Clinical implications of the serum CA19-9 level in "biological borderline resectability" and "biological downstaging" in the setting of preoperative chemoradiation therapy for pancreatic cancer.
Biological factors are emphasized in borderline resectable pancreatic cancer (BRPC), and CA19-9 is an important factor for biological borderline resectability (b-BR). The aim of this study was to investigate the cut-off value of CA19-9 for biological borderline resectability and "biological downstaging" in chemoradiation therapy (CRT) for pancreatic cancer (PC). A total of 407 patients with anatomically resectable PC (a-R) and BRPC (a-BR) received preoperative gemcitabine-based CRT. The b-BR was determined, according to the CA19-9 value prior to preoperative CRT (pre-CA19-9), as the subgroup of a-R cases in which the survival was comparable with that in a-BR cases. "Biological downstaging" was determined based on prognostic analyses regarding the CA19-9 value after preoperative CRT (post-CA19-9) in association with the survival of R cases (a-R cases without the b-BR factor). The 5-year survival of a-R patients with pre-CA19-9 > 120 U/mL was comparable with that of a-BR patients (44% vs 34%, p = 0.082). The survival of b-BR patients with post-CRT CA19-9 ≤ 37 U/mL (normalized) was comparably favorable with that of R patients (56% vs 65%, p = 0.369). The incidence of distant recurrence was higher in b-BR patients without post-CA19-9 normalization than in those with post-CA19-9 normalization (70% vs 50%, p = 0.003), while the incidence of local recurrence was comparable between these two groups (12% vs 13%, p = 0.986). Biological BRPC was determined to be an anatomically resectable disease with pre-CA19-9 > 120 U/mL, and post-CA19-9 normalization indicated "biological downstaging" in b-BR in the preoperative CRT strategy.


The effect of comorbidity on appropriateness ratings for two gastrointestinal procedures.
We evaluated the effect of patients' comorbidity on the appropriateness of performing esophagogastroduodenoscopy or cholecystectomy. A nine-member national physician panel rated 1118 brief clinical scenarios for patients without comorbidity. Ratings were then repeated for patients with increasing degrees of comorbidity. As comorbidity changed from none to medium, 60% of those scenarios that were originally rated as appropriate for endoscopy and cholecystectomy remained appropriate. As high comorbidity was introduced, only 13% of such scenarios remained appropriate for endoscopy, while 33% remained appropriate for cholecystectomy. These findings suggest that, although clinical reasons for performing procedures are a powerful determinant of when they should be used, comorbidity is also important and needs to be included in any assessment of the appropriateness of procedure use.


The effects of local anesthetics on postoperative pain.
This study was performed to determine if intraoperative local anesthesia improved control of postoperative pain after inguinal herniorrhaphy and to compare the effects of two commonly used local anesthetics on pain management. The Gate Control Theory of Pain formed the theoretical basis for this study. A retrospective nonexperimental study in an ex post facto design was used. Data were collected from 1990 through 1997 on 120 patient charts. The use of local anesthetic intraoperatively significantly decreased patients' lengths of stay postoperatively (P = 0.00) and need for postoperative narcotics (P = 0.00). Bupivacaine was found to be superior to lidocaine in decreasing the need for postoperative narcotic analgesia. Researchers concluded that many patients would benefit from intraoperative injection of local anesthesia. This information can affect patient care outcomes through decreasing recovery time, reducing postoperative pain, and reducing health care costs.


[Use of an empirical antiretroviral treatment depends on the primary resistance rate of the human immunodeficiency virus].
The objective of this study was the analysis of the prevalence and type of primary resistance to antiretroviral drugs in patients diagnosed with HIV infection, and to determine the most appropriate empirical treatment to obtain a virological and immunological response. An observational analysis of patients with a de novo diagnosis of HIV infection during the period 2008-2010. Clinical, immunological and virological characteristics, including genotype analysis of resistance to antiretrovirals, were considered as independent variables. The dependent variable was an undetectable HIV viral load after six months of treatment. Data are provided as median (interquartile range) and absolute number (percentage). Seventy-three patients with a de novo diagnosis of HIV infection were included [53 males (73%); 36 (30-46) years-old; prior use of intravenous drugs: 5 patients (7%); hepatitis C virus co-infection: 13 individuals (18%)]. Ten patients (14%) showed symptoms attributable to acute HIV infection. A CD4+ T cell count lower than 350 mm(3) was detected in a 37% (n=27) of all patients. The initiation of antiretroviral therapy followed the GESIDA recommendations (no therapy: 20 patients; tenofovir+emtricitabine+efavirenz: 28 patients; abacavir+lamivudine+efavirenz: 1 patient; tenofovir+emtricitabine+protease inhibitors: 5 patients; abacavir+lamivudine+protease inhibitors: 1 patient; 18 patients were lost in the follow-up). After starting antiretroviral therapy, the resistance analyses detected the existence of primary resistance to antiretrovirals in 12.7% (confidence interval 95%: 3-22) of the patients, distributed as follows: isolated resistance to, nucleosides was detected in 2% (M184V), to nevirapine/efavirenz in 9% (K103N), and combined resistance to nucleosides and non-nucleosides in 2%; there were no cases of resistance to protease inhibitors. Consequently, antiretroviral therapy was changed in 5 (14%) out of 35 patients, attaining an undetectable HIV viral load at 6 months in all of them. The primary resistance to antiretrovirals was not related with epidemiological, virological (including infection by non B subtype) or immunological variables. In the present study, a change in the epidemiological pattern of de novo diagnosis of HIV infection in our area has been observed. The existence of resistance mutations in more than 5% of the new cases is noteworthy. This finding must be considered in order to establish the rules of empirical treatment in our area.


Clinical, microbiological and immunological outcomes with photodynamic therapy as an adjunct to full-mouth scaling in patients undergoing fixed orthodontic treatment.
The purpose of this clinical study was to evaluate the adjunctive role of photodynamic therapy (PDT) in the improvement of clinical, microbiological and immunological parameters among adolescent patients undergoing fixed orthodontic treatment (FOT) during the period of 6 weeks. Fifty adolescent patients undergoing FOT were divided into following two groups; Group-A: PDT as an adjunct to full-mouth scaling (FMS) and, Group-B: FMS alone. Full-mouth plaque scores (PS), bleeding on probing (BOP) and probing depth (PD) were estimated using full-mouth six point periodontal charting. Plaque samples were collected for percentage bacterial counts of P. intermedia and P. gingivalis. Gingival crevicular fluid (GCF) sampling technique was employed for estimation of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) using enzyme-linked immunosorbent assay. All measurements were performed at baseline, 3 weeks and 6 weeks. The mean age of patients in Group-A and Group-B was 15.4 years and 14.2 years, respectively. The mean duration for fixed orthodontic therapy in patients for Group A and B were 1.25 and 1.3 years, respectively. At 3 weeks follow up, both groups showed significant reduction in PS and BOP (p < 0.001). There was a statistically significant difference in BOP and PI at 6 weeks (p < 0.05). There was a statistically significant difference in IL-6 at 3 weeks and TNF-α at 6 weeks between both groups (p < 0.05). The percentage levels for both Pi and Pg significantly reduced at 3 weeks follow up in both the groups, however, these levels were again raised at 6 weeks follow up. There was a statistically significant difference between Group-A and Group-B (p < 0.05) at 3 weeks and 6 weeks follow up. Photodynamic therapy as an adjunct to FMS helps to improve clinical gingival parameters, microbial and inflammatory load. PDT showed additional benefits in reducing bleeding scores in adolescent patients undergoing FOT.


Pseudomalfunctions of dual-chamber pacemakers.
The proliferation of dual-chamber pacemakers has created a host of electrocardiographic problems relating to interpretation. The term "pseudomalfunction" identifies an electrocardiographic finding that looks like pacemaker malfunction but is not. Several different models of dual-chamber pacemakers, which are either presently available or in clinical evaluation, produce different types of pseudomalfunctions. These are classified and described. Intimate knowledge of individual pacemaker characteristics is required for proper evaluation of these units.


Newborn's first bath: any preferred timing? A pilot study from Lebanon.
To try to find the most appropriate time for the newborn's first bath. This prospective randomized study was conducted in one hospital (July-September 2017). A higher percentage of newborns who had a skin-to-skin contact with their mothers had their bath at 24 h vs 2 h after birth (65.2% vs 33.3%; p = 0.01). A higher percentage of mothers who helped in their baby's bath had their baby's bath at 24 h vs 2 h (65.2% vs 5.9%; p < 0.001) and vs 6 h (65.2% vs 15.7%; p < 0.001) respectively. A higher mean incubation time was seen between newborns who had their bath at 2 h (2.10 vs 1.78; p = 0.002) and 6 h (2.18 vs 1.78; p = 0.003) compared to those who had their bath at 24 h respectively. A higher percentage of newborns who took their first bath 24 h after birth were calm compared to crying vigorously (38.6% vs 9.1%; p = 0.04). Delaying newborn first bath until 24 h of life was associated with benefits (reducing hypothermia and vigorous crying, benefit from the vernix caseosa on the skin and adequate time of skin-to-skin contact and mother participation in her child's bathing.


An ab initio molecular orbital study on the characteristics of 8-hydroxyguanine.
To investigate the mechanism by which the 8-hydroxyguanine residue in DNA affects the fidelity of DNA replication, the intrinsic properties of this modified base were investigated using an ab initio molecular orbital method. The most stable 8-hydroxyguanine form was revealed to be 6,8-diketo. The addition of an oxygen atom to the 8 position of a guanine base was shown to change the electrostatic potential of the molecule entirely and to give it a negative character. This effect may influence the local structure of 8-hydroxyguanine-containing DNA and the interaction with DNA polymerase, thereby resulting in infidelity of DNA replication.


