Reoperation for Persistent or Recurrent Neurogenic Thoracic Outlet Syndrome.
Identifying the exact cause for persistent and recurrent neurogenic thoracic outlet syndrome (NTOS) is challenging even with high-resolution imaging of the thoracic outlet. Improvement can be achieved with redo first rib resection, although the posterior first rib remnant is one of several potential points of brachial plexus compression. In approaching reoperative surgery for NTOS, the aim is to provide complete thoracic outlet decompression as guided by the patient's history, physical examination, and adjunctive imaging. This may involve resection of the posterior first rib remnant, scar tissue encasing the brachial plexus, elongated C7 transverse process, cervical rib, and/or pectoralis minor tendon.


Preparation of garlic stem cellulose nanocrystal/leaf extract/chitosan film for black garlic preservation by electrostatic spraying.
In this study, a novel active chitosan (CH) packaging film that incorporates garlic leaf extract (GL) and stem cellulose nanocrystals (CNC) was prepared. The addition of CNC to the CH film increased its tensile strength, hydrophilicity, thermal stability, and water/oxygen barrier and decreased its water contact angle and weight-loss rate, while the addition of GL greatly enhanced its antioxidant and antibacterial activities. SEM and AFM analyses showed that the CNC agglomerates and deposits in the lower layer and the surface roughness of the film was the highest at 1.2 % concentration. The optimal composition of the film was determined to be 0.8 % CNC and 4 % GL by the fuzzy mathematics evaluation method. Then, black garlic was preserved with the optimized coating by electrostatic spraying and was found to slow water loss and migration, while its excellent antioxidant activities decreased the degree of browning during 90 d of storage.


Cobalt nanoparticles & nitrogen-doped carbon nanotubes@hollow carbon with high catalytic ability for high-performance lithium sulfur batteries.
Lithium-sulfur (Li-S) battery has been considered as a potential next-era energy storage device. However, its practical application is limited by the volume change of sulfur and the shuttle effect of lithium polysulfides. To effectively overcome these issues, a hollow carbon decorated with cobalt nanoparticles and interconnected by nitrogen doped carbon nanotubes (Co-NCNT@HC) is developed for high-performance Li-S battery. The uniformly distributed nitrogen and cobalt nanoparticles in Co-NCNT@HC are able to enhance the chemical adsorption capability and fasten the transformation speed of the intermediates, thus effectively inhibit the loss of lithium polysulfides. Moreover, the hollow carbon spheres interconnected by carbon nanotubes are structurally stable and electrically conductive. Due to the unique structure, the Li-S battery enhanced by Co-NCNT@HC shows a high initial capacity of 1550 mAh/g at 0.1 A g-1. Even at a high current density of 2.0 A g-1, after 1000 cycles, it still maintains a capacity of 750 mAh/g with a capacity retention of 76.4% (the capacity decay rate is only 0.037% per cycle). This study provides a promising strategy for the development of high-performance Li-S batteries.


C-peptide exerts antithrombotic effects that are repressed by insulin in normal and diabetic mice.
Diabetic macro- and microangiopathy are associated with a high risk of vascular complications. The diabetic patient exhibits a pathological coagulation state, with an increased synthesis of coagulation factors and plasminogen activator inhibitor 1 (PAI-1) as well as an enhanced aggregation of platelets. Previous studies have shown that C-peptide can reduce leucocyte-endothelial cell interaction and improve microvascular blood flow in patients with type 1 diabetes. In the present study, we examined in vivo whether C-peptide is able to reduce platelet activation and through that microvascular thrombus formation. In the microvessels of cremaster muscle preparations taken from normal and diabetic mice, ferric chloride-induced thrombus formation was analysed using intravital fluorescence microscopy. I.V. administration of C-peptide in high dose (70 nmol/kg), but not in low dose (7 nmol/kg), caused a significant delay in arteriolar and venular thrombus growth in normal and diabetic mice. This effect was repressed by cremaster muscle superfusion with insulin (100 microU/ml) in diabetic animals, but particularly in normal animals. In parallel, immunohistochemistry demonstrated a higher number of PAI-1-expressing vessels in cremaster muscle tissue from control animals and from animals treated with C-peptide and insulin compared with tissue from animals with C-peptide treatment application alone. We conclude that C-peptide possesses antithrombotic actions in vivo. A causal role of PAI-1 in this scenario needs to be further addressed. However, the reversal of C-peptide action by insulin may invalidate the use of this peptide as a treatment option to improve rheology and microcirculation in diabetic patients.


Investigation of the chemical composition-antibacterial activity relationship of essential oils by chemometric methods.
The antibacterial effects of Thymus vulgaris (Lamiaceae), Lavandula angustifolia (Lamiaceae), and Calamintha nepeta (Lamiaceae) Savi subsp. nepeta var. subisodonda (Borb.) Hayek essential oils on five different bacteria were estimated. Laboratory control strain and clinical isolates from different pathogenic media were researched by broth microdilution method, with an emphasis on a chemical composition-antibacterial activity relationship. The main constituents of thyme oil were thymol (59.95%) and p-cymene (18.34%). Linalool acetate (38.23%) and β-linalool (35.01%) were main compounds in lavender oil. C. nepeta essential oil was characterized by a high percentage of piperitone oxide (59.07%) and limonene (9.05%). Essential oils have been found to have antimicrobial activity against all tested microorganisms. Classification and comparison of essential oils on the basis of their chemical composition and antibacterial activity were made by utilization of appropriate chemometric methods. The chemical principal component analysis (PCA) and hierachical cluster analysis (HCA) separated essential oils into two groups and two sub-groups. Thyme essential oil forms separate chemical HCA group and exhibits highest antibacterial activity, similar to tetracycline. Essential oils of lavender and C. nepeta in the same chemical HCA group were classified in different groups, within antibacterial PCA and HCA analyses. Lavender oil exhibits higher antibacterial ability in comparison with C. nepeta essential oil, probably based on the concept of synergistic activity of essential oil components.


Large landslides cluster at the margin of a deglaciated mountain belt.
Landslides in deglaciated and deglaciating mountains represent a major hazard, but their distribution at the spatial scale of entire mountain belts has rarely been studied. Traditional models of landslide distribution assume that landslides are concentrated in the steepest, wettest, and most tectonically active parts of the orogens, where glaciers reached their greatest thickness. However, based on mapping large landslides (> 0.9 km2) over an unprecedentedly large area of Southern Patagonia (~ 305,000 km2), we show that the distribution of landslides can have the opposite trend. We show that the largest landslides within the limits of the former Patagonian Ice Sheet (PIS) cluster along its eastern margins occupying lower, tectonically less active, and arid part of the Patagonian Andes. In contrast to the heavily glaciated, highest elevations of the mountain range, the peripheral regions have been glaciated only episodically, leaving a larger volume of unstable sedimentary and volcanic rocks that are subject to ongoing slope instability.


Histologic classification of gliomas.
Gliomas form a heterogeneous group of tumors of the central nervous system (CNS) and are traditionally classified based on histologic type and malignancy grade. Most gliomas, the diffuse gliomas, show extensive infiltration in the CNS parenchyma. Diffuse gliomas can be further typed as astrocytic, oligodendroglial, or rare mixed oligodendroglial-astrocytic of World Health Organization (WHO) grade II (low grade), III (anaplastic), or IV (glioblastoma). Other gliomas generally have a more circumscribed growth pattern, with pilocytic astrocytomas (WHO grade I) and ependymal tumors (WHO grade I, II, or III) as the most frequent representatives. This chapter provides an overview of the histology of all glial neoplasms listed in the WHO 2016 classification, including the less frequent "nondiffuse" gliomas and mixed neuronal-glial tumors. For multiple decades the histologic diagnosis of these tumors formed a useful basis for assessment of prognosis and therapeutic management. However, it is now fully clear that information on the molecular underpinnings often allows for a more robust classification of (glial) neoplasms. Indeed, in the WHO 2016 classification, histologic and molecular findings are integrated in the definition of several gliomas. As such, this chapter and Chapter 6 are highly interrelated and neither should be considered in isolation.


A spatially structured metapopulation model with patch dynamics.
Metapopulation models that incorporate both spatial and temporal structure are studied in this paper. The existence and stability of equilibria are provided, and an extinction threshold condition is derived which depends on patch dynamics (patch destruction and creation) and metapopulation dynamics (patch colonization and extinction). These results refine threshold conditions given by previous metapopulation models. By comparing landscapes with different spatial heterogeneities with respect to weighted long-term patch occupancies, we conclude that the pattern of a landscape is of overwhelming importance in determining metapopulation persistence and patch occupancy. We show that the same conclusion holds when a rescue effect is considered. We also derive a stochastic differential equations (SDE) model of the Itô type based on our deterministic model. Our simulations reveal good agreement between the deterministic model and the SDE model.


Expression, purification, and biological activity of the recombinant pramlintide precursor.
Pramlintide is an artificially designed protein which has the same function as amylin in human body. This protein is extremely difficult to synthesize through prokaryotic expression method because of its two essential active sites, intrachain disulfide bond and C-terminal amide group. Since α-amidating monooxygenase is widely distributed in human and animal, it is possible to use pramlintide precursor with an additional C-terminal glycine (PAG), which is the potential substrate of α-amidating monooxygenase, for in vivo applications. The recombinant PAG was expressed in Escherichia coli using the small ubiquitin-related modifier (SUMO) as the molecular chaperone, and the optimal fusion expression level reached to 36.3% of the total supernatant protein. Under optimal conditions in a 10-L fermentor, the recombinant PAG was obtained with a purity of greater than 95%, and the average expression level was reached to 20 mg/L. The authenticity and the intrachain disulfide bridge of PAG were confirmed by Western blotting and matrix-assisted laser desorption/ionization coupled to time-of-flight mass spectrometry (MALDI-TOF MS) as well as N-terminal sequencing of protein. Based on an L6 myoblast cell model in vitro and an animal model of gastric emptying in vivo, the results of activity revealed that PAG showed a lower biological activity in vitro but has almost the same activity as the chemically synthesized pramlintide in vivo.


