Context-aware learning for cancer cell nucleus recognition in pathology images.
Nucleus identification supports many quantitative analysis studies that rely on nuclei positions or categories. Contextual information in pathology images refers to information near the to-be-recognized cell, which can be very helpful for nucleus subtyping. Current CNN-based methods do not explicitly encode contextual information within the input images and point annotations. In this article, we propose a novel framework with context to locate and classify nuclei in microscopy image data. Specifically, first we use state-of-the-art network architectures to extract multi-scale feature representations from multi-field-of-view, multi-resolution input images and then conduct feature aggregation on-the-fly with stacked convolutional operations. Then, two auxiliary tasks are added to the model to effectively utilize the contextual information. One for predicting the frequencies of nuclei, and the other for extracting the regional distribution information of the same kind of nuclei. The entire framework is trained in an end-to-end, pixel-to-pixel fashion. We evaluate our method on two histopathological image datasets with different tissue and stain preparations, and experimental results demonstrate that our method outperforms other recent state-of-the-art models in nucleus identification. The source code of our method is freely available at https://github.com/qjxjy123/DonRabbit. Supplementary data are available at Bioinformatics online.


2,5-Hexanedione induces human ovarian granulosa cell apoptosis through BCL-2, BAX, and CASPASE-3 signaling pathways.
Studies have shown that 2,5-hexanedione (2,5-HD) is the main active metabolite of n-hexane in the human body. The toxicity of n-hexane and 2,5-hexanedione has been extensively researched, but toxicity to the reproductive system, especially the impact on female reproductive function, has been less frequently reported. In this study, we exposed human ovarian granulosa cells to 0, 16, 64, and 256 μM 2,5-HD in vitro for 24 h. Through hematoxylin-eosin (HE) staining, Hoechst 33342 staining, transmission electron microscopy, and flow cytometry using FITC-Annexin V/PI double staining, 2,5-HD was demonstrated to cause significant apoptosis of human ovarian granulosa cells in a dose-dependent manner. As part of our continuing studies, we investigated the underlying apoptosis mechanism of human ovarian granulosa cells exposed to 0, 16, 64, and 256 μM 2,5-HD in vitro for 24 h. Real-time quantitative PCR and Western blot analysis were used to detect changes in the expression of the apoptosis-related BCL-2 family (BCL-2, BAX) and CASPASE family (CASPASE-3) with increasing 2,5-HD concentration. The results showed that with increasing 2,5-HD doses, the expression of BCL-2 decreased. However, a marked dose-dependent increase in the expression of BAX and active CASPASE-3 (p17) was observed in human ovarian granulosa cells. These results suggest that the mechanisms of 2,5-HD causing increased apoptosis in human ovarian granulosa cells might be through BCL-2, BAX, and CASPASE-3 signaling pathways.


Augmentation rhinoplasty with soft tissue and cartilage.
Augmentation rhinoplasty using soft tissue and cartilage was performed on 120 patients and the results were reexamined. They were found to be satisfactory and without complication. To narrow a round tip, a resection of two-thirds of the lateral crus cephalad portion and a transection of the caudal portion with a strip resection was done. To elevate the tip, septal cartilage was sutured to one-third of the upper part of medial crus to form a columella cartilage strut. To maintain the strut and to prevent pointing, a fibrous muscle tissue stretching from the medial crus to the upper cartilage or a dermis was transplanted into the area surrounding the septal cartilage tip. For a simple elevation of the dorsum, an onlay graft of dermis was applied, but where further elevation was required, further dermis and conchal cartilage was added for suture and attachment to the dermis.


Phosphorylated α-synuclein in diluted human serum as a biomarker for Parkinson's disease.
Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders, which characterized by increased pathological marker protein, α-synuclein (α-syn) and phosphorylated-Ser129-α-syn in the extracellular fluids. Current methods of measuring the p-Ser129-α-syn concentration in cerebrospinal fluid for PD are based on ELISA method, however, the amount of area under the curve (AUC) to predict PD is around 0.7-0.8. Higher confidence level of AUC in p-Ser129-α-syn quantification for the early diagnosis of PD would be essential. Detection of p-Ser129-α-syn in diluted human serum for diagnosis of PD was investigated by a modified paired surface plasma wave biosensor (PSPWB) using a quarter wave plate for better detection performance. The method combining an immunoassay and non-labeled technique measures the p-Ser129-α-syn level with high sensitivity and specificity. Ten patients with PD at early stage (Hohn & Yahr stage I and II) and 11 age-matched healthy control participants were recruited for measurement of serum p-Ser129-α-syn. AUC of the p-Ser129-α-syn in diluted human serum was 0.92 and it shows that p-Ser129-α-syn in diluted human serum could be used as a sensitive biomarker for the diagnosis of PD in clinics. Results clearly show that the measured p-Ser129-α-syn concentration in diluted human serum displays a statistical significance between health control subjects and PD patients. P-Ser129-α-syn has low abundance in human serum, high detection sensitivity and specificity are critical to the success of the diagnosis of PD in clinics. In this study, a modified PSPWB was developed that the limit of detection at 1 ng/mL for p-Ser129-α-syn (standard) spiked into diluted human serum of a healthy control was performed. This result shows that the modified PSPWB can be used as a platform for detecting p-Ser129-α-syn in diluted human serum as a potential biomarker for PD.


Age and sex influence the response in lipid metabolism of dehydrated Wistar rats.
Aging is associated a decrease in thirst sensation, which makes old people more susceptible to dehydration. Dehydration produces energy metabolism alterations. Our objective was to determinate the effect of water deprivation (WD) in the lipid metabolism of old male and female rats. Here we show that in the state of WD, aging and sex alters retroperitoneal white adipose tissue (R-WAT) weight of rats, WD old female rats had more lipolysis products than old male rats, a sexual dimorphism in the hormonal response related with metabolism of the adipose tissue of old rats during WD, the expression of P-para mRNA in R-WAT did not present any alteration in animals submitted to WD, the expression of Aqp7 mRNA in R-WAT is altered by WD, age, and sex. Also, WD stimulated an increase in the plasma concentration of oxytocin and the expression of mRNA of the oxytocin receptors in R-WAT.


Fluticasone Propionate with Azelastine Versus Standalone Fluticasone Propionate as Nasal Spray in Allergic Rhinitis: A Prospective Comparative Study in a Rural Population of Northern India.
Allergic rhinitis (AR) is a symptomatic condition of the nose, caused by an IgE-mediated inflammation of the nasal membranes. Allergic rhinitis is further split into two categories, based on the duration of symptoms: intermittent (IAR) or persistent (PER) disease. Oral or topical antihistamines and topical nasal steroids are the most popular and efficient treatments for allergic rhinitis. The present prospective comparative study was done between December 2021 to November 2022, with 64 subjects of PER divided into groups A and B. Group A patients received Fluticasone propionate (50 mcg) combined with Azelastine (140 mcg) nasal spray, whereas Group B patients received standalone Fluticasone propionate (50 mcg) nasal spray. In both groups, the difference in mean TSS between the beginning and end of the 4-week study period was statistically significant (p for both < 0.05). After 4 weeks of treatment, Group A had a TSS of 2.02 ± 0.83 and Group B was at 3.80 ± 1.49; the difference between them was statistically significant (p < 0.05). According to results obtained from the current study, while both fluticasone propionate with azelastine nasal spray and standalone fluticasone propionate nasal spray are widely used for control of symptoms in PER, the former offers better results with significant reduction of symptoms when compared to the latter.


Local failure and vertebral body fracture risk using multifraction stereotactic body radiation therapy for spine metastases.
Single-fraction radiation surgery for spine metastases is highly effective. However, a high rate (20-39%) of vertebral body fracture (VBF) has been associated with large, single-fraction doses. We report our experience using multifraction stereotactic body radiation therapy (SBRT). All patients who were treated with multifraction SBRT for spine metastases at our institution between 2009 and 2017 were retrospectively analyzed. SBRT was delivered in 2 to 5 fractions using the Cyberknife System (Accuray, Sunnyvale, CA). Patients were followed clinically and with magnetic resonance imaging every 3 to 6 months. Local control, complications (including VBF), and overall survival were evaluated. Patient, disease, and treatment variables were analyzed for a statistical association with outcomes. A total of 83 patients were treated to 98 spine lesions with a median follow-up of 7.6 months. Histologies included non-small cell lung cancer (NSCLC; 24%), renal cell carcinoma (RCC; 18%), and breast cancer (12%). Surgery or vertebroplasty were performed before SBRT in 21% of cases. Patients received a median SBRT dose of 24 Gy in a median of 3 fractions. Local control was 93% at 6 months and 84% at 1 year. Higher prescribed dose, higher biologic effective dose, higher minimum dose to 90% of the planning target volume, tumor histology, and smaller tumor volume predicted improved local control. The cumulative dose was 23 Gy versus 26 Gy for patients with and without failure (P = .02), higher biologic effective dose 39 Gy versus 46 Gy, (P = .01), and higher minimum dose to 90% of the planning target volume 23 Gy versus 26 Gy (P = .03). VBF occurred in 4.2% of all cases and 5.3% of those without surgery or vertebroplasty prior to SBRT. Only preexisting VBF predicted risk of post-SBRT VBF (P < .01). Multifraction SBRT results in a high local control rate for metastatic spinal disease with a low VBF rate, which suggests a favorable therapeutic ratio compared with single-fraction SBRT.


The hydro-chloride salt of 4-hy-droxy-N,N-di-n-propyl-tryptamine (4-HO-DPT).
The title compound, 4-hy-droxy-N,N-di-n-propyl-tryptammonium (4-HO-DPT) chloride {systematic name: N-[2-(4-hy-droxy-1H-indol-3-yl)eth-yl]-N-propyl-propan-1-aminium chloride}, C16H25N2O+·Cl-, has a singly protonated trypt-ammonium cation and one chloride anion in the asymmetric unit. A series of N-H⋯Cl and O-H⋯Cl hydrogen bonds connect the ions together in ladder chains along [010].


[Mutagenicity of dichloroacetaldehyde and 2,2-dichloro-1,1-dihydroxy-ethanephosphonic acid methyl ester, possible metabolites of the organophosphate pesticide Trichlorphon].
Dichloroacetaldehyde and 2,2-dichloro-1,1-dihydroxy-ethanephosphonic acid methyl ester which are formed solvolytically from desmethyltrichlorphone, an in vivo metabolite of the organophosphorus pesticide Trichlorphone, show in the dominant lethal test in mice at equimolar dosage (1.6 mmol/kg) a mutagenic activity comparable with that of Trichlorphon. Therefore it cannot be ruled out that the genetic effects of this pesticide may be due in part to the action of its degradation products.


