Mental illness in patients with end-stage kidney disease in South Korea: a nationwide cohort study.
The limited literature on mental illness in end-stage kidney disease (ESKD) patients suggests that this disease is common and burdensome but underrecognized in clinical practice. This study aimed to analyze the prevalence of mental illness in ESKD patients. We assessed the prevalence and patterns of mental illnesses in a nationwide cohort of patients diagnosed with ESKD between January 1, 2008, and December 31, 2017. The risk of mental illness was evaluated using a multivariable Cox proportional hazards model. A total of 70,079 patients met all study inclusion criteria. A total of 28.3% of patients had mental illness, and the specific distribution was as follows: depression, 16.8%; anxiety, 20.0%; somatoform/conversion disorder, 0.9%; stress reaction/adjustment disorder, 2.5%; and substance abuse disorder, 0.6%. The frequency of mental illness was highest in patients on hemodialysis (HD), followed by patients on peritoneal dialysis (PD) and kidney transplant (KT) patients. The peak rate of mental illness in HD and PD patients was reached 1 to 2 years after renal replacement therapy initiation, but the peak rate of most mental illnesses in KT patients occurred before surgery. The prevalence of depression was 2.19 times higher in HD patients and 1.97 times higher in PD patients than in KT patients. ESKD patients are at high risk of mental illness, and the prevalence of mental illness is highest in HD patients. Since the onset of mental illness occurs around the initiation of renal replacement therapy, clinicians need to pay attention to mental illness when treating ESKD patients.


Effects of diethylcholine in two animal models of Parkinsonism tremors.
(2-Hydroxyethyl) methyldiethylammonium iodide (diethylcholine; DEC) was tested against trihexyphenidyl for its ability to block tremors in two animal models of Parkinsonism tremors. Both DEC (75 mg/kg) and trihexyphenidyl (10 mg/kg) antagonized physostigmine tremors in mice. Both drugs also blocked tremors in rats which received intracaudate injections of carbachol. DEC was more efficacious than trihexyphenidyl in the rat model. No dose-related inhibition of tremors was seen for trihexyphenidyl (5--20 mg/kg) but inhibition by DEC was dose-related (25--50 mg/kg). The ED50 for tremor inhibition in the rat model by DEC was 33 mg/kg. DEC was also shown to cross the blood-brain barrier in mice. The probable mechanism of action of DEC is discussed.


Clinical charts for surveillance of growth and body proportion development in achondroplasia and examples of their use.
Clinical surveillance of infants and children with achondroplasia necessitates syndrome-specific charts due to extreme short stature with deviating body proportions. Height, arm span and leg length develop far below normal population ranges. We present growth and body proportion charts for ages 0-20 years, constructed from semi-longitudinal standardized measurements of about 450 children, along with some examples of achondroplasia typical and atypical growth pattern. We combine head circumference, height and weight for 0-4 years into one (infancy) page and height and weight for 4-20 years in another (childhood-adolescence) using nonlinear axes to account for the rapidly decreasing growth velocity. Similarly, weight and BMI are based on nonlinear axes to balance wide SD-channels at higher and narrow SD-channels at lower levels of weight/BMI. Charts for following sitting height, sitting height/height ratio, arm span, leg and foot length are also presented. Clinical examples illustrating the applicability of the charts include cases of extreme prematurity, extreme head circumference development before and after shunting, achondroplasia complicated by chromosomal or additional genetic abnormality and by growth hormone deficiency as well as of evaluating growth promoting therapy.


The use of Lactobacillus plantarum 299v (DSM 9843) in cancer patients receiving home enteral nutrition - study protocol for a randomized, double-blind, and placebo-controlled trial.
Nutritional treatment is one of the most important components of multidisciplinary anti-cancer therapy. Home enteral nutrition is considered as a safe procedure, however, it may be associated with the risk of side effects, such as nausea, vomiting, abdominal pain, and diarrhoea. It is uncertain whether diarrhoea is the result of the enteral formula administration or gut dysbiosis. One of the methods which may be used to alter the composition of gut microbiota is the administration of a probiotic strain. Lactobacillus plantarum 299v ingestion was found to diminish the adverse events of irritable bowel syndrome and Clostridium difficile infection - entities that share the symptoms with enteral nutrition side effects. Therefore, the primary aim of this study is to determine the effect of Lactobacillus plantarum 299v on prevention of weight loss of cancer patients receiving home enteral nutrition. The secondary aims are to evaluate the role of this probiotic strain in the improvement of nutritional status, enteral nutrition tolerance, and patients' quality of life. Forty patients with cancer receiving home enteral nutrition will be enrolled in this clinical trial and randomized to receive one capsule of Lactobacillus plantarum 299v (Sanprobi IBS®) twice a day or placebo for 12 weeks in a double-blind manner. Laboratory tests (the level of albumin, total protein, transferrin, and total lymphocyte count), anthropometric parameters (body mass, the content of fat mass, muscle mass, and total body water), Nutritional Risk Screening (NRS 2002), enteral nutrition tolerance as well as quality of life will be measured. Measurements will be obtained at the baseline and after 4 and 12 weeks of treatment. The adverse events observed during administration of enteral nutrition have an negative impact on enteral formula tolerance and as a consequence patients' quality of life. The previous studies have demonstrated that probiotics may reduce the gastrointestinal symptoms related to enteral nutrition. Thus, administration of Lactobacillus plantarum 299v may be effective in improvement of nutritional status, enteral nutrition tolerance, and quality of life of cancer patients receiving home enteral nutrition. ClinicalTrials.gov Identifier: NCT03940768 .


Cooperative effect of BI-69A11 and celecoxib enhances radiosensitization by modulating DNA damage repair in colon carcinoma.
Amplification of PI3K-Akt pathway promotes radioresistance in various cancers including colorectal carcinoma. Local recurrence in colon cancer causes poor prognosis affecting overall survival of cancer-affected patient population. To avoid local recurrence, pre-operative or post-operative additional radiotherapy is given. However, main concern regarding radiotherapy is to increase the radiosensitivity of malignant cell without hampering the activities of normal cells. In this context, addition of two or more than two chemotherapeutic drugs as a radiosensitizer is a common practice in radiation biology. BI-69A11 earlier showed potential apoptosis-inducing effect in melanoma and colon carcinoma. Celecoxib showed anti-cancer effects in both COX-2 dependent and independent pathways and used to act as a radiosensitizing enhancer. Here, we suggest that the combination of BI-69A11 and celecoxib inhibits the phosphorylation of ataxia telangiectasia mutated (ATM) kinase and DNA-PK responsible for ionizing radiation (IR)-induced double-strand break (DSB) repair. Moreover, the combinatorial effect of BI-69A11 and celecoxib attenuates the IR-induced G2/M cell cycle arrest. Furthermore, this combination also impairs IR-induced activation of Akt and downstream targets of ATM. This might lead to induced activation of apoptotic pathway after triple therapy treatment modulating pro-apoptotic and anti-apoptotic proteins. This activation of apoptotic pathway also showed the interdependence of PUMA and BAD in triple combination-treated colon cancer cells in a p53 independent manner. This study reveals the therapeutic potential of the triple combination therapy in prevention of radioresistance. Besides, it also demonstrates the cytotoxic effects of triple combination therapy in colon cancer. This study shows utility and potential implication on safety of the patients undergoing radiation therapy.


Gaps in medical education curricula on skin of color in medical school, residency, and beyond: Part 1.
Various studies have revealed a disproportionately low representation of skin of color (SOC) dermatology in the medical education system of the United States. This disparity contributes to adverse experiences, missed and/or delayed diagnoses, and overall health inequities for individuals of color. The lack of sufficient SOC education begins at the medical school level and continues throughout residency, fellowship, and beyond formal training. This lack of education can be seen in the dearth of images of common and uncommon skin conditions in darker skin in widely used textbooks and educational resources as well as in the lack of formal training in SOC in many residency programs. Thus far, there have been valuable strides to make dermatologic education more inclusive of all skin colors, but there remains significant work to be done. With the population of the United States expected to continue to diversify and with the expectation that SOC will be a trait of over half of the population of the United States by 2050, it is important to strive for health equity by ensuring that comprehensive and inclusive medical training incorporates SOC. This paper will explore the issue of gaps in medical education in SOC dermatology at all levels and offer a strategic call to action to aid in rectifying this situation.


Does Pedicle Screw Fixation Assisted by O-Arm Navigation Perform Better Than Fluoroscopy-guided Technique in Thoracolumbar Fractures in Percutaneous Surgery?: A Retrospective Cohort Study.
A retrospective cohort study. To evaluate the effect of O-arm navigation in percutaneous surgeries for thoracolumbar fracture in comparison to the use of conventional fluoroscopic technique. O-arm navigation is a progressive surgical tool, with extensive research papers reporting its effects. Whereas, there were not many papers describing its accuracy and facet impingement rate when compared with fluoroscopy-guided technique in percutaneous surgeries, especially at varying fracture levels. We conducted a retrospective comparative study of 97 consecutive patients of single-level neurological intact thoracolumbar fractures from November 2015 to October 2017 and they were all treated with percutaneous pedicle screw implantation. Screws were classified as 4 grades of perforations and 3 grades of facet joint violation. The association between variables such as anatomic perforation, functional perforation, and facet impingement were investigated by χ test, Fisher exact test or t test. A P-value of <0.05 was considered statistically significant. A total of 573 pedicle screws were implanted and graded. The overall anatomic perforation rate and functional perforation rate were lower in the O-arm group compared with the fluoroscopy group (8.3% vs. 15.0%, P=0.013, 1.1% vs. 4.2%, P=0.024). At fracture level, the rate of grade 2 perforation of the O-arm group was lower than that of the fluoroscopy group (0% vs. 6.1%, P=0.033). Furthermore, the O-arm group obviously reduced the facet impingement rate both at all levels and at fracture levels (P=0.002; 0.02). In percutaneous pedicle screw placement for neurological intact thoracolumbar fracture, the introduction of O-arm navigation improved accuracy, reduced functional perforations, and minimized serious perforations compared with conventional fluoroscopic technique. It also decreased facet joint violation observably and helped to prevent development of adjacent segment degeneration.


Rapid and quantitative antimalarial drug efficacy testing via the magneto-optical detection of hemozoin.
Emergence of resistant Plasmodium species makes drug efficacy testing a crucial part of malaria control. Here we describe a novel assay for sensitive, fast and simple drug screening via the magneto-optical detection of hemozoin, a natural biomarker formed during the hemoglobin metabolism of Plasmodium species. By quantifying hemozoin production over the intraerythrocytic cycle, we reveal that hemozoin formation is already initiated by ~ 6-12 h old ring-stage parasites. We demonstrate that the new assay is capable of drug efficacy testing with incubation times as short as 6-10 h, using synchronized P. falciparum 3D7 cultures incubated with chloroquine, piperaquine and dihydroartemisinin. The determined 50% inhibitory concentrations agree well with values established by standard assays requiring significantly longer testing time. Accordingly, we conclude that magneto-optical hemozoin detection provides a practical approach for the quick assessment of drug effect with short incubation times, which may also facilitate stage-specific assessment of drug inhibitory effects.


