Neocortical substance P neurons in the baboon: an immunohistochemical finding.
Substance P-like immunoreactive (SP-LI) neurons have been demonstrated, by an avidin-biotin immunohistochemical method, in several neocortical areas in the brains of baboons. These neurons are mostly small in size, and are of many different somatic shapes, including bipolar and multipolar types. They occur in laminae III-VI but are most common in laminae V and VI. It is postulated that these neurons could contribute to previously-described cortical SP-LI fiber networks.


Fluctuating seawater pCO2/pH induces opposing interactions with copper toxicity for two intertidal invertebrates.
Global ocean pCO2 is increasing as a result of anthropogenic CO2 emissions, driving a decline in seawater pH. However, coastal waters already undergo fluctuations in pCO2/pH conditions over far shorter timescales, with values regularly exceeding those predicted for the open ocean by the year 2100. The speciation of copper, and therefore its potential toxicity, is affected by changing seawater pH, yet little is known concerning how present-day natural fluctuations in seawater pH affect copper toxicity to marine biota. Here, we test the hypothesis that a fluctuating seawater pCO2/pH regime will alter the responses of the mussel Mytilus edulis and the ragworm Alitta virens to sub-lethal copper, compared to a static seawater pCO2/pH scenario. Mussels and worms were exposed to 0.1 and 0.25 μM copper respectively, concentrations determined to produce comparable toxicity responses in these species, for two weeks under a fluctuating 12-hour pCO2/pH cycle (pH 8.14-7.53, pCO2 445-1747 μatm) or a static pH 8.14 (pCO2 432 μatm) treatment. Mussels underwent a haemolymph acidosis of 0.1-0.2 pH units in the fluctuating treatments, alongside two-fold increases in the superoxide dismutase activity and DNA damage induced by copper, compared to those induced by copper under static pH conditions. Conversely, ragworms experienced an alkalosis of 0.3 pH units under fluctuating pH/pCO2, driven by a two-fold increase in coelomic fluid bicarbonate. This mitigated the copper-induced oxidative stress to slightly reduce both antioxidant activity and DNA damage, relative to the static pH + copper treatment. These opposing responses suggest that differences in species acid-base physiology were more important in determining toxicity responses than the pH-induced speciation change. With variability in seawater chemistry predicted to increase as climate change progresses, understanding how fluctuating conditions interact with the toxicity of pH-sensitive contaminants will become more crucial in predicting their risk to coastal biota.


Tick-borne encephalitis after vaccination: vaccine failure or misdiagnosis.
The aim of the paper is to present the results of the investigation of a series of four cases of tick-borne encephalitis (TBE) reported from Gorenjska region in Slovenia in 2008 despite vaccination against TBE, propose surveillance case definition for TBE and classification criteria for TBE vaccine failure cases, to discuss challenges in the interpretation of TBE serology results in previously vaccinated patients and propose ascertainment procedures for vaccine failure cases. Establishing surveillance of vaccine failure cases on national and European level is essential for monitoring and evaluating the impact of immunization, evaluation of vaccine effectiveness and early warning for the need to change the vaccination schedule recommendations.


LncRNA ID2-AS1 suppresses tumor metastasis by activating the HDAC8/ID2 pathway in hepatocellular carcinoma.
Metastasis is a core hallmark of cancer that leads to high mortality of cancer patients, especially in hepatocellular carcinoma (HCC). However, the underlying mechanisms of long noncoding RNAs (lncRNAs) in HCC metastasis remain largely unknown. We found that ID2-AS1 expression decreased in metastatic HCC cell lines and HCC tissues, and lower ID2-AS1 expression predicted reduced overall survival in HCC patients. ID2-AS1 significantly suppressed the migration, invasion and metastasis of HCC cells in vitro and in vivo. Mechanistically, ID2-AS1 regulated the transcription of its adjacent gene inhibitor of DNA binding 2 (ID2) by blocking the binding of histone deacetylase 8 (HDAC8) on the ID2 enhancer. Furthermore, ID2-AS1 and ID2 suppressed the Twist-induced epithelial-mesenchymal transition (EMT) in HCC cells. In addition, ID2 expression was also significantly decreased in HCC tissues and was positively correlated with ID2-AS1 in HCC tissues and HCC cell lines. Taken together, our findings demonstrated that ID2-AS1 regulated adjacent ID2 transcription by manipulating chromatin modification and that the newly identified ID2-AS1/ID2 axis suppressed HCC metastasis by regulating EMT processes. Our findings provide insights into the molecular mechanisms underlying the metastasis of HCC cells.


An experimental and theoretical study on the novel (Z)-1-((naphthalen-2-ylamino)methylene)naphthalen-2(1H)-one crystal.
A novel compound has been synthesized, and its structure has been characterized by IR, UV-vis, NMR and X-ray single-crystal determination techniques. The title compound crystallizes in the orthorhombic space group P212121 with a=6.2120(4)Å, b=10.8242(7)Å, c=22.3857(15)Å and Z=4. The crystal structure has intramolecular N-H···O hydrogen bond and C-H···Cg interaction. These hydrogen bonds and interactions are effective in crystal packing. The optimum molecular geometry, conformational analysis, normal mode wavenumbers, infrared and Raman intensities, corresponding vibrational assignments, chemical shift assignments, and thermo-dynamical parameters have been investigated with the help of Density Functional Theory (DFT). Detailed vibrational assignments have been made on the basis of potential energy distribution (PED). In order to understand the electronic transitions of the compound, time dependent DFT (TD-DFT) calculations were performed in gas phase. Also, the dipole moment, linear polarizabilities, anisotropy and first hyperpolarizabilities values have been computed.


Development of Mechanical, Corrosion Resistance, and Antibacterial Properties of Steels.
The total cost and environmental consequences of corrosion problems have become a major challenge to engineers [...].


Induction of pro-viral grass carp Ctenopharyngodon idella Hsp70 instead of Hsc70 during infection of grass carp reovirus.
Grass carp Ctenopharyngodon idella Hsp70 has been identified to play a functional role in viral attachment of type III grass carp reovirus, GCRV-104. However, it remains to be clarified whether Hsc70, sharing 86% identity with Hsp70, plays a similar role during viral infection. In this study, grass carp Hsp70 was shown to be induced by GCRV-104 in different grass carp cell lines, whereas Hsc70 was expressed in a relatively constant level during the infection. The expression patterns of Hsc70 and Hsp70 were similar to their homologs in mammals. Notably, both inhibitor and over-expression assays indicated that Hsp70 was required for efficient viral replication. Thus, our study supported a novel pro-viral property of Hsp70 besides its reported role in the viral attachment. Results herein presented also suggested that the heat shock response of grass carp might be manipulated by aquareovirus to facilitate its replication in fish cells.


Breast cancer presenting as renal colic.
A unique case of breast cancer presenting as renal colic due to ureteral obstruction is presented. Although antemortem diagnosis has been uncommon, ureteral metastases frequently are found in autopsy studies. Improvements in the management of patients with disseminated breast cancer may lead to more frequent recognition of this problem. Therapy should be directed against the tumor in general, and not specifically against the ureteral lesion unless renal function is jeopardized. Hormonal manipulation is the treatment of choice in patients with estrogen receptor-positive tumors. Ureteral catheterization or urinary diversion should be attempted only in combination with systemic injury.


Family evaluation of hospice care: results from voluntary submission of data via website.
The Family Evaluation of Hospice Care (FEHC) survey is a 61-item questionnaire that surveys family members about care provided to the decedent by the hospice. Hospices submit their data to the National Hospice and Palliative Care Organization (NHPCO), where results are tabulated. For the first two quarters of 2004, a total of 29,292 surveys were tabulated. On average, respondents rated their overall satisfaction with care as 47.1 on a 50-point composite scale of five measures of satisfaction. Opportunities for improvement were identified for attending to family needs for support (18.2% of those surveyed reported at least one unmet need), attending to family needs for communication (10-29%), and coordination of care (22.1%). Surrogate reporting of unmet needs for pain, dyspnea, or emotional support ranged from 5.3% to 9.8%. The FEHC is a useful tool for measuring hospice performance and identifies a number of opportunities for improvement.


Exploring the influencing factors of unmet palliative care needs in Chinese patients with end-stage renal disease undergoing maintenance hemodialysis: a cross-sectional study.
The role of palliative care for end-stage renal disease (ESRD) patients have been proven in some developed countries, but it is still unclear in the mainland of China. In fact, patients with ESRD experience many unmet palliative care needs, such as physical, psychological, social and spiritual needs, but the factors influencing these needs have not investigated. A cross-sectional study was conducted at two hemodialysis centers in the mainland of China from January to September 2022. Convenience sampling was used to collect data on the participants' socio-demographics, clinical characteristics, the Palliative Care Outcome Scale (POS), the Dialysis Symptom Index (DSI), the Karnofsky Performance Status Scale (KPS), the Patient Health Questionnaire-9 item (PHQ-9), and the Social Support Rate Scale (SSRS). Data were analyzed using latent profile analysis, Kruskal-Wallis test, one-way analysis of variance (ANOVA), the chi-square test and multinomial logistic regression analysis. Three hundred five participants were included in this study, and divided palliative care needs into three categories: Class 1, mild palliative care needs (n = 154, 50.5%); Class 2, moderate palliative care needs (n = 89, 29.2%); Class 3, severe palliative care needs (n = 62, 20.3%). Based on the analysis of three profiles, the influencing factors of unmet needs were further analyzed. Compared with Class 3, senior high school education, the household per capita monthly income < 2,000, low KPS scores, high PHQ-9 scores, and low SSRS scores were less likely to be in Class 1 (OR = 0.03, P = 0.012; OR = 0.003, P < 0.001; OR = 1.15, P < 0.001; OR = 0.55, P < 0.001; OR = 1.35, P = 0.002; respectively) and Class 2 (OR = 0.03, P = 0.007; OR = 0.05, P = 0.011; OR = 1.10, P = 0.001; OR = 0.60, P = 0.001; OR = 1.32, P = 0.003; respectively), and high symptom severity were less likely to be in Class 1 (OR = 0.82, P = 0.001). Moreover, compared with Class 1, the household per capita monthly income < 2,000 (OR = 16.41, P < 0.001), high symptom severity scores (OR = 1.12, P = 0.002) and low KPS scores (OR = 0.95, P = 0.002) were more likely to be in Class 2. This study showed that almost half of ESRD patients receiving MHD presented moderate to severe palliative care needs, and the unmet needs were mainly affected by education level, financial pressure, functional status, symptom burden and social support. In the future, it is important to identify the populations with the greatest need for palliative care and consider the influencing factors of unmet needs from a comprehensive perspective, so as to help them improve health-related quality of life.


