[Epidemiology of hepatitis A in Sardinia: prevalence of anti-HAV in a sample of workers required to obtain health certificates].
The prevalence of Hepatitis A in South-Sardinia was determined in two samples of students in 1987 and 1988. In this paper we present the results of a seroepidemiologic survey covering a population of workers who were residents of the city of Cagliari or its suburbs. A sample of 299 workers was randomly drawn from a population of workers who went to the public health office to ask for a certificate of good health. A radioimmunoassay test (ABBOTT) was used for detection of anti-HAV. The analysis has been carried out in accordance with the manufacturer's instructions. We also study a sample of 323 students 14-19 years old. The age-specific prevalence was analyzed using an exponential model. The age is denoted by the variable x. The parameter h is the force of infection, the per capita rate at which susceptibles individuals acquire infection. If we take the force of infection as a constant, the fraction y of susceptibles in a population is y = exp (-h x) The anti-HAV prevalente increase with age: in workers 14-19 years of age 44 percent of the tested individuals were antibody positive. The prevalence was 82.7 percent in the population 25-29 years old. Finally we found a nearly total exposure to HAV in persons over 30 years of age. The workers 14-19 years of age showed a higher prevalence than the students did; the difference was statistically significant. The prevalence that we have observed in our study population is lower the one observed in the city of Sassari (North-Sardinia) in 1981. The siero-epidemiological pattern is similar to that prevailing in Greece and France (1979), in Umbria (1978), in the city of Milan (1973). The prevalence was, on the contrary, higher than that observed in North European Countries (1979) and in Venetia (1987). The data from the study population can be fitted satisfactorily with the exponential model (R2 = 0.994). So we can take the force of infection (h = -0.118, se = 0.005 as a constant.(ABSTRACT TRUNCATED AT 250 WORDS)


Potential exposure and health risks of infants following indoor residential pesticide applications.
Air and surface chlorpyrifos residues were measured for 24 hours following a 0.5 percent Dursban broadcast application for fleas inside a residence. Two of the three treated rooms were ventilated following application. Maximum air concentrations were measured 3-7 hours post-application. Peak concentrations in the infant breathing zone were 94 micrograms/m3 in the nonventilated room and 61 micrograms/m3 in the ventilated room, and were substantially higher than concentrations in the sitting adult breathing zone. Concentrations of approximately 30 micrograms/m3 were detected in the infant breathing zone 24 hours post-application. Surface residues available through wipe sampling were 0.7-1.6 micrograms/cm2 of carpet on the day of application and 0.3-0.5 micrograms/cm2 24 hours post-application. Estimated total absorbed doses for infants were 0.08-0.16 mg/kg on the day of application and 0.04-0.06 mg/kg the day following application, with dermal absorption representing approximately 68 percent of the totals. These doses are 1.2-5.2 times the human No Observable Effect Level (NOEL). Exposures to cholinesterase inhibiting compounds following properly conducted broadcast applications could result in doses at or above the threshold of toxicological response in infants, and should be minimized through appropriate regulatory policy and public education.


The use of synchrotron infrared microspectroscopy to demonstrate the effect of intense pulsed light on dermal fibroblasts.
Abstract Intense pulsed light (IPL) has been used extensively to treat striae distensae (SD). Twenty-four patients (21 females and 3 males) with age ranging between 15-42 years with a mean of 24.2 ± 5.89 years were included in this study. All patients were treated with IPL for five sessions and were given 4-week interval between the sessions. Formalin-fixed, paraffin- embedded skin biopsies were cut into 5-μm-thick sections from patients before and after treatments. They were stained with hematoxylin and eosin (H&E) and collagen with Masson trichrome stain. Histological examination of SD revealed epidermal thinning, flattened rete ridges, and fragmentation with degeneration of the collagen and elastic fibers. After IPL treatments, collagen expression was found also to be increased in a highly significant manner and P values were < 0.001 after IPL treatments. The use of synchrotron infrared (IR) microspectroscopy also revealed that amide 1 and beta sheets were expressed in a significant manner after IPL treatment. In conclusion, it was demonstrated that IPL can treat striae through fibroblast stimulation which led to protein expression especially collagen stimulation, and it seems that it is a promising therapeutic modality for striae with minimal side effects.


Salivary duct carcinoma treated with cetuximab-based targeted therapy: A case report.
Salivary duct carcinoma is a highly aggressive disease with a poor prognosis. Surgical resection is currently the only curative treatment, as there is no effective systemic therapy for this malignancy. Recently, trastuzumab has been shown to exhibit therapeutic efficacy in the treatment of salivary duct carcinoma; similarly, molecularly targeted agents, such as cetuximab, are expected to be useful for salivary duct carcinoma treatment. We herein describe the case of a 56-year-old man diagnosed with salivary duct carcinoma in the left submandibular region, with ipsilateral multiple metastases to the neck lymph nodes. Radical resection of the tumor and submandibular gland with neck dissection were performed. One month after radical surgery, computed tomography (CT) scans indicated metastasis in the lower lobe of the left lung. CT-guided transthoracic fine-needle aspiration biopsy revealed a single metastasis and lung metastasectomy was immediately performed. The tumor cells of the primary lesion and those of the lung metastasis were immunohistochemically positive for epidermal growth factor receptor. One month later, multiple right lung metastases appeared, and the patient was treated with cisplatin/5-fluorouracil (5-FU) chemotherapy plus cetuximab, achieving a complete radiographic response. However, multiple lung metastases developed during adjuvant weekly cetuximab monotherapy. Subsequently, treatment with S-1 and weekly cetuximab was initiated, and the multiple lung metastases have been maintained as stable disease for 5 months. To the best of our knowledge, this is the first report of cetuximab use for the treatment of salivary duct carcinoma. Although cisplatin/5-FU chemotherapy plus cetuximab was efficacious in treating the lung metastasis, cetuximab monotherapy was insufficient for controlling tumor growth.


Factors associated with Listeria monocytogenes contamination of cold-smoked pork products produced in Latvia and Lithuania.
A total of 312 samples of sliced, vacuum packaged, cold-smoked pork from 15 meat processing plants in Latvia and Lithuania, obtained over a 15-month period from 2003 until 2004, were analyzed for the presence of Listeria monocytogenes at the end of their shelf-life. Overall, 120 samples (38%) tested positive for L. monocytogenes. Despite the long storing period, the levels of L. monocytogenes in cold-smoked pork products were low. Manufacturing processes were studied at seven meat processing plants. A new approach with a logistic multivariable regression model was applied to identify the main factors associated with L. monocytogenes contamination during the manufacturing of cold-smoked pork products. Brining by injection was a significant factor (odds ratio 10.66; P<0.05) for contamination of product with L. monocytogenes. Moreover, long cold-smoking times (> or = 12 h) had a significant predictive value (odds ratio 24.38; P<0.014) for a sample to test positive for L. monocytogenes. Pulsed-field gel electrophoresis results indicated that various sources of L. monocytogenes contamination existed over periods of time in several meat processing plants. In two meat processing plants, persistent L. monocytogenes strains belonging to serotypes 1/2a and 1/2c were found.


Hyaluronic Acid (HA), Platelet-Rich Plasm and Extracorporeal Shock Wave Therapy (ESWT) promote human chondrocyte regeneration in vitro and ESWT-mediated increase of CD44 expression enhances their susceptibility to HA treatment.
Novel strategies have been proposed for articular cartilage damage occurring during osteoarthritis (OA) and -among these- Extracorporeal Shock Wave Therapy (ESWT), intra-articular injections of Platelet-Rich Plasma (PRP) or Hyaluronic Acid (HA) revealed encouraging results. To investigate the possible mechanisms responsible for those clinical benefits, we established primary cultures of human chondrocytes derived from cartilage explants and measured the in vitro effects of ESW, PRP and HA therapies. After molecular/morphological cell characterization, we assessed those effects on the functional activities of the chondrocyte cell cultures, at the protein and molecular levels. ESWT significantly prevented the progressive dedifferentiation that spontaneously occurs during prolonged chondrocyte culture. We then attested the efficiency of all such treatments to stimulate the expression of markers of chondrogenic potential such as SOX9 and COL2A, to increase the Ki67 proliferation index as well as to antagonize the traditional marker of chondrosenescence p16INK4a (known as Cdkn2a). Furthermore, all our samples showed an ESW- and HA-mediated enhancement of migratory and anti-inflammatory activity onto the cytokine-rich environment characterizing OA. Taken together, those results suggest a regenerative effect of such therapies on primary human chondrocytes in vitro. Moreover, we also show for the first time that ESW treatment induces the surface expression of major hyaluronan cell receptor CD44 allowing the increase of COL2A/COL1A ratio upon HA administration. Therefore, this work suggests that ESW-induced CD44 overexpression enhances the in vitro cell susceptibility of human chondrocytes to HA, presumably favouring the repair of degenerated cartilage.


Virtual reality as a distraction intervention for older children receiving chemotherapy.
The purpose of this pilot study was to describe the perceived effectiveness and feasibility of using virtual reality (VR) as a distraction intervention for children, aged 10-17, receiving outpatient chemotherapy. Treatments for cancer are intensive and difficult to endure. Distraction interventions are effective because the individual concentrates on pleasant or interesting stimuli instead of focusing on unpleasant symptoms. VR is a computer-simulated technique allowing an individual to hear and feel stimuli that correspond with a visual image. Evaluation of the VR intervention demonstrated positive outcomes. Eighty-two percent of the children (n = 11) indicated the chemotherapy treatment with the VR was better than previous chemotherapy treatments. All subjects responded positively when asked if they would like to use the VR again. The intervention was easy to implement, did not require practice to be effective, and required minimal nursing time. Results from this pilot study suggest that VR as a distraction intervention has the potential to enhance positive clinical outcomes. This intervention warrants further investigation with both pediatric and adult populations.


