First report of bacterial leaf spot on Hami melon caused by Pseudomonas aeruginosa in China.
Hami melon (Cucumis melon var. saccharinus) is an economically important crop all over the world. It is being extensively planted in greenhouse in the southwest part of Hainan province, China. A new bacterial leaf spot was observed in a 20 hm2 Hami melon plantation in Huangliu town, Ledong county, Hainan province, in January 2022. The incidence of the disease was approximately 5%. Symptoms were irregularly shaped, brown lesions with yellow haloes on mature leaves, and first appeared as small, dark-green, water-soaking spots. Specimens from the lesion margin were disinfected by submersion in 0.1% mercuric chloride for 1 min, then soaked with 75% alcohol for 30 s, and rinsed with sterilized distilled water. The tissues were then ground in 2 ml of sterile water and allowed to stand for 5min. The supernatant was streaked onto nutrient agar (NA) and incubated for 48h at 30°C. Colonies were round, smooth, colorless, nearly transparent, bead-shaped at first, and then became lightly blue. After being cultured for days on NA at 30℃, the bacteria can turn the media brown. Yellow green pigments (pyoverdin) that fluoresce under ultraviolet light could be produced by the isolates in the Luria Broth. The bacteria were gram-negative, rod shaped with a single polar flagellum, 0.4 to 1.1 × 1.4 to 3.4 µm. Its physiological and biochemical characteristics were as follows: positive for the oxidase, aerobic, arginine dihydrolase, gelatin liquefaction, denitrification, lipase, growth at 41℃, utilization of mannitol, and production of pyocyanin tests; negative for the hydrolysis of starch, levan formation, lecithinase, growth at 4℃, growth in media supplemented with 8.5% NaCl, and utilization of maltose, xylose, and ethylene glycol tests. The 16S rRNA (1,437 bp), gyrB (1,181 bp), and rpoB genes (1,510 bp) were amplified with 27F/1492R (Zhang et al. 2016), UP-1s/UP-2sr(Hannula M,2007), and rpoB-F/rpoB-R (Ogier, JC. et al., 2019) primer sets respectively. One of the 5 isolates collected was sequenced. A BLASTn search of GenBank revealed that the sequence of 16S rRNA gene (OQ918303) had 99.7% identity and 98% coverage comparing with the best hit Pseudomonas aeruginosa strain DSM 50071(NR_117678.1), and both gyrB (OR261077) and rpoB (OR261078) had 99.9% identity and over 98% coverage comparing with P. aeruginosa E90 (CP044006.1). A pathogenicity test was conducted by spraying a suspension of the bacteria (108 CFU/mL) onto 10 Hami melon seedlings with two true leaves. Controls were inoculated with sterile water. All inoculated plants were maintained at 28℃ with 80 to 85% relative humidity in a greenhouse. Dark-green, water soaking spots appeared on the cotyledon and stems of treated seedlings 3-5 days after inoculation, and dark green lesions with halos were observed on the true leaves at the same time. Symptoms did not occur on the control plants. The bacteria which were re-isolated from the inoculated plants were confirmed as P. aeruginosa based on the 16S rRNA gene sequence. The bacterium was not isolated from control plants. P. aeruginosa has been reported to cause disease on a variety of plants including tomato (Zhang et al., 2021), poplar (Liu, et al., 2019), ginseng (Gao et al., 2014), tinda (Mondal et al., 2012), onion (Abd-Alla et al., 2011), tobacco (Yu et al., 2008) and sweet basil (Walker et al., 2004). As far as we know, this is the first report of P. aeruginosa causing leaf spot on Hami melon in China.. This report will contribute to the recognition and diagnosis of the new disease for the Hami melon growers.


Megakaryocyte-bone marrow stromal cell aggregates demonstrate increased colony formation and alkaline phosphatase expression in vitro.
Bone marrow stromal cells (BMSCs) possess certain stem celllike properties and can differentiate to adopt a number of mesenchymal phenotypes. BMSCs are usually investigated in vitro as homogeneous single-cell suspensions; however, these preparations lose much of their osteogenic capacity. Using the fibroblastic colony-forming unit assay, we have compared the proliferation and capacity to express alkaline phosphatase of BMSC-containing aggregates of bone marrow cells with single-cell suspensions of bone marrow cells from the same source. Aggregates were separated from single cells by density gradient centrifugation or cell sieving. The aggregate and single-cell preparations gave rise to similar numbers of colonies; however, the colonies produced by the aggregates were larger and expressed higher levels of alkaline phosphatase. When the aggregates were dissociated, colonies still formed; however, they expressed negligible levels of alkaline phosphatase. Immunomagnetic selection and immunofluorescent staining for CD61, N-methyl-D-aspartate (NMDA) receptor subunit 1, and acetylcholinesterase showed that the majority of the aggregates giving rise to osteoblastic colonies contained megakaryocytes. These data demonstrate that removing BMSCs from their normal environment reduces their osteoblastic capacity and that to achieve their maximal differentiation, BMSCs require direct physical contact with accessory cells such as megakaryocytes. These findings may be of direct relevance to the use of BMSCs for tissue-engineering purposes.


Immunotropic activity of vratizolin (ITCL, Denotivir).
The aim of this study was to evaluate immunotropic properties of vratizolin, a known antiviral drug, in several in vitro and in vivo assays in mouse and human models. We demonstrated that vratizolin exerted strong immunosuppressive actions both in the humoral and cellular immune response to SRBC in mice. The compound affected not only the inductive phase of delayed type hypersensitivity (DTH) but also the effector phase of that response. Vratizolin was effective when given intraperitoneally and orally. The inhibitory action of vratizolin was comparable to that of cyclosporin A (CsA), the reference drug. Vratizolin exhibited also suppressory properties with regard to PHA-induced proliferation of human peripheral blood lymphocytes and that effect exceeded the inhibitory action of CsA. We also showed that vratizolin inhibited to some degree LPS-induced cytokine production in human peripheral blood cultures. The activities of TNF-alpha, IL-1 and IL-6 were inhibited on average by 37, 26 and 35%, respectively. This was in contrast to the effects of CsA which strongly inhibited only IL-1 production. Lastly, we demonstrated that vratizolin markedly inhibited growth of several tumor cell lines. In particular, the compound significantly inhibited growth of mouse leukemia L-1210 and human acute lymphoblastoid leukemia CCRF-CEM cell lines. The presented data suggest that the immunosuppressory action of vratizolin, although similar to that of CsA, is mediated by a different mechanism. The properties of vratizolin, described in this report, indicate that the drug should be further investigated for possible immunosuppressory and antitumor application.


Standards in medical education in the European Union.
Standards in medical education are necessary to enable evaluation of programmes and comparison between institutions. EC Directive 93/16 lays down the standards for both the duration and content of basic medical education in the European Union but the directive is open to wide variations in interpretation. A new approach is needed and the development of common learning outcomes is suggested as a possible solution.


Exosome RNA Unshielding Couples Stromal Activation to Pattern Recognition Receptor Signaling in Cancer.
Interactions between stromal fibroblasts and cancer cells generate signals for cancer progression, therapy resistance, and inflammatory responses. Although endogenous RNAs acting as damage-associated molecular patterns (DAMPs) for pattern recognition receptors (PRRs) may represent one such signal, these RNAs must remain unrecognized under non-pathological conditions. We show that triggering of stromal NOTCH-MYC by breast cancer cells results in a POL3-driven increase in RN7SL1, an endogenous RNA normally shielded by RNA binding proteins SRP9/14. This increase in RN7SL1 alters its stoichiometry with SRP9/14 and generates unshielded RN7SL1 in stromal exosomes. After exosome transfer to immune cells, unshielded RN7SL1 drives an inflammatory response. Upon transfer to breast cancer cells, unshielded RN7SL1 activates the PRR RIG-I to enhance tumor growth, metastasis, and therapy resistance. Corroborated by evidence from patient tumors and blood, these results demonstrate that regulation of RNA unshielding couples stromal activation with deployment of RNA DAMPs that promote aggressive features of cancer. VIDEO ABSTRACT.


Anatomically based approach for endovascular treatment of vertebro-vertebral arteriovenous fistula.
Vertebro-vertebral arteriovenous fistula (VV-AVF) is a rare vascular disorder with an abnormal high-flow shunt between the extracranial vertebral artery (VA), its muscular or radicular branches and an adjacent vein. To date, there are no guidelines on the best treatment for VV-AVF. We present our experience of VV-AVF treatment with covered stents in three patients and detachable coils in two patients. One patient with fistula at the V3 segment had rapid fistula recurrence one week after covered stent treatment. The possible causes of failed treatment in this patient are discussed. The currently available treatment modalities for VV-AVF are also summarized after a literature review. At the end of this article, we propose a new concept of anatomically based approach for endovascular treatment of VV-AVF. Fistula in the V1-2 segments of vertebral artery could be treated safely and effectively by covered stent with the benefit of preserving VA patency. Embolization with variable embolizers should be considered first for fistula in the V3 segment because of the tortuous course and flexibility of the VA in this segment.


HIV-1 Tat peptide immunoconjugates differentially sensitize breast cancer cells to selected antiproliferative agents that induce the cyclin-dependent kinase inhibitor p21WAF-1/CIP-1.
In this study, we evaluated the ability of anti-p21 antibodies conjugated to 17-mer peptides [GRKKRRQRRRPPQGYGC] harboring the membrane-translocating and nuclear import sequences [underlined] of HIV-1 tat protein to inhibit the cyclin-dependent kinase inhibitor, p21(WAF-1/Cip-1) (p21) and differentially sensitize MDA-MB-468 and MCF-7 human breast cancer (BC) cells to the antiproliferative effects of treatments that induce or do not induce p21. BC cells were treated with increasing concentrations of epidermal growth factor (EGF; 0.5-10 nM), the topoisomerase I inhibitor, camptothecin (CPT; 0.1-4 muM), or increasing doses of gamma-radiation (2-20 Gy). Western blot was used to evaluate p21 expression. The effect of treatment on cell cycle distribution was studied. Growth inhibition was measured by the WST-1 assay. Expression of p21 was increased in MDA-MB-468 cells treated with EGF or CPT but not by gamma-irradiation. MCF-7 cells exhibited p21 upregulation following exposure to CPT and gamma-radiation but not EGF. EGF caused cell cycle arrest in G(1) phase for MDA-MB-468 cells. CPT caused G(1)-phase arrest in MDA-MB-468 cells and prolonged S phase in MCF-7 cells. gamma-Radiation caused an increase in cells in G(2)/M phase for MDA-MB-468 and MCF-7. MDA-MB-468 cells were growth-inhibited by EGF, CPT, and gamma-radiation. MCF-7 cells were growth-stimulated by EGF and inhibited by CPT and gamma-radiation. Combining EGF with tat-anti-p21 immunoconjugates (ICs) amplified the growth-inhibitory effect on MDA-MB-468 cells 1.2-fold to 2.3-fold, but had no effect on the growth stimulation of MCF-7 cells by EGF. Tat-anti-p21 ICs sensitized MCF-7 cells 1.4-fold to gamma-radiation but had no effect on the growth of gamma-irradiated MDA-MB-468 cells. Tat-anti-p21 ICs sensitized both MDA-MB-468 and MCF-7 cells 1.7-fold to CPT. We conclude that tat-anti-p21 ICs are promising sensitizers for cytotoxic cancer therapies and that their sensitization is dependent on treatment-related p21 expression. This general approach could potentially be extended to other growth-regulatory molecules that are associated with tumor growth and progression.