Greater impairment of postprandial triacylglycerol than glucose response in metabolic syndrome subjects with fasting hyperglycaemia.
Studies have started to question whether a specific component or combinations of metabolic syndrome (MetS) components may be more important in relation to cardiovascular disease risk. Our aim was to examine the impact of the presence of raised fasting glucose as a MetS component on postprandial lipaemia. Men classified with the MetS underwent a sequential test meal investigation, in which blood samples were taken at regular intervals after a test breakfast (t=0 min) and lunch (t=330 min). Lipids, glucose and insulin were measured in the fasting and postprandial samples. MetS subjects with 3 or 4 components were subdivided into those without (n=34) and with (n=23) fasting hyperglycaemia (≥5.6 mmol/l), irrespective of the combination of components. Fasting lipids and insulin were similar in the two groups, with glucose significantly higher in the men with glucose as a MetS component (P<0.001). Following the test meals, there were higher maximum concentration (maxC), area under the curve (AUC) and incremental AUC (P ≤0.016) for the postprandial triacylglycerol (TAG) response in men with fasting hyperglycaemia. Greater glucose AUC (P<0.001) and insulin maxC (P=0.010) were also observed in these individuals after the test meals. Multiple regression analysis revealed fasting glucose to be an important predictor of the postprandial TAG and glucose response. Our data analysis has revealed a greater impairment of postprandial TAG than glucose response in MetS subjects with raised fasting glucose. The worsening of postprandial lipaemic control may contribute to the greater CVD risk reported in individuals with MetS component combinations which include hyperglycaemia.


The STING pathway: Therapeutic vulnerabilities in ovarian cancer.
Ovarian cancer is the leading cause of mortality due to gynecologic malignancy. The majority of women diagnosed with the most common subtype, high-grade serous ovarian carcinoma (HGSC), develop resistance to conventional therapies despite initial response to treatment. HGSC tumors displaying DNA damage repair (DDR) gene deficiency and high chromosomal instability mainly associate with higher cytotoxic immune cell infiltration and expression of genes associated with these immune pathways. Despite the high level of immune infiltration observed, the majority of patients with HGSC have not benefited from immunomodulatory treatments as the mechanistic basis of this infiltration is unclear. This lack of response can be primarily attributed to heterogeneity at the levels of both cancer cell genetic alterations and the tumour immune microenvironment. Strategies to enhance anti-tumour immunity have been investigated in ovarian cancer, of which interferon activating therapies present as an attractive option. Of the several type I interferon (IFN-1) stimulating therapies, exogenously activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is emerging as a promising avenue. Herein, we highlight our current understanding of how constitutive and induced cGAS-STING pathway activation influences the ovarian tumour microenvironment. We further elaborate on the links between the genomic alterations prevalent in ovarian tumours and how the resultant immune phenotypes can make them more susceptible to exogenous STING pathway activation and potentiate immune-mediated killing of cancer cells. The therapeutic potential of cGAS-STING pathway activation in ovarian cancer and factors implicating treatment outcomes are discussed, providing a rationale for future combinatorial treatment approaches on the backbone of chemotherapy.


Complex-irreversibility and evolution.
Both, irreversibility and evolution, imply order in time. It is argued that the only possible concept of time is a 'system-specific time', and that order in time is convertible into order in space and vice-versa. While life-less, complex systems are irreversible because of their complexity and, hence, not repeatable, living systems are reproduced by irreversible copy-reproduction and by coding. This mode of reproduction results of necessity in an arrow of time of growth and increasing complexity with death as its antagonist, and in obligatory spatial asymmetry. This arrow of increasing organic complexity is simultaneous with, and independent of, the arrow of increasing entropy. - A generalized, organic hierarchy is proposed as the model to study higher evolution. This hierarchy reproduces itself by differential rates of reproduction of its subunits within and between the various hierarchical levels of organization. Phylogenetic change is brought about by a change in this hierarchy's specific phase pattern of growth. Continuous and discrete organization is defined, and it is shown that specific relations between continuous and discrete levels within the hierarchy result in accumulation of neutral alleles. This accumulation is due to complex-irreversibility and causes genetic stabilisation, i.e. heritability, of the species-specific morphology of organisms.


Polycyclic aromatic hydrocarbons sorption on soils: some anomalous isotherms.
The sorption of four polycyclic aromatic hydrocarbons (PAHs), namely acenaphthene (Ac), phenanthrene (Ph), anthracene (An), and fluoranthene (Fl), on soil has been investigated. The kinetics of the sorption is characterised by the presence of two distinct periods. A fast initial stage followed by a second slower sorption process. Various kinetic models (i.e., Elvoich, Lagergren, second order and double exponential models) have been used to fit experimental data. The sorption equilibrium of individual PAHs has been assessed in the 298-333 K temperature range. Unlike Ac, Ph at 333 K and An and Fl at any temperature showed anomalous isotherms. The reason seems to rely on the "trapping" of dissolved PAHs by soil organic matter (SOM) released to water. This abnormal trend was not experienced when the isotherms were obtained for four PAHs mixture. Apparently, the most soluble Ac was capable of binding all the released material so no effect was thereafter observed.


[Determination of N-acetyl tryptophan in albumin solutions. Use of a F.P.L.C. method].
We developed a simple and reproducible technique for measuring N-Acetyl tryptophane in albumin after chromatography.


Progress in the treatment of unruptured aneurysms.
Recent technological progress has reduced the complication rate of unruptured aneurysm. We treated 128 unruptured aneurysms between April 2006 and March 2012. Seventy-six aneurysms (59 %) were clipped and 52 (41 %) were coil embolized. After 2010, we applied new instruments, i.e., near-infrared indocyanine-green videoangiography (ICG), an intraoperative endoscope, preoperative detailed MRI, and a stent-assisted coil embolization. In the results: (1) In 60 aneurysms treated before 2009, three patients showed a deterioration of more than two points in mRS (5 %). In 68 aneurysms treated after 2010, no patients showed deterioration (0 %) (p: n.s.). (2) No patients died and 126 patients (98 %) were discharged to home directly. (3) No patients showed rupture after treatment. In conclusion, the appropriate selection of treatment and recent technological progress have facilitated sophisticated treatment of unruptured aneurysms. Recently, the complication rate in surgery and endovascular surgery for unruptured aneurysms has become acceptably low.


Dissection of serological and cytolytic T lymphocyte epitopes on murine major histocompatibility antigens by a recombinant H-2 gene separating the first two external domains.
A novel H-2 gene in which the first external (N) domain of the H-2Ld antigen was replaced with that of the H-2Dd antigen was constructed and introduced into L cells. A transformant expressing the products of the hybrid gene was studied for binding to monoclonal antibodies specific for H-2Ld and H-2Dd antigens. It was found that serological determinants are distributed both in the N (Dd) and Cl (Ld) domains. Determinants recognized by allospecific cytotoxic T lymphocytes (CTLs) and virus-specific CTLs also mapped to the N and Cl domains. Determinants recognized by vesicular stomatitis virus (VSV)-specific effect cells, however, were not present on the recombinant molecule. These results show that a recombinant gene of two H-2 antigens in which the first external domain has been reshuffled can express a functional H-2 antigen that can then be used to map serological and CTL determinants to specific domains.


Combined surgical treatment of thoracic outlet syndrome: transaxillary first rib resection and transcervical scalenectomy.
Transaxillary first rib resection and transcervical scalenectomy are common procedures used for treatment of thoracic outlet syndrome (TOS). In the early 1980s, some surgeons started to perform both procedures, starting with the scalenectomy and following with a transaxillary first rib resection. The author has found that performing these procedures in the reverse order, starting with the first rib resection and following immediately with a transcervical scalenectomy is an easier approach, providing total decompression, better relief of symptoms, and a lower recurrence rate.


Comparison of fentanyl and halothane as supplement to nitrous-oxide-oxygen anaesthesia for coronary artery surgery.
Twenty unselected patients suffering from incapacitating angina, in spite of medication with nitrates, beta-blockers and calcium antagonists, were studied before and during coronary artery bypass surgery. Fentanyl or halothane was randomly used in combination with nitrous oxide for maintenance of anaesthesia in order to compare the haemodynamic response to surgery and cardiopulmonary bypass with these two anaesthetic regimens. Systemic and pulmonary artery pressure were kept within normal limits with the aid of volume replacement and/or nitroprusside. The haemodynamic response to surgery and bypass was benign and almost identical in the two groups. Cardiac index increased markedly after bypass (P less than 0.02-0.001) from 2.0 to 3.0 1 X min-1 X m-2 due to an increase in heart rate with no change in stroke index (40 ml X m-2). Oxygen delivery remained unchanged at 17 mmol X min-1 X m-2 in spite of a marked reduction in blood erythrocyte volume fraction (B-EVF), from 38% before bypass to 24% after bypass (P less than 0.001). Oxygen uptake remained unchanged until the end of surgery and did not differ between the groups. Systemic vascular resistance, corrected for the change in viscosity due to the altered B-EVF, was unchanged during the study. No difference was observed between the groups in the relation between pulmonary artery diastolic pressure and left ventricular stroke work index or stroke index, either before or at the end of cardiopulmonary bypass when the patients were transfused from the oxygenator.


Optical Properties of Anisotropic Polycrystalline Ce+3 activated LSO.
Polycrystalline cerium activated lutetium oxyorthosilicate (LSO:Ce) is highly desirable technique to make cost effective and highly reproducible radiation detectors for medical imaging. In this article methods to improve transparency in polycrystalline LSO:Ce were explored. Two commercially available powders of different particulate sizes (average particle size 30 and 1500 nm) were evaluated for producing dense LSO:Ce by pressure assisted densification routes, such as hot pressing and hot isostatic pressing. Consolidation of the powders at optimum conditions produced three polycrystalline ceramics with average grain sizes of 500 nm, 700 and 2000 nm. Microstructural evolution studies showed that for grain sizes larger than 1 µm, anisotropy in thermal expansion coefficient and elastic constants of LSO, resulted in residual stress at grain boundaries and triple points that led to intragranular microcracking. However, reducing the grain size below 1 µm effectively avoids microcracking, leading to more favorable optical properties. The optical scattering profiles generated by a Stover scatterometer, measured by a He-Ne laser of wavelength 633 nm, showed that by reducing the grain size from 2 µm to 500 nm, the in-line transmission increased by a factor of 103. Although these values were encouraging and showed that small changes in grain size could increase transmission by almost 3 orders of magnitude, even smaller grain sizes need to be achieved in order to get truly transparent material with high in-line transmission.


