Rapid-eye movement sleep and muscarinic receptor binding in rats are augmented during withdrawal from chronic scopolamine treatment.
The purpose of this study was to determine whether a seven day, once-daily morning administration of scopolamine produces upregulation of muscarinic receptors and augments REMS during withdrawal. After obtaining two, six-hour baseline sleep recordings, beginning at 0900, independent groups of rats were administered either scopolamine or saline every morning for seven days. Six hour sleep recordings were obtained following the first and seventh day of injection and during the two subsequent withdrawal days. After obtaining the last sleep recording the rats were sacrificed and the following brain areas removed: cerebral cortex, hippocampii, caudate nuclei, brainstem, and cerebellum. 3H-QNB was used as the ligand to assess for changes in muscarinic receptor binding. Compared to baseline, scopolamine produced a significant decrease in REMS during the period of drug administration. During the withdrawal days, however, REMS increased during the morning period. Compared to the saline group, the scopolamine treated animals had increased muscarinic receptor binding in the caudate and hippocampus; no significant change in receptor density was observed in the cortex, brainstem or cerebellum.


Characterisation of the complete mitochondrial genome of Bactrocera ruiliensis (Diptera: Tephritidae), with its phylogenetic analysis.
The complete mitochondrial genome (mitogenome) of the Bactrocera ruiliensis (Diptera: Tephritidae: Dacinae) is sequenced and annotated. The mitochondrial genome is 15,870 bp (GenBank No. MN477221) and has an A + T content of 73.3% (A 39.2%; C 16.2%; G 10.3%, and T 34.4%), which is the classical structure for insect mitogenome. All PCGs started with ATN, except ATP8, which is started with TTG; 12 PCGs use TAR (TAA/TAG) as the stop codon, except COX1, which ends with single T--. The phylogenetic tree confirms that B. ruiliensis clustered with other Bactrocera species. This study enriches the mitogenomes of the fruit flies.


Cutaneous immune-related adverse events to checkpoint inhibitors.
The development of immunotherapy has led to a paradigm shift in the treatment of both solid and hematologic malignancies. As immunomodulatory therapies are employed with increasing frequency, a greater number of immune-related adverse reactions are being reported, and the majority of these involve the skin. As a result, dermatologists are increasingly becoming involved in the management of these cutaneous adverse reactions-often providing critical recommendations regarding ongoing cancer treatment. Cutaneous immune-related adverse reactions can vary significantly from patient to patient, making early recognition and timely intervention imperative to mitigate associated morbidity and potential treatment interruption. Although there is considerable overlap in the cutaneous adverse events caused by these immune checkpoint inhibitors, specific eruptions are characteristically associated with particular checkpoint inhibitors. In addition, a patient's comorbidities or immune status can play a significant role in the presentation and management of such adverse reactions. This review characterizes and provides management guidelines for the various cutaneous toxicities associated with checkpoint inhibitor therapy, including CTLA-4 inhibitors, PD-1 inhibitors, and PD-L1 inhibitors. © 2020 Elsevier Inc. All rights reserved.


Coronary flow velocity reserve in the three main coronary arteries assessed with transthoracic Doppler: a comparative study with quantitative coronary angiography.
The purpose of this study was to evaluate the potential of combined use of transthoracic Doppler echocardiographic coronary flow velocity reserve (CFVR) measurements and findings of retrograde coronary flow in the three main coronary arteries for the assessment of borderline (angiographic diameter stenosis, 50%-75%) and high-grade (angiographic diameter stenosis, 76%-100%) coronary artery stenoses. A total of 108 patients scheduled for coronary angiography because of chest pain or acute coronary syndromes were studied. CFVR was measured during adenosine-induced hyperemia in the mid to distal segments of the left anterior descending coronary artery, the marginal branches of the left circumflex coronary artery, and the posterior descending coronary artery, with peak CFVR (pCFVR) <2.0 implying hemodynamic significant stenosis. CFVR results were compared with results from quantitative coronary angiography, with stenosis severity in the left main and three major coronary arteries divided into three groups: (1) diameter stenosis 0% to 49%, (2) diameter stenosis 50% to 75%, and (3) diameter stenosis 76% to 100%. In patients with antegrade flow in the relevant coronary artery segment, CFVR was successfully measured in the mid to distal left anterior descending artery, the marginal branches of the left circumflex artery, and the posterior descending artery in 97%, 63%, and 75% of patients, respectively. CFVR was significantly different among the stenosis groups, with pCFVR of 2.79 ± 0.77 in group 1, 2.01 ± 0.72 in group 2, and 1.50 ± 0.69 in group 3 (P < .001 among groups). Angiography confirmed retrograde flow in seven of the nine arteries found by transthoracic echocardiography. Findings of pCFVR <2.0 or retrograde coronary artery flow correctly identified 42 of 49 patients with stenoses in group 3, with sensitivity, specificity, and positive and negative predictive values of 86%, 70%, 70%, and 85%, respectively. In group 2, pCFVR values were widely distributed above or below the defined pCFVR cutoff value. CFVR measurement in the mid to distal left anterior descending artery was feasible in almost all patients, and in the marginal branches of the left circumflex artery and the posterior descending artery in two thirds and three quarters of patients, respectively. Use of the combined echocardiographic criteria had high precision for diagnosing severe coronary stenoses (diameter stenosis, 76%-100%). The functional significance of angiographically borderline stenoses (diameter stenosis, 50%-75%) may be further differentiated by the use of CFVR measurements.


Characterization of the IgA1 protease from the Brazilian purpuric fever strain F3031 of Haemophilus influenzae biogroup aegyptius.
Brazilian purpuric fever is a severe vascular disease caused by an invasive clone of Haemophilus influenzae biogroup aegyptius, which normally causes self-limiting eye infections. A previous genome subtraction procedure resulted in the isolation of a DNA fragment, which encodes a putative IgA1 protease, specific to the F3031 Brazilian purpuric fever type strain. Cloning and sequencing of the entire F3031 iga1 gene showed that the subtracted DNA fragment encompasses the iga1 region encoding the active site and the cleavage specificity determinant of the protein, which are different from the cognate regions of the proteases produced by other H. influenzae strains. Western and IgA cleavage assays together with clustering analysis showed that the F3031 IgA1 protease is most similar to the type 2 proteases produced by H. influenzae type c and e strains. Analysis of the promoter region of the F3031 iga1 gene revealed the presence of Fur binding sites. However, real-time PCR analysis and transcriptional fusion assays showed that the expression of iga1 is not regulated by iron or hemin under the conditions tested.


Efficacy of Essential Oil Mouthwashes With and Without Alcohol on the Plaque Formation: A Randomized, Crossover, Double-Blinded, Clinical Trial.
Essential oil (EO) mouthwash has been considered as one of the effective chemical agents as an adjunct to mechanical plaque control, without adverse effects compared with chlorhexidine (pigmentation, changes of taste, and formation of supragingival calculus), which limits its continuous use. New EO alcohol-based has emerged with questions regarding contraindications for its daily use. To compare the efficacy of EO mouthwashes with and without alcohol on the early supragingival and subgingival plaque formation using a plaque-free zone score system. This study was a crossover, randomized, double-blind clinical trial. Eleven participants, totaling 396 sites of evaluation, remained 4 days with no mechanical oral hygiene control and only used EO mouthwash with (control) and without alcohol (test) during this period. The presence of the plaque-free zone was recorded every 24 hours. Friedman and Wilcoxon tests were used with a 5% significance level. The control group showed a more significant number of buccal surfaces free of plaque at 48, 72, and 96 hours compared with the test group. Both groups presented satisfactory efficacy up to 72 hours with a significant difference in favor of the control group. The presence of subgingival plaque on both the proximal and free surfaces was significantly higher in the test group. EO with alcohol presented better results in retarding the early supragingival and subgingival plaque formation compared with EO without alcohol.


Feasibility and acceptability of using an IVRS to assess decision making about sun protection.
We developed an interactive voice response system (IVRS), an automated telephone survey technology, to assess real-time decision making about sun protection. We examined the feasibility and acceptability of IVRS in this electronic health (eHealth) context. Melanoma patients who underwent surgery referred their first-degree relatives (FDRs) for participation. Eligible FDRs were contacted twice daily (12:30 pm; 5:00 pm) over 14 consecutive days via IVRS to complete a survey about their sun protection behaviors and decisions about those behaviors. Of the 81 eligible FDRs, 69 (85%) consented to the study, and 53 (77%) completed the study. We assessed adherence with the IVRS via the number and pattern of missing survey items across all answered IVRS calls. About 80% of scheduled IVRS calls were answered (1316/1652). Most surveys (93%) of the IVRS-answered calls were completed. To examine acceptability, we analyzed the program satisfaction survey data collected at the end of the study. Most participants viewed the IVRS to be highly acceptable and easy to use. These findings illustrate that use of real-time IVRS data collection regarding sun protection decision making is feasible and acceptable to higher-risk research participants and could thus be used with time and location-sensitive eHealth support to enhance sun protection decision making.


Percutaneous radiofrequency ablation of clinical stage I non-small cell lung cancer.
This study aimed at retrospectively evaluating the outcomes of radiofrequency ablation of clinical stage I non-small cell lung cancer. This study was carried out on 50 nonsurgical candidates (29 men and 21 women; mean age, 74.7 years) with clinical stage I (IA, n = 38; IB, n = 12) histologically proven non-small cell lung cancer. A total of 52 tumors were treated with 52 ablation sessions. Radiofrequency ablation was performed percutaneously under computed tomography fluoroscopic guidance. The outcomes of radiofrequency ablation were evaluated, including toxicity, local efficacy, and patient survival. Toxicity was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. Local efficacy was evaluated by using computed tomography scan with a contrast medium. The overall, cancer-specific, and disease-free survivals were estimated with Kaplan-Meier analysis. Grade 2 and 3 adverse events occurred after 6 (12%) and 3 (6%) of the 52 sessions, respectively. The median follow-up period was 37 months. Local progression was observed in 16 (31%) of the 52 tumors. The median survival time was 67 months. The overall, cancer-specific, and disease-free survivals were 94%, 100%, and 82% at 1 year, 86%, 93%, and 64% at 2 years, and 74%, 80%, and 53% at 3 years, respectively. Radiofrequency ablation of clinical stage I non-small cell lung cancer was minimally invasive and provided promising patient survival, although the local efficacy needs to be improved.