The effectiveness of surgical versus conservative treatment for symptomatic unilateral spondylolysis of the lumbar spine in athletes: a systematic review.
Spondylolysis is a common cause of low back pain in athletes. Historically, spondylolysis injuries were thought to be mostly bilateral; however advances in lumbar spine imaging have shown that in certain athlete groups, unilateral spondylolysis is highly prevalent. It remains unclear whether athletes with unilateral spondylolysis who undergo surgical repair are able to return to sports as effectively or faster than if they had conservative treatment. To determine the effectiveness of surgical fixation performed after a trial period of conservative management, compared to the effectiveness of conservative management only for unilateral spondylolysis in athletes. Athletes with symptomatic unilateral spondylolysis of the lumbar spine. Types of intervention(s): Surgical interventions which attempted a direct repair of the pars interarticularis, compared to conservative management. Types of studies: Experimental and epidemiological study designs were considered for inclusion. The majority of the studies reviewed consisted of descriptive epidemiological study designs including case series, individual case reports and descriptive cross sectional studies. Types of outcomes: The primary outcome of interest in this review was the ability to return to sport. The effectiveness of surgery on pain and overall function were secondary outcomes of interest. A three-step search strategy that aimed to find both published and unpublished studies was utilized. The search was limited to studies published in the English language between 1 January 1970 and 1 September 2013. The studies were critically appraised using one of the standardized critical appraisal instruments from The Joanna Briggs Institute. Details describing each study and results on effectiveness in promoting the outcomes of interest were extracted from papers included in the review using the standardized data extraction tool from The Joanna Briggs Institute. Due to heterogeneity in the included studies, the results for similar outcome measures were not pooled in statistical meta-analysis. A narrative and tabular format was used to synthesize the results of identified and included studies. Five studies reporting results for the outcomes of interest were critically appraised and included in the review. One study was a quasi-experimental design, while the other four were case series studies. Due to the paucity of data, studies were included regardless of whether their participants were exclusively athletes with unilateral spondylolysis or adults (athletes and non-athletes) with unilateral and bilateral spondylolysis. Sub-group analysis was used to distinguish the findings for the main participant group of interest, namely athletes with unilateral spondylolysis. The limited evidence on the effectiveness of surgical treatment versus conservative treatment for unilateral spondylolysis in athletes does not allow any conclusions to be drawn about the relative effectiveness of surgery versus conservative treatment for facilitating rapid return to sport or a high level of post injury sporting level/performance. It does suggest, however, that for adult athletes for whom conservative treatment has not been successful, surgery is likely to enable return to sport, reduce pain and promote overall function.


Early phase II Gynecologic Oncology Group experience with ifosfamide/mesna in gynecologic malignancies.
Starting in July 1985, the Gynecologic Oncology Group conducted a series of phase II trials with ifosfamide/mesna in advanced or recurrent gynecologic malignancies. Previously untreated patients received 1.5 g/m2 i.v. ifosfamide daily for 5 days. Mesna was given i.v. q4h x 3 following ifosfamide; each dose was 20% of the daily ifosfamide dose. All patients with ovarian and 87% of those with cervical cancer had previously undergone platinum-based therapy. Because of the toxicity encountered in previously treated patients with ovarian carcinoma, the dose of ifosfamide was reduced to 1.2 g/m2 daily in all patients who had received prior chemo- or radiotherapy. In epithelial ovarian carcinoma, responses were observed in 8 (20.0%) of 41 evaluable patients, with 3 (7.0%) complete responses. Response duration was 2.1-20.3+ months, with a median of 6.9+ months. In squamous-cell carcinoma of the cervix, 3 (11.1%) of 27 evaluable patients showed partial responses of 1.8, 2.2, and 3.1 months' duration. Of 26 untreated patients with mixed mesodermal tumors of the uterus, 5 (19.2%) achieved complete and 3 (11.5%) showed partial responses, for an overall response rate of 30.7%. Response duration was 1.4(+)-8.6 months, with a median of 3.8 months. Toxicity included two deaths due to renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.


The SCF-FBXW7 E3 ubiquitin ligase triggers degradation of histone 3 lysine 4 methyltransferase complex component WDR5 to prevent mitotic slippage.
During prolonged mitotic arrest induced by antimicrotubule drugs, cell fate decision is determined by two alternative pathways, one leading to cell death and the other inducing premature escape from mitosis by mitotic slippage. FBWX7, a member of the F-box family of proteins and substrate-targeting subunit of the SKP1-CUL1-F-Box E3 ubiquitin ligase complex, promotes mitotic cell death and prevents mitotic slippage, but molecular details underlying these roles for FBWX7 are unclear. In this study, we report that WDR5 (WD-repeat containing protein 5), a component of the mixed lineage leukemia complex of histone 3 lysine 4 methyltransferases, is a substrate of FBXW7. We determined by coimmunoprecipitation experiments and in vitro binding assays that WDR5 interacts with FBXW7 in vivo and in vitro. SKP1-CUL1-F-Box-FBXW7 mediates ubiquitination of WDR5 and targets it for proteasomal degradation. Furthermore, we find that WDR5 depletion counteracts FBXW7 loss of function by reducing mitotic slippage and polyploidization. In conclusion, our data elucidate a new mechanism in mitotic cell fate regulation, which might contribute to prevent chemotherapy resistance in patients after antimicrotubule drug treatment.


Are nursing home patients with dementia diagnosis at increased risk for inadequate pain treatment?
Mentally impaired and demented nursing home patients are at increased risk of undertreatment for pain. We wanted to examine pain assessment and complaints and pain treatment of nursing home patients according to mental state, and with special regard to treatment of patients with dementia diagnosis and cognitively impaired patients who did not have a dementia diagnosis. Cross sectional study from three nursing homes in Bergen, Norway including 125 persons (median age 84 years), living permanently in a nursing home. Diagnoses and prescribed and administered analgesic drugs were recorded. An experienced nurse interviewed nurses in charge and patients regarding presence of pain during the last week. Patients who were able to answer whether they had experienced pain during the last week were categorised as communicative. Cognitive function was assessed by means of the Abbreviated Mental Test. Seventeen percent of the patients were cognitively intact, 30% cognitively impaired and 54% had a dementia diagnosis. Forty-seven percent of communicative patients complained of pain, nurses reported pain in 67% patients. Twenty-nine percent of the patients had received scheduled analgesics during the last week, cognitively intact patients 38%, cognitively impaired 30%, demented 25% (p = 0.53). Twenty percent were given analgesics PRN: cognitively intact patients 33%, cognitively impaired 27%, demented 12% (p = 0.05). Logistic regression analyses revealed that patients with dementia diagnosis were less likely to receive PRN medication [Adjusted odds ratio (AOR) 0.22 95% confidence interval (CI) 0.06-0.76] compared to mentally impaired patients. Regarding scheduled medication there was no difference between the groups. Nurses' opinion of pain was a significant factor for receiving analgesic drugs, scheduled AOR 3.95 95% CI 1.48-10.5, PRN 3.80-95% CI 1.28-11.3). A label of dementia may bias the interpretation of pain cues of demented patients, while complaints from cognitively impaired patients may be taken for granted. This may contribute to lower use of PRN medication in demented patients compared to cognitively impaired patients.


Development of peroxynitrite-responsive fluorescence probe for recognition of drug-induced liver injury.
Peroxynitrite (ONOO-) as an active substance, is produced during normal physiological process, which plays an important role in maintaining cell REDOX balance and cell function. Moreover, the peroxynitrite is involved in many diseases and especially can be used as a biomarker of drug-induced liver injury (DILI). Therefore, in this work, we synthesized a fluorescent probe JQ-3 for detecting ONOO-. The results showed the probe JQ-3 possessed excellent selectivity, fast response time (10 min) and low detection limit (32 nM). The probe JQ-3 is almost unaffected by pH, showing the potential application in biological systems. Moreover, the probe JQ-3 can be successfully used for the detection of exogenous and endogenous ONOO- in living cells and zebrafish. At the same time, the DILI was successfully recognized by visualizing ONOO- with JQ-3 in living cells and zebrafish. Therefore, the probe JQ-3 provides a potential tool for detecting ONOO- to understand physiological and pathology processes of disease.


Emergency department utilization and subsequent prescription drug overdose death.
Prescription drug overdose (PDO) deaths are a critical public health problem in the United States. This study aims to assess the association between emergency department (ED) utilization patterns in a cohort of ED patients and the risk of subsequent unintentional PDO mortality. Using data from the New York Statewide Planning and Research Cooperative System for 2006-2010, a nested case-control design was used to examine the relationship between ED utilization patterns in New York State residents of age 18-64 years and subsequent PDO death. The study sample consisted of 2732 case patients who died of PDO and 2732 control ED patients who were selected through incidence density sampling. With adjustment for demographic characteristics, and diagnoses of pain, substance abuse, and psychiatric disorders, the estimated odds ratios of PDO death relative to one ED visit or less in the previous year were 4.90 (95% confidence interval [CI]: 4.50-5.34) for those with two ED visits, 16.61 (95% CI: 14.72-18.75) for those with three ED visits, and 48.24 (95% CI: 43.23-53.83) for those with four ED visits or more. Frequency of ED visits is strongly associated with the risk of subsequent PDO death. Intervention programs targeting frequent ED users are warranted to reduce PDO mortality.


Perinatal outcomes and 2017 ACC/AHA blood pressure categories.
To evaluate the association of blood pressure category < 20 weeks according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) criteria with adverse perinatal outcomes. A retrospective cohort study of singleton deliveries between 1/2014 and 10/2017 was undertaken. Blood pressure category assigned by 2017 ACC/AHA criteria applied to blood pressures prior to 20 weeks gestation: normal (systolic < 120 and diastolic < 80), elevated blood pressure (systolic 120-129 and diastolic < 80 mmHg), stage 1 hypertension (systolic 130-139 and/or diastolic 80-89), stage 2 hypertension (prior diagnosis of chronic hypertension or systolic ≥ 140 or diastolic ≥ 90 mmHg). The primary outcome was preeclampsia. Secondary outcomes included preterm birth and postpartum readmission. Chi-square, ANOVA and Kruskal-Wallis tests and multivariable Poisson regression were used for analysis. Of the 6,067 eligible pregnancies, 3,855 (63.5%) had normotensive blood pressure, 1,224 (20.2%) elevated blood pressure, 624 (10.3%) stage 1 hypertension, and 364 (6.0%) stage 2 hypertension. Compared to 4.6% prevalence of preeclampsia among normotensive pregnancies, higher categories were associated with higher preeclampsia prevalence: elevated blood pressure (10.7%, adjusted relative risk (aRR) 2.2, 95% confidence interval (CI) 1.8-2.6), stage 1 hypertension (15.1%, aRR 2.7, 95% CI 2.2-3.4) and stage 2 hypertension (38.7%, aRR 6.2, 95% CI 5.1-7.4). Non-normal categories were also associated with a higher risk of preterm birth and postpartum readmission. Patients with elevated blood pressure and stage 1 and 2 hypertension at < 20 weeks are at increased risk of adverse obstetric perinatal outcomes.


[Anti-immunoglobulins (rheumatoid factors)--immunobiology and significance in pediatrics].
Reactions between immunoglobulins and anti-immunoglobulins in adult and juvenile rheumatoid arthritis are reviewed with special respect to juvenile disease. The practical relevance of the different assays is described and future perspectives developed.


