CpG Island Methylation, Microsatellite Instability, and BRAF Mutations and Their Clinical Application in the Treatment of Colon Cancer.
There have been significant developments in colon cancer research over the last few years, enabling us to better characterize tumors individually and classifying them according to certain molecular or genetic features. Currently, we are able to use KRAS mutational status as a guide to therapy with anti-epidermal growth factor receptor antibodies. Other molecular features under research include BRAF mutation, microsatellite instability, and CpG island methylation. These three molecular features are often associated with tumors that have overlapping phenotypes and can be present simultaneously in the same tumor. However, they carry different prognostic and predictive qualities, making analysis of their interaction relatively complex. Much research thus far has examined the clinical relevance of microsatellite instability in helping determine prognosis and the predictive value of adjuvant 5-fluorouracil chemotherapy in stages II and III colon cancers. BRAF mutation appears to be a biomarker for poor prognosis. CpG island methylation is tightly associated with microsatellite instable tumors and BRAF mutation, but its clinical utility remains uncertain. Hereby, we examine preclinical and clinical data that supports the utilization of all three phenotypes in future research applied to clinical practice.


Rapid Surface Functionalization of Hydrogen-Terminated Silicon by Alkyl Silanols.
Surface functionalization of inorganic semiconductor substrates, particularly silicon, has focused attention toward many technologically important applications, involving photovoltaic energy, biosensing and catalysis. For such modification processes, oxide-free (H-terminated) silicon surfaces are highly required, and different chemical approaches have been described in the past decades. However, their reactivity is often poor, requiring long reaction times (2-18 h) or the use of UV light (10-30 min). Here, we report a simple and rapid surface functionalization for H-terminated Si(111) surfaces using alkyl silanols. This catalyst-free surface reaction is fast (15 min at room temperature) and can be accelerated with UV light irradiation, reducing the reaction time to 1-2 min. This grafting procedure leads to densely packed organic monolayers that are hydrolytically stable (even up to 30 days at pH 3 or 11) and can display excellent antifouling behavior against a range of organic polymers.


[Sepsis. Evaluation of views, necessity of terminology unification and diagnostic criteria].
Critical analysis of modern overview devoted to general infectious-inflammatory process and materials of original research (690 patients) provides a basis for discussion of diagnostic criteria of and new terminology. Wide introduction of researches on classification, criteria of diagnosis and terminology offered by North American conference (R. Bone et al., 1992) into practice is recommended. The given definitions better reflect the essence of homeostatic disorders in septic patients, allow to carry out early change of the program of treatment, to standardize approaches to diagnosis, monitoring and therapy and enable search in epidemiology of sepsis, choice of the best ways of scientific investigation.


Relative influences of establishing operations and reinforcement contingencies on self-injurious behavior during functional analyses.
In the typical functional analysis in which the antecedent and consequent events associated with problem behavior are manipulated, the control condition involves elimination of both the relevant establishing operation (EO) and its associated contingency through a schedule of noncontingent reinforcement (usually fixed-time [FT] 30 s). In some functional analyses, however, antecedent events are manipulated in the absence of differential consequences, and a common test condition in such analyses also involves the delivery of reinforcement on an FT 30-s schedule. Thus, the same schedule of reinforcement (FT 30 s) is not considered to be an EO in the former type of analysis but is considered to be an EO in the latter. We examined the relative influences of EOs and reinforcement contingencies on problem behavior by exposing 6 individuals who engaged in self-injurious behavior (SIB) to four combinations of functional analysis conditions: EO present/contingency present, EO absent/contingency present, EO present/contingency absent, and EO absent/contingency absent. Results indicated that the only condition in which high rates of SIB were observed consistently was one in which the EO and the reinforcement contingency were both present. Implications of these results for the design of functional analysis test and control conditions are discussed.


Toward ultimate nonvolatile resistive memories: The mechanism behind ovonic threshold switching revealed.
Fifty years after its discovery, the ovonic threshold switching (OTS) phenomenon, a unique nonlinear conductivity behavior observed in some chalcogenide glasses, has been recently the source of a real technological breakthrough in the field of data storage memories. This breakthrough was achieved because of the successful 3D integration of so-called OTS selector devices with innovative phase-change memories, both based on chalcogenide materials. This paves the way for storage class memories as well as neuromorphic circuits. We elucidate the mechanism behind OTS switching by new state-of-the-art materials using electrical, optical, and x-ray absorption experiments, as well as ab initio molecular dynamics simulations. The model explaining the switching mechanism occurring in amorphous OTS materials under electric field involves the metastable formation of newly introduced metavalent bonds. This model opens the way for design of improved OTS materials and for future types of applications such as brain-inspired computing.


Translation, Cultural Adaptation, and Evaluation of a Brazilian Portuguese Questionnaire to Estimate the Self-Reported Prevalence of Gluten-Related Disorders and Adherence to Gluten-Free Diet.
A Spanish version of a questionnaire intended to estimate, at the population level, the prevalence rates of self-reported gluten-related disorders and adherence to gluten-free diets has been applied in four Latin American countries. However, idiom issues have hampered the questionnaire application in the Brazilian population. Thus, the aim of the present study was to carry out a translation, cultural adaptation, and evaluation of a Brazilian Portuguese questionnaire to estimate the self-reported prevalence of gluten-related disorders and adherence to gluten-free diets in a Brazilian population. Two bilingual Portuguese-Spanish health professionals carried out the translation of the original Spanish version of the questionnaire to Brazilian-Portuguese. Matching between the two translations was evaluated using the WCopyFind.4.1.5 software. Words in conflict were conciliated, and the conciliated version of the Brazilian Portuguese instrument was evaluated to determine its clarity, comprehension, and consistency. A pilot study was carried out using an online platform. The two questionnaires translated into Brazilian Portuguese were highly matched (81.8%-84.1%). The questions of the conciliated questionnaire were clear and comprehensible with a high agreement among the evaluators (n = 64) (average Kendall's W score was 0.875). The participants did not suggest re-wording of questions. The answers to the questions were consistent after two applications of the questionnaire (Cohen's k = 0.869). The pilot online survey yielded low response rates (9.0%) highlighting the need for face-to-face interviews. The translation and evaluation of a Brazilian Portuguese questionnaire to estimate the self-reported prevalence rates of gluten-related disorders and adherence to gluten-free diets was carried out. The instrument is clear, comprehensible, and generates reproducible results in the target population. Further survey studies involving face-to-face interviews are warranted.


Differential sensitivity of tetrodotoxin of nociceptive neurons in 4 species of leeches.
We have recently shown that the nociceptive neurons (N cells) in the leech can be segregated into a medial type (Nmed) and a lateral type (Nlat) according to their physiological and pharmacological properties. We now report that the Na-dependent action potential (AP) of the 2 cell types in Macrobdella have differential sensitivities to tetrodotoxin and that the APs of the N-cell homologs from different leech species also vary considerably in their response to TTX. The normal AP of the N cells in the 4 leech species was exclusively Na-dependent; its overshoot varied logarithmically with [Na]0, was unaffected by the presence of Mn and absence of Ca, and could not be elicited in Na-free Ringer's solutions. The decrease in the maximal rate of depolarization (Vmax) of the Na-dependent AP of the Nmed cell in Macrobdella produced by TTX followed a reverse Langmuir curve for bimolecular reaction with an ED50 of 9 microM. Almost complete blockage was obtained at 50 microM. In contrast, TTX inhibition of Vmax in the Nlat cell reached saturation at a level of only 55% reduction in Vmax even at doses in excess of 200 microM TTX. The simplest interpretation of these data is that there are 2 types of Na channels in the Nlat cell. This is further supported by the fact that the dose-response data could be well fitted by a Langmuir curve, assuming that the Nlat cell possesses 2 populations of Na conductances--one insensitive to TTX and one (like the Nmed cell) with an ED50 to TTX of 9 microM, the 2 populations being present in a 0.45:0.55 ratio, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Resolving task rule incongruence during task switching by competitor rule suppression.
Task switching requires maintaining readiness to execute any task of a given set of tasks. However, when tasks switch, the readiness to execute the now-irrelevant task generates interference, as seen in the task rule incongruence effect. Overcoming such interference requires fine-tuned inhibition that impairs task readiness only minimally. In an experiment involving 2 object classification tasks and 2 location classification tasks, the authors show that irrelevant task rules that generate response conflicts are inhibited. This competitor rule suppression (CRS) is seen in response slowing in subsequent trials, when the competing rules become relevant. CRS is shown to operate on specific rules without affecting similar rules. CRS and backward inhibition, which is another inhibitory phenomenon, produced additive effects on reaction time, suggesting their mutual independence. Implications for current formal theories of task switching as well as for conflict monitoring theories are discussed.


Changes in temperature alter competitive interactions and overall structure of fig wasp communities.
Organisms exist within ecological networks, connected through interactions such as parasitism, predation and mutualism which can modify their abundance and distribution within habitat patches. Differential species responses make it hard to predict the influence of climate change at the community scale. Understanding the interplay between climate and biotic interactions can improve our predictions of how ecosystems will respond to current global warming. We aim to understand how climate affects the multitrophic biotic interactions as well as the community structure using the enclosed communities of wasps associated with figs as study system. To examine the presence and strength of multitrophic species interactions, we first characterized the multitrophic community of fig wasps associated with Ficus racemosa and then applied hierarchical joint species distribution models, fitted to community monitoring data. We further evaluated the effect of climate on individual species trends as well as interspecific interactions. We found that the competitive balance shifted to favour non-pollinating galling wasps and disadvantage the dominant pollinator in suboptimal conditions. Furthermore, suboptimal conditions for galling wasps facilitated the occurrence of their specialized parasitoid, as changes cascaded across trophic levels and led to alternative community structures. Our results highlight the role of how species interactions can be modified across multiple trophic levels in a fig wasp community according to climate.