Determining human-coronavirus protein-protein interaction using machine intelligence.
The Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) virus spread the novel CoronaVirus -19 (nCoV-19) pandemic, resulting in millions of fatalities globally. Recent research demonstrated that the Protein-Protein Interaction (PPI) between SARS-CoV-2 and human proteins is accountable for viral pathogenesis. However, many of these PPIs are poorly understood and unexplored, necessitating a more in-depth investigation to find latent yet critical interactions. This article elucidates the host-viral PPI through Machine Learning (ML) lenses and validates the biological significance of the same using web-based tools. ML classifiers are designed based on comprehensive datasets with five sequence-based features of human proteins, namely Amino Acid Composition, Pseudo Amino Acid Composition, Conjoint Triad, Dipeptide Composition, and Normalized Auto Correlation. A majority voting rule-based ensemble method composed of the Random Forest Model (RFM), AdaBoost, and Bagging technique is proposed that delivers encouraging statistical performance compared to other models employed in this work. The proposed ensemble model predicted a total of 111 possible SARS-CoV-2 human target proteins with a high likelihood factor ≥70%, validated by utilizing Gene Ontology (GO) and KEGG pathway enrichment analysis. Consequently, this research can aid in a deeper understanding of the molecular mechanisms underlying viral pathogenesis and provide clues for developing more efficient anti-COVID medications.


Cytotoxic and anti-tumour properties of certain taxa of Umbelliferae with special reference to Centella asiatica (L.) Urban.
Centella asiatica (L.) Urban (Umbelliferae) is commonly used in the Ayurvedic system of medicine to treat various diseases. The present study examines the anti-tumour effect of the crude extract (CE) of Centella asiatica as well as its partially purified fractions (AF) from chromatographic procedures by both in vitro short and long term chemosensitivity and in vivo tumour model test systems. AF dose dependently inhibited the proliferation of the transformed cell lines significantly more than did the CE and other solvent fractions. Fifty percent effective doses on hour 3 exposure to AF were 17 and 22 micrograms/ml for Ehrlich ascites tumour cells (EAC) and Dalton's lymphoma ascites tumour cells (DLA), respectively. However, practically no toxic effects were detected in normal human lymphocytes. AF also significiantly suppressed the multiplication of mouse lung fibroblast (L-929) cells at a concentration of 8 micrograms/ml in long term culture. Oral administration of the extracts (CE and AF) retarded the development of solid and ascites tumours and increased the life span of these tumour bearing mice. Tritiated thymidine, uridine and leucine incorporation assay suggest that the fraction acts directly on DNA synthesis.


What undermines healthy habits with regard to physical activity and food? Voices of adolescents in a disadvantaged community.
This study aimed to illuminate factors that undermine the healthy habits of adolescents from a multicultural community with low socioeconomic status (S.E.S.) in Sweden with regard to physical activity (P.A.) and food, as stated in their own voices. Adolescents (n = 53, 12-13 y/o) were recruited from one school situated in a multicultural community characterized by low S.E.S. Embracing an interpretive approach, 10 focus-group interviews were conducted to produce data for the study. The focus-group interviews were audio recorded, transcribed verbatim, and analysed using qualitative content analysis. The analysis resulted in two major themes: (1) the availability of temptations is large, and support from the surroundings is limited; and (2) norms and demands set the agenda. The adolescents' voices illuminate a profound awareness and the magnitude of tempting screen-based activities as undermining their P.A. and healthy food habits. Moreover, several gender boundaries were highlighted as undermining girls' P.A. and healthy food habits. The adolescents' stories illuminated that it is difficult for them, within their environment, to establish healthy habits with regard to P.A. and food. To facilitate the adolescents' healthy habits, we suggest that support from family, friends, the school, and society at large is essential.


Separation of electrocardiographic from electromyographic signals using dynamic filtration.
Trunk muscle electromyographic (EMG) signals are often contaminated by the electrical activity of the heart. During low or moderate muscle force, these electrocardiographic (ECG) signals disturb the estimation of muscle activity. Butterworth high-pass filters with cut-off frequency of up to 60 Hz are often used to suppress the ECG signal. Such filters disturb the EMG signal in both frequency and time domain. A new method based on the dynamic application of Savitzky-Golay filter is proposed. EMG signals of three left trunk muscles and pure ECG signal were recorded during different motor tasks. The efficiency of the method was tested and verified both with the experimental EMG signals and with modeled signals obtained by summing the pure ECG signal with EMG signals at different levels of signal-to-noise ratio. The results were compared with those obtained by application of high-pass, 4th order Butterworth filter with cut-off frequency of 30 Hz. The suggested method is separating the EMG signal from the ECG signal without EMG signal distortion across its entire frequency range regardless of amplitudes. Butterworth filter suppresses the signals in the 0-30 Hz range thus preventing the low-frequency analysis of the EMG signal. An additional disadvantage is that it passes high-frequency ECG signal components which is apparent at equal and higher amplitudes of the ECG signal as compared to the EMG signal. The new method was also successfully verified with abnormal ECG signals.


Visual cortex damage in a ferret model of ocular hypertension.
We aimed to analyze the changes in the visual cortex of a ferret model of ocular hypertension (OH) using cytochrome oxidase (CO) staining. Experimental. OH was induced in 9 ferrets by means of injection of cultured conjunctival cells into the anterior chamber of the right eye. Three ferrets were used as the controls. CO staining was performed to assess the metabolic intensity at the II-III and IVC layers of the visual cortex. The intensities of CO staining in the right and left II-III layers of the primary visual cortex (V1) in the OH ferrets were 39.8 ± 10.3 and 41.9 ± 9.2 arbitrary units, respectively. In the control ferrets, the intensity was 88.1 ± 8.1 arbitrary units. The intensity of CO staining of the II-III layers obtained from the OH eyes was significantly lower than that from the control eyes (unpaired t test, P < .01). The intensities of CO staining in the right and left IVC layers of V1 in the OH ferrets were 60.3 ± 12.8 and 60.0 ± 13.5 arbitrary units, respectively. In the control ferrets, the intensity was 111.4 ± 9.6 arbitrary units. The CO staining intensity of the IVC layer obtained from the OH eyes was significantly lower than that from the control eyes (unpaired t test, P < .01). The CO staining intensity was reduced in the visual cortex from OH eyes. This study revealed that OH causes metabolic change in the visual cortex.


One in five patients with rapidly and persistently controlled early rheumatoid arthritis report poor well-being after 1 year of treatment.
To identify and characterise a subgroup of patients with early rheumatoid arthritis (RA) reporting not feeling well 1 year after treatment initiation despite achieving optimal disease control according to current treatment standards. This observational study included participants of the Care in early RA trial with a rapid and sustained response (DAS28CRP<2.6) from week 16 until year 1 after starting the first RA treatment. Feeling well was assessed at year 1, using five patient-reported outcomes (PROs): pain, fatigue, physical functioning, RA-related quality of life and sleep quality. K-means clustering assigned patients to a cluster based on these PROs. Cohen's d effect size estimated cluster differences at treatment initiation and week 16, for the five clustering PROs, coping behaviour, illness perceptions and social support. Analyses revealed three clusters. Of 140 patients, 77.9% were assigned to the 'concordant to disease activity' cluster, 9.3% to the 'dominant fatigue' cluster and 12.9% to the 'dominant pain and fatigue' cluster. Large differences in pain and fatigue reporting were found at week 16 when comparing the 'concordant' with the 'dominant pain and fatigue' or the 'dominant fatigue' cluster. Small differences in reporting were found for the other PROs. Illness perceptions and coping style also differed in the 'concordant' cluster. Although most patients reported PRO scores in concordance with their well-controlled disease activity, one in five persistent treatment responders reported not feeling well at year 1. These patients reported higher pain and fatigue, and different illness perceptions and coping strategies early in the disease course.


Combining interscalene brachial plexus block with intravenous-inhalation combined anesthesia for upper extremity fractures surgery: a randomized controlled trial.
A parallel-group randomized controlled trial (RCT) was conducted to evaluate the effect of combining the interscalene brachial plexus block (IBPB) with Intravenous-inhalation combined anesthesia to isolated Intravenous-inhalation anesthesia in the upper extremity fractures surgery of elderly patients. One hundred elderly patients who underwent upper extremity surgery were randomly assigned to received isolated Intravenous-inhalation combined anesthesia (group CI, n = 50) and IBPB associated with Intravenous-inhalation combined anesthesia (group NB, n = 50). Associated side effects, recovery time after operation, as well as the dose of intraoperative vasoactive agents and auxiliary drugs were noted. The two groups were not significantly different in gender (P = 0.539), ages (P = 0.683) and weight (P = 0.212). Five patients (10%) in the group NB and 17 patients (34%) in the group CI suffered from preoperative hypotension (P = 0.004). Besides, lower incidence of other adverse effects such as mental stress, incision pain and hypertension were also found in the group NB; however, the differences were not statistically significant (P > 0.05). The consumption of general anesthetics in the group NB was significantly less than that of the group CI (propofol, P = 0.004; lsoflurane, P < 0.001), and the recovery time of the group NB was significantly shorter than that of the group CI (P = 0.020). Combining IBPB with Intravenous-inhalation combined anesthesia in elderly patients hold a greater potential for upper extremity fractures surgery due to its improved clinical effectiveness and fewer side effects.


Effect of pelvis impact angle on stresses at the femoral neck during falls.
Improved understanding is required of how the mechanics of the fall affect hip fracture risk. We used a hip impact simulator to determine how peak stresses at the femoral neck were affected by pelvis impact angle, hip abductor muscle force, and use of a wearable hip protector. We simulated falls from standing (2 m/s impact velocity) involving initial hip abductor muscle forces of 700 or 300 N. Trials were acquired for impact to the lateral aspect of the greater trochanter, and impact to the pelvis rotated 5°, 10° and 15° anteriorly (positive) or posteriorly (negative). Measures were acquired with and without a commercially available hip protector. During trials, we measured three-dimensional forces with a load cell at the femoral neck, and derived peak compressive and tensile stresses. Peak compressive stress increased 37% (5.91 versus 4.31 MPa; p < 0.0005) and peak tensile stress increased 209% (2.31 versus 0.75 MPa; p < 0.0005) when the pelvis impact angle changed from 15° anterior to -15° posterior. For lateral impacts, the peak tensile and compressive stresses averaged 73% and 8% lower, respectively, in the 700 N than 300 N muscle force condition, but the effect was reversed for anteriolateral or posteriolateral impacts. The attenuation in peak compressive stress from the hip protector was greatest for posteriolateral impacts (-15 to -5°; 36-41%), and least for anteriolateral (+15°; 10%). These results clarify the effects on hip fracture risk during a fall of pelvis impact angle and muscle forces, and should inform the design of improved hip protectors.