Evaluating periodontal conditions in patients with von Willebrand's disease in Hospital Universitario de Maracaibo (University Hospital, Maracaibo)-Venezuela.
To evaluate the periodontal conditions of patients with von Willebrand's Disease (vWD who went for dental examination in the "Area of attention to patients with systemic disease" of the University Hospital in Maracaibo, Venezuela. 40 patients (28 female and 12 male), with ages ranging from 10 to 72 years, who regularly attended dental control, were evaluated along with a control group of patients with no hemorrhagic alterations. Periodontal conditions were evaluated using the Löe and Silness Gingival Index (GI) and Greene and Vermillon's Simplified Oral Hygiene Index (SOHI). The results were analyzed using averages, Standard Deviation, Student's T-test and the Chi(2) test, with P<0.0005. 92.5% of the patients had Type 1 vWD and 7.5% had Type 2 or 3. Periodontal Indices: GI (0.70+/-0.40, slight) and SOHI (1,70+/-0,80, acceptable). Comparison with the control group showed that there were statistically significant differences in the SOHI (P = 0.02). Periodontal conditions in patients with vWD regularly attending for dental control were within acceptable parameters. Education of the patient with regard to prevention and opportune treatment is of utmost importance, thereby avoiding the oral hemorrhagic complications produced by the periodontal disease. Of equal importance is multidisciplinary teamwork.


Effectiveness of screen-to-screen and face-to-face learning modalities in dental anatomy module during Covid-19 pandemic.
The Covid-19 pandemic has forced all dentistry faculties to quickly shift to the online supplementation or replacement of traditional modules to pursue education. However, there is limited research evaluating the effectiveness of this education modality on student performance in dental anatomy and manipulation module. Accordingly, it was aimed to compare the influence of different education modalities on the performances of the students enrolled in this module. The students were requested to perform 11 practical assignments throughout the fall term. A total of 220 face-to-face-educated (F2F) and 138 screen-to-screen-educated (S2S) students were included. To evaluate the influence of education modality on the performances of the students, cumulative success scores were calculated and compared using an independent t-test. The grades of the first (maxillary central), sixth (maxillary premolar), and eleventh assignments (mandibular first molar) were also analyzed to understand the manipulation-skill progress of each student within the same year. The grades of above-mentioned three assignments were converted into nominal data (excellent, very good, good, acceptable, and fail) based on certain thresholds, and a chi-square test was conducted. The cumulative success scores in F2F group were significantly lower than those in S2S group (P = 0.02). Differences between the first and eleventh tasks in both education modalities were significant (P < 0.05). The S2S-educated students achieved significantly higher achievement points in the sixth and eleventh assignments (P < 0.001). The S2S education can be suggested as an applicable modality for teaching dental anatomy and manipulation module. However, further work is needed to ascertain whether this result is replicable throughout dental anatomy education.


The current status and future direction of percutaneous peptide immunization against melanoma.
Dendritic cell (DC)-based tumor immunotherapy is widely known to elicit protective anti-tumor immune responses, although the safety and effectiveness have yet to be thoroughly explored. We reported that a disruption in the stratum corneum barrier resulted in enhanced permeability and alterations in the skin immune system in such a way that epidermal Langerhans cells (LCs) functioned as vigorous antigen presenters for T helper (Th) cells and cytotoxic T lymphocytes (CTLs). In both human and murine models, topical application of melanoma-associated antigen peptides onto stratum corneum barrier-disrupted skin, specifically induced tumoricidal immune responses in vivo and in vitro accompanying an increased expression of MHC and co-stimulatory molecules on LCs. In addition, for reasons of simplicity, safety and effectiveness, percutaneous peptide application has demonstrated a certain degree of feasibility in clinical approach in patients with melanoma. In the future, resolution of some of the outstanding issues concerning the selection of the most effective adjuvants in combination with barrier disruption and depletion of regulatory T (Treg) cell-mediated immune suppression would appear as essential to improve percutaneous melanoma immunotherapy.


Noninvasive test for the diagnosis of ovarian hormone-secreting-neoplasm in postmenopausal women.
The diagnosis of ovarian hormone-secreting neoplasm in postmenopausal women is currently based on imaging modalities and selective venography. However, these diagnostic tests are not always accurate. In order to improve and simplify the diagnosis, we propose a noninvasive hormonal test. To report our experience using noninvasive hormonal test for the diagnosis of ovarian hormone producing tumor in two postmenopausal women. Evaluation of androgen and estradiol serum levels following 1. Adrenal hormonal depression, 2. ovarian hormonal depression and 3. ovarian hormonal stimulation. Tertiary care medical center. Changes in androgen and estradiol levels. In the first case, total testosterone, free androgen index and estradiol serum levels decreased following ovarian depression by GnRH-antagonist (6.9 nmol/L, 67 nmol/L and < 70 pmol/L, respectively) and subsequently increased after ovarian stimulation with LH (11.5 nmol/L, 117 nmol/L and 176 pmol/L, respectively). Histological evaluation revealed steroid cell tumor in one ovary. In the second case, estradiol serum levels decreased following ovarian depression by GnRH-antagonist (73 pmol/L) and subsequently increased following ovarian stimulation with FSH (118 pmol/L). Histological evaluation revealed granulosa cell tumor in one ovary. To our knowledge, these are the first cases of ovarian hormone-producing tumors in postmenopausal women diagnosed by noninvasive hormonal test. The proposed test can be considered in postmenopausal women suspected of having androgen and/or estrogen producing tumors.


Multiple forms of SppI (secreted phosphoprotein, osteopontin) synthesized by normal and transformed rat bone cell populations: regulation by TGF-beta.
Metabolic labeling has revealed that rat bone cell populations in culture synthesize several forms of the secreted phosphoprotein, SppI. Most cell populations produced two major [32PO4]-labeled forms that behaved anomolously on SDS-PAGE migrating at 60 kDa and 56 kDa on 10% gels and 55 kDa and 44 kDa on 15% gels. Minor forms of intermediate sizes were also resolved. In normal bone cells the 60 kDa form was predominant and was the only form produced by the clonal bone cell line, RCA 11, whereas the 56 kDa a form predominated in the transformed bone cell line, ROS 17/2.8. In all populations [35S]-methionine-labeling revealed SppIs at approximately 60 kDa but no 56 kDa form. Each form of SppI was specifically cleaved by thrombin which generated fragments of approximately 28 kDa. Transforming growth factor beta 1 increased SppI mRNA levels 3 to 6-fold within 24 h in the normal bone cells, but no increase occurred in the ROS 17/2.8 cells. The elevated expression of SppI was reflected in a selective increase in the synthesis of the [32PO4]-and [35S]-methionine-labeled 60 kDa SppIs.


Designing human m1 muscarinic receptor-targeted hydrophobic eigenmode matched peptides as functional modulators.
A new proprietary de novo peptide design technique generated ten 15-residue peptides targeting and containing the leading nontransmembrane hydrophobic autocorrelation wavelengths, "modes", of the human m(1) muscarinic cholinergic receptor, m(1)AChR. These modes were also shared by the m(4)AChR subtype (but not the m(2), m(3), or m(5) subtypes) and the three-finger snake toxins that pseudoirreversibly bind m(1)AChR. The linear decomposition of the hydrophobically transformed m(1)AChR amino acid sequence yielded ordered eigenvectors of orthogonal hydrophobic variational patterns. The weighted sum of two eigenvectors formed the peptide design template. Amino acids were iteratively assigned to template positions randomly, within hydrophobic groups. One peptide demonstrated significant functional indirect agonist activity, and five produced significant positive allosteric modulation of atropine-reversible, direct-agonist-induced cellular activation in stably m(1)AChR-transfected Chinese hamster ovary cells, reflected in integrated extracellular acidification responses. The peptide positive allosteric ligands produced left-shifts and peptide concentration-response augmentation in integrated extracellular acidification response asymptotic sigmoidal functions and concentration-response behavior in Hill number indices of positive cooperativity. Peptide mode specificity was suggested by negative crossover experiments with human m(2)ACh and D(2) dopamine receptors. Morlet wavelet transformation of the leading eigenvector-derived, m(1)AChR eigenfunctions locates seven hydrophobic transmembrane segments and suggests possible extracellular loop locations for the peptide-receptor mode-matched, modulatory hydrophobic aggregation sites.


Rhodiola Inhibits Atrial Arrhythmogenesis in a Heart Failure Model.
Rhodiola, a popular plant in Tibet, has been proven to decrease arrhythmia. The aim of this study was to elucidate the molecular mechanism and electrophysiological properties of rhodiola in the suppression of atrial fibrillation. This study consisted of 3 groups as follows: Group 1: normal control rabbits (n = 5); Group 2: rabbits with heart failure (HF) created by coronary ligation and who received 2 weeks of water orally as a placebo (n = 5); and Group 3: rabbits with HF who received 2 weeks of a rhodiola 270 mg/kg/day treatment orally (n = 5). The monophasic action potential, histology, and real-time polymerase chain reaction (RT-PCR) analysis of ionic channels and PI3K/AKT/eNOS were examined. Compared with the HF group, attenuated atrial fibrosis (35.4 ± 17.4% vs. 16.9 ± 8.4%, P = 0.05) and improved left ventricular (LV) ejection fraction (51.6 ± 3.4% vs. 68.0 ± 0.5%, P = 0.001) were observed in the rhodiola group. The rhodiola group had a shorter ERP (85.3 ± 6.8 vs. 94.3 ± 1.2, P = 0.002), APD90 (89.3 ± 1.5 vs. 112.7 ± 0.7, P < 0.001) in the left atrium (LA), and decreased AF inducibility (0.90 ± 0.04 vs. 0.42 ± 0.04, P < 0.001) compared with the HF group. The mRNA expressions of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, and SERCA2a in the HF LA were up-regulated after rhodiola treatment. The rhodiola-treated HF LA demonstrated higher mRNA expression of PI3K-AKT compared with the HF group. Rhodiola reversed LA electrical remodeling, attenuated atrial fibrosis and suppressed AF in rabbits with HF. The beneficial electrophysiological effect of rhodiola may be related to upregulation of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, SERCA2a, and activation of PI3K/AKT signaling.


Streptomycin: separation of polysomal and non-polysomal messenger ribonucleoproteins.
In the presence of 0.02 M streptomycin, all of the polysomes precipitate from male cricket (Acheta domesticus) accessory gland and chick embryonic tissue post-mitochondrial fractions. All non-polysomal messenger-like ribonucleoprotein preparations tested remain in solution.


