Application of Platelet Rich Fibrin Matrix to Repair Traumatic Tympanic Membrane Perforations: A Pilot Study.
Trauma in the form of instrumentation, slap, blast, accident, and sporting injury can result in tympanic membrane (TM) perforations which spontaneously recover in 53-94%. The closure rates of TM perforation due to above causes do not vary greatly; however, some otolaryngologists prefer to perform immediate microsurgical procedures to accelerate the recovery process. Our aim is to study the efficacy of Trichloroacetic acid (TCA) Chemical Cauterization (50%) and Platelet rich fibrin (PRF) Plug Myringoplasty technique in healing traumatic tympanic membrane perforations. To evaluate the preoperative and postoperative hearing outcome from the procedure and compare them. Study design is prospective study. A pilot study was carried out amongst selected 25 patients with central perforations in the Department of ENT, for duration of 2 years from July 13 to July 15. All 25 patients underwent PTA assessment & TCA (50%) and Autologous PRF Plug Myringoplasty technique done and follow up to 6 months postoperatively. The success rate traumatic tympanic membrane closure was found to be 92%. Pre- and post-operative hearing assessments of each patient were done & showed statistically significant air-bone gap closure with success rate of 88% (p < 0.05). From this study, the closure rate in traumatic tympanic membrane perforation by TCA (50%) and PRF Plug Myringoplasty technique was 92% with statistically significant hearing improvement (88%). This technique can be recommended as a time and cost effective office based procedure for treatment of traumatic tympanic membrane perforations.


Role of POU1F1 promoting the properties of stemness of gastric carcinoma through ENO1-mediated glycolysis reprogramming.
Cancer stem cells (CSCs), a rare subset of tumor cells, have been recognized as promotive role on tumor initiation and propagation. Among, aerobic glycolysis, widely clarified in multiple tumor cells, is the key for maintaining cancer stemness. Regrettably, it is largely unknown about the connection of cellular metabolic reprogramming and stemness in gastric carcinoma (GC). Two GC parental cells lines PAMC-82 and SNU-16 and their spheroids were obtained to determine the expression status of POU1F1 using quantitative real-time PCR (qRT-PCR) and western blotting analysis, respectively. Gain or loss-of-function assay was employed to assess its biological effects. Sphere formation and transwell assays were performed to evaluate the stem cell-like traits, including self-renewal capacity, migration and invasion. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were conducted for determining the binding relationship of POU1F1 on ENO1 promoter region. Herein, aberrantly upregulated POU1F1 was observed in spheroids, compared with the parental PAMC-82 and SNU-16 cells, which promoted stem cell-like traits, as representing increasing sphere formation, enhanced cell migration and invasion. Additionally, POU1F1 expression was positively with glycolytic signaling, as displaying increasing glucose consumption, lactic acid production, and extracellular acid ratio (ECAR). Furthermore, POU1F1 was identified to be a transcriptional activator of ENO1, of which overexpression remarkably abolished POU1F1 knockdown-mediated blocking effects. Taken together, we draw a conclusion that POU1F1 facilitated the stem cell-like properties of GC cells through transcriptionally augmenting ENO1 to enhance glycolysis.


Phenotypic definition of the progenitor cells with erythroid differentiation potential present in human adult blood.
In Human Erythroid Massive Amplification (HEMA) cultures, AB mononuclear cells (MNC) generate 1-log more erythroid cells (EBs) than the corresponding CD34(pos) cells, suggesting that MNC may also contain CD34(neg) HPC. To clarify the phenotype of AB HPC which generate EBs in these cultures, flow cytometric profiling for CD34/CD36 expression, followed by isolation and functional characterization (colony-forming-ability in semisolid-media and fold-increase in HEMA) were performed. Four populations with erythroid differentiation potential were identified: CD34(pos)CD36(neg) (0.1%); CD34(pos)CD36(pos) (barely detectable-0.1%); CD34(neg)CD36(low) (2%) and CD34(neg)CD36(neg) (75%). In semisolid-media, CD34(pos)CD36(neg) cells generated BFU-E and CFU-GM (in a 1 : 1 ratio), CD34(neg)CD36(neg) cells mostly BFU-E (87%) and CD34(pos)CD36(pos) and CD34(neg)CD36(low) cells were not tested due to low numbers. Under HEMA conditions, CD34(pos)CD36(neg), CD34(pos)CD36(pos), CD34(neg)CD36(low) and CD34(neg)CD36(neg) cells generated EBs with fold-increases of ≈9,000, 100, 60 and 1, respectively, and maturation times (day with >10% CD36(high)CD235a(high) cells) of 10-7 days. Pyrenocytes were generated only by CD34(neg)/CD36(neg) cells by day 15. These results confirm that the majority of HPC in AB express CD34 but identify additional CD34(neg) populations with erythroid differentiation potential which, based on differences in fold-increase and maturation times, may represent a hierarchy of HPC present in AB.


Health Insurance Expansion and Treatment of Pancreatic Cancer: Does Increased Access Lead to Improved Care?
Pancreatic cancer is increasingly common and poised to become the second leading cause of cancer deaths by the year 2020. Surgical resection is the only chance for cure, yet significant disparities in resection rates exist by insurance status. The 2006 Massachusetts health care reform serves as natural experiment to evaluate the unknown impact of health insurance expansion on treatment of pancreatic cancer. Using the Agency for Healthcare Research and Quality's State Inpatient Databases, this cohort study examines nonelderly, adult patients with no insurance, private coverage, or government-subsidized insurance plans, who were admitted with pancreatic cancer in Massachusetts and 3 control states. The primary end point was change in pancreatic resection rates. Difference-in-difference models were used to show the impact of Massachusetts health care reform on resection rates for pancreatic cancer, controlling for confounding factors and secular trends. Before the Massachusetts reform, government-subsidized and self-pay patients had significantly lower rates of resection than privately insured patients. The 2006 Massachusetts health reform was associated with a 15% increased rate of admission with pancreatic cancer (p = 0.043) and a 67% increased rate of surgical resection (p = 0.043) compared with control states. Measured disparities in likelihood of resection by insurance status decreased in Massachusetts and remained unchanged in control states. The 2006 Massachusetts health care reform was associated with increased resection rates for pancreatic cancer compared with control states. Our findings provide hopeful evidence that increased insurance coverage can help improve equity in pancreatic cancer treatment. Additional studies are needed to evaluate the longevity of these findings and generalizability in other states.


Resolution of chronic idiopathic thrombocytopenia purpura following syngeneic peripheral blood progenitor transplant.
Idiopathic thrombocytopenia purpura (ITP) is an acquired disease of children and adults characterized by a low platelet count, an essentially normal bone marrow, and absence of evidence for other disease. We report the use of syngeneic peripheral blood progenitor transplantation (PBPT) in a 19-year-old male with chronic refractory ITP since the age of 5. Engraftment was successful and has resulted in resolution of his disease. We conclude that syngeneic PBPT is a potentially curative option for refractory ITP.


Anuria in transplant patient following inguinal herniorrhaphy.
We report ureteral ligation following inguinal herniorrhaphy in a transplant patient. Successful treatment was accomplished by percutaneous nephrostomy and ureteral reimplantation.


Adverse Events and Complications Associated With Vagal Nerve Stimulation: An Analysis of the Manufacturer And User Facility Device Experience Database.
Drug-resistant epilepsy (DRE) can have devastating consequences for patients and families. Vagal nerve stimulation (VNS) is used as a surgical adjunct for treating DRE not amenable to surgical resection. Although VNS is generally safe, it has its inherent complications. With the increasing number of implantations, adequate patient education with discussion of possible complications forms a critical aspect of informed consent and patient counseling. There is a lack of large-scale reviews of device malfunction, patient complaints, and surgically related complications available to date. Complications associated with VNS implants performed between 2011 and 2021 were identified through a search of the United States Food and Drug Administration Manufacturer And User Facility Device Experience (MAUDE) data base. We found three models on the data base, CYBERONICS, INC pulse gen Demipulse 103, AspireSR 106, and SenTiva 1000. The reports were classified into three main groups, "Device malfunction," "Patient complaints," and "Surgically managed complications." A total of 5888 complications were reported over the ten-year period, of which 501 reports were inconclusive, 610 were unrelated, and 449 were deaths. In summary, there were 2272 reports for VNS 103, 1526 reports for VNS 106, and 530 reports for VNS 1000. Within VNS 103, 33% of reports were related to device malfunction, 33% to patient complaints, and 34% to surgically managed complications. For VNS 106, 35% were related to device malfunction, 24% to patient complaints, and 41% to surgically managed complications. Lastly, for VNS 1000, 8% were device malfunction, 45% patient complaints, and 47% surgically managed complications. We present an analysis of the MAUDE data base for adverse events and complications related to VNS. It is hoped that this description of complications and literature review will help promote further improvement in its safety profile, patient education, and management of both patient and clinician expectations.


Self injurious behavior in autism: clinical aspects and treatment with risperidone.
Self injurious behavior (SIB) is frequent in autistic spectrum disorders. The aim of this study was to investigate the phenomenology of SIB in a group of children with autistic disorder, and to test whether treatment with risperidone might reduce it. A group of eleven children diagnosed with autistic disorder according to the DSM-IV criteria (mean age 8.7+/-2.2 ys) and with severe SIB were recruited for an open study of six months of treatment with risperidone. The Yale-Paris Self-Injurious Behavior Scale was used to delineate the clinical characteristics and as an outcome measure. Head-hitting and hand biting were the most frequent forms of self aggression observed. Nine children presented a mild improvement in SIB and 2 did not show any variation. A decrease in Yale-Paris Self Injurious Behavior Scale score (from M 15.1+/-1.4 to 13.3+/-1.4) was noted mainly due to the reduction of frequency. Side effects of risperidone were not severe.


[Study of ECG in lactating cows. 2: ECG compared to behavior of various parameters of mineral and carbohydrate-fat metabolism].
Four electrocardiographic recordings were taken from 52 cows in a high-performance dairy cattle stock, between the time of calving and the end of the third month of lactation. The voltage of all peaks dropped in the second to fourth weeks after parturition and went up significantly during the second month of lactation. The changes were attributed to tonogenic voltage rise of the heart. Additional tests were applied to 16 cows which had been given increased protein amounts in their feed rations over a prolonged period of time. Their PQ-interval was prolonged in comparison to eight controls.


