Midface Multilayering Filler Injection Technique: Understanding of the Dynamic Facial Anatomy Through a "Smiling Cadavers" Anatomical Study.
Understanding age-related changes in compartmentalized facial fat and their role in facial dynamics and aesthetics is essential to target filler injections for midface rejuvenation. A novel anatomical approach ("smiling cadavers") was used to identify the main midface fat compartments involved during muscular contraction when smiling and their motion and behavior with and without filler injections. Based on these insights and the literature, a multilayering filler injection approach was developed to optimize midface rejuvenation by restoring fat volumes using rheologically different products injected into different fat compartments. Twenty-four hemifacial dissections confirmed the presence of two fat compartment layers, separated by the orbicularis oculi muscle in the horizontal plane and by the septa in the vertical plane, and revealed the anatomical effects of facial movement. The midface is composed of deep static fat compartments and a superficial dynamic adipose layer that follows the facial movements, creating a natural dynamic appearance. A proof-of-concept study involved 130 White patients (36 to 56 years; 91 percent women). After the procedure, 95 percent of patients and 98 percent of practitioners rated facial appearance as "improved" or "much/very much improved." No major complications were reported. The smiling cadavers method enhances understanding of dynamic facial anatomy by showing the superficial and deep fat compartments of the midface at rest and their motion during a procedure to represent a smile. The multilayered injection technique takes into account these anatomical findings to rejuvenate the midface, achieving a natural appearance at rest and during motion.


Insulin receptor endocytosis in the pathophysiology of insulin resistance.
Insulin signaling controls cell growth and metabolic homeostasis. Dysregulation of this pathway causes metabolic diseases such as diabetes. Insulin signaling pathways have been extensively studied. Upon insulin binding, the insulin receptor (IR) triggers downstream signaling cascades. The active IR is then internalized by clathrin-mediated endocytosis. Despite decades of studies, the mechanism and regulation of clathrin-mediated endocytosis of IR remain incompletely understood. Recent studies have revealed feedback regulation of IR endocytosis through Src homology phosphatase 2 (SHP2) and the mitogen-activated protein kinase (MAPK) pathway. Here we review the molecular mechanism of IR endocytosis and its impact on the pathophysiology of insulin resistance, and discuss the potential of SHP2 as a therapeutic target for type 2 diabetes.


Expression of glucocorticoid induced TNF receptor family related protein (GITR) on peripheral T cells from normal human donors and patients with non-infectious uveitis.
The expression of the glucocorticoid induced TNF receptor family related gene (GITR) in subsets of T lymphocytes from human peripheral blood was studied. In normal human peripheral blood mononuclear cells, GITR expression on the resting CD4+ T cells was low but markedly increased after activation. The percentage of GITR+ T cells in the CD4+CD25+ T cell subpopulation (15.1%) was significantly higher than that in the CD4+CD25- T cell subpopulation (5.2%, P<0.01), suggesting a preferential co-expression of GITR with CD25. In a group of patients with non-infectious uveitis, a proposed T helper cell mediated autoimmune ocular disease, the GITR expression on the CD4+ T cells in both the active patients (34.5%) and the inactive patients (19.6%) was significantly higher as compared to that in the normal donors (10.7%; P<0.01 vs. active, P<0.05 vs. inactive). This increased GITR expression in T cells was only seen in the CD4 positive T helper cell subpopulation but not in the CD4 negative T cell subpopulation. GITR expression on the CD4+ T cells decreased when the patients became clinically quiescent. Therefore, GITR is an activation marker for the CD4+ T cells and preferentially co-expressed with CD25 on the CD4+ T cells in human peripheral blood. Its expression correlates with the clinical course of non-infectious uveitis.


Dataset on biochemical inhibiting activities of selected phytochemicals in Azadirachta indica L as potential NS2B-NS3 proteases inhibitors.
The anti-NS2B-NS3 proteases activities of Azadirachta indica L. were investigated via the data obtained from selected bioactive compounds from Azadirachta indica L. The work was investigated using insilico approach and the series of computational software were used to execute the task. The software used were Spartan 14, material studio, Padel, Pymol, Autodock tool, Autodock vina and discovery studio. The obtained descriptors from 2D and 3D of the optimized compounds were screened and they were used to develop QSAR model using material studio software. Also, biological interaction between the selected bioactive compounds from Azadirachta indica L. and NS2B-NS3 proteases (PDB ID: 2fom) were accomplished using docking method and the calculated binding affinity as well as the residues involved in the interaction were reported. More so, the ADMET features for [(5S,6R,7S,8R,9S,10R,11S,12R,13S,17R)-17-(2,5-dihydroxy-2,5-dihydrofuran-3-yl)-11,12-dihydroxy-6‑methoxy-4,4,8,10,13-pentamethyl-1,16-dioxo-6,7,9,11,12,17-hexahydro-5H-cyclopenta[a]phenanthren-7-yl] 3-methylbut-2-enoate (Compound 6) and (10R,13S,14S,17S)-17-[1-(3,4-dihydroxy-5,5-dimethyloxolan-2-yl)ethyl]-4,4,10,13,14-pentamethyl-1,2,5,6,9,11,12,15,16,17-decahydrocyclopenta[a]phenanthren-3-one (compound 12) with lowest binding affinity were investigated and reported.


Should Governments engage health insurance intermediaries? A comparison of benefits with and without insurance intermediary in a large tax funded community health insurance scheme in the Indian state of Andhra Pradesh.
A peculiar phenomenon of engaging insurance intermediaries for government funded health insurance schemes for the poor, not usually found globally, is gaining ground in India. Rajiv Aarogyasri Scheme launched in the Indian state of Andhra Pradesh, is first largest tax funded community health insurance scheme in the country covering more than 20 million poor families. Aarogyasri Health Care Trust (trust), the scheme administrator, transfers funds to hospitals through two routes one, directly and the other through an insurance intermediary. The objective of this paper is to find out if engaging an insurance intermediary has any effect on cost efficiency of the insurance scheme. We used payment data of RAS for the period 2007-12, to find out the influence of insurance intermediary on the two variables, benefit cost ratio defined as benefit payment divided by premium payment, and claim denial ratio defined as benefit payment divided by treatment cost. Relationship between scheme expenditure and number of beds empanelled under the scheme is examined. OLS regression is used to perform all analyses. We found that adding an additional layer of insurance intermediary between the trust and hospitals reduced the benefit cost ratio under the scheme by 12.2% (p-value = 0.06). Every addition of 100 beds under the scheme increases the scheme payments by US$ 0.75 million (p-value < 0.001). The gap in claim denial ratio between insurance and trust modes narrowed down from 2.84% in government hospitals to 0.41% in private hospitals (p-value < 0.001). The scheme is a classic case of Roemer's principle in operation. Introduction of insurance intermediary has the twin effects of reduction in benefit payments to beneficiaries, and chocking fund flow to government hospitals. The idea of engaging insurance intermediary should be abandoned.


Conjugation-dependent recovery of the Na+ pump in a mutant of Vibrio alginolyticus lacking three subunits of the Na+ pump.
The Na+ pump-deficient mutant, Nap1, of Vibrio alginolyticus was found to lack three subunits of Na+-dependent NADH:quinone oxidoreductase complex. Although a spontaneous Na+ pump positive revertant did not appear from Nap1, transconjugants that recovered both the Na+ pump activity and the subunits were isolated from Nap1 conjugated with the wild type. Moreover, the wild type was found to contain two different sizes of plasmids. These results suggest the possibility that the Na+ pump is encoded by a plasmid.


Using search trends to analyze web-based users' behavior profiles connected with COVID-19 in mainland China: infodemiology study based on hot words and Baidu Index.
Mainland China, the world's most populous region, experienced a large-scale coronavirus disease 2019 (COVID-19) outbreak in 2020 and 2021, respectively. Existing infodemiology studies have primarily concentrated on the prospective surveillance of confirmed cases or symptoms which met the criterion for investigators; nevertheless, the actual impact regarding COVID-19 on the public and subsequent attitudes of different groups towards the COVID-19 epidemic were neglected. This study aimed to examine the public web-based search trends and behavior patterns related to COVID-19 outbreaks in mainland China by using hot words and Baidu Index (BI). The initial hot words (the high-frequency words on the Internet) and the epidemic data (2019/12/01-2021/11/30) were mined from infodemiology platforms. The final hot words table was established by two-rounds of hot words screening and double-level hot words classification. Temporal distribution and demographic portraits of COVID-19 were queried by search trends service supplied from BI to perform the correlation analysis. Further, we used the parameter estimation to quantitatively forecast the geographical distribution of COVID-19 in the future. The final English-Chinese bilingual table was established including six domains and 32 subordinate hot words. According to the temporal distribution of domains and subordinate hot words in 2020 and 2021, the peaks of searching subordinate hot words and COVID-19 outbreak periods had significant temporal correlation and the subordinate hot words in COVID-19 Related and Territory domains were reliable for COVID-19 surveillance. Gender distribution results showed that Territory domain (the male proportion: 67.69%; standard deviation (SD): 5.88%) and Symptoms/Symptom and Public Health (the female proportion: 57.95%, 56.61%; SD: 0, 9.06%) domains were searched more by male and female groups respectively. The results of age distribution of hot words showed that people aged 20-50 (middle-aged people) had a higher online search intensity, and the group of 20-29, 30-39 years old focused more on Media and Symptoms/Symptom (proportion: 45.43%, 51.66%; SD: 15.37%, 16.59%) domains respectively. Finally, based on frequency rankings of searching hot words and confirmed cases in Mainland China, the epidemic situation of provinces and Chinese administrative divisions were divided into 5 levels of early-warning regions. Central, East and South China regions would be impacted again by the COVID-19 in the future.


Changes in brain activation during the acquisition of a new bimanual coodination task.
Motor skill acquisition is associated with the development of automaticity and induces neuroplastic changes in the brain. Using functional magnetic resonance imaging (fMRI), the present study traced learning-related activation changes during the acquisition of a new complex bimanual skill, requiring a difficult spatio-temporal relationship between the limbs, i.e., cyclical flexion-extension movements of both hands with a phase offset of 90 degrees. Subjects were scanned during initial learning and after the coordination pattern was established. Kinematics of the movements were accurately registered and showed that the new skill was acquired well. Learning-related decreases in activation were found in right dorsolateral prefrontal cortex (DLPFC), right premotor, bilateral superior parietal cortex, and left cerebellar lobule VI. Conversely, learning-related increases in activation were observed in bilateral primary motor cortex, bilateral superior temporal gyrus, bilateral cingulate motor cortex (CMC), left premotor cortex, cerebellar dentate nuclei/lobule III/IV/Crus I, putamen/globus pallidus and thalamus. Accordingly, bimanual skill learning was associated with a shift in activation among cortico-subcortical regions, providing further evidence for the existence of differential cortico-subcortical circuits preferentially involved during the early and advanced stages of learning. The observed activation changes account for the transition from highly attention-demanding task performance, involving processing of sensory information and corrective action planning, to automatic performance based on memory representations and forward control.


