The need for greater skin of color training: perspectives from communities of color.
More than half of the population will belong to a minority group by the year 2044. Further research needs to be done into the perceptions of those with skin of color regarding their dermatologic care. This study assessed the perceptions and preferences of communities of color regarding the care of their skin and hair. An anonymous, cross-sectional, multiple-choice, online survey was administered from August through October 2021. Participants were recruited using ResearchMatch, a national volunteer health registry supported by the US National Institutes of Health. Eligibility criteria included being 18 years or older, identifying with at least one racial/ethnic group within skin of color, and living in the United States. A total of 547 participants completed the survey, 463 women (84.6%) and 84 men (15.4%) with a mean (standard deviation) age of 44.1 (15.4) years. 301 self-identified as Black (55.0%), 84 Latinx (15.4%), 90 Asian (16.5%), and 72 Multiracial (13.2%). Participants did not feel like dermatologists are trained to treat skin of color (69.5%, n = 380) or ethnic hair (75.1%, n = 411). Participants believed that all dermatologists should have training in skin of color (92.3%, n = 505) and would be more likely to see a dermatologist if they had skin of color training (80.1%, n = 438) as they felt dermatologists who have skin of color training are better equipped to treat their conditions (67.1%, n = 367). Participants were more comfortable receiving treatment at clinics that specialize in skin of color (75.1%, n = 411), but overwhelmingly had never heard of skin of color clinics (94.1%, n = 515). Participants were willing to contribute non-identifiable photos (96.3%, n = 527) and stories about skin and hair diseases (94.1%, n = 515) to create skin of color resources to train dermatologists. Overall, perceptions of communities of color on dermatologic care need to be improved. Greater skin of color training including all races/ethnicities and skin tones is imperative, and greater visibility and resources should also be put into skin of color clinics and formal skin of color research.


Thiopurine dose in intermediate and normal metabolizers of thiopurine methyltransferase may differ three-fold.
Patients with inflammatory bowel disease (IBD) may have different thiopurine dose requirements in relation to thiopurine methyltransferase (TPMT) genotype and/or phenotype. The purpose of this study was to determine thiopurine dose requirements in intermediate versus normal TPMT metabolism status. Consecutive patients starting azathioprine or 6-mercaptopurine for IBD were followed up for 9 months. The thiopurine dose was individualized using 6-thioguanine nucleotide (6-TGN) concentrations (range, 235-450 pmol/8 x 10(8) red blood cells [RBCs]) and clinical status. Additional assessments undertaken every three months included measures of disease activity. Eight (10%) of 77 participants were withdrawn because of protocol violation. Fifty-two (75%) of the remaining 69 subjects ( approximately 90% and 10% with the TPMT*1/*1 and *1/*3 genotypes, respectively) completed follow-up on azathioprine (n = 46) or 6-mercaptopurine (n = 6). The mean initial dose (as azathioprine equivalents) was similar ( approximately 1 mg/kg/d) for the 2 TPMT genotypes, but after 9 months the dose was 50% lower in the TPMT*1/*3 group (0.9 vs 1.8 mg/kg/d, P < .0001). Despite dose adjustment, median 6-TGN concentrations still were 2-fold higher in the TPMT*1/*3 group at the end of the follow-up period (505 vs 273 pmol/8 x 10(8) RBCs, P = .02). This difference was 3-fold when the concentration was adjusted for dose (578 vs 183 pmol/8 x 10(8) per mg/kg/d, P = .0007). Results were similar if TPMT phenotype was used instead of genotype. Clinical outcomes did not differ between groups. Initial target doses to attain therapeutic 6-TGN concentrations (>235 pmol/8 x 10(8) RBCs) in patients with IBD might be 1 and 3 mg/kg/d in intermediate and normal metabolizers, respectively.


Prediction of Radiation-induced Lymphopenia following Exposure of the Thoracic Region and Associated Risk of Infections and Mortality.
Large blood volumes are irradiated when the heart is exposed to radiation. The mean heart dose (MHD) may be a good surrogate for circulating lymphocytes exposure. We investigated the association between MHD and radiation-induced lymphopenia and explored the impact of the end-of-radiation-therapy (EoRT) lymphocyte count on clinical outcomes. In total, 915 patients were analysed: 303 patients with breast cancer and 612 with intrathoracic tumours: oesophageal cancer (291), non-small cell lung cancer (265) and small cell lung cancer (56). Heart contours were generated using an interactive deep learning delineation process and an individual dose volume histogram for each heart was obtained. A dose volume histogram for the body was extracted from the clinical systems. We compared different models analysing the effect of heart dosimetry on the EoRT lymphocyte count using multivariable linear regression and assessed goodness of fit. We published interactive nomograms for the best models. The association of the degree of EoRT lymphopenia with clinical outcomes (overall survival, cancer treatment failure and infection) was investigated. An increasing low dose bath to the body and MHD were associated with a low EoRT lymphocyte count. The best models for intrathoracic tumours included dosimetric parameters, age, gender, number of fractions, concomitant chemotherapy and pre-treatment lymphocyte count. Models for patients with breast cancer showed no improvement when adding dosimetric variables to the clinical predictors. EoRT lymphopenia grade ≥3 was associated with decreased survival and increased risk of infections among patients with intrathoracic tumours. Among patients with intrathoracic tumours, radiation exposure to the heart contributes to lymphopenia and low levels of peripheral lymphocytes after radiotherapy are associated with worse clinical outcomes.


An antigen-specific signal is required for the activation of second-order suppressor T cells in the regulation of delayed-type hypersensitivity to 2,4,6-trinitrobenzene sulfonic acid.
Suppressor T cells (Ts-1) induced with trinitrophenyl (TNP)-conjugated syngeneic spleen cells (TNP-SC) can be enriched on antigen-coated plates and are afferent suppressors. In addition, these suppressor cells produced soluble suppressor factors (TsF) that were active in vivo. Therefore, the Ts-1 cells in the TNP system are very similar to the Ts-1 cells in other systems we have studied earlier. Further characterization of these TsF-1 revealed that TsF-1 obtained from TNP-SC-induced Ts-1 is major histocompatibility complex restricted in its activity. Injection of TNP-specific TsF-1 into naive mice did not induce Ts-2 unless additional corresponding antigen was provided. Moreover, the Ts-2 cells induced by administration of both TsF-1 and trinitrobenzene sulfonic acid were antigen specific rather than antiidiotypic.


Salylic acid minimize cadmium accumulation in rice through regulating the fixation capacity of the cell wall to cadmium.
Although salylic acid (SA) has been linked to how plants react to cadmium (Cd) stress, the exact mechanism is still unknown. The endogenous SA concentration in the rice (Oryza sativa L.) roots was enhanced by Cd stress in the current investigation, and exogenous SA reduced the hemicellulose content in root cell wall, which in turn inhibited its Cd binding capacity. What's more, exogenous SA also decreased the transcription level of genes such as Natural Resistance-Associated Macrophage Protein 5 (OsNRAMP5) and a major facilitator superfamily gene-OsCd1 that responsible for root Cd absorption. Finally, less Cd was accumulated in the rice as a result of the higher expression of Heavy Metal ATPase 3 (OsHMA3), Cation/Ca exchanger 2 (OsCCX2) and Pleiotropic Drug Resistance 9 (OsPDR9/OsABCG36) that were responsible for separating Cd into vacuole and getting Cd out of cells, respectively. In contrast, mutant with low SA level accumulated more Cd. Additionally, SA enhanced endogenous nitric oxide (NO) levels, and its alleviatory effects were mimicked by a NO donor, sodium nitroprusside (SNP). In conclusion, SA enhanced rice's Cd resistance through regulating the binding capacity of the cell wall to Cd, a pathway that might dependent on the NO accumulation.


Cullen's sign - Case report with a review of the literature.
Cullen's sign is described as superficial oedema with bruising in the subcutaneous fatty tissue around the peri-umbilical region. It is also known as peri-umbilical ecchymosis. We report a case of a fifty-three year old gentleman who presented with non-specific abdominal pain. Significant bruising was present within the subcutaneous fatty tissue on the anterior abdominal wall in keeping with 'Cullen's sign.' Of note he denied any alcohol intake and his amylase was normal. A diagnosis of pancreatitis was made following a CT scan of his abdomen. A search of the entire English literature using PubMed with the phrase 'Cullen's sign' has been performed. Papers were reviewed in relation to recognition of this clinical sign, differential diagnosis, and management. Our case and review of the literature highlights the rarity of this clinical sign which a clinician may encounter. In addition we draw to attention the importance of having knowledge of the underlying possible conditions which may lead to this sign, and can be vital in successful acute management.


Association of chicken zona pellucida glycoprotein (ZP) B1 with ZPC induces formation of ZPB1-ZPC fibrous aggregates containing disulfide-bridged ZPB1 dimer.
Egg-envelope, a fibrous extracellular matrix, surrounding an oocyte is constructed from ZPC, ZPX2, both of which are secreted from ovarian granulosa cells, and ZPB1 which is secreted from liver cells and transported into ovary in birds. We report here that in vitro incubation of ZPB1 with ZPC spontaneously produced fibrous aggregates of ZPB1-ZPC hetero-complexes, which were visible under optical microscopy and morphologically resembled the aggregates obtained from mechanically decomposed chicken egg-envelope. Formation of such fibrous aggregates depended on ZPC/ZPB1 ratio, and involved ZPB1 dimerization through disulfide cross-linking, which had been found in authentic egg-envelope developed in hen's ovary. Furthermore, addition of excessive amounts of ZPC to ZPB1 produced soluble but high molecular weight hetero-complexes with increased adherence property against polystyrene ELISA plates. Thus, the specific association between ZPB1 and ZPC could play pivotal roles to initiate complex formation of hetero-polymers of ZP proteins in egg-envelope matrix construction.


Chlorhexidine-calcium phosphate nanoparticles - Polymer mixer based wound healing cream and their applications.
In this work, we developed a wound healing cream composed of two different polymers, namely chitosan and gelatin with chlorhexidine along with calcium phosphate nanoparticles. The physicochemical properties of the prepared cream were investigated based on SEM, EDX, Raman, FTIR and the results indicated that the cream contained gelatin, chitosan, calcium phosphate nanoparticles and chlorhexidine. The maximum swelling ratio studies indicated that the ratio was around of 52±2.2 at pH7.4 and the value was increased in acidic and alkaline pH. The antimicrobial activity was tested against bacteria and the results indicated that, both chlorhexidine and the hybrid cream devoid of chlorhexidine exhibited antimicrobial activity but the chlorhexidine impregnated cream showed three fold higher antimicrobial activity than without chlorhexidine. In vivo wound healing promoting activities of hybrid cream containing 0.4mg/L chlorhexidine were evaluated on surgically induced dermal wounds in mice. The results indicated that the cream with incorporated chlorhexidine significantly enhanced healing compared with the control samples. For the field validations, the veterinary clinical animals were treated with the cream and showed enhanced healing capacity. In conclusion, a simple and efficient method for design of a novel wound healing cream has been developed for veterinary applications.


