Comprehensive chemical profiling and quantitative analysis of ethnicYi medicine Miao-Fu-Zhi-Tong granules using UHPLC-MS/MS.
Developing analytical methods for the chemical components of natural medicines remains a challenge due to its diversity and complexity. Miao-Fu-Zhi-Tong (MFZT) granules, an ethnic Yi herbal prescription, comprises 10 herbs and has been clinically applied for gouty arthritis (GA) therapy. Herein, a series of chemical profiling strategies including in-house library matching, molecular networking and MS/MS fragmentation behavior validation based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) were developed for qualitative analysis of MFZT granules. A total of 207 compounds were identified or characterized in which several rare guanidines were discovered and profiled into alkyl substituted or cyclic subtypes. Moreover, network pharmacology analysis indicated that MFZT's anti-gout mechanism was mostly associated with the nuclear factor kappa-B (NF-κB) signaling, nucleotide oligomerization domain (NOD)-like signaling and rheumatoid arthritis pathways, along with the synergistic effect of 84 potential active compounds. In addition, a quantitative analytical method was developed to simultaneously determine the 29 potential effective components. Among them, berberine, pellodendrine, 3-feruloylquinic acid, neoastilbin, isoacteoside and chlorogenic acid derivatives at higher concentrations were considered as the chemical markers for quality control. These findings provide a holistic chemical basis for MFZT granules and will support the development of effective analytical methods for the herbal formulas of natural medicines.


Microbiome characterization of defensive tissues in the model anemone Exaiptasia diaphana.
Coral reefs are among the most diverse and productive ecosystems on Earth. This success relies on the coral's association with a wide range of microorganisms, including dinoflagellates of the family Symbiodiniaceae that provide coral hosts with most of their organic carbon requirements. While bacterial associates have long been overlooked, research on these microorganisms is gaining traction, and deciphering bacterial identity and function is greatly enhancing our understanding of cnidarian biology. Here, we investigated bacterial communities in defensive tissues (acontia) of the coral model, the sea anemone Exaiptasia diaphana. Acontia are internal filaments that are ejected upon detection of an external threat and release toxins to repel predators. Using culturing techniques and 16S rRNA gene metabarcoding we identified bacterial communities associated with acontia of four Great Barrier Reef-sourced E. diaphana genotypes. We show that bacterial communities are similar across genotypes, and dominated by Alteromonadaceae, Vibrionaceae, Rhodobacteraceae, and Saprospiraceae. By analyzing abundant amplicon sequence variants (ASVs) from metabarcoding data from acontia and comparing these to data from whole anemones, we identified five potentially important bacterial genera of the acontia microbiome: Vibrio, Sulfitobacter, Marivita, Alteromonas, and Lewinella. The role of these bacteria within the acontia remains uninvestigated but could entail assistance in defense processes such as toxin production. This study provides insight into potential bacterial involvement in cnidarian defense tissues and highlights the need to study bacterial communities in individual compartments within a holobiont.


Construction of Practical Haplotype Graph (PHG) with the Whole-Genome Sequence Data.
With the emerging sequencing technologies and cost reduction, the sequence data generation has accelerated from a single individual to multiple (thousands of) individuals of a species. The terabytes of sequence data generated from thousands of individuals include the majority of the redundant sequence which depends on the level of sequence similarity within the population of individuals. Managing large datasets and creating the unique catalogue sequence from such a large population is challenging to analyze, store, and retrieve the information. In this chapter, we discuss the practical haplotype graph (PHG) which addresses the above said challenges and also able to retrieve required information such as variants and sequences more efficiently, which enable researchers to manage and assess large genomic data.


Efficacy and safety of 12 immunosuppressive agents for idiopathic membranous nephropathy in adults: A pairwise and network meta-analysis.
Background: Immunosuppressants have been applied in the remedy of idiopathic membranous nephropathy (IMN) extensively. Nevertheless, the efficacy and safety of immunosuppressants do not have final conclusion. Thus, a pairwise and network meta-analysis (NMA) was carried out to seek the most recommended therapeutic schedule for patients with IMN. Methods: Randomized controlled trials (RCTs) including cyclophosphamide (CTX), mycophenolate mofetil (MMF), tacrolimus-combined mycophenolate mofetil (TAC + MMF), cyclosporine (CsA), tacrolimus (TAC), leflunomide (LEF), chlorambucil (CH), azathioprine (AZA), adrenocorticotropic hormone (ACTH), non-immunosuppressive therapies (CON), steroids (STE), mizoribine (MZB), and rituximab (RIT) for patients with IMN were checked. Risk ratios (RRs) and standard mean difference (SMD) were reckoned to assess dichotomous variable quantities and continuous variable quantities, respectively. Total remission (TR) and 24-h urine total protein (24-h UTP) were compared using pairwise and NMA. Then interventions were ranked on the basis of the surface under the cumulative ranking curve (SUCRA). Results: Our study finally included 51 RCTs and 12 different immunosuppressants. Compared with the CON group, most regimens demonstrated better therapeutic effect in TR, with RR of 2.1 (95% CI) (1.5-2.9) for TAC, 1.9 (1.3-2.8) for RIT, 2.5 (1.2-5.2) for TAC + MMF, 1.9 (1.4-2.7) for CH, 1.8 (1.4-2.4) for CTX, 2.2 (1.0-4.7) for ACTH, 1.6 (1.2-2.1) for CsA, 1.6 (1.0-2.5) for LEF, and 1.6 (1.1-2.2) for MMF. In terms of 24-h UTP, TAC (SMD, -2.3 (95% CI -3.5 to -1.1)), CTX (SMD, -1.7 (95% CI -2.8 to -0.59)), RIT (SMD, -1.8 (95% CI -3.5 to -0.11)), CH (SMD, -2.4 (95% CI -4.3 to -0.49)), AZA (SMD, --4.2 (95% CI -7.7 to -0.68)), and CsA (SMD, -1.7 (95% CI -3 to -0.49)) were significantly superior than the CON group. As for adverse effects (AEs), infections, nausea, emesia, myelosuppression, and glucose intolerance were the collective adverse events for most immunosuppressants. Conclusion: This study indicates that TAC + MMF performed the best in terms of TR, and TAC shows the best effectiveness on 24-h UTP compared with other regimens. On the contrary, there seems to be little advantage on STE alone, LEF, AZA, and MZB in treating patients with IMN compared with CON. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021287013].


Safe Veress needle insertion.
For laparoscopic surgery, the creation of pneumoperitoneum still remains a must. The insertion of a Veress needle or a trocar is never perfectly safe, and almost every kind of intraabdominal organ injury due to these insertions has been reported worldwide. Here, we describe a safe technique for creating pneumoperitoneum. For the creation of pneumoperitoneum, under direct vision, the linea alba was elevated with two towel clips and then the Veress needle was inserted. We reviewed 368 patients operated on with this technique for complication rates. Ultrasound images were obtained before and during abdominal-wall lifting in 10 patients. There were no injuries due to the insertion of the Veress needle or trocars. In 90% of the patients, pneumoperitoneum was created successfully on the first attempt. Ultrasound examination demonstrated a mean extra safe area of 11.8 mm during abdominal-wall lifting with this technique. Elevating the linea alba during Veress-needle insertion is safe.


Advanced imaging for veterinary cancer patients.
This article presents an update on the recent advances made in veterinary advanced imaging specifically with regard to cross-sectional modalities (CT and MRI) and nuclear medicine (positron emission tomography [PET] and PET/CT). A brief summary of technical improvements and a review of recent literature are included to provide an overview of the progress made in this important element of the practicing veterinary oncologist's repertoire. An in-depth summary of PET is also included to introduce the technical aspects and potential clinical and research applications of this novel imaging modality in veterinary medicine.


Hemolytic uremic syndrome related to Shiga-like toxin-producing Escherichia coli with encephalitis hiding a human herpesvirus-6 infection: a case report.
Cardiac and neurological involvement in hemolytic uremic syndrome are life-threatening complications. The most frequent complications of cardiac involvement in hemolytic uremic syndrome are myocarditis and cardiac dysfunction due to fluid overload. Pericarditis remains very rare in hemolytic uremic syndrome. To our knowledge, only five cases of cardiac tamponade associated with hemolytic uremic syndrome have been described in literature. A 27-month-old Caucasian girl presented with symptoms of nonbloody diarrhea and tonic-clonic seizures. The diagnosis of Shiga-like toxin-producing Escherichia coli hemolytic uremic syndrome with central nervous system involvement was made, and stool examination revealed infection with a Shiga-like toxin-producing Escherichia coli. She did not need renal replacement therapy but had severe neurological impairment. The patient's course was complicated by pericardial effusion. A pericardiocentesis was performed via an apical approach because the pericardial effusion was predominantly surrounding the left ventricle. Effusion analysis showed an exudate and positivity for human herpesvirus-6B on polymerase chain reaction with viremia. This finding was consistent with primary human herpesvirus-6 infection with encephalitis. We report this uncommon case of Shiga-like toxin-producing Escherichia coli hemolytic uremic syndrome associated with a severe human herpesvirus-6 infection. Secondary isolated pericardial effusion and atypical neurological involvement are uncommon in Shiga-like toxin-producing Escherichia coli hemolytic uremic syndrome and should lead the physician to perform additional investigations.


Comparison of the patient-derived modified Japanese Orthopaedic Association scale and the European myelopathy score.
To compare the patient-derived modified Japanese Orthopaedic Association (P-mJOA) scale with the European myelopathy score (EMS) for the assessment of patients with degenerative cervical myelopathy (DCM). In this register-based cohort study with prospectively collected data, included patients were surgically treated for DCM and had reported both P-mJOA and EMS scores at baseline, 1-year follow-up, and/or 2-year follow-up to the Swedish Spine Register. P-mJOA and EMS scores were defined as severe (P-mJOA 0-11 and EMS 5-8), moderate (P-mJOA 12-14 and EMS 9-12), or mild (P-mJOA 15-18 and EMS 13-18). P-mJOA and EMS mean scores were compared, and agreement was evaluated with Spearman's rank correlation coefficient (ρ), the intraclass correlation coefficient (ICC), and kappa (κ) statistics. Included patients (n = 714, mean age 63.2 years, 42.2% female) completed 937 pairs of the P-mJOA and the EMS. The mean P-mJOA and EMS scores were 13.9 ± 3.0 and 14.5 ± 2.7, respectively (mean difference -0.61 [95% CI -0.72 to -0.51; p < 0.001]). Spearman's ρ was 0.84 (p < 0.001), and intra-rater agreement measured with ICC was 0.83 (p < 0.001). Agreement of severity level measured with unweighted and weighted κ was fair (κ = 0.22 [p < 0.001]; κ = 0.34 [p < 0.001], respectively). Severity levels were significantly higher using the P-mJOA (p < 0.001). The P-mJOA and the EMS had similar mean scores, and intra-rater agreement was high, whereas severity levels only demonstrated fair agreement. The EMS has a lower sensitivity for detecting severe myelopathy but shows an increasing agreement with the P-mJOA for milder disease severity. A larger interval to define severe myelopathy with the EMS is recommended.