A generic microfluidic biosensor of G protein-coupled receptor activation-monitoring cytoplasmic [Ca(2+)] changes in human HEK293 cells.
Cell lines expressing recombinant G-protein coupled receptors (GPCRs) are activated by specific ligands resulting in transient [Ca(2+)] rises that return to basal levels in 30-60s. Yellow Cameleon 3.6 (YC3.6) is a genetically encoded calcium indicator which can be co-expressed to monitor these cytosolic [Ca(2+)] changes in real-time using Förster (Fluorescence) resonance energy transfer (FRET). On this basis, we designed the prototype of a generic microfluidic biosensor of GPCR activation, imaging [Ca(2+)] changes in recombinant human HEK293 cells, which express a combination of a GPCR (Neurokinin 1) and YC3.6. An internal reference for non-specifically induced [Ca(2+)] changes were YC3.6 cells without GPCR but expressing a red fluorescent protein (mCherry) for identification. These cell lines were grown as a mixed population in a flow cell with a volume of ~50µl and a flow cell surface of 170mm(2). Cells were activated by brief exposures to specific and non-specific analytes using an injection valve with a flexible sample volume (tested range 5-100µl) at a flow speed of 100µl/min. A flow cell surface of 0.2mm(2) with 50 cells was imaged every 2-4s to obtain signal kinetics. The lower limit of detection was 30pM Substance P (SP, 2pg/50µl), and reproducible responses to repeated injections every 3min were obtained at 1nM SP. This biosensor was designed for ~50 cells for statistical reasons, but at a lower limit of 1 receptor- and 1 reference-cell, specific ligand detection is still feasible.


miR-34c may protect lung cancer cells from paclitaxel-induced apoptosis.
MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that negatively regulate the expression of their target genes. They are involved in many biological processes, including cell proliferation, apoptosis and differentiation, and are considered as promising new therapeutic targets for cancer. However, the identity of miRNAs involved in apoptosis and their respective targets remain largely unknown. Given the elevated complexity of miRNA regulation of gene expression, we performed a functional screening as an alternative strategy to identify those miRNAs that in lung cancer cells may interfere with the apoptotic process. To this aim, we generated a derivative of the non-small cell lung carcinoma A549 cell line in which caspase-8, a critical upstream initiator of apoptosis, can be activated by administration of the small dimerizer drug AP20187. We found a number of miRNAs that may rescue cell viability from caspase-8 activation. They included miRNAs already described as oncogenic such as miR-17, miR-135 and miR-520, but also some miRNAs such as miR-124-1 and miR-34c for which a tumor-suppressive role has instead been described or expected. Among them, miR-34c-5p markedly increased resistance to paclitaxel-induced apoptosis. We demonstrate that Bmf (Bcl-2-modifying factor) is a target of miR-34c-5p, and that its silencing, together with that of c-myc, a known target of miR-34c-5p, contributes to resistance to apoptosis induced by paclitaxel through p53 downregulation.


Is victim identity in genocide a question of science or law? The scientific perspective, with special reference to Darfur.
In genocide, victims must represent an ethnic, racial, religious or national group. But is victim identity a question of science or law? Must victims be a socially recognized group or can group identity exist solely in the mind of the perpetrator? This question is relevant to the on-going crisis in Darfur. The "Arab-on-African" violence depicted in the media encompasses identities not shared by Darfurians. This study details an evaluation of victim identity in Darfur, based on field research and literature review. Darfurians are defined by subsistence strategy and economic groups are not protected under genocide law. Whether Darfur is genocide depends on whether victims must conform to scientific group classifications or need only be defined by their relationship to the perpetrators.


PSL, an S phase-related p55 nuclear antigen, associates transiently with chromatin.
An S phase-related nuclear 55K antigen, also designated PSL, has been characterized in various mammalian cells, using a human serum from a patient with autoimmune disorders (Barque et al., EMBO j 2 (1983) 743). In this report, we show by immunoelectron microscopy that the p55 protein associates in situ with the chromatin of rat hepatocytes. This association is a transient one, as indirect immunofluorescence studies show that PSL does not bind to individualized metaphase chromosomes. Furthermore, immunoprecipitation tests indicate that the majority of PSL is in the non-chromosomal cell fraction. These results suggest that this nuclear antigen is directly involved in the DNA replication process.


Involvement of c-Ski oncoprotein in carcinogenesis of cholangiocacinoma induced by Opisthorchis viverrini and N-nitrosodimethylamine.
Opisthorchiasis is the major public health problem in the endemic areas of Thailand and Laos because Opisthorchis viverrini infection causes serious hepatobiliary diseases including CCA. The molecular mechanism of the CCA carcinogenesis induced by the infection remains obscure. To reveal the potential genes and signaling pathways to involve in the carcinogenesis, the present study investigated the expression of c-Ski, an oncogene, and two TGF-β signaling pathway relative genes, TGF-β and Smad4, during the development of CCA induced by O. viverrini infection in hamster model, and in human opisthorchiasis associated CCA. The results showed that the expression of c-Ski gene was greatly up-regulated during the carcinogenesis of CCA in hamster model. The overexpression of c-Ski was confirmed by immunohistological staining result which showed the increased expression of c-Ski protein in cytoplasm of the epithelial lining of hepatic bile ducts. Moreover, the immunohistological staining of the specimens of human opisthorchiasis associated CCA revealed the up-regulated expression of c-Ski and Smad4 proteins in the cytoplasm of the epithelial lining of hepatic bile ducts and stomal fibrosis respectively. The expression of TGF-β and Smad4 were up-regulated, which expression kinetics was time-dependent of CCA development. These results suggest that c-Ski is likely involved in the carcinogenesis of CCA induced by O. viverrini infection through regulating TGF-β signaling pathway.


[Latest Findings on Hydrogel Drug Delivery Systems in the Treatment of Periodontitis].
Hydrogel drug delivery systems possess unique structures and properties and hence can be injected and retained in the periodontal pocket for slow and controlled release of medications with antibacterial, anti-inflammatory, and periodontal tissue regeneration-promotional effects. Due to their safety, practicability, and effectiveness, they show great potential in the treatment of periodontitis. In this paper, we gave an overview of hydrogel drug delivery systems in the treatment of periodontitis, summing up the classification and forms of the drugs delivered and the strengths and weaknesses of common types of hydrogel matrixes. In addition, we discussed properties required for hydrogel drug delivery systems applicable in the treatment of periodontitis, including a certain level of viscosity, suitable degradation cycle, and temperature sensitivity. Finally, we summarized the stimulus responsiveness types of hydrogel drug delivery systems applicable in the treatment of periodontitis, including pH-responsiveness, enzyme-responsiveness, reactive oxygen species-responsiveness, light-responsiveness, and sugar-responsiveness. In the future, researchers should make further investigation into the clinical efficacy of hydrogel drug delivery systems and promote their translation into clinical applications. Additionally, hydrogel drug delivery systems carrying biologic drugs could be further investigated to promote advancement in the field of periodontal tissue regeneration. Furthermore, the response sources, realization strategies, and safe preparation methods of smart hydrogel drug delivery systems should also be further clarified and explored to achieve drug delivery of better efficiency and safety. In addition to drug delivery, hydrogel matrixes with medicinal values also show great promises.


[Dissociative stupor as a postoperative consequence of general anesthesia].
A 31-year-old woman failed to awaken after an uneventful general anesthesia (propofol, alfentanil and 65% N2O in oxygen) for laparoscopic resection of an ovarian cyst. After the operation she was extubated and vital signs were stable. However, the patient remained unresponsive even to painful stimuli for about 2 h. Just before we performed a computed tomogram of the brain to exclude a cerebral lesion we noticed that she blinked. We hypothesized that unconsciousness was due to a dissociative stupor. After administration of sublingual lorazepam the patient woke up promptly and was alert and normal for the rest of the hospital stay. In conclusion, after exclusion of a pharmacological or organic cause for postoperative unconsciousness, dissociative stupor may be a reason for apparent coma after general anesthesia.


Sorted averaging improves quality of auditory steady-state responses.
Increasing signal-to-noise ratio (SNR) is essential for the recording of auditory evoked potentials with electroencephalography (EEG). Several protocols have been proposed to increase the SNR, starting with an averaging of EEG epochs which decreases noise level. Since artifacts decrease the SNR by increasing the noise level, artifact detection and reduction protocols are other important tools to reduce the noise level. The current study focuses on the sorted averaging protocol where the epochs are sort according to their estimated root-mean-square (RMS) amplitude. Calculating an estimated SNR by averaging of the sorted epochs, this process of averaging can be interrupted at the maximum SNR, i.e., at an optimal number of epochs. In contrast to the often used protocol that weighs every epoch by its inverse average root-mean-square amplitude, sorted averaging is a linear operation, i.e., it does not change signal amplitudes. In this study, the sorted averaging is, for the first time, applied to auditory steady-state responses (ASSR) which are evoked by amplitude modulated tones or trains of transient acoustic stimuli. In contrast to other evoked potentials, the ASSR is analyzed in the frequency domain, using the property of auditory system to retain the modulation frequency (or the repetition rate) of the stimulus. ASSR were recorded in 11 subjects with normal hearing. Results of four artifact processing protocols (1) fixed rejection level, (2) adaptive rejection level, (3) weighted averaging and (4) sorted averaging were compared. The results showed a higher normalized SNR with a sorted averaging protocol than with adaptive rejection level and weighted averaging protocols. An advantage of the sorted averaging protocol is that, compared to a fixed-rejection threshold, the ASSR amplitudes were unchanged when the sorted averaging protocol was used, whereas they were significantly reduced by the weighted averaging protocol. The residual noise was also significantly lower for the sorted averaging protocol than for the weighted averaging and adaptive rejection protocols. Thus, the sorted averaging may be a powerful tool to increase the quality of ASSR.


Klinefelter syndrome has increased brain responses to auditory stimuli and motor output, but not to visual stimuli or Stroop adaptation.
Klinefelter syndrome (47, XXY) (KS) is a genetic syndrome characterized by the presence of an extra X chromosome and low level of testosterone, resulting in a number of neurocognitive abnormalities, yet little is known about brain function. This study investigated the fMRI-BOLD response from KS relative to a group of Controls to basic motor, perceptual, executive and adaptation tasks. Participants (N: KS = 49; Controls = 49) responded to whether the words "GREEN" or "RED" were displayed in green or red (incongruent versus congruent colors). One of the colors was presented three times as often as the other, making it possible to study both congruency and adaptation effects independently. Auditory stimuli saying "GREEN" or "RED" had the same distribution, making it possible to study effects of perceptual modality as well as Frequency effects across modalities. We found that KS had an increased response to motor output in primary motor cortex and an increased response to auditory stimuli in auditory cortices, but no difference in primary visual cortices. KS displayed a diminished response to written visual stimuli in secondary visual regions near the Visual Word Form Area, consistent with the widespread dyslexia in the group. No neural differences were found in inhibitory control (Stroop) or in adaptation to differences in stimulus frequencies. Across groups we found a strong positive correlation between age and BOLD response in the brain's motor network with no difference between groups. No effects of testosterone level or brain volume were found. In sum, the present findings suggest that auditory and motor systems in KS are selectively affected, perhaps as a compensatory strategy, and that this is not a systemic effect as it is not seen in the visual system.


