Developmental exposure to 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107): long-term effects on brain development, behavior, and brain stem auditory evoked potentials in rats.
In the present study the developmental neurotoxic effects of the PCB metabolite 4-OH-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) were compared with effects caused by a mixture of parent polychlorinated biphenyl (PCB) congeners (Aroclor 1254). Pregnant female Wistar rats were exposed to 0.5 or 5 mg 4-OH-CB107, or 25 mg Aroclor 1254 per kg body weight from gestation days 10 to 16. Plasma thyroid hormone levels were significantly decreased in the offspring of all treatment groups at postnatal day 4 (PND 4). Behavioral experiments using an open field paradigm revealed an impaired habituation in male offspring of all treatment groups at PND 130. Passive avoidance experiments indicated significant influences on the time course of step-down latencies across trials in exposed male rats. Catalepsy induced by haloperidol showed increases in latencies to movement onset in female offspring exposed to 0.5 mg 4-OH-CB107 compared to Aroclor 1254 treated offspring at PND 168-175. Male offspring exposed to 4-OH-CB107 or Aroclor 1254 showed decreases in latencies compared to control animals. Brain stem auditory evoked potentials (BAEPs) measured at PND 300-310 showed significant increases in auditory thresholds in the low frequency range between Aroclor 1254 and 4-OH-CB107 (5 mg/kg bw) treated animals. Measurements of neurotransmitter levels revealed effects of Aroclor 154 exposure on both the dopaminergic and the serotonergic systems, whereas 4-OH-CB107 exposure affected dopaminergic and noradrenergic systems, with slight but not significant effects on the serotonergic system. These results indicate that 4-OH-CB107 is able to induce long-term effects on behavior and neurodevelopment. The observed effects for 4-OH-CB107 are similar to, but in some aspects different from, the effects observed after Aroclor 1254 exposure.


Postmortem lung biopsies from four patients with COVID-19 at a tertiary hospital in Cape Town, South Africa.
An outbreak of a novel coronavirus in China in late 2019 has resulted in a global pandemic. The virus (SARS-CoV-2) causes a severe acute respiratory syndrome and had been responsible for >14 000 deaths in South Africa (SA) at the time of writing, 30 August 2020. Autopsies in our setting have not been prioritised owing to the infective risks for staff, resulting in a lack of information on the histopathology of the disease in the SA setting. Postmortem biopsies are relatively quick and easy to perform and reduce the infective risk posed by full autopsies. To determine whether postmortem biopsies of lung tissue could be used to determine cause of death in lieu of full autopsies in patients dying from COVID-19. We performed postmortem biopsies of lung tissue on 4 patients with SARS-CoV-2 confirmed by reverse transcriptase polymerase chain reaction who died in the Tygerberg Hospital (Cape Town, SA) intensive care unit (ICU) in June - July 2020, in order to determine their cause of death. The biopsies were performed in the ICU with the necessary personal protective equipment within 2 hours after death. Clinical information was obtained from the hospital records and the histopathology was reviewed by two consultant histopathologists. Microbiology and electron microscopy were also performed on this tissue. All 4 patients were aged >50 years and had multiple comorbidities. Pulmonary pathology was present in only 3 cases, and the findings were surprisingly heterogeneous. One case demonstrated several findings including diffuse alveolar damage, extensive fibrin thrombi in pulmonary arteries with pulmonary infarction, organising pneumonia and bronchopneumonia. Other findings included type 2 pneumocyte hyperplasia, intra-alveolar macrophages and squamous metaplasia. An organising pneumonia was present in 2 other cases, although these findings were not deemed to be severe enough to be the cause of death. Fibrin thrombi were present in pulmonary arteries of 3 cases. One case showed no significant acute pulmonary pathology. The cause of death could only be determined in 1 case. The pulmonary findings we observed are in keeping with those described in the international literature. However, the pathology was surprisingly heterogeneous between cases, and was only deemed severe enough to be the cause of death in 1 of 4 cases. While lung-targeted, standardised postmortem biopsies may be safe, easy to perform and provide useful insights into the disease, they are not suitable to replace full autopsies in determining cause of death.


Proposal for a new definition of congenital complete atrioventricular block.
The classic old definition of congenital heart block by Yater (1929) is still generally accepted: 'Heart block established in a young patient. There must be some evidence of the existence of the slow pulse at a fairly early age and absence of a history of any infection which might cause the condition after birth: notably diphtheria, rheumatic fever, chorea and congenital syphilis'. However, other definitions are used. We systematically reviewed 1825 cases from 38 separate studies. We conclude that complete AV blocks detected in utero in the absence of structural abnormalities differ from blocks detected later in life with respect to pathogenesis (they are generally associated with maternal anti-Ro/SSA antibodies), poorer childhood prognosis, increased risk of developing late-onset dilated cardiomyopathy, different maternal clinical features and increased risk of recurrence in future pregnancies. For these reasons we propose a new modern definition of congenital complete AV block which might be acceptable to cardiologists, rheumatologists, pediatricians and obstetricians: 'an AV block is defined as congenital if it is diagnosed in utero, at birth or within the neonatal period (0-27 days after birth)'.


The equilibrium partition function and base pair binding probabilities for RNA secondary structure.
A novel application of dynamic programming to the folding problem for RNA enables one to calculate the full equilibrium partition function for secondary structure and the probabilities of various substructures. In particular, both the partition function and the probabilities of all base pairs are computed by a recursive scheme of polynomial order N3 in the sequence length N. The temperature dependence of the partition function gives information about melting behavior for the secondary structure. The pair binding probabilities, the computation of which depends on the partition function, are visually summarized in a "box matrix" display and this provides a useful tool for examining the full ensemble of probable alternative equilibrium structures. The calculation of this ensemble representation allows a proper application and assessment of the predictive power of the secondary structure method, and yields important information on alternatives and intermediates in addition to local information about base pair opening and slippage. The results are illustrated for representative tRNA, 5S RNA, and self-replicating and self-splicing RNA molecules, and allow a direct comparison with enzymatic structure probes. The effect of changes in the thermodynamic parameters on the equilibrium ensemble provides a further sensitivity check to the predictions.


Prostaglandin and thromboxane synthesis by microsomes of rabbit ocular tissues.
Microsomes of albino rabbit ocular tissues were incubated with (1-14C)-arachidonic acid for 15 min at 37 degrees C. Thin-layer chromatography revealed that ciliary body-iris microsomes were capable of synthesizing prostaglandin F2alpha (PGF2alpha), PGE2, PGD2, thromboxane B2(TXB2), and 6-keto-PGF1alpha. Indomethacin 14 micrometer in the incubation medium essentially abolished all prostaglandin synthesis detectable by this method. Imidazole 10 mM in the incubation medium inhibited only TXB2 synthesis. Ciliary body-iris microsomes were incubated for 2 min at 0 degrees C with PGH2. The products of this reaction were superfused over spiral strips of rabbit aorta and produced the strong contractions typical of TXA2. Addition to imidazole to the incubation medium blocked the formation of the contracting substance. Incubation of ciliary body-iris microsomes with (1-14C)--8,11,14-eicosatrienoic acid produced PGF1alpha, PGD1, and PGE1 but no evidence of any thromboxane product or 6-keto-PGF1alpha. Conjunctival and corneal microsomes synthesized prostaglandins, although less effectively than ciliary body-iris microsomes, when incubated with (1-14C)-arachidonic acid. Microsomes of sclera, retina-choroid, and lens synthesized little, if any, prostaglandins.


Plant organellar DNA polymerases are replicative and translesion DNA synthesis polymerases.
Genomes acquire lesions that can block the replication fork and some lesions must be bypassed to allow survival. The nuclear genome of flowering plants encodes two family-A DNA polymerases (DNAPs), the result of a duplication event, that are the sole DNAPs in plant organelles. These DNAPs, dubbed Plant Organellar Polymerases (POPs), resemble the Klenow fragment of bacterial DNAP I and are not related to metazoan and fungal mitochondrial DNAPs. Herein we report that replicative POPs from the plant model Arabidopsis thaliana (AtPolI) efficiently bypass one the most insidious DNA lesions, an apurinic/apyrimidinic (AP) site. AtPolIs accomplish lesion bypass with high catalytic efficiency during nucleotide insertion and extension. Lesion bypass depends on two unique polymerization domain insertions evolutionarily unrelated to the insertions responsible for lesion bypass by DNAP θ, an analogous lesion bypass polymerase. AtPolIs exhibit an insertion fidelity that ranks between the fidelity of replicative and lesion bypass DNAPs, moderate 3'-5' exonuclease activity and strong strand-displacement. AtPolIs are the first known example of a family-A DNAP evolved to function in both DNA replication and lesion bypass. The lesion bypass capabilities of POPs may be required to prevent replication fork collapse in plant organelles.


Patient privacy in the era of medical computer networks: a new paradigm for a new technology.
For twenty five years the legal system has tried to protect the privacy of identified patient data contained in information systems. The rapid development of such technology has repeatedly frustrated the public policies incorporated into the legal system. However the newest information technologies provide the possibility of fundamentally changing the way information is stored in the health care system and, by "De personalizing the data," allow restoration of a reasonable level of personal privacy, without interfering with the legitimate needs for medical data. The system would require a secure "identifier control facility" and act as a network "file access table" able to reconstruct widely distributed bits of the patients record. A disaggregated "virtual record" would replace the integrated patient file, and the risks to data privacy inherent in the use of names or permanent identification numbers would be eliminated.


Mechanisms by which dietary fat may stimulate mammary carcinogenesis in experimental animals.
Evidence drawn from epidemiological and experimental studies suggests that dietary fat is an important determinant of breast cancer risk and, in addition, that dietary fat acts as a modulator rather than an initiator of breast carcinogenesis. At present, however, it is not known how dietary fat exerts its tumor-promoting effects. A variety of mechanisms, some involving direct action by fat at the target organ and others involving host-mediated responses, have been proposed. The present status of one of these, namely, a mechanism based on mediation by the endocrine system, and the hormone prolactin in particular, is described. Further studies in laboratory animals are required to determine the precise cellular and molecular events which underlie the fat effect.