A Discrete-Time Event-Driven Near-Optimal Second-Order SMC for Multirobotic System Formation Prone to Network Uncertainties.
In this article, we propose a novel stochastic event-driven near-optimal sliding-mode controller design for addressing the consensus of a multiagent system in a network. The system is prone to external disturbances and network uncertainties, such as losses and delays of data packets. The randomness of network uncertainties introduces stochasticity in the system. The design starts with the formulation of control-affine dynamics based on a single integrator robot model, formation error, and sliding surface dynamics. An event-triggering condition is then derived for an update of control input for each agent. These input updates guarantee desired consensus in finite time with reaching time of each agent's sliding surface having an upper bound. The admissibility of event-driven near-optimal control updates is also ensured for each agent. The near-optimal control design for each agent has achieved through neural-network-based actor-critic architecture. The implementation of Pioneer P3-DX mobile robots illustrates threefold efficacy of the proposed design: 1) advantages of event-driven approach and higher order sliding mode controller; 2) robustness to network uncertainties; and 3) near-optimality in system performance.


Outcome of high-risk stage 3 neuroblastoma with myeloablative therapy and 13-cis-retinoic acid: a report from the Children's Oncology Group.
The components of therapy required for patients with INSS Stage 3 neuroblastoma and high-risk features remain controversial. A retrospective cohort design was used to determine if intensive chemoradiotherapy with purged autologous bone marrow rescue (ABMT) and/or 13-cis-retinoic acid (13-cis-RA) improved outcome for patients with high-risk neuroblastoma that was not metastatic to distant sites. We identified 72 patients with INSS Stage 3 neuroblastoma enrolled between 1991 and 1996 on the Phase 3 CCG-3891 randomized trial. Patients were analyzed on an intent-to-treat basis using a log-rank test. The 5-year event-free survival (EFS) and overall survival (OS) rates for patients with Stage 3 neuroblastoma were 55 +/- 6% and 59 +/- 6%, respectively (n = 72). Patients randomized to ABMT (n = 20) had 5-year EFS of 65 +/- 11% and OS of 65 +/- 11% compared to 41 +/- 11 (P = 0.21) and 46 +/- 11% (P = 0.23) for patients randomized to CC (n = 23), respectively. Patients randomized to 13-cis-RA (n = 23) had 5-year EFS of 70 +/- 10% and OS of 78 +/- 9% compared to 63 +/- 12% (P = 0.67) and 67 +/- 12% (P = 0.55) for those receiving no further therapy (n = 16), respectively. Patients randomized to both ABMT and 13-cis-RA (n = 6) had a 5-year EFS of 80 +/- 11% and OS of 100%. Patients with high-risk Stage 3 neuroblastoma have an overall poor prognosis despite aggressive chemoradiotherapy. Further studies are warranted to determine if myeloablative consolidation followed by 13-cis-RA maintenance therapy statistically significantly improves outcome.


The Role of Empowerment-Based Protective Factors on Substance Use Among Youth of Color.
Youth of color continue to be disproportionately affected by the consequences of engaging in high rates of daily substance use. Racial-ethnic minority adolescents are often viewed through a deficit lens. There is limited research that examines the strengths of these young people and their communities as a prevention strategy to lower rates of drug use. Using an empowerment-based framework, this study examines the role of intrapersonal and cognitive psychological empowerment, community civic engagement, and ethnic identity on 30-day drug use among a sample of youth of color (N=383; 53.1% Female; 75% Hispanic), between 14 and 18 years of age, from a northeastern urban community. Structural equation modeling was used to test indirect and direct associations between constructs. Results revealed that both intrapersonal and cognitive psychological empowerment were associated with lower rates of 30-day substance use mediated by ethnic identity and community civic engagement. Findings from this study contribute to the social work field by highlighting the importance of strengths-based approaches to improving health outcomes and decreasing risky behaviors such as drug use among youth of color.


Burkholderia pseudomallei-loaded cells act as a Trojan horse to invade the brain during endotoxemia.
Neurologic melioidosis occurs in both human and animals; however, the mechanism by which the pathogen Burkholderia pseudomallei invades the central nervous system (CNS) remains unclear. B. pseudomallei-loaded Ly6C cells have been suggested as a putative portal; however, during melioidosis, lipopolysaccharide (LPS) can drive disruption of the blood-brain barrier (BBB). This study aims to test whether the Trojan horse-like mechanism occurs during endotoxemia. The expression levels of cerebral cytokines, chemokines and cell adhesion molecules; the activation of astrocytes, microglia and endothelial cells; and the increased vascular permeability and brain-infiltrating leukocytes were evaluated using B. pseudomallei, B. thailandensis, B. cenocepacia and B. multivorans LPS-induced brains. Accordingly, different degrees of BBB damage in those brains with endotoxemia were established. The B. multivorans LPS-induced brain exhibited the highest levels of disruptive BBB according to the above mediators/indicators. Into these distinct groups of endotoxemic mice, B. pseudomallei-loaded Ly6C cells or free B. pseudomallei were adoptively transferred at equal bacterial concentrations (103 CFU). The bacterial load and number of cases of meningeal neutrophil infiltration in the brains of animals treated with B. pseudomallei-loaded Ly6C cells were higher than those in brains induced by free B. pseudomallei in any of the endotoxemic groups. In particular, these results were reproducible in B. multivorans LPS-induced brains. We suggest that B. pseudomallei-loaded cells can act as a Trojan horse and are more effective than free B. pseudomallei in invading the CNS under septic or endotoxemic conditions even when there is a high degree of BBB disruption.


[The effect of oxcarbamazepine on the clinical effectiveness of dopamine agonists in the treatment of prolactinoma].
The CYP450 enzyme family plays a very important role in the biotransformation of many drugs with a different chemical structure. Therefore, the inhibition or induction of CYP enzymes may be responsible for the development of numerous drug interactions. Moreover, a peculiarity of constitution causes that some persons in particular situations may respond differently to a drug or treatment than do most people. In this article, we show a case of a young woman diagnosed with prolactinoma who was initially successfully treated with bromocriptine. Two years later she developed epilepsy secondary to brain trauma and as a result, she started receiving oxcarbamazepine treatment. Unfortunately, the treatment led to a deterioration of prolactinoma control. To normalize plasma prolactin levels, bromocriptine dose had to be increased and then replaced, initially with cabergoline and later with quinagolide. Only the latter drug effectively reduced plasma prolactin levels and tumor size. This case shows for the first time the existence of a drug interaction between dopamine agonists and any anti-epileptic drug in patients with prolactinoma.


Carnosine exerts antitumor activity against bladder cancers in vitro and in vivo via suppression of angiogenesis.
Carnosine, a naturally occurring dipeptide, was recently reported to exhibit anticancer activity; however, the molecular mechanisms and regulators underlying its activity against tumor-associated angiogenesis remain unidentified. In this study, we evaluated the in vitro and in vivo antitumor effects of carnosine in EJ bladder cancer cells and EJ-xenografted BALB/c nude mice, respectively. In addition, in vitro capillary tube formation of HUVECs, ex vivo aortic ring and in vivo Matrigel plug assays were employed to examine the antiangiogenic potential of carnosine. Carnosine significantly inhibited EJ cell proliferation. Flow cytometric and immunoblot analyses indicated that carnosine modulated regulators of the G1 cell cycle phase, including cyclin D1, CDK4 and p21WAF1. The mitogen-activated protein kinases, ERK and p38, but not JNK or AKT, responded to carnosine. Carnosine inhibited the migratory and invasive potential of EJ cells by inhibiting MMP-9 activity, which was associated with suppression of binding activity of NF-κB, SP-1 and AP-1. In xenograft tumors, carnosine exhibited antitumor activity equivalent to cisplatin, but no weight loss occurred in carnosine-treated mice. In HUVECs, carnosine inhibited VEGF-mediated proliferation, colony tube formation, migration and invasion. The antiangiogenic activity of carnosine was partially due to the suppression of VEGFR-2-mediated ERK/AKT/eNOS signaling and MMP-2. Furthermore, using aortic ring and Matrigel plug assays, we confirmed the antiangiogenic activity of carnosine. Given that targeting tumor-associated angiogenesis is a proven effective therapeutic strategy, our results may provide valuable information for the development of preventive or therapeutic agents for bladder cancer patients.


Chloroquine enhances the cytotoxicity of topotecan by inhibiting autophagy in lung cancer cells.
Although the anti-malaria drug chloroquine (CQ) has been shown to enhance chemotherapy and radiation sensitivity in clinical trials, the potential mechanisms underlying this enhancement are still unclear. Here, we examined the relevant mechanisms by which the multipotent CQ enhanced the cytotoxicity of topotecan (TPT). The lung cancer cell line A549 was treated with TPT alone or TPT combined with CQ at non-cytotoxic concentrations. Cell viability was assessed using the MTT assay. The percentage of apoptotic cells and the presence of a side population of cells were both determined by flow cytometry. Autophagy and the expression of Bcl-2 family proteins were examined by Western blotting. The accumulation of YFP-LC3 dots and the formation of acidic vesicular organelles were examined by confocal microscopy. CQ sensitized A549 cells to TPT and enhanced TPT-induced apoptosis in a Bcl-2 family protein-independent fashion. CQ inhibited TPT-induced autophagy, which modified the cytotoxicity of TPT. However, CQ failed to modify the transfer of TPT across the cytoplasmic membrane and did not increase lysosomal permeability. This study showed that CQ at non-cytotoxic concentrations potentiated the cytotoxicity of TPT by interfering with autophagy, implying that CQ has significant potential as a chemotherapeutic enhancer.


Highly potent and long-acting trimeric and tetrameric inhibitors of influenza virus neuraminidase.
A set of trimeric and tetrameric derivatives 6-11 of the influenza virus neuraminidase inhibitor zanamivir 1 have been synthesized by coupling a common monomeric zanamivir derivative 3 onto various multimeric carboxylic acid core groups. These discrete multimeric compounds are all significantly more antiviral than zanamivir and also show outstanding long-lasting protective activity when tested in mouse influenza infectivity experiments.


The influence of unithiol and spironolactone on the biliary excretion of 203Hg in rat.
Rats with cannulated bile ducts were intravenously given 203HgCl2 in the dose of 120 microgram of Hg2+ per rat. Intramuscular administration of Unithiol (sodium 2,3-dimercaptopropanosulphonate) 4 and 7 h after 203Hg injection markedly increased both biliary and urinary excretion of 203Hg. In rats with Spironolactone (17-Hydroxy-7alpha-mercapto-3-oxo-17alpha-pregn-4-ene-21-carboxylic acid, gamma-lactone, acetate) pretreatment the effect of Unithiol on the biliary excretion of 203Hg was enhanced. Urinary excretion of mercury was lowest in comparison with Unithiol treated group.