Increased intestinal glucose absorption and postprandial hyperglycaemia at the early step of glucose intolerance in Otsuka Long-Evans Tokushima Fatty rats.
Otsuka Long-Evans Tokushima Fatty (OLETF) rats are reported to be obese Type II (non-insulin-dependent) diabetic rats with insulin resistance and impaired insulin secretion. To investigate the contribution of intestinal glucose absorption to postprandial hyperglycaemia, we determined the plasma xylose concentrations after an 0.8 g/kg oral xylose load which was used as a test of small intestinal glucose absorption in 6-week-old OLETF rats and weight-matched Long-Evans Tokushima Otsuka (LETO) rats. An oral glucose tolerance test showed that OLETF rats developed hyperglycaemia at 60 and 90 min after the glucose load, though the fasting plasma glucose concentration, insulin concentration and insulin-induced in vivo glucose utilization rate were similar. Consistently, in an oral D-xylose loading test, the peak concentration of plasma xylose in OLETF rats was increased by 58.7% compared with that of LETO rats (p < 0.005). The disappearance rate of plasma xylose concentrations after intravenous xylose loading did not differ between the two strains. Co-treatment with 0.4 g/kg phlorizin, a specific inhibitor of sodium-dependent glucose transporter 1 (SGLT1), abolished both plasma glucose and xylose concentrations after the loads. Morphological studies showed that both the small intestinal wet weight and surface area were 30% larger in the OLETF rats than in the LETO rats. Furthermore, the SGLT1 mRNA content of OLETF rats also increased compared with LETO rats. These results suggest that an increased SGLT1 expression concomitant with intestinal hypertrophy in OLETF rats is partly associated with postprandial hyperglycaemia before the onset of insulin resistance and hyperinsulinaemia.


A research-based tumor tissue bank of gynecologic oncology: characteristics of nucleic acids extracted from normal and tumor tissues from different sites.
This article describes a gynecology and pathology-oriented tumor tissue bank that is approaching the research requirements of modern molecular oncology and compared characteristics of nucleic acids extracted from preserved tissues. Through August 2000, 8869 specimens, including fresh neoplastic tissues and normal counterparts, body fluids (ascites, tumor content, and blood), and cervical scrapings, were procured from 1853 patients. DNA and RNA were extracted from a random sampling of normal (n = 50) and tumor (n = 53) tissues from the uterine cervix (n = 47), endometrium (n = 24), and ovary (n = 32). As expected, tumor tissues conferred a higher yield of DNA (1.56 +/- 1.24 versus 0.94 +/- 0.72 microg/mg tissue, P = 0.001) and RNA (5.04 +/- 6.21 versus 2.12 +/- 1.76 microg/ml, P < 0.001) than normal tissues. However, the RNA message abundance, as measured by RNA yield/DNA yield, was not different between tumor and normal tissues. With a similar content of DNA in the endometrium, uterine cervix, and ovary, RNA yield was higher in the endometrium than the others (P = 0.013). In tumors from these three sites, similar yields of DNA and RNA were noted. Overall the yield of DNA remained unchanged from specimens preserved for as long as 7 years, although at this length of storage, RNA yield became lower and variable. This study provides the basic characteristics of nucleic acids derived from normal and tumor tissues and ensures future research utility of these frozen specimens.


Association of HLA antigens with thyrotoxic Graves' disease and periodic paralysis in Hong Kong Chinese.
The HLA-A and -B antigen distribution in 132 Hong Kong Chinese patients with Graves' disease, including 24 with thyrotoxic periodic paralysis, was compared with that in 110 controls. The HLA-DR antigen distribution in 68 patients was compared with that in 47 controls. The prevalence of Bw46 was significantly increased in patients with Graves' disease and with periodic paralysis. The prevalence of DRw9 was also slightly increased but not at a statistically significant level. The high prevalence of Bw46 related to patients with early age at onset whereas patients with later age at onset had a significantly increased prevalence of HLA B5. It is suggested that Graves' disease in Chinese is due to two HLA-associated mechanisms in which early-onset disease is associated with Bw46 and late-onset disease with B5.


An endoscopic Doppler probe for assessing intestinal vasculature.
Flexible fiberoptic endoscopes permit the physician to inspect the mucosal surface of the upper gastrointestinal tract and colon. However, this visual inspection provides little information about the underlying vascular supply to the intestinal wall. We tested the hypothesis that a Doppler probe could be constructed small enough to pass through the biopsy channel of a fiber endoscope and be used with it while performing endoscopy. The purpose would be to determine the location of patent arteries or veins, determine the magnitude and waveforms of the velocity in them, and estimate their contribution or potential contribution to intestinal bleeding. For this purpose, a miniature catheter probe (1.8 mm O.D. and 2 m in length) and an electronic range limited pulsed Doppler unit were developed. This probe and unit were studied in a series of 13 dogs to determine efficacy of detecting arterial and venous flow and to test the safety of the device. The duodenum was surgically exposed and opened in the region of the common bile duct (CBD). Arteries and veins surrounding the CBD were studied. Particular attention was directed to arterial structures which clinically pose a risk of bleeding when performing endoscopic papillotomy, a therapeutic technique in which the papilla of Vater is cut to release bile duct stones. The results of the study revealed that the probe could indeed detect arterial and venous structures accurately. There was no evidence that the probe produced any injury to the common bile duct or pancreas by histological or serum amylase studies and the device was determined safe and suitable for clinical evaluation.


The anion exchanger PAT-1 (Slc26a6) does not participate in oxalate or chloride transport by mouse large intestine.
The membrane-bound transport proteins responsible for oxalate secretion across the large intestine remain unidentified. The apical chloride/bicarbonate (Cl-/HCO3-) exchanger encoded by Slc26a6, known as PAT-1 (putative anion transporter 1), is a potential candidate. In the small intestine, PAT-1 makes a major contribution to oxalate secretion but whether this role extends into the large intestine has not been directly tested. Using the PAT-1 knockout (KO) mouse, we compared the unidirectional absorptive ([Formula: see text]) and secretory ([Formula: see text]) flux of oxalate and Cl- across cecum, proximal colon, and distal colon from wild-type (WT) and KO mice in vitro. We also utilized the non-specific inhibitor DIDS (4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid) to confirm a role for PAT-1 in WT large intestine and (in KO tissues) highlight any other apical anion exchangers involved. Under symmetrical, short-circuit conditions the cecum and proximal colon did not transport oxalate on a net basis, whereas the distal colon supported net secretion. We found no evidence for the participation of PAT-1, or indeed any other DIDS-sensitive transport mechanism, in oxalate or Cl- by the large intestine. Most unexpectedly, mucosal DIDS concurrently stimulated [Formula: see text] and [Formula: see text] by 25-68% across each segment without impacting net transport. For the colon, these changes were directly proportional to increased transepithelial conductance suggesting this response was the result of bidirectional paracellular flux. In conclusion, PAT-1 does not contribute to oxalate or Cl- transport by the large intestine, and we urge caution when using DIDS with mouse colonic epithelium.


Micro-CT analysis and leakage of bioceramic retrofillings after ultrasonic and Er:YAG laser cavity preparations: an in vitro study.
The purpose of the study was to determine the influence of preparation techniques on marginal adaptation and sealing of Biodentine™ and TotalFill® RRM bioceramic retrograde fillings. Fifty-two single-root teeth extracted for periodontal reasons were used. Root canals were instrumented using Reciproc Blue #25 and obturated using a single cone technique with an AH Plus® root canal sealer. Retrograde cavities were prepared with Piezomed device (Piezo), Er:YAG laser in short-pulse(SP) and quantum square pulse(QSP) modes and filled with Biodentine™ (BD) or TotalFill® RRM (TF). There were 6 groups (n=8): (1) Piezo BD, (2) Piezo TF, (3) SP BD, (4) SP TF, (5) QSP BD, and (6) QSP TF, and positive and negative controls (n=2). Micro-CT analysis was performed on two samples from each group. Percentage volumes of internal and external voids in apical 1.5 mm were determined. Rhodamine B dye leakage was done on six samples. The samples were cut longitudinally and examined under a stereomicroscope. Digital recordings were analyzed in ImageJ software. The deepest penetration of color in mm was recorded. The data were statistically analyzed using ANOVA and Duncan's test at the level of significance α=0.05. TotalFill® RRM performed significantly better than Biodentine™ in terms of sealing (p<0.05) and marginal adaptation, as evaluated by micro-CT. Sealing was significantly better in SP compared to QSP mode preparations (p<0.05). Differences between Piezomed and laser modes were not significantly different (p>0.05). Sealing was statistically significantly better with TotalFill® RRM compared to Biodentine™ and in Er:YAG SP preparations compared to Er:YAG QSP.


[Occult ventricular bigeminy. Description of a case with extrasystole variable coupling separated by sinus beats in even or odd numbers].
We have analyzed an electrocardiogram showing many unifocal ventricular extrasystoles with wide variations of the coupling intervals. Ventricular bigeminy was frequent but in many instances more than one sinus beat occurred between two consecutive extrasystoles. In such a case the intervening sinus beats occurred indifferently both in odd and even numbers. Moreover, extrasystoles preceded by an even number of sinus beats had a relatively long coupling interval whereas extrasystoles that followed and odd number of sinus beats showed shorter coupling intervals. An opposite pattern of the coupling interval was observed with the extrasystoles that followed an interpolated premature ventricular depolarization. In such a case the coupling interval was long after an odd number of sinus beats and vice versa. This mechanism may be interpreted as due to concealed ventricular bigeminy caused by a ventricular ectopic focus which is surrounded by two different zones of block: a proximal zone of 2:1 block, and a distal one in which the block occurs irregularly. Unlike what appears in typical concealed bigeminy, characterized by only odd numbers of sinus beats between consecutive extrasystoles the intervening sinus complexes are indifferently in odd and even numbers. The constant relationship between the coupling interval and the number (odd or even) of sinus beats by which the extrasystole is preceded, allows us to recognize the presence of an atypical form of concealed bigeminy.


Current surgical treatment for sphenoorbital meningiomas.
Originally, the authors used a combined transcranial-transmalar approach for removal of sphenoorbital tumors. More recently, when computed tomography (CT) scanning became available, surgical management of sphenoorbital meningiomas included resection of the hyperostosis in the pterional region, orbital roof and lateral wall, and middle fossa floor. Thereafter, intradural and intraorbital components are removed, as well as infiltrated dura mater. Finally, a periosteal flap is placed over the dural defect and bone reconstructed with methylmethacrylate. Of 25 patients, there was only one death and all but one showed very good to moderate response to treatment. Four recurrences were observed. Surgical management cannot be uniform in all cases, but must be adapted to each form of presentation. On the basis of the satisfactory results achieved, we feel justified in advising the technique described above with its current modifications.


