An oral multiparticulate, modified-release, hydrocortisone replacement therapy that provides physiological cortisol exposure.
It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified-release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multiparticulate technology. Screening by in vitro dissolution profiles, pharmacokinetic (PK) testing in dexamethasone-suppressed dogs and humans, and comparison with a reference population. Field laboratories and clinical research facility. Formulations were generated using an enteric (delayed release) design configuration with an extended (sustained release) dissolution profile. In vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained-release functionality. PK characterization of DIURF-006 showed that, despite absence of a sustained-release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n = 16) receiving a twice-daily 'toothbrush' regimen (20 mg at 23:00 h and 10 mg at 07:00 h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 h * nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8·5 h vs clock time 08:12 h for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89%, and cortisol levels increased linearly with doses between 5 and 30 mg. A multiparticulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a 'toothbrush' regimen provides physiological cortisol exposure.


Evaluation of replica techniques for the surface ultrastructure of rodent and human palatal mucosa.
Two replicating techniques currently used for scanning electron microscopy were investigated qualitatively and quantitatively. The most accurate and reliable replicating material was an epoxy resin; this was superior to copper plating as the model material, despite some dimensional inaccuracies. The selected method was then used to obtain accurate elastomeric replicas of rodent and human palatal mucosa. Salivary-duct openings, epithelial cell boundaries, desquamating cells and cell-surface micropits were identified. In some areas, coccal organisms could be seen colonizing the epithelial surface.


Human embryonic stem cell-derived mesenchymal cells preserve kidney function and extend lifespan in NZB/W F1 mouse model of lupus nephritis.
Adult tissue-derived mesenchymal stromal cells (MSCs) are showing promise in clinical trials for systemic lupus erythematosus (SLE). However, the inability to manufacture large quantities of functional cells from a single donor as well as donor-dependent variability in quality limits their clinical utility. Human embryonic stem cell (hESC)-derived MSCs are an alternative to adult MSCs that can circumvent issues regarding scalability and consistent quality due to their derivation from a renewable starting material. Here, we show that hESC-MSCs prevent the progression of fatal lupus nephritis (LN) in NZB/W F1 (BWF1) mice. Treatment led to statistically significant reductions in proteinuria and serum creatinine and preserved renal architecture. Specifically, hESC-MSC treatment prevented disease-associated interstitial inflammation, protein cast deposition, and infiltration of CD3(+) lymphocytes in the kidneys. This therapy also led to significant reductions in serum levels of tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6), two inflammatory cytokines associated with SLE. Mechanistically, in vitro data support these findings, as co-culture of hESC-MSCs with lipopolysaccharide (LPS)-stimulated BWF1 lymphocytes decreased lymphocyte secretion of TNFα and IL-6, and enhanced the percentage of putative regulatory T cells. This study represents an important step in the development of a commercially scalable and efficacious cell therapy for SLE/LN.


Integrating microalgae tertiary treatment into activated sludge systems for energy and nutrients recovery from wastewater.
In this study, microalgae digestate and secondary effluent were used to grow microalgae in a tertiary wastewater treatment, and then, the biomass was co-digested for biogas generation. A 30L closed-photobioreactor was used for microalgae cultivation. The biomass, mainly composed by Scenedesmus sp., reached and maintained a concentration of 1.1gTSS/L during 30days. A complete removal of N-NH4+ and P-PO43- and high nitrates and organic matter removals were achieved (58% N-NO3- and 70% COD) with 8d of HRT. The potential biogas production of the cultivated microalgae was determined in batch tests. To improve their biodegradability, a novel method combining their co-digestion with activated sludge after a simultaneous autohydrolysis co-pretreatment was evaluated. After the co-pretreatment, the methane yield increased by 130%. Thus, integrating microalgae tertiary treatment into activated sludge systems is a promising and feasible solution to recover energy and nutrients from waste, improving wastewater treatment plants sustainability.


Chemotherapy response assessment in stage IV melanoma patients-comparison of 18F-FDG-PET/CT, CT, brain MRI, and tumormarker S-100B.
This study aims to compare the use of 18F-FDG-PET/CT, CT, brain MRI, and tumormarker S-100B in chemotherapy response assessment of stage IV melanoma patients. In 25 patients with stage IV melanoma, FDG-PET/CT and S-100B after 2-3 months (three cycles) of chemotherapy was compared with baseline PET/CT and baseline S-100B. Retrospectively, the response was correlated with the outcome. In patients with clinical suspicion for brain metastases, MRI or CCT was performed. There was agreement between FDG-PET/CT and CT regarding response to chemotherapy in all patients. There was a clear trend to a longer OS of PET/CT responders (n=10) compared with PET/CT non-responders (n=15; p=0.072) with remarkably better 1-year OS of 80% compared to 40% (p=0.048). There was a significant longer PFS of PET/CT responders compared with PET/CT non-responders (p=0.002). S-100B was normal at baseline in eight of 22 patients where it was available. Chemotherapy response assessment with S-100B failed to show correlation with OS or PFS. Eleven patients developed brain metastases during treatment, first detected by PET/CT in two and by MRI or CCT in nine of 11 patients. Appearance of brain metastases was associated with a poor survival. 18F-FDG-PET/CT and CT alone are equally suitable for chemotherapy response assessment in melanoma patients and clearly superior to S-100B. PET/CT responders have better early survival, but this is shortlived due to late therapy failure--often with brain recurrence. Additional brain MRI for therapy response assessment in such high-risk patients is mandatory to detect brain metastases missed by PET/CT.


Mechanical Versus Bioprosthetic Valve Replacement in the Tricuspid Valve Position: A Systematic Review and Meta-Analysis.
The ideal prosthesis for tricuspid valve replacement (TVR) continues to be debated. There are few published data comparing mechanical and bioprosthetic valves, and all are retrospective studies with relatively small sample sizes. This study was conducted to compare mechanical and bioprosthetic valves for TVR. A literature search of six databases (PubMed, EMBASE, Ovid, ScienceDirect, JSTOR, and Wiley Blackwell's online library) was performed with the keywords "tricuspid valve disease, tricuspid valve replacement and (bioprosthetic or mechanical)". Primary outcomes were hospital mortality, long-term survival, tricuspid valve reoperation, valve failure, thrombosis, and thrombo-embolism. Risk ratio (RR) was used to compare dichotomous parameters and time-to-event outcomes. "Survival and re-interventions" were pooled using a meta-analysis of hazard ratios (HR). Publication bias was accessed using a funnel plot. A total of 23 retrospective studies involving 945 mechanical and 1,332 biological tricuspid prostheses were included. The studies were published between January 2002 and September 2019. Hospital mortality (30-day mortality) did not differ between groups (RR, 0.83; 95% confidence interval [CI], 0.66-1.05; p=0.12). Long-term survival was evaluated in 15 studies, and it was not significantly different between patients with mechanical compared with those with bioprosthetic valves (pooled HR, 0.97; 95% CI, 0.61-1.54; p=0.88). Freedom from tricuspid valve reoperation was assessed in eight studies, and no difference was found between the groups (pooled HR, 1.03; 95% CI, 0.63-1.69; p=0.89). Valve failure in the 5-year postoperative period was evaluated by seven studies, and there was no statistically significant difference between the two groups (pooled RR, 1.33; 95% CI, 0.42-4.27; p=0.63). The results of this meta-analysis suggest an equal risk of 30-day and late mortality, reoperation, and 5-year valve failure in patients with mechanical versus biological TVR. The choice of the prosthesis in the tricuspid position should depend mainly on the patient's risk factors and no superiority of one prosthesis over the other in this position.


Heterogenity of Echinococcus canadensis genotype 6 - the main causative agent of cystic echinococcosis in Birjand, Eastern Iran.
Little is known about the genotypes of Echinococcus spp. and their life cycles in eastern Iran. We analysed the partial sequences of the nad1 and cox1 genes from 17 isolates from hydatid cyst-infected patients (n=9), camels (n=5) and sheep (n=3) in Birjand, eastern Iran. A new primer pair was also used to amplify the long fragment (1180bp) of the cox1 gene. All camel and eight human isolates were G6 strains of Echinococcus canadensis while one human isolate and the three sheep isolates were G1 genotypes (sheep strain) of E. granulosus sensu stricto (s.s.). Nad1 and cox1 sequence analyses showed high G6 genetic homogeneity, similar to previously reported G6 strains from southeast and central Iran, Sudan and Mauritania. Low nucleotide and haplotype diversity similar to G6 strains from Russia (Altai republic) and Kazakhstan was also found, consistent with a bottleneck effect. In this study, G6 was the most common Echinococcus genotype. Genetic homogeneity of east, southeast and central Iranian G6 and its low genetic diversity may be due limited mobility and contact between humans and camels from other regions because of large, inhospitable deserts.


Analysis of the promoter of the luteinizing hormone/human chorionic gonadotropin receptor gene in neuroendocrine cells.
We investigated the molecular basis of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor gene transcription in immortalized alphaT3 gonadotropes, hypothalamic GT1-7 and hippocampal HN33p neurons. Nuclear run-on transcription, as well as transfection assays with fusion constructs of luciferase and the 5'-flanking region of LH/hCG receptor gene, revealed that GT1-7 neurons transcribe more than the alphaT3 or HN33p cells. Transient transfection of truncated reporter gene constructs and gel mobility shift assays revealed that while all neuroendocrine cells use the same promoter, they contain different levels of promoter binding proteins. Higher levels of these proteins may explain increased transcription of the LH/hCG receptor gene in GT1-7 neurons compared with alphaT3 and HN33p cells.


Untargeted metabolomics identifies potential serum biomarkers associated with Crohn's disease.
Crohn's disease (CD) is well characterized by chronic inflammation of the gastrointestinal tract. The diagnose of CD relays on the comprehensive evaluation of patient symptoms, laboratory examination, radiology, and endoscopy. There is lack of biomarkers or simple test for CD detection. Serum samples from healthy subjects (n = 16) and CD patients (n = 16) were collected and prepared for untargeted metabolomics analysis using the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) method. The alterations of serum metabolites and the potential biomarkers were profiled by statistical analysis. And the associated metabolic pathway was analyzed based on Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The performance of potential biomarkers was assessed by receiver operating characteristic (ROC) analysis. A complete separation between HS and CD groups was seen in OPLS-DA. A total of 108 and 131 significantly altered metabolites in positive and negative ion mode, respectively, were identified, and most of them belong to several pathways ranging from lipid metabolism to amino acid metabolism and energy homeostasis. KEGG analysis revealed that lipid metabolism enriched most significantly. Further, ceramide, phosphatidylethanolamine (PE), and taurochenodeoxycholic acid (TCDCA) presented the highest predictive accuracy of the patients with CD as analyzed by ROC. The current study demonstrated that lipid metabolism is mostly related to CD pathogenesis. Further investigations are indicated to examine the use of lipid-related metabolites of ceramide, PE, and TCDCA as potential biomarkers for CD diagnosis.