Value of Central Venous to Arterial CO2 Difference after Early Goal-directed Therapy in Septic Shock Patients.
Venous to arterial difference of carbon dioxide (Pv-aCO2) tracks tissue blood flow. We aimed to evaluate if Pv-aCO2 measured from a superior central vein sample is a prognostic index (ICU length of stay, SOFA score, 28th mortality rate) just after early goal-directed therapy (EGDT)comparing its ICU admission values between patients with normal and abnormal (>6 mm Hg) Pv-aCO2. As secondary objectives, we evaluated the relationship of Pv-aCO2 with other variables of perfusion during the 24 hours that followed EGDT. Prospective observational study conducted in an academic ICU adult septic shock patients after a 6-hour complete EGTD. Hemodynamic measurements, arterial/central venous blood gases, and arterial lactate were obtained on ICU admission and after 6, 18 and 24 hours. Sixty patients were included. Admission Pv-aCO2 values showed no prognostic value. Admission Pv-aCO2 (ROC curve 0.527 [CI 95% 0.394 to 0.658]) values showed low specificity and sensitivity as predictors of mortality. There was a difference observed in the mean Pv-aCO2 between nonsurvivors (NS) and survivors (S) after 6 hours. Central venous oxygen saturation (ScvO2) and Pv-aCO2 showed significant correlation (R2 = -0.41, P < 0.0001). Patients with normal ScvO2 (>70%) and abnormal Pv-aCO2 (>6 mm Hg) showed higher SOFA scores. Normal Pv-aCO2 group cleared their lactate levels in comparison to the abnormal Pv-aCO2 group. In septic shock, admission Pv-aCO2 after EGDT is not related to worse outcomes. An abnormal Pv-aCO2 along with a normal ScvO2 is related to organ dysfunction. Araujo DT, Felice VB, Meregalli AF, Friedman G. Value of Central Venous to Arterial CO2 Difference after Early Goal-directed Therapy in Septic Shock Patients. Indian J Crit Care Med 2019;23(10):449-453.


Rebuilding hippocampus neural circuit with hADSC-derived neuron cells for treating ischemic stroke.
Human adipose-derived stem cells (hADSCs) have been demonstrated to be a promising autologous stem cell source for treating various neuronal diseases. Our study indicated that hADSCs could be induced into neuron-like cells in a stepwise manner that are characterized by the positive expression of MAP2, SYNAPSIN 1/2, NF-200, and vGLUT and electrophysiological activity. We first primed hADSCs into neuron-like cells (hADSC-NCs) and then intracerebrally transplanted them into MCAO reperfusion mice to further explore their in vivo survival, migration, integration, fate commitment and involvement in neural circuit rebuilding. The hADSC-NCs survived well and transformed into MAP2-positive, Iba1- or GFAP-negative cells in vivo while maintaining some proliferative ability, indicated by positive Ki67 staining after 4 weeks. hADSC-NCs could migrate to multiple brain regions, including the cortex, hippocampus, striatum, and hypothalamus, and further differentiate into mature neurons, as confirmed by action potential elicitation and postsynaptic currents. With the aid of a cell suicide system, hADSC-NCs were proven to have functionally integrated into the hippocampal memory circuit, where they contributed to spatial learning and memory rescue, as indicated by LTP improvement and subsequent GCV-induced relapse. In addition to infarction size shrinkage and movement improvement, MCAO-reperfused mice showed bidirectional immune modulation, including inhibition of the local proinflammatory factors IL-1α, IL-1β, IL-2, MIP-1β and promotion proinflammatory IP-10, MCP-1, and enhancement of the anti-inflammatory factors IL-15. Overall, hADSC-NCs used as an intermediate autologous cell source for treating stroke can rebuild hippocampus neuronal circuits through cell replacement.


Identification of predictors of long-term survival and prognostic outcomes in thymic squamous cell carcinoma: A real-world study.
Although thymic squamous cell carcinoma (TSCC) is among the most prevalent forms of thymic carcinoma, there are relatively few studies on this tumor type, and its staging, optimal treatment strategies, and relevant prognostic factors remain controversial. The present study analyzed 79 patients diagnosed with TSCC between January 2008 and January 2021. Kaplan-Meier curves and Cox univariate and multivariate regression analyses were used to explore factors associated with overall survival (OS) and progression-free survival (PFS) in the overall patient cohort and patient subgroups stratified according to the TNM stage. Time-dependent receiver operating characteristic (ROC) analyses were used to compare the TNM and Masaoka systems as predictors of patient prognosis. The 5- and 10-year OS rates in this study were 65.5% and 49.4%, respectively, with corresponding 5- and 10-year PFS rates of 52.3% and 37.9%. Survival outcomes were better for patients with early-stage disease (p < 0.001) and patients that underwent surgical treatment (p < 0.001). Neither extent of resection (p = 0.820) nor the surgical approach (p = 0.444) influenced patient survival. In individuals with advanced disease, all forms of adjuvant therapy including radiotherapy (p = 0.021), chemotherapy (p = 0.035), and chemoradiation (p = 0.01) significantly improved patient PFS, but only adjuvant chemoradiotherapy improved patient OS (p = 0.035). When predicting the patient survival outcomes, the TNM system was slightly superior to the Masaoka system (area under the ROC curve [AUC] at 5 years: OS, 0.742 vs. 0.723; PFS, 0.846 vs. 0.816). TSCC is an orphan malignancy with a poor prognosis. TNM staging may be superior to Masaoka staging as a predictor of TSCC patient prognosis. Surgery is the mainstay of TSCC treatment. Video-assisted thoracoscopy (VATS) should be considered for selected patients. Multimodal therapy was associated with excellent results for patients with advanced TNM stage, particularly when surgery was accompanied by adjuvant chemoradiation.


A role for collagen XXIII in cancer cell adhesion, anchorage-independence and metastasis.
Collagen XXIII is a transmembrane collagen previously shown to be upregulated in metastatic prostate cancer that has been used as a tissue and fluid biomarker for non-small cell lung cancer and prostate cancer. To determine whether collagen XXIII facilitates cancer cell metastasis in vivo and to establish a function for collagen XXIII in cancer progression, collagen XXIII knockdown cells were examined for alterations in in vivo metastasis as well as in vitro cell adhesion. In experimental and spontaneous xenograft models of metastasis, H460 cells expressing collagen XXIII shRNA formed fewer lung metastases than control cells. Loss of collagen XXIII in H460 cells also impaired cell adhesion, anchorage-independent growth and cell seeding to the lung, but did not affect cell proliferation. Corroborating a role for collagen XXIII in cell adhesion, overexpression of collagen XXIII in H1299 cells, which do not express endogenous collagen XXIII, enhanced cell adhesion. Consequent reduction in OB-cadherin, alpha-catenin, gamma-catenin, beta-catenin, vimentin and galectin-3 protein expression was also observed in response to loss of collagen XXIII. This study suggests a potential role for collagen XXIII in mediating metastasis by facilitating cell-cell and cell-matrix adhesion as well as anchorage-independent cell growth.


Advanced approach for comprehensive mtDNA genome testing in mitochondrial disease.
Mitochondrial disease diagnosis requires interrogation of both nuclear and mitochondrial (mtDNA) genomes for single-nucleotide variants (SNVs) and copy number alterations, both in the proband and often maternal relatives, together with careful phenotype correlation. We developed a comprehensive mtDNA sequencing test ('MitoGenome') using long-range PCR (LR-PCR) to amplify the full length of the mtDNA genome followed by next generation sequencing (NGS) to accurately detect SNVs and large-scale mtDNA deletions (LSMD), combined with droplet digital PCR (ddPCR) for LSMD heteroplasmy quantification. Overall, MitoGenome tests were performed on 428 samples from 394 patients with suspected or confirmed mitochondrial disease. The positive yield was 11% (43/394), including 34 patients with pathogenic or likely pathogenic SNVs (the most common being m.3243A > G in 8/34 (24%) patients), 8 patients with single LSMD, and 3 patients with multiple LSMD exceeding 10% heteroplasmy levels. Two patients with both LSMD and pathogenic SNV were detected. Overall, this LR-PCR/NGS assay provides a highly accurate and comprehensive diagnostic method for simultaneous mtDNA SNV detection at heteroplasmy levels as low as 1% and LSMD detection at heteroplasmy levels below 10%. Inclusion of maternal samples for variant classification and ddPCR to quantify LSMD heteroplasmy levels further enables accurate pathogenicity assessment and clinical correlation interpretation of mtDNA genome sequence variants and copy number alterations.


Barriers to integration of bioinformatics into undergraduate life sciences education: A national study of US life sciences faculty uncover significant barriers to integrating bioinformatics into undergraduate instruction.
Bioinformatics, a discipline that combines aspects of biology, statistics, mathematics, and computer science, is becoming increasingly important for biological research. However, bioinformatics instruction is not yet generally integrated into undergraduate life sciences curricula. To understand why we studied how bioinformatics is being included in biology education in the US by conducting a nationwide survey of faculty at two- and four-year institutions. The survey asked several open-ended questions that probed barriers to integration, the answers to which were analyzed using a mixed-methods approach. The barrier most frequently reported by the 1,260 respondents was lack of faculty expertise/training, but other deterrents-lack of student interest, overly-full curricula, and lack of student preparation-were also common. Interestingly, the barriers faculty face depended strongly on whether they are members of an underrepresented group and on the Carnegie Classification of their home institution. We were surprised to discover that the cohort of faculty who were awarded their terminal degree most recently reported the most preparation in bioinformatics but teach it at the lowest rate.


Detecting the environmental impact of off-road vehicles on Rawdat Al Shams in central Saudi Arabia by remote sensing.
Off-road vehicles can have a devastating impact on vegetation and soil. Here, we sought to quantify, through a combination of field vegetation, bulk soil, and image analyses, the impact of off-road vehicles on the vegetation and soils of Rawdat Al Shams, which is located in central Saudi Arabia. Soil compaction density was measured in the field, and 27 soil samples were collected for bulk density analysis in the lab to quantify the impacts of off-road vehicles. High spatial resolution images, such as those obtained by the satellites GeoEye-1 and IKONOS-2, were used for surveying the damage to vegetation cover and soil compaction caused by these vehicles. Vegetation cover was mapped using the Normalized Difference Vegetation Index (NDVI) technique based on high-resolution images taken at different times of the year. Vehicle trails were derived from satellite data via visual analysis. All damaged areas were determined from high-resolution image data. In this study, we conducted quantitative analyses of vegetation cover change, the impacts of vehicle trails (hereafter "trail impacts"), and a bulk soil analysis. Image data showed that both vegetation cover and trail impacts increased from 2008 to 2015, with the average percentage of trail impacts nearly equal to that of the percentage of vegetation cover during this period. Forty-six species of plants were found to be present in the study area, consisting of all types of life forms, yet trees were represented by a single species, Acacia gerrardii. Herbs composed the largest share of plant life, with 29 species, followed by perennial herbs (12 species), grasses (5 species), and shrubs (3 species). Analysis of soil bulk density for Rawdat Al Shams showed that off-road driving greatly impacts soil density. Twenty-two plant species were observed on the trails, the majority of which were ephemerals. Notoceras bicorne was the most common, with a frequency rate of 93.33 %, an abundance value of 78.47 %, and a density of 0.1 in transect 1, followed by Plantago ovata.