Involvement of neuronal and glial activities in control of the extracellular d-serine concentrations by the AMPA glutamate receptor in the mouse medial prefrontal cortex.
It has been well accepted that d-serine may be an exclusive endogenous coagonist for the N-methyl-d-aspartate (NMDA)-type glutamate receptor in mammalian forebrain regions. We have recently found by using an in vivo dialysis method that an intra-medial prefrontal cortex infusion of S-α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (S-AMPA), a selective AMPA-type glutamate receptor agonist, causes a reduction in the extracellular levels of d-serine in a calcium-permeable AMPA receptor antagonist-sensitive manner. The inhibitory influence by the AMPA receptor on the extracellular d-serine, however, contradicts the data obtained from in vitro experiments that the AMPA receptor stimulation leads to facilitation of the d-serine liberation. This discrepancy appears to be due to the different cell setups between the in vivo and in vitro preparations. From the viewpoints of the previous reports indicating (1) the neuronal presence of d-serine synthesizing enzyme, serine racemase, and d-serine-like immunoreactivity and (2) the same high tissue concentrations of d-serine in the glia-enriched white matter and in the neuron-enriched gray matter of the mammalian neocortex, we have now investigated in the mouse medial prefrontal cortex, the effects of attenuation of neuronal and glial activities, by tetrodotoxin or fluorocitrate, respectively, on the S-AMPA-induced downregulation of the extracellular d-serine contents. In vivo dialysis studies revealed that a local infusion of tetrodotoxin or fluorocitrate eliminated the ability of S-AMPA given intra-cortically to cause a significant decrease in the dialysate concentrations of d-serine without affecting the elevating effects of S-AMPA on those of glycine, another intrinsic coagonist for the NMDA receptor. These findings suggest that the control by the AMPA receptor of the extracellular d-serine levels could be modulated by the neuronal and glial activities in the prefrontal cortex. It cannot be excluded that fluorocitrate would indirectly alter the modulation by changing synaptic neurotransmission via glial activity attenuation as previously reported.


Vegetation changes over time in Prairie Pothole Region reference wetlands.
Periodic assessments of reference condition wetlands are needed to determine changes over time; however, they are rarely conducted. The vegetation from past assessments, 1998 to 2004, was compared to 2016 assessments of 12 reference wetlands in the Missouri Coteau sub-ecoregion of the Prairie Pothole Region using nonmetric multidimensional scaling and permutational multivariate analysis of variance. Analyses indicated the vegetation in the 2016 assessments trended away from the abundance of native highly conservative species as found during the 1998 to 2004 assessments. Instead, the 2016 plant communities trended towards lower abundance of the same native conservative species and higher abundance of non-native species. Both the average coefficient of conservatism values and floristic quality index values significantly declined, supporting the interpretation that reference wetlands were moving towards plant communities with lower abundance of highly conservative species. The assumption that reference wetlands in the Prairie Pothole Region will change little over time is challenged by these findings. Vegetation in refence wetlands within the Prairie Pothole Region is no longer resembles past monitoring and is trending towards a distinct vegetation composition. Future management will need to consider the potential of reference wetlands' vegetation composition moving away from a historic baseline and how this may impact future wetland assessment, especially when vegetation is compared to reference conditions.


Photobiomodulation as oedema adjuvant in post-orthognathic surgery patients: A randomized clinical trial.
Photobiomodulation therapy (PBMT) has been used in multiple applications in general medicine as powerful anti-inflammatory, analgesic and reducing oedema in different parts of the body. The aim of this study is to compare the effect on post-surgical oedema after mandibular orthognathic surgery, between two different laser power densities and oral medication with non-steroidal anti-inflammatory. In a randomized clinical trial, on 60 patients who were subject to mandibular orthognathic surgery were divided into three groups. All groups received sodium naproxen 250mg every 8hours for 6days. Two groups were irradiated with two different laser application protocols and the other was a control group. In G1 group the irradiation parameters three times per week for two weeks were: 940nm, in continuous mode, 2.5W, 120s, 85.71J/cm2, 0.89W/cm2, over the right and left side with a distance from the skin surface of 1mm with the whitening handpiece (spot size of 2.8cm2). In G2, the irradiation parameters three times a week for two weeks were: 940nm, in continuous mode, 4.1W, 120s, 68.33J/cm2, 0.58W/cm2 over the right and left side with a distance from the skin surface of 15mm, with the deep tissue handpiece (spot size of 7.1cm2). In all the groups, millimetric facial measurements were taken from tragus to lateral commissure, and from lateral commissure to gonion in both sides. All differences between T1 and T6 were significant for the three groups, (paired T, P<0.05). The differences between the groups were generally not significant (P>0.05) except for commissure - right and left gonion when compared G1 vs CG (P<0.05) and G2 vs CG (P<0.05). Initial changes (T1-T2) between groups were significantly different except for the measurement from commissure to right tragus G1 vs CG (P=0.411) and from commissure to left tragus G2 vs CG (P=0.94). The faster resolution of the oedema occurred in G2 group. PTBM with an energy density of 68.33J/cm2 was the most effective adjuvant to oral medication with non-steroidal anti-inflammatory, to decrease post-surgical oedema after mandibular orthognathic surgery.


Hyperbolic mapping of human proximity networks.
Human proximity networks are temporal networks representing the close-range proximity among humans in a physical space. They have been extensively studied in the past 15 years as they are critical for understanding the spreading of diseases and information among humans. Here we address the problem of mapping human proximity networks into hyperbolic spaces. Each snapshot of these networks is often very sparse, consisting of a small number of interacting (i.e., non-zero degree) nodes. Yet, we show that the time-aggregated representation of such systems over sufficiently large periods can be meaningfully embedded into the hyperbolic space, using methods developed for traditional (non-mobile) complex networks. We justify this compatibility theoretically and validate it experimentally. We produce hyperbolic maps of six different real systems, and show that the maps can be used to identify communities, facilitate efficient greedy routing on the temporal network, and predict future links with significant precision. Further, we show that epidemic arrival times are positively correlated with the hyperbolic distance from the infection sources in the maps. Thus, hyperbolic embedding could also provide a new perspective for understanding and predicting the behavior of epidemic spreading in human proximity systems.


Identification of 7 stress-related NAC transcription factor members in maize (Zea mays L.) and characterization of the expression pattern of these genes.
NAC proteins are plant-specific transcription factors that play essential roles in plant development and various abiotic stress responses. A comprehensive analysis of maize NAC genes was performed in this study. A total of 157 non-redundant maize NAC genes including seven membrane-bound members were identified and found to be unevenly distributed on 10 maize chromosomes. Motif composition analysis indicated that the maize NAC proteins share three relatively conserved motifs in the NAC domain within the N-terminal region. Phylogenetic analysis of 157 maize NAC proteins accompanied by 117 NAC proteins from Arabidopsis and 151 from rice were presented. The NAC proteins evaluated were divided into two large groups including 18 subgroups. Gene duplication analysis indicated that gene loss occurred during maize evolution. Seven NAC members that belong to the same clade of maize NAC domain genes were isolated, and overlapping expression patterns were observed under various abiotic stresses, including low temperature, high salinity and dehydration, and phytohormone abscisic acid treatments. This suggested that NAC members function as stress-responsive transcription factors in ABA-dependent signaling pathways. Relatively higher expression levels of these selected maize NAC genes were detected in roots. The stress responsive NAC genes may have applications in molecular breeding to improve crop stress tolerance.


Significance of oncocytic features in poorly differentiated thyroid carcinoma - a bi-institutional experience.
Poorly differentiated thyroid carcinoma (PDTC), defined by Turin criteria, comprises a subset of high-grade follicular-derived thyroid carcinomas with intermediate prognosis. While differentiated oncocytic thyroid carcinomas demonstrate clinicopathologic and genetic differences compared to their non-oncocytic counterparts, similar data is limited in oncocytic (Hurthle) PDTCs (OPDTCs). Here, we assessed the impact of various oncocytic cut-offs in PDTCs on clinical, histologic and survival parameters.Our bi-institutional cohort comprised 210 primary PDTCs with available slides reviewed by at least one pathologist. Histologic features, including oncocytic fraction, were recorded. Clinicopathologic data were obtained, including overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), locoregional recurrence free survival (LRRFS), and distant metastasis-free survival (DMFS). Radioactive iodine avidity data was available for 125 PDTCs based on postoperative whole-body scanning.Within our cohort, 39.0% PDTCs had any oncocytic component with 24.8% meeting the 75% World Health Organization (WHO) oncocytic definition. Any oncocytic component and > 25% oncocytic cut-off correlated with decreased DSS and LRRFS, respectively, compared to non-oncocytic PDTCs (NOPDTCs) on univariate and multivariate analysis. The 100% oncocytic cut-off was significant for DSS on univariate analysis but a non-significant trend on multivariate analysis. Any oncocytic cut-off (100%, > 75%, > 50%, > 25%, or > 0%) conferred higher radioactive iodine (RAI)-refractoriness to OPDTCs compared to NOPDTCs. NF1 and PTEN alterations were enriched in OPDTCs (40% vs. 0%, and 60% vs 8%, respectively), whereas NRAS mutations were frequent in NOPDTCs (47% vs. 7%).Among PDTCs, the presence of oncocytes led to downward trend in all outcome parameters, especially for DSS and LRRFS. OPDTCs were enriched in NF1 and PTEN mutations. Consistently, all oncocytic cut-offs were associated with RAI-refractoriness. Accordingly, additional studies are needed to reassess the current 75% cut-off used to define oncocytic thyroid lesions.


Chronic exposure to environmentally relevant concentration of fluoride impairs osteoblast's collagen synthesis and matrix mineralization: Involvement of epigenetic regulation in skeletal fluorosis.
Globally, 200 million people are suffering from toxic manifestations of Fluoride(F), dental and skeletal fluorosis; unfortunately, there is no treatment. To unravel the pathogenesis of skeletal fluorosis, we established fluorosis mice by treating environmentally relevant concentration of F (15 ppm NaF) through drinking water for 4 months. As in skeletal fluorosis, locomotor disability, crippling deformities occur and thus, our hypothesis was F might adversely affects collagen which gives the bone tensile strength. This work inevitably had to be carried out on osteoblast cells, responsible for synthesis, deposition, and mineralization of bone matrix. Isolated osteoblast cells were confirmed by ALP activity and mineralized nodules formation. Expression of collagen Col1a1, Col1a2, COL1A1 was significantly reduced in treated mice. Further, a study revealed the involvement of epigenetic regulation by promoter hypermethylation of Col1a1; expressional alterations of transcription factors, calcium channels and other genes e.g., Cbfa-1, Tgf-β1, Bmp1, Sp1, Sp7, Nf-Kb p65, Bmp-2, Bglap, Gprc6a and Cav1.2 are associated with impairment of collagen synthesis, deposition and decreased mineralization thus, enfeebling bone health. This study indicates the possible association of epigenetic regulation in skeletal fluorosis. However, no association was found between polymorphisms in the Col1a1 (RsaI, HindIII) and Col1a2 (RsaI, HindIII) genes with fluorosis in mice.


