Different concentrations of interleukins in the peritoneal fluid of women with endometriosis: relationships with lymphocyte subsets.
The present study explored the possible relationships between immune cell subsets and interleukin (IL)-12 or IL-13 levels in the peritoneal fluid of patients with and without endometriosis. Peritoneal fluid samples were obtained from 80 women while they were undergoing laparoscopy for pain, infertility, tubal ligation or re-anastomosis. The American Fertility Society scoring system was used to determine the extension of endometriosis. The peritoneal fluid mononuclear cells were analyzed for immunophenotyping using cytometry, whereas peritoneal fluid concentrations of interleukins were measured using two ultrasensitive commercially available enzyme-linked imnunosorbent assay kits. Significantly higher peritoneal fluid IL-12 levels were found in women with moderate or severe endometriosis (stages III and IV) than in healthy controls (p < 0.01). Conversely, subjects with endometriosis showed remarkably lower peritoneal fluid IL-13 concentrations than controls, independent of the severity of the disease (p < 0.05). Considering immune system effectors, patients with endometriosis presented a significantly higher peritoneal fluid CD8+/CD4+ ratio when compared with healthy controls. Moreover, the number of peritoneal fluid CD8+ and CD4+ activated T cells was significantly lower in the former than in the latter group, independent of the endometriosis stage. Connections were observed between peritoneal fluid interleukins and peritoneal fluid T cells: both patients with endometriosis and controls presented an inverse correlation between peritoneal fluid activated T cells and IL-13 levels, and a direct correlation between peritoneal fluid T cells and IL-12 concentrations. These data seem to suggest that a reciprocal modulation exists between peritoneal fluid cytokines and T lymphocyte subsets in patients with endometriosis.


Increased risk of endometriosis in patients with endometritis - a nationwide cohort study involving 84,150 individuals.
To evaluate the incidence of endometriosis among endometritis patients and its association with confounding comorbidities. A population-based, retrospective cohort study of women aged between 20 to 55 years, who were newly diagnosed with endometritis between 2000 to 2013. A total of 16,830 endometritis patients and 67,230 non-endometritis individuals were enrolled by accessing data from the National Health Insurance Research Database of Taiwan. The comorbidities accessed were uterine leiomyoma, rheumatoid arthritis, ovarian cancer, infertility and allergic diseases. The mean follow-up period was 9.15 years for the non-endometritis cohort and 9.13 years for the endometritis cohort. There were significantly higher percentages of uterine leiomyoma, rheumatoid arthritis, infertility, ovarian cancer and allergic diseases in the endometritis cohort than in the non-endometritis cohort. Patients with endometritis had a 1.5-fold increased risk of their condition advancing to endometriosis (HR 1.58, 95% CI 1.48-1.68). Our results suggest that patients with endometritis exhibited a positive correlation in developing endometriosis.


Barriers to restorative care as perceived by dentists in Nigeria.
To identify the barriers to restorative care as perceived by dentists working in urban and semi-urban dental hospitals in Nigeria. The study was cross sectional and the sample consisted of 189 of 280 dentists who consented to, filled out and returned the questionnaire mailed to them. The questionnaire consisted of fifteen itemed statements and the respondents were asked to what extent they agreed or disagreed with each item on a four-point Likert scale; 'not at all', 'slight extent', 'some extent' and 'great extent'. Five barrier factors were extracted from the questionnaire. These were 'beliefs of patients', 'knowledge of patients', 'equipment/materials', 'attitude' and 'motivation of practitioner'. Two questions were not grouped with the barrier factors: 'dentistry is being looked down on by administration' and 'patients prefer extraction to filling'. The barrier factor 'attitude of patients' had the highest score (mean = 3.73), followed by the 'knowledge of patients' (mean = 3.27). The barrier factor 'belief of patients' had the lowest score (mean = 2.43). Within the limitations of the study, the barrier factor 'attitude of patients' was the most important barrier to restorative care as perceived by dentists working in urban and semi-urban regions of Nigeria.


Delivery type not associated with global methylation at birth.
Birth by cesarean delivery (CD) as opposed to vaginal delivery (VD) is associated with altered health outcomes later in life, including respiratory disorders, allergies and risk of developing type I diabetes. Epigenetic gene regulation is a proposed mechanism by which early life exposures affect later health outcomes. Previously, type of delivery has been found to be associated with differences in global methylation levels, but the sample sizes have been small. We measured global methylation in a large birth cohort to identify whether type of delivery is associated with epigenetic changes. DNA was isolated from cord blood collected from the University of Michigan Women's & Children Hospital and bisulfite-converted. The Luminometric Methylation Assay (LUMA) and LINE-1 methylation assay were run on all samples in duplicate. Global methylation data at CCGG sites throughout the genome, as measured by LUMA, were available from 392 births (52% male; 65% CD), and quantitative methylation levels at LINE-1 repetitive elements were available for 407 births (52% male; 64% CD). LUMA and LINE-1 methylation measurements were negatively correlated in this population (Spearman's r = -0.13, p =0.01). LUMA measurements were significantly lower for total CD and planned CD, but not emergency CD when compared to VD (median VD = 74.8, median total CD = 74.4, p = 0.03; median planned CD = 74.2, p = 0.02; median emergency CD = 75.3, p = 0.39). However, this association did not persist when adjusting for maternal age, maternal smoking and infant gender. Furthermore, total CD deliveries, planned CD and emergency CD deliveries were not associated with LINE-1 measurements as compared to VD (median VD = 82.2, median total CD = 81.9, p = 0.19; median planned CD = 81.9, p = 0.19; median emergency CD = 82.1, p = 0.52). This lack of association held when adjusting for maternal age, maternal smoking and infant gender in a multivariable model. Type of delivery was not associated with global methylation in our population, even after adjustment for maternal age, maternal smoking, and infant gender. While type of birth may be associated with later health outcomes, our data suggest that it does not do so through changes in global genomic methylation.


Switching mechanism of photochromic diarylethene derivatives molecular junctions.
The electronic transport properties and switching mechanism of single photochromic diarylethene derivatives sandwiched between two gold surfaces with closed and open configurations are investigated by a fully self-consistent nonequilibrium Green's function method combined with density functional theory. The calculated transmission spectra of two configurations are strikingly distinctive. The open form lacks any significant transmission peak within a wide energy window, while the closed structure has two significant transmission peaks on both sides of the Fermi level. The electronic transport properties of the molecular junction with closed structure under a small bias voltage are mainly determined by the tail of the transmission peak contributed unusually by the perturbed lowest perturbed unoccupied molecular orbital. The calculated on-off ratio of currents between the closed and open configurations is about two orders of magnitude, which reproduces the essential features of the experimental measured results. Moreover, we find that the switching behavior within a wide bias voltage window is extremely robust to both substituting F or S for H or O and varying end anchoring atoms from S to Se and Te.


Increased child abuse in families with twins.
Close spacing of children may be a significant risk factor for subsequent abuse in some families. Twin births are an extreme example of close spacing. Therefore, the authors hypothesized that twin births may predispose to an increased incidence of child abuse. Thirty-eight families with twins were compared with 97 single birth families and matched for birthdate, maternal age, race, and socioeconomic status. Families with twins experienced a significantly higher incidence of child abuse and neglect than did those with single births (p less than .003). A written questionnaire designed to study mothers' feelings and perceptions of support systems showed a significant difference only in greater difficulty in feeding twins as compared with single infants (p less than .001). Mothers of abused children were more likely not to answer the questionnaire at all (p less than .005). Neither mothers of single births nor those of twins felt that health professionals provided adequate education or support following the birth of their infants.


DRESS syndrome with autoimmune hepatitis from strontium ranelate.
Strontium ranelate, which is used for postmenopausal osteoporosis, has been associated with drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, a severe, acute, potentially fatal, multisystem adverse drug reaction characterized by skin rash, fever, hematological abnormalities, and lymphadenopathy with involvement of several internal organs. We report the case of a woman who developed DRESS syndrome with a generalized maculopapular rash, eosinophilia, dyspnea, bilateral cervical lymphadenopathy, and reactivation of Epstein-Barr virus (EBV) with liver damage 3 weeks after administration of strontium ranelate for postmenopausal osteoporosis. Approximately 6 months after total remission of cutaneous symptoms, the patient developed autoimmune hepatitis. This case confirms that strontium ranelate should be considered as a possible factor in the etiopathology of DRESS syndrome as well as in the subsequent development of autoimmune hepatitis. The possibility of developing autoimmune hepatitis as a part of DRESS syndrome related to strontium ranelate use can occur months after the acute episode.


Regulation of Ca2+ signalling and Ca2+-mediated cell death by the transcriptional coactivator PGC-1alpha.
Mitochondrial Ca2+ uptake controls cellular functions as diverse as aerobic metabolism, cytosolic Ca2+signalling and mitochondrial participation in apoptosis. Modulatory inputs converging on the organelle can regulate this process, determining the final outcome of Ca2+-mediated cell stimulation. We investigated in HeLa cells and primary skeletal myotubes the effect on Ca2+ signalling of the transcriptional peroxisome-proliferator-activated-receptor-gamma-coactivator-1alpha (PGC-1alpha), which triggers organelle biogenesis and modifies the mitochondrial proteome. PGC-1alpha selectively reduced mitochondrial Ca2+ responses to cell stimulation by reducing the efficacy of mitochondrial Ca2+ uptake sites and increasing organelle volume. In turn, this affected ER Ca2+ release and cytosolic responses in HeLa cells. Most importantly, the modulation of mitochondrial Ca2+ uptake significantly reduced cellular sensitivity to the Ca2+-mediated proapoptotic effect of C2 ceramide. These results reveal a primary role of PGC-1alpha in shaping mitochondrial participation in calcium signalling, that underlies its protective role against stress and proapoptotic stimuli in pathophysiological conditions.


