B-1 cells are pivotal for in vivo inflammatory giant cell formation.
The mechanisms that govern giant cell (GC) formation in inflammatory, neoplastic and physiologic conditions are far from being understood. Here, we demonstrate that B-1 cells are essential for foreign-body GC formation in the mouse. GCs were analysed on the surface of glass cover slips implanted into the subcutaneous tissue of the animals. It was demonstrated that GCs are almost absent on cover slips implanted into the subcutaneous tissue of BALB/c or CBA/N X-linked immunodeficient mice. As these animals do not have B-1 cells in the peritoneal cavity, they were reconstituted with B-1 cells obtained from cultures of adherent mouse peritoneal cells. Results showed that in B-1-reconstituted animals, the number of GCs on the implant surface surpassed the values obtained with preparations from wild animals. In animals selectively irradiated (pleural and peritoneal cavities) to deplete these cavities of B-1 cells, GCs were also not formed. Enriched suspensions of B-1 cells grown in culture were labelled with [(3)H]-tymidine and injected into the peritoneal cavity of naive mice before implantation of glass cover slips. After 4 days, about 17% of mononuclear cells had their nuclei labelled, and almost 70% of GCs had one or more of their nuclei labelled when analysed by histoautoradiographic technique. A few GCs expressed an immunoglobulin M when analysed by immunostaining and confocal microscopy. Overall, these data demonstrate that B-1 cells are pivotal in the mechanisms of foreign-body GC formation in the mouse.


Evaluation of a novel serum IgG4 assay and determination of reference interval for the Japanese population.
IgG4-related disease (IgG4-RD) is a new syndrome characterized by elevated serum IgG4 concentration and tissue infiltration of IgG4-positive plasma cells. Here, we evaluated the analytical performance of a new IgG4 assay reagent featuring a wide dynamic range, highly specific monoclonal antibody, and the reversed passive latex agglutination assay and determined the IgG4 reference interval (RI) for the Japanese population. Performance evaluations were conducted on precision, linearity, sensitivity, interference, and method comparison with The Binding Site (TBS) and Siemens reagents. The RI was derived by the parametric method from 619 apparently healthy Japanese 18 to 65 years of age. Between-day precisions ranged from 1.99 to 5.52 CV%. Linearity was confirmed up to 5.0 g/l. The limit of quantitation was 0.085 g/l. Interfering substances did not significantly influence values. Method comparison among the 3 reagents yielded correlation coefficients between 0.973 and 0.988. Values for the new reagent matched those of TBS reagent except at a higher concentration range, where reactivity dissociated. The RI was 0.11-1.21 g/l without distinction by sex and age. The novel IgG4 assay reagent demonstrated satisfactory analytical performance for clinical use. Because of matched value with TBS reagent at low concentrations, it is possible to use the IgG4-RD cut-off value determined by TBS reagent.


Critically engaging: integrating the social and the biomedical in international microbicides research.
Randomized controlled trials and critical social theory are known not to be happy bedfellows. Such trials are embedded in a positivist view of the world, seeking definitive answers to testable questions; critical social theory questions the methods by which we deem the world knowable and may consider experiments in the biomedical sciences as social artifacts. Yet both of these epistemologically and methodologically divergent fields offer potentially important advances in HIV research. In this paper, we describe collaboration between social and biomedical researchers on a large, publicly funded programme to develop vaginal microbicides for HIV prevention. In terms of critical engagement, having integrated and qualitative social science components in the protocol meant potentially nesting alternative epistemologies at the heart of the randomized controlled trial. The social science research highlighted the fallibility and fragility of trial data by demonstrating inconsistencies in key behavioural measurements. It also foregrounded the disjuncture between biomedical conceptions of microbicides and the meanings and uses of the study gel in the context of users' everyday lives. These findings were communicated to the clinical and epidemiological members of the team on an ongoing basis via a feedback loop, through which new issues of concern could also be debated and, in theory, data collection adjusted to the changing needs of the programme. Although critical findings were taken on board by the trialists, a hierarchy of evidence nonetheless remained that limited the utility of some social science findings. This was in spite of mutual respect between clinical epidemiologists and social scientists, equal representation in management and coordination bodies, and equity in funding for the different disciplines. We discuss the positive role that social science integrated into an HIV prevention trial can play, but nonetheless highlight tensions that remain where a hierarchy of epistemologies exists alongside competing paradigms and priorities.


Gastric necrosis: a rare complication of gastric banding.
In the last decade, laparoscopic gastric banding has become an increasingly popular surgical option for morbidly obese patients, because of the minimally invasive and easy surgical technique, its reversibility, and the possibility to calibrate the stoma. Gastric necrosis, as a complication of laparoscopic gastric banding, has been only rarely reported. Herein described is the case of a 45-year-old obese patient with gastric necrosis occurring 2 years after the placement of the band. After initial conservative management, the patient underwent urgent surgery. A huge anterior gastric prolapse through the band was found to be responsible for necrosis of the herniated stomach. An upper polar gastrectomy was performed. The mechanisms responsible for this life-threatening complication are discussed.


Pyrolytic oil blended gasoline as future fuel: pyrolysis mechanism, fuel properties, and composition analysis.
In this investigation, waste motor oil (WMO) was pyrolyzed at 550 °C which yielded about 76.73 wt.% of pyrolytic oil (PO). To study the effect of blending with gasoline on the fuel properties and composition, the PO was blended at 5-30% with an augmentation of 5% by volume. The respective fuel properties of all the blends were determined and compared with gasoline. The prime blending percentage of WMO pyrolytic oil (WMOPO) was established based on the gross calorific value obtained. Among all the blends, 5% blending PO (B5) ensued the highest calorific value about 45.63 MJ kg-1 which was adjacent to gasoline. The B5 oil was also having an analogous density as gasoline. The composition analysis visualized that B5 comprised of alkenes (1.25%), cycloalkanes (3.88%), cycloalkenes (2.43%), aromatics (25.38%), and alkanes (53.75%). The results also confirmed the occurrence of 50.52% of C4-C12 compounds. Since the fuel properties and composition of the B5 oil were comparable to the untainted gasoline, it can be a suitable proportion to consider as future fuel if the engine performance and emission analysis show any positive effects.


Proximal gastrectomy and double-tract reconstruction vs total gastrectomy in gastric and gastro-esophageal junction cancer patients - a systematic review and meta-analysis protocol (PROSPERO registration number: CRD42021291500).
In Germany and Western Europe, gastroesophageal junction cancer (AEG) and proximal gastric cancer are currently treated with (transhiatal-extended) total gastrectomy (TG) according to the latest treatment guidelines. TG leads to a severe and long-lasting impairment of postoperative health-related quality of life (HRQoL) of the treated patients. Recent studies have suggested that HRQoL of these patients could be improved by proximal gastrectomy with double-tract reconstruction (PG-DTR) without compromising oncologic safety. Our aim is therefore to conduct a randomized controlled non-inferiority trial comparing PG-DTR with TG in AEG II/III and gastric cancer patients with overall survival as primary endpoint and HRQoL as key secondary endpoint. This protocol is written with reference to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P 2015) statement. We will conduct searches in the electronic databases MEDLINE, Web of Science Core Collection, ScienceDirect, and Cochrane Library. We will also check references of relevant studies and perform a cited reference research. Titles and abstracts of the records identified by the searches will be screened, and full texts of all potentially relevant articles will be obtained. We will consider randomized trials and non-randomized studies. The selection of studies, data extraction, and assessment of risk of bias of the included studies will be conducted independently by two reviewers. Meta-analysis will be performed using RevMan 5.4 (Review Manager (RevMan) Version 5.4, The Cochrane Collaboration). This systematic review will identify the current study pool concerning the comparison of TG and PG-DTR and help to finally refine the research questions and to allow an evidence-based trial design of the planned multicenter randomized-controlled trial. Ethical approval is not required for this systematic review. Study findings will be shared by publication in a peer-reviewed journal. PROSPERO CRD42021291500.


The use of dreams in psychotherapy: practical guidelines.
Although there is a large literature pertaining to the use of the dream in psychoanalysis, there is no systematic approach to working with dreams in psychotherapy. This communication seeks to present some guidelines for the use of the dream in psychotherapy. Reference is made to the significant difference in the "dimensions" of psychoanalysis as compared to psychotherapy. A distinction is drawn between the use of the dream in supportive psychotherapy as contrasted with insight-oriented psychotherapy. In the former, the dream--if used at all--serves supportive functions; in the latter, the goals are to develop better awareness by the patient of himself. Understanding of the dream is reached by inserting it into the context of the patient's psychological life; however, what is actually communicated to the patient will be keyed to the psychologic surface that the patient presents.


Cytomegalovirus retinitis and FK 506.
To report a case of cytomegalovirus (CMV) retinitis in a patient immunosuppressed with FK 506. Interventional case report. Retrospective institutional study. One patient, diagnosed with bilateral CMV retinitis while on immunosuppressive treatment with FK 506, received systemic ganciclovir and intravitreal, slow-release ganciclovir implant in one eye, combined with reduction in FK 506 dose. Main outcome measures were visual acuity and regression of CMV retinitis. Visual acuity at presentation was 20/20 in the right eye and 20/50 in the left eye. During the 6 months of follow-up, there was no change in visual acuity in either eye. The areas of CMV retinitis demonstrated progressive regression, leaving diffuse retinal atrophy. Cytomegalovirus retinitis can be a sight-threatening complication of immunosuppressive treatment with FK 506. Ganciclovir treatment together with a reduction in FK 506 dose was effective in preserving vision.


Beat the clock: paradigms for NTPases in the maintenance of biological fidelity.
Kinetic proofreading is a strategy used by cells to reduce the number of errors made when replicating and expressing genetic information. Recent advances in mRNA splicing suggest a variation on the theme of previously described kinetic proofreading mechanisms, which may apply to other multicomponent assembly processes in the cell.


[Neuropathies following hand surgery under supraclavicular plexus anesthesia].
15 cases with pain in the shoulder girdle following an operation in supraclavicular brachial plexus anesthesia are reported. The pain developped after an interval of several days. According to the neurological findings the diagnosis is regarded as neuralgic amyotrophy. Possible causes are discussed.