Equilibrium Field Theoretic Study of Nanoparticle Interactions in Diblock Copolymer Melts.
Block copolymer matrices are often used to control nanoparticle (NP) dispersion behavior, but the effects of diblock domain interfaces on particle-particle interactions have not been well characterized. In this paper, polymer field theoretic simulations are used to quantify interactions between both bare and grafted spherical NPs in microphase-separated A-B diblock copolymers. It is shown that for bare NPs that have an athermal interaction with and a diameter similar to the B domain, the presence of an A-B interface leads to an effective interaction between the particles with multiple minima separated by a free energy barrier. It is further shown that these effects primarily result from chain stretching and compression near the A-B interface induced by particle-particle interactions as opposed to increases in A-B contact at the interfaces. Grafted chains largely prevent these effects and reduce particle-particle interaction strength. When confined by diblock domain interfaces, grafted chains have a reduced extension compared to what is expected for de-wetted brush chains, as commonly described in homopolymer results. Finally, these studies indicate a new route toward linking spherical NPs in a controlled fashion, allowing for tunable plasmonic properties in the case of metallic NPs.


Clinical presentation and management of alleged sexually assaulted females at Mulago hospital, Kampala, Uganda.
To determine the presentation and treatment offered to sexually assaulted females attending emergency gynaecological ward in Mulago Hospital, Kampala, Uganda. Mulago hospital gynaecological emergency ward. Prospective descriptive study. Fifty eight sexually assaulted females were recruited from 1 st March 2000 to 31 st December 2000. They were interviewed, examined, given appropriate treatment and followed up for three months. Socio demographic characteristics, genital and bodily injuries, relationship to the assailant, and prevalence of sexually transmitted infections. The mean age was 9.5 with a range of 1-35 years. Seventy two percent of the victims were children below 12 years. Fifty percent of the assault occurred at the assailant's home. The majority (79.3%) of the victims knew the assailant and cases of gang rape were only 6.9%. The injuries sustained were extra genital (19.0%), genital (75.4%). The emotional or psychological disturbance was present in 22.4% of the patients. The sexually transmitted infections found included trichomonas vaginalis (1.7%) and syphilis (3.7%). All cases received counseling and prophylactic treatment for sexually transmitted infections. Those in reproductive age group were offered emergency contraception. None of the victims got post exposure HIV therapy because it was not available in the hospital. Sexual assault is common in Uganda and is one of the most dehumanizing human crimes against women. It is associated with adverse medical and social problems. There is urgent need to sensitize the community about reporting early for medical treatment after sexual assault.


Obstructive sleep apnea in Asian primary school children.
The objectives of this study were to examine the prevalence of obstructive sleep apnea (OSA) in primary school children, relationships between OSA and tonsillar hypertrophy, adenoid, and patency of the nasal cavity, and the effects of the tonsillar hypertrophy and adenoid on the nasal patency. An examination of the palatine tonsils and anterior rhinoscopy, completion of a questionnaire survey, a measurement of nasal resistance, an examination for sleep apnea at home using portable polysomnography device, and radiography of pharyngeal tonsil were performed in 152 primary school children. The obstructive apnea hypopnea index (O-AHI) increased with enlargements in the palatine tonsils. The adenoidal nasopharyngeal ratio (A/N ratio) decreased with advances in grade. A significant difference was observed in the O-AHI between those with and without adenoid. The median value of the O-AHI increased with advances in grade. The nasal resistance was significantly higher in the group with adenoid compared as in the group without. It was also higher in the nasal disease group with OSA than in the group without. Full polysomnography(PSG) was recommended in 16 (10.5%) of 152 who underwent the examination using the portable polysomnography device, and of the eight who underwent PSG, six (75%) were confirmed to have OSA, while its prevalence in all subjects was estimated as 7.9%. Disturbances in nasal respiration as well as tonsillar hypertrophy and adenoid were found to be a risk factor of OSA in primary school children.


Transrectal ultrasonography in the diagnosis and management of ejaculatory duct obstruction.
Ejaculatory duct obstruction is a rare but treatable cause of male infertility. The most common etiologies include congenital anomalies of the wolffian and Mullerian ducts, trauma, and inflammation. The diagnosis of ejaculatory duct obstruction should be suspected in any azoospermic patient with low ejaculate volume. Transrectal ultrasonography is now the preferred imaging modality for these patients. Seminal vesicle aspiration documents the presence of obstruction, confirms the presence of intact spermatogenesis, and rules out more proximal obstruction. Seminal vesiculography provides important anatomic information that may be helpful in determining the best method of treatment. It is a useful adjunct during transurethral resection of the ejaculatory ducts. Transurethral resection of the ejaculatory ducts is the standard method of treatment for ejaculatory duct obstruction, but balloon dilation may be preferred in select patients with an extraprostatic obstruction of the ejaculatory ducts. The exact criteria for the diagnosis of partial ejaculatory duct obstruction are still unclear, and therapy for these patients should be considered investigational at this time.


Changes in the Framing of Antimicrobial Resistance in Print Media in Australia and the United Kingdom (2011-2020): A Comparative Qualitative Content and Trends Analysis.
Educating the public about antimicrobial resistance (AMR) is considered a key part of an optimal public health response. In both media depictions and policy discourses around health risks, how a problem is framed underpins public awareness and understanding, while also guiding opinions on what actions can and should be taken. Using a mixed methods approach we analyse newspaper content in Australia and the United Kingdom (UK) from 2011 to 2020 to track how causes, consequences and solutions to AMR are represented in countries with different policy approaches. Analyses demonstrate greater variability in the frames used in UK newspapers reflecting large hospital and community outbreaks and a sustained period of policy reform mid-decade. Newspapers in Australia focus more on AMR causes and consequences, highlighting the importance of scientific discovery, whereas UK coverage has greater discussion of the social and economic drivers of AMR and their associated solutions. Variations in the trends of different frames around AMR in UK newspapers indicate greater levels of public deliberation and debate around immediate and actionable solutions; whereas AMR has not had the same health and political impacts in Australia resulting in a media framing that potentially encourages greater public complacency about the issue.


1-Pamitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol May Reduce Incidence of Gemcitabine-Induced Neutropenia: A Pilot Case-Controlled Study.
Chemotherapy-induced neutropenia (CIN) may compromise planned chemotherapy, resulting in severe infection, dose reduction or delayed treatment. Orally administered 1-pamitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) is a synthetic monoacetyldiglyceride, a product found in the antlers of sika deer. The aim of this study was to evaluate the effectiveness of PLAG for the prevention of CIN. A total of 48 patients with unresectable pancreatic cancer received gemcitabine-based palliative chemotherapy. Among those patients, 16 patients received PLAG (500 mg) twice daily from the start of chemotherapy to the completion. The PLAG group showed a significantly lower incidence of neutropenia (absolute neutrophil count < 1,500 cells/mm3, grade 2-4), as compared to the control group (37.5% vs. 81.3%, P < 0.05). The absolute neutrophil counts (ANCs) of the PLAG group significantly less decreased from the baseline level compared to those of the control group (P < 0.05) and this significant difference in the reduction percentage of ANCs between the two groups was sustained throughout the courses of chemotherapy. No adverse events related to PLAG were observed. PLAG was shown to be clinically effective and safe in reducing the incidence of CIN in pancreatic cancer patients receiving gemcitabine-based chemotherapy.


Potential applications of curcumin and its novel synthetic analogs and nanotechnology-based formulations in cancer prevention and therapy.
Curcumin has attracted great attention in the therapeutic arsenal in clinical oncology due to its chemopreventive, antitumoral, radiosensibilizing and chemosensibilizing activities against various types of aggressive and recurrent cancers. These malignancies include leukemias, lymphomas, multiple myeloma, brain cancer, melanoma and skin, lung, prostate, breast, ovarian, liver, gastrointestinal, pancreatic and colorectal epithelial cancers. Curcumin mediates its anti-proliferative, anti-invasive and apoptotic effects on cancer cells, including cancer stem/progenitor cells and their progenies, through multiple molecular mechanisms. The oncogenic pathways inhibited by curcumin encompass the members of epidermal growth factor receptors (EGFR and erbB2), sonic hedgehog (SHH)/GLIs and Wnt/β-catenin and downstream signaling elements such as Akt, nuclear factor-kappa B (NF-κB) and signal transducers and activators of transcription (STATs). In counterbalance, the high metabolic instability and poor systemic bioavailability of curcumin limit its therapeutic efficacy in human. Of great therapeutic interest, the selective delivery of synthetic analogs or nanotechnology-based formulations of curcumin to tumors, alone or in combination with other anticancer drugs, may improve their chemopreventive and chemotherapeutic efficacies against cancer progression and relapse. Novel curcumin formulations may also be used to reverse drug resistance, eradicate the total cancer cell mass and improve the anticarcinogenic efficacy of the current anti-hormonal and chemotherapeutic treatments for patients with various aggressive and lethal cancers.


Therapeutic applications: natural killer cells in the clinic.
Natural killer (NK) cells recognize targets stressed by malignant transformation or infection (particularly CMV). We now know that NK cells can be long-lived and remember past exposures. They become educated by interaction with MHC class I molecules to gain potent function to kill targets and produce cytokines. In the clinical setting, haploidentical NK cells can be transferred adoptively to treat cancer. Persistence and in vivo expansion of NK cells depends on lymphodepleting chemotherapy to make space for the release of endogenous IL-15. In vivo expansion is also enhanced by cytokine administration. IL-2 has been used at low doses to stimulate NK cells in vivo, but has the down side of stimulating CD25hi regulatory T cells. IL-15 is now being tested and has the advantage of avoiding inhibitory regulatory T cell stimulation. In refractory acute myeloid leukemia, leukemia clearance is correlated with the persistence and in vivo expansion of NK cells after adoptive transfer. Limitations to NK cell therapy include poor in vivo survival and lack of specificity. Monoclonal antibodies and bispecific or trispecific killer engagers to target CD16 on NK cells to enhance recognition of various tumor antigens and ADAM17 inhibition to prevent CD16 shedding after NK cell activation should promote enhanced killing of cancer with specificity. Future strategies to exploit favorable donor immunogenetics or to expand NK cells ex vivo from blood, progenitors, or pluripotent progenitors may overcome immune barriers of adoptive transfer and comparative clinical trials will be needed to test these approaches.