In Vitro Evaluation of Some Endophytic Bacillus to Potentially Inhibit Grape and Grapevine Fungal Pathogens.
Romania has a long history of grapevine culturing and winemaking. However, like any agricultural sector, viticulture faces devastating biological threats. Fungi responsible for grapevine trunk diseases (GTDs) and grape spoilage lead to considerable yield losses and a decline in grapevine quality. In the actual context, many countries, including Romania, have reoriented their approaches to minimize chemical inputs, which have been proven to be toxic and to have negative impacts on the environment, and to replace them with sustainable biocontrol strategies for the wine-growing sector. Within biocontrol strategies, Bacillus spp. is a well-known plant-protective bacteria with antifungal properties. Within this paper, six endophytic bacteria from various plant sources were studied. The bacterial strains were identified as B. pumilus, B. subtilis, and B. velezensis by sequencing their 16S rDNA region. Regardless of the in vitro test methods (using living bacterial cells, bacterial-cell-free supernatant (CFS), and volatile active compounds (VOCs)), B. velezensis strains revealed strong and broad antifungal activity against grape and grapevine fungal pathogens such as Aspergillus spp., Botrytis cinerea, Penicillium expansum, Diplodia seriata, Eutypa lata, Fusarium spp., Clonostachys rosea, Neofusicoccum parvum, and Stereum hirsutum. The functional antifungal genes encoding for difficidin, fengycin, iturins, macrolactin, and mycosubtilin were molecularly detected, which could support the proven antifungal activity of the endophytic strains. Lytic enzymes involved in fungal growth inhibition, such as chitinase, cellulase, and proteases, were also revealed to be produced by some of these bacterial strains. Various other in vitro tests, such as phosphate and phytate solubilization, phytohormone synthesis, the production of enzymes involved in the polyamine biosynthetic pathway, and pH as well as temperature tolerance tests were carried out to reveal the plant-beneficial potential of these bacterial strains. These results revealed that the B. velezensis strains, especially BAHs1, are the most suitable endophytes for grapevine biologic control, which could lead to the future development of sustainable management strategies.


Mismatch negativity: translating the potential.
The mismatch negativity (MMN) component of the auditory event-related potential has become a valuable tool in cognitive neuroscience. Its reduced size in persons with schizophrenia is of unknown origin but theories proposed include links to problems in experience-dependent plasticity reliant on N-methyl-d-aspartate glutamate receptors. In this review we address the utility of this tool in revealing the nature and time course of problems in perceptual inference in this illness together with its potential for use in translational research testing animal models of schizophrenia-related phenotypes. Specifically, we review the reasons for interest in MMN in schizophrenia, issues pertaining to the measurement of MMN, its use as a vulnerability index for the development of schizophrenia, the pharmacological sensitivity of MMN and the progress in developing animal models of MMN. Within this process we highlight the challenges posed by knowledge gaps pertaining to the tool and the pharmacology of the underlying system.


Oxygen Vacancy Induced Atom-Level Interface in Z-Scheme SnO2/SnNb2O6 Heterojunctions for Robust Solar-Driven CO2 Conversion.
The modulation of Z-scheme charge transfer is essential for efficient heterostructure toward photocatalytic CO2 reduction. However, constructing a compact hetero-interface favoring the Z-scheme charge transfer remains a great challenge. In this work, an interfacial Nb-O-Sn bond and built-in electric field-modulated Z-scheme Ov-SnO2/SnNb2O6 heterojunction was prepared for efficient photocatalytic CO2 conversion. Systematic investigations reveal that an atomic-level interface is constructed in the Ov-SnO2/SnNb2O6 heterojunction. Under simulated sunlight irradiation, the obtained Ov-SnO2/SnNb2O6 photocatalyst exhibits a high CO evolution rate of 147.4 μmol h-1 g-1 from CO2 reduction, which is around 3-fold and 3.3-fold of SnO2/SnNb2O6 composite and pristine SnNb2O6, respectively, and favorable cyclability by retaining 95.8% rate retention after five consecutive tests. As determined by electron paramagnetic resonance spectra, in situ Fourier transform infrared spectra, and density functional theory calculations, Nb-O-Sn bonds and built-in electric field induced by the addition of oxygen vacancies jointly accelerate the Z-scheme charge transfer for enhanced photocatalytic performance. This work provides a promising route for consciously modulating Z-scheme charge transfer by atomic-level interface engineering to boost photocatalytic performance.


The Impact of Medical/Behavioral Support Needs on the Supports Needed by Adolescents With Intellectual Disability to Participate in Community Life.
As adolescents with intellectual disability (ID) transition to adulthood, there is a need to plan for effective community-based supports that address the post-school life. There is also a need to plan for the impact of factors (e.g., medical/behavioral support needs) on supports needed for community participation. Data from the Supports Intensity Scale-Adult Version (SIS-A) was used to examine relations between medical/behavior support needs and support needs assessed in the standardized portion of the SIS-A. Results suggested that the presence of medical/behavioral needs had a strong impact on supports needed to participate in the community activities, and that more intensive medical support needs were related to higher support needs in the Home Living, Community Living, and Health and Safety domains.


Single-cell profiling reveals immune disturbances landscape and HLA-F-mediated immune tolerance at the maternal-fetal interface in preeclampsia.
Preeclampsia is a pregnancy-specific disorder that always causes maternal and fetal serious adverse outcome. Disturbances in maternal immune tolerance to embryo at the maternal-fetal interface (MFI) may be associated with preeclampsia onset. Recent studies have revealed the reduced expression pattern of HLA-F at the MFI in preeclampsia, while the mechanism of it mediating maternal fetal immune tolerance has not been revealed. Single-cell RNA sequencing on placental decidua was performed to reveal the immune disturbances landscape at the MFI in preeclampsia. Human Jar cells and NK-92MI cells were employed to study the role of HLA-F in trophoblasts and lymphocyte. A total of 101,250 cells were classified into 22 cell clusters. Disease-related IGFBP1+SPP1+ extracellular villus trophoblast (EVT) was identified in the preeclamptic placental decidua, accompanied by newly discovered immune cellular dysfunction such as reduced ribosomal functions of NK populations and abnormal expression of antigen-presenting molecules in most cell clusters. Certain genes that are characteristic of the intermediate stage of myeloid or EVT cell differentiation were found to have unexplored but important functions in the pathogenesis of preeclampsia; specifically, we detected enhanced cell cross-talk between IGFBP1+SPP1+ EVT2 or SPP1+M1 cells and their receptor cell populations at the MFI of PE patients compared to controls. With respect to HLA-F, mIF staining confirmed its reduced expression in PE samples compared to controls. Over-expression of HLA-F in Jar cells promoted cell proliferation, invasion, and migration while under-expression had the opposite effect. In NK-92MI cells, over-expression of HLA-F increased the secretion of immunoregulation cytokines such as CSF1 and CCL22, and promoted adaptive NKG2C+NK cell transformation. We revealed the immune disturbance landscape at the MFI in preeclampsia. Our findings regarding cellular heterogeneity and immune cellular dysfunction, as revealed by scRNA-seq, and the function of HLA-F in cells provide new perspectives for further investigation of their roles in the pathogenesis of preeclampsia, and then provide potential new therapeutic target.


[Ubiquitin-proteasome pathway as a target for therapeutic strategies].
In Eukaryota, the majority of intracellular proteins are degraded by the ubiquitin-26S proteasome pathway. Through degradation of proteins tagged with polyubiquitin chains, the 26S proteasomes, multicatalytic proteolytic complexes, participate in regulation of key cellular processes such as cell cycle, proliferation and cell differentiation, apoptosis, transcription, signal transduction, morphogenesis, immune response, response to stress and to extracellular effectors, modulation of cell-surface receptors, antigen presentation, proteolysis of enzymes and regulatory proteins, and protein quality control in endoplasmic reticulum. Dysfunction of the ubiquitin-proteasome pathway is associated with many diseases, including cancer, neurodegeneration, autoimmune and inflammatory response, as well as infectious diseases. In recent years, besides proteasomes, the enzymes that drive ubiquitination and deubiquitination have entered clinical trials as potential therapeutic targets. Small molecular inhibitors against proteasomes have been discovered, as well as inhibitors of the ubiquitin cascade enzymes and deubiquitinating enzymes. Second generation inhibitors of proteasomes have been successfully approved for clinical application.


Survival of spores of the UV-resistant Bacillus subtilis strain MW01 after exposure to low-earth orbit and simulated martian conditions: data from the space experiment ADAPT on EXPOSE-E.
In the space experiment "Molecular adaptation strategies of microorganisms to different space and planetary UV climate conditions" (ADAPT), bacterial endospores of the highly UV-resistant Bacillus subtilis strain MW01 were exposed to low-Earth orbit (LEO) and simulated martian surface conditions for 559 days on board the European Space Agency's exposure facility EXPOSE-E, mounted outside the International Space Station. The survival of B. subtilis MW01 spores from both assays (LEO and simulated martian conditions) was determined by a colony-formation assay after retrieval. It was clearly shown that solar extraterrestrial UV radiation (λ≥110 nm) as well as the martian UV spectrum (λ≥200 nm) was the most deleterious factor applied; in some samples only a few spore survivors were recovered from B. subtilis MW01 spores exposed in monolayers. However, if shielded from solar irradiation, about 8% of MW01 spores survived in LEO conditions, and 100% survived in simulated martian conditions, compared to the laboratory controls. The results demonstrate the effect of shielding against the high inactivation potential of extraterrestrial solar UV radiation, which limits the chances of survival of even the highly UV-resistant strain of B. subtilis MW01 in the harsh environments of outer space and the martian surface.


Foetal umbilical artery Doppler in small preterms: (IQ) neurocognitive outcome at 5 years of age.
To investigate whether absent or reversed end-diastolic flow in the umbilical artery (AREDF) is associated with neonatal mortality, morbidity or long-term neurocognitive outcome in extremely preterm infants exposed to preeclampsia or intrauterine growth restriction. Prenatal Doppler data were retrospectively collected for liveborn infants with gestational age (GA) <28 weeks or birth weight (BW) <1000 g, born small for gestational age (SGA- BW <5th percentile for GA) or of mothers with preeclampsia at the four largest university hospitals in Norway during 1999-2000. Neonatal mortality and morbidities, cerebral palsy (CP) and IQ at 5 years of age were compared for infants with or without AREDF. Of 260 infants, 84 were eligible and 71 of them had sufficient Doppler data. Of these, 38 (54%) had AREDF. Of 33 infants born <28 weeks, 7 of 19 (37%) with AREDF and none of 14 without AREDF had severe cerebral haemorrhage (SCH) (p = 0.01). AREDF was not significantly associated with mortality, other NICU morbidities, CP or reduced IQ. For the 38 infants with GA ≥28 weeks, AREDF (19 of 38) was not associated with adverse outcomes. Absent or reversed end-diastolic flow in the umbilical artery (AREDF) was associated with increased risk of SCH in extremely preterm infants (GA <28 weeks).