The character-disordered family: a community treatment model for family sexual abuse.
A collaborative approach to treating sexually abusive families is described, in which such families are viewed as analogous to "character-disordered" individuals. This model, unlike traditional voluntary treatment models, assumes that effective intervention requires authoritative control and careful corrdination of all professional activity. Phases of treatment are outlined and a case history is presented.


Method development and validation for the simultaneous determination of meloxicam and pridinol mesylate using RP-HPLC and its application in drug formulations.
A simple and reliable reversed-phase high-perfomance liquid chromatographic method has been developed and validated for the simultaneous determination of meloxicam and pridinol mesylate in their synthetic mixtures and combined tablet formulations. Both drugs were separated on a 250 mm x 4.6mm C18 column packed with 5 microm particles. The mobile phase, optimized through an experimental design, was a 51:9:40 (v/v/v) mixture of methanol, isopropanol and 50mM potassium phosphate buffer (pH 5.9), pumped at a flow rate of 1.0 ml min(-1). UV detection was performed at 225 nm. The method was validated in the sample concentration ranges of 33.7-61.8 mg l(-1) for meloxicam and 8.8-16.8 mg l(-1) for pridinol mesylate, where it demonstrated good linearity with r=0.9989 and 0.9987 (n=15), respectively. The assay was shown to be repeatable at concentration levels of 70%, 100% and 130%, with relative standard deviation values of 1.09% and 0.82% for meloxicam and pridinol, respectively. For independent 100% level samples, the intra-day precision was 0.4% and 1.0% while the intermediate precision was 0.7% and 1.0% for the drugs. The method demonstrated to be robust, resisting to small deliberate changes in pH, flow rate and composition (organic:aqueous ratio) of the mobile phase. The LOD values were 0.22 and 0.20 mg l(-1), while the LOQ were 1.7 and 1.1 mg l(-1), for meloxicam and pridinol, respectively. The applicability of the method was demonstrated by determining the drug content of two commercial pharmaceutical formulations, where it exhibited good performance.


ZmMYC2 exhibits diverse functions and enhances JA signaling in transgenic Arabidopsis.
ZmMYC2 was identified as the key regulator of JA signaling in maize and exhibited diverse functions through binding to many gene promoters as well as enhanced JA signaling in transgenic Arabidopsis. The plant hormone jasmonate (JA) extensively coordinates plant growth, development and defensive responses. MYC2 is the master regulator of JA signaling and has been widely studied in many plant species. However, little is known about this transcription factor in maize. Here, we identified one maize transcription factor with amino acid identity of 47% to the well-studied Arabidopsis AtMYC2, named as ZmMYC2. Gene expression analysis demonstrated inducible expression patterns of ZmMYC2 in response to multiple plant hormone treatments, as well as biotic and abiotic stresses. The yeast two-hybrid assay indicated physical interaction among ZmMYC2 and JA signal repressors ZmJAZ14, ZmJAZ17, AtJAZ1 and AtJAZ9. ZmMYC2 overexpression in Arabidopsis myc2myc3myc4 restored the sensitivity to JA treatment, resulting in shorter root growth and inducible anthocyanin accumulation. Furthermore, overexpression of ZmMYC2 in Arabidopsis elevated resistance to Botrytis cinerea. Further ChIP-Seq analysis revealed diverse regulatory roles of ZmMYC2 in maize, especially in the signaling crosstalk between JA and auxin. Hence, we identified ZmMYC2 and characterized its roles in regulating JA-mediated growth, development and defense responses.


Surgical resection of subependymal giant cell astrocytomas (SEGAs) and changes in SEGA-related conditions: a US national claims database study.
To compare the prevalence rates of clinical conditions related to subependymal giant cell astrocytomas (SEGAs) before and after SEGA surgery among patients with tuberous sclerosis complex (TSC). Based on three US national claims databases, we analyzed and compared the prevalence rates of 21 SEGA-related conditions (including seizures, hydrocephalus, headaches and stroke or hemiparesis) in the six months preceding surgery with the rates in the second through sixth post-surgery months and in the seventh through twelfth post-surgery months among TSC patients who underwent SEGA surgery during 2000-2009. Repeated measures analysis with a bootstrapping method was used to assess the surgery impact. Patients (N = 47) had a mean age of 11.5 years at their first SEGA surgery, and 66% were male. Compared with the six months preceding surgery, the post-surgery prevalence rates increased by 23-26% for seizures, 21-26% for hydrocephalus, 17-19% for headache and 6-9% for stroke or hemiparesis (all p < 0.05). Repeated measures analysis confirmed the impact of surgery on the prevalence rate of these five conditions (all p < 0.05). SEGA surgery has its important role in SEGA treatment. However, after SEGA surgery this group of TSC patients had increased prevalence rates of seizures, hydrocephalus, vision disorders, headaches, stroke or hemiparesis, and autism. Future research to examine the causes of these symptoms is imperative. The study results have limitations in data source representativeness, coding accuracy, and study design.


S/RV Cri-ba, a hairless mouse strain sensitive to skin tumorigenesis by suboptimal doses of 7,12-dimethylbenz[a]anthracene, initiation-promotion and two stage promotion protocols.
Susceptibility of hairless inbred S/RV Cri-ba or Bare mice to skin tumor development with suboptimal doses of 7,12-dimethylbenz[a]anthracene (DMBA), DMBA-TPA two stage protocol and two stage promotion using 12-O-tetradecanoylphorbol-13-acetate (TPA) as sub-stage 1 promoter and mezerein (MEZ) or phorbol retinoate acetate (PRA) as substage 2 promoter was determined. A single application of 40 or 20 nmol DMBA induced 4-5 papillomas per mouse 40 weeks after initiation while no tumors appeared after similar treatment with 10 or 4 nmol DMBA. Dose response studies for DMBA initiation revealed that 10 nmol DMBA dose saturated the sites for initiation in the resting epidermis. In two stage promotion experiments, MEZ was found to be a potent stage 2 promoter, while PRA acted as a weak complete promoter.


[Paradoxical fluoride phenomena in a Sardegna district].
The authors in epidemiologic research on dental caries of primary-school children in a village having optimufluorotic water, put in evidence fluorine paradox phenomena founding high percentual of cariopatic subjects.


Acadl-SNP based genotyping assay for long-chain acyl-CoA dehydrogenase deficient mice.
The long-chain acyl-CoA dehydrogenase (LCAD) (Acadl=gene; LCAD=protein) deficient mouse model has been important in evaluating the role of mitochondrial fatty acid oxidation of long-chain fatty acids in metabolic disorders. The insertion vector-based gene targeting strategy used to generate this model has made it difficult to distinguish homozygous and heterozygous genotypes containing targeted Acadl alleles in LCAD-deficient mice. Herein, we describe the design and validation of Acadl SNP genotyping methods capable of distinguishing between heterozygous and homozygous LCAD-deficient mice. The Acadl SNP genotyping assays are effective at allelic discrimination of both C57BL/6 and 129 mouse strain-based Acadl alleles under conditions including, both low purity and quantity genomic DNA templates. This makes the method practical and provides the necessary tools for genotyping the LCAD-deficient mouse model.


Intravenous immunoglobulin for prophylaxis or treatment of bacterial infection in neonates.
The high rate of bacterial infection in premature neonates has been correlated with low levels of opsonic antibody. Infants born at term who develop a bacterial infection generally have very low levels of antibody toward the organisms with which they are infected. In order to provide adequate levels of antibacterial antibody to neonates, several strategies have been devised and tested. In this report, studies on animal investigations and clinical trials are reviewed.


HER4 intracellular domain (4ICD) activity in the developing mammary gland and breast cancer.
The HER4 receptor tyrosine kinase was the final member of the EGFR-family to be discovered. In contrast to the other three members of this receptor family which function primarily as mitogenic effectors in the breast, HER4 appears to have multiple divergent functions in the normal and malignant breast. Interestingly, the majority of HER4 activities in the breast including pregnancy induced differentiation and lactation initiation, transcriptional activation, tumor cell proliferation, growth suppression, and induction of apoptosis appear to be mediated by an independently signaling soluble HER4 intracellular domain (4ICD). The 4ICD can accumulate within the nucleus or mitochondria and subcellular localization of 4ICD in part determines the physiological response of breast cells to 4ICD action. Here I will discuss the evidence supporting the role of 4ICD as the critical effector of HER4 signaling in the breast. In addition a developmental and temporal model of 4ICD action in the normal breast and during the progression of breast cancer will be presented to explain the paradox of divergent HER4 and 4ICD activities.


Quantitative succinyl-proteome profiling of Chinese hickory (Carya cathayensis) during the grafting process.
Chinese hickory (Carya cathayensis) is a popular nut plant having high economic value. Grafting is applied to accelerate the transition from vegetative phase to reproductive phase. Lysine succinylation occurs frequently in the proteins associated with metabolic pathways, which may participate in the regulation of the grafting process. However, the exact regulatory mechanism underlying grafting process in Chinese hickory has not been studied at post-translational modification level. A comprehensive proteome-wide lysine succinylation profiling of Chinese hickory was explored by a newly developed method combining affinity enrichment and high-resolution LC-MS/MS. In total, 259 succinylation sites in 202 proteins were identified, representing the first comprehensive lysine succinylome in Chinese hickory. The succinylation was biased to occur in the cytosolic proteins of Chinese hickory. Moreover, four conserved succinylation motifs were identified in the succinylated peptides. Comparison of two grafting stages of Chinese hickory revealed that the differential expressed succinylated proteins were mainly involved in sugar metabolism, carbon fixation, amino acid metabolism and plant-pathogen interaction. Besides, seven heat shock proteins (HSPs) with 11 succinylation sites were also identified, all of which were observed to be up-regulated during the grafting process. Succinylation of the proteins involved in amino acid biosynthesis might be required for a successful grafting. Succinylated HSPs might play a role in stress tolerance of the grafted Chinese hickory plants. Our results can be a good resource for functional validation of the succinylated proteins and a starting point for the investigation of molecular mechanisms during lysine succinylation occurring at grafting site.


New onset or exacerbation of psoriatic skin lesions in patients with definite rheumatoid arthritis receiving tumour necrosis factor alpha antagonists.
Blockage of tumour necrosis factor alpha (TNFalpha) is highly effective in rheumatic diseases, especially in rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis. Furthermore, TNFalpha antagonists have also been shown to significantly reduce psoriatic skin lesions. A series of nine patients with RA who were treated with different types of TNFalpha antagonists and who unexpectedly developed either a new onset or an exacerbation of psoriatic skin lesions are reported.