[Caregivers of people with neurodegenerative diseases: from help to delegation].
Being a caregiver is difficult, even more so when it comes to helping people with a neurodegenerative disease. These caregivers, either family members or close friends, are confronted with an unexpected delegation which can prove to be highly complex as the pitfalls can indeed be significant. Moreover, the support the caregivers can provide depends on the support they can get for themselves.


Kienböck's disease in a patient with Crohn's enteritis treated with corticosteroids.
In a patient with Crohn's enteritis treated with oral corticosteroids simultaneous Kienböck's disease and femoral head osteonecrosis developed 2 years after the administration of corticosteroids. The patient had no history of trauma or any other risk factor known to be associated with Kienböck's disease. This case suggests that corticosteroid administration may be an additional factor in the multifactorial causes of Kienböck's disease.


An interactive videodisk training program in basic cardiac life support: implications for staff development.
Interactive videodisk training programs offer a new instructional approach to demands for technical skills training. This article highlights the demands for staff development providers to address technical skills training through interactive videodisk modalities.


Comparison of high density lipoprotein and serum cholesterol levels in a European and an African community.
Serum and high density lipoprotein cholesterol concentrations have been measured in 210 men and women in a London community and in a Nsukka community. Mean serum cholesterol concentrations were higher in London than in Nsukka. High density lipoprotein cholesterol was, however, higher in Nsukka than in London. Whereas the difference in serum cholesterol reached a statistical level when all the age groups were considered together, there was no statistical difference when the two populations were considered in terms of the young (20-39 year age group) and the middle aged (40-59 year age group). Difference in high density lipoprotein cholestrol, however, reached a statistical level in these two age groups.


Management of complications of wrist arthroplasty and wrist fusion.
The human wrist joint is unique from functional and anatomic standpoints. Numerous articulations exist within the wrist that allow for many options for partial wrist fusion and arthroplasty. In cases of pancarpal disease, fusion or arthroplasty of the entire wrist joint can be performed. Because of the high functional demand of the wrist, many of these surgical options can fail, leading to devastating complications. This article addresses the types of fusions and arthroplasties available for the wrist and discusses the potential complications associated with each. Methods to prevent these complications are presented and those to treat them once they have occurred are discussed.


Combination chemotherapy and IL-15 administration induce permanent tumor regression in a mouse lung tumor model: NK and T cell-mediated effects antagonized by B cells.
Previous studies have demonstrated that IL-15 administration after cyclophosphamide (CY) injection of C57BL/6J mice bearing the i.m. 76-9 rhabdomyosarcoma resulted in a significant prolongation of life. In the present study, we investigated the immune response against the 76-9 experimental lung metastases after CY + IL-15 therapy. Administration of CY + IL-15, but not IL-15 alone, induced prolongation of life and cures in 32% of mice bearing established experimental pulmonary metastases of 76-9 tumor. The CY + IL-15 therapy resulted in increased levels of NK1.1+/LGL-1+ cells, and CD8+/CD44+ T cells in PBL. In vitro cytotoxic assay of PBL indicated the induction of lymphokine-activated killer cell activity, but no evident tumor-specific class I-restricted lytic activity. Survival studies showed that the presence of NK and T lymphocytes is necessary for successful CY + IL-15 therapy. Experiments using knockout mice implied that either alphabeta or gammadelta T cells were required for an antitumor effect induced by CY + IL-15 therapy. However, mice lacking in both alphabeta and gammadelta T cells failed to respond to combination therapy. Cured B6 and alphabeta or gammadelta T cell-deficient mice were immune to rechallenge with 76-9, but not B16LM tumor. B cell-deficient mice showed a significant improvement in the survival rate both after CY and combination CY + IL-15 therapy compared with normal B6 mice. Overall, the data suggest that the interaction of NK cells with tumor-specific alphabeta or gammadelta T lymphocytes is necessary for successful therapy, while B cells appear to suppress the antitumor effects of CY + IL-15 therapy.


Segmental neurofibromatosis in an octogenarian.
A case of segmental neurofibromatosis (SNF) in an octogenarian is presented. The patient's lesions were first noted when he was 74 years of age. This variant of neurofibromatosis (Riccardi's classification, NF-V) is most typically seen in childhood or young adulthood. To the best of our knowledge, our patient's SNF is the first case to present in the eighth decade of life. Physicians working with geriatric patients should be aware of this entity and its lack of genetic heritability or systemic manifestations.


Effect of blood meal and mating on the genital tract ultrastructure in the female camel tick Hyalomma (Hyalomma) dromedarii (Ixodoidea: Ixodidae).
The genital tract ultrastructure in the female Hyalomma (Hyalomma) dromedarii is described during feeding and mating and up to oviposition. The vagina, consisting of vestibular (VV) and cervical (CV) regions, is formed of an epithelium lined internally with a folded cuticular layer and surrounded externally by muscle layers. These facilitate the passage of endospermatophores containing sperm into the receptaculum seminis (RS), and ova to the exterior. A pair of tubular accessory glands (AG) opening at the junction of VV and CV consist of an epithelial layer of undifferentiated cells. As feeding progresses, these cells synthesise their granular secretion which lubricates the egg surface during its passage through VV. The RS, opening anteriorly into the CV, consists of cuboidal cells lined with a thin cuticular layer. These cells become rich in glycogen and lipid vacuoles, possibly acting as a source of energy for various cell activities including granule synthesis and exocytosis. The granules discharge their contents into intercellular spaces distributed throughout the RS wall and communicate with the main lumen via narrow channels. The cell secretion may dissolve the endospermatophore wall to release sperm, while their lysosome-like structures may function in the breakdown of endospermatophoric material taken up by pinocytosis. The connecting tube (CT) opens into the CV anterodorsally and leads into the common oviduct (COV) posteriorly. It consists of an epithelium lined by a closely-adhering cuticular layer, giving the tube lumen the appearance of an undulate labyrinth with a complicated configuration. No secretory activity in the CT has been observed before, during, or after feeding. The paired, non-cuticular oviducts, extending from the ovary and fusing anteriorly to form COV, consist of an epithelium poor in cell organelles. At the final stages of feeding the cell cytoplasm contains large, phagosomal vacuoles penetrated by sperms, in addition to micropinocytotic vesicles which serve to break down the seminal fluid and other materials. The basal membrane is infolded giving characteristic features, which increase dramatically during oviposition, of epithelia involved in ion and water transport. The oviducal secretion may function as a tanning agent to harden the egg-shell and may also act as a lubricant for egg passage.


Facial pain: a possible therapy with stellate ganglion block.
The goal of the present study is to verify the efficacy of stellate ganglion block (SGB) in the treatment of facial pain that can be found in different pathological syndromes, and also to examine whether the efficacy is dependent upon when this therapy is administered. Fifty patients (divided into two randomized groups) with facial pain caused by traumas, iatrogenic issues, herpes zoster, or neurological pathologies participated in this study. The first group (N = 25) was treated with SGB produced by 10 administrations of 10 mg of levobupivacaine given every other day, followed by one administration per month for 6 months thereafter. The second group was treated with the drugs tramadol 100 mg/day and gabapentin 1800 mg/day orally for 6 months; during the 7th month they were given SGB therapy using the same methodology as that described for the first group. Before treatment, the mean visual analog scale (VAS) pain score for the first group was 8.89; after the 10th block treatment it was just 0.2, and it remained at that reduced level for the 6th and 12th months. Before treatment, the mean VAS pain score for the second group was 8.83; after the 20th day on medication it was reduced to 4.1, after 6 months it was 5.7 and after 12 months it was 4.9. Our results indicate that patients must be treated with SGB therapy precociously to receive its full benefits.


Meaning making about performance: A comparison of two specialty feedback cultures.
Specialty trainees often struggle to understand how well they are performing, and feedback is commonly seen as a solution to this problem. However, medical education tends to approach feedback as acontextual rather than located in a specialty-specific cultural world. This study therefore compares how specialty trainees in surgery and intensive care medicine (ICM) make meaning about the quality of their performance and the role of feedback conversations in this process. We conducted a qualitative interview study in the constructivist grounded theory tradition. We interviewed 17 trainees from across Australia in 2020, eight from ICM and nine from surgery, and iterated between data collection and analytic discussions. We employed open, focused, axial and theoretical coding. There were significant divergences between specialties. Surgical trainees had more opportunity to work directly with supervisors, and there was a strong link between patient outcome and quality of care, with a focus on performance information about operative skills. ICM was a highly uncertain practice environment, where patient outcome could not be relied upon as a source of performance information; valued performance information was diffuse and included tacit emotional support. These different 'specialty feedback cultures' strongly influenced how trainees orchestrated opportunities for feedback, made meaning of their performance in their day-to-day patient care tasks and 'patched together' experiences and inputs into an evolving sense of overall progress. We identified two types of meaning-making about performance: first, trainees' understanding of an immediate performance in a patient-care task and, second, a 'patched together' sense of overall progress from incomplete performance information. This study suggests approaches to feedback should attend to both, but also take account of the cultural worlds of specialty practice, with their attendant complexities. In particular, feedback conversations could better acknowledge the variable quality of performance information and specialty specific levels of uncertainty.


Evaluation of the ethmoid skull-base height prior to endoscopic sinus surgery: a preoperative computed tomography evaluation technique.
Iatrogenic ethmoid skull base (ESB) injury during endoscopic sinus surgery (ESS) is a potentially devastating complication. The height of the ESB can vary substantially and should be assessed during preoperative evaluation of the sinus computed tomography (CT) scan. The objective of this study is to describe an objective preoperative CT evaluation technique to assist the surgeon in defining the height of the ESB prior to performing ESS. We propose a technique which measures the height of the ESB from a single horizontal mid-orbital line located on a standardized coronal sinus CT image at the level of the anterior ethmoid artery canal. Utilization of an objective preoperative CT measurement technique may quantify identification of a low ESB and optimize surgical awareness of this potentially dangerous anatomic skull base variation.