Activity against Ostertagia ostertagi of low doses of oxfendazole continuously released from intraruminal capsules in cattle.
Slow release from intraruminal capsules of 0.48 mg/kg oxfendazole per day for 5.5 days gave percentage efficiencies of 99 +/- 0.6, 86.6 +/- 6.3 and 93.1 +/- 4.5 for the removal of adult worms, developing 4th stages and inhibited larvae of Ostertagia ostertagi respectively. These efficiencies were not significantly different from those obtained from a single oral dose of 2.5 mg/kg. Peak plasma levels of oxfendazole were similar for the 2 types of administration but high levels were maintained longer in cattle given capsules.


Mortality Risk Associated With Personality Facets of the Big Five and Interpersonal Circumplex Across Three Aging Cohorts.
To address the common reliance on the global Big Five domains in the personality and longevity literature, the present study examined mortality risk associated with subdimensions of Big Five domains as well as specific traits within the interpersonal circumplex (IPC) model of personality. Data were drawn from three major longitudinal studies of aging that administered the NEO Personality Inventory-Revised, a comprehensive measure of the Big Five, and comprised a total of 4223 participants. Item Response Theory models were used to generate latent trait scores for each of the 30 Big Five facets and eight scales from the IPC. Pooled mortality risk estimates were obtained from demographic-adjusted Cox regression models within each study. With a high degree of consistency, the vulnerability facet of neuroticism was associated with higher mortality risk and the activity facet of extraversion, with lower risk. None of the openness or agreeableness facets were associated with mortality, although the IPC scales submissiveness and hostile submissiveness were linked with elevated risk. All but one of the facets in the conscientiousness domain were robustly and consistently associated with lower mortality risk. Findings indicate that specific facets of neuroticism and extraversion carry greater or lesser mortality risk. Broad composite scales averaging across all facets mask important personality risk factors. In contrast, nearly all facets within the conscientiousness domain confer protection against mortality. Finally, the IPC model may capture more nuanced interpersonal risk factors than the facets of Big Five agreeableness or extraversion. Understanding of the role of personality in longevity requires a more precise approach to conceptualization and measurement than broad, composite constructs usually provide.


Comparative studies on cysteine synthase isozymes from spinach leaves.
Three types of cysteine synthase (CSase, EC 220.127.116.11) isozymes were purified from spinach leaves. Each isozyme was isolated to homogeneity by preparative PAGE. These isozymes were revealed to have different primary structures by amino-acid and proteinase digestion analyses, respectively. The enzymes designated as CSase 1, CSase 2 and CSase 3 with reference to the mobility on native PAGE were characterized with respect to physicochemical and enzymatic properties, and it was found that those enzymes had similar properties. It was also found that CSase 1 could be attributed to chloroplasts.


Regulation of uterine immune function by progesterone--lessons from the sheep.
Survival of the fetal allograft results from orchestrated adjustments in activity of maternal lymphoid cells as well as in trophoblast gene expression. One molecule that regulates uterine immune responsiveness is progesterone. In fact, uterine skin graft survival and susceptibility to bacterial infections are increased by progesterone. This review focuses on the role of progesterone in regulation of uterine immune function in the sheep. While the importance of progesterone as a regulator of immune function likely varies between species, concepts derived from the sheep model may prove pertinent to other species also. The actions of progesterone on uterine immune function in the ewe change during pregnancy. Before day 50 of gestation, i.e. when the uterus is still dependent upon the corpus luteum as a source of progesterone, concentrations of progesterone are probably not high enough at the maternal fetal interface to inhibit lymphocyte activation. During this early period of pregnancy, progesterone inhibits uterine immune function by inducing endometrial secretion of a protein called uterine milk protein (UTMP) that itself is inhibitory to lymphocyte function. After day 50 of pregnancy, it is likely that the placenta produces sufficient amounts of progesterone to directly inhibit lymphocyte proliferation. Additional inhibition is achieved because of sustained synthesis of UTMP. Accordingly, progesterone acts to regulate uterine immune function in ways that allows for inhibition of immune responses at the utero-placental interface without systemic immunosuppression.


Beyond the mouth: the impact of periodontal disease on dementia.
The authors searched Medline via PubMed, Scopus, CINAHL, Web of Science, and PsycINFO for relevant studies published until April 2022. Longitudinal studies that assessed periodontal health as the exposure and cognitive decline and/or dementia as the outcome were included. Case reports, reviews, cross-sectional studies, and animal studies were excluded. DATA EXTRACTION AND SYNTHESIS: Two authors independently reviewed studies for inclusion, extracted data, and assessed study quality. Meta-analysis was conducted to generate pooled odds ratios (ORs) for cognitive decline and hazard ratios (HRs) for dementia. Sources of heterogeneity were explored through subgroup analyses. A total of 24 studies were included for cognitive decline and 23 for dementia. Poor periodontal health was associated with increased odds of cognitive decline (OR = 1.23; 95% CI: 1.05-1.44) and dementia (HR = 1.21; 95% CI: 1.07-1.38). Tooth loss also appeared to increase the risk independently. However, significant heterogeneity existed between studies. Poor periodontal health may increase the risk of cognitive decline and dementia, but the quality of evidence was low. Further high-quality, longitudinal studies with standardized assessments are needed to establish causality.


Enhanced microscopic dynamics in mucus gels under a mechanical load in the linear viscoelastic regime.
Mucus is a biological gel covering the surface of several tissues and ensuring key biological functions, including as a protective barrier against dehydration, pathogen penetration, or gastric acids. Mucus biological functioning requires a finely tuned balance between solid-like and fluid-like mechanical response, ensured by reversible bonds between mucins, the glycoproteins that form the gel. In living organisms, mucus is subject to various kinds of mechanical stresses, e.g., due to osmosis, bacterial penetration, coughing, and gastric peristalsis. However, our knowledge of the effects of stress on mucus is still rudimentary and mostly limited to macroscopic rheological measurements, with no insight into the relevant microscopic mechanisms. Here, we run mechanical tests simultaneously to measurements of the microscopic dynamics of pig gastric mucus. Strikingly, we find that a modest shear stress, within the macroscopic rheological linear regime, dramatically enhances mucus reorganization at the microscopic level, as signaled by a transient acceleration of the microscopic dynamics, by up to 2 orders of magnitude. We rationalize these findings by proposing a simple, yet general, model for the dynamics of physical gels under strain and validate its assumptions through numerical simulations of spring networks. These results shed light on the rearrangement dynamics of mucus at the microscopic scale, with potential implications in phenomena ranging from mucus clearance to bacterial and drug penetration.


Acetylation halts missense mutant p53 aggregation and rescues tumor suppression in non-small cell lung cancers.
TP53 mutations are ubiquitous with tumorigenesis in non-small cell lung cancers (NSCLC). By analyzing the TCGA database, we reported that TP53 missense mutations are correlated with chromosomal instability and tumor mutation burden in NSCLC. The inability of wild-type nor mutant p53 expression can't predict survival in lung cancer cohorts, however, an examination of primary NSCLC tissues found that acetylated p53 did yield an association with improved survival outcomes. Molecularly, we demonstrated that acetylation drove the ubiquitination and degradation of mutant p53 but enhanced stability of wild-type p53. Moreover, acetylation of a missense p53 mutation prevented the gain of oncogenic function observed in typical TP53 mutant-expressing cells and enhanced tumor suppressor functions. Consequently, acetylation inducer targeting of missense mutant p53 may be a viable therapeutic goal for NSCLC treatment and may improve the accuracy of current efforts to utilize p53 mutations in a prognostic manner.


Vaginal nitric oxide in pregnant women with bacterial vaginosis.
To evaluate vaginal nitric oxide (NO) production in response to alterations in the vaginal microbial flora. Cervicovaginal lavage samples from 206 women at 18-22 weeks of gestation were tested for NO, interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1ra), tumor necrosis factor-alpha and the inducible 70 kDa heat shock protein (hsp70). Bacterial vaginosis (BV) was diagnosed based on gram staining of vaginal smears. Elevated NO (>2.14 mmol/L) was associated with a diagnosis of BV (38% versus 11%, P < 0.008) as well as an increased median vaginal IL-1ra concentration (72.5 ng/ml versus 36.6 ng/ml, P = 0.041). Elevated vaginal NO was also associated with vaginal hsp70 and this relationship was independent of BV status or IL-1ra concentrations (P < 0.026). We conclude that vaginal hsp70 release in response to abnormal vaginal microflora may trigger NO production in an attempt to minimize the pathological consequences of this altered milieu.


Aza-Claisen rearrangement of 2-C-hydroxymethyl glycals as a versatile strategy towards synthesis of isofagomine and related biologically important azasugars.
Synthesis of isofagomine has been achieved by implementation of aza-Claisen rearrangement of 2-C-hydroxymethyl glycals as a key step. The above rearrangement has also been utilized in the synthesis of biologically important polyhydroxylated piperidine frameworks such as isogalactofagomine, ent-isogalactofagomine and their analogues and some other azasugars as glycosidase inhibitors.


Prevention of postoperative adhesions by tissue-type plasminogen activator (t-PA) in the rabbit.
The fibrinolytic system of the peritoneum is important in the pathogenesis of adhesions. Plasminogen activator activity is depressed by serosal types of injury, which cause ischemia. Ischemic peritoneum induces fibrinous adhesions. When local fibrinolytic activity is impaired, persistence of fibrin and organisation of the fibrinous adhesions may occur. Peritoneal adhesion in rabbits were created by drying the serosa of the uterine horns and by introducing a small amount of blood intraperitoneally. In one group of rabbits tissue-type plasminogen activator (t-PA) was given intraperitoneally at the end of the operation: another group served as controls. 48 rabbits were operated on. The animals were killed 3 h, 1, 3 and 7 days postoperatively for evaluation of adhesions. All animals of the control group had adhesions. The animals of the t-PA group had less adhesions than the animals of the control group.