Exacerbation of Leishmania (Viannia) shawi infection in BALB/c mice after immunization with soluble antigen from amastigote forms.
The present study aimed to evaluate the effects of immunization with soluble amastigote (AmaAg) and promastigote (ProAg) antigens from Leishmania (Viannia) shawi on the course of infection in BALB/c mice. After immunization with AmaAg, the challenged group showed greater lesion size and parasite load in the skin and lymph nodes, associated with diminished interleukin (IL)-2, IL-4, IL-10, interferon (IFN)-γ and nitrate levels in the supernatant of lymph node cell cultures, together with increases in transforming growth factor (TGF)-β concentrations and humoral immune response. In contrast, immunization with ProAg led to smaller lesion size with reduced numbers of viable parasites in the skin. Protection was associated with increases in IL-12, IFN-γ, TGF-β and nitrates and decreases in IL-4 and IL-10 levels. Concerning humoral immune response, a significant reduction in anti-leishmania immunoglobulin G was verified in the ProAg-challenged group. Analysis of these results suggests that AmaAg induced a suppressive cellular immune response in mice, favouring the spread of infection, whereas ProAg induced partial protection associated with increased cellular immune response.


Nanostructured high-energy cathode materials for advanced lithium batteries.
Nickel-rich layered lithium transition-metal oxides, LiNi(1-x)M(x)O(2) (M = transition metal), have been under intense investigation as high-energy cathode materials for rechargeable lithium batteries because of their high specific capacity and relatively low cost. However, the commercial deployment of nickel-rich oxides has been severely hindered by their intrinsic poor thermal stability at the fully charged state and insufficient cycle life, especially at elevated temperatures. Here, we report a nickel-rich lithium transition-metal oxide with a very high capacity (215 mA h g(-1)), where the nickel concentration decreases linearly whereas the manganese concentration increases linearly from the centre to the outer layer of each particle. Using this nano-functional full-gradient approach, we are able to harness the high energy density of the nickel-rich core and the high thermal stability and long life of the manganese-rich outer layers. Moreover, the micrometre-size secondary particles of this cathode material are composed of aligned needle-like nanosize primary particles, resulting in a high rate capability. The experimental results suggest that this nano-functional full-gradient cathode material is promising for applications that require high energy, long calendar life and excellent abuse tolerance such as electric vehicles.


Efficacy and safety of catheter ablation for atrial fibrillation in congenital heart disease - A systematic review and meta-analysis.
Prevalence of atrial fibrillation (AF) in patients with congenital heart disease (CHD) is on the rise. Anti-arrhythmic drugs are usually the first line of treatment in CHD, however, it is often ineffective and poorly tolerated. We aimed to perform a systematic review to assess the efficacy and safety of catheter ablation for AF in CHD. We performed a comprehensive search on catheter ablation for atrial fibrillation in congenital heart disease up until July 2019 through several electronic databases. Ablation of AF in patients with CHD had a modest 12 months AF freedom ranging from 32.8% to 63%, which can be increased by subsequent/repeat ablation. The complexity of CHD appears to have a significant effect on a study but not in others. Catheter ablation in ASD and persistent left superior vena cava had a high success rate. Overall, catheter ablation is safe whichever the type of CHD is. Catheter ablation for AF in CHD had modest efficacy that can be increased by subsequent/repeat ablation and it also has an excellent safety profile. Ablation in complex CHD could also have similar efficacy, however, it is preferably done by experts in a high volume tertiary center.


Delirium following acute myocardial infarction: incidence, clinical profiles, and predictors.
To examine the incidence, clinical profile, and predictors of delirium following acute myocardial infarction (MI). The study sample included 212 consecutive patients with acute MI who were admitted to the coronary intensive care unit of a university hospital. Delirium was found to occur in 5.7% of the patients. The predictors of delirium were advanced age, higher level of serum potassium at admission, and experience of cardiac arrest during MI. Delirium is reasonably prevalent in patients with acute MI. We propose that patients with the risk factors that have been delineated in this study should be evaluated carefully.


The in vivo apoptotic effect of interferon alfa-2b on rat preneoplastic liver involves Bax protein.
To determine whether interferon alfa (IFN-alpha) prevents in vivo oncogenesis in very-early-stage cancer cells, we evaluated the action of IFN-alpha2b over preneoplastic foci in rats. Animals were divided into 6 groups: subjected to a 2-phase model (diethylnitrosamine [DEN] plus 2-acetylaminofluorene [2-AAF]) of preneoplasia development (group 1), treated with IFN-alpha2b during the 2 phases (group 2), only during initiation with DEN (group 3), only during administration of 2-AAF (group 4), subjected only to an initiation stage (group 5), and treated with IFN-alpha2b during this period (group 6). The numbers of placental form of rat glutathione S-transferase (rGST-P)-positive foci per liver and the foci as percentage of liver were significantly reduced in groups 2, 3, and 6 but not in group 4. Rats treated with IFN-alpha2b showed a higher apoptotic index (AI) in altered hepatic foci (AHF). Levels of p53 and Bax protein in liver lysates were significantly increased in those animals. Similarly, levels of antiapoptotic proteins Bcl-2 and Bcl-x(L) in mitochondrial fraction were decreased. Finally, increased levels of Bax protein were localized in the mitochondria of rats that received IFN-alpha2b, at least during the DEN phase (groups 2, 3, and 6), whereas mitochondrial Bax expression was not increased in group 4. In conclusion, the preneoplastic hepatocytes in rats that received IFN-alpha2b during the initiation stage undergo programmed cell death as a primary result of a significant increase in the amount and translocation to the mitochondria of Bax protein.


Avocado oils and hepatic lipid metabolism in growing rats.
The effect of various avocado oils on liver metabolism was studied in growing female rats. The rats were fed diets containing 10% (w/w) avocado oil for 4 wk. In comparison with rats fed refined avocado oil obtained from cored fruit by centrifugal separation, rats fed unrefined avocado oil obtained by organic solvent extraction from intact fruit, or its unsaponifiable components, showed a significant increase in total liver lipogenesis as well as in phospholipid and triglceride synthesis. Rats fed avocado-seed oil exhibited enhanced [1-14C]acetate incorporation into total liver lipids but showed the same distribution of label in the three main lipid classes as that of rats fed refined avocado oil. In addition, a significant reduction of triglycerides and protein content of plasma very-low-density lipoprotein and high-density lipoprotein fractions was observed in rats fed avocado-seed oil as compared with rats fed refined oil. Electron micrographs suggested that the alterations in hepatic lipogenesis are related to the marked proliferation of the smooth endoplasmic reticulum, which is known to be associated with induction of enzymes involved with lipid biosynthesis. The differences between the animals fed seed oil and those fed the unrefined oils, in the distribution of label within the main lipid classes, indicate that more than one factor is involved in the alterations caused by these oils.


Elevated GIGYF2 expression suppresses tumor migration and enhances sensitivity to temozolomide in malignant glioma.
Glioma is a common type of malignant and aggressive tumor in the brain. Despite progress on mechanistic studies, current understanding of the initiation and progression of glioma remains incomplete. GIGYF2 is a critical regulator in neural development and degeneration, however, its contribution in glioma is not yet elucidated. In this study, using an integrative approach spanning bioinformatic analysis and functional approaches, we explored the potential contribution of GIGYF2 in glioma. Bioinformatic data from public database and our cohort showed that GIGYF2 expression was closely associated with low glioma malignancy and better patient survival. Elevation of GIGYF2 expression impaired cell migration and enhanced temozolomide sensitivity of human glioma cells. We further establish its molecular mechanism by demonstrating that GIGYF2 inhibits MMP-9 mediated cell migration pathway and pro-survival AKT/Bax/Caspase-3 signaling. Our work identifies the suppressive role of GIGYF2 in gliomas, and clarifies the relationship between GIGYF2 expression and glioma malignancy, which may provide a potential target for future interventions.


[Construction of an eukaryotic plasmid encoding HER2 and screening of a cell line stably expressing clones].
To construct an eukaryotic vector encoding extracellular domain of human epidermal growth factor receptors (HER2), pcDNA6/v5-his-HER2, and to screen HER2 positive clones from mouse breast cancer cell line EMT6. The extracellular domain of HER2 was amplified from pcDNA3.1-HER2 by PCR. pcDNA6/v5-his-HER2 was prepared by inserting the fragment into the plasmid pcDNA6/v5-his. Then the recombinant vector was identified by restriction enzyme and sequencing. Next, pcDNA6/v5-his-HER2 was transfected into the EMT6 cell line and the positive clones (EMT6/HER2) were screened with blasticidin. Finally, the expression of HER2 in EMT6/HER2 was detected by RT-PCR and immunohistochemistry. The fragment of HER2 was amplified and pcDNA6/v5-his-HER2 was prepared successfully. No errors were found both in the sequence and ORF of the acquired fragment. The expected fragment of HER2 (1896 bp) was amplified from EMT6/HER2 by RT-PCR and positive signals of HER2 were detected in EMT6/HER2 by immunohistochemistry. An eukaryotic plasmid encoding HER2 (pcDNA6/v5-his-HER2) has been constructed and a cell line expressing HER2 stably has been prepared successfully.


Intra-observer and inter-observer agreements for the measurement of dual-input whole tumor computed tomography perfusion in patients with lung cancer: Influences of the size and inner-air density of tumors.
This study was conducted to assess intra-observer and inter-observer agreements for the measurement of dual-input whole tumor computed tomography perfusion (DCTP) in patients with lung cancer. A total of 88 patients who had undergone DCTP, which had proved a diagnosis of primary lung cancer, were divided into two groups: (i) nodules (diameter ≤3 cm) and masses (diameter >3 cm) by size, and (ii) tumors with and without air density. Pulmonary flow, bronchial flow, and pulmonary index were measured in each group. Intra-observer and inter-observer agreements for measurement were assessed using intraclass correlation coefficient, within-subject coefficient of variation, and Bland-Altman analysis. In all lung cancers, the reproducibility coefficient for intra-observer agreement (range 26.1-38.3%) was superior to inter-observer agreement (range 38.1-81.2%). Further analysis revealed lower agreements for nodules compared to masses. Additionally, inner-air density reduced both agreements for lung cancer. The intra-observer agreement for measuring lung cancer DCTP was satisfied, while the inter-observer agreement was limited. The effects of tumoral size and inner-air density to agreements, especially between two observers, should be emphasized. In future, an automatic computer-aided segment of perfusion value of the tumor should be developed.