Mesenchymal Stem Cells: From Regeneration to Drug Delivery Systems.
Targeting drug delivery has been a focus of researchers in recent years for cancer and other diseases. Many approaches such as liposomes, exosomes, nanoparticles (magnetic), encapsulation etc. have been developed and investigated for their clinical applications. But disadvantages linked to these therapies limit them to be used in clinical settings. Cell based drug delivery systems has emerged as an alternative for these therapies. Among cell types, mesenchymal stem cells (MSCs) proved to a potential cell type for research due to its many characteristics including low immunogenicity, chemotaxis and homing to tumor sites which are considered mandatory for drug delivery. This chapter focuses on the challenges and opportunities in using MSCs as therapeutic carrier of drugs in different ailments.


Impact of Chemoradiation-to-Surgery Interval on Pathological Complete Response and Short- and Long-Term Overall Survival in Esophageal Cancer Patients.
The impact of the neoadjuvant chemoradiation-to-surgery (CRT-S) interval in patients with esophageal cancer is not clear. We aimed to determine the relationship between CRT-S interval and pathological complete response rate (pCR) and overall survival (OS). National Cancer Data Base patients with CRT followed by surgery were studied. CRT-S interval was studied as a continuous (weeks) and categorical variable (quintiles: 15-37, 38-45, 46-53, 54-64, and 65-90 days, with n = 1016, 1063, 1081, 1083, and 938 patients, respectively). A total of 5181 patients were included; 81% had adenocarcinoma. There was a significant increase of pCR rate across quintiles (18%, 21%, 24%, 25%, and 29%, p < 0.001) and per week increase of CRT-S interval [odds ratio (OR) 1.11, p < 0.001]. The 90-day mortality increased as CRT-S increased across quintiles (5.7%, 6.2%, 6.8%, 8.5%, and 8.2%, p = 0.02) and through weeks (OR 1.05, p = 0.03). Mean OS across CRT-S quintiles was 36.4, 35.1, 33.9, 33.2, and 30.7 months, respectively. Multivariate Cox regression showed significantly worse OS per week increase in CRT-S interval [hazard ratio (HR) 1.02, p = 0.02], especially among the last quintile (CRT-S = 65-90 days: HR 1.2, p = 0.009). The squamous cell carcinoma (SCC) and pCR groups had similar OS across CTR-S intervals. Despite the higher pCR rate with longer CRT-S interval, surgery is optimal less than 65 days after CRT to avoid worse 90-day mortality and achieve better OS. In patients with SCC and those with pCR, prolonged CRT-S interval had no impact on OS. Further studies are needed to consolidate our findings.


Residual stresses at the stem-cement interface of an idealized cemented hip stem.
During the operation of total hip arthroplasty, when the cement polymerizes between the stem implant and the bone, residual stresses are generated in the cement. The purpose of this study was to determine whether including residual stresses at the stem-cement interface of cemented hip implants affected the cement stress distributions due to externally applied loads. An idealized cemented hip implant subjected to bending was numerically investigated for an early post-operative situation. The finite element analysis was three-dimensional and used non-linear contact elements to represent the debonded stem-cement interface. The results showed that the inclusion of the residual stresses at the interface had up to a 4-fold increase in the von Mises cement stresses compared to the case without residual stresses.


Comparison of the performance of Tubex® TF, widal immunodiagnostic assay and blood culture in diagnosis of enteric fever in a private tertiary care hospital Peshawar, Pakistan.
To determine and compare the performance of TUBEX®TF, Widal test and blood culture in the diagnosis of enteric fever. The retrospective study was conducted at the Northwest General Hospital and Research Centre, Hayatabad, Peshawar, Pakistan, and comprised medical record from January to December 2018 related to patients who presented with fever. Typhidot, Widal test and blood culture had been performed as part of evaluation. Data was analysed using SPSS 16. Of the 241 patients, 68(28.21%) tested positive for salmonella in blood culture. Among them, TUBEX®TF was positive in 29(42.64%) and Widal was positive in 25(36.76%). TUBEX®TF had positive predictive value 33.33%, negative predictive value 71.77%, sensitivity 42.65% and specificity 62.34%. The corresponding values for Widal were 24.51%, 69.06%, 36.76% and 55.49%. Sensitivity, specificity, positive predictive value and negative predictive value of TUBEX®TF and Widal test were very low compared to blood culture.


Dacarbazine (DTIC) in malignant melanoma: reduced toxicity with protection from light.
Dacarbazine (dimethyl triazeno imidazole carboxamide, DTIC, NSC-45388), is the most effective oncolytic agent in the treatment of advanced malignant melanoma, but its side effects are considerable. These side effects are thought to be due to its photodegradation, which occurs within a few minutes of exposure to light. Fifteen patients with metastatic malignant melanoma were treated with dacarbazine protected from light, without troublesome haematological or other side effects. There was complete disappearance of metastases in 27% of cases and partial response in 47%. All lesions in skin, lungs and liver responded, but only half of the lymph node metastases showed response. It is suggested that dacarbazine should be protected from light during preparation and administration so as to reduce toxicity without influencing response.


Interleukin-17 increased progesterone secretion by JEG-3 human choriocarcinoma cells.
JEG-3 choriocarcinoma cell line has previously been reported to express a receptor for interleukin (IL)-17. The involvement of IL-17 in the production of progesterone and human chorionic gonadotropin by placental trophoblast has not been investigated. The present study investigated the in vitro effect of IL-17 on progesterone and human chorionic gonadotropin (hCG) secretion by JEG-3 cells. Both hormones were quantified using enzyme-linked immunosorbent assays. The results showed that IL-17 significantly increased progesterone secretion at 6 (P < 0.001) and 24 (P < 0.01) hr, while this cytokine had no effect on hCG secretion. Interleukin-17 may regulate the function of JEG-3 cells through increased progesterone secretion.


Intra-subject approach for gait-event prediction by neural network interpretation of EMG signals.
Machine learning models were satisfactorily implemented for estimating gait events from surface electromyographic (sEMG) signals during walking. Most of them are based on inter-subject approaches for data preparation. Aim of the study is to propose an intra-subject approach for binary classifying gait phases and predicting gait events based on neural network interpretation of sEMG signals and to test the hypothesis that the intra-subject approach is able to achieve better performances compared to an inter-subject one. To this aim, sEMG signals were acquired from 10 leg muscles in about 10.000 strides from 23 healthy adults, during ground walking, and a multi-layer perceptron (MLP) architecture was implemented. Classification/prediction accuracy was tested vs. the ground truth, represented by the foot-floor-contact signal provided by three foot-switches, through samples not used during training phase. Average classification accuracy of 96.1 ± 1.9% and mean absolute value (MAE) of 14.4 ± 4.7 ms and 23.7 ± 11.3 ms in predicting heel-strike (HS) and toe-off (TO) timing were provided. Performances of the proposed approach were tested by a direct comparison with performances provided by the inter-subject approach in the same population. Comparison results showed 1.4% improvement of mean classification accuracy and a significant (p < 0.05) decrease of MAE in predicting HS and TO timing (23% and 33% reduction, respectively). The study developed an accurate methodology for classification and prediction of gait events, based on neural network interpretation of intra-subject sEMG data, able to outperform more typical inter-subject approaches. The clinically useful contribution consists in predicting gait events from only EMG signals from a single subject, contributing to remove the need of further sensors for the direct measurement of temporal data.


Giant abdominal stromal cell tumour diagnosed at endoscopic ultrasonography: is there a need for systematic use of endoscopic ultrasonography in submucosal gastric tumours?
A giant abdominal stromal cell tumour was diagnosed at endosonography performed for a relatively small gastric submucosal lesion. Although the case is rare, it draws attention to the need for systematic investigations with endoscopic ultrasonography in any submucosal lesion.


Aspects of spinal deformity in familial dysautonomia (Riley-Day syndrome).
Familial dysautonomia (FD) is a rare autosomal recessive disease occurring in Jews of Ashkenazi descent, with only some 500 recognized cases. The causative gene was identified on chromosome 9. FD is of considerable orthopedic interest, because of the prevalence of skeletal deformity. About 90% of surviving dysautonomic children will develop a spinal curvature, commonly a scoliosis. The scoliotic curve is usually kyphotic rather than lordotic, and appears during the first decade of life. Fifty-one of the 90 reported cases of familial dysautonomia in Israel involved patients who were seen at the scoliosis clinic for assessment and treatment of their spinal deformities. Most of the patients presented with a scoliotic deformity associated in 37 cases with an increased thoracic kyphosis. In our series orthotic treatment and physiotherapy were found to be minimally successful at best. Surgical treatment of the spine was performed in 13 of 51 patients in this series. A retrospective review of these patients' charts and radiographs was carried out. Six years of follow-up are reported. The primary indication for surgery was progression of the spinal curve. Only posterior spinal fusions were performed. Anterior transthoracic procedures were avoided in spite of the significance of the kyphotic deformity, because of the frequency of pulmonary complications. Harrington distraction and compression instrumentation was used. Three-millimeter compression rods were used in a distraction mode in thin, young children. "Harri-Luque" segmental sublaminar wiring technique and Wisconsin spinous process segmental wiring was used in some. In all cases, the spine fusion was supplemented by bank bone only, to avoid the additional trauma of graft removal. We believe that surgical intervention is advantageous, if done early in the evolution of spinal deformity. Greater technical difficulties and a higher complication rate were encountered in this series relative to the problems usually seen after spinal deformity surgery in children; this is all the more important in a disease in which general anesthesia is an additional major complicating factor. It is hoped that the improved physical condition now seen after early gastrostomy and fundoplication will aid in reducing this high complication rate. Only a small degree (about 25%) of correction was achieved in the majority of patients. Some of this apparent rigidity derived from the inability to apply sufficient instrumental corrective force because of the friable osteoporotic bone. After surgery, there was a marked decrease in the frequency of pneumonia and an improvement in the degree of ataxia, for reasons not understood, which led to an obvious improvement in the quality of life.


Hybrid Inside-Out-Outside-In Meniscal Repair Through a Small Skin Incision.
Although the updated generation of all-inside devices for meniscal repair is more convenient to deploy and can provide comparable clinical outcomes with those of the inside-out procedure, the latter is still a very useful technique, giving many advantages over the former. The critical drawback of the conventional inside-out technique is the need for preparation of the accessory incision to prevent the risk of soft-tissue entrapment and neurovascular injury while retrieving the exiting meniscal needles, especially at the posterior corner of the knee. To minimize the space volume of the incision, a small, bluntly dissected track guided by the first exiting meniscal needle is sufficient in our hybrid inside-out-outside-in technique. The guiding cannula for the first meniscal needle passage is a commercial inside-out device, whereas the guiding cannula for retrieval in the subsequent meniscal needle passages is a spinal needle applied in an outside-in manner via the small track. Subsequent meniscal needles can be inserted in an inside-out or outside-in manner according to the design of the suture construct.