Exploring the potential of dietary factors and plant extracts as chemopreventive agents in oral squamous cell carcinoma treatment.
Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a prevalent malignancy having a significant fatality rate worldwide. Despite advancements in conventional treatment modalities, the overall survival rate for OSCC remains low. Therefore, there is a critical need to explore alternative therapeutic approaches that can improve patient outcomes. This review focuses on the potential of dietary factors and plant extracts as chemopreventive agents in treating oral cancer. These compounds possess diverse biological functions encompassing a range of attributes, such as antioxidative, anti-inflammatory, and anticancer capabilities. By targeting multiple cellular pathways involved in carcinogenesis, they possess the capacity to hinder tumor growth and development, promote programmed cell death, and impede the progression of oral cancer. Signaling pathways targeted by natural compounds that have been included in this review include Akt/mTOR/NF-κB signaling, Hippo-Tafazzin signaling pathway, notch signaling pathway, mitochondrial pathway, and Sonic Hedgehog pathway.


Advances in coupling microfluidic chips to mass spectrometry.
Microfluidic technology has shown advantages of low sample consumption, reduced analysis time, high throughput, and potential for integration and automation. Coupling microfluidic chips to mass spectrometry (Chip-MS) can greatly improve the overall analytical performance of MS-based approaches and expand their potential applications. In this article, we review the advances of Chip-MS in the past decade, covering innovations in microchip fabrication, microchips coupled to electrospray ionization (ESI)-MS and matrix-assisted laser desorption/ionization (MALDI)-MS. Development of integrated microfluidic systems for automated MS analysis will be further documented, as well as recent applications of Chip-MS in proteomics, metabolomics, cell analysis, and clinical diagnosis.


Is massive proteinuria associated with maternal and fetal morbidities in preeclampsia?
The aim of this study was to investigate whether massive proteinuria in preeclampsia is associated with maternal and fetal complications. We retrospectively analyzed the clinical records of 233 patients who were diagnosed with preeclampsia. We divided the preeclamptic patients into three groups based on the amount of proteinuria: massive (≥5 g/24 hr), moderate (2 to 5 g/24 hr) and mild (<2 g/24 hr) proteinuria group. We analyzed the clinical characteristics and maternal and neonatal complications among three groups. Gestational age at diagnosis and delivery were lower in women with massive and moderate proteinuria group than women with mild proteinuria group (31.5±3.1 vs. 32.3±3.6 vs. 34.0±3.5 weeks, P<0.001 for gestational weeks at diagnosis; 34.6±3.6 vs. 35.1±4.1 vs. 36.9±4.0 weeks, P=0.001 for gestational age at delivery). In maternal complications, the incidences of pleural effusion and retinal detachment were significantly different among three groups (29.9% vs. 22.4% vs. 9.0%, P=0.004 for pleural effusion; 11.5% vs. 3.0% vs. 1.3%, P=0.009 for retinal detachment). Creatinine levels were higher and albumin levels were lower in the massive proteinuria group than in the moderate and mild groups. However, other maternal and neonatal complications were not significantly different among three groups. Massive proteinuria might be associated with renal albumin excretion-related morbidity, such as pleural effusion, retinal detachment, and low serum albumin levels. Furthermore, it was associated with early-onset preeclampsia and early delivery.


Sorting it out: bedding particle size and nesting material processing method affect nest complexity.
As part of routine husbandry, an increasing number of laboratory mice receive nesting material in addition to standard bedding material in their cages. Nesting material improves health outcomes and physiological performance in mice that receive it. Providing usable nesting material uniformly and efficiently to various strains of mice remains a challenge. The aim of this study was to determine how bedding particle size, method of nesting material delivery, and processing of the nesting material before delivery affected nest building in mice of strong (BALB/cAnNCrl) and weak (C3H/HeNCrl) gathering abilities. Our data suggest that processing nesting material through a grinder in conjunction with bedding material, although convenient for provision of bedding with nesting material 'built-in', negatively affects the integrity of the nesting material and subsequent nest-building outcomes. We also found that C3H mice, previously thought to be poor nest builders, built similarly scored nests to those of BALB/c mice when provided with unprocessed nesting material. This was true even when nesting material was mixed into the bedding substrate. We also observed that when nesting material was mixed into the bedding substrate, mice of both strains would sort their bedding by particle size more often than if it were not mixed in. Our findings support the utility of the practice of distributing nesting material mixed in with bedding substrate, but not that of processing the nesting material with the bedding in order to mix them.


Rate of successful recording of blood flow signals in the middle cerebral artery using transcranial Doppler sonography.
To assess the usefulness of transcranial Doppler sonography, we investigated the rate of blood flow signal recording failure in the middle cerebral artery in Japanese subjects. Furthermore, we studied the effect of increased emitted power on the rate of successful recording in some of the patients in whom recording failure had been detected at the standard transducer power of 100 mW/cm2. To evaluate the rate of successful recording, we measured blood flow signals in 597 patients (age range, 16 to 89 years) for screening of cerebrovascular disease by using a 2-MHz range-gated, pulsed-wave Doppler instrument at the standard transducer power. In 18 elderly patients with recording failure at the standard power, we assessed the effect of increased emitted power of 400 mW/cm2 on flow signal recording. Blood flow signals were recorded in 920 (77.1%) of the 1194 middle cerebral arteries of the 597 patients studied. The rate of successful recording of bilateral middle cerebral artery flow signals (70.9%; 423 of 597 patients) decreased with age, especially in females (17.0% in women aged 70 years or older). In 12 of 18 elderly patients with recording failure at the standard power, blood flow signals could be detected at the increased emitted power of 400 mW/cm2. The rate of successful recording of blood flow signals in Japanese subjects decreases with advancing age, especially in females. Increasing the emitted power markedly improves the successful recording rate.


Passive lung-targeted drug delivery systems via intravenous administration.
The treatment of lung diseases including lung cancer and tuberculosis is one of the most challenging problems in clinical practice, because the conventional drug delivery systems cannot deliver drug effectively to the lung, which result in low therapeutic effect. Therefore, lung-targeted drug delivery systems (LTDDS) that can deliver drug to the lung in an effective way to increase drug concentration in lung tissue and reduce drug distribution in other organs and tissues become an ideal strategy to treat lung diseases. The LTDDS mainly include microparticles (microspheres and microencapsules), liposomes and nanoparticles via intravenous administration, and dry powder carriers and nebulized suspensions via pulmonary inhalation. As lungs possess the large absorptive surface area, the low thickness of the epithelial barrier and good blood supply, pulmonary inhalation has received great attention. Intravenous route is the commonly practiced method for administration of larger doses of drugs into the body. Numerous drugs can be delivered directly into general circulation by avoiding their first-pass metabolism and have potential to transport drugs to the lung via intravenous administration. This present article reviews the development, evaluation and application of LTDDS via intravenous administration for the treatment of lung diseases reported in the past decades.


Isometric Handgrip Exercise Training Improves Spirometric Parameters and Pulmonary Capacity.
Decline in normal physiological pulmonary function has been attributed to premorbid conditions such as prehypertension. Research evidence suggests that physical activity reduces age-related decline in pulmonary function and improves the efficiency of the lungs in prehypertensive patients. However, there is a scarcity of data evidence relating to isometric exercise and pulmonary function. Furthermore, the interrelationship between the intensity and duration of isometric exercise and pulmonary function in these patients is still uncertain. Therefore, this study was undertaken to investigate the effect of isometric handgrip exercise on pulmonary function capacity in adults with prehypertension. To determine the effectiveness of isometric handgrip exercise on pulmonary function capacity in adults with prehypertension. A quasi experiment using a pre- and post-exercise method was carried out in two out-patients hospital settings. The sample comprised 192 sedentary pre-hypertensive subjects, aged between 30-50 years, that were randomly distributed into three groups of 64 participants each. The subjects performed, for 24 consecutive days, an isometric handgrip exercise at 30% Maximum Voluntary Contraction (M.V.C.). At the end of the 24 days, group one (GP1) discontinued, while group two (GP2) continued the exercise protocol for another 24 consecutive days and group three (GP3) continued with the exercise protocol for another 24 consecutive days but at 50% M.V.C. Determinants of lung function (outcomes) were Forced Expiratory Volume in 1 s (FEV1), Forced Vital Capacity (FVC), FEV1/FVC Ratio and Peak Expiratory Flow Rate (PEFR). The study shows that there was no statistically significant difference in the pre- and post-exercise outcomes for FEV1, FVC, FEV1/FVC Ratio and PEFR after 24 days for group 1. In group 2, there was a statistically significant difference in the FVC [(mean = 0.12 ± 0.12), (p = 0.002)], FEV1 [(mean = 0.15 ± 0.17), (p = 0.003)] and PEF [(mean = 0.85 ± 0.35), (p = 0.001)] after 48 days. In group 3, there was a statistically significant difference (p = 0.001) in all the outcomes assessed after 48 days. There was a between groups difference in favour of group 2 compared with group 1 for outcomes of FEV1 [(mean = 0.142 ± 0.68), (p = 0.005)] and PEF [(mean = 0.83 ± 0.19), (p = 0.0031)]. There was statistically significant difference in favour of group 3 compared to group 2, by increasing the exercise intensity from 30% to 50% M.V.C., for outcomes of FVC [mean change = 0.10 ± 0.052), (p = 0.005)], FEV1/FVC [mean change = 3.18 ± 0.75), (p = 0.017)] and PEF [(mean change = 0.86 ± 0.35), (p = 0.001)] after 48 days. Isometric handgrip exercise (after 48 days at 30% to 50% M.V.C.) improves outcomes of pulmonary function capacity in adults with prehypertension. Meanwhile, duration and/or increase in intensity of the isometric effort significantly contributed to the affects attained.