Evaluation of radioiodinated 8-Cyclopentyl-3-[(E)-3-iodoprop-2-en-1-yl]-1-propylxanthine ([*I]CPIPX) as a new potential A1 adenosine receptor antagonist for SPECT.
8-Cyclopentyl-3-[(E)-3-[(131)I]iodoprop-2-en-1-yl]-1-propylxanthine (2*) was generated by iododestannylation of the tributyl-stannyl-precursor with [(131)I]NaI and chloramine T. The radiochemical yield of 2* was 82 +/- 4%, and the purity exceeded 98%. The specific activity was 33 +/- 19 GBq/micromol. Affinities for rat, pig and human A(1) adenosine receptors (A(1)ARs) were in the low nanomolar range, but poor selectivity for the human A(1)AR over the A(2A)AR was found. Additionally, in vitro and ex vivo autoradiographic studies revealed high unspecific binding which makes this ligand unsuitable for SPECT imaging.


Identification of guanine, guanosine, and inosine for α-amylase inhibitors in the extracts of the earthworm Eisenia fetida and characterization of their inhibitory activities against porcine pancreatic α-amylase.
Earthworms are known as a source of a traditional medicine, and bioactive components have been reported. We have reported that a fraction (U3EE) with molecular mass under 3 kDa from the water extract of Eisenia fetida inhibits porcine pancreatic α-amylase (PPA) activity with a half-maximal inhibitory concentration (IC50) of 73.7 ± 4.0 mg/mL. Here we purified PPA-inhibitory components from U3EE by sequential procedures of 85 %-ethanol (EtOH) extraction, solid-phase extraction (SPE), and RP-HPLC. The water eluate from SPE of the 85 %-EtOH extract was a major inhibitory fraction, from which three components were separated by 2nd RP-HPLC and identified with MS, TLC, and UV spectroscopy as guanine (Gua), inosine (Ino), and guanosine (Guo). Kinetic analysis showed that Gua and Guo were non-competitive inhibitors and Ino a mixed-type one, suggesting a key role of the purine ring in inhibition. The inhibitor constants (Ki) of Gua and Guo were 0.28 ± 0.07 and 1.64 ± 0.14 mM, respectively, and Ki and Ki' of Ino in the EI and ESI complexes were 5.8 ± 1.1 and 59 ± 12 mM, respectively. U3EE might be useful for food supplements to prevent obesity and diabetes.


Psychological risk indicators for peri-implantitis: A cross-sectional study.
The aim of this analytical cross-sectional study was to evaluate the association between peri-implantitis and psychological distress, and potentially related/mediating factors such as general health, bruxism, and lifestyle factors. Patients who received dental implants at a private practice in the Netherlands between January 2011 and January 2014 were recalled on a 5-year clinical and radiographic follow-up examination. Presence of peri-implantitis was examined, and patients completed questionnaires measuring psychological distress (Symptom Checklist [SCL]-90), bruxism, general health, and lifestyle factors. Associations between the self-reported factors and peri-implantitis were analysed with univariate and multivariate logistic regression models. A total of 230 patients (with 347 implants) were included in the analysis. Prevalence of (mild to severe) peri-implantitis was 30% (69 patients). Variables that showed a significant univariable association with peri-implantitis (p < .10) were the SCL-90 subdomain depression, smoking, current medical treatment, and lung problems. In the multivariate regression analysis, depression was the only variable that was significantly associated with peri-implantitis (p < .05). The presence of depressive symptoms is a risk indicator for peri-implantitis. Recognizing the potential negative impact of depressive symptoms may allow for better identification of high-risk patients.


A new voice at the table. The chief nursing officer provides a valuable perspective on quality, safety and the bottom line.
The chief nursing officer's perspective on quality and outcomes should be heard at each board meeting.


Hardy's inequalities for the twisted convolution with Laguerre functions.
In this article, two types of Hardy's inequalities for the twisted convolution with Laguerre functions are studied. The proofs are mainly based on an estimate for the Heisenberg left-invariant vectors of the special Hermite functions deduced by the Heisenberg group approach.


3D Exoscopes are Noninferior to Operating Microscopes in Aneurysm Surgery: Comparative Single-Surgeon Series of 52 Consecutive Cases.
The literature on exoscope use in cerebrovascular neurosurgery is scarce, mainly comprising small case series and focused on visualization quality and ergonomics. As these devices become widely used, direct comparison to the operating microscope regarding efficacy and patient safety is necessary. Fifty-two consecutive clipping procedures, performed by 1 senior vascular neurosurgeon, were analyzed. Either an operating microscope with a mouth switch (25 cases with 27 aneurysms; 13 ruptured) or a three-dimensional exoscope with a foot switch (27 cases with 34 aneurysms; 6 ruptured) were used. Durations of major surgical stages, number of device adjustments, numbers of clip repositionings and clips implanted were extracted from surgical videos. Demographic data, imaging characteristics, clinical course and outcomes were extracted from digital patient records. Duration of surgery and different stages did not differ between devices, except for final site inspection. The number of device adjustments was higher with the exoscope. With progressive experience in exoscope use, the number of device adjustments increased significantly, whereas surgery duration remained unchanged. Favorable outcome (modified Rankin Scale score 0-2) was observed in 80% and 88% of patients in the microscope and exoscope groups, respectively. Ischemic events were found in 2 patients in each group; no other complications occurred. In aneurysm clipping, three-dimensional exoscopes are noninferior to operating microscopes in terms of surgery duration, safety, and outcomes, based on our limited series. Progressive experience enables the surgeon to perform significantly more device adjustments within the same amount of surgical time.


Characterisation of the ribosomal binding site for eukaryotic elongation factor 2 by chemical cross-linking.
Ribosomal complexes containing elongation factor 2 (EF-2) were formed by incubation of 80 S ribosomes in the presence of EF-2 and the non-hydrolysable GTP analogue GuoPP[CH2]P. The factor was covalently coupled to the ribosomal proteins located at the factor binding site, by treatment with bifunctional reagents. After isolation of the covalent EF-2.ribosomal protein complexes, the proteins were labelled with 125I and the introduced covalent links cleaved. The ribosomal proteins were identified by electrophoresis in two independent two-dimensional gel systems, followed by autoradiography. After cross-linking with bis(hydroxysuccinimidyl) tartrate (4 A between the reactive groups), protein S3/S3a, S7 and S11 were found as the major ribosomal proteins covalently linked to EF-2. The longer reagent, dimethyl 3,8-diaza-4,7-dioxo-5,6-dihydroxydecanbisimidate (11 A between the reactive groups), covalently coupled proteins S7, S11, L5, L13, L21, L23, L26, L27a and L32 to EF-2. After cross-linking with dimethyl suberimidate (9 A between the reactive groups) proteins S3/3a, S7, S11, L5, L8, L13, L21, L23, L26, L27a, L31 and L32 were identified as belonging to the EF-2-binding site. The results indicate that the ribosomal domain interacting with EF-2 is located on both the small and the large ribosomal subunit close to the subunit interface.


Transgenic mice overexpressing nesfatin/nucleobindin-2 are susceptible to high-fat diet-induced obesity.
Nesfatin/Nucleobindin-2 (Nesf/NUCB2), a precursor of nesfatin-1, an anorexigenic protein, is ubiquitously expressed in peripheral tissues in addition to the hypothalamus. However, the role of intracellular Nesf/NUCB2 has not been established in the periphery. Nesf/NUCB2-transgenic (Tg) mice were generated, and chronological changes of body weight and daily food intake were measured in Nesf/NUCB2-Tg mice fed normal laboratory chow or 45% high-fat diet (HFD). In addition, changes of metabolic markers were evaluated in those mice. No differences were observed in daily food intake and body weight between Nesf/NUCB2-Tg mice (n=11) and their non-Tg littermates (n=11) fed normal chow. Nesf/NUCB2-Tg mice showed increased mRNA expression of oxytocin and corticotropin-releasing hormone and decreased mRNA expression of cocaine- and amphetamine-related transcript in the hypothalamus. Nesf/NUCB2-Tg mice fed 45% HFD (n=6) showed significantly higher increase in body weight than their non-Tg littermates fed the same diet (n=8); however, no difference was observed in daily food intake between these two groups. Further, Nesf/NUCB2-Tg mice fed 45% HFD showed a significant increase in the weight of the liver, subcutaneous fat, and brown adipose tissue and decrease in the expression of uncoupling protein-1 in the subcutaneous fat. Blood glucose levels of Nesf/NUCB2-Tg mice fed 45% HFD were not different from those of their non-Tg littermates fed the same diet. Insulin levels of these Tg mice were significantly higher than those of their non-Tg littermates. Histological analysis showed marked fat deposition in the hepatocytes surrounding the hepatic central veins in Nesf/NUCB2-Tg mice fed 45% HFD. Overexpression of Nesf/NUCB2 did not change food intake, but increased body weight only in Nesf/NUCB2-Tg mice fed HFD. The results of this study indicate that Nesf/NUCB2 was involved in the development of insulin resistance and fat deposition in the liver, independent of the modulation of energy intake.


Flexible transceiver array for ultrahigh field human MR imaging.
A flexible transceiver array, capable of multiple-purpose imaging applications in vivo at ultrahigh magnetic fields was designed, implemented and tested on a 7 T MR scanner. By alternately placing coil elements with primary and secondary harmonics, improved decoupling among coil elements was accomplished without requiring decoupling circuitry between resonant elements, which is commonly required in high-frequency transceiver arrays to achieve sufficient element-isolation during radiofrequency excitation. This flexible array design is capable of maintaining the required decoupling among resonant elements in different array size and geometry and is scalable in coil size and number of resonant elements (i.e., number of channels), yielding improved filling factors for various body parts with different geometry and size. To investigate design feasibility, flexibility, and array performance, a multichannel, 16-element transceiver array was designed and constructed, and in vivo images of the human head, knee, and hand were acquired using a whole-body 7 T MR system. Seven Tesla parallel imaging with generalized autocalibrating partially parallel acquisitions (GRAPPA) performed using this flexible transceiver array was also presented.


