Fanconi anemia complementation group E: clinical and cytogenetic data of the first patient.
The clinical and cytogenetic data of the first patient proven to belong to the fifth Fanconi anemia complementation group are described. The Turkish boy presented with psychomotoric retardation, growth retardation, retarded bone age, brachycephaly, hypotelorism, epicanthus, syndactyly, brachydactyly, renal dystopia, and cryptorchism. In addition, an asymmetrical skeletal anomaly was seen with a double distal phalanx of the left thumb and hypoplasia of the right thumb. Typical hematological features of the disorder developed, at the age of 2.5 years, about 1 year after diagnosis. Cytogenetic studies confirmed the clinical diagnosis and revealed a spontaneous chromosomal instability and hypersensitivity to the cross-linking agents diepoxybutane and Trenimon. The findings in the patient, who is considered to be the standard for the fifth Fanconi anemia complementation group, are compared with data reported for other patients affected with Fanconi anemia.


Expression, purification and characterization of refolded rBm-33 (pepsin inhibitor homolog) from Brugia malayi: a human Lymphatic Filarial parasite.
Bm-33 (pepsin inhibitor homolog) produced by the human filarial parasite Brugia malayi, was expressed in Escherichia coli. Expression of rBm33 in BL21 (DE3), Rosetta-2 gami (DE3) pLysS and GJ1158 bacterial strains, results in the accumulation of a 33 kDa protein in inclusion bodies. Inactive rBm-33 was purified under the denaturing conditions and refolded by step wise dialysis using buffers of pH ranging from 11 to 7. Size exclusion chromatography of rBm-33 (refolded) reveals that nearly 83% of the recombinant protein exhibits pepsin inhibition activity. Circular dichroism studies indicate that the protein is predominantly composed of 85% α-helix. rBm-33 (refolded) was assessed for its pepsin inhibition activity using casein agar plate method, UV-spectroscopy and zymogram analysis. These findings suggest that rBm-33 (refolded) has affinity for human pepsin and completely inhibits the proteolytic activity with the gradual increase in rBm-33 (refolded) concentration. Size exclusion chromatography reveals the formation of rBm-33-pepsin complex and was cross checked using immunoblot with glutaraldehyde cross linking. These findings reveal that rBm-33 (refolded) is in native fold to exhibit pepsin inhibition.


[Looking for "lost occupational cancers": a systematic evaluation of occupational exposure in a case series of cutaneous squamous cell carcinomas in Italy].
Cutaneous carcinomas are tumors with a potential occupational etiology due to exposure to established carcinogens such as polycyclic aromatic hydrocarbons (PAH), ionizing radiation, ultraviolet (UV) radiation and arsenic. The occupational origin of such neoplasms is hugely underestimated in Italy. To asses the proportion of Squamous Cell Carcinomas (SCC) cases with a previous occupational exposure to carcinogens. We systematically evaluated occupational exposure in a series of consecutive cases, discharged in the period 2010-11 from the Dermatology Unit of Varese Hospital, Italy, with a histological diagnosis of SCC. Through a structured telephone interview we identified patients with a potential exposure to skin carcinogens. As a second-level step, an extensive evaluation by an occupational physician was performed to assess the occupational etiology in those selected cases. 105 patients were identified (65 men). 15 male cases out of a total of 85 patients who did the telephone interview, revealed a potential occupational exposure; 7 cases were confirmed as occupational cancers after second-level evaluation (proportion of male occupational cases = 13.2%). UV radiation and PAH were recognized as major causal agents. Applying those results to the national incidence data, we estimated a number of 700 annual occupational cases, 100-fold more than the cases currently evaluated by the Italian National Workers Compensation Authority. Our results revealed that occupational SCC is still at present a substantially "lost disease" in Italy. Greater attention and enhanced collaboration between specialists is thus needed to overcome this tendency.


Avidity determination of IgG directed against tick-borne encephalitis virus improves detection of current infections.
Recently, avidity determination of IgG has been introduced successfully into virus serology as an additional and specific means for confirmation or exclusion of current infections. This simple and highly reproducible method can compensate for problems arising by classical serology, which include lack of detectable IgM responses during primary infections and persistent IgM responses after past infections. We show that avidity determination can be applied successfully for serological diagnosis of TBEV infection. Using the urea denaturation method, primary TBEV infections showed anti-TBEV IgG of low avidity (avidity index < 0.4), whereas sera from individuals with past infections exhibited high avidity IgG. The retrospective analysis of cases with clinical symptoms of TBEV infection in the absence of detectable anti-TBEV IgM showed that a significant number of these cases (5/45) had anti-TBEV IgG of low avidity, indicating current infection. We recommended the use of avidity determination as a method for routine TBEV serology.


ADHESION-DEPENDENT F-ACTIN PATTERN IN AMOEBA PROTEUS AS A COMMON FEATURE OF AMOEBAE AND THE METAZOAN MOTILE CELLS
Adhesion and movement of Amoeba proteus are both dependent on the appropriate arrangement of the F-actin cytoskeleton and on the presence of the cell nucleus. In this study the F-actin organization was examined by routine FITC-phalloidin staining and confocal laser microscopy in intact amoebae and in their nucleated and anucleated fragments, at different levels of cell adherence to the substratum. In the adhering and migrating intact cells and nucleated cell fragments dot-like aggregates of F-actin are scattered over the ventral side at sites close to the substratum. In the case of de-adhesion of nucleated specimens this pattern disappears and F-actin is accumulated in the cell centre and/or dispersed in the cytoplasm. The same actin distribution, without ventral dots, is found in the anucleated fragments which usually fail to attach to the substratum. Re-adhesion of anucleated fragments, induced by a modified substratum or spontaneous, is accompanied by restoration of actin dots at the lower cell side. It is concluded that: (1) adhering specimens of A. proteus display the same dot-like actin pattern on the ventral cell side, as many metazoan motile cells; (2) organization or disorganization of this pattern may occur independently of the presence of the cell nucleus, under the control of cell adhesion to the substratum. Copyright 1998 Academic Press Limited


In vitro lysis of the bloodstream forms of Trypanosoma brucei gambiense by stearylamine-bearing liposomes.
Cytolytic activity of liposomes consisting of stearylamine and phosphatidylcholine (SA/PC-liposomes) was examined in vitro against the bloodstream forms of Trypanosoma brucei gambiense. More than 99% of the cells (2 X 10(6)/ml) were killed within 30 min by treatment with 15 mol% SA/PC-liposomes (100 microM total lipids). As few as 1.2 X 10(12) liposomes per ml (equivalent to 2 nM liposome) showed trypanocidal activity. Fluorescence microscopy of cells treated with the dansylated SA/PC-liposomes suggested that the liposomes bound to and accumulated on the cell surface, eventually damaging the plasma membrane. SA/PC-liposomes showed no significant hemolysis when incubated with human and mouse erythrocytes under conditions that killed greater than 99.9% of the T. b. gambiense trypomastigotes. Human leukocytes were also shown to be less susceptible to SA/PC-liposomes than T. b. gambiense. These results may point to a new direction in strategy for therapy of African trypanosomiasis.


Emerging role of KLF4 in human gastrointestinal cancer.
Recent analyses revealed that Krüppel-like factors (KLFs) play important roles in both normal development and carcinogenesis. Of the 16 known KLFs, KLF4 has been shown to be involved in the regulation of proliferation, differentiation and tumorigenesis of gastrointestinal tract epithelium. Clinical, experimental and mechanistic findings indicate that KLF4 is a bona fide tumor suppressor for both gastric and colorectal cancers. In this review, we summarize how this growing area of research has formed and the challenging new frontiers for better understanding of the oncogenic potential of the KLFs.


Potential of innovations in hygiene management - a managerial perspective.
Assessment of the current situation is crucial before introducing innovative infection prevention measures. According to the literature, hospital managers should take on the role of "power promoters" in adopting infection prevention measures due to their position and decision-making authority. However, there is no empirical evidence for whether or not this assumption is valid. This paper reports German hospital managers' perceptions of current challenges in infection prevention and control and innovative prevention measures. We analysed the managerial promoters and barriers of adopting innovations in order to derive recommendations for improving the innovation process in hospitals using the novel AHOI-approach to actively involve patients and their relatives in anti-infection measures. All 3877 medical, nursing and administrative managers of German hospitals were invited to participate in an online survey. The first set of questions intended to determine their perception of problems of hygiene management in their institution and in particular in the interaction with patients and their relatives. The second set of questions was asked to identify potential challenges and barriers to combating nosocomial infections and involving patients and their relatives in infection prevention. Two hundred six managers from German hospitals participated in the survey. Transmission of pathogens was seen as the main problem in the inpatient area, especially in acute care hospitals and stationary geriatric care. Barriers to the implementation of novel infection prevention concepts were primarily perceived as lack of time and refinancing by health insurance providers. The surveyed hospital managers assessed that the active involvement of patients and their relatives in infection prevention could strengthen the infection prevention of their institution. Hospital managers are open to innovative hygiene interventions. In particular, they welcome the active involvement of patients and their relatives in infection prevention. Therefore, financial and institutional barriers, such as insufficient funding of hygiene management, must be overcome.


Single cell analysis of transcriptome and open chromatin reveals the dynamics of hair follicle stem cell aging.
Aging is defined as the functional decline of tissues and organisms, leading to many human conditions, such as cancer, neurodegenerative diseases, and hair loss. Although stem cell exhaustion is widely recognized as a hallmark of aging, our understanding of cell state changes-specifically, the dynamics of the transcriptome and open chromatin landscape, and their relationship with aging-remains incomplete. Here we present a longitudinal, single-cell atlas of the transcriptome and open chromatin landscape for epithelia cells of the skin across various hair cycle stages and ages in mice. Our findings reveal fluctuating hair follicle stem cell (HF-SC) states, some of which are associated with the progression of the hair cycle during aging. Conversely, inner bulge niche cells display a more linear progression, seemingly less affected by the hair cycle. Further analysis of the open chromatin landscape, determined by single-cell Assay for Transposase-Accessible Chromatin (ATAC) sequencing, demonstrates that reduced open chromatin regions in HF-SCs are associated with differentiation, whereas gained open chromatin regions in HF-SCs are linked to the transcriptional control of quiescence. These findings enhance our understanding of the transcriptional dynamics in HF-SC aging and lay the molecular groundwork for investigating and potentially reversing the aging process in future experimental studies.