Real time detection of acute (IP) cocaine-enhanced dopamine and serotonin release in ventrolateral nucleus accumbens of the behaving Norway rat.
Cocaine (10 mg/kg), administered intraperitoneal (IP), was studied for its effects on dopamine (DA) and serotonin (5-HT) release in ventrolateral nucleus accumbens (vlNAcc) of conscious and behaving male, virus-free, Sprague-Dawley rats with in vivo electrochemistry (voltammetry). Miniature stearate probes detected DA and 5-HT release, on line and within a temporal resolution of seconds. Psychostimulant behaviors, in the form of four behavioral components (i.e., the classically DA-dependent behaviors of locomotor activity [ambulations], rearing, and stereotypy, and a 5-HT-ergic behavior, central ambulations) were studied concurrently with infrared photobeam detection. The results show that (IP) cocaine significantly increased vlNAcc DA release (p < 0.0001) and 5-HT release (p < 0.0012). Each of the four parameters of cocaine-induced psychostimulant behavior was concurrently and significantly increased as well (ambulations: p < 0.0001); rearing p < 0.0008; stereotypy: p < 0.0004; central ambulations: p < 0.0082). Moreover, exactly coincident data points for DA and 5-HT release occurred 10 and 40 min after (IP) cocaine administration. Cocaine-induced DA and 5-HT release were highly and positively correlated during the first hour of study (p < 0.01). As expected, increased DA release in vlNAcc after cocaine administration was significantly and positively correlated with classically DA-dependent behaviors (first- and second-hour effects) (p < 0.01) and with the 5-HT-ergic behavior, central ambulations (p < 0.01). Also, cocaine-induced 5-HT release was significantly and positively correlated with 5-HT behavior (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Proton NMR studies of the GDP.Mg2+ complex of the Ha-ras oncogene product p21.
Two-dimensional proton NMR studies were performed on the c-Ha-ras encoded proto-oncogene product p21C. COSY and NOESY spectra of the p21C.GDP.Mg2+ complex show that the ribose H1 proton of the bound GDP is in close proximity to the aromatic side chain of a phenylalanyl residue. From sequence homology with the bacterial elongation factor Tu (EF-Tu) and the known X-ray structure of the EF-Tu.GDP.Mg2+ complex it may be inferred that the Phe residue in question is either Phe78 or Phe82 in the p21 sequence.


Mild phenotype of Charcot-Marie-Tooth disease type 4B1.
Charcot-Marie-Tooth type 4B1 (CMT4B1) is a rare autosomal recessive demyelinating neuropathy caused by mutation of the myotubularin-related 2 (MTMR2) gene. It is characterized by a severe early-onset motor and sensory neuropathy, and myelin outfoldings on nerve biopsy. We describe a mild phenotype of CMT4B1 in a Japanese patient. She noticed difficulty in walking as an initial symptom at age 13. Her symptoms progressed slowly, and she could still walk at age 34. There was no cranial neuropathy. A nerve conduction study demonstrated demyelinating neuropathy. Sural nerve biopsy revealed a moderate-to-severe loss of myelinated fibers, and many focally folded myelin sheaths. Electron micrographs showed myelin outfoldings and infoldings. DNA tests for CMT showed that she is a homozygote for the MTMR2 p.R628PfsX18 mutation. The mild phenotype in our patient is probably due to the C-terminal position of the frame-shift mutation in MTMR2.


The calcium-binding EF-hand in polycystin-L is not a domain for channel activation and ensuing inactivation.
Polycystin-L (PCL) shares high homology with polycystin-2, the product of polycystic kidney disease gene-2. It was previously shown that the PCL forms a non-selective cation channel activated by calcium influx. However, it remains unclear whether calcium activates/inactivates PCL by binding to the EF-hand motif located on the cytoplasmic carboxyl-terminus. Here we obtained two PCL splice variants from liver (PCL-LV, lacking the EF-hand) and testis (PCL-TS, lacking 45 amino acids on the carboxyl tail) using PCR-based approaches. When expressed in Xenopus oocytes and studied using electrophysiology both splice variants exhibited basal cation channel activity and calcium-induced channel activation. While PCL-TS displayed similar activation to PCL, PCL-LV exhibited a three-fold increased activation. All five PCL C-terminal artificial truncation mutants also exhibited basal and calcium-activated channel activities, in particular the mutant T622X lacking the EF-hand was associated with increased activation. Our data demonstrate that the EF-hand and other parts of the carboxyl tail of PCL are not determinants of channel activation/inactivation although the EF-hand seems to be involved in the modulation of these processes.


Novel treatment of endobronchial inflammatory myofibroblastic tumor in a child.
Isolated endobronchial inflammatory myofibroblastic tumors (IMT) are rare, accounting for about 1% of primary endobronchial tumors in children. The mainstay of treatment for this tumor has been surgical resection. Recently, the identification of anaplastic lymphoma kinase (ALK) gene mutations in half of IMTs and promising results of treatment with ALK inhibitors in other ALK-positive tumors have opened the possibility of alternative approaches. We present a 4-year-old child with an ALK-positive endobronchial IMT, treated with endoscopic resection and neoadjuvant therapy with crizotinib, without evidence of tumor recurrence 2 years after the initial resection.


The Analgesia Nociception Index: a pilot study to evaluation of a new pain parameter during labor.
Objective pain assessment that is not subject to influences from either cultural or comprehension issues is desirable. Analysis of heart rate variability has been proposed as a potential method. This pilot study aimed to assess the performance of the PhysioDoloris™ analgesia monitor which calculates an Analgesia Nociception Index derived from heart rate variability. It was compared with visual analogical pain scores. Forty-five parturients who requested epidural analgesia were recruited. Simultaneous couplets of pain scores and Analgesia Nociception Index values were recorded every 5 min regardless of the presence or absence of uterine contractions. The relationship between indices was characterized, and a cut-off value of Analgesia Nociception Index corresponding to a visual analogical score >30 (range 0-100) was used to determine the positive and negative predictive value of the Analgesia Nociception Index. There was a negative linear relationship between visual analogical pain scores and Analgesia Nociception Index values regardless of the presence of uterine contractions (regression coefficient ± SEM=-0.18 ± 0.032 for entire dataset). Uterine contraction significantly reduced the Analgesia Nociception Index (P<0.0001). Using a visual analogical pain score >30 to define a painful sensation, the lower 95% confidence limit for the Analgesia Nociception Index score was 49. The Analgesia Nociception Index has an inverse linear relationship with visual analogical pain scores. Further studies are necessary to confirm the results of this pilot study and to look at the influence of epidural analgesia on the Analgesia Nociception Index.


The learning community faculty experience: how longitudinal relationships with learners enhance work meaning.
Work meaning has gained attention as an important contributor to physician job engagement and well-being but little is known about how faculty participation in medical school learning communities might influence this phenomena. Our study goals were to determine how physician faculty members may derive meaning from serving as mentors for longitudinal learning communities of medical students, to understand how that meaning may impact other areas of their work, and relate our findings to existing literature and theoretical frameworks. The research team conducted, recorded, transcribed, and coded 25 semi-structured telephone interviews of faculty mentors from four US medical schools with curricular learning communities. The team used an iterative interview coding process to generate final themes and relate these themes to existing literature. The authors identified five themes of meaning faculty derive from participation as learning community mentors: "I am a better professional," "I am more connected," "I am rejuvenated," "I am contributing," and "I am honored." A sixth theme, "I am harmed," encompassed the negative aspects of the learning community faculty experience. The authors found that their identified themes related closely to the theoretical framework for pathways to meaningful work proposed by Rosso et al. The alignment of the themes we identified on the experience of learning community faculty to existing literature on work meaning corroborates the theoretical framework and deepens understanding of beneficial and harmful learning community effects on faculty. As learning communities become increasingly common within medical schools, this understanding may be important for leaders in academic medicine considering potential indirect benefits of this educational model.


A new ionic liquid-water-organic solvent three phase microextraction for simultaneous preconcentration flavonoids and anthraquinones from traditional Chinese prescription.
A novel technique, ionic liquid-water-organic solvent three phase microextraction (ILWOS-3p-ME) was developed and introduced for simultaneous preconcentration and determination of flavonoids and anthraquinones in Chinese herbal formula and its preparations. This technique was performed in one step by using a syringe. High performance liquid chromatography with an UV-detector (HPLC/UV) was subsequently conducted. Two solvents with different densities (organic solvent and ionic liquid with densities less than and higher than water, respectively) were separately placed in a syringe, which was used as an extraction device. A cloudy emulsion was formed by manually shaking the syringe. The mixture was allowed to stand for several minutes; afterward, the emulsion readily separated into three phases: an upper organic solvent extraction phase; a middle aqueous sample phase; and a lower ionic liquid extraction phase. Both the upper and lower layers were transferred to a small Eppendorf (EP) tube. Conducting ILWOS-3P-ME with HPLC/UV, we simultaneously determined the bioactive components of flavonoids and anthraquinones in traditional Chinese medicine. ILWOS-3P-ME is a simple, rapid, practical, and effective method to extract and preconcentrate of different types of trace bioactive components from traditional Chinese medicine simultaneously.


Tetra-ammonium μ-ethyl-enedi-amine-tetra-acetato-1κ3 O,N,O':2κ3 O'',N',O'''-bis-[trioxidotungstate(VI)] tetra-hydrate.
The title compound, (NH4)4[W2(C10H12N2O8)O6]·4H2O, was obtained from a mixture of tungstic acid, ammonia and ethyl-enedi-amine-tetra-acetic acid (H4edta) in a 2:4:1 ratio. The anion of the complex contains two WO3 units and one bridging edta4- ligand. Each central metal atom is tridentately coordinated by nitro-gen and two carboxyl-ate groups of the edta4- ligand, together with the three oxido ligands, producing a distorted octa-hedral coordination environment around each tungsten atom. The center of the carbon-carbon bond of the ethyl-ene bridge represents a crystallographic inversion center. The crystal structure consists of a three-dimensional supra-molecular framework built up by the dinuclear cations, the ammonium counter-ions and the solvent water mol-ecules via hydrogen bonds of the N-H⋯O and O-H⋯O type.


Southern-Brazilian geopropolis: A potential source of polyphenolic compounds and assessment of mineral composition.
Geopropolis is a stingless bee product compose mainly by soil, presenting complex composition geopropolis has bioactive compounds that will depend on geographical characteristics as well bee species, changing their chemical and biological properties. Thus the study aims to evaluate the solubility and chemical stability of geopropolis extracts, through radical capture capacity and reducing capacity. Besides, analysis of free and bonded phenolic compounds, and mineral composition. Geopropolis samples of Melipona mondury, Melipona quadrifasciata, Melipona scutellaris, Melipona seminigra and Tetragonisca angustula were analyzed. Both reducing compounds with a maximum of 2.96% GAE and free radical scavenging potential with a maximum of 5.84% AAE and 8.58% TE increases over 30 days of storage time. Also, methanolic extracts released at least 51% more reducing compounds and exhibited at least 27% more free radical scavenging potential in comparison to ethanolic extracts. The polyphenolic profile shows 31 compounds after acid and alkaline hydrolysis as cinnamic acid, ferulic acid, p-coumaric acid, aromadendrin, vanillin. For the mineral composition, sixteen minerals were found among essential and non-essential, differentiating each sample by chemometric PCA and HCA analysis according to geographic region. Geopropolis is a potential source of natural compounds that could enhance food quality, increasing the bioactive content and preventing oxygen damages in foods, likewise for pharmacological application for healthcare.