Application of first-generation high- and low-dose drug-coated balloons to the femoropopliteal artery disease: a sub-analysis of the POPCORN registry.
Drug-coated balloons (DCBs) have significantly changed endovascular therapy (EVT) for femoropopliteal artery (FPA) disease, in terms of the expansion of indications for EVT for symptomatic lower extremity arterial disease (LEAD). However, whether there is a difference in the performance among individual DCBs has not yet been fully discussed. The present sub-analysis of real-world data from a prospective trial of first-generation DCBs compared the clinical outcomes between high- and low-dose DCBs using propensity score matching methods. The primary endpoint was the restenosis-free and revascularization-free rates at 1 year. We compared 592 pairs matched for patient and lesion characteristics using propensity score matching among a total of 2,507 cases with first-generation DCBs (592 and 1,808 cases in the Lutonix low-dose and In.PACT Admiral high-dose DCB groups, respectively). There were no differences in patient/lesion characteristics, procedural success rates, or complications between the two groups. First-generation low-dose DCB had significantly lower patency (73.3% [95% confidence interval, 69.6%-77.3%] in the low-dose DCB group versus 86.2% [84.1%-88.3%] in the high-dose DCB group; P < 0.001) and revascularization-free (84.9% [81.9%-88.1%] versus 92.5% [90.8%-94.1%]; P < 0.001) rates. Chronic kidney disease on dialysis, cilostazol use, anticoagulant use, and severe calcification had a significant interaction effect in the association (all P < 0.05). EVT to FPA with first-generation DCBs had inferior low-dose patency outcomes as compared with high-dose outcomes in the present cohort. Sub analysis of a prospective multicenter study.


Transient pockets as mediators of gas molecules routes inside proteins: The case study of dioxygen pathway in homogentisate 1,2-dioxygenase and its implication in Alkaptonuria development.
Alkaptonuria (AKU) is an ultra-rare disease caused by mutations in homogentisate 1,2-dioxygenase (HGD) enzyme, characterized by the loss of enzymatic activity and the accumulation of its substrate, homogentisic acid (HGA) in different tissues, leading to ochronosis and organ degeneration. Although the pathological effects of HGD mutations are largely studied, less is known about the structure of the enzyme, in particular the pathways for dioxygen diffusion to the active site, required for the enzymatic reaction, are still uninvestigated. In the present project, the combination of two in silico techniques, Molecular Dynamics (MD) simulation and Implicit Ligand Sampling (ILS), was used to delineate gas diffusion routes in HGD enzyme. A route from the central opening of the hexameric structure of the enzyme to the back of the active site trough the protein moiety was identified as the path for dioxygen diffusion, also overlapping with a transient pocket, which then assumes an important role in dioxygen diffusion. Along the route the sequence location of the missense variant E401Q, responsible for AKU development, was also found, suggesting such mutation to be conducive of enzymatic activity loss by altering the flow dynamics of dioxygen. Our in silico approach allowed also to delineate the route of HGA substrate to the active site, until now only supposed.


A technique to orient a stone cast in the fabrication of a nasal prosthesis.
Obtaining the correct orientation of the stone cast in the fabrication of a nasal prosthesis is a challenging task. The current technique involves repeated trials of the waxed nasal prosthesis on the patient's face to establish its correct position. This article proposes a simplified technique to aid in establishing the proper orientation of the stone cast in an effort to decrease the number of error corrections related to midline discrepancies during the wax sculpting stage.


Proarrhythmic effects of ventricular electrical catheter ablation in dogs.
Electrical catheter ablation of arrhythmogenic sites is a new therapy for ventricular tachycardia that is still being investigated. Recent studies have shown, however, that the procedure itself can provoke serious ventricular arrhythmias. The incidence, course and mechanism of these arrhythmias were studied in 10 beagles treated with a single R wave-synchronized cathodal shock delivered to the endocardial ventricular wall (5 dogs left ventricular, 5 dogs right ventricular). Shocks were delivered at 30 (four dogs), 80 (two dogs) or 250 J (four dogs). Each dog underwent programmed electrical stimulation at or near the ablation site before, within 1 hour after and 1 week after the shock. Holter electrocardiographic monitoring (24 hours) was performed during day 1 and 7 after the shock in all the dogs, and extended Holter monitoring was done during the first 5 days in four dogs. All dogs survived for 1 week. Within 10 minutes after the shock, a sustained ventricular tachycardia was recorded in nine dogs; deterioration into ventricular fibrillation occurred in two dogs. In nine dogs, 60 to 169 monomorphic ventricular tachycardia episodes (mean 101) occurred on day 1 and 0 to 11 (mean 3) occurred on day 7; Holter monitoring failed for technical reasons in one dog. Extended Holter monitoring showed a marked decline in the incidence of tachycardia during the first 3 days. Early activation during ventricular tachycardia was always derived at or near the ablation site, and the QRS configuration during pre- and postablation pacing at this site was identical to the tachycardia configuration. Ventricular tachycardia was never inducible with programmed stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)


Hearing Improvement After Type III Tympanoplasty: A Prospective Observational Study.
To analyse the postoperative hearing results of patients undergoing type III tympanoplasty using sculptured homologous spur cartilage. This prospective study included 156 patients of chronic otitis media (COM), between the ages 10-60 years. All cases underwent type III tympanoplasty with ossiculoplasty using homologous spur cartilage. The study sample of 156 patients contained 107 cases of mucosal type and 49 cases of squamosal type COM. Type III A tympanoplasty was done for 71 cases and type III B tympanoplasty was done for 85. Pure tone audiometry (PTA) was done pre and postoperatively, in all the cases. The patients were followed up for 6 months postoperatively. The average preoperative mean air-bone-gap (ABG) was 43.64 dB, whereas in type III A cases it was 39.7 dB and in type III B it was 46.9 dB. The mean ABG at 6th month follow up was 18.9 dB in the study group. In type III A cases, mean ABG was 15.2 dB and in type III B cases it was 22.11 dB. Homogenous spur cartilage graft can be used for ossicular chain reconstruction with the advantage of very low extrusion rate, technically easy to perform with less risk of residual disease.


Acute myocarditis in dengue hemorrhagic fever: a case report and review of cardiac complications in dengue-affected patients.
We report a case of dengue hemorrhagic fever (DHF) complicated by acute myocarditis and review the literature. A 65-year-old woman experienced DHF due to dengue virus serotype 3, complicated with acute myocarditis and acute pulmonary edema. Clinically this masqueraded as acute myocardial infarction, with an electrocardiographically depressed ST segment in precordial leads and elevated serum cardiac-specific troponin I level. Under supportive management, the patient recovered 3 days later. A total of 18 pertinent articles involving 339 dengue-affected patients with cardiac complications were found by PubMed search. Clinical manifestations of cardiac complications varied considerably, from self-limiting tachy-brady arrhythmia to severe myocardial damage, leading to hypotension and pulmonary edema. Although rare, a fatal outcome was reported in some cases of dengue with cardiac complications. To avoid otherwise preventable morbidity and mortality, physicians should have a high index of suspicion for cardiac complications in patients with dengue illness and should manage this accordingly.


Multiple alternatively spliced transcripts of the receptor tyrosine kinase MuSK are expressed in muscle.
We have cloned and characterized five distinct mouse cDNAs encoding isoforms of MuSK, a receptor tyrosine kinase required for the development of the neuromuscular synapse. Comparison of the cDNA sequences with each other and with the mouse genomic sequence revealed that the cDNAs differ by the presence or absence of three alternatively spliced exons encoding an additional 10, 15 and 8 amino acids respectively. The location and sequences of these exons are conserved in MuSK cDNAs from different species. Examination of mouse genomic sequences revealed that the 15 aa exon sequence is present in a 52 bp exon with a non-canonical 3' splice acceptor site at its 5' end and an internal 3' splice acceptor site consensus 45 bp downstream. Transcripts containing each of the alternatively spliced exons were detected in neonatal and adult mouse muscle, as well as in C2 myotubes. The presence of transcripts encoding MuSK isoforms with distinct extracellular domains in developing mouse muscle suggests that alternative splicing could potentially introduce additional complexity to the activity of MuSK in muscle.


Synthesis and anti-breast cancer activities of substituted quinolines.
Promising anti-breast cancer agents derived from substituted quinolines were discovered. The quinolines were readily synthesized in a large scale from a sequence of reactions starting from 4-acetamidoanisole. The Michael addition product was isolated as the reaction intermediate in the ring closing reaction of 4-amino-5-nitro-2-(3-trifluoromethylphenyloxy)anisole with methyl vinyl ketone leading to 6-methoxy-4-methyl-8-nitro-5-(3-trifluoromethylphenyloxy)quinoline (14). The amino function of 8-amino-6-methoxy-4-methyl-5-(3-trifluoromethylphenyloxy)quinoline, prepared from 14, was connected to various side chains via alkylation with N-(3-iodopropyl)phthalimide, Michael addition with acrylonitrile, and reductive amination with various heterocycle carboxaldehydes, such as imidazole-4-carboxaldehyde, thiophene-2-carboxaldehyde, and 2-furaldehyde. Effects of the substituted quinolines on cell viability of T47D breast cancer cells using trypan blue exclusion assay were examined. The results showed that the IC(50) value of 6-methoxy-8-[(2-furanylmethyl)amino]-4-methyl-5-(3-trifluoromethylphenyloxy)quinoline is 16+/-3nM, the lowest IC(50) out of all the quinolines tested. IC(50) values of three other quinolines are in the nanomolar range, a desirable range for pharmacological testing.


Environmental influence on Pristionchus pacificus mouth form through different culture methods.
Environmental cues can impact development to elicit distinct phenotypes in the adult. The consequences of phenotypic plasticity can have profound effects on morphology, life cycle, and behavior to increase the fitness of the organism. The molecular mechanisms governing these interactions are beginning to be elucidated in a few cases, such as social insects. Nevertheless, there is a paucity of systems that are amenable to rigorous experimentation, preventing both detailed mechanistic insight and the establishment of a generalizable conceptual framework. The mouth dimorphism of the model nematode Pristionchus pacificus offers the rare opportunity to examine the genetics, genomics, and epigenetics of environmental influence on developmental plasticity. Yet there are currently no easily tunable environmental factors that affect mouth-form ratios and are scalable to large cultures required for molecular biology. Here we present a suite of culture conditions to toggle the mouth-form phenotype of P. pacificus. The effects are reversible, do not require the costly or labor-intensive synthesis of chemicals, and proceed through the same pathways previously examined from forward genetic screens. Different species of Pristionchus exhibit different responses to culture conditions, demonstrating unique gene-environment interactions, and providing an opportunity to study environmental influence on a macroevolutionary scale.


