Enhancement of regeneration by Org 2766 after nerve crush depends on the type of neural injury.
The neurotrophic effects of the adrenocorticotropin (ACTH)-(4-9) analog Org 2766 (Met(O2)-Glu-His-Phe-D-Lys-Phe) were studied in rats recovering from a sciatic nerve crush. Org 2766 (10 micrograms/rat s.c., every 48 h) increased the number of myelinated axons reinnervating a previously denervated sciatic nerve by 32% (P less than 0.01), as assessed 13 days after crush lesioning, and facilitated recovery of sensorimotor functioning by 14% (P = 0.05), as measured by foot withdrawal after stimulation of the footsole with hot air. However, these facilitating effects were only seen if the nerve was lesioned using forceps with grooved jaws and not if forceps were used with cross-hatched jaws. Endoneural tubes and Schwann cells of the sciatic nerve appeared to be better preserved after crushing with grooved rather than cross-hatched jaws. Our data indicate that the regeneration-enhancing effects of Org 2766 are dependent on the type of injury applied to the endoneurium and endoneural tubes of the sciatic nerve and suggest that endoneural tissue may mediate the neurotrophic properties of Org 2766.


Replicon hypothesis revisited.
Nearly 70 years after the proposal of semiconservative replication of generic material by Watson and Crick, we now understand many of the proteins involved in the replication of host chromosomes and how they operate. The initiator and replicator, proposed in the replicon hypothesis, are now well defined in both prokaryotes and eukaryotes. On the other hand, studies in prokaryotes and Archaea indicate alternative modes of initiation, which may not depend on an initiator. Here I summarize recent progress in the field of DNA replication and discuss the evolution of replication systems.


Pheochromocytoma, sickle cell disease and pregnancy: a case report.
Pheochromocytomas are rare catecholamine-secreting tumors with a 2-4% maternal morbidity rate and a fetal loss rate of 11%. Sickle cell disease is also associated with increased maternal and fetal mortality. We report the first case of a primigravid woman with both conditions and a successful pregnancy outcome.


Thoracoscopic resection of pericardium for symptomatic congenital pericardial defect.
Congenital defects of the pericardium are rare. Surgical treatment is recommended to relieve symptoms and to prevent cardiac herniation and strangulation. The case of a symptomatic pericardial defect due to a dynamic obstruction of the coronary arteries is described. The diagnosis was suggested by plain chest film, echocardiography, and cardiac catheterization. Confirmation and successful surgical management were accomplished by video-assisted thoracoscopic pericardiectomy.


The roles of non-coding RNAs in vascular calcification and opportunities as therapeutic targets.
Vascular calcification (VC) is characterized by an accumulation of calcium phosphate crystals inside the vessel wall. VC is often associated with diabetes, chronic kidney disease (CKD), atherosclerosis, and cardiovascular disease (CVD). Even though the number of patients with VC remains prevalent, there are still no approved therapies for the treatment of VC. Since the pathogenesis of VC is diverse and involves multiple factors and mechanisms, it is critical to reveal the novel mechanisms involved in VC. Although protein-coding RNAs involved in VC have been extensively studied, the roles of non-coding RNAs (ncRNAs) are not yet fully understood. The field of ncRNAs has recently received attention, and accumulating evidence from studies in VC suggests that ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play an important role in the regulation of VC. NcRNAs can modulate VC by acting as promoters or inhibitors and may be useful in the clinical diagnosis and treatment of VC. In this article, we review and discuss ncRNAs that regulate VC and present the therapeutic implications of these ncRNAs.


aEEG as a useful tool for neuromonitoring in critically ill children - Current evidence and knowledge gaps.
Amplitude-integrated electroencephalography (aEEG) is used in children beyond neonatal age, but systematic investigations have been lacking. This mini-review summarised aEEG studies on children aged one month to 18 years, evaluated the usefulness of aEEG and identified knowledge gaps or limitations. We searched the PubMed database for articles published in English up to September 2020, and 23 papers were identified. aEEG was frequently used to compensate for the absence of continuous full-channel EEG monitoring, particularly for detecting seizures. Interpreting background patterns was based on neonatal classifications, as reference values for older infants and children are lacking. It is possible that aEEG could predict outcomes after paediatric cardiac arrests and other conditions. Gaps in our knowledge exist with regard to normal values in healthy children and the effects of sedation on aEEG background patterns in children. The main application of aEEG was detecting and treating paediatric seizures. Further research should determine reference values and investigate the potential to predict outcome after critical events or in acute neurological disease. It is likely that aEEG will play a role in paediatric critical care in the future.


Differential proteome and functional analysis of NSCLC cell lines in response to Tualang honey treatment.
Honey's therapeutic and nutrition effects have been discovered for centuries. Traditionally, it is applied as a health supplement as well as an alternative treatment for a variety of medical issues ranging from wound healing to anticancer therapy. Tualang honey (TH) is a natural sweet substance produced by Apis dorsata, naturally has a dark brown appearance from its high polyphenolic compounds. TH has been reported to show anticancer effects on various types of cancers including breast, oral, leukemia, cervical and lung cancer through several pathways. The detailed molecular mechanism of anticancer activity of TH as a chemopreventive and therapeutic agent is an interesting endeavor to understand. Despite the anticancer effects of Tualang honey (TH) on various types of cancer have been widely reported, the exact molecular mechanism underlying its' anticancer action remains unpublished. Thus, this study aimed to investigate changes that occur on the proteome profile and the functional analysis of proteins with differential abundances within non-small cell lung cancer (NSCLC) cells that were treated with TH and discover the plausible molecular mechanism governing its' anticancer action. NSCLC cell lines (H23 and A549) were treated with 3.6% and 3.1% v/v of TH for 24 h, respectively. Protein extracts were obtained from control NSCLC cells and TH-treated NSCLC cells. Label-free quantitative proteomic analysis was subsequently performed in nanoACQUITY UPLC with quadrupole-time of flight (Q-TOF) Synapt G2 HDMS mass spectrometer system to identify and quantify proteins of TH-treated NSCLC cells. The gene ontology (GO) PANTHER classification system was performed to categorize the identified proteins based on their protein class, biological processes, and pathway. Meanwhile, the STRING functional protein association network database was used to analyze the functional protein-protein interaction and associated pathways of significantly different proteins of NSCLC cells. A total of 634 and 554 proteins were identified from H23 and A549 cell lines where 88 differential proteins were upregulated and 103 were downregulated in TH-treated H23 cells, whilst 66 differential proteins were upregulated and 61 were downregulated in TH-treated A549 cells. Differently expressed proteins of NSCLC were observed to be associated with the cell cycle, apoptosis, and VEGFA-VEGFR signaling pathway. TH modulated these signaling pathways through downregulation of ELAVL1, H3F3A and PCNA proteins. Three potential protein markers were significantly downregulated in NSCLC cells such as HRAS, HSPB1, and TUBA1C when treated with TH. Our findings suggested the anticancer activity of TH on NSCLC cells through modulation of pertinent cancer-related proteins that are associated with cell proliferation, apoptosis inhibition, and induction of angiogenesis.


Marine debris: Implications for conservation of rocky reefs in Manabi, Ecuador (Se Pacific Coast).
Marine debris (MD) pollution is a problem of global concern because of its impact on marine ecosystems. The current extent of this problem and its implications concerning reef conservation are unknown in Ecuador. The composition and distribution of submerged MD was assessed on two reefs using underwater surveys of geomorphological areas: crest, slope and bottom. MD items were classified according to source and use. Plastic-derived debris represents >90% of total MD found on the reefs, principally composed by plastic containers and nets. 63% of the MD was associated to fishing activities. The composition showed differences between sites and geomorphological areas, monofilament nets were found on the crests, multifilament lines on the slopes and plastic containers on the bottom. MD disposal might be a result of the influx of visitors and fishing activities. Distribution is related to bottom type, level of boating/fishing activity and benthic features.


Cytoprotective Effect of Peptide Sedatin, an Agonist of μ/δ-Opioid Receptors, on Primary Culture of Pulmonary Fibroblasts of Albino Rats under Conditions of Oxidative Stress.
We studied the effects of a synthetic analogue of dermorphin peptide sedatin on DNA synthesis, nucleolar apparatus, and parameters of free radical oxidation in the primary culture of pulmonary fibroblasts under conditions of oxidative stress. Oxidative stress significantly enhanced production of superoxide anion radical in the culture, sufficiently inhibited DNA synthesis in fibroblasts, and reduced the size of cell nuclei and parameters of the nucleolar apparatus. Sedatin prevented accumulation of free radical oxidation products and changes in karyometry parameters induced by oxidative stress. The peptide completely eliminated changes in the parameters of fibroblast nucleolar apparatus and abolished the inhibitory effect of oxidative stress on the number of DNA-synthesizing cells. Pretreatment with non-selective opioid receptor antagonist naloxone hydrochloride partially abolished the effects of sedatin in the primary culture of pulmonary fibroblasts.


Integrated assessment of biomarker responses in caged shrimps (Litopenaeus vannamei) exposed to complex contaminants from the Maluan Bay of China.
The marine shrimp Litopenaeus vannamei were used as an active biomonitoring organism to assess the bioavailability and impact of metal contaminants in seven study sites along the Maluan Bay of China. Metal concentrations in the hepatopancreas of shrimps were determined in conjunction with four biomarkers responses after a 7 day in situ cage exposures. The results showed that contaminant tissue burdens at the deployment sites were greater than those of the reference site, and antioxidant enzyme activities were strongly inhibited compared to those of reference organisms. Variations in these biomarker responses were correlated significantly (p < 0.05 or p < 0.01) with the specific metal pollutants at the study sites, but no significant correlations existed between catalase activity responses and the metal contaminants. This suggests the presence of undetermined contaminants or other exposure routes that may be responsible for the decreased catalase activity. Multivariate analysis revealed a causal relationship between contaminants at each deployment site and the biochemical "response" of the caged shrimps at these sites and demonstrated the presence of two contaminant "hot" spots. This investigation suggested that the incorporation of chemical data on trace metal concentrations with the analysis of antioxidant enzymatic activities in caged shrimps can be a useful tool for the identification of causal toxic contaminants in complex mixtures.


Results of surgical treatment of talipes equino valgus by means of navicular-cuneiform arthrodesis with midcuboid osteotomy.
The results of naviculocuneiform arthrodesis with midcuboid osteotomy for correction of talipes equino valgus are presented. Criteria for this procedure are developed. Overall efficacy of this technique is questioned.