Anaerobic capacity estimated by the sum of both oxygen equivalents from the glycolytic and phosphagen pathways is dependent on exercise mode: Running versus cycling.
The purpose of this study was to verify whether the exercise modality (i.e., running and cycling) alters the magnitude of "anaerobic" capacity estimated by a single supramaximal effort (AC[La]+EPOCfast). Fourteen healthy men (age: 26±9 years) underwent a maximum incremental test and a supramaximal effort to exhaustion at 115% of the intensity associated with maximal oxygen uptake to determine the AC[La]+EPOCfast (i.e., the sum of both oxygen equivalents from the glycolytic and phosphagen pathways), performed on both a treadmill and cycle ergometer. The maximal oxygen uptake during running was higher (p = 0.001; large effect size) vs. cycling (49.2±3.8 mL·kg-1·min-1 vs. 44.7±5.7 mL·kg-1·min-1, respectively). Contrarily, the oxygen equivalent from the glycolytic metabolism was not different between exercise modalities (p = 0.133; small effect size; running = 2.27±0.51 L and cycling = 2.33±0.49 L). Furthermore, the "anaerobic" capacity was likely meaningfully (3.9±0.6 L and 54.1±6.0 mL·kg-1) and very likely meaningfully greater in running than cycling (3.6±0.7 L and 49.2±6.1 mL·kg). Additionally, the contribution of the phosphagen metabolism was higher (p = 0.001; large effect size) for running compared to cycling (1.6±0.3 L vs.1.3±0.3 L respectively). Therefore, the "anaerobic" capacity estimated by the sum of both oxygen equivalents from the glycolytic and phosphagen pathways during a supramaximal effort is influenced by exercise modality and is able to identify the difference in phosphagen metabolic contribution, based on the methodological conditions of this study.


Modulation of dopamine binding in the fetal rat: effects of milk and exogenous opioid manipulation.
Presentation of milk to the newborn rat promotes changes in sensory and motor behavior and concomitant changes in both endogenous opioid and dopamine systems. The present study employed an in vivo binding technique with a tritiated ligand for the D2 receptor ([3H]raclopride) to examine the effects of intraoral milk infusion and opioid manipulations on dopamine activity in the term rat fetus (E21). In Experiment 1, fetuses received a series of milk infusion, which resulted in decreased occupancy at D2 receptors by the endogenous ligand, dopamine, in striatal, septal, and hypothalamic brain regions. In Experiment 2, fetuses were pretreated with morphine, the mu-agonist [D-Ala2,NMe-Phe4,Gly5-ol]-enkephalin (DAMGO), the kappa-agonist U50,488, or saline. Opioid manipulations had no effect on binding at D2 receptors. These results confirm that intraoral milk infusion can modulate activity in the dopamine system of the near-term fetal rat.


Phytohormone release by three isolated lichen mycobionts and the effects of indole-3-acetic acid on their compatible photobionts.
Evidence is emerging that phytohormones represent key inter-kingdom signalling compounds supporting chemical communication between plants, fungi and bacteria. The roles of phytohormones for the lichen symbiosis are poorly understood, particularly in the process of lichenization, i.e. the key events which lead free-living microalgae and fungi to recognize each other, make physical contact and start developing a lichen thallus. Here, we studied cellular and extracellularly released phytohormones in three lichen mycobionts, Cladonia grayi, Xanthoria parietina and Tephromela atra, grown on solid medium, and the effects of indole-3-acetic acid (IAA) on their respective photobionts, Asterochloris glomerata, Trebouxia decolorans, Trebouxia sp. Using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) we found that mycobionts produced IAA, salicylic acid (SA) and jasmonic acid (JA). IAA represented the most abundant phytohormone produced and released by all mycobionts, whereas SA was released by X. parietina and T. atra, and JA was released by C. grayi only. With a half-life of 5.2 days, IAA degraded exponentially in solid BBM in dim light. When IAA was exogenously offered to the mycobionts' compatible photobionts at "physiological" concentrations (as released by their respective mycobionts and accumulated in the medium over seven days), the photobionts' water contents increased up to 4.4%. Treatment with IAA had no effects on the maximum quantum yield of photosystem II, dry mass, and the contents of photosynthetic pigments and α-tocopherol of the photobionts. The data presented may be useful for designing studies aimed at elucidating the roles of phytohormones in lichens.


Protocols, practices, and needs for investigating sudden unexpected infant deaths.
Understanding case identification practices, protocols, and training needs of medical examiners and coroners (MEC) may inform efforts to improve cause-of-death certification. We surveyed a U.S.-representative sample of MECs and described investigation practices and protocols used in certifying sudden unexpected infant deaths (SUID). We also identified MEC training and resource needs. Of the 377 respondents, use of the SUID Investigation Reporting Form or an equivalent was 89% for large, 87% for medium, and 52% for small jurisdictions. Routine completion of infant medical history, witness interviews, autopsy, photos or videos, and family social history for infant death investigations was ≥80%, but routine scene re-creation with a doll was 30% in small, 64% in medium, and 59% in large offices. Seventy percent of MECs reported infant death investigation training needs. Increased training and use of standardized practices may improve SUID cause-of-death certification, allowing us to better understand SUID.


Sex- and race-specific associations of bone mineral density with incident heart failure and its subtypes in older adults.
Previous studies have suggested an association between bone mineral density (BMD) and heart failure (HF) risk that may be race-dependent. We evaluated the relationship between BMD and incident HF in a cohort of older adults, the Health, Aging, and Body Composition (Health ABC) study (n = 2835), and next performed a pooled analysis involving a second older cohort, the Cardiovascular Health Study (n = 1268). Hip BMD was measured by dual-energy X-ray absorptiometry in both cohorts and spine BMD by computed tomography in a subset from Health ABC. In Health ABC, lower BMD at the total hip was associated with higher incident HF in Black women after multivariable adjustment. Similar associations were found for BMD at the femoral neck and spine. In both cohorts, pooled analysis again revealed an association between lower total hip BMD and increased risk of HF in Black women (HR = 1.41 per 0.1-g/cm2 decrement [95% CI = 1.23-1.62]), and showed the same to be true for White men (HR = 1.12 [1.03-1.21]). There was a decreased risk of HF in Black men (HR 0.80 [0.70-0.91]), but no relationship in White women. The associations were numerically stronger with HFpEF for Black women and White men, and with HFrEF for Black men. Findings were similar for femoral neck BMD. Sensitivity analyses delaying HF follow-up by 2 years eliminated the association in Black men. Lower BMD was associated with higher risk of HF and especially HFpEF in older Black women and White men, highlighting the need for additional investigation into underlying mechanisms.


Effect of diisopropylfluorophosphate on the antibody response.
The impact of the in-vivo administration of diisopropylfluorophosphate (DFP) on the antibody response in mice was examined. The antigen-specific plaque-forming cell (PFC) response of mice injected with DFP (4 mg/kg) at the time of immunization with a macrophage-dependent T-cell antigen, trinitrophenylated keyhole limpet hemocyanin (TNP-KLH) or sheep red blood cells (SRBC), was significantly depressed. In contrast, the injection of a similar dose of DFP had no effect on the PFC response of mice immunized with a macrophage-independent B-cell antigen, lipopolysaccharide (LPS). This differential effect suggests a possible detrimental effect of DFP on cells involved in antigen processing and/or presentation which are required for the antibody response to SRBC and TNP-KLH. These results, however, do not exclude T cells as a possible target and the cellular targets of DFP action remain to be established. The DFP-mediated depression of the PFC response to SRBC was still evident when DFP was given as early as 1 day before, but not 1 day after, the injection of antigen, suggesting that DFP may well affect an early event of the antibody response. For the secondary TNP-specific IgM PFC response, a significant depression was observed only when DFP was administered at the time of antigen challenge. The injection of DFP at the time of antigen priming, however, was effective in depressing the IgG, but not the IgM, PFC response. Therefore, DFP may also interfere with the generation of antigen-specific memory cells for the secondary IgG response.


Genomic dissection of endemic carbapenem resistance reveals metallo-beta-lactamase dissemination through clonal, plasmid and integron transfer.
Infections caused by metallo-beta-lactamase-producing organisms (MBLs) are a global health threat. Our understanding of transmission dynamics and how MBLs establish endemicity remains limited. We analysed two decades of blaIMP-4 evolution in a hospital using sequence data from 270 clinical and environmental isolates (including 169 completed genomes) and identified the blaIMP-4 gene across 7 Gram-negative genera, 68 bacterial strains and 7 distinct plasmid types. We showed how an initial multi-species outbreak of conserved IncC plasmids (95 genomes across 37 strains) allowed endemicity to be established through the ability of blaIMP-4 to disseminate in successful strain-genetic setting pairs we termed propagators, in particular Serratia marcescens and Enterobacter hormaechei. From this reservoir, blaIMP-4 persisted through diversification of genetic settings that resulted from transfer of blaIMP-4 plasmids between bacterial hosts and of the integron carrying blaIMP-4 between plasmids. Our findings provide a framework for understanding endemicity and spread of MBLs and may have broader applicability to other carbapenemase-producing organisms.


The natural history of reflux in the lower pole of duplicated collecting systems: a controlled study.
Thirty two children with reflux into the lower pole of duplicated collecting systems, followed non-operatively for one to five years, were compared to a carefully selected control group of similar children who had reflux into a single collecting system. There were no significant differences between the two groups, either in the outcome of reflux or in the incidence of new renal scars. We conclude that reflux into the lower pole of a duplex kidney does not in itself constitute an indication for early surgical treatment.


Using Geriatric Assessment Strategies to Lead End-of-Life Care Discussions.
End-of-life discussions with geriatric oncology patients are a vital part of the comprehensive care of the senior adult patient. Developing a roadmap for these conversations can be challenging. Patients and caregivers may have expectations that are not concordant with what is reasonably achievable if the patient is frail. Measuring baseline cognition, nutritional status, and physical function and discussing goals of care are all essential pieces of information that can be obtained through a comprehensive geriatric assessment (CGA). Objective findings from the CGA can be crucial in developing end-of-life care plans that reflect both the patient's health status and personal values.


The immune mechanisms of abscopal effect in radiation therapy.
Radiation therapy (RT) is a cornerstone in oncologic management and is employed in various curative and palliative scenarios for local-regional control. RT is thought to locally control tumor cells by direct physical DNA damage or indirect insults from reactive oxygen species. Therapeutic effects apart from those observed at the treatment target, that is, abscopal effect, have been observed for several decades, though the underlying mechanisms regulating this phenomenon have been unclear. Accumulating evidence now suggests that the immune system is a major determinant in regulating the abscopal effect. It is now evident that RT may also enhance immunologic responses to tumors by creating an in situ vaccine by eliciting antigen release from dying tumor cells. Harnessing the specificity and dynamic nature of the immune system to target tumors in conjunction with RT is an emerging field with much promise. To optimize this approach, it is important to systematically evaluate the intricacies of the host immune system, the new generation of immunotherapeutics and the RT approach. Here we will discuss the current biologic mechanisms thought to regulate the RT-induced abscopal effect and how these may be translated to the clinical setting.