A new regulatory mechanism of NF-kappaB activation by I-kappaBbeta in cancer cells.
Transglutaminase 2 (TGase 2) catalyzes covalent isopeptide bond formation between glutamine and lysine residues. Recently, we reported that TGase 2 activates nuclear factor-kappa B (NF-kappaB) by depleting inhibitor of NF-kappaBalpha (I-kappaBalpha) levels via polymer formation. Furthermore, TGase 2 expression synergistically increases NF-kappaB activity with canonical pathway. The major I-kappaB proteins such as I-kappaBalpha and I-kappaBbeta resemble each other in both primary sequence and tertiary structure. However, I-kappaBbeta does not degrade fully, while I-kappaBalpha degrades immediately in response to most stimuli. We found that I-kappaBbeta does not contain any of the previously identified TGase 2 target sites. In this study, both an in vitro cross-linking assay and a TGase 2 transfection assay revealed that I-kappaBbeta is independent from TGase 2-mediated polymerization. Furthermore, increased I-kappaBbeta expression reversed NF-kappaB activation in cancer cells, compensating for the loss of I-kappaBalpha via TGase 2 polymerization.


Rationalistic approach in COVID-19 prevention through intervention of Unani medicine prevalent in epidemic - A review.
A novel coronavirus virus (2019-nCoV) emerged in China in December 2019 and achieved a high-risk category by the World Health Organization (WHO). The initial symptoms included fever, cough, dyspnea, and sore throat. The present review aims to evaluate the available evidence for the safety and efficacy of Unani herbal drugs and formulations in the prevention of Wabai Amraz (epidemic diseases) having resemblance to SARS-CoV-2. Sources of data for this paper are classical Unani textbooks, Unani pharmacopeia of India, Indian Medicinal Plants-An Illustrated Dictionary, and published articles in various reputed peer-reviewed journals. Collected information was then critically analyzed. Despite great efforts, no specific treatment has been discovered for coronavirus yet. The best choices, therefore, are prevention and management. The Unani system of medicine offers health protection during epidemics. Three important interventions practised during an outbreak are (i) purification of the environment by using certain herbal drugs as fumigants which include vinegar (acetic acid) alone or combined with Ferula foetida Regel; (ii) promotion of health and immune modulation by using the pharmacopoeial preparations Khamira-e-Khashkhash and Khamira-e-Marwareed. Several single drugs, as well as compound formulations, have been recommended in Unani medicine for the prevention and treatment of infectious diseases. The pharmacopoeial preparation Tiryaq-e-Nazla has been used for respiratory catarrhal inflammations and influenza by Hakims of the medieval period. Scientific research on these drugs reveals the presence of many pharmacologically active substances possessing significant antiviral, antipyretic, anti-tussive, and immune-modulatory properties, which can give new insight into infection and epidemic management.


Novel acetate polyoxomolybdate "host" accommodating a zigzag-chainlike "guest" of five edge-shared sodium cations: Na(21)[[Na(5)(H(2)O)(14)]within[Mo(46)O(134)(OH)(10)(mu-CH(3)COO)(4)]].CH(3)COONa. approximately equal to 95H(2)O.
A novel ESR-silent polyoxomolybdate Na(21)([Na(5)(H(2)O)(14)][Mo(46)O(134)(OH)(10)(mu-CH(3)COO)(4)]).CH(3)COONa.approximately equal to 90H(2)O (3) was simply synthesized in high yield by reducing an acidified aqueous solution of Na(2)MoO(4).2H(2)O and CH(3)COONa.3H(2)O. The structure of 3 is constructed by a 46-member crown-shaped anion, [Na(5)(H(2)O)(14)]within[Mo(V)(20)Mo(VI)(26)O(134)(OH)(10)(mu-CH(3)COO)(4)](21-), 3a, which is built up by three different but related building blocks in a new mode and further connected into layers via Na(+) and hydrogen bonds. Crystal data of compound 3: triclinic space group P(-1); a = 16.4065(3), b = 17.4236(2), c = 20.8247(3) A; alpha= 87.57, beta= 67.9810(10), gamma= 80.6970(10)o; V = 5445.08(14) A(3); Z = 1; D(calcd) = 2.902. Structure solution and refinement are based on 19014 reflections, R = 0.0750.


Cortical blood flow increases induced by stimulation of the substantia innominata in the unanesthetized rat.
The possible implication of projections from the substantia innominata (SI) to the cerebral cortex in the control of local cortical blood flow (CoBF) was studied in adult Fischer rats. Local blood flow (by helium clearance) and tissue gas partial pressures (pO2, pCO2) as metabolic indices, were measured in the frontal and parietal cortices in unanesthetized animals via chronically implanted probes connected to a mass spectrometer. Stimulating electrodes, also implanted chronically, were placed in the region of the SI. Out of 37 correctly located sites, 28 gave rise to cerebrovascular responses without significant hypertension or agitation. Both frontal (+114%) and parietal CoBF (+28%) increased significantly during ipsilateral 50 microA stimulation, but did not further significantly increase at 100 microA. Contralateral stimulation induced only small, non-significant effects. SI stimulation simultaneously increased cortical pO2 and decreased cortical pCO2, significantly more so in the frontal compared to the parietal cortex, and ipsilaterally compared to contralaterally. Both the CoBF and the tissue gas changes induced by SI stimulation were strongly potentiated by infusion of 0.15 mg/kg/h of the cholinomimetic agent physostigmine. The electrocorticogram (ECoG) was not systematically activated during the SI stimulation. The evidence presented favors a role for the cholinergic projections of the SI in control of CoBF (particularly frontal cortex), especially since the flow changes observed showed no obvious dependence on changes in local pCO2 or on paCO2, and could not be attributed to hypertension or behavioral changes.


Effect of exercise on the diurnal variation in energy substrate use during a high-fat diet.
Aerobic exercise increases 24-h fat oxidation following initiation of a high-fat diet. The objective of this study is to examine the time course of increased fat oxidation under exercise and sedentary conditions. Eighteen healthy subjects completed a randomized crossover design (sedentary and exercise visits) staying for five consecutive days in a metabolic chamber each visit. On day 1, 30% of energy intake was from fat; days 2-5 had 50% of energy as fat. During exercise, subjects rode on a stationary cycle at 45% of VO2max for 1 h in the mornings and evenings. Respiratory gases and urinary nitrogen were collected to calculate macronutrient oxidation and non-protein respiratory exchange ratio (NPRER). This data, collected continuously (24-h periods), were subsequently divided into three time segments: (1) exercise + recovery (1000-1200 hours, 2100-2200 hours), (2) sleep (2300-0645 hours), and (3) wake (all remaining hours). NPRER on exercise versus sedentary visits was lower for the sleep segment (0.77 ± 0.01 01 vs. 0.81 ± 0.01, p < 0.001), higher for the exercise + recovery segment (0.88 ± 0.01 vs. 0.86 ± 0.01, p < 0.001), and was not different for the wake segment. Fat oxidation was significantly higher for exercise versus sedentary treatments during sleep (41 ± 2 vs. 31 ± 2 g), wake (62 ± 3 vs. 51 ± 3 g), and exercise + recovery segments (33 ± 3 vs.16 ± 1 g), but so was fat intake by design (171 ± 8 vs. 128 ± 7 g/d). Although exercise showed greater fat oxidation during all segments, dietary fat intake was also higher. Therefore, based on NPRER, the time of day during which the exercise treatment increased the ratio of fat to carbohydrate oxidation was during sleep.


[Metal/alumine metallosis on tibial osteotomy. A case report].
Metallosis is mainly described in the hip joint at the time of wear or inappropriate use. Cases have also been reported in patients with a knee prosthesis, but never after tibial osteotomy. We report a rare case of metallosis resulting from metal-alumina contact after open wedge tibial osteotomy. The patient complained of pain, which was relieved after removal of the plate nine months after the first operation. Intraoperative inspection revealed metallosis at the synthesis site and local plate wear at zone of contact with the ceramic filler. Removal of the plate and cleaning of the metallosis zone led to full relief of the pain at one and a half months.


Hand surgery and hand therapy clinical practice guideline for epidermolysis bullosa.
WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: Epidermolysis bullosa (EB) causes blistering and scarring of the hands resulting in contractures fused web spaces and altered function. Surgery is needed to release contractures and web spaces and hand therapy is essential to maintain results, approaches for both differ. WHAT DOES THIS STUDY ADD?: These guidelines aim to provide information on the surgical and conservative therapeutic hand management of children and adults diagnosed with EB. They are based on available evidence and expert consensus to assist hand surgeons and therapists in decision making, planning and treatment. They highlight the importance of a holistic multidisciplinary team (MDT) approach, where patient priorities are paramount.


Stability in an age-structured metapopulation model.
We present a discrete model for a metapopulation of a single species with overlapping generations. Based on the dynamical behavior of the system in absence of dispersal, we have shown that a migration mechanism which depends only on age can not stabilize a previously unstable homogeneous equilibrium, but can drive a stable uncoupled system to instability if the migration rules are strongly related to age structure.


In-plane rotation analysis by two-wavelength electronic speckle interferometry.
A simple method is presented for the measurement of in-plane rotation (angle and sign) of an object by use of the conventional in-plane sensitive electronic speckle pattern interferometry technique combined with the two-wavelength laser diode method. The advantage of this method is that it can be used to measure the angle of rotation in a simple way by determination of fringe tilt. The experimental setup is described, and results are presented.


Testing between the TRACE model and the fuzzy logical model of speech perception.
The TRACE model of speech perception (McClelland & Elman, 1986) is contrasted with a fuzzy logical model of perception (FLMP) (Oden & Massaro, 1978). The central question is how the models account for the influence of multiple sources of information on perceptual judgment. Although the two models can make somewhat similar predictions, the assumptions underlying the models are fundamentally different. The TRACE model is built around the concept of interactive activation, whereas the FLMP is structured in terms of the integration of independent sources of information. The models are tested against test results of an experiment involving the independent manipulation of bottom-up and top-down sources of information. Using a signal detection framework, sensitivity and bias measures of performance can be computed. The TRACE model predicts that top-down influences from the word level influence sensitivity at the phoneme level, whereas the FLMP does not. The empirical results of a study involving the influence of phonological context and segmental information on the perceptual recognition of a speech segment are best described without any assumed changes in sensitivity. To date, not only is a mechanism of interactive activation not necessary to describe speech perception, it is shown to be wrong when instantiated in the TRACE model.


