM inhibitors as antipsoriatic agents.
As a part of synthetic studies on MMP (matrix metalloproteinase)/ADAM (a disintegrin and metalloproteinase) inhibitors, we have preliminarily communicated that azasugar-based compound 1a exhibited a potential inhibitory activity on some metalloprotease-catalyzed proteolytic reactions. To find promising candidates for the topical treatment of psoriasis, we investigated stability in aqueous solution of compound 1a and its derivative 1b and then optimized the P1' substuent (2-5). In the present study, we synthesized novel derivatives of compound 1a and evaluated their inhibitory activity toward MMP-1, -3, and -9, TACE, and HB-EGF shedding, from a viewpoint of versatility of azasugars as a functional scaffold. As a result, it was found that compound 1b demonstrated desirable inhibitory activity as an antipsoriatic agent, and some of the derivatives showed selective inhibitory activity. In addition, it was found that compound 1b exhibited a significant therapeutic effect on a mouse TPA-induced epidermal hyperplasia model. Therefore, compound 1b could become a promising candidate as a practical antipsoriatic agent.


Kahweol Ameliorates Cisplatin-Induced Acute Kidney Injury through Pleiotropic Effects in Mice.
Cisplatin is an effective chemotherapeutic agent, but its clinical use is frequently limited by its nephrotoxicity. The pathogenesis of cisplatin-induced acute kidney injury (AKI) remains incompletely understood, but oxidative stress, tubular cell death, and inflammation are considered important contributors to cisplatin-induced renal injury. Kahweol is a natural diterpene extracted from coffee beans and has been shown to possess anti-oxidative and anti-inflammatory properties. However, its role in cisplatin-induced nephrotoxicity remains undetermined. Therefore, we investigated whether kahweol exerts a protective effect against cisplatin-induced renal injury. Additionally, its mechanisms were also examined. Administration of kahweol attenuated renal dysfunction and histopathological damage together with inhibition of oxidative stress in cisplatin-injected mice. Increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and decreased expression of manganese superoxide dismutase and catalase after cisplatin treatment were significantly reversed by kahweol. Moreover, kahweol inhibited cisplatin-induced apoptosis and necroptosis in the kidneys. Finally, kahweol reduced inflammatory cytokine production and immune cell accumulation together with suppression of nuclear factor kappa-B pathway and downregulation of vascular adhesion molecules. Together, these results suggest that kahweol ameliorates cisplatin-induced renal injury via its pleiotropic effects and might be a potential preventive option against cisplatin-induced nephrotoxicity.


Circadian variation--increased morning incidence of acute myocardial infarction in patients with coronary artery disease.
To examine whether a circadian variation exists in the onset of symptoms of Acute Myocardial Infarction (AMI) in patients with Coronary Artery Disease (CAD) and to review the characteristics of such variation. Patients with AMI admitted to the coronary care units of two teaching hospitals in the city of Karachi, Dr. Ziauddin Medical University Hospital and National Institute of Cardiovascular Disease. The study population included patients admitted to the coronary care unit. The diagnosis was based on the onset of AMI signs and symptoms and ECG changes. The inclusion criterion was an age less than 76 years. The incidence of Myocardial infarction assessed by the onset of clinical symptoms exhibited a marked circadian variation. Myocardial infarction occurred 2.8 times more frequently during morning hours (period of maximum incidence) as compared to evening (period of minimum incidence). This result extends previous observation of the circadian variation in the incidence of AMI onset. This study also helps in searching the potential triggers to physiological changes that may occur during morning hours. Design and timing of cardioprotective medication may play a crucial role in improving circadian variation and prevention of AMI.


Stable individual differences in physiological response to stressors: implications for stress-elicited changes in immune related health.
Stress reactivity refers to a stable individual difference in response to stressors. This article addresses three questions about reactivity: (1) Are cardiovascular, endocrine, and immune responses to acute laboratory stressors stable over time and across stressor tasks? (2) Are cardiovascular, endocrine, and immune reactors the same people? and (3) Are reactive people more vulnerable to stressor-induced effects on susceptibility to infectious disease? We conclude that for many individual indicators of physiological responsiveness to stressors there is moderate stability over time and across stressor tasks indicating the possible existence of underlying dispositional characteristics; the commonality of immune and cardiovascular and hormonal responses to stress depend on the nature of regulation of the immune response being assessed; reactivity appears to have implications for vulnerability to stressor-associated disease risk (stress-by-reactivity interaction) in the natural environment, but the exact nature of this vulnerability is not as yet entirely clear.


The earliest known crown-Testudo tortoise from the late Miocene (Vallesian, 9 Ma) of Greece.
We here report on fossil remains of the earliest known crown-Testudo, an extant clade of Mediterranean testudinid tortoises from the late Miocene (Vallesian, MN 10) from the hominoid locality Ravin de la Pluie (RPl) in Greece. The material studied is a small, nearly complete carapace with a clearly distinct hypo-xiphiplastral hinge. This supports the sensu stricto generic assignment. This new terrestrial testudinid specimen is characterized by a possible tectiform, narrow, elongated shell with a pentagonal pygal and a long, posteriorly elevated, lenticular and rounded dorsal epiplastral lip. These unique features differ from those of other known Mediterranean hinged forms and allow the erection of the new species Testudo hellenica sp. nov. This taxon is phylogenetically close to two Greek species, the extant T. marginata and the fossil T. marmorum (Turolian, around 7.3 Ma). This record provides evidence for the first appearance of the genus Testudo sensu stricto at a minimum age of 9 Ma.


The effects of information and communication technologies on informal caregivers of persons living with dementia: A systematic review.
Information and communication technology (ICT) has emerged as promising to support health care consumers, including informal caregivers. This systematic review seeks to evaluate the state of the science of ICT interventions on the health of informal dementia caregivers. We searched PubMed, CINAHL, Web of Science, and PsycINFO using concepts associated with ICT, dementia, and caregiver. Studies were assessed using the Quality Assessment Tool for Quantitative Studies. We identified 657 full-text publications. After removal of duplicates and title, abstract, and full-text screening, the quality of 12 studies was assessed. Studies varied in technology, implementation, results, and intervention evaluation. The methodological quality of the ICT intervention studies among dementia family caregivers was moderate to strong, yet outcome measurement was not uniform. The evidence is strongest for various forms of telephone-based interventions. However, there is a need for research that includes heterogeneous participants based on gender, race, and ethnicity.