[Matching training to practice: reworking the training paradigm.]
Due to the increasing complexity of surgical diseases and continuous technological advances, qualifications for general surgeons require an integral practice in order to obtain better results. General surgeons in practice must be capable of making the initial diagnosis and management of a diverse set of surgical conditions and prompt referral to a subspecialist when appropriate. Redesigning surgical training should take into account the needs of training future general surgeons while still preserving some training in the basic aspects of general surgery.


The secret of a natural blond.
Elucidating the molecular mechanisms responsible for changes in gene expression is important for understanding the evolution of morphological traits. A new study identifies the molecular basis of the association between KITLG and blond hair color, presenting an intriguing example of how a single DNA base-pair change in an upstream regulatory element can cause relatively large and specific downstream changes in phenotype.


Autoinhibition of the GEF activity of cytoskeletal regulatory protein Trio is disrupted in neurodevelopmental disorder-related genetic variants.
TRIO encodes a cytoskeletal regulatory protein with three catalytic domains-two guanine exchange factor (GEF) domains, GEF1 and GEF2, and a kinase domain-as well as several accessory domains that have not been extensively studied. Function-damaging variants in the TRIO gene are known to be enriched in individuals with neurodevelopmental disorders (NDDs). Disease variants in the GEF1 domain or the nine adjacent spectrin repeats (SRs) are enriched in NDDs, suggesting that dysregulated GEF1 activity is linked to these disorders. We provide evidence here that the Trio SRs interact intramolecularly with the GEF1 domain to inhibit its enzymatic activity. We demonstrate that SRs 6-9 decrease GEF1 catalytic activity both in vitro and in cells and show that NDD-associated variants in the SR8 and GEF1 domains relieve this autoinhibitory constraint. Our results from chemical cross-linking and bio-layer interferometry indicate that the SRs primarily contact the pleckstrin homology region of the GEF1 domain, reducing GEF1 binding to the small GTPase Rac1. Together, our findings reveal a key regulatory mechanism that is commonly disrupted in multiple NDDs and may offer a new target for therapeutic intervention for TRIO-associated NDDs.


Molecular characteristics of the Mycobacterium tuberculosis LAM-RUS family prevalent in Central Russia.
We analyzed IS6110-associated polymorphisms in the phospholipase C genes of 107 isolates of Mycobacterium tuberculosis selected to be representative of isolates circulating in central Russia. We found that the majority of Latin American-Mediterranean family strains contained an insertion in a unique position in the plcA gene, suggesting a common ancestor. This insertion can serve as a specific genetic marker for this group, which we designate the LAM-RUS family.


Simulation Study of Xylitol-Mediated Effect on NaCl Diffusion Behavior in Cured Pork Tenderloin.
Polyhydroxy alcohol-mediated curing has great potential for producing low-salt cured meat products. This study investigated the mass transfer kinetics and the one-way diffusion simulation of sodium chloride (NaCl) during the curing process. Furthermore, Fick's second law determined the NaCl diffusion coefficient (De) of xylitol-mediated cured pork tenderloin. The results demonstrated that adding xylitol could reduce the De of NaCl. The De of NaCl, calculated using the one-way model, was 1.29 × 10-9 m2·s-1, 1.22 × 10-9 m2·s-1, 1.2 × 10-9 m2·s-1, and 1.15 × 10-9 m2·s-1 when the amount of xylitol added was 0%, 4%, 8%, and 12% (w/w), respectively. This result agrees with the predicted values from the power function time-varying model. Moreover, a three-dimensional simulating model of mass transfers constructed using COMSOL Multiphysics was developed to evaluate the NaCl diffusion in pork tenderloin during the curing process. This model has high accuracy and can be used to describe the diffusion of NaCl in curing. Overall, this study provided a foundation for NaCl diffusion and distribution during the curing process.


A bibliometric analysis of U.S.-based research on the Behavioral Risk Factor Surveillance System.
Since Alan Pritchard defined bibliometrics as "the application of statistical methods to media of communication" in 1969, bibliometric analyses have become widespread. To date, however, bibliometrics has not been used to analyze publications related to the U.S. Behavioral Risk Factor Surveillance System (BRFSS). To determine the most frequently cited BRFSS-related topical areas, institutions, and journals. A search of the Web of Knowledge database in 2013 identified U.S.-published studies related to BRFSS, from its start in 1984 through 2012. Search terms were BRFSS, Behavioral Risk Factor Surveillance System, or Behavioral Risk Survey. The resulting 1,387 articles were analyzed descriptively and produced data for VOSviewer, a computer program that plotted a relevance distance-based map and clustered keywords from text in titles and abstracts. Topics, journals, and publishing institutions ranged widely. Most research was clustered by content area, such as cancer screening, access to care, heart health, and quality of life. The American Journal of Preventive Medicine and American Journal of Public Health published the most BRFSS-related papers (95 and 70, respectively). Bibliometrics can help identify the most frequently published BRFSS-related topics, publishing journals, and publishing institutions. BRFSS data are widely used, particularly by CDC and academic institutions such as the University of Washington and other universities hosting top-ranked schools of public health. Bibliometric analysis and mapping provides an innovative way of quantifying and visualizing the plethora of research conducted using BRFSS data and summarizing the contribution of this surveillance system to public health.


ACOG Committee Opinion No. 526: Standardization of practice to improve outcomes.
Protocols and checklists have been shown to improve patient safety through standardization and communication. Standardization of practice to improve quality outcomes is an important tool in achieving the shared vision of patients and their health care providers.


The disclosure decisions of parents who conceive children using donor eggs.
To identify variables that influence the disclosure decisions of parents who conceive children using donor eggs and to compare such variables among disclosing, nondisclosing, and undecided families. Exploratory, comparative, descriptive. A university hospital-assisted reproductive technology program in the Midwest. Thirty-one couples with children conceived with anonymously donated eggs. Audiotaped telephone interviews, measures of social support and family environment, and a demographic survey. Content analysis of interview transcripts and comparison of recurring themes among groups. The majority of parents intended disclosure. Dominant themes among disclosing parents included the belief that a child has a right to know and concerns about the harmful effects of family secrets. Among nondisclosing parents, common themes were knowing of no compelling reason to tell and perceiving potential harm in telling. Undecided parents reported concerns about how and when to tell and the child's possible reaction. Parents in all groups expressed concern about their disclosure decisions. Dominant decisional influences were beliefs and values and concerns about possible harm. Longitudinal study is needed to determine the impact of disclosure decisions on children, families, and society.


Use of premedication with intravenous immune globulin in Kawasaki disease: A retrospective review.
Kawasaki disease (KD) is a significant febrile illness in children and is the leading cause of acquired pediatric heart disease in developed countries. Its recommended treatment is high-dose intravenous immune globulin (IVIG) plus aspirin. However, IVIG-related adverse events are seen frequently in this population. Premedication is commonly used to reduce this risk, but evidence supporting this practice is conflicting. Ultimately, practices vary among institutions and no standard guidelines regarding IVIG premedication currently exist. Electronic medical records for pediatric patients presenting to an academic, tertiary care medical center diagnosed with KD and who received at least one dose of IVIG were reviewed for: patient demographics, treatment characteristics, premedication use, adverse events, and coronary abnormalities at discharge. Descriptive statistics were used to evaluate study findings. Sixty-six patients receiving a total of 81 distinct IVIG administrations were evaluated. Most patients (64/66, 97%) were premedicated prior to infusion with 26% of patients (17/66) experiencing an IVIG-related adverse event, totaling 25 documented adverse events. The most common events included chills and vomiting. Overall, the average duration of hospitalization was 4.37 days. Despite appropriate medication management, five patients (7.6%) developed coronary abnormalities. Practitioners demonstrated a widespread use of premedication for IVIG. However, 26% of patients still experienced an adverse event. While premedication was not shown to have an adverse impact on patient outcomes, it also did not demonstrate a notable reduction from a historic adverse event incidence.


A prospective study of 39 patients with trigeminal neuralgia treated with percutaneous balloon compression.
Trigeminal neuralgia is the most common facial pain. It may be treated with percutaneous balloon compression (PBC), which is considered to be a safe and efficient procedure. The purpose of this study was to review our results with PBC and to assess the factors influencing the outcome. A multivariate analysis was used to study 39 patients during a 50-month postoperative period. There was predominance of the female gender (54%), the right side of the face (84%) and V2V3 roots of trigeminal nerve (33%). The mean age was 62.3 years. No major complications or deaths occurred. Among all variables, postoperative hypoesthesia was the single prognostic factor capable of positively influencing the results (p=0.02). Most patients (80%) were pain-free after 50 months with a 90% satisfaction rate. PBC was a safe procedure with low morbidity, no mortality, high approval ratings, and was an important improving on patients' quality of life.


An unusual case of severe haematemesis: a cautionary tale.
We present a case of pancreatitis with secondary pseudoaneurysm formation in a branch of the hepatic artery, which fistulated into the common bile duct following endoscopic retrograde cholangiopancreatography. This aneurysm manifested itself clinically with recurrent haematemesis, and was treated by embolisation of the anterior and posterior branches of the right hepatic artery.


Investigating the anti-inflammatory effects of high molecular weight secretions from Limosilactobacillus reuteri PTCC 1655 on LPS-stimulated PMA-differentiated THP-1 cells.
This study was done to investigate the anti-inflammatory effects of high molecular weight secretions from Limosilactobacillus reuteri PTCC 1655 probiotic bacteria on lipopolysaccharide (LPS)-stimulated phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells. After culturing the bacterium, the crude cell-free supernatant was fractionated on the basis of molecular weights using ultrafiltration. Also, a heat-killed and sonicated fraction was obtained from the biomass of the bacterial culture. All fractions were used to measure their anti-inflammatory effects on PMA-differentiated THP-1 cells following LPS stimulation by quantifying various cellular markers of inflammation. The results demonstrated that various L. reuteri PTCC 1655-derived fractions, especially the >100 kDa supernatant fraction decreased some of the inflammatory cytokines and mediators, including tumour necrosis factor-α, interleukin-1, nitric oxide, cyclooxygenase-2, matrix metalloproteinase-9 and interleukin-6, which are critical for the pathogenesis of some inflammatory diseases. It is concluded that the L. reuteri PTCC 1655-derived high molecular weight fractions significantly reduce inflammation and therefore could be appropriate candidates for future medical studies. Providing new insights about the significance of L. reuteri PTCC 1655-derived extracts and their potential to modulate inflammation.