Molecular species of glycerophospholipids and sphingomyelins of human erythrocytes: improved method of analysis.
This study reports the application of modern methods of molecular species analysis in determination of the structure of both major and minor glycerophospholipids and sphingomyelins of human erythrocytes. Individual phospholipid classes were resolved from total lipid extracts by thin-layer chromatography. Diradylglycerols were released by phospholipase C and converted into trimethylsilyl ethers, which were resolved into the alkenylacyl, alkylacyl and diacylglycerol subclasses by normal phase high performance liquid chromatography. Molecular species of diradylglycerols and ceramides were quantitated according to carbon and double bond number by gas liquid chromatography using a fused silica capillary column wall-coated with bonded RTx-2330. The molecular species of ceramides were determined by GC/MS. The diradyl glycerophosphocholines contained 93.0% diacyl, 4.6% alkylacyl and 2.5% alkenylacyl, while the diradyl glycerophosphoethanolamines were made up of 48.8% diacyl, 47.8% alkenylacyl and 3.4% alkylacyl subclasses. Analysis of the molecular species showed that the long chain polyunsaturated acids were mainly combined with C16 in all diradyl GPC subclasses and in diacyl GPE, while in the alkylacyl and alkenylacyl GPE and in diacyl glycerophosphoinositol and diacyl glycerophosphoserine they were combined mainly with C18 saturated fatty chains. In addition to the C16 and C18 alkyl and alkenyl, the ether fractions also contained significant proportions of C20, C22 and C24 chains. The molecular species of the ceramide moieties of the SPH were made up largely of mono- and diunsaturated species. Over 200 molecular species were identified and quantitated in a representative sample of human red blood cells.


Rheumatoid Arthritis Treatment Options and Type 2 Diabetes: Unravelling the Association.
Multiple lines of evidence have increasingly suggested a pathogenic connection between rheumatoid arthritis (RA) and the mechanisms of type 2 diabetes (T2D) in a vicious circle perpetuated by glucose derangement and inflammatory mediators. These findings have been further reinforced by clinical studies showing that the inhibition of interleukin (IL)-1 and IL-6 may allow the treatment of RA and concomitant T2D at the same time. Interestingly, IL-1 inhibition induced a more evident reduction of glycated haemoglobin (HbA1c) in patients with concomitant RA and T2D than in previous studies on IL-1 inhibition in patients with this metabolic disease alone. Thus, the inflammatory pathogenic mechanisms of T2D could be exaggerated in the context of a rheumatic disease, possibly explaining these findings. In fact, IL-1 inhibition could not only palliate glycaemia, but also decrease the progressive decline in insulin secretion associated with T2D, interfering with apoptosis of β-cells, improving their function, and ameliorating the peripheral insulin resistance. Moreover, the maintenance of clinical remission of rheumatic disease could further improve the glucose derangement and reduce the occurrence of T2D in RA. On these bases, the presence of T2D may allow the physicians to perform a better profile of patients with RA according to the principles of precision medicine, tailoring the medical treatment to the individual characteristics. In this context, the benefits of targeting the inflammatory process, mainly by IL-1 inhibition, may be suggested in patients with RA and concomitant T2D.


Fast and precise method for HPLC-size exclusion chromatography with UV and TOC (NDIR) detection: importance of multiple detectors to evaluate the characteristics of dissolved organic matter.
A new type of high-performance liquid chromatography (HPLC)-size exclusion chromatography (SEC) system with ultraviolet (UV) absorbance detection and non-dispersive infrared (NDIR) detection of total organic carbon is described. The introduction of an online degassing tube and a low-volume HPLC column helped to reduce the analytical time and increase the sensitivity of the SEC system. This study is the first in which linear calibration curves (R(2)>0.99) were obtained for both UV absorbance and NDIR data for polystyrene sulfonate standards, which are the most suitable standards for molecular size analysis of aquatic humic substances as well as dissolved organic matter (DOM). Using the calibration curves, the molecular size distribution of DOM in water collected from Lake Kasumigaura and in pore water from lake sediments was estimated. Most of the DOM had a molecular weight less than 4000 Daltons (Da), and the amount of low-molecular-weight DOM (∼ 2000 Da) with low UV absorbance increased with depth in the sediment pore water. This result shows the importance of combining quantitative analysis by NDIR detection with qualitative analysis by UV detection to determine the chemical and physical properties of DOM. The possible sources and reactivity of DOM in Lake Kasumigaura and its sediment pore water are also discussed.


Chocolate and risk of chronic disease: a systematic review and dose-response meta-analysis.
Evidence for the association between chocolate intake and risk of chronic diseases is inconclusive. Therefore, we aimed to synthesize and evaluate the credibility of evidence on the dose-response association between chocolate consumption with risk of all-cause mortality, coronary heart disease (CHD), stroke, heart failure (HF), type 2 diabetes (T2D), colorectal cancer (CRC), and hypertension. Prospective studies were searched until July 2018 in PubMed, Embase, and Web of Science. Random-effects meta-analyses comparing highest versus lowest intake categories, linear, and non-linear dose-response analyses were conducted. The credibility of evidence was evaluated with the NutriGrade scoring-system. Overall, 27 investigations were identified (n = 2 for all-cause mortality, n = 9 for CHD, n = 8 for stroke, n = 6 for HF, n = 6 for T2D, n = 2 for hypertension and CRC, respectively). No associations with HF (RR 0.99, 95% CI 0.94, 1.04) and T2D (RR 0.94, 95% CI 0.88, 1.01) per each 10 g/day increase in chocolate intake were observed in the linear dose-response meta-analyses. However, a small inverse association for each 10 g/daily increase could be shown for the risk of CHD (RR 0.96, 95% CI 0.93, 0.99), and stroke (RR 0.90, 95% CI 0.82, 0.98). The credibility of evidence was rated either very low (all-cause mortality, HF, T2D, CRC or hypertension) or low (CHD, stroke). Chocolate consumption is not related to risk for several chronic diseases, but could have a small inverse association with CHD and stroke. Our findings are limited by very low or low credibility of evidence, highlighting important uncertainty for chocolate-disease associations.


Some misconceptions about the spurious correlation problem in the ecological literature.
It is a common misconception that correlations between variables that share a common term are statistically invalid. Although the idea that such relationships are wholly or partially spurious was rejected decades ago by statisticians, ecologists continue mistakenly to exclude legitimate hypotheses on this basis. Besides directing attention to the statistical literature on the subject, we briefly reconsider the problem from 3 viewpoints: first, the confusion between spurious correlation and spurious inference, second, the problem of concept familiarity and definition, with particular reference to the self-thinning rule for plants, and third, a legitimate concern with measurement error of shared variable components.


MicroRNA-125a/b-5p promotes malignant behavior in multiple myeloma cells and xenograft tumor growth by targeting DIS3.
Multiple myeloma (MM) is a hematological malignancy with a high prevalence and is characterized by the clonal expansion of malignant plasma cells. As a new tumor suppressor, defective in sister chromatid joining (DIS3) was reported to be a gene closely related to MM. This study elucidated the biological functions and underlying mechanisms of DIS3 in MM. DIS3 mRNA and protein levels were detected using RT-qPCR and western blotting, respectively. Methyl thiazolyl tetrazolium assays, flow cytometry analyses, Transwell assays, and wound healing assays were performed to detect the proliferation, apoptosis, invasion, and migration of MM cells. The binding relationship between miR-125a/b-5p and DIS3 was verified using luciferase reporter assays and RNA pulldown assays. Xenograft tumor models were established in nude mice to investigate the effects of miR-125a/b-5p and DIS3 on tumor growth in vivo. DIS3 levels were downregulated in MM cells, and DIS3 upregulation inhibited the malignant behaviors of MM cells. Mechanistically, miR-125a/b-5p directly targeted the 3' untranslated region of DIS3. The expression of miR-125a/b-5p was upregulated in MM cells, miR-125a/b-5p knockdown inhibited the malignant behaviors of MM cells, and the inhibitory effect was reversed by DIS3 downregulation. The results of in vivo experiments indicated that miR-125a/b-5p promoted tumor growth by downregulating DIS3. Overall, miR-125a/b-5p promotes MM cellular processes and xenograft tumor growth by targeting DIS3.


Synthesis of novel analogs of cabergoline: improving cardiovascular safety by removing 5-HT2B receptor agonism.
The dopamine agonist cabergoline has been used to treat prolactinomas, Parkinson's disease, Cushing's disease and sexual dysfunction. However, its clinical use was severely curtailed when it was found that patients taking cabergoline had an increased risk of developing cardiac-valve regurgitation. This potentially life-threatening condition has been associated with drugs, such as cabergoline, that are 5-HT2B receptor agonists. We prepared analogs of cabergoline and have identified several that have limited or no agonism at the 5-HT2B receptor.


Food insecurity in households with young children: A test of contextual congruence.
Household food insecurity, an inability to provide adequate nutrition for a healthy, active lifestyle, affects nearly 1 in 7 households with children in the United States. Though rates of food insecurity declined to pre-recession levels just prior to the COVID-19 pandemic, they are now once again increasing. As a result, in one of the wealthiest countries in the world, millions of young children continue to grow up in households that struggle daily with a problem that is often associated with the developing world. The result is both immediate and long-term health and development deficits for children. We propose that the degree of demographic and socioeconomic congruence between the households of young children and their neighborhood of residence lends unique insights to food insecurity. We examine this using the ECLS-K 2010-2011 for children in families with incomes below 400 percent of the federal poverty line (N = 8600). Results show that congruence between household and neighborhood education and race/ethnicity associates with the likelihood of experiencing food insecurity. For example, households with non-Hispanic black children living in neighborhoods with high proportions of non-Hispanic blacks have significantly lower probabilities of food insecurity than similar households living in neighborhoods with smaller black populations. Similarly, more highly educated families experience lower probability of food insecurity in high education neighborhoods than when they reside in low education neighborhoods. Focusing on neighborhood risk factors as absolute and independent contributors limits our understanding of how families experience food insecurity as well as any policy efforts to address it.


Bypass surgery in a mangled forearm using an intramedullary tunnel through the radius.
Critical ischemia in the upper extremity is rare. A surgical bypass is thought to be the superior treatment option. We describe a rare case where regular tunneling options of the bypass were not available and an intramedullary tunnel was used.