[Low reporting of clinical characteristics of patients with diabetes mellitus included in the main clinical trials on hypertension].
Subjects with diabetes mellitus (DM) are at high risk of cardiovascular events. However, their cardiovascular risk varies according to several clinical characteristics like age, sex, ethnicity, type and duration of the DM, quality of glycemic control, type of hypoglycemic treatment, or the presence of nephropathy or previous cardiovascular events. It is not known if these characteristics have been sufficiently reported in clinical trials on hypertension including subjects with DM. We analyzed randomized controlled clinical trials about treatment of hypertension published before May 2003 with the following characteristics: a) inclusion of subjects with DM and b) a primary end-point including at least one of the following events: myocardial infarction, cerebrovascular disease or total mortality. In these trials we evaluated the above-mentioned clinical characteristics concerning cardiovascular risk. Sixteen trials were eventually analyzed. These trials were classified into: a) trials designed only for subjects with DM (RENAAL, UKPDS 38, UKPDS 39, IDNT); b) trials with a subgroup analysis for subjects with DM (SHEP, Syst-Eur, MICRO-HOPE, HOT, STOP-2, LIFE), and c) trials without a subgroup analysis for subjects with DM (CAPP, NORDIL, INSIGHT, ALLHAT, SANBPSG, CONVINCE). All these trials included a total of 33984 subjects with DM, most of them > or = 55 years old. The percentage of women evaluated ranged from 33.5 to 71.9% although in 2 trials no data were found regarding this percentage (12.5%). There was no information on ethnicity in 10 trials (62.5%), on the type of DM in 7 (43.8%), on the duration of the disease in 13 (81.3%), on the degree of glycemic control in 10 (62.5%), on the type of hypoglycemic treatment in 11 (68.8%), on the presence or absence of nephropathy in 11 (68.8%) and on the presence or absence of previous cardiovascular events in 3 (18.8%). Trials without subgroup analysis for subjects with DM had a lower reporting of the clinical characteristics of the subjects evaluated than the rest of the trials. The reporting of relevant clinical characteristics of cardiovascular risk in subjects with DM in the main clinical trials on hypertension is low, diminishing their external validity. To optimize the therapeutic recommendations in the treatment of hypertension in DM these deficiencies should be overcome.


An intervention to help older adults maintain independence safely.
Older adults who live alone are at risk for problems (e.g., falling, sudden illness). To maintain themselves safely at home they may benefit from planning to prevent problems. The purpose of this study was to evaluate an intervention designed to train family members or friends as to how to help older adults who were living alone make plans to maintain independence safely in their homes and to make behavioral and household changes to enhance safety. Support network members of 19 older adults randomly assigned to the intervention group were taught to use multiple segment vignettes to assist the older adults in creating plans for living safely. Older adults in the control group (n = 21) were asked to engage in an unstructured discussion about home safety with their network members. Older adults in the intervention group developed safer plans and made more household and behavioral changes than did control group adults.


A non-invasive method for silencing gene transcription in honeybees maintained under natural conditions.
In the Apis mellifera post-genomic era, RNAi protocols have been used in functional approaches. However, sample manipulation and invasive methods such as injection of double-stranded RNA (dsRNA) can compromise physiology and survival. To circumvent these problems, we developed a non-invasive method for honeybee gene knockdown, using a well-established vitellogenin RNAi system as a model. Second instar larvae received dsRNA for vitellogenin (dsVg-RNA) in their natural diet. For exogenous control, larvae received dsRNA for GFP (dsGFP-RNA). Untreated larvae formed another control group. Around 60% of the treated larvae naturally developed until adult emergence when 0.5 microg of dsVg-RNA or dsGFP-RNA was offered while no larvae that received 3.0 microg of dsRNA reached pupal stages. Diet dilution did not affect the removal rates. Viability depends not only on the delivered doses but also on the internal conditions of colonies. The weight of treated and untreated groups showed no statistical differences. This showed that RNAi ingestion did not elicit drastic collateral effects. Approximately 90% of vitellogenin transcripts from 7-day-old workers were silenced compared to controls. A large number of samples are handled in a relatively short time and smaller quantities of RNAi molecules are used compared to invasive methods. These advantages culminate in a versatile and a cost-effective approach.


Low-grade appendiceal mucinous neoplasm mimicking an adnexal mass.
We present a rare case of malignant epithelial neoplasm of the appendix, an uncommon disorder encountered in clinical practice, which poses a variety of diagnostic and therapeutic challenges. We report a particular case in which the appendix was abnormally located in the pelvis, mimicking an adnexal mass. Therefore, it was difficult to make the preoperative diagnosis on clinical examination, imaging studies and laboratory tests and we discovered the lesion during the diagnostic laparoscopy. No lymphadenopathy or mucinous ascites were found. The case was completely handled via the laparoscopic approach keeping the appendix intact during the operation. The frozen section, the detailed histopathology overview as well as multiple immunostaining with a complex panel of markers report diagnosed a low-grade appendiceal mucinous neoplasm (LAMN) with no invasion of the wall. No adjuvant therapy was considered needed. At a one-year follow-up oncological assessment, the patient was free of disease. In women with cystic mass in the right iliac fossa an appendiceal mucocele should be considered in the differential diagnosis. Laparoscopic appendectomy can represent an adequate operation for the appendiceal mucinous neoplasm if the histological report is clear and surgical precautionary measures are taken.


Characteristics of clinical trials of influenza and respiratory syncytial virus registered in ClinicalTrials.gov between 2014 and 2021.
The randomized clinical trial (RCT) is the ideal and mandatory type of study to verify the effect and safety of a drug. Our aim is to examine the fundamental characteristics of interventional clinical trials on influenza and respiratory syncytial virus (RSV). This is a cross-sectional study of RCTs on influenza and RSV in humans between 2014 and 2021 registered in ClinicalTrials.gov. A total of 516 studies were identified: 94 for RSV, 423 for influenza, and 1 for both viruses. There were 51 RCTs of RSV vaccines (54.3%) and 344 (81.3%) for influenza virus vaccines (p < 0.001). Twelve (12.8%) RCTs for RSV were conducted only with women, and 6 were conducted only with pregnant women; for RCTs for influenza, 4 (0.9%) and 3, respectively. For RSV, 29 (31%) of the RCTs were exclusive to people under 5 years of age, and 21 (5%) for influenza virus (p < 0.001). For RSV, there are no RCTs exclusively for people older than or equal to 65 years and no phase 4 trials. RCTs on influenza virus and RSV has focused on vaccines. For the influenza virus, research has been consolidated, and for RSV, research is still in the development phase and directed at children and pregnant women.


Hypothalamic paraventricular nucleus, but not vasopressin, participates in chronic hyperactivity of the HPA axis in diabetic rats.
Diabetes mellitus (DM), as chronic stress activates the hypothalamo-pituitary-adrenocortical axis. We examined whether arginine vasopressin (AVP) and the hypothalamic paraventricular nucleus (PVN) participate in DM-induced chronic stress symptoms. AVP-deficient Brattleboro or PVN-lesioned Wistar rats were used with heterozygous or sham-operated controls. The rats were studied 2 wk after a single injection of streptozotocin. The appearance of DM (enhanced water consumption and blood glucose elevation) and the chronic stress-like somatic changes (body weight decrease, thymus involution, adrenal gland hypertrophy) were not influenced by the lack of AVP. By contrast, PVN lesion significantly attenuated DM-induced thymus involution and adrenal gland hypertrophy as well as the increase in water consumption. The corticotropin-releasing hormone mRNA in PVN was diminished by DM and elevated by the lack of AVP without interaction. DM elevated the proopiomelanocortin (POMC) mRNA in the anterior lobe of the pituitary. The lack of AVP had no effect, whereas lesioning the PVN significantly diminished the elevation. The elevated basal corticosterone plasma levels detectable in DM were influenced neither by the lack of AVP nor by lesioning the PVN. Thus the lack of AVP had no influence on DM-induced chronic stress symptoms, but lesioning the PVN attenuated part of them. However, the lack of elevation in POMC mRNA after PVN lesion, together with the maintained corticosterone elevation, suggests that direct adrenal gland activation occurs in untreated DM.


A one year follow-up of relaxation response meditation as a treatment for irritable bowel syndrome.
Ten of thirteen original participants with Irritable Bowel Syndrome (IBS) participated in a one year follow-up study to determine whether the effects of Relaxation Response Meditation (RRM) on IBS symptom reduction were maintained over the long-term. From pre-treatment to one-year follow-up, significant reductions were noted for the symptoms of abdominal pain (p = 0.017), diarrhea (p = 0.045), flatulence (p = 0.030), and bloating (p = 0.018). When we examined changes from the original three month follow-up point to the one year follow-up, we noted significant additional reductions in pain (p = 0.03) and bloating (p = 0.04), which tended to be the most distressing symptoms of IBS. It appears that: (1) continued use of meditation is particularly effective in reducing the symptoms of pain and bloating; and (2) RRM is a beneficial treatment for IBS in the both short- and the long-term.


[Quantitative distribution of nucleolar nucleic acids in the Purkinje cells during vestibular stimulation and immobilization of rats].
The content of nucleic acids in the nucleoli of Purkinje cells was studied under horizontal rotation and immobilization of rats by UV cytophotometry. The histograms of the distribution of nucleolar nucleic acids under both exposures have a common trend towards asymmetry. Unlike the immobilized animals, the rats subjected to rotation show in all the time points a correlation between changes in the total content of nucleic acids in the nucleoli and cytoplasm, and an alteration in the asymmetry of distribution of nucleolar nucleic acids. The changes in the distribution of the latter acids and cytoplasmic RNA under vestibular stimulation are also in good agreement as regards the time and pattern.


Two Neptunium(III) Mellitate Coordination Polymers: Completing the Series Np-Cf of Trans-Uranic An(III) Mellitates.
Two neptunium(III) mellitates, 237Np2(mell)(H2O)9·1.5H2O (Np-1α) and 237Np2(mell)(H2O)8·2H2O (Np-1β), have been synthesized from 237NpCl4(dme)2 by reduction with KC8 and subsequent reaction with an aqueous solution of mellitic acid (H6mell). Characterization by single-crystal X-ray crystallography and UV-vis-NIR spectroscopy confirms that the neptunium is in its +3 oxidation state and both polymorphs are isostructural to the previously reported plutonium mellitates. Of the two morphologies, Np-1α is indefinitely stable in air, while Np-1β slowly oxidizes over several months. This is due to the change in the energy of the metal-ligand charge-transfer absorption exhibited by these compounds attributed to differing numbers of carboxylate bonds to Np(III), where in Np-1β the energy is low enough to result in spontaneous oxidation.


Flexor tenosynovitis of the wrist with carpal tunnel syndrome.
Tubercular tenosynovitis of the wrist with carpal tunnel syndrome (CTS) is a rare occurrence. The authors present a case of tubercular flexor tenosynovitis of the wrist with CTS. A 60-year-old female presented with complaints of swelling in the volar aspect of the right wrist with numbness of the first three fingers for the past 6 months. Clinical and radiological diagnosis of chronic flexor tenosynovitis with median nerve compression neuropathy was made. The patient was operated with carpal tunnel release and total tenosynovectomy. Histopathology showed features suggestive of Koch's etiology. The patient was started with antitubercular therapy (ATT) and followed up regularly. Carpal tunnel symptoms subsided immediately after surgery and there was no recurrence of swelling at the last follow-up. Carpal tunnel release and tenosynovectomy should be performed at the earliest possible and followed up with ATT for better outcomes in tubercular tenosynovitis of the wrist with CTS.