First evidence of introgressive hybridization of apple snails (Pomacea spp.) in their native range.
Genetic variation facilitates both natural range expansions and anthropogenic invasions. Contrary to expectations, hybridization does not always impact negatively on biodiversity. Increasing evidence indicates advantageous roles for introgressive hybridization in maintaining standing genetic variation. Hypothesizing that hybridization may contribute to the evolutionary and invasive success of a diverse group of freshwater snails (Ampullariidae, commonly known as apple snails), we estimated the frequency of hybridization between two globally invasive species of Pomacea, Pomacea canaliculata (Lamarck, 1822) and P. maculata Perry, 1810, in their native range. While previous work in Asia has uncovered the occurrence of extensive hybridization, we provide the first phylogenetic evidence of a high degree of hybridization (30%) between these species in Uruguay and Brazil. Hybrids carried both heterozygous and homozygous combinations of elongation factor 1-α (EF1α) nuclear alleles in both mating directions, indicating that hybridization has occurred over multiple generations and likely preceded introductions outside the native range. Among the five sites in Brazil previously documented as containing only P. maculata, one far northern population (Careiro Castanho), which is thousands of kilometres from the northern range of P. canaliculata, unexpectedly contained hybrids. This may be the result of human-facilitated introductions. Together with recent work from Asia, our investigations in the native range of apple snails support a reframing of historical perspectives of hybridization as a driver of extinction and diversity loss towards a modern paradigm where hybridization may promote diversification and contribute to the survival of evolutionary lineages such as molluscs.


Synthesis of phytochelatins and modulation of antioxidants in response to cadmium stress in Cuscuta reflexa--an angiospermic parasite.
Effect of cadmium on growth, antioxidative enzymes namely catalase, peroxidase, glutathione reductase, level of glutathione and phytochelatin synthesis was investigated in callus and seedlings of Cuscuta reflexa. A time, concentration and tissue dependent response of Cd was observed. Cd inhibited the growth of callus and seedlings by 50% at 300 and 500 micromol/L concentrations, respectively. Shorter exposure of low concentration of Cd led to augmentation of antioxidant activity, both in callus and seedlings, while longer exposure and high concentration of Cd led to a concentration dependent decrease in callus. Analysis of phytochelatin (PC) synthesis in callus and seedlings of C. reflexa revealed both quantitative and qualitative changes. Cd at low concentrations led to synthesis of predominantly PC4, while at higher concentrations, PC3 was the major form being synthesized. Amelioration of antioxidative systems of C. reflexa in response to Cd stress might be playing a protective role, alleviating the damaging effects of ROS, generated during Cd stress. Concomitantly, chelation and sequestering of toxic Cd ions in this parasite was mediated by synthesis of PC. The response to Cd stress shown by this holoparasitic plant was found to be similar to those of non-parasitic plants (hosts).


Dissociative symptoms in schizophrenic patients with positive and negative symptoms.
Given the close historical relationship between schizophrenia and dissociative disorders, namely multiple personality disorder, we assessed 27 ICD-10 diagnosed schizophrenic inpatients for dissociative symptoms using the German version of the Dissociative Experience Scale and compared them to a nonclinical control group matched for gender and age. Other self-report instruments covering general psychopathology, and an expert rating on the predominance of positive or negative schizophrenic symptoms, were also administered. Schizophrenic patients have significantly more dissociative symptoms than controls. Moreover, patients with a plus type of schizophrenia show significantly higher levels of dissociation than patients mainly exhibiting less productive symptoms. However, dissociative phenomena are only significantly correlated with delusions and hallucinatory behavior, and do not show any correlation with other positive symptoms of schizophrenia. Severe dissociative psychopathology is also associated with impairment in other psychopathological dimensions. The implications of these findings are discussed with regard to the theory of dissociation, the differential diagnosis between schizophrenia and dissociative disorders and a possible contribution of dissociative phenomenology to the clinical heterogeneity of schizophrenia.


Trans-genera reconstitution and complementation of an adhesion complex in Toxoplasma gondii.
Eimeria tenella and Toxoplasma gondii are obligate intracellular parasites belonging to the phylum Apicomplexa. In T. gondii, the microneme protein TgMIC2 contains two well-defined adhesive motifs and is thought to be a key participant in the attachment and invasion of host cells. However, several attempts by different laboratories to generate a knockout (KO) of TgMIC2 have failed, implying that TgMIC2 is an essential gene. As Eimeria and Toxoplasma utilize the same mechanisms of invasion and have highly conserved adhesive proteins, we hypothesized that the orthologous molecule in Eimeria, EtMIC1, could functionally substitute in Toxoplasma to allow a knockout of TgMIC2. TgMIC2 is partnered with a protein called TgM2AP, which corresponds to EtMIC2 in Eimeria. Because the activity of TgMIC2 is most likely tightly linked to its association with TgM2AP, it was thought that the activity of EtMIC1 might similarly require its partner EtMIC2. EtMIC1 and EtMIC2 were introduced into T. gondii, and the presence of EtMIC1 allowed the first knockout clone of TgMIC2 to be obtained. The TgMIC2 KO resulted in significantly decreased numbers of invaded parasites compared to the parental clone. In the absence of TgMIC2, TgM2AP was incorrectly processed and mistargeted to the parasitophorous vacuole instead of the micronemes. These findings indicate that the EtMIC1 can compensate for the essential requirement of TgMIC2, but it cannot fully functionally substitute for TgMIC2 in the invasion process or for supporting the correct maturation and targeting of TgM2AP.


Molecular bacteriology in the clinical laboratory.
Identifying organisms in a timely manner has always been one of the greatest challenges for clinical microbiologists. Healthcare providers want rapid results in order to prescribe the appropriate antimicrobial therapy and improve patient care. Some of the more virulent pathogens such as MRSA, VRE, and MTB must be identified as quickly and accurately as possible in order to prevent the spread of the disease to other patients and employees. The need for rapid, molecular methodologies in the clinical bacteriology laboratory was essential to improve patient outcomes. Organisms that use to take days or weeks to identify are now detected in hours or within the same day. The advent of molecular assays has enabled clinical laboratory scientists to report out accurate, sensitive and timely results confirming the critical role they play on the healthcare team.


Qualitative and Quantitative Analysis of ROS-Mediated Oridonin-Induced Oesophageal Cancer KYSE-150 Cell Apoptosis by Atomic Force Microscopy.
High levels of intracellular reactive oxygen species (ROS) in cells is recognized as one of the major causes of cancer cell apoptosis and has been developed into a promising therapeutic strategy for cancer therapy. However, whether apoptosis associated biophysical properties of cancer cells are related to intracellular ROS functions is still unclear. Here, for the first time, we determined the changes of biophysical properties associated with the ROS-mediated oesophageal cancer KYSE-150 cell apoptosis using high resolution atomic force microscopy (AFM). Oridonin was proved to induce ROS-mediated KYSE-150 cell apoptosis in a dose dependent manner, which could be reversed by N-acetylcysteine (NAC) pretreatment. Based on AFM imaging, the morphological damage and ultrastructural changes of KYSE-150 cells were found to be closely associated with ROS-mediated oridonin-induced KYSE-150 cell apoptosis. The changes of cell stiffness determined by AFM force measurement also demonstrated ROS-dependent changes in oridonin induced KYSE-150 cell apoptosis. Our findings not only provided new insights into the anticancer effects of oridonin, but also highlighted the use of AFM as a qualitative and quantitative nanotool to detect ROS-mediated cancer cell apoptosis based on cell biophysical properties, providing novel information of the roles of ROS in cancer cell apoptosis at nanoscale.


[A case of locally advanced rectal cancer successfully resected after preoperative chemotherapy].
We present the case of a patient who was admitted because of acute pan-peritonitis but was found to have locally advanced rectal cancer that was successfully excised after preoperative chemotherapy. A 68-year-old man was transferred to our hospital via an ambulance because of severe lower abdominal pain. His abdominal computed tomography scan showed a huge tumor in the pelvis. An emergency sigmoid colostomy was performed because of panperitonitis. However, his postoperative examinations indicated locally advanced rectal cancer accompanied with extensive urinary bladder invasion but without distant metastasis, and chemotherapy was started. Eventually, the tumor reduced to 47% of its maximum size after 4 courses of FOLFOX6 and 2 courses of FOLFOX6+panitumumab, and radical excision( low anterior rectal resection, partial urinary bladder resection, D3 lymph node dissection, and total mesorectal excision) was performed on the 154th day since the first operation. No cancer cells were detected on microscopic analysis of the margins of the excised specimen. Thus, preoperative chemotherapy is useful for treating locally advanced rectal cancer.


The impact of parametrized convection on cloud feedback.
We investigate the sensitivity of cloud feedbacks to the use of convective parametrizations by repeating the CMIP5/CFMIP-2 AMIP/AMIP + 4K uniform sea surface temperature perturbation experiments with 10 climate models which have had their convective parametrizations turned off. Previous studies have suggested that differences between parametrized convection schemes are a leading source of inter-model spread in cloud feedbacks. We find however that 'ConvOff' models with convection switched off have a similar overall range of cloud feedbacks compared with the standard configurations. Furthermore, applying a simple bias correction method to allow for differences in present-day global cloud radiative effects substantially reduces the differences between the cloud feedbacks with and without parametrized convection in the individual models. We conclude that, while parametrized convection influences the strength of the cloud feedbacks substantially in some models, other processes must also contribute substantially to the overall inter-model spread. The positive shortwave cloud feedbacks seen in the models in subtropical regimes associated with shallow clouds are still present in the ConvOff experiments. Inter-model spread in shortwave cloud feedback increases slightly in regimes associated with trade cumulus in the ConvOff experiments but is quite similar in the most stable subtropical regimes associated with stratocumulus clouds. Inter-model spread in longwave cloud feedbacks in strongly precipitating regions of the tropics is substantially reduced in the ConvOff experiments however, indicating a considerable local contribution from differences in the details of convective parametrizations. In both standard and ConvOff experiments, models with less mid-level cloud and less moist static energy near the top of the boundary layer tend to have more positive tropical cloud feedbacks. The role of non-convective processes in contributing to inter-model spread in cloud feedback is discussed.