Decision-making process reported by Medicare patients who had coronary artery stenting or surgery for prostate cancer.
Patients facing decisions should be told about their options, have the opportunity to discuss the pros and cons, and have their preferences reflected in the final decision. To learn how decisions were made for two major preference-sensitive interventions. Mail survey of probability samples of patients who underwent the procedures. Fee-for-service Medicare beneficiaries who had surgery for prostate cancer or elective coronary artery stenting in the last half of 2008. Patients' reports of which options were presented for serious consideration, the amount of discussion of the pros and cons of the chosen option, and if they were asked about their preferences. The majority (64%) of prostate cancer surgery patients reported that at least one alternative to surgery was presented as a serious option. Almost all (94%) said they and their doctors discussed the pros, and 63% said they discussed the cons of surgery "a lot" or "some". Most (76%) said they were asked about their treatment preferences. Few who received stents said they were presented with options to seriously consider (10%). While most (77%) reported talking with doctors about the reasons for stents "a lot" or "some", few (19%) reported talking about the cons. Only 16% said they were asked about their treatment preferences. While prostate cancer surgery patients reported more involvement in decision making than elective stent patients, the reports of both groups document the need for increased efforts to inform and involve patients facing preference-sensitive intervention decisions.


Immunopotentiator separated from hot water extract of the seed of Benincasa cerifera Savi (Tohgashi).
The separation and properties of a new immuno-potentiator, Benincasa cerifera mitogen (BCM) fraction, were investigated. BCM fraction was separated from hot water extract of the seed of Benincasa cerifera Savi (Tohgashi) by gel filtration using Sepharose 4B. BCM fraction is a heteropolymer consisting of uronic acid, neutral sugars, protein, and phosphorus. The proliferation and differentiation of murine B cells were markedly stimulated by BCM fraction. The in vitro development of peritoneal macrophages into antitumor macrophages was also activated by the addition of BCM fraction to cultures. BCM fraction augmented the IgM and IgG antibody responses against sheep erythrocytes (SRBC) and the induction of delayed-type footpad reaction against SRBC. The antitumor activity of BCM fraction was observed in terms of prolongation of the survival period of mice bearing Meth A fibrosarcoma. After hydrolysis with 1% acetic acid at 100 degrees C for 4 h, marked mitogenic activity was found in a precipitate composed of 29% neutral sugars, 50% uronic acid, 1% protein, and 0.1% phosphorus. The precipitate did not contain detectable amino sugar. The possibility that the biological activities of BCM fraction may be due to contamination by bacterial lipopolysaccharide was ruled out on the basis of the results of chemical analysis and of marked mitogenicity noted in C3H/HeJ spleen cell cultures.


[Determination of antibodies against nicotinic acetylcholine receptor: clinico-immunological correlations in 30 patients with myasthenia gravis].
In 30 patients with myasthenia gravis, serum assays were performed for antibodies to human nicotinic acetylcholine receptor. 19 of 20 generalized forms which were symptomatic and 6 of 9 patients in remission at the time of blood sample had detectable amounts of antibodies. The six highest levels were found in benign courses. 2 patients had a five- and twofold drop in antibody level during rapid deterioration. Patients in remission after thymectomy may still have low to moderate levels, while symptomatic patients occasionally have no detectable antibody.


A chitin-like component in Aedes aegypti eggshells, eggs and ovaries.
An insoluble white substance was prepared from extracts of eggshells of Aedes aegypti, the yellow fever mosquito and dengue vector. Its infrared and proton NMR spectra were similar to that of standard commercial chitin. This putative chitin-like material, also obtained from ovaries, newly laid and dark eggs, was hydrolyzed in acid and a major product was identified by HPLC to be glucosamine. The eggshell acid hydrolysate was also analyzed by ESI-MS and an ion identical to a glucosamine monoprotonated species was detected. The presence of chitin was also analyzed during different developmental stages of the ovary using a fluorescent microscopy technique and probes specific for chitin. The results showed that a chitin-like material accumulates in oocytes during oogenesis. Streptomyces griseus chitinase pre-treatment of oocytes greatly reduced the chitin-derived fluorescence. Chitinase activity was detected in newborn larvae and eggs prior to hatching. Feeding experiments indicated that the chitin synthesis inhibitor lufenuron inhibited chitin synthesis, either when mosquitoes were allowed to feed directly on lufenuron-treated chickens or when an artificial feeding system was used. Lufenuron inhibited egg hatch, larval development and reduced mosquito viability. These data demonstrate for the first time that (1) a chitin-like material is present in A. aegypti eggs, ovaries and eggshells; (2) a chitin synthesis inhibitor can be used to inhibit mosquito oogenesis; and (3) chitin synthesis inhibitors have potential for controlling mosquito populations.


Venous drainage in the craniocervical region.
The venous drainage of the craniocervical junction is made up of jugular veins and particularly the vertebral veins and their anastomoses. The anterior and posterior condylar veins join to form the plexus of the vertebral vein, the supply functions of which can be modified by the presence of the mastoid anastomotic emissary veins which increase the possibilities of drainage at that level.


Functional characterisation of two cytochrome b5-fusion desaturases from Anemone leveillei: the unexpected identification of a fatty acid Delta6-desaturase.
The Ranunculaceae are known to accumulate a wide range of unusual fatty acids in their seed lipids, and this variability has been advocated as a taxonomic marker. The Anemone species, Anemone leveillei L. and Anemone rivularis Buch.-Ham., have previously been reported to accumulate Delta5-desaturated fatty acids in their seed tissue [K. Aitzetmüller (1995) Plant Syst Evol 9:229-240]. Two cDNAs, AL1 and AL2, with similarity to plant cytochrome b5-fusion "front-end" desaturases were isolated from developing seeds of A. leveillei and their function identified by expression in Saccharomyces cerevisiae. AL2 was characterised as a sphingolipid long-chain-base Delta8-desaturase, while AL1 acted as a fatty acid desaturase. However, AL1 did not produce Delta5-desaturated fatty acids as expected; instead, when expressed in transgenic S. cerevisiae or Arabidopsis thaliana this enzyme was functionally characterised as a Delta6-desaturase. Northern analysis confirmed the expression of this gene in seed tissue and leaf tissue of A. leveillei, though Delta6-desaturated fatty acids were found to accumulate only in the leaf tissue. The unexpected characterisation of a Delta6-desaturase in A. leveillei has implications for the use of fatty acids in chemotaxonomic studies. This is also the first report of a higher-plant Delta6-desaturase from a family other than the Boraginaceae.


Time dependent alterations on tyrosine hydroxylase, opioid and cannabinoid CB1 receptor gene expressions after acute ethanol administration in the rat brain.
The aim of this study was to examine the differential regulation after acute ethanol administration on tyrosine hydroxylase, proenkephalin and cannabinoid CB(1) receptor gene expressions in selected areas of the rat brain. Rats received an intragastric administration of 3 g/kg ethanol and were killed by decapitation at 1, 2, 4, 8 and 24 h. The results showed an activation of tyrosine hydroxylase gene expression in the ventral tegmental area and the substantia nigra, increased proenkephalin gene expression in the caudate-putamen, nucleus accumbens core and shell, central and medial amygdala, ventromedial hypothalamic nucleus and the paraventricular hypothalamic nucleus. In contrast, a significant decrease in the cannabinoid CB1 receptor gene expression was found in caudate-putamen, central amygdala and ventromedial hypothalamic nucleus. In conclusion, the results suggest that an acute dose of ethanol induces neuroplastic alterations in proenkephalin, tyrosine hydroxylase and cannabinoid CB1 receptor gene expressions that may contribute to trigger the rewarding effects of ethanol consumption.


IL-1 receptor signaling in the basolateral amygdala modulates binge-like ethanol consumption in male C57BL/6J mice.
Proinflammatory cytokines have been implicated in alcohol-induced neurodegeneration, but the role of the neuroimmune system in alcohol related behaviors has only recently come to the forefront. Herein, the effects of binge-like drinking on IL-1β mRNA and immunoreactivity within the amygdala were measured following the "drinking in the dark" (DID) paradigm, a model of binge-like ethanol drinking in C57BL/6J mice. Moreover, the role of IL-1 receptor signaling in the amygdala on ethanol consumption was assessed. Results indicated that a history of binge-like ethanol drinking promoted a significant increase of IL-1β mRNA expression within the amygdala, and immunohistochemistry analyses revealed that the basolateral amygdala (BLA), but not central amygdala (CeA), exhibited significantly increased IL-1β immunoreactivity. However, Fluoro-Jade® C labeling indicated that multiple cycles of the DID paradigm were not sufficient to elicit neuronal death. Bilateral infusions of IL-1 receptor antagonist (IL-1Ra) reduced ethanol consumption when infused into the BLA but not the CeA. These observations were specific to ethanol drinking as the IL-1Ra did not alter either sucrose drinking or open-field locomotor activity. The current findings highlight a specific role for IL-1 receptor signaling in modulating binge-like ethanol consumption and indicate that proinflammatory cytokines can be induced prior to dependence or any evidence of neuronal cell death. These findings provide a framework in which to understand how neuroimmune adaptations may alter ethanol consumption and therein contribute to alcohol abuse.


Cervical nitric oxide metabolite levels and clinical variables as predictive factors of high-grade cervical intraepithelial neoplasia.
To create a prediction model of high-grade cervical intraepithelial neoplasia (CIN) based on clinical variables and the cervical nitric oxide metabolite (NOx) levels of study participants. This comparative study included 694 women undergoing colposcopy due to abnormal pap smear results. On the basis of the cervical biopsy results, the women were divided into the ≤ CIN 1 or CIN 2-3 group. The two groups were compared in terms of cervical NOx levels and clinical variables. Univariate, multivariate, and receiver-operating characteristic curve analysis were performed. Multivariate analysis showed that CIN 2-3 associated with more than two cervical biopsies [odds ratio (OR) = 5.16], high-grade squamous intraepithelial lesion cytology (OR = 16.19), condom non-use (OR = 4.28), cervical NOx levels ≤ 99.9 μmol/L (OR = 16.62), more than four lifetime male sexual partners (OR = 10.56), and age at first coitus of ≤ 15 years old (OR = 3.54). This combined model had a sensitivity of 86.49 %, a specificity of 90.74 %, a positive predictive value of 64.0 %, and a negative predictive value of 97.2 %. In the present sample, high-grade CIN associated with decreased cervical NOx levels. Thus, along with some clinical variables, cervical NOx levels may be an additional marker of cervical dysplasia.


Quantum Chemical and Molecular Dynamics Studies of MUC1 Calix[4,8]arene Scaffold Based Anticancer Vaccine Candidates.
Functional antitumor vaccine constructs are the basis for active tumor immunotherapy, which is useful in the treatment of many types of cancers. MUC1 is one key glycoprotein for targeting and designing new strategies for multicomponent vaccines. Two self-adjuvant tetravalent vaccine candidates were prepared by clustering four or eight PDTRP MUC1 core epitope sequences on calixarene scaffolds. In this work, the different activities of two molecules with calix[4]arene and calix[8]arene skeleton are rationalized. Quantum mechanics, docking, and molecular dynamics structural optimization were first carried out followed by metadynamics to calculate the energy profiles. Further insights were obtained by complementarity studies of molecular fields. The molecular modeling results are in strong agreement with the experimental in vivo immunogenicity data. In conclusion, the overall data shows that, in the designing of anticancer vaccines, scaffold flexibility has a pivotal role in obtaining a suitable electrostatic, hydrophobic, and steric complementarity with the biological target.