The complete genome sequence of a high pristinamycin-producing strain Streptomyces pristinaespiralis HCCB10218.
Streptomyces pristinaespiralis produces the streptogramin-like antibiotic pristinamycin, which is a mixture of two structurally different components: pristinamycin I (PI) and pristinamycin II (PII). Herein, we report the complete genome sequence of a high pristinamycin-producing strain HCCB10218 (8.5 Mb) obtained by using PacBio RSII combined with Illumina HiSeq 2500 sequencing system. The genome sequence presented here provides clues for the mechanism underlying the higher pristinamycin production of HCCB10218.


An exploration into caring for a stroke-survivor in Lima, Peru: Emotional impact, stress factors, coping mechanisms and unmet needs of informal caregivers.
Understanding local complexities and challenges of stroke-related caregiving are essential to develop appropriate interventions. Our study aimed to characterize the impact of post-stroke care among caregivers in a setting of transitioning economy. Qualitative study based on in-depth interviews with primary caregivers of stroke survivors in Lima, Peru. Transcribed data was organized into the emotional impact of caregiving, main stress factors and coping mechanisms to deal with the caregiving role, as well as the unmet needs of caregivers. We interviewed twelve caregivers, mean age 52.5 years, 8/12 were females, who were either the spouse or child of the stroke survivor. Stroke patients had a median age of 70 years, range 53-85 years. All participants reported having experienced emotional stress and depressive symptoms as a result of caregiving. Although most had family support, reduced social activities and added unanticipated financial burdens increased caregiver's stress. None of the caregivers had received training in post-stroke care tasks after the patient's discharge and only a few had received some psychological support, yet almost all expressed the need to see a professional to improve their mental health. Keeping a positive attitude towards their relative's physical post-stroke condition was a key coping mechanism. In the absence of structured institutional responses, family members endure with the provision of care for stroke survivors, a task escorted by major emotional, financial, and social strains. This burden could be prevented or curtailed if caregivers were to be targeted by interventions providing psychological and financial support, together with basic training on post-stroke care.


Establishment of fluoroscopy views and standardized procedure of percutaneous magic screw insertion for acetabulum fractures.
To place the magic screw more simply, we established a set of reproducible fluoroscopic views and a standardized procedure of magic screw insertion. This study on the magic screw tunnel uses a three-dimensional reconstruction model and a skeleton projection. The 3D model of the pelvis was made to be transparent and it was rotated to the place where the ischial spine was just sheltered by the posterior wall of the acetabulum. The angles of this view projection were recorded in the transverse plane and coronal plane. Six cadaveric pelvises (three males, three female) were used to validate the proper projection angle of the C-arm fluoroscopy. The skeleton specimens were all positioned latericumbent on a radiolucent table. In all pelvis 3D models, all magic cylinders with a 7.3 mm diameter were successfully inserted along the bone structure tunnel in 30 3D pelvic models. The average angle of the transverse view rotated by the C-arm fluoroscopy was 162° in males and 157° in females, the angle of the coronal plane was 22° in males and 24° in females. The average distance between the front wheel of the C-arm machine and the middle axial line of the radiolucent bed was 43 cm in males and 43 cm in females. In skeleton pelvis research, all the screws were safely inserted using this method. The magic screw technique could be a good choice for the treatment of acetabular fractures, especially quadrilateral plate fractures. If the proper fluoroscopy view technique is used properly, the magic screw can be inserted rapidly and safely.


Prediction of short-term neurological outcome in full-term neonates with hypoxic-ischaemic encephalopathy based on combined use of electroencephalogram and neuro-imaging.
In infants with hypoxic-ischaemic encephalopathy (HIE), prediction of the prognosis is based on clinical, neuro-imaging and neurophysiological parameters. EEG, cranial ultrasound, MRI and follow-up findings of 23 infants (GA 35-42 weeks) with HIE were studied retrospectively to assess 1) the contribution of ultrasound, MRI and EEG in predicting outcome, 2) the accuracy of ultrasound as compared to MRI, and 3) whether patterns of brain damage and EEG findings are associated. An abnormal EEG background pattern was highly predictive of adverse outcome [positive predictive value (PPV) 0.88]. If combined with diffuse white and deep and/or cortical grey matter changes on ultrasound or MRI, the PPV increased to 1.00. Abnormal neuro-imaging findings were also highly predictive of adverse outcome. Abnormal signal intensity in the posterior limb of the internal capsule, and diffuse cortical grey matter damage were associated with adverse outcome. MRI showed deep grey matter changes more frequently than ultrasound. Severely abnormal neuro-imaging findings were always associated with abnormal EEG background pattern. Both early EEG and neuro-imaging findings are predictive of outcome in infants with HIE. The predictive value of EEG is strengthened by neuro-imaging.


The role of protein kinase A and cyclin-dependent (CDC2) kinase in the control of basal and IGF-II-induced proliferation and secretory activity of chicken ovarian cells.
The aim of these experiments was to study the role of protein kinase A (PKA), cyclin-dependent kinase 2 (CDC2) and insulin-like growth factor II (IGF-II) in the control of ovarian function in domestic fowl, as well as the role of PKA and CDC2 in mediating the effects of IGF-II on the ovary. For this purpose, we studied the influence of an inhibitor of PKA (KT5720; 50 ng/ml), a CDC2 blocker (olomoucine; 1 microg/ml), IGF-II (0, 1, 10 or 100 ng/ml) and their combinations on cultured fragments of chicken ovarian follicular wall. Accumulation of PKA and CDC2 and secretion of progesterone (P4), testosterone (T), estradiol (E2) and arginine-vasotocin (AVT) were evaluated by using SDS-PAGE-Western blotting and RIA/EIA. IGF-II addition to culture medium stimulated T, E2 and AVT secretion and inhibited P4 secretion. These changes were associated with an increase in PKA and a decrease in CDC2 accumulation. The PKA blocker KT5720, when given alone, increased accumulation of PKA and secretion of T and E2, but not AVT and inhibited P4 secretion. The PKA blocker also prevented and even reversed the effects of IGF-II on PKA and steroid hormones secretion, but enhanced the action of IGF-II on AVT. The inhibitor of CDC2, olomoucine, when given alone, suppressed the expression of CDC2 and the secretion of P4 and AVT (but not T and E2). When given together with IGF-II, it augmented IGF-II-induced suppression of CDC2 and reversed the effects of IGF-II on P4 (but not on T, E2 or AVT). These observations demonstrate the involvement of PKA, CDC2 and IGF-II in regulating the secretory activity of avian ovarian cells. Our data also suggest the involvement of PKA in the mediation of IGF-II effects on P4, T, E2 and AVT secretion. CDC2 can mediate the effects of IGF-II on ovarian P4 secretion but not on other hormones.


TMED10 mediates the loading of neosynthesised Sonic Hedgehog in COPII vesicles for efficient secretion and signalling.
The morphogen Sonic Hedgehog (SHH) plays an important role in coordinating embryonic development. Short- and long-range SHH signalling occurs through a variety of membrane-associated and membrane-free forms. However, the molecular mechanisms that govern the early events of the trafficking of neosynthesised SHH in mammalian cells are still poorly understood. Here, we employed the retention using selective hooks (RUSH) system to show that newly-synthesised SHH is trafficked through the classical biosynthetic secretory pathway, using TMED10 as an endoplasmic reticulum (ER) cargo receptor for efficient ER-to-Golgi transport and Rab6 vesicles for Golgi-to-cell surface trafficking. TMED10 and SHH colocalized at ER exit sites (ERES), and TMED10 depletion significantly delays SHH loading onto ERES and subsequent exit leading to significant SHH release defects. Finally, we utilised the Drosophila wing imaginal disc model to demonstrate that the homologue of TMED10, Baiser (Bai), participates in Hedgehog (Hh) secretion and signalling in vivo. In conclusion, our work highlights the role of TMED10 in cargo-specific egress from the ER and sheds light on novel important partners of neosynthesised SHH secretion with potential impact on embryonic development.


Squamous cell carcinoma of the buccal mucosa: an aggressive cancer requiring multimodality treatment.
In our clinical practice, we have observed a high incidence of locoregional failure in squamous cell carcinoma (SCC) of the buccal mucosa. We analyze our treatment results of this cancer and compare these results with those in the literature. We intend to define the pattern and incidence of failure of buccal cancer and provide information for the design of a better multimodality treatment. During the period from 1983 through 2003, 121 previously untreated patients with M0 stage SCC of the buccal mucosa were treated with a curative intent at our hospital. Twenty-seven patients received surgery alone, 36 had radiotherapy alone, and 58 underwent surgery plus postoperative radiotherapy. The 5-year locoregional control, overall survival, and cause-specific survival rates for all patients were 36.3%, 34.3%, and 36.9%, respectively. The locoregional recurrence rate was 57% for all patients, with 80% occurring in the primary site alone. Patients with T1-2N0 disease who received surgery alone still had a high local recurrence incidence of 41%. For patients with locally advanced disease, surgery plus postoperative radiotherapy achieved better overall survival and locoregional control rates than surgery alone or radiotherapy alone. T classification was the only prognostic factor affecting locoregional control and survival in the surgery alone group, whereas N classification and skin invasion predicted a poorer survival for the surgery plus postoperative radiotherapy group. SCC of the buccal mucosa is an aggressive cancer with a high locoregional failure rate even in patients with T1-2N0 disease. Possible reasons include inadequate treatment and an intrinsically aggressive nature. Postoperative radiotherapy has resulted in a better locoregional control rate for patients with T3-4 or N+ disease and should also be considered for patients with T1-2N0 disease for whom adjuvant therapy after radical surgery currently is not recommended by most guidelines.


