Prospective evaluation of intimate partner violence in fracture clinics (PRAISE-2): protocol for a multicentre pilot prospective cohort study.
One third of women experience intimate partner violence (IPV) in their lifetime. Orthopaedic health care professionals are in a good position to identify women experiencing escalating physical violence and act to promote their immediate safety, connect them to IPV resources, and reduce the risk of further harm. However, there have been no studies that explore whether experiencing a musculoskeletal injury can trigger or worsen IPV, and there have been no studies on how experiences of IPV affect orthopaedic outcomes. The primary objective of the PRAISE-2 pilot study is to assess the feasibility of conducting a large cohort study to determine the association between IPV and injury-related complications. The secondary clinical objectives are to preliminarily explore how a history of IPV affects orthopaedic outcomes and how patterns of IPV change over time following an orthopaedic injury. We will complete a pilot multicentre prospective cohort study of 250 women with musculoskeletal injuries to determine the feasibility of a multinational prospective cohort study that will determine if prior or ongoing IPV affects orthopaedic outcomes following an injury, and how patterns of IPV change over time. Our primary outcome is feasibility measured using recruitment rate (success criterion 50 patients/site in 12 months), adherence to visit windows (success criterion 75%), participant retention (success criterion 85%), and data completeness (success criterion 80%). Our secondary exploratory clinical outcomes are injury-related complications, return to function, new IPV disclosures, utilization and cost of support services, changes in abuse patterns, quality of life, and readiness to make relationship changes. We will assess feasibility based on pre-defined criteria for feasibility success and we will analyze secondary outcomes in an exploratory fashion. The PRAISE-2 pilot study is the first step toward determining how experiences of IPV affect orthopaedic outcomes such as injury-related complications. This study will determine feasibility and assist in the development of large-scale multinational prospective IPV studies for our future IPV research program. This study will engage health care professionals from around the world to increase awareness of how IPV affects patients' musculoskeletal and injury outcomes. clinicaltrials.gov NCT02529267. Registered 20 Aug 2015.


Differential degeneration of the locus coeruleus in dementia subtypes.
Neuronal loss in the locus coeruleus (LC) is common in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). The aims of the present study were to investigate LC degeneration in different dementia disorders including vascular dementia (VaD) and frontotemporal lobar degeneration (FTLD), to compare LC degeneration with severity of pathology in AD and DLB/PDD, to further evaluate the usefulness of a previously presented scoring system and to examine the predictive value of macroscopic assessment of the LC. A horizontal mid-level section of the pons was examined in 200 neuropathologically examined cases with clinical dementia. A previous macroscopic assessment of the LC was performed in 149 of the cases. Cases with DLB/ PDD and AD presented with the highest microscopic LC degeneration scores, with significant differences compared to combined AD + VaD, in turn with a higher score than VaD, FTLD and other dementia disorders. Interrater agreement (weighted kappa;) for LC degeneration scoring was 0.83 - 0.91. DLB/ PDD, AD and AD + VaD were the diagnoses for 85% of the cases with macroscopic LC depigmentation. LC degeneration, which may be macroscopically noted, often indicates synuclein and/or Alzheimer pathology among demented. When clinical information is scarce or inconsistent, a macroscopic assessment of the LC may facilitate focusing of the subsequent neuropathological investigation. Also, the semiquantitative scoring system is a reliable tool for histological assessment of LC degeneration.


Low-dose caudal versus dorsal penile nerve block for postoperative analgesia after circumcision: a randomized comparative study.
Paediatric male circumcision is a painful surgical procedure, which is usually carried out under general anaesthesia. Regional analgesic techniques, including dorsal penile nerve block (DPNB) and caudal nerve block (CNB), are superior to opioid and non-opioid systemic analgesia for postoperative pain control after circumcision. The purpose of our study was to compare the efficacy, duration of postoperative analgesia, and complications of DPNB, CNB, and the combination of 2 blocks. Eighty-one male patients aged from 3 to 12 years scheduled for circumcision were distributed into 3 groups, each consisting of 27 patients; group 1 (DPNB group), group 2 (CNB group), and group 3 for combined blockade. This study compared the 3 groups in terms of intraoperative vital signs: heart rate and blood pressure, postoperative Wong-Baker score, and complications (nausea, vomiting, pruritus, urinary retention, and constipation). The intraoperative haemodynamics did not differ between the 3 groups of the study. There is significant difference in the Wong-Baker scale postoperatively at 1, 3, and 24 hours, being significantly less in the CNB group and combined blockade group than in the DPNB group, but there was no significant difference between the CNB group and the combined blockade group. The incidence of complications showed no significant intergroup difference, except for urinary retention being lower with DPNB. Both caudal and combined blockade were superior to DPNB for intraoperative and postoperative analgesia after circumcision. CNB and combined blockade was associated with significantly higher incidence of urinary retention compared to DPNB. Also, there was no additional benefit to the analgesic efficacy from combining both blocks.


Physician recruiting: do you know where your dollars go?
Time and resources spent on physician recruitment are investments that hospitals often overlook. While they may allocate resources for recruitment, many hospitals fail to analyze the value of recruitment dollars spent. By developing a physician search plan, however, a hospital can evaluate market demand for physicians, review ways to reduce physician turnover, and calculate a hospital's return on recruitment investments.


Modulation of Th1/Th2 balance by Lactobacillus strains isolated from Kimchi via stimulation of macrophage cell line J774A.1 in vitro.
Lactobacilli isolated from Kimchi, a Korean traditional food, were tested for their capacity to modulate the T helper (Th) 1/Th2 balance. Ovalbumin (OVA)-sensitized mouse splenocytes were cultured with 26 strains of lactobacilli; the highest IL-12 induction and lowest IL-4 production were then observed in 4 strains, including Lactobacillus plantarum CJLP55, CJLP56, CJLP133, and CJLP136. These strains produced a larger amount of IL-12, which enhances differentiation and activation of Th1 cells, in macrophage cell-lines more than positive control strains L. casei KCTC 3109(T) and L. rhamnosus GG, although they also induced production of IL-10, which is a suppressor of IL-12. Indeed, CJLP133-stimulated macrophages induced production of more Th1 cytokine IFN-γ and less Th2 cytokine IL-4 than KCTC 3109(T) and GG in co-cultivation with T cells. These findings suggest that lactobacilli from Kimchi may modulate the Th1/Th2 balance via macrophage activation in the hypersensitive reaction caused by Th2 cells. Allergic reactions including asthma and atopy are caused by predominance of Th2 response over Th1 response. Lactobacilli isolated from fermented foods such as yogurt, cheese, and Kimchi showed health-promoting activities. The present study indicated that several lactobacilli strains from Kimchi may reduce allergic reactions through macrophage-mediated induction of Th1 response.


The impact of COVID-19 on routine patient care from a laboratory perspective.
Globally, few studies have examined the effect of the COVID-19 pandemic on routine patient care and follow-up. To evaluate the effect of the COVID-19 response on biochemical test requests received from outpatient departments (OPDs) and peripheral clinics serviced by the National Health Laboratory Service Chemical Pathology Laboratory at Tygerberg Hospital, Cape Town, South Africa (SA). Request volumes were used as a measure of the routine care of patients, as clinical information was not readily available. A retrospective audit was conducted. The numbers of requests received from OPDs and peripheral clinics for creatinine, glycated haemoglobin (HbA1c), lipid profiles, thyroid-stimulating hormone (TSH), free thyroxine, free tri-iodothyronine (fT3), serum and urine protein electrophoresis, serum free light chains and neonatal total serum bilirubin were obtained from 1 March to 30 June for 2017, 2018, 2019 and 2020. The biggest impact was seen on lipids, creatinine, HbA1c, TSH and fT3. The percentage reduction between 1 March and 30 June 2019 and between 1 March and 30 June 2020 was 59% for lipids, 64% for creatinine and HbA1c, 80% for TSH and 81% for fT3. There was a noteworthy decrease in overall analyte testing from March to April 2020, coinciding with initiation of level 5 lockdown. Although an increase in testing was observed during June 2020, the number of requests was still lower than in June 2019. This study, focusing on the short-term consequences of the SA response to the COVID-19 pandemic, found that routine follow-up of patients with communicable and non-communicable diseases was affected. Future studies are necessary to evaluate the long-term consequences of the pandemic for these patient groups.


A hamstring autograft diameter ≤ 8 mm is a safe option for smaller, lighter and female athletes who want to return to pivoting sports after ACL reconstruction : Results from a retrospective evaluation of a local ACL register.
To investigate the association between hamstring autograft diameter and ACL graft failure rate in athletes who successfully returned to pivoting sports after ACL reconstruction. Retrospective evaluation of ACL graft failure rates in athletes who underwent ACL reconstruction with all-inside hamstring autograft and successfully returned to pivoting sports following postoperative rehabilitation. Athletes were divided into a ≤ 8 mm group and a > 8 mm group. Data about return to pivoting sports and ACL graft failures after ACL reconstruction were collected via a digital questionnaire. ACL graft failures were in all cases confirmed by an orthopaedic surgeon and/or MRI. The association between hamstring autograft diameter and ACL graft failure rate was investigated using a Fisher's exact test in the subgroup of athletes who completed the digital questionnaire and returned to pivoting sports. Two-hundred and twenty-nine of the 422 athletes who completed the digital questionnaire (54.2%) returned to a pivoting sport and were included for final analyses. Ninety-seven (42.4%) of the athletes who returned to sport were in the ≤ 8 mm group (8 graft failures) and 132 (57.6%) in the > 8 mm group (10 graft failures). There were significantly more women (49.5 and 13.6% respectively; p < 0.001) and significantly smaller (1.75 and 1.81 m respectively; p < 0.001), lighter (72.2 and 79.6 kg respectively; p < 0.001) and younger (23.6 and 26.1 years old respectively; p = 0.015) athletes in the ≤ 8 mm group compared to the > 8 mm group. There was no significant association between hamstring autograft diameter and ACL graft failure rate. A hamstring autograft diameter of ≤ 8 mm is a legitimate option for smaller, lighter and female athletes without increasing the risk for ACL graft failure. III.


