Stereodivergent approach to the asymmetric synthesis of bacillariolides: a formal synthesis of ent-bacillariolide II.
[reaction: see text] Asymmetric synthesis of densely functionalized bicyclic frameworks for entry into bacillariolides I/III and ent-bacillariolide II is reported. The key features are ring-closing metathesis of a pair of diastereomerically related dienes obtained through a stereodivergent route from a R-(+)-glyceraldehyde derivative, transformation of a nonstereoselective cyclopentene ester enolate alkylation process to a completely stereoselective one through alkylation of a bulky ester enolate with a bulky electrophile, and a remote silyloxymethyl group directed epoxidation.


Bifurcated Nickel-Catalyzed Functionalizations: Heteroarene C-H Activation with Allenes.
A unified strategy for nickel(0)-catalyzed C-H allylations, alkenylations, and dienylations has been realized through versatile hydroarylations of allenes with ample scope. Thus, an inexpensive nickel catalyst modified with a N-heterocyclic carbene ligand enabled the direct transformation of C-H bonds of biologically relevant imidazole and purine derivatives with full control of regio- and chemoselectivity.


Improvement in cerebral metabolism in chronic brain injury after hyperbaric oxygen therapy.
While no research study has yet demonstrated convincing evidence for the efficacy of Hyperbaric Oxygen Therapy (HBOT) in patients with chronic neurological disorders (CND), anecdotal studies have been supportive of its use in improving healing of the damaged brain. The current study hypothesized that (1) individuals with CND show increases in cerebral blood flow and metabolism as measured by Single Positron Emission Computed Tomography (SPECT) in the cerebral hemispheres, but not on measures of cerebellar and pons blood flow; and (2) younger patients show more improvement than older patients. The study used archival data to compare 25 older and 25 younger subjects who were given SPECT scans pretherapy, midtherapy, and posttherapy. ANOVAs using the SPECT scans as a within subjects variable and age as a between subjects variable confirmed the hypothesis that the cerebral measures all changed but that the cerebellar and pons measures did not. Post-hoc t-tests confirmed that there was improvement in blood flow from the beginning to the end of the study. An age effect was found on only two of the five measures; however, there were no interactions. Analysis by post-hoc t-tests showed that the younger group had higher blood flows, but not more improvement than the older group. The results provided the first statistical research data to show the effectiveness of HBOT in improving blood flow in CND. These results indicate that HBOT can be an effective part of the treatment for such clients. The implications of these findings and future research directions were discussed.


Accord No. 00243, 9 February 1988.
This Accord sets forth the Regulations of the Organic Functions of the Ministry of Social Welfare of Ecuador. The following are among the Departments of the Ministry: 1) on the advisory level, the National Council of Minors; 2) on the operative level, the National Directorate for the Protection of Minors, consisting of the Department for the Protection of Minors, the Department for the Rehabilitation of Minors, the Department of Integral Health for Minors, and the Legal-Social Department for the protection of Minors; and a National Directorate of Women, consisting of a Technical Department and a Department of Promotion and Development. The functions of the National Directorate of Women are as follows: 1) to promote the participation of women and women's organizations, encouraging their incorporation into the socioeconomic development of the country; 2) to encourage and orient on a national level the creation of women's groups; 3) to advise and coordinate in the state and private sector the execution of programs and projects designed to improve the condition of Ecuadoran women; 4) to direct and execute programs and projects for women; 5) to promote the strengthening of women's organizations striving to obtain self-management for women and raise their standards of living; 6) to give opinions on the approval of statutes of women's organizations; 7) to supervise the implementation of programs and projects undertaken by organizations that receive contributions from the Ministry; 8) to direct and supervise the organization of a register of information related to women's organizations; and 9) to promote the dissemination of information for the implementation of programs and projects of the Directorate relating to women's organizations.


Lidocaine and Bupivacaine Downregulate MYB and DANCR lncRNA by Upregulating miR-187-5p in MCF-7 Cells.
Background: Breast cancer is the most common malignancy and a leading cause of death among women. The majority of patients require surgery, and retrospective studies have revealed an association between anaesthetic techniques during surgery and clinical outcomes. Local anaesthetics (LAs) influence carcinogenesis by interacting with non-coding RNAs (ncRNAs). However, the detailed mechanisms underlying the association between LAs and ncRNAs remain unclear. Methods: In this study, the effects of two commonly used LAs, lidocaine and bupivacaine, on the malignancy of MCF-7 breast cancer cells were investigated. The expression profiles of the microRNAs (miRNAs) that responded to treatment with LAs were determined through next-generation sequencing. Results: Data from the functional assay revealed that the LAs suppressed the proliferation of MCF-7 cells. The result of next-generation sequencing revealed that 131 miRNAs were upregulated, following treatment with the LAs. Validation using polymerase chain reaction (PCR) identified miR-187-5p as a potential biomarker, and it was selected for further analyses. Prediction with bioinformatics tools and luciferase reporter assays revealed that MYB is a direct target gene of miR-187-5p. Based on the hypothesis that lncRNAs acts as miRNA sponges, the target lncRNA, DANCR, of miR-187-5p was predicted using DIANA-LncBase v2 and validated using luciferase reporter assays. In addition, the reciprocal suppressive effect between DANCR and miR-187-5p was determined. Conclusions: This study suggests that one of the anti-tumour mechanisms of lidocaine and bupivacaine is mediated through the DANCR-miR-187-5p-MYB axis. This may provide a novel molecular mechanism of tumour suppression in breast cancer.


The mucosal attachment to titanium implants with different surface characteristics: an experimental study in dogs.
Findings from in vitro studies have indicated that the orientation and proliferation of cells on titanium surfaces may be influenced by the topography of the surface on which they are grown. It may be argued, therefore, that differences may occur in the mucosal attachment to titanium implants with different surface roughness. The present experiment was performed to study the composition of the soft tissue barrier that formed to implants prepared with well-defined smooth or rough surfaces. Five beagle dogs were used. Four implants made of c.p. titanium were placed in the right edentulous mandibular premolar region. After 3 months, two different types of abutments were connected: one experimental (OA) with a dual, thermal acid-etched surface ('Osseotite'), and one regular (RA) abutment with a 'turned' surface. At the end of a 6-month period during which proper plaque control had been maintained, biopsies including the implant and the surrounding soft and hard tissues were obtained, decalcified and processed for light and electron microscopy. A confocal He-Ne laser profilometer was used to study the surface topography of the abutments. The attachment between the peri-implant mucosa and titanium abutments with either a turned (RA; 'smooth') or acid-etched (OA; 'rough') surface was similar from both a quantitative and a qualitative aspect. The attachment comprised a barrier epithelium and a zone of connective tissue attachment of similar dimension at RA and OA. It was further observed that the 'inner' zone of the connective tissue attachment at both types of abutment was composed of about 30-33% fibroblasts and 63-66% collagen. It was demonstrated that the soft tissue attachment that formed to implants made of c.p. titanium was not influenced by the roughness of the titanium surface.


Experiencing the role of PBL tutor.
The tutor is important for student learning in the PBL group. The students expect the tutor to monitor and steer the group process and to support the learning process, helping students to become aware of their own learning. This study aimed at investigating the PBL tutor's role. Five PBL tutors at the Speech/Language Pathology program were interviewed regarding their view of the tutors' role and what support they need. The analysis of the transcribed interviews focused on finding patterns and variation regarding tutor-activity at different stages in the PBL work and in their views of their progress as tutors. The results indicate that being a tutor is a balancing act and that the tutor need continuous support and input from different sources. Tutors should be encouraged to reflect on their own reactions and interventions and to be explicit and confident in their thoughts about PBL.


anem: A Simple Web-Based Platform to Build Stakeholder Understanding of Groundwater Behavior.
Groundwater supports essential societal and ecological functions by acting as a reservoir that buffers against natural variability. Increasing water scarcity and climate variability have resulted in more intensive management of groundwater resources, but groundwater often remains difficult to understand and manage. With this in mind, we develop a simple platform that provides a straightforward, web-based user interface applicable to a wide variety of end-user scenarios. Groundwater behavior is modeled using the method of images in a new R package, anem, which serves as the engine for the web platform, anem-app, produced using R Shiny. Both tools allow users to define aquifer properties and pumping wells, view maps of hydraulic head, and simulate particle tracking under steady-state conditions. These tools have the advantage of being platform independent and open source, so that they are freely available to anyone with a web browser and internet connection (anem-app) or computing platform with R installed (anem). We designed both tools to lower the learning curve and up-front costs to building simple groundwater models. The simplicity of the web application allows exploration of groundwater behavior under various conditions, and should be especially valuable in low-budget applications where advanced analysis may not be practical or necessary. Integration with the R language allows for advanced analysis and deeper exploration of groundwater dynamics. In this manuscript, we describe how anem and anem-app are built in the R environment and demonstrate how they might be used by planners or stakeholders.


Extensive white matter involvement in patients with frontotemporal lobar degeneration: think progranulin.
Mutations in the progranulin (GRN) gene are responsible for 20% of familial cases of frontotemporal dementias. All cause haploinsufficiency of progranulin, a protein involved in inflammation, tissue repair, and cancer. Carriers of the GRN mutation are characterized by a variable degree of asymmetric brain atrophy, predominantly in the frontal, temporal, and parietal lobes. We describe 4 GRN mutation carriers with remarkable widespread white matter lesions (WML) associated with lobar atrophy shown on magnetic resonance imaging. Four GRN mutation carriers (age at onset, 56-65 years) presenting with severe WML were selected from 31 GRN mutation carriers who were followed up in our dementia centers. The WML were predominantly in the frontal and parietal lobes and were mostly confluent, affecting the periventricular subcortical white matter and U-fibers. In all patients, common vascular, metabolic, inflammatory, dysimmune, and mitochondrial disorders were excluded and none had severe vascular risk factors. Our data suggest that white matter involvement may be linked to progranulin pathological processes in a subset of GRN mutation carriers. The plasma progranulin measurement, which is predictive of GRN mutations, and GRN sequencing should thus be included in investigations of patients with frontotemporal lobar degenerations who show unusual white matter hyperintensities and atrophy on magnetic resonance imaging.