An ncRNA transcriptomics-based approach to design siRNA molecules against SARS-CoV-2 double membrane vesicle formation and accessory genes.
The corona virus SARS-CoV-2 is the causative agent of recent most global pandemic. Its genome encodes various proteins categorized as non-structural, accessory, and structural proteins. The non-structural proteins, NSP1-16, are located within the ORF1ab. The NSP3, 4, and 6 together are involved in formation of double membrane vesicle (DMV) in host Golgi apparatus. These vesicles provide anchorage to viral replicative complexes, thus assist replication inside the host cell. While the accessory genes coded by ORFs 3a, 3b, 6, 7a, 7b, 8a, 8b, 9b, 9c, and 10 contribute in cell entry, immunoevasion, and pathological progression. This in silico study is focused on designing sequence specific siRNA molecules as a tool for silencing the non-structural and accessory genes of the virus. The gene sequences of NSP3, 4, and 6 along with ORF3a, 6, 7a, 8, and 10 were retrieved for conservation, phylogenetic, and sequence logo analyses. siRNA candidates were predicted using siDirect 2.0 targeting these genes. The GC content, melting temperatures, and various validation scores were calculated. Secondary structures of the guide strands and siRNA-target duplexes were predicted. Finally, tertiary structures were predicted and subjected to structural validations. This study revealed that NSP3, 4, and 6 and accessory genes ORF3a, 6, 7a, 8, and 10 have high levels of conservation across globally circulating SARS-CoV-2 strains. A total of 71 siRNA molecules were predicted against the selected genes. Following rigorous screening including binary validations and minimum free energies, final siRNAs with high therapeutic potential were identified, including 7, 2, and 1 against NSP3, NSP4, and NSP6, as well as 3, 1, 2, and 1 targeting ORF3a, ORF7a, ORF8, and ORF10, respectively. Our novel in silico pipeline integrates effective methods from previous studies to predict and validate siRNA molecules, having the potential to inhibit viral replication pathway in vitro. In total, this study identified 17 highly specific siRNA molecules targeting NSP3, 4, and 6 and accessory genes ORF3a, 7a, 8, and 10 of SARS-CoV-2, which might be used as an additional antiviral treatment option especially in the cases of life-threatening urgencies.


[Retinal sensitivity in diabetic macular edema, with and without decreased visual acuity].
To compare retinal sensitivity in diabetics with macular edema, with and without decreased visual acuity. An observational, prospective, cross-sectional comparative study in eyes with diabetic macular edema. The sample was divided into two groups: eyes with visual acuity ""≥ 0.5 (group 1) and < 0.5 (group 2). Foveal sensitivity was compared between groups (Mann-Whitney´s U), stratified according to the center point thickness. Correlations between visual acuity and retinal sensitivity and between visual acuity and macular volume were identified. 81 eyes, 59 from group 1 and 22 from group 2. The mean of retinal sensitivity in group 2 (24.4 ± 6.9 dB) was significantly lower than in group 1 (30.8 ± 3.4; p < 0.001). The correlation between visual acuity and retinal sensitivity was 0.49 (r2 = 0.25), and it was 0.37 in eyes with center point thickness within one standard deviation above the mean and 0.40 in eyes within two standard deviations (p < 0.001). The correlation between visual acuity and macular volume was -0.108 (r2 = 0.026). Retinal sensitivity in eyes with clinically significant macular edema and decreased visual acuity before treatment was significantly lower than in eyes with normal visual acuity; the difference did not change as center point thickness increased.


Substrates for zero temperature coefficient Love wave sensors.
Microacoustic Love wave delay lines show high sensitivity to perturbations such as mass depositions on the wave-guide surface. Furthermore, because of their shear polarization, Love waves are ideally suited for liquid sensing applications. Using a Love wave delay line as feedback element in an oscillator allows the realization of viscosity sensors, and, using a chemical interface, chemical sensors, where the output signal is the oscillation frequency. To achieve a high effective sensitivity, the cross-sensitivity to temperature has to be kept low. We outline the proper choice of a material and especially focus on the influence of crystal cut and the major device design parameters (mass sensitivity and coupling coefficient) on the temperature coefficient of the sensor.


Quantitative and qualitative impairments in skilled reaching in the mouse (Mus musculus) after a focal motor cortex stroke.
Skilled reaching movements are an important aspect of human motor behavior but are impaired after motor system stroke. The purpose of this study was to document skilled movements in mice before and after a focal motor cortex stroke for the purpose of developing a mouse model of human stroke. Male C57/BL6 mice were trained to reach with a forelimb for food pellets and then given a motor cortex stroke, induced by pial stripping, contralateral to their preferred reaching limb. Reaching success and the movements used in reaching were analyzed by frame-by-frame inspection of presurgical and postsurgical video records. Reaching success was severely impaired after the stroke. Improvement in success over 2 postsurgical weeks was moderate. Analysis of 10 movement components comprising reaches pre- and postsurgically indicated that most of the rotatory movements of the limb used for aiming, advancing, pronating, and supinating the paw were impaired. When successful reaches did occur, body movements that compensated for the impairments in limb rotatory movements aided them. The results indicate that skilled reaching in the mouse is impaired by focal motor cortex stroke and they suggest that the mouse, and the skilled reaching task, provides an excellent model for studying impairments, compensation, and recovery after motor system stroke.


Algorithms and tools for protein-protein interaction networks clustering, with a special focus on population-based stochastic methods.
Protein-protein interaction (PPI) networks are powerful models to represent the pairwise protein interactions of the organisms. Clustering PPI networks can be useful for isolating groups of interacting proteins that participate in the same biological processes or that perform together specific biological functions. Evolutionary orthologies can be inferred this way, as well as functions and properties of yet uncharacterized proteins. We present an overview of the main state-of-the-art clustering methods that have been applied to PPI networks over the past decade. We distinguish five specific categories of approaches, describe and compare their main features and then focus on one of them, i.e. population-based stochastic search. We provide an experimental evaluation, based on some validation measures widely used in the literature, of techniques in this class, that are as yet less explored than the others. In particular, we study how the capability of Genetic Algorithms (GAs) to extract clusters in PPI networks varies when different topology-based fitness functions are used, and we compare GAs with the main techniques in the other categories. The experimental campaign shows that predictions returned by GAs are often more accurate than those produced by the contestant methods. Interesting issues still remain open about possible generalizations of GAs allowing for cluster overlapping. We point out which methods and tools described here are publicly available. firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Response to epinephrine in children receiving oral beta-agonists.
Physicians are sometimes concerned that the regular use of oral beta-agonists in the outpatient management of childhood asthma will result in decreased sensitivity or tachyphylaxis to these agents. While tachyphylaxis might not be clinically important during outpatient treatment, it could become significant during the emergency treatment of acute asthmatic attacks. We compared the increase in peak flow measurements before and 20 minutes after the injection of subcutaneous epinephrine hydrochloride in children with acute asthma and found no significant differences between those patients taking and those not taking oral beta-agonists.


Evaluation of the Effectiveness of Video-based Intervention on the Knowledge of Infant Oral Health among New Mothers.
Infant oral health is the foundation upon which preventive dental health education must be built to enhance the conditions for a disease-free oral cavity. Majority of the mothers are ignorant about their oral health and also about the fact that their oral health status affects that of their babies. Educational videotapes have proved to be effective in educating mothers on various child health issues. So the objectives of this study were to educate the mothers about the need for infant oral health care, compare the level of mother's knowledge on infant oral health before and after the video presentation and assess the effectiveness of the presentation. An interactive educational video presentation containing evidence-based information about infant oral health care and prevention was developed. This presentation was based upon information provided by the American Academy of Pediatric Dentistry (AAPD) on anticipatory guidance. It includes the persuasive message on maternal oral health during preconception and pregnancy and its implication on birth outcomes, vertical transmission of Streptococcus mutans, infant oral health, the risk for early childhood caries (ECC), and increased caries experience on permanent teeth if primary teeth are affected. Emergency care for infant oral trauma, consequences of traumatic injuries to the primary dentition from an aspect of possible damage to the developing tooth, dietary habits, and oral hygiene behaviors. It also emphasizes the timing of the first dental visit and the periodicity of dental screenings. The survey was designed to compare the effectiveness of instructional videotaped persuasive messages by using pre- and post-questionnaires. Two hundred mothers of infants below the age of 12 months were included in the study. They were asked to fill out the questionnaires before and after the presentation on the same visit. The results showed a highly significant improvement in knowledge (p< 0.05) as assessed by the proportion of correct responses following a single viewing of the AV-aid. The knowledge of new mothers on infant oral health care was inadequate, and there was an improvement in their knowledge of infant oral health care after the instructional video presentation. An instructional video presentation is an effective tool for improving the oral health knowledge of new mothers. By this study, we want to inculcate the habit of oral hygiene maintenance among the mothers, which indirectly affects the infant's oral health. Through this study, we educated the mothers regarding infant oral health care, which significantly improved their knowledge. Singh R, Patil SS, K Madhu, et al. Evaluation of the Effectiveness of Video-based Intervention on the Knowledge of Infant Oral Health among New Mothers. Int J Clin Pediatr Dent 2022;15(3):280-286.


Endogenous plasma proteins in edematous lungs and alveolar fluid in rabbits.
In this study, we compared two methods of differentiating hydrostatic and permeability types of pulmonary edema. The first method entailed measurement of protein concentrations directly in samples of alveolar fluid (AF); the second method was an indirect technique in which protein concentration in extravascular extracellular water (EVECW) was calculated on the basis of separate measurements of the quantity of protein in the lung and the volume of EVECW. The concentration of albumin (Alb) and gamma-G-globulin was measured in EVECW and alveolar fluid in excised edematous rabbit lungs. Edema was caused by elevation of left ventricular end-diastolic pressure to 25 Torr (hydrostatic edema, HE) or by intravenous oleic acid, 0.09 ml/kg (permeability edema, PE). The volume of distribution of Na+ was utilized as a measure of EVECW in the lung. Protein concentration in EVECW and AF relative to plasma (EV/PL and AF/PL, respectively) was compared in the two types of edema. The EV/PL was 0.61 +/- 0.12 (SD) for Alb in He compared with 1.18 +/- 0.47 in PE (P less than 0.02). The AF/PL was 0.54 +/- 0.12 and 1.25 +/- 0.33 in HE and PE, respectively (P less than 0.001). There was good correlation between EV/PL and AF/PL for Alb (r = 0.74, P less than 0.001) but not for gamma-G-globulin. Thus EV/PL for Alb, AF/PL for Alb, and gamma-G-globulin all differentiated hydrostatic from permeability edema.


