Persistent Single-Neuron Activity during Working Memory in the Human Medial Temporal Lobe.
Working memory is an essential component of human cognition. Persistent activity related to working memory has been reported in many brain areas, including the inferior temporal and prefrontal cortex [1-8]. The medial temporal lobe (MTL) contains "concept cells" that respond invariantly to specific individuals or places whether presented as images, text, or speech [9, 10]. It is unknown, however, whether the MTL also participates in working memory processes. We thus sought to determine whether human MTL neurons respond to images held in working memory. We recorded from patients with chronically intractable epilepsy as they performed a task that required them to remember three or four sequentially presented pictures across a brief delay. 48% of visually selective neurons continued to carry image-specific information after image offset, but most ceased to encode previously presented images after a subsequent presentation of a different image. However, 8% of visually selective neurons encoded previously presented images during a final maintenance period, despite presentation of further images in the intervening interval. Population activity of stimulus-selective neurons predicted behavioral outcome in terms of correct and incorrect responses. These findings indicate that the MTL is part of a brain-wide network for working memory.


SD-OCT findings in polypoidal choroidal vasculopathy.
To examine patients with polypoidal choroidal vasculopathy (PCV), using spectral-domain optical coherence tomography (SD-OCT) to characterise and locate the PCV lesions. A series of 15 eyes of 10 patients diagnosed with PCV were examined. All eyes were imaged with macular SD-OCT. SD-OCT cross-sectional scan findings included atypical and typical pigment epithelial detachments (PEDs). Polyps and neovascularisation were located above Bruch membrane. All 15 eyes (100%) showed sub-retinal fluid (SRF) in association with PEDs. These SD-OCT findings located the vascular lesions of PCV in the sub-retinal pigment epithelium (RPE) space, and strongly suggest that PCV is a variant of type 1 neovascularization.


Phytochemicals modulate pancreatic islet β cell function through glucagon-like peptide-1-related mechanisms.
Glucagon-like peptide-1 (GLP-1) receptor-based therapies have been developed and extensively applied in clinical practice. GLP-1 plays an important role in improving glycemic homeostasis by stimulating insulin biosynthesis and secretion, suppressing glucagon activity, delaying gastric emptying, and reducing appetite and food ingestion. Furthermore, GLP-1 has positive effects on β-cell function by promoting β-cell proliferation and neogenesis while simultaneously reducing apoptosis. Here, we summarize possible mechanisms of action of GLP-1 upon pancreatic islets as well as describe phytochemicals that modulate pancreatic islet β cell function through glucagon-like peptide-1-related mechanisms. Together, this information provides potential lead compound candidates against diabetes that function as GLP-1 receptor-based pharmacotherapy.


A TNF-induced gene expression program under oscillatory NF-kappaB control.
The cytokine tumor necrosis factor (TNF) initiates tissue inflammation, a process mediated by the NF-kappaB transcription factor. In response to TNF, latent cytoplasmic NF-kappaB is activated, enters the nucleus, and induces expression of inflammatory and anti-apoptotic gene expression programs. Recently it has been shown that NF-kappaB displays two distinct activation modes, monophasic and oscillatory, depending on stimulus duration. Characterization of temporal expression patterns for the NF-kappaB network and determination of those genes under monophasic- or oscillatory control has not been experimentally addressed. To identify the kinetics of NF-kappaB-dependent gene expression and determine whether these two types of NF-kappaB translocation modes control distinct gene programs, a detailed kinetic analysis of a validated microarray data set was performed on 74 unique NF-kappaB-dependent genes in response to TNF. Hierarchical clustering identified distinct expression profiles termed the "Early", "Middle", "Late" response groups, peaking 1, 3, and 6 h after stimulation, respectively. These expression patterns were validated by Quantitative Real Time PCR (Q-RT-PCR) and NF-kappaB binding was demonstrated by chromatin immunoprecipitation (ChIP) assays. Each response group was mapped to its molecular function; this analysis indicated that the Early group encodes cytokines or negative regulators of the IKK-NF-kappaB pathway, and the Late group encodes cell surface receptors, adhesion molecules and signal adapters. That similar coordinated sequential cascades of gene expression were also seen in response to stimulation by the cytokine IL-1, and expression patterns observed in MRC-5 fibroblasts indicated that the epithelial NF-kappaB program is relatively stimulus- and cell type-independent. Bioinformatic analysis of the Early and Late gene promoters indicates that although both groups contain similar patterns of NF-kappaB-binding sites, only the Early gene promoters contain NF-kappaB-binding sites located in phylogenetically conserved domains. Stimulation protocols designed to produce either monophasic or oscillatory NF-kappaB activation modes showed that the oscillatory mode is required only for expression of the Late genes. This analysis provides important insights into the TNF-regulated genetic response program in epithelial cells, where NF-kappaB controls sequential expression patterns of functionally distinct genes that depend on its oscillatory activation mode.


Sensitive assay for measurement of volatile borneol, isoborneol, and the metabolite camphor in rat pharmacokinetic study of Borneolum (Bingpian) and Borneolum syntheticum (synthetic Bingpian).
Both Borneolum (Chinese name Bingpian; dextrorotatory borneol) and Borneolum syntheticum (synthetic Bingpian; a mixture of optically inactive borneol and isoborneol) have been used for medicinal purposes in Chinese traditional medicine. The aim of this study was to develop a sensitive assay for measuring volatile ingredients borneol, isoborneol, and their metabolite camphor in pharmacokinetic study of Bingpian. Rat plasma samples were prepared using liquid-liquid microextraction: 70 μL of plasma sample (containing 125 nmol/L naphthalene as the internal standard) was extracted with 35 μL of n-hexane. The resulting n-hexane extract (20 μL) was introduced into a gas chromatography/mass spectrometry system using programmable temperature vaporizing-based large-volume injection. The assay was validated to demonstrate its reliability for the intended use. Using this assay, pharmacokinetic studies of Bingpian, synthetic Bingpian, and Fufang-Danshen tablets (containing synthetic Bingpian) were conducted in rats. The extraction efficiency for the analytes and the internal standard from plasma was almost constant with decrease in n-hexane-to-plasma volume ratio, thus enabling a small volume of extracting solvent to be used for sample preparation, and enhancing the assay sensitivity. The lower quantification limit for measuring borneol, isoborneol, and camphor in plasma was 0.98 nmol/L, which was 33-330 times more sensitive than those reported earlier for Bingpian and synthetic Bingpian. The applicability of the miniaturized liquid-liquid extraction technique could be extended to measure other volatile and nonvolatile medicinal compounds in biomatrices, which can be predicted according to the analytes' octanol/water distribution coefficient (logD) and acid dissociation constant (pKa). This assay is sensitive, accurate and free of matrix effects, and can be applied to pharmacokinetic studies of Bingpian, synthetic Bingpian, and Bingpian-containing herbal products.


Clinical coaching in primary care: Capable of improving control in patients with type 2 diabetes mellitus?
Few clinical coaching studies are both endorsed by real cases and focused on reducing suboptimal diabetes control. We evaluated the effectiveness of coaching on improving type 2 diabetes goals after 3 years of implementation in primary care. A cross-sectional study with follow up was conducted during 2008-2011. Coaching consisted of guiding family doctors to improve their clinical abilities, and it was conducted by a medical doctor trained in skill building, experiential learning, and goal setting. Effectiveness was assessed by means of fasting plasma glucose and glycosylated hemoglobin outcomes. The main analysis consisted of 1×3 and 2×3 repeated measures ANOVAs. A significant coaching×time interaction was observed, indicating that the difference in glucose between primary care units with and without coaching increased over time (Wilks' lambda multivariate test, P<0.0001). Coaching increased 1.4 times (95%CI 1.3, 1.5) the possibility of reaching the fasting glucose goal after controlling for baseline values. There was also a significant improvement in glycosylated hemoglobin (Bonferroni-corrected p-value for pairwise comparisons, P<0.0001). A correctible and even preventable contributing component in diabetes care corresponds to physicians' performance. After 3 years of implementation, coaching was found to be worth the effort to improve type 2 diabetes control in primary care.


Wounding acts as a tumor promoter in chickens inoculated with avian sarcoma virus 17.
Avian sarcoma virus 17 (ASV17) is an acutely transforming retrovirus which carries the oncogene v-jun. The virus induces fibrosarcomas in chickens at the site of inoculation. Here we describe wound-related tumor formation in 77% of chickens inoculated with ASV17 in one wing and wounded by metal clip insertion in the opposite wing. Tumors from both wound-related and inoculation-related sites were histologically diagnosed as fibrosarcomas. Tissues cultured from both tumor sites produced infectious virus in culture and expressed high levels of the v-Jun oncoprotein detectable by immunofluorescent staining. By varying the time of wounding relative to virus inoculation we defined the early stages of wound healing (2-7 days postinoculation) as favoring wound-related tumor formation. Three other acutely transforming retroviruses containing oncogenes coding for nonreceptor protein tyrosine kinases (v-src, v-yes, and v-fps), inoculated in the same manner, induced wound-related tumors in all cases. We conclude that in chickens, ASV17 collaborates with wound healing to promote tumorigenesis by a process which may relate either to a biochemical function of Jun or to a more general, shared characteristic of transforming retroviruses.


Characterization of a dimeric unfolding intermediate of bovine serum albumin under mildly acidic condition.
Protein aggregation is a well-known phenomenon related to serious medical implications. Bovine serum albumin (BSA), a structural analogue of human serum albumin, has a natural tendency for aggregation under stress conditions. While following effect of moderately acidic pH on BSA, a state was identified at pH 4.2 having increased light scattering capability at 350 nm. It was essentially a dimer devoid of disulphide linked large aggregates as observed from 'spin column' experiments, gel electrophoresis and ultra-centrifugations. Its surface hydrophobic character was comparable to the native conformer at pH 7.0 as observed by the extraneous fluorescence probes pyrene and pyrene maleimide but its interactions with 1-anilino 8-naphthelene sulphonic acid was more favorable. Dimerization was irreversible between pH 4.2 and 7.0 even after treatment with DTT. The role of the only cysteine-34 residue was investigated where modification with reagents of arm length bigger than 6 A prevented dimerization. Molecular modeling of BSA indicated that cys-34 resides in a cleft of 6 A depth. This indicated that the area surrounding the cleft plays important role in inducing the dimerization.