Characteristic analysis of volatile avalanche diode threshold switching for bionic nerve synapse applications.
The combination of biological neurology and memristive theory has greatly promoted the development of neuromorphic computing. To build a large-scale artificial intelligence alert system, the exploration of bionic synapses compatible with standard processes has become an urgent problem to be solved in the next step. In response to the above application requirements, this paper proposes a volatile avalanche diode threshold switching (VADTS) that is fully compatible with standard semiconductor technology to simulate the various functions of the synapse. Technology computer-aided design device-level simulation can verify the bionic principle of VADTS. The function of VADTS's bionic synapse was verified by the experimental test platform. The results show that under the action of the excitation signal (11.25 V), the device can continuously change from a high-resistance state to a low-resistance state. When the excitation signal is lower than the threshold, VADTS presents a "no adaptation" state of nerve synapses. When the excitation signal is higher than the threshold and changes continuously, the current changes along with the amplitude of the excitation signal, similar to the "sensitization" state of the nerve synapse.


Pregnancy after breast cancer: a case study resolving the reproductive challenge with a gestational surrogate.
Pregnancy and fertility issues are substantial concerns for the young breast cancer survivor, yet the available literature is hampered by a lack of prospective clinical studies and meaningful long-term outcome data. A lack of reliable information often leads to physician discomfort and patients may be left to navigate the world of fertility preservation and reproductive technology on their own. This case exemplifies some of the many issues that breast cancer survivors may face and adds another dimension to the survivor's dilemma; once fertility options have been preserved, what is the best method to sustain the pregnancy--self or surrogate? For many, the goal of balancing optimal treatment and long-term survival with restoration of a complete quality of life, including childbearing, may be attainable. This discussion highlights the importance of offering young breast cancer patients an opportunity to discuss these issues with their health care providers prior to initiating therapy.


Brain-stem auditory evoked potentials in rats with high-dose pentobarbital.
Brain-stem auditory evoked potentials (BAEPs) are relatively resistant to alteration by barbiturate drugs, but the effects of the high doses that are used clinically to produce deep barbiturate coma for the treatment of intracranial hypertension and postischemic anoxic encephalopathy on BAEPs are unknown. We gave high-dose pentobarbital infusions to mechanically ventilated rats while recording serial BAEPs from the scalp. Pentobarbital progressively suppressed and then abolished all peaks. First the later waves, then all but the first wave, and finally all waves were abolished at intravenous doses of 120, 220, and 260 mg/kg, respectively, in addition to the initial anesthetic dose of 60 mg/kg i.p. The changes were at least partially reversible; peaks returned in reverse order of their disappearance. Peak latencies increased with dose. The results show a significant effect of pentobarbital on BAEPs in the rat, suggesting that BAEPs may be useful in assessing the depth of and recovery from barbiturate coma.


The myristoyl-electrostatic switch: a modulator of reversible protein-membrane interactions.
Hydrophobic insertion of the acyl chain into the bilayer is necessary but not sufficient for the membrane binding of a myristoylated protein. The myristoylated alanine-rich C kinase substrate (MARCKS), Src, ADP-ribosylation factor and human immunodeficiency virus-1 matrix proteins also contain a cluster of basic residues that bind to acidic phospholipids; the hydrophobic and electrostatic interactions act together to anchor the protein to a membrane. For MARCKS, and perhaps other proteins, phosphorylation of serines within its basic cluster reduces the electrostatic attraction, producing translocation of the protein from the membrane to the cytosol by a simple 'electrostatic switch' mechanism.


Implementation of the Tallinn Charter in the WHO European region: where is the evidence? A systematic comparison of online information before and after the end of the year of signature.
The "Tallinn Charter: Health Systems, Health and Wealth" signed by 53 member states of the WHO European Region provides guidance for strengthening health systems. A systematic search was conducted to compare studies and actions related to the commitments of the Tallinn Charter. Target keywords were identified directly from the Charter. Structured web search was conducted on Pubmed/Google. Results for 2007-2010 were analyzed as frequencies before/after the end of the year of signature and classified by relevance and category of content. Searches for 2007-2010 extracted N=717 papers in Medline and N=634 links in Google using combined keywords. Additional N=165 direct links to the Charter were found by Google for 2008-2010. An increase by 18% (scientific literature) and 10% (grey literature) was observed after 2008. The number of conceptual, methodological, analytical or system evaluation reports related to the themes of the Charter increased after 2008, while benchmarking and cross-country comparisons were less frequent. Opposite trends were observed for the grey literature. The implementation of the Tallinn Charter is supported by more information available on the topic. The methodology used to perform a rapid search may be usefully repeated to monitor the process.


Heartbeat classification based on single lead-II ECG using deep learning.
The analysis and processing of electrocardiogram (ECG) signals is a vital step in the diagnosis of cardiovascular disease. ECG offers a non-invasive and risk-free method for monitoring the electrical activity of the heart that can assist in predicting and diagnosing heart diseases. The manual interpretation of the ECG signals, however, can be challenging and time-consuming even for experts. Machine learning techniques are increasingly being utilized to support the research and development of automatic ECG classification, which has emerged as a prominent area of study. In this paper, we propose a deep neural network model with residual blocks (DNN-RB) to classify cardiac cycles into six ECG beat classes. The MIT-BIH dataset was used to validate the model resulting in a test accuracy of 99.51%, average sensitivity of 99.7%, and average specificity of 98.2%. The DNN-RB method has achieved higher accuracy than other state-of-the-art algorithms tested on the same dataset. The proposed method is effective in the automatic classification of ECG signals and can be used for both clinical and out-of-hospital monitoring and classification combined with a single-lead mobile ECG device. The method has also been integrated into a web application designed to accept digital ECG beats as input for analyses and to display diagnostic results.


Effects of non-linear resistance training and curcumin supplementation on the liver biochemical markers levels and structure in older women with non-alcoholic fatty liver disease.
With increasing age, non-alcoholic fatty liver disease is very common among women with low levels of physical activity. Nonlinear resistance training is one of the new methods to help patients who have low levels of physical activity. Curcumin is an herbal supplement that has anti-inflammatory effects. The present study aimed to examine the effects of nonlinear resistance training and curcumin supplementation on the liver structure and biochemical markers in obese older women with non-alcoholic fatty liver disease. Forty-five obese women with non-alcoholic fatty liver disease were randomly assigned into resistance training (RT), curcumin supplement (C), resistance training with curcumin supplement (RTC), and placebo (P) groups. The RT and RTC groups received 12-weeks of nonlinear resistance training while the C and P groups had a normal sedentary lifestyle. Daily, the C and RTC groups received a curcumin capsule while the P and RT groups were given a placebo capsule. Blood sampling and ultrasonography were taken before and after the protocol. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels significantly decreased in the RT and RTC groups (P ≤ 0.05) but not in the C and P groups (P > 0.05). Alkaline phosphatase (ALP), total bilirubin (TB) levels, platelet counts (PLT), and liver structure did not significantly change in all groups (P > 0.05). Resistance training alone and with curcumin supplementation could significantly improve liver function while taking curcumin alone did not have any significant effect on it. 12-week non-linear resistance training has beneficial effects on non-alcoholic fatty liver disease in older obese women.


Localization of human supratemporal auditory areas from intracerebral auditory evoked potentials using distributed source models.
While source localization methods are increasingly developed to identify brain areas underlying scalp electro/magnetoencephalographic data (EEG/MEG), these methods have not yet been used to identify the sources of intracerebral signals which offer highly detailed information. Here, we adapted the minimum current estimates method to intracranial data in order to localize supratemporal sources of intracerebral auditory 1-kHz-tone-evoked potentials occurring within 100 ms after stimulus onset. After an evaluation of localization method and despite inter-subject variability, we found a common spatiotemporal pattern of activities, which involved the first Heschl's gyrus (H1) and sulcus (HS), the Planum Temporale (PT), H2/H3 when present, and the superior temporal gyrus (STG). Four time periods of activity were distinguished, corresponding to the time range of the scalp components P0, Na, Pa/Pb, and N100. The sources of the earliest components P0 (16-19 ms) and Na (20-25 ms) could be identified in the postero-medial portion of HS or H1. Then, several areas became simultaneously active after 25 ms. The Pa/Pb time range (30-50 ms) was characterized by a medio-lateral and postero-anterior propagation of activity over the supratemporal plane involving successively H1/HS, the Planum Temporale, H2/H3 when present, and the STG. Finally, we found to a large extent that the N100 (55-100 ms) involved almost the same areas as those active during the Pa/Pb complex, with a similar propagation of activities. Reconstructing scalp data from these sources on fictive EEG/MEG channels reproduced classical auditory evoked waveforms and topographies. In conclusion, the spatiotemporal pattern of activation of supratemporal auditory areas could be identified on the individual anatomy using current estimates from intracerebral data. Such detailed localization approach could also be used prior to epilepsy surgery to help identify epileptogenic foci and preserve functional cortical areas.


Molecular docking, antiproliferative and anticonvulsant activities of swertiamarin isolated from Enicostemma axillare.
Present study aimed for molecular docking, antiproliferative and anticonvulsant activities of swertiamarin isolated from the successive methanol extract of Enicostemma axillare. Molecular docking of swertiamarin on telomerase targets (PDB ID: 5UGW, 3DU6 and 4ERD), followed by antiproliferative activity on HEp2 and HT-29 cells by MTT and SRB assays. Also tested for anticonvulsant activity by pentylenetetrazole (PTZ, 80 mg/kg bw) induced convulsant. Molecular docking study predicted good total score of the swertiamarin with the selected targets. Swertiamarin possesses antiproliferative activity on HEp-2 and HT-29 cells with lower CTC50 values. It also served as significant anticonvulsant agent with prolonged onset and reduced duration of the seizures. These results confirm that swertiamarin exhibited potential antiproliferative and anticonvulsant activities.