Comparison of an online learning module to hands-on training in teaching a cautery disbudding technique for dairy calves including cornual nerve block application.
Disbudding and dehorning are common procedures on dairy farms. In a recent survey of Ontario dairy producers, 38% reported not using local anesthetic for these procedures. Use of pain control is important for both calf welfare and industry sustainability. Use of local anesthetic requires technical training, typically provided by a veterinarian, although online training videos also exist. Neither method has been studied for efficacy. Our objective was to compare an online module to hands-on training in teaching naïve participants (veterinary students) to effectively carry out a cornual nerve block and disbud a dairy calf. Participants were assigned to either an online or hands-on training group. Although no statistical differences were seen in success of the nerve block, online learners were less confident and had poorer technical skills. While online learning was surprisingly effective for a psycho-motor skill, best practices should include hands-on training.


Distinct features of auditory steady-state responses as compared to transient event-related potentials.
Transient event-related potentials (ERPs) and steady-state responses (SSRs) have been popularly employed to investigate the function of the human brain, but their relationship still remains a matter of debate. Some researchers believed that SSRs could be explained by the linear summation of successive transient ERPs (superposition hypothesis), while others believed that SSRs were the result of the entrainment of a neural rhythm driven by the periodic repetition of a sensory stimulus (oscillatory entrainment hypothesis). In the present study, taking auditory modality as an example, we aimed to clarify the distinct features of SSRs, evoked by the 40-Hz and 60-Hz periodic auditory stimulation, as compared to transient ERPs, evoked by a single click. We observed that (1) SSRs were mainly generated by phase synchronization, while late latency responses (LLRs) in transient ERPs were mainly generated by power enhancement; (2) scalp topographies of LLRs in transient ERPs were markedly different from those of SSRs; (3) the powers of both 40-Hz and 60-Hz SSRs were significantly correlated, while they were not significantly correlated with the N1 power in transient ERPs; (4) whereas SSRs were dominantly modulated by stimulus intensity, middle latency responses (MLRs) were not significantly modulated by both stimulus intensity and subjective loudness judgment, and LLRs were significantly modulated by subjective loudness judgment even within the same stimulus intensity. All these findings indicated that high-frequency SSRs were different from both MLRs and LLRs in transient ERPs, thus supporting the possibility of oscillatory entrainment hypothesis to the generation of SSRs. Therefore, SSRs could be used to explore distinct neural responses as compared to transient ERPs, and help us reveal novel and reliable neural mechanisms of the human brain.


Hubbard model on decorated lattices.
We introduce a family of lattices for which the Hubbard model and its natural extensions can be quasiexactly solved, i.e., solved for the ground and low energy states. In particular, we show rigorously that the ground state of the Hubbard model with off-site Coulomb repulsions on a decorated Kagomè lattice is an ordered array of local currents. The low energy theory describing this chiral state is an S=1 / 2 XY model, where each spin degree of freedom represents the two possible chiralities of each local current.


Multiple-Input-Multiple-Output Filtered Multitone Time Reversal Acoustic Communications Using Direct Adaptation-Based Turbo Equalization.
This paper proposes using direct adaptation (DA)-based turbo equalization in multiple-input-multiple-output (MIMO) filtered multitone (FMT) time reversal (TR) acoustic communications to jointly suppress noise, residual co-channel interference (CCI) and intersymbol interference (ISI) after the TR process. Soft information-based adaptive decision feedback equalization (ADFE) adjusted according to the recursive expected least squares (RELS) algorithm, including interference cancellation and decoding, is used to construct the DA-based turbo equalization. In the proposed method, soft information is exchanged between soft symbols with soft decisions of decoding iteratively, and interference suppression is proceeded successively and iteratively until the performance is stable. The principle of the proposed method is analyzed, and based on the acoustic channel responses measured in a real experiment, the performance is assessed in relation to that of anther two methods. Compared with the MIMO-FMT TR underwater acoustic communication using interference suppression without error control coding (ECC), the proposed method performs better, benefitting from the ECC included in turbo equalization. Additionally, compared with the MIMO-FMT TR underwater acoustic communication using interference suppression based on hard decision equalization and decoding, the proposed method exhibits superior performance by exploiting soft information.


Predicting healthy eating intention and adherence to dietary recommendations during pregnancy in Australia using the Theory of Planned Behaviour.
This study aims to aid in the development of more effective healthy eating intervention strategies for pregnant women by understanding the relationship between healthy eating intention and actual eating behaviour. Specifically, the study explored whether Theory of Planned Behaviour (TPB) constructs [attitude, subjective-norm, perceived-behavioural-control (PBC)] and additional psychosocial variables (perceived stress, health value and self-identity as a healthy eater) are useful in explaining variance in women's 1) intentions to consume a healthy diet during pregnancy and 2) food consumption behaviour (e.g. adherence to food group recommendations) during pregnancy. A cross-sectional sample of 455 Australian pregnant women completed a TPB questionnaire as part of a larger comprehensive web-based nutrition questionnaire. Women's perceived stress, health value and self-identity as a healthy eater were also measured. Dietary intake was assessed using six-items based on the 2013 Australian Dietary Guidelines. Hierarchical multiple linear regression models were estimated (significance level <0.05), which explained 70% of the variance in healthy eating intention scores and 12% of the variance in adherence to food group recommendations. TPB constructs explained 66% of the total variance in healthy eating intention. Significant predictors of stronger healthy eating intention were greater PBC and subjective norm, followed by positive attitude and stronger self-identity as a healthy eater. Conversely, TPB constructs collectively explained only 3.4% of total variance in adherence to food group recommendations. These findings reveal that the TPB framework explains considerable variance in healthy eating intention during pregnancy, but explains little variance in actual food consumption behaviour. Further research is required to understand this weak relationship between healthy eating intention and behaviour during pregnancy. Alternative behavioural frameworks, particularly those that account for the automatic nature of most dietary choices, should also be considered.


Nightly enteral nutrition support of elderly hip fracture patients: a phase I trial.
This non-blinded randomized controlled trial was the first phase of a planned series of investigations designed to test the efficacy of aggressive post-operative enteral nutrition support to decrease the rate of post-operative complications or improve long-term outcomes in specifically defined subgroups of elderly patients who have sustained a hip fracture requiring surgery. Eighteen patients (17 males) were randomized to the treatment (eight male subjects) or control groups. The control group (mean age 76.5+/-6.1 years) received standard post-operative care. Subjects in the treatment group (mean age 74.5+/-2.1 years) received 125 cc/hour of nasoenteral tube feedings over 11 hours each night in addition to standard post-operative nutritional care. Both the treatment and control groups had reduced volitional nutrient intakes for the first 7 post-operative days (3,966+/-2,238 vs. 4,263+/-2,916 kJ/day [948+/-535 vs. 1019+/-697 kcal/day], p=0.815), but the treatment subjects had a greater total nutrient intake (7,719+/-2,109 vs. 4,301+/-2,858 kJ/day [1845+/-504 vs. 1028+/-683 kcal], p=0.012). On average, treatment subjects were tube fed for 15.8+/-16.4 days. There was no difference between the groups (treatment vs. controls) in the rate of post-operative life-threatening complications (25 vs. 30%, p=1.00) or in-hospital mortality (0 vs. 30%, p=0.216). Mortality within 6 months subsequent to surgery was lower in the treatment group compared to the controls (0 vs. 50%, p=0.036). We conclude that nightly enteral feedings are a safe and effective means of supplementing nutrient intake. The greatest impact of nutrition support may be to reduce mortality.


One-step electrochemical growth of a three-dimensional Sn-Ni@PEO nanotube array as a high performance lithium-ion battery anode.
Various well-designed nanostructures have been proposed to optimize the electrode systems of lithium-ion batteries for problems like Li(+) diffusion, electron transport, and large volume changes so as to fulfill effective capacity utilization and increase electrode stability. Here, a novel three-dimensional (3D) hybrid Sn-Ni@PEO nanotube array is synthesized as a high performance anode for a lithium-ion battery through a simple one-step electrodeposition for the first time. Superior to the traditional stepwise synthesis processes of heterostructured nanomaterials, this one-step method is more suitable for practical applications. The electrode morphology is well preserved after repeated Li(+) insertion and extraction, indicating that the positive synergistic effect of the alloy nanotube array and 3D ultrathin PEO coating could authentically optimize the current volume-expansion electrode system. The electrochemistry results further confirm that the superiority of the Sn-Ni@PEO nanotube array electrode could largely boost durable high reversible capacities and superior rate performances compared to a Sn-Ni nanowire array. This proposed ternary hybrid structure is proven to be an ideal candidate for the development of high performance anodes for lithium-ion batteries.


ABCD2 is a direct target of β-catenin and TCF-4: implications for X-linked adrenoleukodystrophy therapy.
X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by mutations in the ABCD1 gene that encodes the peroxisomal ATP-binding cassette (ABC) transporter subfamily D member 1 protein (ABCD1), which is referred to as the adrenoleukodystrophy protein (ALDP). Induction of the ABCD2 gene, the closest homolog of ABCD1, has been mentioned as a possible therapeutic option for the defective ABCD1 protein in X-ALD. However, little is known about the transcriptional regulation of ABCD2 gene expression. Here, through in silico analysis, we found two putative TCF-4 binding elements between nucleotide positions -360 and -260 of the promoter region of the ABCD2 gene. The transcriptional activity of the ABCD2 promoter was strongly increased by ectopic expression of β-catenin and TCF-4. In addition, mutation of either or both TCF-4 binding elements by site-directed mutagenesis decreased promoter activity. This was further validated by the finding that β-catenin and the promoter of the ABCD2 gene were pulled down with a β-catenin antibody in a chromatin immunoprecipitation assay. Moreover, real-time PCR analysis revealed that β-catenin and TCF-4 increased mRNA levels of ABCD2 in both a hepatocellular carcinoma cell line and primary fibroblasts from an X-ALD patient. Interestingly, we found that the levels of very long chain fatty acids were decreased by ectopic expression of ABCD2-GFP as well as β-catenin and TCF-4. Taken together, our results demonstrate for the first time the direct regulation of ABCD2 by β-catenin and TCF-4.