Liposome co-encapsulation as a strategy for the delivery of curcumin and resveratrol.
Curcumin and resveratrol are natural compounds whose strong antioxidant activities are highly beneficial in the human diet. Unfortunately, their physicochemical properties result in poor stability in their chemical and antioxidant activities, which limits their utilization in food and pharmaceutical applications. In this study, liposomal nanoencapsulation was developed as a strategy to overcome these limitations and improve the antioxidant effects of these compounds. The physicochemical characteristics of co-encapsulated liposomes were evaluated and compared to formulations containing each compound individually. Liposomes co-encapsulating curcumin and resveratrol presented a lower particle size, lower polydispersity index and greater encapsulation efficiency. The formulation of liposomes co-loading curcumin and resveratrol at 5 : 1, exhibited the lowest particle size (77.50 nm), lowest polydispersity index (0.193), highest encapsulation efficiency (reaching 80.42 ± 2.12%), and strongest 2,2-diphenyl-1-picrylhydrazyl scavenging, lipid peroxidation inhibition capacity and reducing power. Additionally, liposomes loading both curcumin and resveratrol displayed a higher ability during preparation, storage, heating and surfactant shock than those loaded with individual polyphenol. Infrared spectroscopic and fluorescence techniques demonstrated that the curcumin mainly located in the hydrophobic acyl-chain region of liposomes, while the resveratrol orientated to the polar head groups. These orientations could have synergistic effects on the stabilization of liposomes. Our findings should guide the rational design of a co-delivery liposomal system regarding the location and orientation of bioactive compounds inside the lipid bilayer.


Interindividual variation in mitotic recombination.
Mitotic recombination (MR) between homologous chromosomes is a mutational event that results in loss of heterozygosity in half of the segregants at mitosis. Loss of heterozygosity may have important biological consequences. The purpose of this study was to describe human variation in the spontaneous frequency of MR. Using an immunoselection technique for isolating the somatic mutations that result in loss of expression of one of the codominant alleles at the HLA-A locus, we have measured the frequency and molecular basis of somatic mutations in lymphocytes from a population of young adults. Mutations were classified as being the result of intragenic changes, major deletions, or MR. Here we show that the MR mutation frequency in females was significantly greater than that in males but that intragenic mutation frequency showed no association with sex. Individual variation in MR frequency ranged over more than two orders of magnitude and was not normally distributed. Furthermore, the observed number of individuals from whom no mutants resulting from MR were obtained was significantly greater than was expected. The endogenous level of MR may be under genetic control. Given the association of loss of heterozygosity with cancer initiation and progression, low endogenous MR may confer a reduced lifetime risk of cancer, and the converse may apply.


Review of malaria situation in Cameroon: technical viewpoint on challenges and prospects for disease elimination.
Malaria still has a devastating impact on public health and welfare in Cameroon. Despite the increasing number of studies conducted on disease prevalence, transmission patterns or treatment, there are to date, not enough studies summarising findings from previous works in order to identify gaps in knowledge and areas of interest where further evidence is needed to drive malaria elimination efforts. The present study seeks to address these gaps by providing a review of studies conducted so far on malaria in Cameroon since the 1940s to date. Over 250 scientific publications were consulted for this purpose. Although there has been increased scale-up of vector control interventions which significantly reduced the morbidity and mortality to malaria across the country from a prevalence of 41% of the population reporting at least one malaria case episode in 2000 to a prevalence of 24% in 2017, the situation is not yet under control. There is a high variability in disease endemicity between epidemiological settings with prevalence of Plasmodium parasitaemia varying from 7 to 85% in children aged 6 months to 15 years after long-lasting insecticidal nets (LLINs) scale-up. Four species of Plasmodium have been recorded across the country: Plasmodium falciparum, P. malariae, P. ovale and P. vivax. Several primate-infecting Plasmodium spp. are also circulating in Cameroon. A decline of artemisinin-based combinations therapeutic efficacy from 97% in 2006 to 90% in 2016 have been reported. Several mutations in the P. falciparum chloroquine resistance (Pfcrt) and P. falciparum multidrug resistance 1 (Pfmdr1) genes conferring resistance to either 4-amino-quinoleine, mefloquine, halofanthrine and quinine have been documented. Mutations in the Pfdhfr and Pfdhps genes involved in sulfadoxine-pyrimethamine are also on the rise. No mutation associated with artemisinin resistance has been recorded. Sixteen anopheline species contribute to malaria parasite transmission with six recognized as major vectors: An. gambiae, An. coluzzii, An. arabiensis, An. funestus, An. nili and An. moucheti. Studies conducted so far, indicated rapid expansion of DDT, pyrethroid and carbamate resistance in An. gambiae, An. coluzzii, An. arabiensis and An. funestus threatening the performance of LLINs. This review highlights the complex situation of malaria in Cameroon and the need to urgently implement and reinforce integrated control strategies in different epidemiological settings, as part of the substantial efforts to consolidate gains and advance towards malaria elimination in the country.


Exploring the Role of Family Functioning in the Association Between Frequency of Family Dinners and Dietary Intake Among Adolescents and Young Adults.
Eating meals, particularly dinner, with family members has been associated with improved dietary intake among youths. However, existing studies have not examined how family functioning may moderate or confound this association. To examine whether level of family functioning is associated cross-sectionally with frequency of family dinners and dietary intake among a US national sample of adolescents and young adults. Data from the 2011 questionnaire in the Growing Up Today Study 2 were used for this cross-sectional study. Linear regression models examined the extent to which family dinner frequency was associated with self-reported intake of fruits and vegetables, sugar-sweetened beverages, fast food, and takeout food among 2728 adolescents and young adults (age, 14-24 years). To explore effect modification by family functioning, an interaction term for family functioning and family dinner frequency was included for each dietary outcome. To explore confounding, models adjusted for family functioning were run. All models were stratified by sex and included participant age, educational attainment of mother's spouse or partner, and family structure as covariates. Statistical analysis was conducted between January 1, 2017, and August 31, 2018. Dietary intake measured by consumption of fruits and vegetables, sugar-sweetened beverages, takeout food, and fast food; family dinner frequency per week; and family functioning. Among the 2728 participants, there were 1559 female and 1169 male participants who were 14 to 24 years of age (mean [SD] age, 19.4 [1.9] years) and were living with their parents in 2011. Most participants (2453 of 2649 [92.6%]) identified as white. More frequent family dinners were associated with higher-quality dietary intake regardless of level of family functioning; interactions between family functioning and family dinner frequency were not significant. Associations between family meal frequency and dietary intake outcomes did not change substantively when adjusting for family functioning. In adjusted models, more frequent family dinners were associated with higher intakes of fruits (female participants: β, 0.09 servings/d; 95% CI, 0.04-0.15 servings/d; male participants: β, 0.07 servings/d; 95% CI, 0.01-0.12 servings/d) and vegetables (female participants: β, 0.21 servings/d; 95% CI, 0.12-0.30 servings/d; male participants: β, 0.19 servings/d; 95% CI, 0.09-0.30 servings/d), and lower intakes of fast food (female participants: β, -0.04 times/wk; 95% CI, -0.07 to 0.00 times/wk; male participants: β, -0.10 times/wk; 95% CI, -0.15 to -0.04 times/wk) and takeout foods (female participants: β, -0.04 times/wk; 95% CI, -0.07 to -0.01 times/wk; male participants: β, -0.06 times/wk; 95% CI, -0.10 to -0.02 times/wk). More frequent family dinners were associated with lower intake of sugar-sweetened beverages for male participants only (β, -0.07 servings/d; 95% CI, -0.13 to -0.02 servings/d). More frequent family dinners are associated with healthful dietary intakes among youths, regardless of level of family functioning. Family dinners may be an appropriate intervention target for improving dietary intake among youths.


Blockage of Src by Specific siRNA as a Novel Therapeutic Strategy to Prevent Destructive Repair in Steroid-Associated Osteonecrosis in Rabbits.
Vascular hyperpermeability and highly upregulated bone resorption in the destructive repair progress of steroid-associated osteonecrosis (SAON) are associated with a high expression of VEGF and high Src activity (Src is encoded by the cellular sarcoma [c-src] gene). This study was designed to prove our hypothesis that blocking the VEGF-Src signaling pathway by specific Src siRNA is able to prevent destructive repair in a SAON rabbit model. Destructive repair in SAON was induced in rabbits. At 2, 4, and 6 weeks after SAON induction, VEGF, anti-VEGF, Src siRNA, Src siRNA+VEGF, control siRNA, and saline were introduced via intramedullary injection into proximal femora for each group, respectively. Vascularization and permeability were quantified by dynamic contrast-enhanced (DCE) MRI. At week 6 after SAON induction, proximal femurs were dissected for micro-computed tomography (μCT)-based trabecular architecture with finite element analysis (FEA), μCT-based angiography, and histological analysis. Histological evaluation revealed that VEGF enhanced destructive repair, whereas anti-VEGF prevented destructive repair and Src siRNA and Src siRNA+VEGF prevented destructive repair and enhanced reparative osteogenesis. Findings of angiography and histomorphometry were consistent with those determined by DCE MRI. Src siRNA inhibited VEGF-mediated vascular hyperpermeability but preserved VEGF-induced neovascularization. Bone resorption was enhanced in the VEGF group and inhibited in the anti-VEGF, Src siRNA, Src siRNA+VEGF groups as determined by both 3D μCT and 2D histomorphometry. FEA showed higher estimated failure load in the Src siRNA and Src siRNA+VEGF groups when compared to the vehicle control group. Blockage of VEGF-Src signaling pathway by specific Src siRNA was able to prevent steroid-associated destructive repair while improving reconstructive repair in SAON, which might become a novel therapeutic strategy.


Silencing of WIPK and SIPK mitogen-activated protein kinases reduces tobacco mosaic virus accumulation but permits systemic viral movement in tobacco possessing the N resistance gene.
Infection of tobacco cultivars possessing the N resistance gene with Tobacco mosaic virus (TMV) results in confinement of the virus by necrotic lesions at the infection site. Although the mitogen-activated protein kinases WIPK and SIPK have been implicated in TMV resistance, evidence linking them directly to disease resistance is, as yet, insufficient. Viral multiplication was reduced slightly in WIPK- or SIPK-silenced plants but substantially in WIPK/SIPK-silenced plants, and was correlated with an increase in salicylic acid (SA) and a decrease in jasmonic acid (JA). Silencing of WIPK and SIPK in a tobacco cultivar lacking the N gene did not inhibit viral accumulation. The reduction in viral accumulation was attenuated by expressing a gene for an SA-degrading enzyme or by exogenously applying JA. Inoculation of lower leaves resulted in the systemic spread of TMV and formation of necrotic lesions in uninoculated upper leaves. These results suggested that WIPK and SIPK function to negatively regulate local resistance to TMV accumulation, partially through modulating accumulation of SA and JA in an N-dependent manner, but positively regulate systemic resistance.