FLN29, a novel interferon- and LPS-inducible gene acting as a negative regulator of toll-like receptor signaling.
Lipopolysaccharide (LPS) activates macrophages through toll-like receptor (TLR) 4. Although the mechanism of the TLR signaling pathway has been well documented, the mechanism of the negative regulation in response to LPS, particularly LPS tolerance, is still poorly understood. In this study we identified and characterized a novel interferon- and LPS-inducible gene, FLN29, which contains a TRAF6-related zinc finger motif and TRAF family member-associated NF-kappaB activator-related sequences. The induction of FLN29 was dependent on STAT1. The forced expression of FLN29 in macrophage-like RAW cells resulted in the suppression of TLR-mediated NF-kappaB and mitogen-activated protein kinase activation, while a reduced expression of FLN29 by small interfering RNA partly cancelled the down-regulation of LPS signaling. Furthermore, we demonstrated that NF-kappaB activation induced by TRAF6 and TAB2 was impaired by co-expression of FLN29, suggesting FLN29 may regulate the downstream of TRAF6. Taken together, FLN29 is a new negative feedback regulator of TLR signaling.


Protein-Specific, Multicolor and 3D STED Imaging in Cells with DNA-Labeled Antibodies.
Photobleaching is a major challenge in fluorescence microscopy, in particular if high excitation light intensities are used. Signal-to-noise and spatial resolution may be compromised, which limits the amount of information that can be extracted from an image. Photobleaching can be bypassed by using exchangeable labels, which transiently bind to and dissociate from a target, thereby replenishing the destroyed labels with intact ones from a reservoir. Here, we demonstrate confocal and STED microscopy with short, fluorophore-labeled oligonucleotides that transiently bind to complementary oligonucleotides attached to protein-specific antibodies. The constant exchange of fluorophore labels in DNA-based STED imaging bypasses photobleaching that occurs with covalent labels. We show that this concept is suitable for targeted, two-color STED imaging of whole cells.


Efficacy of radiotherapy and stereotactic radiosurgery as adjuvant or salvage treatment in atypical and anaplastic (WHO grade II and III) meningiomas: a systematic review and meta-analysis.
The role of radiotherapy (RT) and stereotactic radiosurgery (SRS) as adjuvant or salvage treatment in high-grade meningiomas (HGM) is still debated. Despite advances in modern neuro-oncology, HGM (WHO grade II and III) remains refractory to multimodal therapies. Published reports present aggregated data and are extremely varied in population size, exclusion criteria, selection bias, and inclusion of mixed histologic grades, making it extremely difficult to draw conclusions when taken individually. This current work aims to gather the existing evidence on RT and SRS as adjuvants following surgery or salvage treatment at recurrence after multimodality therapy failure and to conduct a systematic comparison between these two modalities. An extensive systematic literature review and meta-analysis were performed. A total of 42 papers were eligible for final analysis (RT n = 27; SRS n = 15) after searching MEDLINE via PubMed, Web-of-science, Cochrane Wiley, and Embase databases. Adjuvant regimens were addressed in 37 papers (RT n = 26; SRS n = 11); salvage regimens were described in 5 articles (RT n = 1; SRS n = 4). The primary outcomes of the study were the overall recurrence rate and mortality. Other actuarial rates (local and distant control, OS, PFS, and complications) were retrieved and analyzed as secondary outcomes. A total of 2853 patients harboring 3077 HGM were included. The majority were grade II (87%) with a mean pre-radiation volume of 8.7 cc. Adjuvant regimen: 2742 patients (76.4% RT; 23.6% SRS) with an overall grade II/III rate of 6.6/1. Lesions treated adjSRS were more frequently grade III (17 vs 12%, p < 0.001), and received subtotal resection (57 vs 27%, p = 0.001) compared to the RT cohort. AdjSRS cohort had a significantly shorter mean follow-up than adjRT (36.7 vs 50.3 months, p = 0.01). The overall recurrence rate was 38% in adjRT vs 25% in adjSRS (p = 0.01), while mortality did not differ between the groups (20% vs 23%, respectively; p = 0.80). The median time to recurrence was 1.5 times longer in the RT group (p = 0.30). Five-year local control was 55% in adjRT and 26% in adjSRS (p = 0.01), while 5-year OS was 73% and 78% (p = 0.62), and 5-year PFS was 62% and 40% in adjRT and adjSRS (p = 0.008). No difference in the incidence of complications (24% vs 14%, p = 0.53). Salvage regimen: 110 patients (37.3% RT; 62.7% SRS) with a grade II/III rate of 8.6/1. The recurrence rate was 46% in salRT vs 24% in salSRS (p = 0.39), time to recurrence was 1.8 times longer in the salRT group (35 vs 18.5 months, p = 0.74). Mortality was slightly yet not significantly higher in salRT (34% vs 12%, p = 0.54). Data on local and distant control were only available for salSRS. The 5-year OS was 49% and 83% (p = 0.90), and the 5-year PFS was 39% and 50% in salRT and salSRS (p = 0.66), respectively. High-grade meningiomas (WHO grade II and III) receiving adjuvant RT showed a higher overall recurrence rate than meningiomas receiving adjuvant SRS. The adjRT cohort, however, achieved higher 5-year LC and PFS rates, thus suggesting a potentially longer time to recurrence compared to adjSRS patients, who, meanwhile, experienced a significantly shorter follow-up. This result must also consider the higher number of grade III lesions and the smaller extent of resection achieved in the adjSRS group. Overall mortality did not differ between the two groups. No differences in outcome measures were observed in salvage regimens.


Health risk behaviors among California college students.
Health risk behaviors among students attending 4-year colleges in California were examined. The Youth Risk Behavior Survey for College Students was administered in a two-stage (29 universities, 5,652 students) random sample. All campuses and 3,810 (69%) students participated in the survey. In the 30 days preceding the survey, 36.7% of the students had binged at least once while drinking; 25.3% had driven after consuming alcohol; 32% had ridden in a car with someone who had been drinking; 17.6% had used marijuana; and 6% had carried a knife, gun, or club. More than half of the students who were sexually active and not married or living with a primary partner had not used a condom the last time they had sexual intercourse. Only 5% of regular bicycle riders always wore a helmet. Fewer than half (44%) reported aerobic physical activity on 3 or more of the preceding 7 days. The results of this study indicate a substantial amount of serious, risky health behaviors among California college students.


G protein-coupled receptor kinase 2, with β-arrestin 2, impairs insulin-induced Akt/endothelial nitric oxide synthase signaling in ob/ob mouse aorta.
In type 2 diabetes, impaired insulin-induced Akt/endothelial nitric oxide synthase (eNOS) signaling may decrease the vascular relaxation response. Previously, we reported that this response was negatively regulated by G protein-coupled receptor kinase 2 (GRK2). In this study, we investigated whether/how in aortas from ob/ob mice (a model of type 2 diabetes) GRK2 and β-arrestin 2 might regulate insulin-induced signaling. Endothelium-dependent relaxation was measured in aortic strips. GRK2, β-arrestin 2, and Akt/eNOS signaling pathway proteins and activities were mainly assayed by Western blotting. In ob/ob (vs. control [Lean]) aortas: 1) insulin-induced relaxation was reduced, and this deficit was prevented by GRK2 inhibitor, anti-GRK2 antibody, and an siRNA specifically targeting GRK2. The Lean aorta relaxation response was reduced to the ob/ob level by pretreatment with an siRNA targeting β-arrestin 2. 2) Insulin-stimulated Akt and eNOS phosphorylations were decreased. 3) GRK2 expression in membranes was elevated, and, upon insulin stimulation, this expression was further increased, but β-arrestin 2 was decreased. In ob/ob aortic membranes under insulin stimulation, the phosphorylations of Akt and eNOS were augmented by GRK2 inhibitor. In mouse aorta, GRK2 may be, upon translocation, a key negative regulator of insulin responsiveness and an important regulator of the β-arrestin 2/Akt/eNOS signaling, which is implicated in diabetic endothelial dysfunction.


Influence of polyclonal immunoglobulins on the polymorphonuclear leukocyte response to lipopolysaccharide of Salmonella enteritidis as measured with luminol-enhanced chemiluminescence.
In gram-negative sepsis, the activation of polymorphonuclear leukocytes (PMN) by lipopolysaccharide (LPS) and the resulting production of superoxide and other oxygen radicals may be an important cause of tissue damage. A suppression of the PMN response to LPS stimulation would be therapeutically beneficial. The aim of this study was to determine whether different polyclonal immunoglobulins (Igs; 5S-Ig, 7S-Ig, and 19S-Ig) influence the PMN response to LPS of Salmonella enteritidis in vitro. The respiratory burst activity of PMN was measured with luminol-enhanced chemiluminescence. After addition of a 5S-Ig solution containing F(ab')2 fragments of IgG and a 19S-Ig solution containing 12% polyclonal IgM, luminol-enhanced chemiluminescence was reduced by 27% (P < 0.05) and 46% (P < 0.005), respectively. However, after addition of a 7S-Ig solution containing polyclonal IgG, luminol-enhanced chemiluminescence was increased fourfold (P < 0.05). The results suggest that the influence of polyclonal Igs on PMN response to LPS stimulation is dependent on the Ig class, F(ab')2 fragments of IgG and IgM leading to LPS neutralization and IgG leading to the production of potentially toxic oxygen radicals.


[Investigation and analysis of the defense mechanism and domestic violence of male patients with somatization disorder].
To evaluate the relationship between the psychological impediment of the patients with somatization disorder (SD) and domestic violence, and to enhance peoples recognition of this kind of patients' harmful action to others so as to attach more importance to the patients and to the improvement of mental health service of the community. Questionnaire scoring was conducted among the wives of the SD group and the control group concerning domestic violence. It was also conducted in the SD group, the control group and the wives of the two groups concerning defense mechanism. The average score on demestic violence of the SD group was significantly higher than that of the normal control. Immature and intermediate defenses were more usual in the SD group than in the normal control (P < 0.01). Psychological impediment of SD patients is an important cause of domestic violence.