Screening tumor stage-specific candidate neoantigens in thyroid adenocarcinoma using integrated exome and transcriptome sequencing.
The incidence of thyroid carcinoma (THCA), the most common endocrine tumor, is continuously increasing worldwide. Although the overall prognosis of THCA is good, patients with distant metastases exhibit a mortality rate of 5-20%. To improve the diagnosis and overall prognosis of patients with thyroid cancer, we screened specific candidate neoantigen genes in early- and late-stage THCA by analyzing the transcriptome and somatic cell mutations in this study. The top five early-stage neoantigen-related genes (NRGs) were G protein-coupled receptor 4 [GPR4], chondroitin sulfate proteoglycan 4 [CSPG4], teneurin transmembrane protein 1 [TENM1], protein S 1 [PROS1], and thymidine kinase 1 [TK1], whereas the top five late-stage NRGs were cadherin 6 [CDH6], semaphorin 6B [SEMA6B], dysferlin [DYSF], xenotropic and polytropic retrovirus receptor 1 [XPR1], and ABR activator of RhoGEF and GTPase [ABR]. Subsequently, we used machine learning models to verify their ability to screen NRGs and analyze the correlations among NRGs, immune cell types, and immune checkpoint regulators. The use of candidate antigen genes resulted in a better diagnostic model (the area under the curve [AUC] value of the early-stage group [0.979] was higher than that of the late-stage group [0.959]). Then, a prognostic model was constructed to predict NRG survival, and the 1-, 3- and 5-year AUC values were 0.83, 0.87, and 0.86, respectively, which were closely related to different immune cell types. Comparison of the expression trends and mutation frequencies of NRGs in multiple tumors revealed their potential for the development of broad spectrum therapeutic drugs. In conclusion, the candidate NRGs identified in this study could potentially be used as therapeutic targets and diagnostic biomarkers for the development of novel broad spectrum therapeutic agents.


Anisotropic Growth of Silver Nanoparticles Is Kinetically Controlled by Polyvinylpyrrolidone Binding.
Polyvinylpyrrolidone (PVP) is used in the synthesis of Ag nanoparticles (NPs) with controlled shape, most commonly producing cubes. The mechanism for shape control is unclear but believed by many to be caused by preferential binding of PVP to Ag(100) facets compared to Ag(111) facets and assumed by most to be the result of thermodynamic control, whereby facets with lower interfacial free energy predominate. To investigate this mechanism, we measured adsorption isotherms of PVP on different-shaped Ag NPs, to determine the thermodynamics of PVP adsorption to Ag(100) and Ag(111) facets. The equilibrium adsorption constant is independent of PVP molecular weight and depends only weakly on NP shape (and thus Ag facet). The equilibrium adsorption constant for PVP on Ag(111) (2.8 M-1) is about half that on Ag(100) (5 M-1). From a Wulff construction, this difference is not nearly enough to produce cubes via thermodynamic control. This result indicates the importance of kinetic control of the Ag nanoparticle shape by PVP, as has recently been proposed.


Krebs cycle rewired for macrophage and dendritic cell effector functions.
The Krebs cycle is an amphibolic pathway operating in the mitochondrial matrix of all eukaryotic organisms. In response to proinflammatory stimuli, macrophages and dendritic cells undergo profound metabolic remodelling to support the biosynthetic and bioenergetic requirements of the cell. Recently, it has been discovered that this metabolic shift also involves the rewiring of the Krebs cycle to regulate cellular metabolic flux and the accumulation of Krebs cycle intermediates, notably, citrate, succinate and fumarate. Interestingly, a new role for Krebs cycle intermediates as signalling molecules and immunomodulators that dictate the inflammatory response has begun to emerge. This review will discuss the latest developments in Krebs cycle rewiring and immune cell effector functions, with a particular focus on the regulation of cytokine production.


Is type III prostatitis also associated with bacterial infection?
To explore whether type III prostatitis is related to bacterial infection by detecting the composition and function of microorganisms in expressed prostatic secretion (EPS) of patients with chronic prostatitis (CP) and healthy people. According to the inclusion and exclusion criteria, 57 subjects were included in our study, divided into the healthy group, type II prostatitis group, and type III prostatitis group. 16s rRNA sequencing technique was used to detect and analyze the microbial composition of EPS in each group. Additionally, the metagenomics sequencing technique was used to further explore the function of different bacteria in the type III prostatitis group. Data analysis was performed by bioinformatics software, and the results were statistically significant when P<0.05. Many microorganisms exist in EPS in both CP patients and healthy populations. However, the relative abundance of Pseudomonas, Haemophilus, Sneathia, Allobaculum, and Enterococcus in CP patients (including type II and III) were significantly different. Still, the relative abundance of different bacteria in type II prostatitis patients was much higher than in type III. The metagenomics sequencing results for the type III prostatitis group showed that the different bacteria had certain biological functions. Based on our sequencing results and previous studies, we suggest that type III prostatitis may also be caused by bacterial infection.


Self-administered hyaluronidase-facilitated subcutaneous immunoglobulin therapy in complicated primary antibody deficiencies.
Hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIg) is a new immunoglobulin product for replacement therapy in patients with primary antibody deficiencies (PAD). The pre-administration of recombinant human hyaluronidase associated with 10% immunoglobulin allowed the infusion of larger (up to 600 ml) amounts of immunoglobulin at a single infusion site, enabling patients to receive the necessary treatment in a single monthly dose. Here, we report the effectiveness and the tolerability of fSCIg in patients with severe PAD-related comorbidities: refractory autoimmune thrombocytopenia; systemic granulomatous disease; severe enteropathy, and Type I diabetes. We conclude that fSCIg could be a feasible option to improve the adherence to replacement therapy also by patients with severe PAD.


Design, synthesis, and biological evaluation of a series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones as dual inhibitors of human immunodeficiency virus type 1 integrase and the reverse transcriptase RNase H domain.
We report herein the synthesis of a series of 19 2-hydroxyisoquinoline-1,3(2H,4H)-dione derivatives variously substituted at position 7 aimed at inhibiting selectively two-metal ion catalytic active sites. The compounds were tested against HIV-1 reverse transcriptase (RT) polymerase, HIV-1 RT ribonuclease H (RNase H), and HIV-1 integrase (IN). Most compounds displayed poor inhibition of RT polymerase even at 50 microM. The majority of the synthesized compounds inhibited RNase H and IN at micromolar concentrations, and some of them were weakly selective for IN. Surprisingly, two new hits were discovered, which displayed a high selectivity for IN with submicromolar IC50 values. These enzymatic inhibitory properties may be related to the metal binding abilities of the compounds. Physicochemical studies were consistent with a 1/1 stoichiometry of the magnesium complexes in solution, and the metal complexation was strictly dependent on the enolization abilities of the compounds. Unfortunately, all tested compounds exhibited high cellular cytotoxicity in cell culture which limits their applications as antiviral agents.


Transport characteristics of ceftibuten, cefixime and cephalexin across human jejunal brush-border membrane.
The transport characteristics of orally active cephalosporins, ceftibuten, cefixime and cephalexin have been examined using brush border membrane vesicles isolated from human jejunum. In the initial uptake of ceftibuten, the stimulation and overshoot phenomena were observed in the presence of an inward H+ gradient. Effects of H+ gradient on the uptake of cefixime and cephalexin were low and no overshoot was observed. These transport characteristics, especially uphill transport phenomena, were in agreement with previous results obtained from rat intestinal brush-border membrane vesicles and suggest that these beta-lactam antibiotics are absorbed by different transport systems, despite their similar molecular structures.


Nonsurgical periorbital and brow rejuvenation.
There is a high patient demand for periorbital rejuvenation because the periorbita are often the first facial areas to show visible signs of aging. In addition to rhytides and skin laxity, aging appearance of the periorbital area is caused by changes in tissue volume resulting from soft-tissue atrophy and bone loss in the aging face. These changes are among the easiest areas to correct using several noninvasive techniques. The author uses three different techniques in his practice. The author shares his experience using three different techniques for nonsurgical periorbital rejuvenation. Patients develop unique crow's feet lines, and treatment with toxins should be adapted to each particular pattern. Low doses generally produce a more natural appearance than high doses. Using hyaluronic acid fillers, three tissue layers within the periorbita can be injected to produce maximally beneficial results and minimize the risk of adverse events. Filling tear troughs depends on whether they occurred early in life or are age-related. The key to avoiding complications is a careful patient analysis and a slow technique. One deformity should not be singled out when rejuvenating the periorbita. The best results are obtained when the entire periorbital area is treated at the same time.


Deposition of Gold Nanotriangles in Large Scale Close-Packed Monolayers for X-ray-Based Temperature Calibration and SERS Monitoring of Plasmon-Driven Catalytic Reactions.
Anisotropic plasmonic particles such as gold nanotriangles have extraordinary structural, optical, and physicochemical properties. For many applications in different fields, it is essential to prepare them in a chemically and physically stable, structurally well-defined manner, e.g., as large and uniform coverage on a substrate. We present a direct method for the large scale close-packed monolayer formation of edge-to-edge ordered, ultrathin crystalline gold nanotriangles on Si wafers or quartz glass via the transfer of these asymmetric particles to the air-liquid interface after adding ethanol-toluene mixtures without any subsequent surface functionalization. X-ray diffraction monitoring of the close-packed, large area monolayer with a mosaicity of less than 0.1° allows for calibrating the temperature of the particles during continuous laser heating. This is important for characterizing the microscopic temperature of the metal particles in the plasmon-driven dimerization process of 4-nitrothiophenol (4-NTP) into 4,4'-dimercaptoazobenzene (DMAB), monitored in real time by surface-enhanced Raman scattering (SERS). The gold nanotriangles can act as a source of hot electrons and initiate the dimerization process.


The hypocholesterolemic action of the undigested fraction of soybean protein in rats.
Soybean protein was exhaustively digested with endo- and exo-type microbial proteases and the effect of the digestible low molecular fraction (LMF) and the undigested high molecular fraction (HMF) on the serum cholesterol level was compared to that of the intact protein in rats given a cholesterol-enriched diet. The HMF, peptides relatively abundant in hydrophobic amino acids, was found to be substantially hypocholesterolemic when fed at the nitrogen level equivalent to that of the 20% soybean protein diet, and not only serum but also liver cholesterol levels were similar to those usually encountered in rats given diets free of cholesterol. There was a dose-dependent reduction of serum and liver cholesterol when casein was replaced stepwise with HMF. The cholesterol-lowering action could be attributable to an increased fecal steroid excretion.