Effect of tilting on the pressor responses to McN-A-343, a muscarinic sympathetic ganglion stimulant.
1 In anaesthetized cats and dogs treated with mecamylamine, the pressor response to McN-A-343 was increased when the animals were changed from a supine to a head-up, tilted position. This potentiation was not seen in rats. 2 The potentiation of the McN-A-343 pressor response was not affected by propranolol, destruction of the brain, or removal of the intestines, spleen or adrenal glands. It was promptly abolished by applying pressure to the lower half of the tilted animal. No increase in the pressor response to McN-A-343 occurred when cats were tilted head down. The potentiated response in tilted cats was abolished by atropine. 3 The pressor effects of adrenaline, noradrenaline, tyramine and angiotensin in cats treated with mecamylamine were either reduced or unchanged when the animal was changed from the supine to the tilted position. In one cat not treated with mecamylamine in which orthostatic hypotension occurred, tilting potentiated the pressor responses to dimethyl phenylpiperazinium iodide. 4 In cats anaesthetized with chloralose, the reflex pressor response to bilateral carotid occlusion was reduced by tilting. After mecamylamine treatment the residual atropine-sensitive response to carotid occlusion was potentiated when the animal was placed in the tilted position. 5 These results suggest that muscarinic stimulation of sympathetic ganglia by McN-A-343 raises blood pressure by predominantly reducing venous capacity, in contrast to noradrenaline and angiotension which increase blood pressure mainly by arterial vasoconstriction. 6 It is not clear whether this is a general property of sympathetic ganglionic stimulation or is restricted to stimulation of muscarinic sites.


Effects of psychotherapy in schizophrenia: I. Design and implementation of a controlled study.
This article describes a 2-year, multi-hospital study on the effects of psychotherapy for nonchronic schizophrenic patients. The design and methods used to evaluate the relative benefits of exploratory, insight-oriented (EIO) psychotherapy and reality-adaptive, supportive (RAS) psychotherapy when both are provided by experienced therapists against the backdrop of good hospital and psychopharmacological management are presented. Similarities and differences between the two therapies and the therapists are outlined. Special attention is given to the problems in implementing research on long-term psychotherapy. Finally, the strengths and limitations of the present study are discussed.


Cancer in Syrian refugees in Jordan and Lebanon between 2015 and 2017.
Protracted conflicts in the Middle East have led to successive waves of refugees crossing borders. Chronic, non-communicable diseases are now recognised as diseases that need to be addressed in such crises. Cancer, in particular, with its costly, multidisciplinary care, poses considerable financial and ethical challenges for policy makers. In 2014 and with funding from the United Nations High Commissioner for Refugees, we reported on cancer cases among Iraqi refugees in Jordan (2010-12) and Syria (2009-11). In this Policy Review, we provide data on 733 refugees referred to the United Nations High Commissioner for Refugees in Lebanon (2015-17) and Jordan (2016-17), analysed by cancer type, demographic risk factors, treatment coverage status, and cost. Results show the need for increased funding and evidence-based standard operating procedures across countries to ensure that patients have equitable access to care. We recommend a holistic response to humanitarian crises that includes education, screening, treatment, and palliative care for refugees and nationals and prioritises breast cancer and childhood cancers.


CCAT2 enhances autophagy-related invasion and metastasis via regulating miR-4496 and ELAVL1 in hepatocellular carcinoma.
Autophagy is thought to contribute to the pathogenesis of many diseases, including cancer. Long non-coding RNA (lncRNA) CCAT2 functions as an oncogene in a variety of tumours. However, it is still unknown whether CCAT2 is involved in autophagy and metastasis of hepatocellular carcinoma (HCC). In our study, we found that lncRNA CCAT2 expression was significantly increased in HCC tissue and was correlated with advanced stage and venous invasion. Further experiments revealed that CCAT2 induced autophagy and promoted migration and invasion in vitro and in vivo. Mechanistic investigations found that CCAT2 involved in HCC by regulating miR-4496/Atg5 in cytoplasm. In nucleus, CCAT2 bound with ELAVL1/HuR to facilitate HCC progression. Our findings suggest that CCAT2 is an oncogenic factor in the progression of HCC with different regulatory mechanisms and may serve as a target for HCC therapy.


Immunization with neural-derived peptides increases neurogenesis in rats with chronic spinal cord injury.
Immunization with neural-derived peptides (INDP) has demonstrated to be a promising therapy to achieve a regenerative effect in the chronic phase of the spinal cord injury (SCI). Nevertheless, INDP-induced neurogenic effects in the chronic stage of SCI have not been explored. In this study, we analyzed the effect of INDP on both motor and sensitive function recovery; afterward, we assessed neurogenesis and determined the production of cytokines (IL-4, IL-10, and TNF alpha) and neurotrophic factors (BDNF and GAP-43). During the chronic stage of SCI, rats subjected to INDP showed a significant increase in both motor and sensitive recovery when compared to the control group. Moreover, we found a significant increase in neurogenesis, mainly at the central canal and at both the dorsal and ventral horns of INDP-treated animals. Finally, INDP induced significant production of antiinflammatory and regeneration-associated proteins in the chronic stages of SCI. These findings suggest that INDP has a neurogenic effect that could improve motor and sensitive recovery in the chronic stage of SCI. Moreover, our results also envision the use of INDP as a possible therapeutic strategy for other trauma-related disorders like traumatic brain injury.


[Prevention, Diagnosis, and Treatment of Pediatric Infections During Natural Disasters].
The objective of this review was to provide guidelines regarding the diagnosis, treatment, and prevention of the most common infectious diseases in children during natural disasters, including floods such as those that occurred in the summer of 2017 in Peru. This instrument should be used by physicians and health personnel working in primary health care. The management of diarrheal, respiratory, skin, and eye diseases, vector-transmitted diseases such as dengue, chikungunya, and Zika, and zoonoses such as leptospirosis is discussed. Emphasis is placed on the essential aspects of health education for the population, particularly preventive health, including the use of potable water, breastfeeding, immunization, hand washing, and vector control.


Confirmation of leucogentian violet in chicken fat by gas chromatography/mass spectrometry.
A gas chromatographic/mass spectrometric (GC/MS) procedure for confirming the identity of leucogentian violet (LGV) in chicken fat was developed for regulatory application. The unused portion of the extract remaining from a determinative procedure was back-extracted into an organic phase, concentrated, and analyzed by GC/MS. Confirmation of the identity of LGV was based on matching the retention times and relative abundances of 6 ions in the extract to corresponding values obtained for the LGV standard. The procedure was validated by replicate analyses of negative control, fortified control, and residue-incurred chicken fat. The presence of LGV was confirmed by the GC/MS procedure in all samples found to contain LGV by prior liquid chromatographic analyses. There were no interferences in the control samples.


Just blowing smoke? Social desirability and reporting of intentions to quit smoking.
Do cigarette smokers really want to quit smoking or do they simply say they do in order to placate others and avoid criticism? In surveys of smokers, stated quit intentions and reports of quit attempts may be biased by social desirability concerns. This makes it difficult to interpret large-scale state and national surveys of smoking behavior that collect data through telephone and face-to-face interviews, methods that tend to evoke high levels of socially desirable responding. The 2007 Health Information National Trends Survey used a dual-frame design to query smokers' quit intentions and past quit attempts in 1 of 2 ways: A self-administered mail survey (low pressure for socially desirable responding; n = 563), or an interviewer-administered telephone survey (high pressure for socially desirable responding; n = 499). Estimates derived from the 2 formats were compared to test for social desirability effects. In both survey modes, approximately two thirds of smokers reported seriously considering quitting in the next 6 months (mail: 64.9%; telephone: 68.9%), and approximately half reported making a quit attempt in the past year (mail: 54.9%; telephone: 52.3%). Neither difference approached significance in logistic regressions controlling for demographics (ps > .24). It appears that a large proportion of smokers in the United States aspire to live smoke-free lives and are not simply responding in a socially desirable manner to deflect criticism in an antismoking social climate. Future research should (1) replicate this study with greater statistical power, (2) examine the possible effects of survey context (e.g., health survey vs. smoking pleasure survey), and (3) explore survey mode effects in specific subpopulations.


First report of macrolide-resistant strains and description of a novel nucleotide sequence variation in the P1 adhesin gene in Mycoplasma pneumoniae clinical strains isolated in France over 12 years.
Mycoplasma pneumoniae isolates are divided in two types based on the sequence variations in the P1 adhesin gene. The type of P1 adhesin gene of 155 clinical isolates of M. pneumoniae collected in France between 1994 and 2006 was determined by a PCR-restriction fragment length polymorphism method. Until 1995, all strains belonged to type 1. In 1996 and 1997, type 1 was still predominant, but type 2 increased. Finally, since 1998, both types were present in about the same proportion. In our study, a novel sequence of the P1 adhesin gene was described in one strain. This strain could not be classified into type 1 or 2 because of variability in both P1 gene repeat elements, RepMP4 and RepMP2/3. This new sequence was certainly issued from recombination with repetitive sequences localized outside of the P1 gene in the M. pneumoniae chromosome. Moreover, MICs of erythromycin, tetracycline, and ciprofloxacin were determined for the 155 isolates. All isolates remained susceptible to tetracycline and ciprofloxacin, but two macrolide-resistant strains, isolated from two children in 1999, were identified. They harbored an A-to-G substitution at position 2058 or 2059 (Escherichia coli numbering) in domain V of 23S rRNA, associated with resistance to macrolides, lincosamides, and ketolides. To our knowledge, this is the first description of macrolide-resistant isolates of M. pneumoniae in France, but at this time, there is no sign of recent diffusion of resistant strains.