Gamma-glutamyl transferase: a novel cardiovascular risk biomarker.
Gamma-glutamyl transferase (GGT) is a second-generation enzymatic liver function test available for several decades, initially used as a sensitive indicator of alcohol ingestion, hepatic inflammation, fatty liver disease, and hepatitis. Longitudinal and cross-sectional investigational studies since 1990 have associated GGT with an increase in all-cause mortality, as well as chronic heart disease events such as congestive heart failure and components of the metabolic syndrome (abnormal body mass index and levels of high-density lipoprotein cholesterol, glucose, triglycerides, and systolic and diastolic blood pressure). In the upper reference range, GGT was found to be an independent biomarker of the metabolic syndrome, with a 20% per GGT quartile trend rise. Additionally, GGT was positively correlated with an 18% per quartile risk of cardiovascular events and a 26% per quartile increased risk of all-cause mortality. Furthermore, it may be considered a biomarker for "oxidative stress" associated with glutathione metabolism and possibly a "proatherogenic" marker because of its indirect relationship in the biochemical steps to low-density lipoprotein cholesterol oxidation. GGT is becoming an important addition to the multimarker approach to cardiovascular risk evaluation. It should be considered a valuable adjunct in stratifying patient risk and in assessing the aggressiveness of appropriate treatment, with hopes of preventing unnecessary cardiac events and deaths in future years.


Minocycline treatment for confluent and reticulated papillomatosis.
We report six cases of confluent and reticulated papillomatosis in which the skin lesions cleared almost completely after treatment with minocycline. Patients with confluent and reticulated papillomatosis often do not respond well to a variety of therapeutic agents. The response of confluent and reticulated papillomatosis to minocycline was first described in 1965. Although the pharmacologic mechanisms of minocycline in confluent and reticulated papillomatosis are unknown, we suggest that it should be considered as a first-choice therapeutic agent because of its marked effectiveness.


Electroencephalographic Neurofeedback to up-regulate frontal Theta rhythms: Preliminary results.
Retrieval of positive Autobiographical Memory (AM) has been reported to increase positive emotions in healthy population. Evidence suggests that positive AM retrieval tasks are correlated with synchronisation of frontal Theta rhythms (4-8Hz). The present study has developed the Electroencephalography (EEG) based Neurofeedback (NF) protocols to promote voluntary elevation or up-regulation of positive AM retrieval related Theta rhythms over F3, Fz, F4 electrode sites (10-20 System). The protocols were evaluated with a human participant in 10-day NF training. It observed that the average amplitude of observed Theta rhythms in each NF regulation block gradually increased over days of training and most was prominent at Fz electrode site. Furthermore, a larger peak at 6Hz was present in the spectrum of the observed Theta with later trial day suggesting up-regulation of Frontal Midline Theta (FmT) rhythms.


A Rho-dependent transcription termination site regulated by bacteriophage P4 RNA immunity factor.
The genes required for replication of the temperate bacteriophage P4, which are coded by the phage left operon, are expressed from a constitutive promoter (PLE). In the lysogenic state, repression of the P4 replication genes is achieved by premature transcription termination. The leader region of the left operon encodes all the genetic determinants required for prophage immunity, namely: (i) the P4 immunity factor, a short, stable RNA (CI RNA) that is generated by processing of the leader transcript; (ii) two specific target sequences that exhibit complementarity with the CI RNA. RNA-RNA interactions between the CI RNA and the target sites on the mRNA leader region are essential for transcription termination. To understand how transcription termination is elicited by the P4 immunity mechanism, it is relevant to identify the transcription termination site. This, however, could not be directly inferred from the 3'-end of the transcription products because of the extensive and complex processing and degradation of the leader RNA. In this work, by making use of a tRNA gene as a reporter, we identify the termination site of the immunity transcripts (timm). This is a Rho-dependent terminator located within the first translated gene of the left operon and is regulated by P4 immunity. Analysis of the P4 transcription pattern in Escherichia coli rho mutants suggests that termination at timm may also be important for the efficient processing of the CI RNA.


The essential oil from Citrus limetta Risso peels alleviates skin inflammation: In-vitro and in-vivo study.
Citrus fruit peels are traditionally used in folk medicine for the treatment of skin disorders but it lacks proper pharmacological intervention. Citrus limetta Risso (Rutaceae) is an important commercial fruit crops used by juice processing industries in all continents. Ethnopharmacological validation of an essential oil isolated from its peels may play a key role in converting the fruit waste materials into therapeutic value added products. To evaluate the chemical and pharmacological (in-vitro and in-vivo) profile of essential oil isolated from Citrus limetta peels (Clp-EO) against skin inflammation for its ethnopharmacological validation. Hydro-distilled essential oil extracted from Citrus limetta peels (Clp-EO) was subjected to gas chromatography (GC) analysis for identification of essential oil constituents and its anti-inflammatory evaluation through in vitro and in vivo models. Chemical fingerprint of Clp-EO revealed the presence of monoterpene hydrocarbon and limonene is the major component. Pre-treatment of Clp-EO to the macrophages was able to inhibit the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in LPS-induced inflammation as well as the production of reactive oxygen species (ROS) in H2O2-induced oxidative stress. In in-vivo study, topical application of Clp-EO was also able to reduce the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear thickness, ear weight, lipid peroxidation, pro-inflammatory cytokines production and ameliorate the histological damage in the ear tissue. In-vitro and in-vivo toxicity study indicate that it is safe for topical application on skin. These findings suggested the preventive potential of Clp-EO for the treatment of inflammation linked skin diseases.


Graft versus host disease following transfusion of normal blood products to patients with malignancies.
A patient undergoing treatment with cytotoxic chemotherapy for Hodgkin's disease developed graft versus host disease (GVHD) following a transfusion of packed red cells. This is the 28th reported patient with a malignancy who did not have a bone marrow transplant and developed GVHD after transfusion of normal blood or blood products. All patients had received cytotoxic chemotherapy prior to acquiring GVHD. The underlying malignancies included lymphoma, acute leukemia, neuroblastoma, rhabdomyosarcoma, and glioblastoma. Twenty-three of the 28 patients died of GVHD. The incidence of transfusion-related GVHD in this patient population is low but the illness is often fatal as treatment is largely ineffective. Transfusion-related GVHD can be prevented by irradiating all blood products with 1500 rad prior to administration.


Coping, social support, and depressive symptoms in adolescent mothers.
The purpose of this study was to determine how the degree of depressive symptomatology among adolescent mothers differentiated maternal outcomes, social support, and coping at 6 months postpartum. Fifty primiparous adolescents, predominantly black and of low income, participated in the study. During a home visit at 6 months postpartum, a research assistant, blind to the study's hypotheses, administered questionnaires related to depressive symptoms, coping with motherhood, social support, maternal confidence, and maternal gratification. Feeding and teaching interactions between mother and child were observed. Fifty-six percent of the subjects had no depressive symptoms (group 1), 20% reported mild symptoms (group 2), and 24% reported moderate to severe symptoms (group 3). Adolescents with mild or moderate depressive symptoms had more negative feeding interactions with their infants, reported less maternal confidence and gratification, and used more emotion-focused coping than their nondepressed counterparts. While the groups did not differ in the frequency with which they received social support, adolescents with mild or moderate depressive symptoms were less satisfied with this support. No differences were found among groups with regard to the size of their conflicted networks. This study extends the research findings related to depressive symptoms among adult mothers to a sample of adolescent mothers. Although the study design is crosssectional and therefore causal sequences cannot be determined, the results identify factors that may place certain adolescents at risk for problems in parenting. The authors suggest screening adolescent mothers during the first postpartum year for symptoms of depression.


Underwater shear-based grooming of marine biofouling using a non-contact Bernoulli pad device.
The biofouling removal ability of a shear-based device was tested on two submerged surface types, Garolite G-10 and Intersleek 1100SR. Each surface was groomed at four frequencies along with a control group. The seven-week grooming study was conducted in Narragansett Bay, Rhode Island. The Bernoulli pad device uses confined radial outflow to generate both surface-normal forces to grip the submerged surface and shear stress to groom the surface without contact. An image-processing algorithm was developed and used to assess the effectiveness of the various grooming protocols, along with direct measurements of chlorophyll a per surface area. The image-processing data showed that the grooming resulted in ∼50% cleanliness on the Garolite at the end of the study whereas the Intersleek was continuously restored to nearly its initial clean state. Chlorophyll a data supported these overall conclusions. These results indicate that surface cleanliness can be maintained effectively on Intersleek using frequent shear-based grooming.


Acute hypertension, but not thrombolysis, increases the incidence and severity of hemorrhagic transformation following experimental stroke in rabbits.
Hemorrhagic transformation (HT) is a poorly understood yet frequent complication of stroke. A transient increase in blood pressure (BP) occurs immediately after experimental embolization in rabbits and we evaluated the relationship between this acute hypertensive response and subsequent hemorrhagic transformation, as well as the attenuation of this hypertensive response with an anesthetic dose of halothane. We also examined embolism-induced HT during infusion of the thrombolytic agents tissue plasminogen activator and streptokinase. A blood clot embolus was injected into the internal carotid artery and flushed into the middle cerebral artery. In the first experiment, BP was monitored in anesthetized or unanesthetized rabbits for 20 min prior to and up to 1 h after embolization. In the second experiment, animals were embolized half-way through an infusion of tPA (3.0 mg/kg; 20% administered as an iv bolus, with the remainder infused over 30 min) or streptokinase (30,000 U/kg iv infused over 30 min). In unanesthetized animals, the HT score (number of brain sections displaying visible HT) was significantly correlated with the peak mean arterial pressure recorded at embolization (r = 0.60, n = 24, P < 0.01). No relationship was observed between BP and HT score in animals anesthetized with halothane. Although HT incidence and extent were significantly related to elevated BP in the unanesthetized animals, halothane administration actually increased HT incidence. Embolization during thrombolytic infusion did not increase the occurrence or severity of HT. These data suggest that acute hypertension, but not ongoing thrombolysis, is a significant risk factor for HT following cerebral embolization.


[Fibrillary glomerulonephritis--a rare cause of nephrotic syndrome].
Fibrillary glomerulonephritis (FGN) is a rarely diagnosed disease with clinical manifestations such as proteinuria, microscopic hematuria, nephrotic syndrome or decreased kidney function. Around one half of patients develop chronic renal failure in the course of several years. The diagnosis of fibrillary glomerulonephritis is to be established only basing on the results of renal biopsy. Pathognomonic is the electron-microscopic examination, evidencing fibrillar deposits in mesangium and in basal membranes of glomeruli. Fibrils are similar to those seen at amyloidosis, however, with larger diameter, non-linear deposition and do not stain with Congo red or thioflavin T. Immunofluorescency test usually shows the presence of IgG, namely the subclasses IgG4, C3 and kappa and lambda of light immunoglobulin chains. The presented case report describes clinical and laboratory findings at a patient suffering from nephrotic syndrome. Results of renal biopsy and detailed histological examinations concluded the diagnosis as fibrillary glomerulonephritis. The patient was treated with a combination of prednisone (1 mg/kg/24 hrs) with cyclophosphamide (2 mg/kg/24 hrs) for six months. This led to a decrease of proteinuria from the initial value of 5.38 g/24 hours to 1.88 g/24 hours, as well as to a partial remission of nephritic syndrome. Glomerular filtration, evaluated using endogenous creatinine clearance, remained within limits of normal values throughout the follow-up, with the value of 2.6 ml/s after the treatment.