Quercetin solubilisation in bile salts: A comparison with sodium dodecyl sulphate.
To understand the bioaccessibility of the flavonoid quercetin we studied its interaction with bile salt micelles. The environmental sensitivity of quercetin's UV-visible absorption spectrum gave information about quercetin partitioning. Two quercetin absorption peaks gave complementary information: Peak A (240-280nm) on the intermicellar phase and Peak B (340-440nm) on the micellar phase. Thus, by altering pH, we showed that only non-ionised quercetin partitions into micelles. We validated our interpretation by studying quercetin's interaction with SDS micelles. Pyrene fluorescence and the quercetin UV-visible spectra show that the adsorption site for pyrene and quercetin in bile salt micelles is more hydrophobic than that for SDS micelles. Also, both quercetin and pyrene reported a higher critical micelle concentration for bile salts than for SDS. Our method of using a flavonoid as an intrinsic probe, is generally applicable to other lipophilic bioactives, whenever they have observable environmental dependent properties.


Impact of first medical contact to revascularisation time on long-term clinical outcomes in ST-segment elevation myocardial infarction patients.
Increased age impacts the first medical contact to revascularisation delay in patients with STEMI. Patients with shorter treatment delays (<90 minutes after first medical contact) have significantly lower major adverse cardiac events rates at 3 years.


The Greenlight Plus Trial: Comparative effectiveness of a health information technology intervention vs. health communication intervention in primary care offices to prevent childhood obesity.
The first 1000 days of a child's life are increasingly recognized as a critical window for establishing a healthy growth trajectory to prevent childhood obesity and its associated long-term comorbidities. The purpose of this manuscript is to detail the methods for a multi-site, comparative effectiveness trial designed to prevent childhood overweight and obesity from birth to age 2 years. This study is a multi-site, individually randomized trial testing the comparative effectiveness of two active intervention arms: 1) the Greenlight intervention; and 2) the Greenlight Plus intervention. The Greenlight intervention is administered by trained pediatric healthcare providers at each well-child visit from 0 to 18 months and consists of a low health literacy toolkit used during clinic visits to promote shared goal setting. Families randomized to Greenlight Plus receive the Greenlight intervention plus a health information technology intervention, which includes: 1) personalized, automated text-messages that facilitate caregiver self-monitoring of tailored and age-appropriate child heath behavior goals; and 2) a web-based, personalized dashboard that tracks child weight status, progress on goals, and electronic Greenlight content access. We randomized 900 parent-infant dyads, recruited from primary care clinics across six academic medical centers. The study's primary outcome is weight for length trajectory from birth through 24 months. By delivering a personalized and tailored health information technology intervention that is asynchronous to pediatric primary care visits, we aim to achieve improvements in child growth trajectory through two years of age among a sample of geographically, socioeconomically, racially, and ethnically diverse parent-child dyads.


[Relationship between oxidative deamination of cerebral seroton in during hibernation and changes in monoamine oxidase activity and temperature].
The highest MAO was found in alert ground squirrels and it became minimum in hibernating animals. The temperature relations of the oxidative serotonin desamination (OSD) in alert ground squirrels was relatively low from 7 to 37 degrees C. At the beginning of hibernation OSD did not differ from that of alert animals at 22--37 degrees C, while at 7--22 degrees C it was significantly lower--about 1.0. In hibernating ground squirrels, high OSD was observed at low and high temperatures in all parts of the brain except hypothalamus. At awaikening OSD remained high.


[Cerebrospinal fluid parameters in Guillain-Barré polyradiculitis. Importance of barrier disorder and intrathecal immunoglobulin synthesis].
With routine CSF determination of 21 patients with GBS the BBB and the intrathecal IgG synthesis was investigated when calculated CSF/serum albumin ratio and CSF IgG-index respectively. Only in 2 of 21 patients (9.5%) an intrathecal IgG synthesis and in 14 of 21 patients (67%) a BBB damage was found. The BBB was considered as an important pathogenetic factor in GBS. A hypothesis for the development of the albumino-cytological dissociation is presented.


iPSCs and small molecules: a reciprocal effort towards better approaches for drug discovery.
The revolutionary induced pluripotent stem cell (iPSC) technology provides a new path for cell replacement therapies and drug screening. Patient-specific iPSCs and subsequent differentiated cells manifesting disease phenotypes will finally position human disease pathology at the core of drug discovery. Cells used to test the toxic effects of drugs can also be generated from normal iPSCs and provide a much more accurate and cost-effective system than many animal models. Here, we highlight the recent progress in iPSC-based cell therapy, disease modeling and drug evaluations. In addition, we discuss the use of small molecule drugs to improve the generation of iPSCs and understand the reprogramming mechanism. It is foreseeable that the interplay between iPSC technology and small molecule compounds will push forward the applications of iPSC-based therapy and screening systems in the real world and eventually revolutionize the methods used to treat diseases.


Cathepsin B-sensitive dipeptide prodrugs. 1. A model study of structural requirements for efficient release of doxorubicin.
A series of lysosomal protease-sensitive peptides attached to doxorubicin (DOX) was prepared as model substrates for internalizing anticancer immunoconjugates and potential antimetastasis prodrugs. Rates of cathepsin B-mediated release of free drug was measured for each, and human plasma stabilities for representative examples.


Total synthesis of xiamenmycin C and all of its stereoisomers: stereochemical revision.
Xiamenmycin C, a potent anti-fibrotic natural product, and all of its stereoisomers have been synthesized and their structures were fully characterized. Based on this study, the originally proposed structure of xiamenmycin C has been accordingly revised to be 2R,3S.


Air pollution and the sequelae of COVID-19 patients: A multistate analysis.
Recent evidence links air pollution to the severity COVID-19 symptoms and to death from the disease. To date, however, few studies have assessed whether air pollution affects the sequelae to more severe states or recovery from COVID-19 in a cohort with individual data. To assess how air pollution affects the transition to more severe COVID-19 states or to recovery from COVID-19 infection in a cohort with detailed patient information. We used a cohort design that followed patients admitted to hospital in the Kaiser Permanente Southern California (KPSC) Health System, which has 4.7 million members with characteristics similar to the general population. Enrollment began on 06/01/2020 and ran until 01/30/2021 for all patients admitted to hospital while ill with COVID-19. All possible states of sequelae were considered, including deterioration to intensive care, to death, discharge to recovery, or discharge to death. Transition risks were estimated with a multistate model. We assessed exposure using chemical transport model that predicted ambient concentrations of nitrogen dioxide, ozone, and fine particulate matter (PM2.5) at a 1 km scale. Each increase in PM2.5 concentration equivalent to the interquartile range was associated with increased risk of deterioration to intensive care (HR of 1.16; 95% CI: 1.12-1.20) and deterioration to death (HR of 1.11; 95% CI: 1.04-1.17). Results for ozone were consistent with PM2.5 effects, but ozone also affected the transition from recovery to death: HR of 1.24 (95% CI: 1.01-1.51). NO2 had weaker effects but displayed some elevated risks. PM2.5 and ozone were significantly associated with transitions to more severe states while in hospital and to death after discharge from hospital. Reducing air pollution could therefore lead to improved prognosis for COVID-19 patients and a sustainable means of reducing the health impacts of coronaviruses now and in the future.


Differential biological responses of adherent and non-adherent (cancer and non-cancerous) cells to variable extremely low frequency magnetic fields.
Extremely low-frequency electromagnetic field (ELF-EMF) induces biological effects on different cells through various signaling pathways. To study the impact of the ELF-EMF on living cells under an optimal physiological condition, we have designed and constructed a novel system that eliminates several limitations of other ELF-EMF systems. Apoptosis and cell number were assessed by flow cytometry and the Trypan Blue dye exclusion method, respectively. In vitro cell survival was evaluated by colony formation assay. The distribution of cells in the cell cycle, intracellular ROS level, and autophagy were analyzed by flow cytometer. Suspended cells differentiation was assessed by phagocytosis of latex particles and NBT reduction assay. Our results showed that response to the exposure to ELF-EMF is specific and depends on the biological state of the cell. For DU145, HUVEC, and K562 cell lines the optimum results were obtained at the frequency of 0.01 Hz, while for MDA-MB-231, the optimum response was obtained at 1 Hz. Long-term exposure to ELF-EMF in adherent cells effectively inhibited proliferation by arresting the cell population at the cell cycle G2/M phase and increased intracellular ROS level, leading to morphological changes and cell death. The K562 cells exposed to the ELF-EMF differentiate via induction of autophagy and decreasing the cell number. Our novel ELF-EMF instrument could change morphological and cell behaviors, including proliferation, differentiation, and cell death.


Clinical significance of circulating tumor cells after chemotherapy in unresectable pancreatic ductal adenocarcinoma.
Circulating tumor cells (CTCs) have emerged as liquid biopsy biomarker providing non-invasive assessment of cancer progression and biology. We investigated whether longitudinal analysis of CTCs could monitor disease progression, response to chemotherapy, and survival in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). A total of 52 patients with PDAC were prospectively enrolled in this study. Peripheral blood samples were serially collected at the time of diagnosis and after chemotherapy with clinical assessments. CTCs were isolated through a centrifugal microfluidic disc, enumerated with immunostaining against Epithelial cell adhesion molecule (EpCAM), Cytokeratin (CK), Plectin-1 and CD45, and identified by an automated imaging system. One or more CTCs were detected in 84.62% patients with unresectable PDAC at the time of diagnosis. CTC numbers were not statistically different across tumor sizes, location and metastatic sites. The absolute number of CTCs after chemotherapy was inversely related to overall survival (OS), and the decreased number of CTCs after chemotherapy was significantly associated with longer OS in patients with PDAC. Identifying CTCs and monitoring CTC changes after chemotherapy could be a useful prognostic marker for survival in patients with unresectable PDACs.


Deep, big, simple neural nets for handwritten digit recognition.
Good old online backpropagation for plain multilayer perceptrons yields a very low 0.35% error rate on the MNIST handwritten digits benchmark. All we need to achieve this best result so far are many hidden layers, many neurons per layer, numerous deformed training images to avoid overfitting, and graphics cards to greatly speed up learning.