Transcranial direct-current stimulation confers neuroprotection by regulating isoleucine-dependent signalling after rat cerebral ischemia-reperfusion injury.
Isoleucine is a branched chain amino acid. The role of isoleucine in cerebral ischemia-reperfusion injury remains unclear. Here, we show that the concentration of isoleucine is decreased in cerebrospinal fluid in a rat model of cerebral ischemia-reperfusion injury, the rat middle cerebral artery occlusion (MCAO). To our surprise, the level of intraneuronal isoleucine is increased in an in vitro model of cerebral ischemia injury, the oxygen-glucose deprivation (OGD). We found that the increased activity of LAT1, an L-type amino acid transporter 1, leads to the elevation of intraneuronal isoleucine after OGD insult. Reducing the level of intraneuronal isoleucine promotes cell survival after cerebral ischemia-reperfusion injury, but supplementing isoleucine aggravates the neuronal damage. To understand how isoleucine promotes ischemia-induced neuronal death, we reveal that isoleucine acts upstream to reduce the expression of CBFB (core binding factor β, a transcript factor involved in cell development and growth) and that the phosphatase PTEN acts downstream of CBFB to mediate isoleucine-induced neuronal damage after OGD insult. Interestingly, we demonstrate that direct-current stimulation reduces the level of intraneuronal isoleucine in cortical cultures subjected to OGD and that transcranial direct-current stimulation (tDCS) decreases the cerebral infarct volume of MCAO rat through reducing LAT1-depencent increase of intraneuronal isoleucine. Together, these results lead us to conclude that LAT1 over activation-dependent isoleucine-CBFB-PTEN signal transduction pathway may mediate ischemic neuronal injury and that tDCS exerts its neuroprotective effect by suppressing LAT1 over activation-dependent signalling after cerebral ischemia-reperfusion injury.


Pneumoperitoneum caused by tubo-ovarian abscess in an elderly patient.
Perforation of the gastrointestinal tract may present with abdominal pain and imaging demonstrating pneumoperitoneum. These findings usually require exploratory laparotomy for diagnosis and treatment. Tubo-ovarian abscess (TOA) is a complication of pelvic inflammatory disease presenting as an encapsulated inflammatory mass, but it can occasionally involve other pelvic organs. TOA is most commonly seen in females of reproductive age. Here we report a case of a 63-year-old female presenting with abdominal pain, fever and vomiting. Chest x rays and computed tomography scan revealed pneumoperitoneum. Emergent exploratory laparotomy was performed, and the findings were consistent with TOA and intact bowel. The patient recovered well after surgery with antibiotic therapy. In conclusion, while pneumoperitoneum is mostly caused by perforation of the gastrointestinal tract, other possibilities such as gynecological complications should be considered.


Disseminated Armillifer Infection in Humans: A Rare Entity.
Armillifer parasites, belonging to the Pentastomida subclass, are commonly known to cause infection in animals, particularly reptiles. Although rare, cases of Armillifer infection in humans have been reported. Most cases are asymptomatic or mildly symptomatic, with severe presentations being uncommon. Symptoms can vary depending on whether the nymph is encysted or actively dying, leading to immune-mediated reactions. Diagnostic imaging findings can be characteristic of Armillifer infection. We present the case of a 61-year-old male from West Africa with a history of snake consumption, who presented with night sweats, fevers, and chills, and imaging consistent with disseminated Armillifer infection.


Design, Synthesis, and Anticancer Evaluation of Novel Tetracaine Hydrazide-Hydrazones.
Tetracaine is an ester derivative used as a local anesthetic molecule. In this study, a series of novel Tetracaine derivatives bearing hydrazide-hydrazone moiety were designed, synthesized, and evaluated for anticancer activity. The structures of these compounds were characterized by spectral (1H NMR,13C NMR, FT-IR, and HRMS analyses) methods. All synthesized compounds were screened for anticancer activity against two different human cancer cell lines (Colo-205 and HepG2). Among the synthesized molecules, compounds 2f and 2m showed the most potent anticancer activity against the Colo-205 cell line (IC50 = 50.0 and 20.5 μM, respectively). Compounds 2k, 2p, and 2s demonstrated the best anticancer activity against the HepG2 cell line (IC50 = 30.5, 35.9, and 20.8 μM, respectively). mRNA transcription levels of Bax and caspase-3 genes were determined by real-time polymerase chain reaction (qRT-PCR) analysis of both Colo-205 and HepG2 cell lines. Doxorubicin was used as a positive sensitivity reference standard. qRT-PCR analysis showed that there was a time-dependent rise in the expression levels of Bax and Caspase 3 on apoptosis. Inhibition of apoptotic proteins PI3K, Akt, PTEN, pPTEN, FoXO1, FoXO3a, TXNIP, and p27 was investigated in Colo-205 and HepG2 cells treated with compounds 2f, 2m, 2k, 2p, and 2s by using Western blotting.


Primary Care Physicians' Knowledge, Perceptions, and Comfort Level in Managing Patients Fasting in Ramadan.
Background: Once a year, Muslims fast from dawn to sunset during the month of Ramadan. While fasting has many positive health implications, it may pose risks to individuals with underlying health issues. Despite the exemption from fasting for those who are ill, many Muslims with chronic conditions choose to fast. It is unclear how many Muslim patients receive counseling on fasting. As such, the purpose of this pilot project was to assess the knowledge, perception, and comfort level of primary care physicians (PCPs) at Dalhousie University's Department of Family Medicine in managing patients choosing to fast during Ramadan. Methods: A 16-item anonymous, self-administered, structured online survey was distributed to PCPs with an academic affiliation with the Department of Family Medicine at Dalhousie University. Participants rated their level of comfort, objective knowledge, and perceptions of managing patients fasting in Ramadan. Results: Many PCPs perceived the importance of understanding Ramadan fasting and its relevance to their patients' health, however, they did not have adequate knowledge about the matter. The majority of PCPs felt they received inadequate training in this area and did not feel comfortable counseling and managing the health of these patients. Conclusions: The findings of this study have outlined a knowledge gap that exists within our PCP community and will help inform and prioritize educational needs and direct efforts to ensure safe patient management during Ramadan.


Comparison of 3D accuracy of three different digital intraoral scanners in full-arch implant impressions.
This in vitro study aimed to evaluate the performance of digital intraoral scanners in a completely edentulous patient with angled and parallel implants. A total of 6 implants were placed at angulations of 0°, 5°, 0°, 0°, 15°, and 0° in regions #36, #34, #32, #42, #44, and #46, respectively, in a completely edentulous mandibular polyurethane model. Then, the study model created by connecting a scan body on the implants was scanned using a model scanner, and a 3D reference model was obtained. Three different intraoral scanners were used for digital impressions (PS group, TR group, and CS group, n = 10 in each group). The distances and angles between the scan bodies in these measurement groups were measured. While the Primescan (PS) impression group had the highest accuracy with 38 µm, the values of 104 µm and 171 µm were obtained with Trios 4 IOSs (TR) and Carestream 3600 (CS), respectively (P = .001). The CS scanner constituted the impression group with the highest deviation in terms of accuracy. In terms of dimensional differences in the angle parameter, a statistically significant difference was revealed among the mean deviation angle values according to the scanners (P < .001). While the lowest angular deviation was obtained with the PS impression group with 0.185°, the values of 0.499° and 1.250° were obtained with TR and CS, respectively. No statistically significant difference was detected among the impression groups in terms of precision values (P > .05). A statistically significant difference was found among the three digital impression groups upon comparing the impression accuracy. Implant angulation affected the impression accuracy of the digital impression groups. The most accurate impressions in terms of both distance and angle deviation were obtained with the PS impression group.


1.9 A structure of the signal receiver domain of the putative response regulator NarL from Mycobacterium tuberculosis.
NarL from Mycobacterium tuberculosis is a putative nitrate response regulator that is involved in the regulation of anaerobic metabolism in this pathogen. The recombinant purified N-terminal signal receiver domain of NarL has been crystallized in space group C222(1), with unit-cell parameters a = 85.6, b = 90.0, c = 126.3 A, and the structure was determined by molecular replacement to 1.9 A resolution. Comparisons with related signal receiver domains show that the closest structural homologue is an uncharacterized protein from Staphylococcus aureus, whereas the nearest sequence homologue, NarL from Escherichia coli, displays larger differences in three-dimensional structure. The largest differences between the mycobacterial and E. coli NarL domains were found in the loop between beta3 and alpha3 in the proximity of the phosphorylation site. The active site in response regulators is similar to that of members of the haloacid dehalogenase (HAD) family, which also form a phospho-aspartyl intermediate. In NarL, the aspartic acid that acts as catalytic acid/base in several HAD enzymes is replaced by an arginine residue, which is less likely to participate in steps involving proton abstraction. This substitution may slow down the breakdown of the phospho-aspartyl anhydride and allow signalling beyond the timescales defined by a catalytic reaction intermediate.


The Medial Stitch in Transosseous-Equivalent Rotator Cuff Repair: Vertical or Horizontal Mattress?
Despite advances in surgical technique, rotator cuff repair retears continue to occur at rates of 10%, 22%, and 57% for small, medium, and large tears, respectively. A common mode of failure in transosseous-equivalent rotator cuff repairs is tissue pullout of the medial mattress stitch. While the medial mattress stitch has been studied extensively, no studies have evaluated a vertical mattress pattern placed near the musculotendinous junction in comparison with a horizontal mattress pattern. Vertical mattress stitches will have higher load to failure and lower gapping compared with horizontal mattress stitches in a transosseous-equivalent rotator cuff repair. Controlled laboratory study. Double-row transosseous-equivalent rotator cuff repairs were performed in 9 pairs of human male cadaveric shoulders (mean age ± SD, 58 ± 10 years). One shoulder in each pair received a medial-row suture pattern using a vertical mattress stitch, and the contralateral shoulder received a horizontal mattress. Specimens were mounted in a materials testing machine and tested in uniaxial tensile deformation for cyclic loading (500 cycles at 1 Hz to 1.0 MPa of effective stress), followed by failure testing carried out at a rate of 1 mm/s. Construct gapping and applied loads were monitored continuously throughout the testing. Vertical mattress sutures were placed in 5 right and 4 left shoulders. Peak cyclic gapping did not differ between vertical (mean ± SD, 2.8 ± 1.1 mm) and horizontal mattress specimens (3.0 ± 1.2 mm) (P = .684). Vertical mattress sutures failed at higher loads compared with horizontal mattress sutures (568.9 ± 140.3 vs 451.1 ± 174.3 N; P = .025); however, there was no significant difference in failure displacement (8.0 ± 1.6 vs 6.0 ± 2.1 mm; P = .092). Failure stiffness did not differ between the suture patterns (P = .204). In transosseous-equivalent rotator cuff repairs near the musculotendinous junction, a vertical mattress suture used as the medial stitch has a higher load to failure but no difference in gapping compared with a horizontal mattress pattern. A vertical mattress suture may offer enhanced strength of repair for transosseous-equivalent repairs.