Psychological Behavior of Frontline Medical Staff in the Use of Preventive Medication for COVID-19: A Cross-Sectional Study.
To understand the current pandemic, levels of anxiety in frontline staff, and whether they have been using medication to prevent COVID-19. Between January 10 and March 10, 2020, 290 frontline staff completed a questionnaire incorporating the Generalized Anxiety Disorder Scale 7 (GAD-7) to indicate their psychological behavior in the use of preventive medication. Of those who participated in the study, 77.6% used preventive medication, with 47.5, 40.9, and 11.6% using these as part of routine preventive treatment, to fight infection after it was contracted, and after occupational exposure, respectively. There was a statistically significant relationship between the anxiety scale scores and the frequency of medication use (P < 0.05). Comparative analyses revealed that the scores of those in the group taking medication after occupational exposure (to respiratory and blood-borne pathogens) were significantly different from other groups. The proportion of participants choosing Western medicine, traditional Chinese medicine, and integrated Chinese and Western medicine was 24.4, 28.0, and 47.6%, respectively. Additionally, the relationship between the anxiety scale scores and the three types of medication was statistically significant (P < 0.05), as was the difference between Western medicine and other groups. According to Multinomial logistic regression based on the adjustment to gender, age, educational level, marital status, current workplace, and profession, participants with moderate to severe anxiety, had higher odds (OR = 10.331, 95%CI:1.453-73.429) of using Western medicine than participants with no anxiety. Participants with moderate anxiety were 6.399 times more likely to use an integrated combination of traditional Chinese and Western medicine compared to those with no anxiety (OR = 6.399, 95%CI:1.007-40.658). Furthermore, those with mild anxiety were 2.656 times more likely to use integrated traditional Chinese and Western medicine than those with no anxiety (OR = 2.657, 95%CI:1.075-6.570). The probability that frontline medical staff with moderate anxiety took preventive medication after occupational exposure to COVID-19 was 8.066 times (OR = 8.066, 95%CI:1.043-62.353) higher than that of staff without anxiety. This study revealed that there was more anxiety among frontline medical staff who took medication after unexpected occupational exposure. There was less anxiety among those using an integrated course of Chinese and Western medicine than Western medicine alone. It was also observed that anxiety affects the types and frequency of the preventive medication taken. Frontline medical staff who suffer from anxiety are also more likely to use medication to prevent COVID-19.


Statins for women with polycystic ovary syndrome not actively trying to conceive.
Statins, as lipid-lowering agents with pleiotropic actions, are likely not only to improve the dyslipidaemia associated with polycystic ovary syndrome but may also exert other beneficial metabolic and endocrine effects. To assess the efficacy and safety of statin therapy for women with polycystic ovary syndrome (PCOS) who are not actively trying to conceive. We searched the following databases (from inception to week 1, July 2011): the Cochrane Menstrual Disorders and Subfertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and CINAHL. We handsearched relevant conference proceedings and references of the identified articles for additional studies. We also contacted experts for further studies in progress. Randomised controlled trials (RCTs) comparing a statin versus placebo or statin in combination with another drug versus another drug alone in women with PCOS. Two review authors performed data collection and analysis independently. Four trials fulfilled the criteria for inclusion. They comprised a total of 244 women with PCOS receiving 12 weeks or 6 weeks of treatment. Two trials (184 women randomised) studied the effects of simvastatin and two trials (60 women randomised) studied the effects of atorvastatin. There was no good evidence that statins improved menstrual regularity, spontaneous ovulation rate, hirsutism or acne, either alone or in combination with the combined oral contraceptive pill (OCP). Nor were there any significant effects on body mass index (BMI). Statins were effective in lowering testosterone levels (nmol/L) (mean difference (MD) -0.90, 95% CI -1.18 to -0.62, P < 0.00001, 3 RCTs, 105 women) when used alone or with the OCP. Statins also improved total cholesterol, low-density lipoprotein (LDL) and triglycerides but had no significant effect on high-density lipoprotein (HDL) levels, high sensitivity (HS) C-reactive protein (HS-CRP), fasting insulin or homeostatic model assessment (HOMA) insulin resistance. No serious adverse events were reported in any of the included studies. Although statins improve lipid profiles and reduce testosterone levels in women with PCOS, there is no evidence that statins improve resumption of menstrual regularity or spontaneous ovulation, nor is there any improvement of hirsutism or acne. There is a need for further research to be performed with large sample sizes and well-designed RCTs to assess clinical outcomes.


Brain cooling efficiency with pH-stat and alpha-stat cardiopulmonary bypass in newborn pigs.
For infant cardiac surgery, recent studies suggest improved neurological outcome after deep hypothermic circulatory arrest when pH-stat cardiopulmonary bypass is used compared with alpha-stat cardiopulmonary bypass. The pH-stat method is hypothesized to protect the brain through improved cooling and/or rewarming. We examined brain cooling and rewarming during pH-stat and alpha-stat cardiopulmonary bypass in 12 newborn pigs. Microthermistors were inserted into the caudate and cortical gray and white matter, and a cranial window was created to map neocortical temperature gradients by using infrared imaging. Piglets were cooled with pH-stat or alpha-stat cardiopulmonary bypass until all brain regions were less than 20 degrees C; then they were subjected to 60 minutes of circulatory arrest, and afterward, rewarmed with cardiopulmonary bypass. During cardiopulmonary bypass cooling, cortical gray and white matter and caudate temperatures were up to 5 degrees C less in pH-stat than in alpha-stat (P<.05), although after 10 minutes of cooling, only cortical white matter temperature remained significantly less in pH-stat. Neocortical thermal gradients during cardiopulmonary bypass cooling were greater in pH-stat versus alpha-stat during the initial 8 minutes (4 degrees C to 5 degrees C versus 2 degrees C to 3 degrees C, P<.01) but were less by 18 to 20 minutes (0.9 degrees C versus 1.7 degrees C, P<.01). Cardiopulmonary bypass cooling time to less than 20 degrees C was shorter for pH-stat than for alpha-stat in cortical gray matter (14 versus 17 minutes, P<.05) and cortical white matter (17 versus 23 minutes, P<.001) but not in caudate (13 versus 16 minutes, P=NS). Cooling time to less than 1 degrees C neocortical thermal gradient was shorter in pH-stat than in alpha-stat (15 versus 23 minutes, P<.001). During rewarming, regional brain temperatures and neocortical thermal gradients were not different between groups. pH-stat improves brain cooling efficiency during cardiopulmonary bypass because all regions cooled more rapidly, especially cortical white matter, and less time was required to achieve uniform cerebral deep hypothermia. pH-stat and alpha-stat cardiopulmonary bypass rewarm the brain similarly after deep hypothermic arrest.


Effectiveness of afatinib in an NSCLC patient with EGFR mutation and early progression to osimertinib: a case report.
Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), shows great clinical activity in non-small cell lung cancer (NSCLC) patients with EGFR mutations regardless of T790M mutation at first-line chemotherapy. Previous studies demonstrated that there are few patients with initial resistance to osimertinib. Here, we describe a case to report the efficacy of afatinib in an EGFR-mutated NSCLC patient with early progression to first-line osimertinib treatment. A 68-year-old Japanese male was diagnosed with stage IVB lung adenocarcinoma with the EGFR L858R mutation in exon 21. Two months after the start of osimertinib, his tumor progressed at the initial response evaluation. Because he refused to receive cytotoxic chemotherapy, afatinib treatment was initiated. He was administered afatinib, and the tumor shrank. After five months of afatinib treatment, nevertheless the primary tumor was not enlarged, he experienced disease progression with leptomeningeal metastasis and passed away. To elucidate the resistance mechanisms of osimertinib in this patient, we performed next-generation sequencing (NGS) on tumor samples from pleural effusions after osimertinib failure. NGS revealed no specific gene mutations causing resistance to osimertinib except for the EGFR L858R mutation; however, his tumor had a relatively high tumor mutational burden. Afatinib is considered an option for EGFR-mutated patients with early progression to osimertinib.


Intracranial ependymomas: The role of advanced neuroimaging in diagnosis and management.
Intracranial ependymomas represent a rare subgroup of glial tumours, showing a wide variety of imaging characteristics, often representing a challenging diagnosis for neuroradiologists. Here, we review the most recent scientific Literature on intracranial ependymomas, highlighting the most characteristic computed tomography and magnetic resonance imaging features of these neoplasms, along with epidemiologic data, recent classification aspects, clinical presentation and conventional therapeutic strategies. In addition, we report an illustrative case of an 18-year-old girl presenting with an intracranial supratentorial, anaplastic ependymoma, with the aim of contributing to the existing knowledge and comprehension of this rare tumour.


Early Mobilization After Basal Joint Arthroplasty: Clinical Results.
Background: Traditional rehabilitation for basal joint arthroplasty involves postoperative immobilization. We hypothesize that early motion is safe and will result in equivalent clinical outcomes to traditional rehabilitation. Methods: Patients undergoing ligament reconstruction and tendon interposition were randomized into 2 rehabilitation protocols. All patients were immobilized postoperatively in a thumb-spica splint for 2 weeks. The accelerated group (Group 1) was transitioned into a removable Carpometacarpal (CMC)-wrap with activity as tolerated, while the traditional group (Group 2) were immobilized for an additional 4 weeks. Patients were examined preoperatively and at 6 weeks, 12 weeks, 6 months, and 1 year postoperatively. Outcome measures included the Disabilities of the Arm, Shoulder and Hand (DASH) score, a visual analog scale for pain (VAS), pinch and grip strength and thumb range of motion. Results: Ninety-three thumbs were randomized, 48 in group 1 and 45 in group 2. There were no statistically significant differences between the 2 groups preoperatively. DASH scores were significantly lower in the accelerated rehabilitation group at 6 weeks postoperatively compared to the traditional rehabilitation group, but these became equivalent by 12 weeks postoperatively. There were no statistically significant differences between the 2 groups with respect to postoperative VAS, key, pinch, or grip strength or thumb range of motion at all time points postoperatively. Conclusions: Early (12-week and 1-year) outcomes suggest early mobilization of patients following CMC arthroplasty does not compromise clinical results. Long-term data will determine the lasting effects of accelerated rehabilitation but may offer earlier return to function than traditional rehabilitation.