A new location to split Cre recombinase for protein fragment complementation.
We have previously described a recombinase-mediated gene stacking system in which the Cre recombinase is used to remove lox-site flanked DNA no longer needed after each round of Bxb1 integrase-mediated site-specific integration. The Cre recombinase can be conveniently introduced by hybridization with a cre-expressing plant. However, maintaining an efficient cre-expressing line over many generations can be a problem, as high production of this DNA-binding protein might interfere with normal chromosome activities. To counter this selection against high Cre activity, we considered a split-cre approach, in which Cre activity is reconstituted after separate parts of Cre are brought into the same genome by hybridization. To insure that the recombinase-mediated gene stacking system retains its freedom to operate, we tested for new locations to split Cre into complementing fragments. In this study, we describe testing four new locations for splitting the Cre recombinase for protein fragment complementation and show that the two fragments of Cre split between Lys244 and Asn245 can reconstitute activity that is comparable to that of wild-type Cre.


Developmental toxicity of flupyrazofos, a new organophosphorus insecticide, in rats.
Flupyrazofos is a new type of pyrazole organophosporus insecticide, which has a high activity against the diamond-back moth (Plutella xylostella). The potential of this agent to induce developmental toxicity was investigated in the Sprague-Dawley rat. One hundred mated females (sperm in vaginal LAVAGE=day 0) were distributed among three treated groups and a control group. Flupyrazofos was administered by gavage to pregnant rats from days 7-17 of gestation at dose levels of 0, 5, 12 and 30 mg/kg/day. All dams were subjected to the caesarean section on day 20 of gestation and their fetuses were examined for external, visceral and skeletal abnormalities. At 30 mg/kg, maternal effects including mortality (4.3%), clinical signs of toxicity, decreased food intake, suppressed body weight, and increased weight of adrenal glands, kidney and heart were observed in dams. Litter values for corpora lutea, implantations, sex ratio and litter size were within the normal range. However, a reduction in the fetal weight and an increase in the incidence of fetal skeletal retardations were observed. At 12 mg/kg, toxic effects including mortality (4.2%), nasal discharge and some fetal skeletal retardation were observed. There were no signs of either maternal toxicity or embryotoxicity at 5 mg/kg. The results show that flupyrazofos induces fetal growth retardation only at maternally toxic doses in rats and the no-observed-adverse-effect levels (NOAELs) of this agent are considered to be 5 mg/kg for both dams and fetuses.


Cholesterol metabolism: from lipidomics to immunology.
Oxysterols, the oxidized forms of cholesterol or of its precursors, are formed in the first steps of cholesterol metabolism. Oxysterols have interested chemists, biologists, and physicians for many decades, but their exact biological relevance in vivo, other than as intermediates in bile acid biosynthesis, has long been debated. However, in the first quarter of this century, a role for side-chain oxysterols and their C-7 oxidized metabolites has been convincingly established in the immune system. 25-Hydroxycholesterol has been shown to be synthesized by macrophages in response to the activation of Toll-like receptors and to offer protection against microbial pathogens, whereas 7α,25-dihydroxycholesterol has been shown to act as a chemoattractant to lymphocytes expressing the G protein-coupled receptor Epstein-Barr virus-induced gene 2 and to be important in coordinating the action of B cells, T cells, and dendritic cells in secondary lymphoid tissue. There is a growing body of evidence that not only these two oxysterols but also many of their isomers are of importance to the proper function of the immune system. Here, we review recent findings related to the roles of oxysterols in immunology.


Principles of multimode pacing.
Although physiologic pacing systems have multiplied recently, their functional evaluation by ECG analysis remains an area of relative complexity. More thorough and detailed specifications of operation are necessary to aid the clinician in his effort to understand and assess the function of a DDD pacer. Elimination of cross-talk via various available methods should simplify interpretation. Awareness by physicians will provide the necessary feedback to the designers to create more physiologic systems in the future.


New permanent endocardial atrial J lead: implantation techniques and clinical performance.
The potential benefits of pacing systems which restore A-V synchrony have long been recognized. However, availability of atrial leads which are easily implanted and which consistently perform well has been limited. A new version of the silicone rubber tined J leads is now available. Changes were made in the insulation material, conductor configuration, tine configuration, and a J memory coil was added. After over three years of use in 100 patients, we conclude that these leads are easier to implant than previous atrial leads, and that they demonstrate excellent clinical performance.


Molecular dynamics simulation of a palmitoyl-oleoyl phosphatidylserine bilayer with Na+ counterions and NaCl.
Two 40 ns molecular dynamics simulations of a palmitoyl-oleoyl phosphatidylserine (POPS) lipid bilayer in the liquid crystalline phase with Na(+) counterions and NaCl were carried out to investigate the structure of the negatively charged lipid bilayer and the effect of salt (NaCl) on the lipid bilayer structure. Na(+) ions were found to penetrate deep into the ester region of the water/lipid interface of the bilayer. Interaction of the Na(+) ions with the lipid bilayer is accompanied by a loss of water molecules around the ion and a simultaneous increase in the number of ester carbonyl oxygen atoms binding the ion, which define an octahedral and square pyramidal geometry. The amine group of the lipid molecule is involved in the formation of inter- and intramolecular hydrogen bonds with the carboxylate and the phosphodiester groups of the lipid molecule. The area per lipid of the POPS bilayer is unaffected by the presence of 0.15M NaCl. There is a small increase in the order parameter of carbon atoms in the beginning of the alkyl chain in the presence of NaCl. This is due to a greater number of Na(+) ions being coordinated by the ester carbonyl oxygen atoms in the water/lipid interface region of the POPS bilayer.


Revisiting Kuo and Belland's exploratory study of undergraduate students' perceptions of online learning: minority students in continuing education.
COVID-19 has forced educators to make rapid changes to their pedagogy in order to shift from face-to-face instruction to online delivery. In this time of rapid change, Kuo and Belland's (Educ Technol Res Dev 64:661-680, 2016) exploratory study that highlights the types of interactions that correlated with African American students' success in an undergraduate course could provide instructors with ideas about how to create more equitable online courses. Thus, this article describes how instructors might consider the cultural and racialized experiences of their students through an asset lens as they design online coursework. Specifically, instructors should attend to students' experiences and determine how students will interact with the content, with the instructor, and with other learners. Implications are described.


Molecular mechanism of ADP-ribose hydrolysis by human NUDT5 from structural and kinetic studies.
Human NUDT5 (hNUDT5) is an ADP-ribose (ADPR) pyrophosphatase (ADPRase) that plays important roles in controlling the intracellular levels of ADPR and preventing non-enzymatic ADP-ribosylation of proteins by hydrolyzing ADPR to AMP and ribose 5'-phosphate. We report the crystal structure of hNUDT5 in complex with a non-hydrolyzable ADPR analogue, alpha,beta-methyleneadenosine diphosphoribose, and three Mg(2+) ions representing the transition state of the enzyme during catalysis. Analysis of this structure and comparison with previously reported hNUDT5 structures identify key residues involved in substrate binding and catalysis. In the transition-state structure, three metal ions are bound at the active site and are coordinated by surrounding residues and water molecules. A conserved water molecule is at an ideal position for nucleophilic attack on the alpha-phosphate of ADPR. The side chain of Glu166 on loop L9 changes its conformation to interact with the conserved water molecule compared with that in the substrate-bound structure and appears to function as a catalytic base. Mutagenesis and kinetic studies show that Trp28 and Trp46 are important for the substrate binding; Arg51 is involved in both the substrate binding and the catalysis; and Glu112 and Glu116 of the Nudix motif, Glu166 on loop L9, and Arg111 are critical for the catalysis. The structural and biochemical data together reveal the molecular basis of the catalytic mechanism of ADPR hydrolysis by hNUDT5. Specifically, Glu166 functions as a catalytic base to deprotonate a conserved water molecule that acts as a nucleophile to attack the alpha-phosphate of ADPR, and three Mg(2+) ions are involved in the activation of the nucleophile and the binding of the substrate. Structural comparison of different ADPRases also suggests that most dimeric ADPRases may share a similar catalytic mechanism of ADPR hydrolysis.


Peri-abortion contraceptive counseling: A systematic review of randomized controlled trials.
To assess the effects of peri-abortion contraceptive counseling interventions. We performed a systematic review of randomized controlled trials (RCTs) that compared the effect of different types of peri-abortion contraceptive counseling interventions and were published as original papers in scientific journals. The literature search was performed in June 2021 in PubMed, Central Cochrane Library (CENTRAL), Scopus, and Google Scholar; without restrictions in language or publication date. Two independent authors identified studies that met the inclusion and exclusion criteria and extracted the data. The risk of bias was assessed using the Cochrane tool, and evidence certainty was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Whenever possible, meta-analyses were performed. The protocol was registered at PROSPERO (CRD42020187354). Eleven RCTs were eligible for inclusion (published from 2004 to 2017), from which nine compared enhanced versus standard counseling. Pooled estimates showed that, compared to standard counseling, enhanced counseling was associated with a higher incidence of effective contraceptive use (>3 months) (relative risk [RR], 1.12; 95% confidence interval [CI], 1.09-1.16), although no significant difference was found in the incidence of long-acting reversible contraceptive use (RR, 1.25; 95% CI, 0.68-2.29), contraceptive uptake (RR, 1.06; 95% CI, 0.98-1.15), and obstetric event occurrence (RR, 0.91; 95% CI, 0.57-1.47). Certainty of evidence was very low for all outcomes. In addition, two studies compared contraceptive counseling provided by physicians versus that provided by non-physicians, which did not show significant differences. Enhanced contraceptive counseling may favor effective contraceptive use but may not affect the rate of obstetric event occurrence. Also, the studies did not find a difference in the effects of counseling interventions given by different providers. Since evidence certainty was very low, future well-designed RCTs are needed to make informed decisions. The study protocol was registered at PROSPERO (CRD42020187354).