Molecular imaging of a glucagonoma with 18F-FDG PET/CT and 68Ga-DOTATATE PET/CT imaging: A case report and review of the literature.
A 35-year-old man presented with significant weight loss of 30 kg over the previous 6 months, with newly diagnosed diabetes. Routine laboratory tests were normal, except for markedly elevated blood glucose. Computed tomography (CT) of the abdomen revealed a large severely enhanced mass replacing most of the pancreas and liver metastatic nodules and multiple paraaortic lymph node metastases, 18F-fluorodeoxygluocse positron emission tomography/computed tomography (18F-FDG PET/CT) was performed and revealed mild FDG uptake in the pancreatic mass, as well as mild uptake in the liver and lymph node metastases. A biopsy of the liver metastasis was consistent glucagonoma that was confirmed with markedly elevated serum glucagon level. Subsequently, 68Ga-DOTATATE PET/CT was performed for better tumor characterization and for assessment of the tumors' response to therapy, 68Ga-DOTATATE scan revealed intense uptake in the pancreatic mass, liver metastases, and paraaortic lymph node metastases. The patient responded well to peptide receptor radionuclide therapy. This case highlights the role of both 68Ga-DOTATATE and 18FDG-PET/CT in the diagnosis and management of a glucagonoma. 68Ga-DOTATATE is the tracer of choice for well-differentiated glucagonoma and offers very high diagnostic accuracy as compared with that of cross-sectional and other functional imaging and enables correct patient selection for peptide receptor radionuclide therapy.


Characterization of the oligosaccharide moiety of VIP receptor from the human pancreatic cell line BxPC-3.
The human pancreatic cell line BxPC-3 displays two classes of binding sites with high and low affinity for VIP. The order of potency of VIP-related peptides in inhibiting either [125I]VIP or [125I]N-AcPACAP27 binding and in stimulating cAMP production was typical of the human VIP receptor. By combining affinity labeling with glycosidase treatments, we have characterized the VIP receptor as a M(r) = 68,200 glycoprotein, consisting of a M(r) = 39,300 polypeptide core with at least three N-linked oligosaccharide chains. In addition, our results revealed the presence of a low amount of sialic acid residues in the carbohydrate moiety of receptor.


Removal of percutaneously inserted central venous catheters in neonates is associated with the occurrence of sepsis.
Clinical signs of sepsis are frequently observed after removal of a percutaneously inserted central venous catheter (PCVC) in neonates admitted at our Neonatal Intensive Care Unit (NICU). To substantiate this finding and to evaluate the effect of antibiotics administered at the time of removal of a PCVC, we conducted a retrospective study among all infants with a PCVC, admitted at our NICU during 2002 and 2005. Clinical data, infectious complications and use of antibiotics were studied retrospectively. A PCVC was inserted in 345 infants. Sepsis occurred in 90/345 (26%) infants, in 50/90 (56%) during indwelling PCVC and in 40/90 (44%) after removal of the PCVC. Of the latter 40 sepsis episodes, 24 (60%) occurred within 5 days after removal of a PCVC with a clustering of 21 cases of sepsis within 72 h after the removal. The remaining 16 episodes occurred after 7 days. Administration of antibiotics during removal of the PCVC significantly reduced the incidence of sepsis: 22/213 (10.3%) cases of sepsis occurred when no antibiotics were administered versus 2/132 (1.5%) cases of sepsis when antibiotics were administered (p = 0.002). Our study suggests that peripherally inserted central venous catheters are associated with sepsis not only during the indwelling period of the catheter, but also after removal. Administration of antibiotics targeted at the time of removal of the catheter significantly reduced the incidence of sepsis. Future prospective studies are warranted to confirm this observation.


Correction: grhl2 determines the epithelial phenotype of breast cancers and promotes tumor progression.
[This corrects the article on p. e50781 in vol. 7.].


A Protection Motivation Theory-Based Empowerment Intervention for Promoting Health Behaviors in Women With Human Papillomavirus: An Experimental Study.
This experimental study on 70 women with human papillomavirus, referred to the specialized obstetrics and gynecology clinics of public hospitals in Iran in 2021, revealed that implementing the protection motivation theory-based empowerment intervention could promote their health behaviors.


Troglitazone-induced changes in adiponectin do not affect endothelial function in diabetes.
Adiponectin has been proposed to be related to endothelial function. We have examined the relationship between the increase in adiponectin levels that is associated with troglitazone treatment and endothelium-dependent vasodilation in type 2 diabetic patients. Seventy-two patients participated in this randomized, placebo-controlled, double-blinded study. High-resolution ultrasound images were used to measure the flow-mediated dilation (endothelium-dependent) and nitroglycerin-induced dilation (endothelium-independent) of the brachial artery. Laser Doppler perfusion imaging was employed to measure the vascular reactivity in the forearm skin. Troglitazone treatment resulted in an average 75% increase in the adiponectin levels, but no changes were observed in the endothelium-dependent vasodilation, any other measurement of vascular reactivity, or any other markers of endothelial activation. Also, no changes were observed in the expression of the receptor for advanced glycation end-products in skin biopsies taken from the forearm. Significant correlations were observed during troglitazone treatment between the changes in the adiponectin levels and the changes in fasting plasma glucose (r = -0.29, p < 0.05), hemoglobin A(1c) (r = -0.30, p < 0.05), total cholesterol (r = 0.25, p < 0.05), and low-density lipoprotein-cholesterol (r = 0.34, p < 0.01). The increase in adiponectin levels after troglitazone treatment is not associated with an improvement in the endothelium-dependent vasodilation, indicating that adiponectin is not a major determinant of endothelial function. In addition, receptor for advanced glycation end-products expression in the skin microcirculation is not affected by troglitazone treatment.


Kinetics of mast cells, eosinophils and phospholipase B activity in the spontaneous-cure response of two strains of mice (rapid and slow responder) to the cestode Hymenolepis nana.
Primary egg-derived infection of Hymenolepis nana (100 eggs) in BALB/c (rapid responder) and C3H (slow responder) mice resulted in increased levels of mucosal mast cells (MMCs), eosinophilia (bone marrow, peripheral, tissue) and phospholipase B activity. The response appeared to be similar in both strains used, with a slight difference in cellular accumulation but a significantly earlier response in BALB/c than in C3H mice. These findings suggest that the prolongation of H. nana infection in C3H mice may be related to the delayed appearance of MMCs and eosinophils, which triggers a slower generation of the intestinal inflammation response. The rapidity with which phospholipase B activity increased was strictly correlated with eosinophil tissue number; this further supports the hypothesis for a direct parallel between eosinophils and phospholipase B activity in infected tissue.


Treatment of clinically diagnosed laryngopharyngeal reflux disease.
To determine the incidence of Helicobacter pylori (HP) stool antigen (HPSA) in patients with laryngopharyngeal reflux disease (LPRD), and to make a comparison of 2 treatment regimens that have been used based on the presence or absence of HPSA positivity in patients with LPRD. Randomized controlled study. Suez Canal University Hospital, Ismalia, Egypt. A total of 212 patients with symptoms of LPRD. Patients were evaluated by laryngoscopy, ambulatory pH monitoring for 24 hours, and HPSA testing. Esomeprazole magnesium as a monotherapy was evaluated vs triple therapy in patients with HP infection. To determine the incidence of HPSA in patients with LPRD, and to make a comparison of 2 treatment regimens that have been used based on the presence or absence of HPSA positivity in patients with LPRD. Persistent dry cough and a feeling of a lump in the throat (globus sensation) were the most frequent symptoms of LPRD, while posterior laryngeal inflammation was the main laryngoscopic finding. Results from the HPSA test were positive in 57% of the studied group. Patients with negative HPSA were treated with esomeprazole as single modality with a reported improvement score of 96.6%. Patients with positive HPSA test results were divided into 2 groups: 1 received only esomeprazole, with reported improvement in 40%, whereas the second group was treated with esomeprazole, plus amoxicillin sodium and clarithromycin (triple therapy) and reported a 90% incidence of symptom improvement. The incidence of HP infection in patients with LPRD in our study was 57%. Triple therapy showed a higher cure rate in patients with HPSA-positive test results.


Two fatal bicyclist injuries from extended rear view mirrors.
Rear view mirrors mounted on the sides of vans and small trucks may extend beyond the sides of the vehicles and pose a hazard to other road users. Case reports of two bicyclists fatally injured by extended rear view mirrors of small trucks are presented.


Determination of twist and handedness of a 39-base pair segment of DNA in solution.
For DNA in solution, there have been two methods for measuring the helical periodicity. One method examines the ladder of discrete bands formed in the electrophoretic pattern of supercoiled DNA. Such a ladder is assumed to reflect the set of differently linked covalently closed molecules. The other method measures the lengths of partial nuclease digestions of DNA segments affixed to flat surfaces. Neither method, however, is able to measure the absolute handedness. X-ray diffraction of DNA oligonucleotides can determine the handedness, but the DNA must necessarily be crystallized. We have developed a new method for determining the helical parameters of a segment of DNA in solution. It is the first non-crystallographic method that can directly determine both the helical periodicity and the absolute handedness of DNA. The results obtained using this method are consistent with the classical Watson-Crick right-handed double helical model.


Serum PCSK9 is positively correlated with disease activity and Th17 cells, while its short-term decline during treatment reflects desirable outcomes in ankylosing spondylitis patients.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) participates in the autoimmune disease pathology by regulating T helper (Th) cell differentiation, NF-κB pathway, toll-like receptor 4, etc. This study intended to investigate the association of serum PCSK9 with disease activity, Th cells, and treatment response in ankylosing spondylitis (AS) patients. Eighty-nine active AS patients were enrolled in this multicenter, prospective study. Serum was collected from AS patients at week (W)0, W4, W8, and W12, as well as from 20 osteoarthritis patients and 20 healthy controls after enrollment to detect PCSK9 by ELISA. Based on the ASAS40 response at W12, AS patients were classified as responders and non-responders. PCSK9 was increased in AS patients versus healthy controls (P < 0.001) and osteoarthritis patients (P = 0.006). In AS patients, PCSK9 was positively linked with C-reactive protein (CRP) (P = 0.003) and ASDAS-CRP (P = 0.017), but not with other clinical properties (P > 0.05). Besides, PCSK9 was negatively correlated with interleukin-4 (P = 0.034), positively associated with Th17 cells (P = 0.005) and interleukin-17A (P = 0.014), but did not relate to Th1 cells, interferon-γ, or Th2 cells (all P > 0.05). Additionally, PCSK9 was decreased from W0 to W12 in general AS patients (P < 0.001) and responders (P < 0.001) but remained unchanged in non-responders (P = 0.129). Moreover, PCSK9 was lower at W4 (P = 0.045), W8 (P = 0.008), and W12 (P = 0.004) in responders versus non-responders. Furthermore, the treatment options did not affect the PCSK9 level (P > 0.05). Serum PCSK9 is positively associated with disease activity and Th17 cells, while its short-term decline reflects desirable treatment response in AS patients.