Comparative histological studies on liver of mice exposed to Cr(VI) and Cr(V) compounds.
Chromium toxicity is strongly dependent on its oxidation state. Cr(VI) is carcinogenic and mutagenic, although its in vivo and in vitro toxic effects are related to its intracellular fate. Inside the cells, Cr(VI) is rapidly reduced to stable Cr(III). As Cr(V) and Cr(IV) species have been reported to be formed in the Cr(VI) reduction pathways, Cr(VI)-induced damage is thought, at least in part, to arise from these hypervalent species. The study of Cr(VI) reduction mechanisms and the characterization of the effects of each reactive intermediate constitute important steps towards a better understanding of chromium toxicity. The purpose of this work is to enlarge the scope of Cr(VI)-induced alterations in mouse to other chromium species. Our studies have led to the in situ preparation of a new Cr(V) complex, 1Cr(V)-BT](2-), a stable compound at neutral pH, which mimics Cr(VI) reduction intermediates. The effect of Cr(V) on the histology of mice liver is assessed and compared with similar Cr(VI) assays. Liver toxicity was examined after single administrations of Cr(VI) or [Cr(V)-BT](2-) to mice. Both compounds produced reversible hepatic damage in a time-dependent manner. However, Cr(V) toxic effects have proved to be more rapid than with Cr(VI), permitting the role of Cr(VI) intermediates formed during intracellular chromium reduction to be highlighted.


Purification and structure of rat erythroid-specific delta-aminolevulinate synthase.
The existence of erythroid form delta-aminolevulinate synthase (ALAS-E) was historically a matter of some controversy. To obtain direct evidence for a unique ALAS-E, we have purified ALAS-E to homogeneity for the first time, from rat reticulocyte lysate. The papain digestion method was used at the initial step of the purification to overcome the difficulty which repeatedly hampered earlier attempts to purify ALAS-E. The size of the purified papain-resistant core catalytic domain of ALAS-E was estimated electrophoretically to be 49,000 Da. The pH optimum (7.6) and apparent Km values for the substrates, glycine (6.5 mM) and succinyl-CoA (2 microM), were similar to those of the non-specific form of delta-aminolevulinate synthase (ALAS-N); but, in contrast to ALAS-N, the substrate inhibition by succinyl-CoA was not evident in ALAS-E. We then isolated cDNA and genomic DNA clones encoding rat ALAS-E. By combining the nucleotide sequence information of the cDNA and genomic clones, the rat ALAS-E precursor is predicted to be composed of 587 amino acids with a calculated molecular mass of 64,841 Da. All the peptide sequences determined directly from the purified protein agreed with those predicted from the nucleotide data, demonstrating the existence of ALAS-E. Analysis of the papain-resistant core domain further revealed that it overlaps with the evolutionally conserved segment that has been noticed by sequence alignment analysis of ALA synthases from various species.


Protein-protein interaction databases: keeping up with growing interactomes.
Over the past few years, the number of known protein-protein interactions has increased substantially. To make this information more readily available, a number of publicly available databases have set out to collect and store protein-protein interaction data. Protein-protein interactions have been retrieved from six major databases, integrated and the results compared. The six databases (the Biological General Repository for Interaction Datasets [BioGRID], the Molecular INTeraction database [MINT], the Biomolecular Interaction Network Database [BIND], the Database of Interacting Proteins [DIP], the IntAct molecular interaction database [IntAct] and the Human Protein Reference Database [HPRD]) differ in scope and content; integration of all datasets is non-trivial owing to differences in data annotation. With respect to human protein-protein interaction data, HPRD seems to be the most comprehensive. To obtain a complete dataset, however, interactions from all six databases have to be combined. To overcome this limitation, meta-databases such as the Agile Protein Interaction Database (APID) offer access to integrated protein-protein interaction datasets, although these also currently have certain restrictions.


Designing for physically disabled users: benefits from human motion capture - a case study.
The present study aimed to improve the design of an interface that may help disabled children to play a musical instrument. The main point is to integrate human motion capture in the design process. The participant performed 20 pointing movements toward four selected locations. A three one-way analysis of variance (ANOVA) was performed in order to determine the most efficient input location. For each button position, we compared (1) the reaction time (RT), (2) the movement time (MT), and (3) the spatial variability of the movements. According to the results obtained for RT and MT, one position was the most efficient button location in order to produce efficient movements. As the case study showed, combining the 3D motion capture system and the statistical analysis led to help the designers their design methodology and crucial choices. Implications for Rehabilitation The paper point out the possibility for designers to use motion capture science to improve the efficiency of the personal interface manipulation to play musical instrument. This experiment with the disabled user allows researcher not only to propose standard procedure to characterize an interface but also to take into account the complete behaviour of the user: from the decision of the movement to the execution of the action. The discussion and the experiment with the disabled user help him to better understand its own difficulties. This kind of experimental procedure helps a lot the user in his future rehabilitation choices and decisions.


Childhood intussusception: US-guided hydrostatic reduction.
Over a 30-month period, real-time ultrasound (US) was performed in 116 children with suspected intussusception. US findings were positive in all 75 cases of intussusception. Except in one case of transient small-bowel intussusception, the authors immediately attempted US-guided hydrostatic reduction in all cases. Reduction was successful in 63 cases (85%), as demonstrated with US and resolution of signs and symptoms of intussusception. Negative sonograms were confirmed with clinical follow-up. Among 11 failed cases, reduction with barium enema was attempted in six, but all attempts failed. No complications have occurred to date. The authors conclude that US is a reliable diagnostic screening modality in cases of suspected intussusception and that US-guided hydrostatic reduction is a promising technique in nonoperative treatment.


Understanding the Clinical Implications of Resident Involvement in Uncommon Operations.
The objective of this study was to examine uncommon operations in greater detail given that the outcomes of uncommon operations are largely understudied. This study examines the incidence of postoperative events and the role of the resident following uncommon operations. We identified uncommon general surgical operations using the ACS National Surgical Quality Improvement Program Participant Use file (2008-2011). Death or serious morbidity (DSM) within 30 days of the operation was the primary outcome of interest. Failure to rescue (FTR) and prolonged operative time (PRopt) were evaluated as secondary outcome measures. PRopt was defined as ≥90 percentile of operative time for each procedure type. Independent multivariate logistic regression models were generated to examine the impact of these descriptors on the outcomes of interest. The dataset utilized was the United States National Surgical Quality Improvement Program Participant Use File which leverages data points from over 700 hospitals that range from primary to quaternary care centers. Resident participation was defined as resident involved (RI) or no resident involved (NRI), and stratified by postgraduate year (PGY): 1-3, 4-5, and 6+. Resident participant data was available for 21,453 (84.5%) uncommon operations with NRI in 25.4% (5447). With regard to resident participation, PGY1-3 were found in 12.6% (2699), PGY4-5 in 50.4% (10,817), and PGY6+ in 11.6% (2490). The overall observed DSM rate was 28.6% and the observed FTR rate was 5.8%. Overall, there was no difference in DSM by RI status (NRI: 1528; 28.1% vs RI: 4602; 28.8%; p = 0.324); however, PGY level was associated with DSM (PGY1-3: 774, 28.7%, PGY4-5: 3210, 29.7%, PGY6+: 618, 24.8%; p < 0.001). Any RI was associated with a lower rate of FTR (5.1%) when compared to NRI (8.3%, p < 0.001) with decreasing FTR events by increasing PGY (PGY1-3: 6.4%, PGY4-5: 5.2%, PGY6+: 3.3%; p < 0.001). After adjustment for patient risk factors, any RI remained associated with a lower likelihood of FTR than NRI (odds ratio: 0.65, 95% confidence interval: 0.49-0.87) while only the PGY4-5 and PGY6+ groups were associated with lower likelihood of FTR in comparison to NRI. RI was associated with PRopt in univariate and multivariable analyses. Uncommon operations were associated with substantial DSM. The involvement of PGY4-5 residents was associated with the greatest likelihood of DSM. With increasing PGY of the involved resident, cases with PGY > 5 demonstrated a lower likelihood of risk-adjusted FTR. The explanation for these findings is not clear; however, the involvement of more senior residents in the technical aspects of uncommon operations may lead to improved results.


Pesticide exports from U.S. ports, 2001-2003.
Analysis of U.S. Custom Service records for 2001-2003 indicates that nearly 1.7 billion pounds of pesticide products were exported from U.S. ports, a rate >32 tons/hour. Exports included >27 million pounds of pesticides whose use is forbidden in the United States. WHO Class 1a and 1b pesticides were exported at an average rate of >16 tons/day. Pesticide exports included >500,000 pounds of known or suspected carcinogens, with most going to developing countries; pesticides associated with endocrine disruption were exported at an average rate of >100 tons/day. Although the rate of export of banned products declined, as did exports of pesticides included in global conventions on Prior Informed Consent and Persistent Organic Pollutions, substantial quantities of hazardous products remain in trade. These products pose unacceptable risks in countries where unsafe use and storage practices are prevalent. Policy makers, growers, and scientists must undertake more aggressive efforts to foster sustainable agricultural practices globally.


The grief process and job loss: a cross-sectional study.
This study assessed the applicability of the grief process to job loss. A pilot study of 10 unemployed men was used to establish a structured interview, and its content analysis, based on a description of the grief process derived from studies of bereavement. Other measures assessed the degree of attachment to the former job. The main study involved 60 men who had lost their jobs during the previous eight years. Individual grief items were found in some of these people, varying in frequency from 10 to 80 per cent. Principal components analysis revealed a general grief component, representing most of the specific items. Twenty-seven per cent of the sample fulfilled a criterion for a clear grief-like response. An overall grief score based on the interview answers was significantly correlated with three different measures of job attachment, and also with questionnaire measures of depression and anxiety. These measures were unrelated to the length of time since job loss, apparently providing no support for stage theories or for more general assumptions of adaptation. However, the cross-sectional nature of the sample complicates this conclusion.