Changes in health-related quality of life in the first year after treatment for prostate cancer: results from CaPSURE.
Treatment for prostate cancer has a significant impact on health-related quality of life (HRQOL). We examined HRQOL immediately after diagnosis and treatment and 1 and 2 years after treatment for a cohort of men with early and late-stage prostate cancer. We studied 692 men enrolled in CaPSURE, a large national observational data base of patients with prostate cancer. General and disease-specific HRQOL were measured with validated instruments at study entry and quarterly thereafter. Individuals were grouped by initial treatment: radical prostatectomy, radiotherapy, hormonal therapy, and observation (ie, no treatment in first year). Trends in HRQOL scores were evaluated immediately after treatment through 2 years, adjusting for age and length of follow-up. Patients who underwent radical prostatectomy demonstrated statistically significant increases in functioning in general and in disease-specific components during the year after treatment when compared with scores immediately after treatment. Patients receiving radiotherapy and hormonal therapy had significant improvements in patient reports of health change during the year. Patients undergoing radical prostatectomy have low HRQOL scores just after treatment in almost all general and disease-specific areas, but at 1 year there is a sharp improvement. Patients undergoing observation, radiotherapy, or hormonal therapy remain stable over time. All treatment groups continue to have decrements in sexual function.


Carbonic anhydrase IX overexpression regulates the migration and progression in oral squamous cell carcinoma.
Carbonic anhydrase IX (CAIX) is reportedly overexpressed in several types of carcinomas and is generally considered a marker of malignancy. The current study investigated the association between membrane expression of CAIX and the clinicopathological characteristics in oral squamous cell carcinoma (OSCC) patients. The study used immunohistochemistry to examine CAIX expression in 271 OSCC specimens by tissue microarray (TMA) and assessed the effect of CAIX overexpression and knockdown on migration of oral cancer cells in vitro. We found that CAIX expression was associated with more advanced clinical stages (p = 0.030) and positive lymph node metastasis (p = 0.026). Importantly, CAIX expression was correlated with a poorer patient prognosis in a univariate survival analysis (p = 0.025). Moreover, CAIX suppression by small interfering RNA (siRNA) significantly reduced cellular migration in OECM-1 oral cancer cell. In conclusion, our study showed that the expression of CAIX in OSCC samples can predict the progression of OSCC and survival of OSCC patients in Taiwan.


Capitate shortening osteotomy with vascularized bone grafting for the treatment of Kienböck's disease in the ulnar positive wrist.
Decompression surgery combined with revascularization surgery may provide better results than either alone in the treatment of Kienböck's disease. This study describes our experience with capitate shortening combined with vascularized bone grafting for the treatment of Kienböck's disease in ulnar neutral and ulnar positive variant patients. Between 1996 and 2004, patients diagnosed with Lichtman stage II or stage IIIA Kienböck's disease with ulnar neutral or ulnar positive wrists were enrolled in this prospective study and had capitate shortening osteotomy with concurrent vascularized bone grafting. Preoperative and postoperative clinical evaluation included wrist arc of motion, grip strength, and overall satisfaction score. Preoperative and postoperative wrist radiographs and preoperative magnetic resonance imaging were performed. Radiographic measurements of preoperative and postoperative ulnar variance and carpal height ratio were also evaluated. The average follow-up period was 41 months (range, 26-65 months). Fourteen patients with an average age of 25 years (range, 16-39 years) were studied. The results show significant improvement in grip strength (58% to 78% of the normal side), satisfaction score, and satisfactory arc of motion. The average carpal height ratio was maintained. Average time to osteotomy healing was 48 days. Capitate shortening osteotomy combined with vascularized bone graft is effective in the treatment of ulnar-positive Kienböck's disease prior to the onset of radiocarpal arthrosis.


Clinical Features and Risk Factors Associated With Multisystem Inflammatory Syndrome in Children With Cancer and COVID-19.
Little is known about the risk of post-COVID-19 multisystem inflammatory syndrome in children (MIS-C) in the setting of childhood cancer. To evaluate factors associated with MIS-C and describe the clinical course of COVID-19 in the setting of MIS-C. Multisite observational cohort study of a registry representing more than 100 US pediatric oncology sites. All included patients were registered between April 1, 2020, and May 18, 2022. Sites submitted deidentified data surrounding sociodemographics, cancer diagnosis and treatment, and COVID-19 course (symptoms, maximum support required, outcome). Patients with MIS-C (n = 24) were compared with matched controls (n = 96). Children (<21 years) with cancer who developed COVID-19 while receiving cancer treatment or within 1 year of completing treatment were characterized based on their development of MIS-C. (1) Clinical and sociodemographic characteristics of children with cancer and COVID-19; and (2) MIS-C. (1) Development of MIS-C among children with cancer and COVID-19; and (2) symptoms and disease severity associated with MIS-C. Among 2035 children with cancer and COVID-19, 24 (1.2%) developed MIS-C. COVID-19 occurred at a median (IQR) age of 12.5 (5.5-17.1) years in those with MIS-C and 11 (6-16) years among matched controls (P = .86). The majority of children with MIS-C had a hematologic cancer (83.3% [n = 20]), were publicly insured (66.7% [n = 16]), and were Hispanic (54.2% [n = 13]). Half (n = 12) had 1 or more noncancer comorbidity. Those with comorbidities were more likely to develop MIS-C than those without (odds ratio [OR], 2.5 [95% CI, 1.1-5.7]). Among children with MIS-C, 100% (n = 24) were admitted to the hospital and 54.2% (n = 13) to the intensive care unit (ICU), while COVID-19 contributed to the death of 20.1% (n = 5); cancer therapy was changed in 62.5% (n = 15). Compared with matched controls, those with MIS-C had higher odds of symptoms classified as systemic (OR, 4.7 [95% CI, 1.4-15.8]) or gastrointestinal (OR, 5.0 [95% CI, 1.7-14.6]) along with higher odds of hospitalization (OR, 42.9 [95% CI, 7.1-258]), ICU admission (OR, 11.4 [95% CI, 3.6-36.4]), and changes to cancer therapy (OR, 24.9 [95% CI, 6.5-94.8]). In this cohort study among children with cancer and COVID-19, those with MIS-C had a more severe clinical course than those without MIS-C. The risk of MIS-C and its severity are important to consider as clinicians monitor patients with COVID-19. These findings can inform their conversations with families regarding COVID-19 risks and the benefits of prevention strategies that are pharmacologic (vaccination) and nonpharmacologic (masking), as well as treatment (antivirals, monoclonal antibodies).


[New perspectives in the approach to diabetic macular edema. Aflibercept therapy].
The VISTA and VIVID trials were conducted to compare the safety and efficacy of two intravitreal injection (IVI) regimens of aflibercept versus macular laser photocoagulation for the treatment of diabetic macular edema (DME). These double-masked, phase III clinical trials randomized (461/402) patients with DME to receive either 2mg aflibercept IVI every 4 weeks (2q4) or 2mg aflibercept IVI every 8 weeks (2q8) after 5 initial monthly doses vs macular laser photocoagularion. The primary efficacy endpoint was the mean change in best corrected visual acuity (BCVA) from baseline to week 52. Secondary efficacy endpoints were the change in central retinal thickness (CRT), the proportion of patients who gained ≥10 amd ≥15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and the change in the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) in near and distance vision. The mean BCVA gains in the 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters (p<0.0001) in VISTA, and 10.5 and 10.7 versus 1.2 letters (p<0.0001) in VIVID. The proportions of patients gaining ≥ 15 letters and the proportion of patients with an improvement of > 2 levels in the severity of diabetic retinopathy was significant in the treatment groups versus the laser group. Mean reductions in CRT in the 2q4 and 2q8 groups vs the laser group were 185.9 and 183.1 versus 73.3 μm (p<0.0001) in VISTA, and 195.0 and 192.4 versus 66.2 μm (p<0.0001) in VIVID. The incidences of ocular and nonocular adverse events were similar in all groups. In conclusion, IIV aflibercept demonstrated statistically significant superiority in improvement in BCVA and reduction in DME over laser, with similar efficacy in the 2q4 and 2q8 groups in VISTA and VIVID.


Development of diagnostic SNP markers and a novel SNP genotyping assay for distinguishing opium poppies.
The opium poppy acts as an important natural pain reliever but is also responsible for increased rates of severe drug abuse and addiction owing to its characteristic psychoactive effect. Non-medical illicit use of the poppy plant is markedly increasing worldwide, thereby highlighting the need for a robust species identification strategy. In this study, we identified SNPs within the region of two universal DNA barcodes, matK (maturase K) and the trnL-trnF (tRNA-Leu [3'exon]-tRNA-Phe [exon] intergenic spacer, that are forensically applicable for distinguishing opium poppy species based on a genetic analysis of 164 samples of family Papaveraceae obtained from locations spanning Jeolla-do and Jeju Island, Republic of Korea. A comparative analysis of the DNA barcode sequences for two narcotic types of the Papaver species (Papaver somniferum, Papaver somniferum subs. setigerum) to eight non-narcotic species revealed three unique nucleotide substitution events. Newly identified SNPs were located at position 255 of matK and at positions 305 and 306 of trnL-trnF; the narcotic species contained C, A, and T, whereas non-narcotic species contained T, G, and C at these positions. Phylogenetic analysis demonstrated that newly identified SNPs, which we named PsMAT255 and PsLF305/306, could be used to clearly differentiate between the narcotic and non-narcotic types of Papaver species based on the patterns of nucleotide variation. These results indicate that the nucleotide differences between the narcotic and non-narcotic species may influence genetic markers. We, therefore, developed a novel SNP-based allelic genotyping assay using the RT-PCR system that can reliably differentiate the narcotic type of the Papaver species. In summary, our findings suggest that the newly identified species-specific SNPs of both matK and trnL-trnF can be used as identification markers of narcotic Papaver species. Furthermore, a newly developed TaqMan allelic discrimination assay may be used as a practically applicable diagnostic method to survey several illicit narcotic specimens carrying the type-specific SNP.


Hydrophilically enhanced 3-carboranyl thymidine analogues (3CTAs) for boron neutron capture therapy (BNCT) of cancer.
Five novel 3-carboranyl thymidine analogues (3CTAs) were designed and synthesized for boron neutron capture therapy (BNCT) of cancer. Phosphorylation of all five 3CTAs was catalyzed by recombinant human thymidine kinase (hTK1) using adenosine triphosphate (ATP) as the phosphate donor. The obtained phosphorylation rates ranged from 4% to 64.5% relative to that of thymidine. The compound with the most favorable hTK1 binding properties had a k(cat)/K(M) value of 57.4% relative to that of thymidine and an IC(50) of inhibition of thymidine phosphorylation by hTK1 of 92 microM. Among the five synthesized 3CTAs, this agent had also the overall most favorable physicochemical properties. Therefore, it may have the potential to replace N5-2OH, the current lead 3CTA, in preclinical studies. An in silico model for the binding of this compound to hTK1 was developed.


