Facile development of biodegradable polymer-based nanotheranostics: Hydrophobic photosensitizers delivery, fluorescence imaging and photodynamic therapy.
Photodynamic therapy (PDT) is reported to be a promising technique to eradicate various cancers. As most of the photosensitizers (PSs) are hydrophobic in nature, thus, the effective delivery of PSs at the targeted site is the main hurdle associated with PDT. Zinc phthalocyanine and Zinc naphthalocyanine are reported as good PSs, however, highly hydrophobic characteristics restrict their use for clinical applications. To circumvent this limitation here we developed the advanced polymer-based nano-delivery system having polyethylene glycol (PEG) coated polymeric core with ~90% PS encapsulation. The PEG coating was responsible for the stabilization of probe in the physiological environment and storage conditions. The developed theranostic probes showed efficient in vitro fluorescence and singlet oxygen quantum yields upon irradiation with 620-750 nm (30 mW/cm2) light. The clathrin-mediated endocytosis (CME) based mechanism of cellular internalization was evaluated. The fluorescence of treated MCF-7 cells showed the ability of the probes as imaging agents. Moreover, up to 65% cell inhibition showed their cytotoxic efficiency. Further, comparatively higher tumor-accumulation of PSs without significant hepato/nephro-toxicity shown in vivo experimentation using breast tumor-bearing female Sprague Dawley (SD) rats suggested the featured passive targeting ability of preparations and clinically safe to be used. The study explored the exceptional delivery system for hydrophobic PSs with commendable theranostic applications.


Thoracolumbar spinal tuberculosis with psoas abscesses treated by one-stage posterior transforaminal lumbar debridement, interbody fusion, posterior instrumentation, and postural drainage.
Retrospective analysis of the clinical efficacy and feasibility of patients with thoracolumbar spinal tuberculosis with psoas abscesses treated by one-stage posterior transforaminal lumbar debridement, interbody fusion, posterior instrumentation, and postural drainage. A total of 18 patients with thoracolumbar tuberculosis (TB), between February 2007 and February 2011, underwent one-stage posterior transforaminal lumbar debridement, interbody fusion, posterior instrumentation, and postural drainage. And the clinical efficacy was evaluated based on surgery duration time, the blood loss, the postural drainage of time, neurological status that was recorded by American Spinal Injury Association (ASIA) Impairment Scale, the fate of bone graft fusion, kyphosis angle, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), which were collected at certain time. The average follow-up period was 34 months (range 18-48 months). 18 patients suffered from seriously neurological deficits pre-operatively, of which 16 patients returned to normal at final follow-up. The surgery duration time was 197 ± 37.9 min, and the blood loss was 815 ± 348.5 ml. The postural drainage of time was 7.2 ± 2.7 days. The psoas abscesses disappeared in all cases, within the time range of 6-9 months (mean 7.4 ± 1.2 months). All patients of the grafted bones were thoroughly fused, with a fusion time ranging from 4 to 12 months (mean 7.8 months). Kyphosis angle was 44.32 ± 7.26° on average pre-operative and returned to 11.72 ± 2.85° at 6 weeks after operation; kyphosis angle was 13.10 ± 2.39° at final follow-up. The values of ESR and CRP were significant declined at 6 weeks post-operative, and returned to normal levels at final follow-up. With standardized anti-TB chemotherapy, thoracolumbar spinal tuberculosis with psoas abscesses could be effectively treated by one-stage posterior transforaminal lumbar debridement, interbody fusion, posterior instrumentation, and postural drainage.


Homokaryon production by electrofusion: a convenient way to produce a large number of viable mammalian fused cells.
A convenient technique to obtain homokaryons is described that provides large amounts of fused mammalian cells. Chinese hamster ovary cells grown in monolayers on a Petri dish are submitted to square wave electric pulses. Viability of cells is observed not to be affected by this electric treatment. The yield of fusion is strongly dependent on the strength of the field (KV/cm range) and on the duration of the pulse (microsecond range). The yield is not improved by accumulation of pulses. Yields up to 80% are obtained and under our experimental conditions 200 000 cells are fused per assay.


A new antimicrobial indoloditerpene from a marine-sourced fungus aspergillus versicolor ZZ761.
A new indoloditerpene (1) and fifteen known compounds (2-16) were isolated from a marine-derived fungus Aspergillus versicolor ZZ761. Structure of the new compound was elucidated as (3 R,9S,12R,13S,17S,18S)-2-carbonyl-3-hydroxylemeniveol based on its HRESIMS data, NMR spectroscopic analyses, the Mosher's method, and ECD calculation. This new indoloditerpene (1) showed antimicrobial activities with MIC values of 20.6 μM against Escherichia coli and 22.8 μM against Candida albicans. Diorcinol (2) and versicolorin B (6) had activities in inhibiting the proliferation of human glioma U87MG and U251 cells with IC50 values of 4.4 and 6.2 μM and 11.3 and 30.5 μM, respectively.


In silico and biochemical analysis of Physcomitrella patens photosynthetic antenna: identification of subunits which evolved upon land adaptation.
In eukaryotes the photosynthetic antenna system is composed of subunits encoded by the light harvesting complex (Lhc) multigene family. These proteins play a key role in photosynthesis and are involved in both light harvesting and photoprotection. The moss Physcomitrella patens is a member of a lineage that diverged from seed plants early after land colonization and therefore by studying this organism, we may gain insight into adaptations to the aerial environment. In this study, we characterized the antenna protein multigene family in Physcomitrella patens, by sequence analysis as well as biochemical and functional investigations. Sequence identification and analysis showed that some antenna polypeptides, such as Lhcb3 and Lhcb6, are present only in land organisms, suggesting they play a role in adaptation to the sub-aerial environment. Our functional analysis which showed that photo-protective mechanisms in Physcomitrella patens are very similar to those in seed plants fits with this hypothesis. In particular, Physcomitrella patens also activates Non Photochemical Quenching upon illumination, consistent with the detection of an ortholog of the PsbS protein. As a further adaptation to terrestrial conditions, the content of Photosystem I low energy absorbing chlorophylls also increased, as demonstrated by differences in Lhca3 and Lhca4 polypeptide sequences, in vitro reconstitution experiments and low temperature fluorescence spectra. This study highlights the role of Lhc family members in environmental adaptation and allowed proteins associated with mechanisms of stress resistance to be identified within this large family.