Nuclear telomerase is less accessible to antibody probing than known nuclear antigens: retrieval with new immunostaining buffer.
Telomerase is an important tumor marker but few antibodies to the enzyme have been described or used without difficulty in histochemical detection. Here we report specific detection of the enzyme in cell and tissue preparations using a new monoclonal antibody (mAb 476) and a new antigen-retrieval buffer (Enhancing buffer). When used to detect telomerase under normal immunostaining conditions in HL-60 cells or tissue sections of hepatocellular carcinoma or metastatic choriocarcinoma, unexpectedly, the antibody stained the cytoplasm rather than the nucleus. Nuclear staining, however, was revealed using the Enhancing buffer. Since other nuclear antigens in the HL-60 cell could be stained both ordinarily and in the Enhancing buffer, nuclear telomerase appears to be shrouded by the nuclear matrix or blocked by accessory proteins. The cytoplasmic activity seen in normal buffer but absent largely from the Enhancing buffer may be an artifact or the nascent, "naked" enzyme. With a known cytoplasmic antigen (proteinase-3) chosen arbitrarily for comparison, the antigenicity was found enhanced, instead, by the Enhancing buffer. The mode of action of the Enhancing buffer differs from that of microwave irradiation or the signal amplification (CSA) used by some investigators. The latter was found to enhance the cytoplasmic reactivity rather than the nuclear reactivity of mAb 476.


Psychoanalysis and dynamic psychotherapy.
Analytic therapists work with a wide range of clients, taking an active role in helping them overcome problems which often stem from their childhood.


Is the 2003 SARS epidemic over? Long-term effects of epidemic exposure on mortality among older adults.
Infectious diseases put health of millions at risk and induce large socioeconomic costs each year. However, the long-term effects of exposure to infectious diseases on the elderly have received minimal attention. Using data from the Chinese Longitudinal Healthy Longevity Survey, this study adopts a differences-in-differences strategy to evaluate the long-term effects of epidemic exposure on old-age mortality. We find that intense exposure to the severe acute respiratory syndrome (SARS) epidemic led to an increase in old-age mortality after the SARS outbreak. We provide some suggestive evidence that exposure to SARS increased psychological stress and limitations in physical activities among old people.


Association of SCN10A Polymorphisms with the Recurrence of Atrial Fibrillation after Catheter Ablation in a Chinese Han Population.
The nonsynonymous SCN10A single nucleotide polymorphism (SNP) rs6795970 has been reported to associate with PR interval and atrial fibrillation (AF) and in strong linkage disequilibrium (LD) with the AF-associated SNP rs6800541. In this study, we investigated whether rs6795970 polymorphisms are associated with AF recurrence after catheter ablation. A total of 502 consecutive patients with AF who underwent catheter ablation were included. AF recurrence was defined as a documented episode of any atrial arrhythmias lasting ≥30 s after a blanking period of 3 months. AF recurrence was observed between 3 and 12 months after catheter ablation in 24.5% of the patients. There was a significant difference in the allele distribution (p = 7.86 × 10-5) and genotype distribution (p = 1.42 × 10-5) of rs6795970 between the AF recurrence and no recurrence groups. In a multivariate analysis, we identified the following independent predictors of AF recurrence: the rs6795970 genotypes in an additive model (OR 0.36, 95%CI 0.22~0.60, p = 7.04 × 10-5), a history of AF ≥36 months (OR 3.57, 95%CI 2.26~5.63, p = 4.33 × 10-8) and left atrial diameter (LAD) ≥40 mm (OR 1.85, 95%CI 1.08~3.19, p = 0.026). These data suggest that genetic variation in SCN10A may play an important role in predicting AF recurrence after catheter ablation in the Chinese Han population.


Structural characterization of immunostimulating protein-sulfated fucan complex extracted from the body wall of a sea cucumber, Stichopus japonicus.
The water soluble protein-sulfated fucan (PSF) complex isolated from the body wall of Stichopus japonicus was fractionated using an anion-exchange chromatography to obtain four purified fractions (F1, F2, F3, and F4) and to investigate their structural characteristics and immuno-enhancing activities. The crude PSF and fractions mostly consisted of neutral sugars, proteins and sulfates in various proportions. Fucose was their major monosaccharide unit with small portion of mannose, glucose and galactose. The molecular weight (Mw) of the crude PSF and fractions ranged from 323.6×103 to 3630.0×103g/mol. The crude PSF, F2, and F3 were potent stimulator of RAW264.7 cells inducing marked nitric oxide (NO) and cytokines production. The glycosidic linkage of polysaccharides was evaluated using GC-MS and confirmed by 2D-NMR. The main backbone of highly immunostimulating F3 fraction was (1→3)-α-l-linked fucosyl residue with sulfation at C-2 and/or C-4.


A polymorphism of the plasminogen activator inhibitor-1 gene promoter and the polycystic ovary syndrome.
To investigate the association of a common 5G/4G polymorphism of the plasminogen activator inhibitor-1 gene (PAI1) with occurrence and clinical characteristics of the polycystic ovary syndrome (PCOS). In a case-control study, we evaluated a series of 106 Caucasian women with PCOS and 102 healthy controls. Women completed a detailed questionnaire and underwent a peripheral venous puncture, ultrasonography, and a standardized oral glucose tolerance test (OGTT). The PAI1 gene promoter polymorphism was evaluated using PCR. Allele and genotype frequencies were not significantly different among women with PCOS and controls (P=0.3 and 0.6, respectively). In women with PCOS, presence of the 5G/4G polymorphism of PAI1 was not associated with changes in serum hormone levels or with clinical characteristics. The 5G/4G polymorphism of the PAI1 promoter is not associated with occurrence and phenotype of the PCOS.


Spatial orientation of the adult cochlea: rotation, tilt, and angle theta 3.
Quantitative description in adult crania of (1) angular orientation of the basal turn of the cochlea relative to the sagittal (termed "rotation") and Frankfort horizontal (termed "tilt") planes, and angle theta 3 [angular relationship of the line defined by the cochlea's spiral center and cochlear (round) window, to the cochlear window]; (2) orientation of the cochlea relative to the plane defined by the horizontal and vertical portions of the facial nerve; (3) orientation of the basal turn of the cochlea relative to the plane of the posterior semicircular canal; and (4) the association of these orientations with the extent of mastoid pneumatization. Postmortem material analysis. From 41 bequeathed anatomical ear-normal cadaveric cranial, high-resolution CT scans were performed of the five crania with the largest and the five with the smallest mastoids. Eleven points in three-dimensional Cartesian space were appointed and studied with the software program FIJI. The median angle values (and ranges) for right ears were: "rotation" 52° (range 47-61); and, "tilt" 84° (79-89). The planes of the cochlear basal turn and facial nerve approximated superimposition: median 15° (2-19). Angle theta 3 for right ears was median 40° (28-44). Bilateral symmetry was found for the relationships between the planes. However, no association of any planar relationship with mastoid pneumatization was suggested. Considering the range of angles found in clinically normal adult specimens, spatial orientation of the cochlea may explain some of the difficulties in implantation.


Ictal epileptic headache: an old story with courses and appeals.
The term "ictal epileptic headache" has been recently proposed to classify the clinical picture in which headache is the isolated ictal symptom of a seizure. There is emerging evidence from both basic and clinical neurosciences that cortical spreading depression and an epileptic focus may facilitate each other, although with a different degree of efficiency. This review address the long history which lead to the 'migralepsy' concept to the new emerging pathophysiological aspects, and clinical and electroencephalography evidences of ictal epileptic headache. Here, we review and discuss the common physiopathology mechanisms and the historical aspects underlying the link between headache and epilepsy. Either experimental or clinical measures are required to better understand this latter relationship: the development of animal models, molecular studies defining more precise genotype/phenotype correlations as well as multicenter clinical studies with revision of clinical criteria for headache-/epilepsy-related disorders represent the start of future research. Therefore, the definition of ictal epileptic headache should be used to classify the rare events in which headache is the only manifestation of a seizure. Finally, using our recently published criteria, we will be able to clarify if ictal epileptic headache represents an underestimated phenomenon or not.


Synthesis of Some New Isoxazoline Derivatives of Chalconised Indoline 2-one as a Potential Analgesic, Antibacterial and Anthelmimtic Agents.
A series of novel 1[5"-(2"'-substituted phenyl)-4",5"'-dihydro isoxazole-3"-yl]-3-[(4 substituted phenyl)imino]1-3-dihydro-2H-indole-2-one were synthesized from different substituted chalconised indole-2,3-dione was prepared from the different chalconised Isatin. The structures of the compounds were elucidated by elemental and spectral (IR, (1)H NMR, and MS) analysis. The synthesized compounds were screened for their analgesic activity by the acetic acid induced Writhing method and in vitro antimicrobial activity against the Gram-positive bacteria-Staphylococcus aureus and the Gram-negative bacteria-Pseudomonas auroginosa, Pseudomonas mirabilis, and E. coli by the cup plate agar diffusion method. Compounds 6a(1), 6a(3), 6b(3), and 6b(2) were found to be active against bacteria. The compounds 6a(1), 6b(3), and 6a(3) show a significant analgesic activity. Synthesized compounds also screened for anthelmintic activity against Pheretima posthuma. Compounds 6a(1), 6b(1), and 6b(3) show significant anthelmintic activity.


Financial support for research training and career development in complementary and alternative medicine from the National Institutes of Health.
Research careers are a relatively new reality for complementary and alternative medicine (CAM) practitioners (eg, chiropractors, naturopaths, doctors of oriental medicine, etc). Before the establishment in 1998 of the National Center for Complementary and Alternative Medicine (NCCAM) as part of the National Institutes of Health (NIH), there were few funding resources available for those interested in a CAM research career and fewer still feasible paths. Now, however, NCCAM provides a broad array of research training and career development awards for those seeking a long-term career in CAM research. These awards include predoctoral and postdoctoral fellowships, individual career development awards, and institutional training awards. The goal of this article is to provide information about current research training funding opportunities from NCCAM and NIH as a whole that are available to CAM practitioners in the context of the historical challenges of transitioning from a clinical career in CAM practice to a CAM research career.