Revascularization for chronic critical lower limb ischemia in octogenarians is worthwhile.
Advanced age is considered a relative contraindication for surgical revascularization in patients with peripheral arterial occlusive disease. Our aim was to analyze the usefulness of endovascular and surgical revascularization in patients older than 80 years with chronic critical leg ischemia (CLI). Our hypothesis was that the clinical benefit of lower extremity revascularization is limited in octogenarians. This was a prospective cohort study with a 1-year follow-up. Subjects included a consecutive series (January 1999 to June 2004) of patients presenting with CLI. Revascularization cohorts were either open surgical or endovascular with conservatively treated patients as a reference group. Prospective follow-up occurred after 30 days and 2, 6, and 12 months. The primary end point was sustained clinical success, defined as a categorical upward shift in clinical symptoms according to Rutherford, without major amputation and without the need for repeated target extremity revascularization (TER). Secondary clinical success was defined accordingly, including repeated TER. Mortality, major amputation, and TER were separately calculated end points. All results were stratified for age categories of nonoctogenarians (<80 years) and octogenarians (> or =80 years). Cumulative outcome was determined by the Kaplan-Meier method, and differences were assessed by log-rank tests. Multivariable analysis was performed by using Cox proportional regression. A total of 376 patients (158 women; mean age, 75.8 +/- 10.7 years) with 416 critically ischemic limbs were analyzed. Overall, 150 patients (39.9%) were older than 80 years, and 85 limbs were treated surgically (26 octogenarians; 30.6%), 207 limbs (96 octogenarians; 46.4%) were treated by endovascular means, and 124 limbs (45 octogenarians; 36.3%) were treated conservatively, including delayed revascularization procedures. Both sustained and secondary clinical success rates, as well as limb salvage rates, were higher in the revascularization cohorts as compared with conservatively treated patients, regardless of age category (P < .001, P < .001, and P = .006, respectively, by Cox proportional hazard model). Mortality was significantly higher in octogenarians (P = .006 by Cox proportional hazard model), particularly within 30 days after surgical revascularization (hazard ratio, 5.35; 95% confidence interval, 1.15-24.9). Patient age category did not affect the rate of major amputations or TER. Individually tailored revascularization improves the outcome of CLI in octogenarians as well as in nonoctogenarians; even so, endovascular revascularization should be preferred in octogenarians because of the higher mortality associated with surgery.


Hookah use among college students from a Midwest University.
National data indicate nearly a quarter of college students smoked from a hookah at some point in their lifetime regardless of gender. To address this issue, researchers assessed the perceptions, knowledge, beliefs of hookah users at a large Midwestern University and also determined what other drug related high-risk behaviors were associated with this behavior. An anonymous, online survey was sent to 2,000 randomly selected undergraduate students from a large Midwestern University. Researchers used a cross sectional research design to determine the prevalence and motivating factors associated with hookah use. Respondents included 438 individuals (60% female) with an average age of 23.1 (SD = 12.32), yielding a response rate of 22%. Approximately 15.4% of the sample had previously smoked hookah, while 6% used hookah within the past 30 days. Common motivating factors associated with smoking hookah included socializing/partying (29%), peer influence (27%), and for relaxation (25%). Correlations were calculated comparing hookah use to other high risk behaviors with the two highest correlations consisted of 30-day tobacco use (r = 0.67) and marijuana (r = 0.39). The results from this study suggest hookah use is limited to a small percentage of students. Students appear to smoke hookah for social reasons and underestimate the addictive properties associated with the product. Researchers and practitioners need to develop and evaluate specific interventions to educate college students about the health hazards associated with hookah use.


Joint effects of carbon nanotubes and copper oxide nanoparticles on fermentation metabolism towards Saccharofermentans acetigenes: Enhancing environmental adaptability and transcriptional expression.
In this study, the joint effects of widely used copper oxide nanoparticles (CuO NPs) and multi-walled carbon nanotubes (MWCNTs) on the fermentation metabolism of a model acetogenic bacterium Saccharofermentans acetigenes were investigated and the underlying mechanisms were further explored. The presence of sole CuO NPs or MWCNTs severely inhibited the acetate generation, while their co-existences did not further decrease the acetate yield as expected. Further analysis indicated the joint effects facilitated the enhancement of bacterial stimulus response to the environment and interspecies communication, which improved adaptive capacity to the adverse environment involved in nanomaterials. Meanwhile, the co-existence reduced inhibitory effects of sole nanomaterial on the gene expressions and catalytic activities of key enzymes involved in glycolysis and pyruvate metabolism. Therefore, the joint effects could enhance environmental adaptation of S. acetigenes and transcriptional expressions of key enzymes for acetic acid production-related processes, alleviating the inhibition of CuO NPs to acetate production.


Combination of adenoviral virotherapy and temozolomide chemotherapy eradicates malignant glioma through autophagic and apoptotic cell death in vivo.
Conditionally replicative adenoviruses (CRAds) represent a novel treatment strategy for malignant glioma. Recent studies suggest that the cytopathic effect elicited by these vectors is mediated through autophagy, a form of programmed cell death. Likewise, temozolomide (TMZ), a chemotherapeutic agent used for the treatment of malignant gliomas, also triggers autophagic cell death. In this study, we examined the potential to combine the two treatments in the setting of experimental glioma. In vitro, pretreatment with TMZ followed by CRAd-Surivin-pk7 enhanced cytotoxicity against a panel of glioma cell lines. Western blot analysis showed increased expression of BAX and p53, decreased expression of BCL2 and elevated level of APG5. Treatment with TMZ followed by CRAd-Survivin-pk7 (CRAd-S-pk7) led to a significant over-expression of autophagy markers, acidic vesicular organelles and light-chain 3 (LC3). These results were further evaluated in vivo, in which 90% of the mice with intracranial tumours were long-term survivors (>100 days) after treatment with TMZ and CRAd-S-pk7 (P<0.01). Analysis of tumours ex vivo showed expression of both LC3 and cleaved Caspase-3, proving that both autophagy and apoptosis are responsible for cell death in vivo. These results suggest that combination of chemovirotherapy offers a powerful tool against malignant glioma and should be further explored in the clinical setting.


Design, Implementation, and Evaluation of a Learning Needs Assessment for Nursing Professional Development Practitioners.
The purpose of this descriptive study was to highlight how a system-level education department operationalized the 2022 Association for Nursing Professional Development Scope and Standards of Practice into a learning needs assessment (LNA) survey. This was a collaborative approach to LNA design, implementation, and evaluation. The LNA conducted among nursing professional development practitioners determined areas for educational improvement, barriers to nursing professional development, and identified standards and competencies critical to improving knowledge acquisition.


Arabidopsis NADPH oxidases, AtrbohD and AtrbohF, are essential for jasmonic acid-induced expression of genes regulated by MYC2 transcription factor.
To clarify genetically the involvement of two Arabidopsis NADPH oxidases (AtrbohD and AtrbohF) in the jasmonic acid (JA) signaling pathway, we characterized single knockout mutants lacking either Atrboh. The accumulation of reactive oxygen species (ROS) and expression of the genes regulated by MYC2, a transcription factor involved in the JA-evoked response, were significantly suppressed by treatment with methyl JA (MeJA) in both mutants. Further experiments using knockout mutants lacking CORONATINE-INSENSITIVE1 (COI1), a master regulator of the JA-evoked response, and MYC2 indicated a possibility that the production of ROS via Atrbohs depends on the function of COI1, but not MYC2.


Skeletal muscle: an unusual site of distant metastasis in gastric carcinoma.
Gastric cancer metastatic to skeletal muscle is an unusual entity. Surgery, systemic chemotherapy, or radiotherapy to the metastatic mass can be treatment options for achiving palliation. A patient with multiple skeletal muscle metastases that occurred during follow-up after gastrectomy and adjuvant chemo-radiotherapy is reported. Magnetic resonance imaging (MRI) demonstrated soft-tissue masses involving the posterior right paralumbar and posterior left paradorsal muscles. Biopsy showed metastatic infiltrating adenocarcinoma. The patient did not respond to palliative chemotherapy. Palliative radiotherapy was administered to the painful mass. Based on this case, the diagnosis of muscle metastases and treatment options for palliation are discussed.


A stoichiometric imprinted chelating resin for selective recognition of copper(II) ions in aqueous media.
This work reports the preparation of a new copper(II) ion-imprinted polymer (IIP) material, using 5,6;14,15-dibenzo-1,4-dioxa-8,12-diazacyclopentadecane-5,14-diene (DBDA15C4) and 2-vinylpyridine (VP) as a non-vinylated chelating agent and a functional vinyl monomer, respectively. The Cu2+ ion can form stable complexes with DBDA15C4 and VP. The stoichiometries of Cu2+-DBDA15C4 and ternary Cu2+-DBDA15C4-VP complexes were elucidated using conductometric and spectrophotometric methods, and found to be Cu2+ (DBDA15C4), Cu2+ (DBDA15C4)2 and Cu2+ (DBDA15C4)(VP)2. The results obtained from solution studies were also supported by ab initio theoretical calculations. The resulting ternary complex Cu2+ (DBDA15C4)(VP)2 was copolymerized with ethyleneglycoldimethacrylate, as a cross-linking monomer, via bulk polymerization method. The imprinted copper ion was removed from the polymeric matrix by 0.1 M HNO3. The Cu2+-imprinted polymer particles were characterized by IR spectroscopy and elemental analysis. Optimum pH range for rebinding of Cu2+ on the IIP and equilibrium binding time were 7.0-7.5 and 45 min, respectively. Sorbent capacity and enrichment factor for Cu2+ were obtained as 75.3+/-1.9 micromol g(-1) and 100, respectively. In selectivity study, it was found that imprinting results in increased affinity of the material toward Cu2+ ion over other competitor metal ions with the same charge and close ionic radius. The prepared IIPs were repeatedly used and regenerated for five times without a significant decrease in polymer binding affinities.