Bacteriophages as Therapeutic and Prophylactic Means: Summary of the Soviet and Post Soviet Experiences.
Bacteriophage (from 'bacteria' and Greek φαγεῖν phagein "to devour" or bacterial eaters) are bacterial viruses that infect and kill bacteria. Bacteriophages (shortly "phages") are among the most common and diverse entities in the biosphere. The estimated number of phages on earth is about 1032. Bacteriophages are often isolated from environmental sources, such as water samples, etc. Felix d'Herelle, one of the discoverers of bacteriophages, was the one who suggested them for therapy of human and animal bacterial infections. This idea was very popular in the world until the advent of antibiotics commercial after which production of therapeutic phages ceased in most of the Western countries, but not in the former Soviet Union. The application of antibiotics in the clinical practice, besides the well-known side effects, entails, in addition, the appearance of the forms of bacteria, resistant to newly synthesized preparations. It was concluded that a European and global strategy to address this gap is urgently needed. Now, faced with the alarming growth of a variety of antibiotic resistant bacterial infections, Western researchers and governments are giving phages a serious look. The phages nowadays are seen as a possible therapy against multi-drug-resistant strains of many bacteria. The therapeutic action of bacteriophages significantly differs from antibiotics, which makes them still active against multi-drug-resistant bacteria. Bacteriophages have a number of other advantages in comparison with antibiotics. First of all, they are efficient against multi-drug-resistant bacteria. The aim of this review was to provide an overview of the past and current experiences in the field of phage therapy in the countries where it has been traditionally applied in the clinical practice. Although the style and quality of old Soviet scientific publications dedicated to phage therapy are not challenging the international standards, there is still valuable information which may not be neglected by modern researchers. This information is especially important as it remained unavailable for the Western scientists before because of the language barriers until now. The goal of this article is to encourage further research on this topic, and facilitate rapid decisions on the development of appropriate regulations, which would ultimately permit the use of phages as therapeutic or preventative medicines in daily clinical practice in the Western countries where multiplying drug-resistant bacteria gradually becomes the greatest life threatening problem.


[Color in dentistry and how to resolve its problems].
As all we know in the most of schools do not teach color knowledges, neither the way to take it in dental office. This article attempt to help to student, dentist and ceramist to understand color, its origin, metamerism phenomenon, dimensions or cualities; so we can refer about color and communicate in proper way. Also we order concepts as rules that they can be useful for helping to resolve this complex problem.


Skimming the surface with Burgess Shale arthropod locomotion.
The first arthropod trackways are described from the Middle Cambrian Burgess Shale Formation of Canada. Trace fossils, including trackways, provide a rich source of biological and ecological information, including direct evidence of behaviour not commonly available from body fossils alone. The discovery of large arthropod trackways is unique for Burgess Shale-type deposits. Trackway dimensions and the requisite number of limbs are matched with the body plan of a tegopeltid arthropod. Tegopelte, one of the rarest Burgess Shale animals, is over twice the size of all other benthic arthropods known from this locality, and only its sister taxon, Saperion, from the Lower Cambrian Chengjiang biota of China, approaches a similar size. Biomechanical trackway analysis demonstrates that tegopeltids were capable of rapidly skimming across the seafloor and, in conjunction with the identification of gut diverticulae in Tegopelte, supports previous hypotheses on the locomotory capabilities and carnivorous mode of life of such arthropods. The trackways occur in the oldest part (Kicking Horse Shale Member) of the Burgess Shale Formation, which is also known for its scarce assemblage of soft-bodied organisms, and indicate at least intermittent oxygenated bottom waters and low sedimentation rates.


Identification of two cyclooxygenase active site residues, Leucine 384 and Glycine 526, that control carbon ring cyclization in prostaglandin biosynthesis.
The cyclooxygenase (COX) reaction of prostaglandin (PG) biosynthesis begins with the highly specific oxygenation of arachidonic acid in the 11R configuration and ends with a 15S oxygenation to form PGG2. To obtain new insights into the mechanisms of stereocontrol of oxygenation, we mutated active site residues of human COX-2 that have potential contacts with C-11 of the reacting substrate. Although the 11R oxygenation was not perturbed, changing Leu-384 (into Phe, Trp), Trp-387 (Phe, Tyr), Phe-518 (Ile, Trp, Tyr), and Gly-526 (Ala, Ser, Thr, Val) impaired or abrogated PGG2 synthesis, and typically 11R-HETE was the main product formed. The Gly-526 and Leu-384 mutants formed, in addition, three novel products identified by LC-MS, NMR, and circular dichroism as 8,9-11,12-diepoxy-13R-(or 15R)-hydro(pero)xy derivatives of arachidonic acid. Mechanistically, we propose these arise from a free radical intermediate in which a C-8 carbon radical displaces the 9,11-endoperoxide O-O bond to yield an 8,9-11,12-diepoxide that is finally oxygenated stereospecifically in the 13R or 15R configuration. Formation of these novel products signals an arrest in the normal course of prostaglandin synthesis just prior to closing of the 5-membered carbon ring, and points to a crucial role for Leu-384 and Gly-526 in the correct positioning of the reacting fatty acid intermediate. Some of the Gly-526 and Leu-384 mutants catalyzed both formation of PGG2 (with the normal 15S configuration) and the 13R- or 15R-oxygenated diepoxides. This result suggests that oxygenation specificity can be determined by the orientation of the reacting fatty acid radical and is not a predetermined outcome based solely on the structure of the cyclooxygenase active site.


Comparison of microwave oven and convection oven for acid hydrolysis of dietary fiber polysaccharides.
Hydrolysis of dietary fiber polysaccharides (DFP) is an integral part of any enzymatic-chemical method for dietary fiber analysis. Residues obtained after enzyme treatments of fiber-containing foods are usually suspended in 12 M sulfuric acid and kept at or slightly above ambient temperature for at least 1 h, and then the mixtures are diluted with deionized water to a final concentration of 1 M or 2 M acid, followed by heating at 100 degrees C in a water bath or convection oven for 1 or 2 h. Under these hydrolytic conditions, some degradation of the released monosaccharides generally takes place over the duration of hydrolysis. We investigated the feasibility of using microwave energy as a heat source to reduce time and minimize degradation. Preliminary tests were done on the well-characterized soy polysaccharide Fibrim. With a microwave digestion system equipped with temperature and pressure monitors and control lines, optimum settings of power (5%, 75%), time (up to 3 min and 30 s), temperature (35 degrees-55 degrees C), and pressure (45-65 psi) were determined for different foods depending on the residue weight and volume of acid. Results were comparable for microwave oven and convection oven hydrolysis of DFP from 5 foods with good correlations for neutral sugar values; r2 = 0.997 for arabinose, 0.925 for galactose, 0.981 for glucose, 0.969 for mannose, and 0.990 for xylose.