Tumor promoters and cocarcinogens in tobacco carcinogenesis.
Cigarette smoke induces carcinoma of the larynx in Syrian golden hamsters and is active as a tumor promoter in hamsters pretreated with a low dose of a PAH, nitrosamine, or nitrosamide. These tumorigenic effects are only observed with total smoke, but not with the gas phase alone. This demonstrates that the tumorigenic agents reside primarily in the particulate phase. According to fractionation experiments, a number of four- and five-ring aromatic hydrocarbons serve as the major tumor initiators in tobacco smoke. Tumor promoters reside primarily in weakly polaric neutral subfractions and in the weakly acidic portion of the particulate matter and include certain unsaturated hydrocarbons and phenolic compounds. Cocarcinogenic activity is a characteristic feature of tobacco smoke and its particulates. Among the cocarcinogens formed during combustion are catechols and certain nontumorigenic aromatic hydrocarbons and terpenes. Nicotine may also serve as a cocarcinogen as is indicated by preliminary data. The action of tumor promoters and cocarcinogens in tobacco carcinogenesis, the precursors for tobacco smoke promoters and cocarcinogens, and methods for their reduction in smoke are discussed.


Upper Bound on the Mutational Burden Imposed by a CRISPR-Cas9 Gene-Drive Element.
CRISPR-Cas9 gene drives (CCGDs) are powerful tools for genetic control of wild populations, useful for eradication of disease vectors, conservation of endangered species and other applications. However, Cas9 alone and in a complex with gRNA can cause double-stranded DNA breaks at off-target sites, which could increase the mutational load and lead to loss of heterozygosity (LOH). These undesired effects raise potential concerns about the long-term evolutionary safety of CCGDs, but the magnitude of these effects is unknown. To estimate how the presence of a CCGD or a Cas9 alone in the genome affects the rates of LOH events and de novo mutations, we carried out a mutation accumulation experiment in yeast Saccharomyces cerevisiae . Despite its substantial statistical power, our experiment revealed no detectable effect of CCGD or Cas9 alone on the genome-wide rates of mutations or LOH events, suggesting that these rates are affected by less than 30%. Nevertheless, we found that Cas9 caused a slight but significant shift towards more interstitial and fewer terminal LOH events, and the CCGD caused a significant difference in the distribution of LOH events on Chromosome V. Taken together, our results show that these genetic elements impose a weak and likely localized additional mutational burden in the yeast model. Although the mutagenic effects of CCGDs need to be further evaluated in other systems, our results suggest that the effect of CCGDs on off-target mutation rates and genetic diversity may be acceptable.


A novel inorganic-organic hybrid borate, poly{[Na(2)(C(4)H(2)O(4))(H(3)BO(3))(H(2)O)(4)]·H(3)BO(3)}.
The structure of the title compound, catena-poly[[[di-μ-aqua-μ-fumarato-μ-(boric acid)-disodium]-di-μ-aqua] boric acid monosolvate], contains two crystallographically independent Na(+) cations, each being six-coordinated by one fumarate O atom, one boric acid O atom and four water O atoms in a distorted octa-hedral geometry. Adjacent [NaO(2)(OH(2))(4)] units share edges and are linked into chains propagating parallel to [100]. The free boric acid mol-ecules are connected to the chains through strong inter-molecular O-H⋯O hydrogen bonds. Additional O-H⋯O hydrogen bonds between the water mol-ecules, the free and coordinated boric acid mol-ecules and the fumarate anion lead to the formation of a three-dimensional supra-molecular structure. With the exception of the two water mol-ecules, all other atoms lie on mirror planes.


[Microfluorimetric study of the effect of almitrine bismesylate (Vectarion) on intrapulmonary neuroepithelial bodies].
As Almitrine bismesylate is a potent peripheral chemo-receptor stimulant we have studied its action, after intra-peritoneal injection, on the intra-neuro-epithelial bodies (NEB) of 24 young rabbits (4 to 17 days old) measuring the intensity of the cytoplasmic fluorescence. The administration of Almitrine bismesylate in pharmacological doses provoked a marked rise (around 25%) in the intensity of fluorescence of NEB compared to a placebo group, indicating a raised cytoplasmic concentration of serotonin. These observations show that Almitrine bismesylate, in stimulating all the peripheral chemo-receptors equally, influences the NEB at the same time corroborating the intra-pulmonary chemoreceptor mature of the latter. The mechanism of action of Almitrine bismesylate on the NEB remains unexplained at a cellular level. Some supplementary studies are planned to elucidate these aspects.


Medium-large polyps of the colon: a contribution for their clinical profile and a proper surveillance.
A retrospective analysis of polypoid lesions of the colon larger than 1 cm was performed with the aim to study their characteristics and a proper surveillance schedule. We reviewed all colon polypoid lesions larger than 1 cm found and treated during the period January 1984- December 1993 that were not considered cancer macroscopically. The records of 361 patients with 391 polyps are the object of this report. The polyps were divided into subgroups according to size: A) less than 20 mm, B) between 21 and 30 mm, and C) larger than 30 mm. Out of 391 polypoid lesions 373 were adenomas: 60% were found in males. The age group distribution showed no differences among the subgroups. The pedunculated type showed a decrease from 69.1% to 43.3% with the increasing of size: inverse figures were observed for sessile polyps. The lesions were mainly located in left colon. Synchronous adenomas were found in 25.4% patients, and metachronous and previous adenomas respectively in 24.8% and 5.2%: no significant difference was present in the subgroups. Synchronous malignancy in the colon was found in 2% of the patients. Histological characteristics demonstrated a decrease of tubular adenoma from 46.5% to 22.6% from subgroup A to C, while villous adenomas increased inversely from 6.6% to 15.1%. The presence of severe dysplasia ranged from 20.9% to 56.1% in subgroups A and C, respectively, and adenomas with invasive cancer showed a significant increase from the subgroup A to C, respectively from 4.3% to 10.5%. During an average 36-month follow-up we observed 2 metachronous colon cancers, surgically treated in Dukes stage B, 84 metachronous adenomas, all less than 10 mm and without malignant alterations. Our data confirm other literature reports regarding the profile of colon adenomas with an increasing risk of malignancy with the increase of size and the presence of villous structure. In our opinion the assessment of a "clean colon" status is important when an adenoma is found in the colon. The proper follow-up for adenomas must be tailored for any individual patient when risk factors such as size, villous structure, personal and family history of neoplastic lesions of the colon are present. The follow-up schedule, presently recommended for colon adenomas, must be flexible according to these parameters.


Papillary and follicular thyroid carcinoma metastatic to the skin: a case report and review of the literature.
Cutaneous metastases from thyroid cancers are rare. We report the case of an otherwise asymptomatic 81-year-old woman with an enlarging scalp lesion. Her solitary skin metastasis was the presenting feature of thyroid carcinoma. Routine histopathology of the lesion was notable for an atypical clear cell neoplasm. Immunohistochemistry was positive for thyroglobulin. Subsequent resection of the thyroid gland identified separate foci (< 1 cm) for both papillary and follicular carcinoma. Although such immunohistochemical staining has been used previously, it has never been reported to provide the definitive diagnosis for a solitary cutaneous metastasis from the thyroid. Previous tumors had anatomic features in a clinical context that permitted identification by routine light microscopy. Clear cell features found in the follicular focus of carcinoma in the thyroid suggest that it is the primary. A worldwide literature review reveals that follicular carcinoma has a greater preponderance than papillary carcinoma for cutaneous metastasis and that the majority of skin metastases from either papillary or follicular thyroid cancer are localized to the head and neck.


Analysis of free-radical scavenging of Yerba Mate (Ilex paraguriensis) using electron spin resonance and radical-induced DNA damage.
Mate (MT) is a popular South American beverage that has been used as a traditional medicine for centuries, spurring recent interest in its nutraceutical properties. MT is prepared as an infusion of leaves from the Yerba Mate (llex paraguriensis) tree. MT has been reported to have antioxidant properties in vitro and in vivo, but these have not been fully characterized in terms of effects against specific radicals. Accordingly, we examined the antioxidant effects of an MT infusion against hydroxyl and superoxide radicals in both chemical and cell culture assays. MT infusions were prepared at 3.10 g/L in boiling water and diluted to experimental dilutions from this stock. Electron spin resonance (ESR) experiments indicated that MT scavenged hydroxyl radicals (produced via the Fenton reaction) and superoxide radicals (produced via the xanthine/xanthine oxidase enzymatic reaction) at all concentrations tested (P < 0.05). Further controls indicated that superoxide radical scavenging was not due to xanthine oxidase inhibition. MT scavenged hydroxyl radicals and decreased cellular oxygen consumption in a dose-dependent manner in Cr(VI)-stimulated RAW 264.7 cells, based on ESR and oxygraph measurements (P < 0.05). Similarly, MT also inhibited hydroxyl-radical-induced lipid peroxidation and DNA damage in a dose-dependent manner in RAW 264.7 cells, based on malondialdehyde and Comet assay data (P < 0.05). This study indicates that MT possesses potent antioxidant effects against hydroxyl and superoxide radicals in both chemical and cell culture systems, as well as DNA-protective properties. These data further clarify the reported antioxidant effects of Yerba Mate infusions.


Risk factors associated with surgical site infection in upper and lower gastrointestinal surgery.
To assess the risk factors of surgical site infection (SSI) in gastrointestinal surgery. Surgical site infection surveillance was conducted in 27 hospitals. The incidence of SSI in the 941 patients studied was 15.5%. The factors associated with SSI were body mass index (BMI), comorbidity, emergency procedures, wound classification, blood loss, the suture material used for intra-abdominal ligation, the method of subcutaneous incision, the frequency of glove changes, and the absence of subcutaneous sutures. In lower alimentary tract procedures, additional factors influencing the incidence of SSI were sex, smoking status, operating time, the suture material used for abdominal wound closure and seromuscular sutures, and the combined resection procedures. According to a multiple logistic regression analysis, the independent risk factors for SSI were as follows: the type of operation, blood loss, wound classification, emergency procedures, the frequency of glove changes, the use of subcutaneous sutures, combined resection procedures, and the material used for seromuscular suturing. Strict asepsis and minimal blood loss were associated with a lower incidence of SSI following gastrointestinal surgery. The use of absorbable suture material may be involved in reducing the risk of SSI.


[Effect of superphonoelectrophoresis on chorioretinal dystrophy].
The effect of a pharmacophysical method superphonophoresis on the course of chorioretinal dystrophy has been studied in 320 patients (640 eyes) with chorioretinal dystrophies treated by an ultrasonic UZT-104 device and a Nion galvanic device. The "superexposure" was phonophoresis of a bipolar drug 10% dimethylsulfoxide, creating the optimal conditions for penetration of the main agent through tissue barrier. The results (improvement of visual acuity, hemodynamics, trophics, shown by a higher linear rate of the blood flow in the orbital artery and middle cerebral arteries) persisted for up to 12 months, moreover, the rate of cellular and tissue metabolism increased (the time of adaptation to darkness decreased and color sensitivity increased).