Mystixin-7 and mystixin-11 increase cytosolic free Ca2+ and inositol trisphosphates in human A-431 cells.
Mystixin-7 and mystixin-11, small peptides structurally related to corticotropin-releasing factor (CRF), have been shown to attenuate vascular leakage in injured skin. The goal of this study was to characterize changes in cytosolic Ca2+ concentration ([Ca2+]i) in human epidermoid A-431 cells treated with these two peptides and to investigate the mechanisms by which these changes occurred. The resting [Ca2+]i in A-431 cells at 37 degrees C was 76 +/- 2 nM (n = 373). When cells were treated with either peptide, [Ca2+]i increased immediately. The increase depended on the peptide concentration, with a median effective concentration of 299 +/- 9 pM for mystixin-7 and 2.23 +/- 0.04 pM for mystixin-11. The increases also depended on extracellular Ca2+ and were blocked by Cd2+, Co2+, verapamil, and nifedipine. alpha-Helical CRF-(9-41), a synthetic CRF receptor antagonist, and pertussis toxin also blocked the increase in [Ca2+]i induced by the two peptides. Taken together, these results suggest that mystixin-7 and mystixin-11 interact with CRF receptors to activate pertussis-sensitive G proteins coupled to L-type Ca2+ channels that allow an uptake of extracellular Ca2+. Because U-73122, an inhibitor of 1,4,5-inositol trisphosphate production, partially inhibited the increase in [Ca2+]i, we measured inositol trisphosphates in cells stimulated by the two peptides. Both increased inositol trisphosphate levels within 1 min. The increase was inhibited by the removal of extracellular Ca2+ or treatment with U-73122. The results suggest that the Ca2+ influx stimulated by mystixin-7 and mystixin-11 induces an increase in inositol trisphosphates, resulting in a mobilization of Ca2+ from 1,4,5-inositol trisphosphate-sensitive Ca2+ pools.


Plasmid cistrons controlling synthesis and excretion of the exotoxin alpha-haemolysin of Escherichia coli.
The synthesis and secretion of the toxic exoprotein alpha-haemolysin of E. coli PM152 is coded by the transmissible plasmid pHly152 (41 x 10(6) dalton) as shown by the transformation of the plasmid DNA and the isolation of mutants that are specifically altered in the synthesis and transport of haemolysin. These mutants were obtained by chemical mutagenesis and insertion of the ampicillin transposon (Tn3) into pHly152. Tn3 transposition was also used for the identification and the location of the cistrons on pHly152 essential for haemolysis. The EcoRI and HindIII fragments of the haemolytic plasmid pHly152 were cloned and used for the complementation of the haemolysis negative Tn3 insertion mutants. A DNA segment of 3.2 x 10(6) dalton could be thus identified which consists of at least three clustered cistrons necessary for haemolysis. Two of these cistrons are required for the formation of active haemolysin. At least one other cistron seems to be involved in the secretion of active haemolysin through the outer membrane of E. coli. The gene products determined by these cistrons were identified in minicells of E. coli. Their molecular properties were determined and their possible function in the formation and secretion of haemolysin will be discussed.


Nodular rheumatoid arthritis (RA): A distinct disease subtype, initiated by cadmium inhalation inducing pulmonary nodule formation and subsequent RA-associated autoantibody generation.
Nodular rheumatoid arthritis (RA) patients have raised rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) levels, and are more likely to smoke than RA patients without nodules. Subcutaneous and pulmonary rheumatoid nodules (granulomas) frequently co-exist. Pulmonary rheumatoid nodules develop prior to RA development and have the immunological machinery to generate RF and ACPAs. Pulmonary granulomas have been observed in animal models exposed to cadmium (Cd) inhalation. Cigarette smoke increases pulmonary Cd exposure. It has been suggested that dust and cigarette smoke co-exposure increases localised pulmonary Cd adsorption. We hypothesise that subcutaneous nodular RA represents a distinct disease subtype induced by pulmonary rheumatoid nodule formation and the generation of high levels of RA associated autoantibodies initiated by Cd inhalation via cigarette smoke. Cohorts of RA patients attending rheumatology clinics in Cornwall, UK (total n = 504) were studied to determine the prevalence of nodular RA, with matched analysis (age, gender and social class) to compare urinary Cd, RF and ACPA levels stratifying for nodular disease and smoking. In cohort 1 45/303 (14.9%) of the RA patients under regular follow up had nodular disease. Of the RA smokers, 30/155 (19%) were nodular and of the RA non-smokers 15/148 (10%) were nodular. Smoking was significantly associated with nodular RA, odds ratio (OR) = 2.48 95% confidence interval (CI) 1.26-4.88, p = 0.008. Raised urinary Cd levels were significantly associated with nodular RA in non-dust exposed individuals, OR 2.26 (95% CI 1.08-4.73), p = 0.03 compared to dust exposed individuals, OR 0.78 (95% CI 0.35-1.76), p = 0.557, despite fewer pack years (py) at diagnosis (16 vs 20 py). Nodular RA smokers had significantly raised RF levels compared to RA smokers without nodular disease (median RF 171.5 (interquartile range (IQR) 48-394) vs median RF 31.7 (IQR 10.3-170.3), p < 0.00001). RF positivity was significantly more prevalent in nodular RA smokers compared to RA smokers without nodular disease (84/89 (94%) vs. 141/199 (71%), OR = 6.9 (95% CI 2.66-17.91), p < 0.00001). ACPA levels were also significantly raised in nodular smokers compared to non-nodular smokers (median ACPA 250 (IQR 145-426) vs 116 (1-257.5), p < 0.00001), as were ACPA positivity rates (83/89 (93%) vs 123/191 (64%), OR = 7.65 (95% CI 3.17-18.4), p < 0.0001). These pilot results support the hypothesis that nodular RA represents a distinct disease subtype initiated by cadmium inhalation, which we suggest induces pulmonary rheumatoid nodule formation and generation of RA-associated autoantibodies.


Endonasal endoscopic versus microscopic transsphenoidal surgery in pituitary tumors among the young: A comparative study & meta-analysis.
The transsphenoidal approach presents unique challenges in young, with scanty literature. This study compares the outcome of pituitary tumors among young in our center between endoscopic(EES) and microscopic(MTS) transsphenoidal surgery, with a meta-analysis. Patients within 20 years were studied for their surgical approach to a favorable outcome of endocrine remission (ER) (functioning) or Gross/Near-Total resection (nonfunctioning), besides the need for retreatment. Relevant studies were pooled and analyzed according to PRISMA guidelines. Out of 64 young patients with pituitary tumors, 48 underwent transsphenoidal surgery using MTS(33) or EES(15). Of these, 21, 14, 5, and 8 had Cushing's, somatotropinomas, prolactinomas, and non-secreting tumors, respectively. Mean symptom duration was 28months, with weight gain(50 %) and visual complaints(29 %) most prevalent. Hypogonadism(21 %) was the most frequent endocrinopathy. The mean tumor volume was 3.8 cm3. Over mean follow-up of 4.4years, favorable outcome was significantly higher after EES than MTS(78.6 % vs. 46.7 %)(odds ratio 4.18, p = 0.05). EES's better outcome was homogeneous across subgroups of age and tumor type, with no significant subgroup difference. Symptom duration was significantly higher among those who required retreatment(p = 0.05), while ER had a non-significant association with tumor volume(p = 0.07). Overall, 40 %, 27 %, 17 %, and 8% were on hydrocortisone, thyroxine, sex hormone, and desmopressin, respectively, at follow-up with no significant difference between EES and MTS. In pooled analysis of literature, both favorable outcome(74 % vs. 48 %,p = 0.02) and retreatment rate(8% vs. 37 %,p = 0.004) were significantly better with EES than MTS. Among young patients with pituitary tumors, the favorable outcome and retreatment rates are better with endonasal endoscopy and associated with symptom duration and tumor volume.


Return to Play After Patellar Tendon Autograft for Primary Anterior Cruciate Ligament Reconstruction in Rugby Players.
There is scant literature on outcomes after anterior cruciate ligament (ACL) reconstruction in rugby players, and no prior study has evaluated the outcomes of bone-patellar tendon-bone (BTB) autograft ACL reconstruction. To assess the rate of return to play, the timing of that return, and the subsequent graft reinjury rate among rugby players after ACL reconstruction with BTB autograft. The ACL registry at a single hospital was screened for professional and amateur rugby players who had undergone a primary ACL reconstruction with BTB autograft. Professional rugby players were those playing for one of the professional provincial teams in Ireland. Outcomes were analyzed for the rate and timing of return to play, functional outcomes, and subsequent graft ruptures. Additionally, outcomes were compared between professional and amateur athletes. Case series; Level of evidence, 4. A total of 126 patients with 24 months of follow-up were enrolled. The overall rate of return to play was 84.9%, with 75.4% returning to the same level of play; 8.7% of patients did not return to play secondary to non-knee-related issues. The mean time to return was 10.9 ± 4.9 months. Among professional rugby players, 93.3% were able to return at a mean time of 9.7 ± 4.4 months; 80% returned to the same level. The mean Anterior Cruciate Ligament-Return to Sport after Injury score was 78.4 ± 20.2, the Cincinnati knee score was 92.5 ± 8.0, the International Knee Documentation Committee score was 88.2 ± 8.1, and the Marx score was 9.7 ± 5.3. Two patients sustained a subsequent rerupture of the reconstructed ACL, and 4 players sustained a contralateral ACL injury within the follow-up interval of 2 years. Rugby players receiving BTB ACL reconstruction demonstrated good clinical outcomes with a high rate of return to sport, with the majority returning before 12 months. The rate of a subsequent ACL injury was low among the authors' cohort at short-term follow-up.


Human Epidermal Growth Factor Receptor 2-Targeted PET/Single- Photon Emission Computed Tomography Imaging of Breast Cancer: Noninvasive Measurement of a Biomarker Integral to Tumor Treatment and Prognosis.
Increased human epidermal growth factor receptor 2 (HER2) expression is a hallmark of aggressive breast cancer. Imaging modalities have the potential to diagnose HER2-positive breast cancer and detect distant metastases. The heterogeneity of HER2 expression between primary and metastatic disease sites limits the value of tumor biopsies. Molecular imaging is a noninvasive tool to assess HER2-positive primary lesions and metastases. Radiolabeled antibodies, antibody fragments, and affibody molecules devise a reliable and quantitative method for detecting HER2-positive cancer using PET. HER2-targeted PET imaging is a valuable clinical tool with respect to both the care and maintenance of patients with breast cancer.


Infective endocarditis.
Infective Endocarditis (IE) is a known and a well-described complication of congenital and acquired heart disease. Its onset may be related to a procedure (which is commonly dental) or to poor dental hygiene. Use of antibiotics prior to the procedure prevents IE. General awareness of dental hygiene and use of prophylactic antibiotic is as much a responsibility of the Pediatrician as it is of the Pediatric Cardiologist. This article reviews the changing epidemiology, pathophysiology, clinical manifestations, and the microbiology of IE. Duke criteria for diagnosis of IE and the role of echocardiography in diagnosis of IE are discussed. There is special emphasis on the prevention of IE.