[Management of diabetic retinopathy and diabetic maculopathy in elderly patients with diabetes mellitus].
The world's population is aging, and simultaneously, the prevalence of diabetes mellitus worldwide is rapidly increasing. Therefore, the clinical management of diabetic retinopathy and diabetic maculopathy in elderly patients with diabetes is increasingly becoming more important. Therefore, collaboration between ophthalmologists and physicians is mandatory. The international clinical diabetic retinopathy and macular edema disease severity scales are very useful for information sharing between ophthalmologists and diabetologists. This review describes a strategy to assess symptoms of diabetes, including the clinical course of retinopathy and maculopathy, pathological changes, and pathogenesis, as well as details an updated treatment modality. Elderly patients tend to present with multiple complications that should be considered by the management team.


Autoencoder assisted subcarrier optimization for nonlinear frequency division multiplexing.
Nonlinear frequency division multiplexing (NFDM) is a novel optical communication technique that can achieve nonlinear free transmission. However, current design of NFDM is analogous to orthogonal frequency division multiplexing (OFDM), where sinc function is utilized as subcarriers, which may not be optimal for nonlinear spectrums. In this paper, we propose an auto-encoder (AE) assisted subcarrier optimization scheme for dual-polarized (DP) NFDM systems. Numerical verifications show that our scheme can improve the Q-factor by 1.54 dB and 0.62 dB compared to sinc subcarrier and linear minimum mean square error (LMMSE) equalization, respectively, in a 960 km transmission scenario. We also analyze the characteristics of the optimized subcarriers and discuss how they enhance the performance. Furthermore, we demonstrate the robustness of the optimized subcarriers to different modulation formats, transmission distances and bandwidth. Our work provides a new idea in subcarrier design for NFDM.


The influence of volume expansion with induced hypertension on vessel reactivities, the blood-brain barrier, and cerebral infarction in cats with one-hour occlusion of the middle cerebral artery.
Thirty anesthetized cats were randomly assigned to three groups of 10 cats each: a 10% hydroxyethyl starch-treated group (10% HAES group), a 6% hydroxyethyl starch-treated group (6% HAES group), or a control group. Cerebral pial arterial reactivities were measured by means of intravital microscopic observation through a cranial window. The middle cerebral artery of the cat was clipped for 1 hour using the transorbital approach, 5 hours later Evans blue dye was injected intravenously, and 30 minutes later the animals was killed. Administration of hydroxyethyl starch or saline was started 15 minutes before clipping and lasted for 1 hour. Total volume administered was 10 ml/kg. Systemic arterial pressure was elevated to about 30 to 40% higher than the resting value by administration of dopamine soon after clipping and maintained for 1 hour. In the hydroxyethyl starch-treated groups, the sizes of infarctions and Evans blue dye leakage were significantly smaller than in the control group. Dye leakage in the 10% HAES group was larger than in the 6% HAES group (statistically significant). Regarding pial arterial reactivities, the caliber of arteries was different in each group after reopening of the clip. Arteries in the control group first returned to some 20% of resting state and redilated 40% or more, arteries in the 6% HAES group returned almost to the resting calibers, and arteries in the 10% HAES group constricted by -20% of the resting calibers. Moreover, 8 of 10 cats in the 10% HAES group showed extravasation of red cells. Only one cat in the 6% HAES group showed extravasation.(ABSTRACT TRUNCATED AT 250 WORDS)


Nutritional Status and its Impact on Clinical Outcomes for Patients Admitted to Hospital with Cirrhosis.
In patients with cirrhosis, nutritional status is an important predictor of clinical outcomes that can be assessed in clinical practice using conventional methods. Previous studies have shown that malnutrition is associated with increased morbidity and mortality in patients with cirrhosis. However, there have been very few reports from Southeast Asia. To determine the prevalence of malnutrition in patients with cirrhosis who are admitted to hospital and to assess its correlation with mortality, complications, length of stay, and total cost of hospitalization. This prospective non-interventional study included 60 consecutive patients with cirrhosis admitted to Rajavithi Hospital, Bangkok, Thailand, from August 2013 to February 2014. Baseline demographic and clinical data during their hospitalizations were collected prospectively. Nutritional status was assessed by subjective global assessment (SGA) and anthropometry (body mass index (BMI) and mid-arm circumference (MAC)). Malnutrition was defined as SGA class B/ C and MAC of < 5th percentile of the age- and gender-matched reference population. Of the 60 patients, 70% were male. The most common causes of cirrhosis were alcohol (50%) and hepatitis C infection (35%). Most patients were classified as Child-Pugh class B (41.7%) or C (36.7%). The mortality rate was 26.7%, and the most common complications were infections (60%) and renal failure (43.3%). The median length of stay in hospital was 8.5 (1-51) days, with a median cost of 1,163 (183-9,969) US dollars. The prevalence of malnutrition varied between 18% and 92% depending on the assessment method employed: 18% were considered malnourished when assessed by BMI, 63% by MAC, 78% by serum albumin, 65% by absolute lymphocyte count, and 92% by SGA. Patients with malnutrition showed a trend toward increased mortality, complications, length of hospital stay and cost; however, the differences were not statistically significant. Significant predictors of mortality included Child-Pugh class B (16% mortality) and C (50% mortality), severe malnutrition as assessed by SGA (35% mortality), presence of ascites (relative risk, RR: 2.3), hepatic encephalopathy (RR: 2.5), hepatorenal syndrome (RR: 4.1) and renal failure (RR: 3.3). Malnutrition is common in hospitalized patients with cirrhosis, and patients with malnutrition showed a trend toward increased complications and mortality. Severe malnutrition, as identified by SGA, and advanced cirrhosis were predictors of in-hospital mortality.


Particle Deformability Enables Control of Interactions between Membrane-Anchored Nanoparticles.
Nanoparticles adsorbed on a membrane can induce deformations of the membrane that give rise to effective interactions between the particles. Previous studies have focused primarily on rigid nanoparticles with fixed shapes. However, DNA origami technology has enabled the creation of deformable nanostructures with controllable shapes and mechanical properties, presenting new opportunities to modulate interactions between particles adsorbed on deformable surfaces. Here we use coarse-grained molecular dynamics simulations to investigate deformable, hinge-like nanostructures anchored to lipid membranes via cholesterol anchors. We characterize deformations of the particles and membrane as a function of the hinge stiffness. Flexible particles adopt open configurations to conform to a flat membrane, whereas stiffer particles induce deformations of the membrane. We further show that particles spontaneously aggregate and that cooperative effects lead to changes in their shape when they are close together. Using umbrella sampling methods, we quantify the effective interaction between two particles and show that stiffer hinge-like particles experience stronger and longer-ranged attraction. Our results demonstrate that interactions between deformable, membrane-anchored nanoparticles can be controlled by modifying mechanical properties of the particles, suggesting new ways to modulate the self-assembly of particles on deformable surfaces.


Single- and multi-trait genomic prediction and genome-wide association analysis of grain yield and micronutrient-related traits in ICARDA wheat under drought environment.
Globally, over 2 billion people suffer from malnutrition due to inadequate intake of micronutrients. Genomic-assisted breeding is identified as a valuable method to facilitate developing new improved plant varieties targeting grain yield and micronutrient-related traits. In this study, a genome-wide association study (GWAS) and single- and multi-trait-based genomic prediction (GP) analysis was conducted using a set of 252 elite wheat genotypes from the International Center for Agricultural Research in Dry Areas (ICARDA). The objective was to identify linked SNP markers, putative candidate genes and to evaluate the genomic estimated breeding values (GEBVs) of grain yield and micronutrient-related traits.. For this purpose, a field trial was conducted at a drought-prone station, Merchouch, Morocco for 2 consecutive years (2018 and 2019) followed by GWAS and genomic prediction analysis with 10,173 quality SNP markers. The studied genotypes exhibited a significant genotypic variation in grain yield and micronutrient-related traits. The GWAS analysis identified highly significantly associated markers and linked putative genes on chromosomes 1B and 2B for zinc (Zn) and iron (Fe) contents, respectively. The genomic predictive ability of selenium (Se) and Fe traits with the multi-trait-based GP GBLUP model was 0.161 and 0.259 improving by 6.62 and 4.44%, respectively, compared to the corresponding single-trait-based models. The identified significantly linked SNP markers, associated putative genes, and developed GP models could potentially facilitate breeding programs targeting to improve the overall genetic gain of wheat breeding for grain yield and biofortification of micronutrients via marker-assisted (MAS) and genomic selection (GS) methods.


Smooth Muscle Cell Differentiation: Model Systems, Regulatory Mechanisms, and Vascular Diseases.
Smooth muscle cell (SMC) differentiation is an important process during vascular development. The highly differentiated mature SMCs play critical roles in maintaining structural and functional integrity of blood vessels. However, SMCs are not terminally differentiated, and their phenotype can be modulated between contractile and proliferative states in response to various environmental conditions. Alterations in SMC phenotype contribute to a number of major cardiovascular diseases such as atherosclerosis, hypertension and restenosis following angioplasty, etc. The goal of this review is to provide a brief overview of the recent advancements in our understanding of SMC differentiation and the development of in vitro SMC differentiation models, with a particular emphasis on examination of molecular mechanisms involved in the regulation of SMC differentiation and phenotypic modulation. J. Cell. Physiol. 231: 777-787, 2016. © 2015 Wiley Periodicals, Inc.


A report of disseminated actinic granuloma: An unusually extensive presentation.
In this report, a case of disseminated actinic granuloma in a 50-year-old female with type 2 diabetes mellitus is described. This case is unique due to the unusually extensive cutaneous involvement of the face, neck, trunk, and extremities at initial presentation. The lesions were in a striking photo-distribution, highlighting ultraviolet light as an important environmental trigger for this process. Interestingly, the patient refused the recommended systemic therapy with hydroxychloroquine, despite her significant burden of skin disease. This refusal stems from an unexpected reluctance on the part of the patient to take this medication due to the publicity and media coverage of side effects associated with inappropriate prescribing of this drug during the COVID-19 pandemic, presenting a new and surprising treatment barrier that clinicians may need to overcome.