Release of particles and metals into seawater following sediment resuspension of a coastal mine tailings disposal off Portmán Bay, Southern Spain.
Portmán Bay in Southern Spain is one of the most extreme cases in Europe of anthropogenic impact on the marine ecosystem by the disposal of mine tailings resulting from the processing of sulphide ores. First, the composition and extent of the surficial deposit were investigated from geochemical and metal analysis on high spatial density of sediment samples. Then, a disturbance experiment was conducted in the coastal area off Portmán Bay in order to investigate the potential impact of mining activities on marine ecosystems. Two research vessels were used for that experiment, one performing as a trawler resuspending bottom sediments while the other monitor the behaviour of turbid plumes thus generated and the evolution of their characteristics through time by using a range of acoustic and optical tools together with water and bottom sediment sampling for biogeochemical and metal analyses. The surficial part of the submarine extension of the mine tailings deposit is highly concentrated in As, Cd, Pb, Fe and Zn with peak concentrations adjacent to the present coastline, from where they decrease seawards before reaching average values for the Mediterranean Sea around 50-m water depth. The artificially triggered resuspension of the surface layer of the deposit led to the formation of resuspension plume about 100 m in width and up to 6 m in height. Resuspended plume was composed of fine particles which rapidly aggregated into flocs of 100 μm. While the biggest particles settled rapidly, the finest fraction remained in suspension during at least 3 h. Resuspended sediment and metal concentrations in particles remained at relatively high levels throughout the experiments following triggering. Fe, Pb, and As concentrations in resuspended particles showed a continuous increase while trawling before decreasing in parallel with the settling down of the resuspended sediments. Those metals have higher affinity with fine particles than with coarse ones, so that while the coarsest fraction from sediment plumes settled first, the finest fraction remained in suspension thus increasing the metals/sediments concentration ratio. On the other hand, Cd and Zn concentrations in suspended particles did not change significantly over time, which is thought to be caused by the fast dissolution of such metals in seawater. Beyond waste dumping itself, the observed increase in some metals in marine particulate material could have a significant impact on the adjacent coastal ecosystems due to their toxicity above certain thresholds. The consequences of the resuspension experiment here presented can be extrapolated to the impact of seafloor mining activities leading to the resuspension of metal-rich particle plumes into the water column. The experimental set-up presented here may be further explored for investigating metal behaviour during seafloor mining activities.


Influence of 48 hours of cold storage in University of Wisconsin organ preservation solution on metabolic capacity of rat hepatocytes.
Suspensions of isolated hepatocytes are a valuable tool to study liver functions. For optimal use of the isolated hepatocytes, methods are needed to preserve the hepatocytes while maintaining their viability, metabolic and transport functions. Until now, little has been known about the maintenance of the drug metabolism capacity and energy state, measured by the so-called energy charge (ATP+1/2ADP)/(ATP+ADP+AMP), in hepatocytes after storage in University of Wisconsin cold storage solution (UW). Consequently, we investigated whether UW, originally designed to preserve organs for transplantation, was suitable for preservation of isolated rat hepatocytes with respect to the maintenance of drug metabolism and levels of energy-rich substrates. Viability of the isolated rat hepatocytes was determined by trypan blue exclusion, ATP content and energy charge after 24 and 48 h of storage in UW at 0 degrees C. Phase I and II metabolic functions of the cells were studied by measuring the cytochrome P450 content and the metabolic rate of lidocaine and 7-ethoxycoumarin. During 48 h of storage of hepatocytes in UW both phase I and phase II metabolism are preserved at control levels. After storage, the viability of the hepatocytes was not changed significantly, and the cells maintained proper cellular ATP content and overall energy charge. These results imply that hepatocytes from a single isolation can be stored in UW solution and used for metabolism experiments for 3 consecutive days, allowing a reduction in the use of experimental animals.


Huntington disease mutation in Venezuela: age of onset, haplotype analyses and geographic aggregation.
The aggregation of patients with Huntington's disease (HD) around Lake Maracaibo, Zulia State, Venezuela, is widely recognized, but the epidemiology of HD in the whole country is relatively unstudied. We have examined 279 individuals from 60 unrelated affected families residing in various areas of Venezuela for the presence of CAG repeats and other features associated with HD. The number of expanded repeats in 139 carriers varied from 35 to 112. Based on our examination of 71 symptomatic individuals, we developed a log-transformed regression equation, y= -0.0238x + 2.6616, to enable the prediction of age of onset in asymptomatic carriers. Intragenic haplotypes were constructed with two VNTRs (variable number of tandem repeats) and two SNPs (single nucleotide polymorphisms) in the promoter region as well as CCG repeat and Delta2642 polymorphisms to assess kinship between families. In 43 of 45 tested families, the haplotype on the mutated chromosome was 1;G;C;7;(A). The other haplotypes observed, 1;G;C;7;(B) and 4;G;C;7;(A), were of Peruvian and French origins, respectively. The geographic source of the first affected ancestor was assessed in 54 families from 15 different states. Residents of the states of Miranda, Lara and Táchira, excluding those of Zulia, had a mutated allele prevalence five- to ninefold higher than that of other areas. A low (approx. 1/200,000) prevalence, a wide-spread distribution with aggregation in some states and a likely remote European Caucasoid origin are defining epidemiologic features of HD in Venezuela.


Associations between Owners' Reports of Unwanted Ridden Behaviour and In-Hand Behaviour in Horses.
An evidence-based understanding of dangerous or unwelcome behaviour in horses would greatly benefit both horses and humans who interact with them. Using owner-reported data from the Equine Behaviour Assessment and Research Questionnaire (E-BARQ), the current study investigated in-hand behaviours associated with dangerous or unwelcome ridden behaviours, notably bolting, rearing and bucking. Respondents (n = 1584) to the ridden horse section of the E-BARQ answered 42 demographic questions, followed by 268 behavioural items. Parallel analysis was conducted to group individual behaviours into rotated components to create independent and dependent indices. Multivariable general linear modelling and ordinal logistic regression were used to identify behaviours associated with bolting, rearing and bucking. Results revealed that safety-from-bolt increased as social confidence with horses (Odds ratio (OR) = 1.06; 95% confidence interval (cf = 1.02-1.09) and other animals (OR = 1.08; cf = 1.03-1.12), compliance in-hand (OR = 1.10; cf = 1.06-1.16) and tolerance of restraint (OR = 1.05; cf = 1.0-1.11) increased; and decreased as loading problems (OR = 0.95; cf = 0.92-0.99) increased. Safety-from-rear increased as tolerance of restraint (OR = 1.07; cf = 1.02-1.12) and social confidence with other animals (OR = 1.05; cf = 1.01-1.09) increased; and decreased as loading problems (OR = 0.94; cf = 0.91-0.98) increased. Safety-from-buck increased as social confidence with horses (b-value = 0.011, p < 0.001) and other animals (b-value = 0.010, p = 0.002), compliance in-hand (b-value = 0.015, p < 0.001), tolerance of restraint (b-value = 0.009, p = 0.027) and tolerance of haltering/bridling (b-value = 0.016, p = 0.010) increased, and it decreased as loading problems increased (b-value = -0.011, p < 0.001). By revealing, for the first time, that specific behaviours on the ground are associated with particular responses in the same horses when ridden, this study advances equitation science considerably. Identification of risk factors for dangerous behaviour while under saddle can improve safety for horses and riders and highlights the importance of effective and humane in-hand training.


Strong adsorption of tetracycline hydrochloride on magnetic carbon-coated cobalt oxide nanoparticles.
The overuse of antibiotics, including tetracycline hydrochloride (TC), seriously threatens human health and ecosystems. In this work, magnetic carbon-coated cobalt oxide nanoparticles (CoO@C) were prepared by one-step annealing method and used as an adsorbent for efficient removal of TC from aqueous solution. The characteristic of the materials was studied by SEM, TEM, and XRD, revealing CoO nanoparticles (≤10 nm) were coated by carbon layer. Several influencial parameters, such as annealing temperature and pH on adsorption of TC, were explored, and found that the maximum adsorption capacity of CoO@C on TC reached as high as 769.43 mg g-1. Furthermore, CoO@C displayed excellent stability and reusability. After four repeated use of the adsorbent, the adsorption capacity still remained at 90% of the initial capacity. The pseudo-second order model and Temkin model proved that it was an exothermic chemical adsorption process. Furthermore, after analysis of FT-IR, Zeta-potential, XPS, the positive charge on the surface of CoO@C forms a strong electrostatic interaction with TC, and in addition, a surface bond is formed between the adsorbent and the TC molecule. This work provides a novel and efficient adsorbent for the purification of TC-containing wastewater.


Synthesis and characterization of FSB@Fe3O4 composites and application in removal of indigo carmine dye from industrial wastewaters.
The syntheses and characterization of fish scale biochar magnetic composites (FSB@Fe3O4) and their applications in the removal of indigo carmine dye from effluents are described. Preparation of the fish scale biochar magnetic composites, FSB@400 °C-Fe3O4, FSB@600 °C-Fe3O4, and FSB@800 °C-Fe3O4, was done following the chemical co-precipitation method. The adsorbents were characterized using peak optical absorbance, functional groups, magnetic strength, surface morphology, particle size, elemental compositions, surface charge, surface area, thermal stability, and crystalline phase, using ultraviolet-visible spectroscopy (UV-vis spec), Fourier transform infrared (FTIR) spectroscopy, vibrating sample magnetometry (VSM), transmission electron microscopy/scanning electron microscopy (TEM/SEM), energy dispersive X-ray (EDX), point of zero charge pH (pHpzc), Brunauer-Emmett-Teller (BET), thermo-gravimetric analysis (TGA), and powder x-ray diffraction (PXRD) techniques, correspondingly. The potential of magnetic composites for the abstraction of indigo carmine dye from wastewater was determined as a function of the initial concentration of indigo carmine dye, contact time, dye solution pH, adsorbent dosage, and solution temperature. The results demonstrated that the quantity (q) of indigo carmine dye adsorbed onto magnetic composites improved with a rise in initial dye concentration, adsorbent load, and solution temperature. Conversely, lower quantities of adsorbed dye were recorded at higher pH levels. The data fitted a pseudo-second-order kinetic model. The Langmuir isotherm gave the best fit (Langmuir>Freundlich>Redlich-Peterson>Toth>Hill>Sips>Temkin) suggesting a uniformly monolayer adsorption. Adsorption of environmental wastewater samples revealed that all the adsorbents can be used to effectively treat industrial wastewaters. The recycling data established that the adsorbents could be used for five consecutive cycles without significant loss of adsorption capacities.


Improved treatment of the breast and supraclavicular fossa based on a simple geometrical principle.
In breast cancer, nodal irradiation has become routine, but adds time and creates concerns for field overlap if the "match" is not accurate. We developed a technique to address these issues by using only one isocenter for both areas. Tangents are designed at simulation. The isocenter is then shifted to the upper border of the breast using a straightforward geometrical calculation. After determining the new isocenter, fields are recreated wherein the tangents are treated with a quarter beam and the supraclavicular field fashioned with a half-beam block. The gantry, collimator, and couch angles of the supraclavicular field are adjusted to achieve an accurate match. Ten patients were evaluated. Doses to the spinal cord and brachial plexus were lowered relative to conventional techniques. The hot spots were not augmented. In comparison with standard arrangements, setup time decreased. Accurate matching was consistently achieved and verified by portal imaging. A new approach for treating the supraclavicular fossa is easily executed. Advantages include negligible doses to the critical neural structures (i.e., spinal cord and brachial plexus), optimized matchline, and reduced setup time.