Rapid and reliable techniques for the laboratory detection of bacterial meningitis.
Microorganisms encountered in cerebrospinal fluid require rapid and accurate means of detection and identification in the laboratory. Although restricted to morphologic study and Gram reaction, the Gram stain of cerebrospinal fluid has been the primary diagnostic tool for preliminary diagnosis of purulent meningitis, with identification of the etiologic agent often made within one to two hours by direct microscopic examination. Gram stain and appropriate culture procedures still provide the basis for comparing other diagnostic methods. Nonimmunologic methods that show promise in being both rapid and reliable include gas-liquid chromatography and the Limulus amebocyte lysate test. Fatty acid and carbohydrate profiles characteristic of Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis, and Staphylococcus aureus in the cerebrospinal fluid of human subjects and animals have been obtained by gas-liquid chromatography. Also, a unique compound has been detected by gas-liquid chromatography in cerebrospinal fluid from patients with tuberculous meningitis. The Limulus test has been reliable in spinal fluid and almost always gives positive results in H. influenzae and other Gram-negative meningitides. Nonspecific test procedures of varying degrees of accuracy and promise include lactic acid, C-reactive protein, and lactate dehydrogenase determination. Direct microscopic examination of cerebrospinal fluid remains the most practical and accurate method for identifying the etiologic basis of bacterial (and fungal) meningitis.


Establishment of a Chemiluminescence Immunoassay Combined with Immunomagnetic Beads for Rapid Analysis of Ochratoxin A.
Ochratoxin A (OTA) is a harmful mycotoxin and secondary metabolite produced by several species of Aspergillus and Penicillium. It is of vital importance to establish a sensitive method to detect OTA in various grains. A novel, highly sensitive chemiluminescence immunoassay was developed to determine OTA in wheat, corn, and poultry feed. The immunomagnetic beads were used as solid phase carriers and separators in the competitive chemiluminescence method. Anti-OTA monoclonal antibodies coated on the magnetic beads were applied as the capturing antibodies, in which OTA would compete with OTA-alkaline phosphatase in binding with OTA antibodies. The proposed method exhibited good linearity (R2 ≥ 0.999), adequate OTA recovery rate (83.60-102.50%), and good repeatability. The sensitivity of the proposed method was 2.05 pg/mL. In addition, the method was highly selective and showed no cross-reactions with other mycotoxins (e.g., AFB1, DON, ZEN). The developed method was applied in the analysis of wheat, corn, and two animal feeds successfully. The results obtained by the chemiluminescence method showed a high correlation with those obtained by the HPLC method (correlation coefficient 0.9958). This strategy shows great potential for other toxic and harmful mycotoxin detection. A novel highly rapid and sensitive chemiluminescence immunoassay was established for quantitation of OTA.


Dynamic Alteration of Neutrophil-to-Lymphocyte Ratio over Treatment Trajectory is Associated with Survival in Esophageal Adenocarcinoma.
Neutrophil-to-lymphocyte ratio (NLR) has been identified as a biomarker for multiple malignancies. There is emerging evidence that implicates neutrophils in cancer progression. Alterations of neutrophil counts and NLR during treatment may reflect a change in oncologic outcome that is more important than baseline values. The aim of this study is to investigate the prognostic role of NLR changes during the treatment trajectory of patients with esophageal adenocarcinoma. NLR values of patients with esophageal adenocarcinoma who underwent surgery between 2005 and 2016 were measured at baseline and in the late postoperative period. Primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcome was pathological response to neoadjuvant chemotherapy. 330 patients were included; mean age was 65.6 years, and 82% were male. Most patients had cT3 (74.8%), cN-positive (59.7%) disease. Two-thirds (65.2%) received neoadjuvant chemotherapy. The independent predictors of OS were pathological N-stage, size of primary tumor, and delta NLR (late - baseline NLR). Patients with persistently elevated NLR did worse than those with decreasing NLR trends between baseline and postoperative time points (3-year OS 43.4% versus 71.3%, p < 0.0001, 3-year DFS 29.7% versus 61.9%, p < 0.0001). High baseline and postoperative NLR were associated with significantly worse OS and DFS. Patients with complete pathological response had lower mean baseline NLR. Dynamic changes in NLR during treatment are associated with survival and may be more informative than static baseline values.


Tetanus toxin. The effect of chemical modifications on toxicity, immunogenicity, and conformation.
Tetanus toxin has been isolated from the extract of Clostridium tetani and analyzed for purity using various methods, e.g. sedimentation velocity, gel filtration, polyacrylamide gel electrophoresis, immunoelectrophoresis, and immunodiffusion. The homogeneous toxin, characterized by a minimum lethal dose of 10 pg (18- to 20-g mouse), was judged to be of high purity. The amino acid composition was determined and found to be in good agreement with reported values for both filtrate and extract toxin. The corrected sedimentation coefficient, so20,w, was found to be 7.5, and the molecular weight was estimated to be 150,000. These values agree closely with those reported by others. The toxin was modified using the conventional formaldehyde reaction to produce toxoid and both reductive methylation and carbamylation, which are highly specific for lysyl residues. Under certain reaction conditions, carbamylation of the toxin completely eliminated toxicity. Whereas reductive methylation yielded a high degree of conversion of lysine to dimethyllysine and monomethyllysine, the toxicity, albeit greatly reduced, was never completely eliminated. The circular dichroic spectrum of each chemically modified toxin was obtained, resolved into Gaussian components, and compared with that of native toxin, which is estimated to contain about 20% alpha helix and 23% beta structure. The far ultraviolet circular dichroic spectra of toxin and toxoid were characterized by negative extrema at 208 nm and 217 nm attributable to ordered secondary structure, and toxin also exhibited a distinct shoulder at 223 nm. Carbamylated toxin and methylated toxin were characterized by negative extrema at 210 nm and 206 nm, respectively, and both exhibited shoulders at 216 to 217 nm and 223 nm. The toxin and derivatives exhibited multiple negative extrema above 250 nm which were assigned to the various aromatic residues. There were differences in the spectra of the toxin and derivatives over the entire wavelength region, thus suggesting changes in the local environment of various chromophores. In particular, the rotational strengths of many of the bands assigned to tryptophan, tyrosine, and phenylalanine were altered in the derivatives. Also, in the far ultraviolet region of the circular dichroic spectrum, the data were suggestive of some reduction in the amount of both alpha helix and beta structure in the derivatives. However, there was no evidence of extensive conformational changes, e.g. unfolding, in the modified toxins. Presently, it is not known if the small conformational differences between toxin and toxoid are important in the loss of toxicity with the retention of immunogenicity in the derivative. The modification data are consistent with the hypothesis that separate amino acid residues are involved in toxicity and immunogenicity.


Spinal cord stimulation improves motor function and gait in spastic paraplegia type 4 (SPG4): Clinical and neurophysiological evaluation.
Hereditary spastic paraplegia is a heterogeneous group of genetic disorders characterized by degeneration of the corticospinal tracts, coursing with progressive weakness and spasticity of the lower limbs. To date, there are no effective treatments for progressive deficits or disease-modifying therapy for those patients. We report encouraging results for spastic paraparesis after spinal cord stimulation. A 51-year-old woman suffering from progressive weakness and spasticity in lower limbs related to hereditary spastic paraplegia type 4 underwent spinal cord stimulation (SCS) and experienced also significant improvement in motor function. Maximum ballistic voluntary isometric contraction test, continuous passive motion test and gait analysis using a motion-capture system were performed in ON and OFF SCS conditions. Neurophysiologic assessment consisted of obtaining motor evoked potentials in both conditions. Presurgical Spastic Paraplegia Rating Scale (SPRS) score was 26. One month after effective SCS was initiated, SPRS went down to 15. At 12 months follow up, she experienced substantial improvement in motor function and in gait performance, with SPRS scores 23 (OFF) and down to 20 (ON). There was an increased isometric muscle strength (knee extension, OFF: 41 N m; ON: 71 N m), lower knee extension and flexion torque values in continuous passive motion test (decrease in spastic tone) and improvement in gait (for example, step length increase). Despite being a case study, our findings suggest innovative lines of research for the treatment of spastic paraplegia.


The management of deep sternal wound infection: Literature review and reconstructive algorithm.
Deep sternal wound infection (DSWI) is an important complication of open thoracic surgery, with a reported incidence of 0.5-6%. Given its association with increased morbidity, mortality, inpatient duration, financial burden, and re-operation rates, an aggressive approach to treatment is mandated. Flap reconstruction has become the standard of care, with studies demonstrating improved outcomes with reduced mortality and resource usage in patients undergoing early versus delayed flap reconstruction. Despite this, no evidence-based standard for the management of DSWI exists. We performed a thorough review of the literature to identify principles in management, using a PRISMA compliant methodology. Ovid-Embase, Medline and PubMed databases were searched for relevant papers using the search terms "deep sternal wound infection," and "post-sternotomy mediastinitis" to December 2019. Duplicates were removed, and the search narrowed to look at specific areas of interest i.e. negative pressure wound therapy, flap reconstruction, and rigid fixation. The reference list of included articles underwent full text review. No randomized controlled trials were identified. We review the current management techniques for patients with DSWI, and raise awareness for the need for further high quality studies, and a standardized national cardiothoracic-plastic surgery guideline to guide management. Based on our findings and the authors' own experience in this area, we provide evidence-based recommendations. We also propose a reconstructive algorithm.


Fos expression in serotonergic midbrain neurons projecting to the paraventricular nucleus of hypothalamus after noxious stimulation of the stomach: a triple labeling study in the rat.
Horseradish peroxidase (HRP) was stereotaxically injected into the paraventricular nucleus of the hypothalamus (PVH) and visceral noxious stimulation was given by an administration of formalin into the stomach. The brain sections were subjected to HRP histochemistry and immunostained with Fos and serotonin antibodies. The periaqueductal gray (PAG) and dorsal raphe nucleus (DR) contained single-labeled (Fos, 5HT, HRP), double-labeled (Fos/HRP, Fos/5HT, HRP/5HT) and triple-labeled (HRP/Fos/5HT) neurons. Triple-labeled neurons were mainly observed in the DR and in discrete areas of the PAG ipsilateral to side of the HRP injection. These findings suggest that a population of serotonergic midbrain neurons receive nociceptive visceral information and project to the PVH.


Lack of bupivacaine kinetic changes induced by flumazenil in mice.
This study was designed to document possible changes in bupivacaine kinetics in mice after a single 1 mg/kg injection of flumazenil. After a single 20 mg/kg i.p. dose of bupivacaine, C max, Vd, Cl and AUC were not significantly modified by flumazenil; even if T max was shown to be significantly shorter when flumazenil was associated, bupivacaine bioavailability did not seem to be modified and thus may not be involved in the explanation of previously reported increasing bupivacaine-induced mortality by flumazenil.