Electron competition among nitrogen oxides reduction during methanol-utilizing denitrification in wastewater treatment.
Limited availability of carbon sources has been regarded as an important factor leading to N2O accumulation during denitrification in wastewater treatment. By varying the carbon (methanol) loading rate to a methanol utilizing denitrifying culture in the presence of various electron acceptors (nitrate, nitrite, N2O and their combinations), this study quantitatively investigated the electron distribution among different nitrogen oxide reductases during denitrification. The results showed that electron competition occurs under not only carbon limiting but also carbon abundant conditions. The electron distribution among the nitrogen oxide reductases is affected by the carbon loading rate, with a lower fraction of electrons distributed to the N2O reductase with reduced carbon loading rate. N2O accumulation occurs when the electron flux going to nitrite reduction is higher than that going to N2O reduction. The study also showed that, for the culture investigated, the carbon to nitrogen ratio is not a key factor leading to N2O accumulation.


The biological properties of immunoglobulin G and its split products [F(ab')2 and Fab].
Antibodies of the IgG class possess antibacterial, antiviral and toxin neutralizing properties and for this reason are administered prophylactically and therapeutically. In the case of the immunoglobulin preparations commercially available for i.v. application a basic distinction must be made between unsplit immunoglobulins and those antibody preparations obtained by enzymatic digestion, such as F(ab')2 or Fab antibodies. This survey deals with the largely experimental evidence describing the biological properties of these preparations. Administration of antibodies in the presence of the corresponding antigens leads to the formation of immune complexes in the organism. These immune complexes can activate, either directly or indirectly, the cellular and humoral systems which are involved in phagocytosis and the elimination of antigens, in the regulation of the body's own antibody production and in inflammatory reactions. As a result of their inability to interact with Fc receptors, immune complexes with F(ab')2 or F(ab) antibodies appear to be less active in the release of inflammation mediators from leucocytes and thrombocytes than immune complexes with unsplit immunoglobulins. These, on the other hand, can antigen-specifically and non-antigen-specifically suppress the immune system which is not the case for immune complexes with F(ab')2 or Fab antibodies. There are indications that these split products also occur in vivo due to the action of tissue and leucocyte proteases. Unlike Fab preparations, F(ab')2 antibodies have antibacterial and antiviral potencies similar to unsplit immunoglobulins, which is probably due to the ability of F(ab')2 molecules to activate complement, not by the classical but by the alternative pathway. Like Fab preparations, F(ab')2 molecules appear to be superior to unsplit IgG in the elimination of haptens. On account of the relatively long period of time unsplit immunoglobulins remain in the blood, they are well suited for prophylactic treatment and substitution over longer periods. The extent to which indications, obtained predominantly from experimental studies, of a reduced release of inflammation mediators, a lack of immune suppression and a lack of augmentation of IgG catabolism would advocate the use of F(ab')2 split products, especially for therapeutic purposes, can only be ascertained after prospective and comparative studies have been carried out.


Physiological time model for predicting adult emergence of western corn rootworm (Coleoptera: Chrysomelidae) in the Texas High Plains.
Field observations at three locations in the Texas High Plains were used to develop and validate a degree-day phenology model to predict the onset and proportional emergence of adult Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae) adults. Climatic data from the Texas High Plains Potential Evapotranspiration network were used with records of cumulative proportional adult emergence to determine the functional lower developmental temperature, optimum starting date, and the sum of degree-days for phenological events from onset to 99% adult emergence. The model base temperature, 10 degrees C (50 degrees F), corresponds closely to known physiological lower limits for development. The model uses a modified Gompertz equation, y = 96.5 x exp (-(exp(6.0 - 0.00404 x (x - 4.0), where x is cumulative heat (degree-days), to predict y, cumulative proportional emergence expressed as a percentage. The model starts degree-day accumulation on the date of corn, Zea mays L., emergence, and predictions correspond closely to corn phenological stages from tasseling to black layer development. Validation shows the model predicts cumulative proportional adult emergence within a satisfactory interval of 4.5 d. The model is flexible enough to accommodate early planting, late emergence, and the effects of drought and heat stress. The model provides corn producers ample lead time to anticipate and implement adult control practices.


Activation of distinct signal transduction pathways in Trypanosoma cruzi isolates with differential capacity to invade host cells.
Mammalian cell invasion by Trypanosoma cruzi requires the activation of signal transduction pathways that result in a Ca(2+) response both in the parasite and the host cell. By using drugs that interfere with the signalling processes, we investigated if the difference in the ability of T. cruzi isolates to invade host cells was associated with the activation of distinct signalling routes in the parasites. Experiments were performed with metacyclic trypomastigotes, the developmental forms that initiate infection in the mammalian host, using the highly invasive isolate CL and the poorly infective isolate G, which belong to distinct phylogenetic lineages. Treatment of parasites with adenylyl cyclase activator forskolin increased the infectivity of the G but not of the CL isolate towards HeLa cells. On the other hand, a specific protein tyrosine kinase inhibitor genistein reduced by approximately 75% the penetration of CL but not of G isolate into HeLa cells. In the CL but not in the G isolate, protein tyrosine kinase mediated the phosphorylation of a 175kDa protein in a manner inducible by a HeLa cell extract. Upon treatment with the phospholipase C inhibitor U73122, or with drugs such as caffeine, which affects Ca(2+) release from inositol-1,4,5-triphosphate-sensitive stores, or thapsigargin, an inhibitor of intracellular Ca(2+) transport ATPases, the infectivity of the CL but not of the G isolate diminished significantly (P<0.005). In both isolates, a combination of ionomycin plus NH(4)Cl or nigericin released Ca(2+) from acidic vacuoles containing a Ca(2+)/H(+) exchange system. This treatment reduced the infectivity of metacyclic forms of the G but not of the CL isolate. Taken together, these data suggest that, for host cell invasion, distinct signalling pathways are activated in metacyclic trypomastigotes of the two isolates, leading to Ca(2+) release from different intracellular compartments.