Effect of the structure and density of chemically bonded C18 phase on the recovery of tryptophan and its metabolites from human urine.
A series of materials with chemically bonded C18 phase for use as the packings in clean-up columns for solid-phase extraction were prepared. The effects of the monomeric and/or polymeric structure of the chemically bonded phase and of the porous structure of the silica gel support on the recovery of tryptophan and two of its metabolites used as test substances were considered. It appeared that the best recoveries of at least 60% of the three test substances were obtained on material of the "monomer" type containing chemically bonded C18 phase characterized by a high coverage density of alpha RP approximately 3.8 mumol/m2. The use of a silica gel support with a larger pore size and volume permits not only the effective isolation of individual substances, e.g., from urine, but also their 5-fold concentration.


C1-2 block vertebra. Fusion of the anterior arch of the atlas with the axis. Follow-up of the fusion in a child.
A peculiar form of C1-2 block vertebra (anterior arch of the atlas with the axis) is described. The progressive ossification is followed up in a child from the age of 9 to 15. The author also reviews the data of his five previously reported cases.


A NIR Turn-on Fluorescent Sensor For Detection of Chloride Ions in vitro and in vivo.
As the most abundant and significant anions in biosystem, chloride ions (Cl-) participate in many important physiological processes. Thus, designing and synthesizing of a simple, sensitive, selective and long wavelength turn-on sensor for the detection and imaging of Cl- in vitro and in vivo is very necessary. Herein, we have developed a simple porphyrin turn-on sensor 5, 10, 15, 20-Tetrakis (4-hydroxyphenyl) porphyrin (THPP) with near infrared emission wavelength (657 nm) for sensing chloride ions with remarkable sensitivity and selectivity. The detection of chloride ions was according to metal displacement assay (MDA) under physiological condition with a detection limit of 7.5 μM, and was applied to image Cl- in vitro and in vivo successfully.


Lewis acid catalyzed sulfur transfer from a sultene to strained cyclic alkenes.
[reaction: see text] Sultene 1 reacts with cyclic alkenes under mild Lewis acid catalysis to form thiiranes diastereoselectively. With 1-methoxycyclooctene as sulfur acceptor, an unexpected insertion product is formed, which provides valuable mechanistic insight into the sulfur-transfer process.


Improvement effects of esculetin on the formation and development of atherosclerosis.
Atherosclerosis is one of the potential causes of death in patients with cardiovascular disease. With the discovery of new anti atherosclerotic drugs becoming the pursuit of the pharmaceutical industry, natural products have attracted more and more attention because of their unique efficacy in the treatment of atherosclerosis. More and more studies have shown that esculetin, a coumarin mainly found in cortex fraxini, can improve atherosclerosis by participating in cellular antioxidant responses and reducing inflammation related pathogenesis. This paper summarizes the researches of esculetin on anti-atherosclerosis in the past two decades. Esculetin plays an anti atherosclerotic role through reducing blood triglyceride level, preventing the proliferation of vascular smooth muscle cells (VSMC) and the production of matrix metallopeptidase 9 (MMP-9), inhibiting the oxidation of low density lipoprotein (LDL) and the secretion of adhesion factors and chemokines, and increasing the outflow level of high density lipoprotein cholesterol (HDL-C). Esculetin is safe and reliable, easy to be absorbed by the body and can be synthesized in a variety of ways. Although there are still few clinical studies on anti-atherosclerosis, in vivo experiments have proved that esculetin has high bioavailability. From the current research, the anti-atherosclerotic effect of esculetin is positive and encouraging. However, much work remains to be done to clarify the molecular mechanism of esculetin in the treatment of atherosclerosis.


Second metatarsophalangeal joint fusion: a new technique for crossover hammertoe deformity. A preliminary report.
The author reports on second metatarsophalangeal joint arthrodesis for the severe crossover hammertoe deformity. Eleven patients underwent an arthrodesis of the second metatarsophalangeal joint with a.062 Kirschner wire intramedullary fixation and a dorsal small bone staple and resection of the proximal phalangeal head of the second digit. Outcomes were retrospectively reviewed at average follow-up time of 19 months. A subjective patient satisfaction survey along with a clinical and radiographic evaluation was undertaken in the postoperative period. Ten of 11 patients scored good to excellent results based on the patient subjective survey at final follow-up. Ten of 11 patients obtained primary arthrodesis. One patient experienced an asymptomatic nonunion. This new technique appears to be reliable for the maintenance of long-term correction of a crossover second toe with arthrodesis of the second metatarsophalangeal joint.


Do Twitter users change their behavior after exposure to misinformation? An in-depth analysis.
Social media platforms have been exploited to disseminate misinformation in recent years. The widespread online misinformation has been shown to affect users' beliefs and is connected to social impact such as polarization. In this work, we focus on misinformation's impact on specific user behavior and aim to understand whether general Twitter users changed their behavior after being exposed to misinformation. We compare the before- and after-exposure behaviors of Twitter users to determine whether they changed their tweeting frequency, tweets sentiment, usage of specific types of words, and the ratio of liberal/conservative media URLs they shared. Our results show that users overall exhibited statistically significant changes in behavior across some of these metrics. Through language distance analysis, we show that exposed users were already different from baseline users before the exposure. We also study the characteristics of several specific user groups, which include liberal/conservative leaning groups and multi-exposure groups. Furthermore, we study whether the users' behavior changes after exposure to misinformation tweets vary based on their follower count or the follower count of the tweet authors. Finally, we examine potential bots' behaviors and find they are similar to that of normal users.


Occupational exposure to cadmium: effect on metallothionein and other biological indices of exposure and renal function.
The effect of duration of employment at a North American cadmium smelter on urinary metallothionein (MT), total protein, beta 2-microglobulin (beta 2-MG), glucose, cadmium, copper and zinc of 53 men was studied. The levels of all urinary parameters increased with the duration of employment. Smoking history did not affect any of the above parameters studied. Although age was responsible for some of the changes noted in protein, glucose and beta 2-MG levels, its effect on MT and cadmium was insignificant. All urinary parameters were significantly related with each other. The relationship of elevated urinary MT levels with respect to renal dysfunction was also examined. Subjects with abnormal renal function excreted significantly higher amounts of MT than did those with normal renal function. The results confirm not only that occupational exposure to cadmium over long periods results in renal dysfunction but also that urinary MT could be used to monitor exposure and ultimately the appearance of the renal dysfunction.


Retracted: Analysis of Agriculture and Food Supply Chain through Blockchain and IoT with Light Weight Cluster Head.
[This retracts the article DOI: 10.1155/2022/1296993.].


Eculizumab for salvage treatment of refractory antibody-mediated rejection in kidney transplant patients: case reports.
Antibody-mediated rejection (AMR) in a group of preoperatively desensitized patients may follow a dreadful course and result in loss of the transplanted kidney. In several cases, conventional therapies including plasmapheresis, intravenous immunoglobulin, and anti-CD 20 therapy can resolve AMR successfully. But in some cases the load of immunoglobulins that can activate complement cascade may submerge the routine desensitization therapy and result in the formation of membrane attack complexes. Eculizumab, monoclonal antibody against C5, was reported to be an option in cases with severe AMR that are resistant to conventional therapy. Here, we present two cases of acute-onset AMR in preoperatively desensitized patients. Eculizumab was used as a salvage agent in addition to conventional therapy. Given the bad prognosis for renal transplants displaying acute injury progressing rapidly to cortical necrosis on the biopsy, the prompt use of eculizumab could have the advantage of immediate effects by stopping cellular injury. This can provide a therapeutic window to allow conventional treatment modalities to be effective and prevent early graft loss.


Does paternal immunocompetence affect offspring vulnerability to maternal androgens? A study in domestic chickens.
Exposure of yolk androgens can positively stimulate chick growth and competitive ability, but may negatively affect immunity. It has been hypothesized that only chicks from immunologically superior fathers can bear the cost of prenatal exposure to high androgen levels. To test this hypothesis, we paired roosters from two selection lines, one up- and one down-selected for natural antibodies (NAbs), with hens from a control line. We measured yolk testosterone and androstenedione levels, and we injected the treatment group of eggs of each female with testosterone suspended in sesame oil and the control group with sesame oil only. We then measured hatching success and growth, and characterized the humoral and cellular immune responses using three different challenges: a phyto-hemagglutinin, a lipopolysaccharide and a sheep red blood cell challenge. We found that the hatching success, body mass, initial levels of natural antibodies and the chicks' immunological responses to the three different challenges and development were affected neither by paternal immunocompetence nor by treatment. These results do not support the hypothesis that chicks from low-NAb line fathers are more sensitive to testosterone exposure during embryonic development than chicks from high-NAb line fathers.


An in vitro model to study the pathogenesis of the early endometriosis lesion.
To determine if whole fragments of endometrium can adhere to peritoneum with intact mesothelium. Tissue culture and immunohistochemical study. University Medical Center. Reproductive-age women undergoing surgery for benign conditions. Whole explants of human peritoneum from the anterior abdominal wall and the posterior surface of the uterus were cultured with whole fragments of mechanically dispersed endometrium. Adhesion of endometrial fragments to the surface of the peritoneum was evaluated. Adherent fragments of endometrium were identified using the dissecting microscope and by performing serial sections of the peritoneum explants for light and confocal laser-scanning microscopy. Immunohistochemical staining of the mesothelium with antibodies to cytokeratin and vimentin was used to ensure an intact layer of mesothelium beneath the endometrial implants. Transmission electron microscopy was also used to evaluate the adhesion of endometrium to the mesothelium. Endometrium was identified attached to the surface of the peritoneum. After 18-24 hours of culture, the majority of implants did not have identifiable mesothelium beneath them, but most had intact mesothelium running up to the point of attachment. Approximately 10% of the endometrial implants had intact mesothelium at the site of attachment. After 1 hour of culture, both endometrial stromal and epithelial cells were attached to intact mesothelium in nearly all cases. Early transmesothelial invasion involves endometrial stromal cells. Endometrial stromal and epithelial cells can attach to the intact mesothelial surface of the peritoneum. Endometrial stromal cell invasion through the mesothelium occurs in less than 18-24 hours.