Synergistic effects on itaconic acid production in engineered Aspergillus niger expressing the two distinct biosynthesis clusters from Aspergillus terreus and Ustilago maydis.
Itaconic acid (IA) is a versatile platform chemical widely used for the synthesis of various polymers and current methods for IA production based on Aspergillus terreus fermentation are limited in terms of process efficiency and productivity. To construct more efficient IA production strains, A. niger was used as a chassis for engineering IA production by assembling the key components of IA biosynthesis pathways from both A. terreus and Ustilago maydis. Recombinant A. niger S1596 overexpressing the A. terreus IA biosynthesis genes cadA, mttA, mfsA produced IA of 4.32 g/L, while A. niger S2120 overexpressing the U. maydis IA gene cluster adi1, tad1, mtt1, itp1 achieved IA of 3.02 g/L. Integration of the two IA production pathways led to the construction of A. niger S2083 with IA titers of 5.58 g/L. Increasing cadA copy number in strain S2083 created strain S2209 with titers of 7.99 g/L and deleting ictA to block IA degradation in S2209 created strain S2288 with IA titers of 8.70 g/L. Overexpressing acoA to enhance the supply of IA precursor in strain S2288 generated strain S2444 with IA titers of 9.08 g/L in shake flask. Recombinant A. niger overexpressing the U. maydis IA biosynthesis pathway was capable of IA accumulation. Combined expression of the two IA biosynthesis pathways from A. terreus and U. maydis in A. niger resulted in much higher IA titers. Furthermore, increasing cadA copy number, deleting ictA to block IA degradation and overexpressing acoA to enhance IA precursor supply all showed beneficial effects on IA accumulation.


[Correlation between psychosocial factors and periodontal disease--a systematic review of the literature].
This is a systematic review of the available empirical studies up to 2004 which deal with the question of the correlation between psychosocial factors/stress and gingival and periodontal disease. The three medical and psychological databases Medline, PsycInfo und Psyndex were searched systematically for relevant literature between 1946 and 2004. 34 empirical studies on humans (16 with and 18 without a control group) and ten empirical studies on animals are presented. Despite serious methodological flaws in many studies, most (particularly the methodologically solid ones) indicated associations between a variety of psychosocial factors and periodontitis incidence and severity. The pathomechanisms between stress and periodontitis should therefore be the subject of further research.


Cardiovascular responses to glibenclamide during endotoxaemia in the pig.
The effects of blockading the ATP-sensitive potassium channel (K+ATP channels) on endotoxin-induced vascular derangements was studied. Escherichia coli endotoxin was infused (20 micrograms/kg per h) intravenously for 180 min into anaesthetized, mechanically ventilated, indomethacin-treated pigs. After 150 min of endotoxaemia, glibenclamide (a K+ ATP channel blocker) was infused intravenously at 2 mg/kg per min for 5 min. The cardiovascular parameters were recorded before (control), every 30 min up to 150 min during endotoxaemia, and then at 5, 15 and 30 min after administration of glibenclamide. Infusion of endotoxin reduced the systemic arterial pressure to 60.6% +/- 3.7% (p < 0.01) and increased the pulmonary arterial pressure by 75.9% +/- 11.0% (p < 0.01) of the control values. Within 5 min, infusion of glibenclamide transiently but significantly reversed the systemic hypotension by raising the systemic vascular resistance, whereas the increased pulmonary arterial pressure was further augmented. Glibenclamide infusion did not influence the cardiac output. Within 30 min, the cardiovascular parameters had returned to the values induced by endotoxin, except for the systemic vascular resistance. Infusion of glibenclamide into normal pigs did not change the systemic pressure or resistance, but the pulmonary pressure and resistance were augmented transiently. These data suggest that, in pigs, the ATP-sensitive K+ channels may be one factor playing a role in the vascular changes due to endotoxaemia, especially in the systemic circulation.


Structural identification and cytotoxic activity of a polysaccharide from the fruits of Lagenaria siceraria (Lau).
A water-soluble polysaccharide, isolated from fruiting bodies of Lagenaria siceraria, is composed of methyl-alpha-d-galacturonate, 3-O-acetyl methyl-alpha-d-galacturonate, and beta-d-galactose in a ratio of nearly 1:1:1. Compositional analysis, methylation analysis, periodate oxidation, and NMR studies ((1)H, (13)C, 2D-COSY, TOCSY, NOESY, HMQC, and HMBC) revealed the presence of the following repeating unit in the polysaccharide: [carbohydrate structure: see text] This polysaccharide showed cytotoxic activity in vitro against human breast adenocarcinoma cell line (MCF-7).


Whole-exome sequencing reveals a novel homozygous mutation in the COQ8B gene associated with nephrotic syndrome.
Nephrotic syndrome arising from monogenic mutations differs substantially from acquired ones in their clinical prognosis, progression, and disease management. Several pathogenic mutations in the COQ8B gene are known to cause nephrotic syndrome. Here, we used the whole-exome sequencing (WES) technology to decipher the genetic cause of nephrotic syndrome (CKD stage-V) in a large affected consanguineous family. Our study exposed a novel missense homozygous mutation NC_000019.9:g.41209497C > T; NM_024876.4:c.748G > A; NP_079152.3:p.(Asp250Asn) in the 9th exon of the COQ8B gene, co-segregated well with the disease phenotype. Our study provides the first insight into this homozygous condition, which has not been previously reported in 1000Genome, ClinVar, ExAC, and genomAD databases. In addition to the pathogenic COQ8B variant, the WES data also revealed some novel and recurrent mutations in the GLA, NUP107, COQ2, COQ6, COQ7 and COQ9 genes. The novel variants observed in this study have been submitted to the ClinVar database and are publicly available online with the accessions: SCV001451361.1, SCV001451725.1 and SCV001451724.1. Based on the patient's clinical history and genomic data with in silico validation, we conclude that pathogenic mutation in the COQ8B gene was causing kidney failure in an autosomal recessive manner. We recommend WES technology for genetic testing in such a consanguineous family to not only prevent the future generation, but early detection can help in disease management and therapeutic interventions.


Results of isolated lateral retinacular reconstruction for iatrogenic medial patellar instability.
The aim of this study was to assess the outcomes of an isolated lateral retinaculum reconstruction for iatrogenic medial patellar instability (IMPI) in patients with continued pain after failed lateral retinacular release (LRR), including associated psychometric analysis. Pain was assessed using the visual analog scale (VAS) and disability was determined with the Lysholm scale. Psychological variables such as anxiety, depression, catastrophizing, and fear-of-movement beliefs were studied by using self-administered psychometric questionnaires. All 17 patients (13 women and 4 men) in this retrospective study had undergone LRR previously for anterior knee pain or lateral patellar instability. Four patients had undergone LRR plus proximal (Insall) realignment, and one had undergone LRR plus a medial tibial tubercle transfer. After their procedures, all had disabling symptoms. All patients underwent reconstructive surgery for IMPI. At a minimum follow-up of 2 years (range, 2 to 8 years), the mean preoperative VAS score was 7.6 (range, 5 to 9) and improved to 1.9 (range, 0 to 8) at the time of final follow-up (P < .001). The mean preoperative Lysholm score was 36.4 (range, 20 to 55), and the knee was described as bad (<65 points) in all cases. Postoperatively, it improved to 86.1 (range, 70 to 94) at final follow-up (P < .001). Before surgery, 4 patients (24%) had the clinical criteria for depression, 10 (59%) had anxiety, 7 (41%) had "catastrophizing" ideas concerning pain, and all (100%) had kinesiophobia (fear of movement). After surgery, none of the patients had depression or anxiety, none had catastrophizing ideation, and only 53% had kinesiophobia. Reconstruction of the deep transverse layer of the lateral retinaculum (LR) using a central strip of the iliotibial band for IMPI in patients with continued pain after failed LRR can successfully treat these severely disabled patients. Level IV, therapeutic case series.


Multispectral autofluorescence characteristics of reproductive aging in old and young mouse oocytes.
Increasing age has a major detrimental impact on female fertility, which, with an ageing population, has major sociological implications. This impact is primarily mediated through deteriorating quality of the oocyte. Deteriorating oocyte quality with biological age is the greatest rate-limiting factor to female fertility. Here we have used label-free, non-invasive multi-spectral imaging to identify unique autofluorescence profiles of oocytes from young and aged animals. Discriminant analysis demonstrated that young oocytes have a distinct autofluorescent profile which accurately distinguishes them from aged oocytes. We recently showed that treatment with the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) restored oocyte quality and fertility in aged animals, and when our analysis was applied to oocytes from aged animals treated with NMN, 85% of these oocytes were classified as having the autofluorescent signature of young animals. Spectral unmixing using the Robust Dependent Component Analysis (RoDECA) algorithm demonstrated that NMN treatment altered the metabolic profile of oocytes, increasing free NAD(P)H, protein bound NAD(P)H, redox ratio and the ratio of bound to free NAD(P)H. The frequency of oocytes with simultaneously high NAD(P)H and flavin content was also significantly increased in mice treated with NMN. Young and Aged + NMN oocytes had a smoother spectral distribution, with the distribution of NAD(P)H in young oocytes specifically differing from that of aged oocytes. Identifying the multispectral profile of oocyte autofluorescence during aging could have utility as a non-invasive and sensitive measure of oocyte quality.


LncRNA SNHG8 Serves as an Oncogene in Breast Cancer Through miR-634/ZBTB20 Axis.
Small nucleolus RNA Host Gene 8 (SNHG8) belongs to a subgroup with long non-coding RNAs. LncRNA SNHG8 presents up-regulated in miscellaneous cancers, like gastric cancer, liver cancer, and esophageal squamous cell cancer. Nevertheless, the expression pattern and the pathological function of lncRNA SNHG8 in breast cancer remain obscure. We examined the expression levels of lncRNA SNHG8 in the tissue samples and cell lines from breast cancer via RT-qPCR in the present study. The functions of lncRNA SNHG8 on the progression of breast cancer cell were examined by CCK-8, EdU, Transwell chamber assays, and flow cytometry analyses. The expression of proteins was assessed using Western blot assay. We found that proliferation, migration, and invasion of breast cancer cells were significantly inhibited due to knockdown of lncRNA SNHG8, while inducing apoptosis of these cells. Mechanistically, SNHG8 functioned as an inhibitor of miR-634 in tumor tissues. LncRNA SNHG8 sponged the miR-634 to increase the expression level of ZBTB20, thus further aggravating the malignancy of breast cancer. Hence, the lncRNA SNHG8-miR-634-ZBTB20 axis may be a promising therapeutic target to treat breast cancers.