Identification of Laying-Related SNP Markers in Geese Using RAD Sequencing.
Laying performance is an important economical trait of goose production. As laying performance is of low heritability, it is of significance to develop a marker-assisted selection (MAS) strategy for this trait. Definition of sequence variation related to the target trait is a prerequisite of quantitating MAS, but little is presently known about the goose genome, which greatly hinders the identification of genetic markers for the laying traits of geese. Recently developed restriction site-associated DNA (RAD) sequencing is a possible approach for discerning large-scale single nucleotide polymorphism (SNP) and reducing the complexity of a genome without having reference genomic information available. In the present study, we developed a pooled RAD sequencing strategy for detecting geese laying-related SNP. Two DNA pools were constructed, each consisting of equal amounts of genomic DNA from 10 individuals with either high estimated breeding value (HEBV) or low estimated breeding value (LEBV). A total of 139,013 SNP were obtained from 42,291,356 sequences, of which 18,771,943 were for LEBV and 23,519,413 were for HEBV cohorts. Fifty-five SNP which had different allelic frequencies in the two DNA pools were further validated by individual-based AS-PCR genotyping in the LEBV and HEBV cohorts. Ten out of 55 SNP exhibited distinct allele distributions in these two cohorts. These 10 SNP were further genotyped in a goose population of 492 geese to verify the association with egg numbers. The result showed that 8 of 10 SNP were associated with egg numbers. Additionally, liner regression analysis revealed that SNP Record-111407, 106975 and 112359 were involved in a multiplegene network affecting laying performance. We used IPCR to extend the unknown regions flanking the candidate RAD tags. The obtained sequences were subjected to BLAST to retrieve the orthologous genes in either ducks or chickens. Five novel genes were cloned for geese which harbored the candidate laying-related SNP, including membrane associated guanylate kinase (MAGI-1), KIAA1462, Rho GTPase activating protein 21 (ARHGAP21), acyl-CoA synthetase family member 2 (ACSF2), astrotactin 2 (ASTN2). Collectively, our data suggests that 8 SNP and 5 genes might be promising candidate markers or targets for marker-assisted selection of egg numbers in geese.


Training AI to Recognize Objects of Interest to the Blind and Low Vision Community.
Recent object detection models show promising advances in their architecture and performance, expanding potential applications for the benefit of persons with blindness or low vision (pBLV). However, object detection models are usually trained on generic data rather than datasets that focus on the needs of pBLV. Hence, for applications that locate objects of interest to pBLV, object detection models need to be trained specifically for this purpose. Informed by prior interviews, questionnaires, and Microsoft's ORBIT research, we identified thirty-five objects pertinent to pBLV. We employed this user-centric feedback to gather images of these objects from the Google Open Images V6 dataset. We subsequently trained a YOLOv5x model with this dataset to recognize these objects of interest. We demonstrate that the model can identify objects that previous generic models could not, such as those related to tasks of daily functioning - e.g., coffee mug, knife, fork, and glass. Crucially, we show that careful pruning of a dataset with severe class imbalances leads to a rapid, noticeable improvement in the overall performance of the model by two-fold, as measured using the mean average precision at the intersection over union thresholds from 0.5 to 0.95 (mAP50-95). Specifically, mAP50-95 improved from 0.14 to 0.36 on the seven least prevalent classes in the training dataset. Overall, we show that careful curation of training data can improve training speed and object detection outcomes. We show clear directions on effectively customizing training data to create models that focus on the desires and needs of pBLV.Clinical Relevance- This work demonstrated the benefits of developing assistive AI technology customized to individual users or the wider BLV community.


A Review of Evolutionary and Cyclical Changes in the Surgical Approach to Aortic Valve Disease.
Aortic valve surgery is no exception to the general rule that history is a cycle in many fields. This manuscript aims to assist readers in transitioning from past to present and on into the future within the field of aortic valve surgery. The existing literature has been examined, including old and modern articles published on pubmed, old articles non visible on pubmed, old and recent books on the history of medicine, looking for similarities and repetitions in techniques and surgical approaches to the aortic valve in the past and the current times. Steps of evolution included a blind approach, plasty procedures under direct visualization of the valve without the aid of cardiopulmonary bypass, prosthetic valve replacements via sternotomies with cardiopulmonary bypass, minimally-invasive access routes, trans-catheter aortic valve implants (TAVI), suture-less prostheses, mini-thoracotomies incorporating suture-less prostheses, and finally, totally-endoscopic aortic valve replacements. After the advent of CPB and several decades of open-heart surgery with full sternotomies, the minimally-invasive approach has re-emerged. Supported by a commitment to smaller incisions and shorter bypass times, the concept is now being aggressively developed. The cycling of science, including the field of aortic valve surgery, means that ingenious theories and concepts that have fallen by the wayside can be brought back and explored again with current tools and enhanced knowledge.


The Clinical Characteristics of Acute Pancreatitis in Gerontal Patients: A Retrospective Study.
The incidence of acute pancreatitis (AP) in ageing patients has increased in recent years, and results regarding the clinical outcomes of these patients are controversial. The aim of this study was to compare the clinical outcomes of AP in ageing patients over 60 years old. Eighty patients aged ≥80 years (oldest group) were compared to 393 patients aged 60 to 79 years (older group). The clinical course and biochemical and radiological data were evaluated. The primary endpoints were mortality rate, intensive care unit (ICU) admission rate and in-hospital length of stay (LOS). The secondary endpoints were the incidence of operative treatment and complications of AP. Abdominal pain (61.3% vs 46.3%, P=0.013) was less common in the oldest group. Jaundice (17.5% vs 8.9%, P=0.021) and dyspnoea (26.3% vs 11.5%, P=0.001) were more obvious in the oldest group than in the older group. The mean BMI was lower in the oldest group than in the older group (21.07±3.18 vs 22.36±2.89, P = 0.001). Age over 80 years (P=0.011) and organ failure (P<0.05) were independent risk factors for mortality. More severe AP (P=0.001), abdominal pain (P=0.033) and organ failure (P<0.05) were associated with the ICU admission rate. Age over 80 years (P=0.001), more severe AP (P=0.001), female sex (P=0.018), jaundice (P=0.038), operative treatment (P<0.05) and organ failure (P<0.05) were risk factors for increased LOS. The oldest group had a higher death rate and longer LOS than the older group. More attention should be given to the clinical symptoms of this frail population. We propose that more comprehensive and goal-directed attendant diagnostic procedures should be performed to detect the disease early and to improve the outcomes of ageing patients.


Celiacomesenteric trunk: a variation that must be known before aortic surgery.
The celiac trunk and the mesenteric arteries may present variations with different clinical significance. A celiacomesenteric trunk was discovered in a patient with mesenteric ischemia and a history of aortic bypass without inferior mesenteric artery reimplantation. Despite thrombectomies and digestive resections, the patient died. Anatomic variations like celiacomesenteric trunk must be known before aortic surgery.


Independent cerebral vasoconstrictive effects of hyperoxia and accompanying arterial hypocapnia at 1 ATA.
Breathing 100% O2 at 1 atmosphere absolute (ATA) is known to be associated with a decrease in cerebral blood flow (CBF). It is also accompanied by a fall in arterial Pco2 leading to uncertainty as to whether the cerebral vasoconstriction is totally or only in part caused by arterial hypocapnia. We tested the hypothesis that the increase in arterial Po2 while O2 was breathed at 1.0 ATA decreases CBF independently of a concurrent fall in arterial Pco2. CBF was measured in seven healthy men aged 21-62 yr by using noninvasive continuous arterial spin-labeled-perfusion MRI. The tracer in this technique, magnetically labeled protons in blood, has a half-life of seconds, allowing repetitive measurements over short time frames without contamination. CBF and arterial blood gases were measured while breathing air, 100% O2, and 4 and 6% CO2 in air and O2 backgrounds. Arterial Po2 increased from 91.7 +/- 6.8 Torr in air to 576.7 +/- 18.9 Torr in O2. Arterial Pco2 fell from 43.3 +/- 1.8 Torr in air to 40.2 +/- 3.3 Torr in O2. CBF-arterial Pco2 response curves for the air and hyperoxic runs were nearly parallel and separated by a distance representing a 28.7-32.6% decrement in CBF. Regression analysis confirmed the independent cerebral vasoconstrictive effect of increased arterial Po2. The present results also demonstrate that the magnitude of this effect at 1.0 ATA is greater than previously measured.


Effects of sublethal concentrations of bifenthrin and deltamethrin on fecundity, growth, and development of the honeybee Apis mellifera ligustica.
Bifenthrin and deltamethrin have been widely used as pesticides in agriculture and forestry and are becoming an increasing risk to honeybees. The honeybee, Apis mellifera ligustica, is widely recognized as a beneficial insect of agronomic, ecological, and scientific importance. It is important to understand what effects these chemicals have on bees. Effects of two pesticides at sublethal concentrations on fecundity, growth, and development of honeybees were examined with the feeding method for a three-year period (2006-2008). It was shown that both bifenthrin and deltamethrin significantly reduced bee fecundity, decreased the rate at which bees develop to adulthood, and increased their immature periods. The toxicity of bifenthrin and deltamethrin on workers of Apis mellifera ligustica was also assessed, and the results from the present study showed that the median lethal effects of bifenthrin and deltamethrin were 16.7 and 62.8 mg/L, respectively.


Effects of KI encapsulation in single-walled carbon nanotubes by Raman and optical absorption spectroscopy.
The effect of KI encapsulation in narrow (HiPCO) single-walled carbon nanotubes is studied via Raman spectroscopy and optical absorption. The analysis of the data explores the interplay between strain and structural modifications, bond-length changes, charge transfer, and electronic density of states. KI encapsulation appears to be consistent with both charge transfer and strain that shrink both the C-C bonds and the overall nanotube along the axial direction. The charge transfer in larger semiconducting nanotubes is low and comparable with some cases of electrochemical doping, while optical transitions between pairs of singularities of the density of states are quenched for narrow metallic nanotubes. Stronger changes in the density of states occur in some energy ranges and are attributed to polarization van der Waals interactions caused by the ionic encapsulate. Unlike doping with other species, such as atoms and small molecules, encapsulation of inorganic compounds via the molten-phase route provides stable effects due to maximal occupation of the nanotube inner space.