Chondroprotective agents: glucosamine and chondroitin.
The near universal finding of the safety of glucosamine and chondroitin combined with some compelling evidence of their efficacy should spur further research into their mechanism of action, optimal dosing, long-term effects on disease modification, and clinical applicability. When recommending a supplement to patients, the clinician should take into account the purity of the ingredients, reputation of the manufacturer, and the molecular weight of chondroitin supplied.


Temperature dependence of the lipid packing in thylakoid membranes studied by time- and spectrally resolved fluorescence of Merocyanine 540.
The lipid packing of thylakoid membranes is an important factor for photosynthetic performance. However, surprisingly little is known about it and it is generally accepted that the bulk thylakoid lipids adopt the liquid-crystalline phase above -30 degrees C and that a phase transition occurs only above 45 degrees C. In order to obtain information on the nature of the lipid microenvironment and its temperature dependence, steady-state and time-resolved fluorescence measurements were performed on the fluorescence probe Merocyanine 540 (MC540) incorporated in isolated spinach thylakoids and in model lipid systems (dipalmitoyl phosphatidylcholine and dioleoyl phosphatidylethanolamine) adopting different phases. It is demonstrated that the degree and way of incorporation differs for most lipid phases--upon selective excitation at 570 nm, the amplitude of the fluorescence component that corresponds to membrane-incorporated MC540 is about 20% in gel-, 60% in rippled gel-, and 90% in liquid-crystalline and inverted hexagonal phase, respectively. For thylakoids, the data reveal hindered incorporation of MC540 (amplitude about 30% at 7 degrees C) and marked spectral heterogeneity at all temperatures. The incorporation of MC540 in thylakoids strongly depends on temperature. Remarkably, above 25 degrees C MC540 becomes almost completely extruded from the lipid environment, indicating major rearrangements in the membrane.


On the nature and specificity of replicating instability in fission yeast.
A strain of fission yeast carrying replicating instability (RI) will segregate mitotically three types of cells: unstable (still RI-carrying) cells, stable identical mutants and stable non-mutants. RI in fission yeast has previously been considered as a specific type of premutational lesion capable of (1) being replicated as such and (2) reverting at an appreciable rate to the normal state as well as changing into a stable mutation. In the present work genetic analysis of a previously studied RI-carrying strain showed this strain to be a diploid, most probably heterozygous for a recessive mutation. It was possible to construct other unstable heterozygous strains segregating predetermined mutants but not to induce RI by UV-irradiation of haploid cells. Thus evidence is presented against the premutational nature of RI in fission yeast.


AIDS and HIV infection: estimates of the magnitude of the problem worldwide in 1985/1986.
This review summarizes observations about the distribution of AIDS and HIV infection throughout the world. The United States has reported the greatest number of cases to the World Health Organization (WHO), but data from many areas are lacking or incomplete, making comparisons between different areas unreliable. Even within the United States, data are difficult to interpret and require careful consideration of the size of the various HIV-risk groups in the population and the degree to which results of studies of selected cohorts within a risk group can be extrapolated to the whole of that population. Outside of the United States, Europe, and Australia, less information is available. Almost every country in South America has reported cases of AIDS, although in most reports the number is small. In Asia, many countries have not yet reported cases or have had only a small number of cases. By the end of 1986, many countries in Africa had not yet reported any AIDS cases to the WHO, even from areas where AIDS is known to occur (i.e., Zaire). However, there is ample evidence from regional studies in Africa that AIDS and HIV infection are a major public health problem. Using admittedly questionable information for estimating the size of the problem worldwide, I project that between two and three million persons worldwide were infected with HIV by 1985/1986. Despite the lack of an effective therapy or vaccine, much can be and is being done to limit the global spread of HIV infection and AIDS.


Serum brain natriuretic peptide and risk of acute kidney injury after cardiac operations in children.
Acute kidney injury (AKI) after pediatric cardiac operations is associated with poor outcomes and is difficult to predict. We conducted a prospective study to evaluate whether preoperative brain natriuretic peptide (BNP) levels predict postoperative AKI among children undergoing cardiac operations. This was a three-center, prospective study (2007-2009) of 277 children undergoing cardiac operations (n = 121, aged <2 years) with available preoperative BNP values. Preoperative BNP was measured and categorized into tertiles. The performance of BNP was evaluated alone and in combination with clinical factors. AKI was defined as doubling of serum creatinine or need for acute dialysis. Postoperative AKI occurred in 165 children (60%), with 118 cases (43%) being mild and 47 cases (17%) severe. Preoperative BNP was not associated with increased risk of mild or severe postoperative AKI and did not significantly improve AKI risk prediction when added to clinical models. Preoperative BNP was, however, associated with several clinical outcomes, including length of stay and mechanical ventilation. The results were similar when the analysis was repeated in the subset of children younger than 2 years of age or when the association of postoperative BNP and AKI was evaluated. Preoperative BNP levels did not predict postoperative AKI in this cohort of children undergoing cardiac operations. Both preoperative and postoperative BNP levels are associated with postoperative outcomes. Clinical Trial Registration at Clinicaltrials.gov as NCT00774137.


An open clinical trial of nifurtimox for arseno-resistant Trypanosoma brucei gambiense sleeping sickness in central Zaire.
Twenty-five patients with arseno-resistant Trypanosoma brucei gambiense sleeping sickness were treated with oral nifurtimox, 12-17 mg/kg/d for 60 d. During treatment, trypanosomes disappeared from the cerebrospinal fluid (CSF) of 7/7 patients; the CSF infections; leucocyte was significantly lower at the end of treatment than before it was begun (pre-nifurtimox: 124.2 (+/- 149.3) per microliter; post-nifurtimox: 11.9 (+/- 12.1) per microliter; P less than 0.001). Nifurtimox was well tolerated, with gastro-intestinal disturbances in 6 patients and a reversible cerebellar syndrome in 2 patients. Among the 19 patients seen at least once at follow-up, 12 (63%) relapsed. The other 7 patients have been followed for 3-18 months, and the CSF remained completely normal in 4 of them. This study confirms that nifurtimox has some activity against T.b. gambiense, but a daily dosage higher than 15 mg/kg/d will be necessary to achieve cure of most patients.