Cognitive Remediation Therapy for Children with Anorexia Nervosa.
Evidence-based treatment programs for children with anorexia nervosa (AN) are scarce, while their prognosis is negative and the incidence rate rises. A new therapeutic approach recently received positive attention: cognitive remediation therapy (CRT). This intervention targets inflexibility and the inability to perceive the bigger picture in persons with AN. So far, studies and case reports have focused on either adolescent or adult patients and less on young children with AN. This case report therefore describes and evaluates the implementation of CRT with a child with AN. A 12-year-old girl with severe chronic AN was treated with 10 sessions of CRT. Her clinical and neuropsychological evaluations before, directly after and 7 months after CRT are reported. Additionally, the patient's written and verbal feedbacks are reviewed. At the 7-month follow-up the patient showed a stable healthy weight and reported a reduced presence of psychopathology. Her neuropsychological performance directly after CRT and after 7 months did not improve. The clinical evaluation of our case report suggests that CRT may be a promising add-on therapy in the clinical treatment of young girls with AN.


Eosinophils and immune mechanisms. VI. The synergistic combination of granulocyte-macrophage colony-stimulating factor and IL-5 accounts for eosinophil-stimulation promoter activity in Schistosoma mansoni-infected mice.
Eosinophil stimulation promoter (ESP) is a lymphokine activity that stimulates eosinophil migration and is produced by mitogen or specific Ag stimulation of spleen cells from mice infected with Schistosoma mansoni. It is also produced by intact, schistosome egg-induced granulomas isolated from the livers of such mice without additional antigenic exposure. The production of ESP activity is decreased during chronic infection in a time course coordinate with granuloma modulation. Characterization of ESP was pursued to determine its relationship to other cytokines and to identify factors that may play a role in granuloma formation and modulation. Chromatographic separations, assays of recombinant cytokines, and cytokine-specific immunodepletions were used in the characterization. ESP+ supernatant fluids contain both granulocyte-macrophage CSF and IL-5. The removal of both granulocyte-macrophage CSF and IL-5 is required to eliminate ESP activity, and together they act synergistically to constitute ESP.


Rapid identification and clinical indices of fear-avoidance in youth with chronic pain.
Pain-related fear and avoidance are increasingly demonstrated to play an important role in adult and childhood chronic pain. The Fear of Pain Questionnaire for Children (FOPQC) is a 24-item measure of pain-related fear-avoidance in youth that has demonstrated good indices of reliability and validity, treatment responsiveness, and associations with brain circuitry alterations. This study describes the development and psychometric examination of the FOPQC-SF, a short form of the original measure. We selected 10 items for the short form that best represented the content and 2-factor (fear and avoidance) structure of the original measure from a cohort of 613 youth (Mage = 14.7 years) with chronic pain. Next, confirmatory factor analyses from a second sample of 526 youth (Mage = 14.7 years) with chronic pain who completed the FOPQC-SF supported the original 2-factor model but indicated that one item should be moved to the avoidance subscale. The FOPQC-SF demonstrates strong internal consistency and moderate-to-strong construct and criterion validity. The 3-month test-retest reliability estimates (N = 94) were strong, and there was preliminary evidence of responsivity to change. To aid integration into intervention trials and clinical practice, we provide clinical reference points and a criterion to assess reliable change. The short form could be used for rapid identification of pain-related fear and avoidance in youth during clinic evaluations, and is optimized for clinical registries.


Sonography with vertical orientation feature predicts worse disease outcome in triple negative breast cancer.
Triple negative breast cancer (TNBC) is a heterogenous disease and associated with unfavorable outcomes. The role of sonographic features and its association with disease outcome in TNBC is uncertain. Our study aimed to determine the prognosis predictive value of sonographic features in TNBC. Women with TNBC patients treated between January 2009 and December 2015 were retrospectively included. Patients' clinic-pathological, sonographic features, recurrence-free survival (RFS), and breast cancer-specific survival (BCSS) events were reviewed and analyzed. Kaplan-Meier analysis and multivariable Cox regression were used to determine the prognostic factors in TNBC. A total of 433 TNBC patients were included. With a median follow-up of 4.8 years, 58 (13.4%) RFS and 35(8.1%) BCSS events were detected. Besides lymphatic vascular invasion (LVI), nuclear grade III, tumor >2.0 cm, and positive axillary lymph node (ALN), multivariable analysis found that vertical orientation in ultrasound imaging was independently associated with worse RFS (Hazard Ratio (HR) = 3.238; 95% Confidential Interval (CI), 1.661-6.312; P = 0.001) and BCSS (HR = 7.028; 95% CI, 3.199-15.436; P < 0.001). TNBC with vertical orientation in ultrasound imaging had higher ALN metastasis burden than those with sonographic parallel features (2.7 ± 1.0 vs 1.5 ± 0.2, P = 0.003). TNBC presenting with vertical orientation in ultrasound imaging was associated with worse disease outcome and a greater number of ALN metastasis.


Expression of cuticular protein genes, BmorCPG11 and BMWCP5 is differently regulated at the pre-pupal stage in wing discs of Bombyx mori.
Through BLAST search of the genomic database of Bombyx mori, we found a clone, BmorCPG11, which has only putative BR-C binding sites in the 2 kb upstream region. Both BmorCPG11 and BR-Z2 were expressed in the cephalic region of the epidermis, differently from BR-Z1 and BR-Z4. BR-Z2 transcripts increased by the addition of 20-hydroxyl-ecdysone (20E), which was slightly inhibited by cycloheximide. BmorCPG11 expression was also induced by the addition of 20E, which was inhibited by cycloheximide. Both BmorCPG11 and BR-Z2 were induced by the 20E pulse treatment, but they were inhibited by the addition of cycloheximide. Both genes showed similar expression pattern in wing discs during the developmental stage and in vitro ecdysone responsiveness, and both showed relatedness. The result of a reporter assay demonstrated the strong relatedness of BmorCPG11 and BR-Z2. The expression profiles of BmorCPG11 and BR-Z2 are different from those of BMWCP5 and βFTZ-F1. The present findings showed different regulation of cuticular protein genes by ecdysone-responsive transcription factors at the pre-pupal stage of wing discs of B. mori.


Lymph node retrieval colon cancer: Are we making the grade?
Adequate lymph node (LN) excision is imperative for pathologic staging and determination of adjuvant treatment. he 2004-2017 National Cancer Database (NCDB) was queried for curative colon cancer resections. Tumors were categorized by location: left, right, and transverse colon cancers. Adequate (12-20 LNs) vs. inadequate (<12 LNs) lymphadenectomy was examined and sub-analysis of <12 LNs, 12-20 LNs or >20 LNs. Primary outcome was predictors of inadequate lymph node retrieval. Of 101,551 patients, 11.2% (11,439) had inadequate lymphadenectomy. The inadequate lymphadenectomy rate steadily decreased. On multivariable analysis, inadequate LN retrieval was associated with transverse (OR 1.49, CI [1.30-1.71]) and left colon cancers (OR 2.66, CI [2.42-2.93], whereas income >$63,333 had decreased likelihood of inadequate LN retrieval (OR 0.68, CI[0.56-0.82]. We are making the grade as NCDB data demonstrates a steady decrease in inadequate lymphadenectomy (2004-2017). There remain socioeconomic risk factors for inadequate lymphadenectomy that need to be addressed.


Investigation of thiol-disulfide homeostasis and ischemia-modified albumin levels in patients with hidradenitis supurativa.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. The pathogenesis of HS is not clear, and the triggering mechanism for the initiation of the disease is still a controversy. The present study aims to investigate the relationship between thiol-disulfide homeostasis (TDH), ischemia-modified albumin (IMA), and HS. To our knowledge, this will be the first report evaluating TDH and IMA status in HS. The study included 30 patients with HS as the patient group and 30 healthy individuals as the control group. For determination of HS severity, Hurley and Hidradenitis suppurativa physician global assessment (PGA) scores were used. One tube venous blood specimen from every participant was obtained. IMA and TDH tests were analyzed in sera of participants. The results were evaluated statistically. Disulfide (p < 0.001), Index I (p = 0.001), and Index II (p = 0.001) levels in HS group were significantly higher than control group. IMA levels in patients with higher Hurley scores are significantly higher (p = 0.032, r = 0.39). A positive correlation was observed between IMA level and disease duration (p = 0.021, r = 0.42). The shift in thiol/disulfide balance toward disulfide and significant increase in IMA levels put out the importance of oxidation status in HS etiopathogenesis.


Anti-inflammatory Evaluation and Toxicological Analysis of Campomanesia xanthocarpa Berg.
Campomanesia xanthocarpa (Myrtaceae) is used in Brazilian traditional medicine against fever, diabetes, hypercholesteremic, obesity, and urinary diseases. In the present study, the compounds 2',6'-dihydroxy-3'-methyl-4'-metoxychalcone and 2',4'-dihydroxy-3',5'-dimethyl-6'-methoxychalcone were identified for the first time in leaves of the C. xanthocarpa. These compounds and the hydroethanolic extract (HECX) significantly inhibited paw edema and reduced both leukocyte migration and the leakage of protein into the pleural cavity. No toxicity was detected by HECX in an acute toxicity test.


Inpatient to outpatient transfer of care in urban patients with diabetes: patterns and determinants of immediate postdischarge follow-up.
A key opportunity for continuing diabetes care is to assure outpatient follow-up after hospitalization. To delineate patterns and factors associated with having an ambulatory care visit, we examined immediate postdischarge follow-up among a cohort of urban, hospitalized patients with diabetes mellitus. Retrospective study of 658 inpatients of a municipal hospital. Primary data sources were inpatient surveys and electronic records. Patients were stratified into outpatient follow-up (69%), acute care follow-up (15%), and those with no follow-up (16%); differences between groups were detected for age (P =.02), percentage discharged with insulin (P =.03), and percentage receiving a full discount for care (P<.001). Among patients with a postdischarge visit, 43% were seen in our specialty diabetes clinic, and 26% in a primary care site. Adjusted analyses showed any follow-up visit significantly decreased with having to pay for care. The odds of coming to the Diabetes Clinic increased if patients were discharged with insulin, had new-onset diabetes, or had a direct referral. In this patient cohort, most individuals accomplished a postdischarge visit, but a substantial percentage had an acute care visit or no documented follow-up. New efforts need to be devised to track patients after discharge to assure care is achieved, especially in this patient population particularly vulnerable to diabetes.