HMGB1 Induces an Inflammatory Response in the Chorioamniotic Membranes That Is Partially Mediated by the Inflammasome.
Spontaneous preterm labor occurs in two subsets of patients with sterile intra-amniotic inflammation, a process induced by alarmins such as high-mobility group box-1 (HMGB1). Inflammasomes are implicated in the process of spontaneous preterm labor. Therefore, we investigated whether HMGB1 initiates an inflammasome-associated inflammatory response in the chorioamniotic membranes. Incubation of the chorioamniotic membranes with HMGB1 1) induced the release of mature IL-1beta and IL-6; 2) upregulated the mRNA expression of the pro-inflammatory mediators NFKB1, IL6, TNF, IL1A, IFNG, and HMGB1 receptors RAGE and TLR2; 3) upregulated the mRNA expression of the inflammasome components NLRP3 and AIM2 as well as NOD proteins (NOD1 and NOD2); 4) increased the protein concentrations of NLRP3 and NOD2; 5) increased the concentration of caspase-1 and the quantity of its active form (p20); and 6) upregulated the mRNA expression and active form of MMP-9. In addition, HMGB1 concentrations in chorioamniotic membrane extracts from women who underwent spontaneous preterm labor were greater than in those from women who had undergone spontaneous labor at term. Collectively, these results show that HMGB1 can induce an inflammatory response in the chorioamniotic membranes, which is partially mediated by the inflammasome. These results provide insight into the mechanisms whereby HMGB1 induces preterm labor and birth in mice and explain why the concentration of this alarmin is increased in women who undergo spontaneous preterm labor.


Mice with reduced levels of p53 protein exhibit the testicular giant-cell degenerative syndrome.
Transgenic mice which carry hybrid p53 promoter-chloramphenicol acetyltransferase (CAT) transgenes were found to express CAT enzymatic activity predominantly in the testes. Endogenous levels of p53 mRNA and protein were lower than in the nontransgenic control mice. The various p53 promoter-CAT transgenic mice exhibited in their testes multinucleated giant cells, a degenerative syndrome resulting presumably from the inability of the tetraploid primary spermatocytes to complete meiotic division. The giant-cell degenerative syndrome was also observed in some genetic strains of homozygous p53 null mice. In view of the hypothesis that p53 plays a role in DNA repair mechanisms, it is tempting to speculate that the physiological function of p53 that is specifically expressed in the meiotic pachytene phase of spermatogenesis is to allow adequate time for the DNA reshuffling and repair events which occur at this phase to be properly completed. Primary spermatocytes which have reduced p53 levels are probably impaired with respect to DNA repair, thus leading to the development of genetically defective giant cells that do not mature.


The mitochondrial proteomic changes of rat hippocampus induced by 28-day simulated microgravity.
A large number of aerospace practices have confirmed that the aerospace microgravity environment can lead to cognitive function decline. Mitochondria are the most important energy metabolism organelles, and some studies demonstrate that the areospace microgravity environment can cause mitochondrial dysfunction. However, the relationships between cognitive function decline and mitochondrial dysfunction in the microgravity environment have not been elucidated. In this study, we simulated the microgravity environment in the Sprague-Dawley (SD) rats by -30° tail suspension for 28 days. We then investigated the changes of mitochondrial morphology and proteomics in the hippocampus. The electron microscopy results showed that the 28-day tail suspension increased the mitochondria number and size of rat hippocampal neuronal soma. Using TMT-based proteomics analysis, we identified 163 differentially expressed proteins (DEPs) between tail suspension and control samples, and among them, 128 proteins were upregulated and 35 proteins were downregulated. Functional and network analyses of the DEPs indicated that several of mitochondrial metabolic processes including the tricarboxylic acid (TCA) cycle were altered by simulating microgravity (SM). We verified 3 upregulated proteins, aconitate hydratase (ACO2), dihydrolipoamide S-succinyltransferase (DLST), and citrate synthase (CS), in the TCA cycle process by western blotting and confirmed their differential expressions between tail suspension and control samples. Taken together, our results demonstrate that 28-day tail suspension can cause changes in the morphology and metabolic function of hippocampus mitochondria, which might represent a mechanism of cognitive disorder caused by aerospace microgravity.


Fission yeast tor1 functions in response to various stresses including nitrogen starvation, high osmolarity, and high temperature.
A target of rapamycin (TOR) protein is a protein kinase that exerts cellular signal transduction to regulate cell growth in response to extracellular nutrient conditions. In the Schizosaccharomyces pombe genome database, there are two genes encoding TOR-related proteins, but their functions have not been analyzed. Here we report that one of the genes, referred to as tor1+, is required for sexual development induced by nitrogen starvation. Ste11 is a key transcription factor for the initiation of sexual development. The expression of ste11+ is normally regulated in tor1- cells; and overexpression of ste11+ hardly rescues the defect in fertility in tor1-. Upon nitrogen starvation, tor1+ cells promote two rounds of the cell cycle to become arrested at the G1 phase before initiation of sexual development. The tor1- cells do not promote such a cell cycle, suggesting that Tor1 is necessary for the response to nitrogen starvation. The tor1- cells show no growth or very slow growth under various stress conditions, including external high pH, high concentrations of salts or sorbitol, and high temperature. These results suggest that Tor1 is necessary for any response to a wide range of stresses. The vegetative growth of tor1- cells is inhibited by rapamycin, although tor1+ cells are resistant to the drug. The tor1- cells are hypersensitive to fluphenazine and cyclosporin A, which specifically inhibit calmodulin and calcineurin, respectively.


A centromeric region on chromosome 6(6H) affects dormancy in an induced mutant in barley.
Genetic control of seed dormancy in barley (Hordeum vulgare L.) has mostly been described in terms of quantitative variation. Although some molecular markers for dormancy QTL have been identified, the corresponding genes involved in the regulation of the process have not been cloned. Induced barley mutants may constitute useful material to study the physiology and genetics of seed dormancy. The objective of this study was to identify the genetic control of this trait in a mutant (TL43) produced in the barley cv. Triumph. This mutant was selected for reduced dormancy and reduced sensitivity to abscisic acid (ABA). Two sets of F6 barley lines were selected for high and low levels of dormancy from a cross between the original dormant parent and the sodium azide-induced non-dormant TL43 mutant. Unexpectedly, given the near-isogenic nature of these two genotypes, polymorphism was detected for an SSR located in the centromeric region of chromosome 6(6H) out of a total of 92 molecular markers evenly distributed along the genome. Fortunately, upon three cycles of intensive divergent selection, every dormant and non-dormant F5 line consistently showed the genotype for this region identical to Triumph and TL43, respectively. Based on the mutagenic effect presumably attributed to sodium azide, mostly single point mutations, it cannot be clearly established if such extensive genomic variation on chromosome 6(6H) is due to the mutagenic treatment or may be an introgression from an unknown source. The means that could originate such heterogeneity are discussed; however, regardless of its origin, this genomic region shows a strong association with the expression of seed dormancy and provides an additional genetic locus for further studies of the mechanistic basis of this complex trait. In addition, since TL43 shows reduced sensitivity to ABA, the response to this hormone was determined on the F6 seed from the two sets of selected F5 lines. The results confirmed that the initial level of dormancy in the seed lot is the most important factor in determining ABA sensitivity.


Methylthiol:coenzyme M methyltransferase from Methanosarcina barkeri, an enzyme of methanogenesis from dimethylsulfide and methylmercaptopropionate.
During growth on acetate, Methanosarcina barkeri expresses catabolic enzymes for other methanogenic substrates such as monomethylamine. The range of substrates used by cells grown on acetate was further explored, and it was found that cells grown on acetate also converted dimethylsulfide (DMS) and methylmercaptopropionate (MMPA) to methane. Cells or extracts of cells grown on trimethylamine or methanol did not utilize either DMS or MMPA. During growth on acetate, cultures demethylated MMPA, producing methane and mercaptopropionate. Extracts of acetate-grown cells possessed DMS- and MMPA-dependent coenzyme M (CoM) methylation activities. The activity peaks of CoM methylation with either DMS or MMPA coeluted upon gel permeation chromatography of extracts of acetate-grown cells consistent with an apparent molecular mass of 470 kDa. A 480-kDa corrinoid protein, previously demonstrated to be a CoM methylase but otherwise of unknown physiological function, was found to methylate CoM with either DMS or MMPA. MMPA was demethylated by the purified 480-kDa CoM methylase, consuming 1 mol of CoM and producing 1 mol of mercaptopropionate. DMS was demethylated by the purified protein, consuming 1 mol of CoM and producing 1 mol of methanethiol. The methylthiol:CoM methyltransferase reaction could be initiated only with the enzyme-bound corrinoid in the methylated state. CoM could demethylate, and DMS and MMPA could remethylate, the corrinoid cofactor. The monomethylamine corrinoid protein and the A isozyme of methylcobamide:CoM methyltransferase (proteins homologous to the two subunits comprising the 480-kDa CoM methylase) did not catalyze CoM methylation with methylated thiols. These results indicate that the 480-kDa corrinoid protein functions as a CoM methylase during methanogenesis from DMS or MMPA.


Radiotherapy-Immunotherapy Combination: How Will We Bridge the Gap Between Pre-Clinical Promise and Effective Clinical Delivery?
Radiotherapy (RT) is highly effective at directly killing tumor cells and plays an important part in cancer treatments being delivered to around 50% of all cancer patients. The additional immunomodulatory properties of RT have been investigated, and if exploited effectively, have the potential to further improve the efficacy of RT and cancer outcomes. The initial results of combining RT with immunomodulatory agents have generated promising data in pre-clinical studies, which has in turn led to a large number of RT and immunotherapy clinical trials. The overarching aim of these combinations is to enhance anti-tumor immune responses and improve responses rates and patient outcomes. In order to maximize this undoubted opportunity, there remain a number of important questions that need to be addressed, including: (i) the optimal RT dose and fractionation schedule; (ii) the optimal RT target volume; (iii) the optimal immuno-oncology (IO) agent(s) to partner with RT; (iv) the optimal site(s)/route(s) of administration of IO agents; and finally, the optimal RT schedule. In this review, we will summarize progress to date and identify current gaps in knowledge that need to be addressed in order to facilitate effective clinical translation of RT and IO agent combinations.


Effect of 910-MHz electromagnetic field on rat bone marrow.
Aiming to investigate the possibility of electromagnetic fields (EMF) developed by nonionizing radiation to be a noxious agent capable of inducing genotoxicity to humans, in the current study we have investigated the effect of 910-MHz EMF in rat bone marrow. Rats were exposed daily for 2 h over a period of 30 consecutive days. Studying bone marrow smears from EMF-exposed and sham-exposed animals, we observed an almost threefold increase of micronuclei (MN) in polychromatic erythrocytes (PCEs) after EMF exposure. An induction of MN was also observed in polymorphonuclear cells. The induction of MN in female rats was less than that in male rats. The results indicate that 910-MHz EMF could be considered as a noxious agent capable of producing genotoxic effects.