Unleashing the power of innovation promoters for sustainable economic growth: a global perspective.
Achieving Sustainable Development Goals (SDGs) in an era of rapid economic growth poses a significant challenge for policymakers and researchers. This study investigates the interconnected relationships between economic growth, innovation promoters, and sustainable development using data from 102 countries between 2016 and 2022. Employing multiple linear regression (MLR) models, we identify crucial factors influencing sustainable development. Our findings reveal a multifaceted relationship between economic growth and sustainable development, emphasizing the need for tailored development strategies. We highlight the diverse roles played by innovation promoters across various country clusters. We discern patterns of change in sustainable development and innovation performance through a comparative analysis of country clusters over time. These insights carry significant implications for policymakers, underscoring the importance of context-specific approaches to achieve SDGs.


Magnetic resonance evaluation of renal artery stenosis in a swine model: performance of low-dose gadobutrol versus gadoterate meglumine in comparison with digital subtraction intra-arterial catheter angiography.
The aim of this study was to compare low-dose imaging with gadobutrol and gadoterate meglumine (Gd-DOTA) for evaluation of renal artery stenosis with 3-T magnetic resonance angiography (MRA) in a swine model. A total of 12 experimental animals were evaluated using equivalently dosed gadobutrol and Gd-DOTA for time-resolved and static imaging. For time-resolved imaging, the time-resolved imaging with stochastic trajectories (TWIST) technique (temporal footprint, 4.4 seconds) was used; a dose of 1 mL of gadobutrol was injected at 2 mL/s and a dose of 2 mL of Gd-DOTA was injected at both 2 and 4 mL/s. For a separate static acquisition, doses were doubled. The static scans were used for stenosis gradation and the time-resolved scans for comparison of enhancement dynamics, signal-to-noise ratio (SNR), and qualitative assessments. The average magnitude of difference in the stenosis measurements with static gadobutrol scans relative to digital subtraction intra-arterial catheter angiography (mean [SD], 7.4% [5.6%]) was less than with both the 2 mL/s (10.6% [6.2%]) and 4 mL/s (11.5% [7.8%]) Gd-DOTA MRA protocols. On time-resolved scans, peak signal-to-noise ratio was greatest with the gadobutrol protocol (P < 0.05), and the gadobutrol TWIST scan was preferred to the TWIST Gd-DOTA scan in terms of image quality and stenosis visualization in every case for every reader. Low-dose gadobutrol (~0.05 mmoL/kg) contrast-enhanced MRA results in improved accuracy of renal artery stenosis assessments relative to equivalently dosed Gd-DOTA at 3 T.


Older Suicide Decedents: Intent Disclosure, Mental and Physical Health, and Suicide Means.
This study examined: (1) associations of suicide intent disclosure with depressed mood and health problems; (2) age-group differences in those associations; and (3) relationship between disclosure and suicide means among suicide decedents aged ≥50 years (N=46,857). Data came from the National Violent Death Reporting Systems, 2005-2014. Data analysis was conducted in 2017. Chi-square tests were used to compare disclosers and nondisclosers on sociodemographic and precipitating factors and suicide means. Logistic regression analyses were used to examine the research questions. The overall disclosure rate was 23.4%. Logistic regression results showed that both depressed mood (AOR=1.57, 95% CI=1.50, 1.65, p<0.001) and health problems (AOR=1.56, 95% CI=1.48, 1.64, p<0.001) were associated with increased odds of disclosure. Compared with decedents aged 50-59 years, those aged 70-79 years and ≥80 years had greater disclosure odds. When interaction terms of age group X health problems were entered in the model, disclosure odds increased among those with health problems in the groups aged 60-69 years (ratio of AOR=1.19, 95% CI=1.06, 1.34, p=0.003), 70-79 years (ratio of AOR=1.29, 95% CI=1.13, 1.48, p<0.001), and ≥80 years (ratio of AOR=1.41, 95% CI=1.20, 1.66, p<0.001). Compared with other suicide means, both firearm use and hanging/suffocation were associated with lower disclosure odds. The older the decedents were, the more likely they were to have disclosed suicidal intent, and health problems largely explained their higher odds of disclosure. Healthcare providers need better preparation to screen and aid those in need to prevent suicide. Social support system members should also be assisted in identifying warning signs and linking older adults to services.


Subluxation of transscleral sutured posterior chamber intraocular lens (TSIOL).
To evaluate factors related to late-onset transscleral sutured posterior chamber intraocular lens (TSIOL) subluxation. Retrospective observational case series. Analysis of subluxated TSIOLs in seven eyes from seven patients treated between May 1999 and May 2001. Mean age at the time of TSIOL surgery was 33 +/- 6 years. Mean time from TSIOL surgery to its subluxation was 78 +/- 19 months. Initial diagnoses requiring TSIOL surgeries were previous history of trauma and Marfan syndrome. Subluxation of TSIOLs was associated with blunt trauma in three eyes, whereas the other four eyes experienced spontaneous lens dislocation. Subluxation of TSIOL is not uncommon in younger patients with history of trauma or Marfan syndrome.