Smoothing, Decomposing and Forecasting Mortality Rates.
The Lee-Carter (LC) model represents a landmark paper in mortality forecasting. While having been widely accepted and adopted, the model has some limitations that hinder its performance. Some variants of the model have been proposed to deal with these drawbacks individually, none coped with them all at the same time. In this paper, we propose a Three-Component smooth Lee-Carter (3C-sLC) model which overcomes many of the issues simultaneously. It decomposes mortality development into childhood, early-adult and senescent mortality, which are described, individually, by a smooth variant of the LC model. Smoothness is enforced to avoid irregular patterns in projected life tables, and complexity in the forecasting methodology is unaltered with respect to the original LC model. Component-specific schedules are considered in projections, providing additional insights into mortality forecasts. We illustrate the proposed approach to mortality data for ten low-mortality populations. The 3C-sLC captures mortality developments better than a smooth improved version of the LC model, and it displays wider prediction intervals. The proposed approach provides actuaries, demographers, epidemiologists and social scientists in general with a unique and valuable tool to simultaneously smooth, decompose and forecast mortality.


Establishing a small animal model for evaluating protective immunity against mumps virus.
Although mumps vaccines have been used for several decades, protective immune correlates have not been defined. Recently, mumps outbreaks have occurred in vaccinated populations. To better understand the causes of the outbreaks and to develop means to control outbreaks in mumps vaccine immunized populations, defining protective immune correlates will be critical. Unfortunately, no small animal model for assessing mumps immunity exists. In this study, we evaluated use of type I interferon (IFN) alpha/beta receptor knockout mice (IFN-α/βR-/-) for such a model. We found these mice to be susceptible to mumps virus administered intranasally and intracranially. Passive transfer of purified IgG from immunized mice protected naïve mice from mumps virus infection, confirming the role of antibody in protection and demonstrating the potential for this model to evaluate mumps immunity.


Lifestyle impact on meal-induced insulin sensitization in health and prediabetes: a focus on diet, antioxidants, and exercise interventions.
The augmented whole-body glucose uptake response to insulin during the postprandial state is described as meal-induced insulin sensitization (MIS). MIS occurs when the presence of food in the upper gastrointestinal tract activates 2 feeding signals (activation of hepatic parasympathetic nerves and elevation of hepatic glutathione level), and causes insulin to release hepatic insulin sensitizing substance (HISS), which stimulates glucose uptake in skeletal muscle, heart, and kidneys. HISS action results in nutrient storage, primarily as glycogen. Impairment of HISS release results in the absence of meal-induced insulin sensitization (AMIS), which causes postprandial hyperglycemia and hyperinsulinemia, and chronically leads to the progression to a cluster of metabolic, vascular, and cardiac dysfunctions, which we refer to as components of the AMIS syndrome. Manipulation of the MIS process in health and in disease, by pharmacological and nonpharmacological interventions, is outlined in this review. High fat or sugar supplemented diet reduces MIS; exercise elevates MIS; and antioxidants protect MIS against reductions associated with diet and age.


Long-term results after ablation for long-standing atrial fibrillation concomitant to surgery for organic heart disease: is microwave energy reliable?
Microwave ablation has been reported as efficient for the surgical treatment of long-standing atrial fibrillation. However, the influence of ablation lesions on long-term results is not known. From August of 2000 to November of 2003, 41 patients underwent a left atrial endocardial microwave ablation procedure after a Cox-Maze-like lesion set for long-standing atrial fibrillation concomitant to surgery for valvular or coronary artery disease. Mitral valve surgery alone or combined was performed in 31 cases (75.6%). The mean diameter of the left atrium was 7.19 +/- 1.44 cm. The mean duration of preoperative atrial fibrillation was 4.7 +/- 3.6 years. Patient follow-up was conducted by means of direct clinical examination, electrocardiography, and transthoracic echocardiography. The mean follow-up was 5.37 +/- 0.91 years. Patient follow-up was achieved in 82% of cases (n = 28). Seven patients (17%) died during follow-up. Stroke was the cause of death in 1 patient with persistence of atrial fibrillation. Major complications occurred in 4 (14.3%) of the patients that were related to the persistence of atrial fibrillation. At 5 years follow-up, 39.3% of patients (11/28) were in sinus rhythm. Seventeen patients (60.7%) were in New York Heart Association classes I and II, and 11 patients (39.3%) were in New York Heart Association class III at the time of follow-up. In our experience, left atrial endocardial microwave ablation for long-standing atrial fibrillation after a Cox-Maze-like ablation lesion set during surgery for organic heart disease is not a reliable method of achieving long-term conversion to sinus rhythm.


Hydrothorax in a PD patient: successful treatment with intrapleural autologous blood instillation.
An 80-year-old female developed massive right hydrothorax at the start of an IPD program. Peritoneal dialysis was interrupted and after complete evacuation of the pleural effusion, 40 ml of the patient's blood was infused into the right pleural cavity. For the first 2 days the patient maintained the Fowler position. Three weeks later, IPD was recommended, but pleural effusion reappeared early on. Infusion of a further 40 ml of the patient's blood was repeated after another pleural evacuation and the dialysis was again stopped for another 3-week period. Subsequently, IPD was restarted with only one-liter exchanges and the patient kept in the Fowler position during the dialysis sessions. After three weeks, standard IPD was started with the patient supine and two-liter exchanges. Hydrothorax did not re-appear and so far (12-month follow-up) no pleural effusion has been noticed. The patient feels well on IPD. Blood instillation was painless and caused one-day fever on the first time only. Pleurodesis achieved with autologous blood is a very safe, simple and effective way of treating hydrothorax in PD patients.


Regulation of GVBD in mouse oocytes by miR-125a-3p and Fyn kinase through modulation of actin filaments.
Meiotically arrested oocytes are characterized by the presence of the nuclear structure known as germinal-vesicle (GV), the breakdown of which (GVBD) is associated with resumption of meiosis. Fyn is a pivotal factor in resumption of the first meiotic division; its inhibition markedly decreases the fraction of oocytes undergoing GVBD. Here, we reveal that in mouse oocytes Fyn is post-transcriptionally regulated by miR-125a-3p. We demonstrate that in oocytes resuming meiosis miR-125a-3p and Fyn exhibit a reciprocal expression pattern; miR-125a-3p decreases alongside with an increase in Fyn expression. Microinjection of miR-125a-3p inhibits GVBD, an effect that is markedly reduced by Fyn over-expression, and impairs the organization of the actin rim surrounding the nucleus. Lower rate of GVBD is also observed in oocytes exposed to cytochalasin-D or blebbistatin, which interfere with actin polymerization and contractility of actin bundles, respectively. By down-regulating Fyn in HEK-293T cells, miR-125a-3p reduces the interaction between actin and A-type lamins, which constitute the nuclear-lamina. Our findings suggest a mechanism, by which a decrease in miR-125a-3p during oocyte maturation facilitates GVBD by allowing Fyn up-regulation and the resulting stabilization of the interaction between actin and A-type lamins.


A Review of the Korean Cultural Syndrome Hwa-Byung: Suggestions for Theory and Intervention.
The purpose of this paper is to review Hwa-Byung, a cultural syndrome specific to Koreans and Korean immigrants. Hwa-Byung is a unique diagnosis and differs from other DSM disorders. However, Hwa-Byung has frequent comorbidity with other DSM disorders such as anger disorders, generalized anxiety disorder, and major depressive disorder. There are several risk factors for Hwa-Byung including psychosocial stress caused by marital conflicts and conflicts with their in-laws. Previous interventions of the Hwa-Byung syndrome were based primarily on the medical model. Therefore, based on previous research, we present a new ecological model of Hwa-Byung. We also recommend some areas of future research as well as present some limitations of our ecological model. Finally, we discuss some treatment issues, particularly for Korean women in the United States.


Pulmonary hypertension in hereditary hemorrhagic telangiectasia: A clinical review.
Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant hereditary disorder characterized by recurrent spontaneous epistaxis, mucocutaneous telangiectasias, and solid organ arteriovenous malformations (AVMs). Pulmonary hypertension (PH) is an increasingly recognized complication in patients with HHT, most often precipitated by high-output heart failure in the presence of hepatic AVMs as well as pulmonary arterial hypertension in the form of a proliferative vasculopathy. The presence of PH in patients with HHT is associated with significant elevations in rates of morbidity and mortality. Additionally, there is growing recognition of a thromboembolic propensity in this population that increases the risk of chronic thromboembolic PH, posing unique clinical considerations regarding the use of anticoagulation. Patients with HHT are also at risk of PH due to disorders commonly seen in the general population, including left-sided heart and lung disease. The etiology of PH in HHT is multifaceted and complex; the diagnostic approach and treatment strategies must consider the underlying pathophysiology of HHT. This comprehensive review summarizes current knowledge of PH in HHT, detailing the pathogenesis of known etiologies, diagnostic evaluation, and suggested treatment modalities as well as emerging therapies that may be of future interest.


Validating a measure of religiousness/spirituality for Native Hawaiians.
Religiousness and spirituality are integral to the human experience. There is emerging literature that shows that religiousness and spirituality are associated with various mental and physical health outcomes. Yet, the development of measures to accurately assess these phenomena in health settings is still in its early stages. The difficulties in developing standardized definitions and measures relate to varying interpretations of religiousness and spirituality, a reluctance to utilize a scientific approach to understand an existential and personal experience, and multicultural distinctions. The potential for designing health interventions in which religiousness and spirituality are integrated rests upon the development of measures that are psychometrically sound. This paper reports on preliminary research that empirically assesses one measure of religiousness and spirituality for Native Hawaiians--a group besieged with an array of health problems. The measure is the Brief Multidimensional Measure of Religiousness/Spirituality (BMMRS) developed by the National Institute on Aging and the Fetzer Institute. This instrument has shown to have appropriate reliability and validity scores. A modified BMMRS was administered to 15 Native Hawaiians who underwent a cultural intervention of exercise, diet, and education in a program called Uli'eo Koa (warrior fitness). The BMMRS was slightly modified based on the literature and earlier research to be more specific to Native Hawaiians. Overall, measures of internal consistency supported the reliability of the BMMRS. The strongest subscales included the domains of "daily spiritual experiences," "religious and spiritual coping," and "religious support." Low internal consistency estimates for the items, "watches/listens to religious programs," "family makes demands," and "significant loss in faith," suggest that these items do not measure the same concept for participants. Although the intercorrelations among the subscales were generally low and with wide variability, 10 of the 17 subscales/single items were moderately to highly correlated with one another, indicating concurrent validity. These subscales, some of which assessed, "daily spiritual experiences," "religious and spiritual coping," and "organizational religiousness," suggest that core ideas on spirituality and religiousness for these participants, broadly reflect both "personal" and "organizational" viewpoints. Caution should be used in interpreting the results of the study because of limitations in the study's design. However, despite these limitations in design, this study provides empirical support for future research on religiousness and spirituality for Native Hawaiians.