Variability of cut-off values for the detection of lupus anticoagulants: results of an international multicenter multiplatform study.
Essentials Between-lab variations of cut-off values in lupus anticoagulant detection are unknown. Cut-off values were calculated in 11 labs each testing plasma from 120 donors with 3 platforms. Major variation was observed even within the same platform. Cut-off values determined in different labs are not interchangeable. Background Cut-off values for interpretation of lupus anticoagulant (LA) detection are poorly investigated. Aims (i) To assess whether results from healthy donors were normally distributed and (ii) the between-laboratories differences in cut-off values for screening, mixing and LA confirmation when calculated as 99th or 95th centiles, and (iii) to assess their impact on the detection rate for LA. Methods Each of 11 laboratories using one of the three widely used commercial platforms for LA detection was asked to collect plasmas from 120 healthy donors and to perform screening, mixing and LA confirmation with two methods (activated partial thromboplastin time [APTT] and dilute Russell viper venom [dRVV]). A common set of LA-positive or LA-negative freeze-dried plasmas was used to assess the LA detection rate. Results were centralized (Milano) for statistical analysis. Results and conclusions (i) Clotting times or ratios for healthy subjects were not normally distributed in the majority of cases. The take-home message is that cut-off values should be determined preferably by the non-parametric method based on centiles. (ii) There were relatively large inter-laboratory cut-off variations even within the same platform and the variability was marginally attenuated when results were expressed as ratios (test-to-normal pooled plasma). The take-home message is that cut-off values should be determined locally. (iii) There were differences between cut-off values calculated as 99th or 95th centiles that translate into a different LA detection rate (the lower the centile the greater the detection rate). The take-home message is that cut-off values determined as the 95th centile allow a better LA detection rate.


Brain TRPV1: a depressing TR(i)P down memory lane?
On sensory neurons, the capsaicin receptor TRPV1 (transient receptor potential, vanilloid subfamily, member 1) functions as a molecular integrator of noxious stimuli and represents a novel target for analgesic drugs. The presence of TRPV1 in the brain is now well established but, despite intensive research, its function is only beginning to be understood. New evidence implies an unexpected role for hippocampal TRPV1 in neuropsychiatric disorders. For instance, it was hypothesized that the effects of the cannabinoid-receptor antagonist rimonabant on mood might be due to its capability to antagonize TRPV1 receptors at high doses. Most studies, however, imply a positive (e.g. anxiolytic) outcome for TRPV1 antagonism. With potent small-molecule TRPV1 antagonists undergoing clinical trials, the effect of brain TRPV1 blockade might determine the future of this class of novel analgesic drugs. Clearly, more research is needed to delineate the biological role of brain TRPV1 receptors.


The influence of pulsatile perfusion on oxygen uptake by the isolated canine hind limb.
The possible advantages of pulsatile over continuous blood flow have intrigued cardiac surgeons for years. This issue may have clinical significance for moderate to long cardiopulmonary bypass procedures. In spite of aggressive investigation, this problem remains controversial. A system permitting perfusion of an isolated canine hind limb with constant flow, Pao2, Paco2, oxygen delivery, temperature, and pHa but variable stroke volume was established. Under stable conditions, oxygen uptake by the limb was constant over a wide range of stroke volumes. Regression equations relating oxygen uptake to stroke volume were calculated and found to have a near zero slope. When the hydrogen ion concentration of the blood perfusing tissue is held constant, the oxygen consumption of that tissue is independent of the pulsatile nature of the perfusing blood.


[Evaluation of matrix metalloproteinases (pro-MMP-1, MMP-2,8) and their inhibitor (TIMP-1) contents in patients with occupational lung diseases].
Studies of matrix metalloproteinases in patients with occupational bronchopulmonary diseases and in individuals exposed to asbestos dust revealed hyperactivated protease system--lower level of MMP-1 proenzyme and increased production of TIMP-1 (metalloproteinases inhibitor)--in all the examinees groups. Patients with pneumoconiosis and occupational dust bronchitis demonstrated increased neutrophilic elastase that is activator of metalloproteinases inducing sclerotic changes and pulmonary fibrosis.


Rewriting the lignin roadmap.
Considerable interest in lignin biosynthesis has been fueled by the many roles that lignin plays in development and in resistance to biotic and abiotic stress, as well as its importance to industry and agriculture. Although the pathway leading to the lignin polymer has been studied for decades, new insights into the enzymes of the pathway have required a complete re-evaluation of how we think lignin precursors are synthesized. Although free hydroxycinnamic acids have long been thought to be key intermediates, it has become apparent that many of the hydroxylation and methylation steps in the pathway occur instead at the level of hydroxycinnamic acid esters, and their corresponding aldehydes and alcohols.


Identification and Characterization of Intraoral and Dermal Fibroblasts Revisited.
Fibroblasts are the common cells used in clinical regenerative medicine and dentistry. These cells are known to appear heterogeneous in vivo. Previous studies have only investigated the biological properties of these cell subpopulations in vitro. Despite sharing similarity in their spindle-shaped appearance, previous literatures revealed that they play distinguished functional and biological activities in the body. This paper highlights the similarities and differences among these cell subpopulations, particularly between intraoral fibroblasts (human periodontal ligament, gingival and oral mucosa fibroblasts) and dermal fibroblasts based on several factors including their morphology, growth and proliferation rate. It could be suggested that each subpopulation of fibroblasts demonstrate different positionspecified gene signatures and responses towards extracellular signals. These dissimilarities are crucial to be taken into consideration to employ specific methodologies in stimulating these cells in vivo. A comparison of the characteristics of these cell subpopulations is desired for identifying appropriate cellular applications.


Recombinant Neorudin for the Prevention of Deep-Vein Thrombosis After Spinal-Cord Injury.
Whether anticoagulant therapy should be used after spinal-cord injury (SCI) surgery was controversial. The anticoagulation characteristics of a newly developed anticoagulant, recombinant neorudin (EPR-hirudin (EH)), were explored using a rat model of SCI to provide a basis for clinical anticoagulation therapy of SCI. A rat model of SCI was developed by Allen's method. Then, thrombosis in the inferior vena cava was induced by ligation. The low-bleeding characteristics of EH were explored by investigating dose-response and time-effect relationships, as well as multiple administration of EH, on thrombus formation complicated with SCI. EH inhibited thrombosis in a dose-dependent manner by reducing the wet weight and dry weight of the thrombus. An inhibiting action of EH on thrombosis was most evident in the group given EH 2 h after SCI. After multiple intravenous doses of EH, thrombosis inhibition was improved to that observed with low molecular weight heparin (LMWH) (87% vs 90%). EH administration after SCI neither increased bleeding in the injured spine nor damaged to nerve function. Bleeding duration and activated partial thromboplastin time were increased in the high-dose EH group compared with that in the normal-saline group, but were lower than those in the LMWH group. EH can reduce thrombus formation in a rat model of SCI, and bleeding is decreased significantly compared with that using LMWH. EH may prevent thrombosis after SCI or spinal surgery.


Occurrence and removal of PPCPs from on-site wastewater using nitrogen removing biofilters.
The presence of pharmaceuticals and personal care products (PPCPs) in the environment is primarily the result of discharge of waste, including from onsite wastewater treatment systems (OWTSs) which are employed by 25% of homes in the United States. However, the occurrence and removal of PPCPs in OWTSs is not well understood, particularly given the large diversity in PPCP compounds as well as in OWTS designs. In this study, we monitored 26 different PPCPs in 13 full-scale nitrogen removing biofilters (NRBs), an innovative/alternative type of OWTS that utilizes an overlying sand layer and an underlying woodchip/sand layer to simultaneously remove nitrogen and other wastewater-derived contaminants. The specific objectives of this study were (i) to measure the occurrence of PPCPs in septic tank effluent (STE) that served as an influent to NRBs, (ii) to quantify PPCP removal in three types of NRB configurations (n = 13), and (iii) to evaluate PPCP removal with depth and environmental conditions in NRBs. Aqueous samples were taken during 42 separate sampling events during 2016 - 2019 and analyzed by liquid chromatography tandem mass spectrometry. Analysis of the STE samples yielded detection of 23 of the 26 PPCPs, with caffeine being the most abundant and frequently detected compound at 52,000 ng/L (range: 190 - 181,000 ng/L), followed by acetaminophen and paraxanthine at 47,500 ng/L (190 - 160,000 ng/L), and 34,300 ng/L (430 - 210,000 ng/L), respectively. Cimetidine, fenofibrate, and warfarin were the only compounds not detected. The average removal of PPCPs by NRBs ranged from 58% to >99% for the various compounds. PPCP removal as a function of depth in the systems showed that 50 to >99% of the observed removal was achieved within the top oxic layer (0 - 46 cm) of the NRBs for 19 analytes. Seven of the compounds had >85% removal by the same depth. These results indicate that NRBs are effective at removing PPCPs and that a large portion of the removal is achieved within the oxic nitrifying layer of the NRBs. Overall, the removal of PPCPs in NRBs was comparable (n = 8) or better (n = 15) than that observed for conventional wastewater treatment plants.


Effects of caloric restriction on inflammatory periodontal disease.
Dietary caloric restriction (CR) has been found to reduce systemic markers of inflammation and may attenuate the effects of chronic inflammatory conditions. The purpose of this study was to examine the effects of long-term CR on naturally occurring chronic inflammatory periodontal disease in a nonhuman primate model. The effects of long-term CR on extent and severity of naturally occurring chronic periodontal disease, local inflammatory and immune responses, and periodontal microbiology, were evaluated in a cohort of 81 (35 female and 46 male; 13-40 y of age) rhesus monkeys (Macaca mulatta) with no previous exposure to routine oral hygiene. CR monkeys had been subjected to 30% CR for 13-17 y relative to control-fed (CON) animals starting at 3-5 y of age. Same sex CR and CON monkeys exhibited similar levels of plaque, calculus, and bleeding on probing. Among CON animals, males showed significantly greater periodontal breakdown, as reflected by higher mean clinical attachment level and periodontal probing depth scores, than females. CR males exhibited significantly less periodontal pocketing, lower IgG antibody response, and lower IL-8 and ss-glucuronidase levels compared to CON males, whereas CR females showed a lower IgG antibody response but comparable clinical parameters and inflammatory marker levels relative to CON females. Long-term CR had no demonstrable effect on the periodontal microbiota. Males demonstrated greater risk for naturally occurring periodontal disease than females. Long-term CR may differentially reduce the production of local inflammatory mediators and risk for inflammatory periodontal disease among males but not females.


Pediatrician perspectives on symptom presentation and treatment of acute allergic reactions.
Anaphylaxis remains difficult to diagnose and epinephrine underused. To better understand the thoughts of pediatricians regarding when acute allergic reactions constitute anaphylaxis and when epinephrine should be given by conducting an anonymous online survey. The survey consisted of 8 case-based scenarios of allergic reactions with the following 2 questions on each case: (1) does this case represent anaphylaxis? and (2) if this patient immediately presented to you, would you treat the patient with epinephrine during the reaction? A total of 1001 responses were analyzed. When assessing all cases combined, there was discordance in whether a case represented anaphylaxis and administration of epinephrine was warranted in 8% of the cases. An average of 5% of all the respondents suggested that the case represented anaphylaxis but would not warrant epinephrine, whereas an average of 3% suggested that the case did not represent anaphylaxis but that epinephrine was warranted. The results of this survey reveal that there is discordance among pediatricians on when an allergic reaction is considered anaphylaxis and when epinephrine is warranted. These data highlight the need for continued improvement of the definition of anaphylaxis and continued need for education regarding the diagnosis and management of anaphylaxis.