Development and internal validation of a Neonatal Healthcare-associated infectiOn Prediction score (NeoHoP score) for very low birthweight infants in low-resource settings: a retrospective case-control study.
Early diagnosis of neonatal infection is essential to prevent serious complications and to avoid unnecessary use of antibiotics. The prevalence of healthcare-associated infections (HAIs) among very low birthweight (VLBW; <1500 g) infants is 20%; and the mortality in low-resource settings can be as high as 70%. This study aimed to develop an Infection Prediction Score to diagnose bacterial HAIs. A retrospective cohort of VLBW infants investigated for HAI was randomised into two unmatched cohorts. The first cohort was used for development of the score, and the second cohort was used for the internal validation thereof. Potential predictors included risk factors, clinical features, interventions, and laboratory data. The model was developed based on logistic regression analysis. The study population of 655 VLBW infants with 1116 episodes of clinically suspected HAIs was used to develop the model. The model had five significant variables: capillary refill time >3 s, lethargy, abdominal distention, presence of a central venous catheter in the previous 48 hours and a C reactive protein ≥10 mg/L. The area below the receiver operating characteristic curve was 0.868. A score of ≥2 had a sensitivity of 54.2% and a specificity of 96.4%. A novel Infection Prediction Score for HAIs among VLBW infants may be an important tool for healthcare providers working in low-resource settings but external validation needs to be performed before widespread use can be recommended.


Hot off the Press: SGEM #226. I Want a New Drug-One That Doesn't Cause an Adverse Drug Event.
Adverse drug events (ADEs) are a significant cause of emergency department (ED) visits in North America and are frequently misdiagnosed. Despite evidence supporting improved health care outcomes for ED patients who have a pharmacist-led medication review, EDs do not have sufficient clinical pharmacists to perform medication reviews on all patients. The study reviewed in this article aimed to validate clinical decision rules for use by clinical pharmacists and physicians to prioritize ED patients with ADEs.


Impact of HPV vaccination on HPV infection and cervical related disease burden in real-world settings (HPV-RWS): protocol of a prospective cohort.
Cervical cancer is one of the most common cancers in women and could be prevented by human papilloma virus (HPV) vaccination. Cervarix, the first available HPV vaccine, has been widely administrated to Chinese women, while little was known about its effect on the prevention and control for HPV related diseases in China. The study aims to assess the impact of Cervarix on HPV infection and cervical related diseases in real world. This is a prospective, multi-age birth cohort study to investigate the incidence and continuous status of HPV infection, and relevant cervical diseases by exposure status (with Cervarix vaccination history or without any HPV vaccination history). It is planned to recruit 12,118 eligible women at age of 9 to 45 years from vaccination clinics or hospital outpatient clinics, and then follow up them for three years. The standard questionnaire will be used to collect information such as demographic characteristics, menstruation and obstetrical histories, history of sexual behavior, personal behavior history, history of disease and pathogen infection, medication history, and family history at baseline. After three years, the changes of these behaviors will be investigated again, and other related health status information will be retrieved from the electronic health records during the follow-up period. If available physically and legally, the cervical cancer screening will be performed, including type-specific HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) testing and contingent thinprep cytologic test (TCT) and colposcopy. The free cervical cancer screening will be captured and uploaded timely to the Yinzhou Regional Health Information Platform (YRHIP); therefore, the long-term outcomes of participants will be monitored. This prospective cohort study will assess the impact of HPV vaccine on HPV infection and related cervical diseases in women aged 9-45 years, which makes up for the lack of evidence in Chinese women. The results of this study will provide support for understanding the impact of HPV vaccination in China, and make a contribution to increasing HPV vaccination and cervical cancer screening coverage in China. This study has been retrospectively registered on clinicaltrials.gov (NCT05341284) on April 22, 2022.


Detection of flunixin in equine urine using high-performance liquid chromatography with particle beam and atmospheric pressure ionization mass spectrometry after solid-phase extraction.
A normal-phase HPLC method combined with particle-beam mass spectrometry (PB-MS) was developed for the analysis of non-steroidal anti-inflammatory drugs (NSAIDs). The forty one NSAIDs analysed responded in one or more (electron impact, positive and negative chemical ionisation) modes and highly characteristic spectra were produced. A mixed-mode solid-phase extraction (SPE) method for isolating acidic NSAIDs was developed using the Bond Elut Certify II cartridge. The average recovery was 88.5%. Flunixin, extracted by SPE from urine of a mare to which the meglumine salt had been administered was positively identified by HPLC-PB-MS and HPLC-atmospheric pressure ionization (API) MS methods.


Creating dynamic images of short-lived dopamine fluctuations with lp-ntPET: dopamine movies of cigarette smoking.
We describe experimental and statistical steps for creating dopamine movies of the brain from dynamic PET data. The movies represent minute-to-minute fluctuations of dopamine induced by smoking a cigarette. The smoker is imaged during a natural smoking experience while other possible confounding effects (such as head motion, expectation, novelty, or aversion to smoking repeatedly) are minimized. We present the details of our unique analysis. Conventional methods for PET analysis estimate time-invariant kinetic model parameters which cannot capture short-term fluctuations in neurotransmitter release. Our analysis--yielding a dopamine movie--is based on our work with kinetic models and other decomposition techniques that allow for time-varying parameters. This aspect of the analysis--temporal-variation--is key to our work. Because our model is also linear in parameters, it is practical, computationally, to apply at the voxel level. The analysis technique is comprised of five main steps: pre-processing, modeling, statistical comparison, masking and visualization. Preprocessing is applied to the PET data with a unique 'HYPR' spatial filter that reduces spatial noise but preserves critical temporal information. Modeling identifies the time-varying function that best describes the dopamine effect on 11C-raclopride uptake. The statistical step compares the fit of our (lp-ntPET) model to a conventional model. Masking restricts treatment to those voxels best described by the new model. Visualization maps the dopamine function at each voxel to a color scale and produces a dopamine movie. Interim results and sample dopamine movies of cigarette smoking are presented.


Ultrastructure of mucoepidermoid carcinoma in minor salivary glands.
Three cases of mucoepidermoid carcinoma of minor salivary glands were studied by electron microscopy. Mucus-secreting cells contained numerous mucous globules and bundles of fine cytoplasmic filaments. Another cell type contained a large number of glycogen particles, akin to tumor cells in glycogen-rich adenocarcinoma, and it is postulated that these cells represent the intermediate cells observed by light microscopy. Epidermoid cells contained a moderate amount of tonofilaments and various numbers of organelles. Mucus-secreting and epidermoid cells that surrounded a cystic space exhibited many microvilli. Results of this study support the theory that mucoepidermoid carcinoma develops from salivary gland duct cells with different cellular differentiation potentials and, in general, agree with the conventional grading system of mucoepidermoid carcinoma.