Effect of non-steroidal anti-inflammatory drugs on the histology of basal cell carcinomas.
Aggressive histology is not rare in BCC. Large studies from referral centers report incidences of aggressive histology BCC ranging from 2.5- 44%. These aggressive BCC are characterized by subclinical extension, invasive behavior, local recurrence and challenging treatment. To examine the association between non-steroidal anti-inflammatory drug (NSAID) use and the different histological subtypes of basal cell carcinoma (BCC). The design was a nested case-control study. The two population-based cohorts were of patients with a primary BCC diagnosis during January and May 2010 (n=136) and NSAID use in the 15 years prior to baseline. All the lesions were excised and analyzed to determinate the histological subtype of BCC as aggressive or non-aggressive. Odds ratios (ORs) and 95% confidence intervals (CIs), using conditional logistic regression, were calculated with the SPSS software to estimate the association of aggressive histological subtypes of BCC and use of NSAID. We controlled the potential confounding factors. The rate of non-aggressive BCC associated with exposure to NSAID was increased (OD: 0.34; 95% CI: 0.14-0.84) after adjusting for covariants. our sample is small. We collected data regarding use of NSAID over a wide time ranges, so that we are unable to propose when the potential benefits of NSAID on the histology of BCC would happen. According to our data, NSAID exposure is associated with a decreased risk of aggressive BCC.


Do Sex-Specific Factors Influence the Surgical Treatment of Facial Skin Cancer?
Facial skin cancer (FSC) is prone to incomplete excision due to the sophisticated anatomy and the aesthetic importance of the face. In this study, we sought to investigate to what extent sex-specific differences and other operation-, patient-, and cancer-specific factors influence the re-resection rate in FSC surgery, in order to provide personalized treatment strategies to patients. In this retrospective study, patients (>18 years) undergoing surgical excision of an FSC were enrolled. Each patient's demographic data, cancer location, the surgical team, primary and secondary surgeries were analyzed. Overall, 469 patients (819 surgeries) were included. The mean age was 69 ± 15 years. No significant association between sex-specific factors (surgeon's sex (OR: 1.09, 95% CI: 0.76-1.56) or patient's sex (OR: 0.85, 95% CI: 0.62-1.17), surgeon-patient sex concordance and discordance) and the likelihood of secondary surgery were found. However, healing by secondary intention (OR: 4.28; 95% CI: 1.94-9.45) and cancer location showed an increased re-resection rate. In conclusion, FSC surgery is a safe method unaffected by sex-specific factors, which had no impact on the re-resection rate. However, in further analysis, the likelihood of a re-resection was influenced by other factors such as healing by secondary intention and cancer location. This knowledge might be useful to provide an algorithm for personalized treatment strategies in the future.


[Young patient with acute monolateral amaurosis].
A 39-year-old patient presented with acute visual loss of the left eye. Although the initial ophthalmological and neurological examinations were uneventful, magnetic resonance imaging (MRI) showed optic canal narrowing and compression of the optic nerve secondary to a prominent posteriorly misplaced ethmoidal cell (so-called Onodi cell). Endonasal ethmoidectomy with decompression of the infected Onodi cell was performed. Microbiological testing showed growth of Haemophilus influenzae. Despite early surgical intervention vision could not be restored.


Glycosaminoglycan-degrading enzymes in the skin of fasted rats.
During fasting of animals, there is decreased content of skin glycosaminoglycans (GAGs) accompanied by decrease in their biosynthesis. Since tissue GAG content depends on both synthesis and degradation of these molecules, we asked whether fasting affects the activity of several tissue glycosidases. Therefore we measured the activity of skin neutral and acidic endoglycosidases, some exoglycosidases: beta-N-acetylhexosaminidase [EC 126.96.36.199], beta-galactosidase [EC 2.1.23], beta-glucuronidase [EC 184.108.40.206], alpha-iduronidase [EC 126.96.36.199], and two sulfatases: arylsulfatase B [EC 184.108.40.206] and 6-sulfatase [EC 126.96.36.199] in the skin of control and fasted rats. Although fasting was accompanied by distinct decrease in the activity of most neutral endoglycosidases, no characteristic changes in the activity of exoglycosidases were found. In contrast, we found that fasting is associated with increase in the activity of acidic endoglycosidases (of lysosomal origin) which degraded hyaluronic acid, chondroitin-4-sulfate, chondroitin-6-sulfate and heparin. The same GAGs were decreased in the skin of fasted rats. Our data suggest that the phenomenon is a result of increased intracellular degradation of these molecules. Therefore, not only decreased biosynthesis of GAGs during fasting, but also increased their intracellular degradation may contribute to decrease in GAG skin content.


[1-9-NαC]-Linusorb B3 (Cyclo-linopeptide A) dimethyl sulfoxide monosolvate.
Crystals of the dimethyl sulfoxide (DMSO) solvate of [1-9-NαC]-linusorb B3 (Cyclo-linopeptide A; CLP-A; C57H84N9O9·C2H6OS), a cyclic polypeptide were obtained following peptide extraction and purification from flaxseed oil. There are four intramolecular N-H⋯O hydrogen bonds. In the crystal, the mol-ecules are linked in chains along the a axis by N-H⋯O hydrogen bonds. Each DMSO O atom accepts a hydrogen bond from an NH group at the Phe6 location in the CLP-A mol-ecule.


Comparison of ego strength between aggressive and non-aggressive alcoholics: a cross-sectional study.
To determine the differences between aggressive and non-aggressive alcoholics in sociodemographic and clinical characteristics and ego strength. This cross-sectional study included 111 aggressive and 123 non-aggressive male alcoholics aged between 25 and 60 years who were admitted to the Department for Alcoholism, University Psychiatric Hospital Vrapče, Zagreb, Croatia, from January to December 2016. All participants met the diagnostic criteria for alcohol dependence according to the Croatian Mini International Neuropsychiatric Interview (MINI), 4th revised edition of Diagnostic and Statistical Manual of Mental Disorders, and the International Classification of Diseases. Participants were clinically assessed by an experienced psychiatrist using a clinical interview, MINI, Questionnaire from the Brown-Goodwin Lifetime History of Aggression, and Ego Identity Scale (EIS) according to Erikson. A clinical psychologist performed cognitive function measurements. EIS scores were analyzed using one-way analysis of variance. In comparison with non-aggressive alcoholics, aggressive alcoholics were more often divorced, unemployed, hospitalized, and first treated for alcoholism at an earlier age (P<0.05 for all). They more frequently experienced depression (42.4% vs 19.4%, P=0.013) and attempted suicide (34.7% vs 6.2%, P=0.003), achieved a lower level of maturity at the second stage of psychosocial development related to shame and doubt (14.0±4.1 vs 17.4±3.7, P=0.013) and at the fourth stage related to inferiority (13.1±6.8 vs 18.1±9.3, P=0.011), and had lower total EIS score (75.8±20.4 vs 85.2±21.5, P<0.012) than non-aggressive alcoholics. Aggressive alcoholics had weaker ego-strength than non-aggressive alcoholics, experienced more depressive reactions and suicide attempts, and showed poorer psychosocial functioning. Oxford Centre for Evidence-based Medicine level of evidence: 3*.


Discovery of hydroxyl 1,2-diphenylethanamine analogs as potent cholesterol ester transfer protein inhibitors.
Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. In an effort to improve the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series, polar groups were introduced to the N-linked quaternary center. Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice.


Effect of digestion on stability of palivizumab IgG1 in the infant gastrointestinal tract.
Potentially, orally administered antibodies specific to enteric pathogens could be administered to infants to prevent diarrheal infections, particularly in developing countries where diarrhea is a major problem. However, to prevent infection, such antibodies would need to resist degradation within the gastrointestinal tract. Palivizumab, a recombinant antibody specific to respiratory syncytial virus (RSV), was used in this study as a model for examining the digestion of neutralizing antibodies to enteric pathogens in infants. The survival of this recombinant IgG1 across digestion in 11 infants was assayed via an anti-idiotype ELISA and RSV F protein-specific ELISA. Concentrations were controlled for any dilution or concentration that occurred in the digestive system using mass spectrometry-based quantification of co-administered, orally supplemented, indigestible polyethylene glycol (PEG-28). Binding activity of Palivizumab IgG1 decreased (26-99%) across each phase of in vivo digestion as measured by both anti-idiotype and RSV F protein-specific ELISAs. Antibodies generated for passive protection of the infant gastrointestinal tract from pathogens will need to be more resistant to digestion than the model antibody fed to infants in this study, or provided in higher doses to be most effective. Binding activity of palivizumab IgG1 decreased (26-99%) across each phase of in vivo infant digestion as measured by both anti-idiotype and RSV F protein-specific ELISAs. Palivizumab was likely degraded by proteases and changes in pH introduced in the gut. Antibodies generated for passive protection of the infant gastrointestinal tract from pathogens will need to be more resistant to digestion than the model antibody fed to infants in this study, or provided in higher doses to be most effective. The monoclonal antibody IgG1 tested was not stable across the infant gastrointestinal tract. The observation of palivizumab reduction was unlikely due to dilution in the gastrointestinal tract. The results of this work hint that provision of antibody could be effective in preventing enteric pathogen infection in infants. Orally delivered recombinant antibodies will need to either be dosed at high levels to compensate for digestive losses or be engineered to better resist digestion. Provision of enteric pathogen-specific recombinant antibodies to at-risk infants could provide a new and previously unexplored pathway to reducing the infection in infants. The strategy of enteric recombinant antibodies deserves more investigation throughout medicine as a novel means for treatment of enteric disease targets.


Progress and prospects of gene therapy in ophthalmology from 2000 to 2022: A bibliometric analysis.
Gene therapy is a treatment approach at the genetic level, which brings great advances in many diseases and develops rapidly in recent years. Currently, its mechanism of action is mainly through the replacement of missing or defective genes, or the reduction of harmful gene products. However, the application of gene therapy in ophthalmology remains limited. A total of 1143 articles and reviews published in the field of ocular gene therapies were found in the Web of Science Core Collection database and used for the bibliometric analysis. CiteSpace was mainly applied to the network analysis of countries, institutions, keywords, and dual-map overlay of journals. The visual analysis of authors, journals, and references was used by VOSviewer. The geographical distribution of publications was conducted by R language. The annual publications are increasing in general. Currently, the USA and the UK are two main sources of publications in this field. Switzerland, Denmark, and Finland are the top 3 countries that establish the most cooperation and exchanges with other countries or regions. The most cited and co-cited journal in this field is Investigative Ophthalmology & Visual Science. Gene therapy studies for eye diseases are mainly focused on retinal dysfunctions by the analysis of references, keywords, and counting of original research, including Leber's congenital amaurosis and retinitis pigmentosa. This study used bibliometrics to analyze overall characteristics and put forward prospects for the future in the field of gene therapy in ophthalmology. Ocular diseases, especially hereditary retinal diseases, will be the major focus of gene therapy in the future.