The myxomatous mitral valve and sudden death.
The clincopathologic features of 14 cases of sudden death attributable to dysrhythmias associated with the myxomatous mitral valve are described. The patients were 14-59 years old (mean 27 +/- 11 years). Eleven were female and three male. Of the seven ECGs available, none showed prolongation of the QT interval, but two showed repolarization abnormalities. The material was classified according to the degree of prolapse in the pathologic specimen. When obvious prolapse was found, the expected auscultatory findings had been documented. In three cases there was minimal prolapse, casting some doubt on the hypothesis that traction on the papillary muscles or diastolic dumping of the leaflets may be implicated in the pathogenesis of the dysrhythmias. In one of the cases with minimal prolapse there was a strong family history of sudden death. Endocardial friction lesions were present in 11 cases, including two of the three with minimal prolapse. In five cases there was a thrombotic lesion in the angle between the posterior leaflet and the left atrial wall containing fibrin and platelets. These abnormalities may be important in the pathogenesis of the ventricular dysrhythmias.


A New Hope in Alzheimer's Disease Psychosis: Pimavanserin.
Alzheimer's disease (AD) ranks first among the causes of dementia worldwide. AD can develop a psychotic manifest at a significant rate. AD prognosis worsens by added psychosis clinic. There is no treatment approved by the United States Food and Drug Administration (FDA) among antipsychotics for Alzheimer's disease Psychosis (ADP). However, pimavanserine, an atypical antipsychotic, has been approved by the FDA for Parkinson's psychosis. It is predicted that pimavanserin, a new antipsychotic, will fill an important gap in this area. In clinical trials, it appears to be effective in the treatment of delusions and hallucinations at psychosis in both Parkinson's and AD. In this systematic review, we evaluated the analysis of current literature data on pimavanserin used in ADP. We searched the existing literature on clinical studies on pimavanserin therapy used in ADP. Data were determined by systematically searching PubMed, MEDLINE, EMBASE, and Google Scholar until December 2022. A total of 35 citations were found and uploaded on the Mendeley program. Abstracts and full texts of literature data were examined. Pimavanserin was observed, and satisfactory results were obtained in treating ADP. Pimavanserin has a unique mechanism of action. Pimavanserin, an atypical antipsychotic drug, has a low affinity for 5-HT2C receptors and has selective 5-HT2A reverse agonist/antagonist action. Pimavanserin has no clinically significant affinity for dopaminergic, histaminergic, muscarinic or adrenergic receptors. This agent may also achieve significant positive results in resistant psychosis treatments.


Variable Practice to Enhance Speech Learning in Ultrasound Biofeedback Treatment for Childhood Apraxia of Speech: A Single Case Experimental Study.
The purpose of this study was to evaluate the role of practice variability, through prosodic variation during speech sound training, in biofeedback treatment for children with childhood apraxia of speech. It was hypothesized that variable practice would facilitate speech sound learning. Six children ages 8-16 years with persisting speech sound errors due to childhood apraxia of speech participated in a single-subject experimental design. For each participant, 2 speech sound targets were treated with ultrasound visual feedback training: one with prosodic variation (i.e., practicing sound targets in words and phrases spoken fast, slow, loud, as a question, command, and declarative), and one without prosodic variation. Each target was treated for half of the 1-hr session for 14 treatment sessions. As measured by standardized effect sizes, all participants showed greater change on generalization probes for sound targets treated under the prosodic variation condition with mean effect sizes (d2) of 14.5 for targets treated with prosodic variation and 8.3 for targets treated without prosodic variation. The average increase in generalization scores was 38% in the prosodic variation condition compared to 31% without. Ultrasound visual feedback may facilitate speech sound learning and learning may be enhanced by treating speech sounds with explicit prosodic variation. https://doi.org/10.23641/asha.5150119.


Controversies surrounding peripheral cannabinoid receptor 1 in fatty liver disease.
Cannabinoid receptor 1 (CB-1) antagonists are potential candidates for treating obesity and metabolic complications. Despite clear metabolic benefits, unwanted side effects in the brain pose issues for patients. With the hope of overcoming this obstacle, CB-1 in peripheral tissues has become a potential drug target. Previous studies had suggested that liver CB-1 would be an excellent target to prevent development of nonalcoholic steatohepatitis (NAFLD). However, in this issue of the JCI, Wang et al. showed that CB-1 was barely detectable in the liver and deletion of CB-1 in hepatocytes provided no metabolic benefits against NAFLD. These contradictory results raise substantial concerns about the potential benefits of peripheral CB-1 blockers against NAFLD.


Mitigating the Impact of the Novel Coronavirus Pandemic on Neuroscience and Music Research Protocols in Clinical Populations.
The COVID-19 disease and the systemic responses to it has impacted lives, routines and procedures at an unprecedented level. While medical care and emergency response present immediate needs, the implications of this pandemic will likely be far-reaching. Most practices that the clinical research within neuroscience and music field rely on, take place in hospitals or closely connected clinical settings which have been hit hard by the contamination. So too have its preventive and treatment measures. This means that clinical research protocols may have been altered, postponed or put in complete jeopardy. In this context, we would like to present and discuss the problems arising under the current crisis. We do so by critically approaching an online discussion facilitated by an expert panel in the field of music and neuroscience. This effort is hoped to provide an efficient basis to orient ourselves as we begin to map the needs and elements in this field of research as we further propose ideas and solutions on how to overcome, or at least ease the problems and questions we encounter or will encounter, with foresight. Among others, we hope to answer questions on technical or social problems that can be expected, possible solutions and preparatory steps to take in order to improve or ease research implementation, ethical implications and funding considerations. Finally, we further hope to facilitate the process of creating new protocols in order to minimize the impact of this crisis on essential research which may have the potential to relieve health systems.