Fatal cerebral oedema in adult diabetic ketoacidosis.
In this report, a case of adult onset fatal cerebral oedema as a rare complication of diabetic ketoacidosis (DKA) is described and confirmed at post-mortem pathological examination. The pathogenesis of cerebral oedema due to DKA is still unknown. Potential mechanisms include the administration of sodium bicarbonate leading to intracellular acidosis, excessive fluid infusion causing swelling of brain tissue, or reduction of plasma osmolarity by a rapid fall in glucose levels causing osmotic swelling.


Expression of Vascular Endothelial Growth Factor-C in the Trabecular Meshwork of Patients with Neovascular Glaucoma and Primary Open-Angle Glaucoma.
To investigate the expression of vascular endothelial growth factor (VEGF)-C and vascular endothelial growth factor receptor (VEGFR)3 in the trabecular meshwork (TM) of patients with glaucoma and cultured TM cells. Methods: The expressions of VEGF-C in angle tissues collected by trabeculectomy from patients with glaucoma and non-glaucomatous choroidal malignant melanoma were analyzed by immunohistochemistry. Additionally, VEGF-C concentrations were determined in the aqueous humor of patients with glaucoma by ELISA. The expressions of VEGFR3, which is a receptor of VEGF-C in cultured TM cells, were analyzed by Western blot analysis and immunocytochemistry. Cultured TM cells were stimulated by oxidative stress, hypoxia, or high glucose conditions, and VEGF-C concentrations in supernatants and cell lysates were determined by ELISA. Results: VEGF-C immunoreactivity was positive in TM tissues of glaucoma patients, but not in those of non-glaucomatous controls. VEGF-C concentrations in the aqueous humor of patients with neovascular glaucoma and primary open-angle glaucoma were lower than those with non-glaucoma patients. VEGFR3 was expressed in cultured TM cells. VEGF-C concentrations in supernatants or cell lysates of TM cells cultured under oxidative stress and hypoxia were significantly elevated compared with those under steady conditions (p < 0.05). VEGF-C concentrations in supernatants and cell lysates of TM cells cultured in high glucose were significantly higher than those in low glucose (p < 0.01). Conclusions: VEGF-C was expressed in TM tissues of patients with glaucoma, which was secreted from cultured TM cells under various pathological conditions. These results suggest that VEGF-C may be involved in the pathology of glaucoma.


Production and release of acylcarnitines by primary myotubes reflect the differences in fasting fat oxidation of the donors.
Acylcarnitines are biomarkers of incomplete β-oxidation and mitochondrial lipid overload but indicate also high rates of mitochondrial fatty acid oxidation. It is unknown whether the production of acylcarnitines in primary human myotubes obtained from lean, metabolically healthy subjects reflects the fat oxidation in vivo. Our objective was to quantify the acylcarnitine production in myotubes obtained from subjects with low and high fasting respiratory quotient (RQ). Fasting RQ was determined by indirect calorimetry. Muscle biopsies from the vastus lateralis muscle were taken from 6 subjects with low fasting RQ (mean 0.79 ± 0.03) and 6 with high fasting RQ (0.90 ± 0.03), and satellite cells were isolated, cultured, and differentiated to myotubes. Myotubes were cultivated with 125 μM (13)C-labeled palmitate for 30 minutes and 4 and 24 hours. Quantitative profiling of 42 intracellular and 31 extracellular acylcarnitines was performed by stable isotope dilution-based metabolomics analysis by liquid chromatography coupled to mass spectrometry. Myotubes from donors with high fasting RQ produced and released significant higher amounts of medium-chain acylcarnitines. High (13)C8 and (13)C10 acylcarnitine levels in the extracellular compartment correlated with high fasting RQ. The decreased expression of medium-chain acyl-coenzyme A dehydrogenase (MCAD) in these myotubes can explain the higher rate of incomplete fatty acid oxidation. A lower intracellular [(13)C]acetylcarnitine to carnitine and lower intracellular (13)C16/(13)C18 acylcarnitine to carnitine ratio indicate reduced fatty acid oxidation capacity in these myotubes. Mitochondrial DNA content was not different. Acylcarnitine production and release from primary human myotubes of donors with high fasting RQ indicate a reduced fatty acid oxidation capacity and a higher rate of incomplete fatty acid oxidation. Thus, quantitative profiling of acylcarnitine production in human myotubes can be a suitable tool to identify muscular determinants of fat oxidation in vivo.


Searching for New Microbiome-Targeted Therapeutics through a Drug Repurposing Approach.
Commonly used non-antibiotic drugs have been associated with changes in gut microbiome composition, paving the way for the possibility of repurposing FDA-approved molecules as next-generation microbiome therapeutics. Herein, we developed and validated an ex vivo high-throughput screening platform─the mini gut model─to underpin human gut microbiome response to molecular modulators. Ten FDA-approved compounds, selected based on maximum structural diversity of molecular fingerprints, were screened against the gut microbiome of five healthy subjects to characterize the ability of human-targeted drugs to modulate the human gut microbiome network. Three compounds, THIP hydrochloride, methenamine, and mesna, have shown promise as novel gut microbiome therapeutics in light of their capability of promoting health-associated features of the gut microbiome. Our findings provide a resource for future research on drug-microbiome interactions and lay the foundation for a new era of more precise gut microbiome modulation through drug repurposing, aimed at targeting specific dysbiotic events.


Famotidine (MK-208) in the treatment of gastric ulcer. Results of a multicenter double-blind controlled study.
The aim of the present investigation was to study the efficacy and safety of famotidine (MK-208), a new, potent, histamine H2 receptor antagonist, in promoting the healing of active gastric ulcer when compared to placebo. Of the 71 patients who took part in this multicenter double-blind study in Italy, 37 were administered famotidine 40 mg once daily and 34 placebo. Treatment duration was for up to 8 weeks, and endoscopic and clinical studies were performed at onset and week 4 and, if necessary, at weeks 6 and 8. All patients were carefully evaluated at regular intervals for adverse drug reactions by clinical and laboratory examinations. By the end of the study, 97% of the ulcers were healed in the famotidine group compared to 66% in the placebo group (p less than 0.01). Day and night pain decreased significantly more in the famotidine group than in the placebo group. Both treatments were well tolerated, and no alterations in laboratory tests were observed. Famotidine, therefore, proved effective in the treatment of gastric ulcer and was well tolerated on a short-term basis.


Development of biologically active GDC for the treatment of cerebral aneurysms.
In Vitro Study: The surface of polystyrene dishes were treated either by: 1) collagen coating without ion implantation, or 2) collagen coating with ion implantation. Ne(+) implantation was performed on area 2 with fluences of 1 x 10(15) at an energy of 150 keV Bovine endothelial cells were cultured on the dishes and the resistance to detachment of cells was evalated with trypsin treatment. Experimental Aneurysm Study: GDCs were coated with either type I collagen, fibronectin, vitronectin, laminin or fibrinogen. Ion implantation was then performed on these protein-coated GDCs. 56 experimental aneurysms were constructed microsurgically in the bilateral common carotid arteries of 28 swine. The aneurysms were embolized with standard GDCs or with ion-implanted protein-coated GDCs. The animals were sacrificed at day 14 after coil placement. The aneurysmal orifice was observed microscopically. In vitro study showed that endothelial cell proliferation and strength of cell attachment were accerelated by ion implantation. On specimens examined 14 days post-embolization, greater fibrous tissue coverage at the neck of the aneurysm was observed macroscopically and microscopically with ion implanted GDCs, whereas only a fibrin-like thin layer covered the standard GDC surfaces. These in vitro and in vivo studied indicate that ion implantation combined with protein coating of GDCs improves cellular adhesion/proliferation. This technology may provide an improvement in clinical outcome of cerebral aneurysms.


Relations of Conspicuous Consumption Tendency, Self-Expression Satisfaction, and SNS Use Satisfaction of Gen Z through SNS Activities.
The purpose of this study was to analyze the relations of conspicuous consumption tendency, self-expression satisfaction, and SNS use satisfaction of Gen Z through SNS activities. For a week from 17-23 March 2021, an online survey was conducted targeting the enrolled students of university in Chungcheongnam-do. Out of a total of 398 questionnaires, a total of 394 questionnaires (98.9%) were used for the final analysis after excluding four questionnaires with low reliability. This study was analyzed using SPSS by IBM 23.0(New York, NY, USA) and AMOS 21.0 (New York, NY, USA). In the results of this study, first, the factors such as imported goods/famous brands, high-priced articles, and status symbol except for pursuit of trend of conspicuous consumption tendency had significant effects on the self-expression satisfaction. Second, the factors such as imported goods/famous brands, high-priced articles, and status symbol except for pursuit of trend of conspicuous consumption tendency of Gen Z through SNS activities had significant effects on the SNS use satisfaction. Third, the self-expression satisfaction of Gen Z through SNS had significant effects on the SNS use satisfaction.


Super-Resolution Imaging of the Filtration Barrier Suggests a Role for Podocin R229Q in Genetic Predisposition to Glomerular Disease.
Diseases of the kidney's glomerular filtration barrier are a leading cause of end stage renal failure. Despite a growing understanding of genes involved in glomerular disorders in children, the vast majority of adult patients lack a clear genetic diagnosis. The protein podocin p.R229Q, which results from the most common missense variant in NPHS2, is enriched in cohorts of patients with FSGS. However, p.R229Q has been proposed to cause disease only when transassociated with specific additional genetic alterations, and population-based epidemiologic studies on its association with albuminuria yielded ambiguous results. To test whether podocin p.R229Q may also predispose to the complex disease pathogenesis in adults, we introduced the exact genetic alteration in mice using CRISPR/Cas9-based genome editing (PodR231Q ). We assessed the phenotype using super-resolution microscopy and albuminuria measurements and evaluated the stability of the mutant protein in cell culture experiments. Heterozygous PodR231Q/wild-type mice did not present any overt kidney disease or proteinuria. However, homozygous PodR231Q/R231Q mice developed increased levels of albuminuria with age, and super-resolution microscopy revealed preceding ultrastructural morphologic alterations that were recently linked to disease predisposition. When injected with nephrotoxic serum to induce glomerular injury, heterozygous PodR231Q/wild-type mice showed a more severe course of disease compared with Podwild-type/wild-type mice. Podocin protein levels were decreased in PodR231Q/wild-type and PodR231Q/R231Q mice as well as in human cultured podocytes expressing the podocinR231Q variant. Our in vitro experiments indicate an underlying increased proteasomal degradation. Our findings demonstrate that podocin R231Q exerts a pathogenic effect on its own, supporting the concept of podocin R229Q contributing to genetic predisposition in adult patients.