Treatment of diabetic perforating ulcers (mal perforant) with local dimethylsulfoxide.
Perforating foot ulcers constitute a major problem in diabetics with peripheral neuropathy for which no specific therapy is available. Twenty patients with chronic, resistant mal perforant were treated by local application of dimethylsulfoxide (DMSO) solution. Complete healing of the ulcers was achieved in 14 patients following 4-15 weeks of daily treatment. Partial resolution was observed in another four patients, and in the remaining two there was no effect. A control group, equal in number, was treated conventionally. Complete healing of the ulcers took place in only two patients. The therapeutic effect of DMSO most probably results from an increase in tissue oxygen saturation via a combined mechanism of local vasodilatation, decreased thrombocyte aggregation, and increased oxygen diffusion. Local DMSO is effective, simple, devoid of systemic side effects, and inexpensive. It should be employed for diabetic foot ulcers prior to the consideration of surgical measures.


Consumption of fresh Iberian pork: Two-stage cluster for the identification of segments of consumers according to their habits and lifestyles.
This study investigates the behaviour of consumers regarding four cuts of Iberian meat with greater presence in the market: tenderloin, secreto, presa and pluma. A sample of 1501 consumers responded to an online survey about their consumption habits for these four cuts, sociodemographic characteristics and lifestyle. From this information, three homogeneous segments of consumers were identified: "unmotivated and indifferent to Iberian meat", "innovators and stakeholders" and "traditional with frequent consumption". The Iberian tenderloin and the secreto were the most consumed cuts in all consumption segments, while the main reason for the lower consumption of presa and pluma was "I don't like it", especially among "unmotivated" consumers.


Regulatory elements that mediate expression of the gene for the angiotensin II type 1a receptor for the rat.
To analyze the mechanism of the cell type-specific expression of rat angiotensin II type 1a receptor (AT1a-R) gene, we isolated the 5'-portion of the gene and identified multiple positive and negative regulatory sequences that regulate its transcription. Primer extension and S1 mapping identified a transcriptional initiation site at 33 (position +1) base pairs (bp) downstream of TATA sequence. The transcriptional activities of various 5'-deletion mutants of the AT1a-R gene upstream region, fused to the chloramphenicol acetyltransferase (CAT) gene, were examined using rat vascular smooth muscle cells (A10) and glial cells expressing AT1a-R mRNA predominantly or PC12 cells expressing AT2-R and very small amounts of AT1a-R mRNA. A 980-bp 5'-flanking sequence contained at least three positive elements, P1 (-560 to -489), P2 (-331 to -201), and P3 (-201 to -61). P1 and P3 were active in the tested three cells, and P2 was functional only in glial and PC12 cells. In addition to these positive elements, there was negative element, N1 (-489 to -331), which was active only in PC12 cells. These elements, when cotransfected with the AT1a-CAT fusion gene, had competitive effects against its promoter activity. The present study suggests the presence of multiple trans-acting factors that act on these positive and negative cis-acting elements and regulate the cell type-specific expression of the rat AT1a-R gene.


Renal injury after muscle extract infusion in rats: absence of toxicity with myoglobin.
A crude muscle extract infused into rats produced oliguria, a precipitous drop in total hemolytic complement, and in circulating white cell and platelets counts. A mild vaso-depressor effects was noted. These changes were not produced by myoglobin or saline infusion. Muscle constituents other than myoglobin are responsible for the systemic and renal nephrotoxic effects observed.


[COPD: a disease with systemic inflammation].
COPD is considered today as an inflammatory disease of the lungs and bronchi, often associated with circulating inflammatory markers and non-respiratory co-morbidities. C-reactive protein is a good example of a circulating biomarker in this disease. Recent studies have shown that it is particularly associated with some phenotypes of COPD, that it is linked with cardiovascular and other co-morbidities, and that it has genetic determinants. In view of reports in the recent literature treatments aimed at decreasing systemic inflammation in COPD, in particular the use of statins, are discussed. Treatment of COPD should no longer be limited to relief of bronchial obstruction, but should, in the future, address the systemic inflammation that characterizes this disease.


International Sleeve Gastrectomy Expert Panel Consensus Statement: best practice guidelines based on experience of >12,000 cases.
Laparoscopic sleeve gastrectomy (LSG) is an emerging surgical approach, but 1 that has seen a surge in popularity because of its perceived technical simplicity, feasibility, and good outcomes. An international expert panel was convened in Coral Gables, Florida on March 25 and 26, 2011, with the purpose of providing best practice guidelines through consensus regarding the performance of LSG. The panel comprised 24 centers and represented 11 countries, spanning all major regions of the world and all 6 populated continents, with a collective experience of >12,000 cases. It was thought prudent to hold an expert consensus meeting of some of the surgeons across the globe who have performed the largest volume of cases to discuss and provide consensus on the indications, contraindications, and procedural aspects of LSG. The panel undertook this consensus effort to help the surgical community improve the efficacy, lower the complication rates, and move toward adoption of standardized techniques and measures. The meeting took place at on-site meeting facilities, Biltmore Hotel, Coral Gables, Florida. Expert panelists were invited to participate according to their publications, knowledge and experience, and identification as surgeons who had performed >500 cases. The topics for consensus encompassed patient selection, contraindications, surgical technique, and the prevention and management of complications. The responses were calculated and defined as achieving consensus (≥70% agreement) or no consensus (<70% agreement). Full consensus was obtained for the essential aspects of the indications and contraindications, surgical technique, management, and prevention of complications. Consensus was achieved for 69 key questions. The present consensus report represents the best practice guidelines for the performance of LSG, with recommendations in the 3 aforementioned areas. This report and its findings support a first effort toward the standardization of techniques and adoption of working recommendations formulated according to expert experience.


PdPtRu trimetallic nanozymes and application to electrochemical immunosensor for sensitive SARS-COV-2 antigen detection.
Herein, a ternary PdPtRu nanodendrite as novel trimetallic nanozyme was reported, which possessed excellent peroxidase-like activity as well as electro-catalytic activity on account of the synergistic effect between the three metals. Based on the excellent electro-catalytic activity of trimetallic PdPtRu nanozyme toward the reduction of H2O2, the trimetallic nanozyme was applied to construct a brief electrochemical immunosensor for SARS-COV-2 antigen detection. Concretely, trimetallic PdPtRu nanodendrite was used to modify electrode surface, which not only generated high reduction current of H2O2 for signal amplification, but also provided massive active sites for capture antibody (Ab1) immobilization to construct immunosensor. In the presence of target SARS-COV-2 antigen, SiO2 nanosphere labeled detection antibody (Ab2) composites were introduced on the electrode surface according sandwich immuno-reaction. Due to the inhibitory effect of SiO2 nanosphere on the current signal, the current signal was decreased with the increasing target SARS-COV-2 antigen concentration. As a result, the proposed electrochemical immunosensor presented sensitive detection of SARS-COV-2 antigen with linear range from 1.0 pg/mL to 1.0 μg/mL and limit of detection down to 51.74 fg/mL. The proposed immunosensor provide a brief but sensitive antigen detection tool for rapid diagnosis of COVID-19.


The association of whole grain consumption with incident type 2 diabetes: the Women's Health Initiative Observational Study.
Whole grains may offer protection from diabetes by decreasing energy intake, preventing weight gain, and direct effects on insulin resistance. This study examined associations of whole and refined grains with incident type 2 diabetes (T2D) ascertained by self-reported medication use in a cohort of postmenopausal women. We included 72,215 women free of diabetes at baseline from the Women's Health Initiative Observational Study. Whole grain consumption was categorized as 0, less than 0.5, 0.5 to 1.0, 1.0 to less than 1.5, 1.5 to less than 2.0, and 2.0 or more servings per day. Proportional hazards regression was performed to estimate hazard ratios (HR) and 95% confidence intervals adjusting for potential confounders. There were 3465 cases of incident T2D over median follow-up of 7.9 years. Adjusted for age and energy intake per day, successively increasing categories of whole grain consumption were associated with statistically significant reduced risk of incident T2D (HRs, 1.00, 0.83, 0.73, 0.69, 0.61, and 0.57; P for trend < 0.0001). Results were attenuated after adjustment for confounders and other dietary components. The reduction in risk of T2D was greater among nonsmokers and those who maintained their weight within 5 pounds with higher consumption of whole grains than smokers and women who gained more weight. This large, prospective study found an inverse dose-response relationship between whole grain consumption and incident T2D in postmenopausal women.


Living beyond expectations: a qualitative study into the experience of long-term survivors with pleural mesothelioma and their carers.
Malignant pleural mesothelioma (MPM) is characterised by poor prognosis and limited treatment options. However, a minority of patients can survive well beyond these bleak estimates. Little is known about the specific experiences and needs of long-term survivors and families. The study aimed to gain in-depth understanding of the experiences of patients diagnosed with MPM 3 or more years, along with their main carer, and to determine the care and support needs of this group. People diagnosed with MPM 3 or more years were recruited via asbestos and mesothelioma social media and support groups. Potential participants were asked to identify someone who acted as their main carer. The study employed a cross-sectional qualitative interview design. A topic guide aided a conversational interview style, conducted remotely and recorded. Patient and carer pairs were interviewed jointly when possible, but were given an option for separate interviews if preferred. Fifteen patients, with 14 identifying a main carer, consented to participation. Recorded interviews were transcribed verbatim, and then anonymised by the interviewer. Framework analysis was used to analyse the data iteratively and to develop final themes. Three themes were developed. Participants 'Living beyond expectations' remained acutely aware that MPM was incurable, but developed a range of coping strategies. Periods of disease stability were punctuated with crises of progression or treatment ending, straining coping. 'Accessing treatment' was important for patients and carers, despite the associated challenges. They were aware options were limited, and actively sought new treatments and clinical trials. 'Support needs' were met by healthcare professionals, voluntary groups and social media networks. Managing patients via regional MPM multidisciplinary teams, facilitating equal access to treatment and trials, could reduce patient and carer burden. Greater awareness and support around crisis points for this group could improve care.