Long-term exposure to food-grade disinfectants causes cross-resistance to antibiotics in Salmonella enterica serovar Typhimurium strains with different antibiograms and sequence types.
Disinfectants are important in the food industry to prevent the transmission of pathogens. Excessive use of disinfectants may increase the probability of bacteria experiencing long-term exposure and consequently resistance and cross-resistance to antibiotics. This study aims to investigate the cross-resistance of multidrug-resistant, drug-resistant, and drug-susceptible isolates of Salmonella enterica serovar Typhimurium (S. Typhimurium) with different sequence types (STs) to a group of antibiotics after exposure to different food-grade disinfectants. A panel of 27 S. Typhimurium strains with different antibiograms and STs were exposed to increasing concentrations of five food-grade disinfectants, including hydrogen peroxide (H2O2), benzalkonium chloride (BAC), chlorine dioxide (ClO2), sodium hypochlorite (NaClO), and ethanol. Recovered evolved strains were analyzed using genomic tools and phenotypic tests. Genetic mutations were screened using breseq pipeline and changes in resistance to antibiotics and to the same disinfectant were determined. The relative fitness of evolved strains was also determined. Following exposure to disinfectants, 22 out of 135 evolved strains increased their resistance to antibiotics from a group of 14 clinically important antibiotics. The results also showed that 9 out of 135 evolved strains had decreased resistance to some antibiotics. Genetic mutations were found in evolved strains. A total of 77.78% of ST34, 58.33% of ST19, and 66.67% of the other STs strains exhibited changes in antibiotic resistance. BAC was the disinfectant that induced the highest number of strains to cross-resistance to antibiotics. Besides, H2O2 induced the highest number of strains with decreased resistance to antibiotics. These findings provide a basis for understanding the effect of disinfectants on the antibiotic resistance of S. Typhimurium. This work highlights the link between long-term exposure to disinfectants and the evolution of resistance to antibiotics and provides evidence to promote the regulated use of disinfectants.


Experience with cerebellopontine angle epidermoids.
Cerebellopontine angle (CPA) epidermoids, although of benign nature, are of considerable neurosurgical interest because of their close proximity and adherence to the cranial nerves and the brain stem. We describe our experience and attempt to correlate the final outcomes with the extent of surgical removal. Twenty-five consecutive patients with CPA epidermoids that were surgically treated were reviewed, and the final outcomes were assessed. Thirteen patients had trigeminal neuralgia. In 7 of the 13 patients, trigeminal neuralgia was the only presenting feature. The epidermoid was confined to the CPA in each of 6 patients, and in each of 18, it had varying degrees of supratentorial extension. One patient had a predominant supratentorial epidermoid with extension to the CPA. The lesions were totally excised in 12 patients. Near-total removal was accomplished in eight patients, and in the remaining five, partial removal was accomplished. Transient worsening of the cranial nerve functions occurred in 11 patients, probably as a result of aggressive dissection of the capsule from the cranial nerves. In 9 of the 11 patients, the cranial nerve functions improved by the time of discharge. All of the patients who had trigeminal neuralgia were relieved of their symptoms. Eighteen patients were followed up for a mean period of 42 months, and none had symptoms of recurrence. Aggressive surgical removal results in transient but significant cranial nerve dysfunction in the postoperative period. A conservative approach is indicated for patients in whom the capsule is adherent to the brain stem and the cranial nerves.


Retinal nerve fiber layer atrophy is associated with physical and cognitive disability in multiple sclerosis.
Studying axonal loss in the retina is a promising biomarker for multiple sclerosis (MS). Our aim was to compare optical coherence tomography (OCT) and Heidelberg retinal tomography (HRT) techniques to measure the thickness of the retinal nerve fiber layer (RNFL) in patients with MS, and to explore the relationship between changes in the RNFL thickness with physical and cognitive disability. We studied 52 patients with MS and 18 proportionally matched controls by performing neurological examination, neuropsychological evaluation using the Brief Repetitive Battery-Neuropsychology and RNFL thickness measurement using OCT and HRT. We found that both OCT and HRT could define a reduction in the thickness of the RNFL in patients with MS compared with controls, although both measurements were weakly correlated, suggesting that they might measure different aspects of the tissue changes in MS. The degree of RNFL atrophy was correlated with cognitive disability, mainly with the symbol digit modality test (r=0.754, P<0.001). Moreover, temporal quadrant RNFL atrophy measured with OCT was associated with physical disability. In summary, both OCT and HRT are able to detect thinning of the RNFL, but OCT seems to be the most sensitive technique to identify changes associated with MS evolution.


The Nottingham Prognostic Index: five- and ten-year data for all-cause survival within a screened population.
The Nottingham Prognostic Index (NPI) is an established prognostication tool in the management of breast cancers (BCs). Latest ten-year survival data have demonstrated an improved outlook for each NPI category and the latest UK five- and ten-year survival from BC has been reported to be 85% and 77%, respectively. We compared survival of each NPI category for BCs diagnosed within the national breast screening service in Wales (Breast Test Wales (BTW)) to the latest data, and reviewed its validity in unselected cases within a screened population. All women screened between 1998 and 2001 within BTW were included. The NPI score for each cancer was calculated using the size, nodal status, and grade of the primary tumour. Survival data (all-cause) were calculated after ten years of follow-up. In the three-year screening period, 199,082 women were screened. A total of 1,712 cancers were diagnosed, and 1,546 had data available for calculating the NPI. Overall five-year and ten-year survival was 94% and 82%, respectively. Overall five-year and ten-year survival (all-cause) has improved even when compared with UK data for BC-specific survival. We found that the NPI remains valid for BC treatment, and that our data provide a reference for updating the all-cause survival of women diagnosed with BCs within a screened population.


Urinary Neutrophil Gelatinase-Associated Lipocalin and Urinary Soluble CXCL16 as Biomarkers of Activity in Pediatric Lupus Nephritis.
One of the challenges of treating patients with lupus nephritis (LN) is to assess disease activity. The aim of this study was to measure the urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary soluble chemokine (C-X-C motif) ligand 16 (CXCL16) levels in children and adolescents with systemic lupus erythematosus (SLE) and investigate whether they are elevated in active LN. This study was conducted on 80 patients diagnosed as SLE by the Systemic Lupus International Collaborating Clinics criteria and 60 apparently healthy individuals as controls. Global and renal disease activities were evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and renal SLEDAI, respectively. uNGAL and urinary CXCL16 were measured for all participants by ELISA. Renal biopsy was done for all cases at initial diagnosis and was graded using ISN/RPS classification. uNGAL and CXCL16 were higher in patients than in the controls (8.9 ± 3.56 ng/dl and 1067 ± 367 ug/L vs. 2.26 ± 1.95 ng/dl and 471 ± 106 ug/L, respectively). uNGAL had higher sensitivity and specificity than urinary CXCL16 as predictor of LN (95% and 90% vs. 85% and 80%, respectively). There was significant positive correlations between uNGAL levels, 24-h urinary proteins (r = 0.732, P = 0.001), and SLEDAI (r = 0.359, P = 0.001). There was also significant positive correlations between urinary CXCL16 levels, 24-h urinary proteins (r = 0.47, P = 0.001), and SLEDAI (r = 0.17, P = 0.001). uNGAL and CXCL16 were reliable indicators of the activity of LN.