In vitro and in vivo effect of HPMA copolymer-bound doxorubicin targeted to transferrin receptor of B-cell lymphoma 38C13.
N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymers containing the anticancer agent doxorubicin and targeted to the transferrin receptor either with anti-mouse CD71 monoclonal antibody (mAb) or with transferrin were synthesized to evaluate their binding and anti-proliferative activity in vitro and anti-tumor potential against 38C13 B-cell lymphoma in vivo. Both the doxorubicin and the targeting moieties were bound to HPMA copolymer chain by aminolysis via a Gly-Phe(D,L)-Leu-Gly spacer to ensure controlled intracellular release of the conjugated drug. We demonstrated that HPMA copolymer-bound doxorubicin targeted to the transferrin receptor with anti-mouse CD71 mAb strongly retards tumor growth, prolongs the survival and completely cures three out of nine experimental mice with established 38C13 tumors. The conjugate targeted with transferrin was less effective in vitro as well as in vivo. It completely cured only one out of seven experimental mice. Free or non-targeted HPMA copolymer-bound doxorubicin showed only a mild anti-tumor effect within the therapeutic schedule used. In vitro, HPMA copolymer-bound doxorubicin targeted with anti-mouse CD71 mAb shows approximately 4-fold higher cytotoxic effect than HPMA copolymer-bound doxorubicin targeted with transferin and 9-fold higher cytotoxic effect than non-targeted HPMA copolymer-bound doxorubicin.


Temporary impairment of semen quality following recent acute fever.
The impact of an acute fever on semen variables is unclear. This paper reports negative effects and recovery of the sperm quality in a man who had an acute fever of 38°-39°C, due to a throat infection. The study evaluated the sperm quality in semen specimens collected, as follows: 1) one month before the fever; 2) 1-day after the fever; 3) 20 days after antimicrobial therapy. The first and third specimens were quite similar for all semen parameters. However, the second specimen showed unexpected results: not only a decrease in the sperm count, but also an increase of small-head sperm. This study aims to discuss this finding's implications for clinical and laboratory practice.


Fusion Oncoproteins in Childhood Cancers: Potential Role in Targeted Therapy.
Cancer remains the leading cause of death from disease in children. Historically, in contrast to their adult counterparts, the causes of pediatric malignancies have remained largely unknown, with most pediatric cancers displaying low mutational burdens. Research related to molecular genetics in pediatric cancers is advancing our understanding of potential drivers of tumorigenesis and opening new opportunities for targeted therapies. One such area is fusion oncoproteins, which are a product of chromosomal rearrangements resulting in the fusion of different genes. They have been identified as oncogenic drivers in several sarcomas and leukemias. Continued advancement in the understanding of the biology of fusion oncoproteins will contribute to the discovery and development of new therapies for childhood cancers. Here we review the current scientific knowledge on fusion oncoproteins, focusing on pediatric sarcomas and hematologic cancers, and highlight the challenges and current efforts in developing drugs to target fusion oncoproteins.


Critical care medicine at Walter Reed Army Medical Center in support of the global war on terrorism.
The military medical experience during wartime is unique and distinct from civilian medical practice. Historically, the military has produced innovations resulting in both civilian and military medical care advances, and our current conflict is no different. In this article, we provide a description of the medical and surgical intensive care units at Walter Reed, their history, and approach to new issues encountered in the care of Operation Iraqi Freedom and Operation Enduring Freedom soldiers. Additionally, descriptive statistics regarding the number of Operation Iraqi Freedom and Operation Enduring Freedom soldiers admitted to the critical care service, basic demographics, general category of injury, and discussion of intensive care unit issues unique to this patient population, such as Acinetobacter and traumatic brain injury, are presented. We intend to provide a general description of our Operation Iraqi Freedom/Operation Enduring Freedom trauma population cared for by the critical care service at Walter Reed Army Medical Center, as well as a discussion of our approach to caring for some of their unique issues, to detail experiences that could translate into improvements for civilian trauma centers.


Demonstration of anaerobic stabilization of black water in accumulation systems under tropical conditions.
The anaerobic digestion of "human waste" was studied at Mlalakuwa residential settlement in Dar-es-Salaam, Tanzania at ambient tropical temperatures (24-31 degrees C). This settlement experiences a high water table with flooding during the rainy season, resulting in a very costly emptying of the latrines once per month. To improve the situation, two plastic tanks (while one is in use, the other one is on stand-by) of 3000 l capacity each, named as Improved Pit-Latrines Without Urine Separation (IMPLWUS), were used as latrine pits. They received faeces+urine+wash water; basically, an accumulation system. Septic tank seed sludge was used. The dissolved chemical oxygen demand (COD(dis)) remaining when the reactor was closed after 380 days was about 8 g COD/l, volatile fatty acids were 100 mg COD/l and total ammonium nitrogen was about 2.8 g N/l, implying the possibility of methanogenesis inhibition. Stability results indicated a need for more degradation time after reactor closure. Estimated biogas production from wastewater generated by 10 people was 544 g COD-CH(4)/day, not enough for cooking purposes.


(1)H NMR-Based Metabolomics Reveals a Pedoclimatic Metabolic Imprinting in Ready-to-Drink Carrot Juices.
Carrots are usually consumed in their native form or processed into many different products. Carrot juice is a popular beverage consumed throughout the world and is attracting increasing attention due to its nutritional value, being a natural source of bioactive compounds. Ready-to-drink carrot juices produced in the same factory were analyzed by (1)H nuclear magnetic resonance (NMR) spectroscopy. The juices were made from carrot roots of the same cultivar grown in three different geographical areas in Italy. More than 30 compounds have been identified and quantified, and the data was subjected to univariate ANOVA and multivariate analyses. Clear geographical-dependent clustering was observed, and the metabolic profiles were related to the different pedoclimatic conditions. The proposed phytoprofiling approach could be employed on an industrial scale to evaluate finished products involving different sites of supply of the raw material, thus improving both the quality and uniformity of the juices.


Clinical manifestations of headache in children younger than 7 years.
Headache is a common symptom during childhood. It is usually persistent and requires special care. This study aimed to identify the characteristics of headache in children <7 years of age. We reviewed 3 years of clinical files on children <7 years of age with a chief complaint of headache. This study included 146 children (66 males, 80 females; mean age, 5.5±1.0 years). Mean symptom duration was 5.8±7.9 months. Attack durations were longer than 2 hours in 31 patients, shorter than 2 hours in 70 patients, and unchecked in 45 patients. Attack frequency was 15.1±10.6 times per month. Pain locations and characteristics were also variable. Mean pain severity score was 5.1±2.2 on the visual analog scale. Of 38 patients who underwent electroencephalography, 9 showed positive findings. Of 41 who underwent brain magnetic resonance imaging, 20 showed positive findings. The diagnoses were migraine (including probable migraine) in 34, tension-type headache in 5, and congenital malformations in 3. Medications were used in 29 patients: acetaminophen in 17, ibuprofen in 8, naproxen sodium in 1, and topiramate or amitriptyline in 3. In children aged <7 years, headache has a relatively benign course, but detailed history taking is needed for more accurate diagnosis.


Video transaction algorithm considering FISCO alliance chain and improved trusted computing.
With the advent of the era of self media, the demand for video trading is becoming more and more obvious. Alliance blockchain has the characteristics of traceable transaction records, tamper proof transaction records, decentralized transactions and faster transaction speed than public chains. These features make it a trading platform. Trusted computing can solve the problem of non Byzantine attack in the aspect of hardware. This paper proposes a video transaction algorithm considering FISCO alliance chain and improved trusted computing. First, an improved trusted computing algorithm is used to prepare a trusted transaction environment. Second, the video summary information extraction algorithm is used to extract the summary information that can uniquely identify the video. Finally, based on the video transactions algorithm of FISCO alliance chain, the video summary information is traded on the chain. Experimental results show that the proposed algorithm is efficient and robust for video transactions. At the same time, the algorithm has low computational power requirements and algorithm complexity, which can provide technical support for provincial and county financial media centers and relevant media departments.


Area-Selective Atomic Layer Deposition for Resistive Random-Access Memory Devices.
Resistive random-access memory (RRAM) is a promising technology for data storage and neuromorphic computing; however, cycle-to-cycle and device-to-device variability limits its widespread adoption and high-volume manufacturability. Improving the structural accuracy of RRAM devices during fabrication can reduce these variabilities by minimizing the filamentary randomness within a device. Here, we studied area-selective atomic layer deposition (AS-ALD) of the HfO2 dielectric for the fabrication of RRAM devices with higher reliability and accuracy. Without requiring photolithography, first we demonstrated ALD of HfO2 patterns uniformly and selectively on Pt bottom electrodes for RRAM but not on the underlying SiO2/Si substrate. RRAM devices fabricated using AS-ALD showed significantly narrower operating voltage range (2.6 × improvement) and resistance states than control devices without AS-ALD, improving the overall reliability of RRAM. Irrespective of device size (1 × 1, 2 × 2, and 5 × 5 μm2), we observed similar improvement, which is an inherent outcome of the AS-ALD technique. Our demonstration of AS-ALD for improved RRAM devices could further encourage the adoption of such techniques for other data storage technologies, including phase-change, magnetic, and ferroelectric RAM.


The Combined Effect of Safety Specific Transformational Leadership and Safety Consciousness on Psychological Well-Being of Healthcare Workers.
Occupational health researchers have begun to realize that the psychological well-being of healthcare workers who are providing treatment against COVID-19 is deteriorating. However, there is minimal research conducted on it, particularly in the context of leadership. The current study aims to fill this important gap by identifying critical factors that can enhance the psychological well-being of healthcare workers. We proposed that safety specific transformational leadership enhances psychological well-being among healthcare workers, and COVID-19 perceived risk mediates this relationship. Furthermore, the safety conscientiousness of healthcare workers was proposed to be a boundary condition that enhances the negative relationship between safety-specific transformational leadership and COVID-19 perceived risk. Data were collected from healthcare workers (N = 232) treating COVID-19 patients in the hospitals of Pakistan through well-established adopted questionnaires. The discriminant and convergent validity of the data was tested through confirmatory factor analysis by using AMOS statistical package. The mediation and moderation hypotheses were tested by using PROCESS Macro by Hayes. The results showed that safety specific transformational leadership enhances psychological well-being among healthcare workers, and COVID-19 perceived risk mediates this relationship. Moderation results also confirmed that safety conscientiousness moderates the relationship between safety specific transformational leadership and COVID-19 perceived risk. This study offers implications for both researchers and practitioners.