Light sensitometry of mammography films at varying development temperatures and times.
Kodak MinR-2000 mammography film is widely used for mammography imaging. The sensitometric indices like base plus fog level (B + F), maximum optical density (OD(max)), average gradient (AG) and speed of this film at varying development temperatures and times were evaluated using a light sensitometer. Totally 33 film strips were cut from a single Kodak MinR-2000 mammography film box and exposed in a light sensitometer operated in the green light spectrum to produce a 21-step sensitometric strip. These exposed film strips were processed at temperatures in the range of 32°C-37°C in the step of 1°C and at processing times in the range of 1-6 minutes in the step of 1 minute. The results of the present study show that the measured base plus fog level of the mammography film was not affected much, whereas significant changes were seen in the OD(max), AG and speed with varying development temperatures and times. The OD(max) values of the film were found in the range of 3.67-3.76, AG values were in the range of 2.48-3.4 and speed values were in the range of 0.015-0.0236 when the processing temperature was varied from 32°C to 37°C. With processing time variation from 1 to 6 minutes, the observed changes in OD(max) values were in the range of 3.54-3.71, changes in AG were in the range of 2.66-3.27 and changes in speed were in the range of 0.011-0.025. Based on these observations, recommendations for optimum processing parameters to be used for this film are made.


Extremely Rare Case of Extra Skeletal Soft Tissue Chondroma of Masseteric Space: a Diagnostic Challengel.
Benign soft tissue chondroma is a rare type of extraskeletal chondrocytic tumour. It usually can be found in skeletal system in extremities. Head and neck region is one of the most uncommon sites for extraskeletal chondroma .Most common site is tongue and there has been paucity of cases arising from the other subsites .We present a case of 56 years gentleman who came to our OPD with a right masticator space swelling. It was nonmalignant on FNAC. He underwent wide local excision through a transparotid approach. Final biopsy & IHC report showed presence of benign chondrocytic neoplasm- soft tissue chondroma (extraskeletal). No further therapy was used and he has been in follow up since then. To our knowledge ,this is the third reported case of masseteric space chondroma. The online version contains supplementary material available at 10.1007/s12070-023-03705-5.


Identification of the gene transcription and apoptosis mediated by TGF-beta-Smad2/3-Smad4 signaling.
Transforming growth factor-beta (TGF-beta) signaling is known to depend on the formation of Smad2/3-Smad4 transcription regulatory complexes. However, the signaling functions of Smad2/3-Smad4 during TGF-beta-induced responses are obscure as TGF-beta also initiates a number of other signaling pathways. In this study, we systematically assessed the contribution of TGF-beta-Smad2/3-Smad4 signaling to both target gene transcription and apoptosis. Individual Smads were selectively knocked down in Hep3B cells by stable RNA interference (RNAi). We identified TGF-beta-responsive genes using genome-wide oligonucleotide microarrays and confirmed their dependency on Smad2, Smad3, or Smad4 by the combination of RNAi and microarray assay. The major finding from our microarray analysis was that of the 2,039 target genes seen to be regulated via TGF-beta induction, 190 were differentially transcriptionally controlled by Smad2-Smad4 and Smad3-Smad4 signaling and the latter control mechanism appeared to be functionally more important. We also found indirect evidence of competition between Smad2 and Smad3 for their activation when controlling the transcription of target genes. Functional analysis revealed that Smad3 and Smad4 were the predominant mediators of TGF-beta-induced apoptosis in Hep3B cells. We provide evidence that up-regulation of Bcl-2-interacting mediator of cell death (Bim), under the transcriptional control of Smad3-Smad4 signaling, is crucial to TGF-beta-induced apoptosis in Hep3B cells.


Effects of psychological distress on perceptions of physical health and use of medical and psychiatric facilities.
Psychological distress not only contributes to bodily symptoms but also affects the way people perceive their physical health status and their use of medical care. Reporting on a program of research, this paper reviews evidence that psychological distress is an important component of illness behavior and response and must be taken into account in the appropriate organization of medical services.


[Current role of the laboratory in the demonstration and follow up of monoclonal immunoglobulinopathy].
The interest of new methodologies (electrophoresis in agarose, immunofixation, quantitation of Ig G, Ig A, Ig M and light chains kappa/lambda ratio) to diagnose monoclonal gammopathies, was discussed. A strategy using a combination of these new procedures was exposed. Serum level of bêta-2 microglobulin can be used to monitor response to therapy in myeloma when the quantitation of monoclonal Ig is not possible.


Ineffective parenting: a precursor to psychopathic traits and delinquency in Hispanic females.
Research studies with antisocial children have posited that multiple etiologies, including ineffective parenting, can produce psychopathic traits. The current study evaluated 136 Hispanic females and found that poor parenting predicted psychopathology and poor behavioral controls. Effective clinical interventions with antisocial children should focus on improving quality of parenting.


Regulation of rat growth hormone receptor gene expression.
A cDNA encoding the growth hormone (GH) receptor was cloned from rat liver. Both the nucleotide and translated amino acid sequence share greater than 70% similarity with the GH receptors from rabbit and human. An RNA probe was generated from this sequence for use in a solution hybridization assay to quantitate GH receptor mRNA expression in rat tissues. Expression was detected in 9/12 tissues examined, with the highest levels observed in the liver. Expression in liver, kidney, heart and muscle was developmentally regulated, being low at birth and rising to adult levels in 5 weeks. No difference was observed between hepatic expression in males and females, although livers from pregnant rats had elevated levels. Hypophysectomy and GH treatment did not affect hepatic GH receptor mRNA levels.


The pH-induced glycosylation of secreted phosphatases is mediated in Aspergillus nidulans by the regulatory gene pacC-dependent pathway.
In this communication, we show that the pacC(c)14 mutation drastically reduced the mannose and N-acetylglycosamine content of the pacA-encoded acid phosphatase secreted by the fungus Aspergillus nidulans when grown at 22 degrees C, pH 5.0, compared to a control strain. The staining after PAGE was not observed for the pacA-encoded acid phosphatase, while the palD-encoded Pi-repressible alkaline phosphatase had an altered electrophoretic mobility. In addition, the secreted acid phosphatase also had a reduced number of isoforms visualized by staining after IEF and glycosylation had a protective effect against its heat inactivation. We also show that a full-length version of gene pacC-1 cloned from Neurospora crassa complemented the pacC(c)14 mutation of A. nidulans, including the remediation of both the acid and alkaline Pi-repressible phosphatases secreted at pH 5.0, which indicates that glycosylation of secreted phosphatases is mediated in A. nidulans by the conserved PacC pathway that governs pH-responsive gene expression.


Attenuation-corrected fluorescence extraction for image-guided surgery in spatial frequency domain.
A new approach to retrieve the attenuation-corrected fluorescence using spatial frequency-domain imaging is demonstrated. Both in vitro and ex vivo experiments showed the technique can compensate for the fluorescence attenuation from tissue absorption and scattering. This approach has potential in molecular image-guided surgery.


The complete development in vitro of the vertebrate phase of the mammalian malarial parasite Plasmodium berghei.
All three 'vertebrate' stages of the rodent malarial parasite Plasmodium berghei berghei were grown in vitro in the absence of the vertebrate host. The parasite was introduced into culture from infected mosquitoes and 2 in vitro culture methods were used sequentially to complete the 'vertebrate' phases of development in hepatoma and erythrocyte host cells. The resultant blood infection produced mature schizonts and male and female gametocytes. The protocol, which is now being extended to the human pathogen P. falciparum, may assist future studies on this important group of parasites.


[The use of natural hitamine-based natural substance at chronic cholecystitis].
The results of application of hitamine, enterosorbent of marine origin, by the patients with chronic noncalculous cholecystitis in the remission phase are cited. It has been established that dietotheraphy in complex with hitamine renders the antiinflammatory and lipidcorrected action, favours the increase of remission terms.


Evaluation of procedures for decontaminating ultrasound probes.
To determine suitable procedures for decontaminating ultrasound probes. We investigated bacterial transmission via ultrasound probes that were not wiped, wiped with a plain paper towel, or wiped with an ethanol-soaked paper towel. The unwiped probes transmitted large numbers of bacteria, which were markedly reduced by wiping the probes with a plain paper towel, and almost completely eliminated by wiping with an ethanol-soaked paper towel. Improperly decontaminated ultrasound probes can transmit bacteria among patients. Ultrasound probes should be decontaminated by wiping with a paper towel after examinations to prevent bacterial transmission. Plain or ethanol-soaked paper towels should be used depending on the situation.


Massive hematemesis and melena stool: A case report of unusual manifestation of Cow's milk protein intolerance.
Cow's milk protein intolerance (CMPI) is a common condition that causes gastrointestinal bleeding in the first year of life. It is the most common cause of chronic blood loss and anemia; however, severe massive hematemesis is an uncommon condition. Herein, we present a case of severe massive hematemesis with melena stool in a six-month-old boy with cow's milk protein intolerance. In this case, we described management used in poor developing countries.


International health experiences in postgraduate medical education: A meta-analysis of their effect on graduates' clinical practice among underserved populationsExpériences internationales de soins de santé en formation médicale post-doctorale : une méta-analyse des effets sur la pratique clinique des diplômés au sein des populations mal desservies.
International health experiences (IHEs) are popular among medical learners and provide a valuable learning experience. IHE participants have demonstrated an increased intention to care for underserved populations in the future, but what is its actual impact on practice? This study evaluates the effect of postgraduate IHE participation on the future careers of clinicians regarding their work among underserved populations. We conducted a systematic review and meta-analysis of peer-reviewed articles comparing the populations served by physicians who had participated in an IHE with those of physicians who had not participated in an IHE. 764 titles were scanned, 28 articles were reviewed, with an eventual 3 studies of fair-good or good quality identified. These addressed physicians' service to domestic underserved populations, and also addressed future service in a low- or middle-income country (LMIC). Meta-analysis demonstrated a statistically-significant increase in service by IHE graduates to domestic underserved populations (OR = 2.12; CI = 95%; P = 0.03). The certainty of the evidence was low due to limitations in study design (non-randomised studies) and inconsistency in effects. Participation in an IHE may cause an increase in care for domestic underserved populations in future clinical practice, though further research from high quality randomised trials is needed to increase the certainty of the effect. Further study is needed to establish whether there is a similar effect with increased future service in a LMIC setting.