An application of an ecological framework to understand risk factors of PTSD due to prolonged conflict exposure: Israeli and Palestinian adolescents in the line of fire.
Adolescents living in Israel and the Palestinian authority are exposed to political violence. This review examines psychosocial risk factors for posttraumatic stress disorder (PTSD) organized within an ecological framework. Relevant articles were identified through PubMed and PsycINFO. Studies measuring risk and/or protective factors for PTSD in the Palestinian and/or Israeli adolescent populations because of conflict exposure from 1990 to present were included. A total of 20 studies met inclusion criteria. Greater violence exposure, poor economic resources, living in rural compared with urban areas, poor family and peer relations, and poor coping skills were associated with PTSD symptoms. The ecological framework is a useful approach to understanding factors affecting adolescent PTSD. Future research should focus on socioecological levels that have received limited attention. (PsycINFO Database Record


Pulmonary adenocarcinoma metastasis to a dorsal root ganglion: a case report and review of the literature.
The dorsal root ganglion is a rare manifestation of metastatic spread. We report what we believe to be the first case of metastasis of a pulmonary adenocarcinoma to the lumbar dorsal root ganglion. Only four descriptions for different primary tumors spreading to the dorsal root ganglion have been described in the literature so far. A 70-year-old Caucasian woman with a four-month history of left-sided lumbar radiculopathy was admitted to our department under the assumption of a herniated lumbar disc. Her past medical history included a pulmonary adenocarcinoma and invasive ductal breast cancer.Lumbar magnetic resonance imaging revealed a space-occupying mass in her left neuroforamen L3-L4 with compression of her L3 nerve root. Neurinoma was taken into account as a differential diagnosis, although not considered typical. Surgery revealed a metastasis of pulmonary adenocarcinoma to her dorsal root ganglion. Dorsal root ganglion metastases seem to be extremely rare and can mimic primary local nerve sheath tumors. Therefore, they usually present as incidental findings. Resection should be performed strictly under intraoperative monitoring as tumor spread between the nerve fibers is commonly observed. Metastases should be taken into account in spinal nerve tumors involving the dorsal root ganglion, especially in patients harboring known malignant diseases. The low incidence means that no clear treatment advice can be given. Resection is possible under intraoperative monitoring and relieves neurological symptoms.


Paroxysmal atrial fibrillation with and without primary atrial vulnerability. Clinical and electrophysiological differences.
Primary atrial vulnerability defined as induction of repetitive atrial firing by a single atrial extrastimulus cannot always be demonstrated in patients with paroxysmal atrial fibrillation. The authors studied the electrophysiological differences between paroxysmal atrial fibrillation with and without primary atrial vulnerability. In 14 of 31 patients with documented history of atrial fibrillation, single extrastimulation at the high right atrium initiated repetitive atrial firing defined as rapid disorganized atrial activity continuing longer than 1 second. In the 14 patients with vulnerable atrium, the atrial effective and functional refractory were periods significantly shorter and the duration of the local atrial electrogram of the premature beat was longer and was fractionated. The % sinus node recovery time was longer in patients without vulnerability. Nine of the 17 patients without atrial vulnerability had sinus node dysfunction, and 4 of the remaining 8 patients had a repetitive type of atrial automatic tachycardia. In contrast, only 3 (21%) of the 14 patients with vulnerability had sinus node dysfunction, and none showed repetitive atrial tachycardia. The high prevalence of sinus node dysfunction or repetitive type of atrial automatic tachycardia in patients without primary atrial vulnerability suggests that these transient electrophysiological modifications which are not dealt with in the basic conditions may have a role in the enhancement of atrial vulnerability.


Low-grade sulfadoxine-pyrimethamine resistance in Plasmodium falciparum parasites from Lubango, Angola.
Malaria is a major parasitic disease, affecting millions of people in endemic areas. Plasmodium falciparum parasites are responsible for the most severe cases and its resistance to anti-malarial drugs is notorious. This is a possible obstacle to the effectiveness of intermittent preventive treatment (IPT) based on sulfadoxine-pyrimethamine (SP) cures administrated to pregnant women (IPTp) during their pregnancy. As this intervention is recommended in Angola since 2006, it has assessed, in this country, the molecular profiles in P. falciparum dhfr and dhps, two polymorphic genes associated to pyrimethamine and sulfadoxine resistance, respectively. Blood samples from 52 falciparum patients were collected in Lubango, Angola and pfdhfr and pfdhps polymorphisms were analysed using nested-PCR and DNA sequencing. In the pfdhfr gene, the 108N mutation was almost fixed (98 %), followed by 59R (63 %), 51I (46 %), 50R and 164L (2 %, respectively). No 16V/S mutations were found. The most common double mutant genotype was CNRN (59 + 108; 46 %), followed by CICN (51 + 108; 29 %) whereas IRN (51 + 59 + 108; 15 %), CNRNVL (59 + 108 + 164; 2 %) and RICN (50 + 51 + 108; 2 %) triple mutant genotypes were detected. Investigations of the pfdhps gene showed that the 437G mutation was the most prevalent (97 %). Only two and one samples disclosed the 540E (7 %) and the 436A (3 %), respectively. Single mutant SGKAA (437; 86 %) was higher than SGEAA (437 + 540; 7 %) or AGKAA (436 + 437; 3 %) double mutants genotypes. No polymorphism was detected at codons 581G and 613T/S. Combining pfdhfr and pfdhps alleles two triple mutant haplotypes (double mutant in dhfr and single mutant in dhps) were observed: the ACICNVI/SGKAA in 14 (56 %) samples and the ACNRNVI/SGKAA in five (20 %) samples. One quadruple mutant haplotype was detected (ACIRNVI/SGKAA) in six (24 %) P. falciparum samples. No quintuple pfdhfr-pfdhps mutant was noted. pfdhfr and pfdhps gene mutations in isolates from Lubango are suggestive of a low-grade SP resistance and IPT for pregnant women and infant based on SP treatment could be effective. Routine molecular studies targeting polymorphism in these two genes need to be routinely conducted at country level.