Lipopolysaccharide induces apoptosis in Carassius auratus lymphocytes, a possible role in pathogenesis of bacterial infection in fish.
Lipopolysaccharide (LPS), the endotoxin of Gram-negative bacteria, is capable of eliciting a wide variety of pathophysiological effects, including endotoxin shock, tissue injury and lethality in both humans and animals. It is also a potent stimulant to initiate the proliferation, differentiation and activation of B lymphocytes and macrophages, resulting in changes of inflammatory cytokines, such as TNF-alpha, IL1-beta, IL6, IL-8 and IL-12, and enhancement of immune responses. However, little is known about its effect on the induction of apoptosis in lymphocytes. In the present study, the lymphocytes from Carassius auratus were employed for this purpose. The cells were exposed to LPS at various doses for different time periods. By careful apoptotic characteristic analysis, such as condensation of nuclear chromatin, fragmentation of genomic DNA and formation of apoptotic bodies, it provided the first evidence that LPS had apoptotic-inducing effect on fish lymphocytes in a time- and dose-dependent manner. LPS exposure induced significant increase of intracellular reactive oxygen species (ROS), loss of mitochondrial transmembrane potential (DeltaPsi), depletion of ATP production, down-regulation of Bcl-2 expression, up-regulation of Bax and mitochondrial NO-synthase (mNOS) expression, and selective activation of caspase-9 rather than caspase-8. Each of these observations suggests that the LPS-induced apoptosis in C. auratus lymphocytes occurs largely via the mitochondrial apoptotic pathway. This observation was different from the mechanism behind the LPS-induced apoptosis in mammalian macrophages/thymocytes that occurs via the TNF-alpha-mediated death-receptor pathway. Our study suggested the existence of a possible novel role in the pathogenesis of Gram-negative bacterial infection in fish and even in mammals, which may contribute to the therapy of bacterial diseases. Also, it will help to gain more insights into the mechanisms of septic shock and of LPS-induced immunosuppression and autoimmunity.


Wireless enzyme sensor system for real-time monitoring of blood glucose levels in fish.
Periodic checks of fish health and the rapid detection of abnormalities are thus necessary at fish farms. Several studies indicate that blood glucose levels closely correlate to stress levels in fish and represent the state of respiratory or nutritional disturbance. We prepared a wireless enzyme sensor system to determine blood glucose levels in fish. It can be rapidly and conveniently monitored using the newly developed needle-type enzyme sensor, consisting of a Pt-Ir wire, Ag/AgCl paste, and glucose oxidase. To prevent the effects of interfering anionic species, such as uric acid and ascorbic acid, on the sensor response, the Pt-Ir electrode was coated with Nafion, and then glucose oxidase was immobilized on the coated electrode. The calibration curve of the glucose concentration was linear, from 0.18 to 144mg/dl, and the detection limit was 0.18mg/dl. The sensor was used to wirelessly monitor fish glucose levels. The sensor-calibrated glucose levels and actual blood glucose levels were in excellent agreement. The fluid of the inner sclera of the fish eyeball (EISF) was a suitable site for sensor implantation to obtain glucose sample. There was a close correlation between glucose concentrations in the EISF and those in the blood. Glucose concentrations in fish blood could be monitored in free-swimming fish in an aquarium for 3 days.


Discordant varicella-zoster virus glycoprotein C expression and localization between cultured cells and human skin vesicles.
Because of its very low titer, varicella-zoster virus (VZV) infectivity is usually transferred by passage of trypsin dispersed infected cells. Previously, we observed that gC biosynthesis was markedly delayed in monolayers inoculated with cell free virus. In this report, we investigated the kinetics of gC expression in more detail and included studies of monolayers inoculated with trypsin dispersed infected cells, the more traditional method of VZV infection. Extensive imaging analyses disclosed that gC was detectable in some inoculum cells, but little gC biosynthesis occurred during the first 48 hpi in the newly infected underlying monolayer. In contrast, during the first 24-48 hpi, expression of VZV gE and gB was easily detectable. Using real-time RT-PCR, we found a delay in accumulation of VZV gC transcripts that paralleled the delay in expression of VZV gC protein. Treatment with hexamethylene bisacetamide (HMBA) increased expression of both gC protein and gC mRNA. HMBA treatment also increased virus titer by 4-fold, but paradoxically reduced plaque size in the titration assay. Finally, we examined skin vesicles from cases of chickenpox and zoster in humans and observed abundant amounts of gC expression. In short, this report documents an unexpected delay in both gC mRNA and protein production under all conditions of VZV infection of cultured cells.


Crying out for help with root exudates: adaptive mechanisms by which stressed plants assemble health-promoting soil microbiomes.
Plants employ immunological and ecological strategies to resist biotic stress. Recent evidence suggests that plants adapt to biotic stress by changing their root exudation chemistry to assemble health-promoting microbiomes. This so-called 'cry-for-help' hypothesis provides a mechanistic explanation for previously characterized soil feedback responses to plant disease, such as the development of disease-suppressing soils upon successive cultivations of take all-infected wheat. Here, we divide the hypothesis into individual stages and evaluate the evidence for each component. We review how plant immune responses modify root exudation chemistry, as well as what impact this has on microbial activities, and the subsequent plant responses to these activities. Finally, we review the ecological relevance of the interaction, along with its translational potential for future crop protection strategies.


Effects of autonomic nervous system on gastric damage by ethanol in the rat.
To study whether or not the autonomic nervous system influences the defense mechanisms of the gastric mucosa, groups of Sprague-Dawley rats were given stimulants and inhibitors of the different components of the vagus and celiac nerves before administration of absolute or 70% w/v ethanol. The effects of vagotomy and sympathectomy on "adaptive cytoprotection" were studied, as were the effects of blocking the muscarinic receptors and stimulation of beta-adrenergic receptors. We found that: (1) cholinomimetic agents and norepinephrine make the damage caused by 70% ethanol worse; (2) atropine is the only agent that fully protects against absolute ethanol; (3) vagotomy and sympathectomy abolish the effects of atropine and adaptive cytoprotection; and (4) beta-adrenergic stimulation replaces conditions that allow adaptive cytoprotection and the protection by anticholinergics. These results suggest that two different reflexes are triggered by ethanol: when low concentrations are given, the beta-adrenergic-mediated effect is prevalent, with protection of the mucosa; when high concentrations are given, the cholinergic-mediated effect is prevalent with damage of the mucosa.


Mass fragmentographic determination of docosenoic acid in rapeseed oils.
A highly sensitive and accurate reference method for determination of docosenoic acid (mainly erucic acid, 22:1n-9) in different rapeseed oils is described. A fixed amount of [1-14C] erucic acid methyl ester (about 1 microgram) is added to a fixed amount of oil. After treatment with sodium methoxide/methanol reagent and extraction with hexane, the amount of unlabeled erucic acid is determined from the ratio between the recordings at m/e 320 and m/e 322 obtained after analysis with a combined gas chromatograph-mass spectrometer equipped with an MID (multiple ion detector). The two ions used correspond to the M-32 peak in the mass spectrum of unlabeled and [1-14C] labeled erucic acid methyl ester. The relative standard deviation of the method is about 1.8%. The method was compared with a gas chromatographic method for determination of erucic acid.


Candidate chemosensory genes identified in Colaphellus bowringi by antennal transcriptome analysis.
Since chemosensory genes play key roles in insect behaviour, they can potentially be used as new targets for pest control. The cabbage beetle, Colaphellus bowringi, is a serious insect pest of cruciferous vegetables in China and other Asian countries. However, a systematic identification of the chemosensory genes expressed in the antennae has not been reported. We assembled the antennal transcriptome of C. bowringi by using Illumina sequencing technology and identified 104 candidate chemosensory genes by analyzing transcriptomic data, which included transcripts encoding 26 odorant-binding proteins (OBPs), 12 chemosensory proteins (CSPs), four sensory neuron membrane proteins (SNMPs), 43 odorant receptors (ORs), nine ionotropic receptors (IRs), and ten gustatory receptors (GRs). The data obtained are similar to those found in other coleopteran species, suggesting that our approach successfully identified the chemosensory genes of C. bowringi. The expression patterns of 43 OR genes, some of which were predominately found in the antenna or associated with sex-biased expression, were analyzed using quantitative real time RT-PCR (qPCR). Our study revealed that a large number of chemosensory genes are expressed in C. bowringi. These candidate chemosensory genes and their expression profiles in various tissues provide further information on understanding their function in C. bowringi as well as other insects, and identifying potential targets to disrupt the odorant system in C. bowringi so that new methods for pest management can be developed.


Validation of physician billing and hospitalization data to identify patients with ischemic heart disease using data from the Electronic Medical Record Administrative data Linked Database (EMRALD).
Reporting of ischemic heart disease (IHD) prevalence in Canada has been based on self-report or patients presenting to hospital. However, IHD often presents and can be managed in the outpatient setting. To determine whether the combination of hospital data and physician billings could accurately identify patients with IHD. A random sample of 969 adult patients from the Electronic Medical Record Administrative data Linked Database (EMRALD) - an electronic medical record database of primary care physicians in Ontario linked to administrative data for the province of Ontario - was used. A number of combinations of physician billing and hospital discharge abstracts were tested to determine the accuracy of using administrative data to identify IHD patients. Two physician billings within a one-year period (with one of the billings by a specialist or a family physician in a hospital or emergency room setting) or a hospital discharge abstract gave a sensitivity of 77.0% (95% CI 68.2% to 85.9%), a specificity of 98.0% (95% CI 97.0% to 98.9%), a positive predictive value of 78.8% (95% CI 70.1% to 87.5%), a negative predictive value of 97.7% (95% CI 96.8% to 98.7%) and a kappa of 0.76 (95% CI 0.68 to 0.83). A combination of physician billing and hospital discharge abstracts can be used to identify patients with IHD. Population prevalence of IHD can be measured using administrative data.


Adsorptive recovery of Au(III) from aqueous solution using crosslinked polyethyleneimine resins.
Resin adsorption is considered as a promising method to recover gold ions from wastewater, but further reduction reaction is required to convert gold ions into particles. In this study, a crosslinked polyethyleneimine resin (CPEIR) was developed via a suspension polymerization of polyethyleneimine (PEI) and ethylene glycol diglycidyl ether (EGDE) for gold recovery. The Au(III) adsorption capacities of CPEIR were significantly impacted by solution pH and initial Au(III) concentrations but unaffected by co-existing metal ions. Compared with commercial anion-exchange resin IRA400, the CPEIR exhibited higher sorption amount and selectivity for Au(III) due to its high density of amine and hydroxyl groups on the surfaces. The adsorption isotherm of Au(III) on CPEIR was well described by the Langmuir equation, and the maximum uptake amount of Au(III) was high up to 943.5 mg/g, much higher than the reported sorbents. The adsorption kinetic data on the CPEIR were fitted well by the Pseudo-second-order equation, and the intraparticle diffusion was found to be the rate-controlling process of Au(III) adsorption. X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) analysis confirmed that Au(III) ions were adsorbed on the CPEIR via electrostatic attraction and chelating interaction, and subsequently the partial loaded Au(III) ions were reduced to elemental gold whereas the hydroxyl groups of CPEIR were oxidized to carbonyl groups.


Post-malaria neurological syndrome: Imported case series and literature review to unscramble the auto-immune hypothesis.
Post-malaria neurological syndrome (PMNS) is a complication that occurs after recovery from a severe Plasmodium falciparum attack. Over the past two decades, the description of several imported cases has confirmed that this syndrome is a clearly distinct entity, different from other post malarial neurological disorders. However, the underlying mechanisms are not yet elucidated. Herein, we present five imported PMNS cases managed in Marseille, France. The detection of neuronal surface antibodies to an encephalitic syndrome of unknown origin allowed us to reveal positivity of anti Voltage-Gated-Potassium Channel antibodies (anti VGKC) in one of them. Using treatment options from other autoimmune encephalitis has to be explored in patients with PMNS.