Release of oxytocin in the hypothalamic paraventricular nucleus, but not central amygdala or lateral septum in lactating residents and virgin intruders during maternal defence.
In lactating rats, the neuroendocrine responses of the oxytocinergic system and the hypothalamo-pituitary-adrenal axis to various kinds of stressors are attenuated. In this study, using intracerebral microdialysis in combination with a highly sensitive radioimmunoassay, we characterised oxytocin (OXT) release within the paraventricular nucleus (PVN), the central amygdala (CeA), and the medio-lateral septum (mS) before, during and after a psycho-social stressor (the maternal defence test) in both the virgin intruder and the lactating resident rat (day 3 of lactation). Within the PVN, local OXT release was found to increase significantly in virgin intruders during exposure to the resident (2.1-fold, P < 0.05), as well as in lactating residents when exposed to the virgin intruder, though to a lesser extent when compared with basal levels (1.7-fold, P < 0.05). In contrast, OXT release remained unchanged within the CeA and the mS of both virgin intruders and lactating residents. Release of OXT under basal conditions was clearly above the detection limit of the radioimmunoassay, and did not differ between lactating and virgin rats in any of the brain regions studied. Our study also demonstrates that recent surgery or ongoing intracerebral microdialysis does not affect the behavioural performance of the intruders or residents when comparing dialysed and non-dialysed rats. The results indicate that exposure to the maternal defence test is a relevant stressor for the brain OXT system which becomes activated in both intruder and resident rats, although to varying degrees depending upon their reproductive status and in a region-dependent manner. The behavioural and/or neuroendocrine functions of intra-PVN released OXT during this psycho-social challenge remain to be clarified.


Study of the aerobic biodegradation of coke wastewater in a two and three-step activated sludge process.
A laboratory-scale biological plant composed of two aerobic reactors operating at 35 degrees C was used to study the biodegradation of coke wastewater. The main pollutants to be removed are organic matter, especially phenols, thiocyanate and ammonium nitrogen. The concentrations of the main pollutants in the wastewater during the study ranged between 922 and 1,980 mg COD/L, 133 and 293 mg phenol/L, 176 and 362 mg SCN/L and 123 and 296 mg NH(4)(+)-N/L. The biodegradation of these pollutants was studied employing different hydraulic residence times (HRT) and final effluent recycling ratios in order to minimize inhibition phenomena attributable to the high concentrations of pollutants. During the optimisation of the operating conditions, the removal of COD, phenols and thiocyanate was carried out in the first reactor and the nitrification of ammonium took place in the second. The best results were obtained when operating at an HRT of 98 h in the first reactor and 86 h in the second reactor, employing a recycling ratio of 2. The maximum removal efficiencies obtained were 90.7, 98.9, 98.6 and 99.9% for COD, phenols, thiocyanate and NH(4)(+)-N, respectively. In order to remove nitrate, an additional reactor was also implemented to carry out the denitrification process, adding methanol as an external carbon source. Very high removal efficiencies (up to 99.2%) were achieved.


Identifying family members who are likely to perceive benefits from providing care to a person with a primary malignant brain tumor.
To identify changes in positive aspects of care (PAC) from the time of diagnosis to four months following the diagnosis in family caregivers of care recipients with primary malignant brain tumors. Longitudinal. Dyads were recruited from neurosurgery clinics in Pittsburgh, PA, at the time of care recipients' diagnosis with a primary malignant brain tumor. A second data collection took place four months following the diagnosis. 89 caregiver and care recipient dyads. Paired t tests were used to examine change in PAC, univariate analyses were used to determine predictors of PAC at four months, Mann-Whitney U tests and t tests were used to examine associations between categorical predictor variables and PAC at four months, and univariate linear regressions were used to examine associations between continuous predictors and PAC at four months. The impact of sociodemographic factors, caregiver-perceived social support, mastery, neuroticism, and marital satisfaction on PAC. Caregivers' PAC scores during the first four months following diagnosis appeared to remain stable over time. Significant differences were found between the care recipient reasoning domain group at diagnosis and PAC score. Care recipients who scored below average were associated with caregivers with higher PAC scores. Caregiver PAC at four months following diagnosis was significantly predicted by care recipient reasoning and caregiver social support. PAC scores appear to remain stable over time, although levels of PAC may be related to care recipients' level of functioning. Future research should focus on the development of interventions for caregivers who report low levels of PAC at the time of diagnosis in an attempt to help these individuals identify PAC in their caregiving situation. Findings have clinical and research implications. Clinicians may be able to better identify caregivers who are at risk for negative outcomes by understanding the risks faced by caregivers of patients with milder symptoms in addition to those caring for more profoundly affected care recipients.


The role of prostaglandins in the excitatory innervation of the rat urinary bladder.
The possible role of PGs in hyoscine-resistant nerve mediated responses of the rat urinary bladder was investigated. Responses to electrical stimulation were inhibited by cinchocaine (30 micronmol/1) but were only partially inhibited by a high concentration of hyoscine (25 micronmol/1) or by the choline uptake inhibitors, hemicholinium-3 (500 micronmol/1) and troxypyrrolidinium (500 micronmol/1). Indomethacin (50 micronmol/1) produced partial blockade (30%) of responses to electrical stimulation without markedly affecting responses to acetylcholine and the degree of blockade was of a similar order in the presence of hyoscine or troxypyrrolidinium. PGE2 (0.028 -2.8 micronmol/1) or F2alpha (0.029 -2.9 micronmol/1) produced a slowly developing increase in tone and spontaneous activity. Responses to electrical stimulation were at most only slightly increased in the presence of either PG. However, the PGs always increased the responses to electrical stimulation after indomethacin, indomethacin plus hyoscine or indomethacin plus troxypyrrolidinium. Responses to acetylcholine in the presence of indomethacin were not increased by PGE2. It is concluded that PGE2 and F2alpha do not function is transmitters responsible for resistance to anti-muscarinic drugs in the bladder but may exert a modulating effect on nervous transmission.


The protein MAP-1B links GABA(C) receptors to the cytoskeleton at retinal synapses.
The ionotropic type-A and type-C receptors for the neurotransmitter gamma-aminobutyric acid (GABA(A) and GABA(C) receptors) are the principal sites of fast synaptic inhibition in the central nervous system, but it is not known how these receptors are localized at GABA-dependent synapses. GABA(C) receptors, which are composed of rho-subunits, are expressed almost exclusively in the retina of adult vertebrates, where they are enriched on bipolar cell axon terminals. Here we show that the microtubule-associated protein 1B (MAP-1B) specifically interacts with the GABA(C) rho1 subunit but not with GABA(A) receptor subunits. Furthermore, GABA(C) receptors and MAP-1B co-localize at postsynaptic sites on bipolar cell axon terminals. Co-expression of MAP-1B and the rho1 subunit in COS cells results in a dramatic redistribution of the rho1 subunit. Our observations suggest a novel mechanism for localizing ionotropic GABA receptors to synaptic sites. This mechanism, which is specific for GABA(C) but not GABA(A) receptors, may allow these receptor subtypes, which have distinct physiological and pharmacological properties, to be differentially localized at inhibitory synapses.


Stimulating anaerobic digestion to degrade recalcitrant organic pollutants: Potential role of conductive materials-led direct interspecies electron transfer.
This review aims to provide a comprehensive understanding of the potential of CMs-dominated DIET in the degradation of recalcitrant organic pollutants in AD. The review covers the mechanisms and efficiencies of recalcitrant organic pollutant degradation by CMs-dominated DIET, the comparison of degradation pathways between DIET and chemical treatment, recent insights on DIET-enhanced degradation, and the evaluation of the potential and future development of CMs-dominated DIET. The review emphasizes the importance of coupled syntrophic microorganisms, electron flux, and physicochemical properties of CMs in enhancing the degradation performance of AD. Additionally, it highlights the advantages of DIET-led syntrophic metabolism over traditional oxidation technologies in terms of environmental friendliness and efficiency. Finally, the review acknowledges the potential risks associated with introducing CMs into AD systems and provides guidance for waste treatment and energy recovery.


Midterm Outcomes of Surgical Repair of Partial Anomalous Pulmonary Venous Connection to SVC.
We explore midterm results after surgical treatment of partial anomalous pulmonary venous connection (PAPVC) to superior vena cava (SVC) in our institution. From 2008 to 2017, 78 patients underwent surgical repair for PAPVC to SVC. Patients were divided into three groups based on surgical techniques: Single-patch repair (n = 20, group A), double-patch repair (n = 31, group B), and Warden repair (n = 27, group C). Their median age was 1.9 years (range: 3 months-13.8 years); median weight was 11.4 kg (range: 4.4-39.7 kg). Clinical, electrocardiographic and echocardiographic were available for all patients. There were no early or late mortality. The mean follow-up duration was 1.8 ± 2.1 years (range: 0.6 months to 8 years). No pulmonary venous obstruction occurred and no residual left-to-right shunts sustained during the follow-up. Reoperation for SVC obstruction was required: 1 (5.3%) in group A, 1 (3.2%) in group B, and 2 (7.4%) in group C (p = 0.78). Four patients (3 in group B, 1 in group C, p = 0.7) presented transient rhythm disturbance at discharge and one patient in group B remains nonsinus rhythm during follow-up. Pacemaker was not required in all patients. PAPVC to SVC can be safely managed by multiple techniques. Careful manipulation nearby sinus node must be emphasized during double-patch repair to prevent injury of sinus node. Obstruction of postoperative SVC stenosis should be paid attention to after Warden procedure. For young patients, operation should not be performed that early, but until preschool age.


Greener approach for the isolation of oleanolic acid from Nepeta leucophylla Benth. Its derivatization and their molecular docking as antibacterial and antiviral agents.
In the present study bioactive methanolic extract along with chloroform and hexane extracts obtained from shade dried leaves of the Himalayan aromatic medicinal plant Nepeta leucophylla Benth. Were screened for the presence of triterpenoids, especially oleanolic acid (OA). Total three compounds oleanolic acid, squalene and linoleic methyl ester were isolated from methanol extract. The percentage yield of OA was 0.11%. Out of these three, OA is more bioactive and was further subjected to derivatization using greener Ultrasonication method. Total three derivatives (3-Acetyl oleanolic acid, 3-Phthaloyl oleanolic acid and 3-Oxo oleanolic acid) were synthesized with 91.16%, 93.98%, and 83.6% respectively. Further, the antioxidant potential of OA and its derivatives were evaluated using DPPH assay which suggested that the 3-Phthaloyl oleanolic acid exhibits highest antioxidant potential with 40.83 ± 1.14% inhibition. OA and its derivatives were screened in-silico antibacterial potential against three bacterial pathogens (E-coli, M. tuberculosis and S. aureus) and antiviral potential against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), Human immunodeficiency virus (HIV) and H1N1 influenza virus. The in-silico results suggested that 3-phthaloyl oleanolic acid showed best H-bonding with FtsA (Staphylococcus aureus), enoyl acyl reductase (E. coli) and arabinosyl transferase (Mycobactrium tuberculosis). 3-Phthaloyl oleanolic acid also showed best H-Bond interactions with the target proteins hemagglutinin (H1N1) and reverse transcriptase (HIV), whereas, oleanolic acid exhibited the best interactions with RNA dependent RNA polymerase (SARS-CoV-2) and thus could be considered for further in vitro studies.