Plasma and urine cyclic nucleotide levels in patients with acute and chronic leukemia.
Plasma and urine levels of cyclic adenosine 3',5'-monophosphate (cAMP) and of cyclic guanosine 3',5'-monophosphate (cGMP) were measured in 35 normal subjects, in 24 patients with nonneoplastic diseases (iron deficiency anemia, peptic ulcer, and cholelithiasis), and in 50 leukemic patients. The leukemic group included patients with acute lymphoblastic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, and chronic myelogenous leukemia. All patients were recently diagnosed and untreated, except for 5 patients with blastic transformation of chronic myelogenous leukemia who had been previously treated. There were no significant differences in plasma and urine cyclic nucleotide levels between normal subjects and patients with nonneoplastic diseases. In leukemic patients, plasma and urine cAMP levels were similar to those of normal subjects, whereas plasma and urine cGMP levels were markedly elevated. There were no significant differences in cGMP values between the various types of leukemia. After starting treatment, plasma cyclic nucleotide levels were periodically measured in 21 of the patients with acute leukemia; cGMP levels were normalized in all the 16 subjects who attained complete remission, whereas both cAMP and cGMP levels were apparently unaffected in the patients who did not respond to treatment. This suggests that plasma or urine cGMP could be used as an additional parameter to monitor the patient's response to treatment.


DOACs vs LMWHs in hospitalized medical patients: a systematic review and meta-analysis that informed 2018 ASH guidelines.
Venous thromboembolism (VTE) is a relatively frequent complication in hospitalized patients, especially in those with risk factors. The benefit of using direct oral anticoagulants (DOACs) for prevention is controversial. This systematic review was performed as part of the American Society of Hematology (ASH) guidelines on VTE, developed in partnership with McMaster University. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Epistemonikos were used as data sources from date of inception to November 2019. We included randomized trials in patients hospitalized for an acute medical disease, evaluating any DOACs vs other pharmacological prophylaxis, and included 3 trials with low risk of bias. We analyzed the effects of DOACs vs low-molecular-weight heparins (LMWHs) at 2 different time points: at the end of the short-term treatment phase (both drugs given for the same period of time) and at the end of the extended prophylaxis period (extended DOACs vs a shorter course of LMWHs). We observed that the use of DOACs did not reduce the risk of pulmonary embolism or symptomatic deep venous thrombosis (DVT) in comparison with LMWHs. However, the risk of major bleeding was slightly increased. Additionally, we observed that the benefit of DOACs previously reported was largely based on the reduction of asymptomatic DVT and was not apparent when only symptomatic events were considered. The use of DOACs in hospitalized medical patients slightly increases the risk of major bleeding with no appreciable benefit over LMWHs.


Crystal structure of phosphatidylglycerophosphatase (PGPase), a putative membrane-bound lipid phosphatase, reveals a novel binuclear metal binding site and two "proton wires".
Phosphatidylglycerophosphatase (PGPase), an enzyme involved in lipid metabolism, catalyzes formation of phosphatidylglycerol from phosphatidylglycerophosphate. Phosphatidylglycerol is a multifunctional phospholipid, found in the biological membranes of many organisms. Here, we report the crystal structure of Listeria monocytogenes PGPase at 1.8 A resolution. PGPase, an all-helical molecule, forms a homotetramer. Each protomer contains an independent active site with two metal ions, Ca(2+) and Mg(2+), forming a hetero-binuclear center located in a hydrophilic cavity near the surface of the molecule. The binuclear center, conserved ligands, metal-bound water molecules, and an Asp-His dyad form the active site. The catalytic mechanism of this enzyme is likely to proceed via binuclear metal activated nucleophilic water. The binuclear metal-binding active-site environment of this structure should provide insights into substrate binding and metal-dependent catalysis. A long channel with inter-linked linear water chains, termed "proton wires," is observed at the tetramer interface. Comparison of similar water chain structures in photosynthetic reaction centers (RCs), Cytochrome f, gramicidin, and bacteriorhodopsin, suggests that PGPase may conduct protons via proton wires.


Laparoscopic cholecystectomy: two-port technique.
Conventional laparoscopic cholecystectomy requires four ports. The present study describes a new laparoscopic cholecystectomy technique using two ports only. Sixty-two consecutive patients with symptomatic gallstones underwent laparoscopic cholecystectomy using this two-port technique. The operation requires a straightforward laparoscope and a percutaneous sling to retract the gallbladder laterally and cephalad. The two-port method was successful in 52 patients; eight required an additional port, and two required conversion to open surgery. Our results showed that the operating time and complication rate were comparable to those in other series using the conventional laparoscopic method. The two-port method is technically more demanding, and should only be used to remove simple, uncomplicated gallbladders. The surgeon should always be prepared to insert more trocars or convert to open procedures when necessary.


Visual detection of the human metapneumovirus using reverse transcription loop-mediated isothermal amplification with hydroxynaphthol blue dye.
Human metapneumovirus (hMPV) is a major cause of acute respiratory infections ranging from wheezing to bronchiolitis and pneumonia in children worldwide. The objective of this study is to develop a visual reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of hMPV and applied to the clinical samples. In this study, visual RT-LAMP assay for hMPV was performed in one step with the addition of hydroxynaphthol blue (HNB), and were used to detect respiratory samples. Six primers, including two outer primers (F3 and B3), two inner primers (FIP, BIP) and two loop primers (LF and LB), were designed for hMPV N gene by the online software. Moreover, the RT-LAMP assay showed good specificity and no cross-reactivity was observed with human rhinovirus (HRV), human respiratory syncytial Virus (RSV), or influenza virus A/PR/8/34 (H1N1). The detection limit of the RT-LAMP assay was approximately ten viral RNA copies, lower than that of traditional reverse transcriptase polymerase chain reaction (RT-PCR) 100 RNA copies. In the 176 nasopharyngeal samples, 23 (13.1%) were conformed as hMPV positive by RT-LAMP, but 18 (10.2%) positive by RT-PCR. Compared with conventional RT-PCR, the visual hMPV RT-LAMP assay performed well in the aspect of detect time, sensitivity, specificity and visibility. It is anticipated that the RT-LAMP will be used for clinical tests in hospital or field testing during outbreaks and in emergency.


Comparative study of drug release from electrospun nanofibers loaded with clotrimazole via two different approaches using a fully automated sequential injection system.
The development of new drug delivery platforms including the use of nanotechnology has been found of great interest in recent years. Two different loading approaches of the model antimycotic drug clotrimazole into the nanofibrous polycaprolactone and polydioxanone structures including electrospinning of a drug-polymer blend and impregnation of nanofibers with drug have been tested. The final amount of clotrimazole in the nanofibrous materials was determined by HPLC analysis and Raman spectroscopy. The electrospinning of blend approach allowed the adsorption of clotrimazole in a quantity of up to 30 % using mixtures with polymer/clotrimazole ratios from 2:1 to 8:1 (w/w). Ethanolic clotrimazole solutions with concentrations from 2.5 to 3.5 mg L-1 were used for adsorbing clotrimazole in blank nanofibers for 1-3 h with final clotrimazole content ranging from 3.0 to 5.7 %. Furthermore, a comparative liberation study including comparison with commercially available creams was carried out in low pressure flow system. The results obtained confirmed well controlled release of clotrimazole from both types of nanofibers. Compared to commercial pharmaceutical formulations containing 1 % clotrimazole where first-order release kinetics was observed, nanofibrous materials provided linear controlled release (zero-order kinetics) in the tested 3 h period.


Effect of posture positions on the evaporative resistance and thermal insulation of clothing.
Evaporative resistance and thermal insulation of clothing are important parameters in the design and engineering of thermal environments and functional clothing. Past work on the measurement of evaporative resistance of clothing was, however, limited to the standing posture with or without body motion. Information on the evaporative resistance of clothing when the wearer is in a sedentary or supine posture and how it is related to that when the wearer is in a standing posture is lacking. This paper presents original data on the effect of postures on the evaporative resistance of clothing, thermal insulation and permeability index, based on the measurements under three postures, viz. standing, sedentary and supine, using the sweating fabric manikin-Walter. Regression models are also established to relate the evaporative resistance and thermal insulation of clothing under sedentary and supine postures to those under the standing posture. The study further shows that the apparent evaporated resistances of standing and sedentary postures measured in the non-isothermal condition are much lower than those in the isothermal condition. The apparent evaporative resistances measured using the mass loss method are generally lower than those measured using the heat loss method due to moisture absorption or condensation within clothing. STATEMENT OF RELEVANCE: The thermal insulation and evaporative resistance values of clothing ensembles under different postures are essential data for the ergonomics design of thermal environments (e.g. indoors or a vehicle's interior environment) and functional clothing. They are also necessary for the prediction of thermal comfort or duration of exposure in different environmental conditions.


What Effect Does International Migration Have on the Nutritional Status and Child Care Practices of Children Left Behind?
Despite an increasing trend in labour migration and economic dependence on foreign migrant workers in Sri Lanka, very little is known about the child care and nutritional status of "children left behind". The aim of this study was to examine the factors influencing the nutritional status and care practices of children left behind. A sample of 321 children, 6-59 months old of international migrant workers from a cross-sectional nationally represented study were included. Care practices were assessed using ten caregiving behaviours on personal hygiene, feeding, and use of health services. Results revealed the prevalence of stunting, wasting and underweight to be 11.6, 18.2 and 24.0 percent, respectively. Father being a migrant worker has a positive effect on childcare practices and birthweight of the child. This study indicates that undernutrition remains a major concern, particularly in the poorest households where the mother is a migrant worker, also each additional 100 g increase in the birthweight of a child in a migrant household, decreases the probability of being wasted, stunted and underweight by 6%, 8% and 23% respectively. In depth study is needed to understand how labour migration affects household level outcomes related to child nutrition and childcare in order to build skills and capacities of migrant families.


[Problems of androgen deficiency associated with somatic diseases in vibration disease patients].
The article deals with new scientific data on influence of industrial vibration on prevalence of androgen deficiency in vibration disease pateints, correlation between androgen deficiency level and general somatic diseases in vibration disease patients, criteria of early diagnosis of the combined pathology.