A deep-learning-based dose verification tool utilizing fluence maps for a cobalt-60 compensator-based intensity-modulated radiation therapy system.
A novel cobalt-60 compensator-based intensity-modulated radiation therapy (IMRT) system was developed for a resource-limited environment but lacked an efficient dose verification algorithm. The aim of this study was to develop a deep-learning-based dose verification algorithm for accurate and rapid dose predictions. A deep-learning network was employed to predict the doses from static fields related to beam commissioning. Inputs were a cube-shaped phantom, a beam binary mask, and an intersecting volume of the phantom and beam binary mask, while output was a 3-dimensional (3D) dose. The same network was extended to predict patient-specific doses for head and neck cancers using two different approaches. A field-based method predicted doses for each field and combined all calculated doses into a plan, while the plan-based method combined all nine fluences into a plan to predict doses. Inputs included patient computed tomography (CT) scans, binary beam masks, and fluence maps truncated to the patient's CT in 3D. For static fields, predictions agreed well with ground truths with average deviations of less than 0.5% for percent depth doses and profiles. Even though the field-based method showed excellent prediction performance for each field, the plan-based method showed better agreement between clinical and predicted dose distributions. The distributed dose deviations for all planned target volumes and organs at risk were within 1.3 Gy. The calculation speed for each case was within two seconds. A deep-learning-based dose verification tool can accurately and rapidly predict doses for a novel cobalt-60 compensator-based IMRT system.


Potential circRNA-disease association prediction using DeepWalk and network consistency projection.
A growing body of experimental studies have reported that circular RNAs (circRNAs) are of interest in pathogenicity mechanism research and are becoming new diagnostic biomarkers. As experimental techniques for identifying disease-circRNA interactions are costly and laborious, some computational predictors have been advanced on the basis of the integration of biological features about circRNAs and diseases. However, the existing circRNA-disease relationships are not well exploited. To solve this issue, a novel method named DeepWalk and network consistency projection for circRNA-disease association prediction (DWNCPCDA) is proposed. Specifically, our method first reveals features of nodes learned by the deep learning method DeepWalk based on known circRNA-disease associations to calculate circRNA-circRNA similarity and disease-disease similarity, and then these two similarity networks are further employed to feed to the network consistency projection method to predict unobserved circRNA-disease interactions. As a result, DWNCPCDA shows high-accuracy performances for disease-circRNA interaction prediction: an AUC of 0.9647 with leave-one-out cross validation and an average AUC of 0.9599 with five-fold cross validation. We further perform case studies to prioritize latent circRNAs related to complex human diseases. Overall, this proposed method is able to provide a promising solution for disease-circRNA interaction prediction, and is capable of enhancing existing similarity-based prediction methods.


MRI of the mandible.
Eighteen patients with abnormalities of the mandible and two normal volunteers were studied with MRI. Correlation was made with MR, CT, plain X-rays, clinical examination, and surgical findings when possible. In primary tumors of the mandible, MR was able to differentiate between solid and cystic lesions. In the cases of secondary invasion of the mandible by malignant tumors, MR was able to demonstrate replacement of the normal high signal bone marrow by low signal tumor. In some cases, the extent of marrow involvement shown on MR and confirmed at surgery was significantly underestimated by clinical examination, plain films, and CT. From this limited experience, it appears that MR may play an important role in imaging pathology of the mandible.


Pharmaceutical Care in Depression: A Survey of Stigma, Confidence, Attitudes, and Barriers.
Patients with depression are in high need of optimal pharmaceutical care as they have poor quality of life and functioning. However, little is known about the delivery of pharmaceutical care to patients with depression in Egypt. This study aimed to detect pharmacists' stigma of patients with depression, assess attitudes toward providing depression care, evaluate pharmacists' confidence with depression medication consultation, and identify barriers in providing pharmaceutical care to patients with depression. A cross-sectional survey was posted on the social media websites of Egyptian pharmacists' groups and associations. The survey collected pharmacists' demographic information, then measured their confidence in medication consultation through the Pharmacists' Confidence scale about Medication Consultation for Depressive Patients (PCMCD), with items to assess stigma of patients with depression and attitudes toward providing care to patients with depression compared with other physical conditions. The pharmacists were also asked about the barriers to providing pharmaceutical care to patients with depression. Totally, 86 pharmacists completed the survey: 56 (65.1%) were aged 30 years or older, and 64 (74.6%) had more than five years of experience. The stigma of patients with depression was generally low. The mean (SD) PCMCD score was 51.4 (6.6), reflecting that most pharmacists were confident about medication consultation for patients with depression. Attitudes toward providing pharmaceutical care to patients with depression were generally positive but significantly lower than those reported for patients with other conditions. Lack of education on mental health was the most commonly reported barrier (81.2%) to providing pharmaceutical care to patients with depression. Participants were confident about medication consultation with a positive attitude toward providing pharmaceutical care. Frequent mental health educational courses, tools, and other methods of consistent engagement that enhance practice, behaviors, and outcomes should be considered for Egyptian pharmacists to improve pharmaceutical care provided to patients with depression.


Sex-biased herbivory in Ephedra trifurca: the importance of sex-by-environment interactions.
We examined patterns of herbivory in the dioecious desert shrub, Ephedra trifurca (Ephedraceae), along a small watershed in the northern Chihuahuan Desert. We documented significant (p=0.002) sexual dimorphism in densities of Lasioptera ephedrae and L. ephedricola (Diptera: Cecidomyiidae), with male E. trifurca supporting higher densities than did females. Densities of gall midges varied significantly (p<0.001) among four sample populations of E. trifurca arrayed along the watershed and exhibited an inverse gradient with elevation. There was also a significant (p=0.006) sex-by-site interaction such that the degree of intersexual variation in gall densities decreased down the watershed. Variation in gall densities and intersexual variation in gall densities exhibited inverse trends with variation in soil water and inorganic nitrogen concentrations along the watershed.


Stimulated renal tubular epithelial cells induce anergy in CD4+ T cells.
Renal tubular epithelial cells (TEC) can express MHC class II molecules in vitro and in vivo. Their ability to also secrete cytokines and express adhesion molecules suggests a possible immune accessory role for TEC. We have previously documented that TEC process and present antigen to T cell hybridomas. However, engagement of the T cell receptor alone is sufficient to induce IL-2 secretion by T cell hybridomas. We now report that presentation of antigen by TEC to a CD4+ T cell clone results in functional inactivation of the T cells. Despite antigen-specific anergy, these T cells are viable and proliferate in response to IL-2. Furthermore, allogeneic antigen presenting cells were unable to restore the T cell proliferative response, suggesting that the mechanism(s) was not entirely costimulator-dependent.


Analysis of the Drosophila and human DPR elements reveals a distinct human variant whose specificity can be enhanced by machine learning.
The RNA polymerase II core promoter is the site of convergence of the signals that lead to the initiation of transcription. Here, we performed a comparative analysis of the downstream core promoter region (DPR) in Drosophila and humans by using machine learning. These studies revealed a distinct human-specific version of the DPR and led to the use of machine learning models for the identification of synthetic extreme DPR motifs with specificity for human transcription factors relative to Drosophila factors and vice versa. More generally, machine learning models could similarly be used to design synthetic DNA elements with customized functional properties.


Antimicrobial effect and mode of action of terpeneless cold-pressed Valencia orange essential oil on methicillin-resistant Staphylococcus aureus.
The objectives of this study were to evaluate the antistaphylococcal effect and elucidate the mechanism of action of orange essential oil against antibiotic-resistant Staphylococcus aureus strains. The inhibitory effect of commercial orange essential oil (EO) against six Staph. aureus strains was tested using disc diffusion and agar dilution methods. The mechanism of EO action on MRSA was analysed by transcriptional profiling. Morphological changes of EO-treated Staph. aureus were examined using transmission electron microscopy. Results showed that 0·1% of terpeneless cold-pressed Valencia orange oil (CPV) induced the cell wall stress stimulon consistent with the inhibition of cell wall synthesis. Transmission electron microscopic observation revealed cell lysis and suggested a cell wall lysis-related mechanism of CPV. CPV inhibits the growth of Staph. aureus, causes gene expression changes consistent with the inhibition of cell wall synthesis, and triggers cell lysis. Multiple antibiotics resistance is becoming a serious problem in the management of Staph. aureus infections. In this study, the altered expression of cell wall-associated genes and subsequent cell lysis in MRSA caused by CPV suggest that it may be a potential antimicrobial agent to control antibiotic-resistant Staph. aureus.


Total body replacement with iliac bone graft and metal plate stabilization in lower cervical spine.
15 patients presented with cervical spine dislocation and kyphotic spondylosis due to traumatic fracture and vertebral body tumour underwent surgical decompression and fixation via the anterior approach in one stage. Decompression was achieved by resection of the body of the vertebra while fixation meant implantation of iliac bone graft with metal plate fixation. Early reduction of the dislocation was impossible or insufficient in most of the cases. Therefore the majority of operations were "late decompression". Patients with root or partial cord lesions had the most significant improvement. In some selected cases, however, who suffered from a total cord lesion due to C6 or C7 fracture-dislocation, surgical decompression of the C7 and/or C8 roots by resection of the C6 or C7 vertebral bodies could lead to useful motor improvement in the hands and the fingers.


Muscle fiber immaturity and inactivity reduce myonecrosis in Duchenne muscular dystrophy.
We report on the first case of X-linked recessive myotubular myopathy (MTM1) coinciding with Duchenne muscular dystrophy (DMD). The muscle biopsy specimens of the patient show only the characteristic findings of MTM1, without the findings of DMD. We theorize that this was caused by the muscle fiber immaturity and inactivity.


The effects of Herba Andrographitis hedgerows on soil erodibility and fractal features on sloping cropland in the Three Gorges Reservoir Area.
To evaluate if hedgerows could improve the soil physicochemical properties and enhance the soil anti-scouring and anti-shearing capabilities, the effects of Herba Andrographitis hedgerows on soil erodibility and fractal features on sloping cropland in the Three Gorges Reservoir Area were investigated. Results showed that: (1) the clay particle accumulation around the hedgerows was significantly affected by the hedgerows; (2) the fractal dimension of soil particles was positively correlated with both silt and clay contents and had a negative linear correlation with sand content; (3) fine-grained content significantly influenced fractal dimension of the soil particles; (4) soil erodibility K was significantly and positively correlated with the sand content (correlation coefficient r=0.870), but significantly and negatively correlated with the silt content (r=-0.538), clay content (r=-0.739), organic carbon content (r=-0.603), the aggregation degree (r=-0.486), and soil fractal dimension (r=-0.538); and (5) the contents of organic matter and clay particles in the soil were found to be the effective indicators for soil erodibility at the Three Gorges Reservoir Area. The hedgerows may improve soil fractal features and decrease soil erodibility. The effective distance between hedgerows on a slope of 10° was less than 6 m.