Photochemical In Situ Exfoliation of Metal-Organic Frameworks for Enhanced Visible-Light-Driven CO2 Reduction.
Two novel two-dimensional metal-organic frameworks (2D MOFs), 2D-M2 TCPE (M=Co or Ni, TCPE=1,1,2,2-tetra(4-carboxylphenyl)ethylene), which are composed of staggered (4,4)-grid layers based on paddlewheel-shaped dimers, serve as heterogeneous photocatalysts for efficient reduction of CO2 to CO. During the visible-light-driven catalysis, these structures undergo in situ exfoliation to form nanosheets, which exhibit excellent stability and improved catalytic activity. The exfoliated 2D-M2 TCPE nanosheets display a high CO evolution rate of 4174 μmol g-1 h-1 and high selectivity of 97.3 % for M=Co and Ni, and thus are superior to most reported MOFs. The performance differences and photocatalytic mechanisms have been studied with theoretical calculations and photoelectric experiments. This study provides new insight for the controllable synthesis of effective crystalline photocatalysts based on structural and morphological coregulation.


Direct synthesis of β-N-glycosides by the reductive glycosylation of azides with protected and native carbohydrate donors.
A simple and straightforward method for the stereocontrolled synthesis of β-linked N-glycosides uses alkyl and aryl azides as the nitrogen source. The N-glycosides are formed in high yields and with high β selectivities (typically >70% yield, >15:1 β:α selectivity). This approach is also amenable to the synthesis of N-glycosylated amino acids and peptides (see example, Fmoc=9-fluorenylmethoxycarbonyl).


A monoclonal antibody to hemoglobin F.
A monoclonal antibody BMU7-17 which recognizes an antigenic site unique to the cyanogen bromide fragment, CB2 (residues 56 through 133) of the gamma-chain of human hemoglobin has been produced using cell hybridization techniques. The antibody does not crossreact with hemoglobin A, the isolated alpha- or beta-chains, or with hemoglobin of various mammals. Affinity chromatography on Staphylococcal protein A-Sepharose 4B and radial immuno-diffusion revealed the antibody to be of the mouse IgG 1 class. BMU7-17 identifies F cells in adult and in cord blood specimens, as demonstrated by an indirect immunofluorescence assay. The dissociation constant of the antibody as determined using tritiated hemoglobin F with a double antibody radioimmunoassay has a Kd = 1.2 X 10(-9) moles by Scatchard plot analysis.


Murine models of advanced maternal age: a systematic review and meta-analysis.
Animal models have been developed to aid understanding of the increased incidence of adverse pregnancy complications observed in women of advanced maternal age (AMA). This systematic review of murine models of AMA demonstrates consistent effects of decreased litter size and fetal weight; this supports the future use of these models to determine pathophysiological mechanisms and test therapeutic strategies to improve poor pregnancy outcomes in AMA. Advanced maternal age (AMA; ≥35 years of age) is associated with an increased risk of adverse pregnancy outcomes. To explore causes of adverse pregnancy outcomes in AMA, and to test candidate therapies, an increasing number of murine AMA models have been developed. The aim of this study was to systematically review the literature to assess whether murine AMA models demonstrate a reproducible effect on pregnancy outcomes. PubMed, Ovid, Web of Science and Google Scholar were searched. Studies that reported on pregnancy outcomes in AMA mice and rats were included; the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool evaluated the risk of bias. Eleven mouse and six rat studies were included. AMA mice and rats had reduced litter size (standardised mean difference (SMD): -1.59, 95% confidence interval (CI): -1.84, -1.34 for mice; SMD: -1.66, 95% (CI): -2.09, -1.23 for rats) and reduced fetal weight (SMD: -0.87, 95% CI: -1.24, -0.49 for mice; SMD: -1.05, 95% CI: -1.40, -0.69 for rats). Placental weight was increased in AMA mice (SMD: 0.62, 95% CI: 0.16, 1.08). Subgroup analysis indicated that C57Bl/6 mice had less heterogeneity than other, mostly outbred, mouse strains with regards to litter size (C57 strain I2 = 68.2% vs other strain types I2 = 85.7%). The risk of bias was high, mostly due to the lack of methodological detail and unclear reporting of findings. Murine models of AMA demonstrate similar adverse pregnancy outcomes to those observed in large human epidemiological studies. The reproducible phenotypes in AMA murine models allow the exploration of mechanisms underpinning poor pregnancy outcomes and the pursuit of therapeutic interventions.


Purification of nuclei and preparation of nuclear envelopes from skeletal muscle.
The nuclear envelope is a complex membrane-protein system that is notoriously difficult to purify because it has many connections to both nuclear and cytoplasmic components. This difficulty is compounded by the fact that the nature of these connections vary in different cell types, and so methods must be significantly adapted according to the cell type from which nuclear envelopes are being purified. Here we present a detailed method for purification of nuclear envelopes from one of the most intransigent tissues: skeletal muscle. We further note in the procedure how this method differs from that for other tissues. Identification of nuclear envelope-specific proteins is principally encumbered by endoplasmic reticulum contamination; therefore, we also present a method to purify sarcoplasmic reticulum from muscle.


Ideas and technical innovation: a guide for the aligned perforation of vertebral pedicles.
This report presents a guide for aligned perforation of vertebral pedicles. In multi-segment fixation of the spine there are technical problems with the placement of aligned pedicular screws when using rods of a wider diameter. To overcome this problem, a device has been developed to aid the placement of aligned pedicular implants along the longitudinal axis of the spine. The device consists of a track along which flat metal tabs containing orifices slide in both directions. The proximal and distal pedicles are first perforated by the standard technique and Kirschner or Steinman wires are passed through the tabs, fixing the device. The next step is the placement of the tabs in an appropriate position for the perforation of the remaining pedicles. These perforations can be made with drills or probes, according to the preference of the surgeon. After perforation, the Kirschner or Steinman wire is introduced in order to help fixate the device. This procedure is repeated until all pedicles have been perforated. The final steps involve the removal of the wires and of the device, and placement of the pedicular screws.