Patient teaching for elders.
There are many myths regarding elders' abilities to learn, which may affect the nurse's approach to the older person during patient teaching. Physiological changes of aging have an effect on learning and must be considered by the nurse when a teaching plan is developed. The older person has the capability to learn and probably will do so when the time is right, when the plan is right, and when motivated to learn. Learning is facilitated by a one-to-one encounter, but also may occur in a group or community setting.


Loss of the Incretin Effect in Type 2 Diabetes: A Systematic Review and Meta-analysis.
Loss of the incretin effect (IE) in type 2 diabetes (T2D) contributes to hyperglycemia and the mechanisms underlying this impairment are unclear. To quantify the IE impairment in T2D and to investigate the factors associated with it using a meta-analytic approach. PubMed, Scopus, and Web-of-Science were searched. Studies measuring IE by the gold-standard protocol employing an oral glucose tolerance test (OGTT) and an intravenous glucose infusion at matched glucose levels were selected. We extracted IE, sex, age, body mass index (BMI), and hemoglobin A1c, fasting values, and area under curve (AUC) of glucose, insulin, C-peptide, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1). In subjects with T2D, we also recorded T2D duration, age at diagnosis, and the percentage of subjects taking antidiabetic medications. The IE weighted mean difference between subjects with T2D and those with normal glucose tolerance (NGT) was -27.3% (CI -36.5% to -18.1%; P < .001; I2 = 86.6%) and was affected by age (P < .005). By meta-regression of combined NGT and T2D data, IE was inversely associated with glucose tolerance (lower IE in T2D), BMI, and fasting GIP (P < .05). By meta-regression of T2D studies only, IE was associated with the OGTT glucose dose (P < .0001). IE from insulin was larger than IE from C-peptide (weighted mean difference 11.2%, CI 9.2-13.2%; P < .0001; I2 = 28.1%); the IE difference was inversely associated with glucose tolerance and fasting glucose. The IE impairment in T2D vs NGT is consistent though considerably variable, age being a possible factor affecting the IE difference. Glucose tolerance, BMI, and fasting GIP are independently associated with IE; in subjects with T2D only, the OGTT dose is a significant covariate.


Putative acidic amino acid transmitters in the cerebellum. II. Electron microscopic localization of transport sites.
In structurally preserved cerebellar slices, the sites of high affinity uptake of acidic amino acids were analyzed using the nonmetabolizable analogue, D-[3H]aspartate. Electron microscopic autoradiography showed the greatest accumulation of grains to be over glial structures. The labelling of the perikarya, dendrites and axons of the putatively glutamatergic granule cells was very low. However, "hypothetical grain" analysis indicated that the terminals of these cells are probable sources of radioactivity even though they contained less than 9% of the total grains in the molecular layer. The resolution of the autoradiographic technique did not permit definitive conclusion, as the parallel fibre terminals are too small and are ensheathed by thin glial processes. Nevertheless, further supporting evidence for some D-[3H]aspartate uptake into parallel fibre terminals was obtained using mechanically chopped cerebellar slices in which compared with glia presynaptic structures are selectively preserved. It is concluded that in line with hypotheses relating to the compartmentation of glutamate metabolism, the principal sites of uptake of acidic amino acids in the cerebellum are the glial cells. The results have clear implications regarding the use of high affinity uptake as a marker for glutamatergic nerve terminals.


The impact of nurse short message services and telephone follow-ups on diabetic adherence: which one is more effective?
To compare the effectiveness of two methods of follow-up: short message service and telephone follow-up on type 2 diabetes adherence for three months. Using telemedicine approaches may preserve appropriate blood glucose levels and may improve adherence to diabetes control recommendations in diabetic patients. A quasi-experimental, two-group, pretest and post-test design was used in this study to evaluate the effectiveness of nurse's follow-up via cellular phones and telephones. The sample consisted of 77 patients with type 2 diabetes that randomly were assigned to two groups: telephone follow-up (n = 39) and short message service (n = 38). Telephone interventions were applied by a researcher for three months; twice a week for the first month and every week for the second and third month. For three successive months, the short message service group that received messages about adherence to therapeutic regimen was examined. The data gathering instrument included data sheets - to record glycosylated haemoglobin - and the questionnaire related to adherence therapeutic regimen. Data gathering was carried out at the beginning of the study and after three and six months. The data were analysed using descriptive and inferential statistic methods with SPSS version 11.5. Results showed that both interventions had significant mean changes in glycosylated haemoglobin. For the telephone group (p < 0.001), a mean change of -0.93 and for the short message service group (p < 0.001), a mean change of -1.01. There was no significant difference in diet adherence (p = 0.000), physical exercise (p = 0.000) and medication taking (p = 0.000) adherence in either groups. Intervention using short message services of cellular phones and nurse-led-telephone follow-up improved HbA1c levels and adherence to diabetes therapeutic regimen for three months in type 2 diabetic patients. Both of follow-up intervention uses in this study can decrease HbA1c levels and escalate adherence to diabetes control recommendations in people with type 2 diabetes for three months.


Study of enzyme inhibitors in the rheumatoid pannus-cartilage area.
Immunoperoxidase studies were carried out on the pannus-cartilage junction (PCJ) of patients with rheumatoid arthritis (RA) and psoriatic arthritis to investigate the distribution of the enzyme inhibitors alpha 2 macroglobulin (alpha 2 M) and alpha 1 antitrypsin (alpha 1 AT). Comparisons were made with the equivalent synovial cartilage junctional area in osteoarthritis (OA). In all 12 patients with RA, prominent deposits of alpha 2 M and alpha 1 AT were found within the PCJ whereas in OA patients and the case of psoriatic arthritis fewer or no deposits were seen. Inhibitors were localised in pannus synovial lining cells, perivascular inflammatory cells, macrophage and fibroblast-like cells invading the cartilage as well as along the junctional cartilage matrix and in the adjacent pannus-free cartilage. Deposits of immunoglobulins were found in similar areas to enzyme inhibitors. The presence of enzyme inhibitors at the PCJ suggests that this area is not unprotected against enzymatic attack. Thus the concept that pannus is a prime area for cartilage damage because aggressive, invasive cells release destructive enzymes in an environment free from inhibitors should be reviewed.


Trends in mortality for cancers, comparing multiple- and underlying-cause rates, in an English population 1979-1999.
In compiling official mortality statistics, rules for selecting the underlying cause of death have changed twice in the last 20 years in England. Mortality statistics for most types of cancer were not greatly affected, but there were significant effects on coding for cancers of colon, liver, breast, prostate, testis and bladder, and for lymphoma and leukaemia.


Positive fallout from the bomb.
Atmospheric isotopes left behind by atomic weapons tests provide the foundation for an unusual method for determining the age and turnover rate of human cells.


Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism.
Inflammation, a common denominator among the diverse list of neurodegenerative diseases, has recently been implicated as a critical mechanism responsible for the progressive nature of neurodegeneration. Microglia are the resident innate immune cells in the central nervous system and produce a barrage of factors (IL-1, TNFalpha, NO, PGE2, superoxide) that are toxic to neurons. Evidence supports that the unregulated activation of microglia in response to environmental toxins, endogenous proteins, and neuronal death results in the production of toxic factors that propagate neuronal injury. In the following review, we discuss the common thread of microglial activation across numerous neurodegenerative diseases, define current perceptions of how microglia are damaging neurons, and explain how the microglial response to neuronal damage results in a self-propelling cycle of neuron death.


Induction chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus: impact of increased dosage on long-term results.
This study analyzed the impact on long-term results of an increase in the dosage of an induction chemoradiotherapy protocol for squamous cell carcinoma (SCC) of the thoracic esophagus. Two groups were considered among 177 patients who underwent preoperative chemoradiotherapy for SCC of the thoracic esophagus. Group A includes 111 patients (from 1987 to 1995) who were submitted to cisplatin and 5-fluorouracil (two cycles) and radiotherapy (3,000 cGy). Group B includes 66 patients (from 1995 to 2002) in which the doses were raised both in terms of chemotherapy (three cycles) and radiotherapy (5,000 cGy). The induction treatment was completed in most of the patients (92.1%) with an acceptable treatment-related mortality (2.6%). Surgery was accomplished in 148 patients; 78.4% and 92.4% in groups A and B, respectively (p = 0.015). The postoperative in-hospital mortality was 8.8%. Tumor resection was possible in 91.8% with a better R0-resection rate for group B (83.9%; p = 0.004). Responders represented 34.9% of the patients with 20.1% of "complete" responses (29.5% in group B; p = 0.018). The overall 5-year survival rate was improved in group B (30.2%; p = 0.017), and when survival analysis was restricted to responders (70.1%; p = 0.027). No differences in feasibility and complication rate were observed during the two study periods. A higher rate of R0-resections was achieved in group B. The increased dosage led to an increased rate of complete responses and to an improved overall 5-year survival.


Identification of a scavenger receptor homologue on nonspecific cytotoxic cells and evidence for binding to oligodeoxyguanosine.
In mammals scavenger receptors (SR) are expressed by monocytic-macrophage lineage cells and B-cells. Studies of various teleost species have indirectly demonstrated the presence of SR receptors on phagocytic or endothelial cells by showing the uptake of SR ligands (i.e. derivatised (acetylated) lipoproteins) by these cells. In the present study, nonspecific cytotoxic cells (NCC) were examined for membrane expression of an SR-like protein. Approximately 15-25% of purified NCC expressed scavenger receptor class A (SR-A) demonstrated by binding by a monoclonal (2F8) specific for mouse SR-A (types I, II). Flow cytometric analysis determined that SR binding cells had the same size and 'side scatter' characteristics as NCC. Two colour flow analysis of NCC demonstrated that only a subset of NCC expressed the SR-A-like protein and non-NCC were SR-A negative. Membrane expression of SR on NCC was confirmed by fluorescence microscopy. Analysis of the tissue distribution of SR bearing cells demonstrated that in both catfish and tilapia, SR-A was expressed by NCC in the peripheral blood, spleen and anterior kidney. Experiments were also done to determine if the ligands known to bind mammalian SR-A had a similar specificity for the teleost receptor. Cold competition binding experiments determined that anti-SR-A antibody competed with and reduced biotinylated polyguanosine 20-mer binding to NCC by approximately 40%. Two other types of ligands known to bind (mammalian) SR-A (i.e. polyvinyl sulphate and dextran sulphate) likewise decreased anti-SR-A antibody binding to NCC by 40%. These studies for the first time demonstrated that NCC express the teleost orthologue of mammalian SR-A, suggesting that NCC may participate in physiologic regulation of lipid metabolism in addition to functions of innate immunity.