Medication-related osteonecrosis of the jaw, a risk to reassess in osteoporotic patients.
The use of antiresorptive drugs concerns many medical specialties either in relation to their prescription for osteoporosis or cancer, or in relation to the treatment of their side effects. In the literature, less than 10% of medication-related osteonecrosis of the jaw are related to patients treated for osteoporosis, while 90% are found in patients treated for cancer. Despite the increasing number of osteoporotic patients taking high doses of antiresorptive drugs, only few studies describe this topic. The main aim of this study was to highlight the occurrence of medication-related osteonecrosis of the jaw in osteoporotic patients compared to cancer patients. The second aim was to highlight risk factors in the two groups, to try to understand the high number of osteoporotic patients in our population. A retrospective study was conducted between December 2004 and March 2021 to identify all cases of medication-related osteonecrosis of the jaw in our department with emphasis on the osteoporotic population. Demographic, systemic and local risk factors were collected as well as the type, dose and duration of the anti-resorptive drugs treatment. Evolution and follow-up were also recorded. One hundred sixty five patients presented with medication-related osteonecrosis of the jaw, of whom 67 (40,6%) were osteoporotic. Seventeen (25,4%) patients were males and 50 females (74,6%). Risk factors were tobacco consumption (28,4%), anemia (20,9%), alcohol consumption (19,4%). Use of corticoids or anticoagulant/antithrombotic therapy was related in 20,9% and 16,4%, respectively. The mean age at MRONJ diagnosis was 74,4 (50-98). The mean follow up time was 23,7 months (1-110). Unlike the literature where medication-related osteonecrosis of the jaw in osteoporotic patients represents less than 10%, the rate in our series was much higher and represents 40% of the patients. This highlights the importance of a complete dental examination before and during antiresorptive drugs treatment, even in the case of osteoporotic patients.


Genetic basis of response to 50 generations of selection on body weight in inbred mice.
A long-established inbred strain of mice was divergently selected for body weight for 50 generations. Selection of new mutations affecting the trait eventually led to a divergence of approximately three phenotypic standard deviations between the high and low lines. Heritability for body weight increased at a rate between 0.23% and 0.57% per generation from new mutations, depending on the genetic model assumed. About two-thirds of the selection response was in the upward direction. The response was episodic, suggesting a substantial contribution from the selection of mutations with large effects on the trait. A maximum likelihood procedure was used to estimate the number of factors contributing to the response using data from line crosses, with models of n equivalent gene effects (i.e., to estimate the Wright-Castle index), or n genes with variable effects. The results of the analysis of data from a cross between the selected high line and an unselected control line indicated that two major factors were involved, with the suggestion of an additional minor factor.


Palliative care needs of patients living with end-stage kidney disease not treated with renal replacement therapy: An exploratory qualitative study from Blantyre, Malawi.
The burden of end-stage kidney disease (ESKD) in sub-Saharan Africa is increasing rapidly but the palliative care needs of patients living with ESKD are not well described. Resource limitations at both health system and patient level act as major barriers to patients receiving renal replacement therapy (RRT) in the form of dialysis. We undertook an exploratory qualitative study to describe the palliative care needs of patients with ESKD who were not receiving RRT, at a government teaching hospital in Blantyre, Malawi. A qualitative, explorative and descriptive design was used. Study participants were adults aged > 18 years with an estimated glomerular filtration rate < 15 ml/min on two separate occasions, three months apart, who either chose not to have or were not deemed suitable for RRT. Data were collected by means of semi-structured interviews. In October and November 2013, interviews were conducted with 10 adults (7 women with median age of 60.5 years). All were hypertensive and four were on treatment for HIV. Four themes emerged from the data: changes in functional status because of physical symptoms, financial challenges impacting hospital care, loss of role within the family and the importance of spiritual and cultural beliefs. This study reports on four thematic areas which warrant further quantitative and qualitative studies both in Malawi and other low-resource settings, where a growing number of patients with ESKD unable to access RRT will require palliative care in the coming years.


Associations of childhood, maternal and household dietary patterns with childhood stunting in Ethiopia: proposing an alternative and plausible dietary analysis method to dietary diversity scores.
Identifying dietary patterns that consider the overall eating habits, rather than focusing on individual foods or simple counts of consumed foods, better helps to understand the combined effects of dietary components. Therefore, this study aimed to use dietary patterns, as an alternative method to dietary diversity scores (DDSs), and investigate their associations with childhood stunting in Ethiopia. Mothers and their children aged under 5 years (n = 3788) were recruited using a two-stage random cluster sampling technique in two regions of Ethiopia. Socio-demographic, dietary and anthropometric data were collected. Dietary intake was assessed using standardized dietary diversity tools. Household, maternal and child DDSs were calculated and dietary patterns were identified by tetrachoric (factor) analysis. Multilevel linear and Poisson regression analyses were applied to assess the association of DDSs and dietary patterns with height-for-age z score (HAZ) and stunting, respectively. The overall prevalence of stunting among children under-five was 38.5% (n = 1459). We identified three dietary patterns each, for households ("fish, meat and miscellaneous", "egg, meat, poultry and legume" and "dairy, vegetable and fruit"), mothers ("plant-based", "egg, meat, poultry and legume" and "dairy, vegetable and fruit" and children ("grain based", "egg, meat, poultry and legume" and "dairy, vegetable and fruit"). Children in the third tertile of the household "dairy, vegetable and fruit" pattern had a 0.16 (β = 0.16; 95% CI: 0.02, 0.30) increase in HAZ compared to those in the first tertile. A 0.22 (β = 0.22; 95% CI: 0.06, 0.39) and 0.19 (β = 0.19; 0.04, 0.33) increase in HAZ was found for those in the third tertiles of "dairy, vegetable and fruit" patterns of children 24-59 months and 6-59 months, respectively. Those children in the second (β = -0.17; 95% CI: -0.31, -0.04) and third (β = -0.16; 95% CI: -0.30, -0.02) tertiles of maternal "egg, meat, poultry and legume" pattern had a significantly lower HAZ compared to those in the first tertile. No significant associations between the household and child "egg, meat, poultry and legume" dietary patterns with HAZ and stunting were found. Statistically non-significant associations were found between household, maternal and child DDSs, and HAZ and stunting. A higher adherence to a "dairy, vegetable and fruit" dietary pattern is associated with increased HAZ and reduced risk of stunting. Dietary pattern analysis methods, using routinely collected dietary data, can be an alternative approach to DDSs in low resource settings, to measure dietary quality and in determining associations of overall dietary intake with stunting.


Probing the mechanical folding kinetics of TAR RNA by hopping, force-jump, and force-ramp methods.
Mechanical unfolding and refolding of single RNA molecules have previously been observed in optical traps as sudden changes in molecular extension. Two methods have been traditionally used: "force-ramp", with the applied force continuously changing, and "hopping". In hopping experiments the force is held constant and the molecule jumps spontaneously between two different states. Unfolding/refolding rates are measured directly, but only over a very narrow range of forces. We have now developed a force-jump method to measure the unfolding and refolding rates independently over a wider range of forces. In this method, the applied force is rapidly stepped to a new value and either the unfolding or refolding event is monitored through changes in the molecular extension. The force-jump technique is compared to the force-ramp and hopping methods by using a 52-nucleotide RNA hairpin with a three-nucleotide bulge, i.e., the transactivation response region RNA from the human immunodeficiency virus. We find the unfolding kinetics and Gibbs free energies obtained from all three methods to be in good agreement. The transactivation response region RNA hairpin unfolds in an all-or-none two-state reaction at any loading rate with the force-ramp method. The unfolding reaction is reversible at small loading rates, but shows hysteresis at higher loading rates. Although the RNA unfolds and refolds without detectable intermediates in constant-force conditions (hopping and force-jump), it shows partially folded intermediates in force-ramp experiments at higher unloading rates. Thus, we find that folding of RNA hairpins can be more complex than a simple single-step reaction, and that application of several methods can improve understanding of reaction mechanisms.


Effect of palmitoleic acid on bradykinin-induced endothelium-dependent relaxation in isolated pig ciliary artery.
Endothelial-dependent relaxation has been reported to be impaired in some normal tension glaucoma patients. The present study investigates whether the gap junction uncoupling agent palmitoleic acid (PA) affects bradykinin-induced endothelium-dependent relaxation in isolated pig ciliary artery. In a myograph system (isometric force measurement), vessels precontracted with the thromboxane A2 agonist U 46619 ( approximately 0.1 micrometer) were relaxed by increasing concentrations (cumulative) of bradykinin (0.003 - 3 micrometer). Experiments were repeated in the presence of 100 micrometer L-NAME (inhibitor of nitric oxide formation) and/or 100 micrometer PA. Some experiments were conducted in vessels with a non-functional endothelium (intentionally and mechanically damaged). All experiments were conducted in the presence of 10 microM indomethacin (cyclooxygenase inhibitor). In a concentration-dependent manner, bradykinin evoked a relaxation (101 +/- 2 %) that was abolished in vessels with a non-functional endothelium (maximal relaxation: 7 +/- 1 %, p < 0.001). In the presence of L-NAME, relaxations induced by bradykinin were almost completely inhibited (maximal relaxation: 25 +/- 5 %, p < 0.001). Relaxations evoked by bradykinin were not significantly affected by PA (either in the presence or in the absence of L-NAME). The bradykinin-induced relaxation, known to be associated in porcine ciliary arteries with an electrical coupling between endothelial and smooth muscle cells, appears to be unaffected by the gap junction uncoupling agent palmitoleic acid. Further investigations are needed to understand the physiology of the endothelium-dependent ocular blood flow modulation that is considered to be dysregulated in some glaucoma patients.


Answers to wh-questions: a developmental study.
Forty children aged 3-6 years responded to items representing nine wh-question forms. Questions referred to three types of referential sources (conditions) based on immediacy and visual availability. The hierarchies of wh-question forms based on degree of difficulty were similar to those described in previous investigations. However, a significant interaction between referential conditions and wh-form was found to influence the relative complexity of the stimulus questions. The children were significantly less successful in giving appropriate and accurate responses when the question referred to objects, persons, or events not represented in the immediate setting. Recognition and delivery of the general category or kind of information required by a wh-form (functional appropriateness) appeared to predate substantially the ability to respond with fact, accuracy, logic, and credibility (functional accuracy). The results suggest consideration and control of referential source as well as appropriateness/accuracy response criteria in the evaluation and treatment of language-disordered children.


Effects of CpG-ODN on gene expression in formation of foam cells.
To investigate the effects of CpG-oligodeoxynucleotide (CpG-ODN) on the formation of macrophage foam cells and related gene expression. A gene expression profile was examined by microarray techniques, and mRNA expression was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The cholesterol and cholesteryl ester contents of cells were determined by high performance liquid chromatography. CD36, LPL, and Fcgamma2b, which were related to lipid metabolism and the formation of macrophage foam cells, were upregulated after CpG-ODN stimulation. The mRNA expression related to the formation of foam cells was confirmed by semiquantitative RT-PCR. Moreover, histochemical analysis confirmed that lipid deposits inside cells increased after CpG-ODN treatment. However, using flow cytometry, we found that CpG-ODN had no effect on the expression of membrane receptors. CpG-ODN up-regulated the expression of genes in macrophage foam cell formation.