Non-neuronal cholinergic system and signal transduction pathways mediated by band 3 in red blood cells.
Non-neuronal acetylcholine (ACh) and acetylcholinesterase (AChE) have been recognized in the past. Vascular ACh has been associated by us with the regulation of microcirculatory flow by modulating nitric oxide (NO) intracellular mobilization, metabolism (NOx) and release from erythrocytes, as well as the glycolytic flux. Velnacrine maleate is a well-known AChE inhibitor which plays a competitive role by decreasing NO-mediated erythrocyte responses. A plausible hypothesis to explain the mechanisms underlying those events hinges on the NO translocation among nitrosylated molecules and phosphorylated/dephosphorylated states of band 3 protein, processed by major tyrosine-kinases (PTK: p72syk, p53/56lyn and p59/61hck) and phosphotyrosine-phosphatases (PTP). To assess this hypothesis under the influence of AChE effectors (acetylcholine/velnacrine), blood samples from healthy donors were harvested and Western blot analysis was subsequently used to determine the degree of band 3 phosphorylation, in the presence and absence of PTK/PTP inhibitors. NO and nitrites/nitrates were quantified using an amperometric method and the Griess Reaction, respectively, in erythrocyte suspensions. Measurements of erythrocyte metabolites (2,3-bisphosphoglycerate; glyceraldehyde 3-phosphate dehydrogenase; glucose-6-phosphodehydrogenase; lactate), hemoglobin and cyclic nucleotides were conducted afterwards. Increased levels of phosphorylated-band 3 obtained upon p72syk inhibition suggest p59/61hck and p53/56lyn as secondary involved kinases. As to NO/NOx quantification, in the presence of PTKi we reported higher levels with velnacrine-AChE, as opposed to acetylcholine-AChE. Calpeptin, a PTP inhibitor which triggers full band 3-phosphorylation, led to the opposite NO mobilization, being reinforced by ACh. Oxy-hemoglobin, glyceraldehyde 3-phosphate dehydrogenase and glucose-6-phosphodehydrogenase were found to decrease with ACh, whereas P50, lactate and both cGMP/cAMP happened to increase. Changes on human erythrocyte NOx mobilization and metabolic fluxes occur under influence of non-neuronal ACh/AChE, in turn dependent on the degree of band 3-phosphorylation. Since these vascular events may potentially change under pathological conditions, coadjuvant drugs could become accessible in the setting of microcirculation disease.


Formulation of zinc foliar sprays for wheat grain biofortification: a review of current applications and future perspectives.
Agronomic biofortification of wheat grain with zinc can improve the condition of about one billion people suffering from zinc (Zn) deficiency. However, with the challenge of cultivating high-yielding wheat varieties in Zn-deficient soils and the global need to produce higher-quality food that nourishes the growing population, innovation in the strategies to deliver Zn directly to plants will come into play. Consequently, existing foliar formulations will need further refinement to maintain the high agronomic productivity required in competitive global grain markets while meeting the dietary Zn intake levels recommended for humans. A new generation of foliar fertilisers that increase the amount of Zn assimilated in wheat plants and the translocation efficiency of Zn from leaves to grains can be a promising solution. Research on the efficacy of adjuvants and emerging nano-transporters relative to conventional Zn forms applied as foliar fertilisers to wheat has expanded rapidly in recent years. This review scopes the range of evidence available in the literature regarding the biofortification of bread wheat (Triticum aestivum L.) resulting from foliar applications of conventional Zn forms, Zn nanoparticles and novel Zn-foliar formulations. We examine the foliar application strategies and the attained final concentration of grain Zn. We propose a conceptual model for the response of grain Zn biofortification of wheat to foliar Zn application rates. This review discusses some physiological aspects of transportation of foliarly applied Zn that need further investigation. Finally, we explore the prospects of engineering foliar nano-formulations that could effectively overcome the physicochemical barrier to delivering Zn to wheat grains.


Endobronchial hamartoma.
We have reported a case of endobronchial hamartoma in a mainstem bronchus. Diagnosis of these rare lesions may be difficult when chronic pulmonary destruction has occurred; biopsy of the tumor may show cellular atypia due to inflammation. Although bronchoscopic removal or removal by bronchotomy or sleeve resection with preservation of the lung may be possible, when irreversible lung damage has occurred because of chronic obstruction and suppuration, pulmonary resection may be indicated.


Autophagic perturbation caused by reduced lysosomal activity positively regulates cell competition.
Newly emerging transformed epithelial cells are recognized and apically removed by surrounding normal cells through a biological event termed "cell competition". However, little is known about the mechanisms underlying this process. In a recent study, we describe that RASG12V/RasV12-transformed cells surrounded by normal cells exhibit decreased lysosomal activity accompanied with accumulation of autophagosomes. Restoration of low lysosomal activity or inhibition of autophagosome formation significantly antagonizes apical extrusion of RASG12V cells, suggesting that non-degradable autophagosomes are required for cell competition. Notably, analysis of a cell competition mouse model demonstrates that macroautophagy/autophagy-ablated RASG12V cells are less readily eliminated by cell competition, and remaining transformed cells destroy ductal integrity, leading to chronic pancreatitis. Thus, our findings illuminate a critical role for non-degradable autophagosomes in cell competition and reveal a homeostasis-preserving role of autophagy upon emergence of transformed cells.


Gamma secretase inhibitors: a patent review (2013 - 2015).
Gamma secretase (GS) is an intricate and multi-subunits complex, and it can cut various transmembrane proteins. Now it is a therapeutic target for a number of diseases. However, due to some side effects, the clinical development of GSI is not successful. Therefore, searching for effective GSIs has become a key point in drug discovery. Areas covered: This review discusses the structure and function of GS and various types of GSIs. And this article seeks to give an overview of the patents or applications published from 2013 to 2015 in which novel chemical classes are claimed to inhibit the GS. Expert opinion: Firstly, further understanding the structure and function of GS to elucidate the disease mechanism and develop AD therapies is urgent. Secondly, if the bioequivalence, pharmacokinetics and selectivity can be improved greatly, some failed clinical inhibitors still can become the promising compounds for clinical trials. Thirdly, some weaknesses are exposed during the development of GSI, especially the insufficient potency, low brain penetration and poor selectivity. Finally, to find potent and selective GSI is the major direction in future. Moreover, to find new indications and dosing regimens in a trial of GSIs also can be seen as new ways.


Update on the disposition of military insanity acquittees.
There has been little study of the use of the insanity defense within the military judicial system, and aggregated data concerning such cases are not readily available when needed. Useful information is not consolidated in a central location, hindering potential research and the development of systemic improvements. One key area that would benefit from closer analysis is the process of the disposition of insanity acquittees. The Manual for Courts-Martial (2000 ed. Washington, DC: U.S. Government Printing Office) provides limited guidance in procedures to disposition, outlining the process in rather broad terms. The result is often a time-consuming and resource-draining process that can create significant burdens for both the military legal and health care systems. The need to address challenges within the system is discussed, and the creation of a centralized databank as a step toward improving this system is recommended.


Minimum Core Data Elements for Evaluation of TAVR: A Scientific Statement by PASSION CV, HVC, and TVT Registry.
Transcatheter aortic valve replacement (TAVR) is the standard of care for severe, symptomatic aortic stenosis. Real-world TAVR data collection contributes to benefit/risk assessment and safety evidence for the U.S. Food and Drug Administration, quality evaluation for the Centers for Medicare and Medicaid Services and hospitals, as well as clinical research and real-world implementation through appropriate use criteria. The essential minimum core dataset for these purposes has not previously been defined but is necessary to promote efficient, reusable real-world data collection supporting quality, regulatory, and clinical applications. The authors performed a systematic review of the published research for high-impact TAVR studies and U.S. multicenter, multidevice registries. Two expert task forces, one from the Predictable and Sustainable Implementation of National Cardiovascular Registries/Heart Valve Collaboratory and another from The Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry convened separately and then met to reconcile a final list of essential data elements. From 276 unique data elements considered, unanimous consensus agreement was achieved on 132 "core" data elements, with the most common reasons for exclusion from the minimum core dataset being burden or difficulty in accurate assessment (36.9%), duplicative information (33.3%), and low likelihood of affecting outcomes (10.7%). After a systematic review and extensive discussions, a multilateral group of academicians, industry representatives, and regulators established 132 interoperable, reusable essential core data elements essential to supporting more efficient, consistent, and informative TAVR device evidence for regulatory submissions, safety surveillance, best practice, and hospital quality assessments.


Structural Mechanisms of Peptide Recognition and Allosteric Modulation of Gene Regulation by the RRNPP Family of Quorum-Sensing Regulators.
The members of RRNPP family of bacterial regulators sense population density-specific secreted oligopeptides and modulate the expression of genes involved in cellular processes, such as sporulation, competence, virulence, biofilm formation, conjugative plasmid transfer and antibiotic resistance. Signaling by RRNPP regulators include several steps: generation and secretion of the signaling oligopeptides, re-internalization of the signaling molecules into the cytoplasm, signal sensing by the cytosolic RRNPP regulators, signal-specific allosteric structural changes in the regulators, and interaction of the regulators with their respective regulatory target and gene regulation. The recently determined structures of the RRNPP regulators provide insight into the mechanistic aspects for several steps in this signaling circuit. In this review, we discuss the structural principles underlying peptide specificity, regulatory target recognition, and ligand-induced allostery in RRNPP regulators and its impact on gene regulation. Despite the conserved tertiary structure of these regulators, structural analyses revealed unexpected diversity in the mechanism of activation and molecular strategies that couple the peptide-induced allostery to gene regulation. Although these structural studies provide a sophisticated understanding of gene regulation by RRNPP regulators, much needs to be learned regarding the target DNA binding by yet-to-be characterized RNPP regulators and the several aspects of signaling by Rgg regulators.


Activation of caspase-like proteases and induction of apoptosis by isopentenyladenosine in tobacco BY-2 cells.
The effects of isopentenyladenosine (iPA) on tobacco (Nicotiana tabacum L.) BY-2 cells were examined. The number of BY-2 cells decreased in a time- and concentration-dependent manner after being exposed to micromolar concentrations of iPA. This decrease was mainly due to a loss of cell viability, since no substantial changes in cell cycle progression were revealed by flow-cytometric analysis. Dying cells exhibited the typical morphological and biochemical hallmarks of apoptosis, including cell shrinkage, chromatin condensation, and degradation of nuclear DNA to nucleosomal size fragments. Caspase-1-like and caspase-3-like proteases also became activated, the former being dominant. Inhibitor-sensitivity studies revealed that although synthetic caspase inhibitors failed to prevent cell death they markedly reduced cell death in tobacco BY-2 cells, Nu-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, a specific inhibitor for caspase-1, being the most effective. Our results indicate that caspase-like proteases, and particularly caspase-1-like protease, might be critically implicated in iPA-induced apoptosis of BY-2 cells. Finally, the outcome of inhibiting adenosine kinase by 4-amino-3-iodo-1(beta- D-ribofuranosyl)pyrazolo[3,4-d]-pyrimidine revealed that intracellular phosphorylation of iPA is required for its cytotoxicity to develop.