Molecular and Physiological Characterization of Fluoroquinolone-Highly Resistant Salmonella Enteritidis Strains.
Four clinical isolates of Salmonella Enteritidis, susceptible to ciprofloxacin, and their spontaneous ciprofloxacin resistant (MICs from 8 to 16 μg/mL) and highly resistant (MIC 2048 μg/mL) mutants were used to gain an insight into the dynamics of development of fluoroquinolone (FQs) resistance in S. Enteritidis serovar. The first two high-frequency (i.e., mutations that occurred in each tested strain) mutations occurred in the gyrA, resulting in amino acid substitutions S83Y and S83F as well as D87G. Amino acid substitution D87G was significantly associated with the highly resistant mutants. Another high-frequency mutation, deletion in the ramRA intergenic region, was determined among the same group of highly resistant mutants. More importantly, each of these deletion mutations affected the RamR binding site. The effect of one 41 bp deletion mutation was empirically tested. The results showed that the deletion was responsible for resistance to ceftiofur and amoxicillin/clavulanic acid and decreased susceptibility to azithromycin and tetracycline. Performing gene expression assays across all ciprofloxacin susceptible groups, we found a consistent and significant upregulation of the ramA, acrB, and tolC (efflux pump associated genes) and downregulation of ompF (porin), clearly illustrating the importance of not only efflux but also porin-mediated permeability in the development of FQs resistance. Our data also showed that S. Enteritidis could acquire multiple mutations in QRDR region, further resulting in no up regulation of the ramA, acrB and tolC genes. These QRDR mutations and no activation of the AcrAB efflux pump seem to preserve the fitness of this organism compared to the S. Enteritidis strains that did not acquire multiple QRDR mutations. This report describes the dynamics of FQ-associated mutations in the highly resistant in FQ mutants in S. Enteritidis. In addition, we characterized a deletion in the ramRA integenic region, demonstrating that this frequent mutation in the highly resistant FQ mutants provide resistance or reduce susceptibility to multiple families of antibiotics.


Valorization of Chicken Feet By-Product of the Poultry Industry: High Qualities of Gelatin and Biofilm from Extraction of Collagen.
In this research, products with high quality were obtained from natural sources. The sensorial qualities, chemical characterization, and physical properties of gelatin extracted from chicken feet were compared with commercial gelatins. The extraction process was performed using acetic acid on a concentration ranging from 0.318% to 3.682%, processing time between 1.0 h and 8.4 h and extraction temperature between 43.3 °C and 76.8 °C. After the end of each assay, the yield was measured. Results showed that, under the best conditions, the collagen extraction yield was above 8%, and comprised 78.525 g/100 g of protein. Collagen analyzed by ICP-MS was composed of 99.44% of macro-minerals that are of great importance to human health. ATR-FTIR analysis showed that approximately 70.90% of the total protein from chicken feet is collagen, whereas, in commercial gelatin, only 30.31% is collagen. When comparing chicken gelatin with commercial gelatin, most sensory attributes were similar and chicken gelatin gained acceptance by more than 80% of the consumers. Additionally, the collagen films obtained from chicken feet and swine showed water absorption, odors, and texture characteristics similar to commercial material, such as latex and celofane. Consequently, due to its similarity to human skin, it is possible to apply it as a biocurative.


Trends in cancer incidence in Uruguay: 2002 -2015.
Uruguay is the south American country which has the highest cancer incidence and mortality rates. The National Cancer Registry collects data on cancer cases nationwide since 1989 and has reached high quality standards in the last decades. This is the first report on incidence trends. Data from the National Cancer Registry of all new cases of invasive cancer from twelve sites diagnosed in 2002-2015 was analyzed. Age-standardized rates were calculated. Trends of incidence rates were analyzed using joinpoint regression models. For both, men and women, incidence rates trends for all cancer sites, colo-rectal and bladder cancer remained stable. Esophageal and gastric cancers descended while thyroid and kidney cancer incidence increased. In men lung cancer decreased; testicular cancer increased, and prostate cancer increased at the beginning of the period and decreased in the final years. In women, lung cancer increased, breast cancer remained stable and cervical cancer presented a significant decline from 2005 to 2010 and reached a plateau since then. Cancer incidence dynamics are complex and affected not only by Public Health policies such as tobacco control, vaccination and screening programs, but also by environmental and life style changes and the attitude of the medical community towards the application of diagnostic and therapeutic tools. The aim of this paper is to analyze cancer incidence time trends in the country and provide possible explanations to them.


Use of multisequence 3.0-T MRI to detect severe traumatic brain injury and predict the outcome.
The aim of this study was to evaluate multisequence 3.0-T MRI in the detection of severe traumatic brain injury (sTBI) and in predicting the outcome. 32 patients with sTBI were prospectively enrolled, and multisequence 3.0-T MRI was performed 4-8 weeks post injury. Quantitative data were recorded on each sequence. The ability to display the parenchymal lesions was compared with that of 64-slice spiral CT. The clinical and radiological results were correlated with the Glasgow Outcome Scale Extended scores 6 months after injury. 3.0-T MRI could display more lesions than CT, especially when the lesion was deeply located. The lesion volumes and diffuse axonal injury (DAI) scores were different between good and poor outcome groups on fluid attenuated inversion recovery (p < 0.05). The apparent diffusion coefficient (ADC) values of the splenium of the corpus callosum and brain stem were also different (p < 0.05). Patients with unfavourable outcome showed a significantly higher volume of haemorrhage on susceptibility-weighted imaging than those with favourable outcomes and had haemorrhages generally located more deeply. Logistic regression analysis revealed that the location of haemorrhage and the ADC values of the splenium of the corpus callosum were independent risk factors for poor outcome, with an overall predictive accuracy of 91.4%. The joint use of conventional and advanced sequences of 3.0-T MRI can comprehensively detect the pathological changes occurring after sTBI. Haemorrhagic and non-haemorrhagic DAIs in deep structures strongly suggest poor outcome. This article improves the understanding of advanced MRI sequences in the detection of patients with sTBI and prediction of prognosis.


Health literacy among refugees in Sweden - a cross-sectional study.
Refugees have poorer health compared to indigenous populations, which may be explained by lower health literacy, i.e. not being able to access, understand, appraise or apply health information. This study aims to determine levels of functional and comprehensive health literacy, and factors associated with inadequate health literacy, in refugees coming to Sweden. A cross-sectional study was performed among 455 adult refugees speaking Arabic, Dari, Somali or English. Participants in 16 strategically selected language schools for immigrants responded to a questionnaire. Health literacy was measured using the Swedish Functional Health Literacy Scale and the HLS-EU-Q16 questionnaire. Uni- and multivariate statistical methods were used to investigate group differences. The majority of the participating refugees had inadequate or limited functional health literacy and comprehensive health literacy. About 60% of them had inadequate functional health literacy and 27% had inadequate comprehensive health literacy. Low education and/or being born in Somalia were factors associated with an increased risk of having inadequate functional health literacy. Having inadequate functional health literacy was associated with an increased risk of having inadequate comprehensive health literacy. The majority of refugees in the language schools had limited or poor health literacy. Health literacy should be taken into consideration in contexts and in activities addressing migrants. More research is needed to better understand health literacy among refugees and to develop strategies and methods to increase health literacy and make life easier for those with low health literacy.


Regulation of cobalamin biosynthetic operons in Salmonella typhimurium.
Transcription of cobalamin (cob) biosynthetic genes in Salmonella typhimurium is repressed by cobalamin and by molecular oxygen. These genes seem to be subject to catabolite repression, and they are maximally expressed under conditions of anaerobic respiration of glycerol-fumarate. A 215-fold increase in the expression of cob genes occurs when S. typhimurium shifts from aerobic growth on glucose to anaerobic respiration of glycerol-fumarate under strictly anoxic growth conditions. Exogenous cyclic AMP substantially stimulates the transcription of cob-lac fusions during aerobic growth. However, cyclic AMP is not absolutely required for the expression of the pathway, nor does it mediate the aerobic control. Cobalamin biosynthesis is not seen under aerobic growth conditions, even when transcription is stimulated by the addition of cyclic AMP. Hence, additional control mechanisms triggered by the presence of molecular oxygen must operate independently from transcription effects on the cob operons.


UVA generates pyrimidine dimers in DNA directly.
There is increasing evidence that UVA radiation, which makes up approximately 95% of the solar UV light reaching the Earth's surface and is also commonly used for cosmetic purposes, is genotoxic. However, in contrast to UVC and UVB, the mechanisms by which UVA produces various DNA lesions are still unclear. In addition, the relative amounts of various types of UVA lesions and their mutagenic significance are also a subject of debate. Here, we exploit atomic force microscopy (AFM) imaging of individual DNA molecules, alone and in complexes with a suite of DNA repair enzymes and antibodies, to directly quantify UVA damage and reexamine its basic mechanisms at a single-molecule level. By combining the activity of endonuclease IV and T4 endonuclease V on highly purified and UVA-irradiated pUC18 plasmids, we show by direct AFM imaging that UVA produces a significant amount of abasic sites and cyclobutane pyrimidine dimers (CPDs). However, we find that only approximately 60% of the T4 endonuclease V-sensitive sites, which are commonly counted as CPDs, are true CPDs; the other 40% are abasic sites. Most importantly, our results obtained by AFM imaging of highly purified native and synthetic DNA using T4 endonuclease V, photolyase, and anti-CPD antibodies strongly suggest that CPDs are produced by UVA directly. Thus, our observations contradict the predominant view that as-yet-unidentified photosensitizers are required to transfer the energy of UVA to DNA to produce CPDs. Our results may help to resolve the long-standing controversy about the origin of UVA-produced CPDs in DNA.