Physician Gender and Lifestyle Counselling to Prevent Cardiovascular Disease: A Nationwide Representative Study.
Primary care physicians (PCPs) have a key role in the prevention of cardiovascular diseases (CVD). However, it is not clear whether lifestyle counselling behaviour differs between female and male PCPs. Nonetheless, this information might be helpful to develop need-based advanced training for female and male PCPs. Therefore, our aim was to identify potential gender differences in the implementation of health promotion and the prevention of CVD in primary care. In a Germany-wide survey called the ÄSP-kardio Study, we collected data from 4074 PCPs (40% female; from October 2011 to March 2012). We compared the provision of prevention measures, the attitude towards counselling, and the potential barriers in counselling among female and male German PCPs. We used chi(2) tests, Mann-Whitney U tests, and logistic regression analysis. We found differences in all of the above-mentioned aspects. Female PCPs were less likely to perceive barriers than male and more likely to ask patients about lifestyle, for example, nutrition (OR=1.62, P≤0.001). Additionally, female PCPs were more likely to feel well prepared (84.2% vs. 76.0%, P≤0.001) and successful (75.6% vs. 68.0%, P≤0.001). Male PCPs were more likely to mention barriers in daily practice that hinder lifestyle counselling. Overall, both female and male PCPs had a positive attitude towards lifestyle counselling. Nevertheless, in view of the barriers that they indicated, incentives such as better reimbursement may help output-oriented PCPs to translate their positive attitude into action. Moreover, awareness of gender differences may help PCPs to acquire the specific advanced training that they need for effective lifestyle counselling in CVD. Significance for public healthLifestyle counselling is an important instrument to reduce the burden of cardiovascular disease. Here, primary care physicians (PCPs) play an important role as health advisors. Our study was able to identify deficits in the health promotion behaviour of PCPs. Because of the gender differences revealed in our study, male PCPs in particular should be sensitized to the importance and the potentials of prevention and health promotion. Overcoming the barriers of prevention and health promotion identified by the PCPs may be an important starting point. If, for instance, PCPs were better financially compensated for offering lifestyle counselling, which was rated as the most important barrier, it is conceivable that more PCPs would start to incorporate such measures into their daily routine. Additionally, a stronger focus on prevention and health promotion during advanced training programs for PCPs could increase the use of lifestyle counselling.


Ion-selective detection by plasticized poly(vinyl chloride) membrane in glass nanopipette with alternating voltage modulation.
An alternating current (AC) voltage modulation was applied to ion-selective observations with plasticized poly(vinyl chloride) membranes in glass nanopipettes. The liquid confronting the membranes in the nanopipettes, the conditioning process, and AC voltage modulation play important roles in the ion-selective detection. In the AC detection system developed by us, where distilled water was used as the liquid within the nanopipettes, potassium ions were selectively detected in the sample solution of sodium and potassium ions because sodium ions were captured at the membrane containing bis(12-crown-4) ionophores, before the saturation of the ionophores. The membrane lost the selectivity after the saturation. On using sodium chloride as the liquid within the nanopipette, the membrane selectively detected potassium and sodium ions before and after the saturation of ionophores, respectively. The ion-selective detection of our system can be explained by the ion extraction-diffusion-dissolution mechanism through the bis(12-crown-4) ionophores with AC voltage modulation.


MRI and x-ray CT study of spatial distribution of core breakdown in 'Conference' pears.
Two non-destructive tomographic techniques, X-ray CT imaging and magnetic resonance imaging (MRI), were applied to study the development of core breakdown disorder in 'Conference' pears (Pyrus communis cv. Conference). This disorder, which is characterized by brown discoloration of the tissue and development of cavities, is induced by elevated CO(2) and decreased O(2) levels during controlled atmosphere storage. Tomographic images of pears stored for 10 months under disorder inducing conditions, were acquired with both techniques and compared to the actual slices. Both X-ray and MRI were able to differentiate between unaffected tissue, brown tissue and cavities. A simple image-processing program, based on threshold values, was developed to determine the area percentage of affected and unaffected tissue as well as the cavity and core area per slice. For all three imaging techniques the area percentage brown tissue per slice increased with the diameter of the pear, but was systematically underestimated by 12% and 6% for, respectively, X-ray and MRI, compared to the actual slices. The area percentage cavity corresponded very well for all techniques. It was also found that the contours of the brown tissue were parallel to the fruit boundaries, suggesting a relation between the disorder symptoms and gas diffusion properties of the fruit. It was concluded that MRI is the most appropriate technique to study the development of core breakdown disorder during postharvest storage in future experiments.


Dual inhibition of PI3K/Akt signaling and the DNA damage checkpoint in p53-deficient cells with strong survival signaling: implications for cancer therapy.
Natural (intrinsic) resistance of many tumor types to DNA damaging agents is closely associated with their capacity to undergo robust cell cycle arrest in G(2)/M. G(2) arrest is regulated by the DNA damage checkpoint and by survival signaling, with a potential role of PI3K/Akt in checkpoint function. In this work, we wanted to clarify if inhibition of multiple checkpoint/survival pathways may confer better efficacy in the potentiation of genotoxic agents compared to inhibition of either pathway alone. We compared the influence of UCN-01, which affects both the DNA damage checkpoint and PI3K/Akt-mediated survival signaling, with the PI3K inhibitors wortmannin and LY294002 in p53-deficient M1 acute myeloid leukemia cells treated with the DNA damaging agent cisplatin. Our results show that direct inhibition of PI3K/Akt in G(2)-arrested cells by wortmannin or LY294002 strongly enhanced the cytotoxicity of cisplatin without influencing the G(2) checkpoint. Unexpectedly, dual inhibition of both survival and checkpoint signaling by UCN-01, also increased the cytotoxicity of cisplatin, but to a lesser degree than wortmannin or LY294002. The differences in cytotoxicity were accompanied by differences in cell death pathways: direct inhibition of PI3K/Akt was accompanied by rapid apoptotic cell death during G(2), whereas cells underwent mitotic transit and cell division followed by cell death during G(1) when both checkpoint and survival signaling were inhibited. Our results elucidate a novel function for PI3K/Akt as a survival factor during DNA damage-induced G(2) arrest and could have important pharmacological consequences for the application of response modulators in p53-deficient tumors with strong survival signaling.


Hormonal changes during a prolonged tamoxifen treatment in patients with advanced breast cancer.
The effect of tamoxifen (TAM) on the serum levels of sexual hormones and on the sex hormone-binding globulin (SHBG) was investigated in 30 postmenopausal patients with advanced breast cancer. To study the 'prolactin reserve capacity' of the pituitary gland, thyrotrophin-releasing hormone (TRH) and sulpiride-induced prolactin release were measured prior to TAM treatment, then in the 2nd and 8th week of the therapy. The TRH (400 micrograms i.v.)-induced prolactin secretion was significantly suppressed by TAM after an 8-week treatment, but only in responding cases. Maximal prolactin stimulation occurred at the 15th min after TRH injection, being equal to 5,600 +/- 800 mlU/l in cancer patients, and decreasing to 2,400 +/- 150 mlU/l after 8 weeks. TAM did not suppress the sulpiride-inducable prolactin release either in responders or in nonresponders.


Neuropsychological treatment and longtime follow-up in an aphasic patient with very severe head trauma.
A 44-year old man with very severe head trauma had pronounced global aphasia and dyslogia for months. He received intensive neuropsychological treatment during the first two posttraumatic years and gradual improvement occurred. Notwithstanding sensory aphasia and at least moderate dementia, the patient then got sheltered work in a library. At that time a general follow-up examination took place and information on memory, language, and personality was obtained from the spouse. The procedure was repeated in exactly the same way ten years later. The great improvement in language and cognitive functions that had occurred during the decennium revealed itself in daily life as well as in clinical and psychometric findings. The case described shows that recovery neuropsychological functions can take place during many years after very severe head trauma.


[Phenazepam: to the question of the efficacy and safety of benzodiazepine derivatives].
The widespread use of benzodiazepines in general medicalpractice in patients with complaints of anxiety and insomnia is due to a combination of efficacy and relative safety. Benzodiazepines have several advantages over other groups of sedatives: a wider range of doses between anxiolytic and sedative effect, a higher ratio between the average lethal and average effective doses, the lower risk of abuse. However, with prolonged use of even therapeutic doses of benzodiazepines (more than 6 months), the risk of dependence may increase - more often with the use of high-potency short-acting drugs. Nevertheless, this risk with the correct use of drugs is greatly exaggerated. In many patients, prolonged therapy with benzodiazepines causes an improvement in the condition without the development of serious side effects. Do not abandon the use of this group of substances, following prejudices, but the appointment of benzodiazepines requires a thorough diagnostic assessment of the patient's condition and rational use of drugs.


Inhibition of apolipoprotein B secretion by IL-6 is mediated by EGF or an EGF-like molecule in CaCo-2 cells.
Small intestinal mucosal inflammation observed in celiac disease is associated with the local release of growth factors and various cytokines. In a previous study, we investigated the effect of various cytokines on triacylglycerol and apoB secretion by CaCo-2 cells and observed that TNF-alpha, IL-1 beta, and particularly IL-6, decreased apolipoprotein (apo) B and triacylglycerol secretion. In this study, we explored possible mechanisms to explain the inhibitory effect of IL-6 on apoB secretion. IL-6, 10 ng/mL, added to the basolateral medium of CaCo-2 cells grown on semi-permeable filters, decreased apoB secretion by 42%. Adding a blocking monoclonal antibody (mAb 528) to the EGF receptor completely prevented this effect. IL-6 decreased the amount of EGF receptor protein and the binding of iodinated EGF to its receptor by 50% and 30%, respectively. Incubation of cells with various ligands to the EGF receptor, such as EGF, TGF-alpha, HB-EGF, and amphiregulin, also decreased apoB secretion. Inhibition of apoB secretion by EGF was prevented by the mAb 528 or an EGF neutralizing antibody. In a dose-dependent manner, the neutralizing antibody to EGF prevented the decrease in secretion of apoB, triacylglycerol mass, and cell-surface binding of labeled EGF caused by IL-6. Similar to the effects of IL-6, EGF decreased the secretion of triacylglycerol mass and the synthesis and secretion on newly synthesized apoB. The results suggest that, in CaCo-2 cells, IL-6 causes the release of EGF or an EGF-like molecule. By binding to cell surface EGF receptors, the molecule then causes a decrease in triacylglycerol and apoB secretion.