Blood glucose control by intermittent loop closure in the basal mode: computer simulation studies with a diabetic model.
A semiclosed loop, bedside insulin infusion system using a simple basal infusion algorithm consisting of a linear transition between two insulin delivery rates as blood glucose (BG) increases has been developed. A theoretical study using computer simulation has now been undertaken to examine the effect of BG sampling frequency and algorithm parameters on BG control. A model for BG control by exogenous insulin in the individual with diabetes was developed from a model for healthy subjects and from clinical data in the literature. Results of computer simulation using this model showed a decrease in BG stability as the sampling interval increased from 1 to 4 h. Simulations also showed a decrease in BG stability as the sensitivity of the control algorithm increased. Choice of an appropriate basal control algorithm involved a compromise between stability, sampling interval, and metabolic control. We conclude that satisfactory metabolic control can be obtained using intermittent BG sampling in the basal state; sampling at intervals of 3 h combined with a basal control algorithm whereby insulin delivery rate increases linearly from 0.5 to 2.5 U/h over the BG range 2-12 mmol/L appears suitable for most diabetic persons. Three-hour sampling offers a good compromise between degree of metabolic control and clinical effort involved.


Anabolic steroid use among substance abusers in treatment.
Increasing illicit use of anabolic steroids in adolescent and young adult populations has been reported. To determine the scope of this problem and its relationship to psychoactive substance abuse, we evaluated the prevalence of anabolic steroid use among individuals seeking inpatient treatment for substance abuse. A randomized mail survey of 175 inpatient substance abuse treatment directors elicited information regarding the prevalence of anabolic steroid use for inpatients treated in 1989 and the first half of 1990. Additionally, directors were surveyed for experience with DSM-III-R psychoactive substance dependence criteria for anabolic steroid use. Only 19% of centers responding had treated at least one individual using anabolic steroids. Facilities encountering anabolic steroid users reported a prevalence of less than 1% among all admissions. Anabolic steroid users were seen more commonly in privately funded facilities. Directors reported a majority of anabolic steroid users had at least three DSM-III-R psychoactive substance dependence criteria for anabolic steroid use. Treatment directors rarely found anabolic steroid use acknowledged as a problem by users and rarely found anabolic steroid use a primary reason for treatment. Users of illicit anabolic steroids may have significant clinical differences compared with users of other psychoactive substances of abuse and dependence.


Accumulating mutations of p53 in colon tumor and hairy cell leukemia do not arise from methylation/deamination processes, but rather from nucleotide deletions and insertions.
Mutations of the p53 gene may alter the specific regulatory domains of the protein. We examined the conserved domains III, IV and V by SSCP using PCR primers covering exons 5, 6, 7 and 8 from hairy cell leukemia (HCL), polyps, colorectal and gastric carcinomas. A low rate of p53 mutations was detected in HCL and polyps. These mutations may predict the risk of malignant development. However, multiple mutations were a frequent occurrence in tumors. Sequence analysis of our samples did not demonstrate the high frequency of transition mutations (C-->T) that would be predicted if the major course of p53 mutations is deamination of 5-methylcytosine (5mC). Rather, most mutations were found to be single base insertions or deletions.


Structure of bottle-brush brushes under good solvent conditions: a molecular dynamics study.
We report a simulation study for bottle-brush polymers grafted on a rigid backbone. Using a standard coarse-grained bead-spring model extensive molecular dynamics simulations for such macromolecules under good solvent conditions are performed. We consider a broad range of parameters and present numerical results for the monomer density profile, density of the untethered ends of the grafted flexible backbones and the correlation function describing the range that neighboring grafted bottle-brushes are affected by the presence of the others due to the excluded-volume interactions. The end beads of the flexible backbones of the grafted bottle-brushes do not access the region close to the rigid backbone due to the presence of the side chains of the grafted bottle-brush polymers, which stretch the chains further in the radial directions. Although a number of different correlation lengths exist as a result of the complex structure of these macromolecules, their properties can be tuned with high accuracy in good solvents. Moreover, qualitative differences with 'typical' bottle-brushes are discussed. Our results provide a first approach to characterizing such complex macromolecules with a standard bead-spring model.


Silicone Membranes to Inhibit Water Uptake into Thermoset Polyurethane Shape-Memory Polymer Conductive Composites.
Electroactive shape memory polymer (SMP) composites capable of shape actuation via resistive heating are of interest for various biomedical applications. However, water uptake into SMPs will produce a depression of the glass transition temperature (Tg ) resulting in shape recovery in vivo. While water actuated shape recovery may be useful, it is foreseen to be undesirable during early periods of surgical placement into the body. Silicone membranes have been previously reported to prevent release of conductive filler from an electroactive polymer composite in vivo. In this study, a silicone membrane was used to inhibit water uptake into a thermoset SMP composite containing conductive filler. Thermoset polyurethane (PU) SMPs were loaded with either 5 wt% carbon black (CB) or 5 wt% carbon nanotubes (CNT) and subsequently coated with either an Al2O3- or silica-filled silicone membrane. It was observed that the silicone membranes, particularly the silica-filled membrane, reduced the rate of water absorption (37 °C) and subsequent Tg depression versus uncoated composites. In turn, this led to a reduction in the rate of recovery of the permanent shape when exposed to water at 37 °C.


Search for a liquid-liquid critical point in models of silica.
Previous research has indicated the possible existence of a liquid-liquid critical point (LLCP) in models of silica at high pressure. To clarify this interesting question we run extended molecular dynamics simulations of two different silica models (WAC and BKS) and perform a detailed analysis of the liquid at temperatures much lower than those previously simulated. We find no LLCP in either model within the accessible temperature range, although it is closely approached in the case of the WAC potential near 4000 K and 5 GPa. Comparing our results with those obtained for other tetrahedral liquids, and relating the average Si-O-Si bond angle and liquid density at the model glass temperature to those of the ice-like β-cristobalite structure, we conclude that the absence of a critical point can be attributed to insufficient "stiffness" in the bond angle. We hypothesize that a modification of the potential to mildly favor larger average bond angles will generate a LLCP in a temperature range that is accessible to simulation. The tendency to crystallize in these models is extremely weak in the pressure range studied, although this tendency will undoubtedly increase with increasing stiffness.