Effectiveness of speech therapy for aphasic stroke patients. A randomised controlled trial.
Aphasic stroke patients were randomly allocated to either a speech therapy group receiving treatment twice a week for 24 weeks or a no-treatment control group. Patients in both groups improved and there were no significant differences in language recovery between the 104 patients allocated to the treatment group and the 87 allocated to the no-treatment group. This treatment regimen, which is representative of clinical practice, is ineffective for most aphasic stroke patients.


Early diagnosis of spontaneous bacterial peritonitis: values of ascitic fluid variables.
In a search for clinical and laboratory factors that would aid in early diagnosis of spontaneous bacterial peritonitis, we identified two groups of patients with chronic liver disease and ascites: 1) 38 patients with 40 episodes of spontaneous bacterial peritonitis, and 2) 39 randomly selected patients with 40 sterile paracenteses who were matched for severity of liver dysfunction as a reference group. A variety of clinical and laboratory features were examined. The absolute lymphocyte count in peripheral blood was lower for the spontaneous bacterial peritonitis group (mean = 703/mm3 vs. 1,212/mm3, p less than 0.005). Four ascitic fluid variables, i.e., a white blood cell count of greater than or equal to 300/mm3, a polymorphonuclear leukocyte count of greater than or equal to 240/mm3, an ascitic fluid/serum LDH ratio of greater than or equal to 0.4, or an ascitic fluid/serum glucose ratio of less than or equal to 1.0, could separate the spontaneous bacterial peritonitis and reference groups with both sensitivity and specificity of greater than 70%. Although ascitic fluid total leucocyte and polymorphonuclear leucocyte counts are appropriate indicators for the early diagnosis of spontaneous bacterial peritonitis, the possibility of their false positivity should be warranted. The use of multiple tests including ascitic fluid/serum LDH and glucose ratios has better positive predictive value than a single test alone.


SMAD7 rs12953717 polymorphism contributes to increased risk of colorectal cancer.
Mothers against decapentaplegic homolog 7 (SMAD7) rs12953717 polymorphism has been implicated to alter the risk of colorectal cancer (CRC), but the results are controversial. The objective of this study was to quantitatively evaluate the association between SMAD7 rs12953717 polymorphism and CRC susceptibility. A comprehensive search was conducted to identify all eligible studies of SMAD7 rs12953717 polymorphism and CRC risk. Pooled odds ratio and 95% confidence interval were calculated using a fixed or random effects model. Statistical analysis was performed with Review Manager 5.0 and Stata 11. A total of 11 case-control studies, including 12,058 cases and 11,444 controls, were identified. The combined results based on all studies suggested that rs12953717 was associated with CRC risk under all genetic models. When stratifying for race, the data showed that the rs12953717 was associated with a significantly increased CRC risk under all genetic models in Caucasians. Statistically significant association was found in all genetic models except in recessive model comparison in the subgroup of Asians. After stratifying the studies by study design, there was a significant association between rs12953717 polymorphism and CRC risk under all genetic models in the subgroup of population-based studies. Our study suggests that rs12953717 polymorphism is associated with an increased CRC risk.


Safeguarding patients through continuing competency.
To ensure patient safety, it is crucial that nursing change the paradigm from demonstrating competency to continuing competency.


High-flexion knee designs: more hype than hope? In opposition.
High-Flexion knee designs are emerging to allow a safe prosthetic environment to facilitate higher ranges of motion than designs of the past. Early biochemical and clinical data support this effort.


Physical training under the influence of beta blockade in rats: effect on adrenergic responses.
Rats were trained by daily swimming or running exercises with and without daily propranolol injections. Both training methods resulted in cardiac enlargement, but only swimming exercise caused hypertrophy of the brown adipose tissue. These changes were antagonized by beta blockade. The size of the adrenals reflected the stress of the treatments, but other known stress parameters, such as the size of the thymus or sexual organs dit not. Only swimming training without beta blockade sensitized the rats to the calorigenic action of noradrenaline. The cooling rate of the rats in water, when taking into account the insulative capacity of the body, was decreased in swimming-trained as well as in propranolol-treated rats but increased in running-trained rats. The latter two changes may be due to circulatory alterations, while the delayed body cooling in swimming-trained rats probably results from increased heat production capacity. Training-induced resting bradycardia and enhanced tachycardic response to isoprenaline were observable only in the animal groups trained without beta blockade. The pressor response to noradrenaline tended to be higher in the trained groups and the propranolol-treated group than in the controls and was smaller in the animal groups trained under the influence of beta blockade. On the other hand, the hypotonic response to isoprenaline was smaller in the propranolol-treated and running-trained animals. The results emphasize the importance of the sympathetic nervous system in the adaptation of an organism to physical training.


Elimination of Dietary Triggers Is Successful in Treating Symptoms of Gastroesophageal Reflux Disease.
The relationship between aliments and pathophysiological abnormalities leading to gastroesophageal reflux disease (GERD) symptoms elicitation is unclear. Nevertheless, patients often report symptoms after ingestion of specific foods. To identify in primary care setting the presence of foods able to trigger GERD symptoms, and evaluate whether a consequent specific food elimination diet may result in clinical improvement. Diagnosis of GERD and quantification of reflux symptoms were done according to GERD-Q questionnaire (positive when > 8). During clinical data collection, patients were asked to report aliments associated with their symptoms. Also, a precompiled list of additional foods was administered to them. Then, patients were requested to eliminate the specific foods identified, and to come back for follow-up visit after 2 weeks when GERD-Q questionnaire and clinical data collection were repeated. One-hundred GERD (mean GERD-Q score 11.6) patients (54 females, mean age 48.7 years) were enrolled. Eighty-five patients reported at least one triggering food, mostly spicy foods (62%), chocolate (55%), pizza (55%), tomato (52%), and fried foods (52%). At follow-up visit, the diagnosis of GERD was confirmed in only 55 patients, and the mean GERD-Q score decreased to 8.9. Heartburn reporting decreased from 93 to 44% of patients, while regurgitation decreased from 72 to 28%. About half of the patients agreed to continue with only dietary recommendations. Most patients with GERD can identify at least one food triggering their symptoms. An approach based on abstention from identified food may be effective in the short term.


Immunological deficiencies: more frequent than they seem to be.
A review article was carried out, addressing the clinical and epidemiological characteristics of immune system deficiencies, which are associated with or predispose to recurrent infectious processes, autoimmune diseases, auto inflammatory diseases, or neoplasms, and which are classified as inborn errors of immunity (IEI) and secondary immunodeficiencies (SID). Emphasis was placed on the classification of the main signs and symptoms for each organ and system, which will serve as warning signs, to guide the pediatrician in the investigation of the main IEI. In addition, the main secondary changes in the immune system triggered by infections (with emphasis on COVID-19), drugs, chronic diseases, metabolic and nutritional disorders were identified. This review included articles published in the last five years and that were identified in the MEDLINE platform (PubMed). The recurrence of infectious processes, associated with the severity of the condition and/or unusual profile of the infectious agent, always related to the age range of symptom onset, are the most important findings for suspected diagnosis. Considering this scenario, immunity disorders should be part of the investigation carried out by the general pediatrician, whether they are the innate errors of immunity (primary immunodeficiencies) or secondary immunodeficiencies, so that the diagnosis is attained as early as possible and therapeutic measures are implemented, reducing the morbidity and mortality of these patients.


Mild traumatic brain injury exacerbates Parkinson's disease induced hemeoxygenase-2 expression and brain pathology: Neuroprotective effects of co-administration of TiO2 nanowired mesenchymal stem cells and cerebrolysin.
Mild traumatic brain injury (mTBI) is one of the leading predisposing factors in the development of Parkinson's disease (PD). Mild or moderate TBI induces rapid production of tau protein and alpha synuclein (ASNC) in the cerebrospinal fluid (CSF) and in several brain areas. Enhanced tau-phosphorylation and ASNC alters the molecular machinery of the brain leading to PD pathology. Recent evidences show upregulation of constitutive isoform of hemeoxygenase (HO-2) in PD patients that correlates well with the brain pathology. mTBI alone induces profound upregulation of HO-2 immunoreactivity. Thus, it would be interesting to explore whether mTBI exacerbates PD pathology in relation to tau, ASNC and HO-2 expression. In addition, whether neurotrophic factors and stem cells known to reduce brain pathology in TBI could induce neuroprotection in PD following mTBI. In this review role of mesenchymal stem cells (MSCs) and cerebrolysin (CBL), a well-balanced composition of several neurotrophic factors and active peptide fragments using nanowired delivery in PD following mTBI is discussed based on our own investigation. Our results show that mTBI induces concussion exacerbates PD pathology and nanowired delivery of MSCs and CBL induces superior neuroprotection. This could be due to reduction in tau, ASNC and HO-2 expression in PD following mTBI, not reported earlier. The functional significance of our findings in relation to clinical strategies is discussed.


Confirmation of a balanced chromosomal translocation using molecular techniques.
Investigation of a couple, who had produced three babies with cri du chat syndrome, showed initially that the mother had an apparent deletion of chromosome 5. It seemed likely that she had a balanced chromosomal translocation but it proved impossible to detect the second chromosome involved using routine cytogenetic methods. Molecular techniques using quantitative hybridization dosage studies were performed and these showed that the mother had a double dose of DNA in the suspected deleted area of chromosome 5. Further studies, using in situ hybridization techniques, revealed that the missing segment of chromosome 5 had translocated onto the short arms of a C group chromosome and further analysis of prometaphase chromosomes showed the presence of a balanced translocation, 46,XY,t(5;9)(5qter----5p14.1::9p22----9pter;9 qter----9p22::5p14.1----5pter). As a result of these findings, it was possible to offer prenatal diagnosis to the patient in future pregnancies, by detecting the presence of a balanced or unbalanced translocation in the fetus using molecular and cytogenetic techniques.


Moniliformin production byFusarium species isolated from Argentinian corn.
Forty-one isolates ofFusarium obtained from the main Argentinian corn production area were tested for their ability to produce moniliformin. One of 22 isolates ofF. moniliforme, 2/10 of F.proliferatum and 3/9 ofF. subglutinans, produced moniliformin in a range between 0,3 to 2,7 mg/g. These data represent the first report of the production of moniliformin byFusarium species from section Liseola in Argentina.