Structural mimicry of a-loop tyrosine phosphorylation by a pathogenic FGF receptor 3 mutation.
The K650E gain-of-function mutation in the tyrosine kinase domain of FGF receptor 3 (FGFR3) causes Thanatophoric Dysplasia type II, a neonatal lethal congenital dwarfism syndrome, and when acquired somatically, it contributes to carcinogenesis. In this report, we determine the crystal structure of the FGFR3 kinase domain harboring this pathogenic mutation and show that the mutation introduces a network of intramolecular hydrogen bonds to stabilize the active-state conformation. In the crystal, the mutant FGFR3 kinases are caught in the act of trans-phosphorylation on a kinase insert autophosphorylation site, emphasizing the fact that the K650E mutation circumvents the requirement for A-loop tyrosine phosphorylation in kinase activation. Analysis of this trans-phosphorylation complex sheds light onto the determinants of tyrosine trans-phosphorylation specificity. We propose that the targeted inhibition of this pathogenic FGFR3 kinase may be achievable by small molecule kinase inhibitors that selectively bind the active-state conformation of FGFR3 kinase.


Phenotype and function of dendritic cells of patients with systemic lupus erythematosus.
Dendritic cells (DC) regulate the activation and differentiation of T cells. They are activated by signals of inflammation and tissue damage, and thus could play a role in the amplification and perpetuation of autoimmune diseases such as systemic lupus erythematosus (SLE). Here we analyzed the phenotype of circulating DC from patients with SLE and studied their differentiation from monocytes. Peripheral blood DC exhibited increased levels of activation in patients with SLE. Although their in vitro differentiation process occurred normally, their responses to activation stimuli (LPS, TNF-α plus PGE(2), anti-CD40) were abnormal when compared to DC differentiated from healthy monocytes. When incubated in the presence of IL-10, DC from patients with SLE were able to induce tolerance to allogeneic antigens in a normal manner. Our results suggest that DC from patients with SLE are abnormal, in part due to the effect of abundant pro-inflammatory signals, but also because of intrinsic cellular defects that alter their responses to activation stimuli.


Self-initiated conversion of paroxysmal atrial flutter utilizing a radio-frequency pacemaker.
A patient is described with drug-resistant recurrent paroxysmal atrial flutter. Electrophysiologic studies demonstrated that flutter was inducible with rapid atrial stimulation (stimulation rates of 375 to 400/min) and convertible with rapid atrial stimulation (rates of 400 to 460/min). Because of the latter response, a radio-frequency atrial pacemaker was implanted, which allowed self-initiated conversion of flutter episodes with rapid stimulation.


Extragonadal germ-cell tumours.
The case histories of two patients with an extragonadal germ-cell tumour are discussed. One had a retroperitoneal embryonal carcinoma, and the other had a mediastinal choriocarcinoma-seminoma. The pathogenesis, symptomatology, diagnosis and treatment of these rare tumours are discussed in some detail.?


Molecular Signature Predictive of Long-Term Liver Fibrosis Progression to Inform Antifibrotic Drug Development.
There is a major unmet need to assess the prognostic impact of antifibrotics in clinical trials because of the slow rate of liver fibrosis progression. We aimed to develop a surrogate biomarker to predict future fibrosis progression. A fibrosis progression signature (FPS) was defined to predict fibrosis progression within 5 years in patients with hepatitis C virus and nonalcoholic fatty liver disease (NAFLD) with no to minimal fibrosis at baseline (n = 421) and was validated in an independent NAFLD cohort (n = 78). The FPS was used to assess response to 13 candidate antifibrotics in organotypic ex vivo cultures of clinical fibrotic liver tissues (n = 78) and cenicriviroc in patients with nonalcoholic steatohepatitis enrolled in a clinical trial (n = 19, NCT02217475). A serum protein-based surrogate FPS was developed and tested in a cohort of compensated cirrhosis patients (n = 122). A 20-gene FPS was defined and validated in an independent NAFLD cohort (adjusted odds ratio, 10.93; area under the receiver operating characteristic curve, 0.86). Among computationally inferred fibrosis-driving FPS genes, BCL2 was confirmed as a potential pharmacologic target using clinical liver tissues. Systematic ex vivo evaluation of 13 candidate antifibrotics identified rational combination therapies based on epigallocatechin gallate, which were validated for enhanced antifibrotic effect in ex vivo culture of clinical liver tissues. In patients with nonalcoholic steatohepatitis treated with cenicriviroc, FPS modulation was associated with 1-year fibrosis improvement accompanied by suppression of the E2F pathway. Induction of the PPARα pathway was absent in patients without fibrosis improvement, suggesting a benefit of combining PPARα agonism to improve the antifibrotic efficacy of cenicriviroc. A 7-protein serum protein-based surrogate FPS was associated with the development of decompensation in cirrhosis patients. The FPS predicts long-term fibrosis progression in an etiology-agnostic manner, which can inform antifibrotic drug development.


Activation of adenosine A2 receptors enhances high K(+)-evoked taurine release from rat hippocampus: a microdialysis study.
The present study was designed to examine which type of adenosine receptors was involved in enhancement of high K(+)-evoked taurine release from in vivo rat hippocampus using microdialysis. Perfusion with 0.5 or 5.0 mM adenosine enhanced high K(+)-evoked taurine release. Perfusion with 2 microM R(-)-N6-2-phenylisopropyladenosine (PIA), a selective adenosine A1 receptor agonist, did not modulate taurine release. Perfusion with 1 microM 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective adenosine A1 receptor antagonist, increased taurine release. On the other hand, perfusion with 20 microM 2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethyl-carboxamide-adenos ine (CGS21680), a selective adenosine A2A receptor agonist, enhanced taurine release, while perfusion with 1 mM 3,7-dimethyl-propagylxanthine (DMPX), an adenosine A2 receptor antagonist, did not affect taurine release. These results demonstrate that adenosine enhances high K(+)-evoked taurine release via activation of adenosine A2A receptors from both neurons and glial cells of in vivo rat hippocampus.


Comment on 'Birdstrikes and barcoding: can DNA methods help make the airways safer?'.
GenBank is the database of record for public sequence data. Results reported in the scientific literature that are based on sequence data cannot be evaluated if the underlying data is not in the public record.


Effects of Extracellular pH on Dental Pulp Cells In Vitro.
The proliferation and migration of dental pulp stem cells (DPSCs), a population comprised of dental pulp cells (DPCs), are important processes for pulp tissue repair. Dental pulp is exposed to changes in extracellular pH under various conditions, such as acidosis and exposure to caries-associated bacteria or a pulp capping agent. The objective of this study was to investigate the effects of extracellular pH on DPC proliferation and migration in vitro. To evaluate the proliferation potency of DPCs in various extracellular pH conditions, 2 × 10(4) cells were seeded into 35-mm dishes. The following day, we changed to NaHCO3-free medium, which was adjusted to different extracellular pH levels. After 120 hours, DPCs cultured in media from a pH of 3.5 to 5.5 showed cell death, those cultured in conditions from a pH of 6.5 to 7.5 showed growth arrest or cell death, and those grown at a pH of 9.5 showed mild proliferation. The migratory activity of living DPCs was not affected by extracellular pH. For histologic analysis, human teeth possessing a small abscess in the coronal pulp chamber were sliced for histologic analysis. Proliferating cell nuclear antigen (PCNA) immunolocalization was used as an index of cell proliferation for the sections and cultured cells. Acidic extracellular pH conditions resulted in reduced numbers of PCNA-positive DPCs in the dishes. As for pulp tissue affected by a small abscess, a PCNA-negative pulp cell layer was observed in close proximity to the infectious lesion. Together, these results suggest that an acidic extracellular pH condition is associated with DPC growth arrest or cell death.


Effects of aspirin and indomethacin on cerebral circulation in the conscious rat: evidence for a physiological role of endogenous prostaglandins.
The purpose of this work was to evaluate the effects of equipotent doses of two different inhibitors of cyclo-oxygenase, indomethacin and aspirin, on cerebral blood flow and cerebral vascular resistances in the conscious undisturbed rat, using the reference sample radioactive microsphere method. We found that both, aspirin (50 mg/kg) and indomethacin (5 mg/kg) at 3, 15 and 60 min after their intravenous administration, increased cerebral vascular resistances and decreased cerebral blood flow to a similar extent. Both drugs completely abolished the hypotensive effect of 5 mg/kg i.v. arachidonic acid and they did not change arterial PO2, PCO2 or pH values. We conclude that the pharmacological inhibition of cyclooxygenase in the conscious undisturbed rat leads to a cerebral vasoconstriction and consequently to a decrease in cerebral blood flow. Our results evidence that prostaglandins are a physiological factor that actively contributes to the maintenance of cerebral circulation.


Catheter ablation of atrial fibrillation in patients with mechanical mitral valve: long-term outcome of single procedure of pulmonary vein antrum isolation with or without nonpulmonary vein trigger ablation.
It is unclear whether extended pulmonary vein antrum isolation (PVAI) plus nonpulmonary vein (non-PV) trigger elimination prevents more arrhythmia recurrence than PVAI alone in patients with mechanical mitral valve (MMV) undergoing AF ablation. This study compared the efficacy and long-term outcome of 2 ablation strategies--PVAI alone versus extended PVAI plus non-PV trigger elimination--for the treatment of AF in patients with MMV. One hundred and nine consecutive AF patients with MMV were divided into 2 groups: standard PVAI was performed in group 1 (N = 45); in group 2 (N = 64) PVAI was extended to the LA posterior wall, LA septum, and CS; and all non-PV triggers were eliminated. Patients were followed up for 3 years. At the 12th month, 7 (15.6%) patients in group 1, and 39 (60.9%) patients in group 2 were arrhythmia free (log-rank P < 0.001). Four patients (8.9%; 3 cases of AT and 1 case of AF) from group 1, and 12 patients (18.8%; 9 cases of AT, and 3 cases of AFL) from group 2 experienced very late recurrence. At 36 ± 7 months follow-up, the cumulative recurrence after a single procedure was 42/45 (93.3%) in group 1, and 37/64 (57.8%) in group 2 (log-rank P < 0.001). Compared with the standard PVAI alone, a strategy including extended PVAI and non-PV trigger elimination is associated with a higher 12-month and long-term arrhythmia-free survival in patients with MMV undergoing AF ablation. Very late recurrence may occur years after the initial procedure with focal AT as the most common type of recurrent arrhythmia.