Reproductive period and dementia: A 44-year longitudinal population study of Swedish women.
Longitudinal studies examining the effect of endogenous estrogens on dementia risk are needed to understand why women have higher dementia incidence than men after age 85. A population-based sample of women with natural menopause (N = 1364) from Gothenburg, Sweden, was followed from 1968-2012. Information on endogenous estrogens (age at menarche and menopause, number of pregnancies, and months of breastfeeding) was obtained from interviews in 1968-1992. Dementia was diagnosed according to established criteria based on information from neuropsychiatric examinations and close informant interviews. We found that longer reproductive period was associated with increased risk of dementia (hazard ratio [HR] per year 1.06, 95% confidence interval [CI] 1.03-1.20) and Alzheimer's disease (AD) (1.06, 1.02-1.11), particularly for those with dementia (1.10, 1.04-1.17) and AD (1.15, 1.06-1.26) onset after age 85. These results may explain why women have higher dementia incidence compared to men after age 85, the age with the highest number of dementia cases.


System reliability, performance and trust in adaptable automation.
The present study examined the effects of reduced system reliability on operator performance and automation management in an adaptable automation environment. 39 operators were randomly assigned to one of three experimental groups: low (60%), medium (80%), and high (100%) reliability of automation support. The support system provided five incremental levels of automation which operators could freely select according to their needs. After 3 h of training on a simulated process control task (AutoCAMS) in which the automation worked infallibly, operator performance and automation management were measured during a 2.5-h testing session. Trust and workload were also assessed through questionnaires. Results showed that although reduced system reliability resulted in lower levels of trust towards automation, there were no corresponding differences in the operators' reliance on automation. While operators showed overall a noteworthy ability to cope with automation failure, there were, however, decrements in diagnostic speed and prospective memory with lower reliability.


ALK-positive large B-cell lymphomas express a terminal B-cell differentiation program and activated STAT3 but lack MYC rearrangements.
ALK-positive large B-cell lymphoma is an aggressive lymphoid neoplasm characterized by a monomorphic proliferation of immunoblast-like cells expressing a plasmablastic phenotype and carrying ALK rearrangements. MYC rearrangements are frequent in plasmablastic lymphomas, advanced plasma cell myelomas and a subgroup of diffuse large B-cell lymphomas, but their presence in ALK-positive large B-cell lymphomas is unknown. MYC expression is downregulated by BLIMP1, a master modulator of plasma cell differentiation. BLIMP1 and MYC are upregulated by STAT3, a signal transducer activated by ALK. To determine the role of BLIMP1, MYC and STAT3 in the pathogenesis of ALK-positive large B-cell lymphomas, we investigated MYC rearrangement and the expression of MYC, phosphorylated STAT3, BLIMP1, PAX5 and XBP1 in 12 ALK-positive large B-cell lymphomas. All cases expressed ALK with a granular cytoplasmic pattern. Nine cases had a split signal consistent with an ALK rearrangement. Three additional cases showed a deletion of the 5' or 3' end of the ALK probe consistent with cryptic translocation. PAX5 was virtually negative in all cases tested, whereas BLIMP1 was expressed in all tumors and XBP1 in 11 of 12. Phosphorylated STAT3 was observed in all cases with a strong and diffuse nuclear pattern. MYC rearrangements were not identified in any tumor, but MYC gains and amplification were detected in six cases and one case, respectively. MYC protein was expressed in all tumors independently of MYC gene alterations. These results indicate that ALK-positive large B-cell lymphomas express a complete plasmablastic differentiation program but, contrary to plasmablastic lymphomas, do not have MYC rearrangements. STAT3 is constantly activated and may be an alternative mechanism to promote MYC expression in these tumors. The relevance of the ALK/STAT3 pathway in the pathogenesis of ALK-positive large B-cell lymphomas may offer an attractive target for new therapies.


Preparation and characterization of NaCS-CMC/PDMDAAC capsules.
A novel capsule system composed of sodium cellulose sulfate (NaCS), carboxymethyl cellulose (CMC) and poly[dimethyl(diallyl)ammonium chloride] (PDMDAAC) was prepared for improving the properties of NaCS/PDMDAAC capsules. The process parameters, such as CMC concentration (0, 2, 4, 6 and 8 g/L), NaCS concentration (20, 25, 30, 35 and 40 g/L), PDMDAAC concentration (20, 30, 40, 50, 60, 70 and 80 g/L), reaction time and temperature were investigated to understand their effects on the diameter, membrane thickness and mechanical strength of capsules. The optimum operation conditions for preparing NaCS-CMC/PDMDAAC capsules were determined as 6-8 g/L CMC, 35-40 g/L NaCS, 60 g/L PDMDAAC and polymerization for 30-40 min. Diffusion of substances with low molecular weight into capsules was investigated, and diffusion coefficients were calculated according to the developed model. The yeast of Candida krusei was chosen as representative cell to evaluate the effects of different cell loading on capsule mechanical strength. Meanwhile the encapsulated osmophilic C. krusei cells were cultured in 250 mL shaking flasks for 72 h to determine the cell leaking properties in short and long term.


Transcriptional regulation and its misregulation in disease.
The gene expression programs that establish and maintain specific cell states in humans are controlled by thousands of transcription factors, cofactors, and chromatin regulators. Misregulation of these gene expression programs can cause a broad range of diseases. Here, we review recent advances in our understanding of transcriptional regulation and discuss how these have provided new insights into transcriptional misregulation in disease.


(R,S)-trihexyphenidyl, acting via a muscarinic receptor-independent mechanism, inhibits hippocampal glutamatergic and GABAergic synaptic transmissions: Potential relevance for treatment of organophosphorus intoxication.
Preclinical studies have reported that, compared to the muscarinic receptor (mAChR) antagonist atropine, (R,S)-trihexyphenidyl (THP) more effectively counters the cholinergic crisis, seizures, and neuropathology triggered by organophosphorus (OP)-induced acetylcholinesterase (AChE) inhibition. The greater effectiveness of THP was attributed to its ability to block mAChRs and N-methyl-d-aspartate-type glutamatergic receptors (NMDARs) in the brain. However, THP also inhibits α7 nicotinic receptors (nAChRs). The present study examined whether THP-induced inhibition of mAChRs, α7 nAChRs, and NMDARs is required to suppress glutamatergic synaptic transmission, whose overstimulation sustains OP-induced seizures. In primary hippocampal cultures, THP (1-30 μM) suppressed the frequency of excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs, respectively) recorded from neurons in nominally Mg2+-free solution. A single sigmoidal function adequately fit the overlapping concentration-response relationships for THP-induced suppression of IPSC and EPSC frequencies yielding an IC50 of 6.3 ± 1.3 μM. Atropine (1 μM), the NMDAR antagonist d,l-2-amino-5-phosphonopentanoic acid (D,L-AP5, 50 μM), and the α7 nAChR antagonist methyllycaconitine (MLA, 10 nM) did not prevent THP-induced inhibition of synaptic transmission. THP (10 μM) did not affect the probability of transmitter release because it had no effect on the frequency of miniature IPSCs and EPSCs recorded in the presence of tetrodotoxin. Additionally, THP had no effect on the amplitudes and decay-time constants of miniature IPSCs and EPSCs; therefore, it did not affect the activity of postsynaptic GABAA and glutamate receptors. This study provides the first demonstration that THP can suppress action potential-dependent synaptic transmission via a mechanism independent of NMDAR, mAChR, and α7 nAChR inhibition.


[Result-related success rates of cataract operations. Results of a systematic literature review].
This systematic literature review, including 7 publications released since 2000, provides references for outcome indicators of cataract surgery for quality management initiatives. The reported relative numbers of cases achieving visual rehabilitation and refractive accuracy were determined and compared. With one exception the success rates did not represent benchmarks defined as best possible outcome but describe the results of data collected in a population during routine clinical practice. A best corrected visual acuity (BCVA) of ≥ 0.5 was achieved in 84-93% of all patients and in 95-99% of patients without preoperative visually impairing comorbidities. A refractive accuracy (absolute deviation of target refraction from spherical equivalent) of ≤ 1 D was reported in 72-97% of the patients. The success rates of these well established outcome indicator levels were high. Differences between operators were more distinguishable and the clinical relevance higher with less liberal indicator levels. A BCVA ≥ 1 was realized in 30-47% of all patients and in 52-62% of patients without visually impairing comorbidities. A total of 45-80% of the patients showed a refractive accuracy of ≤ 0.5 D. Exogenous factors not influencable by the surgeon have a relevant impact on the success rates. The literature review confirms the strong association of visually impairing comorbidities and BCVA outcome. Based on literature methodological problems of quality management systems for cataract surgery are discussed. While voluntary initiatives have the ability to solve these difficulties appropriate concepts for mandatory procedures are currently lacking.


Higher breastfeeding performance index is associated with lower risk of illness in infants under six months in Ethiopia.
Breastfeeding performance index is an explanatory attempt to summarize key breastfeeding practices by summarizing the different dimensions of breastfeeding practices into a single summary variable. Breastfeeding performance index is used to assess optimal breastfeeding practices by constructing a single composite index that includes timely initiation of breastfeeding, prelacteal feeding, current breastfeeding status, bottle feeding, any liquid given(except medicine) in the last 24 h, formula given in the last 24 h, any solid food given in the last 24 h. This study aimed to assess optimal breastfeeding practices of 0-6 month infants using breastfeeding performance index (BPI) and its association with childhood illness in Ethiopia. A secondary data analysis was carried out based on the Ethiopia Demographic and Health Survey (EDHS) 2011 data. The BPI was created using seven components by giving equal weight for all components during scoring. The data were described using descriptive statistics and analyzed using multivariable logistic regression. The prevalence of low, medium, and high BPI was 18.41, 57.96 and 23.63 % respectively. The mean BPI score was 4.38 (SD 1.25; 95 % CI 4.31, 4.45). Multivariable logistic regression analysis showed that those infants who had low BPI score were 2.22 times (AOR = 2.22; 95 % CI 1.20, 4.11) and medium BPI category had 2.15 times at higher odds (AOR = 2.15; 95 % CI 1.23, 3.75) of developing diarrhea compared to infants in the highest BPI category. Being in the lower BPI category was significantly associated with higher odds of having fever (AOR = 1.73; 95 % CI 1.06, 2.80). Being in the medium index category was also associated with higher odds of having short and rapid breaths (AOR = 2.02; 95 % CI 1.01, 4.04). More than 80 % of the infants did not receive optimal breastfeeding practices based on the Breastfeeding Performance Index. Lower BPI was statistically associated with diarrhea, fever and short and rapid breaths illness in the last 2 weeks. This study implicates the importance of optimal breastfeeding to reduce childhood illness.