Matched case-control analysis of outcomes following surgical resection of incidental meningioma.
The management of incidentally discovered meningioma remains controversial. We sought to compare outcomes following surgical resection of incidental meningioma to a matched cohort of symptomatic meningiomas. A retrospective single-center case-control study was conducted for patients undergoing resection of incidental meningioma from 2000 to 2019. A 1:1 case-control matching for incidental and symptomatic meningioma was performed using the following variables: age at initial visit, gender, tumor location/size, and presence of peritumoral edema. Primary outcomes included (1) WHO grading/histopathological subtype/MIB-1 index, (2) extent of resection (gross total resection or subtotal resection), and (3) recurrence. Outcomes were compared between groups using descriptive/bivariate analyses. A total of 91 incidental meningiomas were analyzed. Trauma was the most common reason (n = 19, 21%) to obtain imaging, and tumor size the leading reason to operate (n = 37, 41%). Median time-to-surgery from initial clinical encounter was 5-months (Q1:3, Q3:16.5). More incidental meningioma patients (n = 47, 52%) were privately insured compared to their matched symptomatic cohort (n = 30, 33%) (P = 0.006). Patients with incidental meningioma had significantly higher mean Karnofsky Performance Scale at time-of-surgery (93.2, SD:11.1 vs. 81.4, SD:12.7) (P < 0.001). There were no significant differences in primary/secondary outcomes between the groups. Incidental meningioma was not associated with recurrence on Cox proportional hazards analysis (HR: 0.795, 95%CI: 0.3-2.1, P = 0.637). Matched case-control analysis demonstrated no significant differences in clinical, histopathological, and functional outcomes following resection of incidental and symptomatic meningioma. While non-operative management with close follow-up and serial imaging is preferred for incidental meningiomas, those undergoing resection when indicated can anticipate similar safety and efficacy as symptomatic meningiomas.


Outcome of corticotropin stimulation testing in women with androgen excess and ovulatory dysfunction.
Our objective was to evaluate women with clinical signs or chemical evidence of androgen excess by corticotropin stimulation testing. Seventy-six women with evidence of androgen excess were evaluated by corticotropin stimulation testing. Results were examined by plasma levels of dehydroepiandrosterone sulfate, androstenedione, and testosterone. Conception in those infertile women with androgen excess was also assessed. Data were evaluated with Fisher's exact test. Of 41 women with dehydroepiandrosterone sulfate levels greater than 2.8 micrograms/ml, 17 (41.5%) had a positive corticotropin stimulation test (stimulated 17 alpha-hydroxyprogesterone value exceeded baseline value by 2.7 times). No statistically significant association was found between androstenedione or testosterone excess and a positive corticotropin stimulation test. In 14 infertile women with dehydroepiandrosterone sulfate levels greater than 2.8 micrograms/ml and a positive corticotropin stimulation test, 7 (50%) conceived when given low-dose prednisone (p less than 0.005). Corticotropin stimulation testing is warranted in women with clinical signs of androgen excess and dehydroepiandrosterone sulfate levels greater than 2.8 micrograms/ml.


Genetic Counseling Milestones: A Framework for Student Competency Evaluation.
Graduate medical education has recently increased focus on the development of medical specialty competency milestones to provide a targeted tool for medical resident evaluation. Milestones provide developmental assessment of the attainment of competencies over the course of an educational program. An educational framework is described to explore the development of Genetic Counseling Milestones for the evaluation of the development of genetic counseling competencies by genetic counseling students. The development of Genetic Counseling Milestones may provide a valuable tool to assess genetic counseling students across all program activities. Historical educational context, current practices, and potential benefits and challenges in the development of Genetic Counseling Milestones are discussed.


A two-stage model of peer influence in adolescent substance use: individual and relationship-specific differences in susceptibility to influence.
A two-stage model of peer influence was proposed. The model served as a framework for examining individual and relationship-specific differences in susceptibility to influence. The two stages are (1) the acquisition of a peer context and (2) conforming to the behavior of a peer. Data from a four-wave longitudinal study were used to assess (1) the initial selection of cigarette- and alcohol-using peers and (2) influence from peers. Relationship factors and variables identified as risk factors for substance use were hypothesized to increase susceptibility to peer influence. The results indicated that adolescents who did not value school achievement or spending time with parents were more apt than others to choose friends who smoked cigarettes more than they did. Adolescents who chose friends who drank more than they did not differ from other adolescents on any of the risk factors. Thus, low-risk adolescents were as likely to acquire a friend context where drinking was likely to occur as were adolescents who had more risk factors. When the second stage was examined, only high peer acceptance and high friendship quality resulted in adolescents being more apt to conform to their friend's substance-use behaviors.


Demonstration of laminin, a basement membrane glycoprotein, in routinely processed formalin-fixed human tissues.
Laminin was demonstrated by immunoperoxidase and immunofluorescence staining in sections of normal human tissues fixed in formalin and routinely processed in paraffin. Exposure of the sections to a solution of pepsin (Burns et al. (1980) Histochemistry 67:73-78) revealed the antigenicity of this basement membrane glycoprotein. Sections from paraffin blocks stored for years at room temperature could be stained with this procedure. Normal human tissues, developing fetal tissues and tumors could be stained with this method. The staining patterns were similar to those seen in unfixed frozen sections. It thus appears that basement membrane components can be detected by immunohistological means from routinely processed histological samples, once the sections are pretreated with proteases. Staining for laminin could be used in embryonic studies and in histopathology to study the relation of cells to basement membranes and for the visualization of normal and abnormal vascularization.


Multiple cytolytic T-cell clones with distinct cross-reactivity patterns coexist in anti-self + hapten cell lines.
C57BL/10 T cells sensitized with TNBS-treated syngeneic cells and maintained in culture by repeated stimulations exhibit high cytolytic activity toward syngeneic TNBS-treated target cells with marked cross-reactivity on TNBS-treated target cells from mice of independent H-2 haplotypes (ten tested). The analysis of the reactivities of 48 T-cell clones derived by limiting dilution from such T-cell populations revealed three types of cytotoxic T-cell clones: (1) clones restricted by H-2Kb + TNP without cross-reaction on TNBS-treated or untreated target cells of other tested mouse haplotypes; (2) clones that lysed H-2b + TNP and also TNBS-treated target cells from not more than one, two or three different H-2 haplotypes; (3) clones that lysed untreated H-2k target cells. No T-cell clone was found to exhibit the wide pattern of cross-reactivity on any TNBS-treated mouse cell, characteristic of the original T-cell populations, indicating that these were composed of individual T-cell clones specific for TNP + private or for TNP + distinct "public" H-2 determinants. Correlation with described serological public H-2 specificities was possible for some cytotoxic T-cell clone reactivity, but not for others. The general pattern of T-cell reactivity as revealed by clonal analysis in this study, as well as in published work, includes cross-reactions between self H-2a + X and allogeneic H-2n + X, between self H-2a + X and unmodified allogeneic H-2n, or between allogeneic H-2n and allogeneic H-2m + X, and is consistent with the hypothesis that MHC-class restriction is the main rule in T-cell recognition.


Recovery of bone mass and normalization of bone turnover in long-term survivors of allogeneic bone marrow transplantation.
Osteoporotic fractures are potential long-term complications of bone marrow transplantation (BMT). We previously reported that bone mineral density (BMD) of patients undergoing allogeneic BMT decreased by 6% to 9% during the first 6 months after BMT and that bone turnover rate was still increased 1 year after BMT. BMT patients do not need lifelong immunosuppressive treatment, which should offer favorable circumstances for the recovery of BMD. Thus, 27 (14 women, 13 men) of 29 long-term survivors of our previous study were invited to a follow-up study at a median of 75 months after BMT. From 12 months after BMT the BMD of the lumbar spine had increased by 2.4% (P = 0.002). The respective changes in femoral sites were +4.1% in the femoral neck (P = 0.087), 4.0% in the trochanter (P = 0.095), +4.7% in Ward's triangle (P = 0.072) and +1.4% in the total hip (P = 0.23). The markers of bone formation, serum osteocalcin and type I procollagen aminoterminal propeptide (PINP) had returned to control levels, but out of the markers of bone resorption the mean level of serum type I carboxyterminal telopeptide (ICTP) was 41% higher (P = 0.0001) and that of urinary type I collagen N-terminal telopeptide/creatinine (NTx) 41% lower (P = 0.0002) in patients than in controls. The mean serum 25-hydroxyvitamin D [25(OH)D] was 33% lower in patients (P = 0.0002), most of whom had hypovitaminosis D [serum 25(OH)D < or = 37 nmol/l]. Except for two, males had serum testosterone level lower than before BMT and four men had hypogonadism. In conclusion, in long-term survivors of allogeneic BMT BMD recovers and bone turnover state normalizes as compared to the situation 1 year after BMT. More attention should be paid to the vitamin D status of all recipients and to possible hypogonadism of male patients.


The effect of pH and nitrite concentration on the antimicrobial impact of celery juice concentrate compared with conventional sodium nitrite on Listeria monocytogenes.
The objectives of this study were to evaluate the impact of pH and nitrite from celery juice concentrate (CJ) on the growth of Listeria monocytogenes in broth and on ham slices, and to evaluate the impact of pH and nitrite from CJ on quality attributes of the ham. The pH of both broth and ham were increased by the addition of CJ. The CJ was less effective than conventional nitrite at 100 mg/kg nitrite in broth, but in ham, the CJ treatments at both 100 and 200 mg/kg resulted in growth of L. monocytogenes (p>0.05) similar to that of the conventional nitrite at the same concentrations. Reducing the pH of CJ before addition to the ham had greater impact on L. monocytogenes growth at 200 mg/kg nitrite than at 100 mg/kg. Celery juice concentrate may increase meat product pH which could have implications for the antimicrobial impact of nitrite in some products.


Differential expression of the human, mouse and rat IGF-II genes.
The IGF-II gene is a complex transcription unit. Multiple transcripts are synthesized as a result of alternate promoter usage and the splicing of unique 5' untranslated regions to common coding exons. In order to characterize the mechanisms of IGF-II gene regulation we performed comparative studies to define essential features of IGF-II expression in human, rat and mouse. Homologous promoter regions of the human, mouse and rat IGF-II genes were fused to the luciferase reporter gene and expression was measured in various cell lines that have an endogenously active or inactive IGF-II gene expression pattern, respectively. The transient promoter activity of the human, mouse and rat IGF-II constructs was further compared with the endogenous activity of the IGF-II gene in various tissues and cell lines of human, mouse and rat origin. The results indicate that in transient expression assays employing heterologous systems (e.g., mouse promoter in human cells), most IGF-II promoter constructs are active, albeit at low levels. Maximal promoter activity is only observed, however, in homologous systems (e.g., human promoter constructs tested in human cells). This suggests that each promoter, despite the strong sequence conservation of the homologous human, rat and mouse promoters, is adapted to the levels of the transcription factors present in its natural environment. Finally, IGF-II gene expression is not only regulated at the level of transcription but also depends on mRNA stability. We show that human, rat and also mouse IGF-II mRNAs are subjected to specific endonucleolytic cleavage, suggesting that specific cleavage of IGF-II mRNAs must be of general physiological importance.