The two putative comS homologs of the biotechnologically important Bacillus licheniformis do not contribute to competence development.
In Bacillus subtilis, natural genetic competence is subject to complex genetic regulation and quorum sensing dependent. Upon extracellular accumulation of the peptide-pheromone ComX, the membrane-bound sensor histidine kinase ComP initiates diverse signaling pathways by activating-among others-DegQ and ComS. While DegQ favors the expression of extracellular enzymes rather than competence development, ComS is crucial for competence development as it prevents proteolytic degradation of ComK, the key transcriptional activator of all genes required for the uptake and integration of DNA. In Bacillus licheniformis, ComX/ComP sensed cell density negatively influences competence development, suggesting differences from the quorum-sensing-dependent control mechanism in Bacillus subtilis. Here, we show that each of six investigated strains possesses both of two different, recently identified putative comS genes. When expressed from an inducible promoter, none of the comS candidate genes displayed an impact on competence development neither in B. subtilis nor in B. licheniformis. Moreover, disruption of the genes did not reduce transformation efficiency. While the putative comS homologs do not contribute to competence development, we provide evidence that the degQ gene as for B. subtilis negatively influences genetic competency in B. licheniformis.


[Factor analysis and method exploring for lymph nodes harvest in gastric cancer].
The number of lymph node dissection and positive lymph nodes are the necessary guarantees for patients to achieve accurate staging after gastric cancer surgery. On the basis of the minimum number of lymph nodes dissection recommended by the NCCN guidelines, as many as possible lymph node yields will be most likely to benefit patients. Many factors can influence the number of lymph node yields including surgery, patient, tumor pathology and postoperative sorting factors. Compared with traditional manual nodal dissection method, fat-clearing technique and methylene blue staining method can improve the number of lymph nodes detection, while lymphatic tracers, such as carbon nanoparticles, are conducive to show lymphatic vessels, contributing to the dissection of small lymph nodes. The initial results from People's Liberation Army General Hospital show that lymph node packet submission after isolation by surgeon yields more lymph nodes. For the establishment of standards, lymph node retrieval-related procedures need further in-depth exploration and investigation.


The normative dimension and legal meaning of endangered and recovery in the U.S. Endangered Species Act.
The ethical, legal, and social significance of the U.S. Endangered Species Act of 1973 (ESA) is widely appreciated. Much of the significance of the act arises from the legal definitions that the act provides for the terms threatened species and endangered species. The meanings of these terms are important because they give legal meaning to the concept of a recovered species. Unfortunately, the meanings of these terms are often misapprehended and rarely subjected to formal analysis. We analyzed the legal meaning of recovered species and illustrate key points with details from "recovery" efforts for the gray wolf (Canis lupus). We focused on interpreting the phrase "significant portion of its range," which is part of the legal definition of endangered species. We argue that recovery and endangerment entail a fundamentally normative dimension (i.e., specifying conditions of endangerment) and a fundamentally scientific dimension (i.e., determining whether a species meets the conditions of endangerment). Specifying conditions for endangerment is largely normative because it judges risks of extinction to be either acceptable or unacceptable. Like many other laws that specify what is unacceptable, the ESA largely specifies the conditions that constitute unacceptable extinction risk. The ESA specifies unacceptable risks of extinction by defining endangered species in terms of the portion of a species' range over which a species is "in danger of extinction." Our analysis indicated that (1) legal recovery entails much more than the scientific notion of population viability, (2) most efforts to recover endangered species are grossly inadequate, and (3) many unlisted species meet the legal definition of an endangered or threatened species.


Postural performance assessment in aging people with diabetes and diabetic peripheral neuropathy using a Wii balance board.
To determine the effect of sensory perturbations on static postural control in older people with type 2 diabetes mellitus by comparing postural outcomes of people with and without diabetic neuropathy using a Wii Balance Board (WBB). Static postural balance assessments were performed in 31 participants: nine with type 2 diabetes mellitus; 12 with diabetic neuropathy; and 10 non-diabetic controls. Participants stood on the WBB under sensory perturbations (visual and proprioceptive). Body balance was analysed using centre of pressure ellipse area, mean velocity, and sample entropy. The effects of within-participant factors, sensory perturbations and the between-participants factor 'group' on outcomes were analysed using a multivariate analysis of variance model. Type 2 diabetes mellitus participants with and without neuropathy showed altered postural performance under sensory perturbations compared to non-diabetic participants. Moreover, participants with diabetic neuropathy showed impaired postural performance when one perceptual system was disturbed. Finally, participants with type 2 diabetes mellitus without neuropathy decreased their postural performance when both sensory disturbances were present. The Wii Balance Board can be a useful alternative for balance impairment screening related to diabetic neuropathy and contribute as an affordable source of insight in early interventions in integral diabetes care.Implications to rehabilitationOlder people with diabetic peripheral neuropathy depend on visual and somatosensory cues to keep their static postural balance.Static balance assessment using the Wii Balance Board allows the identification of alterations in postural performance in participants with diabetes.This low-cost method used can be considered as a complement to integral diabetes care.


Phylogeographic variation within the Buff-browed Foliage-gleaner (Aves: Furnariidae: Syndactyla rufosuperciliata) supports an Andean-Atlantic forests connection via the Cerrado.
We evaluated whether the Andean and the Atlantic forests acted as refugia during the Quaternary, and tested biogeographic hypotheses about the regions involved in the connectivity between those biomes (through the Chaco or the Cerrado). To achieve these goals we selected the Buff-browed Foliage-gleaner Syndactyla rufosuperciliata (Aves, Furnariidae) as a study system, a taxon distributed between the Andean and Atlantic forest. We first explored the historical connectivity between regions through niche modeling. We subsequently used DNA sequences (n = 71 individuals) and genomic analyses (ddRADseq, n = 33 individuals) to evaluate population genetic structure and gene flow within this species. Finally, we performed population model selection using Approximate Bayesian Computation. Our findings indicate that the Andean and the Atlantic forests acted as refugia, and that the populations of the focal species from both regions contacted through the Cerrado region, thus suggesting that the historical dynamics of Andean and Atlantic forests are important for the evolution of forest birds in the region. The results are in agreement with studies of other organisms and may indicate a more general pattern of connectivity among biomes in the Neotropics. Finally, we recommend recognizing both the Andean and the Altantic forests lineages of S. rufosuperciliata as independent species.


Drug Repurposing-Based Brain-Targeting Self-Assembly Nanoplatform Using Enhanced Ferroptosis against Glioblastoma.
Glioblastoma (GBM), the most aggressive and lethal form of malignant brain tumor, is a therapeutic challenge due to the drug filtration capabilities of the blood-brain barrier (BBB). Interestingly, glioblastoma tends to resist apoptosis during chemotherapy, but is susceptible to ferroptosis. Developing therapies that can effectively target glioblastoma by crossing the BBB and evoke ferroptosis are, therefore, crucial for improving treatment outcomes. Herein, a versatile biomimetic nanoplatform, L-D-I/NPs, is designed that self-assembled by loading the antimalarial drug dihydroartemisinin (DHA) and the photosensitizer indocyanine green (ICG) onto lactoferrin (LF). This nanoplatform can selectively target glioblastoma by binding to low-density lipoprotein receptor-related protein-1 (LRP1) and crossing the BBB, thus inducing glioblastoma cell ferroptosis by boosting intracellular reactive oxygen species (ROS) accumulation and iron overload. In addition, L-D-I/NPs have demonstrated the ability to effectively suppress the progression of orthotopic glioblastoma and significantly prolong survival in a mouse glioblastoma model. This nanoplatform has facilitated the application of non-chemotherapeutic drugs in tumor treatment with minimal adverse effects, paving the way for highly efficient ferroptosis-based therapies for glioblastoma.


Structural changes to resorbable calcium phosphate bioceramic aged in vitro.
This work investigates the effect of mammalian cell culture conditions on 3D printed calcium phosphate scaffolds. The purpose of the studies presented was to characterise the changes in scaffold properties in physiologically relevant conditions. Differences in crystal morphologies were observed between foetal bovine serum-supplemented media and their unsupplemented analogues, but not for supplemented media containing tenocytes. Scaffold porosity was found to increase for all conditions studied, except for tenocyte-seeded scaffolds. The presence of tenocytes on the scaffold surface inhibited any increase in scaffold porosity in the presence of extracellular matrix secreted by the tenocytes. For acellular conditions the presence or absence of sera proteins strongly affected the rate of dissolution and the distribution of pore diameters within the scaffold. Exposure to high sera protein concentrations led to the development of significant numbers of sub-micron pores, which was otherwise not observed. The implication of these results for cell culture research employing calcium phosphate scaffolds is discussed.


Implementation plans for the Korean certified tumor registrar qualification system.
Cancer registration data is used to understand the nation's cancer burden, and to provide significant baseline data for cancer control efforts, as well as, research on cancer incidence, mortality, survival, and prevalence. A system that approves, assesses, and manages the qualification of specialists, responsible for performing cancer registration, has not been developed in Korea. This study presents ways to implement a certification system designed for the qualification of tumor registrars in Korea. Requirements for implementing a certified tumor registrar qualification system were determined by reviewing the system for establishing qualifications in Korea and the American qualification system via the National Cancer Registrars Association (NCRA). Moreover, a survey was conducted on Korean medical records administrators, who had taken the U.S. Certified Tumor Registrar (CTR) examination, in order to review their opinions regarding these requirements. This study verified the feasibility of a qualification examination based on the opinions of CTR specialists by determining the following: items, and the associated ratings, of the qualifications necessary to register individuals as certified tumor registrars in a private qualification system; status of human resources required for the examination or training processes; plans regarding the organization needed for management, and operation of qualifications, examination standards, subject areas, examination methods, examination qualifications, or education and training programs. The implementation of a certified tumor registrar qualification system will lead to enhanced job competency for specialists and a qualitative improvement of cancer registration data. It will also reliably foster human resources that will lay the groundwork needed to establish scientific and reasonable national cancer management policies.


Flat Oral Glucose Tolerance Test During Pregnancy: Maternal Characteristics and Risk for Adverse Outcomes.
Flat oral glucose tolerance test (OGTT) curve is characterized by low glucose levels, seemingly nonresponsive to glucose load. Few studies have explored flat OGTT during pregnancy and have yielded conflicting results, some suggesting risk for fetal growth restriction. This study evaluated the characteristics and perinatal outcomes of women with a flat OGTT during pregnancy. We found that a flat OGTT curve occurs in younger, leaner pregnant women. Also, flat OGTT curve was significantly associated with a male fetus and higher levels of pregnancy-associated plasma protein A at the first-trimester screening. Although flat OGTT can possibly reflect some degree of hyperinsulinemia, it is generally not associated with adverse maternal or neonatal outcomes.