Leptin gene polymorphism affects leptin level in childhood asthma.
Leptin may induce inflammation in asthma by activation of Th2 cells. It has also been demonstrated that leptin expression increases upon inflammation and that asthmatic patients show increased serum leptin levels. We hypothesized that the polymorphism in leptin (LEP) and leptin receptor (LEPR) genes is associated with childhood asthma and may affect their serum level. To our knowledge, there are no reports analyzing LEP and LEPR polymorphisms in association with their serum levels in childhood asthma. We analyzed 35 subjects: 25 asthmatic pediatric patients and 10 healthy children aged from 6 to 18. The diagnosis of allergic asthma was based on clinical manifestation, lung function, positive skin prick tests and increased immunoglobulin E levels. The polymorphisms were genotyped with use of polymerase chain reaction-restriction fragment length polymorphism method. Serum levels of leptin and leptin receptor were determined using BioVendor enzyme-linked immunosorbent assay kits. Statistical analysis was done with Statistica v.12. We observed that leptin levels were increased in asthmatic subjects as compared to healthy controls and were significantly higher during exacerbation than in the asymptomatic period (P = 0.025). We observed that LEP polymorphism (rs13228377) was associated with higher serum leptin levels in asthma and these two variables had high predictive value for asthma risk (P = 0.007, odds ratio 17.5, predictive accuracy 83.9%). LEPR polymorphisms did not show association with its serum level and asthma risk. LEP polymorphism may increase asthma risk via influence on its serum level.


Bloom's syndrome protein response to ultraviolet-C radiation and hydroxyurea-mediated DNA synthesis inhibition.
Bloom's syndrome (BS) arises through mutations in both copies of the BLM gene that encodes a RecQ 3'-5' DNA helicase. BS patients are predisposed to developing all the cancers that affect the general population, and BS cells exhibit marked genetic instability. We showed recently that BLM protein contributes to the cellular response to ionizing radiation by acting as downstream ATM kinase effector. We now show that following UVC treatment, BLM-deficient cells exhibit a reduction in the number of replicative cells, a partial escape from the G2/M cell cycle checkpoint, and have an altered p21 response. Surprisingly, we found that hydroxyurea-treated BLM-deficient cells exhibit an intact S phase arrest, proper recovery from the S phase arrest, and intact p53 and p21 responses. We also show that the level of BLM falls sharply in response to UVC radiation. This UVC-induced reduction in BLM does not require a functional ATM gene and does not result from a subcellular compartment change. Finally, we demonstrate that exposure to UVC and hydroxyurea treatment both induce BLM phosphorylation via an ATM-independent pathway. These results are discussed in the light of their potential physiological significance with regard to the role of BLM in the cellular pathways activated by UVC radiation or HU-mediated inhibition of DNA synthesis.


Masseter muscle cross over flap in primary closure of oral-oropharyngeal defects.
A new technique of closure of the oral-oropharyngeal defects after tumour surgery in selected cases, using the masseter cross-over flap, has been described.


A case of synchronous bilateral lung cancers: EML4-ALK positive adenocarcinoma in the right lung and adenocarcinoma in situ (the former bronchioloalveolar carcinoma) in the left lung.
Recently it has been revealed that lung adenocarcinomas with distinct gene mutations or fusions are associated with particular histopathological entities. For example, epidermal growth factor receptor (EGFR) gene mutations are often associated with well differentiated adenocarcinoma of the lung with bronchioloalveolar pattern. On the other hand, echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene in a subset of lung adenocarcinoma is related to mucinous cribriform histology. Reported herein is a case of synchronous EML4-ALK positive lung adenocarcinoma and adenocarcinoma in situ in the bilateral lungs of a 55-year-old Japanese woman. The woman had EML4-ALK positive lung adenocarcinoma in the right lower lung while adenocarcinoma in situ in the left upper lung, which was EML4-ALK negative. To our knowledge, this is the first report of synchronous, bilateral lung adenocarcinomas composed of EML4-ALK positive and negative ones.


Exocytotic fusion pore stability and topological defects in the membrane with orientational degree of ordering.
Regulated exocytosis is a process that strongly depends on the formation and stability of the fusion pore. It was indicated experimentally and theoretically that narrow and highly curved fusion pore may be stabilized by accumulation of anisotropic membrane components possessing orientational ordering. On the other hand, narrow fusion pore may also undergo repetitive opening and closing, disruption in the so called kiss and run process or become completely opened in the process of full fusion of the vesicle with the membrane. In this paper we attempt to elucidate the subtle interplay between the stabilizing and destabilizing processes in the fusion neck. A possible physical mechanism which may lead to disruption of the stable fusion pore or complete fusion of the vesicle with the membrane is discussed. It is indicated that topologically driven defects of the in-plane orientational membrane ordering in the region of the fusion pore may disrupt the fusion. Alternatively, it may facilitate repetitive opening and closing of the fusion pore or induce full fusion of the vesicle with the target membrane.


Performance and emission characteristics analysis of thermal barrier coated diesel engine using palm biodiesel.
Various research works are being undertaken around the world on the subject of thermal efficiency improvisation and emission reduction from diesel engines. This research work analyzes the performance and emission characteristics of a thermal barrier coated diesel engine which used palm biodiesel. The piston and cylinder liners were coated with equal percentages of alumina (Al2O3) and yittria-stabilized zirconia (YSZ) powder using plasma spraying coating method. The piston was coated with 100 μm thickness and the two cylinder liners were coated with 150 and 200 μm thicknesses and were used to analyze the performance and emission characteristics. Test results of the thermal barrier coated engine using palm biodiesel were compared with the results derived from the base engine. The tests revealed an increase of 3.8% specific fuel consumption (SFC) as an average when neat palm biodiesel was used in the base engine. Interestingly, the palm biodiesel used in the 150- and 200-μm thick thermal barrier coated engine was responsible for a significant decrease of the SFC by an average of 4.18% and 8.05% respectively. The brake thermal efficiency was found to decrease on an average of 1.02% when tests were run using the neat palm biodiesel in the base engine. But an average proportionate increase of 0.72% and 2.19% was visible when palm biodiesel was used in the tests conducted on the 150- and 200-μm thick thermal barrier coated engine. There was also an understandable brake specific reduction of 0.991 g/kWh carbon monoxide (CO) emission and 0.025 g/kWh unburned hydrocarbon (HC) levels. The nitrogen oxide (NOx) emission was observed as 14.06 g/kWh in the 200-μm thick thermal barrier coated engine which was slightly higher when the results were compared with that of the uncoated engine. The novelty of this research investigation is based on the usage of yttrium-stabilized zirconia and alumina thermal barrier coating on the cylinder liner and piston head of engine. This is justified due to the fact that most of the previous investigations undertaken focused on the thermal barrier coating in the piston, valve, and cylinder head alone. The utility factor of the palm biodiesel (B 100) in the low heat rejection engine has also proved to be another significant and novel factor in the present investigation outlined in this paper. This is mainly due to the fact that the ongoing investigations in this realm concentrated only on blends of 20 to 30% of palm biodiesel with diesel fuel in the low heat rejection diesel engine.


Determinants for in vivo anti-tumor effects of PEG liposomal doxorubicin: importance of vascular permeability within tumors.
To elucidate the determinants of the in vivo anti-tumor efficacy of polyethylene glycol (PEG)-modified liposomal doxorubicin (DOX), we examined its anti-tumor effect against three different tumor cell lines (Lewis lung cancer (LLC), Colon-26 (C26) and B16BL6 melanoma (B16)) in vitro and in vivo. In vitro, LLC was the most sensitive tumor to DOX and liposomal DOX based on the MTT assay. However, the strongest in vivo anti-tumor effect was observed in the C26 tumor-bearing mice. The in vivo accumulation of radiolabelled PEG liposome in the C26 tumor after intravenous injection was significantly larger than in other tumors. The extent of vascularity assessed by immunohistochemical staining of CD31 was not directly related with the tumor accumulation of PEG liposome. On the other hand, Evans blue extravasation and secretion of VEGF in C26 tumors were higher than in LLC tumors, clearly demonstrating that the vasculature permeability was higher within C26 tumors. These results indicated that the vascular permeability within the tumor substantially affects the tumor accumulation of PEG liposome and may be one of the important determinants in the in vivo anti-tumor efficacy of PEG liposomal DOX.


Effect of aerosil dispersions on the nematic-to-isotropic interface.
The effect of silica aerosils on the kinetics of the first-order nematic-isotropic (NI) phase transition is phenomenologically described in the framework of the time-dependent Landau-Ginzburg equation. A steady-state solution to the equation is presented such that the NI interface may propagate with a solitary-like wave profile under constant quenching. The results provide a plausible basis for the interpretation of the dynamical effects of quenched disorder in the liquid-crystal systems, caused by randomly interconnected porous media, such as aerosils. In the low silica aerosil rho(s) ( < or =0.1 g/cm;3) regime, the calculated values of the interface velocity v(T,rho(s)), the interface thickness kappa(T,rho(s)), and the critical radius of a spherical nucleus of new nematic phase in a bulk isotropic environment, composed of polar molecules, such as 4-n-octyl- 4(')- cyanobiphenyl and 4-n-heptyl- 4(')- cyanobiphenyl shows that the effect of silica aerosils on the kinetics is reflected in a shifting of the set of temperature-dependent curves to lower temperature values.-1.


Vascular disease in scleroderma: angiogenesis and vascular repair.
Vascular abnormalities are one of the primary pathologic components of scleroderma. An early vascular indicator is aberrant nail fold capillaries that appear to undergo a switch from a pro- to anti-angiogenic process. Later in the disease process, ineffective and aberrant wound healing becomes apparent with frequent and widespread fibrosis. Pulmonary hypertension, largely due to the loss of pulmonary arterial vasculature, is frequently observed in late stages of the disease. The common theme of all these processes is abnormal regeneration of the vasculature and ongoing vascular losses due to defective maintenance of the vasculature. Although most aspects of vascular injury in scleroderma are poorly understood, certain biologic themes are beginning to emerge that are important in understanding scleroderma-related vascular disease.


Training in minimally invasive surgery in urology: European Association of Urology/International Consultation of Urological Diseases consultation.
To describe the progress being made in training for minimally invasive surgery (MIS) in urology. A group of experts in the field provided input to agree on recommendations for MIS training. A literature search was carried out to identify studies on MIS training, both in general and specifically for urological procedures. The literature search showed the rapidly developing options for e-learning, box and virtual training, and suggested that box training is a relatively cheap and effective means of improving laparoscopic skills. Development of non-technical skills is an integral part of surgical skills training and should be included in training curricula. The application of modular training in surgical procedures showed more rapid skills acquisition. Training curricula for MIS in urology are being developed in both the USA and Europe. Training in MIS has shifted from 'see-one-do-one-teach-one' to a structured learning, from e-learning to skills laboratory and modular training settings.