Effect of anticoagulation with citrate versus heparin on the adsorption of coagulation factors to blood purification resins with different charge.
In liver failure, hydrophobic toxins accumulate in the blood circulation. To support hepatic function, extracorporeal blood purification systems have been developed, in which both cationic and neutral adsorbents are used to remove albumin-bound metabolites from blood. An issue of these systems is the additional removal of coagulation factors containing negatively charged γ-carboxyglutamate (Gla) domains, which, in physiological conditions, are shielded by calcium ions. We hypothesized that complexation of calcium ions by citrate leads to exposure of negative Gla domains, resulting in their binding to the positively charged adsorbents. The data presented here confirm that the binding of coagulation factors containing Gla domains to positively charged polymers is enhanced in the presence of citrate as compared to heparin. This effect increased with increasing charge density of the polymer and has important implications for the clinical application of positively charged polymers.


Differential expression of facilitative glucose transporter (GLUT) genes in primary lung cancers and their liver metastases.
Glucose uptake is mediated by members of the facilitative glucose transporter (GLUT) family. Malignant cells take up more glucose than their normal counterparts. The aim of this study was to investigate the gene expression levels of the GLUT family, especially GLUT1, GLUT3, and GLUT5 in primary lung cancer, metastatic liver tumors, and normal lung tissues, and to compare the expression levels of primary and metastatic tumors with those of normal tissues. We analyzed 105 autopsy samples (35 primary lung tumors, 35 corresponding normal lung tissues, 25 normal liver tissues, and 10 metastatic liver tumors) from 35 patients using the quantitative reverse transcription polymerase chain reaction. The GLUT1 gene expression levels in primary lung tumors were significantly higher than those in normal lung tissues. In liver metastatic lesions, the GLUT3 and GLUT5 gene expression levels were significantly higher than those in primary lung tumors, but there were no differences in GLUT1 expression levels between primary and metastatic liver tumors. Our results show that the gene expression pattern of the GLUT family is different between primary and metastatic liver tumors and suggest that the energy transporters in metastatic tumors may be different from those in primary tumors.


ATP-loaded immunoliposomes specific for cardiac myosin provide improved protection of the mechanical functions of myocardium from global ischemia in an isolated rat heart model.
Earlier demonstrated cardio-protection by ATP-loaded liposomes (ATP-L) was further improved by attachment of cardiac myosin-specific monoclonal 2G4 antibody onto the surface of ATP-L. ATP-IL were infused for 1 min duration before starting the global ischemia for 25 min followed by reperfusion for 30 min in an isolated rat heart. The left ventricular developed pressure at the end of reperfusion in ATP-IL group significantly recovered to above 80% of the baseline compared to ca 25% in the Kreb's-Henseleit (KH) buffer, ca 60% in the IL, and ca 70% in the ATP-L treated groups. At the end of the reperfusion, left ventricular end diastolic pressure significantly reduced to 15 +/- 2 mmHg in ATP-IL group compared to 59 +/- 6 mmHg in the KH buffer, 31 +/- 4 mmHg in the IL and 23 +/- 3 mmHg in the ATP-L controls. The extent of preservation depended on the amount of the antibody present on the surface of the ATP-IL.


Diverticular disease of the small bowel: report of 27 cases.
Diverticula of the small bowel are usually asymptomatic but occasionally can present with serious complications. Because of the rarity of small bowel diverticulosis and the limited case number in most published reports, we analyzed one of the largest series with symptomatic small bowel diverticular disease. In this retrospective review, we studied 27 symptomatic patients with diverticula of the small bowel that was treated surgically. The study included 13 male and 14 female patients (age range, 30-87 years; mean age, 69.3 years). Fourteen patients underwent an elective operation for chronic refractory symptoms. Thirteen patients underwent emergency surgery because of rupture of the diverticula and associated peritonitis, diverticulitis and small bowel obstruction, or lower gastrointestinal bleeding. Surgical treatment consisted of resection of the intestinal segment containing the diverticula. All patients were symptom-free postoperatively and no "short bowel" problems developed. Abdominal pain, gastrointestinal bleeding, and bowel obstruction were the most common clinical symptoms. Small bowel diverticulosis should be treated surgically only when refractory symptoms or severe complications are present.


Colloidal Interactions of Microplastic Particles with Anionic Clays in Electrolyte Solutions.
Homoaggregation of polystyrene microplastics (MPs) and heteroaggregation of MPs with anionic clay minerals, namely, layered double hydroxide (LDH), in different salt (NaCl, CaCl2, and Na2SO4) solutions were systematically investigated using light scattering techniques. The salt type and ionic strength had significant effects on the stability of both MPs and LDH particles individually and the results could be explained by DLVO theory and the Schulze-Hardy rule. However, once stable colloidal dispersions of the individual particles were mixed, heteroaggregation occurred between the oppositely charged MPs and LDH, which was also confirmed by transmission electron microscopy and X-ray scattering. Adsorption of the LDH particles resulted in neutralization and reversal of MPs surface charge at appropriate LDH doses. Once LDH adsorption neutralized the negative charges of the MP spheres, rapid aggregation was observed in the dispersions, whereas stable samples formed at high and low LDH concentrations. The governing interparticle interactions included repulsive electrical double-layer forces, as well as van der Waals and patch-charge attractions, the strength of which depended on the mass ratio of the interacting particles and the composition of the aqueous solvent. Our results shed light on the colloidal behavior of MPs in a complex aquatic environment and, in the long term, are also useful for developing LDH-based approaches for water remediation to remove contamination with MP particles.


Interfacial Reduction Nucleation of Noble Metal Nanodots on Redox-Active Metal-Organic Frameworks for High-Efficiency Electrocatalytic Conversion of Nitrate to Ammonia.
Electrochemically converting nitrate to ammonia is a promising route to realize artificial nitrogen recycling. However, developing highly efficient electrocatalysts is an ongoing challenge. Herein, we report the construction of stable and redox-active zirconium metal-organic frameworks (Zr-MOFs) based on Zr6 nanoclusters and redox-reversible tetrathiafulvalene (TTF) derivatives as inorganic nodes and organic linkers, respectively. The redox-active Zr-MOF can facilitate the in situ reduction of noble metal precursors free of external reductants and realize the uniform nucleation of noble metal nanodots (NDs) on Zr-MOF, achieving the preparation of M-NDs/Zr-MOF (M = Pd, Ag, or Au). The highly porous Zr-MOF with good conductivity can facilitate the mass transfer process. Among the M-NDs/Zr-MOF catalysts, Pd-NDs/Zr-MOF exhibits the highest electrocatalytic activity, delivering a NH3 yield of 287.31 mmol·h-1·g-1cat. and a Faradaic efficiency of 58.1%. The proposed interfacial reduction nucleation strategy for anchoring M NDs on Zr-MOFs can be applied to other challenging energy conversion reactions.


Pristine and Antibiotic-Loaded Nanosheets/Nanoneedles-Based Boron Nitride Films as a Promising Platform to Suppress Bacterial and Fungal Infections.
In recent years, bacteria inactivation during their direct physical contact with surface nanotopography has become one of the promising strategies for fighting infection. Contact-killing ability has been reported for several nanostructured surfaces, e.g., black silicon, carbon nanotubes, zinc oxide nanorods, and copper oxide nanosheets. Herein, we demonstrate that Gram-negative antibiotic-resistant Escherichia coli (E. coli) bacteria are killed as a result of their physical destruction while contacting nanostructured h-BN surfaces. BN films, made of spherical nanoparticles formed by numerous nanosheets and nanoneedles with a thickness <15 nm, have been obtained through a reaction of ammonia with amorphous boron. The contact-killing bactericidal effect of BN nanostructures has been compared with a toxic effect of gentamicin released from them. For a wider protection against bacterial and fungal infection, the films have been saturated with a mixture of gentamicin and amphotericin B. Such BN films demonstrate a high antibiotic/antimycotic agent loading capacity and a fast initial and sustained release of therapeutic agents for 170-260 h depending on the loaded dose. The pristine BN films possess high antibacterial activity against E. coli K-261 strain at their initial concentration of 104 cells/mL, attaining >99% inactivation of colony forming units after 24 h, same as gentamicin-loaded (150 μg/cm2) BN sample. The BN films loaded with a mixture of gentamicin (150 and 300 μg/cm2) and amphotericin B (100 μg/cm2) effectively inhibit the growth of E. coli K-261 and Neurospora crassa strains. During immersion in the normal saline solution, the BN film generates reactive oxygen species (ROS), which can lead to accelerated oxidative stress at the site of physical cell damage. The obtained results are valuable for further development of nanostructured surfaces having contact killing, ROS, and biocide release abilities.


May the Force and Mass Be With You-Evidence-Based Contribution of Mechano-Biological Descriptors of Resistance Exercise.
Skeletal muscle is one of the most important tissues of the human body. It comprises up to 40% of the body mass and is crucial to survival. Hence, the maintenance of skeletal muscle mass and strength is pivotal. It is well-established that resistance exercise provides a potent anabolic stimulus to increase muscle mass and strength in men and women of all ages. Resistance exercise consists of mechano-biological descriptors, such as load, muscle action, number of repetitions, repetition duration, number of sets, rest interval between sets, frequency, volitional muscular failure, and range of motion, which can be manipulated. Herein, we discuss the evidence-based contribution of these mechano-biological descriptors to muscle mass and strength.


Universal Level Designations for Hospitalized Pediatric Patients in Evacuation.
Children comprise approximately 22% of the population in the United States.1 In a widespread disaster such as a hurricane, pandemic, wildfire or major earthquake, children are at least proportionately affected to their share of the population, if not more so. They also have unique vulnerabilities including physical, mental, and developmental differences from adults, which make them more prone to adverse health effects of disasters.2-4 There are about 5000 pediatric critical care beds and 23 000 neonatal intensive care beds out of 900 000 total hospital beds in the United States.5 While no mechanism exists to consistently track pediatric acute care beds nationally (especially in real time), a previous study6 showed a 7% decline in pediatric medical-surgical beds between 2002 and 2011. This study also estimated there are about 30 000 acute care pediatric beds nationally. Finding appropriate hospital resources for the provision of care for pediatric disaster victims is an important concern for those charged with triaging patients in a major event.