Patterns of energy content in plants from the venezuelan paramos.
Determinations of energy and ash content were made on the organs of some common plant species from an elevational gradient in the Venezuelan páramos. The results indicate differences in energy content among the life forms sampled. Giant rosette plants show the highest values in the roots while woody plants have the highest energy content in the leaves. The reproductive organs show a higher energy content than the vegetative organs. There is a tendency to increase energy content as elevation and environmental stress increase. The adaptive significance of these patterns is discussed. The high average energy value for páramo plants, 20.18 KJ/g ash free dry weight, is similar to values reported for alpine tundra plants and conifer forests.


Simple device for the tape recording of complex behavioral situation on one track.
A low cost electronic device is described to record on one a.m. tape track the occurrence of any combination of four signals. The fast read out of recorded signals makes the apparatus reliable and helpful for coding behavioral situation and automatic averaging of event related phenomena. A detailed circuitry is included and discussed.


Effect of eculizumab treatment in patients with paroxysmal nocturnal hemoglobinuria with or without high disease activity: Real-world findings from the International Paroxysmal Nocturnal Hemoglobinuria Registry.
The effects of eculizumab treatment in paroxysmal nocturnal hemoglobinuria (PNH) patients with or without high-disease activity (HDA), defined by LDH ≥ 1.5 × ULN and history of major adverse vascular events (MAVEs; including thrombotic events [TEs]); anemia; and/or physician-reported abdominal pain, dyspnea, dysphagia, erectile dysfunction, fatigue, and/or hemoglobinuria, in the International PNH Registry were evaluated. Registry patients were stratified by baseline HDA and eculizumab-treatment status. Longitudinal changes in laboratory and clinical PNH-related endpoints were evaluated using linear mixed models (continuous variables) or Poisson regression (incidence rates). As of May 1, 2017, 3009 patients (HDA/eculizumab-treated, n = 913; HDA/never-treated, n = 651; no-HDA/eculizumab-treated, n = 173; no-HDA/never-treated, n = 1272) were analyzed. Higher proportions of eculizumab-treated patients had HDA and history of MAVEs. In patients with and without HDA, respectively, eculizumab treatment resulted in reductions from baseline for (1) LDH ratio (mean [SD]: -5.3 [4.0] and -2.3 [3.8]); (2) incidence rate ratio (IRR) for MAVEs (-80% and -70%); (3) IRR for TEs (-80% for both); and (4) units of red blood cell transfusions per year (from 6.8 to 2.8 and 3.6 to 2.5 units). Eculizumab treatment in a real-world setting improved outcomes, including substantial decreases in hemolysis, MAVE rates, TEs, and transfusions in PNH patients regardless of HDA.


Acral lentiginous melanoma in situ: dermoscopic features and management strategy.
Diagnosis of acral lentiginous melanoma in situ (ALMIS) is challenging. However, data regarding ALMIS are limited in the literature. The aim of this study was to investigate the clinical and dermoscopic features of ALMIS on palmoplantar surfaces. Patients with ALMIS and available dermoscopic images were retrospectively reviewed at our institution between January 2013 and February 2020. Clinical and dermoscopic features were analysed and compared between small (< 15 mm) and large (≥ 15 mm) ALMIS. Twenty-one patients with ALMIS were included in this study. Mean patient age was 58.5 (range 39-76) years; most lesions were located on the sole (90.5%). The mean maximal diameter was 19.9 ± 13.7 mm (mean ± standard deviation). Statistical analysis of dermoscopic features revealed that parallel ridge patterns (54.5% vs. 100%, P = 0.035), irregular diffuse pigmentation (27.3% vs. 100%, P = 0.001) and grey colour (18.2% vs. 90%, P = 0.002) were significantly less frequent in small lesions than in large lesions. We have also illustrated two unique cases of small ALMIS; their evolution and follow-up dermoscopic examination are provided. In conclusion, this study described detailed dermoscopic findings of ALMIS. Based on the present study and a review of the literature, we proposed a dermoscopic algorithm for the diagnosis of ALMIS.


A prospective study of early removal of the urethral catheter after colorectal surgery in patients having epidural analgesia as part of the Enhanced Recovery After Surgery programme.
Early removal of the urethral catheters is part of the enhanced postoperative recovery programme (ERAS). The effect of epidural anaesthesia on urinary retention was investigated in patients after colorectal resection. A prospective cohort study of all patients having colorectal surgery within an ERAS programme that included insertion of an epidural catheter over the last 5 years. Two-hundred and ten patients had an epidural and a urethral catheter postoperatively. The duration of catheterization was not recorded in one patient who was therefore excluded from the study. One-hundred and eighteen patients had a trial without catheter (TWOC) prior to stopping the epidural (early TWOC). Ninety-one patients had TWOC after the epidural was stopped (late TWOC). Sixteen (7.6%) patients went into urinary retention (14 early TWOC and two late TWOC). The rate of urinary retention in the early TWOC group was significantly higher than that in the late TWOC group (11.9% vs 2.2%; χ(2), P = 0.009). Those who underwent a laparoscopic resection were significantly more likely to have undergone an early TWOC (χ(2), P = 0.001); however, there was no difference in retention rates between open and laparoscopic surgery (χ(2), P = 0.402). Pelvic surgery was not significantly associated with an increased risk of postoperative urinary retention (χ(2), P = 0.627). Male sex was not significantly associated with urinary retention (χ(2), P = 0.087). In the early TWOC group 86% had the catheter removed within 24 hours of surgery. Early TWOC with epidural analgesia running significantly increases the risk of urinary retention; however, it was still successful in 88% of patients.


Acetylated flavonol triglycosides from Ammi majus L.
Two new acetylated flavonol triglycosides: kaempferol and isorhamnetin 3-O-[2"-(4"'-acetylrhamnosyl)-6"-glucosyl] glucosides, were isolated and identified from the aerial parts of Ammi majus L. In addition, three known flavonol glycosides namely; isorhamnetin-3-O-rutinoside, kaempferol-3-O-glucoside and isorhamnetin-3-O-glucoside were detected.


Airway epithelial development and function: A key player in asthma pathogenesis?
Though asthma is a common and relatively easy to diagnose disease, attempts at primary or secondary prevention, and cure, have been disappointing. The widespread use of inhaled steroids has dramatically improved asthma control but has offered nothing in terms of altering long-term outcomes or reversing airway remodeling and impairment in lung function. The inability to cure asthma is unsurprising given our limited understanding of the factors that contribute to disease initiation and persistence. New data have focused on the airway epithelium as a potentially key factor orchestrating the different stages of asthma. In this review we summarize for the clinician the current evidence on the central role of the airway epithelium in asthma pathogenesis and the factors that may alter epithelial integrity and functionality.


Preventing venous thromboembolism in elective upper limb surgery.
Deep venous thrombosis (DVT) and pulmonary embolism (PE) have considerable clinical and economic consequences. The prevention of venous thrombosis and PE are increasingly seen as quality markers for surgery. Guidance is available from a number of sources to stratify risk for different patients and procedures and to define an appropriate standard of care. Despite this, best practice is unclear. We reviewed the available guidance for orthopedic surgeons undertaking elective upper limb surgery with respect to prescribing DVT prophylaxis. Material was identified from publications produced by professional and regulatory bodies, including United States Surgeon General, United Kingdom Department of Health, the American Academy of Orthopaedic Surgeons, the Scottish Intercollegiate Guideline Network, the National Institute for Clinical Excellence, and the American College of Chest Physicians, as well as a structured MEDLINE database search. The picture is particularly confused in the case of elective upper limb surgery. Much of the evidence for prescribing DVT prophylaxis is related to lower limb surgery or trauma surgery. Failing to prescribe prophylaxis against venous thromboembolism (VTE) may be presented as a failure of care. We present a review of current guidance and the supporting evidence in order to establish evidence-based best practice and a standard of care for elective upper limb surgery. Review Article.


[Diagnostic accuracy of three technologies for the diagnosis of multi-drug resistant tuberculosis].
Multi-drug resistant (MDR-TB) and extensively drug-resistant (XDR-TB) tuberculoses are a global public health problem. Their timely detection might reduce the burden of the disease and the economic impact on health systems worldwide. To conduct a literature review of the diagnostic accuracy of three molecular tests to detect multi-drug resistant and extensively drug-resistant tuberculoses. A systematic literature review following Cochrane methodology was carried out to study the diagnostic accuracy of three molecular tests to detect MDR-TB and XDR-TB in previous studies among immunocompetent population. Articles indexed in Medline and Embase were reviewed starting in 2007. Diagnostic accuracy was reported by sensitivity, specificity, and positive and negative predictive values of each test. In total, 8, 12 and 13 studies were included to assess the diagnostic accuracy of GeneXpert MTB/RIF®, GenoType MTBDRplus® and GenoType MTBDRsl®, respectively. The specificity of GeneXpert MTB/RIF® ranged between 91 and 100%, and its sensitivity between 33.3 and 100%. The sensitivity of GenoType® MTBDRplus® ranged between 88 and 100%. The sensitivity and specificity of GenoType MTBDRsl® to evaluate drug resistance ranged between 56 and 100% and 21 and 100%, respectively. The three diagnostic tests evaluated have shown an adequate diagnostic accuracy to detect MDR and XDR tuberculoses.


Neonatal jaundice: magnitude of the problem in Cairo University's neonatal intensive Care unit as a referral center.
Neonatal jaundice is one of the most common physiologic problems requiring medical attention in newborns. It is benign in most cases; however, high levels of bilirubin are neurotoxic and can lead to serious brain damage. This study aimed at assessment of magnitude of neonatal jaundice in cases of neonatal hyperbilirubinemia admitted into neonatal intensive care unit (NICU), Cairo University Pediatric Hospital and to detect possible etiologies, management and outcome. The present work is a retrospective study, included 789 neonates suffered from hyperbilirubinemia over a two-year period. Intensive phototherapy and exchange transfusion were used together in 6 cases. Two hundreds and twenty-two cases (28.1%) had exchange transfusion once, 44 cases had it twice, 6 cases had it 3 times and one case had it 4 times. Number of exchange transfusion significantly affects mortality among cases (P= 0.02). Neonatal hyperbilirubinemia is an existing problem in our NICU. Intensive phototherapy is an excellent substitute for exchange transfusion. Respiratory distress and sepsis are significantly higher among dead cases. Screening for risk factors is needed to avoid critical hyperbilirubenemia.