HIV, highly active antiretroviral therapy and the heart: a cellular to epidemiological review.
The advent of potent highly active antiretroviral therapy (HAART) for persons infected with HIV-1 has led to a "new" chronic disease with complications including cardiovascular disease (CVD). CVD is a significant cause of morbidity and mortality in persons with HIV infection. In addition to traditional risk factors such as smoking, hypertension, insulin resistance and dyslipidaemia, infection with HIV is an independent risk factor for CVD. This review summarizes: (1) the vascular and nonvascular cardiac manifestations of HIV infection; (2) cardiometabolic effects of HAART; (3) atherosclerotic cardiovascular disease (ASCVD) risk assessment, prevention and treatment in persons with HIV-1 infection.


Fibrinous tissue glue in artery anastomosis. Physiological, histological and scanning evaluation.
Twelve arterial anastomoses are performed using fibrinous tissue glue. Long term patency is controlled. Histological and scanning electron microscopical evaluation of the clot formation is performed.


Local circuit regulation of paraventricular nucleus stress integration: glutamate-GABA connections.
Limbic neurocircuits play a central role in regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis. Limbic influences on adrenocortical hormone secretion are mediated by transynaptic activation or inhibition of hypophysiotrophic neurons in the medial parvocellular paraventricular nucleus (PVN). Projections from the ventral subiculum, prefrontal cortex, medial amygdala, lateral septum, paraventricular thalamus and suprachiasmatic nucleus (SN) terminate in the immediate surround of the PVN, an area heavily populated by GABAergic interneurons. As such, these regions are positioned to modulate paraventricular output via excitation or inhibition of interneuronal projections into the PVN. In addition, the same limbic and diencephalic regions have projections to local PVN-projecting hypothalamic and basal telencephalic nuclei, including the dorsomedial and medial preoptic nuclei and the bed nucleus of the stria terminalis. These regions are involved in both inhibitory and excitatory regulation of the stress axis, indicating that they contain heterogeneous neuronal populations whose relative impact on the PVN is determined by the nature of afferent stimuli. Thus, limbic modulation of the pituitary-adrenocortical system appears to be a multisynaptic process integrated at the level of local PVN-projecting neurocircuits. Local circuits are likely the primary integrators of anticipatory stress responses, and may indeed be the focus of HPA dysfunction seen with aging or affective disease.


High β-carotene concentration in plasma enhances cyclic progesterone production in nonpregnant Japanese Black cows.
β-Carotene is an essential nutrient in cattle reproduction. The objective of this study was to evaluate the effect of β-carotene supplementation on ovarian activities throughout the estrous cycle in nonpregnant Japanese Black cows. The estrous cycles of eight nonpregnant Japanese Black cows were synchronized using a double synch protocol, and the cows were divided into two groups. The cows in the β-carotene (BC) group received supplementation with 1000 mg/day β-carotene for 46 days including the synchronization period. The cows in the control (C) group did not receive β-carotene supplementation. The results showed that β-carotene supplementation at 1000 mg/day was sufficient to maintain a high plasma β-carotene concentration and increase the plasma retinol concentration and that β-carotene supplementation had no significant effects on the dominant follicle diameter, total number of estrus behaviors, or length of the estrous cycle. In contrast, the areas under the P4 concentration curves in the BC group were higher than those obtained for the C group. In conclusion, a high plasma β-carotene concentration in Japanese Black cows promotes P4 production in the luteal phase of the estrous cycle and total P4 production throughout the estrous cycle without changing the length of the estrous cycle.


Selective enhancement of the fluorescent pseudomonad population after amending the recirculating nutrient solution of hydroponically grown plants with a nitrogen stabilizer.
Fluorescent pseudomonads have been associated, via diverse mechanisms, with suppression of root disease caused by numerous fungal and fungal-like pathogens. However, inconsistent performance in disease abatement, after their employment, has been a problem. This has been attributed, in part, to the inability of the biocontrol bacterium to maintain a critical threshold population necessary for sustained biocontrol activity. Our results indicate that a nitrogen stabilizer (N-Serve, Dow Agrosciences) selectively and significantly enhanced, by two to three orders of magnitude, the resident population of fluorescent pseudomonads in the amended (i.e., 25 microg ml(-1) nitrapyrin, the active ingredient) and recycled nutrient solution used in the cultivation of hydroponically grown gerbera and pepper plants. Pseudomonas putida was confirmed as the predominant bacterium selectively enhanced. Terminal restriction fragment length polymorphism (T-RFLP) analysis of 16S rDNA suggested that N-Serve selectively increased P. putida and reduced bacterial diversity 72 h after application. In vitro tests revealed that the observed population increases of fluorescent pseudomonads were preceded by an early growth suppression of indigenous aerobic heterotrophic bacteria (AHB) population. Interestingly, the fluorescent pseudomonad population did not undergo this decrease, as shown in competition assays. Xylene and 1,2,4-trimethylbenzene (i.e., the inert ingredients in N-Serve) were responsible for a significant percentage of the fluorescent pseudomonad population increase. Furthermore, those increases were significantly higher when the active ingredient (i.e., nitrapyrin) and the inert ingredients were combined, which suggests a synergistic response. P. putida strains were screened for the ability to produce antifungal compounds and for the antifungal activity against Pythium aphanidermatum and Phytophthora capsici. The results of this study suggest the presence of diverse mechanisms with disease-suppressing potential. This study demonstrates the possibility of using a specific substrate to selectively enhance and maintain desired populations of a natural-occurring bacterium such as P. putida, a trait considered to have great potential in biocontrol applications for plant protection.


Sau-PCR, a novel amplification technique for genetic fingerprinting of microorganisms.
The proposed technique is based on the digestion of genomic DNA with the restriction endonuclease Sau3AI and subsequent amplification with primers whose core sequence is based on the Sau3AI recognition site. The method was tested on strains of lactic acid bacteria but could be proposed for virtually any culturable organism from which DNA can be extracted.


Evidence that contaminated surfaces contribute to the transmission of hospital pathogens and an overview of strategies to address contaminated surfaces in hospital settings.
Evidence that contaminated surfaces contribute to the transmission of hospital pathogens comes from studies modeling transmission routes, microbiologic studies, observational epidemiologic studies, intervention studies, and outbreak reports. This review presents evidence that contaminated surfaces contribute to transmission and discusses the various strategies currently available to address environmental contamination in hospitals.


Type-specific primer-mediated direct sequencing of consensus primer-generated PCR amplicons of human papilloma viruses: a new approach for the simultaneous detection of multiple viral type infections.
Consensus degenerate primers specific for the L1 and E1 regions were used to amplify anogenital HPV-DNA fragments. The mixture of the viral fragments was then directly sequenced with HPV-6, -11, -16, -18 and -33 type-specific computer-designed oligonucleotides as sequencing primers. The linking of a consensus primer-generated PCR amplification with type-specific primer-mediated direct sequencing and computer data bank analysis provided precise, more objective viral detection in the simultaneous presence of different HPV types. The method was successfully adapted for viral typing in clinical lesions which simultaneously contained different anogenital HPV sequences.


Comparative clinical study testing the effectiveness of school based oral health education using experiential learning or traditional lecturing in 10 year-old children.
School based oral health education through traditional lecturing has been found successful only in improving oral health knowledge, while has low effectiveness in oral hygiene and gingival health. The aim of this study was to evaluate the effectiveness of experiential learning (EL) oral health education to traditional lecturing (TL), on enhancing oral health knowledge, attitude and behavior as well as oral hygiene, gingival health and caries of 10-year-old children. Eighty-four children were recruited for the EL and 100 for the TL group from 3 locations in Greece. Data regarding oral health knowledge, attitude and behavior were collected via questionnaires. Data regarding dental plaque, gingivitis and caries were collected by clinical examination. The evaluation using questionnaires and clinical examination was assessed at baseline and 6 and 18 months afterwards. Two calibrated pediatric dentists examined the students using a periodontal probe and artificial light. Modified hygiene index (HI) was used for dental plaque recording, the simplified gingival index (GI-S) was used for gingivitis and DMFT, based on BASCD criteria, for dental caries. Based on a dedicated manual, the teacher applied in the classroom the oral health educational program using EL. EL group had statistically significant better hygiene than the TL at 6 months (p < 0.05). Within the same group, both groups had enhanced oral health knowledge at 6 and 18 months (p < 0.05) and improved oral health behavior (p > 0.05) and attitude (p > 0.05) at 6 months in comparison to baseline. EL program was found more successful than TL in oral hygiene improvement. Both oral health education programs improved the oral health knowledge, attitude and behavior of children. ClinicalTrials.gov (NCT02320162).


Properties of FDA-approved small molecule protein kinase inhibitors: A 2023 update.
Owing to the dysregulation of protein kinase activity in many diseases including cancer, this enzyme family has become one of the most important drug targets in the 21st century. There are 72 FDA-approved therapeutic agents that target about two dozen different protein kinases and three of these drugs were approved in 2022. Of the approved drugs, twelve target protein-serine/threonine protein kinases, four are directed against dual specificity protein kinases (MEK1/2), sixteen block nonreceptor protein-tyrosine kinases, and 40 target receptor protein-tyrosine kinases. The data indicate that 62 of these drugs are prescribed for the treatment of neoplasms (57 against solid tumors including breast, lung, and colon, ten against nonsolid tumors such as leukemia, and four against both solid and nonsolid tumors: acalabrutinib, ibrutinib, imatinib, and midostaurin). Four drugs (abrocitinib, baricitinib, tofacitinib, upadacitinib) are used for the treatment of inflammatory diseases (atopic dermatitis, psoriatic arthritis, rheumatoid arthritis, Crohn disease, and ulcerative colitis). Of the 72 approved drugs, eighteen are used in the treatment of multiple diseases. The following three drugs received FDA approval in 2022 for the treatment of these specified diseases: abrocitinib (atopic dermatitis), futibatinib (cholangiocarcinomas), pacritinib (myelofibrosis). All of the FDA-approved drugs are orally effective with the exception of netarsudil, temsirolimus, and trilaciclib. This review summarizes the physicochemical properties of all 72 FDA-approved small molecule protein kinase inhibitors including lipophilic efficiency and ligand efficiency.


Investigating convergent actions of genes linked to familial Parkinson's disease.
Mutations in LRRK2 are among the most frequent genetic changes identified in Parkinson's disease (PD), but how LRRK2 contributes to the pathophysiology of PD is not known. To investigate how expressing wild-type or G2019S LRRK2 modifies cellular responses to rotenone, a mitochondrial toxin. We investigated the vulnerability to mitochondrial toxins in Caenorhabditis elegans expressing wild-type or G2019S LRRK2. We observed a powerful role for LRRK2 in mitochondrial biology. Overexpressing LRRK2 strongly protects C. elegans against rotenone toxicity. The G2019S LRRK2 construct also protected LRRK2 against rotenone, but to a lesser degree than wild-type LRRK2. Knockdown of lrk-1 potentiated rotenone toxicity. These data suggest that LRRK1/2 regulate mitochondrial physiology.