Infant lung function and maternal physical activity in the first half of pregnancy.
Physical activity (PA) in pregnancy is important for maternal and possibly offspring health. To study the early origins of lung function we aimed to determine whether PA in the first half of pregnancy is associated with lung function in healthy 3-month-old infants. From the general population-based Preventing Atopic Dermatitis and Allergies in Children birth cohort recruiting infants antenatally in Norway and Sweden, all 812 infants (48.8% girls) with available tidal flow-volume measures in the awake state at 3 months of age and mid-pregnancy data on PA were included. PA was self-reported by the mothers and, based on intensity, we categorised them as active or inactive during pregnancy. Furthermore, we defined active mothers as fairly or highly active. The main outcome was a ratio of time to peak tidal expiratory flow to expiratory time (t PTEF/t E) <0.25. Associations were analysed by logistic regression, adjusting for maternal age, education, parity, pre-pregnancy body mass index, in utero nicotine exposure and parental atopy. The mean±sd t PTEF/t E was 0.391±0.08 and did not differ significantly according to maternal PA level in pregnancy. The 290 infants of inactive mothers had higher odds of having t PTEF/t E <0.25 compared to infants of all active mothers (OR 2.07, 95% CI 1.13-3.82; p=0.019) and compared to infants (n=224) of fairly active (OR 2.83, 95% CI 1.26-7.24; p=0.018) but not highly active mothers (n=298). Based on self-reported maternal PA in the first half of pregnancy, 3-month-old infants of inactive compared to active mothers had higher odds of a low t PTEF/t E.


Five Year Survival in Medicare Patients Undergoing Interventions for Peripheral Arterial Disease: a Retrospective Cohort Analysis of Linked Registry Claims Data.
To justify the up front risks of offering elective interventions for intermittent claudication (IC), patients should have reasonable life expectancy to derive durable clinical benefits. Open surgery for chronic limb threatening ischaemia (CLTI) is maximally beneficial in patients surviving ≥ 2 years. The aim was to assess long term survival after IC and CLTI interventions. In a retrospective cohort analysis, the Vascular Quality Initiative (VQI) registry from 1 January 2010 to 31 May 2021 was queried for peripheral vascular intervention (PVI), infra-inguinal bypasses (IIB), and supra-inguinal bypasses (SIB) for IC and CLTI across 286 US centres. VQI linkage to Medicare insurance claims provided five year survival data. Multivariable analysis identified factors associated with five year mortality. There were 31 457 PVIs (44.7% IC, 55.3% CLTI), 7 978 IIBs (26.9% IC, 73.1% CLTI), and 2 149 SIBs (50.1% IC, 49.9% CLTI) recorded in the VQI. Among the PVI, IIB, and SIB cohorts, average ages were 75, 73, and 72 years, respectively. Respective five year mortality after PVI for IC and CLTI was 37.2% and 71.1%; after IIB for IC and CLTI it was 37.8% and 60%; and after SIB for IC and CLTI it was 33.8% and 53.8%. On multivariable analysis, across all procedures, end stage renal disease, CLTI, congestive heart failure, anaemia, chronic obstructive pulmonary disease, and prior amputation were independently associated with increased mortality. Pre-admission home living and pre-operative aspirin use were independently associated with decreased mortality. Long term survival in Medicare patients undergoing interventions in VQI centres for peripheral arterial disease is poor. Two thirds of CLTI patients and over one third of IC patients were not alive at five years. Intervening for IC in patients with high mortality risk should be avoided. For CLTI patients identified with decreased survival likelihood, intervention durability may be less important than invasiveness. Pre-operative medical optimisation should always be undertaken.


The genetic toxicology of paracetamol and aspirin: a review.
Paracetamol and aspirin are the two most widely used analgesics available for human use without prescription in several parts of the world. Paracetamol has an antipyretic activity, and aspirin has both antipyretic and anti-inflammatory activities. Characterization of the mutagenicity and clastogenicity of these drugs is essential for their overall safety assessment. In the present review, an attempt is made to evaluate the genotoxic effects of these two widely used analgesics based on available literature.


Therapeutic effects of extracts from Radix Toddaliae Asiaticae on collagen-induced arthritis in Balb/c mice.
Radix Toddaliae Asiaticae (RTA), also named "Sanbaibang", is the dry root bark of Toddalia asiatica (L.) Lam. and has long been used as a traditional ethnic Chinese medicine for its considerable activity to alleviate pain and inflammation for patients suffering from rheumatism. It contains coumarin, alkaloids, triterpenes and volatile oils. Information regarding the anti-arthritis activity of RTA in vivo or in vitro is limited yet. In the present study, the aim is to investigate the therapeutic potential and underlying mechanisms of the ethyl alcohol extract (EtOH) and ethyl acetate fraction (EtOAc) from RTA on collagen II-induced arthritis (CIA) in mice. CIA animal model was performed by subcutaneous injection of type II bovine collagen (CII) on the 1st day and the 14th day of the experiment. Ethyl alcohol extract (542.8, 271.4, 135.7 mg/kg), ethyl acetate fraction (260.8, 130.4, 65.2 mg/kg) was orally administrated from the second antigen immunization for 3 weeks. Progression of edema of paws and knee joints was measured using a vernier caliper every 3 days from the 10th day after the first injection to the end of the experiment. The spleen index was measured and the knee joint changes were observed by pathological sections. ELISA was used to measure cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and interleukin-10 (IL-10) in mice serum according to the manufacturer's instructions. Administration of ethyl alcohol extract and ethyl acetate fraction remarkably reduced paws and joints swelling and decreased the spleen indexes. Histopathological examination demonstrated that RTA effectively protected bone and cartilage of knee joint from erosion, lesion and deformation versus those from the control group. Besides, the concentration of cytokines like TNF-α, IL-1β, IL-6 were significantly lower than the ones from the control group respectively, while cytokine like IL-10 was remarkably higher compare with the control group. In this present study, it is demonstrated that administration of RTA has potential and therapeutic effect on CIA. The data suggests that RTA could have a contributory ethno-pharmacological role in improved management of RA patients.


Familial hypocalciuric hypercalcaemia: a study of four kindreds.
Four kindreds with hereditary hypercalcaemia have been investigated. Thirty-seven of 72 subjects examined had hypercalcaemia with an autosomal dominant pattern of inheritance. Hypercalcaemic patients had total serum calcium of 2.91 +/- 0.12 mmol l-1. Serum parathyroid hormone (PTH) was normal while daily urinary calcium excretion was subnormal (below 2.5 mmol) in 45%. Comparison with an age-matched group of patients with primary hyperparathyroidism gave a small overlap regarding serum human PTH, urinary calcium and the ratio between calcium clearance and creatinine clearance. Family screening therefore is of diagnostic importance. Twelve subjects had been subjected to parathyroid surgery before the correct diagnosis was settled, none of the cases had an adenoma. Three patients became normocalcaemic and the others had persistent hypercalcaemia. One male non-abuser had seven episodes of acute pancreatitis before surgery and none after. The findings in all four kindreds are compatible with familial hypocalciuric hypercalcaemia (FHH). This hereditary disorder of unknown aetiology, therefore, also exists in Scandinavia. It is of importance to consider FHH in the differential diagnosis of hypercalcaemia, since this disorder usually has a benign prognosis if untreated.


The effect of a 'recall-system' in the treatment of alcoholic patients.
In a service specializing in alcohol and drug abuse in Brazil, a 'recall system' was developed in order to decrease the drop out level, which is high in this kind of treatment. The effect of this procedure was measured in two groups: in the 82 patients with the 'recall system', the drop out rate after 12 months was 45%. In 227 patients without this system the drop out rate was 84%. The difference in drop out rate was significant (p less than 0.01) only during the first 6 months of treatment.


Corrigendum: Melatonin Promotes the Therapeutic Effect of Mesenchymal Stem Cells on Type 2 Diabetes Mellitus by Regulating TGF-β Pathway.
[This corrects the article DOI: 10.3389/fcell.2021.722365.].


Endocan: A novel inflammatory indicator in cardiovascular disease?
Endothelial dysfunction is considered as an early change in atherogenesis. Raised levels of systemic inflammatory markers are associated with cardiovascular disease (CVD). Endocan (previously known as endothelial cell specific molecule-1, ESM-1), is a potential immunoinflammatory marker that may be linked to CVD. Endocan is released by vascular endothelial cells in several organs. Endocan may play an important role in regulating cell adhesion and raised plasma levels may reflect endothelial dysfunction. Endocan levels are elevated in conditions such as chronic kidney disease, renal transplant rejection, tumor progression and hypertension. Endocan is a potential inflammatory and CVD marker. Further studies are needed to assess the relevance of endocan in clinical practice.


Serum human epididymis protein 4 concentrations are associated with severity of patients with pulmonary tuberculosis.
Human epididymis protein 4 (HE4) has been recognized as a biomarker which elevated in various diseases. The aim of this study was to evaluate the value of serum HE4 in pulmonary tuberculosis (PTB). Serum HE4 concentrations were determined in 127 PTB, 88 chronic bronchitis (CHB), and 105 healthy control subjects by chemiluminescent microparticle immunoassay. Receiver operating characteristic (ROC) curves and Spearman's correlation analysis were performed for investigating value of HE4. Serum HE4 concentrations were significantly increased in PTB (62.8 pmol/L, IQR 45.8-90.7), compared with that of CHB (50.2 pmol/L, IQR 42.3-64.3, P = 0.0002) and normal control (35.4 pmol/L, IQR 31.1-42.9, P < 0.0001). ROC curve suggested that the AUC of HE4 used to discriminate PTB from CHB was 0.647 (95% CI, 0.574-0.719), with the cutoff value, sensitivity, specificity, PPV, and NPV at 71.9 pmol/L, 0.417, 0.852, 0.672 and 0.543, respectively. Meanwhile, compared with mild to moderated PTB, the levels of HE4 in advanced PTB were significantly elevated (75.8 vs. 57.7 pmol/L, P = 0.0052). What's more, the levels of HE4 in PTB were found to be significantly associated with the albumin, CRP, and cavity (r = -0.2996, P = 0.0006, r = 0.265, P = 0.0026, r = 0.4699, P < 0.0001, respectively). Elevated serum HE4 concentration could be used as a biomarker for the diagnosis and assessment of disease severity in PTB.