Serum IL-6 and TNF-α Levels Are Correlated with Disease Severity in Patients with Ankylosing Spondylitis.
Previous studies have shown that a number of cytokines participate in the regulation of ankylosing spondylitis (AS). To investigate the potential role of interleukin (IL)-6 and tumor necrosis factor- α (TNF-α) in AS pathogenesis, this study examined the serum levels of IL-6 and TNF-α in patients with AS and its clinical association with disease activity. The serum concentrations of IL-6 and TNF-α from 80 patients with AS and 46 healthy control patients (HCs) were examined by electrochemiluminescence immunoassay. The correlations between the serum IL-6 and TNF-α levels and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), computed tomography (CT) imaging-based classification, and laboratory indicators were analyzed using the Spearman correlation test. Compared to HCs, patients with AS showed higher levels of IL-6 and TNF-α. There was also a positive correlation between the serum IL-6 and TNF-α levels and the BASDAI, the progression of AS, and the CT imaging-based classification. The serum levels of IL-6 correlated closely with C-reactive protein and the erythrocyte sedimentation rate. More important, patients with AS with hip joint involvement exhibited a significant elevation of serum levels of TNF-α, and higher IL-6 was detected in patients with the involvement of joints other than the hip and sacroiliac joints. The serum levels of IL-6 and TNF-α can function as important indicators for auxiliary diagnosis and disease activity evaluation of AS.


Differential coupling of mu-, delta-, and kappa-opioid receptors to G alpha16-mediated stimulation of phospholipase C.
The mu-opioid receptor has recently been shown to stimulate phosphoinositide-specific phospholipase C via the pertussis toxin-sensitive G16 protein. Given the promiscuous nature of G16 and the high degree of resemblance of signaling properties of the three opioid receptors, both delta- and kappa-opioid receptors are likely to activate G16. Interactions of delta- and kappa-opioid receptors with G16 were examined by coexpressing the opioid receptors and G alpha16 in COS-7 cells. The delta-selective agonist [D-Pen2,D-Pen5] enkephalin potently stimulated the formation of inositol phosphates in cells coexpressing the delta-opioid receptor and G alpha16. The delta-opioid receptor-mediated stimulation of phospholipase C was absolutely dependent on the coexpression of G alpha16 and exhibited appropriate ligand selectivity and dose dependency. Similar transfection studies revealed only weak stimulation by the mu-opioid receptor, whereas the kappa-opioid receptor produced moderate phospholipase C activity. G alpha16 thus appeared to interact differentially with the three opioid receptors. Radioligand binding assays indicate that the mu-opioid receptor was expressed at a lower level than those of the delta- and kappa-opioid receptors. To examine if differential coupling to G alpha16 is prevalent, a panel of Gs- or Gi-coupled receptors was coexpressed with G alpha16 in COS-7 cells and assayed for agonist-induced stimulation of phospholipase C. Activation of alpha2- and beta2-adrenergic, dopamine D1 and D2, adenosine A1, somatostatin-1 and -2, C5a, formyl peptide, and luteinizing hormone receptors all resulted in stimulation of phospholipase C, with maximal stimulations ranging from 1.5- to almost 17-fold. These findings suggest that the promiscuous G alpha16 can in fact discriminate among different receptors and that such preferential interaction might in part be due to the abundance of receptors.


Dynamical regimes of a paramagnetic particle circulating a magnetic bubble domain.
We study the dynamics of a single paramagnetic colloidal particle dispersed in water and circulating around a cylindrical magnetic domain ("magnetic bubble") when driven by an external rotating magnetic field. We record the particle trajectories and measure its angular displacement by changing the strength, frequency, and ellipticity of the applied magnetic field and show that this simple system exhibits several interesting phenomena, from synchronous-asynchronous rotations, to localized oscillations. We complement the experimental results with numerical simulations which explore the dynamical regimes of the rotating particle.


Three-dimensional dynamic measurement of unstable temperature fields by multi-view single-shot phase-shifting digital holography.
A multi-view phase measurement system based on single-shot phase-shifting digital holography is proposed to dynamically obtain three-dimensional (3-D) information of an unstable temperature field. The proposed system consists of a laser, three polarization imaging cameras, and the corresponding optical components. The laser beam emitted from the laser is separated by the fibers into three pairs that contain three object beams and three reference beams. The object beams pass through the object in three different directions and interfere with the reference beams at the image sensor plane respectively. The recording of the three cameras is triggered simultaneously, which enables the phase measurement of dynamic objects from different viewpoints. We successfully measured the 3-D distributions of an unstable temperature field in the experiments with the proposed system.


Relevance of the immunoglobulin VH somatic mutation status in patients with chronic lymphocytic leukemia treated with fludarabine, cyclophosphamide, and rituximab (FCR) or related chemoimmunotherapy regimens.
Although immunoglobulin V(H) mutation status (IgV(H) MS) is prognostic in patients with chronic lymphocytic leukemia (CLL) who are treated with alkylating agents or single-agent fludarabine, its significance in the era of chemoimmunotherapy is not known. We determined the IgV(H) somatic mutation status (MS) in 177 patients enrolled in a phase 2 study of fludarabine, cyclophosphamide, and rituximab (FCR) and in 127 patients treated with subsequent chemoimmunotherapy protocols. IgV(H) MS did not impact significantly on the complete remission (CR) rate of patients receiving FCR or related regimens. However, CR duration was significantly shorter in patients with CLL that used unmutated IgV(H) than those whose CLL used mutated IgV(H) (TTP 47% vs 82% at 6 years, P < .001). In a multivariate model considering all baseline characteristics, IgV(H) MS emerged as the only determinant of remission duration (hazard ratio 3.8, P < .001). Our results suggest that postremission interventions should be targeted toward patients with unmutated IgV(H) status.


Schiff Base Complex Cocatalyst with Coordinatively Unsaturated Cobalt Sites for Photoelectrochemical Water Oxidation.
Integrating inorganic oxygen evolution cocatalysts (OECs) with photoanodes is regarded as an available strategy to increase the photogenerated charge utilization for accelerated water oxidation kinetics. Nevertheless, most widely used transition metal (oxyhydr)oxides OECs suffer from inevitable charge recombination at photoanode/OECs interfaces and underabundant catalytic active sites. Herein, a cobalt-organic complex with microflower-like features (denoted as MF) was constructed by coordination of Schiff base ligands and Co2+ metal ions and then decorated on porous BiVO4 employed as photoanodes for photoelectrochemical (PEC) water oxidation. The as-synthesized BiVO4/MF photoanode achieves a photocurrent density of 4.38 mA cm-2 and at 1.23 VRHE in 0.5 M Na2SO4 electrolyte under simulated 1 sun illumination, over approximately 5.48 times larger than that of BiVO4 counterpart, and exhibits a 120 mV cathodic shift of onset potential with outstanding photostability. Systematic characterizations reveal that the improved PEC efficiency is mainly attributed to the well-designed coordinatively unsaturated Co2+ sites, which not only serve as powerful photohole extraction engines along reversed interfacial Co-O-Bi bonds to promote charge transfer across the BiVO4/complex interface but also act as reaction active centers by accelerating surface water oxidation kinetics. This work provides new insights for designing highly effective OECs for PEC water oxidation.


Base-Mediated Borylsilylation/Silylation of Ammonium Salts with Silylborane.
This work describes a base-mediated borylsilylation of benzylic ammonium salts to synthesize geminal silylboronates bearing benzylic proton under mild reaction conditions. Deaminative silylation of aryl ammonium salts was also achieved in the presence of LiOtBu. This strategy which is featured with high efficiency, mild reaction conditions, and good functional group tolerance provides efficient routes for late-stage functionalization of amines.


Establishing thresholds for cytokine storm and defining their relationship to disease severity in respiratory viral infections.
Previous studies have identified cytokines associated with respiratory virus infection illness outcome. However, few studies have included comprehensive cytokine panels, longitudinal analyses, and/or simultaneous assessment across the severity spectrum. This, coupled with subjective definitions of cytokine storm syndrome (CSS), have contributed to inconsistent findings of cytokine signatures, particularly with COVID severity. Here, we measured 38 plasma cytokines and compared profiles in healthy, SARS-CoV-2 infected, and multisystem inflammatory syndrome in children (MIS-C) patients (n = 169). Infected patients spanned the severity spectrum and were classified as Asymptomatic, Mild, Moderate or Severe. Our results showed acute cytokine profiles and longitudinal dynamics of IL1Ra, IL10, MIP1b, and IP10 can differentiate COVID severity groups. Only 4% of acutely infected patients exhibited hypercytokinemia. Of these subjects, 3 were Mild, 3 Moderate, and 1 Severe, highlighting the lack of association between CSS and COVID severity. Additionally, we identified IL1Ra and TNFa as potential biomarkers for patients at high risk for long COVID. Lastly, we compare hypercytokinemia profiles across COVID and influenza patients and show distinct elevated cytokine signatures, wherein influenza induces the most elevated cytokine profile. Together, these results identify key analytes that, if obtained at early time points, can predict COVID illness outcome and/or risk of complications, and provide novel insight for improving the conceptual framework of hypercytokinemia, wherein CSS is a subgroup that requires concomitant severe clinical manifestations, and including a list of cytokines that can distinguish between subtypes of hypercytokinemia.


Isolation and characterization of BHK cells sensitive to ionizing radiation and alkylating agents.
A host-cell viral suicide enrichment procedure was used to isolate BHK strains sensitive to ionizing radiation. Of six strains surviving infection with irradiated herpes simplex virus (HSV), three were found to be more sensitive to ionizing radiation than the parental BHK cells. Thus the D0's of strains V1, V2, and V5 were 1.59, 1.41, and 1.49 Gy, respectively, while the D0 for the parental BHK strain was 1.79. Strains V1 and V2 were studied in more detail and found to exhibit hypersensitivity to ethyl methanesulfonate (EMS), methyl methanesulfonate, and N-methyl-N'-nitro-N-nitrosoguanidine, but not to uv radiation. Susceptibility to mutation in response to EMS was also compared in BHK and strains V1 and V2. The frequency of induction of ouabain-resistant cells was 140% of the parental strain in the case of strain V1 and 58% of the parental strain in the case of strain V2.