ATP-competitive inhibitors block protein kinase recruitment to the Hsp90-Cdc37 system.
Protein kinase clients are recruited to the Hsp90 molecular chaperone system via Cdc37, which simultaneously binds Hsp90 and kinases and regulates the Hsp90 chaperone cycle. Pharmacological inhibition of Hsp90 in vivo results in degradation of kinase clients, with a therapeutic effect in dependent tumors. We show here that Cdc37 directly antagonizes ATP binding to client kinases, suggesting a role for the Hsp90-Cdc37 complex in controlling kinase activity. Unexpectedly, we find that Cdc37 binding to protein kinases is itself antagonized by ATP-competitive kinase inhibitors, including vemurafenib and lapatinib. In cancer cells, these inhibitors deprive oncogenic kinases such as B-Raf and ErbB2 of access to the Hsp90-Cdc37 complex, leading to their degradation. Our results suggest that at least part of the efficacy of ATP-competitive inhibitors of Hsp90-dependent kinases in tumor cells may be due to targeted chaperone deprivation.


Highly fluorescent hematoporphyrin modified graphene oxide for selective detection of copper ions in aqueous solutions.
Here, a highly sensitive and selective copper ion (Cu2+) fluorescence sensor is reported. The Hematoporphyrin functionalized Graphene Oxide (HP-GO) fluorescence sensor were synthesized via esterification reaction between Graphene Oxide and Hematoporphyrin (HP). The HP-GO sensor was fully characterized by Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), Scanning Electrom Microscopy (SEM), UV-Vis spectroscopy, Transmission Electron Microscopy (TEM), Fluor meter spectroscopy, X-Ray photoelectron spectroscopy(XPS), and Raman spectroscopy measurements. The HP-GO sensor advertised two linear regions over the range of 0-1.18 × 103 nM and 3.93 × 103 to 47.27 nM of copper (II) with detection limit of 54 nM in the aqueous solution. The selectivity of HP-GO for Cu2+ is much higher than that of other metal ions due to the presence of aza macrocyclic ring on the surface of HP-GO which has a high binding affinity with Cu2+. Additionally, the HP-GO shows wide pH viable range (pH 6-10). The effect of other metal ions on the fluorescence intensity of the HP-GO was also studied and other metal ions show a low interference response in the detection of Cu2+. HP-GO sensor manifests advantages of high reproducibility (The quenched fluorescence of HP/GO-Cu can be recovered by EDTA), attractive long term fluorescence stability (>21 days) in water, also remarkable selectivity regarding number of metal ions (Na+, K+, Ca2+, Fe3+, Fe2+, Al3+, Pb2+, Mn2+, Mg2+, Co2+, Ni2+, Cr6+, Cd2+, Hg2+, and Zn2+), low toxicity and can detect Cu2+ in real water samples which acquire well for its promising in environmental applications.


The efficacy and mechanism of Angelica sinensis (Oliv.) Diels root aqueous extract based on RNA sequencing and 16S rDNA sequencing in alleviating polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) leads to persistent anovulation, hyperandrogenism, insulin resistance, and polycystic ovary, and is mainly characterized by menstrual disorders, and reproductive dysfunction. Angelica sinensis (Oliv.) Diels root has been used in many classical formulas of traditional Chinese medicine, and is commonly used to treat various gynecological diseases. To investigate the protective effect of water extract of A. sinensis root (WEA) on PCOS rats, and the mechanism by RNA sequencing, and 16S rDNA sequencing. The PCOS rat model was established by letrozole combined with high-fat diet (gavage; 2 months), and treated with WEA (gavage; 2 g/kg, 4 g/kg or 8 g/kg; 1 month). To evaluate the therapeutic effect of WEA on PCOS rats, vaginal smear, hematoxylin-eosin staining, and biochemical indicators detection were performed. The rat ovarian tissue was analyzed by RNA sequencing, and the results were verified by qRT-PCR, and Western blot. 16S rDNA sequencing was used to analyze the gut microbiota of rats. The results of the vaginal smear, and hematoxylin-eosin staining showed that WEA improved estrous cycle disorder, and ovarian tissue lesions. WEA (4 g/kg or 8 g/kg; 1 months) alleviated hormone disorders, insulin resistance, and dyslipidemia. RNA sequencing showed that WEA intervention significantly changed the expressions of 2756 genes, which were enriched in phosphatidylinositol3-kinase/phosphorylated protein kinase B (PI3K/AKT), peroxisome proliferator-activated receptor (PPAR), mitogen-activated protein kinase (MAPK), AMP-activated protein kinase (AMPK), and insulin signaling pathways. 16S rDNA sequencing found that WEA increased the species diversity of gut microbiota, and regulated the abundance of some microbiota (genus level: Dubosiella, Bifidobacterium, Coriobacteriaceae (UCG-002), and Treponema; species level: Bifidobacterium animalis, Lactobacillus murinus, and Lactobacillus johnsonii). WEA regulated hormone, and glycolipid metabolism disorders, thereby relieving the PCOS induced by letrozole combined with high-fat diet. The mechanism was related to the regulation of PI3K/AKT, PPAR, MAPK, AMPK, and insulin signaling pathways in ovarian tissues, and the maintenance of gut microbiota homeostasis. Clarifying the efficacy and mechanism of WEA in alleviating PCOS based on RNA sequencing and 16S rDNA sequencing will guide the more reasonable clinical use of WEA.


A family of small nucleoplasmic RNAs with common structural features.
The four small nucleoplasmic RNAs designated as U1, U2, U4 and U5 RNA have a common structural domain or domain A. It is characterized by the presence of consensus sequence Pu-A-(U)5-G-Pup in a free single-stranded region and of the sequence Py-N-Py-Gp in the top loop of a hairpin located at the 3' end of the free region. Domain A is likely to be involved in a function common to the four small RNAs. Other domains possibly involved in the specific function of U1 and U5 RNAs are also presented. Several molecular forms of a same U RNA may be found in a same cellular type. These variant U RNAs are particularly numerous for U5 RNA. The possible origin of such new molecular forms is discussed in relation to multigene families for U RNAs. U1, U2, U4 and U5 RNAs are capped (with trimethylguanosine) and the consensus sequence for their 6 first nucleotides is A-(Py)5p. Thus, their 5' end resembles that of premessenger RNA, also capped (with monomethylguanosine) and bearing A-(Py)5p. Both classes of RNA are synthesized by RNA polymerase B, but the presence of a "TATA box" upstream of the capsite has not yet been demonstrated for U RNA genes. U1, U2, U4 and U5 RNAs bear a sequence C-Py-Pu at their 3' end or very close to it. This trinucleotide might be part of a site of post-transcriptional cleavage of U RNA precursors.(ABSTRACT TRUNCATED AT 250 WORDS)


Variations of the flexor digitorum superficialis of the small finger.
Normal functional variations of the flexor digitorum superficialis were clinically determined by use of the standard and modified superficialis flexion tests in 50 normal subjects. Forty hands of 20 cadavers were dissected to correlate the anatomic variations with the clinical findings. A flexor digitorum superficialis-independent pattern was found 58% of the time. A flexor digitorum superficialis-common pattern was found 21% of the time. A flexor digitorum superficialis-absent pattern was found 21% of the time. The right and left hands were asymmetric 26% of the time. All cadaver hands had a flexor digitorum superficialis tendon present in the palm and finger. The variability in flexor digitorum superficialis function may be explained by interconnections between the flexor digitorum superficialis of the small finger and either the flexor digitorum superficialis of the ring finger or the flexor digitorum profundus of the small finger.


Anxiety and prevalence of psychiatric disorders among patients awaiting surgery for suspected ovarian cancer.
The goal of the current study was to determine the anxiety level and prevalence of psychiatric disorders among patients awaiting surgery for ovarian tumors. Also analyzed were the predictive factors for psychiatric disorders and changes after surgical diagnosis. Patients who underwent surgery for ovarian tumors were examined before and after surgery with the MINI International Neuropsychiatric Interview, the Spielberger State-Trait Anxiety Inventory (STAI) and the Mausley Personality Inventory (MPI). Participants diagnosed with cancer were examined a third time after being given an explanation about whether or not adjuvant chemotherapy was required. Twenty-seven participants completed the study and were analyzed. Nine (33.3%) of these 27 participants were diagnosed as having adjustment disorder. There were no differences in the demographic data, STAI trait anxiety score and MPI score between the participants with or without adjustment disorder. At the pre-surgical interview, the STAI state anxiety score of the participants was high (49.5 +/- 10.30). After pathological examination of the tumors, it was found that 12 patients had cancer (malignant group) and 15 patients had a benign tumor (benign group). At pre-surgery, the prevalence of adjustment disorder and the level of anxiety in the benign group were similar to those in the malignant group. There was a second surge of anxiety in patients who needed chemotherapy. The above findings demonstrate that patients with suspected ovarian cancer experience a high level of anxiety. Physicians should be aware of the risk of adjustment disorder in these patients. Additionally, ovarian cancer patients need psychological assessment during the course of treatment.


Trackable life: Data, sequence, and organism in movement ecology.
Over the past decade an increasing number of ecologists have begun to frame their work as a contribution to the emerging research field of movement ecology. This field's primary object of research is the movement track, which is usually operationalized as a series of discrete "steps and stops" that represent a portion of an animal's "lifetime track." Its practitioners understand their field as dependent on recent technical advances in tracking organisms and analyzing their movements. By making movement their primary object of research, rather than simply an expression of deeper biological phenomena, movement ecologists are able to generalize across the movement patterns of a wide variety of species and to draw on statistical techniques developed to model the movements of non-living things. Although it can trace its roots back to a long tradition of statistical models of movement, the field relies heavily on metaphors from genomics; in particular, movement tracks have been seen as similar to DNA sequences. Though this has helped movement ecology consolidate around a shared understanding of movement, the field may need to broaden its understanding of movement beyond the sequence if it is to realize its potential to address urgent concerns such as biodiversity loss.


Synthesis, anti-plasmodial and cytotoxic evaluation of 1H-1,2,3-triazole/acyl hydrazide integrated tetrahydro-β-carboline-4-aminoquinoline conjugates.
A series of 1H-1,2,3-triazole/acylhydrazide-tethered tetrahydro-β-carboline-4-aminoquinoline conjugates was synthesized with an aim to study their anti-plasmodial structure-activity relationship. The presence of 1H-1,2,3-triazole-core along with a flexible alkyl chain length on aminoquinoline core has favourable influence on the anti-plasmodial activity against Chloroquine-resistant W2 strain of P. falciparum while the introduction of hydrazine core not only diminished the activities but also resulted in increased cytotoxicity against mammalian Vero cells.


Serum soluble E-cadherin level in patients with endometriosis.
To investigate the serum sE-cadherin level in patients with endometriosis and the alterations of that level in healthy control during the menstrual cycle. Thirty-two patients with endometriosis and 30 healthy women were tested for serum sE-cadherin levels by enzyme-linked immunosorbent assay. The serum sE-cadherin levels in healthy control did not vary throughout the menstrual cycle, which were lower than those in patients with endometriosis. E-cadherin might be involved in endometrial shedding during menstruation in endometriosis patients. The serum sE-cadherin assay might be helpful as a serum marker for the diagnosis and management of endometriosis.