The recognition of red blood cells by macrophages: role of phosphatidylserine and possible implications of membrane phospholipid asymmetry.
The recognition of phosphatidylserine (PS) by macrophages was investigated using inside-out (IO) red blood cell (RBC) ghosts and RBC displaying PS in their surface membranes. This was accomplished by employing unmodified pathologic sickle RBC which contain endogenous PS in their outer membrane leaflet, and RBC modified by the transfer of an exogenous fluorescent PS analog. Proper insertion of exogenous PS was confirmed by monitoring the degree to which cell-associated lipid fluorescence was dequenched following transfer of 1-acyl-2-[(N-4-nitro-benzo-2-oxa-1,3 diazole) aminocaproyl] phosphatidylserine (NBD-PS) from a population of self-quenched donor vesicles. Inside-out RBC ghosts were endocytosed approximately 3 times faster than were right side-out control populations. Similarly, using NBD-PS vesicles at concentrations at which dilution of all the cell-associated analog in the recipient RBC could be unequivocally confirmed, we observed that the uptake of NBD-PS treated RBC by macrophages was significantly increased over that of control RBC populations. Fluorescence and electron microscopic observations revealed the formation of typical RBC-macrophage rosettes that were morphologically distinct from opsonized RBC-macrophage rosettes. Enhanced RBC binding to macrophages was also obtained with deoxygenated reversibly sickled cells (RSC); the enhancement correlated with increased exposure of outer leaflet PS in these cells. These findings suggest that PS is recognized by macrophages and that its exposure in the outer leaflet of RBC may have significant pathophysiologic implications.


Bronchoscopy in the preoperative staging of oesophageal cancer below the tracheal bifurcation: a prospective study.
Oesophageal cancer located above the level of the tracheal bifurcation is frequently complicated by its spread into the airways and by the simultaneous occurrence of malignant bronchial tumours. Although bronchoscopy is an essential procedure in identifying malignant tumoral invasion of the airways and detection of primary airway tumours in patients with suprabifurcal oesophageal cancer, its role in patients with infrabifurcal oesophageal cancer is not clear. This study aimed to assess the value of fibreoptic bronchoscopy in the preoperative staging of oesophageal cancer located below the level of the tracheal bifurcation. In a prospective protocol, bronchoscopic findings were correlated with the results of other staging procedures, operative results and survival in 51 patients with oesophageal cancer located below the level of the tracheal bifurcation. One unsuspected primary bronchial cancer in a patient with squamous cell oesophageal cancer and one case of lower lobe invasion of an oesophageal adenocarcinoma were found. By excluding from surgery these two patients in whom curative resection was not possible bronchoscopy was the sole decisive staging investigation in 6.5% of potentially operable and 3.9% of all patients. Suspect macroscopic abnormalities were shown in 15.7% of the patients at bronchoscopy. Taking bronchoscopic biopsy as the gold standard the positive predictive value for all macroscopic abnormalities was only 25% (95% confidence interval (CI) 3.2-65.1%). The overall accuracy of bronchoscopy with biopsy and brush and washing cytology in proving or excluding airway invasion in otherwise potentially operable patients was 100% (95% CI 89.4-100%). Bronchoscopy is useful in the preoperative staging of oesophageal carcinoma located below the level of the tracheal bifurcation, particularly if the oesophageal cancer is of the squamous cell type.


Regulation of cholesterol and bile acid homoeostasis in bile-obstructed rats.
We examined how total blockage of biliary excretion, the major pathway through which cholesterol and bile acids are removed from the body, affects liver function, cholesterol and bile acid metabolism and homoeostasis. After 4 weeks of bile-duct ligation, rats showed impaired liver function, as documented by elevations in serum bilirubin and alkaline phosphatase activity. Moreover, bile-duct ligation decreased by about 30% both the amount of microsomal cytochrome P-450 in the liver and the elimination of aminopyrine in vivo, a reliable index in vivo of microsomal mixed-function oxidase activity. Cholesterol and bile acid contents in livers of bile-duct-ligated rats were doubled compared with sham-operated controls. Despite the increase in the contents of cholesterol and bile acids in liver, activities of the respective rate-limiting enzymes, 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7 alpha-hydroxylase, were doubled. Serum concentrations of bile acids and free cholesterol increased 25- and 4-fold respectively. The large increase in serum bile acids was associated with a 380-fold increase in the urinary excretion of bile acids. Although there is a general decrease in cytochrome P-450 content and drug metabolism involving cytochrome P-450-containing hydroxylases, the activity of cholesterol 7 alpha-hydroxylase, also a cytochrome P-450-containing enzyme, is actually increased. These data show that complete obstruction of the bile duct results in the selective impairment of microsomal cytochrome P-450. Increased activity of 7 alpha-hydroxylase, bile acid synthesis and urinary excretion provides an alternative excretory pathway that helps to maintain cholesterol homoeostasis when the biliary excretory pathway is eliminated.


Prognostic markers and putative therapeutic targets for hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the fifth most frequent human cancer and a fatal disease. Therapies with pharmacological agents do not improve the prognosis of patients with unresectable HCC. This emphasizes the need to identify new targets for early diagnosis, chemoprevention, and treatment of the disease. Available evidence indicates that clinical outcome of HCC could reflect the genetic predisposition to cancer development and progression. Numerous loci controlling HCC progression have been identified in rodents. In this review, we describe results of recent studies on effector mechanisms of susceptibility/resistance genes, responsible for HCC progression, aimed at identifying new putative prognostic markers and therapeutic targets of this tumor. Highest c-myc amplification and overexpression, alterations of iNOS crosstalk with IKK/NF-kB and RAS/ERK signaling, ubiquitination of ERK and cell cycle inhibitors, and deregulation of FOXM1 and cell cycle key genes occur in rapidly progressing dysplastic nodules and HCC, induced in genetic susceptible rat strains, compared to the lesions of resistant rats. Notably, alterations of these mechanisms in human HCC subtypes with poorer or better prognosis, are similar to those present in genetically susceptible and resistant rats, respectively, and function as prognostic markers and therapeutic targets. Attempts to cure advanced HCC by molecular therapy directed against specific targets led to modest survival benefit. Thus, efforts are necessary to identify and test, in pre-clinical and clinical studies, new therapeutic targets for combined molecular treatments of HCC. They may take advantage from the comparative analysis of signal transduction in HCCs differently prone to progress, in rats and humans.


COVID-19 pandemic and alcohol consumption: Impacts and interconnections.
Alcohol consumption is associated with multiple diseases and might contribute to vulnerability to SARS-CoV-2 infection. It can also catalyze exacerbations of mental and organic illnesses and predispose to behaviors with an increased risk of infection, severity of disease but also independently of sociopathic behavior and violence. Globally, millions of premature deaths from excessive alcohol consumption occur each year. This paper discusses the effects of increased alcohol consumption and the most important consequences on the health of the population during the social isolation and lockdown during current COVID-19 pandemic.


[Production of slides using a microdatamat].
For production of dias for presentation of scientific data, a personal computer, a dias programme and a camera are necessary. A microdatamat with a 80286 precessor, 20 MB hard disc and an EGA colour screen are the minimum configurations which can be recommended. A hard disc between 40 and 85 MB and a VGA screen provide a better solution. Out of the numerous dias programmes, Harvard Graphics appears to be suitable for production of dias for scientific use. In this programme, it is easy to combine text, graphic and hand drawing. Many other excellent programmes such as 35 mm Express and Mirage are also available. In the choice of camera, a solution of at least 4,000 x 4,000 lines is required and the camera concerned must be capable of working with recognized statistical and graphic parcels as more special graphs cannot be produced in ordinary dias programmes. Among the numerous cameras, the following may be mentioned: Montage which costs of 70,000 Danish crowns (approximately 6,000 pounds), Matrix PCR at 100,000 Danish crowns (approximately 9,000 pounds), Matrix QCR-Z at 200,000 Danish crowns (approximately 18,000 pounds) and Lasergraphic's two models at 60,000 and 120,000 Danish crowns, respectively (approximately 5,000 pounds and 10,000 pounds). In the price class of about 100,000 Danish crowns, Matrix PCR can be recommended particularly as this camera has an excellent optic and advanced self calibrating system. Among the cheaper cameras. Montage is recommended which e.g. functions well with Harvard Graphics.(ABSTRACT TRUNCATED AT 250 WORDS)


Smart Water Management Platform: IoT-Based Precision Irrigation for Agriculture.
The smart management of freshwater for precision irrigation in agriculture is essential for increasing crop yield and decreasing costs, while contributing to environmental sustainability. The intense use of technologies offers a means for providing the exact amount of water needed by plants. The Internet of Things (IoT) is the natural choice for smart water management applications, even though the integration of different technologies required for making it work seamlessly in practice is still not fully accomplished. The SWAMP project develops an IoT-based smart water management platform for precision irrigation in agriculture with a hands-on approach based on four pilots in Brazil and Europe. This paper presents the SWAMP architecture, platform, and system deployments that highlight the replicability of the platform, and, as scalability is a major concern for IoT applications, it includes a performance analysis of FIWARE components used in the Platform. Results show that it is able to provide adequate performance for the SWAMP pilots, but requires specially designed configurations and the re-engineering of some components to provide higher scalability using less computational resources.


Substrate-modulated thermal fluctuations affect long-range allosteric signaling in protein homodimers: exemplified in CAP.
The role of conformational dynamics in allosteric signaling of proteins is increasingly recognized as an important and subtle aspect of this ubiquitous phenomenon. Cooperative binding is commonly observed in proteins with twofold symmetry that bind two identical ligands. We construct a coarse-grained model of an allosteric coupled dimer and show how the signal can be propagated between the distant binding sites via change in slow global vibrational modes alone. We demonstrate that modulation on substrate binding of as few as 5-10 slow modes can give rise to cooperativity observed in biological systems and that the type of cooperativity is given by change of interaction between the two monomers upon ligand binding. To illustrate the application of the model, we apply it to a challenging test case: the catabolite activator protein (CAP). CAP displays negative cooperativity upon association with two identical ligands. The conformation of CAP is not affected by the binding, but its vibrational spectrum undergoes a strong modification. Intriguingly, the first binding enhances thermal fluctuations, yet the second quenches them. We show that this counterintuitive behavior is, in fact, necessary for an optimal anticooperative system, and captured within a well-defined region of the model's parameter space. From analyzing the experimental results, we conclude that fast local modes take an active part in the allostery of CAP, coupled to the more-global slow modes. By including them into the model, we elucidate the role of the modes on different timescales. We conclude that such dynamic control of allostery in homodimers may be a general phenomenon and that our model framework can be used for extended interpretation of thermodynamic parameters in other systems.