Phasic modulation of reticulospinal neurones during fictive locomotion and other types of spinal motor activity in lamprey.
The intracellular activity of different types of reticulospinal neurones was studied during fictive locomotion and other types of spinal motor activity in an in vitro preparation of the lamprey brainstem-spinal cord. The examined neurones included large Müller cells of the rhombencephalic and mesencephalic reticular formation, the Mauthner cell, and neurones in the posterior rhombencephalic reticular nucleus with different sizes and conduction velocities. During bouts of fictive swimming initiated spontaneously or by stimulation of the trigeminal nerve or spinal cord, the Müller cells were depolarized and fired action potentials. Bulbar Müller cells in addition showed a phasic modulation of membrane potential with excitation in phase with ipsilateral motoneurones of the rostral spinal cord. The Mauthner cell was depolarized in phase with contralateral motoneurones. Many neurones in the posterior rhombencephalic reticular nucleus showed modulation in phase with ipsilateral motoneurones during fictive swimming. Such oscillations were observed in both fast-conducting neurones, located mainly in the medial part of the nucleus, and slower conducting cells with a more lateral distribution. All examined reticulospinal neurones showed a strong coupling also with other types of spinal motor activity, such as slow alternating bursting and synchronous bilateral ventral root bursts, but the reticulospinal activity had no correlation with respiratory activity recorded from the Xth nerve. The consequences of a phasic reticulospinal activity during locomotion are discussed.


M184I/V substitutions and E138K/M184I/V double substitutions in HIV reverse transcriptase do not significantly affect the antiviral activity of EFdA.
4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a potent nucleoside analogue inhibitor of HIV that has an unusually long half-life. Cell culture selections with either EFdA or lamivudine using both subtype B and non-B clinical isolates selected the M184I/V substitutions in reverse transcriptase (RT). Unlike lamivudine, however, EFdA retained significant activity against viruses containing the M184I/V substitutions. In other clinical trials that evaluated rilpivirine together with emtricitabine in first-line therapy, the emergence of both the M184I/V and E138K mutations in RT was demonstrated. Moreover, the M184I/V and E138K substitutions were shown to be compensatory for each other with regard to both efficiency of RT activity and viral replicative capacity. This creates concern that E138K might emerge as a compensatory mutation for M184I/V in the aftermath of the use of EFdA. We wished to determine whether the E138K mutation in HIV RT together with M184I/V would compromise the activity of EFdA. Recombinant viruses containing the M184I/V and/or E138K substitutions were generated by site-directed mutagenesis and evaluated in tissue culture for susceptibility to various nucleoside compounds, including EFdA. Susceptibility to EFdA was retained in M184I/V viruses that also contained the E138K substitution. Moreover, the E138K substitution was not generated in these studies under selection pressure with EFdA. These findings help to alleviate concern that EFdA may not be active against viruses that contain both the M184I/V and E138K substitutions in RT.


Patterns of Chromosomal Aberrations in Solid Tumors.
Chromosomal abnormalities are a defining feature of solid tumors. Such cytogenetic alterations are mainly classified into structural chromosomal aberrations and copy number alterations, giving rise to aneuploid karyotypes. The increasing detection of these genetic changes allowed the description of specific tumor entities and the associated patterns of gene expression. In fact, tumor-specific landscapes of gross genomic copy number changes, including aneuploidies of entire chromosome arms and chromosomes result in a global deregulation of the transcriptome of cancer cells. Furthermore, the molecular characterization of cytogenetic abnormalities has provided insights into the mechanisms of tumorigenesis and has, in a few instances, led to the clinical implementation of effective diagnostic and prognostic tools, as well as treatment strategies that target a specific genetic abnormality.


The Efficacy and Safety of Chemotherapy in Patients With Nonsmall Cell Lung Cancer and Interstitial Lung Disease: A PRISMA-Compliant Bayesian Meta-Analysis and Systematic Review.
Chemotherapy plays a critical and venturous role against the co-morbidity of nonsmall cell lung cancer and interstitial lung disease (NSCLC-ILD).We performed a Bayesian meta-analysis and systematic review to evaluate the safety and efficacy of the chemotherapy in NSCLC-ILD patients.EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov (up to January 2015).We included all study designs except case reports, all studies with NSCLC-ILD patients and all the possible chemotherapy regimens.Quality was assessed by a components approach. We derived summary estimates using Bayesian method through WinBUGS (version 1.4.3, MRC Biostatistics Unit, Cambridge, UK).Seven studies involving 251 patients with NSCLC-ILD were included in the meta-analysis. The treatment response (complete remission, 0; [partial remission, 39.1%; 95% credible interval [CrI], 32.6-45.7]; [stable disease, 36%; 95% CrI, 29.6-42.2]; [PD, 15.4%; 95% CrI, 11.3-19.8]; [nonevaluable, 6.4%; 95% CrI, 2.7-10.1]; [overall response rate, 41.3%; 95% CrI, 35.3-47.4]; [disease control rate, 77.7%; 95% CrI, 72.2-82.7]) were comparable to that of patients with NSCLC alone; the survival outcomes (median overall survival, median progression-free survival, and 1-year survival rate) were slightly worse, especially the lower 1-year survival rate. Platinum-based doublets as first-line chemotherapy may be related to higher incidence of acute exacerbation-ILD in first line chemotherapy (AE, 8.47%; 95% CrI, 5.04-12.6).The data selection bias and small patient number make the meta-analysis of treatment response and conclusions generated from these data inaccurate.The present meta-analysis suggests that chemotherapy might be an effective therapy for patients with NSCLC-ILD, but it might be associated with higher incidence of acute exacerbation.


The Life Cycle and Ultrastructure of the Host Response of the Smut Pathogen Anthracocystis destruens on Broomcorn Millet.
Broomcorn millet smut caused by the fungus Anthracocystis destruens is one of the most destructive diseases in broomcorn millet production. The life cycle of A. destruens and host defense responses against A. destruens remain elusive. Here we investigated the disease symptom development and the parasitic process of A. destruens as well as the ultrastructure of the host-pathogen interface. The results showed that there are four typical symptoms of broomcorn millet smut, which are blackfly, cluster leaves, hedgehog head, and incomplete fruiting. A. destruens colonizes all tissues of broomcorn millet but produces teliospores only in the inflorescence. After infection, A. destruens proliferates in the host, likely in a systemic manner. Ultrastructural study of the infected inflorescence showed that the pathogen grows intercellularly and intracellularly within the host. The host activates defense response to prevent pathogen infection, accumulation of callose analogs and highly electron-dense deposits to resist A. destruens infection.


Development of new CoMFA and CoMSIA 3D-QSAR models for anti-inflammatory phthalimide-containing TNFalpha modulators.
In the present study, we describe a new 3D-QSAR analysis of 42 previously reported thalidomide analogues, with the ability to modulate the pro-inflammatory cytokine TNFalpha, by using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Three statistically significant models were obtained. The best resulting CoMFA and CoMSIA models have conventional r(2) values of 0.996 and 0.983, respectively. The cross-validated q(2) values are 0.869 and 0.868, respectively. The analysis of CoMFA and CoMSIA contour maps provided insight into the possible sites for structural modification of the thalidomide analogues for better activity and reduced toxicity.


Programmable Site-Specific Nucleases for Targeted Genome Engineering in Higher Eukaryotes.
Recent advances in the targeted genome engineering enable molecular biologists to generate sequence specific modifications with greater efficiency and higher specificity in complex eukaryotic genomes. Programmable site-specific DNA cleavage reagents and cellular DNA repair mechanisms have made this possible. These reagents have become powerful tools for delivering a site-specific genomic double-strand break (DSB) at the desired chromosomal locus, which produces sequence alterations through error-prone non-homologous end joining (NHEJ) resulting in gene inactivations/knockouts. Alternatively, the DSB can be repaired through homology-directed repair (HDR) using a donor DNA template, which leads to the introduction of desired sequence modifications at the predetermined site. Here, we summarize the role of three classes of nucleases; zinc finger nucleases (ZFNs), transcription activator like effector nucleases (TALENs), and clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) system in achieving targeted genome modifications. Further, we discuss the progress towards the applications of programmable site-specific nucleases (SSNs) in treating human diseases and other biological applications in economically important higher eukaryotic organisms such as plants and livestock. J. Cell. Physiol. 231: 2380-2392, 2016. © 2016 Wiley Periodicals, Inc.


Maximal androgen blockade for advanced prostate cancer.
Maximal androgen blockade (MAB) refers to the combination of medical (gonadotrophin-releasing hormone agonist) or surgical castration with an anti-androgen for the treatment of advanced prostate cancer. A substantial body of basic research has improved our understanding of the interactions between the anti-androgens, the androgen receptor, and androgen response elements in the genome. Anti-androgens act by two primary mechanisms: inhibition of ligand (androgen) binding to the androgen receptor, and inhibition of androgen-independent activation of the receptor. The latter mechanism occurs via several pathways, including inhibiting nuclear co-activators, activating co-suppressors, and inhibiting transcription of a variety of androgen-regulated genes. It is more accurate to refer to these compounds as androgen-receptor antagonists, since they inhibit activation whether this is androgen-mediated or not. Within the class of non-steroidal anti-androgens, there is variation in the degree to which ligand-independent activation is inhibited. Over the last 25 years, approximately 30 clinical trials have addressed the benefit of MAB versus monotherapy. Most of these trials have evaluated flutamide or nilutamide. Several meta-analyses suggest a modest survival benefit of these drugs, amounting to an 8% mortality reduction at 5 years. Preclinical data and two randomized trials -- one historic and one current -- suggest that bicalutamide may be a more effective drug in this respect. This requires confirmation pending further maturity of the current trial, which is the only one directly comparing bicalutamide plus castration to castration alone. In prostate cancer patients at high risk for mortality (based on extent of disease or prostate-specific antigen kinetics), combination therapy with bicalutamide should be considered in preference to monotherapy.


Compound heterozygote state for GgammaAgamma(deltabeta) degrees -thalassemia and hereditary persistence of fetal hemoglobin.
We report a hitherto undescribed interaction of a deletional (deltabeta) degrees -thalassemia and a deletional hereditary persistence of fetal hemoglobin (HPFH) in an adult Thai individual. He was a 40-year-old Thai male who had the following hematologic data: Hb 13.9 g/dL, Hct 43.8%, MCV 78.0 fL, MCH 24.7 pg, MCHC 31.6 g/dL, and RDW 17.1%. Hemoglobin analysis revealed 97% Hb F with Ggamma-globin chain predominant. Globin gene analyses demonstrated that he carried the GgammaAgamma(deltabeta) degrees -thalassemia deletion in trans to the HPFH-6. Hematologic data of the patient were compared to those of the heterozygotes for these high-Hb F determinants found in his parents and an unrelated Thai patient with a compound HPFH-6/deletion-inversion Ggamma(Agammadeltabeta) degrees -thalassemia previously described.