The medical status of methadone maintenance patients in treatment for 11-18 years.
To assess the safety and potential health consequences of long-term methadone maintenance treatment, we identified 111 male patients admitted to methadone maintenance treatment between 1965 and 1968, still enrolled in 1980 and in continuous treatment for at least 10 years. We were able, between 1980 and 1985, to examine patients or review records of 110 patients (99%). Most medical diagnoses, symptomatic complaints, physical examination findings and laboratory test results occurred with similar frequency in the long-term methadone maintenance patients and in a group of 56 long-term heroin addicts. These data suggest that prolonged methadone maintenance treatment is safe and is not associated with unexpected adverse effects.


Development of antimicrobial oxidized cellulose film for active food packaging.
Foodborne diseases caused by bacteria have aroused ongoing concerns for food safety. Most existing packaging plastics bring pollution and potential toxicity. Here antimicrobial dialdehyde cellophane (DACP) was developed by periodate oxidation. The structure, mechanical properties, optical properties, and barrier properties of DACP were characterized. The antimicrobial activity of DACP against four Gram-positive bacteria was studied. The packaging effect of DACP for food with high water content was evaluated, including strawberry and tofu. The antimicrobial activity of DACP improved with increased aldehyde content. Compared with the polyethylene film and cellophane, our DACP exhibited excellent antimicrobial effect and extended the shelf life of food significantly, which shows promising prospects in food packaging.


Invertebrate models of neurologic disease: insights into pathogenesis and therapy.
The search for cures of human diseases can be very slow, expensive, and serendipitous. Roughly five decades of basic research in a handful of model systems has revealed that most animals are quite similar to one another especially at the cellular and molecular levels. The commonalities allow one to use animal models to investigate human disease mechanisms. Here, we review contributions demonstrating the use of invertebrate models to investigate human neurodegenerative diseases. We conclude that the integration of fly and worm models into programs seeking to identify therapeutic strategies for neurodegenerative disease can significantly speed progress toward finding cures for these devastating diseases.


Intravoxel incoherent motion MR imaging: comparison of diffusion and perfusion characteristics between nasopharyngeal carcinoma and post-chemoradiation fibrosis.
To compare the intravoxel incoherent motion (IVIM) diffusion and perfusion characteristics of nasopharyngeal carcinoma (NPC) and post-chemoradiation fibrosis to aid in their differentiation. Fifty-three (64 %) patients with newly diagnosed NPC and 30 (36 %) patients with biopsy-proven post-chemoradiation fibrosis were recruited into tumour and fibrosis groups respectively. Diffusion-weighted magnetic resonance (MR) imaging was performed using 13 b values (0-1,000 s/mm(2)). Their respective IVIM parameters (D, pure diffusion; f, perfusion fraction; D, pseudodiffusion coefficient) were obtained. D and f were significantly lower in NPC (D = 0.752 ± 0.194 × 10(-3) mm(2)/s, P <0.001; f = 0.122 ± 0.095, P <0.001) than in fibrosis (D = 1.423 ± 0.364 × 10(-3) mm(2)/s; f = 0.190 ± 0.120); while D was significantly higher in NPC (111.366 ± 65.528 × 10(-3) mm(2)/s, P <0.001) than in fibrosis (77.468 ± 62.168 × 10(-3) mm(2)/s). Respective cut-off values with sensitivity, specificity and accuracy were: D = 1.062 × 10(-3) mm(2)/s (100 %, 100 %, 100 %); f = 0.132 (66.0 %, 100 %, 78.3 %); D = 85.283 × 10(-3) mm(2)/s (100 %, 90.7 %, 96.4 %). NPC and post-chemoradiation fibrosis have distinctive IVIM parameters. IVIM MR imaging is potentially useful in discrimination between NPC and fibrosis. • New MRI techniques offer greater help in the assessment of nasopharyngeal carcinoma. • Tumour and post-chemoradiation fibrosis have distinctive intravoxel incoherent motion diffusion/perfusion parameters. • Non-invasive IVIM MRI may help differentiate between tumour and fibrosis. • Pure diffusion is a robust independent discriminating factor which improves diagnostic confidence.


Pre-irradiation haematological effects of the bacterial extract Broncho-Vaxom and postirradiation acceleration recovery from radiation-induced haematopoietic depression.
Effects of the bacterial extract Broncho-Vaxom (BV), free of endotoxin, on haematopoietic parameters of peripheral blood, bone marrow, spleen and thymus were investigated in normal and irradiation-myelosuppressed C57BL/6 mice. BV in normal (nonirradiated) mice induced transient lymphocytopenia and increased granulocytes, particularly neutrophils, six to nine hours after administration. Elevated numbers of peripheral blood macroreticulocytes were observed during the third hour. In the splenic red pulp, enhancing haemopoietic activity, foci of fibroblasts began to appear more frequently from the first hour to 24 h. In lymphatic follicles of the spleen and thymus, the incidence of macrophages or monocytes began to increase three hours after BV application. Twenty-four hours later thymus weight decreased by 27%. In the bone marrow, enhanced proliferation of eosinophils was observed from hour nine, with maximum proliferation at hour 24. BV treatment 24 h before irradiation had a notable radio-protective effect, manifested by accelerated haemopoietic recovery during the postirradiation period. Accelerated myelopoiesis, erythropoiesis and megakaryocytopoiesis resulted in accelerated peripheral blood recovery. However, BV had no effect on thymus reparation as suggested by similar effects in BV protected and BV nonprotected animals during the entire period which followed a 6.5 Gy dose.


Interactive influence of biotic and abiotic cues on the plasticity of preferred body temperatures in a predator-prey system.
The ability to modify phenotypes in response to heterogeneity of the thermal environment represents an important component of an ectotherm's non-genetic adaptive capacity. Despite considerable attention being dedicated to the study of thermally-induced developmental plasticity, whether or not interspecific interactions shape the plastic response in both a predator and its prey remains unknown. We tested several predictions about the joint influence of predator/prey scents and thermal conditions on the plasticity of preferred body temperatures (T (p)) in both actors of this interaction, using a dragonfly nymphs-newt larvae system. Dragonfly nymphs (Aeshna cyanea) and newt eggs (Ichthyosaura alpestris) were subjected to fluctuating cold and warm thermal regimes (7-12 and 12-22°C, respectively) and the presence/absence of a predator or prey chemical cues. Preferred body temperatures were measured in an aquatic thermal gradient (5-33°C) over a 24-h period. Newt T (p) increased with developmental temperature irrespective of the presence/absence of predator cues. In dragonflies, thermal reaction norms for T (p) were affected by the interaction between temperature and prey cues. Specifically, the presence of newt scents in cold regime lowered dragonfly T (p). We concluded that predator-prey interactions influenced thermally-induced plasticity of T (p) but not in a reciprocal fashion. The occurrence of frequency-dependent thermal plasticity may have broad implications for predator-prey population dynamics, the evolution of thermal biology traits, and the consequences of sustaining climate change within ecological communities.


Absence of effect of 16,16-dimethyl prostaglandin E2 on reduction of gastric mucosal blood flow caused by indomethacin in rats.
The effects of 16,16-dimethyl prostaglandin E2 PGE2 on gastric mucosal blood flow and gastric mucosal damage were tested in rats given indomethacin. Blood flow was measured by hydrogen gas clearance. Indomethacin given intragastrically reduced the blood flow in nonlesion areas and the levels of PGE2 and 6-keto-PGF1 alpha in the gastric mucosa and caused mucosal damage in a dose-related way. Indomethacin (20 mg/kg) significantly reduced the blood flow 30 min after administration, and the reduction increased until 90 min. Then the flow plateaued until 240 min. Gastric mucosal damage caused by 20 mg/kg of indomethacin and evaluated by only gross observations, began at 60 min and developed with time until 240 min after administration. 16,16-Dimethyl PGE2 (5 micrograms/kg) did not affect the reduction of blood flow caused by indomethacin during 240 min of measurements, but it significantly inhibited the indomethacin-induced mucosal damage evaluated by gross observations. These results suggest that prevention by 16,16-dimethyl PGE2 of grossly observed gastric mucosal damage caused by indomethacin was not related by preservation of the gastric mucosal blood flow in the areas without lesions.


Four-peptide-nanotube bundle formation by self-assembling of cyclic tetra-β-peptide using G-quartet motif.
A hydrophilic cyclic tetra-β-peptide having guanine at the side chain (CPG) was synthesized to construct a four-peptide-nanotube bundle with the formation of guanine quadruplex (G-quartet). CPG was so soluble in water that molecular association of CPG was very limited in water. However, in the presence of potassium ion, circular dichroism spectral change showed initial molecular association due to the G-quartet formation followed by a slow growth into peptide nanotubes. Transmission electron microscope observation and electron diffraction analysis revealed that CPG self-assembled into a four-peptide-nanotube bundle with a uniform diameter of 7-8 nm.


Kinetic determination of vitamin B12 in pharmaceuticals by the continuous addition of reagent technique.
An automatic kinetic method for the determination of micro amounts of vitamin B12 in pharmaceutical samples based on the fast formation of a coloured complex between the cobalt contained by this vitamin and PAR [4-(2-pyridilazo)resorcinol] in a weakly alkaline medium and on the use of the continuous addition of reagent technique for the mixing of sample and reagent is reported. The reaction is monitored by measuring the changes in the absorbance at 510 nm characteristic of the complex formed. The linear range of the determination is 1.1-34.5 micrograms ml-1 and the relative standard deviation is 1.2%. The sample throughput is 75 h-1 (triplicate runs). The results obtained in analyses of pharmaceutical samples showed excellent correlation with nominal contents and the results of atomic absorption spectrophotometric analyses.


Dual lifestyle of Porphyromonas gingivalis in biofilm and gingival cells.
Porphyromonas gingivalis is deeply involved in the pathogenesis of marginal periodontitis, and recent findings have consolidated its role as an important and unique pathogen. This bacterium has a unique dual lifestyle in periodontal sites including subgingival dental plaque (biofilm) and gingival cells, as it has been clearly shown that P. gingivalis is able to exert virulence using completely different tactics in each environment. Inter-bacterial cross-feeding enhances the virulence of periodontal microflora, and such metabolic and adhesive interplay creates a supportive environment for P. gingivalis and other species. Human oral epithelial cells harbor a large intracellular bacterial load, resembling the polymicrobial nature of periodontal biofilm. P. gingivalis can enter gingival epithelial cells and pass through the epithelial barrier into deeper tissues. Subsequently, from its intracellular position, the pathogen exploits cellular recycling pathways to exit invaded cells, by which it is able to control its population in infected tissues, allowing for persistent infection in gingival tissues. Here, we outline the dual lifestyle of P. gingivalis in subgingival areas and its effects on the pathogenesis of periodontitis.