Impact of Programmed Death Ligand 1 Expression in Advanced Non-Small-Cell Lung Cancer Patients, Treated by Chemotherapy (GFPC 06-2015 Study).
Few data have been published on the clinical and histopathological characteristics of advanced non-small-cell lung cancer (NSCLC) patients with high PD-L1 expression versus intermediate or none and the prognostic value of PD-L1 expression for patients treated with chemotherapy is unknown. This study was undertaken to prospectively assess the prognostic value of tumor-cell (TC) and immune-cell (IC) PD-L1 expressions for advanced NSCLC patients. It was a prospective, multicenter study on advanced NSCLC patients, with performance status 0/1, scheduled, consecutively, to receive first-line platin-based chemotherapy. PD-L1 expression was determined immunochemically (Dako Autostainer and monoclonal antibody 22C3) and its impact on progression-free survival (PFS) and overall survival (OS) assessed. Among 198 patients screened in 19 centers, 140 were included median age: 66.5 ± 10 years; 76.4% men; 79.3% Caucasians; 10.7% nonsmokers; 63.6% adenocarcinomas; <1%, 1-50% and ≥50% TC PD-L1-expression rates were 47.1%, 25.7% and 27.2% of patients, respectively; respective null, intermediate and high rates on ICs were 35.7%, 38.6% and 25.7%. Second- and third-line chemotherapies were administered to 58.6% and 26.4% of the patients, respectively. None received immunotherapy. First-, second- and third-line median (95% CI) PFS lasted 4.6 (3.6-5.2), 3.7 (2.3-4.7) and 2.2 (1.5-4.3) months, respectively; median OS was 16.9 (11.4-19.9) months. No significant PFS and OS differences were observed according to TC or IC PD-L1 expression. According to the results of this prospective, multicenter study, neither TC nor IC PD-L1 expression appears to be prognostic for chemotherapy-managed advanced NSCLC patients.


A class of secreted mammalian peptides with potential to expand cell-cell communication.
Peptide hormones and neuropeptides are signaling molecules that control diverse aspects of mammalian homeostasis and physiology. Here we provide evidence for the endogenous presence of a sequence diverse class of blood-borne peptides that we call "capped peptides." Capped peptides are fragments of secreted proteins and defined by the presence of two post-translational modifications - N-terminal pyroglutamylation and C-terminal amidation - which function as chemical "caps" of the intervening sequence. Capped peptides share many regulatory characteristics in common with that of other signaling peptides, including dynamic physiologic regulation. One capped peptide, CAP-TAC1, is a tachykinin neuropeptide-like molecule and a nanomolar agonist of mammalian tachykinin receptors. A second capped peptide, CAP-GDF15, is a 12-mer peptide cleaved from the prepropeptide region of full-length GDF15 that, like the canonical GDF15 hormone, also reduces food intake and body weight. Capped peptides are a potentially large class of signaling molecules with potential to broadly regulate cell-cell communication in mammalian physiology.


The molecular mechanism of actions and clinical utilities of tumor infiltrating lymphocytes in gastrointestinal cancers: a comprehensive review and future prospects toward personalized medicine.
Gastrointestinal (GI) cancers remain a significant global health burden, accounting for a substantial number of cases and deaths. Regrettably, the inadequacy of dependable biomarkers hinders the precise forecasting of patient prognosis and the selection of appropriate therapeutic sequencing for individuals with GI cancers, leading to suboptimal outcomes for numerous patients. The intricate interplay between tumor-infiltrating lymphocytes (TILs) and the tumor immune microenvironment (TIME) has been shown to be a pivotal determinant of response to anti-cancer therapy and consequential clinical outcomes across a multitude of cancer types. Therefore, the assessment of TILs has garnered global interest as a promising prognostic biomarker in oncology, with the potential to improve clinical decision-making substantially. Moreover, recent discoveries in immunotherapy have progressively changed the landscape of cancer treatment and significantly prolonged the survival of patients with advanced cancers. Nonetheless, the response rate remains constrained within solid tumor sufferers, even when TIL landscapes appear comparable, which calls for the development of our understanding of cellular and molecular cross-talk between TIME and tumor. Hence, this comprehensive review encapsulates the extant literature elucidating the TILs' underlying molecular pathogenesis, prognostic significance, and their relevance in the realm of immunotherapy for patients afflicted by GI tract cancers. Within this review, we demonstrate that the type, density, and spatial distribution of distinct TIL subpopulations carries pivotal implications for the prediction of anti-cancer treatment responses and patient survival. Furthermore, this review underscores the indispensable role of TILs in modulating therapeutic responses within distinct molecular subtypes, such as those characterized by microsatellite stability or programmed cell death ligand-1 expression in GI tract cancers. The review concludes by outlining future directions in TIL-based personalized medicine, including integrating TIL-based approaches into existing treatment regimens and developing novel therapeutic strategies that exploit the unique properties of TILs and their potential as a promising avenue for personalized cancer treatment.


Fluid cognitive ability is associated with greater exposure and smaller reactions to daily stressors.
The authors of this study investigated whether fluid cognitive ability predicts exposure and emotional reactivity to daily stressors. A national sample of adults from the Midlife in the United States study and the National Study of Daily Experiences (N = 1,202) who had a mean age of 57 years (SD = 12; 56% women, 44% men) completed positive and negative mood reports as well as a stressor diary on 8 consecutive evenings via telephone. Participants also completed a telephone-based battery of tests measuring fluid cognitive ability. Higher levels of fluid cognitive ability were associated with greater exposure to work- and home-related overload stressors. Possessing higher levels of fluid cognitive ability was associated with smaller stressor-related increases in negative mood, primarily for interpersonal tensions and network stressors, and smaller stressor-related decreases in positive mood for interpersonal tensions. Furthermore, fluid cognitive ability was unrelated to subjective severity ratings of the stressors reported. Discussion focuses on the role of fluid cognitive ability in daily stress processes.


[Pharmacological protection of the brain during surgery in patients with giant cerebral aneurysms].
The authors discuss the results of pharmacological protection of the brain, consisting in intraarterial or intravenous infusion of drugs (sodium thiopental, nimodipine, ketamine) during intracranial interventions in 13 patients with giant arterial aneurysms of the anterior portions of Willis' circle. In some patients drug protection of the brain prevented the development of ischemic focus in the basin of temporarily occluded vessel. Intraarterial infusion of protector drugs is preferable because it allows decreasing the doses and severity of untoward hemodynamic effects.


The inhibitor of apoptosis protein MoBir1 is involved in the suppression of hydrogen peroxide-induced fungal cell death, reactive oxygen species generation, and pathogenicity of rice blast fungus.
The inhibitor of apoptosis protein (IAP) family has been identified in a variety of organisms. All IAPs contain one to three baculoviral IAP repeat (BIR) domains, which are required for anti-apoptotic activity. Here, we identified a type II BIR domain-containing protein, MoBir1, in the rice blast fungus Magnaporthe oryzae. Expression of the MoBIR1 gene in Saccharomyces cerevisiae suppressed hydrogen peroxide-induced cell death and delayed yeast cell chronological aging. Delayed aging was found to require the carboxyl terminus of MoBir1. M. oryzae transformants overexpressing the MoBIR1 gene demonstrated increased growth rate and biomass, delayed mycelial aging, and enhanced resistance to hydrogen peroxide but reduced reactive oxygen species generation and virulence. Moreover, MoBIR1-overexpressing transformants exhibited anti-apoptotic activity. However, MoBIR1 silencing resulted in no obvious phenotypic changes, compared with the wild-type M. oryzae strain Guy11. Our findings broaden the knowledge on fungal type II BIR domain-containing proteins.


Synthesis, anti-inflammatory activity, and in vitro antitumor effect of a novel class of cyclooxygenase inhibitors: 4-(aryloyl)phenyl methyl sulfones.
Following our previous research on anti-inflammatory drugs (NSAIDs), we report on the design and synthesis of 4-(aryloyl)phenyl methyl sulfones. These substances were characterized for their capacity to inhibit cyclooxygenase (COX-1 and COX-2) isoenzymes. Molecular modeling studies showed that the methylsulfone group of these compounds was inserted deep in the pocket of the human COX-2 binding site, in an orientation that precludes hydrogen bonding with Arg120, Ser353, and Tyr355 through their oxygen atoms. The N-arylindole 33 was the most potent inhibitor of COX-2 and also the most selective (COX-1/COX-2 IC(50) ratio was 262). The indole derivative 33 was further tested in vivo for its anti-inflammatory activity in rats. This compound showed greater inhibitory activity than ibuprofen. Other compounds (20, 26, 9, and 30) showed strong activity against carrageenan-induced inflammation. The latter compounds showed a weak capacity to inhibit the proliferation of human cell lines K562, NCI-H460, and HT-29 in vitro.


The age-specific cumulative incidence of infection with pandemic influenza H1N1 2009 was similar in various countries prior to vaccination.
During the influenza pandemic of 2009 estimates of symptomatic and asymptomatic infection were needed to guide vaccination policies and inform other control measures. Serological studies are the most reliable way to measure influenza infection independent of symptoms. We reviewed all published serological studies that estimated the cumulative incidence of infection with pandemic influenza H1N1 2009 prior to the initiation of population-based vaccination against the pandemic strain. We searched for studies that estimated the cumulative incidence of pandemic influenza infection in the wider community. We excluded studies that did not include both pre- and post-pandemic serological sampling and studies that included response to vaccination. We identified 47 potentially eligible studies and included 12 of them in the review. Where there had been a significant first wave, the cumulative incidence of pandemic influenza infection was reported in the range 16%-28% in pre-school aged children, 34%-43% in school aged children and 12%-15% in young adults. Only 2%-3% of older adults were infected. The proportion of the entire population infected ranged from 11%-18%. We re-estimated the cumulative incidence to account for the small proportion of infections that may not have been detected by serology, and performed direct age-standardisation to the study population. For those countries where it could be calculated, this suggested a population cumulative incidence in the range 11%-21%. Around the world, the cumulative incidence of infection (which is higher than the cumulative incidence of clinical disease) was below that anticipated prior to the pandemic. Serological studies need to be routine in order to be sufficiently timely to provide support for decisions about vaccination.