Measuring Transendothelial Electrical Resistance (TEER) for Dengue Infection Studies.
A growing body of evidence demonstrates that endothelial cells (ECs) play a prominent role in immune-enhanced pathology seen in dengue virus (DENV) infection that might contribute to vascular permeability and hemorrhagic manifestations in severe dengue cases. However, it remains a question of whether DENV infection of ECs directly causes permeability or if extra-endothelial factors such as immune cell activation or antibody-dependent enhancement (ADE) are required. In this chapter, we detail the measurement of the transendothelial electrical resistance (TEER), a quantitative technique to measure the integrity of tight junction dynamics in cell culture models of endothelial monolayers and show that DENV infection of ECs does not cause endothelial permeability in vitro.


Design and preliminary analysis of a study to assess intra-device and inter-device variability of fluorescence spectroscopy instruments for detecting cervical neoplasia.
A study was designed to assess variability between different fluorescence spectroscopy devices. Measurements were made with all combinations of three devices, four probes, and three sets of standards trays. Additionally, we made three measurements on the same day over 2 days for the same combination of device, probe, and standards tray to assess reproducibility over a day and across days. The devices consisted of light sources, fiber-optics, and cameras. We measured thirteen standards and present the data from the frosted cuvette, water, and rhodamine standards. A preliminary analysis was performed with the data that were wavelength calibrated and background subtracted; however, the system has not been corrected for systematic intensity variations caused by the devices. Two analyses were performed on the rhodamine, water, and frosted cuvette standards data. The first one is based on first clustering the measurements and then looking for association between the 5 factors (device, probe, standards tray, day, measurement number) using chi-squared tests on the cross-tabulation of cluster and factor level. This showed that only device and probe were significant. We then did an analysis of variance to assess the percent variance explained by each factor that was significant from the chi-squared analysis. The data were remarkably similar across the different combinations of factors. The analysis based on the clusters showed that sometimes devices alone, probes alone, but most often combinations of device and probe caused significant differences in measurements. The analysis showed that time of day, location of device, and standards trays do not vary significantly; whereas the devices and probes account for differences in measurement. We expected this type of significance using unprocessed data since the processing corrects for differences in devices. However, this analysis on raw data is useful to explore what combination of device and probe measurements should be targeted for further investigation. This experiment affirms that online quality control is necessary to obtain the best excitation-emission matrices from optical spectroscopy devices. The fact that the device and probe are the primary sources of variability indicates that proper correction for the transfer function of the individual devices should make the measurements essentially equivalent.


Local knowledge and socio-economic determinants of traditional medicines' utilization in livestock health management in Southwest Nigeria.
Smallholder livestock farmers in Nigeria utilize traditional medicines derived from medicinal plants (PMs) for the maintenance of their animals' health. This study was designed to determine the PMs used in the study area and their level of utilization by livestock farmers, compare the level of utilization of PMs across the three states surveyed and identify the socio-economic factors influencing farmer's utilization of PMs. Thirty-five PMs were identified. Farmers had considerable knowledge about the identified PMs but about 80.0% of them used the PMs to poor/moderate extent. There were statistical differences in the utilization level of PMs among the three states. Six socio-economic variables were found to be statistically significant in influencing PMs' utilization. Farmer's age, household size, distance to the nearest veterinary hospital/clinic and extent of travels, had positive effects while negative effects were exhibited by farm income and number of heads of livestock. It was concluded that there was considerable knowledge about PMs and that utilization of PMs varied between the three states. It was recommended that local knowledge of PMs be preserved in the study area through screening and documentation.


Conservative surgery for transitional cell carcinoma of the renal pelvis.
From 1972 to 1986, 14 patients underwent a conservative operation for transitional cell carcinoma of the renal pelvis. Most of these patients had low grade (12), noninvasive (10) tumors involving a solitary functioning kidney (12). The operations performed were open pyelotomy with tumor excision and fulguration (8 patients), partial nephrectomy (5) and percutaneous nephroscopic fulguration (1). There was 1 operative death. Of the 13 surviving patients 8 (62 per cent) remained free of transitional cell carcinoma postoperatively, while 5 (38 per cent) had recurrent disease. Six patients (46 per cent) presently are free of tumor 6 months to 5 years postoperatively. Conservative surgical techniques can provide satisfactory treatment for selected patients with renal pelvic transitional cell carcinoma when preservation of functioning renal parenchyma is necessary to avoid kidney failure.


What is the relevance of bioinformatics to pharmacology?
Although bioinformatics achieved prominence because of its central role in genome data storage, management and analysis, its focus has shifted as the life sciences exploit these data. In pharmacology, genomic, transcriptomic and proteomic data are being used in the quest for drugs that fulfill unmet medical needs, are disease modifying or curative and are more effective and safer than current drugs. Bioinformatics is used in drug target identification and validation and in the development of biomarkers and toxicogenomic and pharmacogenomic tools to maximize the therapeutic benefit of drugs. Now that the 'parts list' of cellular signalling pathways is available, integrated computational and experimental programmes are being developed, with the goal of enabling in silico pharmacology by linking the genome, transcriptome and proteome to cellular pathophysiology.


Adverse events of immune checkpoint inhibitors in hepatocellular carcinoma: a systemic review and meta-analysis.
The introduction of immune checkpoint inhibitors (ICIs) has reshaped the therapy of hepatocellular carcinoma (HCC). ICIs are a novel therapy with frequent adverse events (AEs), including treatment-related adverse events (trAEs) and immune-related adverse events (irAEs). However, no comprehensive overview of the toxicity spectrum of ICIs in HCC patients has been provided. Electronic databases were searched to identify eligible studies. A meta-analysis of the incidence rate of AEs in HCC patients treated with ICIs was performed. Lastly, the prognostic value of irAEs in HCC patients treated with ICIs was verified. Forty-seven studies with 6472 participations met the inclusion criteria. The pooled all-grade trAEs incidence rate was 83.4% (95% confidence interval [95% CI] 77.0-89.1%), ≥ grade 3 trAEs incidence rate was 33.0% (95% CI 26.9-39.5%), all-grade irAEs incidence rate was 34% (95% CI 22-47%), and ≥ grade 3 irAEs incidence rate was 9% (95% CI 5-14%). Aspartate aminotransferase (AST) increase (38%, 95% CI 35-40%) is the most common trAEs. Fatigue (14%, 95% CI 7-23%) is the most common irAEs. The pooled results also showed that 18.8% (95% CI 13.2-25.2%) of patients required systemic steroid therapy due to AEs, while 6.6% (95% CI 4.6-9.0%) of patients withdrew from treatment due to AEs. Additionally, patients experiencing irAEs may have a better progression-free survival (PFS) (multivariate analysis: hazard ratio [HR] = 0.41, 95% CI 0.27-0.61, I2 = 36.3%) but not overall survival (OS) (multivariate analysis: HR = 0.54, 95% CI 0.22-1.36, I2 = 83.2%) than those with no irAEs. Our study presents a systemic assessment of the AEs profile in HCC patients receiving ICIs, providing important reference for clinicians on toxicity profile. Besides, patients with irAEs may have a better PFS. More large-scale and prospective studies are needed to confirm our conclusions.


Tumor-specific delivery of BSH-3R for boron neutron capture therapy and positron emission tomography imaging in a mouse brain tumor model.
Glioblastoma, a malignant brain tumor with poor disease outcomes, is managed in modern medicine by multimodality therapy. Boron neutron capture therapy (BNCT) is an encouraging treatment under clinical investigation. In malignant cells, BNCT consists of two major factors: neutron radiation and boron uptake. To increase boron uptake in cells, we created a mercapto-closo-undecahydrododecaborate ([B12HnSH](2-)2Na(+), BSH) fused with a short arginine peptide (1R, 2R, 3R) and checked cellular uptake in vitro and in vivo. In a mouse brain tumor model, only BSH with at least three arginine domains could penetrate cell membranes of glioma cells in vitro and in vivo. Furthermore, to monitor the pharmacokinetic properties of these agents in vivo, we fused BSH and BSH-3R with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA); DOTA is a metal chelating agent for labeling positron emission tomography (PET) probe with (64)Cu. We administered BSH-DOTA-(64)Cu and BSH-3R-DOTA-(64)Cu to the tumor model through a mouse tail vein and determined the drugs' pharmacokinetics by PET imaging. BSH-3R showed a high uptake in the tumor area on PET imaging. We concluded that BSH-3R is the ideal boron compound for clinical use during BNCT and that in developing this compound for clinical use, the BSH-3R PET probe is essential for pharmacokinetic imaging.


Life events and social rhythms in bipolar spectrum disorders: an examination of social rhythm sensitivity.
To examine the presence of an underlying social rhythm sensitivity in individuals with bipolar spectrum disorders. The present study examined the impact of life events on sleep loss and social rhythm disruption in 184 individuals with bipolar spectrum disorders (BSD) compared to 197 demographically similar normal controls (NC) drawn from the Longitudinal Investigation of Bipolar Spectrum Disorders (LIBS) project. Life events data were obtained at three time points, each spaced four months apart, and included information on the intensity of the event (high or low), valence (negative or positive), and levels of sleep loss and social rhythm disruption brought about the event. We hypothesized that BSD participants would exhibit higher levels of social rhythm disruption and sleep loss than normal controls as a consequence of the same life events. BSD participants experienced significantly more social rhythm disruption and sleep loss following all classes of life events. The cross-sectional design of this study limits the strength of the conclusions that can be drawn, primarily cause and effect relationships between social rhythms and symptoms. Findings support the presence of an underlying social rhythm sensitivity in individuals with bipolar spectrum disorders. An additive effect of sleep loss and social rhythm disruption may contribute to subsequent mood symptomatology. Results from this study may inform early psychosocial interventions for at-risk individuals.


Function and therapeutic value of astrocytes in diabetic cognitive impairment.
Diabetic cognitive impairment (DCI) is a complex complication of diabetes in the central nervous system, and its pathological mechanism is still being explored. Astrocytes are abundant glial cells in central nervous system that perform diverse functions in health and disease. Accumulating excellent research has identified astrocyte dysfunction in many neurodegenerative diseases (such as Alzheimer's disease, aging and Parkinson's disease), and summarized and discussed its pathological mechanisms and potential therapeutic value. However, the contribution of astrocytes to DCI has been largely overlooked. In this review, we first systematically summarized the effects and mechanisms of diabetes on brain astrocytes, and found that the diabetic environment (such as hyperglycemia, advanced glycation end products and cerebral insulin resistance) mediated brain reactive astrogliosis, which was specifically reflected in the changes of cell morphology and the remodeling of signature molecules. Secondly, we emphasized the contribution and potential targets of reactive astrogliosis to DCI, and found that reactive astrogliosis-induced increased blood-brain barrier permeability, glymphatic system dysfunction, neuroinflammation, abnormal cell communication and cholesterol metabolism dysregulation worsened cognitive function. In addition, we summarized effective strategies for treating DCI by targeting astrocytes. Finally, we discuss the application of new techniques in astrocytes, including single-cell transcriptome, in situ sequencing, and prospected new functions, new subsets and new targets of astrocytes in DCI.