Life history variation among low-arctic clones of obligately parthenogenetic Daphnia pulex: a diploid-polyploid complex.
Laboratory life table experiments were conducted using nine clones of obligately parthenogenetic Daphnia pulex that were collected from a site in the Canadian low-arctic. Two of the nine clones were diploids, while the other seven clones were polyploids. Significant clonal differences in age at first reproduction, size at first reproduction, number of offspring in each of the first three broods, offsrring sizes for the first two broods, and intrinsic rates of natural increase were detected. Differences in life histories were evident between polyploids and diploids. Generally, polyploid clones reached maturity at later ages, matured at larger sizes, produced smaller broods, and larger offspring than the diploid clones. The data are discussed in reference to potential biotic (i.e. invertebrate predation) and abiotic factors (i.e. physicochemical gradients) that may influence life history variation in this clonal assemblage.


Proximal tibial osteotomy. A new fixation device.
A new internal fixation device was applied to 41 proximal tibial osteotomies to ensure against loss of postoperative correction. An oblique osteotomy was stabilized by two screws and a five-hole one-half tubular plate. Thirty-six patients with 41 proximal tibial osteotomies were reviewed for an average roentgenographic follow-up time of 22.6 months (range, six to 48 months) with no loss of correction. In addition, 16 patients with 19 osteotomies and a minimum clinical follow-up time of two years were reviewed using the Hospital for Special Surgery knee scoring system; these early results demonstrated a similar outcome to previously published series. The new fixation device is simple to use, permits early postoperative motion, and maintains the exact correction obtained at the time of surgery.


Pharmacology of recombinant human GABA(A) receptor subtypes measured using a novel pH-based high-throughput functional efficacy assay.
To facilitate the discovery of novel compounds that modulate human GABA(A) receptor function, we have developed a high throughput functional assay using a fluorescence imaging system. L(tk-) cells expressing combinations of human GABA(A) receptor subunits were incubated with the pH-sensitive dye 2',7'bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein, then washed and placed in a 96-well real-time fluorescence plate reader. In buffer adjusted to pH 6.9 there was a robust and persisting acidification response to addition of GABA, which was antagonised by the GABA(A) receptor antagonist bicuculline. The concentration-response relationship for GABA was modulated by allosteric ligands, including benzodiazepine (BZ) site agonists and inverse agonists. The effects of BZ site ligands on the pH response to GABA for receptors containing alpha1beta3gamma2, alpha3beta3gamma2 or alpha5beta3gamma2 subunits were well correlated with results from electrophysiological studies on the same receptor subunit combinations expressed in Xenopus oocytes. Most modulatory compounds tested were found to be relatively unselective across the three subunit combinations tested; however, some showed subtype-dependent efficacy, such as diazepam, which had highest agonist effects on the alpha3beta3gamma2 subtype, substantial but lesser agonism on alpha1beta3gamma2 and still substantial but the least agonism on alpha5beta3gamma2. This indicates that the alpha subunit within the recombinant receptor expressed in L(tk-) cells can affect the efficacy of the response to some BZ compounds. Inhibitors of Na(+)/Cl(-) cotransport, anion/anion exchange and the gastric type of H(+)/K(+) ATPase potently inhibited GABA-evoked acidification, indicating that multiple transporters are involved in the GABA-evoked pH change. This novel fluorescence-based high throughput functional assay allows the rapid characterization of allosteric ligands acting on human GABA(A) receptors.


Primary surgery as a frontline treatment for synchronous metastatic gastrointestinal stromal tumors: an analysis of the Kinki GIST registry.
To investigate the outcomes of a combined treatment regimen comprising primary surgery and tyrosine kinase inhibitor (TKI) therapy for synchronous metastatic gastrointestinal stromal tumors (GIST). We analyzed retrospectively 14 cases of synchronous metastatic GIST from the Kinki GIST registry between 2003 and 2007. The primary tumor was located in the stomach, small intestine, and rectum in seven, six, and one patients, respectively. Metastatic tumors developed in the liver, peritoneum, other sites, and multiple organs in three, six, two, and three patients, respectively. The R0 resection rate was 42.9 % and the 5-year overall survival rate was 69.3 %. There was no significant difference in the 5-year overall survival rate between patients who underwent R0/R1 and those who underwent R2 resection (71.4 vs. 68.6 %). There was a strong correlation between survival time from diagnosis and the duration of imatinib therapy (Pearson's correlation coefficient, 0.86; p < 0.001). Although the role of surgery in the treatment of synchronous metastatic GIST is still unclear, primary surgery as the sole frontline treatment may not have a survival benefit: Continuous TKI therapy is more important for prolonging survival.


Priorities for professionalism: what do surgeons think?
To gain an understanding of the relative importance of the nine surgical competencies and their 27 attributes defined by the Royal Australasian College of Surgeons (RACS), which together provide the curriculum framework for today's surgeons. Between 9 August and 30 September 2010, trainees and Fellows of the RACS across Australia and New Zealand actively involved in educational activities rated, via questionnaire, the importance of the RACS competencies (technical expertise, communication, professionalism, medical expertise, judgement and decision making, scholarship and teaching, collaboration and teamwork, management and leadership, and health advocacy) and associated attributes. Importance ranking of competencies and their attributes for surgical education and training. Of 3054 questionnaires distributed, 1834 (60%) were returned. We identified clear priorities in the perceived relative importance of the nine competencies and 27 attributes. The most important attributes were competence, insight, and recognising conditions amenable to surgery; least important were responding to community and cultural needs, supporting others, and maintaining personal health and wellbeing. Key differences were noted for the competency of collaboration and teamwork, which was ranked as more important by trainees than by Fellows. Female trainees and Fellows regarded all attributes as more important than did male trainees and Fellows. In a complex environment with multiple pressures, the priorities of the competencies are important. Trainees and Fellows had a very similar approach to the prioritisation of the attributes. Of concern is the lesser importance given to attributes beyond individual expertise.


Safety evaluation of a male injectable antifertility agent, styrene maleic anhydride, in rats.
Injection of a polymer, styrene maleic anhydride (SMA), into the lumen of the vas deferens of rats, was observed to have effective and reversible contraception. The safety evaluation of the polymer, for 90 days, was carried out in Charles Foster male rats. There have been no significant changes in any of the toxicity parameters in the test animals as compared to the control animals. Hence, it is concluded that the compound is non-toxic to rodents.


Structural and Functional Insights into the Cryoprotection of Membranes by the Intrinsically Disordered Dehydrins.
Dehydration can be due to desiccation caused by a lack of environmental water or to freezing caused by a lack of liquid water. Plants have evolved a large family of proteins called LEA (late embryogenesis abundant) proteins, which include the intrinsically disordered dehydrin (dehydration protein) family, to combat these abiotic stresses. Although transcription and translation studies have shown a correlation between dehydration stress and the presence of dehydrins, the biochemical mechanisms have remained somewhat elusive. We examine here the effect and structure of a small model dehydrin (Vitis riparia K2) on the protection of membranes from freeze-thaw stress. This protein is able to bind to liposomes containing phosphatidic acid and protect the liposomes from fusing after freeze-thaw treatment. The presence of K2 did not measurably affect liposome surface accessibility or lipid mobility but did lower its membrane transition temperature by 3 °C. Using sodium dodecyl sulfate as a membrane model, we examined the NMR structure of K2 in the presence and absence of the micelle. Biochemical and NMR experiments show that the conserved, lysine-rich segments are involved in the binding of the dehydrin to a membrane, whereas the poorly conserved φ segments play no role in binding or protection.


The Brighton Collaboration standardized template for collection of key information for benefit-risk assessment of nucleic acid (RNA and DNA) vaccines.
Nucleic acid (DNA and RNA) vaccines are among the most advanced vaccines for COVID-19 under development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of nucleic acid vaccines. This will facilitate the assessment by key stakeholders of potential safety issues and understanding of overall benefit-risk. The structured assessment provided by the template can also help improve communication and public acceptance of licensed nucleic acid vaccines.


Elder maltreatment items, subgroups, and types: policy and practice implications.
An examination of 288 validated instances of elder maltreatment suggests that these phenomena pose questions as diverse as those faced in identifying child and spouse maltreatment. A partial typology is offered to guide further investigations. Implications for policy and practice suggest a cautious approach to value-laden issues while recognizing the need for intervention.


Phase I study of obinutuzumab (GA101) in Japanese patients with relapsed or refractory B-cell non-Hodgkin lymphoma.
As CD20 has become an established target for treating B-cell malignancies, there is interest in developing anti-CD20 antibodies with different functional activity from rituximab that might translate into improved efficacy. Obinutuzumab (GA101) is a glycoengineered, humanized type II anti-CD20 monoclonal antibody that has demonstrated superior activity to type I antibodies in preclinical studies and is currently being investigated in phase III trials. In this phase I dose-escalating study in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma, the primary endpoint was to characterize the safety of GA101; secondary endpoints were efficacy, pharmacokinetics and pharmacodynamics. Patients received up to nine doses of GA101 with up to 52 weeks' follow up. Most adverse events were grade 1 or 2 infusion-related reactions, and 10 grade 3/4 adverse events occurred. No dose-limiting toxicities were observed and the maximum tolerated dose was not identified. Out of 12 patients, 7 responded (end-of-treatment response rate 58%), with 2 complete responses and 5 partial responses. Responses were observed from low to high doses, and no dose-efficacy relationship was observed. B-cell depletion occurred in all patients after the first infusion and was maintained for the duration of treatment. Serum levels of GA101 increased in a dose-dependent fashion, although there was inter-patient variability. This phase I study demonstrated that GA101 has an acceptable safety profile and offers encouraging activity to Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma.


Hepatic Pseudoaneurysm Incidence After Liver Trauma.
Posttraumatic hepatic artery pseudoaneurysm is a potentially devastating complication after complex liver injury. Increasing computed tomography (CT) use may lead to more frequent identification of posttraumatic hepatic complications. This study was designed to determine the rate of hepatic pseudoaneurysm after traumatic liver injury. We conducted a retrospective review of patients at an urban level 1 trauma center over 5 y (2012-2016). Injury characteristics, patient management, and complications were extracted from trauma registry data and chart review. Six hundred thirty-four hepatic injuries (11 no grade/no CT, 159 grade I, 154 grade II, 165 grade III, 93 grade IV, and 52 grade V) were identified from our trauma registry. No patient with a grade I or II injury had a subsequent bleeding complication. Eighteen patients had a documented hepatic pseudoaneurysm: grade III n = 3 (1.8%), grade IV n = 6 (6.5%), grade V n = 9 (17.3%). The median time to pseudoaneurysm identification was 6.5 d. Seven pseudoaneurysms were found on asymptomatic surveillance CT-angiography on average 5 d after injury. Eleven patients were symptomatic at the time of CT-angiography performed at a median of 9 d after admission. Of the 11 symptomatic patients, four were in hemorrhagic shock, and two died from hepatic-related complications. The incidence of hepatic artery pseudoaneurysm increases with higher grade liver injury. Aggressive surveillance for hepatic pseudoaneurysm with interval CT-angiography 5-7 d postinjury may be warranted, especially for grade IV and V injuries.