Hmox1 is Identified as a Ferroptosis Hub Gene and Associated with the M1 Type Microglia/Macrophage Polarization in Spinal Cord Injury: Bioinformatics and Experimental Validation.
Ferroptosis and immune cell infiltration are important pathological events in spinal cord injury (SCI), but links between ferroptosis and immune microenvironment after SCI were rare reported. In our study, 77 FRDEGs were screened at 7 days after SCI. GO analysis of FRDEGs showed that aging (GO:0007568; P-value = 1.11E-05) was the most remarkable enriched for biological process, protein binding (GO:0005515; adjusted P-value = 4.44E-06) was the most significantly enriched for molecular function, cytosol (GO:0005829; adjusted P-value = 1.51E-04) was the most prominent enriched for cellular component. Meanwhile, Ferroptosis was significantly enriched both in KEGG (rno04216; adjusted P-value = 0.001) and GSEA (NES = 1.35; adjusted P-value = 0.004) analysis. Next, Hmox1 (Log2Fold change = 6.52; adjusted P-value = 0.004) was identified as one of hub genes in SCI-induced ferroptosis. In the results of immune cell infiltration analysis, proportion of microglia/macrophage was significantly increased after SCI, and Hmox1 was found to positively correlate to the M1 type microglia/macrophage abundance. Finally, effects of Hmox1 on ferroptosis and M1 type polarization were validated in vivo and in vitro. Summarily, we found that Hmox1 was the hub gene in SCI-induced ferroptosis and associated with the M1 type polarization.


Melatonin ameliorates hippocampal nitric oxide production and large conductance calcium-activated potassium channel activity in chronic intermittent hypoxia.
Melatonin protects against hippocampal injury induced by intermittent hypoxia (IH). IH-induced oxidative stress is associated with decreases in constitutive production of nitric oxide (NO) and in the activity of large conductance calcium-activated potassium (BK) channels in hippocampal neurons. We tested the hypothesis that administration of melatonin alleviates the NO deficit and impaired BK channel activity in the hippocampus of IH rats. Sprague-Dawley rats were injected with melatonin (10 mg/kg, i.p.) or vehicle before daily IH exposure for 8 hr for 7 days. The NO and intracellular calcium ([Ca2+]i) levels in the CA1 region of hippocampal slices were measured by electrochemical microsenor and spectrofluorometry, respectively. The activity of BK channels was recorded by patch-clamping electrophysiology in dissociated CA1 neurons. Malondialdehyde levels were increased in the hippocampus of hypoxic rats and were lowered by the melatonin treatment. Levels of NO under resting and hypoxic conditions, and the protein expression of neuronal NO synthase (nNOS) were significantly reduced in the CA1 neurons of hypoxic animals compared with the normoxic controls. These deficits were mitigated in the melatonin-treated hypoxic rats with an improved [Ca2+]i response to acute hypoxia. The open probability of BK channels was decreased in the hypoxic rats and was partially restored in the melatonin-treated animals, without alterations in the expression of channel subunits and unitary conductance. Acute treatment of melatonin had no significant effects on the BK channel activity or on the [Ca2+]i response to hypoxia. Collectively, these results suggest that melatonin ameliorates the constitutive NO production and BK channel activity via an antioxidant mechanism against an IH-induced down-regulation of nNOS expression in hippocampal neurons.


IABP-Related vascular complications: who is responsible--the patient, the surgeon or the sheath? Part I: sheath-related complications.
An intra-aortic balloon pump (IABP) is frequently used as a mechanical support during the treatment of low cardiac output syndrome. The use of a sheath during IABP treatment can be associated with ischaemic complications in the extremities. The aim of our study was to determine the isolated role of sheaths in the development of vascular complications following IABP catheterisation. We evaluated a total of 81 patients who had received an IABP for haemodynamic stability, between January 2003 and October 2007, following cardiovascular surgery. To eliminate surgical-related variables, only patients with IABPs and size 8.5 or 9 French catheters (inserted by experienced cardiovascular surgeons using the percutaneous Seldinger technique) were included in the study. To eliminate patient-related variables, patients with a known risk factor for either thrombosis, embolus or peripheral arterial disease were excluded from the study. The patients were divided into two groups: Group 1 (sheathed catheter group; n=42), Group 2 (sheathless catheter group; n=39). Ischaemic complications were observed in a total of five patients. Four of these patients were from Group 1 and one was from Group 2. Sheathed catheterisation was found to increase the risk of vascular complications in patients who underwent IABP application. Therefore sheathless catheterisation is recommended for IABP application.


Lesions of uncertain malignant potential in the breast (B3): what do we know?
Breast lesions classified as of uncertain malignant potential (B3) on biopsy form a diverse group of abnormalities, which pose a diagnostic and management challenge. In this paper, we discuss the imaging and pathology features as well as the management of the most controversial B3 lesions, consisting of papillary lesions, complex sclerosing lesions/radial scars, lobular intraepithelial neoplasia, and atypical epithelial proliferation of ductal type. As there is an association with malignancy at the time of diagnosis, as well as an increase in the risk of subsequent development of cancer, a multidisciplinary discussion is almost always required to tailor treatment.


Promotional etiology for common childhood acute lymphoblastic leukemia: the infective lymphoid recovery hypothesis.
This paper speculates on the role of infection in modifying a young child's risk of promoting precursor B-cell acute lymphoblastic leukemia (ALL). It is suggested that the heat shock instigated by infections, particularly in infancy, stimulates Th1 pro-inflammatory cytokines and an apoptosis-inhibitory environment. This infective stress also increases the number of cooperating oncogenic mutations in pre-leukemic cells, especially if the primary adaptive immune response is delayed. The glucocorticoid release that follows leads to acute thymic involution, a decline in antitumor immunity, and maturation arrest of B-lymphocytes. The infective lymphoid recovery hypothesis addresses an apparent contradiction-that a non-hygienic environment primes the adaptive immune response and is protective against childhood ALL, while multiple infections occurring later increase the risk of childhood ALL. In affluent (compared to less-affluent) societies, the characteristic ALL incidence peak in early childhood, and the shortened time to diagnosis, arise from surviving recurrent infections and the accumulated loss and recovery of lymphoid tissue. Evidence supporting the hypothesis, such as the role of lymphoid tissue reconstitution cytokines that stimulate proliferation stress on B-cell progenitors, comes from the study of children with congenital syndromes that are susceptible to leukemia.


Cerebral perfusion and neurological examination characterise neonatal opioid withdrawal syndrome: a prospective cohort study.
To test the hypothesis that cerebral blood flow (CBF) assessed with arterial spin labelling (ASL) MRI is increased and standardised neurological examination is altered in infants with neonatal opioid withdrawal syndrome (NOWS) compared with those without. Prospective cohort study. Level IV neonatal intensive care unit and outpatient primary care centre. Infants with NOWS receiving pharmacological treatment and unexposed controls matched for gestational age at birth and post-menstrual age at MRI. CBF assessed by ASL on non-sedated 3-Tesla MRI and standardised Hammersmith Neonatal Neurological Examination (HNNE) within 14 days of birth. Thirty infants with NOWS and 31 control infants were enrolled and included in the final analysis. Global CBF across the brain was higher in the NOWS group compared with controls (14.2 mL/100 g/min±5.5 vs 10.7 mL/100 g/min±4.3, mean±SD, Cohen's d=0.72). HNNE total optimality score was lower in the NOWS group compared with controls (25.9±3.6 vs 28.4±2.4, mean±SD, Cohen's d=0.81). A penalised logistic regression model including both CBF and HNNE items discriminated best between the two groups. Increased cerebral perfusion and neurological examination abnormalities characterise infants with NOWS compared with those without intrauterine drug exposure and suggest prenatal substance exposure affects fetal brain development. Identifying neurological and neuroimaging characteristics of infants with NOWS can contribute to understanding mechanisms underlying later outcomes and to designing potential new treatments.


Impact of prepubertal bovine ovarian tissue pre-freeze holding duration on follicle quality.
Ovarian tissue cryopreservation prior to gonadotoxic treatment is the only recommended option for fertility preservation in prepubertal girls. Due to the technical complexity of this technique, limited number of centres across the world are equipped to offer the facility. Hence, the retrieved ovarian tissue needs to be maintained at hypothermic temperature (4 °C) for long time during shipment. The time taken between tissue retrieval and cryopreservation could influence the functionality of cells during fertility restoration. This study explored the tissue integrity and follicle quality of ovarian cortical slices subjected to pre-freeze holding for various time durations in vitro. Prepubertal bovine ovarian tissue from < 12 months old animals were handled at hypothermic holding (4 °C) for 0, 24, 48 and 72 h. The tissues were assessed for follicle viability through confocal analysis of live-dead labelled samples, and follicle quality and tissue integrity through histology. Results have shown that follicle viability, and overall follicle quality were not significantly affected at the end of 72 h hypothermic holding. Though, the observation reassures extended hypothermic holding prior to freezing, findings need to be validated in human tissue prior to use in clinical fertility preservation programs.


Highly efficient sorghum transformation.
A highly efficient microprojectile transformation system for sorghum (Sorghum bicolor L.) has been developed by using immature embryos (IEs) of inbred line Tx430. Co-bombardment was performed with the neomycin phosphotransferase II (nptII) gene and the green fluorescent protein (gfp) gene, both under the control of the maize ubiquitin1 (ubi1) promoter. After optimization of both tissue culture media and parameters of microprojectile transformation, 25 independent transgenic events were obtained from 121 bombarded IEs. The average transformation frequency (the total number of independent transgenic events divided by the total number of bombarded IEs) was 20.7% in three independent experiments. Transgenic events were confirmed by both PCR screening and Southern hybridization of genomic DNA from primary transgenics (T₀). More than 90% of transformants were fertile and displayed normal morphology in a containment glasshouse. Co-transformation rate of the nptII and gfp genes was 72% in these experiments. The segregation of nptII and gfp in T₁ progenies was observed utilizing fluorescence microscopy and geneticin selection of seedlings indicating both were inherited in the T₁ generation. The transformation procedure, from initiating IEs to planting putative transgenic plantlets in the glasshouse, was completed within 11-16 weeks, and was approximately threefold more efficient than the previously reported best sorghum transformation system.