Alterations in Cytosolic and Mitochondrial [U-13C]Glucose Metabolism in a Chronic Epilepsy Mouse Model.
Temporal lobe epilepsy is a common form of adult epilepsy and shows high resistance to treatment. Increasing evidence has suggested that metabolic dysfunction contributes to the development of seizures, with previous studies indicating impairments in brain glucose metabolism. Here we aim to elucidate which pathways involved in glucose metabolism are impaired, by tracing the hippocampal metabolism of injected [U-13C]glucose (i.p.) during the chronic stage of the pilocarpine-status epilepticus mouse model of epilepsy. The enrichment of 13C in the intermediates of glycolysis and the TCA cycle were quantified in hippocampal extracts using liquid chromatography-tandem mass spectroscopy, along with the measurement of the activities of enzymes in each pathway. We show that there is reduced incorporation of 13C in the intermediates of glycolysis, with the percentage enrichment of all downstream intermediates being highly correlated with those of glucose 6-phosphate. Furthermore, the activities of all enzymes in this pathway including hexokinase and phosphofructokinase were unaltered, suggesting that glucose uptake is reduced in this model without further impairments in glycolysis itself. The key findings were 33% and 55% losses in the activities of pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase, respectively, along with reduced 13C enrichment in TCA cycle intermediates. This lower 13C enrichment is best explained in part by the reduced enrichment in glycolytic intermediates, whereas the reduction of key TCA cycle enzyme activity indicates that TCA cycling is also impaired in the hippocampal formation. Together, these data suggest that multitarget approaches may be necessary to restore metabolism in the epileptic brain.


Vision screening of specialized populations.
This paper describes the vision screening tests for specialized populations as used by the Community Eye Care Services Program of the Pennsylvania College of Optometry. Referral criteria have been elaborated. This paper is designed to help those who are interested in organizing such a screening.


[Study on meteorological factors-based neural network model of malaria].
In order to provide reliable data for strategies development on prevention, a meteorological factors-based predicating model for malaria forecast was studied. Data on malaria occurrence and climate changes from 1994 to 1999 in counties in Yunnan province was collected and analyzed with software packages of FoxPro 6.0 and Excel 5.0. The forecasting model for malaria occurrence was established, using the Neural Network Toolbox of Matlab 6.1 software package. In the studies of forecasting model, data of malaria and meteorological factors from 1994 to 1999 in Honghe state in Yunnan province was chosen. The meteorological factors included average monthly pressure, air temperature, relative humidity, monthly maximum air temperature, minimum air temperature, rainfall, rainday, evaporation and sunshine hours in the study. The established forecasting model was also tested and verified. The BP network model was established according to data of diseases and meteorological factors from Honghe state in Yunnan province. After training the neural network for 100 times, the error of performance decreased from 3.23608 to 0.035862. Verified by fact data of malaria, the efficiency of malaria forecasting was 84.85%. Neural network model was effective for forecasting malaria. It showed advantages as: strong ability for analysis, lower claim for data, convenient and easy to apply etc. Neural network model might be used as a new method for malaria forecasting.


Biosynthesis of medium-chain triacylglycerols and phospholipids by HepG-2 cells.
In an attempt to understand the metabolism by the liver of fatty acids (FA) of different chain length, we have studied the incorporation of [1(-14)C]-labeled C2, C8, C10, C12, and C16 into cellular lipids by HepG-2 cells. Over 90% of the radiolabeled FA were detected in phospholipids (PL) and triacylglycerols (TAG). The incorporation of C12 and C16 was three to four times higher than that of C8 and C10 (and reached 35 nmoles per mg protein after 1.5 h). The radioactivity of C2, C8, and C10 was recovered mainly in PL. C12 and C16 were incorporated at approximately equal amounts into PL and TAG. The radioactivity of both C2 and C8 was recovered exclusively in long-chain FA, suggesting oxidation of C8 into C2 units prior to FA synthesis. C10 likewise yielded mainly long-chain FA. However 10% of unchanged C10 was found in PL and up to 30% in TAG. 14C-C12 was largely incorporated unchanged. Under these conditions, the presence of C10 and C12 in PL and TAG was shown also by gas-liquid chromatography. In the presence of either C2, C8, or C10, up to 30% of 14C-monounsaturated FA were detected in PL and TAG. With C12 and C16, the fraction of 14C-monounsaturated FA was much smaller suggesting that extensive desaturation occurred during de novo synthesis.


Predictive coding, multisensory integration, and attentional control: A multicomponent framework for lucid dreaming.
Lucid dreaming (LD) is a mental state in which we realize not being awake but are dreaming while asleep. It often involves vivid, perceptually intense dream images as well as peculiar kinesthetic sensations, such as flying, levitating, or out-of-body experiences. LD is in the cross-spotlight of cognitive neuroscience and sleep research as a particular case to study consciousness, cognition, and the neural background of dream experiences. Here, we present a multicomponent framework for the study and understanding of neurocognitive mechanisms and phenomenological aspects of LD. We propose that LD is associated with prediction error signals arising during sleep and occurring at higher or lower levels of the processing hierarchy. Prediction errors are resolved by generating a superordinate self-model able to integrate ambiguous stimuli arriving from sensory periphery and higher-order cortical regions. While multisensory integration enables lucidity maintenance and contributes to peculiar kinesthetic experiences, attentional control facilitates multisensory integration by dynamically regulating the balance between the influence of top-down mental models and the precision weighting of bottom-up sensory inputs. Our novel framework aims to link neural correlates of LD with current concepts of sleep and arousal regulation and provide testable predictions on interindividual differences in LD as well as neurocognitive mechanisms inducing lucid dreams.


Cryptotanshinone reverses reproductive disturbances in rats with dehydroepiandrosterone-induced polycystic ovary syndrome.
Polycystic ovarian syndrome (PCOS), with a prevalence of 5-8%, is the most common endocrine disorder in women of reproductive age. Although cryptotanshinone (CRY) has been shown to effectively reverse reproductive disturbances, it remains poorly understood whether it can be used to treat PCOS. Here we used an established rat model of PCOS. Prepubertal female Sprague-Dawley rats were subcutaneously injected with dehydroepiandrosterone (DHEA) 60 mg/kg/day for 3 weeks. Those in the DHEA group were given normal saline, while the CRY group was given 27 mg/kg by gastrogavage for 3 weeks. DHEA-treated rats had irregular estrous cycles and significantly increased ovarian weight compared to control rats (P < 0.05), and 3 weeks of treatment with CRY in DHEA-treated rats significantly decreased ovarian weight (P < 0.05). CRY decreased the levels of testosterone, estradiol, and luteinizing hormone (LH) as well as the LH/follicle stimulating hormone ratio (P < 0.05). CRY decreased inhibin B and follistatin mRNA and protein expression but upregulated activin A mRNA and protein expression in the ovarian tissue of rats with PCOS (P < 0.05). These results suggest that CRY treatment could reverse reproductive disturbances in rats with PCOS.


Perceptions of sexual risk behavior among Palestinian youth in the West Bank: a qualitative investigation.
Young people in the Middle East and North Africa (MENA) are profoundly affected by violence, high unemployment, and economic hardship. Experiences of community-level violence and personal trauma increase the likelihood that young people will engage in risky behaviors that include smoking, drug use, and unsafe sex. Little is known about the sexual behavior of young people in the region, particularly in the occupied Palestinian territory (oPt). Our aim in this study was to gain an insight into the perceived prevalence and patterns of sexual behavior among Palestinian youth. The study was based on ten focus groups and 17 in-depth interviews with young people aged 16-24 years as part of the formative phase of a cross-sectional representative study of risk behaviors in the West Bank, including Jerusalem, in 2012. The sample was selected using a combination of purposive and convenience sampling. Qualitative analysis was used to code detailed notes of focus groups and interviews. Based on participants' reports, different types of sexual activity outside marriage were not uncommon, even in conservative communities. The most reported sexual activity was non-penetrative sex: oral and anal intercourse, and virtual sex. Some young people had sexual intercourse with sex workers; they went to brothels in Israel and to brothels operating clandestinely in the West Bank, including East Jerusalem. Most respondents were of the opinion that young people did not usually use protection during sexual intercourse. Many reported that youth engage in different types of sexual activity outside marriage for several reasons: to challenge the culture, financial constraints and inability to marry, basic human need, personal pleasure, suppression, to kill boredom, and to prove manhood. In contrast with the conservative social context of the occupied Palestinian territory (oPt), the findings suggest that sexual activities outside marriage may be more common than is currently assumed. Sexual behavior in the oPt is a concern because of the low awareness of the potential health consequences. The results draw attention to the need to incorporate sexual reproductive health into the national agenda and ensure that it is included in the programs of national institutions.


Clinical significance of human intestinal spirochetosis--a morphologic approach.
Intestinal spirochetosis (IS) is a condition defined morphologically by the presence of spirochetal microorganisms attached to the apical cell membrane of the colonic and rectal epithelium. Intestinal spirochetes comprise a heterogeneous group of bacteria. In humans Brachyspira aalborgi and Brachyspira pilosicoli predominate. Prevalence rates of IS are low where living standards are high, in contrast to poorly developed areas where IS is common. Homosexuals and HIV-infected individuals are at high risk of being colonized. Clinical significance in individual cases has remained unclear up to now. A review of the literature reveals that invasion of spirochetes beyond the surface epithelium is associated with gastrointestinal symptoms which respond to antibiotic treatment (metronidazole), whereas patients lacking this feature are mostly asymptomatic. Homosexual and HIV-positive men are more likely to be symptomatic irrespective of invasion. Rare cases of spirochetemia and multiple organ failure have been reported in critically ill patients.


[Water, lithium and sodium: watch out for dangerous injuries].
Nephrogenic diabetes insipidus due to the inability of the kidneys to concentrate urine is frequently observed during lithium therapy. Lithium concentrates into principal cells in collecting ducts in the kidney and downregulates aquaporin 2 expression, which reduces renal reabsorption of water. This disease is characterized by polyuria - polydipsia leading to intracellular dehydration and hypernatremia. Water deprivation test is performed to confirm insipidus diabetes. The desmopressin permits to distinguish nephrogenic from cranial insipidus diabetes. We report the case of a 64 years old women who presented with global dehydration and severe hypernatremia. Four years ago, she was hospitalized for nephrogenic diabetes insipidus related to a self-induced lithium intoxication. Persistent nephrogenic insipidus diabetes after cessation of lithium therapy are described in literature, and this hypothesis may be consistent with this case report.