Biocompatibility and osteogenesis of the castor bean polymer doped with silica (SiO2) or barium titanate (BaTiO3) nanoparticles.
To evaluate the biocompatibility and osteogenesis of castor oil polymer doped with SiO2 or BaTiO3 nanoparticles. Twenty four male rats Wistar were submitted to bone defect filled with castor oil polymer. The animals were distributed in two experimental groups had been formed with 12 animals each: Group 1 - Castor oil polymer doped with 0.30 grams of SiO2 replacing 0.30 grams of CaCO3. Group 2 - Castor oil polymer doped with 0.30 grams of BaTiO3 replacing 0.30 grams of CaCO3. Euthanasia occurred 30 and 60 days after surgery and the femurs were sent to histological analysis and MEV. The implants were biocompatible and allowed for progressive osteogenesis through osteoconduction in both observation periods. There was significant bone neoformation at 30 and 60 days in both groups within the histomorphometric evaluation, but group 1's osteogenesis was lesser in the 30 and 60-day periods observed when compared to the animals of group 2. The MEV morphometric evaluation evidenced a lesser percentage of osseous tissue filling within the BaTiO2-doped polymer. The castor oil polymer doped with SiO2 or BaTiO3 remained biocompatible and allowed for progressive osteogenesis in both observation periods.


Spontaneous abortion in patients with insulin-dependent diabetes mellitus: the effect of preconceptional diabetic control.
Fifty-nine of 94 pregnant women with juvenile-onset insulin-dependent diabetes who attended a preconceptional clinic were periodically examined by a diabetologic team. Glycemic control was obtained by intensified insulin therapy and monitored by blood glucose self-monitoring. These women were compared with the 35 pregnant women who did not receive preconceptual glycemic control. The initial glucose and maternal hemoglobin A1 values of the latter group experiencing spontaneous abortions were significantly higher (p less than 0.001) when compared with women receiving preconceptional diabetologic counseling whose pregnancies continued beyond 22 weeks' gestation. The frequency of spontaneous abortions among patients not seen before pregnancy was significantly higher (p less than 0.001), in contrast to attending women, whose rate represented the normal rate in the general population. We confirm the evidence accumulated in the recent literature that poor metabolic control around conception and in the early weeks of pregnancy may be the determining factor favoring abortion.


Testing the role of myeloid cell glucose flux in inflammation and atherosclerosis.
Inflammatory activation of myeloid cells is accompanied by increased glycolysis, which is required for the surge in cytokine production. Although in vitro studies suggest that increased macrophage glucose metabolism is sufficient for cytokine induction, the proinflammatory effects of increased myeloid cell glucose flux in vivo and the impact on atherosclerosis, a major complication of diabetes, are unknown. We therefore tested the hypothesis that increased glucose uptake in myeloid cells stimulates cytokine production and atherosclerosis. Overexpression of the glucose transporter GLUT1 in myeloid cells caused increased glycolysis and flux through the pentose phosphate pathway but did not induce cytokines. Moreover, myeloid-cell-specific overexpression of GLUT1 in LDL receptor-deficient mice was ineffective in promoting atherosclerosis. Thus, increased glucose flux is insufficient for inflammatory myeloid cell activation and atherogenesis. If glucose promotes atherosclerosis by increasing cellular glucose flux, myeloid cells do not appear to be the key targets.


Young offenders and alcohol: a survey of the drinking behaviour of a Borstal population.
The results of a survey, based on previous Scottish studies, of the drinking behaviour of 100 English Borstal trainees are reported. It was found that a large proportion (38 per cent) of the young offenders in the sample reported drinking immediately before committing either their present or a previous offence. Whilst little evidence for different criminal behaviour in this "alcohol group" was found, substantial differences in drinking behaviour were reported and examined. These differences included amount typically drunk, frequency of drunkenness and motivation for drinking. It is suggested that whilst a direct causal relationship between alcohol and crime remains to be satisfactorily proved, the present results strongly indicate the need for alcohol treatment programmes in young offender establishments and seek to contribute towards a basis from which such programmes might be built.


Role of the social milieu in health and wellness.
Can "we" be modified? The impact of the social milieu on health and wellness is not a new concept. Before the invention of an effective pharmacopoeia, manipulation of the social environment was one of the few tools available to physicians. Modern medicine continues to focus on individual rather than community efforts at risk reduction. To understand health and wellness, we must look not only at bodies and illnesses but also at communities and social structure. This article discusses the impact of spirituality and religion, education, economics, and politics on health and wellness. The impact of these issues on health will drive system-level change in global health.


Flexural strength of an infused ceramic, glass ceramic, and feldspathic porcelain.
In-Ceram material is a relatively new all-ceramic restorative material with improved properties that require research. The clinical selection of restorative materials is based on a number of parameters such as esthetics, fit, and strength. This study determined the flexural strength of In-Ceram system components and compared the core material with conventional feldspathic ceramics and with Dicor all-ceramic restorative material. Four-point flexural strength values of bend bars of each ceramic were 18.39 +/- 5.00 MPa for In-Ceram sintered alumina, 76.53 +/- 15.23 MPa for In-Ceram infusion glass, and 236.15 +/- 21.94 MPa for In-Ceram infused alumina core. Flexural strength of self-glazed feldspathic porcelain was 69.74 +/- 5.47 MPa, as-cast Dicor ceramic 71.48 +/- 7.17 MPa, and polished Dicor ceramic was 107.78 +/- 8.45 MPa.


A Preliminary Investigation of Embedding In Vitro HepaRG Spheroids into Recombinant Human Collagen Type I for the Promotion of Liver Differentiation.
In vitro three-dimensional (3D) hepatic spheroid culture has shown great promise in toxicity testing because it better mimics the cell-cell and cell-matrix interactions found in in vivo conditions than that of the traditional two-dimensional (2D) culture. Despite embedding HepaRG spheroids with collagen type I (collagen I) extracellular matrix (ECM) revealed a much better differentiation capability, almost all the collagen utilized in in vitro hepatocytes cultures is animal-derived collagen that may limit its use in human toxicity testing. Here, a preliminary investigation of HepaRG cells cultured in different dimensionalities and with the addition of ECM was performed. Comparisons of conventional 2D culture with 3D spheroid culture were performed based on their functional or structural differences over 7 days. Rat tail collagen (rtCollagen) I and recombinant human collagen (rhCollagen) I were investigated for their ability in promoting HepaRG spheroid differentiation. An immunofluorescence analysis of the hepatocyte-specific functional protein albumin suggested that HepaRG spheroids demonstrated better hepatic function than spheroids from 2D culture, and the function of HepaRG spheroids improved in a time-dependent manner. The fluorescence intensities per unit area of spheroids formed by 1000 cells on days 7 and 10 were 25.41 and 45.38, respectively, whereas almost undetectable fluorescence was obtained with 2D cells. In addition, the embedding of HepaRG spheroids into rtCollagen and rhCollagen I showed that HepaRG differentiation can be accelerated relative to the differentiation of spheroids grown in suspension, demonstrating the great promise of HepaRG spheroids. The culture conditions established in this study provide a potentially novel alternative for promoting the differentiation of HepaRG spheroids into mature hepatocytes through a collagen-embedded in vitro liver spheroid model. This culture method is envisioned to provide insights for future drug toxicology.


A Prospective Study of Comparison Between Fine Needle Aspiration Cytology (FNAC) with Histopathological Diagnosis (HPE) in Neck Masses.
FNAC is easy to perform, is minimally invasive and is economical. It has better patient compliance and the cytological diagnosis can be made before any definitive treatment is planned. This prospective study was carried out in a tertiary care hospital of a medical college having 100 cases in study. The statistical analysis included sensitivity, specificity, positive predictive value, negative predictive value. On cytological examination, 94/100 were benign, 6 malignant or suspicious. On HPE, 92 were benign while 5 malignant from suspicious and malignant cases leaving 3 discordant cases. Sensitivity, specificity, positive predictive value, negative predictive value which was 71.4%, 98.9%, 83.3%,97.8% respectively in our case series. FNAC is a safe, simple procedure. It gives a reliable pre-operative cytological diagnosis based on which surgical procedures or conservative management can be confidently executed. An attempt is made hereby to compare our results with worldwide documented literature. However pitfalls of this method should be kept in mind with careful observation and adequate clinical suspicion.


ADAP status now: what you can do.
This short review of the current state of the AIDS Drug Assistance Program tells how you can get involved.


In vivo changes in plasma acute phase protein levels in the rat induced by slow release of IL-1, IL-6 and TNF.
Administration of large doses of cytokines by injection is required to induce changes in acute phase protein levels. Comparisons were made in the rat of the effects of administering recombinant human cytokines by injection with continuous release from implanted osmotic minipumps. Continuous release of interleukin-1beta (0.2-2.1 ng h(-1)) induced dose-related changes in the plasma levels of albumin, seromucoid proteins, haptoglobin and caeruloplasmin; interleukin-1alpha had similar effects but required higher doses (2-21 ng h(-1)). Tumour necrosis factor alpha (50 ng h(-1)) only significantly increased seromucoid levels, whereas IL-6 (3-30 ng h(-1)) induced haptoglobin and caeruloplassynthesis. This method provides a better technique for studying the in rive effects of cytokines which may be relevant to the release mechanisms in inflammation.


Vitamin D and vitamin D receptor polymorphism in Asian adolescents with primary dysmenorrhea.
The expression of vitamin D receptor in the normal endometrium and ovaries supports the role of vitamin D in local immunity and inflammatory cytokines regulation. This study aimed to detect the relation between serum 25(OH)D and primary dysmenorrhea in Asian Adolescents. Two hundred and five (205) adolescents complaining of primary dysmenorrhea (study group) were compared in this prospective study to matched controls (210 controls) after informed consent following the Helsinki Declaration. After thorough evaluation, including a thorough history and pelvic ultrasound examination, blood samples were collected from the studied adolescents to measure serum 25(OH)D and for vitamin D receptor TaqI (rs731236) genotyping. The studied adolescents' data were analyzed using the Pearson's correlation to detect the relation between serum 25(OH)D and primary dysmenorrhea (primary outcome). The secondary outcome measures the odds of primary dysmenorrhea in Asian adolescents with vitamin D receptor TaqI (rs731236) polymorphism. The serum 25(OH)D was significantly lower in the studied-dysmenorrhea group compared to controls (16.17 ± 7.36 versus 17.65 ± 6.36 ng/ml, respectively), (P = 0.01). The correlation analysis showed a significant negative correlation between the serum 25(OH)D and visual analogue scale of dysmenorrhea (r = -0.9003, P < 0.0001). The studied-dysmenorrhea cases with vitamin D receptor T/t and t/t genotypes had significantly lower serum 25(OH)D (16.7 ± 8.05 and 14.4 ± 4.1 ng/ml, respectively) compared to controls (18.97 ± 6.7 and 21.4 ± 2.45 ng/ml, respectively), (P = 0.02 and 0.004, respectively). The VDR T/t and t/t polymorphisms significantly increase the odds of primary dysmenorrhea (OR 1367.2, P < 0.0001 and OR 106.2, P = 0.001, respectively). The serum 25(OH)D was significantly lower in the studied-dysmenorrhea group compared to controls. The studied-dysmenorrhea cases with VDR T/t and t/t TaqI genotypes had significantly lower serum 25(OH)D compared to controls. The VDR T/t and t/t polymorphisms significantly increase the odds of primary dysmenorrhea.