[Clinical Trial of Intraoperative Tissue Identification for Breast-Conserving Surgery Using Bio-impedance Spectroscopy].
To evaluate the effectiveness of bio-impedance spectroscopy (BIS) analysis for marginal tissue malignancy/benignancy identification during Breast-Conserving Surgery (BCS). A multicenter parallel-group clinical trial was conducted with the patients who received breast conserving surgery in 2 hospitals. One hundred and fifty breast tissue specimens were collected and analyzed by BIS, frozen section biopsy and paraffin section biopsy respectively. Results were compared and statistical analysis was implemented. For BIS technique to identify malignant/benign marginal tissues, the sensitivity was 92.98%, and the specificity was 94.62%. The coherence of BIS results and frozen section biopsy results was significant, and the Kappa value was higher than 0.75. The mean measuring time of BIS was 2.63 min, which was shorter than frozen section biopsy (18.97 min) and paraffin section biospy (1.12 d). BIS technique likely has high accuracy in tissue identification so has potential to be adopted as a real-time indicator for marginal tissue malignancy/benignancy identification during breast-conserving surgery.


Mismatch negativity for speech sounds in temporal lobe epilepsy.
The mismatch negativity (MMN) is an electrophysiological trace of change detection, measured by electroencephalography (EEG), and is a reliable marker for pre-attentive auditory sensory memory. We used a phonetic oddball paradigm in patients with temporal lobe epilepsy (TLE) to elicit the MMN response at fronto-central sites and the mismatch positivity (MMP) response at mastoid sites. The MMN in 26 patients was compared with that of 26 age- and gender-matched healthy control participants. Electroencephalography responses were recorded during the presentation of speech sounds: the vowels 'a' and 'o' in alternation. Average waveforms were obtained for standard and deviant trials. We found that the MMP response at bilateral mastoid sites was reduced, whereas the MMN response at fronto-central sites did not change significantly. These results support the view that the MMN is generated by separable sources in the frontal and temporal lobes and that these sources are differentially affected by TLE.


Contraception Delivery in Pediatric and Specialist Pediatric Practices.
To characterize pediatricians' knowledge, attitudes, and self-efficacy around contraception. Cross-sectional survey. United States. National sample of pediatricians. Assessment of behaviors of providing contraception. Reproductive health practice score. Two hundred twenty-three usable surveys were received, from 163 contraceptive prescribers and 60 nonprescribers. The mean reproductive health practice score was 43.1 (SD, 8.2; total possible score, 84). Prescribers differed in their mean reproductive health score (46.0; SD, 7.0) from nonprescribers (34.0; SD, 4.5; P < .001). Prescribers vs nonprescribers differed in their attitude and efficacy in providing contraception. More prescribers believed it was their responsibility to ask about patients' need for birth control, were confident in their ability to prescribe contraception options, and provided contraception to minors despite parental disapproval. Neither group was confident in their ability to place intrauterine devices or believed that the literature supports intrauterine device placement in adolescents. Only efficacy was related to prescribing contraception in a multivariate regression analysis (odds ratio, 1.7; P < .001). In this study, we showed that most pediatricians are contraception prescribers but the overall reproductive health score was low for prescribers and nonprescribers. The odds of prescribing contraception increased with higher self-efficacy scores rather than knowledge alone. Many prescribers and nonprescribers would not prescribe birth control if parents disapproved and do not believe it is their responsibility to assess patients' need for birth control. In addition very few pediatricians have training in long-acting reversible contraception, despite being the recommended method for adolescents.


Radical prostatectomy. Patterns of local failure and survival in 67 patients.
Sixty-seven patients with localized carcinoma of the prostate were treated by radical prostatectomy unaided by adjunctive hormonal therapy. Seven patients (10%) have been lost to follow-up, and 13 patients (19%) have died of other causes without evidence of prostate cancer. The crude or direct survival free of disease for traced patients with clinical Stage B1 nodules (11) and clinical B2 lesions (20) followed for at least fifteen years is 36 per cent and 25 per cent, respectively; the crude or direct survival free of disease for pathologic B (29) and C (12) tumors followed for fifteen years is 31 per cent and 8 per cent, respectively. The local failure incidence at fifteen years for pathologic Stage B tumors is 17 per cent and for pathologic C tumors 31 per cent. Capsular invasion alone on histologic examination did not increase the rate of local or distant failure above that noted for tumors that were entirely intracapsular. However, seminal vesicle invasion is associated with a 44 per cent local failure and 66 per cent distant failure rate. The interval between radical prostatectomy and first failure averaged sixty-nine months (median 56 months) and with hormonal therapy the interval between first failure and death averaged seventy months (median 62 months). The patients who underwent radical prostatectomy in this series represent 22 per cent of the 318 patients presenting with localized prostate cancer between 1960 and 1974. A 1.5-cm nodule was found in 5.5 per cent of the presenting population, and all but one of these patients were treated by radical prostatectomy.


Diffusion-weighted MRI in assessment of renal dysfunction.
Diffusion-weighted magnetic resonance imaging (DW-MRI) in renal diseases is an evolving field and its potential is yet to be fully realized. To study the relationship between apparent diffusion coefficient (ADC) values of renal parenchyma and serum markers of renal function and stage of chronic kidney disease (CKD). A retrospective review was performed of all adult patients who underwent DW-MRI (at b-values of 0 and 500 s/mm(2)) for renal lesions from January 2009 to September 2010 and revealed 88 patients, of which 22 patients had renal dysfunction and 66 had normal renal function. Of these 22, 15 patients were known cases of CKD and were staged depending on disease severity. ADC values were determined for renal parenchyma and compared. Receiver operating characteristic (ROC) curves were drawn to establish cut-off ADC values. Pearson's correlation coefficient (R) was calculated between ADC and renal function parameters. ADC values in patients with renal dysfunction were significantly lower than in patients with normal renal function (2.1133 ± 0.2851 vs. 2.3198 ± 0.1246 (×10(-3) mm(2)/s)). ADC values lower than 2.0354 (×10(-3) mm(2)/s) were seen only with renal dysfunction and higher than 2.4516 (×10(-3) mm(2) /s) were seen only with normal function. There was significant inverse correlation between ADC and serum creatinine (R = -0.530), blood urea (R= -0.502), and significant linear correlation (R = 0.784) with estimated glomerular filtration rate (eGFR). ADC values showed a statistically significant decreasing trend with increasing stage of CKD. ADC values may serve as an additional marker for the presence and degree of renal dysfunction.


In situ revascularization with rifampicin-soaked silver polyester graft for aortic infection: Results of a retrospective monocentric series of 18 cases.
To evaluate the short and long-term results of in situ prosthetic graft treatment using rifampicin-soaked silver polyester graft in patients with aortic infection. All the patients surgically managed in our center for an aortic infection were retrospectively analyzed. The primary endpoint was the intra-hospital mortality, secondary outcomes were limb salvage, persistent or recurrent infection, prosthetic graft patency, and long-term survival. From January 2004 to December 2015, 18 consecutive patients (12 men and 6 women) were operated on for aortic infection. Six mycotic aneurysms and 12 prosthetic infections, including 8 para-entero-prosthetic fistulas, were treated. In 5 cases, surgery was performed in emergency. During the early postoperative period, we performed one major amputation and two aortic infections were persistent. Intra-hospital mortality was 27.7%. The median follow-up among the 13 surviving patients was 26 months. During follow-up, none of the 13 patients presented reinfection or bypass thrombosis. This series shows that in situ revascularization with rifampicin-soaked silver polyester graft for aortic infection have results in agreement with the literature in terms of intra-hospital mortality with a low reinfection rate.


Does Exercise Attenuate Disease Progression in People With Parkinson's Disease? A Systematic Review With Meta-Analyses.
Exercise has many benefits for people with Parkinson's disease (PD) and has been suggested to modify PD progression, but robust evidence supporting this is lacking. This systematic review (PROSPERO registration: CRD42020169999) investigated whether exercise may have neuroplastic effects indicative of attenuating PD progression. Six databases were searched for randomized controlled trials (RCTs) that compared the effect of exercise to control (no or sham exercise) or to another form of exercise, on indicators of PD progression (eg, brain-derived neurotrophic factor [BDNF], brain activation, "off" Unified Parkinson's Disease Rating Scale [UPDRS] scores). Trial quality was assessed using the Physiotherapy Evidence Database Scale. Random-effects meta-analyses were performed where at least 3 comparable trials reported the same outcome; remaining results were synthesized narratively. Forty-nine exercise trials involving 2104 PD participants were included. Compared to control, exercise improved "off" UPDRS motor scores (Hedge's g -0.39, 95% CI: -0.65 to -0.13, P = .003) and BDNF concentration (Hedge's g 0.54, 95% CI: 0.10-0.98, P = .02), with low to very low certainty of evidence, respectively. Narrative synthesis for the remaining outcomes suggested that compared to control, exercise may have neuroplastic effects. The exercise versus exercise comparisons were too heterogenous to enable pooling of results. This review provides limited evidence that exercise may have an attenuating effect on potential markers of PD progression. Further large RCTs are warranted to explore differential effects by exercise type, dose and PD stage, and should report on a core set of outcomes indicative of PD progression.


Epidemiological models of Mycobacterium tuberculosis complex infections.
The resurgence of tuberculosis in the 1990s and the emergence of drug-resistant tuberculosis in the first decade of the 21st century increased the importance of epidemiological models for the disease. Due to slow progression of tuberculosis, the transmission dynamics and its long-term effects can often be better observed and predicted using simulations of epidemiological models. This study provides a review of earlier study on modeling different aspects of tuberculosis dynamics. The models simulate tuberculosis transmission dynamics, treatment, drug resistance, control strategies for increasing compliance to treatment, HIV/TB co-infection, and patient groups. The models are based on various mathematical systems, such as systems of ordinary differential equations, simulation models, and Markov Chain Monte Carlo methods. The inferences from the models are justified by case studies and statistical analysis of TB patient datasets.