A positive feedback loop involving nuclear factor IB and calpain 1 suppresses glioblastoma cell migration.
Glioblastoma (GBM) is a brain tumor that remains largely incurable because of its highly-infiltrative properties. Nuclear factor I (NFI)-type transcription factors regulate genes associated with GBM cell migration and infiltration. We have previously shown that NFI activity depends on the NFI phosphorylation state and that calcineurin phosphatase dephosphorylates and activates NFI. Calcineurin is cleaved and activated by calpain proteases whose activity is, in turn, regulated by an endogenous inhibitor, calpastatin (CAST). The CAST gene is a target of NFI in GBM cells, with differentially phosphorylated NFIs regulating the levels of CAST transcript variants. Here, we uncovered an NFIB-calpain 1-positive feedback loop mediated through CAST and calcineurin. In NFI-hyperphosphorylated GBM cells, NFIB expression decreased the CAST-to-calpain 1 ratio in the cytoplasm. This reduced ratio increased autolysis and activity of cytoplasmic calpain 1. Conversely, in NFI-hypophosphorylated cells, NFIB expression induced differential subcellular compartmentalization of CAST and calpain 1, with CAST localizing primarily to the cytoplasm and calpain 1 to the nucleus. Overall, this altered compartmentalization increased nuclear calpain 1 activity. We also show that nuclear calpain 1, by cleaving and activating calcineurin, induces NFIB dephosphorylation. Of note, knockdown of calpain 1, NFIB, or both increased GBM cell migration and up-regulated the pro-migratory factors fatty acid-binding protein 7 (FABP7) and Ras homolog family member A (RHOA). In summary, our findings reveal bidirectional cross-talk between NFIB and calpain 1 in GBM cells. A physiological consequence of this positive feedback loop appears to be decreased GBM cell migration.


A case of anomalous arrangement of the pancreaticobiliary ductal system demonstrated by intraductal ultrasonography.
A 55-yr-old female was hospitalized with epigastric pain. Conventional ultrasonography revealed marked dilation of the common bile duct (CBD). Endoscopic retrograde cholangiopancreatography showed fusiform dilation of the CBD. The common channel of the pancreatic duct and choledochus was 20 mm long. A diagnosis of congenital choledochal dilation accompanied by anomalous arrangement of the pancreaticobiliary ductal system (AAPBDS) was made. Intraductal ultrasonography (IDUS) was performed. IDUS demonstrated the union of the pancreatic duct and choledochus within the pancreatic parenchyma. This meant that the union existed outside the duodenal wall, confirming the diagnosis of AAPBDS. Although endoscopic retrograde cholangiopancreatography alone could show the maljunction in this case, simultaneous IDUS will be useful in making an accurate diagnosis of AAPBDS.


Cancer mortality and morbidity among rubber workers.
Mortality and morbidity from cancer among a cohort of 13,570 white male rubber workers were examined. Each man worked for at least 5 years at the Akron, Ohio, plant of the B. F. Goodrich Company. The potential period of follow-up was from January 1, 1940 to June 30, 1976. Departmental work histories were based primarily on records maintained by Local no. 5, United Rubber Workers. The occurrence of cancer was measured by death certificates and by a survey of Akron-area hospital tumor registries from 1964 to 1974. Two types of analyses were made: 1) an external comparison of mortality rates of rubber workers versus rates of U.S. white males, and 2) an internal comparison of cancer morbidity rates among persons who were employed in various work areas of the plant. Excess cases of specific cancers (observed/expected numbers) among workers in specific work areas included: stomach and intestine: rubber making (30/14.4); lung: tire curing (31/14.1), fuel cells and/or deicers (46/29.1); bladder: chemical plant (6/2.4), and tire building (16/10.7); skin cancer: tire assembly (12/1.9); brain cancer: tire assembly (8/2.0); lymphatic cancer: tire building (8/3.2); and leukemia: calendering (8/2.2), tire curing (8/2.6), tire building (12/7.5), elevators (4/1.4), tubes (4/1.6), and rubber fabrics (4/1.1). Agents that may be responsible for these excesses were considered.


Assessing the Effect of Iron on Oral Health Status among the General Population Residing in High and Low Levels of Iron Blocks in Namakkal District, Tamil Nadu, India: A Cross-Sectional Study.
This study aims to assess the effect of iron on oral health status among the general population residing in high and low levels of iron blocks in the Namakkal district of Tamil Nadu, India. A cross-sectional study was conducted to assess the impact of iron on oral health among people in the Namakkal district of Tamil Nadu, India. The sample size was estimated to be 600, which were equally divided into two groups based on the high and low levels of iron (300 samples) content of water in the Namakkal district based on the multistage random sampling method. A pre-tested structured questionnaire was used to collect the demographic data and oral hygiene practices of the people. Dental stains were recorded using a modified Lobene stain index. P value < 0.05 was considered to be statistically significant. The area and intensity of the dental stains were not significant with age, gender, and blocks. There was no statistically significant difference between the high iron and low iron blocks for the area (A), intensity (I), and I × A of stains. The study concludes that the water samples with both high and low levels of iron had a strong impact on the oral health of the people.


[Development of polyaxial locking plate screw system of sacroiliac joint].
To develop an instrument for sacroiliac joint fixation with less injury and less complications. Firstly, 18 adult pelvic specimens (8 males and 10 females) were used to measure the anatomical data related to the locking plates and locking screws on the sacrum and ilium, and the polyaxial locking plate screw system of the sacroiliac joint was designed according to the anatomic data. This system was made of medical titanium alloy. Then 4 adult male plevic specimens were harvested and the experiment was divided into 3 groups: group A (normal pelvic), group B (the dislocated sacroiliac joint fixed with sacroiliac screws), and group C (the dislocated sacroiliac joint fixed with polyaxial locking plate screw system). The vertical displacement of sacroiliac joint under the condition of 0-700 N vertical load and the horizontal displacement on angle under the condition of 0-12 N·m torsional load were compared among the 3 groups by using the biological material test system. Finally, the simulated application test was performed on 1 adult male cadaveric specimen to observe soft tissue injury and the position of the locking plate and screw by X-ray films. According to the anatomic data of the sacrum and ilium, the polyaxial locking plate screw system of the sacroiliac joint was designed. The biomechanical results showed that the vertical displacement of the sacroiliac joint under the condition of 0-700 N vertical load in group A was significantly bigger than that in group B and group C (P < 0.05), but there was no significant difference between group B and group C (P > 0.05). The horizontal displacement on angle under the condition of 0-12 N·m torsional load in group A was significantly less than that in group B and group C (P < 0.05). The horizontal displacement on angle under the condition of 0-6 N·m torsional load in group B was bigger than that in group C, and the horizontal displacement on angle under the condition of 6-12 N·m torsional load in group B was less than that in group C, but there was no significant difference between group B and group C (P > 0.05). The test of simulating application showed that the specimen suffered less soft tissue injury, and this instrument could be implanted precisely and safely. The polyaxial locking plate screw system of the sacroiliac joint has the advantages of smaller volume and less injury; polyaxial fixation enables flexible adjustment screw direction. The simulated application test shows satisfactory fixing effect.


Increased risk of preterm birth among non- smoking, non- alcohol drinking women with maternal periodontitis.
The aim of this case-control study was to examine the association between periodontitis and preterm birth among non-smoking, non-alcohol drinking women. The cases were 130 women who delivered a live singleton newborn before 37 weeks gestation. A random sample of 260 women who delivered a normal child on the same day as the cases were selected as controls. Periodontal examinations were performed during 24-hour period postpartum at bedside. Other related information was collected by structured questionnaire and medical records. Multiple logistic regression analysis was performed controlling for age, ethnicity, place of residence, education, occupation, income, pre-pregnancy body mass index (BMI), weight gain, antenatal care (ANC), parity, systematic infections, genitourinary infections, antibiotics used, and history of periodontal treatment. Periodontitis (defined as presence of at least 4 teeth having > or = 1 site with a probing depth (PD) > or = 4 mm, clinical attachment loss (CAL) > or = 3 mm and bleeding on probing (BOP) after 10 seconds at the same site) was diagnosed in 33.9% of cases and 10.4% of controls. Periodontitis was significantly associated with preterm birth (adjusted OR = 4.47, 95%Cl= 2.43, 8.20). These findings suggest that periodontitis may increase the risk of preterm delivery even among women who do not smoke or drink.


[Nutritive physiological effect of dietary fats in rations for growing swine. 2. Effect of an isocaloric exchange of carbohydrate energy versus fat energy in piglets on growth and various metabolic parameters in the subsequent fattening period].
The influence of different feeding regimes of piglets on fattening performance and blood composition of the subsequent fattening period (30-100 kg) was examined. Three groups of pigs fed on an isocaloric and isonitrogenous basis with rations containing either 5% fat (groups I), 18% fat (group II) or 35% fat (group III) until body weight of 30 kg, were fed ad libitum one diet from 30 kg onwards. At a body weight of 45 and 93 kg the blood concentrations of insulin, glucose, urea, free fatty acids, neutral lipids and cholesterol in response to feeding and of insulin and glucose in response to an oral glucose load was determined in pigs provided with a permanent jugular vein catheter. Moreover, the in-vitro fat synthesis from glucose was measured. At the end of the experiment the body composition was determined by chemical analysis of the carcass. Neither feed intake, daily body weight gain nor feed conversion differed significantly among the groups. Blood urea levels of the three groups did not suggest a different protein utilization. Neither feed consumption nor oral intake of glucose affected the insulin and glucose response of the three groups differently. The concentrations of free fatty acids, neutral lipids and cholesterol did not differ clearly among the groups although occasionally significance of difference was observed. In group I the in-vitro synthesis of fat was increased (p less than 0.05) at a body weight of 45 kg and appeared to be higher at a body weight of 93 kg as compared to the high fat group (group III). No clear differences between the groups were observed in the chemical composition of the carcasses. It is concluded, that isocaloric replacement of carbohydrates by fat in the diet of piglets does not affect protein and fat retention in the subsequent fattening period.