Urban transmission of urinary schistosomiasis in Dar es Salaam, Tanzania.
A cross sectional survey for Schistosoma haematobium infections was undertaken in 12 primary schools in the city of Dar es Salaam. The prevalence in the schools ranged from 5.3 to 55.1%, with an overall prevalence of 19.3%. More males (23.5%) than females (15.0%) were infected, and the highest prevalence was recorded in the 11-16 year age group. Intensity of infection was high, ranging from 12 to 96 eggs/10 ml urine in individual schools. 26% of the infected excreted more than 50 eggs/10 ml urine, and high rates of haematuria and proteinuria were observed in infected children. Interviews indicated that the majority of the children had acquired their infection in the city. Malacological surveys showed two potential vectors, Bulinus (Physopsis) globosus and B. (Ph.) nasutus, to be common in Dar es Salaam. Laboratory and field findings confirmed that these two species were vectors of S. haematobium. Factors responsible for continued transmission in this urban environment are discussed.


Stable and Biocompatible Mushroom β-Glucan Modified Gold Nanorods for Cancer Photothermal Therapy.
Naturally occurring β-glucans have been widely regarded as a natural source for functional foods and pharmaceuticals due to their immunomodulatory property and antitumor activity. However, physicochemically stable and biocompatible β-glucans are rarely explored as a carrier for nanomaterials to overcome the problems of aggregation and nanotoxicity. Here, we developed highly stable and biocompatible mushroom β-glucan coated gold nanorods (AuNR-Glu) for cancer photothermal therapy by integrating Pleurotus tuber-regium sclerotial β-glucan (Glu) and plasmonic gold nanorods (AuNRs) possessing photothermal property in the second near-infrared (NIR-II) window. AuNR-Glu showed high colloidal stability in various biological media, even in simulated gastric fluid. Moreover, AuNR-Glu had low cytotoxicity and high photothermal stability, which are excellent characteristics for photothermal agents for cancer therapy. In vitro experiments showed that AuNR-Glu nanohybrid was effective against MCF-7 (only 4.5 ± 0.9% viability) at a low dose of 20 μg/mL under NIR-II at a safe laser power density (0.75 W/cm2). Natural mushroom β-glucans are potential functional polymers that can be used to fabricate nanohybrids for biomedical applications.


The Clinical, Microbiological, and Immunological Effects of Probiotic Supplementation on Prevention and Treatment of Periodontal Diseases: A Systematic Review and Meta-Analysis.
(1) Background: Periodontal diseases are a global health concern. They are multi-stage, progressive inflammatory diseases triggered by the inflammation of the gums in response to periodontopathogens and may lead to the destruction of tooth-supporting structures, tooth loss, and systemic health problems. This systematic review and meta-analysis evaluated the effects of probiotic supplementation on the prevention and treatment of periodontal disease based on the assessment of clinical, microbiological, and immunological outcomes. (2) Methods: This study was registered under PROSPERO (CRD42021249120). Six databases were searched: PubMed, MEDLINE, EMBASE, CINAHL, Web of Science, and Dentistry and Oral Science Source. The meta-analysis assessed the effects of probiotic supplementation on the prevention and treatment of periodontal diseases and reported them using Hedge's g standardized mean difference (SMD). (3) Results: Of the 1883 articles initially identified, 64 randomized clinical trials were included in this study. The results of this meta-analysis indicated statistically significant improvements after probiotic supplementation in the majority of the clinical outcomes in periodontal disease patients, including the plaque index (SMD = 0.557, 95% CI: 0.228, 0.885), gingival index, SMD = 0.920, 95% CI: 0.426, 1.414), probing pocket depth (SMD = 0.578, 95% CI: 0.365, 0.790), clinical attachment level (SMD = 0.413, 95% CI: 0.262, 0.563), bleeding on probing (SMD = 0.841, 95% CI: 0.479, 1.20), gingival crevicular fluid volume (SMD = 0.568, 95% CI: 0.235, 0.902), reduction in the subgingival periodontopathogen count of P. gingivalis (SMD = 0.402, 95% CI: 0.120, 0.685), F. nucleatum (SMD = 0.392, 95% CI: 0.127, 0.658), and T. forsythia (SMD = 0.341, 95% CI: 0.050, 0.633), and immunological markers MMP-8 (SMD = 0.819, 95% CI: 0.417, 1.221) and IL-6 (SMD = 0.361, 95% CI: 0.079, 0.644). (4) Conclusions: The results of this study suggest that probiotic supplementation improves clinical parameters, and reduces the periodontopathogen load and pro-inflammatory markers in periodontal disease patients. However, we were unable to assess the preventive role of probiotic supplementation due to the paucity of studies. Further clinical studies are needed to determine the efficacy of probiotic supplementation in the prevention of periodontal diseases.


Correlates of Non-suicidal Self-Injury and Suicide Attempts in Bulimic Spectrum Disorders.
The aim of this study was to examine the implication of personality, impulsivity, and emotion regulation difficulties in patients with a bulimic-spectrum disorder (BSD) and suicide attempts (SA), BSD patients with non-suicidal self-injury (NSSI), and BSD patients without these behaviors. One hundred and twenty-two female adult BSD patients were assessed using self-report questionnaires. Patients were clustered post-hoc into three groups depending on whether they presented BSD without NSSI or SA (BSD), BSD with lifetime NSSI (BSD + NSSI) or BSD with lifetime SA (BSD + SA). The BSD + NSSI and BSD + SA groups presented more emotion regulation difficulties, more eating and general psychopathology, and increased reward dependence in comparison with the BSD group. In addition, BSD + SA patients specifically showed problems with impulse control, while also presenting higher impulsivity than both the BSD and BSD + NSSI groups. No differences in impulsivity between the BSD and BSD + NSSI groups were found. The results show that BSD + NSSI and BSD + SA share a common profile characterized by difficulties in emotion regulation and low reward dependence, but differ in impulsivity and cooperativeness. This suggests that self-injury, in patients without a history of suicide attempts (i.e., BSD + NSSI), may have a regulatory role rather than being due to impulsivity.


Oesophageal epiphrenic diverticulum: an unusual presentation and review.
Epiphrenic pulsion diverticula are rare and often asymptomatic. We describe a case presenting in an unusual fashion, and review the controversy over the management of this condition with regard to the requirement for myotomy and antireflux surgery. We believe that both procedures are necessary, but believe that both procedures are necessary, but optimal management strategies are unlikely to be resolved as the rarity of the condition precludes largescale prospective studies.


Identification of fibronectin in preparations of osteoarthritic human cartilage.
Several high molecular weight proteins were observed in dissociative extracts of osteoarthritic, but not of normal, human cartilage. By gel electrophoresis, by DEAE-cellulose and gelatin-agarose chromatography, and immunologically, they were found to be identical to fibronectin. Incorporation of tritiated proline into these proteins indicated that this material was not a synovial fluid contaminant. Interactions with the proteoglycans suggested that, in articular cartilage, the role of fibronectin may be more closely associated with proteoglycans than with collagen. The appearance of fibronectin in the diseased cartilage suggests that this may be a feature of the chondrocyte's repair response to the loss of extracellular matrix.


The Hematopoietic Microenvironment: Stromal Cell Types: Characterization and Function In Situ and In Vitro.
The murine hematopoietic stroma is essential for the homing and the continued replication of hematopoietic stem cells following transplantation and appears to control their lineage proliferation. In our studies it has been found to consist of 3 cell types with differing antigenic displays, growth factor responses and interactions when placed in culture. These characteristics are in keeping with their classifications as myofibroblasts, endothelial like cells and macrophages, respectively. Cell adhesion molecules (CAMs) and early acting cytokines have been found to be associated with these cell types. Only the myofibroblast type has been found to support proliferation of the descendants of long term repopulating stem cells (LTRC) plated over their confluent layer. The endothelial like cell type, and possibly the macrophage, were found to suppress not only the growth of LTRC but, also, that of the myofibroblasts obtained from the same marrow samples. Culture medium obtained from near-confluent growth of the endothelial like cells contained a growth inhibiting molecule of less than 3000 da. capable of inhibiting cells of several types, including the stromal myofibroblasts. The endothelial like cells were shown to unilaterally express VCAM-1 in culture, as well as vWf and endothelial cell specific antigens. Tissue sections of femurs from normal irradiated recipients taken 1 hour post-transplantation revealed Lac-Z marked donor stem cells lodged just external to the endothelial lining of thin walled vessels and in contact with myofibroblasts. Previous studies had shown that some stem cells enter replication at these sites within 48 hours of lodgment. It is suggested that a balance of growth stimulation versus suppression may be maintained between the myofibroblasts and the endothelial like cell types, respectively, in the functioning marrow stroma. Both the myofibroblastoid and the endothelial like stromal cells of old mice displayed a reduced replicative rate in vivo and a reduced replicative capacity in vitro. This suggests that treatments that induce damage to the marrow microenvironment may be especially destructive in aged individuals. In recent experiments it has become clear that the stromal cell population that includes cells identifiable as alkaline phosphatase positive myofibroblasts also contains cells that produce osteocalcin, osteonectin and bone sialoprotein, and deposit von Kossa positive calcium. Whether this results from a single cell lineage or two lineages of similar morphology and alkaline phosphatase expression is under investigation.


Detection of normal spinal veins by using susceptibility-weighted imaging.
To evaluate the visualization of the spinal veins using susceptibility-weighted imaging (SWI). A 1.5-T magnet equipped with a spine matrix coil was used. Axial SWI scans of 20 healthy volunteers were obtained with a three-dimensional fast low-angle shot (3D-FLASH) sequence. Maximum intensity projection (MIP) of the phase images were reconstructed and five MIP images (at the levels of T11, T11/12, T12, T12/L1, and L1) were selected for the evaluation. The anterior median vein (AMV), posterior median vein (PMV), anterior radiculomedullary vein (ARV), posterior radiculomedullary vein (PRV), and sulcal vein (SV) were evaluated using a 4-grade scale (0, none; 1, weak; 2, moderate; and 3, prominent). The AMV was detected in all the subjects (100%). The detection rates of the other veins were lower: PMV, 65%; right ARV, 45%; left ARV, 15%; right PRV, 10%; left PRV, 30%; and SV, 0%. The average scores for AMV, PMV, right ARV, left ARV, right PRV, left PRV, and SV were 0.98, 0.24, 0.20, 0.08, 0.08, 0.14, and 0, respectively. SWI of the spine is feasible. The extrinsic spinal veins can be visualized by SWI without using contrast materials.