Human growth hormone stimulates liver regeneration in rats.
To study the effect of human growth hormone (hGH) on liver regeneration in rats, 200 micrograms hGH was administered to partial hepatectomized rats twice a day for three days. The bw of hGH-treated rats was higher than that in untreated rats. After three day administration, the liver weight was 3.18 +/- 0.13 g, significant higher than that of untreated rats (2.68 +/- 0.17 g). Human GH also stimulated the mitosis in the liver. Serum insulin-like growth factor I (IGF-I) and albumin levels were significantly increased and urea nitrogen levels were significantly decreased in hGH-treated rats compared with those in untreated rats. When 120 micrograms/day IGF-I was continuously administered to partial hepatectomized rats for three days, the bw and the liver weight were not higher than those of controls. These data indicate that hGH directly stimulates liver regeneration and recover liver dysfunction in rats.


Effect of methylimidazole-induced hypothyroidism in a model of low retinal neovascular incidence.
To determine the effect of methylimidazole (MMI)-induced hypothyroidism in a newborn rat model of low retinal neovascular (NV) incidence. Control and MMI-exposed newborn rats were raised either in room air or variable oxygen (40/15) until P14. All groups were then exposed to room air between postnatal day (P)14 and P20. Dams drank either tap water or water containing MMI. Eyes of animals in all groups were enucleated, and retinas were removed and stained with adenosine diphosphatase and analyzed for peripheral avascularity, vascular density, and NV incidence and severity. In the control group, MMI treatment did not promote the development of retinal NV although a linear relationship (r = 0.99, P < 0.01) was found between increased MMI dose and lower peripheral retinal vascular densities. In all the 40/15 groups, peripheral retinal vascular densities were lower (P < 0.05) than normal and were not a function of MMI dose. Increased MMI dose produced increased retinal incidence of NV (r = 0.99, P < 0.05). These data are consistent with the notions that thyroid function contributes to normal retinal vascular density and that hypothyroidism can play a permissive role in the development of retinal NV.


Subcellular distribution of selenium during uptake and its influence on mitochondrial oxidations in germinating Vigna radiata L.
The metabolic significance of Se in plants is not well documented, though the presence of many selenoenzymes in bacteria and the essentiality of Se in higher animals is established. Since germination is an active process in plant growth and metabolism, the effect of Se was investigated in germinating Vigna radiata L, a nonaccumulating Se-deficient legume. Growth and protein were enhanced in seedlings supplemented with selenium (Se) as sodium selenite in the medium up to 1 microgram/mL. The pattern of uptake of 75Se in the differentiating tissues and the subcellular distribution were investigated. The percentage of incorporation of 75Se was greater in the mitochondria at the lowest level (0.5 micrograms/mL) of Se supplementation compared to higher levels of Se exposure. Proteins precipitated from the postmitochondrial supernatant fractions, when separated by means of polyacrylamide gel electrophoresis (PAGE), indicated a major selenoprotein in the seedlings germinated at 2.0 micrograms/mL Se. In seedlings grown with supplemented Se, enhanced respiratory control ratio and succinate dehydrogenase activity were observed in the mitochondria of tissues, indicative of a role for Se in mitochondrial membrane functions.


GABAB-receptor activation alters the firing pattern of dopamine neurons in the rat substantia nigra.
Previous electrophysiological experiments have emphasized the importance of the firing pattern for the functioning of midbrain dopamine (DA) neurons. In this regard, excitatory amino acid receptors appear to constitute an important modulatory control mechanism. In the present study, extracellular recording techniques were used to investigate the significance of GABAB-receptor activation for the firing properties of DA neurons in the substantia nigra (SN) in the rat. Intravenous administration of the GABAB-receptor agonist baclofen (1-16 mg/kg) was associated with a dose-dependent regularization of the firing pattern, concomitant with a reduction in burst firing. At higher doses (16-32 mg/kg), the firing rate of the DA neurons was dose-dependently decreased. Also, microiontophoretic application of baclofen regularized the firing pattern of nigral DA neurons, including a reduction of burst firing. Both the regularization of the firing pattern and inhibition of firing rate produced by systemic baclofen administration was antagonized by the GABAB-receptor antagonist CGP 35348 (200 mg/kg, i.v.). The GABAA-receptor agonist muscimol produced effects on the firing properties of DA neurons that were opposite to those observed following baclofen, i.e., an increase in firing rate accompanied by a decreased regularity. The NMDA receptor antagonist MK 801 (0.4-3.2 mg/kg, i.v.) produced a moderate, dose-dependent increase in the firing rate of the nigral DA neurons as well as a slightly regularized firing pattern. Pretreatment with MK 801 (3.2 mg/kg, i.v., 3-10 min) did neither promote nor prevent the regularization of the firing pattern or inhibition of firing rate on the nigral DA neurons produced by baclofen. The present results clearly show that GABAB-receptors can alter the firing pattern of nigral DA neurons, hereby counterbalancing the previously described ability of glutamate to induce burst firing activity on these neurons.


A phase II trial of m-AMSA in head and neck cancer.
Twenty patients with advanced epidermoid carcinoma from primary sites in the head and neck region received adequate trials of therapy with m-AMSA, at starting doses of 90 or 120 mg/m2. Despite the good median performance status of the group (median 80) and the fact that 50% of the patients had received no prior chemotherapy, only one minor response was achieved. AMSA appears to have no useful activity in this dose and schedule in patients with epidermoid head and neck cancer.


A data driven machine learning approach to differentiate between autism spectrum disorder and attention-deficit/hyperactivity disorder based on the best-practice diagnostic instruments for autism.
Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two frequently co-occurring neurodevelopmental conditions that share certain symptomatology, including social difficulties. This presents practitioners with challenging (differential) diagnostic considerations, particularly in clinically more complex cases with co-occurring ASD and ADHD. Therefore, the primary aim of the current study was to apply a data-driven machine learning approach (support vector machine) to determine whether and which items from the best-practice clinical instruments for diagnosing ASD (ADOS, ADI-R) would best differentiate between four groups of individuals referred to specialized ASD clinics (i.e., ASD, ADHD, ASD + ADHD, ND = no diagnosis). We found that a subset of five features from both ADOS (clinical observation) and ADI-R (parental interview) reliably differentiated between ASD groups (ASD & ASD + ADHD) and non-ASD groups (ADHD & ND), and these features corresponded to the social-communication but also restrictive and repetitive behavior domains. In conclusion, the results of the current study support the idea that detecting ASD in individuals with suspected signs of the diagnosis, including those with co-occurring ADHD, is possible with considerably fewer items relative to the original ADOS/2 and ADI-R algorithms (i.e., 92% item reduction) while preserving relatively high diagnostic accuracy. Clinical implications and study limitations are discussed.


[Opportunities for artificial intelligence in radiation protection : Improving safety of diagnostic imaging].
Imaging of structures of internal organs often requires ionizing radiation, which is a health risk. Reducing the radiation dose can increase the image noise, which means that images provide less information. This problem is observed in commonly used medical imaging modalities such as computed tomography (CT), positron emission tomography (PET), single photon emission computed tomography (SPECT), angiography, fluoroscopy, and any modality that uses ionizing radiation for imaging. Artificial intelligence (AI) can improve the quality of low-dose images and help minimize radiation exposure. Potential applications are explored, and frameworks and procedures are critically evaluated. The performance of AI models varies. High-performance models could be used in clinical settings in the near future. Several challenges (e.g., quantitative accuracy, insufficient training data) must be addressed for optimal performance and widespread adoption of this technology in the field of medical imaging. To fully realize the potential of AI and deep learning (DL) in medical imaging, research and development must be intensified. In particular, quality control of AI models must be ensured, and training and testing data must be uncorrelated and quality assured. With sufficient scientific validation and rigorous quality management, AI could contribute to the safe use of low-dose techniques in medical imaging.


A Group Contingency Plus Self-Management Intervention Targeting At-Risk Secondary Students' Class-Work and Active Engagement.
The purpose of the present study is to show that an independent group contingency (GC) combined with self-management strategies and randomized-reinforcer components can increase the amount of written work and active classroom responding in high school students. Three remedial reading classes and a total of 15 students participated in this study. Students used self-management strategies during independent reading time to increase the amount of writing in their reading logs. They used self-monitoring strategies to record whether or not they performed expected behaviors in class. A token economy using points and tickets was included in the GC to provide positive reinforcement for target responses. The results were analyzed through visual inspection of graphs and effect size computations and showed that the intervention increased the total amount of written words in the students' reading logs and overall classroom and individual student academic engagement.


Generation of auditory brain stem responses (ABRs). II. Effects of surgical section of the trapezoid body on the ABR in guinea pigs and cat.
Auditory brain stem potentials were recorded between the skull and a non-cephalic reference electrode in guinea pig and cat before and after midline section of the trapezoid body from a ventral approach. The ABR after complete section was altered: N2 was delayed, P3 and N3 were lost, P4 and N4 were shortened in latency but only N4 was attenuated in amplitude. With partial section of the trapezoid body the amplitude of P3 was linearly related to the extent of the section. Recordings from the surface of the trapezoid body before and after section revealed a loss of activity contralateral to the ear stimulated and a preservation of activity ipsilateral to the section. Binaural interaction in P4 and N4 was attenuated in a linear manner as a function of the extent of trapezoid body section. This study suggests that auditory brain stem structures contralateral to the midline of the trapezoid body generate components N2, P3, N3, N4, whereas auditory structures ipsilateral to the midline generate components P1, N1, P2 and P4.