Hypersomnia and periodic breathing. Report of a case and review of the literature.
A patient with hypersomnia and periodic breathing has been studied. Both airflow obstruction and an abnormally of the respiratory control mechanism were implicated in the pathogenesis of the ventilatory arrhythmia. It is suggested that the older terms "Pickwick" syndrome and primary alveolar hypoventilation are abandoned for more descriptive terms, e.g. "hypersomnia with periodic breathing".


Improved method for measuring the catalytic activity of tryptophan synthase alpha subunit in cell extracts.
An improved method has been developed for measuring the catalytic activity of tryptophan synthase alpha-subunit in cell extracts using the indole-3-glycerol phosphate (InGP)----tryptophan reaction. The method involves the chemical and enzymatic synthesis of the substrate InGP immediately before use and avoids the preparation of salt-free hydroxylamine. The method is more convenient, safer and more reliable than the traditional method employing the InGP----indole reaction.


Sinusitis as an emergency.
The manifestations of diseases of the paranasal sinuses that may present as acute emergency situations and the more common complications of these diseases are briefly reviewed with suggestions for initial evaluation therapy.


Intracoronary ethyl alcohol or phenol injection ablates aconitine-induced ventricular tachycardia in dogs.
The hypothesis whether localized ventricular tachycardia could be ablated by myocardial necrosis induced with chemical agents injected into a coronary artery was tested. In 59 anesthetized dogs, a diagonal branch of the left anterior descending coronary artery was cannulated either occlusively or nonocclusively. Localized ventricular tachycardia was induced by injecting approximately 0.01 ml of 30 micrograms/ml of aconitine solution into the left ventricular wall perfused by the cannulated diagonal branch in 54 dogs. In eight untreated control dogs, aconitine-induced ventricular tachycardia lasted 10.2 +/- 2.3 minutes or degenerated into ventricular fibrillation after 7.0 +/- 4.0 minutes. In the remaining 46 dogs, 1 ml of saline solution, 25, 50 or 100% ethyl alcohol or 0.94 ml (mean [range 0.4 to 2.0]) of 25% phenol at room temperature was injected into the occluded coronary artery and 1 ml of 100% ethyl alcohol at body temperature was injected into the nonoccluded coronary artery. Ventricular tachycardia was eliminated in 9 (82%) of 11 dogs receiving phenol, 7 (88%) of 8 dogs receiving 100% ethyl alcohol occlusively, 6 (75%) of 8 dogs receiving 100% ethyl alcohol nonocclusively and 6 (67%) of 9 dogs receiving 50% ethyl alcohol for an entire follow-up period of 10 to 60 minutes. However, saline solution and 25% ethyl alcohol suppressed ventricular tachycardia only transiently in 8 (53%) of 15 and 3 (60%) of 5 dogs, respectively. Left ventricular end-diastolic pressure rose from 8.0 to 11.2 mm Hg (p less than 0.05) immediately after injection of 100% ethyl alcohol in seven dogs.(ABSTRACT TRUNCATED AT 250 WORDS)


ALA-PDT regulates macrophage M1 polarization via ERK/MAPK-NLRP3 pathway to promote the early inflammatory response.
Photodynamic therapy (PDT) is a promising new approach to promote wound healing and its effectiveness has been demonstrated in both clinical and animal studies. Macrophages are the key cells in wound healing and inflammatory response. However, the mechanism of action of PDT on macrophages in promoting wound healing is still unclear. In this study, RAW264.7 cells were used. We analyzed the expression levels of macrophage markers arginase 1 (Arg-1), CD206, iNOS, CD86, and inflammatory factors IL-6, TNF-α, and IL-1β by reverse transcription-polymerase chain reaction and Western blot, Milliplex microtubule-associated protein multiplex assay was performed to analyze the expression of inflammatory factors in the supernatant. Live cell Imaging System to observe the dynamic process of macrophage phagocytosis. Western blot was performed to observe the activation of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) and NOD-like receptor protein 3 (NLRP3) inflammasome. 5-Aminolevulinic acid (ALA)-PDT increased the expression of M1 marker iNOS/CD86 and decreased the expression of Arg-1/CD206 in RAW264.7 cells, while, proinflammatory factors IL-6, TNF-α, and IL-1β expression was enhanced and macrophage phagocytosis was increased. We also found that these phenomena were associated with activation of the ERK/MAPK-NLRP3 pathway. ALA-PDT promotes early inflammatory responses by regulating macrophage M1 polarization through the ERK/MAPK-NLRP3 pathway. It also promotes macrophage phagocytosis.


The novel HLA-B*14:118 allele characterized by two different sequencing-based typing techniques.
HLA-B*14:118 differs from HLA-B*14:93 by two non-synonymous and one synonymous nucleotide substitution in exon 2.


Structural studies on the capsular polysaccharide from Klebsiella serotype K64.
Partial hydrolysis with acid, methylation analysis (including uronic acid degradation), Smith degradation, and p.m.r. spectroscopy have been used to determine the primary structure of the capsular polysaccharide of Klebsiella serotype K64. The hexasaccharide repeating-unit, which also contains one O-acetyl substituent, comprises a 4)-alpha-D-GlcpA-(1 leads to 3)-alpha-D-Manp-(1 leads to 3)-beta-D-Glcp-(1 leads to 4)-alpha-D-Manp-(1 leads to chain with a 4,6-O-(1-carboxyethylidene)-beta-D-glucopyranosyl and an L-rhamnosyl group attached to the 4-linked D-mannosyl residue at 0-2 and 0-3, respectively.


[Treatment for refractory non-neurogenic overactive bladder].
The aim was to synthesize current knowledge on refractory overactive bladder treatments. A systematic literature review based on PubMed, Embase and Google Scholar was conducted in July 2020. Today, refractory overactive bladder treatment includes tibial nerve stimulation, whether percutaneously or transcutaneously, sacral neuromodulation, and botulinum toxin A detrusor injections. These conservative treatments have marginalized surgical treatments, which mainly involve supratrigonal cystectomy with augmentation cystoplasty. Several potential new treatments are being evaluated but can only be currently offered as part of clinical research protocols. "Conservative" treatments for refractory overactive bladder have been shown to be effective. Other treatments could enrich the treatment options.


Pulsed dye laser lithotripsy of bile duct stones.
Efficacy and safety of pulsed dye laser lithotripsy was tested in 25 consecutive patients in whom bile duct stones could not be extracted after endoscopic sphincterotomy. The patients had one to six (mean, 1.8) bile duct stones (diameter, 10-35 mm; mean, 18 mm) located in the common bile duct (18 cases), the intrahepatic bile ducts (6 cases), or in a long cystic duct stump (1 case). Different approaches were tested depending on the presence of a T tube and on the localization of the bile duct stones. When a T tube was present (7 cases), the lithotripsy was performed under direct vision using a choledochoscope inserted through the T-tube tract. In 18 patients without a T tube in place, the lithotripsy was performed under fluoroscopy using a retrograde approach in case of common bile duct stones (14 cases) or under choledochoscopy using a percutaneous transhepatic approach in case of intrahepatic bile duct stones (4 cases). Fragmentation of all the bile duct stones and a complete bile duct clearance were obtained in all 11 cases with procedures performed under direct vision as compared with only 5 of 14 cases with procedures under fluoroscopic control. Moreover, 6 of the 9 failures using the latter approach were offered another session using a choledochoscope inserted through a percutaneous transhepatic tract and were also successfully treated. No complication related to the laser beam was noted. It is concluded that pulsed dye laser lithotripsy of bile duct stones (that are unable to be removed by standard endoscopic techniques) is safe and efficacious provided that it is performed under direct vision. Technical refinements are needed before this procedure can be reliably performed under fluoroscopy.


Retracted: WeChat-Based Comprehensive Education on Egg White Protein Intake for Patients Undergoing Peritoneal Dialysis: A Combined Prospective and Retrospective Study.
[This retracts the article DOI: 10.1155/2022/5651992.].


Inhibitory effect of prolonged administration of cysteamine on experimental carcinogenesis in rat stomach induced by N-methyl-N'-nitro-N-nitrosoguanidine.
The effect of cysteamine (2-aminoethanethiol hydrochloride) on the incidence and histology of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was investigated in inbred Wistar rats. Prolonged administration of 25 or 50 mg per kg body weight of cysteamine after treatment with MNNG for 25 weeks significantly reduced the incidence and number of adenocarcinomas of the glandular stomach. Histological examination showed that the adenocarcinomas that did develop in rats treated with these 2 doses of cysteamine had high mucin-producing activity. Furthermore, treatment with cysteamine caused significant increases in serum gastrin level and gastric acid secretion, together with significant decreases in the antral mucosal pH and the labelling indices of pyloric and oxyntic gland mucosae and gastric cancer. These findings indicate that cysteamine inhibits the development of gastric adenocarcinomas and that its effect may be related to decreasing proliferation of cells in the gastric mucosae.


Altered Proteomic Profile of Exosomes Secreted from Vero Cells Infected with Porcine Epidemic Diarrhea Virus.
Porcine epidemic diarrhea virus (PEDV) infection causes severe diarrhea in pigs and can be fatal in newborn piglets. Exosomes are extracellular vesicles secreted by cells that transfer biologically active proteins, lipids, and RNA to neighboring or distant cells. Herein, the morphology, particle size, and secretion of exosomes derived from a control and PEDV-infected group are examined, followed by a proteomic analysis of the exosomes. The results show that the exosomes secreted from the Vero cells had a typical cup-shaped structure. The average particle size of the exosomes from the PEDV-infected group was 112.4 nm, whereas that from the control group was 150.8 nm. The exosome density analysis and characteristic protein determination revealed that the content of exosomes in the PEDV-infected group was significantly higher than that in the control group. The quantitative proteomics assays revealed 544 differentially expressed proteins (DEPs) in the PEDV-infected group's exosomes compared with those in the controls, with 236 upregulated and 308 downregulated proteins. The DEPs were closely associated with cellular regulatory pathways, such as the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, extracellular matrix-receptor interaction, focal adhesion, and cytoskeletal regulation. These findings provide the basis for further investigation of the pathogenic mechanisms of PEDV and the discovery of novel antiviral targets.


Substrate interferences in identifying flammable liquids in food, environmental and biological samples: case studies.
The analysis of samples for traces of ignitable liquids is most often connected with suspected arson cases. In such cases, samples taken from the point of origin of the fire are analyzed for the presence of ignitable liquids. However, sometimes, in cases not connected with arson, there is a need to detect and identify traces of ignitable liquids. Three examples of such cases are given in this paper. Aqueous samples (polluted water, juice and blood) were analyzed using a procedure routinely used in the analyses of fire debris. The procedure consists of passive adsorption of volatile organic compounds on Tenax, followed by thermal desorption and chromatographic analysis. Results showed that analysis of such untypical samples may be connected with unusual matrix effects, not frequently encountered in fire debris samples.