Joint associations of multiple leisure-time sedentary behaviours and physical activity with obesity in Australian adults.
Television viewing and physical inactivity are independently associated with risk of obesity. However, how the combination of multiple leisure-time sedentary behaviours (LTSB) and physical activity (LTPA) may contribute to the risk of obesity is not well understood. We examined the joint associations of multiple sedentary behaviours and physical activity with the odds of being overweight or obese. A mail survey collected the following data from adults living in Adelaide, Australia (n = 2210): self-reported height, weight, six LTSB, LTPA and sociodemographic variables. Participants were categorised into four groups according to their level of LTSB (dichotomised into low and high levels around the median) and LTPA (sufficient: >/= 2.5 hr/wk; insufficient: < 2.5 hr/wk). Logistic regression analysis examined the odds of being overweight or obese (body mass index >/= 25 kg/m2) by the combined categories. The odds of being overweight or obese relative to the reference category (low sedentary behaviour time and sufficient physical activity) were: 1.54 (95% confidence interval [CI]: 1.20-1.98) for the combination of low sedentary behaviour time and insufficient physical activity; 1.55 (95% CI: 1.20-2.02) for the combination of high sedentary behaviour time and sufficient physical activity; and 2.26 (95% CI: 1.75-2.92) for the combination of high sedentary behaviour time and insufficient physical activity. Those who spent more time in sedentary behaviours (but were sufficiently physically active) and those who were insufficiently active (but spent less time in sedentary behaviour) had a similar risk of being overweight or obese. Reducing leisure-time sedentary behaviours may be as important as increasing leisure-time physical activity as a strategy to fight against obesity in adults.


Place and Grid Cells in a Loop: Implications for Memory Function and Spatial Coding.
Place cells in the hippocampus and grid cells in the medial entorhinal cortex have different codes for space. However, how one code relates to the other is ill understood. Based on the anatomy of the entorhinal-hippocampal circuitry, we constructed a model of place and grid cells organized in a loop to investigate their mutual influence in the establishment of their codes for space. Using computer simulations, we first replicated experiments in rats that measured place and grid cell activity in different environments, and then assessed which features of the model account for different phenomena observed in neurophysiological data, such as pattern completion and pattern separation, global and rate remapping of place cells, and realignment of grid cells. We found that (1) the interaction between grid and place cells converges quickly; (2) the spatial code of place cells does not require, but is altered by, grid cell input; (3) plasticity in sensory inputs to place cells is key for pattern completion but not pattern separation; (4) grid realignment can be explained in terms of place cell remapping as opposed to the other way around; (5) the switch between global and rate remapping is self-organized; and (6) grid cell input to place cells helps stabilize their code under noisy and/or inconsistent sensory input. We conclude that the hippocampus-entorhinal circuit uses the mutual interaction of place and grid cells to encode the surrounding environment and propose a theory on how such interdependence underlies the formation and use of the cognitive map.SIGNIFICANCE STATEMENT The mammalian brain implements a positional system with two key pieces: place and grid cells. To gain insight into the dynamics of place and grid cell interaction, we built a computational model with the two cell types organized in a loop. The proposed model accounts for differences in how place and grid cells represent different environments and provides a new interpretation in which place and grid cells mutually interact to form a coupled code for space.


Acute rejection of porcine small bowel allograft. An extended histological scoring system.
Using nonimmunosuppressed piglet small bowel grafts, we performed a detailed histological study on acute rejection and analyzed altogether 45 different histological parameters throughout the bowel wall, in 10 allografts and 6 autografts. Heterotopic grafts were followed by full-thickness biopsies every other day beginning on the 3rd day after transplantation. The parameters were scored from 0 to 3 according to the severity of the change and the values of every variable were compared statistically between the 2 groups. The earliest significant changes, beginning on days 3-5, were infiltration of inflammatory cells and pyroninophilia among these cells in lamina propria; edema, fibrosis, and inflammation in submucosa and muscularis; vacuolar degeneration of myocytes; and endothelial and intimal changes in vessels. Villous blunting and cuboidal epithelium were the other early markers. On day 7, the epithelial and vascular changes became most significant. We want to emphasize especially the vascular parameters: endothelial swelling and proliferation, intimal thickening, intramural inflammation, and obliteration of the lumen. The dilatation of lymph vessels and changes of Peyer's patches had no value in the estimation of rejection. All allografts became necrotic by day 11 after transplantation.


[Incomplete ciliary axonema: anther cause of ciliary dysmotility syndrome?].
Immotile cilia syndrome is associated with different ciliary defects, although the clinical presentation is similar in every case. A study was made of a 36-year-old woman with recurrent respiratory infections since birth, chronic sinusitis and chronic bronchitis with bronchiectasias. Her medical history included a tubaric pregnancy and two miscarriages. Nasal mucociliary transport was investigated on two occasions at a 1-year interval using an isotopic technique. Ciliary ultrastructure was studied by electron microscopy after obtaining two biopsies from the inferior and middle turbinates separated by a 1-year interval. The sweat test and blood immunoglobulins were normal. The absence of mucociliary transport was verified on both occasions. An abnormality was observed in 30% of the cilia in the form of semicircular ciliary cross-sections, with only 7 pairs of peripheral microtubules. The central pair was normal. We termed this anomaly "incomplete ciliary axonema" and believe that it could be another cause of immotile cilia syndrome.


Factors influencing detection of tolerance in Staphylococcus aureus.
The phenomenon of tolerance to cloxacillin and methicillin was studied in Staphylococcus aureus. It was demonstrated that the minimal bactericidal concentrations showed marked differences, depending on the method of detection used. These differences resulted from carry-over of the antibiotic to the subculture plates. When carry-over of the antibiotic was prevented by the addition of beta-lactamase to the nutrient medium, the antibiotics were no longer bactericidal. At a certain antibiotic concentration and at higher concentrations, however, each strain showed a certain survival percentage after 24 h. The tolerance percentage was determined for 15 strains. The values found for the individual strains ranged from less than 0.1 to 11% for cloxacillin and methicillin. since these percentages were reproducible within narrow limits, they could be regarded as a characteristic of the strains. The tolerance percentage was independent of the growth phase of the initial cultures.


Gene therapy, fundamental rights, and the mandates of public health.
Recent and near-future developments in the field of molecular biology will make possible the treatment of genetic disease on an unprecedented scale. The potential applications of these developments implicate important public policy considerations. Among the questions that may arise is the constitutionality of a state-mandated program of gene therapy for the purpose of eradicating certain genetic diseases. Though controversial, precedents of public health jurisprudence suggest that such a program could survive constitutional scrutiny. This article provides an overview of gene therapy in the context of fundamental rights and the mandates of public health.


Silver acetate mouth spray as an aid in smoking cessation: results of a double-blind trial.
We studied the use of an aversive technique to improve the outcome of smoking-cessation efforts. We hypothesized that a silver acetate mouth spray, which produces a strong aversive taste when cigarettes are smoked, would increase the quit rate among smokers. Our study was a double-blind, placebo-controlled trial that was carried out in a private family practice office in an urban area. We studied 42 smokers, who were recruited by advertisement and who were motivated to quit by self-report. They were randomly assigned active spray or placebo spray; all were given a written list of behavioral suggestions. The spray was to be used every 2 hours for 3 weeks during which time the subjects were to keep diaries of cigarette smoking and spray use. Biochemical measures (salivary thiocyanate and cotinine) were recorded at entry, at 3 weeks, and at 3 months. Thirty smokers completed the study. No differences were found between the two groups in quit rate or number of cigarettes smoked. Silver acetate aversive spray did not increase quit rate among motivated smokers.


Metagenomic next-generation sequencing of radial ultrasound bronchoscopy-guided "cocktail" specimens as an efficient method for the diagnosis of focal pulmonary infections: a randomised study.
To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of focal pulmonary infections by using radial ultrasound bronchoscopic "cocktail" specimens. From March 2019 to May 2020, 90 patients with focal pulmonary infections [locatable by a radial probe endobronchial ultrasound (RP-EBUS)] treated by the Department of Respiratory and Critical Care Medicine at the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital (Suzhou, China) were randomly allocated to the "cocktail" group, transbronchial brushing (TBBr) group or bronchoalveolar lavage fluid (BALF) group; 30 patients were assigned to each group. Using the extracted material, the diagnostic efficacy of the mNGS test for pathogen detection was compared across the three groups, and the effect of an antibiotic treatment on detection rate was assessed. The sensitivity of mNGS analysis in cocktail group, TBBr group and BALF group was 90% (27/30), 66.7 (20/30) and 50% (15/30), respectively. The analysis of the sensitivity of the positive test, the detection rate of multiple pathogens, and the effect of antibiotics on the detection rate by mMGS indicated that the "cocktail" group was significantly higher number of samples positive for pathogens than the TBBr group (P<0.05), and the TBBr group was significantly higher number of samples positive for pathogens than the BALF group (P<0.05). "Cocktail" specimens had high sensitivity in the identification of focal pathogens, and the use of antibiotics had little effect on the results of the mNGS analysis. These clinically valuable results can be used in the diagnosis and treatment of patients with focal pulmonary infections.


Efficacy of airway pressure release ventilation for acute respiratory distress syndrome: a systematic review with meta-analysis.
For many years, airway pressure release ventilation (APRV) has been used to manage patients with lung conditions such as acute respiratory distress syndrome (ARDS). However, it is still unclear whether APRV improves outcomes in critically ill ARDS patients who have been admitted to an intensive care unit (ICU). In this study, randomized controlled trials (RCTs) were used to compare the efficacy of APRV to traditional modes of mechanical ventilation. RCTs were sourced from PubMed, Cochrane, and Embase databases (the last dates from August 8, 2019). The Cochrane Handbook for Systematic Reviews of Interventions was used to assess the risk of bias. The relative risk (RR), mean difference (MD), and 95% confidence intervals (CI) were then determined. Article types such as observational studies, case reports, animal studies, etc., were excluded from our meta-analysis. In total, the data of 6 RCTs and 360 ARDS patients were examined. Six studies with 360 patients were included, our meta-analysis showed that the mean arterial pressure (MAP) in the APRV group was higher than that in the traditional mechanical ventilation group (MD =2.35, 95% CI: 1.05-3.64, P=0.0004). The peak pressure (Ppeak) was also lower in the APRV group with a statistical difference noted (MD =-2.04, 95% CI: -3.33 to -0.75, P=0.002). Despite this, no significant beneficial effect on the oxygen index (PaO2/FiO2) was shown between the two groups (MD =26.24, 95% CI: -26.50 to 78.97, P=0.33). Compared with conventional mechanical ventilation, APRV significantly improved 28-day mortality (RR =0.66, 95% CI: 0.47-0.94, P=0.02). All the included studies were considered to have an unclear risk of bias. We determined that for critically ill patients with ARDS, the application of APRV is associated with an increase in MAP. Inversely, a reduction of the airway Ppeak and 28-day mortality was recorded. There was no sufficient evidence to support the idea that APRV is superior to conventional mechanical ventilation in improving PaO2/FiO2.