Extracanal invasive root resorption: a perplexing oddity.
Extracanal invasive resorption originates in the periodontal ligament, making it difficult to determine during treatment whether all resorption cells have been eliminated. Consequently, periodontal defects and recurrence of the process are quite common. This process can occur supraosseously or subosseously and treatment may or may not include endodontic therapy. The pathogenesis, diagnosis, and treatment modalities are presented along with a clinical case with an 18-month follow-up as an example of the challenges associated with treatment of this lesion.


Inhibition of nuclear factor kappa B attenuates proinflammatory cytokine and inducible nitric-oxide synthase expression in postischemic myocardium.
We have previously reported that induction of nuclear factor-kappa B (NF-kappa B) occurs in a biphasic manner in postischemic myocardium. Because interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-alpha), and inducible nitric-oxide synthase (iNOS) contain kappa B-response elements, and since transforming growth factor-beta 1 (TGF-beta 1) down-modulates both cytokine and iNOS expression, we studied their temporal expression during myocardial ischemia/reperfusion (I/R). Northern and Western analyses showed low levels of IL-6 and no signal for IL-1 beta, TNF-alpha and iNOS under basal conditions. Their expression rose significantly over sham-operated controls by 1 h reperfusion, and persisted high for various periods. Under basal conditions, low levels of TGF-beta 1 were detected, which rose significantly at 3 h reperfusion, and remained high until 24 h reperfusion. Administration of diethyldithiocarbamate (DDC) inhibited induction of NF-kappa B and concomitantly the expression of IL-1 beta, IL-6, TNF-alpha as well as iNOS. However, expression of TGF-beta was not altered. Our results indicate that ischemia/reperfusion induces NF-kappa B, and upregulates kappa B-response genes. Administration of DDC inhibits NF-kappa B levels, and attenuates expression of inflammatory cytokines and iNOS.


The NEWS2 score predicts prolonged hospitalization in the intensive care unit in major surgery patients.
Gynecological malignancies are significant causes of mortality and morbidity in women worldwide. Although surgery is an important treatment method, both the extent of the surgery and the factors related to the patient affect postoperative processes. The National Early Warning Score 2 (NEWS2) is a simple, inexpensive, and safe early warning score developed in 2012 and updated in 2017. Although it is not commonly used in surgical patients, its use in patients who will undergo major surgery may provide insights about the postoperative process. This study investigates the importance of NEWS2 and its relationship in patients with for major gynecologic oncology surgery. Forty-four patients with gynecologic malignancies scheduled for major abdominal surgery were included in this study. Patients with a NEWS-2 score of <3 were included in group 1, and patients with a NEWS-2 score of more than 3 were included in groups 2. NEWS2 Score, Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation 2 scores (APACHE 2) were calculated. In addition, postoperative routine clinical and laboratory parameters were evaluated. Operation time, duration of intubation in the intensive care unit (ICU), the length of the intensive care stay, and length of hospitalization were recorded. Duration of intubation in the ICU in group 1 with a NEWS2 <3 [8.2 (0-18) vs 16.2 (3-39), respectively; p<0.01], ICU length of stay [21.6 (4-27) vs 47.3 (4-113), respectively; p<0.01], length of hospitalization [11.6 (5-56) vs 18.6 (8-67), respectively; p<0.01]. NEWS2 >3 was significantly higher compared to group 2. The SOFA score was significantly higher in group 2 compared with group 1 [1.2±0.5 vs 4.1±1.9; respectively; p<0.01]. In the correlation analysis, the NEWS2 score level was positively correlated with the SOFA score (p<0.001, r=0.81) and hospitalization time (p<0.001, r=0.60) and neutrophil lymphocyte ratio (NLR) (p<0.001, r=0.47). These findings suggest that the NEWS2 score may be correlated with the length of intensive care intubation, length of intensive care stay, and length of hospitalization. NEWS2 is an effective and simple scoring system that provides information about postoperative outcomes in gynecologic oncology patients scheduled for major surgery.


Treatment of esophageal cancer with vindesine: an open trial.
Fifty-two patients with advanced esophageal cancer have been entered in an open study with vindesine. The regimen consisted of vindesine at a dose of 3 mg/m2 as a continuous infusion over 48 hours followed by 3 mg/m2 iv weekly for 4 weeks and then by monthly maintenance therapy using the same dose. Objective response was seen in 14 (27%) patients. Patients who responded to treatment had significant prolongation of survival. Major pretreatment prognostic factors included performance status and serum albumin concentration. It is concluded that vindesine has definite, although limited, activity against esophageal cancer.


Shadow cell differentiation in endometrioid carcinomas of the uterus. Its frequent occurrence and beta-catenin expression.
Shadow cell differentiation (SCD) is typical for pilomatrixoma and related follicular tumors of the skin. However, it has been described rarely in some extra-cutaneous lesions such as gonadal teratoma, craniopharyngioma, odontogenic cyst, and in rare visceral carcinomas (lung, bladder, gallbladder, uterus, ovary, and colon). In our practice, we have noticed that the occurrence of shadow cells is not very rare in endometrioid carcinoma (EC) of the uterus. For exact determination of SCD in these tumors, we reviewed 59 consecutive cases of uterine EC. The series included curettage and hysteroscopic specimens. We have found SCD in 9 (15.3 %) of the tumors. In these cases, the age of the patients and FIGO grade did not differ significantly from other ECs. Immunohistochemically, all ECs with SCD showed nuclear expression of beta-catenin in areas of SCD, indicating a possible role of the Wnt signaling pathway in tumorigenesis as well as a role of nuclear accumulation of beta-catenin by trans-differentiation from glandular toward squamous and shadow cell phenotypes. We have found that the relatively frequent presence of SCD in ECs can assists in the diagnosis of these tumors.


Ruxolitinib - better prognostic impact in low-intermediate 1 risk score: evaluation of the 'rete ematologica pugliese' (REP) in primary and secondary myelofibrosis.
We evaluated ruxolitinib in 65 patients with myelofibrosis according to age, sex, time of diagnosis, grade of fibrosis, prognostic score risk, Janus kinase (JAK) status, primary or secondary myelofibrosis, previous treatment, and dosage. Outcome measures were response rate, time to response, duration of response, and event-free survival and survival. Kaplan and Meier curves show a significant difference in event-free survival according to the prognostic score, in favor of patients with low int1 (p = 0.0009). The Cox stepwise model confirmed the result, the int2 high-risk score being the most powerful negative independent parameter (0.001), followed by JAK (0.008); other parameters, such as diagnosis more than 5 years earlier, grade III-IV fibrosis, and ruxolitinib dose have a negligible impact. Time to response was shorter (p = 0.001) in primary myelofibrosis. In conclusion, ruxolitinib is effective, with a better outcome in patients with a low-int1 risk score. This may suggest considering an earlier administration in the disease course.


[Historical perspective of smallpox in Mexico: emergence, elimination, and risk of reemergence due to bioterrorism].
Smallpox has been considered a disease of historical interest. However, given the 2001 terrorist events in the U.S. with intentional release of spores of Bacillus anthracis, and the current political worldwide agenda, the risk of bioterrorism has become a global public health concern. The risk of an intentional release of Variola virus as a biological weapon mandates a critical review of the historical impact of the disease in our country and the possible risk of its intentional reemergence. Smallpox was introduced into susceptible Indian populations in the Americas in the 16th century, contributing to the collapse of the Aztec Empire. Francisco Xavier Balmis start a vaccination campaign in the New World, and his efforts are considered the first eradication campaign of vaccine preventable diseases. Due to his efforts, smallpox was eliminated in Mexico in 1951. In the posteradication era, there is small but finite risk of intentional release of Variola virus. In response to this risk, Mexico has developed a comprehensive National preparedness plan. The impact of a new epidemic of smallpox will be considered a catastrophic event from both a historical and public health perspectives.


Factors associated with preoperative anxiety levels of Turkish surgical patients: from a single center in Ankara.
Preoperative anxiety and stress are undoubtedly a difficult experience in patients undergoing elective surgery. These unpleasant sensations depend on several factors. The objective of this study was to evaluate the preoperative anxiety levels in a sample of Turkish population, as well as the underlying causes using the Spielberger State-Trait Anxiety Inventory (STAI anxiety) scale. The study was conducted according to the Declaration of Helsinki and was approved by the local ethical committee. All participants gave written informed consent upon having received detailed information on the study. Upon entry in the study, state and trait anxiety questionnaires were completed by 186 patients scheduled for elective surgery. The influencing factors in regard to age, sex, educational status and others were also reported. There was a statistically significant positive correlation between state and trait anxiety scores in this Turkish population. While the most important predictive factors that affected state-STAI scores were age, sex and duration of sleep the night before surgery; educational status and age were the best predictors for determining the variation in trait-STAI scores. The factors affecting anxiety levels in different populations might vary among different countries. Interestingly, in this sample of Turkish population, the trait anxiety levels were found to be higher from state-anxiety levels, especially in women and less educated people. Thus, doubts about operation and anesthesia are overlooked. This could be attributed to the low to intermediate life standards of people admitted to our hospital.


Effects of selection index coefficients that ignore reliability on economic weights and selection responses during practical selection.
In practical breeding, selection is often performed by ignoring the accuracy of evaluations and applying economic weights directly to the selection index coefficients of genetically standardized traits. The denominator of the standardized component trait of estimated genetic evaluations in practical selection varies with its reliability. Whereas theoretical methods for calculating the selection index coefficients of genetically standardized traits account for this variation, practical selection ignores reliability and assumes that it is equal to unity for each trait. The purpose of this study was to clarify the effects of ignoring the accuracy of the standardized component trait in selection criteria on selection responses and economic weights in retrospect. Theoretical methods were presented accounting for reliability of estimated genetic evaluations for the selection index composed of genetically standardized traits. Selection responses and economic weights in retrospect resulting from practical selection were greater than those resulting from theoretical selection accounting for reliability when the accuracy of the estimated breeding value (EBV) or genomically enhanced breeding value (GEBV) was lower than those of the other traits in the index, but the opposite occurred when the accuracy of the EBV or GEBV was greater than those of the other traits. This trend was more conspicuous for traits with low economic weights than for those with high weights. Failure of the practical index to account for reliability yielded economic weights in retrospect that differed from those obtained with the theoretical index. Our results indicated that practical indices that ignore reliability delay genetic improvement. Therefore, selection practices need to account for reliability, especially when the reliabilities of the traits included in the index vary widely.