Impact of the Obesity Paradox Between Sexes on In-Hospital Mortality in Cardiogenic Shock: A Retrospective Cohort Study.
Background Several studies have shown that obesity is associated with better outcomes in patients with cardiogenic shock (CS). Although this phenomenon, the "obesity paradox," reportedly manifests differently based on sex in other disease entities, it has not yet been investigated in patients with CS. Methods and Results A total of 1227 patients with CS from the RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With Cardiogenic Shock) registry in Korea were analyzed. The study population was classified into obese and nonobese groups according to Asian Pacific criteria (BMI ≥25.0 kg/m2 for obese). The clinical impact of obesity on in-hospital mortality according to sex was analyzed using logistic regression analysis and restricted cubic spline curves. The in-hospital mortality rate was significantly lower in obese men than nonobese men (34.2% versus 24.1%, respectively; P=0.004), while the difference was not significant in women (37.3% versus 35.8%, respectively; P=0.884). As a continuous variable, higher BMI showed a protective effect in men; conversely, BMI was not associated with clinical outcomes in women. Compared with patients with normal weight, obesity was associated with a decreased risk of in-hospital death in men (multivariable-adjusted odds ratio [OR], 0.63; CI, 0.43-0.92 [P=0.016]), but not in women (multivariable-adjusted OR, 0.94; 95% CI, 0.55-1.61 [P=0.828]). The interaction P value for the association between BMI and sex was 0.023. Conclusions The obesity paradox exists and apparently occurs in men among patients with CS. The differential effect of BMI on in-hospital mortality was observed according to sex. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02985008.


A Giant Intramedullary Spinal Tumor.
Intramedullary tumors of the spinal cord account for 2%-4% of all central nervous system tumors. Surgical resection with intraoperative neuromonitoring, although challenging, remains the mainstay of treatment with the goal to prevent neurologic decline. We present a case of an unusual anaplastic glioma of the thoracic spinal cord in a 42-year-old male that spanned 7 vertebral levels and could not be definitively characterized using the 2021 World Health Organization Classification of Central Nervous System Tumors.


[Acupuncture for treatment of kinetic insufficiency of kidney-qi and study on the mechanism].
To observe the therapeutic effect of acupuncture on kinetic insufficiency of kidney-qi and to study on the mechanism. Forty-four healthy professional sportsmen were randomly divided into an acupuncture group and a control group. They trained for 4 weeksq with regular detection. In the latter 2 weeks, the acupuncture group received scalp and body-acupuncture. Three weeks later, signs of insufficiency of kidney-qi appeared in most of the sportsmen in the two groups. Two weeks after treatment, in the acupuncture group the signs improved, and testosterone (T) and estradiol (E2) levels increased (P < 0.05); the symptoms did not significantly improve and the T and EZ levels decreased in the control group (P < 0.05). Acupuncture therapy can regulate excitatory and inhibitory functions of the nervous system, improve symptoms of kinetic insufficiency of kidney-qi, and has regulative and repairing action on the sexual glands and adrenal gland.


Integrated analysis of circulating and tissue proteomes reveals that fibronectin 1 is a potential biomarker in papillary thyroid cancer.
Papillary thyroid cancer (PTC) is the most frequent subtype of thyroid cancer, but 20% of cases are indeterminate (i.e., cannot be accurately diagnosed) based on preoperative cytology, which might lead to surgical removal of a normal thyroid gland. To address this concern, we performed an in-depth analysis of the serum proteomes of 26 PTC patients and 23 healthy controls using antibody microarrays and data-independent acquisition mass spectrometry (DIA-MS). We identified a total of 1091 serum proteins spanning 10-12 orders of magnitude. 166 differentially expressed proteins were identified that participate in complement activation, coagulation cascades, and platelet degranulation pathways. Furthermore, the analysis of serum proteomes before and after surgery indicated that the expression of proteins such as lactate dehydrogenase A and olfactory receptor family 52 subfamily B member 4, which participate in fibrin clot formation and extracellular matrix-receptor interaction pathways, were changed. Further analysis of the proteomes of PTC and neighboring tissues revealed integrin-mediated pathways with possible crosstalk between the tissue and circulating compartments. Among these cross-talk proteins, circulating fibronectin 1 (FN1), gelsolin (GSN) and UDP-glucose 4-epimerase (GALE) were indicated as promising biomarkers for PTC identification and validated in an independent cohort. In differentiating between patients with benign nodules or PTC, FN1 produced the best ELISA result (sensitivity = 96.89%, specificity = 91.67%). Overall, our results present proteomic landscapes of PTC before and after surgery as well as the crosstalk between tissue and the circulatory system, which is valuable to understand PTC pathology and improve PTC diagnostics in the future.


Glutathione-S-transferases M1/T1 gene polymorphisms and endometriosis: a meta-analysis in Chinese populations.
In view of the controversies surrounding the glutathione-S-transferases (GST) M1/T1-endometriosis association, a meta-analysis of the GSTM1/GSTT1 genetic association studies of endometriosis was performed in Chinese populations. PubMed, Springer Link, OvidSP, and Chinese databases were searched for related studies. A total of nine studies on GSTM1-endometriosis involved 874 cases and 997 controls, and five studies on GSTT1 involved 404 cases and 513 controls were included in this meta-analysis. Overall, the null genotype of GSTM1/GSTT1 was significantly related to endometriosis risk in Chinese populations (GSTM1, OR = 2.21, 95% CI: 1.22-4.01; GSTT1, OR = 2.31, 95% CI: 1.34-3.99). In subgroup analyses stratified by ethnicity and source of controls, the same results were observed in Chinese Han and population-based studies. The sensitivity analysis confirmed the reliability and stability of the meta-analysis. No publication bias was found among studies by Egger's test. In conclusion, our meta-analysis supports that the GSTM1/GSTT1 null genotype might contribute to individual susceptibility to endometriosis in Chinese populations, especially in Chinese Han.


Multisystem inflammatory syndrome in adults: A case in a previously healthy adult.
A 25-year-old previously healthy female presented to the emergency department (ED) with 5 days of rash, fevers, shortness of breath, and generalized weakness. She had presented to another ED 4 days previously and noted that her rash had improved, but her other symptoms were worsening. She had recovered from COVID-19, confirmed by positive antigen test 5 weeks prior. On ED arrival, she was afebrile and persistently tachycardic to a rate of 120 beats per minute, despite aggressive fluid resuscitation with 3L of IV crystalloid. She was found to have a troponin elevated to 0.06 ng/mL in addition to a d-dimer elevated to 1.42 mcg/mL FEU. She was admitted to the hospital where she developed hypotension requiring vasopressor support and was admitted to the intensive care unit (ICU). A transthoracic echocardiogram revealed a newly reduced ejection fraction of 31%. She was diagnosed with multisystem inflammatory syndrome in adults (MIS-A). The patient received intravenous immunoglobulin and methylprednisolone 60 mg Q12 hours while admitted. She was discharged on hospital day 3 with a prednisone taper and is currently doing well at her most recent follow-up with infectious disease.


Ecological compensation--a complication for testing life-history theory.
Mortality, growth and birth rates cannot vary independently in stable populations, environmental change of one variable must be accompanied by compensatory variation of another. Ecological compensation is recognized if the stable populations are genetically identical. Ecological compensation, if it operates, constrains the direction of evolutionary change, and predictions that ignore it may be in error.


[Effects of opioid peptides on rats with a second heart transplanted into the abdominal cavity].
To determine whether opioid peptides have direct effects on myocardium we compared the effects of enkephalin analogs DAGO and DADL on both an innervated heart and a denervated heterotopically transplanted heart in the same animal. DAGO and DADL injected intravenously into anesthetized rats with two hearts produced hypotension, fall in end-systolic left ventricular pressure of both recipient's and donor's heart, bradycardia and decreasing of contractility in recipient's heart. Opioid peptides exerted no chronotropic effect and a slight positive inotropic effect on denervated transplanted heart. Both bradycardia and decreasing of contractility in recipient's heart have the neurogenic origin.


Forbush decreases: Algorithm generated dataset.
Efforts to correctly detect Forbush decreases (FDs) in the cosmic ray (CR) intensity flux are ongoing (see [2], [7]). The FD data presented here are a part of the data generated in [6] in a recent investigation of the effects of CR anisotropies on the simultaneity of FDs. A part of the simultaneous and non-simultaneous FDs detected from both raw and Fourier transformed CR data are presented. Some of the filtered CR anisotropies are also presented. The datasets are interesting as they provide an opportunity to investigate the interaction of CR anisotropies on FDs. [6] identified FDs from both raw and Fourier transformed CR data. For the FDs identified in the raw data, the impact of diurnal anisopropy was not removed. Additionally, FDs were identified using a careful adjustment for diurnal anisotropy. The results of FD catalogues for ten CR stations are presented. All are calculated with the same method and selection criteria. Thus these catalogues can be united contrary to the indication of [1], allowing comparison of Chree, regression or correction analysis based on CR data from isolated neutron monitors [9]. These data can also be used in the analysis of FD event simultaneity. Several claims on FD event simultaneity by some authors ([5], [8]) using few FDs can be verified using the data. The diagrams show the relationships between raw and Fourier transformed CR data as well as CR anisotropic variations at different locations. The similarities and differences between these figures could be used to discuss the impact of rigidity on diurnal anisotropy and FDs. The quantitative amplitudes of the diurnal anisotropy calculated at the time of FDs could be useful in such investigation. Okike [6] calculated the amplitude of diurnal anisotropies accompanying FDs and are presented here. The large number of strong and small FDs selected from each station for the year 2003 may encourage reanalysis of previous work employing only 3 or 4 FDs in each year. Many studies relating FDs to terrestrial effects have focused on a single FD without strong evidence that it is generalizable to others. This may attract criticism that the conclusions drawn do not extend to all FDs. The diagrams presented here are similar to those presented in [6] for the Climax station. Rather than display separate FD events, the complete intensity variation together with the accompanying FDs are clearly displayed. Solar wind plasma data may be displayed alongside the data for comparative purposes. It is hoped that this approach will answer the numerous objections made to solar-terrestrial analysis involving FDs.