Matching-adjusted indirect comparison of bleeding outcomes in severe haemophilia A: Comparing valoctocogene roxaparvovec gene therapy, emicizumab prophylaxis, and FVIII replacement prophylaxis.
Head-to-head evaluation of valoctocogene roxaparvovec, the first gene therapy approved for haemophilia A, with emicizumab is not available. Therefore, phase 3 trial data were indirectly compared. To compare bleeding rates in trials evaluating 6 × 1013 vg/kg valoctocogene roxaparvovec (GENEr8-1; NCT03370913), 1.5 mg/kg emicizumab dosed every week (HAVEN 3; NCT02847637), and FVIII prophylaxis (270-902) in participants with severe haemophilia A (FVIII ≤1 IU/dL). Valoctocogene roxaparvovec versus emicizumab and FVIII prophylaxis as used in 270-902 versus emicizumab cross-trial comparisons were performed using matching-adjusted indirect comparison (MAIC). Individual participant data from GENEr8-1 and 270-902 were weighted to equalise aggregate participant baseline characteristics from HAVEN 3. After MAIC weighting, annualised bleeding rates (ABR) and proportions of participants without bleeds were compared for treated bleeds, all bleeds, treated joint bleeds, and treated spontaneous bleeds. After MAIC weighting, ABR for all bleeds was statistically significantly lower with valoctocogene roxaparvovec than emicizumab (rate ratio [95% CI], .55 [.33-.93]). Additionally, significantly higher proportions of participants had no treated joint bleeds (odds ratio [95% CI], 2.75 [1.20-6.31]) and no treated bleeds (3.25 [1.53-6.90]) with valoctocogene roxaparvovec versus emicizumab. When compared with the mainly standard half-life FVIII prophylaxis regimens in 270-902, mean ABRs (except for all bleeds) were significantly lower, and significantly higher proportions reported 0 bleeds for all outcomes with emicizumab. Valoctocogene roxaparvovec provided generally lower bleeding rates and higher probability of no bleeds, including treated joint bleeds, than emicizumab. Emicizumab was more effective than FVIII prophylaxis regimens used in 270-902.


Patient expectations and awareness of information regarding adverse reactions in drug labelling in China.
Background The misunderstanding of adverse drug reaction labelling information is not conducive to the rational use of drugs. There has been no research on how doctors can effectively transmit information on adverse drug reactions to patients in China. Objective To assess how well patients understand the adverse reactions presented in the labelling of drugs and how much information they want from their doctor regarding the adverse reactions. Setting The study was conducted in secondary medical institutions, tertiary medical institutions and community healthcare centres in Shanghai. Method A cross-sectional self-administered survey was conducted from November 2018 to March 2019. Mixed methods involving paper questionnaires and online surveys (scan a QR code by the WeChat app) were used. Main outcome measure Participants' demand for adverse reaction information. Results A total of 295 people completed the questionnaires, of which 31.8% of people thought that the greater the number of adverse reactions listed on the label of a drug, the more insecure they felt about that drug. At the same time, 30.13% of people thought that if the adverse reactions listed on a label were undefined, then the drug was safe for use (for example, some Chinese patent medicines). Most of the respondents (45.4%) thought that it was better to give a brief description of possible adverse reactions and to answer patients' questions in detail only if necessary. Conclusions Most patients wanted doctors to give them a brief introduction to serious and common adverse reactions when they prescribed drugs, and only a small percentage of people wanted to obtain all the information about adverse reactions. It was found that many people misunderstood the contents of the adverse reactions provided on the labels and equated the number of adverse reactions with drug safety.


Possible role of sildenafil in inhibiting rat vas deferens contractions by influencing the purinergic system.
To evaluate the effect of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-selective type 5 phosphodiesterase, on isolated rat vas deferens and its connections with the purinergic system. Epididymal and prostatic portions of isolated vas deferens were placed in organ baths containing Krebs' solution. Contractions were induced by noradrenaline (NA), adenosine triphosphate (ATP), alpha,beta-methylene ATP and electrical field stimulation (EFS). The effect of sildenafil on the contractions was compared with suramin and Evans blue (EB). NA, ATP, alpha,beta-methylene ATP and EFS caused contractions in both portions of vas deferens. NA-induced contractions were unaffected by sildenafil and suramin but potentiated by EB. ATP-induced contractions were non-competitively inhibited in both portions by sildenafil and suramin but potentiated by EB. alpha,beta-methylene ATP-induced contractions were unaffected by sildenafil but were inhibited in both portions by suramin and EB. EFS-induced contractions were inhibited by sildenafil and suramin while potentiated by EB. Sildenafil inhibited the contractions in both portions of vas deferens, as did suramin. We have suggested that purinergic system has a role in this antagonism and it seems to be mediated by an ATP-dependent mechanism instead of a receptor interaction.


Transient ischemia stimulates glial fibrillary acid protein and vimentin gene expression in the gerbil neocortex, striatum and hippocampus.
Astrocytic activation plays a major role in homeostatic maintenance of the central nervous system in response to neuronal damage. To assess the reactivity of astrocytes in transient cerebral ischemia of the gerbil, we studied the levels of glial fibrillary acidic protein (GFAP) and its mRNA. GFAP mRNA increased by 4 h after carotid artery occlusion, reached peak levels by 72 h with a 12-fold increase over control and then started declining as early as 96 h postischemia. An examination of the specific regions of the brain revealed an increase in GFAP mRNA associated with the forebrain, midbrain, hippocampus and striatum. GFAP mRNA in the non-ischemic cerebellum however, remained expressed at constitutively low levels. Immunoblot analysis with anti-GFAP antibodies demonstrated a 2- to 3-fold increase in the protein after 24 and 48 h of reperfusion. Pretreatment with pentobarbital and 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine (HWA 285), the drugs that have been shown to protect against ischemic damage, prevented the increase in GFAP mRNA in the cortex following ischemic injury. Forebrain ischemia also induced vimentin mRNA and protein quantities by 12 h of reperfusion in the cortex. The levels of c-fos and preproenkephalin mRNA increased rapidly within 1 h after ischemic injury, demonstrating a temporal difference in mRNA changes following ischemia. These results indicate that an increase in GFAP and vimentin, the two glial intermediate filament proteins in the area of the ischemic lesion may be associated with a glial response to injury.


Potential applications of global protein expression analysis (proteomics) in morbid obesity and bariatric surgery.
Global protein expression analysis, known as proteomics, has emerged as a novel scientific technology currently successfully applied to several fields of medicine including cancer and transplantation. Thereby, a thorough exploration of the pathogenic mechanisms and a better understanding of the pathophysiology of diseases as well as identification of diagnostic biomarkers have been achieved. In this paper, we outline the basic principles and potential applications of this promising tool in bariatric surgery where proteomics might hold great potential for new insights into diagnostic and therapeutic decision making based on improved knowledge of metabolic regulations pre- and postsurgical interventions in morbidly obese patients.


Complications in cerebral angiography with iohexol (Omnipaque) and meglumine metrizoate (Isopaque cerebral).
The complications of cerebral angiography have been recorded in 1509 examinations with metrizoate (Isopaque Cerebral) and in 1000 examinations with iohexol (Omnipaque). The frequency of complications was 2.0 percent for metrizoate and 1.3 percent for iohexol. Permanent sequelae were seen in 4 patients, 3 in the metrizoate and one in the iohexol group. One of these patients died, probably from thromboembolism. Blood coagulation parameters were studied during the angiography in 22 patients and only minor, probably clinically insignificant changes were found, with no difference between the two contrast media.


Practical solutions for implementation of blood cholesterol guidelines in clinical practice.
Underutilization of lipid-lowering therapy (LLT) and failure to attain guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals are important quality gaps in cardiovascular risk optimization, especially among patients with atherosclerotic cardiovascular disease (ASCVD). Large database analyses demonstrate an unmet need for improved LDL-C measurement, and that nearly 75% of patients with ASCVD have an LDL-C level above guideline-recommended levels, and greater than 50% are not treated with statins or ezetimibe. Proposed solutions for overcoming these obstacles to optimal lipid management include provider- and patient-facing educational interventions, health information technology strategies, implementation of incentive-based care, advocacy efforts, and systems-based process innovations. While individual interventions may not be enough to overcome the totality of barriers to optimal LLT, comprehensive multifaceted approaches that address barriers at the provider, patient, and healthcare delivery level are likely to offer the greatest likelihood of success and improved patient outcomes.


Genetic influences on tolerance development with chronic oxotremorine infusion.
Mice of four inbred strains (BALB, C57BL, DBA and C3H) were administered either saline or oxotremorine, a muscarinic agonist, at a dose of 0.5 mg/kg/hr by constant infusion through cannulas implanted in the right jugular veins. Chronic treatment resulted in the development of tolerance to the effects of oxotremorine both on rotarod performance and on body temperature. For drug-treated BALB mice, the dose-response curves for both measures were parallel to those for saline-treated mice, while for DBA and C3H mice the slopes of the dose-response curves were significantly less for treated mice than they were for controls. The equi-effective doses for the drug-treated animals were at least 8-fold greater than those for saline-treated mice. Drug treatment resulted in a significant decrease in the total number of muscarinic receptors in cortex as measured by the binding of [3H]quinuclidinyl benzilate (QNB) without effect on the KD for this ligand. Similarly, drug treatment did not affect the affinity of carbamylcholine as an inhibitor of QNB binding, but did significantly decrease the levels of both the high- and low-affinity agonist binding sites in cortex. The number of M1 muscarinic receptors measured by high affinity [3H]pirenzepine (PZ) binding was also significantly decreased in cortex without effect on the KD. The experiments were extended to five other brain regions. Full saturation curves were not constructed, however. Oxotremorine treatment significantly reduced QNB binding in every brain region. While the binding to agonist affinity states measured by carbamylcholine inhibition of QNB binding and M1 receptor levels measured by high affinity PZ binding tended to decrease with oxotremorine treatment not all changes were statistically significant. The changes in muscarinic receptor subtype levels induced by oxotremorine infusion did not differ among the strains. The results demonstrate that chronic treatment with a muscarinic agonist results in substantial tolerance to the effects of the drug in all four mouse strains. Although some differences in tolerance development exist, these differences are not readily explained by differences in the number or affinity states of brain muscarinic receptors.