[Antibacterial activity of sponge associated marine bacterium Pseudoalteromonas sp. NJ6-3-1 regulated by quorum sensing].
We chose a sponge-associated marine-bacterium Pseudoalteromonas piscicida NJ6-3-1 to study whether its antibacterial activity were regulated by quorum sensing. We studied the relationship between the antibacterial activity and bacterial density under various growth conditions. To simulate the natural competitive environment, we monitored the antibacterial activity at low cell density when the species were co-cultured with Staphylococcus aureus. Antibacterial activity correlated closely with cell density. Marine bacterium NJ6-3-1 started producing antibacterial compounds when cell density reached the threshold value of OD(630) = 0.4. Some signal molecules existing in the metabolites of S. aureus could induce the production of antibacterial substance by marine-bacteria NJ6-3-1 even cell density below the required threshold. The results provide preliminary evidence to support the hypothesis that the antibacterial activity of NJ6-3-1 was regulated by the quorum sensing system of intraspecies and interspecies.


A free clinic for youth in an academic department of pediatrics.
The Gainesville Youth Clinic was organized to meet a community need for medical care of nonuniversity youth and to provide experience in adolescent medicine to pediatric house officers. Demographic and clinical data were gathered in three studies spanning the first 15 months of operation. The clinic sees 2,200 patients (3,000 visits) annually; two thirds are girls, 98% are white, and 90% are 15 to 25 years old. The population was not predominantly transient; parental occupations were mostly professional or skilled. Educational level was consistent with age; one third of the patients are students at present. Genitourinary problems, principally venereal infection, account for nearly one third of all visits and suspected pregnancy or birth control another one fourth. The clinic experience has emphasized the youth cultural influences on health, increased the participant's insight into the emotional turmoil of adolescence, and has suggested a style and design for providing primary care to this population consistent with the academic objectives of a pediatric department.


Power and polarization monitor development for high power millimeter-wave.
A new type monitor of power and polarization states of millimeter-waves has been developed to be installed at a miter-bend, which is a part of transmission lines of millimeter-waves, for electron cyclotron resonance heating on the Large Helical Device. The monitor measures amplitudes and phase difference of the electric field of the two orthogonal polarizations which are needed for calculation of the power and polarization states of waves. The power and phase differences of two orthogonal polarizations were successfully detected simultaneously.


Predicting hospitalisations related to ambulatory care sensitive conditions with machine learning for population health planning: derivation and validation cohort study.
To predict older adults' risk of avoidable hospitalisation related to ambulatory care sensitive conditions (ACSC) using machine learning applied to administrative health data of Ontario, Canada. A retrospective cohort study was conducted on a large cohort of all residents covered under a single-payer system in Ontario, Canada over the period of 10 years (2008-2017). The study included 1.85 million Ontario residents between 65 and 74 years old at any time throughout the study period. Administrative health data from Ontario, Canada obtained from the (ICES formely known as the Institute for Clinical Evaluative Sciences Data Repository. Risk of hospitalisations due to ACSCs 1 year after the observation period. The study used a total of 1 854 116 patients, split into train, validation and test sets. The ACSC incidence rates among the data points were 1.1% for all sets. The final XGBoost model achieved an area under the receiver operating curve of 80.5% and an area under precision-recall curve of 0.093 on the test set, and the predictions were well calibrated, including in key subgroups. When ranking the model predictions, those at the top 5% of risk as predicted by the model captured 37.4% of those presented with an ACSC-related hospitalisation. A variety of features such as the previous number of ambulatory care visits, presence of ACSC-related hospitalisations during the observation window, age, rural residence and prescription of certain medications were contributors to the prediction. Our model was also able to capture the geospatial heterogeneity of ACSC risk in Ontario, and especially the elevated risk in rural and marginalised regions. This study aimed to predict the 1-year risk of hospitalisation from ambulatory-care sensitive conditions in seniors aged 65-74 years old with a single, large-scale machine learning model. The model shows the potential to inform population health planning and interventions to reduce the burden of ACSC-related hospitalisations.


Quantum spherical spin models.
A recently introduced class of quantum spherical spin models is considered in detail. Since the spherical constraint already contains a kinetic part, the Hamiltonian need not have kinetic term. As a consequence, situations with or without momenta in the Hamiltonian can be described, which may lead to different symmetry classes. Two models that show this difference are analyzed. Both models are exactly solvable and their phase diagram is analyzed. A transversal external field leads to a phase transition line that ends in a quantum critical point. The two considered symmetries of the Hamiltonian considered give different critical phenomena in the quantum critical region. The model with momenta is argued to be analog to the large-N limit of an SU(N) Heisenberg ferromagnet, and the model without momenta shares the critical phenomena of an SU(N) Heisenberg antiferromagnet.


Electro-deposition and re-oxidation of carbon in carbonate-containing molten salts.
The electrochemical deposition and re-oxidation of solid carbon were studied in CO3(2-) ion-containing molten salts (e.g. CaCl2-CaCO3-LiCl-KCl and Li2CO3-K2CO3) at temperatures between 500 and 800 °C under Ar, CO2 or N2-CO2 atmospheres. The electrode reactions were investigated by thermodynamic analysis, cyclic voltammetry and chronopotentiometry in a three-electrode cell under various conditions. The findings suggest that the electro-reduction of CO3(2-) is dominated by carbon deposition on all three tested working electrodes (Ni, Pt and mild steel), but partial reduction to CO can also occur. Electro-re-oxidation of the deposited carbon in the same molten salts was investigated for potential applications in, for example, direct carbon fuel cells. A brief energy and cost analysis is given based on results from constant voltage electrolysis in a two-electrode cell.


Plasma advanced glycation end products and soluble receptor for advanced glycation end products as indicators of sterol content in human carotid atherosclerotic plaques.
Advanced glycation end products (AGEs) are independently related to cardiovascular disease (CVD) and favor cholesterol and oxysterol accumulation in macrophage foam cells. Soluble RAGE (sRAGE) impairs cellular AGE signaling alleviating the deleterious effects of AGE in atherogenesis. The association between plasma AGEs and sRAGE with the content of cholesterol, markers of cholesterol synthesis and absorption, and oxysterols in atherosclerotic plaques was evaluated in subjects undergoing carotid endarterectomy.Plasma and carotid plaques were obtained from symptomatic (n = 23) and asymptomatic subjects (n = 40). Lipids from plaques were extracted and sterols (oxysterols, cholesterol, desmosterol, lathosterol, sitosterol, and campesterol) were determined by using gas chromatography/mass spectrometry. Plasma total AGEs and pentosidine were measured by using fluorimetry and sRAGE by using ELISA.In symptomatic subjects´ atherosclerotic plaques, an increased amount of cholesterol (3x) and oxysterols [7 α-hydroxycholesterol (1.4x); 7 β-hydroxycholesterol (1.2x); 25-hydroxycholesterol (1.3x); 24-hydroxycholesterol (2.7x), and 27-hydroxycholesterol, (1.15x)], with exception to 7 ketocholesterol, were found in comparison to asymptomatic individuals. Plasma total AGEs and pentosidine significantly and positively correlated to sterols accumulated in the atherosclerotic lesion, including cholesterol, desmosterol, campesterol, sitosterol, and oxysterols. On the other hand, sRAGE inversely correlated to total AGEs and pentosidine in plasma, and with major species of oxysterols, cholesterol, and markers of cholesterol synthesis and absorption in the atherosclerotic lesion. In multiple regression analyses, it was observed a significant inverse correlation between sRAGE and 24-hydroxycholesterol and desmosterol, and a positive significant correlation between pentosidine and 24-hydroxycholesterol, 27-hydroxycholesterol, and campesterol.In conclusion, the plasma concentration of AGEs and sRAGE is a tool to predict the accumulation of sterols in atherosclerotic lesions in symptomatic and asymptomatic individuals, helping to prevent and improve the management of acute cardiovascular complications.


Absorbable vs Nonabsorbable Sutures for Achilles Tendon Repair: A Systematic Review and Meta-analysis.
Nonabsorbable sutures are still the main choice for acute Achilles tendon rupture (AATR) repair due to strength provided. However, the rerupture rates, infection risks, foreign body reaction, and postsurgical recovery differences between absorbable and nonabsorbable suture materials in AATR repair have not been carefully reviewed. A systematic review was done on PubMed, EBSCO, Cochrane Central Register of Controlled Trials, and Embase to find research studies in relation to complications associated with AATR repair using the PRISMA guidelines. The risk of bias from each study included will be assessed using the Cochrane Risk of Bias Tool for randomized study (RoB 2) and Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) for nonrandomized study. Five studies with a total of 255 patients, 105 in the absorbable suture group and 150 in the nonabsorbable suture group, were included for analysis. Risk of rerupture, infection, and foreign body reaction shown no significant difference between groups, and the mean difference of recovery scores were similar. Existing literature shows that absorbable sutures appear to be associated with similar outcomes to nonabsorbable sutures regarding rates of rerupture, infection, foreign body reaction, and outcomes grading following surgical repair of acute Achilles tendon repair.