Krypton filled flashlamp: a possible new light source for near infrared spectroscopy in vivo.
We have designed a reliable and flexible low cost instrument for NIR spectroscopy. A krypton filled flashlamp was used as inexpensive light source. Providing a number of suitable emission peaks in the NIR, this flashlamp is ideal for NIR spectroscopy. Application to other NIR spectroscopy systems, e.g. to CCD (Charge Coupled Device) spectrophotometers, should be possible. The introduced system was tested on human arm tissue during arterial occlusion. Results equivalent to those described by other authors could be obtained by this new technical approach.


Macrophage chemotaxis in experimental tooth movement in the rat.
Extracts from tissue surrounding teeth being moved contained chemotactic activity for peritoneal exudate cells (PEC). The tissue was homogenized, extracted and diafiltered using a 100,000 mol. wt cut-off filter. The filtrate contained statistically-significant chemotactic activity, whereas the retentate did not. Further fractionation of the filtrate using an isoelectric focusing column produced a filtrate fraction in the pH range between 5.0 and 6.8 which was chemotactically active. This sample was analysed for purity and mol. wt using sodium dodecylsulphate polyacrylamide-gradient gel electrophoresis (SDS-PAGE). Gels of the active fraction stained with Coomassie blue showed two distinct bands with molecular weights of 69,000 and 60,000.


Prevention of acute liver injury by suppressing plasma kallikrein-dependent activation of latent TGF-β.
Acute liver injury (ALI) is highly lethal acute liver failure caused by different etiologies. Transforming growth factor β (TGF-β) is a multifunctional cytokine and a well-recognized inducer of apoptotic and necrotic cell death in hepatocytes. Latent TGF-β is activated partly through proteolytic cleavage by a serine protease plasma kallikrein (PLK) between the R58 and L59 residues of its propeptide region. Recently, we developed a specific monoclonal antibody to detect the N-terminal side LAP degradation products ending at residue R58 (R58 LAP-DPs) that reflect PLK-dependent TGF-β activation. This study aimed to explore the potential roles of PLK-dependent TGF-β activation in the pathogenesis of ALI. We established a mouse ALI model via the injection of anti-Fas antibodies (Jo2) and observed increases in the TGF-β1 mRNA level, Smad3 phosphorylation, TUNEL-positive apoptotic hepatocytes and R58-positive cells in the liver tissues of Jo2-treated mice. The R58 LAP-DPs were observed in/around F4/80-positive macrophages, while macrophage depletion with clodronate liposomes partly alleviated the Jo2-induced liver injury. Blocking PLK-dependent TGF-β activation using either the serine proteinase inhibitor FOY305 or the selective PLK inhibitor PKSI-527 or blocking the TGF-β receptor-mediated signaling pathway using SB431542 significantly prevented Jo2-induced hepatic apoptosis and mortality. Furthermore, similar phenomena were observed in the mouse model of ALI with the administration of acetaminophen (APAP). In summary, R58 LAP-DPs reflecting PLK-dependent TGF-β activation may serve as a biomarker for ALI, and targeting PLK-dependent TGF-β activation has potential as a therapeutic strategy for ALI.


Effect of aging on mitochondrial and nuclear DNA oxidative damage in the heart and brain throughout the life-span of the rat.
The oxygen radical-induced DNA lesion 8-oxo,7,8-dihydro-2'-deoxyguanosine (8-oxodG) is the most commonly measured marker of oxidative DNA damage, which is currently considered a main cause of aging. However, a detailed study of the age-related variations of this marker in both mitochondrial (mtDNA) and nuclear (nDNA) DNA of post-mitotic organs throughout the life span has not been previously performed. In this investigation 8-oxodG steady-state levels were simultaneously measured in mtDNA and nDNA in the heart and brain of Sprague-Dawley rats at up to five different ages covering most of the adult life span, 4, 8, 12, 17 and 24 months of age, using exactly the same digestion of DNA to deoxynucleosides and chromatographic procedures for mtDNA and nDNA. 8-oxodG levels were maintained without changes during young and middle age in all cases, but showed statistically significant increases at the older ages studied in the majority of the kinds of DNA investigated. These age-related increases in oxidative damage occurred in brain nDNA at 17 and 24 months of age, in heart nDNA at 24 months of age, and in brain mtDNA at 24 months of age, whereas no significant age-related changes were detected in heart mtDNA. Besides, 8-oxodG levels were various fold higher in mtDNA than in nDNA, both in brain and heart, at all the ages studied. The results show that oxidative damage to DNA is higher in the mtDNA than in the nDNA of post-mitotic tissues throughout the whole life span of the rat and that and increase in mtDNA and nDNA oxidative stress occurs in most cases in old animals.


Brain organization underlying superior mathematical abilities in children with autism.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits. While such deficits have been the focus of most research, recent evidence suggests that individuals with ASD may exhibit cognitive strengths in domains such as mathematics. Cognitive assessments and functional brain imaging were used to investigate mathematical abilities in 18 children with ASD and 18 age-, gender-, and IQ-matched typically developing (TD) children. Multivariate classification and regression analyses were used to investigate whether brain activity patterns during numerical problem solving were significantly different between the groups and predictive of individual mathematical abilities. Children with ASD showed better numerical problem solving abilities and relied on sophisticated decomposition strategies for single-digit addition problems more frequently than TD peers. Although children with ASD engaged similar brain areas as TD children, they showed different multivariate activation patterns related to arithmetic problem complexity in ventral temporal-occipital cortex, posterior parietal cortex, and medial temporal lobe. Furthermore, multivariate activation patterns in ventral temporal-occipital cortical areas typically associated with face processing predicted individual numerical problem solving abilities in children with ASD but not in TD children. Our study suggests that superior mathematical information processing in children with ASD is characterized by a unique pattern of brain organization and that cortical regions typically involved in perceptual expertise may be utilized in novel ways in ASD. Our findings of enhanced cognitive and neural resources for mathematics have critical implications for educational, professional, and social outcomes for individuals with this lifelong disorder.


Selection of antileishmanial sesquiterpene lactones from SistematX database using a combined ligand-/structure-based virtual screening approach.
Leishmaniasis refers to a complex of diseases, caused by the intracellular parasitic protozoans belonging to the genus Leishmania. Among the three types of disease manifestations, the most severe type is visceral leishmaniasis, which is caused by Leishmania donovani, and is diagnosed in more than 20,000 cases annually, worldwide. Because the current therapeutic options for disease treatment are associated with several limitations, the identification of new potential leads/drugs remains necessary. In this study, a combined approach was used, based on two different virtual screening (VS) methods, which were designed to select promising antileishmanial agents from among the entire sesquiterpene lactone (SL) dataset registered in SistematX, a web interface for managing a secondary metabolite database that is accessible by multiple platforms on the Internet. Thus, a ChEMBL dataset, including 3159 and 1569 structures that were previously tested against L. donovani amastigotes and promastigotes in vitro, respectively, was used to develop two random forest models, which performed with greater than 74% accuracy in both the cross-validation and test sets. Subsequently, a ligand-based VS assay was performed against the 1306 SistematX-registered SLs. In parallel, the crystal structures of three L. donovani target proteins, N-myristoyltransferase, ornithine decarboxylase, and mitogen-activated protein kinase 3, and a homology model of pteridine reductase 1 were used to perform a structure-based VS, using molecular docking, of the entire SistematX SL dataset. The consensus analysis of these two VS approaches resulted in the normalization of probability scores and identified 13 promising, enzyme-targeting, antileishmanial SLs from SistematX that may act against L. donovani. A combined approach based on two different virtual screening methods (structure-based and ligand-based) was performed using an in-house dataset composed of 1306 sesquiterpene lactones to identify potential antileishmanial (Leishmania donovani) structures.


Prognostic value of the Leibovich prognosis score supplemented by vascular invasion for clear cell renal cell carcinoma.
We assessed whether supplementing the Leibovich prognosis score with vascular invasion would improve prognostic value to predict metastatic disease in patients with nonmetastatic clear cell renal cell carcinoma. We retrospectively evaluated the pathology records of 1,754 patients with nonmetastatic clear cell renal cell carcinoma treated with surgery between 1984 and 2006 at a single tertiary academic center. The Leibovich prognosis score was supplemented by additional scoring for vascular invasion. Metastasis-free survival was assessed using the Kaplan-Meier method for each score category. A Cox regression model was used for multivariate testing. Predictive accuracy was determined by the Harrell concordance index and decision curve analysis. Median followup was 84 months. Ten-year metastasis-free survival probability for a score of 0 to 1 and 2 to 8 or greater was 95%, 83%, 78%, 81%, 69%, 51%, 15% and 13%, respectively. The concordance index was 0.792 compared to 0.778 from our external validation of the Leibovich prognosis score using routine pathological findings (p <0.05). Decision curve analysis also favored the predictive ability of the novel model. Adding vascular invasion improved the predictive accuracy of our validation data by 1.4% over that of the Leibovich prognosis score. Patients with a score of 7 or greater had a more than 85% probability of metastatic disease at 10 years. Thus, they could be considered candidates for adjuvant treatment trials.


Dynamic frequency feature selection based approach for classification of motor imageries.
Electroencephalography (EEG) is one of the most popular techniques to record the brain activities such as motor imagery, which is of low signal-to-noise ratio and could lead to high classification error. Therefore, selection of the most discriminative features could be crucial to improve the classification performance. However, the traditional feature selection methods employed in brain-computer interface (BCI) field (e.g. Mutual Information-based Best Individual Feature (MIBIF), Mutual Information-based Rough Set Reduction (MIRSR) and cross-validation) mainly focus on the overall performance on all the trials in the training set, and thus may have very poor performance on some specific samples, which is not acceptable. To address this problem, a novel sequential forward feature selection approach called Dynamic Frequency Feature Selection (DFFS) is proposed in this paper. The DFFS method emphasized the importance of the samples that got misclassified while only pursuing high overall classification performance. In the DFFS based classification scheme, the EEG data was first transformed to frequency domain using Wavelet Packet Decomposition (WPD), which is then employed as the candidate set for further discriminatory feature selection. The features are selected one by one in a boosting manner. After one feature being selected, the importance of the correctly classified samples based on the feature will be decreased, which is equivalent to increasing the importance of the misclassified samples. Therefore, a complement feature to the current features could be selected in the next run. The selected features are then fed to a classifier trained by random forest algorithm. Finally, a time series voting-based method is utilized to improve the classification performance. Comparisons between the DFFS-based approach and state-of-art methods on BCI competition IV data set 2b have been conducted, which have shown the superiority of the proposed algorithm.