Modeling of phytoextraction efficiency of microbially stimulated Salix dasyclados L. in the soils with different speciation of heavy metals.
Bioaugmentation of soils with selected microorganisms during phytoextraction can be the key solution for successful bioremediation and should be accurately calculated for different physicochemical soil properties and heavy metal availability to guarantee the universality of this method. Equally important is the development of an accurate prediction tool to manage phytoremediation process. The main objective of this study was to evaluate the role of three metallotolerant siderophore-producing Streptomyces sp. B1-B3 strains in the phytoremediation of heavy metals with the use of S. dasyclados L. growing in four metalliferrous soils as well as modeling the efficiency of this process based on physicochemical and microbiological properties of the soils using artificial neural network (ANN) analysis. The bacterial inoculation of plants significantly stimulated plant biomass and reduced oxidative stress. Moreover, the bacteria affected the speciation of heavy metals and finally their mobility, thereby enhancing the uptake and bioaccumulation of Zn, Cd, and Pb in the biomass. The best capacity for phytoextraction was noted for strain B1, which had the highest siderophore secretion ability. Finally, ANN model permitted to predict efficiency of phytoextraction based on both the physicochemical properties of the soils and the activity of the soil microbiota with high precision.


Ancestral state reconstructions require biological evidence to test evolutionary hypotheses: A case study examining the evolution of reproductive mode in squamate reptiles.
To understand evolutionary transformations it is necessary to identify the character states of extinct ancestors. Ancestral character state reconstruction is inherently difficult because it requires an accurate phylogeny, character state data, and a statistical model of transition rates and is fundamentally constrained by missing data such as extinct taxa. We argue that model based ancestral character state reconstruction should be used to generate hypotheses but should not be considered an analytical endpoint. Using the evolution of viviparity and reversals to oviparity in squamates as a case study, we show how anatomical, physiological, and ecological data can be used to evaluate hypotheses about evolutionary transitions. The evolution of squamate viviparity requires changes to the timing of reproductive events and the successive loss of features responsible for building an eggshell. A reversal to oviparity requires that those lost traits re-evolve. We argue that the re-evolution of oviparity is inherently more difficult than the reverse. We outline how the inviability of intermediate phenotypes might present physiological barriers to reversals from viviparity to oviparity. Finally, we show that ecological data supports an oviparous ancestral state for squamates and multiple transitions to viviparity. In summary, we conclude that the first squamates were oviparous, that frequent transitions to viviparity have occurred, and that reversals to oviparity in viviparous lineages either have not occurred or are exceedingly rare. As this evidence supports conclusions that differ from previous ancestral state reconstructions, our paper highlights the importance of incorporating biological evidence to evaluate model-generated hypotheses.


Effect of Metformin Versus Placebo on New Primary Cancers in Canadian Cancer Trials Group MA.32: A Secondary Analysis of a Phase III Randomized Double-Blind Trial in Early Breast Cancer.
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Metformin has been associated with lower cancer risk in epidemiologic and preclinical research. In the MA.32 randomized adjuvant breast cancer trial, metformin (v placebo) did not affect invasive disease-free or overall survival. Here, we report metformin effects on the risk of new cancer. Between 2010 and 2013, 3,649 patients with breast cancer younger than 75 years without diabetes with high-risk T1-3, N0-3 M0 breast cancer (any estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2) were randomly assigned to metformin 850 mg orally twice a day or placebo twice a day for 5 years. New primary invasive cancers (outside the ipsilateral breast) developing as a first event were identified. Time to events was described by the competing risks method; two-sided likelihood ratio tests adjusting for age, BMI, smoking, and alcohol intake were used to compare metformin versus placebo arms. A total of 184 patients developed new invasive cancers: 102 metformin and 82 placebo, hazard ratio (HR), 1.25; 95% CI, 0.94 to 1.68; P = .13. These included 48 contralateral invasive breast cancers (27 metformin v 21 placebo), HR, 1.29; 95% CI, 0.72 to 2.27; P = .40 and 136 new nonbreast primary cancers (75 metformin v 61 placebo), HR, 1.24; 95% CI, 0.88 to 1.74; P = .21. Metformin did not reduce the risk of new cancer development in these nondiabetic patients with breast cancer.


Hydrogen bonding effects in adsorption of water-alcohol mixtures in zeolites and the consequences for the characteristics of the Maxwell-Stefan diffusivities.
This work highlights a variety of peculiar characteristics of adsorption and diffusion of polar molecules such as water, methanol and ethanol in zeolites. These peculiarities are investigated with the aid of configurational-bias Monte Carlo (CBMC) simulations of adsorption isotherms, and molecular dynamics (MD) simulations of diffusivities in FAU, MFI, DDR, and LTA zeolites. Because of strong hydrogen bonding, significant clustering of the guest molecules occurs in all investigated structures. Because of molecular clustering, the inverse thermodynamic factor 1/Gamma(i) identical with (d[ln c(i)])/(d[ln f(i)]) exceeds unity for a range molar concentrations c(i) within the micropores. The degree of clustering is lowered as the temperature is increased. For the concentration ranges for which 1/Gamma(i) > 1, the Fick diffusivity, D(i), for unary diffusion is often lower than both the Maxwell-Stefan, D(i), and the self-diffusivity, D(i,self). For water-alcohol mixtures, the hydrogen bonding between water and alcohol molecules is much more predominant than for water-water, and alcohol-alcohol molecule pairs. Consequently, the adsorption of water-alcohol mixtures shows significant deviations from the predictions of the ideal adsorbed solution theory (IAST). The water-alcohol bonding also leaves its imprint on the mixture diffusion characteristics. The Maxwell-Stefan diffusivity, D(i), of either component in water-alcohol mixtures is lower than the corresponding values of the pure components; this behavior is distinctly different from that for mixtures of nonpolar guest molecules. The binary exchange coefficient D(12) for water-alcohol mixtures is also significantly lower than either self-exchange coefficients D(11) and D(22) of the constituent species. This implies that correlation effects are significantly stronger in water-alcohol mixtures than for the constituent species. Correlation effects are found to be significant for water-alcohol mixture diffusion in DDR and LTA zeolites, even though such effects are negligible for the pure constituents. The major conclusion to emerge from this investigation is that, unlike mixtures of nonpolar molecules, it is not possible to estimate water-alcohol mixture adsorption and diffusion characteristics on the basis of pure component data.


On the applicability of local softness and hardness.
Global hardness and softness and the associated hard/soft acid/base (HSAB) principle have been used to explain many experimental observed reactivity patterns and these concepts can be found in textbooks of general, inorganic, and organic chemistry. In addition, local versions of these reactivity indices and principles have been defined to describe the regioselectivity of systems. In a very recent article (Chem.-Eur. J. 2008, 14, 8652), the present authors have shown that the picture of these well-known descriptors is incomplete and that the understanding of these reactivity indices must be "reinterpreted". In fact, the local softness and hardness contain the same "potential information" and they should be interpreted as the "local abundance" or "concentration" of their corresponding global properties. In this contribution, we analyze the implications of this new point of view for the applicability of these well-known descriptors when comparing two sites in three situations: two sites within one molecule, two sites in two different, but noninteracting molecules, and two sites in two different, but interacting, molecules. The implications on the HSAB principle are highlighted, leading to the discussion of the role of the electrostatic interaction.


A hierarchical unsupervised growing neural network for clustering gene expression patterns.
We describe a new approach to the analysis of gene expression data coming from DNA array experiments, using an unsupervised neural network. DNA array technologies allow monitoring thousands of genes rapidly and efficiently. One of the interests of these studies is the search for correlated gene expression patterns, and this is usually achieved by clustering them. The Self-Organising Tree Algorithm, (SOTA) (Dopazo,J. and Carazo,J.M. (1997) J. Mol. Evol., 44, 226-233), is a neural network that grows adopting the topology of a binary tree. The result of the algorithm is a hierarchical cluster obtained with the accuracy and robustness of a neural network. SOTA clustering confers several advantages over classical hierarchical clustering methods. SOTA is a divisive method: the clustering process is performed from top to bottom, i.e. the highest hierarchical levels are resolved before going to the details of the lowest levels. The growing can be stopped at the desired hierarchical level. Moreover, a criterion to stop the growing of the tree, based on the approximate distribution of probability obtained by randomisation of the original data set, is provided. By means of this criterion, a statistical support for the definition of clusters is proposed. In addition, obtaining average gene expression patterns is a built-in feature of the algorithm. Different neurons defining the different hierarchical levels represent the averages of the gene expression patterns contained in the clusters. Since SOTA runtimes are approximately linear with the number of items to be classified, it is especially suitable for dealing with huge amounts of data. The method proposed is very general and applies to any data providing that they can be coded as a series of numbers and that a computable measure of similarity between data items can be used. A server running the program can be found at: http://bioinfo.cnio.es/sotarray.


Kidney α-intercalated cells and lipocalin 2: defending the urinary tract.
A growing body of evidence indicates that the kidneys contribute substantially to immune defense against pathogens in the urinary tract. In this issue, Paragas et al. report that α-intercalated cells (A-ICs) within the nephron collecting duct sense infecting Gram-negative bacteria, resulting in simultaneously secretion of the iron chelating protein lipocalin 2 (LCN2) and protons, which acidify the urine. A-IC-specific LCN2 and proton secretion markedly reduced the ability of infecting uropathogenic E. coli (UPEC) to grow and sustain infection. The capacity of A-ICs to sense and actively promote clearance of infecting bacteria in the lower urinary tract represents a novel function for these specialized kidney cells, which are best known for their role in modulating acid-base homeostasis.