Comparison of Thymulin Activity with Other Measures of Marginal Zinc Deficiency.
Activity of the immunoregulatory peptide thymulin reflects differences in zinc status. This study compared thymulin activity with four other zinc status measures in rats fed zinc at either 5 or 25 ppm. Rats fed the lower zinc showed the following results compared with rats with adequate zinc intake: serum thymulin activity 61% lower, serum zinc 31% lower, serum extracellular superoxide dismutase 18% lower, serum 5'-nucleotidase activity 26% lower, and liver metallothionein 28% lower. Thus, thymulin activities showed more sensitivity to restricted zinc intake than did four other parameters.


Interaction of peptides spanning the transmembrane domain of caveolin-1 with model membranes.
Caveolin-1 has an atypical membrane-spanning domain comprising of 34 residues. Caveolin-1 targets to lipid droplets under certain conditions, where they are involved in signaling and cholesterol balance. In the present study, membrane association of synthetic peptides corresponding to the membrane-spanning domain of caveolin-1 has been investigated to obtain an insight into the topology of transmembrane region in the lipid bilayer and the effect of truncations in this sequence, as observed in the targeting to lipid droplets, by using model membranes. Fluorescence studies revealed strong association of the peptide corresponding to the membrane-spanning domain of caveolin-1 with anionic lipids as compared with zwitterionic lipids, which is consistent with the location of this domain in the cytoplasmic side of the plasma membrane. Association of a short 9 residue peptide corresponding to the C-terminus of caveolin-1 membrane-spanning domain with lipid vesicles revealed the importance of this region for association with model membranes. Our investigations indicate that the peptide corresponding to the membrane-spanning domain of caveolin-1 does not span the lipid bilayer. We propose that both caveolin scaffolding domain and transmembrane segment of caveolin-1 contribute to the strong association with the plasma membrane rendering the protein highly detergent resistant.


Solitary peripheral osteoma of the jaws: report of case and review of literature.
Solitary osteomas of the jaws are uncommon. Only 12 previous case reports provided acceptable clinical and histologic data. One new case is added. Most of the tumors occurred in the mandible; only three were intraoral. Histologically, eight were compact and five were cancellous osteomas.


Induction of aminolevulinate synthase and porphyrins in cultured liver cells maintained in chemically defined medium. Permissive effects of hormones on induction process.
Primary liver cells, isolated from 16- 17-day-old chick embryos, were incubated in a serum-free chemically defined medium (Ham's F12) supplemented with hormones for up to 6 days. The culture method also includes the complete removal of contaminating red cells before the initiation of culture. On the 2nd day in cluture, the level of amino-levulinate (ALA) synthase activity in response to allylisopropylacetamide (AIA) was increased 6-fold in cells grown in F12. Insulin, hydrocortisone, and triiodothyronine alone had no appreciable effects on ALA synthase levels. On the other hand, when added with AIA, insulin, insulin plus hydrocortisone, insulin plus hydrocortisone triiodothyronine increased ALA synthase levels 17-, 50-, 110-fold, respectively. The maximally induced levels of ALA synthase activity by AIA in the presence of insulin, hydrocortisone, and triiodothyronine were approximately 15 nmol of ALA/mg of protein/h, 37 degrees or 3 micronmol of ALA/g of tissue/h, 37 degrees, a value similar to that found in ovo or at least 5 times greater than that found in rat liver. The morphology of hepatocytes was maintained for at least 6 days in culture, although the induction of ALA synthase was reduced after the 4th day unless triiodothyronine was present. Dibutyryl adenosine 3':5'-monophosphate (10(8) M) or glucagon (5x10(8) M) had little effect on the induced as well as noninduced levels of ALA synthase or porphyrins. These data demonstrate a "permissive" effect of insulin, hydrocortisone, and triiodothyronine on the induction of ALA synthase and porphyrins by AIA in cultured chick embryo liver cells. In the absence of insulin hydrocortisone, or triiodothyronine, AIA produces only a slight increase in ALA synthase activity or porphyrins (or both); on the other hand, it produces a marked increase in the enzyme activity and porphyrins when these hormones are added to the culture medium. The term "permissive" is applied to these hormone-dependent effects. A sensitive spectrofluorometric method for heme quantitation allowed us to follow changes in the cellular heme content in hemoglobin-free cultured liver cells. Heme content in the cultured liver cells was approximately 250 pmol/mg of protein at the initiation of culture but gradually declined to 175 pmol/mg of protein at the initiation of culture but gradually declined to 175 pmol/mg of protein during 48 h of incubation. The apparent decrease in heme content may be accounted for by the concomitant increase in protein content in these cells.


4-Aminoquinoline compounds from the Spanish flu to COVID-19.
In 1918, quinine was used as one of the unscientifically based treatments against the H1N1 virus during the Spanish flu pandemic. Originally, quinine was extracted from the bark of Chinchona trees by South American natives of the Amazon forest, and it has been used to treat fever since the seventeenth century. The recent COVID-19 pandemic caused by Sars-Cov-2 infection has forced researchers to search for ways to prevent and treat this disease. Based on the antiviral potential of two 4-aminoquinoline compounds derived from quinine, known as chloroquine (CQ) and hydroxychloroquine (HCQ), clinical investigations for treating COVID-19 are being conducted worldwide. However, there are some discrepancies among the clinical trial outcomes.Thus, even after one hundred years of quinine use during the Spanish flu pandemic, the antiviral properties promoted by 4-aminoquinoline compounds remain unclear. The underlying molecular mechanisms by which CQ and HCQ inhibit viral replication open up the possibility of developing novel analogs of these drugs to combat COVID-19 and other viruses.


Effects of maternal stress on methylmercury-induced developmental toxicity in mice.
The developmental toxicity of combined exposure to maternal restraint stress and methylmercury chloride (MMC) was assessed in Swiss mice. On day 10 of gestation, four groups of plug-positive female mice were treated (p.o.) with a single dose of 12.5 or 25 mg MMC/kg. Immediately after MMC exposure, two of those groups were subjected to restraint for 14 hr. Control groups included restrained and unrestrained pregnant mice nonexposed to MMC. Combined exposure to 25 mg MMC/kg and restraint enhanced MMC-induced maternal toxicity, which included deaths and decreased body weight gain and food consumption. The number of nonviable implants was also increased significantly following concurrent exposure to MMC (25 mg/kg) and restraint, with the percentage of postimplantation loss increased from 64% (MMC alone) to 100% (MMC plus restraint). However, the types and incidence of internal and skeletal anomalies observed after administration of 12.5 mg MMC/kg were not increased by maternal restraint. These results suggest that maternal stress would enhance the MMC-induced maternal and embryo/fetal toxicity at doses of MMC that are highly toxic to the dams, whereas at doses that are less acutely toxic the role of maternal stress would not be significant.


The impact of tritium phytoremediation on plant health as measured by fluorescence.
Phytoremediation, using plants for soil, sediment, or water contaminant clean-up, is an established technology dependent on plant health. Tritium (3H), a radioactive isotope of hydrogen that is generally found in the environment as tritiated water (HTO), is a low-level beta emitter with a half-life of 12.32 years. Chlorophyll fluorescence (CF) for monitoring risk assessment of tritium to plant health was conducted at the Tritium Irrigation Facility (TIF) located on the US Department of Energy's Savannah River Site (SRS) near Aiken, SC. Two fluorometers were evaluated in conjunction with phytoremediation at the 25 -acre TIF where tritiated groundwater is being spray-irrigated on a mixed coniferous/deciduous forested watershed as a means of reducing tritium release to a nearby stream that serves as a tributary to the Savannah River. Tritium activity in irrigated water averaged 104 + 42 pCi mL-1 during the 2003 project. Fluorescence parameters measured by the two fluorometers were well correlated with each other (p < 0.0001). Tritium in water respired from oak leaves ranged up to 1845.13 pCi ml-1 and 2138.22 pCi ml-1 in pine needles. Trees in both the test and control sites were approximately 15 years old. Here we demonstrated that fluorescence parameters provide an effective way to estimate the impact of HTO on plant health in a noninvasive, extremely rapid, and cost-effective manner. In the current study applying fluorometry, plants within the TIF phytoremediation site exposed to the site tritiated water were not significantly impacted by the tritium phytoremediation based on CF parameters as compared to the control, a nascent non-irrigated site.


Corneal endothelial assessment in xeroderma pigmentosum: a case-control study.
To analyze and compare corneal endothelial mosaic in terms of endothelial cell population, morphology and irregularity in patients with xeroderma pigmentosum (XP) with clear corneas with normal age and sex matched subjects using specular microscopy. Nine patients with XP without corneal involvement were evaluated in the study. An age and sex matched group of nine healthy subjects participated as control group. Evaluation of corneal endothelial layer was performed using specular microscopy. Each study group consisted of five males and four females with total mean age of 28 ± 11.3 years (12-46 years). Endothelial cell density was significantly lower in patients with XP in comparison with controls (P < 0.002). Maximum and minimum cell areas were significantly higher in XP group (P < 0.016 and P < 0.029, respectively). Although central corneal thickness was higher in controls, the difference was not statistically significant (P = 0.106). Furthermore, our study showed that the patients with XP had no difference with controls in terms of coefficient of variation of cell areas. This study showed that endothelial cell population can decrease in patients with XP, although other specular microscopic variables such as coefficient of variation and central corneal thickness may remain within normal values.


Diamine oxidase, a plasma biomarker in rats to GI tract toxicity of oral fluorouracil anti-cancer drugs.
Diamine oxidase (DAO; EC 188.8.131.52), which catabolizes a variety of substrates including histamine and diamines, is the degradative enzyme of the catabolic pathway of polyamines found in high activity in the mature upper villus cells of the rat intestinal mucosa [Luk, G.D., Bayless, T.M., Baylin, S.B., 1983. Plasma post-heparin diamine oxidase. Sensitive provocative test for quantitating length of acute intestinal mucosal injury in the rat. J. Clin. Invest. 71, 1308-1315; Wolvekamp, M.C.J., de Bruin, R.W.F., 1994. Diamine oxidase: an overview of historical, biochemical and functional aspects. Dig. Dis. 12, 2-14]. Rats were given 1-week repeated oral administration of anti-cancer drugs S-1, containing FT+CDHP+Oxo, and FCD, containing FT+CDHP, and the ameliorating effect of Oxo on the rat gastrointestinal (GI) tract toxicity from 5-FU was evaluated by measuring plasma DAO activity which is related to the enzyme located in the rat intestinal mucosa. Plasma DAO activity in the FCD-treated group was significantly less than that in the S-1-treated group while the jejunal mucosal area in the FCD group was significantly smaller than that in the S-1 group. In addition the histopathological findings in the FCD group showed villus atrophy in the jejunal mucosa which was not observed in the S-1 group. The degree of these findings correlated with the plasma DAO levels. Therefore, the protective effect of Oxo on 5-FU-induced GI tract toxicity was clarified by measuring plasma DAO activity in rats. In summary, DAO is a very sensitive plasma biomarker and will be useful for the quantitative evaluation of the small intestinal mucosal lesions induced by the anti-cancer drug, 5-FU, in rats.