N-(2-hydroxyl)-propyl-3-trimethylammonium chitosan chloride/carboxymethyl cellulose films filled with in-situ crystallized calcium carbonate.
The research and development of substitutes for petroleum-based plastics has become a hot topic. The N-(2-hydroxyl)-propyl-3-trimethylammonium chitosan chloride (HTCC, 10 wt%)/sodium carboxymethyl cellulose (CMC) films have showed enhanced mechanical properties, which also provide a potential substitute to petroleum-based plastics. In this paper, calcium carbonate was crystallized (cry-CaCO3) in HTCC/CMC film-forming solutions, and the effects of the cry-CaCO3 particles on HTCC/CMC film properties including microstructures, mechanical properties, thermal stability, whiteness, and wettability were characterized. An HTCC/CMC film with commercially available CaCO3 (com-CaCO3) was used as a control. The results showed that the cry-CaCO3 promoted the homogeneous distribution of the HTCC/CMC matrix and significantly improved mechanical properties, but showed little effect on the thermal stability, whiteness and wettability of the films. To reveal the affecting mechanism of cry-CaCO3 on HTCC/CMC film properties, the cry-CaCO3 particles were isolated from film-forming solutions and characterized by scanning electron microscope (SEM), powder X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), thermogravimetric analysis (TGA) methods. The results showed that the HTCC/CMC matrix modulated spherical CaCO3 particles, and the macromolecules were encapsulated in cry-CaCO3 particles, decreasing their adhesion to the HTCC/CMC matrix while increasing their distribution in the HTCC/CMC matrix. The strong electrostatic, hydrogen bonding and flexible interaction between CMC and cry-CaCO3 particles played a key role in improving the mechanical properties of HTCC/CMC films.


SCID mice show a similar susceptibility to Angiostrongylus cantonensis as do wild-type mice of the C.B-17 strain.
C.B-17-SCID/SCID (SCID) mice infected with Angiostrongylus cantonensis yielded a high percentage of worm recovery and did not show any body weight loss until day 24 postinfection. Unexpectedly, C.B-17-+/+(+/+) mice also produced a similar worm burden containing well-developed worms. This is probably attributable to the observation that +/+ mice failed to induce eosinophilia in cerebrospinal fluid (CSF) despite their production of antigen-specific IgA and IgGI; +/+ mice have defective bone-marrow eosinopoiesis, which in turn results in reduced blood and CSF eosinophilia. Interleukin 5 (IL-5) production in +/+ mice is similar to that in BALB/c and C57BL/6 mice. However, bone-marrow eosinopoiesis in response to IL-5 is markedly suppressed in +/+ mice. This is probably associated with impaired expression of common beta-chain mRNA in bone-marrow cells of +/+ mice, which leads to the failure of bone-marrow eosinopoiesis. Hence, +/+ mice may serve as a useful model for the elucidation of eosinophil production in the mouse and for determination of the relationship between parasite infection and the eosinophil.


Approaches to decolonising forensic curricula.
Forensic science in UK Higher Education involves a constellation of subdisciplines, each with a biography shaped by a colonial past. Deeper examinations of the structures of curriculum design allow educators to address where colonial assumptions may reside and the impact of these legacies on the present. One process to assist this endeavour is Decolonising the Curriculum (DtC), which seeks to question and dismantle colonial structures of knowledge and support contextualisation to broaden, rather than narrow, the curricula. DtC toolkits, like those developed at the University of Winchester in the south of England, may provide practical support to programme teams to reflect on how colonial attitudes shape new and existing curricula. DtC may be seen as supporting existing quality processes that are part of the reflection cycle and tested through institutional and other accreditation quality procedures. Toolkits support programme teams to identify existing good practices and areas requiring further reflection and development. We offer perspectives on areas that would benefit from critical evaluation when teaching subjects with foundations in race science, colonial attitudes, and social injustice. The paper focuses on three main approaches to support decolonial discourse: sustained historical inquiry, questioning ethnic classifications and identity, and the presentation of international forensic work. Rather than seeing DtC as a threat to educational quality, it may be more constructively seen as an integral part of quality processes in curriculum design to support more diverse, inclusive, and authentic learning in forensic Higher Education.


Early experience with the PlantTan Fixator Plate for 2 and 3 part fractures of the proximal humerus.
This study reports the early results for clinical and radiological outcome of fixation of completely displaced or grossly angulated (>90 degrees ) 2 and 3 part fractures of the proximal humerus using the PlantTan Fixator Plate (Medizentechnik, Aachen, Germany). Using a deltopectoral approach the humeral head articular fragment was reduced onto the humeral shaft and fixed with the implant, tuberosity fragments were held with transosseous sutures. Early passive, progressing to active, physiotherapy was instituted from the first postoperative day. No other fixation or bone graft was used. In 15 patients, with 16 injured shoulders and an average age of 63 years the mean follow up was 17 months. As a percentage of the normal side the Constant-Murley score for those patients retaining the implant was mean 74% (range 36%-100%). There were six shoulders with score >80% (Good), four shoulders with score between 60 and 79% (Satisfactory) and four shoulders <60% (Poor). Four shoulders (all in patients over the age of 70 years), developed avascular necrosis. Of these, one patient underwent shoulder replacement hemiarthroplasty and one patient underwent removal of the implant. We have demonstrated functional outcome similar to other modes of internal fixation in patients under 70 years. It cannot be recommended for elderly patients (over 70 years) as it is associated with a high incidence of avascular necrosis and fixation failure.


Hijama (wet cupping therapy) enhances oral and dental health by improving salivary secretion volume and pH in adult patients at King Abdul Aziz University Hospital (KAUH), Jeddah, KSA: A controlled trial study.
The aim of this study was to explore the potential effect of Hijama in promoting oral health by analyzing its effects in modulating saliva flow and pH. An open-label, non-randomized controlled trial design was conducted at the Hijama clinic of Y.A. Jameel Scientific Chair of Prophetic Medical Applications at King Abdul Aziz University Hospital (KAUH), Jeddah, KSA. Forty-one healthy volunteers were divided into two groups: Hijama (intervention, N = 21) and control (N = 20). Saliva volume and pH were measured in salivary samples collected in a standardized fashion, 1 h before admission to the Hijama room (pre-Hijama) and 30 min after the procedure (post-Hijama) in both groups. The Hijama group underwent an additional salivary collection 7 days after Hijama. Early post-Hijama assessment showed an increase in saliva volume by an average of 1 mL in the Hijama group, whereas that in the control group decreased by 0.6 mL (p < 0.001; large effect size, Cohen's d = 1.24). Saliva pH also increased in the Hijama group by an average 0.22 but decreased by 0.08 in controls (p < 0.001; large effect size, Cohen's d = 1.22). The multivariate model demonstrated that Hijama explained 48.8% of the variability of both pH and volume together (group × time effect, eta squared = 0.488, p < 0.001), whereas time and sex had no effect. At 7 days post-Hijama, both the volume and pH of saliva had increased in the Hijama group with respect to the early post-Hijama time point; however, only the volume increase was statistically significant. Hijama enhanced salivary function and induced a significant increase in saliva volume and pH, which was maintained 7 days after the intervention. Further studies are warranted to identify other effects of Hijama on salivary glands and explore its long-term efficacy and clinical applications.


Diagnosis of Li-Fraumeni Syndrome: Differentiating TP53 germline mutations from clonal hematopoiesis: Results of the observational AGO-TR1 trial.
The Li-Fraumeni cancer predisposition syndrome (LFS1) presents with a variety of tumor types and the TP53 gene is covered by most diagnostic cancer gene panels. We demonstrate that deleterious TP53 variants identified in blood-derived DNA of 523 patients with ovarian cancer (AGO-TR1 trial) were not causal for the patients' ovarian cancer in three out of six TP53-positive cases. In three out of six patients, deleterious TP53 mutations were identified with low variant fractions in blood-derived DNA but not in the tumor of the patient seeking advice. The analysis of the TP53 and PPM1D genes, both intimately involved in chemotherapy-induced and/or age-related clonal hematopoiesis (CH), in 523 patients and 1,053 age-matched female control individuals revealed that CH represents a frequent event following chemotherapy, affecting 26 of the 523 patients enrolled (5.0%). Considering that TP53 mutations may arise from chemotherapy-induced CH, our findings help to avoid false-positive genetic diagnoses of LFS1.


Physiological properties of tandem muscle spindles in neck and hind-limb muscles.
Although tandem muscle spindle complexes are found in small but significant numbers in most muscles, experimental investigation of their properties has been problematic because of the difficulty of distinguishing their afferents from those of "normal" single spindles. Of particular interest are the afferents from b2c capsules of tandem spindles, which unlike normal spindles contain only a static b2 nuclear bag fibre and some nuclear chain fibres. The absence of a dynamic b1 nuclear bag fibre from b2c spindles has engendered much speculation as to their response properties and their possible role in motor control. We have recently developed a method for the identification of afferents from b2c spindles in electrophysiological experiments, using infusion or topical application of succinylcholine (SCh). SCh causes the contraction of the dynamic b1 and static b2 nuclear bag intrafusal fibres, and paralyses the nuclear chain fibres. Afferents from b2c spindles are characterized by a strong "biasing" of their discharge rate to about 100 impulses per second (i.p.s.) when activated by SCh (reflecting the contraction of the static b2 fibre), while primary afferents from normal b1b2c spindles show a large increase in dynamic sensitivity as well as "biasing" (reflecting the contraction of both dynamic b1 and static b2 bag fibres). Histological examination of tenuissimus spindles activated by SCh has confirmed this relationship between the pattern of activation by SCh and the number of intrafusal nuclear bag fibres in the spindle. In this paper we review the value of SCh as a means of testing spindle afferents for functional inputs from sensory terminals on the nuclear bag fibres, and discuss the properties of b2c afferents from tandem spindles in the context of their possible function.


Immunohistochemical localization of endothelin in human vascular endothelial cells.
The cellular localization of endothelin (ET), a novel vasoconstrictor peptide, was studied in human vascular tissues by immunohistochemistry. Distinct and diffuse staining for ET-like immunoreactivity was demonstrated in the cytoplasm of vascular endothelial cells, but not in smooth muscle cells or adventitial fibroblasts. The specificity was confirmed by the negative results following immunoabsorption. These findings suggest that human vascular endothelial cells function as an endocrine and/or paracrine cells for ET secretion.