[Study of postinhibitory "rebound" in individual motor units of human hand muscles].
Analysis of poststimulus histograms and interspike intervals of firing motor units showed that the burst following the silent period under evoked muscle contraction is the result of synchronous motoneuron escape from inhibition. Under strong evoked isotonic muscle contraction a true facilitation was revealed. The latency of this facilitation was too long for spinal monosynaptic reflex related to spindles elongation at the muscle relaxation stage.


An intron is required for dihydrofolate reductase protein stability.
We compared the expression of dihydrofolate reductase minigenes with and without an intron. The levels of protein were significantly higher in the presence of dihydrofolate reductase intron 1. However, mRNA levels in both constructs were comparable. In addition, the RNA transcribed from either construct was correctly polyadenylated and exported to the cytoplasm. The intron-mediated increase in dihydrofolate reductase protein levels was position-independent and was also observed when dihydrofolate reductase intron 1 was replaced by heterologous introns. The translational rate of dihydrofolate reductase protein was increased in transfectants from the intron-containing minigene. In addition, the protein encoded by the intronless construct was unstable and subject to lysosomal degradation, thus showing a shorter half-life than the protein encoded by the intron-containing minigene. We conclude that an intron is required for the translation and stability of dihydrofolate reductase protein.


Fetal and neonatal iron deficiency but not copper deficiency increases vascular complexity in the developing rat brain.
Anemia caused by nutritional deficiencies, such as iron and copper deficiencies, is a global health problem. Iron and copper deficiencies have their most profound effect on the developing fetus/infant, leading to brain development deficits and poor cognitive outcomes. Tissue iron depletion or chronic anemia can induce cellular hypoxic signaling. In mice, chronic hypoxia induces a compensatory increase in brain blood vessel outgrowth. We hypothesized that developmental anemia, due to iron or copper deficiencies, induces angiogenesis/vasculogenesis in the neonatal brain. To test our hypothesis, three independent experiments were performed where pregnant rats were fed iron- or copper-deficient diets from gestational day 2 through mid-lactation. Effects on the neonatal brain vasculature were determined using quantitative real-time polymerase chain reaction to assess mRNA levels of angiogenesis/vasculogenesis-associated genes and GLUT1 immunohistochemistry to assess brain blood vessel density and complexity. Iron deficiency, but not copper deficiency, increased mRNA expression of brain endothelial cell- and angiogenesis/vasculogenesis-associated genes (i.e. Glut1, Vwf, Vegfa, Ang2, Cxcl12, and Flk1) in the neonatal brain, suggesting increased cerebrovascular density. Iron deficiency also increased hippocampal and cerebral cortical blood vessel branching by 62 and 78%, respectively. This study demonstrates increased blood vessel complexity in the neonatal iron-deficient brain, which is likely due to elevated angiogenic/vasculogenic signaling. At least initially, this is probably an adaptive response to maintain metabolic substrate homeostasis in the developing iron-deficient brain. However, this may also contribute to long-term neurodevelopmental deficits.


Systemic adverse drug reactions secondary to anti-VEGF intravitreal injection in patients with neovascular age-related macular degeneration.
The wet form of age related macular degeneration (AMD), known also as exudative or neovascular, is characterized by the formation of a pathological choroidal neovascular membrane (CNV) responsible for most cases of severe blindness. Vascular endothelial growth factor (VEGF) is a homodimeric glycoprotein acting as a growth factor selective for endothelial cells; it regulates angiogenesis and enhances vascular permeability and plays a leading role in this disorder. The consistent association between CNV and increased VEGF-A expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of neovascular AMD. The importance of VEGF for the development of AMD-related CNV has led to the development of a strategy able to block its pathologic effects. The rationale is that a blockade of VEGF actions could be effective in arresting choroidal angiogenesis and also reducing the vascular permeability, which is frequently the main cause of visual acuity deterioration. However, VEGF has also important functions in vascular physiology. The effects of anti-VEGF therapy may inhibit these functions. Herein we report the systemic adverse events secondary to intravitreal administration of these compounds i.e. the main cardiovascular effects (thrombosis, hemorrhage, hypertension, proteinuria), as well as the less frequent cerebrovascular accidents, myocardial infarction, transient ischemic attacks, deep vein thrombosis, pulmonary embolism and thrombophlebitis.


Chikungunya Virus Evades Antiviral CD8+ T Cell Responses To Establish Persistent Infection in Joint-Associated Tissues.
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes explosive epidemics of a febrile illness characterized by debilitating arthralgia and arthritis that can endure for months to years following infection. In mouse models, CHIKV persists in joint tissues for weeks to months and is associated with chronic synovitis. Using a recombinant CHIKV strain encoding a CD8+ T cell receptor epitope from ovalbumin, as well as a viral peptide-specific major histocompatibility complex class I tetramer, we interrogated CD8+ T cell responses during CHIKV infection. Epitope-specific CD8+ T cells, which were reduced in Batf3-/- and Wdfy4-/- mice with known defects in antigen cross-presentation, accumulated in joint tissue and the spleen. Antigen-specific ex vivo restimulation assays and in vivo killing assays demonstrated that CD8+ T cells produce cytokine and have cytolytic activity. Despite the induction of a virus-specific CD8+ T cell response, the CHIKV burden in joint-associated tissues and the spleen were equivalent in wild-type (WT) and CD8α-/- mice during both the acute and the chronic phases of infection. In comparison, CD8+ T cells were essential for the control of acute and chronic lymphocytic choriomeningitis virus infection in the joint and spleen. Moreover, adoptive transfer of virus-specific effector CD8+ T cells or immunization with a vaccine that induces virus-specific effector CD8+ T cells prior to infection enhanced the clearance of CHIKV infection in the spleen but had a minimal impact on CHIKV infection in the joint. Collectively, these data suggest that CHIKV establishes and maintains a persistent infection in joint-associated tissue in part by evading CD8+ T cell immunity.IMPORTANCE CHIKV is a reemerging mosquito-transmitted virus that in the last decade has spread into Europe, Asia, the Pacific Region, and the Americas. Joint pain, swelling, and stiffness can endure for months to years after CHIKV infection, and epidemics have a severe economic impact. Elucidating the mechanisms by which CHIKV subverts antiviral immunity to establish and maintain a persistent infection may lead to the development of new therapeutic strategies against chronic CHIKV disease. In this study, we found that CHIKV establishes and maintains a persistent infection in joint-associated tissue in part by evading antiviral CD8+ T cell immunity. Thus, immunomodulatory therapies that improve CD8+ T cell immune surveillance and clearance of CHIKV infection could be a strategy for mitigating chronic CHIKV disease.


Hysteretic behaviour in a vacuum deposited submonolayer of single ion magnets.
With element-specific X-ray absorption spectroscopy and X-ray magnetic circular dichroism we have investigated submonolayer coverages of TbPc2 and DyPc2 molecules sublimated on highly ordered pyrolytic graphite. We have studied the field dependence of the magnetization of the central lanthanide ion at very low temperatures. Even in zero applied magnetic field we still observe a remanence in the magnetization. Since there are neither intermolecular coupling nor magnetic interactions with the substrate, this remanent behaviour results just from single-ion anisotropy. On the very inert surface of graphite at temperatures between 0.5 K and 2 K the spin relaxation is slow enough to observe a memory effect in the timescale of the experimental measurements.


Association between development of lower lip cancer and tobacco habits.
Tobacco use is considered to increase the risk of tumor induction. The purpose of this case-controlled investigation was to assess the association of tobacco habits and development of squamous cell carcinoma of the lower lip. Sixty-one patients treated for lower lip cancer, aged between 42 and 90 years, were studied. Age- and sex-matched healthy controls showed a similar exposure to tobacco in years and a comparable distribution of tobacco habits. Although the mean exposure factor (duration times exposure) was greater in the tumor group, no intimate correlation between lip cancer and tobacco was demonstrated. However, an increased, although small, occurrence of herpes labialis lesions was found in cancer patients. The hypothesis is presented that smokers experiencing recurrent herpes simplex virus 1 (HSV-1) infections are more liable to tumor initiation, which issue will be subjected to a future study.


Operative Treatment of Tarlov Cysts - Outcomes and Predictors of Improvement after Surgery: A Series of 97 Consecutive Patients and a Systematic Review of Literature.
A register-based retrospective series and a systematic review of literature. Tarlov cysts are meningeal cysts typically found in the sacral region. They have a dualistic nature ranging from an incidental finding to a symptomatic pathology. There are no established treatment protocols and predictors of operative outcome. Therefore, we aimed to study the outcome of surgical treatment for Tarlov cysts and to characterize patient-, and treatment-related factors predicting outcomes. A systematic review of previous literature was performed and a retrospective cohort of all patients operated on for Tarlov cysts at BLINDED between 1995 and 2020 was collected. Patient records were evaluated along with radiological images. Ninety-seven consecutive patients were identified with follow-up data available for 96. Improvement of symptoms after surgery was observed in 76.0% of patients (excellent or good patient-reported outcome) and the complication rate was 17.5%. Sacral or lower back pain as a preoperative symptom was associated with improvement after surgery (P = .007), whereas previous lower back surgery was more common in patients who did not benefit from surgery (P = .034). No independent predictors of outcome were identified in a regression analysis. This is the second-largest study on the treatment of Tarlov cysts ever published. Operative treatment in a selected patient population will likely produce improvement in the symptoms when balanced with the complication rate and profile of surgery. Preoperative lower back or sacral pain is a potential indicator for improvement after surgery.