Productive performance and urinary excretion of mimosine metabolites by hair sheep grazing in a silvopastoral system with high densities of Leucaena leucocephala.
The aim of this study was to evaluate daily weight gain (DWG), total dry matter (DM) intake, rumen degradability of forage, and urinary excretion of mimosine metabolites by hair sheep in a silvopastoral system with high densities of Leucaena leucocephala. A completely randomized design was carried out with two treatments: treatment 1 (T1) silvopastoral system with leucaena at a density of 35,000 plants/ha and treatment 2 (T2), leucaena at a density of 55,000 plants/ha. Leucaena was associated with tropical grasses Panicum maximum and Cynodon nlemfluensis. Twenty-four male Pelibuey lambs of 23.2 ± 3.4 kg live weight (LW) were used (12 lambs per treatment). Results showed differences (P < 0.05) in DWG of T1 (106.41 ± 11.66 g(-1) sheep(-1)) with respect to that of T2 (81.33 ± 11.81 g(-1) sheep). Voluntary intake was higher in lambs from T1 (83.81 ± 04.07 g DM/kg LW(0.75)) with respect to that from T2 (71.67 ± 8.12 g DM/kg LW(0.75)). There was a difference in color of urine between sheep of T1 and T2, the latter giving positive results for the presence of metabolites derived from mimosine (3-4 dihydroxypyridine and 2-3 dihydroxy pyridone). Rumen degradability of DM of L. leucocephala was higher (P < 0.05) compared to that of P. maximum and C. nlemfluensis (72.94 ± 0.40 vs. 67.06 ± 1.50 and 63.25 ± 1.51 %, respectively). It is concluded that grazing at high densities of L. leucocephala affects daily weight gain of hair sheep, possibly due to ingestion of high amounts of mimosine which may exert an adverse effect on voluntary intake.


The amplitude of the c wave in the human ERG as a function of the luminous energy of the stimulus.
Variation of the stimulus intensity and duration over a wide range causes a change in amplitude of the c wave. If the energy of the applied stimulus is kept constant, however, stimuli of 0.05-4 s duration effected c waves that were nearly equal in amplitude. As patients consider shorter stimuli with higher intensities to be more comfortable in ERG recording, stimuli of a duration of 2-4 s seem most appropriate for clinical testing.


Coix lacryma-jobi chymotrypsin inhibitor displays antifungal activity.
A novel chymotrypsin inhibitor, named ClCI, was purified from coix seed (Coix lacryma-jobi L.) by aqueous two-phase extraction, chymotrypsin-Sepharose 4B affinity chromatography and centrifugal ultrafiltration. ClCI was a 7.9 kDa competitive inhibitor with pI 6.54. The inhibition constants (Ki) for bovine pancreatic chymotrypsin and bacterial subtilisin were 1.27 × 10-10 M and 1.57 × 10-9 M respectively. ClCI had no inhibitory activity against bovine trypsin and porcine elastase. ClCI had wide pH stability and good heat resistance. It can maintain >90% inhibition activity against chymotrypsin at 20-80 °C for 1 h. The primary structure of ClCI was highly similar (57%-92%) to those of several inhibitors belonging to the Gramineae crop potato protease inhibitor- I superfamily and showed the typical sequence motif of the protease inhibitor of the seed storage protein group. ClCI (12.5 mg) inhibited mycelial growth of the phytopathogenic fungi Mycosphaerella melonis, Helminthosporium turcicum, Alternaria solani, Phytophthora capsici, Isariopsis griseola, and Colletotrichum gloeosporioides, and caused 89% inhibition of the proteases from spore germination of plant-pathogenic fungi. The results of the present study indicate that ClCI had biotechnological potential as an alternative agent to combat the important phytopathogenic fungi.


Malignant involvement of the knee synovium in a patient with metastastic oesophageal adenocarcinoma.
We describe the case of a malignant arthritis of the knee. This is the first description with an oesophageal adenocarcinoma being the primary site of the malignancy. Diagnosis of this rare condition can be made by cytological examination of joint fluid or by synovial biopsy. X-ray of the joint can, as in our case, be negative. There is no standard therapy and the prognosis seems to be poor. Although rare, malignant synovitis represents an important differential diagnosis in patients with an unexplained monoarthritis, as it can be the first sign of malignancy or the only site of metastic disease.


16S rRNA gene profiling of rhizospheric microbial community of Eichhornia crassipes.
The rhizosphere of a plant is an important interface for the plant-microbe interaction that plays a significant role in the uptake and removal of heavy metal from contaminated sites. Eichhornia crassipes is a free-floating macrophyte and a well-known metal hyperaccumulator. It is a promising plant, which harbors a diverse microbial community in its rhizosphere. Therefore it is hypothesized that it can be a good habitat for microorganisms that supports plant growth and increases its phytoremediation potential. The rhizospheric DNA was extracted from the procured plant samples. The library was prepared and sequenced using the Illumina platform. 16S rRNA data from the Next Generation Sequencing (NGS) platform was analyzed using the QIIME software package. Alpha diversity was estimated from statistical indices i.e. Shannon index, Chao1 index, and observed species. The rarefaction plots, rank abundance curve, krona graph, and heat map were generated to study the rhizospheric community in detail. Metagenome consisted of 225,408 flash reads, 185,008 non-chimeric sequences with 17,578 Operational Taxonomic Units (OTU's), and 4622 OTU's without singletons. The data of present study are available at NCBI Bioproject (PRJNA631882). The taxonomic analysis of OTU's showed that the sequences belonged to major Phyla revealing the dominance of Proteobacteria, Bacteroidetes, Cyanobacteria, and Verrucomicrobia. The most abundant Genera in the sampled rhizosphere recorded were Thiothrix and Flavobacterium.


Lentiviral vector-mediated siRNA knockdown and concurrent rescue of Murine CIN85.
RNA interference (RNAi), an evolutionarily conserved process of gene silencing, is now a common tool in gene functional studies. However, potential "off-target effects" is one of major concerns in RNAi experiment associated with false positive results. Apart from continuing improvement in small interfering RNA (siRNA) designs, there is no method available to prevent the generation of "off-target effects" resulted from possible identity between siRNA and abundant cellular mRNA transcripts. In the present study, we have developed a lentiviral vector-mediated system that allows efficient siRNA silencing and concurrent rescue of targeted genes. While this approach does not eliminate potential "off-target effects," concurrent rescue of a target gene allows a definite judgment with regard to a phenotype change, either from expected siRNA silencing or "off-target effects." The system has been validated with murine CIN85 gene and may be generally applicable in molecular studies from broad fields.


Improving the prescribing of antibiotics for urinary tract infection.
In recent years there have been changes in the recommended antibiotic treatment for urinary tract infections (UTIs). In particular, the use of amoxycillin or co-trimoxazole is now discouraged, with amoxycillin-potassium clavulanate, cephalexin and trimethoprim becoming first-line agents for uncomplicated lower UTIs. To examine whether academic detailing, performed by a pharmacist, could modify prescribing practices for antibiotics used in the treatment of UTI in the community setting. The intervention was conducted in Southern Tasmania, using the remainder of the State as a control area. The target group of general practitioners was sent educational material designed to assist in the appropriate prescribing of antibiotics in the treatment of UTI. A pharmacist then visited each general practitioner and discussed the rational use of antibiotics for UTIs directly with him/her. Outcomes were measured using evaluation feedback from the general practitioners and pharmacoepidemiological data, which were not linked to diagnosis. The key variable examined was the total defined daily doses (DDDs) dispensed for the recommended first-line agents (amoxycillin-potassium clavulanate, cephalexin and trimethoprim) compared with amoxycillin (3 g single-dose form) and co-trimoxazole. The educational programme was very well received by the general practitioners. Changes in the prescribing of antibiotics commonly used for UTIs were evident in both study regions over the course of the study, but the improvements were significantly greater in the intervention area. Educational programmes utilizing academic detailing by pharmacists can modify prescribing practices within the community setting.


In vitro antibacterial activity and beta-lactamase stability of the new carbapenem SM-7338.
The in vitro activity of the new carbapenem SM-7338 was tested in comparison with imipenem, ceftazidime, cefotaxime, flomoxef, cefuzonam and cefmetazole against 2850 clinical bacterial isolates. SM-7338 showed good activity against a broad spectrum of gram-positive and gram-negative bacteria. SM-7338 was very active against gram-negative bacteria, inhibiting all Enterobacteriaceae, except 25% of Serratia marcescens isolates, at a concentration of 0.78 mg/l. SM-7338 inhibited the majority of Pseudomonas spp. at concentrations of less than or equal to 3.13 mg/l, its activity being twofold higher than that of imipenem. However, the activity of SM-7338 against gram-positive cocci was about one-fourth that of imipenem. Against anaerobes, SM-7338 also had the best activity of the beta-lactams tested. The compound was inactive against methicillin-resistant staphylococci, Enterococcus faecium, Xanthomonas maltophilia and Flavobacterium spp., as were the other beta-lactams. SM-7338 was quite stable in the presence of various types of beta-lactamase, but was hydrolyzed by Xanthomonas maltophilia beta-lactamase, as was imipenem. This high degree of stability was responsible for the potent activity of SM-7388 against beta-lactamase-producing species such as Enterobacter cloacae, Citrobacter freundii and Proteus vulgaris. SM-7338 also showed bactericidal activity against clinical isolates at the MIC or at concentrations slightly above the MIC.


Cardiac pathology and outcomes vary between Kawasaki disease and PIMS-TS.
Overlapping clinical features promoted the discussion of whether Kawasaki disease (KD) and PIMS-TS share pathophysiological features and disease outcomes. Medical records from English patients with KD (2015-02/20, N = 27) and PIMS-TS (02/2020-21, N = 34) were accessed to extract information. Children with PIMS-TS were older and more frequently of minority ethnicity background. They patients more commonly exhibited cytopenias and hyperferritinemia, which associated with diffuse cardiac involvement and functional impairment. In some PIMS-TS cases, cardiac pathology developed late, but outcomes were more favorable. In both, KD and PIMS-TS, baseline coronary diameter was a predictor of outcomes. PIMS-TS treatment more frequently included respiratory and cardiovascular support, and corticosteroids with IVIG. Cardiac involvement in PIMS-TS may be the result of a cytokine storm. Though more severe and diffuse when compared to KD, cardiac involvement of PIMS-TS has a more favorable prognosis, which may, after recovery, mitigate the need for long-term follow up.