Pediatric Giant Craniopharyngioma: Surgical Field Soak in Diluted Nimodipine Solution Reduces Cerebral Vasospasm.
Craniopharyngioma is a slow-growing benign tumor, accounting for 5.6%-13% of primary intracranial tumors in children. The present patient showed a huge cyst, and computed tomography scan of the brain revealed a 9.2- × 8.7- × 7.0-cm giant cystic lesion with calcification located in the suprasellar cistern. A review of the literature showed the present case is the biggest craniopharyngioma reported. After the tumor was removed, vasospasm appeared in the surgical area. The surgical field was soaked in diluted nimodipine solution for 12 minutes, including the exposed nerve and blood vessel, especially the optic nerve and middle cerebral artery, which led to vasospasm recovery. At 3-month follow-up, there was slight subdural hygroma; contrast magnetic resonance imaging scan did not reveal any residual tumor or recurrence.


Possible evidence for contribution of arbuscular mycorrhizal fungi (AMF) in phytoremediation of iron-cyanide (Fe-CN) complexes.
Arbuscular mycorrhizal fungi (AMF) are integral functioning parts of plant root systems and are widely recognized for enhancing contaminants uptake and metabolism on severely disturbed sites. However, the patterns of their influence on the phytoremediation of iron-cyanide (Fe-CN) complexes are unknown. Fe-CN complexes are of great common interest, as iron is one of the most abundant element in soil and water. Effect of ryegrass (Lolium perenne L.) roots inoculation, using mycorrhizal fungi (Rhizophagus irregularis and a mixture of R. irregularis, Funneliformis mosseae, Rhizophagus aggregatus, and Claroideoglomus etunicatum), on iron-cyanide sorption was studied. Results indicated significantly higher colonization of R. irregularis than the mixture of AMF species on ryegrass roots. Series of batch experiments using potassium hexacyanoferrate (II) solutions, in varying concentrations revealed significantly higher reduction of total CN and free CN content in the mycorrhizal roots, indicating greater cyanide decrease in the treatment inoculated with R. irregularis. Our study is a first indication of the possible positive contribution of AM fungi on the phytoremediation of iron-cyanide complexes.


TET1 mediated male reproductive toxicity induced by Bisphenol A through Catsper-Ca2+ signaling pathway.
Bisphenol A (BPA) exposure has many adverse effects on the reproductive system in animals and humans. Ten-eleven translocation 1 (TET1) is closely related to a variety of biological processes through regulating the dynamic balance of DNA demethylation and methylation. However, the role and mechanism of TET1 during BPA induced reproductive toxicity are largely unknown. In this study, mouse spermatogonia cell line GC-2 was treated with BPA in the final concentration of 0, 20, 40 and 80 μM for 72 h. The cell model of differential TET1 gene expression was established to explore the role and mechanism. We found that the growth rate of GC-2 cells, and the intracellular calcium level decreased significantly with the increase of BPA dose, while TET1 and Catsper1-4 expression level decrease with a dose-dependent relationship. Furthermore, TET1 overexpression promoted the proliferation of GC-2 cell, the increase of calcium ion concentration, and the expression level of Catsper1-4, while knockdown of TET1 leads to the opposite results. Mechanistically, TET1 expression promoted the hydroxymethylation of Catsper1-4 and reduced their methylation level. In addition, the expression level of Catsper1-4 was positively correlated with TET1 gene expression level in semen samples of the population. Our study revealed for the first time that TET1 gene regulates the expression of related molecules in the Catsper calcium signal pathway through its hydroxymethylation modification to affect the calcium level, thereby participating in the process of BPA induced damage. These results indicated that TET1 gene may be a potential biomarker of BPA induced male reproductive toxicity.


C6N3: A novel 2D carbon nitride with sp-N as support for efficient hydrogen production.
Two-dimensional (2D) carbon nitrides (CxNy) have great potential in advanced fields such as energy harvest and storage. We report a novel 2D CxNy, C6N3, comprising sp-N and sp2-C atoms. Density functional theory calculations indicate that electronically, thermally, and dynamically stable C6N3 is metallic even when cut into very narrow nanoribbons. C6N3 adsorbed single atoms of 3d, 4d, and 5d transition metals to fabricate single-atom catalysts (SACs) for an electrocatalytic hydrogen evolution reaction (HER). Among all SACs studied, Ti-, Cr-, Zr-, and Hf-embedded C6N3 had excellent overall performance including promising stability, moderate binding strength of H and H2, and good electrical conductivity. Our results suggest a novel C6N3 with an sp-N skeleton that has great potential for HER. More investigations are needed to further understand the properties and applications of C6N3 in other fields.


Natural immunogenic properties of bioinformatically predicted linear B-cell epitopes of dengue envelope and pre-membrane proteins.
The natural antibody responses to B-cell epitopes from dengue structural proteins were assessed using immune sera from people having well-defined past dengue infections with one of the four serotypes. Based on an immune-computational analysis previously conducted, nineteen epitopes from the envelope (E) and eight epitopes from pre-membrane (prM), which were more than 50% conserved across all the four DENV serotypes, were selected. Peptides to represent these B-cell epitopes were obtained from commercially available arrays, and were subjected to enzyme linked immunosorbent assay with sera obtained from dengue seropositive healthy volunteers (DENV1 n = 12: DENV2 n = 12: DENV3 n = 12 and DENV4 n = 12), and 10 dengue seronegative healthy volunteers from Sri Lanka. The cut-off value for the positive antibody response was set by taking the mean response of a peptide to the negative sera plus three standard deviations. The peptides (N = 7) showing the broad immune responses were used to generate antibodies in three mice (Balb/c) batches. The mice antisera were then subjected to microneutralization assays against all the four DENV serotypes. An EC50 viral neutralization ≥ 40 times the serum dilution was considered as neutralizing. Five of the E-peptide and two prM peptides were recognised by most individuls exposed to infections with each of the four serotypes, showing a serotype cross-reactive broad antibody response. The mice immune sera against the peptides representing the five E protein epitopes neutralized all the four DENV serotypes. Two of these five epitopes are from the Domain II, whereas one of them includes the whole bc-loop region. The antibody responses of highly conserved epitopes across the serotypes, were broadly responsive with sera of all four DENV serotypes collected from individuals infected with only one DENV serotype. Weakly conserved epitopes showed rather specific antibody responses dominated by one or few serotypes.


Pseudo-porphyria in a patient with hepatocellular carcinoma.
An elderly woman was found to have hepatocellular carcinoma and, incidental to this, markedly elevated levels of porphobilinogen in urine and serum. The delta-aminolevulinic acid levels in urine and serum were normal, but there was a distinct increase of porphyrins in urine and feces. Neither the patient nor her family gave a history suggestive of a clinical porphyria. The patient died from the carcinoma without ever exhibiting porphyric symptoms. It is assumed that the hepatocellular carcinoma produced the excessive amounts of porphobilinogen.


Gut Microbiota, Immune System, and Bone.
The gut microbiota (GM) is the whole of commensal, symbiotic, and pathogenic microorganisms living in our intestine. The GM-host interactions contribute to the maturation of the host immune system, modulating its systemic response. It is well documented that GM can interact with non-enteral cells such as immune cells, dendritic cells, and hepatocytes, producing molecules such as short-chain fatty acids, indole derivatives, polyamines, and secondary bile acid. The receptors for some of these molecules are expressed on immune cells, and modulate the differentiation of T effector and regulatory cells: this is the reason why dysbiosis is correlated with several autoimmune, metabolic, and neurodegenerative diseases. Due to the close interplay between immune and bone cells, GM has a central role in maintaining bone health and influences bone turnover and density. GM can improve bone health also increasing calcium absorption and modulating the production of gut serotonin, a molecule that interacts with bone cells and has been suggested to act as a bone mass regulator. Thus, GM manipulation by consumption of antibiotics, changes in dietary habits, and the use of pre- and probiotics may affect bone health. This review summarizes evidences on the influence of GM on immune system and on bone turnover and density and how GM manipulation may influence bone health.


Exercise intervention during pregnancy can be used to manage weight gain and improve pregnancy outcomes in women with gestational diabetes mellitus.
The study aimed to evaluate whether exercise intervention can be applied to pregnant women with gestational diabetes mellitus (GDM) for controlling gestational weight gain (GWG) and combating GDM-related outcomes. Retrospective six months analysis of 14,168 single pregnant women without diabetes from 15 hospitals in Beijing in 2013. Each participant's demographic data, interventions condition and medical information were collected individually by questionnaires and relying on medical records. The level of statistical significance was set equal to 0.05. 2750 (19.4%) pregnant women were diagnosed with GDM, 74.9% of them received exercise intervention during pregnancy, and the starting time was 25.8 ± 3.7 gestational weeks. Women with GDM with exercise intervention (GDM-E) had the lowest BMI increase during late and mid-pregnancy than women with GDM without exercise intervention (GDM-nE) (2.05 ± 1.32 kg/m(2) vs. 2.40 ± 1.30 kg/m(2), p < 0.01) and non-GDM women (2.05 ± 1.32 kg/m(2) vs. 2.77 ± 1.21 kg/m(2), p < 0.01). Moreover, GDM-E group experienced a significantly lower risk of preterm birth (5.58% vs. 7.98%, p < 0.001), low birth weight (1.03% vs. 2.06 %, p < 0.001) and macrosomia (9.51 % vs. 11.18%, p > 0.05) than GDM-nE group. After including dietary factors in the analysis, women with GDM without either dietary or exercise intervention (GDM-nDnE) had the highest risk of preterm birth(OR = 1.64, 95 % CI, 1.14-2.36), while women with GDM with dietary intervention only (GDM-DnE) had the highest risk of low birth weight (OR = 3.10, 95 % CI, 1.23-7.81). However, women with GDM with both dietary and exercise intervention had the lowest rate of macrosomia. Exercise intervention is a suitable non-invasive therapeutic option that can be readily applied to manage weight gain and improve pregnancy outcomes in women with GDM.


Tetanus toxoid microspheres consisting of biodegradable poly(lactide-co-glycolide)- and ABA-triblock-copolymers: immune response in mice.
Tetanus toxoid (TT) was microencapsulated using poly(lactide-co-glycolide) (PLGA) with molar compositions of 50:50, 75:25 or an ABA-triblock-copolymer consisting of PLGA A-blocks attached to a central polyoxyethylene-B-block with a W/O/W (water/oil/water) double emulsion technique. The TT microspheres (MS) were evaluated with respect to protein integrity during antigen release in-vitro and compared with aluminum-adsorbed TT in a mouse model for in-vivo induction of tetanus-specific antibodies as well as protection against a subcutaneous tetanus toxin challenge. The more hydrophilic ABA-triblock-copolymer protected the TT against the deleterious microenvironmental conditions in the degrading MS and provided a prolonged antigen release. In spite of the distinct differences in the in-vitro release patterns MS from PLGA and ABA-triblock-copolymer did not show significant differences in the in-vivo induction of tetanus-specific antibodies. Both preparations elicited antibody titers nearly as high as conventional aluminum-adsorbed TT, which lasted for 29 weeks and were protective against a challenge with 100 x LD(50) tetanus toxin. TT-MS boosted mice which were preimmunized with aluminum-adsorbed as well as with microencapsulated TT. TT-MS are suitable candidates for single shot vaccine delivery systems which elicit a long lasting and protecting immune response.