Neural substrates of acupuncture in the modulation of cravings induced by smoking-related visual cues: an fMRI study.
Cue reactivity is a key factor in modulating motivational and goal-directed behaviors associated with compulsive drug intake and relapse. Smoking-associated cues produce smoking urges and cravings and are accompanied by the activation of brain regions involved in attention, motivation, and reward. We investigated whether acupuncture ameliorates cravings induced by smoking-related visual cues, and we explored the neural mechanisms underlying the effects of acupuncture on modulating smoking urges. After 36 h of smoking abstinence, 25 right-handed male smokers underwent fMRI, during which smoking-related and neutral visual cues were presented. Twelve subjects were treated with real acupuncture (RA) at HT7 and 13 subjects received sham acupuncture (SA). During the scanning sessions, craving scores to smoking-related visual cues were assessed before and after RA or SA treatment. The differences in brain responses to smoking vs. neutral cues after treatment between the RA and SA groups were detected using three-way ANOVAs (Cue × Session × Group). After treatment, the craving scores were significantly decreased in the RA group, as compared to the SA group. When we explored the neural substrates of acupuncture on the modulation of cravings induced by smoking cues, significant differences were found in the medial prefrontal cortex, the premotor cortex, the amygdala, the hippocampus, and the thalamus. These findings suggest that acupuncture alleviates cue-induced cravings through the regulation of activity in brain regions involved in attention, motivation, and reward relative to craving scores in the initial abstinence phase.


The use of dual growing rods to correct spinal deformity secondary to a low-grade spinal cord astrocytoma.
Pediatric intramedullary spinal cord astrocytomas are rare, and the majority are low grade, typically carrying a low risk of mortality, but a high risk of morbidity. Quality of life is, therefore, an important consideration in treating concomitant progressive kyphoscoliosis. Compared with fusion-based spinal stabilization, fusionless techniques may limit some complications related to early instrumentation of the developing spine. Another consideration is the timing of radiation therapy relative to both spinal maturity and spinal instrumentation. To date, there have been no reports of the use of a fusionless technique to treat spinal deformity secondary to an intramedullary spinal cord tumor. Herein, we report the use of fusionless spinal stabilization with dual growing rods in a boy with low-grade spinal cord astrocytoma after radiation therapy.


Integrin α3 is required for high-frequency repetitive transcranial magnetic stimulation-induced glutamatergic synaptic transmission in mice with ischemia.
Repetitive transcranial magnetic stimulation (rTMS) is an effective therapy in post-stroke motor recovery. However, the underlying mechanisms of rTMS regulates long-lasting changes with synaptic transmission and glutamate receptors function (including AMPARs or NMDARs) remains unclear. Mice were received 10-Hz rTMS treatment once daily on the third day after photothrombotic (PT) stroke for 18 days. Motor behaviors and the Western blot were used to evaluate the therapeutic efficacy of 10-Hz rTMS in the mice with PT model. Moreover, we used wild-type (WT) and NEX-α3-/- mice to further explore the 10-Hz rTMS effect. We found that 10-Hz rTMS improved the post-stroke motor performance in the PT mice. Moreover, the levels of AMPAR, vGlut1, and integrin α3 in the peri-infarct were significantly increased in the rTMS group. In contrast, 10-Hz rTMS did not induce these aforementioned effects in NEX-α3-/- mice. The amplitude of AMPAR-mediated miniature excitatory postsynaptic currents (EPSCs) and evoked EPSCs was increased in the WT + rTMS group, but did not change in NEX-α3-/- mice with rTMS. In this study, 10-Hz rTMS improved the glutamatergic synaptic transmission in the peri-infract cortex through effects on integrin α3 and AMPARs, which resulted in motor function recovery after stroke.


Absence of the mid-sized neurofilament subunit decreases axonal calibers, levels of light neurofilament (NF-L), and neurofilament content.
Neurofilaments (NFs) are prominent components of large myelinated axons and probably the most abundant of neuronal intermediate filament proteins. Here we show that mice with a null mutation in the mid-sized NF (NF-M) subunit have dramatically decreased levels of light NF (NF-L) and increased levels of heavy NF (NF-H). The calibers of both large and small diameter axons in the central and peripheral nervous systems are diminished. Axons of mutant animals contain fewer neurofilaments and increased numbers of microtubules. Yet the mice lack any overt behavioral phenotype or gross structural defects in the nervous system. These studies suggest that the NF-M subunit is a major regulator of the level of NF-L and that its presence is required to achieve maximal axonal diameter in all size classes of myelinated axons.


Polyp of the uterine cervix with heterologous fatty tissue.
This report documents an uncommon case of choristomatous cervical polyp-containing fat tissue. The patient was a 24-year-old female who presented with irregular intermenstrual bleeding. On examination, a polypoid lesion with smooth outlines, measuring 1 cm in diameter was removed. Microscopic examination demonstrated abnormal fibrous stroma, devoid of endocervical glands, containing mature adipose tissue, and thick-walled blood vessels. The lesion was covered by a typical mature squamous cell outer lining. To the best of our knowledge, this is only the second report of an adipose tissue arising from the cervical wall. Further clinicopathologic considerations are needed to elucidate the origin of the fatty component in cervical polyps.


Cathodoluminescence evaluation of oxygen vacancy population in nanostructured titania thin films for photocatalytic applications.
Room-temperature results of cathodoluminescence (CL) spectroscopy investigations are presented for nanostructured titanium dioxide (anatase) thin films (500 nm thick) deposited via RF magnetron sputtering on high-purity silica substrates. The collected CL bands of the anatase thin films, as deposited and after different annealing cycles, showed a broad morphology consisting of three Voigtian bands located at 500, 550, and 610 nm that were partially overlapping. The overall CL emission increased with increasing temperature and time of the annealing cycle as a consequence of the increased crystallinity of the thin film. A clear trend was found for the oxygen-vacancy-related band (located at 610 nm), whose relative intensity decreased, as compared with the as-grown sample, after annealing in air; the higher the annealing temperature, the lower the relative intensity. We evaluated the photoactivity of the nanostructured thin film samples by measuring their photocatalytic activity in aqueous solution toward the degradation of phenol. A relationship between the decrease in oxygen vacancy concentration as a consequence of the annealing and the increase in the photoactivity was highlighted.


The Longitudinal Course of Fatigue in Antineutrophil Cytoplasmic Antibody-associated Vasculitis.
Fatigue is common and burdensome in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). This study aimed to understand how fatigue changes over time following treatment initiation and to determine whether individuals with the poorest prognosis can be robustly identified. One hundred forty-nine patients with AAV and new-onset disease recruited to 2 clinical trials (RITUXVAS and MYCYC) were followed for 18 months. Fatigue was measured at baseline and 6-month intervals using the vitality domain of the Medical Outcomes Study Short Form-36 quality of life questionnaire and compared to a cohort of 470 controls. Group-based trajectory modeling (GBTM) determined trajectories of the symptom to which baseline characteristics and ongoing fatigue scores were compared. Fatigue levels at diagnosis were worse in patients than controls [median (interquartile range; IQR) 30 (10-48) vs 70 (55-80); p < 0.001], with 46% of patients reporting severe fatigue. Fatigue improved after 6 months of treatment but remained worse than in controls (p < 0.001). GBTM revealed varied trajectories of fatigue: low fatigue stable (n = 23), moderate baseline fatigue improvers (n = 29), high baseline fatigue improvers (n = 61), and stable baseline high fatigue (n = 37). Participants who followed stable high fatigue trajectories had lower vasculitis activity compared to improvers, but no other demographic or clinical variables differed. This study longitudinally measured fatigue levels in patients with AAV. Although most patients improved following treatment, an important subgroup of patients reported persistently high levels of fatigue that did not change. Few clinical or laboratory markers distinguished these patients, suggesting alternative interventions specific for fatigue are required. [clinicaltrialsregister.eu, RITUXVAS EudraCT number: 2005-003610-15; MYCYC EudraCT number: 2006-001663-33].


[Clinical and gender characteristics of tobacco dependence in addiction psychiatrists].
To study clinical and gender characteristics of tobacco dependence in addiction treatment specialists in comparison with physicians of other specialties. A total of 21 addiction psychiatrists and 154 doctors of various therapeutic specialties were examined. All physicians were stratified into two groups and then each group was subdivided into male and female subgroups. A questionnaire developed by one of the authors and the Fagerström Test for Nicotine Dependence were used for standardization of the study. In addiction psychiatrists, the prevalence of tobacco dependence among female addiction psychiatrists was higher than that of the female doctors of other specialties. Persistent smoking was formed earlier, and awareness of the urge to smoke appeared later compared to physicians of other specialties. The degree of tobacco dependence was higher in addiction psychiatrists of both genders. Affective component was dominated in the tobacco withdrawal syndrome in female addiction psychiatrists.


Early cognitive deficits in Swedish gene carriers of Huntington's disease.
The primary focus of this study was to examine whether there is early neuropsychological impairment in presymptomatic Huntington's disease (HD). A broad neuropsychological assessment battery was administered to 24 asymptomatic gene carriers (HD+) and 31 noncarriers (HD-). The gene carriers revealed inferior cognitive functioning as compared with the noncarriers in memory and executive functions. When the gene carriers were assigned to 2 groups based on predicted years to onset (with 15 and over being HD+ late and under 15 being HD+ near), the HD+ near group performed significantly worse than the HD+ late group in all domains but ability to shift conceptually and visuospatial memory. Results suggest that early cognitive deficits are detectable prior to motor symptoms, first in memory functions and then in executive functions and perceptual motor speed.


Systematic Comparison of Biomaterials-Based Strategies for Osteochondral and Chondral Repair in Large Animal Models.
Joint repair remains a major challenge in orthopaedics. Recent progress in biomaterial design has led to the fabrication of a plethora of promising devices. Pre-clinical testing of any joint repair strategy typically requires the use of large animal models (e.g., sheep, goat, pig or horse). Despite the key role of such models in clinical translation, there is still a lack of consensus regarding optimal experimental design, making it difficult to draw conclusions on their efficacy. In this context, the authors performed a systematic literature review and a risk of bias assessment on large animal models published between 2010 and 2020, to identify key experimental parameters that significantly affect the biomaterial therapeutic outcome and clinical translation potential (including defect localization, animal age/maturity, selection of controls, cell-free versus cell-laden). They determined that mechanically strong biomaterials perform better at the femoral condyles; while highlighted the importance of including native tissue controls to better evaluate the quality of the newly formed tissue. Finally, in cell-laded biomaterials, the pre-culture conditions played a more important role in defect repair than the cell type. In summary, here they present a systematic evaluation on how the experimental design of preclinical models influences biomaterial-based therapeutic outcomes in joint repair.