The effect of surgical treatment on secondary hyperaldosteronism and relative hyperinsulinemia in primary hyperparathyroidism.
To evaluate the renin-aldosterone system and insulin secretion in hyperparathyroidism and their effects on blood pressure regulation. Studies were carried out on patients with primary hyperparathyroidism (PHPT) prior to and following removal of the parathyroid tumor. Sixteen normotensive and euglycemic patients with PHPT were studied. The following parameters were measured: basal and stimulated plasma renin activity (PRA) and aldosterone (ALD) secretion: parathormone (PTH) and serum electrolytes. Insulin and glucose levels were measured during an oral glucose tolerance test. Systolic but not diastolic blood pressure showed a decrease following surgery, from 123.3+/-13.0/80+/-8.6 to 116.7+/-13.5/77.3+/-8.8 mmHg. The decrease in the systolic pressure was not clinically significant. After surgery, both the basal and stimulated PRA and ALD values decreased, and the preoperative pathological values returned to normal: PRA basal: 1.79 --> 0.70 ng/ml/h, P=0.0049; PRA stimulated: 7.76 --> 1.90 ng/ml/h, P=0.0031; ALD basal: 111.5 --> 73.0 pg/ml, P=0.0258; ALD stimulated: 392.5 --> 236.0 pg/ml, P=0.0157. The postoperative decrease in the PRA correlated with the changes in PTH levels (r=0.5442, P < 0.05, n=16) but did not correlate with the changes in serum calcium concentrations. Both the fasting and stimulated insulin levels decreased after surgery but remained within the normal range: insulin fasting: 10.2 --> 5.0 mIU/l, P=0.0218; insulin area under the curve: 5555 --> 3296 mIU/l*min, P=0.0218. There was no correlation between the changes in insulin levels and PTH or ion levels. Sodium, potassium and blood glucose levels remained unaffected by parathyroid surgery. In a population of normotensive hyperparathyroid patients an increased activity of the renin-aldosterone system related to PTH was found and surgery resulted in a small and insignificant decrease in blood pressure. This change was accompanied by a significant decrease in the activity of the renin-aldosterone system indicating the role of the renin-aldosterone system in the regulation of blood pressure in PHPT. Both fasting and stimulated insulin values decreased following removal of the parathyroid tumor, but with no individual correlation with PTH and calcium levels.


Is there a role for acupuncture in endometriosis pain, or 'endometrialgia'?
Endometriosis is a common cause of pelvic pain in women, many of whom suffer a progression of symptoms over their menstrual life. Symptoms may include combinations of abnormal visceral sensations and emotional distress. Endometriosis pain, or 'endometrialgia' often has a negative influence on the ability to work, on family relationships and sense of worth. Endometrialgia is often considered to be a homogeneous sensory entity, mediated by a specialised high threshold sensory system, which extends from the periphery through the spinal cord, brain stem and thalamus to the cerebral cortex. However, multiple mechanisms have been detected in the nervous system responsible for the pain including peripheral sensitisation, phenotypic switches, central sensitisation, ectopic excitability, structural reorganisation, decreased inhibition and increased facilitation, all of which may contribute to the pain. Although the causes of endometrialgia can differ (eg inflammatory, neuropathic and functional), they share some characteristics. Endometrialgia may be evoked by a low intensity, normally innocuous stimulus (allodynia), or it may be an exaggerated and prolonged response to a noxious stimulus (hyperalgesia). The pain may also be spontaneous in the absence of any apparent peripheral stimulus. Oestrogens and prostaglandins probably play key modulatory roles in endometriosis and endometrialgia. Consequently many of the current medical treatments for the condition include oral drugs, like non-steroid anti-inflammatory drugs, contraceptives, progestogens, androgenic agents, gonadotrophin releasing hormone analogues, as well as laparoscopic surgical excision of the endometriosis lesions. However, management of pain in women with endometriosis is currently inadequate for many. Possibly acupuncture and cognitive therapy may be used as an adjunct.


Reduction in frataxin causes progressive accumulation of mitochondrial damage.
Frataxin protein controls iron availability in mitochondria and reduced levels lead to the human disease, Friedreich's ataxia (FRDA). The molecular aspects of disease progression are not well understood. We developed a highly regulatable promoter system for expressing frataxin in yeast to address the consequences of chronically reduced amounts of this protein. Shutting off the promoter resulted in changes normally associated with loss of frataxin including iron accumulation within the mitochondria and the induction of mitochondrial petite mutants. While there was considerable oxidative damage to mitochondrial proteins, the petites were likely due to accumulation of mitochondrial DNA lesions and subsequent DNA loss. Chronically reduced frataxin levels resulted in similar response patterns. Furthermore, nuclear DNA damage was detected in a rad52 mutant, deficient in double-strand break repair. We conclude that reduced frataxin levels, which is more representative of the disease state, results in considerable oxidative damage in both mitochondrial and nuclear DNA.


Binding of fluorescein monoglucuronide to human serum albumin.
The binding to human albumin of fluorescein monoglucuronide, a fluorescent metabolite of fluorescein, was studied using two methods: pressure dialysis and fluorescence polarization. Both methods indicated that fluorescein monoglucuronide binds to human albumin more loosely than fluorescein. The free fraction in human plasma estimated from the dissociation constant and the number of binding sites was in a range from 31 to 37%. Fluorescence of fluorescein was significantly quenched by the albumin binding, but fluorescence of fluorescein monoglucuronide was not affected by albumin. The relative molar intensity of fluorescence between these fluorophores varied from 3.2 to 37.3, depending on the excitation wavelength.


[Variations in blood testosterone levels of prepubertal foxes and during the seasonal genital cycle of the adult male fox (Vupes vulpes) in captivity].
Plasma testosterone levels have been determined by radioimmunoassay on peripheral venous blood samples of young and adult foxes at different times of their genital activity. In the cub, the testosterone levels increase from November to January; at this time, the young is pubescent. In the adult, the testosterone levels are low from April to November. At this time, the levels increase and reach a maximum value from December to February, which is the mating season. Some high testosterone levels observed in summer prove that the endocrine activity of the testis persists during the out-breeding season.


Do newly formed word representations encode non-criterial information?
Lexical stress is useful for a number of language learning tasks. In particular, it helps infants segment the speech stream and identify phonetic contrasts. Recent work has demonstrated that infants aged 1;0 can learn two novel words differing only in their stress pattern. In the current study, we ask whether infants aged 1;0 store stress information in their representations of words even when it not required for the task. To this end, we taught infants novel, three-syllable word-object pairings. At test, we manipulated the word by presenting infants with forms that shared the stress pattern of the familiar words but differed in the segments, and forms that shared the segments of the familiar word but differed in the stress pattern. Our findings reveal that infants' representations of new words include word-level stress information and do not simply contain the information critical for distinguishing between different forms.


Degradation of Fe/N/C catalysts upon high polarization in acid medium.
A comprehensive study of the degradation of a highly active Fe/N/C catalyst in acid medium is reported. An accelerated aging protocol was applied in the temperature range of 20 to 80 °C. From fundamental rotating-disc electrode studies and polymer electrolyte membrane fuel cell investigations combined with identical-location electron microscopy and Mößbauer spectroscopy at various stages of degradation, important insights into the structural and chemical changes of the catalyst were obtained. Most importantly, the degradation is strongly enhanced at elevated temperature, which is correlated to (i) increased carbon-corrosion rate and (ii) parallel non-preferential dissolution of the FeNx-based active sites. The degradation not only leads to a decreased ORR kinetics over time but also induces significant charge- and mass-transport resistances due to the collapse of the electrode structure.


Evaluation of different platelet-rich concentrates effects on early soft tissue healing and socket preservation after tooth extraction.
The present study aimed to analyze the early soft tissue healing characteristics and Fractal Dimension (FD) of extraction sockets preserved by Leukocyte-platelet-rich fibrin (L-PRF) and titanium prepared platelet-rich fibrin (T-PRF). 57 single-tooth extraction sockets were included in the study, three groups were prepared: post-extraction sockets filled with L-PRF (n=19) and T-PRF (n=19), and control group; naturally healing sockets (n=19). Three months after tooth extraction, FD measurement was made in the center of the healing socket. The Landry Wound Healing Index (LWHI) and H2O2 bubbling test results for the complete wound epithelization (CWE) rates were recorded 1 and 2 weeks postoperatively. All patients were asked to record a visual analog scale (VAS) value for pain and the number of analgesics taken during the 3 days after the extraction. CWE using H2O2 test result showed a significantly lower rate in the controls than in L-PRF and T-PRF groups at 1st week. At 2nd weeks, both of the test groups showed 100% CWE compared with only 40.7% in the control group. The VAS pain score was significantly higher in the control group than in L-PRF and T-PRF groups on the 1st day. However, no significant difference was found among the groups on 2nd day. FD value of control group was significantly lower than the L-PRF group and T-PRF group. T-PRF and L-PRF similarly enhanced wound epithelization and reduced postoperative discomfort at extraction sockets. The T-PRF procedure resulted in higher FD compared to the L-PRF and control group.


In vivo microbubble detection in decompression sickness using a second harmonic resonant bubble detector.
A resonant bubble detection method based on a second harmonic technique has been used to monitor the femoral vascular system of dogs subjected to rapid decompression. For this study, the detector consisted of two acoustic transducers mounted at right angles to each other that were packaged in a perivascular cuff configuration. This detector responds selectively only to bubbles near resonant size (4.2 mum in diameter); solid particles and large bubbles produce no response. The detector was used to monitor a total of 15 dogs. Eleven dogs were subjected to a series of simulated underwater dives until acute symptoms of decompression sickness occurred; 4 dogs served as controls. In the dived group, either the femoral vein or the femoral artery was monitored. Resonant bubbles were observed in the femoral veins of all 6 dogs monitored at this location. During arterial monitoring, most dogs showed no response, but an occasional weak response was observed in 2 of the dogs. No resonant bubbles were detected in the femoral artery or the femoral vein in any of the controls. The data suggest that this bubble detection method is feasible for in vivo use. Furthermore, 4 mum diameter bubbles are much more prevalent in the veins of dogs suffering from decompression sickness than they are in dog arteries, presumably because they are filtered out effectively by the pulmonary circulation. Modifications of this method are discussed to enhance its accuracy and applicability for quantifying bubble size, location, and number.