The underlying psychopathology of eating disorders and social phobia: a structural equation analysis.
This study investigates the underlying psychopathology of disordered eating and social phobia behaviours by examining the interrelationships between variables thought to be common to both. The participants were 252 female tertiary students. Each completed measures of eating behaviours, social phobia, body esteem, fear of negative evaluation, social support, self-acceptance, and general psychopathology. Structural equation modelling was used to determine if fear of negative evaluation and social support had a direct or indirect effect on the behaviours of disordered eating, social phobia, and body esteem. Findings indicated that fear of negative evaluation had a direct and indirect effect on the behaviours associated with eating disorders and social phobia, and only an indirect effect on body esteem. Social support indirectly affected eating disorders, social phobia, and body esteem. Implications from this study are that social support, fears of being criticised or rejected by others, and low self-acceptance are important variables in the assessment of eating disorders and social phobia.


[Climatic characteristics of the arid zone during the formation of the "afganets" wind].
A statistical analysis has been performed of disturbances arising in meteorological parameters and atmospheric electrical field during various stages of "afganets" wind blowing (in the sun cycle XXI).


Spontaneous remission of Cushing's disease. A case report and review of the literature.
A 70 year old man whose severe Cushing's disease remitted spontaneously is described. Medical therapy was instituted as a temporary measure prior to planned adrenalectomy. The patient showed dramatic improvement during medication and has remained well for two and a half years following the discontinuation of drug therapy. The literature is reviewed for other cases of spontaneous resolution of Cushing's.


AutoMate Express™ forensic DNA extraction system for the extraction of genomic DNA from biological samples.
The AutoMate Express™ Forensic DNA Extraction System was developed for automatic isolation of DNA from a variety of forensic biological samples. The performance of the system was investigated using a wide range of biological samples. Depending on the sample type, either PrepFiler™ lysis buffer or PrepFiler BTA™ lysis buffer was used to lyse the samples. After lysis and removal of the substrate using LySep™ column, the lysate in the sample tubes were loaded onto AutoMate Express™ instrument and DNA was extracted using one of the two instrument extraction protocols. Our study showed that DNA was recovered from as little as 0.025 μL of blood. DNA extracted from casework-type samples was free of detectable PCR inhibitors and the short tandem repeat profiles were complete, conclusive, and devoid of any PCR artifacts. The system also showed consistent performance from day-to-day operation.


Incidence of hemidiaphragmatic paresis after peripheral nerve stimulator versus ultrasound guided interscalene brachial plexus block.
We compared interscalene brachial plexus block (ISBPB) using peripheral nerve stimulation (PNS) and ultrasound (US) techniques. The primary outcomes were the incidence of hemidiaphragmatic paresis (HDP) and the duration of the block. Secondary outcomes were the block success rate, time to conduct the block, onset of sensory block, and dermatomal spread, postoperative pain by Numeric Rating Scale (NRS), duration of postoperative analgesia and incidence of complications. We conducted a prospective, randomized, and observer-blinded study in 60 patients undergoing shoulder arthroscopy under block plus general anesthesia. ISBPB was performed with 10 ml of 0.5% bupivacaine using either PNS (Group PNS, n = 30) or US (Group US, n = 30). Hemidiaphragmatic function, the primary outcome, was assessed by ultrasonographic evaluation of diaphragmatic movement and pulmonary function tests using a bedside spirometer (forced vital capacity, forced expiratory volume in 1 s and peak expiratory flow rate). General anesthesia was administered to all the patients for surgery. P < 0.05 test was considered to be statistically significant. Twelve patients in Group PNS had HDP and none in Group US (P < 0.0001). PFTs were also significantly reduced in Group PNS (P < 0.0001). The time to conduct the block and sensory onset time both were less in Group US (P < 0.05). The groups did not differ in block success rate, duration of analgesia, and NRS. Other complications like incidence of Horner's syndrome and vascular puncture were comparable in both the groups. PNS guided ISBPB with 10 ml of 0.5% bupivacaine is associated with a higher incidence of HDP as compared to US guided ISBPB. There is no significant difference in quality or duration of analgesia in the two groups.


Laparoscopic Versus Open Colorectal Surgery in the Emergency Setting: A Systematic Review and Meta-analysis.
This systematic review and meta-analysis aimed to compare published outcomes of patients undergoing laparoscopic versus open emergency colorectal surgery, with mortality as primary outcome. In contrast to the elective setting, the value of laparoscopic emergency colorectal surgery remains unclear. PubMed, Embase, the Cochrane Library, and CINAHL were searched until January 6, 2021. Only comparative studies were included. Meta-analyses were performed using a random-effect model. The Cochrane Risk of Bias Tool and the Newcastle-Ottawa Scale were used for quality assessment. Overall, 28 observational studies and 1 randomized controlled trial were included, comprising 7865 laparoscopy patients and 55,862 open surgery patients. Quality assessment revealed 'good quality' in 16 of 28 observational studies, and low to intermediate risk of bias for the randomized trial. Laparoscopy was associated with significantly lower postoperative mortality compared to open surgery (odds ratio [OR] 0.44; 95% confidence interval [CI], 0.35-0.54). Laparoscopy resulted in significantly less postoperative overall morbidity (OR, 0.53; 95% CI, 0.43-0.65), wound infection (OR, 0.63; 95% CI, 0.45-0.88), wound dehiscence (OR, 0.37; 95% CI, 0.18-0.77), ileus (OR, 0.68; 95% CI 0.51-0.91), pulmonary (OR, 0.43; 95% CI, 0.24-0.78) and cardiac complications (OR, 0.56; 95% CI, 0.35-0.90), and shorter length of stay. No meta-analyses were performed for long-term outcomes due to scarcity of data. The systematic review and meta-analysis suggest a benefit of laparoscopy for emergency colorectal surgery, with a lower risk of postoperative mortality and morbidity. However, the almost exclusive use of retrospective observational study designs with inherent biases should be taken into account.


Prognostic significance of total disease length in esophageal cancer.
This study tested the hypothesis that endoluminal ultrasound (EUS) defined total length of disease (including both the primary tumor and the position and number of proximal and distal lymph nodes-ELoD) and the associated EUS lymph node metastasis count (ELNMC) are better predictors of outcome than endoscopic esophageal cancer (OC) length and radiological tumor node metastasis stage in patients who undergo potentially curative treatment with surgery or definitive chemoradiotherapy (dCRT). A total of 645 consecutive patients diagnosed with OC and managed by a multidisciplinary team were staged by CT and EUS. The primary outcome measure was survival from date of diagnosis. A total of 323 patients received surgery (208 neoadjuvant chemotherapy), and 322 who were deemed unsuitable for surgery received dCRT. Univariable analysis revealed that survival was related to EUS T (p < 0.0001), N (p < 0.0001), EUS primary tumor length (p = 0.037), ELoD (p = 0.011), ELNMC (p < 0.0001), and treatment type (p = 0.001). Multivariable analysis revealed two factors: ELoD (hazard ratio (HR), 0.961; 95 % confidence interval (CI), 0.925-0.998; p = 0.041) and ELNMC (HR, 1.08; 95 % CI, 1.015-1.15; p = 0.016) were independently associated with survival. ELoD and ELNMC should become part of routine OC radiological staging to optimize stage-directed therapeutic outcomes.


In vitro activity of linezolid against Clostridium difficile.
We examined the in vitro activity of linezolid against Clostridium difficile, including isolates with reduced susceptibility to metronidazole or vancomycin. The MIC at which 50% of the isolates were inhibited (MIC50) and MIC90 were 0.5 and 2 microg/ml, respectively (range, 0.03 to 4 microg/ml). MICs were always <or= 4 microg/ml, and thus, all isolates were considered susceptible.


Lack of clinical impact of 18 F-fluorodeoxyglucose positron emission tomography with simultaneous computed tomography for stage I and II Merkel cell carcinoma with concurrent sentinel lymph node biopsy staging: A single institutional experience from Westmead Hospital, Sydney.
18 F-fluorodeoxyglucose (FDG) positron emission tomography with simultaneous computed tomography (PET-CT) FDG PET-CT plays an important clinical role in the staging and management of Merkel cell carcinoma (MCC) although its role in stage I and II disease relative to a sentinel lymph node biopsy (SLNB) is undefined. This study aimed to compare the clinical impact of FDG PET-CT and SLNB on management in stage I and II MCC. This was a retrospective observational study. Between 2000 and 2014, 65 patients with biopsy-proven MCC (all stages) underwent a staging FDG PET-CT as part of their investigations in Westmead Hospital, Sydney. Since 2006, 26 patients have had an SLNB and of these, 16 underwent both an SLNB and FDGPET-CT. All 16 patients had a histological diagnosis consistent with MCC without clinical evidence of regional or distant metastases prior to SLNB and FDG PET-CT (stages IB and IIB). These patients were assessed with respect to MCC staging and the subsequent change of patient management post-SLNB and FDG PET-CT. The SLNB identified occult lymph node metastases in 10 patients (63%), with FDG PET-CT positive in only one patient (6%). Of the six SLNB-negative patients, none demonstrated additional metastases on the FDG PET-CT. In patients with stage I and II MCC, FDG PET-CT is less sensitive than an SLNB in detecting occult metastatic lymph nodes. The routine use of FDG PET-CT in these patients may not be justified.


Influence of control selection in nested case-control studies: the example of exposure to antiretroviral treatment (ART) and the risk of myocardial infarction (MI) in the French Hospital Database on HIV (FHDH-ANRS CO4).
Soon after availability of protease inhibitors (PIs), a duration-related effect relationship between PI and myocardial infarction (MI) was shown. New antiretroviral treatments (ARTs) have allowed more individualized regimens. To study their influence established risk factors of MI and additional therapeutic options such as lipid-lowering drugs will have to be taken into account. A nested case-control is an interesting alternative raising the choice of controls. With the previous full cohort analysis as reference, we investigated the influence of control selection in nested case-control studies sampled in this cohort by testing nine sampling scenarios. During the period 1996-1999, 49 MI occurred among male patients exposed to PI and followed-up in the French Hospital Database on HIV (FHDH-ANRS CO4). For each case, controls were selected using incidence-density sampling. The influence of additional matching criteria was tested. Random sampling and analysis was repeated 100 times with varying control-case ratios. When controls were randomly selected among patients of the same age who were free of MI at the date MI was diagnosed in the case, we observed a duration-related effect relationship between PI and MI in agreement with the results of the full cohort analysis. The use of four controls per case was sufficient. Estimates obtained with simple sampling were more precise than those obtained when controls were also matched for year of enrollment, initial CD4 cell count and HIV transmission group. To study ARTs as MI risk factors, nested case-control using incidence-density sampling without additional matching is one appropriate option.


[Genetic aspects of male infertility].
Cytogenetic analyses performed in infertile men showed a frequency of genetic abnormalities definitely higher than in normal population. Cytogenetic analysis is perfectly justified in infertile men with normal phenotype.