Evidence of a protein C-like anticoagulant system in bony fish.
Evidence is presented, confirming the presence of an anticoagulant system in the plasma of Atlantic salmon (Salmo salar L) and rainbow trout (Oncorhynchus mykiss Walbaum) (Order: Teleostei, Family: Salmonidae) that bears striking similarities with the protein C anticoagulant system in mammals; its vitamin K-dependence was documented through a warfarin feeding trial. A potent activator of this system is the protein C activator from the venom of the Central American Moccasin, Agkistrodon bilineatus. When activated, the system splits the tripeptide substrate glu-pro-arg-pNa, which is the substrate preferred for the in vitro assay of human protein C. It also prolongates the plasma activated partial thromboplastin time, indicating that the system is of clinical relevance. A temperature dependence of the plasma protein C-like activity was evident, the mean activity being 5- to 10-fold higher, but also more variable, in both species in summer and early fall, than it was in winter. There was also a species difference, with rainbow trout having the higher levels. In man, subnormal values of protein C implies an increased risk of thrombosis. Whether this applies to fish is not known. It is, however, a fact that microvascular thromboses are prevalent in farmed Atlantic salmon in winter, whereas thrombotic disease is not a problem in rainbow trout; in the present study plasma protein C-like activity was 30% (of a human reference plasma) in salmon at 4 degrees C compared to a level of 60% in rainbow trout. A complicating factor for the assay of protein C-like activity in salmonid plasma, is the poor stability of the inhibitory system upon storage. Consequently, assays have to be done with freshly prepared citrated plasma.


The effect of fiber on satiety and food intake: a systematic review.
Epidemiologic studies have shown that fiber intake is associated with a lower body weight. Satiety and energy intake are possible explanations for this effect. The purpose of this study was to recommend fiber types and doses that are effective in reducing appetite and energy intake. A systematic review was conducted using the American Dietetic Association's evidence analysis process as a guide. Studies were identified from PubMed and bibliographies of review articles. Studies measuring appetite, food and/or energy intake with a treatment period of ≤24 hours, a reported fiber type and amount, a low- or no-fiber control, and healthy human participants were included. Forty-four publications were identified, from which 107 treatments were analyzed. Thirty-eight fiber sources were identified. The percentage of treatments that significantly reduced subjective appetite rating compared with the control was 39%. The percentage that significantly reduced food or energy intake was 22%. The satiety-enhancing effects of β-glucan, lupin kernel fiber, rye bran, whole grain rye, or a mixed high-fiber diet were supported in more than one publication. Most fibers do not reduce appetite or energy intake in acute study designs. KEY TEACHING POINTS: • Dietary fiber intake is associated with lower body weight in epidemiologic studies. • Most acute fiber treatments (61%) did not enhance satiety. • Most acute fiber treatments (78%) did not reduce food intake. • Neither fiber type nor fiber dose were related to satiety response or food intake.


Emotion Recognition Abilities in Adults with Anorexia Nervosa are Associated with Autistic Traits.
Difficulties in socio-emotional functioning are proposed to contribute to the development and maintenance of anorexia nervosa (AN). This study aimed to examine emotion recognition abilities in individuals in the acute and recovered stages of AN compared to healthy controls (HCs). A second aim was to examine whether attention to faces and comorbid psychopathology predicted emotion recognition abilities. The films expressions task was administered to 148 participants (46 AN, 51 recovered AN, 51 HC) to assess emotion recognition, during which attention to faces was recorded using eye-tracking. Comorbid psychopathology was assessed using self-report questionnaires and the Autism Diagnostic Observation Schedule-2nd edition (ADOS-2). No significant differences in emotion recognition abilities or attention to faces were found between groups. However, individuals with a lifetime history of AN who scored above the clinical cut-off on the ADOS-2 displayed poorer emotion recognition performance than those scoring below cut-off and HCs. ADOS-2 scores significantly predicted emotion recognition abilities while controlling for group membership and intelligence. Difficulties in emotion recognition appear to be associated with high autism spectrum disorder (ASD) traits, rather than a feature of AN. Whether individuals with AN and high ASD traits may require different treatment strategies or adaptations is a question for future research.


Pomegranate juice and extracts provide similar levels of plasma and urinary ellagitannin metabolites in human subjects.
Pomegranate juice (PJ), a rich source of polyphenols including ellagitannins, has attracted much attention due to its reported health benefits. This has resulted in the consumption of liquid and powder pomegranate extracts as alternatives to PJ. Therefore establishing the bioavailability of polyphenols from these extract preparations is necessary. Sixteen healthy volunteers sequentially consumed, with a 1-week washout period between treatments, PJ (8 ounces, Wonderful fruit variety), a pomegranate polyphenol liquid extract (POMxl, 8 ounces), and a pomegranate polyphenol powder extract (POMxp, 1,000 mg). The three interventions provided 857, 776, and 755 mg of polyphenols as gallic acid equivalents, respectively. Plasma bioavailability, judged based on ellagic acid levels over a 6-hour period, did not show statistical differences in area under the curve for the three interventions: 0.14 +/- 0.05, 0.11 +/- 0.03, and 0.11 +/- 0.04 micromol . hour/L for PJ, POMxl, and POMxp, respectively. The time of maximum concentration was delayed for POMxp (2.58 +/- 0.42 hours) compared to PJ (0.65 +/- 0.23 hours) and POMxl (0.94 +/- 0.06 hours). Urolithin-A glucuronide, a urinary metabolite of ellagic acid, was not significantly different with the three interventions, reaching levels of approximately 1,000 ng/mL. This study demonstrates that ellagitannin metabolites, delivered from pomegranate fruits, as PJ, POMxl, and POMxp, reach equivalent levels with a delay in time of maximum concentration of POMxp compared to PJ and POMxl.


Genomic organization of the murine polysialyltransferase gene ST8SiaIV (PST-1).
Polysialic acid (PSA) is an important regulator of cellular interactions. Two enzymes (ST8SiaII and ST8SiaIV) are capable of synthesizing PSA. In the present study, the gene encoding the murine ST8SiaIV (PST-1) has been isolated and characterized. In contrast to the ST8SiaII (STX) gene which contains six exons and spans about 80 kb, the ST8SiaIV gene comprises only five exons spanning over at least 55 kb. However, alignment of the two genes revealed that exon-intron boundaries of exons 2-5 of ST8SiaIV and exons 3-6 of ST8SiaII are located at identical sites. Differences are restricted to the 5'-region encoded by one exon in the case of ST8SiaIV, whereas the corresponding region of ST8SiaII is interrupted by a very long intron. 5'-RACE analysis of the ST8SiaIV transcript using mRNA from AtT20 cells identified two transcription start sites at positions -324 and -204 relative to the translation start codon. The promoter region of ST8SiaIV lacks TATA- and CAAT-like sequences and is enriched in G+C (60%). The promoter contains putative Sp1, AP-1, AP-2, and PEA3 binding sites, as well as a purine- and a pyrimidine-rich region. Luciferase reporter gene assays demonstrated that the region between nucleotides -443 and -162 is sufficient to direct gene expression. The induction of luciferase activity was 30- and 10-fold in the PSA-positive AtT20 and CHO cells, but only 5- and 7-fold in the PSA-negative NIH-3T3 cells and in a PSA-negative subline of AtT20. Thus, although decreased in activity in PSA-negative cell lines, the basal promoter is not sufficient for the strong cell-type and tissue specific regulation of the ST8SiaIV gene, suggesting regulatory elements in the more upstream 5'-region.


[Angioprotective properties of blood sugar lowering drugs from the group of inhibitors of dipeptidyl peptidase-4].
Diabetes mellitus (DM) is a major health problem in all developed countries. It contributes to the development of atherosclerosis and increases the risk of cardiovascular events so blood glucose level correction is essential to preventing these complications. The relatively new and promising class of anti-diabetic drugs is dipeptidyl peptidase-4 inhibitors. By improving carbohydrate metabolism, they have angioprotective effects, such as anti-inflammatory and anti-atherosclerotic ones, including atherosclerotic plaque stabilization, improve endothelial function, lower blood pressure, and reduce the severity of albuminuria, which may have clinical implications for the prevention of macrovascular complications of type 2 DM.


Repeated delivery of adeno-associated virus vectors to the rabbit airway.
Efficient local expression from recombinant adeno-associated virus (rAAV)-cystic fibrosis (CF) transmembrane conductance regulator (CFTR) vectors has been observed in the airways of rabbits and monkeys for up to 6 months following a single bronchoscopic delivery. However, it is likely that repeated administrations of rAAV vectors will be necessary for sustained correction of the CF defect in the airways. The current study was designed to test the feasibility of repeated airway delivery of rAAV vectors in the rabbit lung. After two doses of rAAV-CFTR to the airways, rabbits generated high titers of serum anti-AAV neutralizing antibodies. Rabbits then received a third dose of a rAAV vector containing the green fluorescent protein (GFP) reporter gene packaged in either AAV serotype 2 (AAV2) or serotype 3 (AAV3) capsids. Each dose consisted of 1 ml containing 5 x 10(9) DNase-resistant particles of rAAV vector, having no detectable replication-competent AAV or adenovirus. Three weeks later, GFP expression was observed in airway epithelial cells despite high anti-AAV neutralizing titers at the time of delivery. There was no significant difference in the efficiency of DNA transfer or expression between the rAAV3 and rAAV2 groups. No significant inflammatory responses to either repeated airway exposure to rAAV2-CFTR vectors or to GFP expression were observed. These experiments demonstrate that serum anti-AAV neutralizing antibody titers do not predict airway neutralization in vivo and that repeated airway delivery rAAV allows for safe and effective gene transfer.


Meeting the online educational needs of international health promoters: an evaluation of a comprehensive, multilingual global training program in tobacco control.
An evaluation of a global online training program in tobacco control offered in multiple languages was conducted to identify ways in which the varied online educational needs of its international participants could be more effectively met. An online survey was administered to a sample of training participants to solicit feedback regarding course content and delivery. In addition, participants' training site usage patterns were examined. Findings showed high levels of satisfaction with training content and delivery, as well as of knowledge acquisition and utilization. Respondents indicated that it was important that course content be current and relevant to their practice. Although findings are consistent with best practices for online continuing education, in practice it is challenging to keep material updated, incorporate examples and case studies from the participants' countries, and integrate adequate opportunities for interactivity when a course has geographically and linguistically diverse participants. Low-cost, technologically appropriate solutions should be developed to maximize the effectiveness of similar continuing education programs for health promoters worldwide.