Perceptions about mental healthcare for people with epilepsy in Africa.
Mental illness is commonly comorbid with epilepsy. In sub-Saharan Africa there exists limited access to neurological and psychiatric services predisposing to a "treatment gap" in epilepsy and mental healthcare. To understand healthcare providers' knowledge, attitudes, and management practices toward epilepsy and comorbid mental illness in sub-Saharan Africa. A cross-sectional online survey following the STROBE guidance was conducted among healthcare providers in sub-Saharan Africa. Eleven questions looking to ascertain clinician demographics, knowledge of epilepsy, and comorbid mental illness as well as management practices were developed. Of 203 responses most (92%) respondents recognized a bi-directional relationship between mental health and epilepsy. However, mental illness screening in people newly diagnosed with epilepsy was infrequently performed (14%). Only 1 in 7 (16%) respondents had high confidence in their clinical competence at managing psychiatric comorbidities. Most would value further training (74%) and improvements to be made in current management practices within their local healthcare settings (94%). This pilot study highlights the need to improve the awareness of management of mental disorders in populations with epilepsy within sub-Saharan Africa in health providers there.


[Diabetes mellitus in the elderly : epidemiological, pathophysiological and clinical aspects].
Diabetes mellitus is an illness to be considered differently according to patient's age. In the elderly, it is necessary to check classical complications or other cardiovascular risk factors, but also to take into account general health and patient's autonomy. Both aims and treatments should be adjusted accordingly on an individual basis.


Tolerability of fluoxetine in posttraumatic stress disorder.
In response to earlier reports that raised concerns about the tolerability of fluoxetine in the treatment of posttraumatic stress disorder (PTSD), this study was conducted to systematically delineate treatment-emergent symptoms (TES) associated with fluoxetine treatment of PTSD. Sixty-five patients with PTSD enrolled in one of two identical-protocol, 12-week studies and received double-blind fluoxetine or placebo. TES data were obtained using a patient-rated checklist, Severity of Symptoms Scale (SOSS). Only a single patient discontinued treatment due to medication side effects. Compared to placebo, only three statistically significant TES (nausea, diarrhea, and thirst) occurred more frequently in fluoxetine subjects. Fluoxetine was not associated with any statistically significant activating effects. There were no statistically significant associations between the total number of TES experienced and treatment, gender, or comorbid depressive or panic disorders. This systematic assessment of TES indicated that PTSD patients tolerated fluoxetine well without pronounced activating side effects.


A detailed protocol for RNA cleavage assay in sympathetic neurons.
This protocol illustrates the use of an in vitro assay to study the cleavage of the IMPA1 3'UTR by the endonuclease Ago2 in sympathetic neurons. The procedure includes the preparation of cytoplasmic protein extracts and also describes the synthesis and labeling of the RNA probe. The protocol can be applied to other cell systems, RNA transcripts, and endonucleases to confirm the role of known cleavage site(s) and cleavage proteins, or to investigate new ones. For complete details on the use and execution of this protocol, please refer to Andreassi et al. (2021).


In Operando Identification of In Situ Formed Metalloid Zincδ+ Active Sites for Highly Efficient Electrocatalyzed Carbon Dioxide Reduction.
Electrochemical CO2 -to-CO conversion provides a possible way to address problems associated with the greenhouse effect; however, developing low-cost electrocatalysts to mediate high-efficiency CO2 reduction remains a challenge on account of the limited understanding of the nature of the real active sites. Herein, we reveal the Znδ+ metalloid sites as the real active sites of stable nonstoichiometric ZnOx structure derived from Zn2 P2 O7 through operando X-ray absorption fine structure analysis in conjunction with evolutionary-algorithm-based global optimization. Furthermore, theoretical and experimental results demonstrated that Znδ+ metalloid active sites could facilitate the activation of CO2 and the hydrogenation of *CO2 , thus accelerating the CO2 -to-CO conversion. Our work establishes a critical fundamental understanding of the origin of the real active center in the zinc-based electrocatalysts for CO2 reduction reaction.


Accumulation of fibrosis and altered perifollicular stromal differentiation in vitrified-thawed human ovarian tissue xenografted to nude mice.
Ovarian tissue cryopreservation and its auto-transplantation is promising technique in fertility preservation. Longevity of grafted tissue is limited though mechanism of follicle reduction is not fully understood. We evaluated histological alteration of vitrified-thawed ovarian tissue that grafted to nude mice. Human ovarian tissue was cryopreserved by vitrification. After thawing, they were grafted to mesentery of nude mice. Twelve weeks after transplantation, the implants were removed and histologically examined. The presence of follicles, the degree of fibrosis, and TUNEL staining in surrounding cortex were evaluated. The stromal expressions of alpha-smooth muscle actin (aSMA) were determined. Normal ovarian cortex was decreased, and fibrotic area were significantly increased after grafting. The distributions of developmental stage of follicles shifted toward activation of follicular growth. Stromal TUNEL staining was increased in frozen/thawed tissue. The expression of aSMA were found in perifollicular stroma of growing follicles, which were decreased in grafted tissue associated with reduction of cortical stroma. Fibrosis, reduced cortical stroma, and activation of dormant follicles were concomitantly observed in grafted ovarian cortex, which may relate to limited longevity. Perifollicular aSMA expression can be regarded as a marker of the competence of cortical stroma that regulate follicular development.


Validation of a Chinese version of the short-form Cataldo lung cancer stigma scale.
Lung cancer stigma is a widespread psychosocial problem. We developed a short form of the Cataldo lung cancer stigma scale for Chinese people with lung cancer (CLCSS-C-SF) and compared its psychometric properties with those of the full and short versions. This was a secondary analysis using data from the full CLCSS-C, distress thermometer and perceived social support of Chinese people with lung cancer (N = 394). Exploratory and confirmatory factor analysis (CFA) were used to identify factor structure and assess construct validity. The internal consistency and concurrent and known-group validity were evaluated. The 22-item CLCSS-C-SF comprised four factors. The convergent validity evaluated using average variance extracted and discriminant validity were acceptable. Cronbach's alphas, concurrent and known-group validity were satisfactory for three versions. Only the four-factor model proposed was validated by CFA. The CLCSS-C-SF is reliable and valid and can be used in Chinese lung cancer populations.


Steroidal control of sexual behavior in the rough-skinned newt (Taricha granulosa): effects of testosterone, estradiol, and dihydrotestosterone.
Adult, sexually mature, male rough-skinned newts (Taricha granulosa) obtained from a wild population were castrated and received Silastic capsules containing testosterone (T), estradiol (E), or 5 alpha-dihydrotestosterone (DHT). The newts received three capsules of T, either one or three capsules of E or DHT, or combined treatments with these two steroids. When tested for sexual responsiveness after 32 and 34 days of steroid treatment, no group differed from the castrated controls (C). After 74 and 75 days of treatment, more T-implanted than C newts were sexually responsive, but the newts treated with E, DHT, or these two steroids in combination did not differ behaviorally from the C group. The diameter of the vas deferens was greater in the T- and DHT-treated males than in the C males, indicating that the implants adequately replaced testicular androgens. Together with other studies on this and other species, these results confirm the participation of testosterone in the regulation of sexual behaviors in male amphibians. Furthermore, these results indicate that in this amphibian, the behavioral effects of T are mediated directly by this steroid, not indirectly by enzymatic conversion to DHT or E.


Beliefs about prognosis and outcomes for people with mental disorders: A cross-cultural study of Bachelor of Nursing students from the US and China.
The purpose of this study is to examine and compare the US and Chinese Bachelor of Nursing students' beliefs about prognosis and long-term outcomes for people with depression and schizophrenia following interventions. A total of 310 nursing students in the US (n = 152) and China (n = 158) completed a survey questionnaire between April 2016 and April 2017. Overall, the Chinese students rated prognosis and outcomes more negatively than did the US students. The main finding suggests the need for cultural-specific pedagogical considerations to be given to mental health education in undergraduate nursing curricula in the US and China.


New multiplex conventional PCR and quadruplex real-time PCR assays for one-tube detection of Phyllosticta citricarpa, Elsinoë fawcettii, Elsinoë australis, and Pseudocercospora angolensis in Citrus: development and validation.
Phyllosticta citricarpa, Elsinoë fawcettii, Elsinoë australis, and Pseudocercospora angolensis are major pathogens of citrus crops worldwide and can cause non-characteristic symptoms that may lead to confusion regarding the causative agent. These fungi are subject to international phytosanitary regulations, and testing on fruits or leaves requires accurate and easy-to-use tools. New multiplex conventional PCR and real-time PCR assays were developed here to achieve highly accurate simultaneous detection of all four fungal pathogens in fruit tissues. We designed new oligonucleotide combinations for P. citricarpa, E. fawcettii, and E. australis and combined them with already available primers and hydrolysis probes to be used in either PCR assay. The limit of detection for multiplex conventional PCR was as low as 100 pg μL-1 for P. citricarpa, E. fawcettii, and E. australis and 10 pg μL-1 of target DNA per reaction tube for P. angolensis. The quadruplex real-time PCR assay successfully yielded repeatable positive results with as low as 242, 243, 241, and 242 plasmidic copies of target DNA of P. citricarpa, E. fawcettii, E. australis, and P. angolensis, respectively. Moreover, analysis of 60 naturally infected citrus samples yielded 100% concordant results by both assays. Our validation experiment revealed that the multiplex real-time PCR assay showed high specificity except a cross-reaction with P. paracitricarpa DNA. Sensitivity, repeatability, reproducibility, and robustness were verified, and the assay could be used following different DNA extraction procedures, supporting fitness for routine analysis. These new multiplex tools should be of great interest as cost-effective solutions for regulatory authorities and diagnostic laboratories, enabling testing for four important pathogens in single-tube reactions. KEY POINTS: • Development of new conventional PCR and qPCR assays for four citrus pathogens. • Very low limits of detection were found for multiplex conventional PCR. • qPCR had high specificity, sensitivity, repeatability, reproducibility, and robustness.


Internal setting expansion of a dental casting investment measured with strain gauges.
A study was undertaken to investigate the feasibility of using strain gauges to evaluate the internal setting expansion of dental casting investments. A strain gauge was invested in the center of a casting ring to determine the linear setting expansion at the site of the wax pattern. The findings suggest that strain gauges can be used to measure setting expansion internally more accurately than volumetric or external surface measurement techniques. It was also found that winged strain gauges were more stable in the investment than wingless strain gauges.


Kinetics of chlorophyll fluorescence at 77K in Chlorella and chloroplasts. Effects of CCCP, ferricyanide and DCMU.
The kinetics of chlorophyll fluorescence at 77K were studied in Chlorella cells and spinach chloroplasts. During a first illumination, the rise is polyphasic with at least three phases. The slowest one is irreversible and corresponds to the cytochrome oxidation. The dark regeneration of half the variable fluorescence is biphasic, the fast phase being inhibited by 3-(3,4-dichlorophenyl)-1, 1-dimethylurea (DCMU) both in Chlorella and chloroplasts. The fluorescence rise during a second illumination is still biphasic. Carbonyl cyanide m-chlorophenylhydrazone (CCCP) slows down the fluorescence rise in Chlorella but has no effect on the dark regeneration. It does not affect the fluorescence of chloroplasts. Ferricyanide which oxidizes cytochrome beta-559 at room temperature produces a quenching of the variable fluorescence and an acceleration of the fluorescence rise during the first illumination. Our results fit the idea of the heterogeneity of the Photosystem II centers at low temperature.