Assessment of placenta accreta spectrum at vaginal birth after cesarean delivery.
Previous cesarean delivery is a risk factor for developing placenta accreta spectrum in a subsequent pregnancy and patients with antenatally suspected placenta accreta spectrum frequently undergo planned cesarean hysterectomy. There is a paucity of data regarding unsuspected placenta accreta spectrum among patients undergoing trial of labor after cesarean delivery for attempted vaginal birth after cesarean delivery. This study aimed to investigate the incidence, characteristics, and delivery outcomes of patients with placenta accreta spectrum diagnosed at the time of vaginal birth after cesarean delivery. The Healthcare Cost and Utilization Project's National Inpatient Sample was retrospectively queried to examine 184,415 patients with a history of low transverse cesarean delivery who had vaginal delivery in the current index hospital admission between 2017 and 2020. Those with placenta previa, previous vertical cesarean delivery, other uterine scars, and uterine rupture were excluded. This study identified placenta accreta spectrum cases using the World Health Organization International Classification of Disease, Tenth Revision, codes of O43.2. Coprimary outcomes were (1) the incidence rate of placenta accreta spectrum at vaginal birth after cesarean delivery; (2) clinical and pregnancy characteristics related to placenta accreta spectrum, assessed with multivariable binary logistic regression model; and (3) delivery outcomes associated with placenta accreta spectrum by fitting propensity score adjustment. The secondary outcome was to conduct a systematic literature review using 3 public search engines (PubMed, Cochrane, and Scopus). Data on incidence rate and maternal morbidity related to placenta accreta spectrum at vaginal birth after cesarean delivery were evaluated. The incidence rate of placenta accreta spectrum at vaginal birth after cesarean delivery was 8.1 per 10,000 deliveries. Most placenta accreta spectrum cases were placenta accreta (83.3%). In a multivariable analysis, older maternal age, tobacco use, preeclampsia, multifetal pregnancy, fetal anomaly, preterm premature rupture of membrane, chorioamnionitis, low-lying placenta, and preterm delivery were associated with an increased risk of placenta accreta spectrum (all, P<.05). Of these factors, low-lying placenta had the largest odds for placenta accreta spectrum (526.3 vs 7.3 per 10,000 deliveries; adjusted odds ratio, 35.02; 95% confidence interval, 18.19-67.42). Patients in the placenta accreta spectrum group were more likely to have postpartum hemorrhage (80.0% vs 5.5%), blood product transfusion (23.3% vs 1.0%), shock or coagulopathy (20.0% vs 0.2%), and hysterectomy (43.3% vs <0.1%) than those without placenta accreta spectrum (all, P<.001). In a systematic literature review, a total of 212 studies were screened, and none of these studies examined the incidence and morbidity of placenta accreta spectrum at vaginal birth after cesarean delivery. This nationwide assessment suggests that although placenta accreta spectrum with vaginal birth after cesarean delivery is uncommon (1 of 1229 cases), the diagnosis of placenta accreta spectrum at vaginal birth after cesarean delivery is associated with significant maternal morbidity. In addition, the data suggest that low-lying placenta in the setting of previous low transverse cesarean delivery warrants careful evaluation for possible placenta accreta spectrum before a trial of labor.


Sensitisation of an Azole-Resistant Aspergillus fumigatus Strain containing the Cyp51A-Related Mutation by Deleting the SrbA Gene.
Azoles are widely used for controlling fungal growth in both agricultural and medical settings. The target protein of azoles is CYP51, a lanosterol 14-α-demethylase involved in the biosynthesis of ergosterol. Recently, a novel azole resistance mechanism has arisen in pathogenic fungal species Aspergillus fumigatus. Resistant strains contain a 34-bp or 46-bp tandem repeat (TR) in the promoter of cyp51A, and have disseminated globally in a short period of time. In this study, we investigated whether an azole-resistant strain with a 46-bp TR (TR46/Y121F/T289A) could be sensitised to azoles by deletion of srbA, encoding a direct regulator of cyp51A. The loss of SrbA did not affect colony growth or conidia production, but decreased expression of cyp51A. The srbA deletion strain showed hyper-susceptibility to medical azoles as well as azole fungicides, while its sensitivity to non-azole fungicides was unchanged. This is the first demonstration that deletion of a regulator of cyp51A can sensitise an azole-resistant A. fumigatus strain. This finding may assist in the development of new drugs to help combat life-threatening azole-resistant fungal pathogens.


Pharmacokinetics and Bioequivalence of a Generic and a Branded Pazopanib Tablet in Healthy Chinese Subjects.
This study aimed to evaluate the bioequivalence of two pazopanib tablet formulations in healthy Chinese subjects. A randomized, open-label, single-dose, two-period, two-sequence, crossover study was conducted under fasting conditions. A total of 32 eligible subjects were randomly administered a single dose of a 200-mg generic or branded pazopanib tablet with a 16-day washout period. Blood samples were collected before and up to 72 hours after dosing. Pharmacokinetic parameters were analyzed with noncompartmental analysis. Safety assessments included physical examinations, laboratory tests, and adverse events reporting. Maximum plasma concentration (Cmax ), area under the plasma concentration-time curve (AUC) from zero to the last quantifiable concentration (AUC0-t ), and AUC from zero to infinity (AUC0-∞ ) were similar between the generic and branded products (all P > .05). The 90% confidence intervals of the geometric mean ratio of the test/reference products for Cmax , AUC0-t , and AUC0-∞ were 89.1%-117.1%, 81.9%-108.5%, and 82.4%-109.6%, respectively. There were no serious adverse events during the study. The newly developed generic pazopanib tablet was bioequivalent to the reference product under fasting conditions. Both formulations were well tolerated in healthy Chinese volunteers.


Normal atrial conduction in medically treated patients with bulimia nervosa.
Bulimia nervosa (BN) patients are characterized by binge eating followed by compensatory behaviors. Ingestion of emetic substances, characteristic to some BN patients, has been reported to be associated with supraventricular arrhythmias. To evaluate atrial electrocardiographic markers for supraventricular arrhythmias in patients with BN. The cohort included 31 patients with BN and sex- and age-matched controls. Twelve-lead electrocardiography was conducted on all participants under strict standards. P wave length and P wave dispersion in each patient were computed from a randomly selected beat and an averaged beat constructed from 7-12 beats, included in a 10-s ECG. No statistically significant differences were found between the groups for minimal, maximal, and average P wave duration and P wave dispersion, calculated either from a random beat or averaged beats. BN patients who are medically monitored and treated, have normal P wave parameters and P wave dispersion, and therefore do not appear to have an increased risk for developing supraventricular arrhythmias. Future research should focus on evaluating the effect of acute ingestion of emetic drugs on resting ECG of BN patients, as well as using signal averaging techniques and prolonged ECG-Holter monitoring.


The Tel Hashomer camptodactyly syndrome: report of a new case and review of the literature.
We report on a new case of Tel Hashomer camptodactyly syndrome and review the literature. This syndrome is characterized by skeletal dysplasia, muscle hypoplasia, camptodactyly, and abnormal dermatoglyphics. The inheritance is autosomal recessive with probable partial expression in the heterozygote.


Comparative analysis of human-derived feeder layers with 3T3 fibroblasts for the ex vivo expansion of human limbal and oral epithelium.
Corneal transplantation with cultivated limbal or oral epithelium is a feasible treatment option for limbal stem cell deficiency (LSCD). Currently utilized co-culture of stem cells with murine 3T3 feeder layer renders the epithelial constructs as xenografts. To overcome the potential risks involved with xenotransplantation, we investigated the use of human-derived feeder layers for the ex vivo expansion of epithelial (stem) cells. Human limbal and oral epithelium was co-cultured with mouse 3T3 fibroblasts, human dermal fibroblasts (DF), human mesenchymal stem cells (MSC), and with no feeder cells (NF). Cell morphology was monitored with phase-contrast microscopy, and stem cell characteristics were assessed by immunohistochemistry, real-time PCR for p63 and ABCG2, (stem cell markers), and by colony-forming efficiency (CFE) assay. Immunohistochemical analysis detected positive staining for CK3 (cornea specific marker) and Iβ1 and p63 (putative stem cell markers) in all culture conditions. The level of Iβ1 and p63 was significantly higher in both limbal and oral cells cultured on the 3T3 feeder, as compared to the MSC or NF group (p<0.01). This level was comparable to the cells cultured on DF. Expression of p63 and ABCG2 in limbal and oral epithelial cells in the 3T3 and DF groups was significantly higher than that in the MSC or NF group (p<0.01). No statistical difference was detected between 3T3 and DF groups. The CFE of both limbal and oral cells co-cultured on 3T3 fibroblasts was comparable to cells grown on DF, and was significantly higher than that of cells co-cultured with MSC or NF (p<0.01). Epithelial cells grown on a DF feeder layer maintained a stem cell-like phenotype, comparable to cells grown on a 3T3 feeder layer. In conclusion, DF provides a promising substitute for 3T3 feeder cells during cultivation of xenobiotic-free corneal equivalents.


Giant axonal neuropathy (GAN): case report and two novel mutations in the gigaxonin gene.
Giant axonal neuropathy (GAN) is an autosomal recessive neurologic disorder clinically characterized by a severe polyneuropathy, CNS abnormalities, and characteristic tightly curled hair. Recently, mutations in the gigaxonin gene have been identified as the underlying genetic defect. The authors report two novel mutations confirming that GAN is caused by mutations in the gigaxonin gene and raise the question whether some mutations may cause a mild subclinical neuropathy.