The prevalence and clinical implications of pancreatic fat accumulation identified during a medical check-up.
Fatty pancreas (FP) is characterized by pancreatic fat accumulation and the subsequent development of pancreatic and metabolic complications. However, FP has not been categorized in the manual for abdominal ultrasound in cancer screening and health check-ups in Japan, and the pathology of FP has not been fully elucidated.Nine hundred and nineteen people who underwent a medical check-up had the severity of their pancreatic fat accumulation categorized after transabdominal ultrasonographic examination. The relationships between FP, lifestyle-related diseases, and fatty liver disease at this time were assessed using stratification analysis.The prevalence of FP was 46.8% (430/919). People with FP were more likely to be male and had higher prevalences of lifestyle-related diseases, including fatty liver disease. Men and women were similarly represented in each tertile of pancreas brightness. Older age; high waist circumference, triglyceride and glucose index, serum low-density lipoprotein-cholesterol, hepatic steatosis index; and low serum amylase were associated with the presence of severe FP. Moreover, the group with severe liver steatosis had a higher prevalence of FP and a higher pancreatic brightness score. Logistic regression analysis showed that individuals with liver steatosis were more likely to have severe FP.The severity of FP is associated with features of lifestyle-related diseases and the severity of liver steatosis. These findings suggest that high visceral fat content is associated with more severe fatty pancreas as a phenotype of ectopic fat accumulation, as well as fatty liver disease.


Drug-repositioning opportunities for cancer therapy: novel molecular targets for known compounds.
Drug repositioning is gaining increasing attention in drug discovery because it represents a smart way to exploit new molecular targets of a known drug or target promiscuity among diverse diseases, for medical uses different from the one originally considered. In this review, we focus on known non-oncological drugs with new therapeutic applications in oncology, explaining the rationale behind this approach and providing practical evidence. Moving from incompleteness of the knowledge of drug-target interactions, particularly for older molecules, we highlight opportunities for repurposing compounds as cancer therapeutics, underling the biologically and clinically relevant affinities for new targets. Ideal candidates for repositioning can contribute to the therapeutically unmet need for more-efficient anticancer agents, including drugs that selectively target cancer stem cells.


Impact of the post-COVID-19 condition on health care after the first disease wave in Lombardy.
Lombardy was affected in the early months of 2020 by the SARS-CoV-2 pandemic with very high morbidity and mortality. The post-COVID-19 condition and related public health burden are scarcely known. Using the regional population administrative database including all the 48,932 individuals who survived COVID-19 and became polymerase-chain-reaction negative for SARS-CoV-2 by 31 May 2020, incident mortality, rehospitalizations, attendances to hospital emergency room, and outpatient medical visits were evaluated over a mid-term period of 6 months in 20,521 individuals managed at home, 26,016 hospitalized in medical wards, and 1611 in intensive care units (ICUs). These data were also evaluated in the corresponding period of 2019, when the region was not yet affected by the pandemic. Other indicators and proxies of the health-care burden related to the post-COVID condition were also evaluated. In individuals previously admitted to the ICU and medical wards, rehospitalizations, attendances to hospital emergency rooms, and out-patient medical visits were much more frequent in the 6-month period after SARS-CoV-2 negativization than in the same prepandemic period. Performances of spirometry increased more than 50-fold, chest CT scans 32-fold in ICU-admitted cases and 5.5-fold in non-ICU cases, and electrocardiography 5.6-fold in ICU cases and twofold in non-ICU cases. Use of drugs and biochemical tests increased in all cases. These results provide a real-life picture of the post-COVID condition and of its effects on the increased consumption of health-care resources, considered proxies of comorbidities.


Second eye involvement in age-related macular degeneration: a four-year prospective study.
Age-related macular degeneration (AMD) usually affects both eyes over time. Among patients with advanced AMD in one eye estimates of the risk to the second eye have been diversely reported. Therefore we examined, over a four year period, the rate of second eye involvement in 41 patients with either exudative or advanced atrophic AMD in one eye, and early macular changes in the second eye with best corrected vision of 20/30 or better. The cumulative risk of developing either exudative AMD or atrophic AMD and 20/80 or less vision in the second eye was 23% at four years. The cumulative risk of losing 10 or more letters on the ETDRS visual acuity chart in the second eye was 35% at four years. These results are discussed in relation to previously reported rates of second eye involvement in AMD.


Radiation exposure during panoramic radiography in children.
In an effort to determine the amount of radiation exposure a child receives during a panoramic radiograph and to evaluate the effect of a protective thyroid collar, dosimeter readings were made on twenty-nine child patients at fourteen anatomic sites. The levels of radiation recorded were similar to those previously recorded for adults and phantoms, except for greater doses in the thyroid area. Placement of a lead-lined thyroid collar resulted in significant reduction of the thyroid doses.


Combination therapy for multiple myeloma.
The effect of six different chemotherapy regimens were evaluated in 462 previously untreated patients with multiple myeloma. In comparison with other treatments, drug combinations that included vincristine and were given at 3-week intervals were associated with higher response rates and longer survival times. No gain was noted from the use of Adriamycin or from combinations of alkylating agents unless vincristine was given and the treatment intervals were short. Seventy-one responding patients were allocated at random to maintenance treatment with intermittent courses of either azathioprine--prednisone or a combination of melphalan--cyclophosphamide--carmustine (BCNU)--prednisone. The survival time was not prolonged with either maintenance treatment in comparison with that for responding patients continued on other therapies or on no therapy in previous studies. Attempts to reduce tumor was maximally with a change in the therapeutic modality, such as with immunotherapy or radiotherapy, remain to be evaluated.


Pseudo Wellens T-waves in patients with suspected myocardial infarction: how cardiac magnetic resonance imaging can help the diagnosis.
Wellens' syndrome is characterized by symmetrically inverted T-waves in the precordial leads suggestive of impending myocardial infarction due to a critical proximal left anterior descending (LAD) stenosis. We describe three unusual cases of patients with such electrocardiographic abnormality in which coronary angiography ruled out the presence of critical coronary stenosis and cardiac magnetic resonance imaging excluded the presence of acute or chronic myocardial infarction.


Efficient Brain Tumor Detection with Lightweight End-to-End Deep Learning Model.
In the field of medical imaging, deep learning has made considerable strides, particularly in the diagnosis of brain tumors. The Internet of Medical Things (IoMT) has made it possible to combine these deep learning models into advanced medical devices for more accurate and efficient diagnosis. Convolutional neural networks (CNNs) are a popular deep learning technique for brain tumor detection because they can be trained on vast medical imaging datasets to recognize cancers in new images. Despite its benefits, which include greater accuracy and efficiency, deep learning has disadvantages, such as high computing costs and the possibility of skewed findings due to inadequate training data. Further study is needed to fully understand the potential and limitations of deep learning in brain tumor detection in the IoMT and to overcome the obstacles associated with real-world implementation. In this study, we propose a new CNN-based deep learning model for brain tumor detection. The suggested model is an end-to-end model, which reduces the system's complexity in comparison to earlier deep learning models. In addition, our model is lightweight, as it is built from a small number of layers compared to other previous models, which makes the model suitable for real-time applications. The optimistic findings of a rapid increase in accuracy (99.48% for binary class and 96.86% for multi-class) demonstrate that the new framework model has excelled in the competition. This study demonstrates that the suggested deep model outperforms other CNNs for detecting brain tumors. Additionally, the study provides a framework for secure data transfer of medical lab results with security recommendations to ensure security in the IoMT.


Evaluating child sexual abuse. Observations regarding ano-genital injury.
The records of 944 children who had been examined by one pediatrician for alleged sexual abuse were analyzed. Sixty-four percent of the females and 34 percent of the males had positive findings suggestive of ano-genital injury. The data indicated that in girls with no evidence of injury, the hymenal opening diameter varied directly with age, but in those with evidence of injury, the opening size could not be correlated with age.


HIC1 tumour suppressor gene is suppressed in acute myeloid leukaemia and induced during granulocytic differentiation.
A hallmark of acute myeloid leukaemia (AML) is a block in differentiation caused by deregulated gene expression. The tumour suppressor Hypermethylated In Cancer 1 (HIC1) is a transcriptional repressor, which is epigenetically silenced in solid cancers. HIC1 mRNA expression was found to be low in 128 patient samples of AML and CD34+ progenitor cells when compared with terminally differentiated granulocytes. HIC1 mRNA was induced in a patient with t(15;17)-positive acute promyelocytic leukaemia receiving all-trans retinoic acid (ATRA) therapy. We therefore investigated whether HIC1 plays a role in granulocytic differentiation and whether loss of function of this gene might contribute to the differentiation block in AML. We evaluated HIC1 mRNA levels in HL-60 and U-937 cells upon ATRA-induced differentiation and in CD34+ progenitor cells after granulocyte colony-stimulating factor-induced differentiation. In both models of granulocytic differentiation, we observed significant HIC1 induction. When HIC1 mRNA was suppressed in HL-60 cells using stably expressed short hairpin RNA targeting HIC1, granulocytic differentiation was altered as assessed by CD11b expression. Bisulphite sequencing of GC-rich regions (CpG islands) in the HIC1 promoter provided evidence that the observed suppression in HL-60 cells was not because of promoter hypermethylation. Our findings indicate a role for the tumour suppressor gene HIC1 in granulocytic differentiation. Low expression of HIC1 may very well contribute to pathogenic events in leukaemogenesis.


Independent induction of caspase-8 and cFLIP expression during colorectal carcinogenesis in sporadic and HNPCC adenomas and carcinomas.
TNF-Related Apoptosis Inducing Ligand (TRAIL) is a promising agent for the induction of apoptosis in neoplastic tissues. Important determinants of TRAIL sensitivity are two intracellular proteins of the TRAIL pathway, caspase-8 and its anti-apoptotic competitor cellular Flice-Like Inhibitory Protein (cFLIP). The aim of this study was to investigate basic expression of caspase-8 and cFLIP in normal colorectal epithelium (n=20), colorectal adenomas (n=66) and colorectal carcinomas (n=44) using immunohistochemistry performed on both sporadic and Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Lynch syndrome)-associated adenomas and carcinomas. Expression of both caspase-8 and cFLIP was similar in cases with sporadic and hereditary origin. Expression of caspase-8 in colorectal adenomas and carcinomas was increased when compared to normal colon tissue (P=0.02). Nuclear, paranuclear as well as cytoplasmic localizations of caspase-8 were detected. Immunohistochemistry revealed an upregulation of cFLIP in colorectal carcinomas in comparison to normal epithelium and colorectal adenomas (P<0.001). A large variation in the caspase-8/cFLIP ratio was observed between the individual adenomas and carcinomas. Caspase-8 and cFLIP are upregulated during colorectal carcinogenesis. Upregulation of caspase-8 and/or downregulation of cFLIP may be interesting approaches to maximize TRAIL sensitivity in colorectal neoplasms.