[Increasing effectiveness by sectorization of psychiatric care--an epidemiologic study].
Results of social-psychiatric analyses explained the lacks of the traditional psychiatric homes. This perception led to development of new systems of care in an international scope, which are based on the principle of sectorial psychiatric care. Based on epidemiological data (distribution of diagnoses, space of origin, duration of stay, number of patients treated, first and repeated admission), the alteration of the spectrum of performances of the Psychiatric Clinic of the KMU Leipzig is analysed. To sectorial principle this Clinic attends to all psychiatric patients of the district Leipzig South requiring stationary treatment since 1976. The increase of performances of the clinic and the improved care about psychiatric patients by sectors as well became obviously.


Proton catalysis in the redox responsivity of a mini-sized photochromic diarylethene.
A thermally irreversible dithienylethene (DTE) photochrom can be turned into a thermally reversible one in presence of Cu(II) triflate. A ring opening (DTEC closed→DTEO open) occurs through the formation of a copper-containing fast transient intermediate. Stopped-flow experiments monitored at 410 and 780 nm have allowed to show that the stoichiometry of this intermediate is DTE/Cu=1:1. At longer monitoring times (i.e., several seconds after mixing), the intermediate undergoes a slow decay while the residual DTEC closed form opens. A joint detailed kinetic and electrochemical analysis has unveiled a proton catalysis scenario in which electron transfer between DTEC and Cu(II), ligand exchange, protonation-deprotonation equilibria of the cation radicals and ring opening are embedded into two main reaction cycles. At the beginning of the reaction, Cu(II) is reduced into Cu(I) and DTE is degraded without ring opening. Then, as the reaction progresses, the triflic acid released from the Cu(II) reduction switches-on a propagation cycle during which ring opens without any more Cu(II) consumption. Cyclic voltammetry, spectro-electrochemical measurements, delayed photocoloration experiments in presence of Cu(II) and acid-base additions have confirmed the main features of the proton catalysis.


Acute creatine supplementation and performance during a field test simulating match play in elite female soccer players.
This study investigated the effects of acute creatine (Cr) supplementation on the performance of elite female soccer players undertaking an exercise protocol simulating match play. On two occasions, 7 days apart, 12 players performed 5 x 11-min exercise testing blocks interspersed with 1 min of rest. Each block consisted of 11 all-out 20-m running sprints, 2 agility runs, and 1 precision ball-kicking drill, separated by recovery 20-m walks,jogs, and runs. After the initial testing session, subjects were assigned to either a CREATINE (5 g of Cr, 4 times per day for 6 days) or a PLACEBO group (same dosage of a glucose polymer) using a double-blind research design. Body mass (BM) increased (61.7 +/- 8.9 to 62.5 < or = 8.9 kg, p < .01) in the CREATINE group; however, no change was observed in the PLACEBO group (63.4 < or = 2.9 kg to 63.7 +/- 2.5 kg). No overall change in 20-m sprint times and agility run times were observed, although the CREATINE group achieved faster post-supplementation times in sprints 11, 13, 14, 16, 21, 23, 25, 32, and 39 (p <.05), and agility runs 3, 5, and 8 (p < .05). The accuracy of shooting was unaffected in both groups. In conclusion, acute Cr supplementation improved performance of some repeated sprint and agility tasks simulating soccer match play, despite an increase in BM.


Emerging approaches for decoding neuropeptide transmission.
Neuropeptides produce robust effects on behavior across species, and recent research has benefited from advances in high-resolution techniques to investigate peptidergic transmission and expression throughout the brain in model systems. Neuropeptides exhibit distinct characteristics which includes their post-translational processing, release from dense core vesicles, and ability to activate G-protein-coupled receptors (GPCRs). These complex properties have driven the need for development of specialized tools that can sense neuropeptide expression, cell activity, and release. Current research has focused on isolating when and how neuropeptide transmission occurs, as well as the conditions in which neuropeptides directly mediate physiological and adaptive behavioral states. Here we describe the current technological landscape in which the field is operating to decode key questions regarding these dynamic neuromodulators.


The ten point clock test: a quick screen and grading method for cognitive impairment in medical and surgical patients.
The objective of this study was to evaluate the clinical utility of the ten point clock test in screening for and grading cognitive deficits in medical and surgical patients. The setting was the hospital and clinics of Virginia Mason Medical Center, a tertiary referral center. Consecutive samples of hospitalized patients, and clinic outpatients--with and without a dementia--were administered the ten point clock test as well as a number of other neuropsychological tests and measures of cognitive impairment. Clock scores correlated with neuropsychological test scores and with the mini-mental state examination. They were stable from rater to rater, and from day to day in stable patients. The mean clock score of elderly outpatient controls was 8.5, significantly different from the mean of 5.5 scored by patients with a dementia. A cut off score of seven identified 76 percent of outpatients with dementia and 78 percent of elderly controls. Clock scores correlated well with nurses' ratings of their inpatients' cognitive deficits (Spearman's rs = -0.61). The test was easy to administer, even to hospitalized patients. The ten point clock test is reliable, valid, and useful as a quick screen and grading method for cognitive deficits in medical and surgical patients.


Dynamic heterogeneities in the out-of-equilibrium dynamics of simple spherical spin models.
The response of spherical two-spin interaction models, the spherical ferromagnet (s-FM) and the spherical Sherrington-Kirkpatrick (s-SK) model, is calculated for the protocol of the so-called nonresonant hole burning (NHB) experiment for temperatures below the respective critical temperatures. It is shown that it is possible to select dynamic features in the out-of-equilibrium dynamics of both models, one of the hallmarks of dynamic heterogeneities. The behavior of the s-SK model and the s-FM model in three dimensions is very similar, showing dynamic heterogeneities in the long-time behavior, i.e., in the aging regime. The appearance of dynamic heterogeneities in the s-SK model explicitly demonstrates that these are not necessarily related to spatial heterogeneities. For the s-FM model, it is shown that the nature of the dynamic heterogeneities changes as a function of dimensionality. With the increasing dimension, the frequency selectivity of the NHB diminishes and the dynamics in the mean-field limit of the s-FM model becomes homogeneous.


Genetic features of a translation initiation system composed of IRES element, nucleotide context surrounding the initiation codon, and translation initiation region of classical swine fever virus RNA.
Nucleotide and codon usage are typically examined to investigate viral evolution. In this study, we analyzed the genetic information of 46 strains of classical swine fever virus (CSFV) RNA, nucleotide usage in the internal ribosome entry site (IRES), the nucleotide context surrounding the initiation codon, and synonymous codon usage in the translation initiation region. Phylogenetic analysis of the IRES element indicated that the genetic diversity of this element is generally similar to the phylogenetic clusters of CSFV genotypes. Nucleotides surrounding the initiation codon of CSFV RNA were generally more stable (ACAUGGCACAUGGAGUUG) compared to the internal AUG in the CSFV coding sequence. The second codon position after the initiation codon was generally selected to be GAG, which has lower tRNA abundance in pigs than its synonymous member (GAA). Regarding the synonymous codon usage bias in the CSFV translation initiation region, some codons showing low tRNA abundance in pigs are more frequently located in the translation initiation region than in the open reading frame of CSFV. Although CSFV, similarly to other RNA viruses, has a high mutation rate in nature, the regulatory features of nucleotide and synonymous codon usage of the IRES element, the nucleotide context surrounding the initiation codon and the translation initiation region in CSFV RNA have been 'branded' in the system of translation initiation to accommodate gene expression mediated by the cap-independent translation mechanism.


Risk Stratification With Coccidioidal Skin Test to Prevent Valley Fever Among Inmates, California, 2015.
Two California state prisons (A and B) have very high rates of coccidioidomycosis (Valley Fever). The prison health care service sought to improve their prevention strategy by risk stratification with a newly available spherulin-based Coccidioides delayed-type hypersensitivity test. Of the 36,789 voluntarily screened inmates, 4.7% experienced adverse reactions. A positive test (8.6% of those tested) was independently associated with (1) incarceration at prisons A and B, (2) admission to prison from a Coccidioides-endemic county, (3) length of stay at prisons A and B, and (4) increasing age. These findings suggest that the test is safe and performing well at risk stratification; the prison system now restricts inmates with negative tests from prisons A and B. This novel use of the test might benefit other coccidioidomycosis prevention programs.


Targeted co-delivery of Beclin 1 siRNA and FTY720 to hepatocellular carcinoma by calcium phosphate nanoparticles for enhanced anticancer efficacy.
FTY720, known as fingolimod, is a new immunosuppressive agent with effective anticancer properties. Although it was recently confirmed that FTY720 inhibits cancer cell proliferation, FTY720 can also induce protective autophagy and reduce cytotoxicity. Blocking autophagy with Beclin 1 siRNA after treatment with FTY720 promotes apoptosis. The objective of this study was to enhance the anticancer effect of FTY720 in hepatocellular carcinoma (HCC) by targeted co-delivery of FTY720 and Beclin 1 siRNA using calcium phosphate (CaP) nanoparticles (NPs). First, the siRNA was encapsulated within the CaP core. To form an asymmetric lipid bilayer structure, we then used an anionic lipid for the inner leaflet and a cationic lipid for the outer leaflet; after removing chloroform by rotary evaporation, these lipids were dispersed in a saline solution with FTY720. The NPs were analyzed by transmission electron microscopy, dynamic light scattering and ultraviolet-visible spectrophotometry. Cancer cell viability and cell death were analyzed by MTT assays, fluorescence-activated cell sorting analysis and Western blotting. In addition, the in vivo effects of the NPs were investigated using an athymic nude mouse subcutaneous transplantation tumor model. When the CaP NPs, called LCP-II NPs, were loaded with FTY720 and siRNA, they exhibited the expected size and were internalized by cells. These NPs were stable in systemic circulation. Furthermore, co-delivery of FTY720 and Beclin 1 siRNA significantly increased cytotoxicity in vitro and in vivo compared with that caused by treatment with the free drug alone. The CaP NP system can be further developed for co-delivery of FTY720 and Beclin 1 siRNA to treat HCC, enhancing the anticancer efficacy of FTY720. Our findings provide a new insight into HCC treatment with co-delivered small molecules and siRNA, and these results can be readily translated into cancer clinical trials.


Differences of Host Country-Destination Image Assessment for International Students According to Risk Perception in COVID-19 Tourism.
The study examined the comparative assessment of destination image according to the perception of COVID-19 and travel risk among international students. The online survey was administered to 786 international students enrolled in universities in Korea. Cluster analysis was performed, and three distinct clusters were identified based on risk perception. Destination image attributes were generated into four underlying dimensions: social environment, tourist environment, destination environment, and imagery, using the exploratory factor analysis. A revised Importance-Performance Analysis (IPA) method was utilized to assess the destination image of Korea and used to compare the expected performance of the attributes on each cluster. In addition, a revised IPA grid of each cluster was presented to unveil the satisfaction attributes of the destination image and suggest communication strategies. This study provides practical insights to destination marketers and organizations to design marketing strategies for international students. Further practical and theoretical implications are discussed.