High-efficiency omnidirectional photoresponses based on monolayer lateral p-n heterojunctions.
Electrical and optical properties of lateral monolayer WSe2-MoS2 p-n heterojunctions were characterized to demonstrate a high responsivity of 0.26 A W-1 with an excellent omnidirectional photodetection capability. The heterojunction functioning as a diode exhibits a prominent gate-tuning behavior with an ideality factor of 1.25. In addition, ultrafast photoresponse, low-light detectability, and high-temperature operation have been achieved. These unique characteristics pave a way for the future development of sub-nano semiconductor devices.


Contribution of the length of the HN protein and the sequence of the F protein cleavage site to Newcastle disease virus pathogenicity.
Newcastle disease virus (NDV) possesses two envelope spike glycoproteins: the haemagglutinin-neuraminidase (HN) protein and the fusion (F) protein. The HN protein, which is responsible for virus attachment to sialic acid-containing receptors, varies in length due to differences in the sizes of the ORFs. An HN protein precursor of 616 aa has been found in avirulent but not in virulent NDV strains, whereas an HN protein of 571 aa can be detected in highly virulent strains only. An HN protein of 577 aa is present in virulent and avirulent strains. The F protein, which mediates virus-cell fusion, requires proteolytic activation at an internal cleavage site, whose amino acid composition determines cleavability by various proteases. Here, the functional significance of the length of the HN protein in combination with F protein cleavage sites typical for virulent (velogenic and mesogenic) or avirulent (lentogenic) strains was investigated. To this end, site-directed mutagenesis was used to construct recombinant NDV on the basis of an infectious clone of the lentogenic vaccine virus Clone-30. Only recombinant NDV expressing an F protein with a multibasic cleavage site typical of virulent strains was able to spread efficiently in cell culture, irrespective of the size of the HN protein. Moreover, as determined by the intracerebral pathogenicity index (ICPI) in 1-day-old, specific-pathogen-free chickens, pathogenicity was influenced by the cleavability of the F protein and not by the length of the HN protein. The maximum ICPI value obtained for these recombinants was 1.3, as compared to a possible maximum of 2. This demonstrates that the modifications introduced did not result in the conversion of the lentogenic Clone-30 to a velogenic strain with an ICPI value of >1.5 and suggests the involvement of additional virulence determinants that contribute to the pathogenicity of NDV.


Analytical ultracentrifugation and agarose gel electrophoresis as tools for studying chromatin folding in solution.
Analytical ultracentrifugation and agarose gel electrophoresis each can be used to accurately quantify changes in structure that accompany chromatin folding in solution. Analytical ultracentrifugation directly measures the extent of compaction of each species present in a chromatin sample under a wide range of solution conditions. Agarose gel electrophoresis yields information about changes in the average surface charge density, size and/or shape, and conformational flexibility during chromatin folding. When used together, these methodologies are particularly powerful. Protocols for the characterization of chromatin folding by analytical ultracentrifugation and agarose gel electrophoresis are described. Discussion focuses on analysis and interpretation of experimental chromatin folding data.


Incidence and overall survival of malignant ameloblastoma.
Malignant ameloblastoma, comprising metastasizing ameloblastoma and ameloblastic carcinoma, represents 1.6-2.2% of all odontogenic tumors. Due to its rare nature, malignant ameloblastoma has only been reported in the literature in small case series or case reports. Using the Surveillance, Epidemiology and End-Results (SEER) database, we have performed a population-based study to determine the incidence rate and the absolute survival of malignant ameloblastoma. Using the International Classification of Diseases for Oncology (ICD-O) codes 9310/3 and 9270/3, data from the SEER database were used to calculate the incidence rate and absolute survival rate of population with malignant ameloblastoma. The overall incidence rate of malignant ameloblastoma was 1.79 per 10 million person/year. The incidence rate was higher in males than females and also higher in black versus white population. The median overall survival was 17.6 years from the time of diagnosis and increasing age was associated with a statistically significant poorer survival. To our best knowledge, we report the largest population-based series of malignant ameloblastoma. The incidence rate was 1.79 per 10 million person/year and the overall survival was 17.6 years.


Evaluation of a Newly Designed Microperforated Titanium Membrane with Beta-Tricalcium Phosphate for Guided Bone Regeneration in Dog Mandibles.
This study evaluated the efficacy of newly designed, laser-perforated pure titanium membranes for guided bone regeneration using beta-tricalcium phosphate (β-TCP), and compared them with the existing membrane. Bilateral acute lateral ridge defects were created in the mandibles of 12 dogs (four defects per animal), which were then randomly divided into two groups (six dogs each). The twenty-four bone defects in each group were then further divided into five groups. The groups were as follows: (1) F001M0, a prototype membrane without a frame plus β-TCP (n = 5); (2) F001M1, a prototype membrane with a frame plus β-TCP (n = 5); (3) FBS, an existing control membrane plus β-TCP (n = 5); (4) control 1, β-TCP without membrane and with covering flap only (n = 5); and (5) control 2, no treatment (no β-TCP and no membrane) (n = 4). In all groups where β-TCP was used, it was mixed with peripheral blood. The animals were necropsied at 6 or 12 weeks postoperatively (six dogs each), and samples were collected and processed for radiographic, histologic, and histomorphometric analyses. Among the three membrane groups, regenerated tissue and bone volume was greatest in the F001M1 group at both 6 and 12 weeks postoperatively, although differences among groups were not statistically significant. Bone mineral density was similar among the membrane groups. Histologic analysis revealed that immature fibroblasts were present on the laser-perforated portion at 6 weeks, which induced vascularization. In addition, more calcified bone was replaced beneath the prototypes than beneath the FBS membrane at 12 weeks. Histomorphometric analyses revealed that the calcific osseous areas at 12 weeks after surgery were significantly greater in the F001M1 and F001M0 groups than in the FBS group (P = .021, P = .032). Furthermore, the fibrous tissue areas beneath the membrane at 12 weeks postoperatively were significantly smaller in the prototype groups than in the FBS group (P = .02, P = .02). The efficacies of both prototype membranes were not inferior to that of the FBS membrane, indicating that they may facilitate bone regeneration and maturation when β-TCP mixed with autologous blood is employed.