Improved section adhesion for immunocytochemistry using high molecular weight polymers of L-lysine as a slide coating.
Poly-L-lysine (PPL) has been used to coat glass slides in the preparation of tissue sections for immunocytochemical staining. The adhesive properties of different molecular weight (m.w.) polymers of L-lysine have been tested on pre-fixed cryostat sections which were subjected to a 3 day washing treatment. It has been found that the higher the molecular weight of the polymer, the greater the adhesive force it provides. PLL (m.w. 350,000) at concentrations in the range of 0.05-0.1% was found to be the most effective polymer.


Responding to intrusions in obsessive-compulsive disorder: the roles of neuropsychological functioning and beliefs about thoughts.
The aim of the current study was to examine cognitive and psychological factors hypothesized to affect responding to intrusions in obsessive-compulsive disorder (OCD). A group of individuals diagnosed with OCD (N = 22) was compared to a social phobia (SP) group (N = 25) and a nonclinical control group (N = 24). Participants performed a battery of neuropsychological tasks, completed self-report measures, and engaged in a self-relevant thought suppression task. Participants in the OCD group demonstrated worse working memory and response inhibition on the neuropsychological tasks and had increased intrusions during the suppression task relative to comparison groups. They also reported more distress during the task relative to the nonclinical group, but not the SP group. Regression analyses revealed that beliefs about thought control failures, but not working memory or response inhibition, was associated with increased frequency of intrusions and greater distress during suppression. Future studies may include a more comprehensive battery of cognitive tests and have a larger sample size. Findings support cognitive-behavioural models of OCD that emphasize the role of meta-beliefs in explaining the struggle with obsessional thoughts.


A field study to estimate heavy metal concentrations in a soil-rice system: Application of graph neural networks.
Accurate prediction of the concentration of heavy metals is of great significance for assessing the quality of agricultural products and reducing health risks. However, the complexity and interconnectivity of the farmland ecosystem restricts the improvement of the prediction accuracy of traditional methods. This research explored the application potential of graph neural network (GNN) technology, which can extract and learn information in large-scale networks in detail, in the field of heavy metal prediction for the first time. In this study, a heavy metal prediction model for rice, CoNet-GNN, was proposed with 17 environmental factors as input variables using the co-occurrence network and GNN. Experimental results using a dataset from a field study showed that the R2 of CoNet-GNN for predicting Cd, Pb, Cr, As, and Hg had outstanding values of 0.872, 0.711, 0.683, 0.489, and 0.824, respectively. Sensitivity analysis further indicated that CoNet-GNN had good stability and robustness. Compared with random forest, gradient boosting, and multilayer perceptron, CoNet-GNN made a remarkable improvement to the prediction accuracy of all studied heavy metals. Therefore, CoNet-GNN can effectively simulate the rich relationships and laws between various factors in the soil-rice system and effectively characterize the influence diffusion path. Furthermore, it provides new ideas for heavy metal prediction based on network research methods and expands the technical scope of heavy metal evaluation.


Knowledge, attitude, and practice of institutional dental professionals regarding management of patients taking oral antithrombotic medications.
Nowadays, there is an increasing number of patients prescribed regular antithrombotics. With these long-term medications, complications like postoperative bleeding are extremely important. Despite available guidelines on this issue, disparities in approach have been noticed. The current study aimed to explore the knowledge, attitude, and practice of dental professionals associated with a dental school in Saudi Arabia regarding the management of patients with oral antithrombotic medications. A cross-sectional study was conducted on institutional-based dental professionals in Saudi Arabia. Fifty-six subjects, including 12 interns, 20 demonstrators, and 24 faculty members were included in the study. A modified semistructured questionnaire comprising 20 questions was used to gather respondents' knowledge, attitude, and practice related to oral antithrombotic medications. The chi-square test was applied for computing inferential statistics. Spearman correlation coefficient was performed for significant variables. The faculty members had comparable knowledge (P = .010) as well as practice (P = .001) levels, and significantly outscored the other two groups. The interns displayed a significantly higher knowledge score over the demonstrators, whereas the reverse scenario was seen for practice scores. Interestingly, participants were frequently found to be significantly overestimating the bleeding risk for procedures falling into the "no risk" category. A significantly positive correlation regarding the professional level could be shown in all domains. Professionals need to regularly update about novel anticoagulants, and should strictly comply with the established practice guidelines, thus improving the quality, safety, and value of dental health care.


A standardised comment scheme for routine pulmonary function test results.
Observed values of ventilatory capacity, gas transfer and lung volumes in 840 patients were used to formulate a standardised scheme of descriptive comments. Response to bronchodilators was also defined. Absolute differences between measured and predicted values are used to identify normal and abnormal patterns of results, together with an overall pattern. The algorithms are suitable for computer use. The scheme has been in routine manual use for four years and can be used by any laboratory in which the necessary quality control standards are applied.


Percutaneous rotational and aspiration atherectomy in infrainguinal peripheral arterial occlusive disease: a multicenter pilot study.
To report a safety and efficacy study of the first rotational aspiration atherectomy system (Pathway PV) for the treatment of arterial lesions below the femoral bifurcation. From December 2005 to February 2006, 15 patients (9 men; mean age 71+/-9 years) with Rutherford stage 2 to 5 lower limb ischemia were enrolled at 3 study sites. Target lesions were in the superficial femoral (n = 7, 47%), popliteal (n = 7, 47%), and posterior tibial (n = 1, 6%) arteries. Mean diameter stenosis was 97%+/-10%; mean lesion length was 61+/-62 mm (range 5-250). The primary study endpoint was the 30-day serious adverse event (SAE) rate. Interventional success (residual stenosis <30%) was achieved in all lesions (100%). Stand alone atherectomy was performed in 6 (40%) patients, adjunctive balloon angioplasty in 7 (47%), and stenting/endografting in 2 (13%). The SAE rate at 30 days was 20% (3/15), including 1 perforation due to an unrecognized displacement of the guidewire (sealed with an endograft), 1 false aneurysm at the puncture site (successful duplex-guided compression therapy), and 1 dissection in conjunction with a distal embolism (stent implantation and aspiration thrombectomy). Primary patency rates measured by duplex ultrasound at 1 and 6 months were 100% and 73%, respectively; the TLR rate was 0% after 6 months. The ankle-brachial index increased significantly from 0.54+/-0.3 at baseline to 0.89+/-0.16, 0.88+/-0.19, and 0.81+/-0.20 (p<0.05) at discharge, 1 month, and 6 months, respectively. Mean Rutherford categories were 2.92+/-1.19 (range 1-5), 0.64+/-1.12 (range 0-1), and 0.83+/-1.33 (range 0-3) at the same time points (p<0.05). The application of this new atherectomy device was feasible in all cases. The serious adverse event rate was moderate; however, all events were solved during the index procedure. The 0% 6-month TLR rate is promising.


A mutation in canine CLN5 causes neuronal ceroid lipofuscinosis in Border collie dogs.
Neuronal ceroid lipofuscinosis (NCL) is a neurodegenerative disease found in Border collie dogs, humans, and other animals. Disease gene studies in humans and animals provided candidates for the NCL gene in Border collies. A combination of linkage analysis and comparative genomics localized the gene to CFA22 in an area syntenic to HSA13q that contains the CLN5 gene responsible for the Finnish variant of human late infantile NCL. Sequencing of CLN5 revealed a nonsense mutation (Q206X) within exon 4 that correlated with NCL in Border collies. This truncation mutation should result in a protein product of a size similar to that of some mutations identified in human CLN5 and therefore the Border collie may make a good model for human NCL. A simple test was developed to enable screening of the Border collie population for carriers so the disease can be eliminated as a problem in the breed.


Modified Rose Bengal assay for surface hydrophobicity evaluation of cationic solid lipid nanoparticles (cSLN).
Surface hydrophobicity of nanocarriers influences protein binding and subsequently fate of nanoparticles in blood circulation. Therefore, characterization of surface hydrophobicity of nanocarriers provides important preclinical information. Here, a modified classical adsorption method for the needs of characterization of cationic solid lipid nanoparticles (cSLN) was developed. We have identified possible method limitations that should be considered when performing the analysis, i.e. the problems associated with particle separation from the dispersion and their own absorbance in visible spectrum. We propose two modified methods for performing the assay overcoming the stated limitations. We also discuss here evaluation by different approaches (calculation of binding constants or partitioning quotient) and their suitability for the prepared cSLN formulation. Overall, we confirmed that our modified adsorption method can provide useful information about surface properties of (cationic) SLN, however, performing and evaluation of the assay need special attention in order to obtain the desired results.


High-dose-rate brachytherapy of a single implant with two fractions combined with external beam radiotherapy for hormone-naive prostate cancer.
To evaluate the preliminary outcomes of high-dose-rate (HDR) brachytherapy of a single implant with two fractions and external beam radiotherapy (EBRT) for hormone-naive prostate cancer. Between March 2000 and Sept 2003, a total of 53 patients with tumor Stage T1c-T3b N0 M0 prostate cancer were treated with HDR brachytherapy boost doses (7.5 Gy/fraction) and 50-Gy EBRT during a 5.5-week period. Median follow-up was 61 months. Patients were divided into groups with localized (T1c-T2b) and advanced disease (T3a-T3b). We used the American Society for Therapeutic Radiology and Oncology (ASTRO) definition for biochemical failure. According to recommendations of the Radiation Therapy Oncology Group-ASTRO Phoenix Consensus Conference, biochemical failure-free control rates (BF-FCRs) at 3 years were investigated as 2 years short of the median follow-up. Between April 2000 and Sept 2007, Common Terminology Criteria for Adverse Events Version 2.0 late Grade 2 genitourinary and gastrointestinal toxicity rates were 0% and 3.8%, respectively. Erectile preservation was 25% at 5 years. Overall survival was 88.1% and cause-specific survival was 100%. At 3 years, ASTRO BF-FCRs of the localized and advanced groups were 100% and 42%, respectively (p = 0.001). The HDR brachytherapy of a single implant with two fractions plus EBRT is effective in treating patients with localized hormone-naive prostate cancer, with the least genitourinary and gastrointestinal toxicities; however, longer median BF-FCR follow-up is required to assess these findings.