Integrated analysis reveals critical glycolytic regulators in hepatocellular carcinoma.
Cancer cells primarily utilize aerobic glycolysis for energy production, a phenomenon known as the Warburg effect. Increased aerobic glycolysis supports cancer cell survival and rapid proliferation and predicts a poor prognosis in cancer patients. Molecular profiles from The Cancer Genome Atlas (TCGA) cohort were used to analyze the prognostic value of glycolysis gene signature in human cancers. Gain- and loss-of-function studies were performed to key drivers implicated in hepatocellular carcinoma (HCC) glycolysis. The molecular mechanisms underlying Osteopontin (OPN)-mediated glycolysis were investigated by real-time qPCR, western blotting, immunohistochemistry, luciferase reporter assay, and xenograft and diethyl-nitrosamine (DEN)-induced HCC mouse models. Increased glycolysis predicts adverse clinical outcome in many types of human cancers, especially HCC. Then, we identified a handful of differentially expressed genes related to HCC glycolysis. Gain- and loss-of-function studies showed that OPN promotes, while SPP2, LECT2, SLC10A1, CYP3A4, HSD17B13, and IYD inhibit HCC cell glycolysis as revealed by glucose utilization, lactate production, and extracellular acidification ratio. These glycolysis-related genes exhibited significant tumor-promoting or tumor suppressive effect on HCC cells and these effects were glycolysis-dependent. Mechanistically, OPN enhanced HCC glycolysis by activating the αvβ3-NF-κB signaling. Genetic or pharmacological blockade of OPN-αvβ3 axis suppressed HCC glycolysis in xenograft tumor model and hepatocarcinogenesis induced by DEN. Our findings reveal crucial determinants for controlling the Warburg metabolism in HCC cells and provide a new insight into the oncogenic roles of OPN in HCC. Video Abstract.


The influence of sympathetic nerves on transcutaneous oxygen tension in normal and ischemic lower extremities.
The authors evaluated the relationship between sympathetic nerve activity and transcutaneous oxygen tension (TcpO2) in normal and ischemic lower extremities. Dorsal foot TcpO2 was measured by using oxygen-sensing electrodes with surface temperatures of 42 degrees C and 45 degrees C; in theory, changes in sympathetic activity should affect vasomotor tone and TcpO2 in skin beneath an electrode at 42 degrees C (submaximal vasodilation), but not at 45 degrees C (maximal vasodilation). The vasodilation index (TcpO2 at 42 degrees C/TcpO2 at 45 degrees C) was created as an index of vasomotor tone (vasodilation index increases as tone decreases). In normal limbs (n = 24) averages for TcpO2 at 42 degrees C, TcpO2 at 45 degrees C, and vasodilation index were 30.3 mmHg, 62.1 mmHg, and 0.47, respectively. In subjects (n = 5) with quadriplegia and reduced sympathetic tone secondary to cervical cord trauma, TcpO2 at 42 degrees C and vasodilation index were increased (45.0 mmHg and 0.61); TcpO2 at 45 degrees C did not change. When normal subjects (n = 7) were chilled for twenty minutes with a cooling blanket at 5 degrees C (to increase sympathetic tone) average vasodilation index dropped from 0.50 to 0.29. Among ischemic limbs (n = 34) vasodilation index was highly variable (range: 0-0.77); in general, vasodilation index fell as the ischemia worsened. In a subset of patients with ischemic limbs, the vasodilation index increased after the limb was wrapped in a warm dressing (average vasodilation index = 0.25 without dressing, 0.37 with dressing). The authors conclude: TcpO2 can be used to assess the degree of vasomotor tone (and sympathetic activity) in skin; tone generally increases as ischemia worsens; and local warmth can improve cutaneous circulation in ischemic limbs.


Inhibition of microtubule dynamics impedes repair of kidney ischemia/reperfusion injury and increases fibrosis.
The microtubule cytoskeleton is composed of α-tubulin and β-tubulin heterodimers, and it serves to regulate the shape, motility, and division of a cell. Post-translational modifications including acetylation are closely associated with the functional aspects of the microtubule, involving in a number of pathological diseases. However, the role of microtubule acetylation in acute kidney injury (AKI) and progression of AKI to chronic kidney disease have yet to be understood. In this study, ischemia/reperfusion (I/R), a major cause of AKI, resulted in deacetylation of the microtubules with a decrease in α-tubulin acetyltransferase 1 (α-TAT1). Paclitaxel (taxol), an agent that stabilizes microtubules by tubulin acetylation, treatment during the recovery phase following I/R injury inhibited tubular cell proliferation, impaired renal functional recovery, and worsened fibrosis. Taxol induced α-tubulin acetylation and post-I/R cell cycle arrest. Taxol aggregated the microtubule in the cytoplasm, resulting in suppression of microtubule dynamics. Our studies have demonstrated for the first time that I/R induced deacetylation of the microtubules, and that inhibition of microtubule dynamics retarded repair of injured tubular epithelial cells leading to an acceleration of fibrosis. This suggests that microtubule dynamics plays an important role in the processes of repair and fibrosis after AKI.


Revisiting the treatment strategy for rectal cancer through the pattern of local recurrence.
Local recurrence after rectal cancer surgery is categorized as lymphatic spread (pelvic sidewall node (PSN)) and other types. This study aimed to investigate the risk factors associated with different patterns of local recurrence and to optimize the treatment strategy after rectal cancer surgery. Patients with cStage I-III rectal cancer who underwent surgery at our institute were included in this study. Local recurrence was categorized as follows: (1) PSN recurrence and (2) "other" types of local recurrence. The risk factors associated with each type of recurrence (metastasis) were investigated. A total of 212 patients with mid/low rectal cancer were included in this study (cStage I: 66; cStage II/III: 146). Additional treatment was employed in selected patients with high-risk features (n = 45; pelvic sidewall dissection: 18; preoperative chemo (radio)therapy: 37). Potential lateral node metastasis was significantly associated with PSN enlargement on imaging findings (no/yes, odds ratio (OR): 9.1; p = 0.007). The "other" local recurrence type was significantly associated with 3 different factors as follows: clinical circumferential resection margin (no/yes; OR: 18.0; p = 0.001), tumor histology (well and moderately/poorly differentiated, OR: 17.3; p = 0.008), and tumor diameter (p = 0.018). Among 146 cStage II/III patients, 66 (45.2%) who did not have any of the abovementioned 4 risk factors experienced no local recurrence even when no additional treatment was employed. Risk factors may differ for different types of postoperative local recurrence patterns in rectal cancer. Recognizing these risk factors based on pretreatment findings can allow the optimization of treatment strategies for rectal cancer.


Quantitative ultrastructural analysis of the neurofilament 200-positive axons in the rat dental pulp.
Previous studies have suggested that myelinated axons lose their myelin and become thinner in their peripheral course to the target organ. In this study, we investigated the morphologic changes of pulpal myelinated axons between their root portion (radicular pulp) and their terminal area (peripheral pulp). Sections of pulp of the rat upper molar teeth were immunostained for the marker of myelinated axons neurofilament (NF) 200. The proportion of NF200+ myelinated and unmyelinated fibers and their sizes were analyzed by using quantitative electron microscopy. The axon area, myelin thickness, and fraction of NF200+ myelinated axons of all NF200+ axons were significantly lower in peripheral than in radicular pulp. In addition, large unmyelinated axons were frequently observed in peripheral pulp. These results suggest that pulpal innervation originates predominantly from myelinated axons, and the myelinated axons undergo extensive morphologic changes during their course from the radicular to the peripheral pulp.


[Postsynaptic potentials of trigeminal nerve nucleus motor neurons evoked by stimulation of the dental pulp in cats].
PSPS of the digastric and masseter motoneurons evoked by stimulation of the upper canine pulp of the ipsi- and contralateral side were studied in the nembutal-chloralose anesthetized cats. Stimulation by single volleys of tooth pulp evoked EPSP and action potentials in digastric motoneurons (latency for ipsilateral pulp was 4.0-5.5 ms, for contralateral--7.0-8.0 ms) and IPSP in masseter motoneurons (latency for ipsilateral pulp was 3.5-4.2 ms, for contralateral--3.8-5.5 ms). All PSPS were polysynaptic.


Control of endothelial function and angiogenesis by PGC-1α relies on ROS control of vascular stability.
Peroxisome proliferator activated receptor g co-activator 1alpha (PGC-1α) is a regulator of oxidative metabolism and reactive oxygen species (ROS) homeostasis that has been show to play a relevant role in angiogenesis. PGC-1α KO mice show reduced vascular density in the retinas and KO primary vascular endothelial cells (ECs) migrate faster than the wild type, an effect that can be rescued by antioxidants, suggesting that excessive ROS levels might be relevant in PGC-1 α role in angiogenesis. This study aims to investigate the role of ROS homeostasis on the regulation by PGC-1 α of angiogenesis. We found that endothelial cells (ECs) from mice deleted for PGC-1 α display attenuated adhesion to the extracellular matrix, together with slower spreading, reduced formation of cellular junctions, a disorganized cytoskeleton and random motility, and a enhanced tip phenotype. Aditionally, PGC-1 α -deleted ECs exhibit an altered response to vascular endothelial growth factor-A (VEGF-A). In vivo, deletion of PGC-1 α results in addition to reduced retinal vascular density, sparse pericyte coverage. Exposure of PGC-1 α deleted mice to hyperoxia during retinal vascular development exacerbates these vascular abnormalities and mice show extensive retinal hemorrhaging, with highly unstructured areas and very poor perfusion, compared with wild-type mice. Structural analysis demonstrates a reduction of endothelial VE-cadherin, suggesting defective inter-cellular junctions. Interestingly, this hyperoxia-induced phenotype is partially reversed by antioxidant administration, indicating that elevated production of mitochondrial reactive oxygen species (ROS) in the absence of PGC-1 α is functionally important. Finally, in vitro studies show that antioxidant treatment improves VEGF-A signaling, suggesting that toxic effect of ROS may be caused by the alteration of the VEGF-A signaling pathway. In summary, our findings indicate that PGC-1 α control of ROS homeostasis plays an important role in the control of de novo angiogenesis, and is required for vascular stability.