Effect of Subjective Economic Status During the COVID-19 Pandemic on Depressive Symptoms and Suicidal Ideation Among South Korean Adolescents.
This study identified the relationships between perceived household economic status and household economic downturn due to COVID-19 and adolescent depressive symptoms and suicidal ideation. Participants for this study were extracted from the 13th Korea Youth Risk Behavior Web-Based Survey, conducted from August to November 2020. The participants comprised 54,948 middle and high school students selected by stratified random cluster sampling. The prevalence rates of depressive symptoms and suicidal ideation were 25.2% and 10.9%, respectively. Multivariate logistic regression analysis showed that lower perceived household economic status significantly predicted higher prevalence of depressive symptoms and suicidal ideation. Participants who perceived that their household economic status had declined because of COVID-19 were more likely to have experienced depression and suicidal ideation. These results were similar regardless of the participants' perceptions of household economic status. This study found that in the ongoing pandemic, there is a need for an active mental health promotion program for adolescents from low-income households, especially those who experienced a recent decline in the household economy.


Sudden cardiac death in adults: causes, incidence and interventions.
Many nurses will be familiar with the unexpected death of an adult patient following a sudden, life-threatening cardiac event. It is a situation that demands sensitive nursing care and skilled interventions to provide a foundation for recovery and promote healthy bereavement. This article examines the causes and incidence of sudden cardiac death in adults. Possible reactions of those who are suddenly bereaved are described and immediate care interventions aimed at dealing with the grief process are discussed. The article concludes by identifying ways in which the incidence of sudden cardiac death may be reduced.


Isolation of type II pneumocytes by laser flow cytometry.
The isolation of a pure population of type II pneumocytes from adult rabbit lung by the technique of multiparameter laser flow cytometry is reported here. Lipophilic phosphine-3R was used to stain cell dissociated from lungs by elastase and trypsin. Type II cells were then sorted by simultaneous measurement of high phosphine-3R fluorescent staining of lamellar bodies and intermediate intensity of low-angle light scatter. We were able to obtain an essentially pure population (98%) at sorting rates of 5 X 10(5) lamellar-body-containing cells per hour. The cell sorter technique offers an attractive alternative to the density gradient isolation of type II cells, particularly in terms of detailed population analysis. In addition, refinements in cell sorter methods offer the potential to discriminate differentiating type II cells with few lamellar bodies that do not segregate on the basis of buoyant density.


Mycobacterium tuberculosis directs T helper 2 cell differentiation by inducing interleukin-1β production in dendritic cells.
Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), resides and replicates within phagocytes and persists in susceptible hosts by modulating protective innate immune responses. Furthermore, M. tuberculosis promotes T helper 2 (Th2) immune responses by altering the balance of T cell polarizing cytokines in infected cells. However, cytokines that regulate Th2 cell differentiation during TB infection remain unknown. Here we show that IL-1β, produced by phagocytes infected by virulent M. tuberculosis strain H37Rv, directs Th2 cell differentiation. In sharp contrast, the vaccine strain bacille Calmette-Guérin as well as RD-1 and ESAT-6 mutants of H37Rv failed to induce IL-1β and promote Th2 cell differentiation. Furthermore, ESAT-6 induced IL-1β production in dendritic cells (DCs), and CD4(+) T cells co-cultured with infected DCs differentiated into Th2 cells. Taken together, our findings indicate that IL-1β induced by RD-1/ESAT-6 plays an important role in the differentiation of Th2 cells, which in turn facilitates progression of TB by inhibiting host protective Th1 responses.


Integration of papillomavirus DNA near myc genes in genital carcinomas and its consequences for proto-oncogene expression.
DNA sequences of specific human papillomavirus (HPV) types are found integrated in the cell genome in most invasive genital carcinomas. We have determined the chromosomal localization of integrated HPV type 16 (HPV-16) or HPV-18 genomes in genital cancers by in situ hybridization experiments. In three cancers, HPV sequences were localized in chromosome band 8q24.1, in which the c-myc gene is mapped, and in one cancer HPV sequences were localized in chromosome band 2p24, which contains the N-myc gene. In three of the four cases, the proto-oncogene located near integrated viral sequences was found to be structurally altered and/or overexpressed. These data indicate that HPV genomes are preferentially integrated near myc genes in invasive genital cancers and support the hypothesis that integration plays a part in tumor progression via an activation of cellular oncogenes.


Humidity/Oxygen-Insensitive Organic Synaptic Transistors Based on Optical Radical Effect.
For most organic synaptic transistors based on the charge trapping effect, different atmosphere conditions lead to significantly different device performance. Some devices even lose the synaptic responses under vacuum or inert atmosphere. The stable device performance of these organic synaptic transistors under varied working environments with different humidity and oxygen levels can be a challenge. Herein, a moisture- and oxygen-insensitive organic synaptic device based on the organic semiconductor and photoinitiator molecules is reported. Unlike the widely reported charge trapping effect, the photoinduced free radical is utilized to realize the photosynaptic performance. The resulting synaptic transistor displays typical excitatory postsynaptic current, paired-pulse facilitation, learning, and forgetting behaviors. Furthermore, the device exhibits decent and stable photosynaptic performances under high humidity and vacuum conditions. This type of organic synaptic device also demonstrates high potential in ultraviolet B perception based on its environmental stability and broad ultraviolet detection capability. Finally, the contrast-enhanced capability of the device is successfully validated by the single-layer-perceptron/double-layer network based Modified National Institute of Standards and Technology pattern recognition. This work could have important implications for the development of next-generation environment-stable organic synaptic devices and systems.


Characterization of differentiated subcutaneous and visceral adipose tissue from children: the influences of TNF-alpha and IGF-I.
The relationship between subcutaneous and visceral adipocyte metabolism and development has been extensively studied in adult but not in pediatric tissue. Our aim was to isolate, develop, characterize, and compare primary cell cultures of subcutaneous and visceral preadipocytes from 16 normal prepubertal children (10 male and 6 female). Subculture techniques were developed to increase cell number and allow differentiation using a chemically defined serum-free medium. Removal of insulin from the differentiation medium prevented adipogenesis in both subcutaneous and visceral preadipocytes, whereas coincubation with rosiglitazone markedly enhanced glycerol-3-phosphate dehydrogenase activity, peroxisome proliferator-activated receptor gamma expression, and triglyceride accumulation in cells from both fat depots. Adiponectin secretion increased with differentiation from undetectable levels at day 0. Histological analyses demonstrated significant differences in lipid droplet number and size, with subcutaneous cells having fewer but larger vesicles compared with visceral cells. Downregulation and reorganization of the cytoskeleton appeared comparable. We further demonstrate regional differences in adipogenesis manipulation. Tumor necrosis factor-alpha was more effective at inhibiting differentiation in subcutaneous cells, whereas insulin-like growth factor-I stimulated differentiation more effectively in visceral cells. Insulin-like growth factor binding protein-3 enhanced differentiation equally. These observations may have important physiological and pharmacological implications for the development of obesity in later life.


The ubiquitous carrier protein--a window to metabolite biosynthesis.
Nature has developed a remarkable strategy to isolate metabolites from the milieu of the cell for chemical modification through the use of carrier proteins. Common to both primary and secondary metabolic pathways, acyl-carrier proteins constitute a conserved protein architecture which mediate the biosynthesis of a variety of metabolic products. Analogies have been made between the carrier protein and solid phase resin for chemical synthesis, as both entities provide a mechanism to separate compounds of interest from complex mixtures for selective chemical modification. However, there is significantly more to the carrier protein than an attachment point. In this review, we aim to systematically characterize the role of carrier proteins in various metabolic pathways and outline their utility in biosynthesis and biotechnology; 185 references are cited.


A rapidly developing lung mass diagnosed as desmoplastic small round cell tumor.
We present a case of a young male who presented with complaints of fever along with cough and sputum. He was diagnosed with having right pleural effusion. He was already taking anti-tubercular therapy for one month before presentation. He was started on intravenous antibiotics and continued on anti-tubercular therapy in our hospital, based on his high leukocyte count, pleural fluid analysis, and ultrasonographic report of multiple hypoechoic areas in the liver. His symptoms continued to worsen and he subsequently developed mediastinal widening and a left lung mass. Commuted tomography (CT)-guided biopsy of the lung mass revealed a desmoplastic small-round-cell tumor. Desmoplastic small-round-cell tumor is a rare and aggressive tumor, which presents rarely as a mediastinal and lung mass. This tumor has very poor prognosis.


Nuclear polarization effects in cryptochrome-based magnetoreception.
The mechanism of the magnetic compass sense of migratory songbirds is thought to involve magnetically sensitive chemical reactions of light-induced radical pairs in cryptochrome proteins located in the birds' eyes. However, it is not yet clear whether this mechanism would be sensitive enough to form the basis of a viable compass. In the present work, we report spin dynamics simulations of models of cryptochrome-based radical pairs to assess whether accumulation of nuclear spin polarization in multiple photocycles could lead to significant enhancements in the sensitivity with which the proteins respond to the direction of the geomagnetic field. Although buildup of nuclear polarization appears to offer sensitivity advantages in the more idealized model systems studied, we find that these enhancements do not carry over to conditions that more closely resemble the situation thought to exist in vivo. On the basis of these simulations, we conclude that buildup of nuclear polarization seems unlikely to be a source of significant improvements in the performance of cryptochrome-based radical pair magnetoreceptors.


Interlayer structures of the chiral smectic liquid crystal phases revealed by resonant X-ray scattering.
The structures of the liquid crystalline chiral subphases exhibited by several materials containing either a selenium or sulphur atom have been investigated using a resonant x-ray scattering technique. This technique provides a unique structural probe for the ferroelectric, ferrielectric, antiferroelectric, and SmC(*)(alpha) phases. An analysis of the scattering features allows the structural models of the different subphases to be distinguished, in addition to providing a measurement of the helical pitch. This paper reports resonant scattering features in the antiferroelectric hexatic phase, the three- and four-layer intermediate phases, the antiferroelectric and ferroelectric phases and the SmC(*)(alpha) phase. The helicoidal pitch has been measured from the scattering peaks in the four-layer intermediate phase as well as in the antiferroelectric and ferroelectric phases. In the SmC(*)(alpha) phase, an investigation into the helical structure has revealed a pitch ranging from 5 to 54 layers in different materials. Further, a strong resonant scattering signal has been observed in mixtures of a selenium containing material with as much as 90% nonresonant material.