Evaluation of pediatric percutaneous nephrolithotomy experience of an adult-trained surgeon.
The aim of our study is to evaluate the pediatric percutaneous nephrolithomy (PCNL) learning curve of a surgeon. The cases of the first 70 pediatric patients with renal stone disease who underwent PCNL by a surgeon who had performed 120 PCNLs on adults at our clinic were analyzed retrospectively. The patients were divided into two groups depending on their date of surgery (n=35), and the localization of the stone, stone burden, access numbers on the kidney, stone-free rates, blood transfusion in the perioperative-postoperative period, duration of hospitalization, and complications were recorded. The mean of patients in group 1 was 11.45 ± 3.93 (2-16) years, while the same value for group 2 was 8.42 ± 4.21 (1-16) years (P<0.005). There was no statistically significant difference between the two groups regarding stone surface area (group 1: 332.57 ± 192.46 [100-700] mm(2); group 2: 322.85 ± 165.20 [150-900] mm(2)), number of access, stone localization, duration of hospitalization, duration of surgery, blood replacement, and Double-J implantation (P>0.005). While the stone-free rate was 82.85% for group 1, it was 100% for group 2 (P>0.005). Pediatric PCNL can be performed safely after 120 adult PCNL procedures, although this number varies from one surgeon to another. After the first 35 pediatric PCNL experiences, PCNL can safely be performed even on very young children, and higher stone-free rates can be obtained.


Estimating the cost consequence of the early use of botulinum toxin in post-stroke spasticity: Secondary analysis of a randomised controlled trial.
To estimate the cost-consequence of treating spasticity early with botulinum toxin in the acute stroke unit. Secondary cost-consequence analysis, using data from a double-blind randomised-controlled trial. Single-centre specialised stroke unit. Patients with Action Research Arm Test grasp-score of <2 and who developed spasticity within six weeks of a first stroke were randomised to receive injections of: 0.9% sodium-chloride solution (placebo) or onabotulinumtoxin-A (treatment). Resource use costs were calculated for the study. Mean contracture costs for each group were calculated. The Barthel Index and Action Research Arm Test were used to generate a cost per unit of improvement. There were no significant differences associated with early treatment use. The mean contracture cost for the treatment group was £817 and for the control group was £2298 (mean difference = -£1481.1(95% CI -£2893.5, -£68.7) (p = 0.04). The cost per unit of improvement for the Barthel Index was -£1240 indicating that the intervention costs less and is more effective. The cost per unit of improvement for the Action Research Arm Test was -£450 indicating that the intervention costs less and is more effective. Treating spasticity early in stroke patients at risk of contractures with botulinum toxin leads to a significant reduction in contracture costs. The cost per improvement of Barthel and Action Research Arm Test indicates that the intervention costs less and is more effective. EudraCT(2010-021257-39) and ClinicalTrials.gov-Identifier:NCT01882556.


Curcumin inhibits glyoxalase 1: a possible link to its anti-inflammatory and anti-tumor activity.
Glyoxalases (Glo1 and Glo2) are involved in the glycolytic pathway by detoxifying the reactive methylglyoxal (MGO) into D-lactate in a two-step reaction using glutathione (GSH) as cofactor. Inhibitors of glyoxalases are considered as anti-inflammatory and anti-carcinogenic agents. The recent finding that various polyphenols modulate Glo1 activity has prompted us to assess curcumin's potency as an Glo1 inhibitor. Cultures of whole blood cells and tumor cell lines (PC-3, JIM-1, MDA-MD 231 and 1321N1) were set up to investigate the effect of selected polyphenols, including curcumin, on the LPS-induced cytokine production (cytometric bead-based array), cell proliferation (WST-1 assay), cytosolic Glo1 and Glo2 enzymatic activity, apoptosis/necrosis (annexin V-FITC/propidium iodide staining; flow cytometric analysis) as well as GSH and ATP content. Results of enzyme kinetics revealed that curcumin, compared to the polyphenols quercetin, myricetin, kaempferol, luteolin and rutin, elicited a stronger competitive inhibitory effect on Glo1 (K(i) = 5.1+/-1.4 microM). Applying a whole blood assay, IC(50) values of pro-inflammatory cytokine release (TNF-alpha, IL-6, IL-8, IL-1beta) were found to be positively correlated with the K(i)-values of the aforementioned polyphenols. Moreover, whereas curcumin was found to hamper the growth of breast cancer (JIMT-1, MDA-MB-231), prostate cancer PC-3 and brain astrocytoma 1321N1 cells, no effect on growth or vitality of human primary hepatocytes was elucidated. Curcumin decreased D-lactate release by tumor cells, another clue for inhibition of intracellular Glo1. The results described herein provide new insights into curcumin's biological activities as they indicate that inhibition of Glo1 by curcumin may result in non-tolerable levels of MGO and GSH, which, in turn, modulate various metabolic cellular pathways including depletion of cellular ATP and GSH content. This may account for curcumin's potency as an anti-inflammatory and anti-tumor agent. The findings support the use of curcumin as a potential therapeutic agent.


Extension of the sasCIF format and its applications for data processing and deposition.
Recent advances in small-angle scattering (SAS) experimental facilities and data analysis methods have prompted a dramatic increase in the number of users and of projects conducted, causing an upsurge in the number of objects studied, experimental data available and structural models generated. To organize the data and models and make them accessible to the community, the Task Forces on SAS and hybrid methods for the International Union of Crystallography and the Worldwide Protein Data Bank envisage developing a federated approach to SAS data and model archiving. Within the framework of this approach, the existing databases may exchange information and provide independent but synchronized entries to users. At present, ways of exchanging information between the various SAS databases are not established, leading to possible duplication and incompatibility of entries, and limiting the opportunities for data-driven research for SAS users. In this work, a solution is developed to resolve these issues and provide a universal exchange format for the community, based on the use of the widely adopted crystallographic information framework (CIF). The previous version of the sasCIF format, implemented as an extension of the core CIF dictionary, has been available since 2000 to facilitate SAS data exchange between laboratories. The sasCIF format has now been extended to describe comprehensively the necessary experimental information, results and models, including relevant metadata for SAS data analysis and for deposition into a database. Processing tools for these files (sasCIFtools) have been developed, and these are available both as standalone open-source programs and integrated into the SAS Biological Data Bank, allowing the export and import of data entries as sasCIF files. Software modules to save the relevant information directly from beamline data-processing pipelines in sasCIF format are also developed. This update of sasCIF and the relevant tools are an important step in the standardization of the way SAS data are presented and exchanged, to make the results easily accessible to users and to promote further the application of SAS in the structural biology community.


[Tumor biology of oropharyngeal carcinoma].
Etiologically, oropharyngeal squamous cell carcinoma (OPSCC) can be divided into OPSCC caused by noxious agents and human papillomavirus (HPV)-driven carcinoma. These types differ with regard to clinical features and prognosis-differences which are rooted in the underlying molecular biology of the tumor. The aim of this work is to provide an overview of the molecular biological characteristics of the genetics, epigenetics, and immunology of OPSCC. A literature review was performed on a selection of genetic, epigenetic, and immunological factors characterizing OPSCC. The understanding of genetic aberrations and their consequences for cancerogenesis and tumor biology is increasing. Epigenetic phenomena are complementing functional relationships. However, epigenetic mechanisms of gene regulation are complex and much research is still required in this field. Immunological aspects of cancer molecular biology have moved into the focus in light of recent advances in the field of immunotherapy. The tumor biology of OPSCC is primarily defined by its HPV status. Additionally, HPV-independent genetic, epigenetic, and immunological signatures are being defined. From these advances, rationales for new treatment concepts may evolve.


Killed but metabolically active microbes: a new vaccine paradigm for eliciting effector T-cell responses and protective immunity.
We developed a new class of vaccines, based on killed but metabolically active (KBMA) bacteria, that simultaneously takes advantage of the potency of live vaccines and the safety of killed vaccines. We removed genes required for nucleotide excision repair (uvrAB), rendering microbial-based vaccines exquisitely sensitive to photochemical inactivation with psoralen and long-wavelength ultraviolet light. Colony formation of the nucleotide excision repair mutants was blocked by infrequent, randomly distributed psoralen crosslinks, but the bacterial population was able to express its genes, synthesize and secrete proteins. Using the intracellular pathogen Listeria monocytogenes as a model platform, recombinant psoralen-inactivated Lm DeltauvrAB vaccines induced potent CD4(+) and CD8(+) T-cell responses and protected mice against virus challenge in an infectious disease model and provided therapeutic benefit in a mouse cancer model. Microbial KBMA vaccines used either as a recombinant vaccine platform or as a modified form of the pathogen itself may have broad use for the treatment of infectious disease and cancer.


The anxiolytic-like effect of an essential oil derived from Spiranthera odoratissima A. St. Hil. leaves and its major component, β-caryophyllene, in male mice.
Spiranthera odoratissima A. St. Hil. (manacá) is used in folk medicine to treat renal and hepatic diseases, stomachache, headaches and rheumatism. A central nervous system (CNS) depressant effect of the hexane fraction from the ethanolic extract of this plant has been described. β-caryophyllene, the main component of this essential oil, is a sesquiterpene compound with anti-inflammatory properties that has been found in essential oils derived from several medicinal plants. This work is aimed to evaluate the pharmacological activity of the essential oil obtained from S. odoratissima leaves (EO) and its major component on the murine CNS; we aimed to evaluate a possible anxiolytic-like effect and the underlying mechanisms involved. In an open field test, EO (500 mg/kg) and β-caryophyllene (50, 100 and 200 mg/kg) increased the crossing frequency (P<0.05) and, EO (250 and 500 mg/kg) and β-caryophyllene (200 mg/kg) increased the time spent in the center (P<0.05) without altering total crossings of the open field. EO and β-caryophyllene did not alter the number of falls in the rota-rod test (P>0.05). In the pentobarbital-induced sleep test, EO (500 mg/kg) and β-caryophyllene (200 and 400 mg/kg) decreased the latency to sleep (P<0.05), and EO (125, 250 and 500 mg/kg) (P<0.001) and β-caryophyllene (200 and 400 mg/kg) (P<0.05 and P<0.001) increased the sleep time. In anxiety tests, EO (500 mg/kg) and β-caryophyllene (100 and 200 mg/kg) increased head-dipping behavior (P<0.05) in the hole-board test, entries (P<0.05) into and time spent (P<0.05) on the open arms of the elevated plus maze (EPM), and number of transitions (P<0.05) and time spent in the light compartment (P<0.05) of a light-dark box (LDB). We further investigated the mechanism of action underlying the anxiolytic-like effect of EO and β-caryophyllene by pre-treating animals with antagonists of benzodiazepine (flumazenil) and 5-HT(1A) (NAN-190) receptors prior to evaluation using EPM and LDB. The anxiolytic-like effects of EO were significantly reduced by pre-treatment with NAN-190 (P<0.05) but not flumazenil (P>0.05). The anxiolytic-like effects of β-caryophyllene were not blocked by either NAN-190 or flumazenil (P>0.05). In conclusion, these results suggest that the essential oil derived from S. odoratissima produces an anxiolytic-like effect without altering motor performance and that this effect is mediated by 5-HT(1A) but not via benzodiazepine receptors. In addition, the major component, β-caryophyllene, also has an anxiolytic-like effect that may contribute to the effects of EO, but this effect does not seem to be mediated via 5-HT(1A) or benzodiazepine receptors.