Hypofractionated adjuvant radiotherapy with helical tomotherapy after radical prostatectomy: planning data and toxicity results of a Phase I-II study.
To report on planning and toxicity findings of hypofractionated adjuvant radiotherapy with helical Tomotherapy (HTT) after radical prostatectomy (RP) for prostate carcinoma (pCa). Fifty consecutive patients submitted to RP for pT2R1/pT3a/pT3b-pN0 pCa were enrolled in a Phase I-II trial to receive 58Gy/20 fractions (5/week) on tumoral bed. Endpoint was to verify a risk of toxicity and biochemical failure not exceeding that observed in our Institutional 3DCRT, conventionally fractionated series (153 patients). Toxicities were graded according the RTOG scoring system. Excellent coverage of PTV and high homogeneity of dose distribution were always achieved. Median follow-up was 25 months. Acute G2-3 RTOG genitourinary (GU) and acute G2 intestinal toxicities were similar (12% vs 15.6% and 4% vs 7%, respectively), while acute G2 proctitis was 0% vs 9% in HTT and 3DCRT group, respectively. Similarly, late Grade 2 gastrointestinal sequelae were 0% vs 8.5%. The incidence of late urethral stricture, 8% and 9% in HTT and 3DCRT group, respectively, is comparable to that of RP-only series. Acute toxicity and early late toxicity outcomes of a moderately hypofractionated regimen with HTT post-RP are excellent. A longer follow-up is needed to fully assess the validity of this approach.


Plant stress and insect behavior: cottonwood, ozone and the feeding and oviposition preference of a beetle.
Adults and larvae of the beetle Plagiodera versicolora preferred to feed on and consumed more of cottonwood, Populus deltoides, plant material that had been previously exposed to an acute dose of ozone (0.20 ppm, 5 h), compared to controls in choice experiments. However, females preferred to oviposit on the unexposed controls. Results were consistent for 2 cottonwood clones over 3 years in disc, leaf and whole-plant choice tests. The differential feeding and oviposition response of this insect to stressed plants could have at least 3 unexpected consequences: 1. An immediate increase in damage to stressed trees, but a subsequent decrease in damage. 2. A subsequent increase in damage to unstressed adjacent trees. 3. Changes in the insect and pathogen communities of both stressed and unstressed trees. These complex scenarios show that predicting outcomes of plant stress on plant-insect interactions will require comprchensive examination of behavioral, growth and reproductive responses of insects to stressed plants.


Therapeutic Prospects of Gene Therapy for Atrial Fibrillation.
Atrial Fibrillation (AF) is one of the most common types of cardiac arrhythmias experienced in clinical practice, increasing the risk of stroke, dementia, myocardial infarction and death. Currently available options for the treatment of AF use either pharmacological agents or catheter-based ablation therapies to restore sinus rhythm or control the ventricular response rate. These current treatment options are suboptimal at best, motivating research into discovering more effective and innovative ways to treat AF. Gene therapy is being explored for its potential to treat various human conditions including cardiac arrhythmias. Gene transfer vectors with increasing transduction efficiency and biosafety have been developed and trialled for cardiovascular disease treatment. With an improved understanding of the molecular mechanisms of AF, several gene therapy targets have been identified and evaluated in an attempt to rate or rhythm control the heart during AF. This review will discuss the gene therapy vectors in use today and methods for delivery of these vectors to the atrium. Further, it will evaluate several gene therapy strategies and approaches for sinus rhythm restoration and ventricular rate control that have the potential to emerge as a therapy for AF.


Pelvic lipomatosis: a nonsurgical diagnosis.
Pelvic lipomatosis is rare in Europe. Preoperative diagnosis is seldom reached and subsequent explorative procedures are necessary. Typical roentgenographic findings are presented. The possibility of an early presurgical diagnosis is emphasized.


Fine-structural localization of proenkephalin mRNAs in the hypothalamic magnocellular dorsal nucleus of the guinea pig: a comparison of radioisotopic and enzymatic in situ hybridization methods at the light- and electron-microscopic levels.
With the aim of localizing proenkephalin mRNAs in neurons of the hypothalamic magnocellular dorsal nucleus of the guinea pig, we compared the in situ hybridization signals obtained on Vibratome sections with a method employing either a biotinylated or a digoxigenin-labeled oligonucleotide detected by means of the alkaline phosphatase reaction. Since the hybridization approach using the biotinylated probe was more sensitive than the digoxigenin method, the ultrastructural localization of hybrids in neurons of the magnocellular dorsal nucleus was studied by the use of the former procedure, and was further compared with results of in situ hybridization using a 35S-labeled probe. Biotin was detected via an amplified avidin-biotin-peroxidase complex. Radioactive hybrids were localized over extended cytoplasmic compartments rich in rough endoplasmic reticulum and also in nuclear indentations. The method based on biotinylated probe proved to be sensitive and provided high-resolution labeling in well-preserved specimens. Proenkephalin mRNAs were clearly localized within circumscribed cytoplasmic compartments. The immunoprecipitates were mainly observed within the rough endoplasmic reticulum, especially at the periphery of the cell. The reticulum was dominated by elongated parallel cisternae. The labeling also appeared in a paranuclear position, mainly in nuclear indentations. The labeling was found on the outer surface of the endoplasmic lamellae. The remainder of the reticulum was unlabeled. Neuronal processes were free of labeling.


Systemic activity of nifluridide against sucking lice and the common scabies mite on cattle.
Psoroptes ovis [Hering] mites and sucking lice (Linognathus vituli Linnaeus) were eliminated from light to heavily infested calves with a single subcutaneous injection of nifluridide in five separate experiments. The compound was incorporated in a copolymer vehicle in a sesame oil suspension. In the first two experiments, mites were eliminated within 10 days following a 20 mg kg-1 injection. Eight out of 9 calves were cleared of mites within 7 days post injection of nifluridide at 4, 6 and 9 mg kg-1 in the third experiment. At the end of the 65 day trial, no live mites were isolated from any of the treated animals. In the last two experiments nifluridide eliminated sucking lice populations at all dosage levels. Complete control of the biting lice (Bovicola bovis) was not obtained. No toxic signs were observed in treated calves.


High-dose carboplatin and regimen-related toxicity following autologous bone marrow transplant.
Pharmacokinetic analysis of carboplatin dosing suggests a more accurate prediction of toxicity when the dose is based on the area under the plasma concentration vs time curve (AUC) instead of body surface area (BSA). We retrospectively calculated the carboplatin AUC of 117 patients who received an autologous stem cell transplant following a conditioning regimen consisting of carboplatin 1800 mg/m(2) and cyclophosphamide 6000 mg/m(2) to identify whether higher carboplatin exposure resulted in an increase in regimen-related non-hematologic toxicities. The most common non-hematologic toxicities were gastrointestinal and hepatic. Twenty (17%) patients experienced additional > or =grade 2 toxicity, specifically, renal toxicity significantly associated with a higher median AUC of 10.2 mg/ml(-1) min (P = 0.001). Prior platinum therapy was also significantly associated with toxicity (P = 0.052). While carboplatin dose based on BSA varied minimally (median 990 (range 450-1340) mg, the calculated AUC showed a near four-fold range of exposure (median 7.8 (range 3.6 to 13.8) mg/ml(-1) min). These data suggest a relationship between non-hematologic adverse events and the estimated AUC. Prospective trials will be necessary to identify the target carboplatin AUC which optimizes outcome and minimizes toxicity in the autologous transplant setting.


Treatment with unfunded drugs in oncology: the impact of access programmes and clinical trials.
Where proven cancer therapies remain unfunded, patients are faced with difficult decisions regarding personally covering some or all of the treatment cost. Clinical trials provide an alternative form of access to unfunded drugs. To examine the patient population and utilisation of the colorectal cancer cetuximab Interim Access Programme (IAP) in Australia. We retrospectively analysed de-identified data collected as part of the costsharing colorectal cancer cetuximab IAP in Australia, which extended from June 2005 until November 2009. The impact of the CO20 clinical trial that opened in early 2008 and provided free access to cetuximab was also examined. Eight hundred and fifty-eight patients received ≥1 treatment on the IAP. The median age of participants was lower than the general colorectal cancer population (61 vs 71 years). A greater uptake by males was limited to patients over 65 years old. Socioeconomic status correlated with programme enrolment, and there appeared to be lower uptake among regional patients. The majority (93%) of patients received combination treatment with irinotecan, with a trend towards increasing use of single-agent cetuximab over time. The median time-on-treatment was longer in patients treated with combination therapy than with monotherapy (12 vs 8 weeks). The CO20 trial had minimal impact on IAP enrolment and approximately doubled the number of Australian patients receiving cetuximab. Patients' age and gender in older patients impacted on participation in the IAP. Both the IAP and the CO20 trial contributed to a substantial proportion of Australian patients accessing an unfunded treatment, with an estimated 50% of the eligible patient population receiving cetuximab.


Usefulness of the computed tomography and magnetic resonance in evaluation of progress of treatment of the neoplasmatic diseases in children.
Neoplastmatic diseases constitute about 1% diseases in children in Poland, what makes about 1200 new incidents during one year. Fast diagnosis in those illnesses is crucial in treatment results. The point of this work was to value usefulness of CT and MRI in diagnostics of neoplasmatic diseases in children. The retrospective study involved 121 children examined in CT and MRI because of suspicion or during treatment of neoplasmatic disease. Together 184 CT and 119 MRI examination were performed. Eventually in 106 children neoplasmatic disease was diagnosed. In 16 cases neoplasm was excluded. In the analyzed group of patients acute lymphoblastic and non lymphoblastic leukemia was diagnosed in 68 children (55.7%); among them mycosis was identified after radiological examinations in 7 cases (10.3%). 8 children (6.6%) with non Hodgkin lymphoma and 11 (9%) with Hodgkin lymphoma were examined. Nephroblastoma was found after MRI and CT in 6 cases (4.9%). Presence of tumors, that were classified histopatologically as PNET, was confirmed in 4 children. In 15 cases after MRI and CT neoplasmatic disease was excluded. Depending on the kind of sickness MRI and CT may fulfill basic or subsidiary role in diagnostic and estimating the progress of treatment in neoplasmatic diseases among children.