Contractile history affects sag and boost properties of unfused tetanic contractions in human quadriceps muscles.
A period of extra-efficient force production ("boost") followed by a decline in force ("sag") is often observed at the onset of unfused tetanic contractions. We tested the hypothesis that in human muscle boost and sag are diminished in repeated contractions separated by short rest periods and are re-established or enhanced following long rest periods. Two sets of 3 unfused tetanic contractions were evoked in the right quadriceps muscle group of 29 participants via percutaneous stimulation of the femoral nerve. Contractions consisted of 20 pulses evoked at inter-pulse intervals of 1.25 × twitch time to peak torque. Contractions were evoked 5 s apart and sets were evoked 5 min apart. The ratio of the angular impulse of pulses 1-10 to the angular impulse of pulses 11-20 was used as the boost indicator. By this metric, boost was higher (P < 0.05) in the first relative to the second and third contractions within a set, but did not differ between sets (Set 1: 1.31 ± 0.15, 1.18 ± 0.12, 1.14 ± 0.12 vs Set 2: 1.34 ± 0.17, 1.17 ± 0.13, 1.14 ± 0.13). Sag (the percent decline in torque within each contraction) was also higher (P < 0.05) in the first relative to the second and third contractions within a set, but did not differ between sets (Set 1: 40.8 ± 7.5%, 35.4 ± 6.8%, 33.2 ± 7.8% vs Set 2: 42.1 ± 8.0%, 35.5 ± 6.8%, 33.9 ± 7.2%). Participants' sex and resistance training background did not influence boost or sag. Boost and sag are sensitive to contractile history in whole human quadriceps. Optimizing boost may have application in strength and power sports.


[Hormone receptors and hormone action (author's transl)].
All hormones act only on their target tissues. The ability of a tissue to react to a hormone is due to the presence of a receptor in or at the cell. There are two classes of hormone receptors: those bound to the membrane and those present in the cytosol. Peptide hormones generally act through membrane receptors. The interaction of a hormone with its receptors leads to an activation of the adenylate cyclase and the production of cyclo-AMP, the second messenger. In cases where several hormones act on the same tissue (example: adipose tissue) they must interact with their specific receptors, but presumably with the same adenylate cyclase. This interaction is discussed. The receptors for steroid hormones are not membrane-bound, but present in the cytosol. They are specific proteins which bind the hormone rather tightly. This results in a change in protein conformation, sometimes accompanied by a dimerization; the modified receptor is then transferred to the cell nucleus where it stimulates transcription. The control mechanisms of transcription are discussed; the most probable mode of action is removal of a repressor or repressor-like component from chromatin which results in deinhibition of transcription. mRNA is then produced and translated into protein. Post-transcriptional controls have been postulated, but never unequivocally demonstrated.


[Studies on chemical components and pharmacological activities of geobiontic type medicinal plants in Orchidaceae family].
Geobiontic type medicinal plants subjected to Orchidaceae family are used as important traditional Chinese medicine. Scientists are paying more attentions to their chemical components and pharmacology recently. This paper reviewed their chemical components involved in phenanthrene, bibenzene, flavone, sterol, terpenes, alkoloids and pharmacology such as antibacterium, cytotoxic activity, antihyperliposis effects. All these information are beneficial to reveal the relative among these medicinal plants in Orchidaceae family and are helpful to develop new drugs.


The yielding, plastic flow, and fracture behavior of ultra-high molecular weight polyethylene used in total joint replacements.
The yielding, plastic flow, and fracture behavior of UHMWPE plays an important role in wear and failure mechanisms of total joint replacement components. The primary objective of this study was to compare the yielding, plastic flow, and fracture behavior of two implantable grades of UHMWPE (GUR 1120 vs 4150 HP). The first part of this work explored the hypothesis that up to the polymer yield point, the monotonic loading behavior of UHMWPE displays similar true stress strain behavior in tension and compression. Uniaxial tension and compression tests were conducted to compare the equivalent true stress vs strain response of UHMWPE up to 0.12 true strain. During monotonic loading, the equivalent true stress strain behavior was similar in tension and compression up to the yield point. However, investigation of the unloading behavior and permanent plastic deformations showed that classical deviatoric rate independent plasticity theory may dramatically overpredict the permanent strains in UHMWPE. A secondary goal of this study was to determine the ultimate true stress and strain for UHMWPE and to characterize the fracture surfaces after failure. Using a fracture mechanics approach, the critical flaw sizes were used in combination with the true ultimate stresses to predict the fracture toughness of the two resins. A custom video-based strain measurement system was developed and validated to characterize the true stress-strain behavior up to failure and to verify the accuracy of the incompressibility assumption in calculating the true stress-strains up to failure. In a detailed uncertainty analysis, theoretical expressions were derived for the relative uncertainty in digital video-based estimates of nominal strain, true strain, homogeneous stress, and true stress. Although the yielding behavior of the two UHMWPE resins was similar, the hardening and plastic flow behavior clearly discriminated between the GUR 1120 and 4150 HP. A statistically significant difference between the fracture toughness of the two resins was also evident. The long-term goal of this research is to provide detailed true stress strain data for UHMWPE under uniaxial tension and compression for future numerical simulations and comparison with more complex multiaxial loading conditions.


Questionnaire survey on the conceptual framework, optimal evaluation, and support measures for children's language disorders in Japan using the Delphi method.
To compile the opinions of native Japanese speakers on the conceptual framework, optimal evaluation, and support measures for children with language disorders to devise materials on which a consensus can be formed. A quantitative descriptive study using the Delphi method. Using the Delphi method, 43 clinicians with at least 15 years of experience working professionally with children's language disorders in Japan were surveyed three times via a web-based questionnaire. Thirty-nine items that were carefully selected by the working group were surveyed, and the agreement level was set to ≥80%. We investigated the following aspects related to developmental language disorder (DLD) among Japanese children: definition, core symptoms, evaluation of core symptoms, relationship with a second language, relationship with other related disorders, support systems, and information availability. Overall, 43 qualified panel members were included in this study. Among the 39 items in the questionnaire, a high level of consensus (≥80%) from the responses of the participants was achieved for five items in Round 1, whereas no consensus (<50%) was achieved for seven items. After revising and integrating the questionnaires into 22 items, we conducted Rounds 2 and 3 and obtained high and medium levels of agreement in 20 items on disease concept, core symptoms, coexisting disorders, and manner of support of DLD in children. Our results clarify the previously ambiguous image of DLD in Japan. Information-sharing strategies that connect professionals, patients, their families, and community members are required in the future. 5.


The development of laminar staining for neuron-specific enolase in the rat somatosensory cortex.
The expression of the enzyme neuron-specific enolase (NSE) in the central nervous system (CNS) has been used as a developmental marker based on observations that it is expressed shortly after the arrival of afferent inputs. The immunostaining pattern of NSE was examined in the laminae of the somatosensory cortex of the rat and the relationship of this staining pattern with previous data on the timing of afferent and efferent arrival was determined. Male rat pups were sacrificed on postnatal days 1 (24 h after birth), 3, 5, 8, 10, 12, 15 and 20, and as an adult (over 90 days of age). Sections were stained with an anti-NSE antibody using the avidin-biotin immunocytochemical method. Sections from day 1 animals revealed stained cells in the subplate layer and cortical plate, presumably in cells destined to form layers VI and V. By day 8 there was staining in layers II, III, V and VI, the same layers that exhibited staining in the adult rat. This appears consistent with the arrival of afferents and efferents which is completed by approximately postnatal day 7. On day 10, there was a change in the staining pattern: cell staining in layer VI was decreased and then increased gradually up to adult levels by day 20. A stable pattern of NSE staining was not observed previous to day 20. These results suggest that changes in NSE expression following the initial arrival of afferents may relate to maturation of the neurons.


Machine learning for classification of cutaneous sebaceous neoplasms: implementing decision tree model using cytological and architectural features.
This observational study aims to describe and compare histopathological, architectural, and nuclear characteristics of sebaceous lesions and utilized these characteristics to develop a predictive classification approach using machine learning algorithms. This cross-sectional study was conducted on Iranian patients with sebaceous tumors from two hospitals between March 2015 and March 2019. Pathology slides were reviewed by two pathologists and the architectural and cytological attributes were recorded. Multiple decision tree models were trained using 5-fold cross validation to determine the most important predictor variables and to develop a simple prediction model. This study assessed the characteristics of 123 sebaceous tumors. Histopathological findings, including pagetoid appearance, neurovascular invasion, atypical mitosis, extensive necrotic area, poor cell differentiation, and non-lobular tumor growth pattern, as well as nuclear features, including highly irregular nuclear contour, and large nuclear size were exclusively observed in carcinomatous tumors. Among non-carcinomatous lesions, some sebaceoma and sebaceous adenoma cases had features like high mitotic activity, which can be misleading and complicate diagnosis. Based on multiple decision tree models, the five most critical variables for lesion categorization were identified as: basaloid cell count, peripheral basaloid cell layers, tumor margin, nuclear size, and chromatin. This study implemented a machine learning modeling approach to help optimally categorize sebaceous lesions based on architectural and nuclear features. However, studies of larger sample sizes are needed to ensure the accuracy of our suggested predictive model.


Treatment of recurrent aspiration pneumonia in end-stage dementia: preferences and choices of a group of elderly nursing home residents.
Clinicians are often faced with the dilemma of how best to manage patients with advanced dementia who present to the hospital with repeated episodes of aspiration pneumonia. Rarely, if at all, are the opinions of the group that is most likely to be directly affected, that is the older nursing home resident, sought. This study seeks to fill that gap. To study the choices and preferences of a group of elderly nursing home residents in the treatment of recurrent aspiration pneumonia on a background of severe disability from end-stage dementia. A descriptive cross-sectional interview study using a hypothetical scenario carried out in six nursing homes within eastern Sydney, from June to August 2000. Views and attitudes towards hospitalization, antibiotic use, tube feeding and other treatment measures, given a situation of recurrent aspiration pneumonia and end-stage dementia, were obtained. Fifty-two elderly nursing home residents who were cognitively intact and not depressed were interviewed. Most of the subjects would prefer further hospital admissions (61.5%, P<0.1) and would choose to have antibiotic treatment (73.1%, P<0.001). Slightly more than half would not agree to artificial ventilation. Sixty-nine percent of the respondents would not agree to feeding via a nasogastric tube (P<0.05) and 71% would not agree to a feeding gastrostomy (P<0.001). Most would agree to a modified diet (75%, P<0.0001) and to continue oral feeding despite the attendant risk of re-aspiration (59.6%, P<0.01). The participants generally preferred to be treated in a hospital setting given the scenario. Most disagreed with the use of artificial feeding.