2D- and 3D-QSAR Modeling of Imidazole-Based Glutaminyl Cyclase Inhibitors.
Glutaminyl Cyclase (QC) is a novel target in the battle against Alzheimer's disease, a highly prevalent neurodegenerative disorder. QC inhibitors have the potential to be developed as therapeutically useful anti-Alzheimer's disease agents. Linear and non-linear 2D-Quantitative Structure-Activity Relationship (QSAR) models were developed using Stepwise Multiple Linear Regression (S-MLR) and neural networks. Partial least squares (PLS) method was used to develop a 3D-QSAR model. Also, the developed models were used in virtual screening of the ZINC database to identify potential QC inhibitors. The 2D neural network model showed superior predictive ability, as demonstrated by the validation parameters R2 = 0.933, Q2 = 0.886 and R2 pred = 0.911. The 3D-QSAR model's steric and electrostatic fields' isocontour maps were visualized and revealed important structural requirements associated with good activity. The virtual screening identified six compounds as potentially active QC inhibitors with improved pharmacokinetic profiles. The developed QSAR models can be used to predict the activity of compounds not yet synthesized and prioritized for their synthesis and biological evaluation. Also, potentially active QC inhibitors have been identified with attractive lead-like properties that can be used to develop anti- Alzheimer's disease agents.


Genome-wide identification and skin expression of immunoglobulin superfamily in discus fish (Symphysodon aequifasciatus) reveal common genes associated with vertebrate lactation.
Discus Symphysodon spp. employs an unusual parental care behavior where fry feed on parental skin mucus after hatching. Studies on discus immunoglobulin superfamily (IgSF) especially during parental care are scarce. Here, a total of 518 IgSF members were identified based on discus genome and clustered into 12 groups, unevenly distributing on 30 linkage groups. A total of 92 pairs of tandem duplication and 40 pairs of segmental duplication that underwent purifying selection were identified. IgSF genes expressed differentially in discus skin during different care stages and between male and female parents. Specifically, the transcription of btn1a1, similar with mammalian lactation, increased after spawning, reached a peak when fry started biting on parents' skin mucus, and then decreased. The expression of btn2a1 and other immune members, e.g., nect4, fcl5 and cd22, were up-regulated when fry stopped biting on mucus. These results suggest the expression differentiation of IgSF genes in skin of discus fish during parental care.


[Effects on the shear bond strength of orthodontic brackets with different concentration of fluorided etching fluid].
This study was to find out the most suitable concentration of added NaF to enough bonding strength of brackets. Sixty-four teeth were randomly divided into A, B, C and the control group. NaF of four different concentrations (1.23%, 2%, 3% and 0%) was added into 35% phosphoric acid. The four group teeth were etched with four kinds of fluoride etching fluid respectively and were bonded with brackets. Four specimens in each group were selected by turns after 1, 4, 12 and 24 weeks of bonding. The shear bond strength of the teeth were tested, and the adhesive residual index (ARI) of bonding interface were recorded. The shear bond strength at four test time in each group was no significant (P > 0.05). There was statistical difference of the shear bond strength between four groups (P < 0.05), and group C was lower than the other groups. The ARI was no statistical difference between four groups. The effects of etching and bonding had no significant changes when the concentration of added NaF was no more than 2%. The shear bond strength decreased while the concentration of NaF was higher than 3%.


Effects of adding potassium iodate to milk before UHT treatment. I. Reduction in the amount of deposit on the heated surfaces.
Additions of potassium iodate to milk at 0.05 and 0.1 mM (10 and 20 ppm) before UHT treatment markedly reduced the rate at which pressure built up during processing. This permitted the use of longer processing times before unacceptable pressures were reached in the heat exchangers. Iodate reduced the amount of protein deposited, particularly in the higher temperature sections of the plant, but had no effect on the deposition of minerals. The more compact nature of the highly mineral deposits offered less resistance to the flow path. Reduction in the amount of protein deposited is likely to be caused by increased denaturation of beta-lactoglobulin and oxidation of heat activated sulphydryl groups by the iodate, thus reducing the formation of high molecular weight polymers of sulphur-containing proteins at the heated surfaces. Increasing the level of sulphydryl groups in the milk through the addition of L-cysteine-HCl caused an increase in the amount of deposit formed during UHT treatment. Whilst little detrimental effect on the quality of milk resulted from additions of iodate at 0.05 mM, milks with 0.1 mM-iodate became bitter during subsequent aseptic storage. Bitterness was a result of iodate-induced proteolysis of casein.


Glass yttrium-90 microspheres for patients with colorectal liver metastases.
Total calculated uniform liver doses of up to 150 Gy were achieved using glass yttrium-90 microspheres administered via the hepatic artery and targeted to tumour using angiotensin II in seven patients with colorectal liver metastases. No toxicity was observed. Hepatic metastatic progression was delayed in six patients. Median survival was 11 months (range 5-25 + months).


Pharmacognostic characterization, wound healing and toxicity assessment of the stem bark of Xylia evansii Hutch (Leguminosae).
Xylia evansii is widely used in traditional medicine to stop bleeding gums and treat wounds. This study was undertaken to assess the wound healing activity and toxicity profile of the stem bark methanol extract of X. evansii (XES). Wound healing activity was determined by the dermal excision model in rats. The free radical scavenging capacity, antioxidant activity, total phenolic and flavonoid contents were evaluated by the 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, total antioxidant capacity (TAC), aluminum chloride colorimetric and Folin Ciocalteu methods respectively. Acute and sub-acute oral toxicity assessment was performed following the Organization for Economic Co-operation and Development guidelines. Significant (p < 0.05) dose-dependent wound healing effect, similar to that of 1 % silver sulphadiazine was elicit by the 10, 15 and 20 %w/w XES ointments. The highest effect was demonstrated by XES 20 %w/w which resulted in 98.3 % wound surface closure by day 9 of treatment (p < 0.0001). The total phenolic and flavonoid contents were determined to be 381.2 ± 12.57 mg/g gallic acid equivalent (GAE) and 460 ± 29.07 mg/g quercetin equivalent respectively. XES exhibited remarkable free radical scavenging effect (IC50 = 68.13 ± 1.87 μg/mL) and had a total antioxidant capacity of 279.2 ± 32.08 mg/g GAE. The LD50 of XES was estimated to be > 5000 mg/kg. In sub-acute toxicity, 28 days treatment with XES (250, 500, 1000 mg/kg body weight) did not result in any significant (p > 0.05) change in the body weight or weight of the heart, lung, spleen, liver and kidneys. The haematological and biochemical profiles of XES-treated rats were not significantly (p > 0.05) affected after 4-weeks treatment with XES, except for platelet count which increased significantly (p < 0.0001) in a non-dose-dependent manner. Histopathological examination did not reveal any toxic effect to liver cells, however at 1000 mg/kg XES, slight abnormalities were identified in the glomeruli. Microscopy of the powdered stem bark displayed calcium oxalate crystals, pitted vessels and lignified fibres. Tannins, flavonoids, coumarins, saponins, triterpenes and alkaloids were identified in the bark. This is the first report on the wound healing potential and safety profile of X. evansii, giving scientific credence to its use in traditional medicine.


A comprehensive overview of urogenital, anorectal and oropharyngeal Neisseria gonorrhoeae testing and diagnoses among different STI care providers: a cross-sectional study.
Gonorrhoea, caused by Neisseria gonorrhoeae (NG), can cause reproductive morbidity, is increasingly becoming resistant to antibiotics and is frequently asymptomatic, which shows the essential role of NG test practice. In this study we wanted to compare NG diagnostic testing procedures between different STI care providers serving a defined geographic Dutch region (280,000 inhabitants). Data on laboratory testing and diagnosis of urogenital and extragenital (i.e. anorectal and oropharyngeal) NG were retrieved from general practitioners (GPs), an STI clinic, and gynaecologists (2006-2010). Per provider, we assessed their contribution regarding the total number of tests performed and type of populations tested, the proportion of NG positives re-tested (3-12 months after treatment) and test-of-cure (TOC, within 3 months post treatment). Overall, 17,702 NG tests (48.7% STI clinic, 38.2% GPs, 13.1% gynaecologists) were performed during 15,458 patient visits. From this total number of tests, 2257 (12.7%) were extragenital, of which 99.4% were performed by the STI clinic. Men were mostly tested at the STI clinic (71%) and women by their GP (43%). NG positivity per visit was 1.6%; GP 1.9% (n = 111), STI clinic 1.7% (n = 131) and gynaecology 0.2% (n = 5). NG positivity was associated with Chlamydia trachomatis positivity (OR: 2.06, 95% confidence interval: 1.46-2.92). Per anatomical location, the proportion of NG positives re-tested were: urogenital 20.3% (n = 36), anorectal 43.6% (n = 17) and oropharyngeal 57.1% (n = 20). NG positivity among re-tests was 16.9%. Proportions of NG positives with TOC by anatomical location were: urogenital 10.2% (n = 18), anorectal 17.9% (n = 7) and oropharyngeal 17.1% (n = 6). To achieve best practice in relation to NG testing, we recommend that: 1) GPs test at extragenital sites, especially men who have sex with men (MSM), 2) all care providers consider re-testing 3 to 12 months after NG diagnosis and 3) TOC is performed following oropharyngeal NG diagnosis in settings which provide services to higher-risk men and women (such as STI clinics).


High density lipoprotein from coronary artery disease patients caused abnormal expression of long non-coding RNAs in vascular endothelial cells.
Increased evidence has showed that normal high density lipoprotein (HDL) could convert to dysfunctional HDL in diseases states including coronary artery disease (CAD), which regulated vascular endothelial cell function differently. Long non-coding RNAs (lncRNAs) play an extensive role in various important biological processes including endothelial cell function. However, whether lncRNAs are involved in the regulation of HDL metabolism and HDL-induced changes of vascular endothelial function remains unclear. Cultured human umbilical vein endothelial cells (HUVECs) were treated with HDL from healthy subjects and patients with CAD and hypercholesterolemia for 24 h, then the cells were collected for lncRNA-Seq and the expressions of lncRNAs, genes and mRNAs were identified. The bioinformatic analysis was used to evaluate the relationship among lncRNAs, encoding genes and miRNAs. HDL from healthy subjects and patients with CAD and hypercholesterolemia leaded to different expressions of lncRNAs, genes and mRNAs, and further analysis suggested that the differentially expressed lncRNAs played an important role in the regulation of vascular endothelial function. Thus, HDL from patients with CAD and hypercholesterolemia could cause abnormal expression of lncRNAs in vascular endothelial cells to affect vascular function.