Assessing the prevalence of hybridization between sympatric Canis species surrounding the red wolf (Canis rufus) recovery area in North Carolina.
Predicting spatial patterns of hybridization is important for evolutionary and conservation biology yet are hampered by poor understanding of how hybridizing species can interact. This is especially pertinent in contact zones where hybridizing populations are sympatric. In this study, we examined the extent of red wolf (Canis rufus) colonization and introgression where the species contacts a coyote (C. latrans) population in North Carolina, USA. We surveyed 22,000km(2) in the winter of 2008 for scat and identified individual canids through genetic analysis. Of 614 collected scats, 250 were assigned to canids by mitochondrial DNA (mtDNA) sequencing. Canid samples were genotyped at 6-17 microsatellite loci (nDNA) and assigned to species using three admixture criteria implemented in two Bayesian clustering programs. We genotyped 82 individuals but none were identified as red wolves. Two individuals had red wolf mtDNA but no significant red wolf nDNA ancestry. One individual possessed significant red wolf nDNA ancestry (approximately 30%) using all criteria, although seven other individuals showed evidence of red wolf ancestry (11-21%) using the relaxed criterion. Overall, seven individuals were classified as hybrids using the conservative criteria and 37 using the relaxed criterion. We found evidence of dog (C. familiaris) and gray wolf (C. lupus) introgression into the coyote population. We compared the performance of different methods and criteria by analyzing known red wolves and hybrids. These results suggest that red wolf colonization and introgression in North Carolina is minimal and provide insights into the utility of Bayesian clustering methods to detect hybridization.


In vitro and in vivo evaluation of levodopa-loaded nanoparticles for nose to brain delivery.
Parkinson's disease (PD) is a neurodegenerative disease which is characterized by the loss of dopaminergic neurons in the brain. Levodopa is the drug of choice in the treatment of PD but it exhibits low oral bioavailability (30%) and very low brain uptake due to its extensive metabolism by aromatic amino acid decarboxylase in the peripheral circulation. Moreover, levodopa has psychic, gastrointestinal, and cardiovascular side effects, and most importantly, short and frequent stimulation of dopamine receptors lead to undesirable conditions such as dyskinesia over time. The challenges are to increase the therapeutic efficiency, the bioavailability and decreasing the unfavourable side effects of levodopa. Biocompatible nano-sized drug carriers could address these challenges at molecular level. For this purpose, levodopa-loaded Poly (lactide-co-glycolide) acid nanoparticles were prepared by double emulsion-solvent evaporation method for nose to brain drug delivery. Parameters such as homogenization speed, and external and internal phase content were modified to reach the highest loading efficiency. F1-1 coded formulation showed prolonged release up to 9 h. Carbodiimide method was used for surface modification studies of nanoparticles. The efficacy of the selected nanoparticle formulation has been demonstrated by in vivo experiments in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced PD model in mice.


SILICON PHOTOMULTIPLIERS FOR MEDICAL IMAGING AND DOSIMETRY-AN OVERVIEW.
Silicon photomultipliers (SiPMs) are an enabling solid-state technology for low light sensing, with single photon sensitivity and photon number resolving capability. They feature an extremely high internal gain at the 10(6) level, comparable to photomultiplier tubes (PMTs), with the advantage of low operating voltage (~50 V compared to ~1000 V for PMT) and low energy consumption. The solid-state technology makes SiPMs compact, insensitive to magnetic fields and with an extreme flexibility in the design to cope with different applications. The fast development of the multiplication avalanche opens up the possibility to achieve time resolution at the 30 ps level. Dynamic range is however limited compared to PMT and the dark count rate relatively high, yet today at the level of 50 kHz/mm(2) at room temperature. Interfaced with scintillation material, SiPMs provide a powerful platform for medical imaging applications (in positron emission tomography/computed tomography and in positron emission tomography/magnetic resonance), for X-ray quality control as well as for novel compact radiation protection instruments. This article gives an overview of SiPMs for medical imaging and dosimetry. In addition, a learning and training program targeted to graduate students is described.


[Fibronectin: an early marker of pre-eclampsia].
Plasma fibronectin concentration was determined by immuno-nephelometer analysis in 316 pregnant women between 22 and 38 weeks. The plasma fibronectin concentration increases progressively during normal pregnancy. From 22 to 30 weeks, the 90th percentile is 350 mg/l, and from 30 to 38 weeks it is 400 mg/l. 29 patients had a fibronectin level greater than 400 mg/l. Of this group, 95% of the creatinine's clearance were significantly lowered. From 30 weeks of gestation, the correlation between an elevated level of fibronectin and the development of hypertension is 100%. Our results confirm that this glycoprotein may be an early indicator of preeclampsia.


Effective number of breeders provides a link between interannual variation in stream flow and individual reproductive contribution in a stream salmonid.
The effective number of breeders that give rise to a cohort (N(b)) is a promising metric for genetic monitoring of species with overlapping generations; however, more work is needed to understand factors that contribute to variation in this measure in natural populations. We tested hypotheses related to interannual variation in N(b) in two long-term studies of brook trout populations. We found no supporting evidence for our initial hypothesis that N^(b) reflects N^(c) (defined as the number of adults in a population at the time of reproduction). N^(b) was stable relative to N^(C) and did not follow trends in abundance (one stream negative, the other positive). We used stream flow estimates to test the alternative hypothesis that environmental factors constrain N(b). We observed an intermediate optimum autumn stream flow for both N^(b) (R(2) = 0.73, P = 0.02) and full-sibling family evenness (R(2) = 0.77, P = 0.01) in one population and a negative correlation between autumn stream flow and full-sib family evenness in the other population (r = -0.95, P = 0.02). Evidence for greater reproductive skew at the lowest and highest autumn flow was consistent with suboptimal conditions at flow extremes. A series of additional tests provided no supporting evidence for a related hypothesis that density-dependent reproductive success was responsible for the lack of relationship between N(b) and N(C) (so-called genetic compensation). This work provides evidence that N(b) is a useful metric of population-specific individual reproductive contribution for genetic monitoring across populations and the link we provide between stream flow and N(b) could be used to help predict population resilience to environmental change.