Flavour spectrum of the Puff family of disposable e-cigarettes.
In January 2020, the US Food and Drug Administration prohibited the sale of flavours (except for menthol and tobacco) in prefilled pod devices such as JUUL to decrease youth vaping. Excluded from the prohibition were disposable devices. To determine the scope and scale of flavours marketed by Puff Bar, a leading disposable brand, and related products. Disposable e-cigarette flavours were identified via online searches encompassing vendor websites, wholesale distributors, manufacturers (eg, made-in-china.com), and social media channel, Instagram, between June and August 2020. The 'Puff' brand name and iconic cloud logo appear on a variety of products of differing sizes and nicotine e-liquid volumes. Among Puff Bar and its copycats (Puff-a-Likes), 139 flavours were identified. Fruit flavours predominated comprising 82.2% of the flavour varieties (fruit 50%, fruit and menthol/mint 23.6%, and fruity drinks 8.6%). A prevalent new flavour category which combines fruit with menthol/mint (Ice) was offered in 33 varieties such as Lychee Ice, Lush Ice and Banana Ice. Disposable e-cigarette brands are undertaking measures to escape tobacco regulation (eg, non-tobacco-sourced nicotine) and flavour limitations via post-market flavour additions to unflavoured nicotine e-liquid. The proliferation of flavoured disposable e-cigarette products, many of which are designed to emulate popular pod devices, illustrates that narrowly limited flavour regulations covering only a single category are destined to fail. To be effective in youth protection, flavour regulations need to apply to all recreational nicotine-containing products and need to include measures to counter post-market flavour addition.


ISSR markers show differentiation among Italian populations of Asparagus acutifolius L.
Asparagus acutifolius L. is a dioecious and native plant species, widely distributed in the Mediterranean Basin. It is known for its fine flavour and could represent an important resource for cultivation programs in desert areas. Few molecular studies have been performed on this species. In the present paper, the ISSR technique was employed to study genetic diversity in Italian A. acutifolius. Twenty-three primers produced a total of 228 polymorphic fragments used to evaluate genetic variation. FST (0.4561) and Theta B (0.4776) values indicate a wide genetic variation among the samples examined. The distance UPGMA tree grouped together the genotypes strictly according to their geographical origin, showing that each sample is genetically structured and can be considered a distinct population. AMOVA analysis further confirmed genetic structuring of the populations. Population-specific fragments were also detected. The results suggest that ISSR markers are useful in distinguishing the populations of A. acutifolius according to geographical origin, and confirm the importance of genetic studies for designing germplasm conservation strategies.


Genotyping of Coxiella burnetii from domestic ruminants in northern Spain.
Information on the genotypic diversity of Coxiella burnetii isolates from infected domestic ruminants in Spain is limited. The aim of this study was to identify the C. burnetii genotypes infecting livestock in Northern Spain and compare them to other European genotypes. A commercial real-time PCR targeting the IS1111a insertion element was used to detect the presence of C. burnetii DNA in domestic ruminants from Spain. Genotypes were determined by a 6-loci Multiple Locus Variable number tandem repeat analysis (MLVA) panel and Multispacer Sequence Typing (MST). A total of 45 samples from 4 goat herds (placentas, N = 4), 12 dairy cattle herds (vaginal mucus, individual milk, bulk tank milk, aerosols, N = 20) and 5 sheep flocks (placenta, vaginal swabs, faeces, air samples, dust, N = 21) were included in the study. Samples from goats and sheep were obtained from herds which had suffered abortions suspected to be caused by C. burnetii, whereas cattle samples were obtained from animals with reproductive problems compatible with C. burnetii infection, or consisted of bulk tank milk (BTM) samples from a Q fever surveillance programme. C. burnetii genotypes identified in ruminants from Spain were compared to those detected in other countries. Three MLVA genotypes were found in 4 goat farms, 7 MLVA genotypes were identified in 12 cattle herds and 4 MLVA genotypes were identified in 5 sheep flocks. Clustering of the MLVA genotypes using the minimum spanning tree method showed a high degree of genetic similarity between most MLVA genotypes. Overall 11 different MLVA genotypes were obtained corresponding to 4 different MST genotypes: MST genotype 13, identified in goat, sheep and cattle from Spain; MST genotype 18, only identified in goats; and, MST genotypes 8 and 20, identified in small ruminants and cattle, respectively. All these genotypes had been previously identified in animal and human clinical samples from several European countries, but some of the MLVA genotypes are described here for the first time. Genotyping revealed a substantial genetic diversity among domestic ruminants from Northern Spain.


Spontaneous lambda OR mutations suppress inhibition of bacteriophage growth by nonimmune exclusion phenotype of defective lambda prophage.
Survivor clones with defects in gene functions that participate in the replicative killing of thermally induced Escherichia coli constructs with integrated lambda N through P or cIII through P gene fragments were selected at a frequency of about 10(-6). Among the population of survivors, clones were identified that exhibited normal lambda immunity at 30 degrees C, as shown by their ability to prevent the plating of lambda wild type and to support the plating of a nearly identical heteroimmune bacteriophage lambda imm434. However, when placed at 42 degrees C to inactivate the cIts857 repressor, these survivor isolates excluded the plating of both lambda wild-type and lambda imm434 phages, a phenotype designated nonimmune exclusion (Nie). Spontaneous mutants of lambda wild type were isolated that overcame the Nie phenotype and would plaque at 42 degrees C on cell lawns of these isolates. The acquired lambda se mutations suppressed nonimmune exclusion, prevented lysogenization by interrupting repressor expression from PRM, and made the phage insensitive to replicative inhibition. The se mutations were genetically mapped and sequenced within the rightward lambda operator site.


The cystic fibrosis gut as a potential source of multidrug resistant pathogens.
The emergence of multidrug resistant (MDR) pathogens represents a profound threat to global health. Individuals with CF have amongst the highest cumulative antibiotic exposure of any patient group, including to critically-important last-line agents. While there is little evidence that antibiotic resistance in airway pathogens results in worse clinical outcomes for CF patients, the potential emergence of MDR pathogens in non-respiratory systems, as a consequence of CF care, represents a potential health threat to the wider population, including family and carers. Stool from 19 adults with CF and 16 healthy adult controls was subjected to metagenomic sequencing, to assess faecal resistome, and culture-based analysis. Resistant isolates were identified phenotypically, and genetic determinants of resistance characterised by whole genome sequencing. CF and control faecal resistomes differed significantly (P = 0.0003). The proportion of reads that mapped to mobile genetic elements was significantly higher in CF (P = 0.014) and the composition was significantly different (P = 0.0001). Notably, CF patients displayed higher carriage of plasmid-mediated aminoglycoside-modifying genes ant(6)-Ib, aac(6')-Ip, and aph(3')-IIIa (P < 0.01). Culture-based analysis supported higher aminoglycoside resistance, with a higher proportion of aminoglycoside-resistant, Gram-negative bacteria (P < 0.0001). Isolated extended spectrum beta lactamase (ESBL)-positive Escherichia coli from CF stool exhibited phenotypic resistance to tobramycin and gentamicin. Genomic analysis showed co-localisation of both aminoglycoside resistance and ESBL genes, consistent with MDR emergence through horizontal gene transfer. The carriage of potentially transmissible resistance within the adult CF gut microbiome is considerably greater than in healthy individuals and could contribute to the emergence and dissemination of MDR pathogens.


[The Dead Sea--a unique resort for patients suffering from joint diseases].
The Dead Sea area is an excellent and unique resort for patients suffering from a wide range of inflammatory and non-inflammatory joint diseases. Factors contributing to the beneficial effect are the high concentration of salts and minerals in the Dead Sea water and in the water from springs in the area, medical mud, and the unique climatic conditions including high barometric pressure, relative low humidity and high temperatures. This review describes the various balneotherapy modalities and the existing body of research describing their utility. Balneotherapy significantly improves most patients' conditions and in some cases leads to complete remission of several months duration. Although of importance, balneotherapy is not curative. An important advantage of balneotherapy is the lack of serious adverse effects, and, in contrast to some physicians' beliefs, the scarcity of contraindications for therapy at the Dead Sea area.


EGFI: drug-drug interaction extraction and generation with fusion of enriched entity and sentence information.
The rapid growth in literature accumulates diverse and yet comprehensive biomedical knowledge hidden to be mined such as drug interactions. However, it is difficult to extract the heterogeneous knowledge to retrieve or even discover the latest and novel knowledge in an efficient manner. To address such a problem, we propose EGFI for extracting and consolidating drug interactions from large-scale medical literature text data. Specifically, EGFI consists of two parts: classification and generation. In the classification part, EGFI encompasses the language model BioBERT which has been comprehensively pretrained on biomedical corpus. In particular, we propose the multihead self-attention mechanism and packed BiGRU to fuse multiple semantic information for rigorous context modeling. In the generation part, EGFI utilizes another pretrained language model BioGPT-2 where the generation sentences are selected based on filtering rules. We evaluated the classification part on 'DDIs 2013' dataset and 'DTIs' dataset, achieving the F1 scores of 0.842 and 0.720 respectively. Moreover, we applied the classification part to distinguish high-quality generated sentences and verified with the existing growth truth to confirm the filtered sentences. The generated sentences that are not recorded in DrugBank and DDIs 2013 dataset demonstrated the potential of EGFI to identify novel drug relationships. Source code are publicly available at https://github.com/Layne-Huang/EGFI.


A comparison of trapping methods for Tabanidae (Diptera) in North Queensland, Australia.
The ability to monitor the abundance and diversity of tabanid flies over wide areas requires effective and low-cost surveillance methods. Such monitoring activities help to quantify the risk of transmission of pathogens by tabanids. Here we examine the effectiveness and practicality of two types of trap (canopy traps and Nzi traps) and two types of attractant (octenol and carbon dioxide) for monitoring tabanid flies in tropical Australia. The Nzi trap consistently caught more tabanids and more species of tabanids than the canopy trap. It was also more robust and therefore required less maintenance in remote locations. The use of attractants substantially increased capture rates, both of individuals and species, and traps using both attractants were consistently the most effective. However, in remote locations, where it is not possible to check traps frequently, the use of attractants may not be feasible. When attractants were not used, the canopy trap caught very few tabanids, but the Nzi trap remained effective enough to be useful as a monitoring device. In addition, the number of tabanid species caught by the Nzi traps remained high, and included those that were most abundant. We therefore conclude that, in this region, Nzi traps are preferable for tabanid monitoring and that attractants greatly improve their effectiveness. However, for longterm monitoring, especially in remote locations, Nzi traps without attractants are a satisfactory option.