Rationale for initial clinical trials and future development of radioprotectors.
Over the past two decades a number of chemical radioprotectors have been developed which, although toxic, appear to be usable in clinically relevant doses. Because of differences in blood flow, radiochemical action in hypoxic cells, and active concentration in certain normal tissues, these compounds exhibit differential protection of normal tissue versus tumor. The best, currently available protector, WR-2721, is active in skin, intestine, marrow, mucosa, and salivary glands with lesser activity in kidney and lung and none in brain. Clinical trials have been designed in the Radiation Therapy Oncology Group based on this knowledge. Phase I studies involve patients requiring palliative radiotherapy for tumors located in or adjacent to tissues which are known to be protected. These studies use excalating doses of WR-2721, starting at 50 mg/m2 and will determine the maximum tolerated dose of drug, first as single doses and then as 1X, 3X, and 5X weekly for 3 and 6 weeks. Concomitant radiotherapy is given and normal tissue response at conventionl doses observed. Phase II studies will be site specific based on phase I results and doses. They will be radiation dose ranging studies designed to determine the maximum acceptable radiation dose at each site with WR-2721 protection. These new, higher doses will then be compared to conventional radiotherapy without protector, seeking increased tumor control in phase III studies. WR-2721 is not the ideal sensitizer since it does not protect all normal tissues. It is particularly important to develop compounds which can protect the brain, spinal cord, and lung. A large effort in new drug development will be justified if an improved therapeutic ratio is observed with WR-2721.


Indian monsoon variability on millennial-orbital timescales.
The Indian summer monsoon (ISM) monsoon is critical to billions of people living in the region. Yet, significant debates remain on primary ISM drivers on millennial-orbital timescales. Here, we use speleothem oxygen isotope (δ(18)O) data from Bittoo cave, Northern India to reconstruct ISM variability over the past 280,000 years. We find strong coherence between North Indian and Chinese speleothem δ(18)O records from the East Asian monsoon domain, suggesting that both Asian monsoon subsystems exhibit a coupled response to changes in Northern Hemisphere summer insolation (NHSI) without significant temporal lags, supporting the view that the tropical-subtropical monsoon variability is driven directly by precession-induced changes in NHSI. Comparisons of the North Indian record with both Antarctic ice core and sea-surface temperature records from the southern Indian Ocean over the last glacial period do not suggest a dominant role of Southern Hemisphere climate processes in regulating the ISM variability on millennial-orbital timescales.


The dynamic influence of genetic variation on the susceptibility of sheep to gastrointestinal nematode infection.
The interaction between sheep and the nematode Teladorsagia circumcincta is one of the best understood of all host-parasite interactions. Following infection, there is considerable variation among lambs in the number of nematode eggs produced, the number of early fourth-stage larvae and the number of adult worms in the mucosa. These traits have a high variance to mean ratio (i.e. they are overdispersed or aggregated among hosts), they are skewed and approximately negative binomially distributed. The sources of overdispersion are differences among lambs in the ingestion of infective larvae and the immune response. Both forces can produce aggregation but their relative importance is unknown. The key components of variation can be identified by variance analysis. The sum of the average effects of polymorphic genes is known as additive genetic variation and this increases essentially from zero at one month of age to quite high values at six months of age. The major mechanism underlying genetic variation appears to be the differences among individuals in immune responses. Two of the major sources of variation in immune responses are differences in antigen recognition and differences in the type of cytokines produced. Genes that influence both these sources of variation are associated with differences in resistance to nematode infection. Therefore, much of the heterogeneity among animals in parasite transmission appears to be due to genetic variation in immune responsiveness.


Characterization and experimental infection of Flexibacter maritimus (Wakabayashi et al. 1986) in hatcheries of post-larvae of Litopenaeus vannamei Boone, 1931.
A preliminary study to characterize filamentous bacteria, whose presence is related to high mortality of Litopenaeus vannamei larvae cultured in Santa Catarina State, Brazil, is reported. The extract of infected larvae was diluted in different concentrations, cultured in marine agar (Difco, Marine Agar 2216) and incubated at 30 degrees C for 48 hours. The biochemical characterization included hydrolytic reactions of starch, gelatin and tyrosine, growth in TCBS agar, growth in 0 and 37 per thousand salinity, pigment production in tyrosine agar, production of H2S, nitrate reduction, congo red reaction, oxidase and catalase. The isolated bacteria belong to the species Flexibacter maritimus, Gram-negative bacilli of 0.4-0.5 microm width and 15 microm length. Experiments were carried out on pathogenicity of F. maritimus in post-larvae of L. vannamei. Survival and symptoms in L. vannamei post-larvae 24 hours after inoculation with F. maritimus and its growth in marine agar were evaluated. Mortality was detected around 92,5% as well as symptoms like melanized lesions in several parts of body, discolouration of gills, bad formation of appendages and of the last abdominal segment, low motility and feeding reduction. The experimental infection results suggested that isolated bacteria of the genus Flexibacter are pathogenic to the shrimp Litopenaeus vannamei post-larvae.


Will knowledge of gene-based colorectal cancer disease risk influence quality of life and screening behavior? Findings from a population-based study.
Several gene variants conveying a modestly increased risk for disease have been described for colorectal cancer. Patient acceptance of gene variant testing in clinical practice is not known. We evaluated the potential impact of hypothetical colorectal-cancer-associated gene variant testing on quality of life, health habits and cancer screening behavior. First-degree relatives of colorectal cancer patients and controls from the Seattle Colorectal Cancer Familial Registry were invited to participate in a web-based survey regarding testing for gene variants associated with colorectal cancer risk. 310 relatives and 170 controls completed the questionnaire. Quality of life for the hypothetical carrier state was modestly and nonsignificantly lower than current health after adjustment for sociodemographic and health factors. In the positive test scenario, 30% of respondents expressed willingness to change their diet, 25% to increase exercise, and 43% to start colorectal cancer screening. The proportions willing to modify these habits did not differ between groups. Testing for gene variants associated with colorectal cancer risk may not influence quality of life, but may impact health habits and screening adherence. Changing behaviors as a result of testing may help to reduce cancer incidence and mortality, particularly among those at higher risk for colorectal cancer.


Low laser therapy as an effective treatment of recurrent aphtous ulcers: a clinical case reporting two locations.
Apthous ulcers, commonly referred to as canker sores, are the most common ulcerative lesions of the oral mucosa. These are usually painful and are associated with redness and occasional bleeding from the affected area(s). Low Level Laser Therapy (LLLT) has shown excellent results in relieving the pain and complete remission of the oral ulcers. Through a clinical case, we report two locations of oral ulcers treated successfully with diode laser.


Best Practices for Robotic Surgery Programs.
Robotic surgical programs are increasing in number. Efficient methods by which to monitor and evaluate robotic surgery teams are needed. Best practices for an academic university medical center were created and instituted in 2009 and continue to the present. These practices have led to programmatic development that has resulted in a process that effectively monitors leadership team members; attending, resident, fellow, and staff training; credentialing; safety metrics; efficiency; and case volume recommendations. Guidelines for hospitals and robotic directors that can be applied to one's own robotic surgical services are included with examples of management of all aspects of a multispecialty robotic surgery program. The use of these best practices will ensure a robotic surgery program that is successful and well positioned for a safe and productive environment for current clinical practice.


[Survival rate of the cemented Charnley total hip endoprosthesis and modifying parameters].
To analyse survival of cemented Charnley prostheses, and influencing factors. 539 patients (mean age: 62 years) undergoing 426 primary, and 200 revision Charnley hip arthroplasties, were examined. The indications for primary operation was idiopathic coxarthrosis in 239 cases (56.1%), and rheumatic coxarthrosis in 56 cases (13.1%). Reasons for revision surgery included aseptic loosening in 123 cases (61.5%), septic loosening in 36 cases (18%), and prosthetic fracture in 13 cases (6.5%). After a mean follow-up of 4.4 years, patients were scored using the Merle d'Aubigne evaluation. The average postoperative score for primary operations was 14.8 points, and for revision surgery 13.1 points. The respective pre-operative scores were 8.2 and 8.1. Radiographic investigation revealed peri-articular calcifications in 28.4% of the primary operations, and in 28.5% of the revisions. Radiolucent lines or protrusions were found in 29.8% of the primary, and in 42.0% of the revisions. At follow-up, 45 implants in 41 patients had been replaced. Kaplan-Meier survival rates for the primary group were 99.6% after one year, 92.8% after five years, 78.3% after 10 years, and 45.9% after 15 years. The respective figures for the revision group were 98.2%, 85.3%, 59.7% and 31.3%. The largest difference was seen in the eleventh year. Patient age had no significant influence for the first 12 years. In the primary group, body mass index showed a significant influence only after 15 years. Analysis of the indications for surgery revealed a slightly higher survival rate in the arthrosis group (84%) vis-a-vis the dysplasia group (83.3%), and a significantly higher rate vis-a-vis patients with rheumatoid arthritis (42%). Such factors as age, diagnosis and weight had an influence only over the long term. Significant differences between primary and revision operations were not found.


Adoptive Transfer of Tumor-Specific Th2 Cells Eradicates Tumors by Triggering an In Situ Inflammatory Immune Response.
Adoptive cell therapy (ACT) trials to date have focused on transfer of autologous tumor-specific cytotoxic CD8+ T cells; however, the potential of CD4+ T helper (Th) cells for ACT is gaining interest. While encouraging results have been reported with IFNγ-producing Th1 cells, tumor-specific Th2 cells have been largely neglected for ACT due to their reported tumor-promoting properties. In this study, we tested the efficacy of idiotype-specific Th2 cells for the treatment of mice with MHC class II-negative myeloma. Th2 ACT efficiently eradicated subcutaneous myeloma in an antigen-specific fashion. Transferred Th2 cells persisted in vivo and conferred long-lasting immunity. Cancer eradication mediated by tumor-specific Th2 cells did not require B cells, natural killer T cells, CD8+ T cells, or IFNγ. Th2 ACT was also curative against B-cell lymphoma. Upon transfer, Th2 cells induced a type II inflammation at the tumor site with massive infiltration of M2-type macrophages producing arginase. In vivo blockade of arginase strongly inhibited Th2 ACT, consistent with a key role of arginase and M2 macrophages in myeloma elimination by Th2 cells. These results illustrate that cancer eradication may be achieved by induction of a tumor-specific Th2 inflammatory immune response at the tumor site. Thus, ACT with tumor-specific Th2 cells may represent a highly efficient immunotherapy protocol against cancer. Cancer Res; 76(23); 6864-76. ©2016 AACR.