Prognosis of Hepatocellular Carcinoma Among Cancer Survivors with Other Types of Primary Tumors.
The clinical characteristics and outcomes of secondary hepatocellular carcinoma (HCC) in cancer survivors with other prior malignancies remain poorly understood. We aimed to depict the features of HCC patients with other prior cancer and to examine the prognostic effect of prior cancer in those patients. All patients diagnosed with HCC between 2004 and 2014 were identified from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier curves and Cox regression analysis were conducted to determine survival differences and impact of prior cancer history. In total, 32,343 eligible patients with HCC were included in the current study, and 2830 (8.7%) of those patients had prior cancer. Patients who had prior cancer were older and more frequently at localized or regional stages of HCC compared to those without a history of cancer. No differences in overall or cancer-specific survival rates were observed among patients with or without prior cancer, as revealed by the Kaplan-Meier curves. In multivariable Cox regression analysis, a history of cancer was not a prognostic factor for worse overall (HR = 0.99, 95%CI 0.94-1.03, P = 0.577) or HCC-specific (HR = 1.01, 95%CI 0.96-1.06, P = 0.802) survival after adjustment for various covariates. Subsequent HCC in cancer survivors has several different clinical characteristics compared with primary HCC. A history of prior cancer did not significantly contribute to a worse prognosis for subsequent HCC.


An audit of upper gastrointestinal endoscopy in Australian facilities--results of a pilot study.
To test the endoscopy audit protocol for larger prospective study. Prospective medical audit. Sixty two endoscopies provided both patient data and suggestions for improvement in the protocol.


LYC loaded ferritin nanoparticles for intracerebral delivery and the attenuation of neurodegeneration in D-gal-induced mice.
Recombinant human H-ferritin nanocage (rHuHF) loaded with natural antioxidative lycopene molecules (LYC) was successfully constructed for the first time, aiming to enrich LYC in the brain and explore the regulation mechanism of this nanoparticles on neurodegeneration. Here, the mouse model was constructed via D-galactose-induced neurodegeneration based on behavioural analysis, histological observation, immunostaining analysis, Fourier transform infrared microscopy, and Western blotting analysis for the regulation of rHuHF-LYC. rHuHF-LYC improved the behaviour of mice in a dose-dependent manner. Besides, rHuHF-LYC can attenuate neuronal damage, maintain the number of Nissl body, increase the level of unsaturated fat, inhibit the activation of glial cells, and prevent excessive accumulation of neurotoxic proteins in the hippocampus of mice. More importantly, synaptic plasticity was activated in response to the regulation of rHuHF-LYC with excellent biocompatibility and biosafety. This study proved the validity of the direct use of natural antioxidant nano drugs for treating neurodegeneration, providing a promising therapeutic option against further imbalances in the degenerative brain microenvironment.


Rapid detection of IDH2 (R140Q and R172K) mutations in acute myeloid leukemia.
NADP-dependent enzyme isocitrate dehydrogenase (IDH) mutations, IDH1 and IDH2, have been described in acute myeloid leukemia (AML) using next generation sequencing approaches. IDH2 mutations are heterozygous; they alter a single arginine residue at position 140 or 172 and have distinct prognostic significance. The current detection methods of IDH2 mutations are laborious and time consuming as they require DNA sequencing. Herein, we report a new allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR) method to detect the IDH2 mutations. Analysis of leukemic DNA samples from 120 AML patients enabled to identify IDH2 mutations in 22 cases which were confirmed by direct DNA sequencing. Of these, 17 harbored IDH2 (R140Q) and 5 IDH2 (R172K) mutations. Serial dilution experiments showed that the assay enable to detect mutations in 10⁻³ dilutions. Our ASO-PCR method appears useful for routine diagnostic screening of these prognostically relevant alterations in AML and may be conveniently included in the diagnostic workup.


Intrapancreatic accessory spleen: mimic of pancreatic endocrine tumor diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy.
Intrapancreatic accessory spleen forms a well-defined nodule within the tail of the pancreas and is commonly mistaken by imaging studies as a neuroendocrine tumor. We report three cases of intrapancreatic accessory spleen diagnosed by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) biopsy. Imaging studies showed well-circumscribed nodules in the tail of the pancreas. Two lesions were clinically suspicious for pancreatic neuroendocrine tumors and one appeared to be a cyst. EUS-guided FNA revealed predominantly small lymphocytes with a subset of histiocytes, conspicuous eosinophils, and plasma cells. There was also characteristic CD8 positive immunostaining of endothelial cells in cell block sections. We report the first series of accessory spleen in the pancreas diagnosed by EUS-guided FNA with the aid of CD8 immunostaining of splenic sinus endothelial cells.


Second-trimester miscarriage: a review of postnatal investigations and subsequent pregnancy outcomes.
Second-trimester loss is pregnancy loss after the 12th and before the 24th completed weeks of pregnancy. This study aims to review cases of second-trimester miscarriage who attended a large maternity hospital and to examine pregnancy outcomes in this group of women. This study is a review of cases of second-trimester miscarriage using descriptive, exploratory design, involving a retrospective chart review. In this study, 106 cases of second-trimester miscarriage were reviewed. The cause of the miscarriage was found in 42.5% (n = 45) of cases. The majority of women, 84.5% (n = 82) had a normal pelvic ultrasound scan and 18.3% (n = 17) of cases were diagnosed with antiphospholipid syndrome. In women who became pregnant again, 60.9% (n = 39) had a live birth. Establishing the cause of second-trimester miscarriage can be challenging, despite completing all recommended investigations. Outcomes in subsequent pregnancies are reassuring. This review highlights the need to undertake all recommended investigations to elicit the cause of second-trimester miscarriage and underpins the need for further research in this area.


Cancer cachexia: what is known about its etiology and what should be the current treatment approach?
Cancer cachexia, defined as involuntary weight loss and tissue wasting due to cancer, negatively influences physical condition, quality of life and prognosis. Well known causes, such as ileus or hypercalcemia, do not suffice to explain the entire phenomenon. Metabolic changes induced by the tumor and/or host are supposed to play a deciding role. In the present review current insights into the etiology and treatment are discussed.


Profile of genes showing increased expression following dopamine and methamphetamine exposure in an immortalized neuronal cell line.
Methamphetamine (METH) is a drug of abuse with well-described neurodegenerative effects. Some of the METH-induced degenerative manifestations are thought to be due to increased dopamine (DA) release in the cytoplasm of nerve terminals and subsequent extravasation in the synaptic cleft. Using an immortalized neural cell line, we have made use of the comprehensive cDNA array technology in order to compare and contrast the molecular effects of DA and METH. We found that the two compounds do have many similar but also different effects. Since these neural cells produce no DA, these results demonstrate that many of the METH-induced responses attributed to DA might, in fact, be intrinsic to METH itself. More biochemical studies are needed to investigate DA-independent METH deleterious events in the central nervous system.


Identification of a novel variant in the phosphoenolpyruvate carboxykinase gene promoter in Japanese patients with type 2 diabetes.
Phospho enolpyruvate carboxykinase (PEPCK) plays an important role in gluconeogenesis and hepatic glucose production. To test the hypothesis that mutations of the PEPCK gene promoter contribute to the increased hepatic glucose production that leads to diabetes, we screened for polymorphisms of the PEPCK promoter region in 252 Japanese type 2 diabetic patients and 188 non-diabetic control subjects. A novel variant at position - 232 (C to G) was found at a similar frequency in type 2 diabetes patients (32 %) and control subjects (35 %) (p = 0.26). However, patients with the - 232 G/G genotype had an earlier age of onset than those with the - 232 C/C or - 232 C/G genotypes (p = 0.028). As the variant might well otherwise influence hormonal action, we transfected PEPCK-luciferase fusion gene constructs with the variant into human hepatoma cells and examined the response to dexamethasone, insulin, and cAMP. The reporter assay showed no significant difference in hormonal responses with the fusion gene containing the variant. Accordingly, the single-base variant at position - 232 of the PEPCK gene promoter is most probably not a major contributor to the pathogenesis of type 2 diabetes. However, this variation may be useful as a genetic marker for other metabolic disorders, especially in Japanese.


Words Matter: Examining Gender Differences in the Language Used to Evaluate Pediatrics Residents.
Gender disparities in academic medicine continue to be pervasive. Written evaluations of residents may provide insight into perceptions of residents by faculty, which may influence letters of recommendation for positions beyond residency and reinforce perceived stereotype threat experienced by trainees. To examine language used in faculty evaluations of pediatrics residents to determine if there are differences in language used with respect to gender of resident. All faculty evaluations of residents in 3 consecutive intern classes from 2016 to 2018 were collected and redacted for name and gender identifiers. We performed a qualitative analysis of written comments in 2 mandatory free text sections. The study team initially coded text collectively, generating a code book, then individually to apply the coding scheme. Next, evaluations were unblinded to gender. Code applications were aggregated by resident, and frequencies of code application by resident were compared by standardized mean differences to detect imbalances between genders. A total of 448 evaluations were analyzed: 88 evaluations of 17 male residents, and 360 evaluations of 70 female residents. Codes more frequently applied to women included "enthusiasm," and "caring," while codes more frequently applied to men included "intelligence," and "prepared." A conceptual model was created to reflect potential impacts of these differences using a lens of social role theory. We identified differences in the way male and female residents are evaluated by faculty, which may have negative downstream effects on female residents, who may experience negative self-perception, differential development of clinical skills, and divergent career opportunities as a result.


Gene therapy for disorders of the central nervous system.
Though heavily hyped in the early 1990s as the answer to many genetic diseases, gene therapy has largely failed to live up to its promises up to now. The scientific challenges of conveying replacement genes into the brain have prevented it from having an impact on more than a handful of conditions. In addition, gene therapy has been beset by safety problems. During the last 5 years, new vectors and techniques have started to resolve not only safety issues that once held gene therapy back but also markedly to improve efficient gene delivery within the brain and even the spinal cord. Brain gene therapy will not be suitable for every neurological disease, but considerable progress made in the field means we can now envisage that CNS gene therapy will be able to treat many neurological conditions that are not obviously treatable in any other way.


World Water Day: A global awareness campaign to tackle the water crisis.
World Water Day (WWD) has been celebrated on 22 March every year since 1993. It is an opportunity to learn more about water and its centrality in our lives and for the environment, and promote sustainable behaviours and actions towards this precious resource.


Cell cycle activation linked to neuronal cell death initiated by DNA damage.
Increasing evidence indicates that neurodegeneration involves the activation of the cell cycle machinery in postmitotic neurons. However, the purpose of these cell cycle-associated events in neuronal apoptosis remains unknown. Here we tested the hypothesis that cell cycle activation is a critical component of the DNA damage response in postmitotic neurons. Different genotoxic compounds (etoposide, methotrexate, and homocysteine) induced apoptosis accompanied by cell cycle reentry of terminally differentiated cortical neurons. In contrast, apoptosis initiated by stimuli that do not target DNA (staurosporine and colchicine) did not initiate cell cycle activation. Suppression of the function of ataxia telangiectasia mutated (ATM), a proximal component of DNA damage-induced cell cycle checkpoint pathways, attenuated both apoptosis and cell cycle reentry triggered by DNA damage but did not change the fate of neurons exposed to staurosporine and colchicine. Our data suggest that cell cycle activation is a critical element of the DNA damage response of postmitotic neurons leading to apoptosis.