C766T low-density lipoprotein receptor-related protein 1 (LRP1) gene polymorphism and susceptibility to breast cancer.
Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor with an important role in regulating the activity of proteinases in extracellular matrix. Several studies have also described its role in intracellular signaling. Previous studies showed that the expression of LRP1 is related to invasiveness of cancer cells. However, recent data on LRP1 suggest that this receptor can also be involved in tumor establishment and progression. We investigated an association between the C766T polymorphism of the third exon of the LRP1 gene and breast cancer in a sample of women of Caucasian origin. Allele and genotype frequencies of this polymorphism were assessed in 164 women with breast cancer and in 183 age-compatible women without a history of any cancer disease. An increase in LRP1 T allele frequency in subjects with breast cancer was observed compared with controls (0.21 versus 0.15, P = 0.01963). A significant excess of genotypes with the T allele (homozygotes plus heterozygotes) was also observed (odds ratio 1.743, 95% confidence interval 1.112-2.732). The T allele of the C766T polymorphism in the LRP1 gene is associated with an increased risk of breast cancer development in women of Caucasian origin.


Transgenesis and Genome Engineering: A Historical Review.
Our ability to modify DNA molecules and to introduce them into mammalian cells or embryos almost appears in parallel, starting from the 1970s of the last century. Genetic engineering techniques rapidly developed between 1970 and 1980. In contrast, robust procedures to microinject or introduce DNA constructs into individuals did not take off until 1980 and evolved during the following two decades. For some years, it was only possible to add transgenes, de novo, of different formats, including artificial chromosomes, in a variety of vertebrate species or to introduce specific mutations essentially in mice, thanks to the gene-targeting methods by homologous recombination approaches using mouse embryonic stem (ES) cells. Eventually, genome-editing tools brought the possibility to add or inactivate DNA sequences, at specific sites, at will, irrespective of the animal species involved. Together with a variety of additional techniques, this chapter will summarize the milestones in the transgenesis and genome engineering fields from the 1970s to date.


Total hip arthroplasty in Denmark: incidence of primary operations and revisions during 1996-2002 and estimated future demands.
The annual number of total hip arthroplasties (THA) has increased in Denmark over the past 15 years. There is, however, limited detailed data available on the incidence of THAs. We calculated the incidence rates (IR) of primary THA and revision in Denmark between 1996 and 2002 and estimated the demands for primary THA in Denmark until 2020. We used data from the Danish Hip Arthroplasty Registry, a nationwide and population-based clinical database, to identify patients who had undergone primary THA (n = 37,144) or revision arthroplasties (n = 6446). Age and sex-specific data on the Danish population were obtained from the StatBank Denmark. All IRs were standardized according to two standards, i.e. the Danish population in 1996 and the European standard population (18 age groups). The future demands for primary THA were estimated using the age and sex-specific incidence of primary THA for 2002 as a reference, and taking into account the expected changes in the age distribution of the population and the trend in IRs seen in Denmark between 1996 and 2002. The annual overall standardized IRs of primary THAs and revisions increased from 101 (95% confidence interval (CI): 97.6-104) to 134 (CI: 131-138) and from 19.2 (CI: 17.9-20.5) to 21.1 (CI: 19.8-22.4) per 100,000 inhabitants from 1996 to 2002, respectively (IRs adjusted to the Danish population in 1996). The IRs of primary THAs and revisions increased by 30% and 10% during this period. The relative increase in IRs of primary THAs was found to be similar in both women and men. The increase was higher among patients aged 50-59 years, however. Furthermore, a decrease in IRs was seen in patients who underwent primary THA due to rheumatoid arthritis. IRs of primary THAs have been estimated to increase by 22% in 2020 compared with 2002, based only on the expected changes in the age distribution of the population. However, assuming that the annual age and sex-independent increase in the IRs seen in the period 1996-2002 will continue, the IR of primary THA is estimated to increase by as much as 210% in 2020. The overall annual standardized IRs of primary THAs and revisions in Denmark increased during the period from 1996 to 2002. Moreover, the demands for THA procedures in the coming decades may exceed the current capacity due to the ageing population and a continued age and sex-independent increase in surgical activity.


Sex and age affect acute and persisting COVID-19 illness.
Long COVID is associated with neurological and neuropsychiatric manifestations. We conducted an observational study on 97 patients with prior SARS-CoV-2 infection and persisting cognitive complaints that presented to the University Health Network Memory Clinic between October 2020 and December 2021. We assessed the main effects of sex, age, and their interaction on COVID-19 symptoms and outcomes. We also examined the relative contribution of demographics and acute COVID-19 presentation (assessed retrospectively) on persistent neurological symptoms and cognition. Among our cohort, males had higher hospitalization rates than females during the acute COVID-19 illness (18/35 (51%) vs. 15/62 (24%); P = .009). Abnormal scores on cognitive assessments post-COVID were associated with older age (AOR = 0.84; 95% CI 0.74-0.93) and brain fog during initial illness (AOR = 8.80; 95% CI 1.76-65.13). Female sex (ARR = 1.42; 95% CI 1.09-1.87) and acute shortness of breath (ARR = 1.41; 95% CI 1.09-1.84) were associated with a higher risk of experiencing more persistent short-term memory symptoms. Female sex was the only predictor associated with persistent executive dysfunction (ARR = 1.39; 95% CI 1.12-1.76) and neurological symptoms (ARR = 1.66; 95% CI 1.19-2.36). Sex differences were evident in presentations and cognitive outcomes in patients with long COVID.


Early low-grade proteinuria: causes, short-term evolution and long-term consequences in renal transplantation.
Proteinuria 1 year after transplantation is associated with poor renal outcome. It is unclear whether low-grade (<1 g/24 h) proteinuria earlier after transplantation and its short-term change affect long-term graft survival. The effects of proteinuria and its change on long-term graft survival were retrospectively assessed in 484 renal transplant recipients. One- and 3-month proteinuria correlated with donor age, donor cardiovascular death, prolonged cold and warm ischemia times and acute rejection. One- and 3-month proteinuria (per 0.1 g/24 h, hazard ratio (HR): 1.07 and 1.15, p<0.0001)-especially low-grade proteinuria (HR: 1.20 and 1.26, p<0.0001)-were powerful, independent predictors of graft loss. Its short-term reduction correlated with arterial pressure (AP) (the lower the 3-month diastolic and 12-month systolic AP, the lower the risk of increasing proteinuria during 1-3 months and 3-12 months periods, respectively: Odds ratio (OR) per 10 MmHg: 0.78, p=0.01 and 0.85, respectively, p=0.02), and was associated with decreased long-term graft loss (per 0.1 g/24 h: HR: 0.88 and 0.98, respectively, p<0.0001), independently of initial proteinuria. Early low-grade proteinuria due to pre-transplant renal lesions, ischemia-reperfusion and immunologic injuries is a potent predictor of graft loss. Short-term reduction in proteinuria is associated with improved long-term graft survival.


Predictive Value of Pooled Cerebral Blood Volume Mapping for Final Infarct Volume in Patients with Major Artery Occlusions. A Retrospective Analysis.
Detection of ischemic core and collateral status is helpful to predict clinical success of thrombectomy in acute cerebral artery occlusion. Angiographic flat panel detector computed tomography (CT) with pooled blood volume (PBV) data acquisition was described to be helpful to estimate ischemic core in stroke patients prior to thrombectomy and to depict cerebral vessels. We therefore retrospectively evaluated preinterventional PBV data of a large collective of ischemic stroke patients prior to thrombectomy to test its predictive value on final infarct considering PBV maps and collateral status. We used PBV data from 101 patients with acute cerebral artery occlusion prior to successful thrombectomy to reconstruct PBV maps and collateral status maps. Suspected ischemic core and collateral status were correlated to final infarct on follow-up multislice CT. Furthermore, the influence of time window and patient age was taken into consideration. In 75.2% (95% confidence interval CI 66-82%), suspected ischemic core (PBV) matched with final infarct and in 24.8% (95% CI 17-34%) final infarct was overestimated. In all patients, collateral status could be evaluated, and the better the collateral status, the smaller the final infarct (p = 0.016). Although not statistically significant, poor collaterals seem to be a risk factor for overestimation of final infarct on PBV maps. In patients >80 years old predictive value of PBV and collateral status is better than in patients ≤80 years old (p = 0.04). Increasing time window did not have significant impact on predictive value of PBV and collateral status. The PBV data are useful to expeditiously exclude infarct growth and estimate collateral status prior to thrombectomy after a longer interval between initial multislice CT magnetic resonance imaging (MRI) and intervention. However, because of overestimating final infarct in 25% of patients, PBV data presuming large infarct should not be used as the only basis for excluding patients from effective stroke treatment at this point in time.


Effects of 8 weeks functional training programme on posture control and functional mobility in spastic hemiplegic cerebral palsy.
To determine the impacts of functional training versus conventional training on posture control and functional mobility in spastic hemiplegic cerebral palsy children. The randomised clinical trial was conducted at the Rehab Cure physiotherapy centre, Lahore, Pakistan, from January to September 2020, and comprised children of either gender aged 4-14 years, diagnosed with cerebral palsy, gross motor functional classification system level II or III, and no mental retardation. The subjects were randomised into conventional therapy group A and functional training group B. Intensity of exercises was gradually increased each week, starting from 10 reps to 20 reps. The subjects received treatment 3 times a week for 8 weeks, and each session lasted 45-60 min. Paediatric Balance Scale, Trunk Control Measurement Scale, Five Times Sit to Stand Test and Timed-Up-and-Go test were used at baseline and post-intervention. Data was analysed using SPSS 21. Of the 14 subjects, there were 7(50%) in each of the two groups. Overall, there were 8(57.14%) males and 6(42.86%) females with a mean age of 7.57±1.86 years. Significant improvement was noted in both groups post-intervention (p<0.05), but intergroup differences were not significant (p>0.05). Both functional training and conventional therapy significantly improved postural control and functional mobility in spastic cerebral palsy children, but intergroup differences were not significant. IRCT20200909048676N1.


Brook Trout (Salvelinus fontinalis) and Brown Trout (Salmo trutta) summer thermal habitat use in streams with sympatric populations.
This study addresses the need to examine the thermally mediated interactions of fish with their natural environment by investigating the shift in thermal habitat occupation for sympatric Brook and Brown Trout populations. We observed upstream Brook Trout and Brown Trout population shifts during the summer, with thermal habitats showing an increased number of Brown Trout, while some sites also displayed a decrease in the number of Brook Trout. Overall, there was an increased incidence of overlapping habitat occupation at the end of the summer. Brown Trout occupied optimal resting and feeding thermal habitat locations, which can potentially affect growth rates and Brook Trout's survival. Population shifts did not occur at elevated water temperatures as expected but seem driven by temperatures that are optimal for growth. Observed population shifts can lead to increased interactions between the two species throughout the summer. The results provide a better understanding of how future, longer-term, thermal habitat modifications may modify species interactions, which are critical for salmonid conservation efforts.