Selenium accumulation in lettuce germplasm.
Selenium (Se) is an essential micronutrient for animals and humans. Increasing Se content in food crops offers an effective approach to reduce the widespread selenium deficiency problem in many parts of the world. In this study, we evaluated 30 diverse accessions of lettuce (Lactuca sativa L.) for their capacity to accumulate Se and their responses to different forms of Se in terms of plant growth, nutritional characteristics, and gene expression. Lettuce accessions responded differently to selenate and selenite treatment, and selenate is superior to selenite in inducing total Se accumulation. At least over twofold change in total Se levels between cultivars with high and low Se content was found. Synergistic relationship between Se and sulfur accumulation was observed in nearly all accessions at the selenate dosage applied. The change in shoot biomass varied between lettuce accessions and the forms of Se used. The growth-stimulated effect by selenate and the growth-inhibited effect by selenite were found to be correlated with the alteration of antioxidant enzyme activities. The different ability of lettuce accessions to accumulate Se following selenate treatment appeared to be associated with an altered expression of genes involved in Se/S uptake and assimilation. Our results provide important information for the effects of different forms of Se on plant growth and metabolism. They will also be of help in selecting and developing better cultivars for Se biofortification in lettuce.


The multiple, complex roles of versican and its proteolytic turnover by ADAMTS proteases during embryogenesis.
Embryonic development is an exceptionally dynamic process, requiring a provisional extracellular matrix that is amenable to rapid remodeling, and proteolytic or non-proteolytic mechanisms that can remodel the major components of this matrix. Versican is a chondroitin-sulfate proteoglycan that forms highly hydrated complexes with hyaluronan and is widely distributed in the provisional matrix of mammalian embryos. It has been extensively studied in the context of cardiovascular morphogenesis, neural crest cell migration and skeletal development. Analysis of Vcan transgenic mice has established the requirement for versican in cardiac development and its role in skeletogenesis. The ADAMTS family includes several versican-degrading proteases that are active during remodeling of the embryonic provisional matrix, especially during sculpting of versican-rich tissues. Versican is cleaved at specific peptide bonds by ADAMTS proteases, and the cleavage products are detectable by neo-epitope antibodies. Myocardial compaction, closure of the secondary palate (in which neural crest derived cells participate), endocardial cushion remodeling, myogenesis and interdigital web regression are developmental contexts in which ADAMTS-mediated versican proteolysis has been identified as a crucial requirement. ADAMTS proteases are expressed coordinately and function cooperatively in many of these contexts. In addition to versican clearance, ADAMTS proteases generate a bioactive versican fragment containing the N-terminal G1 domain, which we have named versikine. This review promotes the view that the embryonic extracellular matrix has evolved not only to provide a permissive environment for embryo growth and morphogenesis, but through its dissolution to influence and regulate cellular processes.


Materials: unidirectional solidification of cast iron.
The segregation of sulfur in liquid cast iron was studied under conditions of microgravity on Spacelab 1. A rod of cast iron containing carbon, silicon, sulfur, and phosphorus was unidirectionally solidified at four different rates. The influence of sulfur on the graphite structure and the stability of an aluminum oxide skin deposited on the surface of the specimen were investigated.


Detection of Nocardia by 16S Ribosomal RNA Gene PCR and Metagenomic Next-Generation Sequencing (mNGS).
In this study, the aim was to investigate the discriminatory power of molecular diagnostics based on mNGS and traditional 16S ribosomal RNA PCR among Nocardia species. A total of fourteen clinical isolates from patients with positive Nocardia cultures and clinical evidence were included between January 2017 and June 2020 in HeNan Provincial People's Hospital. DNA extraction and 16S rRNA PCR were performed on positive cultures, and pathogens were detected by mNGS in these same samples directly. Among the 14 Nocardia isolates, four species were identified, and N. cyriacigeorgica (8 cases) is the most common species. Twelve of the 14 Nocardia spp. isolates were identified by the two methods, while two strains of N. cyriacigeorgica were not identified by mNGS. All tested isolates showed susceptibility to trimethoprim-sulfamethoxazole (SXT), amikacin and linezolid. Apart from Nocardia species, other pathogens such as Acinetobacter baumannii, Klebsiella pneumonia, Aspergillus, Enterococcus faecalis, Human herpesvirus, etc., were detected from the same clinical samples by mNGS. However, these different pathogens were considered as colonization or contamination. We found that it is essential to accurately identify species for determining antibiotic sensitivity and, consequently, choosing antibiotic treatment. 16S rRNA PCR was useful for identification of nocardial infection among species, while this technique needs the clinicians to make the pre-considerations of nocardiosis. However, mNGS may be a putative tool for rapid and accurate detection and identification of Nocardia, beneficial for applications of antimicrobial drugs and timely adjustments of medication.


Genetic and symbiotic diversity of nitrogen-fixing bacteria isolated from agricultural soils in the western Amazon by using cowpea as the trap plant.
Cowpea is a legume of great agronomic importance that establishes symbiotic relationships with nitrogen-fixing bacteria. However, little is known about the genetic and symbiotic diversity of these bacteria in distinct ecosystems. Our study evaluated the genetic diversity and symbiotic efficiencies of 119 bacterial strains isolated from agriculture soils in the western Amazon using cowpea as a trap plant. These strains were clustered into 11 cultural groups according to growth rate and pH. The 57 nonnodulating strains were predominantly fast growing and acidifying, indicating a high incidence of endophytic strains in the nodules. The other 62 strains, authenticated as nodulating bacteria, exhibited various symbiotic efficiencies, with 68% of strains promoting a significant increase in shoot dry matter of cowpea compared with the control with no inoculation and low levels of mineral nitrogen. Fifty genotypes with 70% similarity and 21 genotypes with 30% similarity were obtained through repetitive DNA sequence (BOX element)-based PCR (BOX-PCR) clustering. The 16S rRNA gene sequencing of strains representative of BOX-PCR clusters showed a predominance of bacteria from the genus Bradyrhizobium but with high species diversity. Rhizobium, Burkholderia, and Achromobacter species were also identified. These results support observations of cowpea promiscuity and demonstrate the high symbiotic and genetic diversity of rhizobia species in areas under cultivation in the western Amazon.


Molecular detection of Bartonella quintana DNA in the dental pulp of a homeless patient.
Dental pulp has been proposed as a suitable tissue sample for the identification of pathogenic organisms. Using PCR with two specific gene targets, Bartonella quintana DNA was detected in the dental pulp extracted from the tooth of a homeless patient. The patient had been bacteremic 6 months previously but was not when the tooth was sampled.


A cross-sectional study to evaluate utility measure and health-related quality of life (HRQoL) among patients with severe uncontrolled asthma in Spain.
The utility measure is a method to quantify health-related quality of life according to the preference values that patients attach to their health status. This study aimed to estimate the utility measure of patients with controlled and uncontrolled severe asthma (SA) in Spain, separately. Additionally, other characteristics (sociodemographic, clinical, and healthcare resource use [HCRU]) were also assessed for both SA populations. This cross-sectional study included 159 patients with SA in Spain. Data were collected from medical records and directly from the patients during the study visit. Asthma Control Questionnaire (ACQ)-5 was used to classify patients with controlled and uncontrolled SA. Most of the patients were female (72.0% uncontrolled SA and 63.6% controlled SA). The mean (SD) EuroQol-5D (EQ-5D-5L) score was 0.88 (0.14) and 0.70 (0.25) in controlled and uncontrolled SA, respectively. The mean (SD) Asthma Quality-of-Life-5D (AQL-5D) score was 0.93 (0.09) and 0.85 (0.09) in controlled and uncontrolled SA, respectively. Emergency visits (19.2 vs. 2.7%) and hospitalizations (7.7% vs. no hospitalization) were more common among uncontrolled SA than controlled SA. Mean (SD) number of visits to primary care and pneumologists in uncontrolled SA vs. controlled SA was 4.1 (2.8) vs. 2.5 (3.0) and 3.7 (3.5) vs. 2.8 (2.2), respectively. The study provides data on utility measures among patients with SA in Spain for the first time. Patients with uncontrolled SA had lower HRQoL and higher HCRU than patients with controlled SA. Therefore, the implementation of measures that improve HRQoL among patients with uncontrolled SA is highly recommended.


People have the power. Electricity production, renewable energy transition, and communities empowerment across 11 Nordic-Baltic countries.
Stakeholders and communities' involvement is vital for shaping novel intergenerational resource governance frameworks. This is crucial for modelling upcoming energy transitions towards cleaner and more sustainable production systems. New models envisage energy mixes in which renewable resources are prominent and offer sustainable development advantages. Examining electricity production figures is, hence, necessary to understand trends and formulate policies and actions. This paper aims at drafting the state-of-the-art of electricity production in the Nordic-Baltic Sea area, moving an exploratory regional appraisal. Aggregated and disaggregated data on electricity production sources are explored and compared for all the eleven selected countries-at domestic, sub-regional, and regional levels. The region shows great national diversity, which implies diversified energy policies. Thus, the role of local initiatives-such as power grid implementation-in local communities empowerment is revealed. From this outcome, possible strategies are prescribed locally to assist the regional sustainable energy appraisal and furnish indications for the European energy and ecological transition.


Neuroadaptive Biochemical Mechanisms of Remote Ischemic Conditioning.
This review summarizes the currently known biochemical neuroadaptive mechanisms of remote ischemic conditioning. In particular, it focuses on the significance of the pro-adaptive effects of remote ischemic conditioning which allow for the prevention of the neurological and cognitive impairments associated with hippocampal dysregulation after brain damage. The neuroimmunohumoral pathway transmitting a conditioning stimulus, as well as the molecular basis of the early and delayed phases of neuroprotection, including anti-apoptotic, anti-oxidant, and anti-inflammatory components, are also outlined. Based on the close interplay between the effects of ischemia, especially those mediated by interaction of hypoxia-inducible factors (HIFs) and steroid hormones, the involvement of the hypothalamic-pituitary-adrenocortical system in remote ischemic conditioning is also discussed.


Descending phlebography: a comparison of three methods and an assessment of the normal range of deep vein reflux.
Twenty-three legs in 13 patients without evidence of deep vein disease have been examined by descending phlebography using 3 techniques: with the patient semi-erect with no Valsalva manoeuvre with the patient semi-erect with a controlled Valsalva manoeuvre and with the patient supine with a standard Valsalva manoeuvre. It is concluded that the examination performed with the patient supine, using a standard Valsalva manoeuvre, is the most convenient and easiest to interpret of the variation. It is also suggested that deep vein reflux up to Grade 2 is within the normal range.