Low-grade salivary duct carcinoma or low-grade intraductal carcinoma? Review of the literature.
Low-grade salivary duct carcinoma (LG-SDC) is a rare neoplasm characterized by predominant intraductal growth, luminal ductal phenotype, bland microscopic features, and favorable clinical behavior with an appearance reminiscent of florid to atypical ductal hyperplasia to low grade intraductal breast carcinoma. LG-SDC is composed of multiple cysts, cribriform architecture with "Roman Bridges", "pseudocribriform" proliferations with floppy fenestrations or irregular slits, micropapillae with epithelial tufts, fibrovascular cores, and solid areas. Most of the tumor cells are small to medium sized with pale eosinophilic cytoplasm, and round to oval nuclei, which may contain finely dispersed or dark condensed chromatin. Foci of intermediate to high grade atypia, and invasive carcinoma or micro-invasion have been reported in up to 23 % of cases. The neoplastic cells have a ductal phenotype with coexpression of keratins and S100 protein and are surrounded by a layer of myoepithelial cells in non-invasive cases. The main differential diagnosis of LG-SDC includes cystadenoma, cystadenocarcinoma, sclerosing polycystic adenosis, salivary duct carcinoma in situ/high-grade intraductal carcinoma, and papillary-cystic variant of acinic cell carcinoma. There is no published data supporting the continuous classification of LG-SDC as a variant of cystadenocarcinoma. Given that most LG-SDC are non-invasive neoplasms; the terms "cribriform cystadenocarcinoma" and LG-SDC should be replaced by "low-grade intraductal carcinoma" (LG-IDC) of salivary gland or "low-grade intraductal carcinoma with areas of invasive carcinoma" in those cases with evidence of invasive carcinoma.


Architecture of coatomer: molecular characterization of delta-COP and protein interactions within the complex.
Coatomer is a cytosolic protein complex that forms the coat of COP I-coated transport vesicles. In our attempt to analyze the physical and functional interactions between its seven subunits (coat proteins, [COPs] alpha-zeta), we engaged in a program to clone and characterize the individual coatomer subunits. We have now cloned, sequenced, and overexpressed bovine alpha-COP, the 135-kD subunit of coatomer as well as delta-COP, the 57-kD subunit and have identified a yeast homolog of delta-COP by cDNA sequence comparison and by NH2-terminal peptide sequencing. delta-COP shows homologies to subunits of the clathrin adaptor complexes AP1 and AP2. We show that in Golgi-enriched membrane fractions, the protein is predominantly found in COP I-coated transport vesicles and in the budding regions of the Golgi membranes. A knock-out of the delta-COP gene in yeast is lethal. Immunoprecipitation, as well as analysis exploiting the two-hybrid system in a complete COP screen, showed physical interactions between alpha- and epsilon-COPs and between beta- and delta-COPs. Moreover, the two-hybrid system indicates interactions between gamma- and zeta-COPs as well as between alpha- and beta' COPs. We propose that these interactions reflect in vivo associations of those subunits and thus play a functional role in the assembly of coatomer and/or serve to maintain the molecular architecture of the complex.


Pharmaceutical and Biomedical Applications of Green Synthesized Metal and Metal Oxide Nanoparticles.
Due to the rapid growth in life threatening diseases such as cancer, diabetes, chronic wound and HIV/AIDS along with rise of side effects of the current treatments, world is now focusing to utilize new treatment options. Currently, the development of green nanotechnology field seems as a potential alternate for diseases diagnosis and treatment by preparation of various sizes and shapes of nanomaterials. This review is to present the explored biological sources in synthesis of nanomaterials particularly metal and metal oxides nanoparticles and critical review of the applications of biosynthesized nanoparticles in pharmaceutical and biomedical fields. In this review, the various biological sources including bacteria, fungi, algae and plants used in synthesis of nanomaterials and mechanism involved in preparation are elaborated. In addition, biosynthesized nanomaterials applied as drug delivery system for anticancer, antibiotic, antidiabetic agent and functioned as potential diagnostic, antimicrobial, anticancer and wound healing candidates are comprehensively reviewed. The synthesized metal and metal oxides from green protocol proved to have advantages such as being biocompatible, effective and cheap. Furthermore, the green synthesized metal and metal oxide nanoparticles showed to possess prominent physical, chemical and biological properties that can be efficiently utilized for pharmaceutical and biomedical applications. The information gathered in this review will provide a baseline for exploring more potential usage of green synthesized metal and metal oxide nanomaterials for various other applications. However, a concrete understanding of the safety of these nanomaterials is still needed to minimize the potential side effects.


[Disinfection of sewage waters from rendering plants by means by peracetic acid].
In our experiments, peracetic acid -- known in commerce as "Wolfasteril" was tested as a new and efficient disinfectant to disinfect sewage waters from rendering plants. Peracetic acid was used in experiments in concentration of 0.1 to 1.0% for 30 sec. to 60 min. As a comparative agent, 5% chloramine was used. Results obtained in preliminary and main experiments proved that peracetic acid is fully appropriate to disinfect biologically cleaned sewage waters in rendering plants. Sewage waters supplying the main stream has to pass mostly a short section after having left the water clariflier. Consequently, the concentration of 1% peracetic acid acting for 30 sec. is the optimum one. The recommendation of this application norm for peracetic acid in water clarifiers from rendering plants being at least suitable in controlling disasters.


Serum anti-mullerian hormone levels reflect the size of the primordial follicle pool in mice.
Reproductive aging is the decline of female fertility with age. It is caused by the decrease in the number of growing follicles, resulting from primordial follicle pool depletion. Recently, we have shown that anti-Müllerian hormone (AMH) is produced by growing follicles, and studies in women indicate that serum AMH levels decrease with age and correlate with antral follicle count. However, whether serum AMH levels correlate directly with the size of the primordial follicle pool cannot be determined in women. In this work, we describe studies in mice in which we determined the dynamics of ovarian follicles during aging. Furthermore, we describe the development of a mouse AMH ELISA, allowing us to measure AMH levels in mice, for the first time. We observed that serum AMH levels decline with increasing age, whereas expression of AMH in individual growing follicles, studied by immunohistochemistry, did not change with age. Thus, the decline in serum AMH correlates directly with the decline in the number of growing follicles (r = 0.86, P < 0.0001). We observed that the number of growing follicles correlated with the number of primordial follicles (r = 0.93, P < 0.0001). Similarly, we found a strong correlation between AMH levels and number of primordial follicles (r = 0.83, P < 0.0001). In conclusion, serum AMH levels reflect the size of the primordial follicle pool in aging mice. Therefore, AMH is an excellent marker to assess the quantitative aspect of ovarian reserve, which may be useful for women at risk for early ovarian aging such as survivors of childhood cancers.


Regulation of rat AMP deaminase 3 (isoform C) by development and skeletal muscle fibre type.
AMP deaminase (AMPD) is characterized by a multigene family in rodents and man. Highly conserved rat and human AMPD1 and AMPD2 genes produce protein products that exhibit cross-species immunoreactivities (AMPD1, rat isoform A and human isoform M; AMPD2, rat isoform B and human isoform L). A third gene, AMPD3, has been described in humans, but antisera raised against its purified protein product (isoform E) reportedly does not cross-react with a third activity purified from rat tissues (isoform C). This study was designed to address this latter issue by cloning, sequencing and expressing rat AMPD3 cDNA species. Similarly to the human AMPD3 gene, the rat AMPD3 gene produces multiple transcripts that differ at or near their 5' ends. The boundary at which these alternative sequences diverge is precisely conserved in both species. Across the region that is common to all rat and human AMPD3 cDNA species, nucleotide and predicted amino acid sequences are 89% and 93% identical respectively, although the rat open reading frame is lacking two separate in-frame codons in the 5' end. Extreme 5' regions between the two species are entirely divergent, and one alternative rat sequence is predicted to confer at least 36 additional N-terminal residues to its encoded AMPD3 polypeptide. A comparison of 3' untranslated regions indicates that the rat sequence is 250 bp longer and contains multiple consensus polyadenylation signals. Examination of relative rat AMPD3 gene expression shows (1) variable patterns of alternative mRNA abundance across adult tissues, (2) developmental regulation in skeletal muscle and liver, and (3) greater mRNA abundance in adult red (soleus) than in mixed (plantaris) and white (outer gastrocnemius) skeletal muscle. Finally, baculoviral expression of rat and human AMPD3 proteins produces enzymes that are chromatographically and kinetically similar. Moreover, both recombinant activities immunoreact with anti-C and anti-E serum. These combined results demonstrate that rat isoform C and human isoform E are homologous cross-species AMPD3 proteins.


Overactive Bladder and Cognitive Impairment: The American Urogynecologic Society and Pelvic Floor Disorders Research Foundation State-of-the-Science Conference Summary Report.
Overactive bladder (OAB) is prevalent in older adults in whom management is complicated by comorbidities and greater vulnerability to the cognitive effects of antimuscarinic medications. The aim of this study is to provide a comprehensive evidence-based summary of the 2021 State-of-the-Science (SOS) conference and a multidisciplinary expert literature review on OAB and cognitive impairment. The American Urogynecologic Society and the Pelvic Floor Disorders Research Foundation convened a 3-day collaborative conference. Experts from multidisciplinary fields examined cognitive function, higher neural control of the OAB patient, risk factors for cognitive impairment in older patients, cognitive effects of antimuscarinic medications for OAB treatment, OAB phenotyping, conservative and advanced OAB therapies, and the need for a multidisciplinary approach to person-centered treatment. Translational topics included the blood-brain barrier, purine metabolome, mechanotransduction, and gene therapy for OAB targets. Research surrounding OAB treatment efficacy in cognitively impaired individuals is limited. Short- and long-term outcomes regarding antimuscarinic effects on cognition are mixed; however, greater anticholinergic burden and duration of use influence risk. Oxybutynin is most consistently associated with negative cognitive effects in short-term, prospective studies. Although data are limited, beta-adrenergic agonists do not appear to confer the same cognitive risk. The 2021 SOS summary report provides a comprehensive review of the fundamental, translational, and clinical research on OAB with emphasis on cognitive impairment risks to antimuscarinic medications. Duration of use and antimuscarinic type, specifically oxybutynin when examining OAB treatments, appears to have the most cognitive impact; however, conclusions are limited by the primarily cognitively intact population studied. Given current evidence, it appears prudent to minimize anticholinergic burden by emphasizing nonantimuscarinic therapeutic regimens in the older population and/or those with cognitive impairment.