Calculation of absolute protein-ligand binding constants with the molecular dynamics free energy perturbation method.
Reliable first-principles calculations of protein-ligand binding constants can play important roles in the study and characterization of biological recognition processes and applications to drug discovery. A detailed procedure for such a calculation is outlined in this chapter. The methodology is computationally implemented using the molecular dynamics sampling of relevant configurational spaces and free energy perturbation techniques. The procedure is illustrated with the model system of the phosphotyrosine peptide binding to the Src SH2 domain.


The role of iodine in carcinogenesis.
Iodine is an essential nutrient for the normal growth and development of humans and animals and is necessary for normal metabolism and regulation of thyroid hormones. Iodine excess can produce thyrotoxicosis but not cancer. However, radioiodine is carcinogenic for the thyroid gland. Dietary iodine deficiency is associated with goiter in humans and animals. The goiter develops because of a feedback system between thyroid hormones, the pituitary gland, and the hypothalamus, and it regulates the synthesis and release of thyroid-stimulating hormone. Chronic hypersecretion of thyroid-stimulating hormone causes profound goiter (diffuse thyroid hyperplasia), which appears to be related to carcinogenesis. Chronic dietary iodine deficiency in rats leads to thyroid follicular adenomas by 12 months and follicular carcinomas by 18 months. An increased risk of thyroid cancer has been reported in humans with goiter and those living in some iodine-deficient areas of the world. In very recent animal studies, iodine deficiency, chemical goitrogens, and thyroid toxins have been shown to have potent tumor-promoting effects. In rats, iodine deficiency is a much more effective tumor promoter than it is a carcinogen, suggesting that a similar relationship may exist in human populations. These studies suggest that a major role of iodine is to prevent the formation of thyroid tumors in humans and animals.


The HPV E6 oncoprotein targets histone methyltransferases for modulating specific gene transcription.
Expression of viral proteins causes important epigenetic changes leading to abnormal cell growth. Whether viral proteins directly target histone methyltransferases (HMTs), a key family enzyme for epigenetic regulation, and modulate their enzymatic activities remains elusive. Here we show that the E6 proteins of both low-risk and high-risk human papillomavirus (HPV) interact with three coactivator HMTs, CARM1, PRMT1 and SET7, and downregulate their enzymatic activities in vitro and in HPV-transformed HeLa cells. Furthermore, these three HMTs are required for E6 to attenuate p53 transactivation function. Mechanistically, E6 hampers CARM1- and PRMT1-catalyzed histone methylation at p53-responsive promoters, and suppresses the binding of p53 to chromatinized DNA independently of E6-mediated p53 degradation. p53 pre-methylated at lysine-372 (p53K372 mono-methylation) by SET7 protects p53 from E6-induced degradation. Consistently, E6 downregulates p53K372 mono-methylation and thus reduces p53 protein stability. As a result of the E6-mediated inhibition of HMT activity, expression of p53 downstream genes is suppressed. Together, our results not only reveal a clever approach for the virus to interfere with p53 function, but also demonstrate the modulation of HMT activity as a novel mechanism of epigenetic regulation by a viral oncoprotein.


Safety and effectiveness of response-guided therapy using pegylated interferon and ribavirin for chronic hepatitis C virus infection in patients on maintenance dialysis.
Treatment of hepatitis C virus (HCV) infection in patients with end-stage renal disease (ESRD) is difficult. Addition of ribavirin to pegylated-interferon (Peg-IFN) may help to improve the treatment response. Further, treatment duration could be shortened using a response-guided treatment (RGT) approach. We retrospectively reviewed records of treatment-naïve adult patients with ESRD and chronic HCV infection who had been treated with Peg-IFN and low-dose ribavirin using a RGT approach. Rapid responders (undetectable HCV-RNA at 4 weeks) received treatment for 12 weeks, and slow responders (HCV-RNA detectable at 4 weeks, but undetectable or with >2.0 log10 reduction at week 12) for 24 (genotype 3; GT3) or 48 (genotype 1; GT1) weeks. In those without such reduction (null responders), treatment was discontinued. Of 26 non-cirrhotic patients (GT1 15, GT3 11) treated, four (15%; GT1 3, GT3 1) were null responders. Twenty-two (85%) patients had either rapid (n = 14 (54%); GT1 10, GT3 4) or slow response (n = 8 (31%); GT1 2, GT3 6). Of them, 21 patients had undetectable RNA at the end of treatment; one could not complete the treatment and was lost thereafter. There were no deaths during treatment. Three patients relapsed and three others died in 6 months after stopping treatment. Overall, 15/26 (58%) patients attained SVR24. Fourteen patients underwent transplantation beginning one month after treatment completion, and all were relapse-free after 17 (14-24) months of follow-up. RGT using Peg-IFN and ribavirin was effective in ESRD patients on maintenance dialysis. Renal transplant was safely done within one month of completing such treatment.


Orthodontic treatment of a patient with Lowe syndrome.
This article describes the orthodontic treatment of a patient with Lowe syndrome. The objective of the treatment was to improve the patient's dental relationships and consequently his quality of life. This was achieved by maxillary expansion and extraction of the mandibular central incisors and maxillary deciduous canines. The teeth were aligned and leveled with a fixed orthodontic appliance. Satisfactory results were obtained at the end of treatment, with substantial improvement in dental esthetics, occlusal function, and facial profile.


The homeodomain transcription factor Orthopedia is involved in development of the Drosophila hindgut.
The Drosophila hindgut is commonly used model for studying various aspects of organogenesis like primordium establishment, further specification, patterning, and morphogenesis. During embryonic development of Drosophila, many transcriptional activators are involved in the formation of the hindgut. The transcription factor Orthopedia (Otp), a member of the 57B homeobox gene cluster, is expressed in the hindgut and nervous system of developing Drosophila embryos, but due to the lack of mutants no functional analysis has been conducted yet. We show that two different otp transcripts, a hindgut-specific and a nervous system-specific form, are present in the Drosophila embryo. Using an Otp antibody, a detailed expression analysis during hindgut development was carried out. Otp was not only expressed in the embryonic hindgut, but also in the larval and adult hindgut. To analyse the function of otp, we generated the mutant otp allele otpGT by ends-out gene targeting. In addition, we isolated two EMS-induced otp alleles in a genetic screen for mutants of the 57B region. All three otp alleles showed embryonic lethality with a severe hindgut phenotype. Anal pads were reduced and the large intestine was completely missing. This phenotype is due to apoptosis in the hindgut primordium and the developing hindgut. Our data suggest that Otp is another important factor for hindgut development of Drosophila. As a downstream factor of byn Otp is most likely present only in differentiated hindgut cells during all stages of development rather than in stem cells.


A retrospective analysis of the TATs of children at risk who subsequently broke down.
A retrospective evaluation of stories told to three Thematic Apperception Test (TAT) cards by children at risk isolated six characteristics that were associated with functioning six to 10 years later. The characteristics included lack of individual initiative, denial of mother-child relationships, denial of negative outcomes, and lack of autonomy. The TATs of children at risk (due to one parent's hospitalization for a psychotic illness) who subsequently suffered major decompensation themselves (requiring hospitalization or intensive outpatient therapy) could be discriminated from those of children at risk with apparently normal development. The TAT characteristics were independent of the level of adjustment at the time the TATs were administered, not related to the child's IQ, socioeconomic status, race, or other family characteristics, and moderately negatively correlated with story length.


The role of line-field confocal optical coherence tomography (LC-OCT) in the diagnosis of eccrine poroma: A case report.
Poroma is skin cancer that arises from the sweat gland cells. Its diagnosis could be difficult. Line-field optical coherence tomography (LC-OCT) is a novel imaging technique that has shown promise in the diagnosis and monitoring of various skin conditions. We report a case of poroma diagnosed by LC-OCT.


Therapeutic plasma exchange for hypertriglyceridemia induced pancreatitis: A rapid and practical approach.
Acute hypertriglyceridemia induced pancreatitis (HTP) presents with a more severe clinical course compared to other etiologies of pancreatitis. Therapeutic plasma exchange (TPE) is a potential treatment option for lowering plasma triglycerides and possibly decreasing morbidity and mortality. However, clinical data regarding its effectiveness are limited. We retrospectively examined the clinical data and outcomes of 13 consecutive episodes of HTP in which TPE was employed to reduce plasma triglycerides during a 15-month period. The TPE was initiated at a median of 19 hours from the time of presentation. We performed 1.2-1.5 volume TPEs with 5% albumin as the replacement fluid. After only one TPE procedure, the mean plasma triglycerides values decreased from 2993 mg/dl to 487 mg/dl with a reduction of 84%. All 13 patients survived with a mean length of hospital stay of 9.5 days. There were no complications related to TPE. One TPE procedure is an effective method for reducing plasma triglycerides and possibly decreases the length of hospital stay in patients admitted with HTP.


Perioperative anesthetic management for esophagectomy.
Esophageal resection is a formidable operation associated with high morbidity and mortality. Anesthetic management may contribute to the containment of respiratory failure and anastomotic leakage by the use of thoracic epidural analgesia, protective ventilation strategies, prevention of tracheal aspiration, and judicious fluid management.


Laparoscopic-assisted robotic distal gastrectomy for gastric cancer by Billroth II reconstruction.
There are several reconstructions in distal gastrectomy for gastric cancer, and there is no clear definition regarding the method selection. The optimal reconstruction is likely to vary according to the surgical setting, and the optimal reconstruction for robotic distal gastrectomy is urgently needed. In addition, as robotic gastrectomy is getting popular, cost and operative time are pressing issues of robotic gastrectomy. Gastrojejunostomy was planned with Billroth II reconstruction using a linear stapler arranged specifically for a robotic approach. After firing the stapler, the common insertion orifice of the stapler was closed using a 30 cm long non-absorbable barbed suture, and continuously, the afferent loop of the jejunum was lifted to the stomach with the same barbed suture. In addition, we introduced laparoscopic-assisted robotic gastrectomy, using extracorporeally inserted laparoscopic devices from the assistant port. Scissors, clips, and linear staplers were all laparoscopic tools inserted extracorporeally. Twenty-one gastric cancer patients underwent laparoscopic-assisted robotic distal gastrectomy by Billroth II reconstruction with our modifications. There were no anastomosis-related complications such as leakage, stenosis, or bleeding. There were 2 cases of aspiration pneumonia (Clavien-Dindo grade 2), 1 case of pancreatic juice leakage (grade 3a), and 1 case of delayed gastric emptying (grade 1). We successfully arranged Billroth II reconstruction for robotic distal gastrectomy with fewer operative and postoperative complications. Laparoscopic-assisted robotic gastrectomy using extracorporeally inserted devices, and continuous suturing using a barbed suture will reduce the time and cost of robotic gastrectomy.