Monitoring the turbidity and surface temperature changes and effects of the 17 August 1999 earthquake in the Izmit Gulf, Turkey by the Landsat TM/ETM data.
The temporal turbidity and surface temperature changes and effects of the 17 August 1999 earthquake in the Izmit Gulf, Turkey have been investigated using Landsat TM/ETM data. The gulf is in the Mediterranean-Black Sea transition climatic zone and is partially surrounded by green vegetation cover and degraded and densely urbanized-industrialized areas. Landsat TM/ETM data acquired in 1990-1999 confirms increase in turbidity. Turbidity is always low in the southern part and high in the northern part of the gulf, because the more urbanized and industrialized areas are located in the northern part. The Landsat-7 ETM data acquired in the same year (1999) shows seasonal changes in turbidity. Moreover, the two high turbidity and surface temperature anomalies, one of which is parallel to the 17 August 1999 earthquake surface rupture (east-west) and the other which is in the northwest-southeast direction were mapped from Landsat-5 TM data acquired the day (18.08.1999) following the earthquake in the east end of the gulf. On the basis of turbidity implying the sea bottom movement, it is possible to state that a second rupture in the northwest and southeast direction could have occurred at the sea bottom during the earthquake. The distribution of the seismicity centers and the orientation of the lineaments in the area support this finding.


Performance of multiplex serology in discriminating active vs past Helicobacter pylori infection in a primarily African American population in the southeastern United States.
To feasibly analyze associations of Helicobacter pylori (H. pylori) with disease in large cohort studies, assays are needed to assess H. pylori prevalence in existing biospecimens. However, serology has traditionally been unable to distinguish active from past infection. We sought to determine the sensitivity of seropositivity to H. pylori proteins to detect active infection. We measured antibody responses to 13 H. pylori proteins using multiplex serology in serum samples of a training (n = 78) and validation set (n = 49) collected concurrently from patients undergoing urea breath test (UBT). To determine sensitivity of seropositivity to H. pylori proteins for active infection, a cutoff was applied to achieve 90% specificity. Antibody levels were retested in a subset of participants (n = 16) 6 months after baseline. With a specificity of 91%, seropositivity to H. pylori proteins VacA, GroEl, HcpC, and HP1564 ascertained active infection from 100% to 75% sensitivity. Positivity to a combination of these proteins (≥2 out of the 4) resulted in specificity of 90% and sensitivity of 100%. The validation set replicated results from the training set. Among those participants with successful H. pylori eradication after baseline, antibody levels decreased significantly for VacA, HcpC, and HP1564 when assessed 6 months later. Utilizing the cutoffs for seropositivity established through comparison with UBT, seropositivity to ≥2 of the H. pylori proteins VacA, GroEl, HcpC, and HP1564 determines active H. pylori infection at high specificity and sensitivity and may approximate the prevalence of active H. pylori infection in large cohorts.


The influence of superior labrum anterior to posterior (SLAP) repair on restoring baseline glenohumeral translation and increased biceps loading after simulated SLAP tear and the effectiveness of SLAP repair after long head of biceps tenotomy.
Biomechanical studies have shown increased glenohumeral translation and loading of the long head biceps (LHB) tendon after superior labrum anterior to posterior (SLAP) tears. This may explain some of the typical clinical findings, including the prevalence of humeral chondral lesions, after SLAP lesions. The first hypothesis was that SLAP repair could restore the original glenohumeral translation and reduce the increased LHB load after SLAP lesions. The second hypothesis was that SLAP repair after LHB tenotomy could significantly reduce the increased glenohumeral translation. Biomechanical testing was performed on 21 fresh frozen human cadaveric shoulders with an intact shoulder girdle using a sensor-guided industrial robot to apply 20 N of compression in the joint and 50 N translational force at 0°, 30°, and 60° of abduction. LHB loading was measured by a load-cell with 5 N and 25 N preload. Type IIC SLAP lesions were created arthroscopically, and a standardized SLAP repair was done combined with or without LHB tenotomy. No significant difference of glenohumeral translation and increased LHB load in SLAP repair compared with the intact shoulder was observed under 5 N and 25 LHB preload, except for anterior translation under 25 N LHB preload. After LHB tenotomy after SLAP lesions, no significant difference of translation was observed with or without SLAP repair. SLAP repair without associated LHB tenotomy helps normalize glenohumeral translation and LHB loading. The stabilizing effect of the SLAP complex is dependent on the LHB. After biceps tenotomy, SLAP repair does not affect glenohumeral translation.


Predictive modeling of single-cell DNA methylome data enhances integration with transcriptome data.
Single-cell DNA methylation data has become increasingly abundant and has uncovered many genes with a positive correlation between expression and promoter methylation, challenging the common dogma based on bulk data. However, computational tools for analyzing single-cell methylome data are lagging far behind. A number of tasks, including cell type calling and integration with transcriptome data, requires the construction of a robust gene activity matrix as the prerequisite but challenging task. The advent of multi-omics data enables measurement of both DNA methylation and gene expression for the same single cells. Although such data is rather sparse, they are sufficient to train supervised models that capture the complex relationship between DNA methylation and gene expression and predict gene activities at single-cell level. Here, we present methylome association by predictive linkage to expression (MAPLE), a computational framework that learns the association between DNA methylation and expression using both gene- and cell-dependent statistical features. Using multiple data sets generated with different experimental protocols, we show that using predicted gene activity values significantly improves several analysis tasks, including clustering, cell type identification, and integration with transcriptome data. Application of MAPLE revealed several interesting biological insights into the relationship between methylation and gene expression, including asymmetric importance of methylation signals around transcription start site for predicting gene expression, and increased predictive power of methylation signals in promoters located outside CpG islands and shores. With the rapid accumulation of single-cell epigenomics data, MAPLE provides a general framework for integrating such data with transcriptome data.


In vitro study of the modulatory effects of heat-killed bacterial biomass on aquaculture bacterioplankton communities.
Recent studies have shown that the addition of non-viable microbial biomass or their components (postbiotics) to fish feed can modulate the gut microbiome and positively influence fish health in aquaculture systems. However, no information was hitherto available on the use of non-viable microbial biomass to manipulate aquaculture bacterioplankton communities. To fill this gap, here we used an in vitro model to assess the effects of heat-killed biomasses of an antagonistic strain Pseudoalteromonas rubra SubTr2 and a non-antagonist strain Escherichia coli DH5α on bacterioplankton communities of a recirculating aquaculture system (RAS). Our results showed that these biomasses can have generalist and species-specific effects on aquaculture bacterioplankton structure and function. In addition, they enriched the abundance of bacterial predators, reduced bacterial load and potentially influenced nutrient cycling and pathogen development in aquaculture water. Despite its preliminary nature, for the first time, this study showed that heat-killed microbial biomass has potential application as an in situ modulator of bacterioplankton in aquaculture systems.


Absorption of intranasal salmon calcitonin in normal subjects and hypogonadic men.
The absorption kinetics of intranasal salmon calcitonin were assessed in 4 normal subjects and 9 patients with Klinefelter's syndrome. After administration, absorption occurred within 5 minutes. There was a highly significant correlation between the amount administered and the amount absorbed (r = -0.83, P less than 0.0005).


Inflamation of the testis and epidididymis in an otherwise healthy child: is it a true bacterial urinary tract infection?
The exact etiology of acute gonadal inflamation (EO) in children is unknown. Bacterial infection and underlying urological abnormalities are thought to be the main causes, and hence antibiotic treatment and further invasive urinary tract imaging studies are usually recommended. The purpose of this study was to assess the role of bacterial infection in pediatric acute EO. We retrospectively searched our electronic medical archive for children under the age of 18 years with the diagnosis of acute EO between 1997 and 2002. Patients' charts were retrieved and reviewed for clinical and laboratory data. During 1997-2002, 193 patients with acute EO were treated. There were two subgroups according to the results of urinary cultures: 182 children (94.3%) had negative urine cultures and 11 (5.7%) had positive cultures. In the negative culture group the mean age was 9.8+/-3.2 years (0.5-17). Medical history for urological disease was negative in all patients. Presenting symptom was scrotal pain in 165 (90.7%), and only three patients (1.6%) had accompanying urinary symptoms. Physical examination was normal besides tender gonad. Urinalysis was completely normal in 169 (92.9%) patients. Scrotal Doppler ultrasound (US) demonstrated non-specific inflammatory process in 146 patients (80%), in nine (5%) torsion of the appendix testis was documented and in 27 (14.8%) scrotal US was normal. Follow up was available in 40% all of whom had an uneventful recovery with normal physical examination. In the positive culture group of 11 patients, the mean age was 11+/-6.7 years (3 months to 16 years), and eight patients (73%) had a known congenital urological abnormality. Presenting symptom was pain in five (45.4%) and pain with swelling in six (55.6%). Accompanying dysuria, frequency and urgency occurred in eight (72.7%) patients. Urinalysis was abnormal in 10 (90.9%). US demonstrated increased blood flow to the gonad in 10 (90.9%). Negative history for urological disease, absence of urinary symptoms and normal urinalysis make the diagnosis of bacterial EO unlikely. In this setting, once testicular torsion was excluded, there is no justification for antimicrobial treatment or further imaging of the urinary tract.