[VEGF overespression promotes the proliferation and differentiation of human adipose-derived stem cells].
Objective To investigate the effect of vascular endothelial growth factor (VEGF) overexpression on the phenotype, proliferation and multilineage differentiation ability of human adipose-derived stem cells (hADSCs). Methods Passage-2 hADSCs were transfected with pIRES2-EGFP-VEGF plasmid using DOTAP liposomal technique, whereas hADSCs in control group were transfected in absence of plasmid. The success of transfection was confirmed by immunofluorescent cytochemistry. Phenotype differences between the two groups were detected using flow cytometry. Proliferation ability was assessed using MTT assay. Adipogenic and osteogenic differentiation were induced and confirmed using Oil Red O staining and alizarin red staining. Results The transfected hADSCs expressed EGFP and VEGF, whereas no EGFP was observed in the untransfected hADSCs. Both groups of hADSCs showed high expressions of CD29, CD44, CD90, and low expressions of CD31 and CD45. Compared with the untransfected hADSCs, the transfected hADSCs exhibited significantly increased proliferation ability as well as the number of lipid droplets, calcium nodules, and the stained area. Conclusion VEGF overexpression promotes proliferation and multilineage differentiation potential of hADSCs without evident phenotype changes.


The Neural Basis Linking Achievement Motivation With Procrastination: Left Precuneus Connectivity With Right Anterior Cingulate Cortex.
Procrastination adversely affects individual's learning, working, health, and well-being, which troubles many people around the world. Previous studies have indicated that people with higher achievement motivation tend to have less procrastination. However, how achievement motivation is linked with procrastination at the neural level is still poorly understood. Here, we adopted the voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) methods to study this issue. The VBM analysis revealed that higher achievement motivation was correlated with larger gray matter volumes in left precuneus (lPre). Furthermore, the RSFC results showed that the functional connectivity between lPre and right anterior cingulate cortex (rACC) was positively associated with achievement motivation and negatively correlated with procrastination. More importantly, a mediation analysis demonstrated that achievement motivation fully mediated the relation between lPre-rACC connectivity and procrastination. These findings suggested that lPre-rACC coupling might be the neural correlate underlying the association between achievement motivation and procrastination.


Physiological and pathological processes of synaptic plasticity and memory in drug discovery: Do not forget the dose-response curve.
The response of a biological system to an endogenous or exogenous molecule depends upon the dose. For this reason, performing dose-response curves is crucial to understand physiological and pathophysiological phenomena, and to predict the effect of a drug. Most of the studies in pharmacological research have been performed according to the classical threshold model, focusing on higher doses able to ensure a biological effect. However, recent evidences pointed out the need to investigate the effect of low doses. Indeed, several molecules behave in a hormetic fashion, i.e. low-doses stimulate whereas high-doses inhibit a biological response. This is particularly interesting in CNS, where several physiological molecules involved in neuronal transmission during learning and memory have shown a biphasic effect that might represent the link between physiology and pathology. In this review we will focus on cholinergic, glutamatergic and nitrinergic transmission, because of their central role in learning and memory and their impairment in neurodegenerative disorders such as Alzheimer's disease. Pre-clinical studies performed on healthy adult animals and aged animals, as well as transgenic animal models of AD, have suggested a biphasic DR for acetylcholine, glutamate and nitric oxide. This stresses the relevance to perform DR curves when studying the mechanisms underlying synaptic plasticity and memory, the pharmacological profile of cognitive-enhancing drugs acting on these systems, and the possibility to combine low/ineffective doses of drugs that might have additive/synergistic effects, reducing the unwanted side effects associated to the high doses.


Analysis of clinical pharmacist interventions in the neurology unit of a Brazilian tertiary teaching hospital.
It is estimated that around five to 10.0% of hospital admissions occur due to clinical conditions resulting from pharmacotherapy. Clinical pharmacist's activity can enhance drug therapy's effectiveness and safety through pharmacotherapy interventions (PIs), thus minimizing drug-related problems (DRPs) and optimizing the allocation of financial resources associated with health care. This study aimed to estimate the DRPs prevalence, evaluate PI which were performed by clinical pharmacists in the Neurology Unit of a Brazilian tertiary teaching hospital and to identify factors associated with the occurrence of PI-related DRP. A single-arm trial included adults admitted in the referred Unit from 2012 July to 2015 June. Patients were evaluated during their hospitalization period and PIs were performed based on trigger DRPs that were detected in medication reconciliation (admission or discharge) or during inpatient follow-up. Student's t-test, Chi-square test, Pearson and Multiple logistic regression models to analise the association among age, number of drugs, hospitalization period, and number of diagnoses with occurrence of DRPs. Analyses level of significance was 5%. In total 409 inpatients were followed up [51.1% male, mean age of 49.1 (SD 16.5)]. Patients received, on average, 11.9 (SD 5.8) drugs, ranging from two to 38 drugs per patient, and 54.3% of the sample presented at least one DRP whose most frequent description was "untreated condition". From all 516 performed PIs that resulted from DRPs, 82.8% were accepted and the majority referred to "drug introduction" (27.5%). Multiple logistic regression showed that age, length of hospital stay, number of drugs used, diagnosis of epilepsy, multiple sclerosis and myasthenia gravis would be clinical variables associated with DRP (p < 0,05). Monitoring the use of drugs allowed the clinical pharmacist to detect DRPs and to suggest interventions that promote rational pharmacotherapy.


Ba adsorption on the stoichiometric and defective TiO(2) (110) surface from first-principles calculations.
A theoretical study on Ba adsorption on the rutile TiO(2) (110) surface has been carried out by means of plane-wave, plane augmented waves potential, density functional theory calculations. A model consisting on a (4 x 1) unit cell, which corresponds to coverage of 0.125 monolayer (ML), has been used and several potential adsorption sites on the stoichiometric surface have been tried. It has been found that the most stable site is with the Ba atom in a position where it is bound to two bridging oxygen atoms and an in-plane oxygen atom forming equivalent bonds (OB site). The adsorption energy is 0.71 eV referred to the formation of Ba bulk and is about 0.3 eV more stable than other adsorption sites. The Ba-surface interaction produces some surface relaxation in all cases. The OB site is stable at moderate temperatures; however, after extensive molecular dynamic calculations it is found that atoms diffuse on the surface by means of a jumping mechanism among several stable positions. The presence of bridging oxygen vacancies does not alter significantly this picture since the adsorption close to defects is not energetically favorable and the atoms tend to move away from vacancies. A strong covalent character has been found in the nature of the bonding, which contrasts with previous suggestions of the existence of Ba(2+) species on the surface. When the coverage is increased to 0.25 ML by adding a Ba atom to the supercell, there is a significant repulsion between Ba atoms that move away from each other to occupy OB sites. Thus, the adsorption energy values per atom diminish. For the stoichiometric surface two equivalent adsorption patterns are found, whereas only one is found for the defective surface.


Role of pan immune inflammatory value in the evaluation of hepatosteatosis in children and adolescents with obesity.
Inflammation is a feature of non-alcoholic fatty liver disease progression and plays an important role in hepatic steatosis and fibrosis. Since there are no studies in the literature showing the relationship between hepatosteatosis with the systemic immune-inflammation index (SII) and pan-immune inflammation value (PIV), we aimed to evaluate the relationship between these biomarkers and hepatosteatosis in childhood. We included 133 consecutive obese children and adolescents aged 6-18 years into this single-center, retrospective, and cross-sectional study. Anthropometric, physical examination, radiological and laboratory data were obtained and recorded from the file records of each case. When we grouped the patient population according to the grade of hepatosteatosis, there was a statistically significant difference between the groups in terms of SII and PIV values (p<0.05, for both). In the analyzes performed to identify independent predictors of hepatosteatosis pubertal status (p=0.019) and PIV value (p<0.001) were found to be significant as independent predictors. Moreover, in the analysis performed to predict severity of hepatic steatosis, regression analysis was performed by dividing the groups into groups with and without severe adiposity. As a result of this analysis, HOMA-IR (p=0.019) and PIV value (p=0.028) were found to be significant in the prediction of severe hepatic adiposity. Our findings showed that increased PIV levels were associated with the presence and severity of hepatic steatosis, but not with SII.


Genetic studies in relation to Kuru. VI. Evaluation of increased liability to Kuru in Gc Ab-Ab individuals.
The validity of the reported association between GcAb and kuru is analyzed. Phenotypes with one or more GcAb genes have an increased incidence of the disease at the expense of Gc 1-1 and Gc 2-2. Incidence ratios of kuru associated with various phenotypes examined over the linguistic groups studied indicate that only Gc Ab-Ab persons have a significantly greater chance of dying of kuru. The association X2 for the incidence ratio for those phenotypes possessing only one GcAb gene is significant, but there is significant heterogeneity between groups studied. Those of the Gc Ab-Ab phenotype are six times as likely to contract kuru as the baseline group. Criticisms of this analysis include difficulties defining an adequate control group in such heterogeneous populations, errors in determination of Gc phenotypes, inclusion of persons incubating kuru in the control groups, and questions of validity of statistical tests in isolated inbred populations.


Repair of the abdominal donor-site fascial defect with small intestinal submucosa (Surgisis) after TRAM flap breast reconstruction.
We report the successful use of Surgisis in the repair of the abdominal donor site fascial defect following a free transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction. No abdominal wall weakness in the flap donor site was evidenced by a series of clinical examinations to at least 14 months after Surgisis placement. A well-formed and thickened fascial layer at the abdominal donor fascial repair site was revealed by computed tomography scan. This objective finding, along with our clinical observation, supports the use of Surgisis for repair of the abdominal donor site fascial defect following a TRAM flap harvesting.


Polycyclic aromatic hydrocarbons associated with particles in ambient air from urban and industrial areas.
This study takes into consideration an analysis of the chemical polycyclic aromatic hydrocarbon (PAH) profile and its distribution in inhalable and respirable particulate matter in urban and industrial areas in La Plata, Argentina, and Leipzig, Germany. Representative samples from three locations in La Plata (industrial, traffic influenced and control area) and two locations in Leipzig (traffic influenced and control area) were obtained in summer and winter. The sampling of particulate matter was carried out with high volume collectors using cascade impactors to separate six size fractions. PAHs were extracted with hexane through a solid-liquid equilibrium extraction and analysed by HPLC/UV/fluorescence detection. The results showed a PAH seasonal behaviour in both regions, with lower contents in summer and higher ones in winter. Highest concentrations of total PAHs were found in the industrial area in La Plata. The size distribution of particles demonstrates the greater relevance of smaller particles. More than 50% of PAHs were associated with particles of less than 0.49 microm. Moreover, this particle size fraction was associated with traffic, whereas other sources of combustion were related also to particles between 0.49 and 0.95 microm. Considering the ratio of benzo(ghi)perylene (BgP)/benzo(a)pyrene (BaP) as an indicator for traffic influence, it was observed that La Plata City was more affected than Leipzig by the same proportion in summer and in winter. The BgP/InP (indeno(123-cd)pyrene) ratio was lower in winter than in summer in both places and indicates the presence of domestic combustion sources. It is important to point out the significance of using fingerprint compound ratios to identify possible sources of pollution with PAHs bound to particles.