Periodic repolarization dynamics as a risk predictor after myocardial infarction: Prospective validation study.
Periodic repolarization dynamics (PRD) is a novel electrocardiographic phenomenon that refers to sympathetic activity-associated low-frequency modulations of cardiac repolarization. Retrospective post-myocardial infarction (MI) studies revealed that increased PRD indicates an increased risk of subsequent death. This is the first prospective study to validate PRD in patients after MI receiving up-to-date treatment. Four hundred fifty-five survivors of MI (age ≤80 years) in sinus rhythm were enrolled. PRD was assessed from 20-minute electrocardiographic recordings (2048 Hz) and prospectively dichotomized at 5.75 deg2. Primary and secondary end points were total mortality and cardiovascular mortality, respectively. Multivariable analyses additionally included Global Registry of Acute Coronary Events score (dichotomized at >140), left ventricular ejection fraction (dichotomized at ≤35%), diabetes mellitus, and deceleration capacity of heart rate (dichotomized at ≤2.5 ms). The prognostic power of PRD was evaluated using receiver operating characteristic curve analysis, Cox regression analysis, and the integrated discrimination improvement index. During a median follow-up period of 27 months, 47 patients died. Twenty-three of these deaths were classified as cardiovascular. Increased PRD was significantly associated with both end points, yielding areas under receiver operating characteristic curves of 69.3% (60.2%-77.8%) and 79.1% (69.7%-86.7%) for total mortality and cardiovascular mortality, respectively (P < .001 for both). In multivariable analysis, increased PRD indicated a 2.2- and 9.5-fold risk of total mortality and cardiovascular mortality (P = .024 and P = .003, respectively). Addition of PRD to the models significantly improved the integrated discrimination improvement index for total (P = .047) and cardiovascular mortality (P = .007). PRD is a strong and independent predictor of total mortality and cardiovascular mortality in patients after MI treated with contemporary therapy.


Endoscopic ultrasound and pancreatic applications: what the radiologist needs to know.
As the technology has improved, endoscopic ultrasound (EUS) has taken on an important role in the diagnosis of a number of different neoplastic and non-neoplastic pancreatic diseases. EUS can provide high-resolution images with subtle anatomic detail, and has also taken on an important role in the targeted biopsy of the pancreas and adjacent structures. This review seeks to familiarize radiologists with the role of EUS in the diagnosis of chronic and autoimmune pancreatitis, solid pancreatic masses, and cystic pancreatic neoplasms.


Decoding radiology reports: Potential application of OpenAI ChatGPT to enhance patient understanding of diagnostic reports.
To evaluate the complexity of diagnostic radiology reports across major imaging modalities and the ability of ChatGPT (Early March 2023 Version, OpenAI, California, USA) to simplify these reports to the 8th grade reading level of the average U.S. adult. We randomly sampled 100 radiographs (XR), 100 ultrasound (US), 100 CT, and 100 MRI radiology reports from our institution's database dated between 2022 and 2023 (N = 400). These were processed by ChatGPT using the prompt "Explain this radiology report to a patient in layman's terms in second person: <Report Text>". Mean report length, Flesch reading ease score (FRES), and Flesch-Kincaid reading level (FKRL) were calculated for each report and ChatGPT output. T-tests were used to determine significance. Mean report length was 164 ± 117 words, FRES was 38.0 ± 11.8, and FKRL was 10.4 ± 1.9. FKRL was significantly higher for CT and MRI than for US and XR. Only 60/400 (15%) had a FKRL <8.5. The mean simplified ChatGPT output length was 103 ± 36 words, FRES was 83.5 ± 5.6, and FKRL was 5.8 ± 1.1. This reflects a mean decrease of 61 words (p < 0.01), increase in FRES of 45.5 (p < 0.01), and decrease in FKRL of 4.6 (p < 0.01). All simplified outputs had FKRL <8.5. Our study demonstrates the effective use of ChatGPT when tasked with simplifying radiology reports to below the 8th grade reading level. We report significant improvements in FRES, FKRL, and word count, the last of which requires modality-specific context.


Non-invasive brain stimulation in early rehabilitation after stroke.
The new tendency in rehabilitation involves non-invasive tools that, if applied early after stroke, promote neurorecovery. Repetitive transcranial magnetic stimulation and transcranial direct current stimulation may correct the disruption of cortical excitability and effectively contribute to the restoration of movement and speech. The present paper analyses the results of non-invasive brain stimulation (NIBS) trials, highlighting different aspects related to the repetitive transcranial magnetic stimulation frequency, transcranial direct current stimulation polarity, the period and stimulation places in acute and subacute ischemic strokes. The risk of adverse events, the association with motor or language recovery specific training, and the cumulative positive effect evaluation are also discussed.


Dependence of the expression of the radiation-induced gene conversion to arginine independence in diploid yeast on the amino acid concentration: effect on allelic mapping.
The yield of radiation-induced gene conversion to arginine independence in diploid yeast depended on the concentration of the amino acid both in the plating medium and in the intracellular pool. By depletion of the level of arginine in the intracellular pool of amino acid or by provision of arginine at 0.4 mg/l of the plating medium the yield was varied by a factor as high as 20. This may be important in studies of the genetic mapping of alleles based on the slope of conversion frequency versus dose line.


Co-delivery of a trimeric spike DNA and protein vaccine with aluminum hydroxide enhanced Th1-dominant humoral and cellular immunity against SARS-CoV-2.
Protein subunit vaccines have been used as prophylactic vaccines for a long time. The well-established properties of these vaccines make them the first choice for the coronavirus disease 2019 (COVID-19) outbreak. However, it is not easy to develop a protein vaccine that induces cytotoxic T lymphocyte responses and requires a longer time for manufacturing, which limits the usage of this vaccine type. Here, we report the combination of a recombinant spike (S)-trimer protein with a DNA vaccine-encoded S protein as a novel COVID-19 vaccine. The recombinant S protein was formulated with different adjuvants and mixed with the DNA plasmid before injection. We found that the recombinant S protein formulated with the adjuvant aluminum hydroxide and mixed with the DNA plasmid could enhance antigen-specific antibody titers, neutralizing antibody titers. We further evaluated the IgG2a/IgG1 isotype and cytokine profiles of the specific boosted T-cell response, which indicated that the combined vaccine induced a T-helper 1 cell-biased immune response. Immunized hamsters were challenged with severe acute respiratory syndrome coronavirus 2, and the body weight of the hamsters that received the recombinant S protein with aluminum hydroxide and/or the DNA plasmid was not reduced. Alternatively, those that received control or only the DNA plasmid immunization were reduced. Interestingly, after the third day of the viral load in the lungs, the viral challenge could not be detected in hamsters immunized with the recombinant S protein in aluminum hydroxide mixed with DNA (tissue culture infectious dose < 10). The viral load in the lungs was 109 , 106 , and 107 for the phosphate-buffered saline, protein in aluminum hydroxide, and DNA-only immunizations, respectively. These results indicated that antiviral mechanisms neutralizing antibodies play important roles. Furthermore, we found that the combination of protein and DNA vaccination could induce relatively strong CD8+ T-cell responses. In summary, the protein subunit vaccine combined with a DNA vaccine could induce strong CD8+ T-cell responses to increase antiviral immunity for disease control.


Adherence, expectations and the placebo response: why is good adherence to an inert treatment beneficial?
The current study sought to better understand why good adherence to a placebo treatment has been reliably associated with health benefits. We proposed a model where initial expectations shape adherence, which then influences subsequent expectations that affect placebo response. Seventy-two participants were told that they were enrolling in a study of physical activity and memory, and were asked to increase their physical activity by 35% for two weeks (placebo treatment). Adherence to this physical activity target was measured by pedometer. Expectations and short-term memory (free recall) were assessed before and after physical activity. Initial expectations predicted adherence to physical activity (r = .27, p < .03), but adherence did not predict subsequent expectations (r = .06, p = .60). Testing a multi-step meditational model revealed that initial expectations predicted better memory even after controlling for adherence, subsequent expectations, baseline memory and gender (c' = 1.10, 95% CI = .46-1.74). Stronger expectations for memory improvement predicted better memory performance, but adherence and later expectations did not mediate this association. Good adherence to a placebo may reflect strong treatment expectations which may convey benefits by enhancing the non-specific effects of treatment.


[The conversion of endourological operations: a failure or healthy "clinical thinking"?].
From a lot of 2567 of endourological "low" (TURP, TURB, UIO) and "high" (PNL, URSR, URSA) interventions there are analyzed 48 cases in which there was necessary the conversion to classical surgery. In endourology, just like in laparoscopic surgery, the conversion is divided into conversion of necessity and optional conversion. A reference is made to the way of solving these conversions. The main conclusion is that the urologist has to apply equally and efficiently both classical and endourological procedures.


Improving the quality of apple purée.
The aim of the present study was to evaluate the effect of addition of 5% of apple peel powder (APP) and sugars (1, 5% of glucose, fructose, sucrose or trehalose) in apple purée on its phenolic composition and antioxidant activity (AOA). Apple purée samples were processed by freezing and freeze-drying. Apple purées containing APP showed higher phenolics, and AOA than the purées without APP. In freeze-dried samples the highest retention of individual polyphenols was achieved with addition of 1% of fructose or trehalose. However, in frozen samples the best impact on polyphenol retention had 5% of sucrose or trehalose. The results from this study showed the antioxidant potential of apple peel as a naturally-sourced antioxidants as well as a new insight into phenol-sugar interaction. These new findings could be of interest for the development of new food products rich in antioxidants which can improve human health.


Current development of instrumentation for arthroscopy.
The advances in the field of arthroscopy have been keyed to the development of instrumentation. The most significant innovation has occurred in conjunction with the visualization system itself--cutting instrumentation for resection of soft tissues in bone and, more recently, in joints other than the knee. A brief history of the development of arthroscopic instrumentation is provided in this article.


Combined effects of mobile phase composition and temperature on the retention of phenolic antioxidants on an octylsilica polydentate column.
Combined effects of temperature and mobile-phase composition on retention and separation selectivity of phenolic acids and flavonoid compounds were studied in liquid chromatography on a polydentate Blaze C8 silica based column. The temperature effects on the retention can be described by van't Hoff equation. Good linearity of lnk versus 1/T graphs indicates that the retention is controlled by a single mechanism in the mobile phase and temperature range studied. Enthalpic and entropic contributions to the retention were calculated from the regression lines. Generally, enthalpic contributions control the retention at lower temperatures and in mobile phases with lower concentrations of methanol in water. Semi-empirical retention models describe the simultaneous effects of temperature and the volume fraction of the organic solvent in the mobile phase. Using the linear free energy-retention model, selective dipolarity/polarizability, hydrogen-bond donor, hydrogen-bond acceptor and molecular size contributions to retention were estimated at various mobile phase compositions and temperatures. In addition to mobile phase gradients, temperature programming can be used to reduce separation times.