"Silent" Sleep Apnea in Dentofacial Deformities and Prevalence of Daytime Sleepiness After Orthognathic and Intranasal Surgery.
The purposes of this study were to determine the occurrence of undiagnosed "silent" obstructive sleep apnea (OSA) in dentofacial deformity (DFD) patients at initial surgical presentation and to report on the level of daytime sleepiness in DFD patients with OSA and chronic obstructive nasal breathing (CONB) after undergoing bimaxillary, chin, and intranasal surgery. A retrospective cohort study of patients with a bimaxillary DFD and CONB was implemented. Patients were divided into those with no OSA (group I) and those with OSA (group II). Group II was further subdivided into patients referred with polysomnogram (PSG)-confirmed OSA (group IIa) and those with a diagnosis of OSA only after surgical consultation, airway evaluation, and a positive PSG (group IIb). Group II patients were analyzed at a minimum of 1 year after surgery (range, 1 to 10 years) for daytime sleepiness with the Epworth Sleepiness Scale. Patients with postoperative excessive daytime sleepiness were assessed for risk factors and continued need for OSA treatment. Patients in group II were studied to determine which DFD patterns were most associated with OSA. We compared the prevalence of OSA between our study population and the general population. Two hundred sixty-two patients met the inclusion criteria. Of these, 23% (60 of 262) had PSG-confirmed OSA (group II). This rate was much higher than that found in the general population. Of the patients, 7% (19 of 262) were known to have OSA at initial surgical consultation (group IIa). An additional 16% (41 of 262) were later confirmed by PSG to have OSA (group IIb). Patients with primary mandibular deficiency and short face DFDs were most likely to have OSA (P < .001 and P = .001, respectively). In group II, 91% (55 of 60) rated their daytime sleepiness as "not sleepy" at a minimum of 1 year after surgery. A significant association was found between group II patients with postoperative excessive daytime sleepiness ("sleepy" or "very sleepy") and a preoperative body mass index category of overweight (P = .026). Our study found silent OSA to be frequent in the DFD population. The prevalence of OSA in DFD patients exceeded that estimated in the general population, with retrusive jaw patterns most affected. In DFD patients also presenting with OSA and CONB, we confirmed low levels of daytime sleepiness long-term after simultaneous bimaxillary orthognathic, chin, and intranasal surgery.


Music therapy as a tool for assessing hand use and communicativeness in children with Rett Syndrome.
A six-year-old girl with Rett syndrome was assessed in a multi-disciplinary specialist therapy clinic and aspects of her responsiveness and developmental potential were found in the music therapy assessment. Functional hand use, eye-referencing, motivated and intentional communication were observed and reported through video analysis of a 30 min session of music therapy employing improvisational methods. Absent or reduced hand clasping/plucking, interactive turn-taking, primary and secondary inter-subjectivity, and vocalisation with appropriate emotional expression were evident. Stable truncal positioning and occasional gentle restraint of either hand improved both spontaneous and prompted activity.


Left atrial appendage function and structure predictors of recurrent atrial fibrillation after catheter ablation: A meta-analysis of observational studies.
The results of studies evaluating the left atrial appendage (LAA) function and structure as predictors of atrial fibrillation (AF) recurrence after catheter ablation (CA) are contradictory. Therefore, we performed a meta-analysis to assess whether the LAA function and structure can predict the recurrence of AF after CA. The PubMed, EMBASE, Web of Science, and Cochrane library databases were used to conduct a comprehensive literature search. Finally, 37 studies encompassing 11 LAA parameters were included in this meta-analysis. Compared with those in the non-recurrence group, the recurrence group had increased LAA volume (SMD 0.53, 95% CI [0.36, 0.71] p < 0.00001), LAA volume index, LAA orifice area, and LAA orifice short/long axis and decreased LAA emptying flow velocity (SMD -0.54, 95% CI [-0.68, -0.40], P < 0.00001), LAA filling flow velocity, and LAA ejection fraction, while there was no significant difference in LAA morphology or LAA depth. Large LAA structure of pre-ablation (LAA volume, orifice area, orifice long/short axis, and volume index) and decreased LAA function of pre-ablation (LAA emptying flow velocity, filling flow velocity, ejection fraction, and LASEC) increase the odds of AF recurrence after CA. [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022324533].


An insight into the role of barrier related skin proteins.
It is well-known that intercellular lipids in the stratum corneum (SC) of the skin play an important role in maintaining barrier function, and many types of penetration enhancers affecting lipids are used in topical products to improve transdermal drug permeability. Recently, it was reported that functional proteins in tight junctions of the epidermis are important for barrier function. In this study, the effects of penetration enhancers such as fatty esters, amines/amides, and alcohols on the barrier function of the skin were evaluated in rat skin and normal human-derived epidermal keratinocytes (NHEK). All penetration enhancers decreased the electrical impedance (EI), however, the potencies of some penetration enhancers were not equal between rat skin and NHEK. The differences were clarified by immunohistochemical studies: some fatty esters decreased the immunoreactivity of involucrin and keratin 10 in the upper layer of the epidermis, while alcohols decreased the immunoreactivity of desmoglein-1, claudin-1, and E-cadherin located in the lower layer of the epidermis. From these results, it is suggested that penetration enhancers show new action mechanisms disturbing barrier-related proteins in epidermis, which are classified into two categories depending on their action sites.


Comparing in vivo biodistribution with radiolabeling and Franz cell permeation assay to validate the efficacy of both methodologies in the evaluation of nanoemulsions: a safety approach.
The Franz cells permeation assay has been performed for over 25 years. However, the advent of nanotechnology created a whole new world, especially with regard to topical products. In this new global scenario an increasing number of nanostructure-based delivery systems (NDSs) have emerged and a global warning relating to the safety of these NDSs is arising. This work studied the efficacy of the Franz cells assay, comparing it with the radiolabeling biodistribution test. For this purpose a formulation of sunscreen based on an NDS was developed and characterized. The results demonstrated both that the NDS did not present in vitro cytotoxicity and that the radiolabeling biodistribution test is more precise for the evaluation of NDS cosmetics than the Franz cells assay, since it detected the permeation of the NDS at a picogram order. Due to this fact, and considering all the concerns related to NDSs and nanoparticles in general, more precise methods must be used in order to guarantee the safe use of these new classes of products.


Combined autoimmune disease in a patient with AIDS.
Immune dysregulation in HIV-infected patients, along with the new medications for treatment of AIDS that possess immunomodulating potential, may lead to an increased incidence of autoimmune diseases in this patient population. However, the presence of combined autoimmune diseases in an AIDS patient is rare. Relapsing polychondritis (RP) is an uncommon inflammatory disease manifested by recurrent attacks of auricular chondritis. The presence of type II and IX collagen antibodies, and their association with HLA-DR4 and other autoimmune diseases, suggests that antiself reactions may be present. Sarcoidosis is a granulomatous disease manifested by inflammation of the lungs, eyes and joints. In the peripheral blood there is depressed cellular immunity and enhanced humoral immunity. We here describe a case of coexisting RP and sarcoidosis in an AIDS patient.


Contribution to the taxonomy of scaly crickets (Orthoptera: Mogoplistidae: Mogoplistinae) from Southeast Asia.
Three new species of scaly crickets are described: Ornebius xinyao sp. n. from Singapore; Ornebius dowwiangkanae sp. n. and Terraplistes ingrischi sp. n. from Thailand. Ornebius insculptus Tan & Ingrisch, 2013 from Singapore is also corrected for nomenclatural error from the original name Ornebius insculpta.


Evidence of ACL healing on MRI following ACL rupture treated with rehabilitation alone may be associated with better patient-reported outcomes: a secondary analysis from the KANON trial.
Evaluate the natural course of anterior cruciate ligament (ACL) healing on MRI within 5 years of acute ACL rupture and compare 2-year and 5-year outcomes based on healing status and treatment group. Secondary analysis of 120 Knee Anterior Cruciate Ligament Nonsurgical vs Surgical Treatment (KANON) trial participants randomised to rehabilitation and optional delayed ACL reconstruction (ACLR) or early ACLR and rehabilitation. ACL continuity on MRI (Anterior Cruciate Ligament OsteoArthritis Score 0-2) was considered evidence of ACL healing. Outcomes included Knee Injury and Osteoarthritis Outcome Score (KOOS), KOOS patient acceptable symptomatic state (PASS) and treatment failure criteria. Linear mixed models were used to estimate adjusted mean differences (95% CIs) in patient-reported sport and recreational function (KOOS-Sport/Rec) and quality of life (KOOS-QOL) at 2 and 5 years, between participants with MRI evidence of ACL healing and those who had (1) no evidence of ACL healing, (2) delayed ACLR or (3) early ACLR. MRI evidence of ACL healing at 2-year follow-up was observed in 16 of 54 (30%, 95% CI 19 to 43%) participants randomised to optional delayed ACLR. Excluding participants who had delayed ACLR, 16 of 30 (53%, 36-70%) participants managed with rehabilitation-alone displayed MRI evidence of ACL healing. Two-year outcomes were better in the healed ACL group (n=16) compared with the non-healed (n=14) (mean difference (95% CI) KOOS-Sport/Rec: 25.1 (8.6-41.5); KOOS-QOL: 27.5 (13.2-41.8)), delayed ACLR (n=24) (KOOS-Sport/Rec: 24.9 (10.2-39.6); KOOS-QOL: 18.1 (5.4-30.8)) and early ACLR (n=62) (KOOS-Sport/Rec: 17.4 (4.1-30.7); KOOS-QOL: 11.4 (0.0-22.9)) groups. Five-year KOOS-QOL was better in the healed versus non-healed group (25.3 (9.4-41.2)). Of participants with MRI evidence of ACL healing, 63-94% met the PASS criteria for each KOOS subscale, compared with 29-61% in the non-healed or reconstructed groups. MRI appearance of ACL healing after ACL rupture occurred in one in three adults randomised to initial rehabilitation and one in two who did not cross-over to delayed ACLR and was associated with favourable outcomes. The potential for spontaneous healing of the ACL to facilitate better clinical outcomes may be greater than previously considered. ISRCTN84752559.