Compliance and Toxicity of Total Neoadjuvant Therapy for Rectal Cancer: A Secondary Analysis of the OPRA Trial.
Patients with locally advanced rectal cancer treated with total neoadjuvant therapy (TNT) may achieve organ preservation without a compromise to oncologic outcomes. However, reports on patient compliance with TNT and with treatment-related toxicities are limited. The OPRA trial assessed organ preservation rates and oncologic outcomes in patients with clinical stage II/III rectal adenocarcinoma randomized to induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Systemic chemotherapy consisted of 8 cycles (16 weeks) of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or 5 cycles (15 weeks) of capecitabine and oxaliplatin (CAPEOX). Patients received >4500 cGy of radiation with sensitizing capecitabine or fluorouracil. In this report, we compare compliance and treatment-related toxicity in patients receiving INCT-CRT versus CRT-CNCT. Additionally, we evaluate the association of compliance to chemotherapy, compliance to chemoradiation, and toxicity with organ preservation and disease-free survival (DFS). Of the 324 patients randomized, fewer patients started chemoradiation in the INCT-CRT group compared with the CRT-CNCT group (93% vs 98%, P = .03), and fewer patients started systemic chemotherapy in the CRT-CNCT group compared with the INCT-CRT group (94% vs 99%, P = .04). Order of TNT did not affect the ability to complete all intended cycles of FOLFOX (86% INCT-CRT vs 83% CRT-CNCT, P = .60) or CAPEOX (74% INCT-CRT vs 77% CRT-CNCT, P = .80). A total of 97% of INCT and 98% of CRT-CNCT patients received >4500 cGy radiation (P = .93). Sixty-four patients (41%) treated with INCT-CRT and 57 CRT-CNCT patients (34%) experienced a grade 3+ adverse event (P = .30). Compliance and toxicity were not associated with organ preservation or DFS. We identified only minor differences in treatment compliance between patients treated with INCT-CRT and CRT-CNCT. No difference in adverse events was observed between groups. Treatment compliance and toxicity did not correlate with organ preservation rates or DFS.


Viral Bcl-2 homologs and their role in virus replication and associated diseases.
Cellular Bcl-2 family proteins regulate a critical step in the mammalian programmed cell death pathway by modulating mitochondrial permeability and function. Bcl-2 family proteins are also encoded by several large DNA viruses, including all known gamma herpesviruses, adenoviruses, and several other unrelated viruses. Viral Bcl-2 proteins can prevent cell death but often escape cellular regulatory mechanisms that govern their cellular counterparts. By evading the "altruistic" suicide of infected cells, viruses can ensure replication and propagation in the infected host, but sometimes in surprising ways. Many human cancers and other disorders are associated with viruses that encode Bcl-2 homologs. Here we consider the available mechanistic data for viral compared to cellular Bcl-2 protein function along with relevance to the virus life cycle and human disease states.


Substituted E-3-(2-Chloro-3-indolylmethylene)1,3-dihydroindol-2-ones with antitumor activity.
The synthesis and antitumor activity of a new series of E-3-(2-chloro-3-indolylmethylene)1,3-dihydroindol-2-ones is described. Several compounds were active on the primary test (three human cell lines) and entered the second level (60 human cell lines). All of them were potent growth inhibitors with GI(50) ranging from -5.32 to -7.27. Four are now under review by BEC (Biological Evaluation Committee of the NCI). The most potent antitumor derivatives were also evaluated as cardiotonic agents (in view of a possible coanthracyclinic activity). In order to find a possible mechanism of action their effects on cell cycle progression in an adenocarcinoma cell line (HT29) were tested, evidencing that these molecules are able to block HT29 in mitosis. The introduction of new substituents in the indolinone moiety while maintaining the same chloroindole portion generated interesting derivatives. 3-(2-Chloro-5-methoxy-6-methyl-3-indolylmethylene)5-hydroxy-1,3-dihydroindol-2-one was the most active of the whole series. It was more potent than vincristine against seven of the nine tumors considered. Moreover it was selective towards some cell lines such as MDA-MB-435 (breast), OVCAR-3 (ovarian) and SK-MEL-28 (melanoma). Even the introduction of a benzyl ring at the nitrogen of the chloroindole portion, gave rise to potent compounds.


Accuracy of a calculating system in transcribing output from a reaction rate analyser.
A system for the mechanized calculation and transcription of output from a reaction rate analyser has been evaluated in the performance of 8 enzyme assays, many of which show anomalous kinetic behaviour with regard to "lag" or "accelerated" phases or "blank" reactions. For all of these enzymes, a cycle of three consecutive 18-second readings per assay proved optimal, the result being based upon the final output value unless this showed marked discrepancy with the second value, in which circumstances it is helpful to refer to a strip chart recording of the progress curve. Excellent agreement was obtained with manually-derived results and the system functioned without downtime for more than one year. Marked descrepancies between manual and mechanised results were invariably traced to technician error.


Psychological distress of inmates at a women's prison in Lima after the first wave of COVID-19 in November 2020.
A descriptive study was carried out to establish the levels of psychological distress amongst female inmates at a high-security prison in Lima in November 2020, after the first wave of COVID-19. The Brief Symptoms Inventory-18 (BSI-18) was applied to a representative sample of 314 female inmates who agreed to participate in the study. Results showed that 34.6% of the inmates could be considered as cases of psychological distress. Moreover, the depression subscale had the highest score, followed by the anxiety and the somatisation subscales. The most prevalent symptom was "feeling blue". The prevalence of distress symptoms was analyzed, taking into account the effects of the first wave of COVID-19, the suspension of family visits, the restriction of treatment and leisure activities, etc. Gender aspects were also taken into consideration.


Fractures of the triquetrum.
The commonest carpal fractures are those of the carpal scaphoid. Triquetral fractures are relatively uncommon, but when present, often go undiagnosed or are misdiagnosed as lunate fractures. Clinical suspicion and careful evaluation of the appropriate radiographs, especially an oblique view, should ensure the diagnosis.


Role of proteins and lipids in non-linear Arrhenius plots of Drosophila mitochondrial succinate-cytochrome c reductase studied by rebinding experiments.
Abrupt changes in the Arrhenius activation energy of membrane-bound enzymes have often been correlated with changes in the physical state of membrane phospholipids. Similar changes in activation energy have also been found in soluble enzymes. The possibility exists, therefore, that in some of the membrane-bound enzymes the changes might reflect intrinsic changes of the proteins independent of changes in the membrane phospholipids. This hypothesis was investigated using Drosophila mitochondria isolated from wild type and the mutant Ocd ts-1. In this mutant it has been shown that succinate-cytochrome c reductase exhibits a change in Arrhenius activation energy at 18 degrees C which is not found in the wild type (Sondergaard, L., Nielsen, N.C. and Smillie, R.M. (1975) FEBS lett. 50, 126-129). A quantitative thin-layer chromatographic analysis of mitochondrial phospholipids showed sphingomyelin to be more abundant in the wild type than in the mutant (5.2% and 4.3% of the total phospholipids, respectively). Since it was shown that the succinate-cytochrome c reductase had a lipid requirement for full activity, reciprocal rebinding experiments were done. These experiments showed that the reconstituted membranes exhibited the change in activation energy at 18 degrees C only when the protein moiety came from mutant mitochondria, that is, the change was independent of the source of the phospholipids used.


Perioperative management and outcome of fracture treatment in patients with haemophilia without inhibitors.
Fractures in persons with haemophilia (PWH) are not uncommon and require an interdisciplinary approach to maintain haemostasis during surgical treatment. The aim of this study was to evaluate the perioperative management and outcome in PWH following fracture fixation compared to a matched non-haemophilic control group. A cohort of 44 PWH who underwent 46 surgical fracture fixations was retrospectively compared to 46 non-haemophilic patients (matched-pair controls). Patients were classified according to the fracture localization: (i) proximal upper extremity (PrUEx; n = 7), (ii) distal upper extremity (DiUEx; n = 12), (iii) proximal lower extremity (PrLEx; n = 13) and (iv) distal lower extremity (DiLEx; n = 14). Both groups were assessed for length of hospital stay, duration of surgery, drainage use and complication rates. There was no significant difference regarding the duration of the preoperative hospital stay between PWH and controls. Only PWH who were operated at the DiUEx stayed significantly longer in hospital (4.8 ± 3.7 days) than controls (2.2 ± 2.3 days; P = 0.039). Operation time was significantly longer in PWH with fractures treated at the DiLEx (64.9 ± 26.6 min) compared to the controls (49.8 ± 37.9 min; P = 0.035). Neither frequency nor duration of surgical drainage placement differed significantly between the two groups. The overall complication rate in both groups was low without a statistically significant difference. An optimal interdisciplinary perioperative management provided the surgical treatment of fractures in PWH can be performed safely with a low complication rate.


[Acoustic and vestibular effects of superior semicircular canal dehiscence].
A dehiscence of the superior semicircular canal is associated with many middle and inner ear symptoms of varying specificity. Concerning the pathophysiology, the way in which these symptoms are connected to a postulated missing bony layer of the superior semicircular canal remains to be completely clarified. In particular, it is unclear why a bony dehiscence might induce symptoms at all; as shown by recent experimental investigations, the natural in vivo coverage of the superior semicircular canal by dura, cerebrospinal fluid and brain prevents changes in inner ear impedance. Diagnosis of superior semicircular canal dehiscence is currently based on a combination of different tests. While cranial computed tomography (with its limited visual resolution) has proven to be largely unsuitable, ocular vestibular-evoked myogenic potentials (oVEMP) are considered an important component of diagnosis. In addition to symptomatic treatment, isolated cases also present the option of highly invasive surgical intervention. Although the majority of published case reports document positive clinical outcomes for operated patients, these procedures are associated with considerable perioperative risks.


Sperm cells as vectors for introducing foreign DNA into eggs: genetic transformation of mice.
Mature mouse sperm cells incubated in an isotonic buffer with cloned DNA capture DNA molecules over a 15 min period. Spermatozoa incubated with pSV2CAT plasmid in either circular or linear form were used to fertilize mouse eggs in vitro. Sequences complementary to pSV2CAT were identified in approximately 30% of 250 progeny by Southern blotting. A genomic library was constructed from the DNA of a positive mouse. Three positive clones were identified and two adjacent HincII restriction fragments of 240 and 370 bp showed identical sequences to the corresponding fragments of the pSV2CAT plasmid. F1 progeny showed paternal and maternal transmission of the transgenes from founders. CAT gene expression was detected on tissues of adult F1 individuals, preferentially on tails and muscle. We conclude that transgenic mice can be obtained using sperm cells as foreign DNA vectors.