Impact of different feedstocks derived biochar amendment with cadmium low uptake affinity cultivar of pak choi (Brassica rapa ssb. chinensis L.) on phytoavoidation of Cd to reduce potential dietary toxicity.
Biochar has become eco-friendly amendment used for phytoavoidation with low cadmium (Cd) accumulating cultivars of crops to ensure food safety in Cd contaminated soils. In this study, biochar with different waste feedstock material were evaluated for their effectiveness on essential trace metals mobility, Cd bioavailability and its accumulation in two contrasting Cd accumulating cultivars of pak choi (Brassica rapa ssp. chinensis L.) grown in Cd contaminated Mollisol soil. A greenhouse experiment was conducted with plants grown in Cd contaminated soil that had been amended with biochar derived from barley straw, tomato green waste, chicken manure, duck manure and swine manure at application rate of 0%, 2.5% and 5.0% (w/w). The results showed that soil pH was significantly increased by all treatments. Biochar increased plant dry biomass, micronutrients bioavailability with significant differences in the Cd sorption capacity, with the effectiveness higher with increasing biochar application rate. However, tomato green waste (TGW) and chicken manure (CM) derived biochar were more effective than the other biochar in reducing Cd mobilization in soil by 35-54% and 26-43% and reduced its accumulation in shoots of pak choi cultivars by 34-76% and 33-72% in low Cd accumulator cultivar and 64-85% and 55-80% in high Cd accumulator cultivar than the control. Overall, results indicate that TGW and CM biochar can efficiently immobilize Cd, thereby reducing bioavailability in Cd contaminated Mollisol soil to ensure food safety.


Characterization of Grades of HPMCAS Spray Dried Dispersions of Itraconazole Based on Supersaturation Kinetics and Molecular Interactions Impacting Formulation Performance.
The objective was to characterize hydroxypropyl methylcellulose acetate succinate (HMPCAS) grades L, M, and H to enhance itraconazole (ITZ) release and permeation from spray dried dispersions (SDDs), and to investigate underpinning molecular ITZ-HPMCAS interactions that differentiated grade performance. ITZ or its SDDs were subjected to solution stabilization assessment, one-dimensional proton nuclear magnetic resonance (NMR) spectroscopy, saturation transfer difference NMR studies, small volume dissolution, solid state transformation studies, and in vitro dissolution/permeation flux studies. HPMCAS-L was the best performing grade overall and exhibited greatest ITZ supersaturation concentration, small volume dissolution, and in vitro dissolution/permeation flux. Meanwhile, H grade retarded ITZ precipitation to the greatest extent in solution stabilization studies and exhibited greater hydrophobic interaction with ITZ in NMR studies. However, this apparent advantage of H grade through hydrophobic interactions between drug-polymer appeared to limit overall dissolution/permeation performance of SDD. In vitro SDD studies and drug-polymer interaction studies provided insight into the performance of HPMCAS grades, as well as the relative contributions of various mechanisms that polymer can promote ITZ absorption from SDD.


Thermal desorption characterisation of molecularly imprinted polymers. Part I: A novel study using direct-probe GC-MS analysis.
A novel thermal desorption technique using a direct-probe device (Chromatoprobe) attached to a gas chromatograph-mass spectrometer is presented for the thermal pretreatment, characterisation and analysis of molecularly imprinted polymers. The technique is demonstrated as effective for the removal of volatile materials, including template and unreacted monomers, from methacrylic acid-ethylene glycol dimethacrylate copolymers imprinted with 2-aminopyridine. Mass spectrometry is a powerful technique for polymer bleed characterisation. Thermal desorption studies on reloaded template and related compounds are reported as a means of assessing polymer morphology, specific binding by imprinted polymers compared with reference non-imprinted polymers and selective binding by an imprinted polymer for its template. Calibration studies on the thermal desorption technique using an internal standard are presented with R(2) > 0.999. The technique provides a novel method for assessment of polymer thermal stability, composition and morphology.


The effects of complex metal oxide mixtures on three soil invertebrates with contrasting biological traits.
For regulatory purposes, the concentration addition model is the default first tier for assessing joint-action toxicity of metal mixtures. Although many researchers have evaluated binary and ternary mixtures, fewer have investigated joint-action toxicity in more complex mixtures, where deviations from additivity are more likely due to the greater number of potential interactions. In this study, we tested fixed ratios of five metals (lead, copper, nickel, zinc, cobalt) as metal oxide mixtures on three soil invertebrate species (Enchytraeus crypticus, Folsomia candida, Oppia nitens) at different dose effect levels (EC10-EC90) in an acid sandy forest and a loamy soil. Total metal concentrations for mixture ratios in soil did not explain or correlate with species responses. For F. candida, toxicity was linked to metal solubility, while for O. nitens and E. crypticus, toxicity did not correlate with total or extractable metals. In O. nitens and E. crypticus, however, soil ingestion could be an important route of exposure. Analysing the joint effect of metal mixtures, F. candida response was globally additive, while E. crypticus and O. nitens both presented synergistic effects at low-dose effect levels. Estimations at the EC50 level underestimated the deviations from additivity which were larger at higher and especially lower effect levels. Testing across different effect concentrations (EC10-EC90) was an important tool allowing the identification of these larger deviations from additivity outside the EC50 threshold. Considering most protection thresholds are set below the EC50 level, and it was in this low effect range where the highest synergisms were observed, risk assessment schemes should test additivity at the target protection level using representative test organisms.


Validation of Transvaginal Hysterectomy Surgical Model - Modification of the Flowerpot Model to Improve Vesicovaginal Plane Simulation.
To establish face and construct validity for a novel variation of American College of Obstetrics and Gynecology "Flowerpot Model" for transvaginal hysterectomy (TVH) surgical simulation with improved vesicovaginal dissection during surgical education simulation. Cross-sectional face and construct validation study using the "Flowerpot Model." The vesicovaginal dissection plane was modified to include additional felt and balloon materials to simulate the bladder. Single academic center. Fourteen residents and fellows, postgraduate year (PGY) 2 to 6, subdivided into junior (n = 8) with ≤10 prior TVH surgeries and senior groups (n = 6) with >10 prior TVH surgeries performed. All subjects watched a brief introductory video and then were filmed simulating a TVH. For face validity, subjects completed an anatomic checklist and pre/post simulation satisfaction survey. For construct validation, 2 independent, blinded expert surgeons (M.A. and J.M.) graded films using the Global Rating Scale of Operative Performance (GRS). Primary outcome was mean GRS between groups. The junior group consisted of PGY 2 to 3 with ≤ 10 prior TVH, median 7.5 (interquartile range [IQR] 6.75) and senior group PGY 3 to 6 with >10 TVH, median 19 (IQR 10) (p <.01). Subjects were "satisfied" or "very satisfied" with bladder and anterior peritoneal fold simulation (92%) and found vesicovaginal dissection "realistic" (100%). GRS score was significantly different between groups (juniors, 19.5 [IQR 5] vs seniors, 28.5 [IQR 8.5]; p = .048). Intergrader correlation was high (ρ = 0.87, p <.01). Surgeon volume of prior TVH was not significantly correlated to average GRS score, ρ = 0.49 (p = .10). The model improved comfort and confidence scores in the junior group more than senior group (p = .04), but senior group still had higher post simulation confidence scores than the junior group (p = .02). Face and construct validity with the modified Flowerpot Model was demonstrated. This low fidelity model is capable of simulation of a TVH with a novel vesicovaginal dissection. Prior surgical experience was not correlated to GRS score or time to procedure completion.


The added value of umbilical vein flow in predicting fetal macrosomia at 36 weeks of gestation: A prospective cohort study.
Current models based on fetal biometry and maternal characteristics have a poor performance in predicting macrosomia. The primary aim of this study was to elucidate the diagnostic performance of fetal venous and arterial Dopplers in predicting macrosomia in the third trimester of pregnancy; the secondary aim was to build a multiparametric prediction model including pregnancy, ultrasound and Doppler characteristics able to predict macrosomia accurately. Prospective cohort study including 2156 singleton pregnancies scheduled for routine ultrasound assessment at 36 weeks of gestation. Fetal biometry, estimated fetal weight (EFW), pulsatility index of the uterine, umbilical, and middle cerebral arteries, cerebroplacental ratio and umbilical vein blood flow (UVBF) normalized for fetal abdominal circumference (UVBF/AC) were recorded. Primary outcome was the prediction of fetal macrosomia, defined as a birthweight >90th percentile; secondary outcome was the prediction of newborns >4000 g. Logistic regression and area under the curve (AUC) analyses were used to analyze the data. Fetal macrosomia complicated 9.8% of pregnancies, and 7.7% of newborns had a birthweight >4000 g. At multivariate logistic regression analysis, maternal body mass index (adjusted odds ratio [aOR] 1.23), pregestational diabetes (aOR 1.83), a prior newborn with a birthweight >95th centile (aOR 1.49), EFW (aOR 2.23) and UVBF (aOR1.84) were independently associated with macrosomia, whereas gestational diabetes mellitus (P = .07) or any of the other Doppler parameters were not. EFW had an AUC of 0.750 and of 0.801 alone and in association with maternal characteristics for the prediction of macrosomia, respectively. The addition of UVBF to this model significantly improved the prediction of fetal macrosomia provided by maternal and ultrasound parameters with an AUC of 0.892 (De Long P = .044 and P = .0078, respectively). The predictive performance for birthweight >4000 g was similar and significantly improved when UVBF was included in the diagnostic algorithm. Umbilical vein blood flow evaluation in the third trimester improves the diagnosis of fetal macrosomia. The optimal diagnostic performance for macrosomia is achieved by a multiparametric model including umbilical vein flow, maternal characteristics and EFW.