Serum ferritin is an independent prognostic factor in Chinese with myelodysplastic syndromes classified as IPSS Intermediate-1.
The International Prognostic Staging System (IPSS) for myelodysplastic syndromes (MDS) was developed predominately in patients of European ancestry and is not validated in Asians. In a recently revised IPSS (IPSS-R), several new prognostic variables are included, i.e. age, Eastern Cooperative Oncology Group performance score (ECOG PS), serum ferritin and lactate dehydrogenase. Chinese with MDS offer a unique opportunity to distinguish the prognostic impacts of haemoglobin (HGB) concentration, red blood cell (RBC) transfusions and serum ferritin because in China, patients rarely receive RBC transfusions unless the HGB concentration is <6.0 g/dl. We studied prognostic variables in 191 untreated Chinese primary patients with MDS intermediate-1 (INT-1) in the IPSS. Serum ferritin level ≥500 µg/l at diagnosis was a strong independent predictor of survival. Although baseline serum ferritin level was inversely correlated with baseline HGB, it was the serum ferritin, not the baseline HGB level, that was significantly correlated with survival in Chinese patients. A new prognostic scoring system including the ECOG PS, absolute neutrophil level, serum ferritin, percentage of bone marrow blasts and poor karyotype was developed for Chinese with IPSS INT-1 MDS. This revised scoring system identified a subgroup of Chinese with MDS and INT-1 IPPS who have a poor prognosis and may benefit from more intensive therapy.


Effects of the training status on the hormonal response and recovery from high-intensity isokinetic exercise: comparisons between endurance-trained athletes and sedentary subjects.
Aims of the study were: to determine the differences in the mechanical, hormonal and lactate responses to a high-intensity isokinetic exercise in two groups of endurance-trained athletes (EA, n = 11) and sedentary subjects (SED, n = 11); to evaluate the relationships between the hormonal and lactate responses; to evaluate the effects of the training status on the pituitary responsiveness to the exercise. EA and SED completed, for each leg, 4 sets of 20 maximal concentric contractions of the knee extensor muscle groups at 180 degrees s-1 angular velocity. Blood and saliva for hormonal and lactate determinations were sampled before, immediately after the test and during the subsequent recovery of 2 hours. The exercise was completed by all subjects and elicited significant mechanical and biochemical responses both in EA and in SED subjects. No differences were found between the two groups both in the mechanical performances and in the increases of lactate and hormones of the pituitary-adrenal axis or in the comparison of the slopes of adrenocorticotropic hormone (ACTH), cortisol, and dehydroepiandrosterone recovery after the peak. The correlation analyses showed significant positive relationships between lactate peak values and percentages of change for ACTH (r2 = 0.16, P < 0.05), salivary cortisol (r2 = 0.42, P < 0.01), and serum cortisol (r2 = 0.56, P < 0.001). The adrenocortical activation was found, in this particular setting, at least partly dependent on the muscular lactate production, while no effect of the training status on the pituitary responsiveness to exercise was evident, as it was indirectly confirmed by no abnormalities in the rates of hormonal recovery after the exercise session.


Somatic APC and K-ras codon 12 mutations in aberrant crypt foci from human colons.
Aberrant crypt foci (ACF) are microscopic lesions which have been postulated to precede the development of adenomatous polyps, the precursors to colorectal cancer. APC and ras gene mutations have been shown to be important early molecular events in the development of colorectal neoplasms. The objective of this study was to establish the nature and frequency of these two genetic alterations in ACF harvested from human colorectal resection specimens. One hundred and fifty-four ACF comprised of between 1 and 56 crypts were harvested from the grossly normal mucosa of colorectal resection specimens of 28 patients with varying pathological diagnoses. One hundred and twenty-five ACF from 20 colons were screened for the presence of K-ras codon 12 mutations with a polymerase chain reaction/restriction enzyme-based method. The APC gene mutation cluster region was screened in 65 ACF from 20 colons using a polymerase chain reaction/single strand conformation polymorphism technique. Putative mutations were confirmed by direct sequencing. K-ras codon 12 mutations were identified in 13% (16 of 125) of ACF. We also identified APC mutations in 4.6% (3 of 65) of ACF. The results of this study demonstrate that both APC and K-ras mutations occur in ACF. These observations support the role of the ACF as a colorectal cancer precursor and provide further insight into the early genetic changes which occur during colorectal tumorigenesis.


Subcutaneous emphysema following severe vomiting after emerging from general anesthesia.
Postoperative nausea and vomiting-related subcutaneous emphysema is an unexpected complication, especially after uneventful surgery and anesthesia. Here we report and discuss two cases of subcutaneous emphysema following severe retching and vomiting which resolved spontaneously after several days.


Embedded centrosymmetric multilayer stacks as complete-transmission quarter-wave and half-wave retarders under conditions of frustrated total internal reflection.
A centrosymmetric multilayer stack of two transparent materials, which is embedded in a high-index prism, can function as a complete-transmission quarter-wave or half-wave retarder (QWR or HWR) under conditions of frustrated total internal reflection. The multilayer consists of a high-index center layer sandwiched between two identical low-index films with high-index-low-index bilayers repeated on both sides of the central trilayer, maintaining the symmetry of the entire stack and constituting a QWR (Delta(t)=90 degrees or 270 degrees ) or HWR (Delta(t)=180 degrees ) in transmission. A QWR design at wavelength lambda=1.55 microm is presented that employs an 11-layer stack of Si and SiO(2) thin films, which is embedded in a GaP cube prism. The intensity transmittances for the p and s polarizations remain >99% and Delta(t) deviates from 90 degrees by <+/-3 degrees over a 100 nm spectral bandwidth (1.5< or =lambda< or =1.6 microm), and by < or =+/-7 degrees over an internal field view of +/-1 degrees (incidence angle 44 degrees < or = phi(0)< or =46 degrees inside the prism). An HWR design at lambda=1.55 microm employs seven layers of Si and SiO(2) thin films embedded in a Si cube, has an average transmittance >93%, and Delta(t) that differs from 180 degrees by <+/-0.3 degrees over a 100 nm bandwidth (1.5< or =lambda< or =1.6 microm) and by <+/-17 degrees over an internal field view of +/-1 degree . The sensitivity of these devices to film-thickness errors is also considered.


Possible involvement of protein kinase C and calcium ion in growth factor-induced expression of c-myc oncogene in Swiss 3T3 fibroblasts.
The addition of platelet-derived growth factor and fibroblast growth factor to quiescent cultures of Swiss 3T3 fibroblasts rapidly induced protein kinase C activation and Ca2+ mobilization and afterwards markedly increased c-myc mRNA levels. 1-Oleoyl-2-acetylglycerol, a membrane-permeable synthetic diacylglycerol, and 12-O-tetradecanoylphorbol 13-acetate, a tumor-promoting phorbol ester, stimulated protein kinase C activation without Ca2+ mobilization. Inversely, Ca2+ ionophores, A23187 and ionomycin, elicited Ca2+ mobilization without protein kinase C activation. Both protein kinase C-activating and Ca2+-mobilizing agents were able to increase c-myc mRNA levels in an additive manner. Prolonged treatment of the cells with phorbol 12,13-dibutyrate, another protein kinase C-activating phorbol ester, led to the down-regulation and complete disappearance of protein kinase C. In these cells, 1-oleoyl-2-acetylglycerol and 12-O-tetradecanoylphorbol 13-acetate did not increase c-myc mRNA levels, but platelet-derived growth factor, fibroblast growth factor, and the Ca2+ ionophores, all of which still induced Ca2+ mobilization, stimulated the increase of c-myc mRNA levels. These results strongly suggest that both protein kinase C and Ca2+ may be involved in platelet-derived growth factor- as well as fibroblast growth factor-induced expression of the c-myc oncogene in Swiss 3T3 cells.


Presynaptic facilitation of dopamine release through D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors on synaptosomes from the rat striatum.
Purified synaptosomes from the rat striatum were superfused continuously with [3H]tyrosine in order to estimate the release of newly synthesized [3H]dopamine. When tested from 10(-6) to 10(-3) M, several excitatory amino acids or their analogues markedly stimulated the release of [3H]dopamine, their apparent rank order of potency being kainate greater than glutamate = D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) greater than homocysteate greater than quisqualate greater than aspartate greater than ibotenate. N-acetyl-aspartyl-glutamate was without effect. In addition, in the range of concentrations of 10(-6) to 10(-3) M, the maximal response of glutamate was higher than that of kainate, AMPA or homocysteate, whereas the effects of quisqualate, aspartate and ibotenate, particularly, were of lower amplitude. In favor of the existence of glutamate receptors of the AMPA type on dopaminergic nerve terminals, the stimulatory effect of AMPA (5 x 10(-5) M) on [3H]dopamine release was antagonized by 6,7-dinitroquinoxaline-2,3-dione, 6-cyano-7-nitro-quinoxaline-2,3-dione, tau-D-glutamyl-amino-methyl-sulphonate and tau-D-glutamyl-glycine tested at 10(-4) M. 6,7-Dinitroquinoxaline-2,3-dione was the most potent, whereas L-glutamate diethylester was without effect. As expected D-2-amino-5-phosphonovalerate did not affect the AMPA-evoked response. Further experiments indicated that kainate and quisqualate stimulate the release of [3H]dopamine by acting on quisqualate/kainate or AMPA receptors. The quisqualate-evoked desensitization of AMPA receptors was prevented by concanavalin A (10(-7) M).(ABSTRACT TRUNCATED AT 250 WORDS)


iASPP inhibition: increased options in targeting the p53 family for cancer therapy.
Strategies to induce p53 for cancer therapy offer appeal but many tumors harbor inactivating p53 mutations. One way to address this situation may be to activate the p53-related protein p73, which functions similarly, but unlike p53, is rarely lost or mutated in cancer. Along these lines, a recent study reports that a p53-derived peptide that targets iASPP-a common negative regulator of p53 family members--can effectively trigger tumor cell death by a p73-dependent mechanism. These findings promote further study of iASPP targeting as a therapeutic strategy to activate p73.