Examining the mechanisms that link β-amyloid and α-synuclein pathologies.
β-amyloid (Aβ) and α-synuclein (α-syn) are aggregation-prone proteins typically associated with two distinct neurodegenerative disorders: Alzheimer's disease (AD) and Parkinson's disease. Yet α-syn was first found in association with AD plaques several years before being linked to Parkinson's disease or Lewy body formation. Nowadays, a large subset of AD patients (~50%) is well recognized to co-exhibit significant α-syn Lewy body pathology. Unfortunately, these AD Lewy body variant patients suffer from additional symptoms and an accelerated disease course. Basic research has begun to show that Aβ and α-syn may act synergistically to promote the aggregation and accumulation of each other. While the exact mechanisms by which these proteins interact remain unclear, growing evidence suggests that Aβ may drive α-syn pathology by impairing protein clearance, activating inflammation, enhancing phosphorylation, or directly promoting aggregation. This review examines the interactions between Aβ and α-syn and proposes potential mechanistic links between Aβ accumulation and α-syn pathogenesis.


2020-2021 AMMI Canada guidance on the use of antiviral drugs for influenza in the setting of co-circulation of seasonal influenza and SARS-CoV-2 viruses in Canada.
We provide an update to the Association of Medical Microbiology and Infectious Disease Canada foundation guidance for the upcoming 2020-2021 influenza season in Canada. Important issues for this year include the implications of co-circulation of SARS-CoV-2, the role of diagnostic testing, and a restatement of dosing and administration recommendations for neuraminidase inhibitors in various age groups and underlying health conditions. Although peramivir and baloxivir are now licensed in Canada, neither is currently marketed, so this guidance focuses on further optimizing the use of oseltamivir and zanamivir.


Interactions between freshwater snails and tadpoles: competition and facilitation.
Freshwater snails and anuran tadpoles have been suggested to have their highest population densities in ponds of intermediate size where abiotic disturbance (e.g. desiccation) is low and large predators absent. Both snails and tadpoles feed on periphytic algae and, thus, there should be a large potential for competitive interactions to occur between these two distantly related taxa. In a field experiment we examined the relative strength of competition between two closely related snail species, Lymnaea stagnalis and L. peregra, and between L. stagnalis and tadpoles of the common frog, Rana temporaria. Snail growth and egg production and tadpole size at and time to metamorphosis were determined. Effects on the common food source, periphyton, were monitored with the aid of artificial substrates. Periphyton dry weight was dramatically reduced in the presence of snails and/or tadpoles. There were no competitive effects on growth or egg production of the two snail species when they were coexisting. Mortality of L. peregra was high (95%) after reproduction, but independent of treatment. Growth of L. stagnalis was reduced only at the highest tadpole densities, whereas egg production was reduced both by intraspecific competition and by competition with tadpoles. Differences in egg production were retained after tadpole metamorphosis. Tadpole larval period increased, weight of metamorphosing frogs decreased and growth rate was reduced as a function of increasing tadpole density. However, contrary to expectation, snails had a positive effect on tadpole larval period, weight and growth rate. Further, in experimental containers without snails there was a dense growth of the filamentous green alga Cladophora sp. We suggest that the facilitative effects of snails on tadpoles are due to an "indirect mutualistic" mechanism, involving competition between food sources of different quality (microalgae and Cladophora sp.) and tadpoles being competitively dominant over snails for the preferred food source (microalgae). In the presence of tadpoles snails will be forced to feed on low-quality Cladophora, increasing nutrient turnover rates, which results in enhanced productivity of microalgae, increasing tadpole food resources. Thus, tadpoles have a negative effect on snails through resource depression, while snails facilitate tadpole growth through an indirect enhancement of food availability.


Child injuries in Lebanon: assessing mothers' injury prevention knowledge attitude and practices.
Childhood injury is a neglected public health problem with a sizeable burden on children's well-being and their families. This study aims to describe the pattern and types of childhood injuries and to determine the level of mothers' Knowledge, Attitude, and Practices (KAP) towards childhood injury prevention in Lebanon. The study further examines the association between childhood injury occurrence and mothers' supervision. This cross-sectional study recruited mothers of children aged up to 10 years from multiple sites (i.e., a medical center, a private clinic, a healthcare facility, and a refugee camp clinic). Data were collected on mothers' KAP toward childhood injuries using self-administrated questionnaires. A summation score for KAP correct answers was calculated and descriptive and statistical analyses were performed to measure the association between the outcomes. A total of 264 mothers were surveyed and injury data were collected on their 464 children. The prevalence of childhood injury was 20% in the past 12 months, mostly sustained by males (53.8%) and children aged 5-10 years (38.7%). The most common type of injury was fall (48.4%), followed by burns (%7.5), and sports injuries (7.5%). Hospitalized children were more likely to be males and older than 5 years (p < 0.001). More than one-third of the mothers demonstrated poor knowledge, while the majority showed poor practice (54.4%), and fair attitude (45.6%) towards child injury prevention. Children of working mothers have three times higher odds of sustaining injuries (OR: 2.95, 95% CI: 1.60;5.47) compared to those of non-working mothers, accounting for possible confounders (p = 0.001). Childhood injuries represent a major health problem in Lebanon. Findings from this study showed that mothers are less knowledgeable and unprepared to prevent their children from getting injured. Educational programs are much needed to address the gap in the mothers' KAP toward child injury prevention. Further studies are recommended to understand the cultural context and examine its key determinants to identify effective strategies and develop tailored interventions for preventing childhood injuries.


Localization of acid phosphatase in lysosomes of pituitary folliculo-stellate cells following estrogen withdrawal from primed male rats.
Acid phosphatase was localized in lysosomes of non-granulated, folliculo-stellate pituitary cells 72 h after estrogen was withdrawn from primed male rats. The appearance of lysosomes and the accumulation of lipid droplets in folliculo-stellate cells coincide with the clearance of lipid from pituitary mammotropes. Positive identification of lysosomes supports our proposal in a previous study that folliculo-stellate cells are phagocytic.


Articaine Infiltrations of the Mandibular Lateral Incisor-Is It Volume or Location of the Infiltrations That Affect Success? A Prospective, Randomized Crossover Study.
A combination labial infiltration (1.8 mL) plus lingual infiltration (1.8 mL) of 4% articaine with 1:100,000 epinephrine in the mandibular lateral incisor was found superior to a labial infiltration of 1.8 mL of the same solution. However, it is not known whether the volume or the location had the greatest effect. Therefore, the purpose of this prospective, randomized crossover study was to determine the anesthetic efficacy of a labial infiltration of a 3.6 mL volume of 4% articaine with 1:100,000 epinephrine compared with labial infiltration (1.8 mL) plus lingual infiltration (1.8 mL) of 4% articaine with 1:100,000 epinephrine in the mandibular lateral incisor. One hundred subjects randomly received 2 sets of injections, using 4% articaine with 1:100,000 epinephrine, consisting of labial and lingual infiltrations of 1.8 mL (3.6 mL total) and 2 labial infiltrations of 1.8 mL (3.6 mL total) of the mandibular lateral incisor in 2 separate appointments. Electric pulp testing was used to determine anesthetic success (highest 80/80 reading). The data were analyzed statistically. The labial and lingual combination exhibited a significantly higher anesthetic success rate (97%) when compared with the 2 labial infiltrations (74%) and had significantly higher 80/80s readings from 1 minute to 58 minutes. Within the limitations of this clinical study, a combination labial plus lingual infiltration using a 3.6-mL volume of 4% articaine with 1:100,000 epinephrine significantly increased pulpal anesthetic success for the mandibular lateral incisor when compared with a labial infiltration using a 3.6-mL volume of articaine. Therefore, location of the infiltrations was more important than volume.


BRAF V600 Mutation Detection in Plasma Cell-Free DNA: NCCTG N0879 (Alliance).
To evaluate the prognostic significance of detectable circulating cell-free DNA (cfDNA) BRAF V600E/K mutations in patients with advanced melanoma enrolled in a clinical trial without BRAF-targeted therapy. BRAF V600E/K mutation status was determined on archived tissue and pretreatment stored plasma from 149 patients with unresectable stage IV melanoma who were enrolled between May 5, 2010 and May 2, 2014 in the North Central Cancer Treatment Group/Alliance N0879 randomized phase 2 clinical trial. Results were reported as presence or absence of cfDNA BRAF V600E/K detection of assay vs tissue. Progression-free survival (PFS) and overall survival (OS) were assessed for patients with and without detectable BRAF mutation. In total, 63 of 149 (42.3%) patients had BRAF V600E/K results for tissue and blood, and 20 of 63 (31.7%) patients had tissue-diagnosed mutant BRAF. Of these, 11 of 20 (55.0%) patients had detectable plasma cfDNA BRAF. Among patients with tissue-mutant BRAF V600E/K, PFS and OS were shorter for those with corresponding cfDNA mutations (PFS, 5.8 vs 12.0 months; P=.051; OS, 9.2 vs 27.1 months; P=.054). Our assay demonstrated sensitivity of 55% (95% CI, 0.322 to 0.768), specificity of 97.7% (95% CI, 0.932 to 1.000), positive predictive value of 91.7% (95% CI, 0.760 to 1.000), and negative predictive value of 82.4% (95% CI, 0.719 to 0.928). In advanced melanoma, detectable cfDNA BRAF V600E/K mutation is present in about half the patients with stage IV with BRAF-mutant melanoma tumor tissue and appears to confer a poorer prognosis when detectable. Given the poorer prognosis, cfDNA can be used to risk-stratify patients with metastatic melanoma in practice or clinical trials.Trial Registration: clinicaltrials.gov Identifier: NCT00976573.


Relationship between the trochlear groove angle and patellar cartilage morphology defined by 3D spoiled gradient-echo imaging.
To examine whether the femoral trochlear groove angle (TGA) is a determinant of the patellar cartilage volume and patellar cartilage damage. Patellar cartilage was evaluated by MR imaging in 66 patients (22 males and 44 females) with knee pain. Fat-suppressed 3D spoiled gradient-echo images were used to calculate the cartilage volume and to grade the cartilage damage. The proximal and distal TGAs were measured from axial PD-weighted FSE MR images with fat suppression. For every increase in the TGA at the distal femur, the patellar cartilage volume was significantly increased by 6.07 × 10(-3) cm(3) (95% CI: 1.27 × 10(-3), 10.9 × 10(-3)) after adjustment for age, gender, and patellar bone volume (P < 0.05). The MR grade of medial patellar cartilage damage progressed as the distal TGA became narrower, although there was no significant correlation between the distal TGA and the MR grading of patellar cartilage damage. A more flattened distal TGA was associated with increased patellar cartilage volume. However, there was no association between TGA and patellar cartilage defects.