Unstable Distal Radius Fractures Treated by Volar Locking Anatomical Plates.
Fracture of the distal end of radius represents the most common fracture of the upper extremity accounting for 16-20% of all fractures. Plating is now emerging as the gold standard for management of distal radius fractures due to increased rate of complications such as malunion, subluxation/dislocation of distal radio-ulnar joint or late collapse of fracture. Procedures such as closed reduction and cast immobilization, ligamentotaxis with external fixator and percutaneous pin fixation are no longer acceptable. The purpose of the study was to evaluate the functional and radiological outcome of unstable distal radius fractures treated with the volar locking plate. We reviewed 53 patients from January 2011 to December 2015, treated for unstable distal radius fractures using a volar locking compression plate. Standard radiographic and clinical assessment after 12 months (range 12-16 months) were measured and final functional and radiological outcome were assessed using the Modified Mayo wrist scoring system and Sarmiento's modification of Lindstorm criteria respectively. There were 42 males and 11 females with an average age of 39.12±31.78 years (18-71 years). At the end of 12 months, 36 patients had an excellent radiological outcome and 10 patients had good radiological outcome as per Sarmiento's modification of Lindstorm criteria. Eleven patients had an excellent functional outcome and 26 patients had a good functional outcome as per modified Mayo wrist scoring system. There was one case of superficial wound infection which subsided with intravenous antibiotics. The volar locking plate fixation helps in early mobilization of the wrist, restores anatomy, allows early return to function, prevents secondary loss of reduction and hence is an effective treatment for unstable fractures of the distal radius.


A study of arthritis in Papua New Guinea.
A study was undertaken of 182 Melanesian patients with arthritis who were admitted to three major hospitals in Papua New Guinea between 1977 and 1982. There were 118 male and 64 female subjects, whose mean ages were 29 years and 25 years respectively. A diagnosis was made in 101 cases (55.5%) but in 81 cases, because assessment and management had been inadequate, a diagnosis could not be made. The commonest cause was infectious arthritis (44%), followed by rheumatoid arthritis (14%), gout (8%), and reactive arthritis (8%). In the 44 subjects with infectious arthritis, gonorrhea was the cause in 25 cases (57%) and in a further six cases (14%) it was attributed to Ross River virus infection. In five cases, arthritis was believed to be caused by Wuchereria bancrofti infection. In several cases, chronic arthritis was present in association with ankylosing spondylitis, psoriasis, systemic lupus erythematosus, dermatomyositis, or systemic sclerosis.


XIAP inhibitor embelin induces autophagic and apoptotic cell death in human oral squamous cell carcinoma cells.
Embelin is an active ingredient of traditional herbal remedies for cancer and other diseases. Recently, it has been suggested that autophagy may play an important role in cancer therapy. However, little data are available regarding the role of autophagy in oral cancers. Therefore, we conducted this study to examine whether Embelin modulates autophagy in Ca9-22. Our results showed that Embelin had anticancer activity against the Ca9-22 human tongue squamous cell, and we observed that autophagic vacuoles were formed by MDC and AO. We also analyzed Embelin-treated Ca9-22 cells for the presence of biochemical markers and found that it directly affected the conversion of LC3-II, the degradation of p62/SQSTM1, full-length cleavage formation of ATG5-ATG12 complex and Beline-1, and caspase activation. Rescue experiments using an autophagy inhibitor showed Embelin-induced cell death in Ca9-22, confirming that autophagy acts as a pro-death signal. Furthermore, Embelin exhibited anticancer activity against Ca9-22 via both autophagy and apoptosis. These findings suggest that Embelin may potentially contribute to oral cancer treatment and provide useful information for the development of a new therapeutic agent.


Mayer-Rokitansky-Kuster-Hauser syndrome in a young female: diagnosis and treatment: a case report.
Mayer-Rokitansky-Kuster-Hauser Syndrome is a rare condition in which Müllerian system does not develop and ends up with rudimentary upper vagina and the uterus. As compared to normal physiology of the ovaries and puberty, the patients present with primary amenorrhoea a key clinical symptom. However, the exact aetiology of the disease is still unknown. A few reports considered environmental and epigenetic changes, hormonal imbalance, and cellular receptor abnormalities as possible risk factors associated with the disease. This case was reported at the Department of Family Medicine, The Indus Hospital, Karachi. A 24-year-old woman, married for eight months, presented with primary amenorrhoea and painful intercourse. Upon detailed clinical evaluation and relevant radiological and diagnostic investigation, an assessment, of Mayer-Rokitansky syndrome was made.


Buoyancy of African black and European white males.
Twenty-six male swimmers (13 Blacks, 13 Whites) matched for age, weight, and stature were subjects in the comparison of anthropometric characteristics and horizontal and vertical buoyancies. Subjects were tested in a swimming pool in the horizontal position. The time necessary for the body to return to the vertical position defined horizontal buoyancy. Vertical buoyancy was the hydrostatic lift necessary to maintain the subject immersed to the nose. The results indicated similarities in arm span, trunk flexibility, and full inspiration and exhalation of Black and White subjects. However, there were differences in body fat distribution (P ≤ 0.05) and buoyancies (P ≤ 0.01), with Whites storing more fat and having better buoyancy than Blacks. Am. J. Hum. Biol. 9:87-92 © 1997 Wiley-Liss, Inc.


Prognostic impact of ventilatory efficiency in heart disease patients with preserved exercise tolerance.
The minute ventilation/carbon-dioxide output (VE/VCO2) slope as a marker of cardiac events has been established in patients with severe heart failure, but it is not known whether it is useful for other heart diseases. The present study investigated 215 patients with various heart diseases (age 59+/-11 years; ischemic heart disease, n=89; dilated cardiomyopathy, n=38; valvular disease, n=37; hypertensive heart disease, n=33; others, n=18) who underwent cardiopulmonary exercise testing to determine the VE/VCO(2) slope. Patients were divided into 2 groups according to the VE/VCO2 slope and were followed-up for 3 years. Forty-eight cardiac events (6 deaths, 42 re-hospitalizations) occurred during the observation period. Patients with a VE/VCO2 slope >34 had a significantly higher 3-year cardiac event rate (32.1%) than patients with VE/VCO2 slope <34 (18.9%, p<0.05). When patients were selected with relatively preserved peak oxygen uptake values (>16 ml . kg (-1) . min(-1)), patients with VE/VCO2 slope >34 still demonstrated a significantly higher cardiac event rate than other patients (35.0% vs 13.3%, p<0.01). The VE/VCO2 slope may be a prognostic indicator of cardiac events in a heterogeneous group of patients with heart disease, independent of exercise tolerance.


Mechanical strength of trabecular bone at the knee.
Interest in the biomechanical properties of trabecular bone has expanded in response to the problems related to total and partial joint replacement with the knee joint constituting a main focus of attention. This relatively recent development has left a number of fundamental problems unanswered, especially related to the machining, storage and testing of trabecular bone specimens. Nevertheless, these studies have contributed to the understanding of the mechanical function of trabecular bone. Regarding the role of trabecular bone at the knee joint, the following conclusions may be emphasized (conclusions drawn from the author's previous studies (I-X) are shown in italics): (1) Trabecular bone is almost exclusively responsible for the transmission of load at the proximal tibial epiphysis from the knee joint to the metaphysis. The peripheral shell surrounding the epiphysis is not composed of cortical bone and plays a negligible role in load transmission. (2) The compressive strength and stiffness of trabecular bone is primarily dependent upon the apparent density, trabecular architecture and the strength of the bone material. Direct and indirect sources suggest that the true material strength of trabecular bone is less than that of cortical bone. The epiphyseal trabecular architecture, featuring a marked polarity with alignment of primary trabeculae at right angles to the joint surface, is responsible for functional anisotropy which points to the axial compressive properties as the more important mechanical parameters. (3) Tensile and shear properties are of special relevance to mechanical loosening of implants. These properties may be derived from the apparent density, and a close empirical relation to the axial compressive strength and stiffness is suggested. (4) The foam-like structure of trabecular bone is the basis for the large energy absorptive capacity. (5) The pattern of axial compressive stiffness and strength at the normal proximal tibia differs little among individuals. Supporting the medial tibial plateau is a large high strength area with maximal strength centrally and slightly anteriorly, while laterally there is a restricted area of relatively high strength posteriorly with a lower maximal value than medially. Bone strength is significantly reduced within ten millimeters of the subchondral bone plate, and this reduction continues distally at the lateral condyle. At both condyles strength is reduced towards the periphery with very low values being obtained at the margins of the condyles and at the intercondylar region. Absolute bone strength values are influenced by the level of physical activity.(ABSTRACT TRUNCATED AT 400 WORDS)


Serbia National Poison Control Centre: organization and current activities.
Ministry of Health of the former Federal Republic of Yugoslavia established the National Poison Control Centre in 1995. However, that was only the formally solution since clinical, analytical and experimental services in toxicology had worked independently for at least 40 years. Besides the Headquarters, NPCC has currently 2 main units, the Clinic of Emergency and Clinical Toxicology and Pharmacology and the Institute of Toxicology and Pharmacology. The latter is consisted of Toxicological Information Department, Department of Analytical Toxicology and Department of Experimental Toxicology and Pharmacology. The Mobile Toxicological Chemical Unit is a separate department that is activated from personnel of the NPCC in a case of chemical accidents and/or disasters. Clinical, information and analytical parts of NPCC have a 365-day/24-hour working service. The Clinic of Emergency and Clinical Toxicology and Pharmacology is a place where the intoxicated patients are treated, including those that need the intensive care measures. Toxicological Information Department uses the data from a self-made computer Database for different information purposes. Department of Analytical Toxicology is equipped with a lot of contemporary analytical equipment that is giving the opportunity of identification and quantification of chemicals/metabolites/degradation products in biological material, food, water, air and soil. Basic pharmacological and toxicological research of chemicals and pre-clinical investigations of antidotes are realized in the Department of Experimental Toxicology and Pharmacology. In terms of medical prevention and rational treatment of human poison exposures in Serbia, the current organization of NPCC has so far proven to be effective.