Antiepileptic drug monotherapy for epilepsy in the elderly: A systematic review and network meta-analysis.
To estimate the comparative efficacy and safety of antiepileptic drugs (AEDs) in the elderly with new-onset epilepsy. We searched electronic databases for randomized controlled trials (RCTs) of monotherapy AEDs to treat epilepsy in elderly. The following outcomes were analyzed: seizure freedom and withdrawal from the study for any cause at 6 and 12 months; withdrawal from the study for any adverse event (AE) at 12 months; and occurrence of any AE at 12 months. Effect sizes were estimated by network meta-analyses within a frequentist framework. The hierarchy of competing interventions was established using the surface under the cumulative ranking curve (SUCRA) and mean ranks. Five RCTs (1425 patients) were included. Included AEDs were carbamazepine immediate- and controlled-release (CBZ-IR, CBZ-CR), gabapentin (GBP), lacosamide (LCM), lamotrigine (LTG), levetiracetam (LEV), phenytoin (PHT), and valproic acid (VPA). At the pairwise and network meta-analyses, there were no differences in any of the comparison according to 6- and 12-month seizure freedom. The treatment with CBZ-IR and CBZ-CR was associated with a higher risk of withdrawal than LTG, LEV, or VPA, and CBZ-IR had the overall highest probability of discontinuation across all AEDs. According to SUCRA, the following had the greatest likelihood ranking best for seizure freedom at 6 and 12 months: LCM, LTG, and LEV. CBZ-CR and CBZ-IR had the highest probabilities of being worst for the 12-month retention. CBZ-IR, CBZ-CR, and GBP had the highest probabilities of withdrawal from the study for AEs, , and VPA had the highest probability of being the best-tolerated option. Although no significant difference in efficacy was found across treatments, LCM, LTG, and LEV had the highest probability of ranking best for achieving seizure freedom. CBZ-IR and CBZ-CR showed a poor tolerability profile, leading to higher withdrawal rates compared to LEV and VPA.


Analytical determination of bisphenol A (BPA) and bisphenol analogues in paper products by GC-MS/MS.
Bisphenol A (BPA; 4-[2-(4-hydroxyphenyl)propan-2-yl]phenol), a suspected endocrine disruptor with a weak estrogenic activity, is used in a variety of consumer products, including food-contact materials made of paper and cardboard products. Due to restrictions on the use of BPA because of its potential health risks, BPA is gradually being replaced by other bisphenols because no limitations exist for these substances. This study presents a method for the simultaneous analysis of BPA, bisphenol AF (BPAF), bisphenol B (BPB), bisphenol E (BPE), bisphenol F (BPF) and bisphenol S (BPS) in paper and board products using gas chromatography-tandem mass spectrometry (GC-MS/MS). Paper samples were extracted by liquid extraction, as well as by Folch extraction, derivatised with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and the results compared. The developed method showed good linearity (R2 > 0.9965) and precision, yielding relative standard deviations (RSDs) of less than 16.6% for reproducibility and 19.8% for repeatability. The limits of detection and limits of quantification for the different bisphenols ranged from 0.23 to 2.70 µg kg-1 paper and from 0.78 to 9.10 µg kg-1 paper, respectively. Analysis of different paper products (recycled, virgin fibre) showed that all the analysed bisphenols were present in the samples, except for BPAF and BPB. A calculation of the 'worst-case' scenario assuming a maximum potential migration of 100% of the analytes into food showed that the analysed products can be assumed to be safe regarding the migration of bisphenols.


In vitro incorporation of progesterone-1,2-3H in Fallopian tube and uterus of rat during pregnancy and postpartum period.
In vitro incorporation of 3H-progesterone into rat Fallopian tube and uterus during pregnancy and postpartum period is studied. The uptake of progesterone in oviduct and uterus falls sharply during mid-pregnancy (day 8-12 postcoitum) followed by a significantly high uptake prior to parturition. At the time of parturition, the tubal incorporation of radioactivity declines but resumes a rising profile towards day 5 postpartum. Similar pattern of uptake is observed in the uterus.


Elevated Levels of SOX10 in Serum from Vitiligo and Melanoma Patients, Analyzed by Proximity Ligation Assay.
The diagnosis of malignant melanoma currently relies on clinical inspection of the skin surface and on the histopathological status of the excised tumor. The serum marker S100B is used for prognostic estimates at later stages of the disease, but analyses are marred by false positives and inadequate sensitivity in predicting relapsing disorder. To investigate SOX10 as a potential biomarker for melanoma and vitiligo. In this study we have applied proximity ligation assay (PLA) to detect the transcription factor SOX10 as a possible serum marker for melanoma. We studied a cohort of 110 melanoma patients. We further investigated a second cohort of 85 patients with vitiligo, which is a disease that also affects melanocytes. The specificity of the SOX10 assay in serum was high, with only 1% of healthy blood donors being positive. In contrast, elevated serum SOX10 was found with high frequency among vitiligo and melanoma patients. In patients with metastases, lack of SOX10 detection was associated with treatment benefit. In two responding patients, a change from SOX10 positivity to undetectable levels was seen before the response was evident clinically. We show for the first time that SOX10 represents a promising new serum melanoma marker for detection of early stage disease, complementing the established S100B marker. Our findings imply that SOX10 can be used to monitor responses to treatment and to assess if the treatment is of benefit at stages earlier than what is possible radiologically.


Co-methylation analysis in lung tissue identifies pathways for fetal origins of COPD.
COPD likely has developmental origins; however, the underlying molecular mechanisms are not fully identified. Investigation of lung tissue-specific epigenetic modifications such as DNA methylation using network approaches might facilitate insights linking in utero smoke (IUS) exposure and risk for COPD in adulthood.We performed genome-wide methylation profiling for adult lung DNA from 160 surgical samples and 78 fetal lung DNA samples isolated from discarded tissue at 8-18 weeks of gestation. Co-methylation networks were constructed to identify preserved modules that shared methylation patterns in fetal and adult lung tissues and associations with fetal IUS exposure, gestational age and COPD.Weighted correlation networks highlighted preserved and co-methylated modules for both fetal and adult lung data associated with fetal IUS exposure, COPD and lower adult lung function. These modules were significantly enriched for genes involved in embryonic organ development and specific inflammation-related pathways, including Hippo, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), Wnt, mitogen-activated protein kinase and transforming growth factor-β signalling. Gestational age-associated modules were remarkably preserved for COPD and lung function, and were also annotated to genes enriched for the Wnt and PI3K/AKT pathways.Epigenetic network perturbations in fetal lung tissue exposed to IUS and of early lung development recapitulated in adult lung tissue from ex-smokers with COPD. Overlapping fetal and adult lung tissue network modules highlighted putative disease pathways supportive of exposure-related and age-associated developmental origins of COPD.


STROMAL CHANGES IN LEUKAEMIC AND RELATED BONE MARROW PROLIFERATIONS.
The stromal structure of the bone marrow was studied in 96 cases of leukaemia and related disorders. The reticulin stroma forms an integral component of any given marrow proliferation and may often be increased in amount, sometimes normal, and occasionally decreased. The pattern is often indeterminate but certain distinguishable patterns may be found, including a sinusoidal pattern in myelofibrotic chronic myeloses, a pattern characterized by an abundance of hyperplastic capillaries and arterioles often seen in lymphoid leukaemias, and one with irregular focal reticulin proliferation in many acute undifferentiated leukaemias.Adventitious collagen fibres are demonstrable in about half of all myeloses, acute and chronic, leukaemic and aleukaemic, and may be diffuse or focal. They apparently develop from thickening and collapse and condensation of the basic reticulin network, not from any primary fibroblastic proliferation. The development of fibrosis does not denote an aetiological relationship between the conditions in which it occurs, since it appears to be a non-specific sequel to marrow exhaustion and marrow necrosis. There is no justification for the diagnosis of acute or ;malignant' myelofibrosis as a disease entity in cases of acute leukaemia with marrow fibrosis.Osteolytic change due to resorption of bony trabeculae is a common event in all the conditions studied and may be accompanied by remoulding of the eroded trabeculae. Fibre bone formation is found in about 15% of cases, including acute lymphoblastic leukaemias and acute undifferentiated leukaemias, but is extensive and well-developed only in cases of primary myelofibrosis.


Distributed three-dimensional fiber Bragg grating refractometer for biochemical sensing.
We demonstrate a three-dimensional (3-D) distributed refractometer that measures refractive index in a small volume. The sensor is based on an evanescent-wave fiber Bragg grating that is interrogated by low-coherence spectral interferometry. The measurement can be performed on a short time scale without the need for a mechanical scan. The new sensor was used to simultaneously measure glucose concentration in several droplets along a single sensor and to interrogate the time-dependent evaporation process of a water droplet. The new measurement technique might enable novel 3-D distributed sensors to be developed and multiple discrete measurements to be made in a small volume.


The efficacy of sulbactam-ampicillin in the therapy of respiratory disease associated with ampicillin resistant Pasteurella species in housed calves.
Sulbactam-ampicillin is a combination of sulbactam, a beta-lactamase inhibitor, and ampicillin, a broad spectrum beta-lactam antibiotic. The efficacy of sulbactam-ampicillin was evaluated in the treatment of calf respiratory disease associated with ampicillin-sensitive and ampicillin-resistant strains of Pasteurella haemolytica and Pasteurella multocida. Treatment with sulbactam-ampicillin was compared with treatment with ampicillin alone in 123 Friesian calves, between three and five weeks old, exhibiting clinical signs of respiratory disease. Seven of the 59 calves treated with ampicillin died whereas only one death occurred in the 64 calves treated with sulbactam-ampicillin. In the calves which survived, treatment with sulbactam-ampicillin resulted in a significantly better clinical response, as measured by the reduction in severity of clinical signs. The results of bacteriological examinations indicated that there was a marked increase in the proportion of ampicillin-resistant isolates of P haemolytica subsequent to treatment with ampicillin, whereas the proportion of ampicillin-resistant isolates of P. haemolytica recovered from calves treated with sulbactam-ampicillin had declined. The superior efficacy of sulbactam-ampicillin observed in this study is explained by the inhibitory effect of sulbactam on beta-lactamases produced by resistant bacteria, thus rendering them susceptible to the ampicillin.


An ethnographic study of classifying and accounting for risk at the sharp end of medical wards.
An understanding of how staff identify, classify, narrativise and orient to patient safety risks is important in understanding responses to efforts to effect change. We report an ethnographic study of four medical wards in the UK, in hospitals that were participating in the Health Foundation's Safer Patients Initiative, an organisation-wide patient safety programme. Data analysis of observations and 49 interviews with staff was based on the constant comparative method. We found that staff engaged routinely in practices of determining what gets to count as a risk, how such risks should properly be managed, and how to account for what they do. Staff practices and reasoning in relation to risk emerged through their practical engagement in the everyday work of the wards, but were also shaped by social imperatives. Risks, in the environment we studied, were not simply risks to patient safety; when things went wrong, professional identity was at risk too. Staff oriented to risks in the context of busy and complex ward environments, which influenced how they accounted for risk. Reasoning about risk was influenced by judgements about which values should be promoted when caring for patients, by social norms, by risk-spreading logics, and by perceptions of the extent to which particular behaviours and actions were coupled to outcomes and were blameworthy. These ways of identifying, evaluating and addressing risks are likely to be highly influential in staff responses to efforts to effect change, and highlight the challenges in designing and implementing patient safety interventions.