Neuronal hyperexcitability induced by repeated brief episodes of hypoxia in rat hippocampal slices: involvement of ionotropic glutamate receptors and L-type Ca(2+) channels.
Repeated exposures of rat hippocampal slices to short episodes of hypoxia induce a sustained decrease in the threshold of the development of stimulus-evoked epileptiform discharges in CA1 pyramidal neurons. We have previously demonstrated that the K(+)(o)-induced hyperexcitability required functional L-type voltage-dependent Ca(2+) channels and NMDA-receptors, but was independent of AMPA/kainate-receptor activation. As hypoxia/ischaemia can lead to increased K(+)(o), the epileptiform activity observed after exposure to these challenges could also result from high K(+)(o). The purpose of this study was: (i) to determine whether ionotropic glutamate receptors and L-type Ca(2+) channels are involved in the development of epileptiform activity induced by repeated exposures of hippocampal slices to hypoxia; and (ii) to compare the properties of hypoxia- and high K(+)(o)-induced hyperexcitability. Population spike of presynaptic fibres with field excitatory postsynaptic potential from the stratum radiatum, and population spike of CA1 pyramidal neurons from the stratum pyramidale, were recorded simultaneously in the CA1 area of rat hippocampal slices in response to electrical stimulation of the Schaffer collateral/commissural fibres. Repeated, brief hypoxic episodes induced a sustained decrease in the threshold for development of evoked epileptiform discharges that was associated with long-term potentiation of the CA3-CA1 synapses, but without EPSP-spike potentiation (i.e. in contrast to high K(+)(o)-induced hyperexcitability). The selective antagonist of NMDA receptors, D-APV (25 microM), and the selective blocker of L-type Ca(2+) channels, nifedipine (10 microM) depressed the development of hypoxia-induced hyperexcitability. However, in contrast to high K(+)(o)-induced hyperexcitability, hypoxia-induced hyperexcitability was also blocked by the AMPA/kainite-receptor antagonist, CNQX (5 microM). The present findings confirm that repeated, brief episodes of hypoxia, like exposure to high extracellular K(+), can induce a pro-epileptic state in the CA1 neuronal network, but that the mechanisms leading to hyperexcitability are different for the two stimuli.


Death and Plasticity in Clones Influence Invasion Success.
Although invasion processes have been intensely studied, the mechanisms underlying the success of some invasive clonal species remain a mystery. Using the specific example of Carpobrotus edulis, we illustrate how invasion success can be facilitated by a unique spatiotemporal regulation of growth and senescence of plant parts.


Stability and motion of a hairpin and the corresponding mismatched duplex: a theoretical exploration using molecular mechanics and normal mode analysis of 2D NMR results on d(GCCGCAGC).
The oligomer d(GCCGCAGC) can adopt two different conformations: i) a duplex with two mismatched A.C base pairs and ii) a hairpin with two C.G base pairs and a single stranded loop. We report molecular mechanics, normal mode analysis, and thermodynamic stability calculations for both structures. We show that the energy-minimized structure and harmonic-dynamics results are in complete agreement with the observed NOE spectrum and imino proton exchange data. We conclude that the high stability of the hairpin structure over the duplex at low salt concentration is due to the higher vibrational entropy contribution to the system free energy by the single stranded loop and to the lack of minor groove phosphate/phosphate electrostatic repulsions that tend to destabilize the duplex.


Rheological evaluation of silicon/carbopol hydrophilic gel systems as a vehicle for delivery of water insoluble drugs.
The present study analyzed the thickening properties of Carbopol 974 and 971 in a 50:50 mixture of water/Silsense A-21, a new cationic silicon miscible in any proportion with water. Samples were prepared by simply dispersing different Carbopol amounts (0.5-4%) at room temperature or at 70 degrees C without neutralizing. Temperature sweep and time sweep analysis did not reveal significant structural changes at increasing temperature in the samples prepared following the first procedure. On the other hand systems obtained at 70 degrees C possessed higher elastic character particularly at polymer concentration higher than 2% (w/v). Analysis of the G' and G'' vs frequency curves by using different fitting equations (linear fitting, power law) gave information about the viscoelastic properties of the systems. The fitting of the frequency spectra and the calculation of the relaxation times from the master curves outlined the structural differences within the samples prepared with the two different procedures, confirming stronger gel-like behaviour for the samples prepared by the heating procedure. High preparation temperature promoted the polymer-solvent interactions, aiding the solvation of Carbopol. Heating facilitated polymer-solvent and polymer-polymer interaction, giving rise to a better organised structure typical of gel-like systems. Furthermore this preparation method provided good stability properties as shown by the stress sweeps tests performed during the three months of storage. The interpretation of the rheological results was supported by statistical analysis. A design methodology (screening and optimisation) was also applied in order evaluate the influence on dynamic rheological moduli of several parameters (polymer type and concentration, preparation method, temperature of the tests). This last method showed the relevance of the interaction of two main factors: polymer concentration and preparation procedure. Thus, statistical analysis confirmed that temperature increased the polymer-solvent interaction and improved the viscoelastic properties of the systems, particularly when Carbopols were present in considerable amounts.


Genomics to immunotherapy of ovarian clear cell carcinoma: Unique opportunities for management.
Ovarian clear cell carcinoma (OCCC) is distinctive from other histological types of epithelial ovarian cancer, with genetic/epigenetic alterations, a specific immune-related molecular profile, and epidemiologic associations with ethnicity and endometriosis. These findings allow for the exploration of unique and specific treatments for OCCC. Two major mutated genes in OCCC are PIK3CA and ARID1A, which are frequently coexistent with each other. Other genes' alterations also contribute to activation of the PI3K (e.g. PIK3R1 and PTEN) and dysregulation of the chromatin remodeling complex (e.g. ARID1B, and SMARKA4). Although the number of focal copy number variations is small in OCCC, amplification is recurrently detected at chromosome 20q13.2 (including ZNF217), 8q, and 17q. Both expression and methylation profiling highlight the significance of adjustments to oxidative stress and inflammation. In particular, up-regulation of HNF-1β resulting from hypomethylation contributes to the switch from anaerobic to aerobic glucose metabolism. Additionally, up-regulation of HNF-1β activates STAT3 and NF-κB signaling, and leads to immune suppression via production of IL-6 and IL-8. Immune suppression may also be induced by the increased expression of PD-1, Tim-3 and LAG3. Mismatch repair deficient (microsatellite instable) tumors as found in Lynch syndrome also induce immune suppression in some OCCC. In a recent phase II clinical trial in heavily-treated platinum-resistant ovarian cancer, two out of twenty cases with a complete response to the anti-PD-1 antibody, nivolumab, were OCCC subtypes. Thus, the immune-suppressive state resulting from both genetic alterations and the unique tumor microenvironment may be associated with sensitivity to immune checkpoint inhibitors in OCCC. In this review, we highlight recent update and progress in OCCC from both the genomic and immunologic points of view, addressing the future candidate therapeutic options.


Stabilizing Metal Halide Perovskites for Solar Fuel Production: Challenges, Solutions, and Future Prospects.
Metal halide perovskites (MHPs) are emerging photocatalyst materials that can enable sustainable solar-to-chemical energy conversion by virtue of their broad absorption spectra, effective separation/transport of photogenerated carriers, and solution processability. Although preliminary studies show the excellent photocatalytic activities of MHPs, their intrinsic structural instability due to the low formation energy and soft ionic nature is an open challenge for their practical applications. This review discusses the latest understanding of the stability issue and strategies to overcome this issue for MHP-based photocatalysis. First, the origin of the instability issue at atomic levels and the design rules for robust structures are analyzed and elucidated. This is then followed by presenting several different material design strategies for stability enhancement, including reaction medium modification, material surface protection, structural dimensionality engineering, and chemical composition engineering. Emphases are placed on understanding the effects of these strategies on photocatalytic stability as well as the possible structure-performance correlation. Finally, the possible future research directions for pursuing stable and efficient MHP photocatalysts in order to accelerate their technological maturity on a practical scale are outlined. With that, it is hoped to provide readers a valuable snapshot of this rapidly developing and exciting field.


Morphometry of pancreatic beta cell populations during larval growth and metamorphosis of Rana catesbeiana.
Insulin secreting (beta) cell and pancreas volumes were estimated from bullfrogs at different stages in the life cycle. Estimations were made after immunostaining and planimetry of serial pancreas sections. The beta cell volume increased during larval life and is the most likely source of the increased insulin-like immunoreactivity extracted from tadpole pancreases (J. Hulsebus and E. S. Farrar (1985) Gen. Comp. Endocrinol. 58, 114-119). Metamorphic climax was associated with a loss of pancreas and beta cell volumes and insulin-like immunoreactivity. The beta cell pancreatic volume increased following metamorphosis and growth continued in juveniles and adults. The beta cell mass formed a relatively constant percentage of the total pancreatic volume throughout the life cycle.


Early diagnosis of herpes simplex virus encephalitis in childhood by the enzyme-linked immunosorbent assay.
IgG antibody of cerebro-spinal fluid (CSF) and serum IgM antibody were determined by the enzyme-linked immunosorbent assay (ELISA) in 3 patients with herpes simplex virus encephalitis (HSVE). The ELISA detected the early rise of IgG antibody for herpes simplex virus (HSV) in CSF on the 3rd/4th day from onset of symptoms and IgM antibody in serum similarly on the 3rd/4th day, respectively. CSF albumin, IgG index and daily IgG synthesis during the early phase of HSVE showed significantly high levels. However, there was no significant increase of complement-fixing antibody and neutralizing antibody for HSV of serum and CSF in 2 of 3 patients. The ELISA turned out to be a more sensitive and convenient test for the early diagnosis of HSVE.


Survey data of multidrug-resistant tuberculosis, Tuberculosis patients characteristics and stress resilience during COVID-19 pandemic in West Sumatera Province, Indonesia.
This set of data presents a survey data describing multidrug-resistant tuberculosis, tuberculosis patients characteristics and stress resilience during COVID-19 pandemic in West Sumatera Province, Indonesia. The data were gathered from multidrug-resistant tuberculosis, tuberculosis patients through a survey distributed by an online questionnaire, assesing patients characteristics (age, sex, level of education, working status, history of close contact to patients with multidrug resistant tuberculosis and tuberculosis, smoking, alcohol consumption, cavitary pulmonary, diabetes mellitus, nutritional status and tuberculosis outside the lung) and stress resilience (3 items), from 15th July until 7th August 2020. The samples were collected 73 multidrug resistant tuberculosis patients and 219 tuberculosis patients in West Sumatera Province, Indonesia who were willing to fill an online questionnaire. SPSS version 23.0 was used to analyzed the data by descriptive and inferential statistics. The data will help to identify mental health problems and potentially as a warning sign that can support for health education interventions among multidrug-resistant tuberculosis and tuberculosis patients during COVID-19 pandemic.


[Studies on cell-mediated immunity in patients with chronic lymphatic leukemia].
More than 100,000 variables (anamnestic, clinical, serological, radiological and histological individual findings) of 142 patients with rheumatoid arthritis underwent a factor analysis. In the calculatory statistical course by means of information densification we established a few basic variables, called factors. The interpretation of these factors showed apart from logical and pathogenetic connection also relations which gave an impetus for further clinical research.