M1 acetylcholine receptors in somatostatin interneurons contribute to GABAergic and glutamatergic plasticity in the mPFC and antidepressant-like responses.
Alterations in glutamatergic and GABAergic function in the medial prefrontal cortex (mPFC) are prevalent in individuals with major depressive disorder, resulting in impaired synaptic plasticity that compromises the integrity of signal transfer to limbic regions. Scopolamine, a non-selective muscarinic receptor antagonist, produces rapid antidepressant-like effects by targeting M1-type acetylcholine receptors (M1R) on somatostatin (SST) interneurons. So far, these effects have been investigated with relatively short-term manipulations, and long-lasting synaptic mechanisms involved in these responses are still unknown. Here, we generated mice with conditional deletion of M1R (M1f/fSstCre+) only in SST interneurons to determine the role of M1R in modulating long-term GABAergic and glutamatergic plasticity in the mPFC that leads to attenuation of stress-relevant behaviors. We have also investigated whether the molecular and antidepressant-like effects of scopolamine could be mimicked or occluded in male M1f/fSstCre+ mice. M1R deletion in SST-expressing neurons occluded the rapid and sustained antidepressant-like effects of scopolamine, as well as scopolamine-induced increases in c-Fos+/CaMKIIα cells and proteins necessary for glutamatergic and GABAergic function in the mPFC. Importantly, M1R SST deletion resulted in resilience to chronic unpredictable stress in behaviors relevant to coping strategies and motivation, and to a lesser extent, in behaviors relevant to avoidance. Finally, M1R SST deletion also prevented stress-induced impairments in the expression of GABAergic and glutamatergic markers in the mPFC. These findings suggest that the antidepressant-like effects of scopolamine result from modulation of excitatory and inhibitory plasticity via M1R blockade in SST interneurons. This mechanism could represent a promising strategy for antidepressant development.


The structure of the Rous sarcoma virus glycoprotein complex.
The viral envelope glycoprotein gp85 is released from purified Rous sarcoma virus by treatment with 2-mercaptoethanol, while the second surface antigen gp35 remains associated with the membrane of intact virus particles. The data represented substantiate and extend previous observations on the Rous sarcoma virus glycoprotein complex.


Maximum voluntary ventilation as a sensitive measure to monitor the ventilatory function in cervical spondylotic myelopathy.
A prospective clinical cohort study. To test if maximum voluntary ventilation (MVV), which is currently underutilized in diseases, serves for assessing subclinical ventilatory impairment in cervical spondylotic myelopathy (CSM). Kochi Medical School, Japan. We studied ventilatory function in 49 CSM patients and 20 age- and sex-matched control patients with either lumbar stenosis or lower limb osteoarthritis. All patients underwent ventilatory function studies consisting of flow volume curves, vital capacity (VC) and the MVV in 12 s before and after surgery. Tetraparesis was assessed by the functional scale of the Japanese Orthopaedic Association (JOA). The CSM group had significantly smaller %forced VC , %peak expiratory flow rate (%PEFR) and %MVV than the control group preoperatively. In contrast to the control group, the CSM group showed a significant increase in %MVV from 74.9±18.7% preoperatively to 80.3±19.0% postoperatively (P<0.005), but not in any other ventilatory measures. This postoperative increase in %MVV significantly correlated with the JOA score (r=0.493; P<0.001). As a possible effect of diaphragmatic recovery, the %PEFR significantly increased postoperatively only in patients with the primary site of involvement at or rostral to C3-4. Of the various ventilatory measurements, MVV was most sensitive to changes in tetraparesis in CSM, presumably because MVV, unlike the other ventilatory measures, reflects the coordination in addition to the strength of respiratory muscles.


[Innovative approaches to diagnosis and treatment of occupational diseases (on joint diseases model)].
The authors studies features of structure and functional state of knee joints in occupational diseases. Findings are peripheral circulatory disorders, changes in all hemostasis levels, with trend to increased platelets aggregation, hyperfibrinogenemia, hypercoagulation and fibrinolysis system disorders. Considering the diagnosis, the authors specified treatment algorithms for occupational osteoarthrosis.


Using dynamic monitoring of choices to predict and understand risk preferences.
Navigating conflict is integral to decision-making, serving a central role both in the subjective experience of choice as well as contemporary theories of how we choose. However, the lack of a sensitive, accessible, and interpretable metric of conflict has led researchers to focus on choice itself rather than how individuals arrive at that choice. Using mouse-tracking-continuously sampling computer mouse location as participants decide-we demonstrate the theoretical and practical uses of dynamic assessments of choice from decision onset through conclusion. Specifically, we use mouse tracking to index conflict, quantified by the relative directness to the chosen option, in a domain for which conflict is integral: decisions involving risk. In deciding whether to accept risk, decision makers must integrate gains, losses, status quos, and outcome probabilities, a process that inevitably involves conflict. Across three preregistered studies, we tracked participants' motor movements while they decided whether to accept or reject gambles. Our results show that 1) mouse-tracking metrics of conflict sensitively detect differences in the subjective value of risky versus certain options; 2) these metrics of conflict strongly predict participants' risk preferences (loss aversion and decreasing marginal utility), even on a single-trial level; 3) these mouse-tracking metrics outperform participants' reaction times in predicting risk preferences; and 4) manipulating risk preferences via a broad versus narrow bracketing manipulation influences conflict as indexed by mouse tracking. Together, these results highlight the importance of measuring conflict during risky choice and demonstrate the usefulness of mouse tracking as a tool to do so.


The Diagnostic Value of Diffusion-Weighted Imaging in Differentiating Metastatic Lymph Nodes of Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.
Accurate lymph node staging is crucial for proper treatment planning for metastasis in patients with head and neck squamous cell carcinoma. Our aim was to evaluate the diagnostic performance of DWI for differentiating metastatic cervical lymph nodes from benign cervical lymph nodes in patients with head and neck squamous cell carcinoma and to identify optimal cutoff values for ADC. A computerized literature search was performed to identify relevant original articles in Ovid MEDLINE and EMBASE. Studies evaluating the diagnostic performance of DWI for differentiating metastatic cervical lymph nodes from benign cervical lymph nodes were selected. Diagnostic meta-analysis was conducted with a bivariate random-effects model, and a hierarchical summary receiver operating characteristic curve was obtained. Meta-regression was also performed. Nine studies with 337 patients were included. In all studies, ADC values derived from metastatic lymph nodes were significantly lower than ADC values derived from benign lymph nodes. The median ADC cutoff value was 0.965 × 10-3 mm2/s. The pooled sensitivity and specificity for the diagnostic performance of DWI in differentiating metastatic lymph nodes from benign lymph nodes were 90% (95% CI, 84%-94%) and 88% (95% CI, 80%-93%), respectively. In the meta-regression, sensitivity was significantly higher in the studies using a 3-mm slice thickness (93% [95% CI, 88%-98%]) than in studies using a slice thickness of >3 mm (86% [95% CI, 77%-95%], P < .01). A small number of studies were included in our meta-analysis. DWI demonstrated high diagnostic performance for differentiating metastatic lymph nodes from benign lymph nodes in patients with head and neck squamous cell carcinoma, and the median ADC cutoff value was 0.965 × 10-3 mm2/s. A 3-mm DWI slice thickness can provide a slight improvement in sensitivity.


Transformation of normal hamster cells by benzo(a)pyrene diol-epoxide.
The frequency of cell transformation was determined after treatment of normal hamster embryo cells with benzo(a)pyrene (BP) and six of its metabolites. These metabolites included the trans 4,5-, 7,8- and 9,10-dihydrodiols; the 4,5-epoxide; and two stereoisomers of the non-K-region diol epoxides r-7, t-8-dihydroxy t-9, 10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epoxide 1) and r-7, t-8, dihydroxy c-9, 10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epoxide 11). The trans 7,8-dihydrodiol was more active than the other two dihydrodiols tested and was also more active than the parent hydrocrabon BP. Of the three epoxides tested, the diol-epoxide 1 was more active than the 4,5-epoxide and diol-epoxide 11. The results suggest that diol-epoxide 1 is a major cell-transforming metabolite of BP.


Comparison of liver disease state progression in patients with eradication of versus persistent infection with hepatitis C virus: Markov chain analysis.
To investigate the long-term prognosis of liver disease in patients with hepatitis C virus (HCV) eradication after antiviral therapy versus those with persistent HCV infection. Four hundred and eighty patients (5259 person-years [PYs]) who received interferon-based therapy and achieved sustained virologic response and 848 patients (3853 PYs) with persistent HCV infection were included. In the analysis of 1-year liver disease state transition probability matrices using Markov chain models, progression to cirrhosis from the chronic hepatitis state was observed (0.00%-0.63%) in patients with HCV eradication. Among patients with chronic hepatitis or cirrhosis and HCV eradication, hepatocellular carcinoma (HCC) development was observed in males aged ≥ 50 years (0.97%-1.96%) and females aged ≥ 60 years (0.26%-5.00%). Additionally, in patients with cirrhosis and HCV eradication, improvement to chronic hepatitis was also observed (4.94%-10.64%). Conversely, in patients with chronic hepatitis and persistent HCV infection, progression to cirrhosis was observed in males aged ≥ 30 years and female aged ≥ 40 years (0.44%-1.99%). In males aged ≥ 40 years and female aged ≥ 50 years with cirrhosis, the transition probability for HCC was relatively high (4.17%-14.02%). Under the assumption of either chronic hepatitis or cirrhosis at age 40 or 60 years as the starting condition for simulation over the next 30 or 40 years, respectively, the probability of HCC was higher in patients with persistent HCV infection than those with HCV eradication. In conclusion, HCV eradication can reduce the risk of developing cirrhosis or HCC in patients with chronic HCV infection.


Quality evaluation of commercial Huang-Lian-Jie-Du-Tang based on simultaneous determination of fourteen major chemical constituents using high performance liquid chromatography.
Huang-Lian-Jie-Du-Tang (HLJDT), comprising Coptidis Rhizoma, Scutellariae Radix, Phellodendri Cortex and Gardeniae Fructus, is one of the commonly used Chinese medicine formulas for clearing heat and detoxifying. Quality control of the herbal complex like Chinese medicine formulas still remains a challenge. The successful approval of botanical drug Veregen by FDA indicated the importance of quantitative analysis in quality control of herbal medicines. In this study, an effective quantitative method based on conventional HPLC-DAD was developed for simultaneous determination of fourteen major ingredients (seven alkaloids, four flavonoids, three terpenes) in HLJDT. The established method was well validated in terms of linearity, sensitivity, precision, accuracy and stability and then successfully applied to quality evaluation of commercial HLJDT samples. The developed method can quantitatively determine up to 70% of the chemicals of commercial HLJDT sample and effectively revealed the significant variation in the quality of the commercial HLJDT samples collected from different locations.