Stigma and Discrimination of HIV/AIDs Recipients of Care in Western Uganda: Experiences and Roles of Expert Clients.
Stigma and discrimination (SAD) remains a major challenge facing HIV/AIDs management in most countries of sub-Saharan Africa. Expert clients can potentially play a role in the fight against SAD. Our study explored the experiences and the role of expert clients in reducing SAD among people living with HIV/AIDs enrolled on care in health facilities in Western Uganda. We conducted a phenomenological qualitative study among (12) twelve purposively selected expert clients at four health facilities in Sheema district, Western Uganda. In-depth interviews were conducted using an interview guide. Data were transcribed verbatim, translated to English, manually coded and analysed manually by thematic content. Four themes emerged describing the experiences of expert clients in reducing HIV/AIDs SAD; 1) Feeling of inner satisfaction, 2) Challenging work environment, 3) Acquisition of skills and 4) Disclosure dilemma. The roles of expert clients in reducing HIV-related SAD included 1) Facilitating status disclosure, 2) Identifying and helping clients with stigma/discrimination, 3) Linking patients to the health care system and 4) Promotion of positive living. Expert clients had numerous experiences and play a key role in the fight against SAD. Expert clients should be included as one of the stakeholders in the efforts to reduce or eradicate SAD in the management of HIV/AIDs.


Predicting the progression to super-refractory status epilepticus: A machine-learning study.
Super-refractory status epilepticus (SRSE) is a status epilepticus (SE) that continues or recurs ≥24 h after the onset of anesthesia. We aimed to identify the predictors of progression to SRSE and the risk of 30-day mortality in patients with SRSE by using a machine learning technique. We reviewed consecutive SE episodes in patients aged ≥14 years at Baggiovara Civil Hospital (Modena, Italy) from 2013 to 2021. A classification and regression tree analysis was performed to develop a predictive model of progression to SRSE in SE patients. In SRSE patients, a multivariate analysis was conducted to identify predictors of 30-day mortality. We included 705 patients, 16% of whom (113/705) progressed to SRSE. Acute symptomatic hypoxic etiology and age ≤ 68.5 years predicted the highest risk (87.1%) of progression to SRSE. Etiology other than acute symptomatic hypoxic and absence of NCSE predicted the lowest risk (3.6%) of progression to SRSE. The predictive model was accurate in 96.1% of patients not evolving to SRSE and in 48.7% of those evolving to SRSE. Among patients with SRSE, 46.9% (53/113) died within 30 days compared to 25.2% (149/592) of patients without SRSE (p < 0.001). Among patients with SRSE, older age was associated with increased 30-day mortality (odds ratio 1.075; 95% confidence interval: 1.031-1.112; p = 0.001). Acute symptomatic hypoxic etiology and younger age are major predictors of progression to SRSE. In patients with SRSE, older age is associated with increased risk of short-term mortality.


Evolution of Staphylococcus aureus during human colonization and infection.
The diversification of bacterial pathogens during infection is central to their capacity to adapt to different anatomical niches, evade the host immune system, and overcome therapeutic challenges. For example, antimicrobial treatment may fail due to the development of resistance during infection, which is often accompanied by transition to a less virulent state during chronic, persistent infection. In this review, the adaptation of the major human pathogen Staphylococcus aureus to its host environment during infection will be discussed, particularly in the context of new sequencing technologies which have opened a gateway towards understanding of the molecular processes underlying those adaptations. We now have the capacity to address previously intractable questions regarding bacterial diversification during infection which will ultimately lead to enhanced understanding of pathogenesis and the nature of epidemics, and will inform the design of effective therapeutic measures.


Using an OSCE to assess the potential for assistive technology to enhance communication between student pharmacists and simulated patients who are deaf/hard of hearing.
To evaluate the usefulness of assistive technology in health care interactions between student pharmacists and simulated patients who are deaf/hard of hearing and to assess changes in confidence and comfort levels (among both groups) when using assistive technology. Forty-nine second-year student pharmacists were enrolled in a pharmacy communication laboratory course and 8 undergraduate students were recruited during Fall 2019. The first communication laboratory interaction consisted of student pharmacists using their normal mode of communication with role-played patients who are deaf/hard of hearing to establish baseline measures; a pretest survey was administered to each participant at the conclusion of this 10-minute laboratory interaction. In the second laboratory interaction, student pharmacists used the app to assist in communicating with the simulated patients who are deaf/hard of hearing. Posttests were administered at the conclusion of this laboratory interaction. Most student pharmacists and simulated patients who are deaf/hard of hearing reported feeling able to effectively communicate their needs to the other individual in their dyad (pharmacist or patient) during their health care interactions. Using an iPad (Apple Inc) app to communicate significantly increased student pharmacist and simulated patient comfort with health care communication from preintervention to postintervention. The use of assistive technology in simulated communication laboratory interactions can enhance student pharmacist comfort in health care interactions with patients who are deaf/hard of hearing.


Anthelmintic activity of praziquantel on Raillietina tetragona in chickens.
Praziquantel was tested against mature (17-day-old) and immature (7-day-old) Raillietina tetragona in experimentally infected chickens using single oral doses of 10, 7.5, 5, or 2.5 mg/kg body wt. The compound showed potent anticestodal activity, with 100% efficacy at 10, 7.5, and 5 mg/kg against immature worms and an efficacy of 100% 97.1%, and 95% against mature worms when given at 10, 5, and 2.5 mg/kg, respectively. Residual worms surviving drug treatment had less biomass than the controls. Praziquantel appears to be well tolerated by chickens, and treated birds showed no clinical reactions at any of the doses tested.


No evidence for an independent retinotopic reference frame for inhibition of return.
Inhibition of return (IOR) represents a delay in responding to a previously inspected location and is viewed as a crucial mechanism that sways attention toward novelty in visual search. Although most visual processing occurs in retinotopic, eye-centered, coordinates, IOR must be coded in spatiotopic, environmental, coordinates to successfully serve its role as a foraging facilitator. Early studies supported this suggestion but recent results have shown that both spatiotopic and retinotopic reference frames of IOR may co-exist. The present study tested possible sources for IOR at the retinotopic location including being part of the spatiotopic IOR gradient, part of hemifield inhibition and being an independent source of IOR. We conducted four experiments that alternated the cue-target spatial distance (discrete and contiguous) and the response modality (manual and saccadic). In all experiments, we tested spatiotopic, retinotopic and neutral (neither spatiotopic nor retinotopic) locations. We did find IOR at both the retinotopic and spatiotopic locations but no evidence for an independent source of retinotopic IOR for either of the response modalities. In fact, we observed the spread of IOR across entire validly cued hemifield including at neutral locations. We conclude that these results indicate a strategy to inhibit the whole cued hemifield or suggest a large horizontal gradient around the spatiotopically cued location. PUBLIC SIGNIFICANCE STATEMENT: We perceive the visual world around us as stable despite constant shifts of the retinal image due to saccadic eye movements. In this study, we explore whether Inhibition of return (IOR), a mechanism preventing us from returning to previously attended locations, operates in spatiotopic, world-centered or in retinal, eye-centered coordinates. We tested both saccadic and manual IOR at spatiotopic, retinotopic, and control locations. We did not find an independent retinotopic source of IOR for either of the response modalities. The results suggest that IOR spreads over the whole previously attended visual hemifield or there is a large horizontal spatiotopic gradient. The current results are in line with the idea of IOR being a foraging facilitator in visual search and contribute to our understanding of spatiotopically organized aspects of visual and attentional systems.


Expression of human pyruvate carboxylase in insect cells using the baculovirus system.
Constructs containing cDNA encoding human pyruvate carboxylase (PC) with and without a hexahistidine (6x His) tag at the N-terminal of the mature enzyme have been cloned under the control of the polyhedrin promoter. These two constructs were co-transfected with the baculovirus genome into Sf9 cells to produce recombinant baculoviruses harbouring human PC cDNA. The expression of human PC under the control of the polyhedrin promoter was found to be at its highest level at 4 days post-infection. The expressed material accounted for up to 70% of total cellular protein with 5% of this expressed material being found in the soluble fraction. The recombinant human 6x His-PC isolated with a purity of approximately 50% using a Ni-NTA agarose column was found to have the specific activity of 7U/mg, which was similar to that produced from a 293T stable line [Biochem. Biophys. Res. Commun. 266 (1999) 512]. This is the first report of a heterologous expression system for recombinant human PC.


Safrole-DNA adduct in hepatocellular carcinoma associated with betel quid chewing.
Betel quid chewing, which contributes high concentration of safrole in saliva, is a popular oral habit in Taiwan. Safrole is a documented rodent hepatocarcinogen, yet its hepatocarcinogenic potential in human is not known. Here, we used LC/ESI-ITMS(n) and LC/QTOF-MS confirmed safrole-dGMP as reference standard to detect the safrole-DNA adduct in hepatic tissues from HBsAg-/HCV-seronegative hepatocellular carcinoma patients by (32)P-postlabeling. We first synthesized and confirmed safrole-dGMP by LC/MS. Two isomeric safrole-dGMPs were characterized as N(2)-(trans-isosafrol-3'-yl) deoxyguanosine and N(2)-(safrol-1'-yl) deoxyguanosine. This technique was able to detect hepatic safrole-DNA adduct in mice that were treated with safrole but not sensitive enough to detect safrole-DNA adduct in human samples. Using the nuclease P1 version of the (32)P-postlabeling technique, we detected the presence of safrole-DNA adduct in two out of 28 hepatic tissues from hepatocellular carcinoma patients, and only these two patients had a history of betel quid chewing lasting more than 10 years. From co-chromatography with the mass confirmed safrole-dGMPs, this safrole-DNA adduct was identified as N(2)-(trans-isosafrol-3'-yl) deoxyguanosine. These results suggest that betel quid-containing safrole might be involved in the pathogenesis of hepatocellular carcinoma in human beings and LC/MS has the potential to identify DNA adducts in clinical samples.