Early detection of pregnancy and embryonic loss in dairy cattle by ELISA tests.
Over a 25-month period 8118 blood samples were assayed for the presence of the serum pregnancy specific-protein B (PSPB) and progesterone (P4) concentrations on three Hungarian large-scale dairy farms. Pregnancy (n = 4085) was checked by BioPRYN assay at 30-36 days post-insemination (PI). Samples from all cows that tested not pregnant and from cows with an optical density (OD) reading in the BioPRYN test that was between 0% and 30% above the cutoff OD value were tested for serum P4 concentration. According to serum P4 concentration, cows were assigned to three categories: high (>4 ng/ml), medium (2-4 ng/ml) and low (<2 ng/ml) serum progesterone. The authors predicted a presumed (low) or possible (medium) late embryonic loss (LEL) or maintenance of the pregnancy (high). A total of 710 LELs were detected (17.4%) and 31.8% of them were predicted because of a low OD value at 30-36 days after insemination. Lower PSPB serum level significantly refers for LEL (p < 0.0001). The prediction rate for the true embryonic loss was 31.8% when OD cutoff from 0% to + 30% of cutoff was examined while it was 62.5% when the threshold was OD cutoff of 0% to 10% of cutoff. The authors conclude that BioPRYN was useful for prediction of a part of LEL in dairy cows and serum P4 concentration in these cows related to the rate of LEL.


Drosophila homeodomain protein REPO controls glial differentiation by cooperating with ETS and BTB transcription factors.
In Drosophila, cell-fate determination of all neuroectoderm-derived glial cells depends on the transcription factor Glial cells missing (GCM), which serves as a binary switch between the neuronal and glial cell fates. Because the expression of GCM is restricted to the early phase of glial development, other factors must be responsible for the terminal differentiation of glial cells. Expression of three transcription factors, Reversed Polarity (REPO), Tramtrack p69 (TTK69) and PointedP1 (PNTP1), is induced by GCM in glial cells. REPO is a paired-like homeodomain protein, expressed exclusively in glial cells, and is required for the migration and differentiation of embryonic glial cells. To understand how REPO functions in glial terminal differentiation, we have analyzed the mechanism of gene regulation by REPO. We show that REPO can act as a transcriptional activator through the CAATTA motif in glial cells, and define three genes whose expression in vivo depends on REPO function. In different types of glial cells, REPO can act alone, or cooperate with either TTK69 or PNTP1 to regulate different target genes. Coordination of target gene expression by these three transcription factors may contribute to the diversity of glial cell types. In addition to promoting glial differentiation, we found that REPO is also necessary to suppress neuronal development, cooperating with TTK69. We propose that REPO plays a key role in both glial development and diversification.


The effect of coil phenotypes and genotypes on the fecundity and viability of Partula suturalis and Lymnaea stagnalis: implications for the evolution of sinistral snails.
Why are sinistral snails so rare? Two main hypotheses are that selection acts against the establishment of new coiling morphs, because dextral and sinistral snails have trouble mating, or else a developmental constraint prevents the establishment of sinistrals. We therefore used an isolate of the snail Lymnaea stagnalis, in which sinistrals are rare, and populations of Partula suturalis, in which sinistrals are common, as well as a mathematical model, to understand the circumstances by which new morphs evolve. The main finding is that the sinistral genotype is associated with reduced egg viability in L. stagnalis, but in P. suturalis individuals of sinistral and dextral genotype appear equally fecund, implying a lack of a constraint. As positive frequency-dependent selection against the rare chiral morph in P. suturalis also operates over a narrow range (< 3%), the results suggest a model for chiral evolution in snails in which weak positive frequency-dependent selection may be overcome by a negative frequency-dependent selection, such as reproductive character displacement. In snails, there is not always a developmental constraint. As the direction of cleavage, and thus the directional asymmetry of the entire body, does not generally vary in other Spiralia (annelids, echiurans, vestimentiferans, sipunculids and nemerteans), it remains an open question as to whether this is because of a constraint and/or because most taxa do not have a conspicuous external asymmetry (like a shell) upon which selection can act.


Potentially toxic theophylline ingestions: are heroic measures indicated?
We have treated six patients with theophylline overdoses, all of whom had high blood theophylline levels but lacked symptoms of serious toxicity. All improved with conservative therapy. While other reports of theophylline overdose describe aggressive therapy in patients with high blood levels and serious toxic signs, we believe blood levels cannot be used to predict serious toxic reactions. The symptoms that precede toxic convulsions--excitation, irritability, twitching, and alertness--are more valuable than blood medication levels as indicators of the need for aggressive therapy.


Neoadjuvant trastuzumab induces apoptosis in primary breast cancers.
Greater understanding of the cellular response in trastuzumab-treated patients will provide insight into the clinical management of patients. We performed a neoadjuvant trial in 35 patients with locally advanced HER-2/neu overexpressing breast cancers who received weekly trastuzumab given as a single agent for the first 3 weeks, followed by a combination of trastuzumab and docetaxel for 12 weeks before surgery. Sequential core biopsies were taken at baseline and within weeks 1 and 3 after the first dose of trastuzumab. Clinical response to trastuzumab was assessed by tumor measurements on day 22 before chemotherapy. Core biopsies were assessed by immunohistochemistry for cell cycle and proliferation (Ki67, p27, phosphorylated [p] -MAPK), apoptosis and survival (apoptotic index, p-Akt), epidermal growth factor receptor, and total and p-HER-2. There was early tumor regression with a median decrease of -20.0% (range. 0% to 60.4%) after only 3 weeks of trastuzumab, and eight patients (23%) had a partial response. Consistent with the clinical regressions, apoptosis was significantly induced (median increase from 3.5% to 4.7%; P = .006) within week 1, a 35% increase above baseline. No significant change in epidermal growth factor receptor score was observed in week 1, without changes in total or p-HER-2 expression. Tumors with high baseline Ki67 were less likely to respond (P = .02). In primary breast cancers, trastuzumab substantially induces apoptosis, providing a molecular explanation for both its therapeutic efficacy and its successful combination with cytotoxic chemotherapy.


Multivariate calibration of covalent aggregate fraction to the raman spectrum of regular human insulin.
Insulin aggregates were prepared by exposing samples of formulated regular human insulin to agitation at 60 degrees C. Aliquots were drawn from the samples periodically over a time range spanning 192 h, and their aggregate compositions were determined with size exclusion chromatography. The complete data set was composed of 39 separate aliquots. The Raman spectra of three separate 10 microL volumes from each aliquot were measured using the drop-coat deposition Raman (DCDR) method. The spectra were calibrated to aggregate composition by partial least squares regression (PLS), resulting in linear calibration (R(2) = 0.997) with a root mean squared error of calibration (RMSEC) of 1.3% and a root mean squared error of cross validation (RMSECV) of 5.1% in aggregate composition. Though the time required for aggregates to form under stressed conditions showed substantial sample-to-sample variation, the correlation between aggregate composition and Raman spectrum was remarkably consistent, indicating that Raman spectroscopy may be a viable screening method for aggregation of protein drugs.


Biomolecules from Fossilized Hot Spring Sinters: Implications for the Search for Life on Mars.
Hot spring environments are commonly dominated by silica sinters that precipitate by the rapid cooling of silica-saturated fluids and the activity of microbial communities. However, the potential for preservation of organic traces of life in silica sinters back through time is not well understood. This is important for the exploration of early life on Earth and possibly Mars. Most previous studies have focused on physical preservation in samples <900 years old, with only a few focused on organic biomarkers. In this study, we investigate the organic geochemistry of hot spring samples from El Tatio, Chile and the Taupo Volcanic Zone, with ages varying from modern to ∼9.4 ka. Results show that all samples contain opaline silica and contain hydrocarbons that are indicative of a cyanobacterial origin. A ∼3 ka recrystallized, quartz-bearing sample also contains traces of cyanobacterial biomarkers. No aromatic compounds were detected in a ∼9.4 ka opal-A sample or in a modern sinter breccia sample. All other samples contain naphthalene, with one sample also containing other polyaromatic hydrocarbons. These aromatic hydrocarbons have a thermally mature distribution that is perhaps reflective of geothermal fluids migrating from deep, rather than surface, reservoirs. These data show that hot spring sinters can preserve biomolecules from the local microbial community, and that crystallinity rather than age may be the determining factor in their preservation. This research provides support for the exploration for biomolecules in opaline silica deposits on Mars.


New and under explored epigenetic modulators in search of new paradigms.
Aberrant regulation of epigenetic pathways causes many diseases including aging, cancer, diabetes, viral pathogenesis, drug addiction etc. and it has been estimated that epigenetic aberrations are at least ten to forty times more frequent in cancers than genetic mutations. Present epigenetic modulators hold great promise for a variety of diseases, and important tools for biological applications but these molecules have many dose limiting toxicities and existing paradigms lack desired efficacy. Synthesis and biological studies of epigenetic modulators have been attractive targets for medicinal and synthetic organic chemists in recent years. This review article provides deep insight into the new and under explored epigenetic modulators. These molecules have the potential to be used as unique template with novel pharmacophores.


Blood absolute T cell counts may predict 2-month treatment response in patients with pulmonary tuberculosis.
Little is known about the usefulness of lymphocyte subsets as early predictors of anti-tuberculosis (TB) treatment response in immuno-competent patients. Among a total of 64 patients with culture positive pulmonary TB, 29 remained sputum smear/culture positive or had delayed resolution on CXR (slow responders (SR)), and 35 had sputum culture conversion to negative and rapid resolution on CXR (fast responders (FR)) after two months of anti-tuberculosis treatment. Clinical parameters and lymphocyte subsets were investigated. A larger proportion of patients in the SR group had cavities on CXR, bilateral lung involvement, positive acid-fast bacilli stains, and complaint of cough at diagnosis than those in the FR group. Absolute counts of CD3+ T cells (p = 0.016) and CD8+ T cells (p=0.012) at diagnosis were both significantly higher in the SR group. This trend was present throughout the 6-month treatment course. Absolute T cell counts (odds ratio (OR) 1.002, 95% confidence interval (CI) 1.0-1.004), positive sputum acid fast bacilli stain (OR 6.69, 95% CI 1.37-32.77) and bilateral lung involvement on CXR (OR 13.114, 95% CI 1.87-92.14) at diagnosis were independent predictors for a slow response. Combining these three predictors, a prediction score (PS) could be calculated to display an optimal discrimination for slow response (area under the curve (AUC)=0.855, p < 0.001), whereas absolute T cell counts yielded the highest discriminative value on an individual level (AUC= 0.676, p=0.015). A higher T cell count at diagnosis in patients with TB may predict a slow response to two months of treatment. The calculation of a PS further increased predictive accuracy and performance.