Methods and Considerations for Dynamic Analysis of Functional MR Imaging Data.
Functional MR imaging (fMR imaging) studies have recently begun to examine spontaneous changes in interregional interactions (functional connectivity) over seconds to minutes, and their relation to natural shifts in cognitive and physiologic states. This practice opens the potential for uncovering structured, transient configurations of coordinated brain activity whose features may provide novel cognitive and clinical biomarkers. However, analysis of these time-varying phenomena requires careful differentiation between neural and nonneural contributions to the fMR imaging signal and thorough validation and statistical testing. In this article, the authors present an overview of methodological and interpretational considerations in this emerging field.


Sonographic assessment of the distal femoral and proximal tibial ossification centers in the prediction of pulmonic maturity in normal women and women with diabetes.
A noninvasive method for the assessment of fetal pulmonic maturity via the sonographic characterization of fetal distal femoral and proximal tibial epiphyseal ossification centers was evaluated. The study population included 82 patients in the third trimester of pregnancy, 47 of whom had uncomplicated gestations, while 35 had insulin-dependent diabetes. In uncomplicated pregnancies a distal femoral epiphysis measuring greater than or equal to 3 mm in the axial plane or the sonographic identification of a proximal tibial epiphysis of any dimension correlated with pulmonic maturity. The combination of a distal femoral epiphysis greater than or equal to 3 mm and the presence of a proximal tibial epiphysis was highly correlated with a lecithin/sphingomyelin ratio greater than or equal to 2:1 (sensitivity 100%, specificity 63%, negative predictive value 100%, and false-negative rate 0%). The Kappa value (K) for testing the agreement between ultrasound results and amniocentesis results was 0.39 (p less than 0.002). In diabetic pregnancies neither a distal femoral epiphysis greater than or equal to 3 mm nor a proximal tibial epiphysis of any dimension correlated precisely with the presence of phosphatidyl glycerol in the amniotic fluid. However, the combination of a distal femoral epiphysis greater than or equal to 3 mm and a proximal tibial epiphysis greater than or equal to 2 mm improved the prediction of phosphatidyl glycerol (sensitivity 83%, specificity 79%, negative predictive value 96%, false-negative rate 17%). The K value in this instance was 0.36 (p greater than or equal to 0.19). It is concluded that the sonographic assessment of the distal femoral and proximal tibial epiphyses and their dimensions in the axial plane may be useful as markers for pulmonic maturity in uncomplicated pregnancies.


Investigation of Penicillium chrysogenum Isolates for their Suitability as Starter Cultures.
One hundred twenty three isolates ofP. chrysogenum were biologically tested in brine shrimp test and screened withStaphylococcus aureus for the detection of antibacterial activity. Furthermore, they were chemically examined (thin layer chromatographic method, TLC) for the synthesis of 8 mycotoxins (citrinin, cyclopiazonic acid, mycophenolic acid, patulin, penicillic acid, PR-toxin, ochratoxin A, and roquefortine). The results indicated that 85% of the tested isolates produce roquefortine and one isolate produces cyclopiazonic acid. Considering the results of the chemical assay for mycotoxins as well as the results of the brine shrimp test and the detection of antibacterial activity, 119 (97%) of the tested isolates are not suitable to be used as starter cultures for mould-fermented meats. The extracts of only 4 isolates were subjected to further biological tests in mice and the results indicated that only one isolate was non-toxinogenic.


Percutaneous Endoscopic Lumbar Discectomy Using a Double-Cannula Guide Tube for Large Lumbar Disc Herniation.
To compare the effect of percutaneous endoscopic lumbar discectomy (PELD) using a double-cannula guide tube (DGT), traditional PELD, and open lumbar discectomy (OLD) to treat large lumbar disc herniations (LLDHs). Seventy patients who presented with LLDH without cauda equina syndrome and were treated with surgery in our hospital from October 2015 to October 2017 were included. The detailed index included the visual analog scale (VAS) for back and radicular leg pain and the Oswestry Disability Index (ODI) in the immediate preoperative period and at the final follow-up. The operation time, radiation exposure time, surgical satisfaction rate, and modified MacNab criteria score were also recorded. The leg and back pain of the patients in these groups improved significantly in the postoperative period. No significant differences were observed in leg pain improvement between the other two groups; however, patients in the PELD group (with or without DGT) presented with significantly higher improvement in back pain than the OLD group (t = 9.965, p < 0.001). The final ODI scores were 12.1 ± 4.9, 11.2 ± 2.9, and 16.4 ± 3.6 in the PELD, PELD-DGT, and OLD groups, respectively. Patients in the PELD and PELD-DGT groups presented with significantly lower postoperative ODI scores than those in the OLD group (t = 20.834, p < 0.001). The mean postoperative hospital stays were significantly shorter in the PELD group and PELD with DGT group than in the OLD group (t = 46.688, p < 0.001). The mean operation time was significantly shorter in the PELD-DGT group than those in the PELD group (t = 25.281, p = 0.001). No perioperative complications were observed in either group. Based on the modified MacNab criteria, excellent and good outcomes were achieved in 20 out of 21 patients (95.2%) in the PELD group, 23 out of 24 patients (95.8%) in the PELD-DGT group, and 22 out of 25 patients (88.0%) in the OLD group. The rates of excellent and good outcomes were higher in the PELD and PELD-DGT groups than in the OLD group, but there were no significant differences (χ2 = 1.454, p = 0.835). PELD using DGT is a safe and effective option for LLDH and features advantages such as improvements in back pain, a lower hospitalization cost than OLD, a shorter operation time, and less fluoroscopy than traditional PELD.


Pharmaceutical compounds used in the COVID-19 pandemic: A review of their presence in water and treatment techniques for their elimination.
During the COVID-19 pandemic, high consumption of antivirals, antibiotics, antiparasitics, antiprotozoals, and glucocorticoids used in the treatment of this virus has been reported. Conventional treatment systems fail to efficiently remove these contaminants from water, becoming an emerging concern from the environmental field. Therefore, the objective of the present work is to address the current state of the literature on the presence and removal processes of these drugs from water bodies. It was found that the concentration of most of the drugs used in the treatment of COVID-19 increased during the pandemic in water bodies. Before the pandemic, Azithromycin concentrations in surface waters were reported to be in the order of 4.3 ng L-1, and during the pandemic, they increased up to 935 ng L-1. Laboratory scale studies conclude that adsorption and advanced oxidation processes (AOPs) can be effective in the removal of these drugs. Up to more than 80% removal of Azithromycin, Chloroquine, Ivermectin, and Dexamethasone in aqueous solutions have been reported using these processes. Pilot-scale tests achieved 100% removal of Azithromycin from hospital wastewater by adsorption with powdered activated carbon. At full scale, treatment plants supplemented with ozonation and artificial wetlands removed all Favipiravir and Azithromycin, respectively. It should be noted that hybrid technologies can improve removal rates, process kinetics, and treatment cost. Consequently, the development of new materials that can act synergistically in technically and economically sustainable treatments is required.


EMPTY PERICARP11 serves as a factor for splicing of mitochondrial nad1 intron and is required to ensure proper seed development in maize.
Group II introns are common in the mitochondrial genome of higher plant species. The splicing of these introns is a complex process involving the synergistic action of multiple factors. However, few of these factors have been characterized in maize. In this study, we found that the Empty pericarp11 (Emp11) gene, which encodes a P-type pentatricopeptide repeat (PPR) protein, is required for the development of maize seeds. The loss of Emp11 function seriously impairs embryo and endosperm development, resulting in empty pericarp seeds in maize, and alteration in Emp11 expression leads to quantitative variation in kernel size and weight. We found that the emp11 mutants showed a failure in nad1 intron splicing, exhibited a severe reduction in complex I assembly and activity, mitochondrial structure disturbances, and an increase in alternative oxidase AOX2 and AOX3 levels. Interestingly, the emp11 phenotype was very severe in the W22 inbred line but could be partially recovered in B73 BC2F2 segregating ears. These results suggest that EMP11 serves as a factor for the splicing of mitochondrial nad1 introns and is required for mitochondrial function to ensure proper seed development in maize.


Repeated allergic asthma in early versus late pregnancy differentially impacts offspring brain and behavior development.
Stress during pregnancy and maternal inflammation are two common prenatal factors that impact offspring development. Asthma is the leading chronic condition complicating pregnancy and a common source of prenatal stress and inflammation. The goal of this study was to characterize the developmental impact of repeated allergic asthma inflammation during pregnancy on offspring behavioral outcomes and brain inflammation. Pregnant female C57BL/6 mice were sensitized with ovalbumin (OVA) or PBS vehicle control and then randomly assigned to receive daily aerosol exposures to the same OVA or PBS treatment during early, gestational days (GD) 2-GD9, or late pregnancy, GD10-GD17. Maternal sera were collected after the first and last aerosol induction regimen and measured for concentrations of corticosterone, anti-OVA IgE, and cytokine profiles. Juvenile male and female offspring were assessed for locomotor and social behaviors and later as adults assessed for anxiety-like, and marble burying behaviors using a series of behavioral tasks. Offspring brains were evaluated for region-specific differences in cytokine concentrations. In early gestation, both PBS and OVA-exposed dams had similar serum corticosterone concentration at the start (GD2) and end (GD9) of daily aerosol inductions. Only OVA-exposed dams showed elevations in cytokines that imply a diverse and robust T helper cell-mediated immune response. Male offspring of early OVA-exposed dams showed decreases in open-arm exploration in the elevated plus maze and increased marble burying without concomitant changes in locomotor activity or social interactions. These behavioral deficits in early OVA-exposed male offspring were associated with lower concentrations of G-CSF, IL-4, IL-7, IFNγ, and TNFα in the hypothalamus. In late gestation, both PBS and OVA-exposed dams had increased corticosterone levels at the end of daily aerosol inductions (GD17) compared to at the start of inductions (GD10). Male offspring from both PBS and OVA-exposed dams in late gestation showed similar decreases in open arm exploration on the elevated plus maze compared to OVA male offspring exposed in early gestation. No behavioral differences were present in female offspring across all treatment groups. However, females of dams exposed to OVA during early gestation displayed similar reductions as males in hypothalamic G-CSF, IL-7, IL-4, and IFNγ. The inflammatory responses from maternal allergic asthma in early gestation and resulting increases in anxiety-like behavior in males support a link between the timing of prenatal insults and sex-specific developmental outcomes. Moreover, the heightened stress responses in late gestation and concomitant dampened inflammatory response to allergic asthma suggest that interactions between the maternal immune and stress-response systems shape early life fetal programming.