Model studies toward the synthesis of dihydropyrimidinyl and pyridyl alpha-amino acids via three-component Biginelli and Hantzsch cyclocondensations.
A novel and versatile strategy for the synthesis of heterocyclic alpha-amino acids has been described. The use of components (aldehyde or beta-ketoester) bearing a masked glycinyl moiety in Biginelli and Hantzsch cyclocondensations allowed access to the 4-dihydropyrimidinyl-alpha-glycines, 4-dihydropyrimidinyl-alpha-alanines, 4-pyridyl-alpha-alanines, and 2-pyridyl-alpha-alanines classes. Dihydropyrimidinyl-amino acids were obtained as a mixture of diastereoisomers due to the formation of the stereocenter at C4 of the dihydropyrimidinone ring. Individual stereoisomers were isolated as pure compounds and their structures were assigned with the aid of X-ray crystallography and chiroptical properties. The enantiomeric purity of a representative selection of the above amino acids was greater than 96% as verified by derivatization to the corresponding Mosher's amides and subsequent (1)H and (19)F NMR spectroscopy. Incorporation of the 4-pyridyl-alpha-alanine derivative into a peptide chain is also described.


Nod2 deficiency is associated with an increased mucosal immunoregulatory response to commensal microorganisms.
On the basis of previous studies demonstrating that a breach of the colonic epithelial barrier is associated with a microbiota-dependent increase in lamina propria (LP) regulatory cells, we investigated if the lack of spontaneous intestinal inflammation observed in nucleotide-binding oligomerization domain 2 (Nod2)-/- mice was due to enhanced intestinal regulatory function. We found that the LP CD4+ T-cell population of Nod2-/- mice contains an increased percentage of CD4+ regulatory T cells bearing transforming growth factor -β/latency peptide (LP CD4+LAP (latency-associated peptide) + T cells) both under baseline conditions and following an intentional breach of the colonic barrier induced by ethanol administration. In addition, we found that Nod2-/- mice manifest decreased severity of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-colitis and that TNBS-colitis in Nod2-/- or Nod2+/+ mice is ameliorated by adoptive transfer of LP cells from ethanol-treated mice before, but not after, depletion of LAP+ T cells. This increased regulatory T-cell response in Nod2-/- mice could explain why NOD2 polymorphisms in humans are not in themselves sufficient to establish inflammatory lesions.


Development of membrane filter holder (MFH) method for recovery of heat-injured Escherichia coli O157:H7 and Salmonella typhimurium.
A method of recovering sublethally heat-injured bacteria was developed with specific apparatus (membrane filter holder; MFH) which was originally used for Iso-Grid Hydrophobic membrane. filter holder. The procedure used a non-selective agar underlayed with a selective medium with a MFH. A non-selective agar was poured on upper part (compartment A) of MFH, and then injured foodborne pathogens were inoculated on the non-selective medium. After 3-h repair incubation period, selective agar was added to the bottom of the chamber (compartment B) of the MFH and further incubated. By diffusing through the non-selective top agar, selective agents from the underlay medium impart selectivity to the system. Using the MFH method, recovery of heat-injured foodborne pathogens (Escherichia coli O157:H7 and Salmonella typhimurium) were not different (P > 0.05) from recoveries with non-selective media (TSA). However, the recoveries of foodborne pathogens on MFH were significantly higher (P < 0.05) than those of direct plating on selective medium such as SMAC (MacConkey Sorbitol Agar) or XLD (Xylose Lysine Desoxycholate). In conclusion, the MFH method is a simple and convenient method for recovery of heat-injured foodborne pathogens.


13C NMR quantification of mono and diacylglycerols obtained through the solvent-free lipase-catalyzed esterification of saturated fatty acids.
In the present investigation, we studied the enzymatic synthesis of monoacylglycerols (MAG) and diacylglycerols (DAG) via the esterification of saturated fatty acids (stearic, palmitic and an industrial residue containing 87% palmitic acid) and glycerol in a solvent-free system. Three immobilized lipases (Lipozyme RM IM, Lipozyme TL IM and Novozym 435) and different reaction conditions were evaluated. Under the optimal reaction conditions, esterifications catalyzed by Lipozyme RM IM resulted in a mixture of MAG and DAG at high conversion rates for all of the substrates. In addition, except for the reaction of industrial residue at atmospheric pressure, all of these products met the World Health Organization and European Union directives for acylglycerol mixtures for use in food applications. The products were quantified by (13)C NMR, with the aid of an external reference signal which was generated from a sealed coaxial tube filled with acetonitrile-d3. After calibrating the area of this signal using the classical external reference method, the same coaxial tube was used repeatedly to quantify the reaction products.


Impaired brain activity in cirrhotic patients with minimal hepatic encephalopathy: Evaluation by near-infrared spectroscopy.
Near-infrared spectroscopy (NIRS) is a tool that could non-invasively measure the regional cerebral oxygenated hemoglobin (oxy-Hb) concentration with high time resolution. The aim of the present study is to reveal the time-dependent regional cerebral oxy-Hb concentration change coupled with brain activity during task performance in patients with minimal hepatic encephalopathy (MHE). Cerebral oxy-Hb concentration was measured by using NIRS in 29 cirrhotic patients without overt hepatic encephalopathy (HE). Of those, 16 patients who had abnormal electroencephalography findings were defined as having MHE. Responsive increase in oxy-Hb during a word-fluency task was compared between MHE and non-MHE patients. There was no difference in the maximum value of oxy-Hb increase between patients with and without MHE (0.26 ± 0.12 vs 0.32 ± 0.22 mM·mm, P = 0.37). However, the pattern of the time course changes of oxy-Hb was different between the two groups. The MHE group was characterized by a gradual increase of oxy-Hb throughout the task compared to steep and repetitive increase in the non-MHE group. Increase in oxy-Hb concentration at 5 s after starting the task was significantly small in the MHE group compared to the non-MHE (0.03 ± 0.05 vs 0.11 ± 0.09 mM·mm, P = 0.006). The cerebral oxygen concentration is poorly reactive in response to tasks among cirrhotic patients without overt HE but having abnormal electroencephalography findings. These impaired responses in regional cerebral oxy-Hb concentration may be related to the latent impairment of brain activity seen in MHE.


Chronic oral depleted uranium leads to reproductive damage in male rats through the ROS-hnRNP A2/B1-COX-2 signaling pathway.
Depleted uranium (DU) is widely used in civil and military activities. The testis is one of the target organs of DU chronic toxicity. In this study, male SD rats were chronically exposed to DU by 3, 30, 300 mg U/kg through oral intake. After 6 months and 12 months of exposure, it was found that DU could lead to increased oxidative stress levels, decreased glutathione S-transferases (GSTs) expression, resulting in testicular injury and decreased serum testosterone (T) level in rats. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) expression increases with the increase of DU exposure dose. After upregulation of hnRNP A2/B1 expression, the GC-1 cell injury caused by DU is aggravated, suggesting that hnRNP A2/B1 may play an important role in the reproductive toxicity of DU. At the same time, 12 months after chronic oral exposure to DU, the expression level of cyclooxygenase-2 (COX-2) and proinflammatory factor prostaglandin E2 (PGE2) in testicular tissue were increased, and the level of hnRNP A2/B1 caused by DU was decreased by reactive oxygen scavenger N-acetylcysteine (NAC). As hnRNP A2/B1 is a COX-2 regulator, DU may lead to the upregulation of hnRNP A2/B1 expression through the increase of oxidative stress level in germ cells, which in turn leads to the increase of COX-2 and PGE2 level, and ultimately result in the reproductive toxicity. In this study, the regulation mechanism of the ROS-hnRNP A2/B1-COX-2 pathway on DU-induced reproductive damage in male rats was hypothesized, providing a new target for the prevention and treatment of chronic poisoning of DU.


Multi-label zero-shot human action recognition via joint latent ranking embedding.
Human action recognition is one of the most challenging tasks in computer vision. Most of the existing works in human action recognition are limited to single-label classification. A real-world video stream, however, often contains multiple human actions. Such a video stream is usually annotated collectively with a set of relevant human action labels, which leads to a multi-label learning problem. Furthermore, there are a great number of meaningful human actions in reality but it would be extremely difficult, if not impossible, to collect/annotate sufficient video clips regarding all these human actions for training a supervised learning model. In this paper, we formulate a real-world human action recognition task as a multi-label zero-shot learning problem. To address this problem, a joint latent ranking embedding framework is proposed. Our framework holistically tackles the issue of unknown temporal boundaries between different actions within a video clip for multi-label learning and exploits the side information regarding the semantic relationship between different human actions for zero-shot learning. Specifically, our framework consists of two component neural networks for visual and semantic embedding respectively. Thus, multi-label zero-shot recognition is done by measuring relatedness scores of concerned action labels to a test video clip in the joint latent visual and semantic embedding spaces. We evaluate our framework in different settings, including a novel data split scheme designed especially for evaluating multi-label zero-shot learning. The experimental results on two weakly annotated multi-label human action datasets (i.e. Breakfast and Charades) demonstrate the effectiveness of our framework.


Secular trends in treatment and control of type 2 diabetes in an American Indian population: a 30-year longitudinal study.
Treatment guidelines for diabetes have become increasingly stringent as most research shows that more aggressive intervention reduces the risks for complications. Community data on the effect of these interventions are lacking. Changes in the pharmacologic treatment of diabetes, blood pressure, and cholesterol in adults with diabetes were analyzed in a longitudinal population-based study of American Indians from 10 independent 3-year time intervals between 1975 and 2004. Trends in drug use were assessed by logistic regression models and trends in glycemia, blood pressure, and cholesterol were assessed by linear models. Among the study participants, the use of any medicine for the treatment of diabetes increased from 53% in 1975-1978 to 67% in 2002-2004, Ptrend<0.0001. The use of insulin as a single agent declined, and the use of combinations of insulin and oral agents increased. In 1990-1992, 23% of subjects had an A1C<7% and by 2002-2004, the proportion had increased to 33%, Ptrend<0.0001. The use of anti-hypertensive medicine increased from 21% in 1975-1977 to 58% in 2002-2004, Ptrend<0.0001, coincident with a decline in mean systolic blood pressure from 137 mmHg in 1975-1977 to 123 mmHg in 2002-2004, Ptrend<0.0001. The use of lipid-lowering medicine also increased with an accompanying increase in HDL and a decrease in non-HDL cholesterol concentration. Major changes in community treatment patterns for diabetes and related conditions coincided with improvements in glycemia, blood pressure, and cholesterol.