A note on 'aging-pharmacodynamics' with application to the analysis of the age-dynamics of adipocyte response to epinephrine and insulin.
This note aims at clearing some semantic problems in the literature concerning the analysis of the effect of age on dose-response curves as well as standardize the way such data should be presented. In particular it is shown how to assess the age-dynamics (i.e. the pattern of change as a mathematical function of age) of the sensitivity of a receptor system to a given agent, of the quantitative overall changes of the cellular response apparatus which affect response capacity, and of the interaction between different simultaneously acting agents. The concepts and theory are illustrated using as an example the in vitro isolated rat fat cell (or adipocyte) which we have recently studied extensively with regards to the age-dynamics of its lipolytic response to epinephrine and insulin. This 'aging-pharmacodynamics' analysis has led to the surprising conclusion of a rebound effect of age (decrease at maturity followed by increase at old age) on the sensitivity of the fat cell to epinephrine and to its antagonist (with respect to lipolysis) insulin, as well as a negative correlation of these sensitivities with fat cell size.


Distributions of VA/Q in dog lungs obtained with the 50 compartment and the log normal approach.
From the lung wash-out ratios of six inert gases that were intravenously administered to 26 anaesthetized normal dogs, 120 distributions of ventilation--perfusion ratios (VA/Q) were determined, using two different techniques: the 50 compartment approach developed by Wagner et al. (1974a) and a least squares curve fitting method, comparing observed and calculated inert gas data corresponding to a single log normal distribution. The latter is defined by three parameters, the (geometric) mean VA/Q, the standard deviation of log VA/Q and a shunt fraction. A unimodal log normal fit was almost always obtained, but in 14 cases the 50 compartment approach yielded a bimodal distribution, which gave a better fit to the data in 7 cases. In most other cases the log normal distribution fitted better; the mean VA/Q's were about equal, but the standard deviations obtained from the log normal fit were often much less. It appears that, whereas in the log normal approach distributions of any sharpness can be fitted, the computer technique used in the 50 compartment approach, involving a smoothing algorithm, shortens and broadens any sharp and narrow peak in them. The effect of different smoothing factors in the 50 compartment approach was investigated. The PaO2 predicted from either distribution was about the same and somewhat less than the actual PaO2, so that one model is not superior to the other in describing oxygen transfer in the lung.


Hypercomplex cell types in area 18 of the cat.
Single unit recording has revealed the same orientation sensitive cell classes in cat area 18 as are to be found in area 17. These include particularly the various types of hypercomplex cell belonging to the S, C, and B cell families.


Cellular mechanisms underlying EEG waveforms during coma.
This paper describes the various electroencephalographic (EEG) patterns expressed by the comatose brain, starting with the sleep-like oscillations associated with light coma. Deeper coma generally displays a burst-suppression pattern characterized by alternating episodes of isoelectric (flat) EEG and bursting slow waves. The latter are the result of cortical hyperexcitability, as demonstrated by intracellular recordings in anesthetized animals. Further deepening of the coma yields to continuous isoelectric EEG and eventually results in a newly discovered type of spiky waves that have been termed ν-complexes. They originate in the hippocampus as a result of intrinsically generated oscillations (ripples) in the delta range.


Activation of peroxymonosulfate by CoFe2O4 loaded on metal-organic framework for the degradation of organic dye.
The magnetic composite CoFe2O4/ZIF-8 based on metal organic framework (MOF) with high specific surface area and high activity was synthesized by solvothermal method. The prepared catalysts were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), vibration sample magnetometer (VSM) and N2 adsorption-desorption isotherms, respectively. After characterization, CoFe2O4/ZIF-8 was applied to heterogeneous activation of peroxymonosulfate (PMS) for degrading methylene blue (MB). The result showed that the 0.075-CoFe2O4/ZIF-8 sample had the excellent catalytic activity. After catalytic reaction for 60 min, the degradation efficiency of MB (20 mg/L) reached about 97.9% at room temperature of 20 °C. The quenching experiment and electron paramagnetic resonance (EPR) analysis indicated that SO4- and OH radicals were the main active species in MB degradation. Meanwhile, the possible MB degradation mechanism was proposed. After four catalytic cycles, the degradation efficiency of MB has not been greatly reduced, indicating the practical application potential of CoFe2O4/ZIF-8 in water pollution cleanup.


Evaluation of safety, pharmacokinetics, and efficacy of vorinostat, a histone deacetylase inhibitor, in the treatment of gastrointestinal (GI) cancer in a phase I clinical trial.
Control of epigenetic changes using histone deacetylase inhibitors (HDACi) is thought to be a promising target in therapy of gastrointestinal (GI) cancer. In this study, we evaluated the safety, pharmacokinetics, and efficacy of two dosing regimens of vorinostat, an oral HDACi, in patients with GI tumors. Patients received either vorinostat 300 mg bid for 3 consecutive days followed by 4 rest days per cycle (n = 10) or vorinostat 400 mg qd for 21 consecutive days per cycle (n = 6). Pharmacokinetic parameters were assessed for the first treatment cycle. Efficacy was determined through evaluation of tumors and assessment of treatment response. The median treatment duration of 300 mg bid was 52.0 days and of 400 mg qd was 51.5 days. The most common drug-related adverse events were anorexia, nausea, fatigue, and hyperglycemia. Two patients taking 400 mg qd had dose-limiting toxicities (DLTs) of thrombocytopenia. No patients taking 300 mg bid experienced DLT. Five patients taking 300 mg bid and 2 patients taking 400 mg qd maintained stable disease for >8 weeks, with the maximum duration of 245 days. Mean drug exposure (±SD) was generally higher with 400 mg qd (area under the curve [AUC(0-∞)] of 7.75 ± 2.79 μM h on Day 1 post-dose) compared with 300 mg bid (AUC(0-∞) of 3.94 ± 1.56 μM h on Day 1 post-dose). Vorinostat 300 mg bid for 3 consecutive days followed by 4 days of rest was better tolerated in patients with GI cancer than a higher once daily dose. Additionally, there were patients in both groups who achieved stable disease, most maintaining it for longer than 8 weeks, suggesting vorinostat as a possible active agent in the treatment of GI cancer.


Emotional and behavioral attitudes of Tunisian youth towards childhood leukemia: health education and primary prevention in perspective.
Given the increasing blood cancer incidence in Tunisia and recent discoveries proving the involvement of environmental factors, this study examined the environmental health literacy (EHL) of Tunisian secondary school students concerning not only this disease, but also their emotional and behavioral attitudes towards leukemia risks. A cross-sectional survey was conducted among Tunisian youths (N = 372, 16-20 years; 68% females, 32% males). Data collection took place in four representative public secondary schools in the North, Center, and South of Tunisia. Students completed a paper and pencil questionnaire and described their EHL level of blood cancer, as well as their attitudes and interests in this disease. The statistical software (SPSS, v.25.0) was used to analyze the data collected. The results indicated low EHL levels of leukemia. Most youths failed to identify all the leukemogenic (except tobacco and pollution) and non- leukemogenic risk factors. Pesticide use and exposure to low frequency electromagnetic radiation were not considered risk factors. Proximity to heavy-traffic roads and benzene exposure were not perceived by youth as risk factors. Despite these low levels, most participants were interested in having more information about leukemia and cancers in general. This investigation shows a lack of knowledge about leukemia. Low EHL levels will incite educational actors and curriculum designers to optimize content and innovate ICT adapted to this environmental health challenge.


Assessment of genetic diversity of Bacillus spp. isolated from eutrophic fish culture pond.
The genus Bacillus comprises of a diverse group with a wide range of nutritional requirements and physiological and metabolic diversity. Their role in nutrient cycle is well documented. 16S rDNA sequences do not always allow the species to be discriminated. In this study 40 Bacillus spp. obtained from fish culture pond and 10 culture type strains were analysed for their genomic diversity by PCR-RFLP of intergenic spacer region of 16S-23S and HSP60 genes. TaqI digestion of PCR products amplified by ITS PCR did not render distinctive RFLP patterns. Numerical analysis of ITS PCR-RFLP pattern differentiated the isolates into 11 clusters. Same species were found to be grouped in different clusters. But PstI digested PCR products amplified from HSP60 gene of the isolates showed distinctive RFLP patterns. The dendrogram constructed from HSP60 PCR-RFLP delineated the isolates into 11 clusters also. All the clusters, except cluster I grouped only one type of species. The results showed that Bacillus spp. could be clearly distinguished by PCR-RFLP of HSP60 gene. Therefore, the HSP60 gene is proposed as an additional molecular marker for discrimination of Bacillus group.


Antepartum complications in twin pregnancies.
Women with twin pregnancies have some unique problems and some that occur more frequently than those seen in singleton pregnancies. Examples of the former are the vanishing twin and death of one fetus. Examples of the latter are congenital anomalies, hydramnios, hypertension, and anemia. Prenatal care must be altered because of these complications, and perinatal morbidity and mortality are increased.


Bleb formation in the renal epithelial cell line LLC-PK1 exposed to N2-methyl-9-hydroxyellipticinium acetate (celiptium).
In this short communication, the authors describe the dose-dependent formation, by the antitumour drug celiptium in vitro, of blebs in pig kidney epithelial cells, illustrating it by scanning electron micrographs. The mechanism of renal injury by celiptium is discussed by a survey of the relevant literature.


Potential of coculture in vitro models to study inflammatory and sensitizing effects of particles on the lung.
Exposure to particulate matter (PM) like nanoparticles (NPs) has increased in the last century due to increased combustion processes, road traffic, etc. In addition, the progress in chemical and cosmetic industry led to many new compounds, e.g. fragrances, which humans are exposed to every day. Many chemicals are known to act as contact and some as respiratory sensitizers, causing allergic reactions. Exposure to small particles of less than 100 nm in diameter is linked with an increased risk of respiratory diseases, such as asthma or rhinitis. To date already more than 1000 customer products contain eNPs without knowing much about the health effects. In comparison to chemicals, the mechanisms by which PM and eNPs can cause sensitization are still not fully understood. Validated and regulatory accepted in vitro models to assess this hazard in its full range are still missing. While a huge number of animal studies contributed to our knowledge about sensitization processes, knowledge on involved cellular mechanisms is still limited. In this review relevant in vitro models to study and elucidate these mechanisms in more detail are presented and their potential to serve as part of a tiered testing strategy is discussed.