Abnormal linear growth in paediatric adrenal diseases: Pathogenesis, prevalence and management.
Abnormal adrenal function can interfere with linear growth, potentially causing either acceleration or impairment of growth in paediatric patients. These abnormalities can be caused by direct effects of adrenal hormones, particularly glucocorticoids and sex steroids, or be mediated by indirect mechanisms such as the disturbance of the growth hormone-insulin-like growth factor-1 axis and aromatization of androgens to oestrogens. The early diagnosis and optimal treatment of adrenal disorders can prevent or minimize growth disturbance and facilitate improved height gain. Mechanisms of growth disturbance in the following abnormal states will be discussed; hypercortisolaemia, hyperandrogenaemia and obesity. Prevalence and features of growth disturbance will be discussed in ACTH-dependent and ACTH-independent Cushing's syndrome, adrenocortical tumours, premature adrenarche, congenital adrenal hyperplasia and adrenal insufficiency disorders. Recommendations for management have been included.


Protease required for processing picornaviral coat protein resides in the viral replicase gene.
Partial purification of the encephalomyocarditis protease synthesized in extracts from rabbit reticulocytes shows that the activity responsible for cleaving coat precursor protein cosediments with a previously unmapped virus-coded protein with an apparent molecular weight of 20,000. Tryptic analysis shows that this protein is derived from protein D, a virus-coded component of the encephalomyocarditis RNA polymerase.


Hypertension is an independent predictor of mean platelet volume in patients with acute ischaemic stroke.
Mean platelet volume (MPV) was shown to be significantly increased in patients with acute ischaemic stroke, especially in non-lacunar strokes. Moreover, some studies concluded that increased MPV is related to poor functional outcome after ischaemic stroke, although this association is still controversial. However, the determinants of MPV in patients with acute ischaemic stroke have never been investigated. We recorded the main demographic, clinical and laboratory data of consecutive patients with acute (admitted within 24 h after stroke onset) ischaemic stroke admitted in our Neurology Service between January 2003 and December 2008. MPV was generated at admission by the Sysmex XE-2100 automated cell counter (Sysmex Corporation, Kobe, Japan) from ethylenediaminetetraacetic acid blood samples stored at room temperature until measurement. The association of these parameters with MPV was investigated in univariate and multivariate analysis. A total of 636 patients was included in our study. The median MPV was 10.4 ± 0.82 fL. In univariate analysis, glucose (β= 0.03, P= 0.05), serum creatinine (β= 0.002, P= 0.02), haemoglobin (β= 0.009, P < 0.001), platelet count (β=-0.002, P < 0.001) and history of arterial hypertension (β= 0.21, P= 0.005) were found to be significantly associated with MPV. In multivariate robust regression analysis, only hypertension and platelet count remained as independent determinants of MPV. In patients with acute ischaemic stroke, platelet count and history of hypertension are the only determinants of MPV.


Genetic data of 15 STR forensic loci in eastern Chinese population.
Allele frequencies for the 15 short tandem repeats (STR) loci D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, CSF1PO, TH01, D16S539, D2S1338, TPOX D19S433 (AmpFLSTR Identifiler) were determined in a population sample of unrelated individuals living in eastern China.


Familial fragile 8q22 involved as a cancer breakpoint in cells of a large bowel tumor.
A familial fragile 8q22 and an interferon-induced fragile 16q22 were found in two sisters. Eight years previously, both sisters developed an endometrial adenocarcinoma and now one of them presented with an adenocarcinoma of the colon. An 8q22 deletion was found in all the cells of the colonic tumor and seemed to be the primary initiating change. Other nonrandom and possibly promoting aberrations were also present, among others, a 16q22 deletion. The possibility exists that a familial fragile 8q22 may predispose to cancer and a fragile 16q22 may have promoting capacities.


[Brachytherapy for oesophageal cancer].
The main indication of oesophageal brachytherapy is palliative: it can improve dysphagia in patients with a tumor not suitable for surgery or chemoradiotherapy. A randomized clinical trial showed that survival without dysphagia and quality of life was improved by endoluminal brachytherapy in comparison to self-expansible metallic stents. It also increases the duration of palliation after laser deobstruction. Its role as a curative treatment of locally advanced tumors is still discussed: in combination with external beam radiotherapy, it seems that brachytherapy increased the rate of severe toxicity (haemorrhages, fistula, stenosis). In superficial lesions, brachytherapy with or without external beam radiotherapy seems logical but large prospective studies are missing in this setting.


Immunometabolic approaches to prevent, detect, and treat neonatal sepsis.
The first days of postnatal life are energetically demanding as metabolic functions change dramatically to accommodate drastic environmental and physiologic transitions after birth. It is increasingly appreciated that metabolic pathways are not only crucial for nutrition but also play important roles in regulating inflammation and the host response to infection. Neonatal susceptibility to infection is increased due to a functionally distinct immune response characterized by high reliance on innate immune mechanisms. Interactions between metabolism and the immune response are increasingly recognized, as changes in metabolic pathways drive innate immune cell function and activation and consequently host response to pathogens. Moreover, metabolites, such as acetyl-coenzyme A (acetyl-CoA) and succinate have immunoregulatory properties and serve as cofactors for enzymes involved in epigenetic reprogramming or "training" of innate immune cells after an initial infectious exposure. Highly sensitive metabolomic approaches allow us to define alterations in metabolic signatures as they change during ontogeny and as perturbed by immunization or infection, thereby linking metabolic pathways to immune cell effector functions. Characterizing the ontogeny of immunometabolism will offer new opportunities to prevent, diagnose, and treat neonatal sepsis.


Twigs-derived activated carbons via H3PO4/ZnCl2 composite activation for methylene blue and congo red dyes removal.
This work is aimed at evaluating the conversion of Pterocarpus indicus twigs into activated carbon via composite chemical activation for methylene blue and congo red dyes adsorption. The activated carbons were prepared by single-step chemical activation using zinc chloride and/or phosphoric acid at different mass impregnation ratios at 600 °C for 90 min. The activated carbons were characterized for textural properties and surface chemistry. The batch adsorption was investigated at different concentrations (5-1,000 mg/L), contact times (2-540 min) and temperatures (30-60 °C). Phosphoric acid-activated twigs carbon showed a high surface area of 1,445 m2/g with maximum methylene blue adsorption capacity of 438 mg/g. On the other hand, a composite-activated carbon yields a 217 mg/g of congo red removal. The adsorption data for both dyes fitted well with Langmuir and pseudo-second-order kinetics models, indicating the predominance of chemical adsorption through monolayer coverage of dye molecules on the homogenous surface of activated carbon. The thermodynamics properties of dye adsorption onto twigs-derived activated carbons indicated that the process is endothermic, spontaneous and favourable at high temperature. Overall, activated carbons derived from Pterocarpus indicus twigs could be effectively used for dye wastewater treatment.


Purification and characterization of purple acid phosphatase PAP1 from dry powder of sweet potato.
Purple acid phosphatase (PAP) was purified from sweet potato dry powder, which is used as a food additive. Spectrometric and enzymatic analyses, and analysis of the amino-terminal sequence indicated that the purified purple acid phosphatase was PAP1. High activity in neutral and acidic conditions, broad substrate specificity, and good thermal stability of PAP1 suggest the possibility of practical applications of PAP1.


A continuous fluorescence assay for lecithin cholesterol acyltransferase.
A continuous fluorescence assay was adapted to the measurement of the phospholipase reaction of lecithin cholesterol acyltransferase (LCAT). The fluorescent phospholipid 1-acyl-2-(N-4-nitrobenzo-2-oxa-1,3-diazole)aminocaproyl phosphatidylcholine (C6-NBD-PC) in micelle form reacted with LCAT to yield NBD-caproic acid, resulting in up to 5-fold increases in fluorescence in 30 min. The reaction rates were optimal in mixtures containing 0.1 M NaCl and 4 mM beta-mercaptoethanol at 37 degrees C. Apolipoprotein A-I did not activate the enzyme and bovine serum albumin bound monomeric substrate and interfered with the fluorescence assay. Under similar reaction conditions, bee venom phospholipase A2 was almost 100-fold more reactive than LCAT.


Evidence for functional asymmetry in the olfactory system of the Senegalese sole (Solea senegalensis).
The two olfactory epithelia of flatfish of the family Soleidae are essentially in contact with two distinct environments; the upper (right) side samples open water while the lower (left) side samples interstitial water. This study assessed whether there are differences in the responsiveness of the two epithelia by use of the electro-olfactogram in the Senegalese sole (Solea senegalensis). The upper epithelium was significantly more responsive to the basic amino acids (L-lysine and L-arginine), glycine, and L-threonine than the lower epithelium. The lower epithelium was significantly more responsive to aromatic amino acids (L-tryptophan, L-tyrosine, L-DOPA, and L-phenylalanine), L-leucine, and L-asparagine than the upper. Both epithelia had similar responsiveness to the sulphur-containing amino acids (L-cysteine and L-methionine), L-alanine, L-serine, and L-glutamine. Neither side was responsive to the acidic amino acids (L-aspartate and L-glutamate) or the D-isomers of any amino acid tested. The upper olfactory organ was much more responsive to conspecific-derived stimuli (bile and intestinal fluid) than the lower organ. We suggest that these differences in responsiveness may be related to different functional roles of the upper and lower epithelia in feeding and chemical communication.


Reconstruction of bremsstrahlung spectra from attenuation data using generalized simulated annealing.
A generalized simulated annealing algorithm, combined with a suitable smoothing regularization function is used to solve the inverse problem of X-ray spectrum reconstruction from attenuation data. The approach is to set the initial acceptance and visitation temperatures and to standardize the terms of objective function to automate the algorithm to accommodate different spectra ranges. Experiments with both numerical and measured attenuation data are presented. Results show that the algorithm reconstructs spectra shapes accurately. It should be noted that in this algorithm, the regularization function was formulated to guarantee a smooth spectrum, thus, the presented technique does not apply to X-ray spectrum where characteristic radiation are present.