Pressure-induced interface keratitis: a late complication following LASIK.
Interface inflammation is a common complication of laser in situ keratomileusis (LASIK). The most well-described presentation is diffuse lamellar keratitis (DLK), which typically develops early after LASIK and responds quickly to topical steroids. In this report, we describe a novel presentation of interface inflammation that resembles DLK in appearance but presents late in the postoperative period, is associated with increased intraocular pressure, and is exacerbated by steroid treatment. A retrospective case series and chart review of all patients treated in our tertiary care private practice for late-onset interface inflammation associated with elevated intraocular pressure. Ten eyes in 6 patients with late-onset interface inflammation and increased intraocular pressure were identified. At presentation, all patients were presumed to have classic DLK and were treated initially with aggressive topical steroids. Eight of the 10 eyes were receiving topical steroids at the time of presentation. The average time of presentation was 17 days after LASIK (range, 7-34). Elevated intraocular pressure was noted on average 28 days after presentation (range, 8-69). Lamellar inflammation was exacerbated by topical steroids. Resolution of the interface inflammation did not occur until intraocular pressure was controlled. This case series describes a clinically distinct form of interface inflammation that presents late and is associated with elevated intraocular pressure. The lamellar inflammation was refractory to topical steroids and only resolved when pressure was controlled. These findings suggest that elevated intraocular pressure can contribute to interface inflammation. Postoperative assessment of intraocular pressure is essential in patients presenting with flap inflammation.


[Patient with atypical neurocytoma - case report].
Neurocytoma represents a rare tumor of the central nervous system usually slowly growing and generally with good prognosis after surgical resection with or without adjuvant radiotherapy. A 25-year- old woman presented with sudden fainting. During the initial workup, brain CT was completed with finding of tumor inside the third ventricle spreading into both lateral ventricles. The patient underwent partial surgical resection followed by radical gross resection, no adjuvant radiotherapy was indicated during the initial treatment and the patient was followed up with regular brain MRIs and clinical examinations. Thirty six months after the initial resection, there was progression on MRI and radiotherapy was recommended. At this moment, patient is 12 months after radiotherapy with stable disease on MRI and with good stable performance status. One of the greatest problems in the management of neurocytoma is the timing of adjuvant radiotherapy. From published data, it is clear that adjuvant radiotherapy increases local control; however, this has to be considered carefully against the possible risks from late side effects of radiotherapy considering long-time survival of the patients.


Sandwich double-decker Er(iii) and Yb(iii) complexes containing naphthalocyanine moiety: synthesis and investigation of the effect of a paramagnetic metal center.
Novel heteroleptic Er(iii) and Yb(iii) naphthalocyaninato-phthalocyaninates containing an octa-phenyl or octa-phenoxysubstituted naphthalocyanine deck were synthesised and identified by 1H NMR, EPR and high resolution MALDI-TOF/TOF mass spectrometry. Direct synthesis of novel homoleptic Yb(iii) bis (octa-phenylnaphthalocyaninate) was carried out. Downfield lanthanide induced shifts of the aromatic protons in target compounds were observed compared with the corresponding diamagnetic Lu(iii) complexes. In the near-IR absorption spectra, an increase in ionic radius from Lu(iii) to Er(iii) resulted in a bathochromic shift of the intervalence band up to 1473 nm. This work presents the first experimental EPR study of Yb(iii) bis naphthalocyaninate, where a set of magnetic parameters and properties (including spin, magnitude and sign of magnetic anisotropy parameter D, increased splitting in a crystal field, ferromagnetic f-π interaction etc.) were determined and interpreted by both EPR and SQUID techniques and supported by theoretical considerations.


GLP-1R agonists promote normal and neoplastic intestinal growth through mechanisms requiring Fgf7.
Glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L cells promotes nutrient disposal via the incretin effect. However, the majority of L cells are localized to the distal gut, suggesting additional biological roles for GLP-1. Here, we demonstrate that GLP-1 receptor (GLP-1R) signaling controls mucosal expansion of the small bowel (SB) and colon. These actions did not require the epidermal growth factor (EGF) or intestinal epithelial insulin-like growth factor (IGF1) receptors but were absent in Glp1r(-/-) mice. Polyp number and size were increased in SB of exendin-4-treated Apc(Min/+) mice, whereas polyp number was reduced in SB and colon of Glp1r(-/-):Apc(Min/+) mice. Exendin-4 increased fibroblast growth factor 7 (Fgf7) expression in colonic polyps of Apc(Min/+) mice and failed to increase intestinal growth in mice lacking Fgf7. Exogenous exendin-4 and Fgf7 regulated an overlapping set of genes important for intestinal growth. Thus, gain and loss of GLP-1R signaling regulates gut growth and intestinal tumorigenesis.


Impact of Recycler Information Sharing on Supply Chain Performance of Construction and Demolition Waste Resource Utilization.
In recent years, the generation of a large amount of construction and demolition waste (CDW) has threatened the public environment and human health. The inefficient supply chain of CDW resource utilization hinders the green development of countries around the world, including China. This study aims to reveal the impact of information sharing regarding recyclers' market demand forecast on the performance of CDW resource utilization supply chains. Therefore, this paper uses the incomplete information dynamic game method to establish and solve the decision-making model of the construction and demolition waste resource utilization supply chain under the conditions of recyclers sharing and not sharing their information. The paper then obtains the Bayesian equilibrium solution and the optimal expected profit for each party. Finally, a numerical simulation was used in order to verify the validity of the model and conclusions. The main conclusions are as follows. In the CDW resource utilization supply chain, if the recycler is more pessimistic about the market's demand forecast, their information sharing makes the remanufacturer more motivated to improve their level of environmental responsibility. In addition, information sharing by recyclers is always beneficial in increasing the profit of the remanufacturer, but it also may make the recycler lose profit. When the efficiency of the environmental responsibility investment of remanufacturers is in a high range, information sharing increases the profits of recyclers. Conversely, information sharing has no significant effect on the profits of recyclers. The impact on the profits of the entire CDW resource utilization supply chain depends on the intensity of competition among channels, the market share of offline recycling channels and the efficiency of environmental responsibility investments.


Crystallization and preliminary X-ray crystallographic studies of human voltage-dependent anion channel isoform I (HVDAC1).
The major channel by which metabolites can pass through the outer mitochondrial membrane is formed by the voltage-dependent anion-channel (VDAC) family. Functionally, VDAC is involved in the limited exchange of ATP, ADP and small hydrophilic molecules across the outer membrane. Moreover, there is compelling evidence that VDAC isoforms in mammals may act in the cross-talk between mitochondria and the cytoplasm by direct interaction with enzymes involved in energy metabolism and proteins involved in mitochondrial-induced apoptosis. To obtain a high-resolution structure of this channel, human VDAC protein isoform I was overproduced in Escherichia coli. After refolding and testing the correct fold using circular dichroism, a subsequent broad-range screening in different detergents resulted in a variety of crystals which diffracted to 3.5 A resolution. The crystal lattice belongs to the trigonal space group P321, with unit-cell parameters a = 78.9, c = 165.7 A and one monomer in the asymmetric unit.


Analysis of queries sent to PubMed at the point of care: observation of search behaviour in a medical teaching hospital.
The use of PubMed to answer daily medical care questions is limited because it is challenging to retrieve a small set of relevant articles and time is restricted. Knowing what aspects of queries are likely to retrieve relevant articles can increase the effectiveness of PubMed searches. The objectives of our study were to identify queries that are likely to retrieve relevant articles by relating PubMed search techniques and tools to the number of articles retrieved and the selection of articles for further reading. This was a prospective observational study of queries regarding patient-related problems sent to PubMed by residents and internists in internal medicine working in an Academic Medical Centre. We analyzed queries, search results, query tools (Mesh, Limits, wildcards, operators), selection of abstract and full-text for further reading, using a portal that mimics PubMed. PubMed was used to solve 1121 patient-related problems, resulting in 3205 distinct queries. Abstracts were viewed in 999 (31%) of these queries, and in 126 (39%) of 321 queries using query tools. The average term count per query was 2.5. Abstracts were selected in more than 40% of queries using four or five terms, increasing to 63% if the use of four or five terms yielded 2-161 articles. Queries sent to PubMed by physicians at our hospital during daily medical care contain fewer than three terms. Queries using four to five terms, retrieving less than 161 article titles, are most likely to result in abstract viewing. PubMed search tools are used infrequently by our population and are less effective than the use of four or five terms. Methods to facilitate the formulation of precise queries, using more relevant terms, should be the focus of education and research.


Phase II trial of combined regional hyperthermia and gemcitabine for locally advanced or metastatic pancreatic cancer.
Despite advances in cancer therapy, treating pancreatic cancer remains one of the major challenges in the field of medical oncology. We conducted this phase II study to evaluate the efficacy and safety of regional hyperthermia combined with gemcitabine for the treatment of unresectable advanced pancreatic cancer. Eligibility criteria included histologically proven, locally advanced or metastatic pancreatic cancer. Gemcitabine was administered intravenously at a dose of 1000 mg/m(2) on days 1, 8, and 15 every 4 weeks. Regional hyperthermia was performed once weekly, 1 day preceding or following gemcitabine administration. The primary end point was the 1-year survival rate. Secondary objectives were determination of tumour response and safety. We enrolled 18 patients with advanced pancreatic cancer between November 2008 and May 2010. The major grade 3-4 adverse events were neutropenia and anaemia; however, there were no episodes of infection. The objective response rate (ORR) and disease control rate (ORR + stable disease) were 11.1% and 61.1%, respectively. Median overall survival (OS) was 8 months, and the 1-year survival rate was 33.3%. Median OS of patients with locally advanced pancreatic cancer was 17.7 months. Regional hyperthermia combined with gemcitabine is well tolerated and active in patients with locally advanced pancreatic cancer.