Proposal to consistently apply the International Code of Nomenclature of Prokaryotes (ICNP) to names of the oxygenic photosynthetic bacteria (cyanobacteria), including those validly published under the International Code of Botanical Nomenclature (ICBN)/International Code of Nomenclature for algae, fungi and plants (ICN), and proposal to change Principle 2 of the ICNP.
This taxonomic note was motivated by the recent proposal [Oren & Garrity (2014) Int J Syst Evol Microbiol 64, 309-310] to exclude the oxygenic photosynthetic bacteria (cyanobacteria) from the wording of General Consideration 5 of the International Code of Nomenclature of Prokaryotes (ICNP), which entails unilateral coverage of these prokaryotes by the International Code of Nomenclature for algae, fungi, and plants (ICN; formerly the International Code of Botanical Nomenclature, ICBN). On the basis of key viewpoints, approaches and rules in the systematics, taxonomy and nomenclature of prokaryotes it is reciprocally proposed to apply the ICNP to names of cyanobacteria including those validly published under the ICBN/ICN. For this purpose, a change to Principle 2 of the ICNP is proposed to enable validation of cyanobacterial names published under the ICBN/ICN rules.


[New Treatment for Vascular Thrombosis Prevention in Patients With Atrial Fibrillation: Left Atrial Appendage Occlusion].
Atrial fibrillation (AF) is a common type of arrhythmia that increases significantly the risk of blood clots in the heart and of stroke. Therefore, stroke prevention is a key goal of AF treatment. In the past, patients were required to take anticoagulants for the remainder of their life, to regularly the monitor international normalized ratio (INR) of prothrombin time (PT), and to avoid possible negative interactions with various drugs and foods. Left atrial appendage occlusion (LAAO), a novel device and technique, was thus developed for AF patients with contraindications to anticoagulants and a high risk of bleeding. When using this technique, the occluder is placed on the left atrial appendage in order to effectively prevent blood stasis and thrombi accumulation. Transesophageal echocardiogram and computed tomography are conducted prior to the LAAO procedure, which is similar to the procedure used for cardiac catheterization. After the LAAO procedure, the patient remains in the intensive care unit (ICU), where vital signs, bleeding at the puncture site, and pericardial tamponade complications are monitored. Health education on daily activities, anticoagulant use, and regular follow-up should be given prior to hospital discharge. While LAAO may not reduce the incidence of stroke, the benefits of this procedure include a significant reduction in bleeding complications as compared to procedures that use oral anticoagulants. Further studies including long-term follow up and in-depth examinations of this procedure are necessary. The present article offers a reference for clinical staffs who are responsible for the care of patients treated using the LAAO procedure.


In vitro Lipolysis as a Tool for the Establishment of IVIVC for Lipid-Based Drug Delivery Systems.
In vitro lipolysis has emerged as a powerful tool in the development of in vitro in vivo correlation for Lipid-based Drug Delivery System (LbDDS). In vitro lipolysis possesses the ability to mimic the assimilation of LbDDS in the human biological system. The digestion medium for in vitro lipolysis commonly contains an aqueous buffer media, bile salts, phospholipids and sodium chloride. The concentrations of these compounds are defined by the physiological conditions prevailing in the fasted or fed state. The pH of the medium is monitored by a pH-sensitive electrode connected to a computercontrolled pH-stat device capable of maintaining a predefined pH value via titration with sodium hydroxide. Copenhagen, Monash and Jerusalem are used as different models for in vitro lipolysis studies. The most common approach used in evaluating the kinetics of lipolysis of emulsion-based encapsulation systems is the pH-stat titration technique. This is widely used in both the nutritional and the pharmacological research fields as a rapid screening tool. Analytical tools for the assessment of in vitro lipolysis include HPLC, GC, HPTLC, SEM, Cryo TEM, Electron paramagnetic resonance spectroscopy, Raman spectroscopy and Nanoparticle Tracking Analysis (NTA) for the characterization of the lipids and colloidal phases after digestion of lipids. Various researches have been carried out for the establishment of IVIVC by using in vitro lipolysis models. The current publication also presents an updated review of various researches in the field of in vitro lipolysis.


[A midline vertebral artery aneurysm operated via transoral transclival approach (author's transl)].
A detail of an unsuccessful trial of transoral transclival operation for an aneurysm arising from the left vertebral artery was reported. The patient was 66 years old male who had bronchial asthma and difficulty in phonation and swallowing. The angiograms showed that the aneurysm, 1.5X1.5X2.0 cm in size, was situated in the midline at the level of caudal one-third of the clivus. A transoral transclival operation was performed following preoperative tracheostomy and gastrostomy to improve his pulmonary and nutritional condition. A midline incision on the palate was followed by the removal of the posterior half of palatal bone. The upper part of incision on the retropharyngeal mucosa was placed approximately 1 cm off the midline to facilitate closure afterwords. A caudal 1/3 of the clivus, anterior arch of the atlas and a part of the odontoid process were removed. The aneurysm, fusiform in shape, was then collapsed by needle puncture after the left vertebral artery was trapped between the posterior inferior cerebellar artery and the vertebro-basilar junction. Closure of the dura with a fascial patch was incomplete due to an extensive incision and coagulation of the dura. Closure of the retropharyngeal mucosa around the orifice of the Eustachian tube was also incomplete in spite of the paramedian incision described above. Postoperative course was complicated by an frequent occurrence of the attack of bronchial asthma causing loss of gastic juice from the gastrostomy and resultant hypoproteinemia, although the recovery of lower cranial nerve palsy was good. There was no signs of infection until the 21st postoperative day when meningitis developed. The patient died in the 28th postoperative day. The importance of complete closure of the dura and retropharyngeal mucosa to prevent meningial infection was discussed. Since the mucosa around the orifice of Eustachian tube was extremely friable and the closure was almost impossible, the risk of meningial infection was considered to be high, especially when the intradural procedure was necessary through transoral high clivotomy.


Impact of inflammation on early hematopoiesis and the microenvironment.
Steady-state hematopoiesis is maintained by slowly dividing, self-renewing hematopoietic stem cells (HSCs) and their offspring, lineage-specified downstream progenitors in bone marrow (BM). It was previously thought that hematopoietic stresses such as infection or other inflammatory stimuli, are mostly recognized by terminally differentiated immune cells, i.e., front-line defenders at the local site of reaction, and that they produce factors that directly act on hematopoietic stem and progenitors (HSPCs) in BM and subsequently stimulate them to rebuild and sustain the hemato-lymphatic system. However, accumulating evidence now indicates that primitive HSPCs, as well as microenvironmental cells in BM are also able to sense systemically migrating hematopoietic stress signals, and respond by orchestrating on-site hematopoiesis via direct and indirect mechanisms. While inflammation has many beneficial roles in activating the immune system for defense or facilitating tissue repair, it also shows detrimental effects if sustained chronically, i.e., might lead to HSPC damage as bone marrow failure or leukemia. Thus, inflammation requires tight control of initiation and termination in time and space dependent manner.


Combined Clinical Phenotype and Lipidomic Analysis Reveals the Impact of Chronic Kidney Disease on Lipid Metabolism.
Chronic kidney disease (CKD) results in significant dyslipidemia and profound changes in lipid and lipoprotein metabolism. The associated dyslipidemia, in turn, contributes to progression of CKD and its cardiovascular complications. To gain an in-depth insight into the disorders of lipid metabolism in advanced CKD, we applied UPLC-HDMS-based lipidomics to measure serum lipid metabolites in 180 patients with advanced CKD and 120 age-matched healthy controls. We found significant increases in the levels of total free fatty acids, glycerolipids, and glycerophospholipids in patients with CKD. The levels of free fatty acids, glycerolipids, and glycerophospholipids directly correlated with the level of serum triglyceride and inversely correlated with the levels of total cholesterol and eGFR. A total of 126 lipid species were identified from positive and negative ion modes. Out of 126, 113 identified lipid species were significantly altered in patients with CKD based on the adjusted FDR method. These results pointed to profound disturbance of fatty acid and triglyceride metabolisms in patients with CKD. Logistic regression analysis showed strong correlations between serum methyl hexadecanoic acid, LPC(24:1), 3-oxooctadecanoic acid, and PC(20:2/24:1) levels with eGFR and serum creatinine levels (R > 0.8758). In conclusion, application of UPLC-HDMS-based lipidomic technique revealed profound changes in lipid metabolites in patients with CKD. The observed increases in serum total fatty acids, glycerolipids, and glycerophospholipids levels directly correlated with increased serum triglyceride level and inversely correlated with the eGFR and triglyceride levels.


Association of statins with aortic, peripheral, and visceral artery aneurysm development.
Objectives Prior studies examining the effects of statins on arterial aneurysm development and progression yielded conflicting results due to their smaller size and presence of residual confounders. The objective of this study is to examine the association of statins with risk of being diagnosed with aortic, peripheral, and visceral artery aneurysm. Methods This was a retrospective cohort study of Tricare enrollees (from 1 October 2003 to 31 March 2012). Main outcomes were diagnosis of aortic, peripheral, or visceral artery aneurysm and undergoing aortic aneurysm repair procedure during follow-up period. Using 115 baseline characteristics, we generated a propensity score to match statin users and nonusers and examine the odds of outcomes (primary analysis). Secondary analysis examined outcomes at various subcohorts. Results Out of 10,910 statin users and 49,545 nonusers, we propensity score-matched 6728 pairs of statin users and nonusers. Statin users and nonusers had similar odds of being diagnosed with aortic, peripheral, and visceral artery aneurysms (odds ratio [OR]: 1.06, 95% confidence interval [95% CI]: 0.85-1.33) and of undergoing aortic aneurysm repair procedures (OR: 0.54, 95% CI: 0.22-1.35). Secondary analysis showed a tendency toward fewer aortic aneurysm procedures among statin users that did not reach statistical significance. However, high-intensity statin users in comparison to non-intensive statin users had higher adjusted odds of aortic, peripheral, and visceral artery aneurysms (OR: 1.76, 95% CI: 1.37-2.25, p < .0001). Conclusions This study does not support a clinically significant benefit or harm from statins regarding development of arterial aneurysm. However, secondary analyses may support the hypothesis proposed by previous research proposing a bidirectional role for statins.


High dose-rate brachytherapy treatment delivery: report of the AAPM Radiation Therapy Committee Task Group No. 59.
The goals of this task group are to examine the current high dose-rate (HDR) treatment delivery practices and to prepare a document to assure safe delivery of HDR treatments. The document consists of detailed HDR procedures for design of an HDR brachytherapy program, staffing and training, treatment specific quality assurance, and emergency procedures. The document provides an extensive quality assurance (QA) check list. It reviews all aspects of HDR treatment delivery safety, including prescription, treatment plan, treatment delivery, and radiation safety.