[The effect of chromatin remodeling and modification on RNA-polymerase-mediated transcription initiation].
As eukaryotes are characterized by the presence of chromatin (intricately packaged DNA), special mechanisms are required for preparing the DNA template for operation of the transcription machinery. Recently, a close association between the chromatin state and transcription was found and numerous transcription factors modifying the physical and chemical chromatin state were revealed. This review presents a brief description of transcription initiation on the DNA template within chromatin.


Stakeholder Perspectives on the Impact of COVID-19 on the Implementation of a Community-Clinic Linkage Model in New York City.
Community-clinical linkage models (CCLM) have the potential to reduce health disparities, especially in underserved communities; however, the COVID-19 pandemic drastically impacted their implementation. This paper explores the impact of the pandemic on the implementation of CCLM intervention led by community health workers (CHWs) to address diabetes disparities among South Asian patients in New York City. Guided by the Consolidated Framework for Implementation Research (CFIR), 22 stakeholders were interviewed: 7 primary care providers, 7 CHWs, 5 community-based organization (CBO) representatives, and 3 research staff. Semi-structured interviews were conducted; interviews were audio-recorded and transcribed. CFIR constructs guided the identification of barriers and adaptations made across several dimensions of the study's implementation context. We also explored stakeholder-identified adaptations used to mitigate the challenges in the intervention delivery using the Model for Adaptation Design and Impact (MADI) framework. (1) Communication and engagement refers to how stakeholders communicated with participants during the intervention period, including difficulties experienced staying connected with intervention activities during the lockdown. The study team and CHWs developed simple, plain-language guides designed to enhance digital literacy. (2) Intervention/research process describes intervention characteristics and challenges stakeholders faced in implementing components of the intervention during the lockdown. CHWs modified the health curriculum materials delivered remotely to support engagement in the intervention and health promotion. (3) community and implementation context pertains to the social and economic consequences of the lockdown and their effect on intervention implementation. CHWs and CBOs enhanced efforts to provide emotional/mental health support and connected community members to resources to address social needs. Study findings articulate a repository of recommendations for the adaptation of community-delivered programs in under-served communities during a time of public health crises.


Smoking during pregnancy--effects on the fetal thyroid function.
Infants delivered at term by mothers smoking at least 10 cigarettes daily during pregnancy (n = 46) were found to be growth retarded compared to infants of non-smoking mothers (n = 49), birthweights 3,445 +/- 385 (SD) g and 3,667 +/- 392 g respectively (p less than 0.05) in the two groups. Cord serum thyrotropin (TSH) was significantly decreased (8.2 +/- 4.0 U/l vs. 10.3 +/- 4.9 U/l) and free thyroxine index (FT4I)/TSH ratio significantly increased (18.8 +/- 9.0 vs. 14.4 +/- 7.6) (p less than 0.05) in the smoking group compared to infants of non-smokers. Cord serum thyroxine (T4) and FT4I were higher in the smoking group (149.0 +/- 22.4 nmol/l and 125.5 +/- 14.9 respectively) compared to infants of non-smoking mothers (140.6 +/- 21.6 nmol/l and 120.0 +/- 16.5 respectively), with borderline statistical significance (0.05 less than p less than 0.10). The results indicate that infants of smoking mothers may have a hyperfunction of the thyroid gland at birth compared to infants of non-smokers, with a negative feed-back on TSH production from the pituitary gland. Increased metabolic rate and oxygen consumption caused by fetal thyroid hyperfunction may be pathogenetic factors for the fetal growth retardation caused by maternal smoking.


Patterns and effects of social integration on housing stability, mental health and substance use outcomes among participants in a randomized controlled Housing First trial.
Recent research has shown that social integration, involving community integration and social support, can be protective resources for the health of homeless individuals. However, it is not clear how social integration affects health in the transition from homelessness into housing, and subsequent housing retention. This paper examines, through mixed quantitative and qualitative methods, how social integration changes over time, and how these changes relate to housing stability, substance use and mental health outcomes among a sample of homeless individuals experiencing mental illness participating in the At Home/Chez Soi Housing First randomized controlled trial in Canada. Longitudinal quantitative data (baseline, 6, 12, 24 month) and qualitative data ( 18 month) from the five trial sites (Moncton, Montreal, Toronto, Winnipeg and Vancouver) were examined using mixed models, mediation analyses, and thematic analysis. Social integration (i.e., social network size, social interest, psychological integration) increased over time among study participants, with social network size increasing significantly more among Housing First participants than Treatment as Usual participants. Social network size mediated the effect of the intervention on the percentage of days in stable housing, indicating that the Housing First intervention may have increased participants' social network size, which in turn increased the percentage of days stably housed. No significant mediation of social integration on the effects of the intervention on mental health and substance use outcomes was found. Findings from the qualitative interviews support and expand upon these quantitative findings.


Implications of oral streptococcal bacteriophages in autism spectrum disorder.
Growing evidence suggests altered oral and gut microbiota in autism spectrum disorder (ASD), but little is known about the alterations and roles of phages, especially within the oral microbiota in ASD subjects. We enrolled ASD (n = 26) and neurotypical subjects (n = 26) with their oral hygiene controlled, and the metagenomes of both oral and fecal samples (n = 104) are shotgun-sequenced and compared. We observe extensive and diverse oral phageome comparable to that of the gut, and clear signals of mouth-to-gut phage strain transfer within individuals. However, the overall phageomes of the two sites are widely different and show even less similarity in the oral communities between ASD and control subjects. The ASD oral phageome exhibits significantly reduced abundance and alpha diversity, but the Streptococcal phages there are atypically enriched, often dominating the community. The over-representation of Streptococcal phages is accompanied by enriched oral Streptococcal virulence factors and Streptococcus bacteria, all exhibiting a positive correlation with the severity of ASD clinical manifestations. These changes are not observed in the parallel sampling of the gut flora, suggesting a previously unknown oral-specific association between the excessive Streptococcal phage enrichment and ASD pathogenesis. The findings provide new evidence for the independent microbiome-mouth-brain connection, deepen our understanding of how the growth dynamics of bacteriophages and oral microbiota contribute to ASD, and point to novel effective therapeutics.


Breast cancer in women at high risk: the role of rapid genetic testing for BRCA1 and -2 mutations and the consequences for treatment strategies.
Specific clinical questions rise when patients, who are diagnosed with breast cancer, are at risk of carrying a mutation in BRCA1 and -2 gene due to a strong family history or young age at diagnosis. These questions concern topics such as 1. Timing of genetic counseling and testing, 2. Choices to be made for BRCA1 or -2 mutation carriers in local treatment, contralateral treatment, (neo)adjuvant systemic therapy, and 3. The psychological effects of rapid testing. The knowledge of the genetic status might have several advantages for the patient in treatment planning, such as the choice whether or not to undergo mastectomy and/or prophylactic contralateral mastectomy. The increased risk of developing a second breast cancer in the ipsilateral breast in mutation carriers, is only slightly higher after primary cancer treatment, than in the general population. Prophylactic contralateral mastectomy provides a substantial reduction of contralateral breast cancer, although only a small breast cancer specific survival benefit. Patients should be enrolled in clinical trials to investigate (neo)-adjuvant drug regimens, that based on preclinical and early clinical evidence might be targeting the homologous recombination defect, such as platinum compounds and PARP inhibitors. If rapid testing is performed, the patient can make a well-balanced decision. Although rapid genetic counseling and testing might cause some distress, most women reported this approach to be worthwhile. In this review the literature regarding these topics is evaluated. Answers and suggestions, useful in clinical practice are discussed.


What is the advance of extent of resection in glioblastoma surgical treatment-a systematic review.
Glioblastoma multiform (GBM) is the most common malignant brain tumor characterized by poor prognosis, increased invasiveness, and high relapse rates. The relative survival estimates are quite low in spite of the standard treatment for GBM in recent years. Now, it has been gradually accepted that the amount of tumor mass removed correlates with longer survival rates. Although new technique advances allowing intraoperative analysis of tumor and normal brain tissue and functional paradigms based on stimulation techniques to map eloquent areas have been used for GBM resection, visual identification of tumor margins still remains a challenge for neurosurgeons. This article attempts to review and summarize the evolution of surgical resection for glioblastomas.


Next-generation rotavirus vaccine developers meeting: Summary of a meeting sponsored by PATH and the bill & melinda gates foundation (19-20 June 2019, Geneva).
Despite the contribution of currently licensed live, oral rotavirus vaccines (LORVs) to alleviating the burden of severe disease and death from rotavirus gastroenteritis, those vaccines have proven less efficacious in resource-limited settings than in high- and middle-income countries. It has been proposed that the residual burden of rotavirus disease might be overcome with parenterally administered vaccines, or next-generation rotavirus vaccines (NGRV). To better define the progress of development of these vaccines, a meeting of vaccine developers and manufacturers engaged in NGRV research and development was convened in Geneva in June 2019. Several NRGVs are in various stages of preclinical development, and two have already entered clinical testing. The vaccine platforms include subunit protein, inactivated whole virus, virus-like particle and RNA-based vaccines. Meeting participants included groups involved in NGRV development, scientists investigating correlates of protection of rotavirus vaccines, and representatives of international organizations with insight into considerations for vaccine introduction. This report summarizes the presentations shared at the meeting.


North American egg parasite successfully controls a different host genus in South America.
Telenomus alsophilae, a parasite of the eggs of the geometrid Alsophila pometaria in North America, was introduced into Columbia, South America, for the biological control of a pest host in another genus, Oxydia trychiata. Successful results were obtained with this unorthodox procedure to control a forest insect.


Developmentally induced, muscle-specific trans factors control the differential splicing of alternative and constitutive troponin T exons.
Alternative RNA splicing is a ubiquitous process permitting single genes to encode multiple protein isoforms. Here we report experiments in which a gene construct, containing combinatorial Troponin T (TnT) exons that manifest an exceptional diversity of alternative splicing in vivo, has been transfected into muscle and nonmuscle cells. Analyses of the spliced RNAs show that the alternative TnT exons retain their capacity for differential splicing in the modified minigene context when introduced into a variety of nonmuscle and muscle cells. The patterns of alternative splicing differ depending on cell type. Only in differentiated myotubes are the alternative exons normally incorporated during splicing, reproducing their behavior in the native gene; they are excluded in nonmuscle cells and myoblasts that do not express the endogenous TnT. These results provide proof that trans factors required for correct alternative splicing are induced during myogenesis. Surprisingly, such factors are also required for the correct splicing of constitutive TnT exons.