Lymphocyte stimulation in multiple sclerosis patients untreated and treated with transfer factor. Long-term studies on the effect of different stimulants on myo-(2-3H)inositol incorporation into phosphatidylinositol of lymphocytes.
The lymphocytes from controls, untreated MS and MS patients treated with transfer factor were stimulated with PHA, PWM, PPD, LPS and MA and the increased incorporation of myoinositol into phosphatidylinositides was determined. As compared with controls, the untreated MS patients revealed significantly lower index of stimulation with PHA, LPS, PPD and MA. The response of lymphocytes from MS patients treated with transfer factor was intermediate. No correlation between disease progression and stimulation of inositol incorporation was observed. Analysis of variance showed that the myoinositol test is not applicable in long-term studies to distinguished single subjects, however it is useful to determine differences between MS patients and controls.


Umbilical cord prolapse.
Umbilical cord prolapse is an obstetric emergency that can have negative outcomes for the fetus. It is diagnosed by a palpable or visible cord and is often accompanied by severe, rapid fetal heart rate decelerations. Cases of cord prolapse should be delivered as soon as possible, usually by cesarean section. While awaiting delivery, the fetal presenting part should be elevated off the cord either manually or by filling the bladder. Although an untreated case of umbilical cord prolapse can lead to severe fetal morbidity and mortality, prompt and appropriate management leads to good overall outcomes.


Imaging of the posterior pelvic floor.
Disorders of the posterior pelvic floor are relatively common. The role of imaging in this field is increasing, especially in constipation, prolapse and anal incontinence, and currently imaging is an integral part of the investigation of these pelvic floor disorders. Evacuation proctography provides both structural and functional information for rectal voiding and prolapse. Dynamic MRI may be a valuable alternative as the pelvic floor muscles are visualised, and it is currently under evaluation. Endoluminal imaging is important in the management of anal incontinence. Both endosonography and endoanal MRI can be used for detection of anal sphincter defects. Endoanal MRI has the advantage of simultaneously evaluating external sphincter atrophy, which is an important predictive factor for the outcome of sphincter repair. Many aspects of constipation and prolapse remain incompletely understood and treatment is partly empirical; however, imaging has a central role in management to place patients into treatment-defined groups.


Susceptibility of Tmax to tracer delay on perfusion analysis: quantitative evaluation of various deconvolution algorithms using digital phantoms.
The time-to-maximum of the tissue residue function (T(max)) perfusion index has proven very predictive of infarct growth in large clinical trials, yet its dependency on simple tracer delays remains unknown. Here, we determine the dependency of computed tomography (CT) perfusion (CTP) T(max) estimates on tracer delay using a range of deconvolution techniques and digital phantoms. Digital phantom data sets simulating the tracer delay were created from CTP data of six healthy individuals, in which time frames of the left cerebral hemisphere were shifted forward and backward by up to ±5 seconds. These phantoms were postprocessed with three common singular value decomposition (SVD) deconvolution algorithms-standard SVD (sSVD), block-circulant SVD (bSVD), and delay-corrected SVD (dSVD)-with an arterial input function (AIF) obtained from the right middle cerebral artery (MCA). The T(max) values of the left hemisphere were compared among different tracer delays and algorithms by a region of interest-based analysis. The T(max) values by sSVD were positively correlated with 'positive shifts' but unchanged with 'negative shifts,' those by bSVD had an excellent positive linear correlation with both positive and negative shifts, and those by dSVD were relatively constant, although slightly increased with the positive shifts. The T(max) is a parameter highly dependent on tracer delays and deconvolution algorithm.


Meat safety legislation and its opportunities and hurdles for innovative approaches: A review.
Albert Einstein has been quoted "We cannot solve our problems with the same thinking we used when we created them". Innovations are necessary to meet future challenges regarding sustainability, animal welfare, slaughter hygiene, meat safety and quality, not at least for optimal balance between these dimensions. The red meat safety legislation texts from Europe, New Zealand, USA, and global guidelines, were analysed for normative formulations ("how it is or should be done") that may create non-intentional hurdles to innovation and new technology. Detailed descriptions of slaughtering techniques and meat processes may hinder innovative processing from being investigated and implemented. The identified problematic normative phrases typically either conserve conventional technologies or organisation of the work, prescribe solutions where no established method, objective criteria or limits exits, or put forward visions impossible to obtain. The Codex Alimentarius was found to have less normative formulations and more functional demands ("what to achieve") than the national and regional regulations. European, New Zealand's and US' legislation share many similarities and challenges, and they all reflect the prevailing processing methods. Consequences are briefly commented, and alternative objective functional demands suggested. Normative legislation texts provide familiar context easier to understand, but also make legislation voluminous. This review underlines the mutual dependency between risk-based legislation and conditional flexibility, and between functional demands and control activities targeted on measurable objective criteria. The legislation does not have to be either or. Objective normative phrases in legislation can function as a least common multiple if alternative methods are allowed on condition that they fulfil objective criteria. Context and practical advice should mainly come from textbooks, consultants, white papers and in Food Business Operator's own guidelines, among others.


Association of established thyroid peroxidase autoantibody (TPOAb) genetic variants with Hashimoto's thyroiditis.
Hashimoto's thyroiditis (HT) is the most common form of autoimmune thyroid diseases (AITD) characterized by progressive destruction of thyroid tissue that may lead to hypothyroidism. High thyroid autoantibodies against thyroid peroxidase (TPOAb) levels are present in 90% of patients with HT and serve as a clinical marker for the detection of early AITD/HT. The main aim of our study was to test whether recently identified genetic variants associated with TPOAb are also involved in HT development. A total of 504 unrelated individuals, including 200 patients with HT and 304 controls, were involved in this study. Diagnosis of HT cases was based on clinical examination, measurement of thyroid hormones (TSH and fT4) and antibodies (TgAb, TPOAb) and ultrasound examination. We selected and genotyped 14 known TPOAb-associated genetic variants. Case-control logistic regression model was used to test the association of selected genetic variants with HT. Additionally, we tested association of the same genetic variants with thyroid related quantitative traits (TPOAb levels, TgAb levels and thyroid gland volume) using linear regression. Three genetic variants showed nominal association with HT; rs10774625 in ATXN2 gene (p = 0.0149, OR = 0.73, CI = 0.56-0.94), rs7171171 near RASGRP1 gene (p = 0.0356, OR = 1.4, CI = 1.02-1.92) and rs11675434 in TPO gene (p = 0.041, OR = 1.31, CI = 1.01-1.69). Two of these SNPs (rs1077462, rs11675434) also showed association with TPOAb levels (p = 0.043, β = -0.39; p = 0.042, β = 0.40, respectively) and one (rs7171171) was associated with thyroid gland volume (p = 0.0226, β = -0.21). Our findings suggest that variants inside or near TPO, ATXN2 and RASGRP1 genes are associated with HT. Identified loci are novel to HT and represent good basis for further exploration of HT susceptibility.


Lipopolysaccharide exposure during late embryogenesis results in diminished locomotor activity and amphetamine response in females and spatial cognition impairment in males in adult, but not adolescent rat offspring.
Numerous basic and epidemiological studies have connected prenatal maternal immune activation with the occurrence of schizophrenia and/or autism. Depending on subtle differences in protocols of the used animal model, a variety of behavioral abnormalities has been reported. This study investigated behavioral differences in Wistar rat offspring of both genders, exposed to the 100 μg/kg per day dose of lipopolysaccharide (LPS) in late embryogenesis (embryonic days 15 and 16), while tested at their adolescent and young adult age (postnatal days 40 and 60, respectively). Immune activation was confirmed by detecting high levels of TNF-α and IL-6 in dam blood withdrawn 2h after the first dose of LPS. The animals were assessed in three consecutive trials of locomotor activity (novelty exploration, response to i.p. saline injection and challenge with 0.5mg/kg amphetamine), Morris water maze and social interaction tests. Overt behavioral dysfunction was perceived in adult rats only, and these changes were gender-distinctive. When compared with control rats, LPS females displayed baseline hypolocomotion and a decreased reactivity to amphetamine, while LPS males exhibited spatial learning (acquisition trials) and memory (probe trial) impairments. Prenatal treatment did not affect the time spent in social interaction. As maternal exposure to LPS in late gestation resulted in behavioral changes in offspring in early adulthood, it may model schizophrenia-like, but not autism-like endophenotypes. However, lack of a potentiated response to amphetamine testified that this model could not mimic positive symptoms, but rather certain traits of cognitive dysfunction and deficit symptoms, in males and females, respectively.


Optimally-weighted non-linear beamformer for conventional focused beam ultrasound imaging systems.
A novel non-linear beamforming method, namely, filtered delay optimally-weighted multiply and sum (F-DowMAS) beamforming is reported for conventional focused beamforming (CFB) technique. The performance of F-DowMAS was compared against delay and sum (DAS), filtered delay multiply and sum (F-DMAS), filtered delay weight multiply and sum (F-DwMAS) and filter delay Euclidian weighted multiply and sum (F-DewMAS) methods. Notably, in the proposed method the optimal adaptive weights are computed for each imaging point to compensate for the effects due to spatial variations in beam pattern in CFB technique. F-DowMAS, F-DMAS, and DAS were compared in terms of the resulting image quality metrics, Lateral resolution (LR), axial resolution (AR), contrast ratio (CR) and contrast-to-noise ratio (CNR), estimated from experiments on a commercially available tissue-mimicking phantom. The results demonstrate that F-DowMAS improved the AR by 57.04% and 46.95%, LR by 58.21% and 53.40%, CR by 67.35% and 39.25%, and CNR by 44.04% and 30.57% compared to those obtained using DAS and F-DMAS, respectively. Thus, it can be concluded that the newly proposed F-DowMAS outperforms DAS and F-DMAS. As an aside, we also show that the optimal weighting strategy can be extended to benefit DAS.


Erratum: Bicyclol attenuates high fat diet-induced non-alcoholic fatty liver disease/non-alcoholic steatohepatitis through modulating multiple pathways in mice.
[This corrects the article DOI: 10.3389/fphar.2023.1157200.].


Lactobacillus rhamnosus GG and HbA1c in middle age and older adults without type 2 diabetes mellitus: A preliminary randomized study.
Probiotic supplementation improves glycemic control in persons with diabetes and the current study examined whether these benefits extend to healthy individuals. The current study was a 90-day placebo-controlled, double-blind, randomized clinical trial of Lactobacillus rhamnosus GG in healthy middle-aged and older adults. Fasting blood glucose and HbA1c were quantified at baseline and follow up. ANCOVA controlling for baseline values showed group differences in follow up HbA1c [F (1,90) = 8.44, p = 0.005]; HbA1c values increased in the placebo group, though remained stable in the probiotic group. If replicated, Lactobacillus rhamnosus GG may protect against changes in glycemic control.