Keratin-rhamnolipids and keratin-sodium dodecyl sulfate interactions at the air/water interface.
Keratin-surfactant interactions at the air/solution interface may be indicative for skin irritation by surfactants. In this study pure keratin was extracted from chicken feathers as described by Schrooyen at al. and the adsorption properties of biologically produced rhamnolipids (RL) and sodium dodecyl sulfate (SDS) mixed with keratin molecules were investigated by surface tension measurements. Keratin was added in three specific amounts to RL and SDS aqueous solutions of varying concentrations, respectively, and keratin-RL and keratin-SDS interactions were investigated at pH 6.2 and 5.0. The surface tension measurements showed that surfactant-keratin complexes were formed in the solutions at pH 6.2. At low RL concentrations the added amount of keratin decreased the surface tension as a result of the hydrophobic keratin-RL complexes formed, which have covered the air/solution interface. Beginning from moderate RL concentrations, less surface active keratin-RL complexes were formed due to hydrophilization of the former complexes and they were removed from the interface to the bulk phase as a result of the competitive adsorption mechanism and pure RL molecules covered the interface gradually. At low SDS concentrations surface tension decrease was also observed by the covering of the air/solution interface with keratin-SDS complexes. At moderate SDS concentrations the keratin-SDS complexes exhibited a more surface active feature. Unlike the keratin-RL complexes, they have remained at the interface until the higher SDS concentrations and keratin ratios. However, at the minimum surface tension value of the pure SDS at its CMC value, the surface tension of the keratin-SDS mixture reached the value of pure SDS solution and the air/solution interface has been covered again only with pure SDS monomers. The keratin-surfactant solutions prepared at pH 5 showed lower surface tension values compared to that measured at pH 6.2 and the surface tension behavior of RL and SDS resembled each other. Above a certain surfactant concentration the addition of keratin to surfactant solutions rendered the surface less surface active compared to their pure surfactant solutions at pH 5.0. The consideration of the surface tension behavior of two anionic surfactants has shown that the RL-keratin interactions are milder than SDS-keratin interactions at pH 6.2 and 5.0.


beta-Glucuronidase activity in trained red and white skeletal muscle of mice.
We studied the effects of prolonged running exercise (5 days a week, 1.5 h per day at a speed of 17.6 m/min) on the activity of some acid hydrolases (beta-glucuronidase, beta-N-acetylglucosaminidase, acid phosphatase and cathepsin D) and three enzymes of energy metabolism (cytochrome c oxidase, lactate dehydrogenase and creatine kinase) in the distal and in the proximal, the predominantly white and red parts, respectively, of the vastus lateralis-muscle from mice. The acid hydrolase activity levels were 1.24--1.69 higher in untrained red muscle compared to untrained white muscle. The light training applied increased the activity of beta-glucuronidase in both red and white muscle. No other significant training effects were observed in the enzyme activities measured.


Confinement hinders motility by inducing RhoA-mediated nuclear influx, volume expansion, and blebbing.
Cells migrate in vivo through complex confining microenvironments, which induce significant nuclear deformation that may lead to nuclear blebbing and nuclear envelope rupture. While actomyosin contractility has been implicated in regulating nuclear envelope integrity, the exact mechanism remains unknown. Here, we argue that confinement-induced activation of RhoA/myosin-II contractility, coupled with LINC complex-dependent nuclear anchoring at the cell posterior, locally increases cytoplasmic pressure and promotes passive influx of cytoplasmic constituents into the nucleus without altering nuclear efflux. Elevated nuclear influx is accompanied by nuclear volume expansion, blebbing, and rupture, ultimately resulting in reduced cell motility. Moreover, inhibition of nuclear efflux is sufficient to increase nuclear volume and blebbing on two-dimensional surfaces, and acts synergistically with RhoA/myosin-II contractility to further augment blebbing in confinement. Cumulatively, confinement regulates nuclear size, nuclear integrity, and cell motility by perturbing nuclear flux homeostasis via a RhoA-dependent pathway.


Human T-cell lymphotropic virus type I in Iranian-born Mashhadi Jews: genetic and phylogenetic evidence for common source of infection.
High prevalence of human T-cell lymphotropic virus type I (HTLV-I) infection and disease has been identified among Iranian-born Mashhadi Jews, an ethnically segregated, highly inbred population. To determine the origin and genetic diversity of HTLV-I in this group, 1,039 bp spanning selected regions of the HTLV-I gag, pol, env and pX genes were enzymatically amplified and sequenced directly from DNA of five Mashhadi Jews (three with spastic myelopathy and two asymptomatic carriers). Alignment and comparison of these sequences with cosmopolitan and Australo-Melanesian topotypes of HTLV-I indicated that the HTLV-I strains from Mashhadi Jews, which were > or = 99.9% identical among themselves, exhibited considerable sequence similarity (> or = 99%) to HTLV-I strains from southern India, suggesting a common source of infection. Phylogenetic analysis, using the maximum parsimony method, was consistent with a single-source introduction of HTLV-I into the Mashhadi Jewish community.


Origin, dynamics, and implications of extracellular DNA pools in marine sediments.
In marine sediments, DNA occurs both inside and outside living organisms. DNA not enclosed in living cells may account for the largest fraction of total DNA, and include molecules locked within dead cells, organic and inorganic aggregates, adsorbed onto mineral matrices, and viral DNA. This DNA comprises genetic material released in situ from sediment microbial communities, as well as DNA of pelagic and terrestrial origin deposited to the seafloor. DNA not enclosed in living cells undermines the assumption of a direct link between the overall DNA pool and the local, currently living microbial assemblages, in terms of both microbial cell abundance and diversity. At the same time, the extracellular DNA may provide an integrated view of the biodiversity and ecological processes occurring on land, in marine water columns, and sediments themselves, thereby acting as an archive of genetic information which can be used to reconstruct past changes in source environments. In this review, we identify and discuss DNA pools in marine sediments, with special focus on DNA not enclosed in living cells, its origin, dynamics, and ecological and methodological implications. Achievements in deciphering the genetic information held within each DNA pool are presented along with still-standing challenges and major gaps in current knowledge.


Establishment and characterization of a novel cell line (SCCOHT-CH-1) and PDX models derived from Chinese patients of small cell ovarian carcinoma of the hypercalcemic type.
Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a rare and aggressive malignancy that poses a significant clinical challenge due to its grim prognosis. Unfortunately, only three SCCOHT cell lines are currently available for scientific research. In this study, we have successfully established a novel SCCOHT cell line from a recurrent lesion of a SCCOHT patient, named SCCOHT-CH-1. We comprehensively characterized the novel cell line by employing techniques such as morphological observation, CCK-8 assay, Transwell assay, clone formation assay, short tandem repeat sequence (STR) analysis, karyotype analysis, immunohistochemical staining, western blot assay, and xenograft tumor formation assay. SCCOHT-CH-1 cells were small circular and had a unique STR profile. The population-doubling time of SCCOHT-CH-1 was 33.02 h. The cell line showed potential migratory and invasive ability. Compared with another SCCOHT cell line COV434, SCCOHT-CH-1 exhibited higher expression of AKT, VIM, and CCND1. At the same time, SCCOHT-CH-1 has the ability of tumorigenesis in vivo. We also successfully constructed three patient-derived xenograft (PDX) models of SCCOHT, which were pathologically diagnosed to be consistent with the primary tumor, accompanied by loss of SAMRCA4 protein expression. The establishment of SCCOHT-CH-1 cell line and PDX models from Chinese people represent a pivotal step toward unraveling the molecular mechanism of SCCOHT and fostering the development of targeted interventions to tackle this challenging malignancy.


Simultaneous and rapid screening of live and dead E. coli O157:H7 with three signal outputs: An all-in-one biosensor using phage-apoferritin@CuO2 signal tags on MXenes-modified electrode platform.
Simultaneous detection of live and dead bacteria is a huge challenge for food safety. To solve this issue, an all-in-one biosensor for bacteria was developed using the phage-apoferritin@CuO2 (phage-Apo@CP) probe on an antimicrobial peptide (AMP)/MXenes-modified detection platform. With the specific recognition of AMP and phage-Apo@CP, the biosensor for the target Escherichia coli O157:H7 (E. coli O157:H7) presented multi-mode (bioluminescent, colorimetric, and electrochemical) signals to simultaneously measure live and dead bacteria. The bioluminescent signal caused by the adenosine triphosphate (ATP) from the bacteria was used to quantify live bacteria. The colorimetric and voltammetric signals triggered by ·OH and Cu2+ from the probe with the assistance of acid could rapidly screen and quantitative determination of total E. coli O157:H7 concentration. Thus, the dead one was obtained according to the total and live ones. All three signals could be mutually corrected to improve the accuracy. The biosensor was successfully used for on-site measurement of live and dead E. coli O157:H7 in food samples with the limit of detection of 30 CFU/mL for live ones and 6 CFU/mL for total bacteria within 50 min. This work presents a novel pathway for rapid and simultaneous quantification of both live and dead bacteria.


The relationship between heated cigarette smoking and blood white blood cell count: a population-based cross-sectional study.
Conventional cigarette smoking increases inflammation and white blood cell (WBC) counts. However, there have been limited studies on the relationship between heated cigarette smoking and WBC counts. This study aimed to examine this relationship using nationally representative population-based health data. This was a population-based cross-sectional study. The Korea National Health and Nutrition Examination Survey database was used to analyze this relationship. Data related to sex, age, body mass index (BMI), WBC count, and smoking history were obtained from the database. The smoking-related questionnaires included smoking status, smoking type (heated or conventional cigarettes), and smoking amount. The summary statistics of the WBC counts were calculated according to sex, smoking status, and smoking type. In addition, the exposure-response relationship between the smoking amount and WBC count was examined by smoking type, controlling for sex, age, and BMI. In total, 9747 WBC measurements were used in the analyses. WBC count increased in conventional cigarette smokers, while there was no significant difference in WBC count between heated cigarette smokers and non-smokers. The WBC count showed a positive dose-response relationship with the smoking amount in both conventional and heated cigarette smokers. The results confirm that conventional cigarette smoking increases WBC counts. Furthermore, the results suggest that heated cigarette smoking does not lead to a significant increase in WBC counts, although it indicates a potential dose-response relationship with WBC count. Further research with larger sample sizes is needed to confirm whether these results reflect true associations.