In Vitro Activity of Two Novel Antimicrobial Compounds on MDR-Resistant Clinical Isolates.
The development of novel antibiotics is mandatory to curb the growing antibiotic resistance problem resulting in difficult-to-treat bacterial infections. Here, we have determined the spectrum of activity of cystobactamids and chelocardins, two novel and promising classes of molecules with different modes of action. A panel of 297 clinically relevant Gram-negative and Gram-positive isolates with different antibiotic susceptibility profiles, going from wild type to multi- or even extremely drug resistant (MDR, XDR) and including carbapenem-resistant isolates, were tested using broth microdilution assays to determine the minimal inhibitory concentrations (MICs), MIC50s and MIC90s of two cystobactamids derivatives (CN-861-2 and CN-DM-861) and two chelocardin derivatives (CHD and CDCHD). Cystobactamids revealed potent activities on the majority of tested Enterobacterales (MIC50s ranging from 0.25 to 4 µg/mL), except for Klebsiella pneumoniae isolates (MIC50s is 128 µg/mL). Pseudomonas aeruginosa and Acinetobacter baumannii showed slightly higher MIC50s (4 µg/mL and 8 µg/mL, respectively) for cystobactamids. Chelocardins inhibited the growth of Enterobacterales and Stenotrophomas maltophilia at low to moderate MICs (0.25-16 µg/mL) and the chemically modified CDCHD was active at lower MICs. A. baumannii and P. aeruginosa were less susceptible to these molecules with MICs ranging from 0.5 to 32 µg/mL. These molecules show also interesting in vitro efficacies on clinically relevant Gram-positive bacteria with MICs of 0.125-8 µg/mL for cystobactamids and 0.5-8 µg/mL for chelocardins. Taken together, the cystobactamid CN-DM-861 and chelocardin CDCHD showed interesting antibiotic activities on MDR or XDR bacteria, without cross-resistance to clinically relevant antibiotics such as carbapenems, fluoroquinolones, and colistin.


Projected Wine Grape Cultivar Shifts Due to Climate Change in New Zealand.
Climate change has already been affecting the regional suitability of grapevines with significant advances in phenology being observed globally in the last few decades. This has significant implications for New Zealand, where the wine industry represents a major share of the horticultural industry revenue. We modeled key crop phenological stages to better understand temporal and spatial shifts in three important regions of New Zealand (Marlborough, Hawke's Bay, Central Otago) for three dominant cultivars (Merlot, Pinot noir, and Sauvignon blanc) and one potential new and later ripening cultivar (Grenache). Simulations show an overall advance in flowering, véraison, and sugar ripeness by mid-century with more pronounced advance by the end of the century. Results show the magnitude of changes depends on the combination of greenhouse gas emission pathway, grape cultivar, and region. By mid-century, in the Marlborough region for instance, the four cultivars would flower 3 to 7 days earlier and reach sugar ripeness 7 to 15 days earlier depending on the greenhouse gas emission pathway. For growers to maintain the same timing of key phenological stages would require shifting planting of cultivars to more Southern parts of the country or implement adaptation strategies. Results also show the compression of time between flowering and véraison for all three dominant cultivars is due to a proportionally greater advance in véraison, particularly for Merlot in the Hawke's Bay and Pinot noir in Central Otago. Cross-regional analysis also raises the likelihood of the different regional cultivars ripening within a smaller window of time, complicating harvesting schedules across the country. However, considering New Zealand primarily accommodates cool climate viticulture cultivars, our results suggest that late ripening cultivars or extended ripening window in cooler regions may be advantageous in the face of climate change. These insights can inform New Zealand winegrowers with climate change adaptation options for their cultivar choices.


Inflammatory Profile in Left Ventricular Apical Thrombus.
To investigate the relationship between systemic immune inflammation index (SII), C-reactive protein/albumin ratio (CAR), lymphocyte/CRP ratio (LCR), and apical thrombus development. Observational, cross-sectional study. Place and Duration of the Study: Bursa City Hospital, Turkey, from 1st January to 31st March 2023. Twenty-two patients with a clinical presentation of acute anterior myocardial infarction and diagnosed with LVAT during follow-up were included. Sixty-eight patients with acute anterior myocardial infarction (AMI) were selected as the control group (comparison). Clinical and demographic characteristics, laboratory data, echocardiographic findings, coronary angiography, and percutaneous coronary intervention data were recorded. SII was calculated by the formula Neutrophil (N) × Platelet (P) / Lymphocyte (L). CAR and LCR values were also determined. While there was no significant difference between the two groups in terms of SII, CAR was significantly higher and LCR was significantly lower in the apical thrombus group. The cut-off value for CAR was 0.165 (sensitivity=63.64%, specificity=74.60%, AUC=0.718; p <0.05). For LCR, the AUC value of 0.382 and below was found to indicate the presence of apical thrombus with a probability of 69.8% (sensitivity=68.18%, specificity=67.16%, p= 0.002). No significant relationship was found between SII and apical thrombus in the detection of LVAT, whereas high CAR and low LCR were associated with the presence of apical thrombus. Left ventricular apical thrombus, Apical aneurysm, C-reactive protein/albumin ratio, Lymphocyte/C-reactive protein ratio, Systemic immune inflammation index.


Self-management: an approach to patients with insulin-dependent diabetes mellitus.
Patients have been shown to be able to monitor their blood glucose and administer insulin to optimize and normalize blood glucose levels. There are now three reflectance meters available whose measurements correlate well with laboratory measurement of blood glucose, with a correlation coefficient between 0.92 and 0.97. A stepwise approach toward blood glucose control has been found to be most valuable. The initial phase of the program involves patients performing blood glucose measurements before and 1 h after each meal, in addition to times when patients feel hypo- or hyperglycemic. This phase of the program demonstrates the vagaries of glucose control and emphasizes to the patients the dichotomy between symptoms and actual glucose levels. The patient is also taught during this period the risk factors associated with hyperglycemia that may contribute to vascular disease in the future. Subsequently, insulin is adjusted so that patients are given an insulin regimen that will coordinate peaks of insulin with peaks of blood glucose associated with a meal pattern. Patients are taught by health professionals and in a group setting to calibrate insulin calories and exercise depending on blood glucose readings. Such a program is received enthusiastically by patients and physicians. The major disadvantage lies in the cost of the meter and the reagent strips. Nevertheless, such programs may be cost effective because of the avoidance of diabetes-related hospitalizations.