Retransplantation after single lung transplantation.
Our lung transplant program started in June 1989 with primary grafts including 21 heart-lung, 11 single lung, and 5 bilateral sequential single lung transplantation. Three patients required retransplantation for single lung and 2 patients for heart-lung grafts. The primary cause of death after lung transplantation is chronic graft dysfunction--bronchiolitis obliteran--though other causes, namely acute graft failure, have been mentioned. Retransplantation is considered to be the only treatment option. In experienced centers, the 1- and 5-year survivals are not as good as for other organ transplantations and for retransplantations the outcome is even worse. Our objective herein was to describe factors to be taken into account for retransplantation in our program, including the timing and indication for retransplantation and the presence of comorbidities. In our experience of 11 single lung transplantations, 3 (27.3%) were retransplantations. The 3 patients were 3, 5, and 2 years after primary transplantation. The indications were overexpansion of the remaining lung compressing the new lung in one and bronchiolitis obliterans in the others. One patient with emphysema died in hospital after retransplantation because of acute myocardial infarction. One patient with lymphangioleiomyomatosis (LAM) disease died of lung complication after sudden cardiac arrest at 1.5 years after retransplantation. One patient with idiopathic pulmonary fibrosis is still alive at 5 years after retransplantation. Bronchiolitis obliterans was a common reason for retransplantation among our patients as well as in other reports. Bronchiolitis exists with superimposed infection for years if it is the mild form. However, the clinical setting is progressively worse if it could not be controlled leading to retransplantation. At this stage, progressive deterioration of lung function must be considered because of inadequate therapy for infection. Finally, when there is infection usually both lungs are involved. The decision whether to replace the transplanted lung or the remaining lung is a concern, especially when the donor availability is scarce. In conclusion, lung retransplantation is the only treatment option for severe graft dysfunction, if there is no other therapy that can prolong life. Though bronchiolitis obliterans often is the indication for retransplantation, bronchiolitis itself is the signal of retransplantation.


Excitatory actions of tetrahydro-9-aminoacridine (THA) on hippocampal pyramidal neurons.
The action of tetrahydro-9-aminoacridine (THA) on guinea pig pyramidal neurons was examined using intracellular recording in an in vitro hippocampal slice preparation. THA had a powerful excitatory action on pyramidal neurons, causing depolarization, increased firing, and an increase in input resistance. This excitatory action of THA persisted in atropine and in tetrodotoxin. The estimated reversal potential of this THA effect was near -90 mV. These results indicate that THA has a direct excitatory action on pyramidal neurons independent of its anticholinesterase activity, resulting from blockade of a conductance carried predominantly by potassium ions.


Investigating algae for CO2 capture and accumulation and simultaneous production of biomass for biodiesel production.
Carbon capture and sequestration technologies are used to reduce carbon emissions. Membranes, solvents, and adsorbents are the three major methods of CO2 capture. One of the promising methods is the use of algae to absorb CO2 from flue gases and convert it into biomass. Algae have great potential as renewable fuel sources and CO2 capture using photosynthesis for carbon fixation has also attracted much attention. This paper presents an extensive and in-depth report on the utilization of algae for carbon capture and accumulation. This is done in conjunction with cultivating the algae for the production of biomass for biodiesel production. Different systems are investigated for algae cultivation as well as carbon capture to effectively mitigate carbon emissions. The performance and productivity of these biosystems depend on various conditions including algae type, light sources, nutrients, pH, temperature, and mass transfer. Macroalgae and microalgae species were explored to determine their suitability for carbon capture and sequestration, along with the production of biodiesel. The steps for producing biodiesel were comprehensively reviewed, which are harvesting, dehydrating, oil extraction, oil refining, and transesterification. This technology combines active carbon capture with the potential of biodiesel production.


Including the method of detection for breast cancer in the Surveillance, Epidemiology, and End Results database is long overdue.
Debates about breast cancer screening have continued in part because the Surveillance, Epidemiology, and End Results database, which began in 1974, has never included the method of detection so that it has been impossible to determine the role that early detection has played in the major decline in deaths from breast cancer that we have seen in the US since 1990. Method of detection should be added to the Surveillance, Epidemiology, and End Results database as soon as possible.


[Long-haul intensive care transports by air].
The need for inter-hospital transports over long distances aboard air ambulances or airlines has increased in recent years, both in the civil as well as the military sector. More often severely ill intensive care patients with multiple organ failure and appropriate supportive care (e.g. mechanical ventilation, catecholamines, dialysis, cardiac assist devices) are transported by air. Despite the fact that long-haul intensive care transports by air ambulance and airlines via Patient Transport Compartment (PTC) are considered established modes of transport they always provide a number of challenges. Both modes of transport have distinct logistical and medical advantages and disadvantages. These-as well as the principal risks of an air-bound long-haul intensive care transport -have to be included in the risk assessment and selection of means of transport. Very often long-haul intensive care transports are a combination of air ambulance and scheduled airlines utilizing the PTC.


Roles and significance of chelating agents for potentially toxic elements (PTEs) phytoremediation in soil: A review.
Phytoremediation is a biological remediation technique known for low-cost technology and environmentally friendly approach, which employs plants to extract, stabilise, and transform various compounds, such as potentially toxic elements (PTEs), in the soil or water. Recent developments in utilising chelating agents soil remediation have led to a renewed interest in chelate-induced phytoremediation. This review article summarises the roles of various chelating agents and the mechanisms of chelate-induced phytoremediation. This paper also discusses the recent findings on the impacts of chelating agents on PTEs uptake and plant growth and development in phytoremediation. It was found that the chelating agents have increased the rate of metal absorption and translocation up to 45% from roots to the aboveground plant parts during PTEs phytoremediation. Besides, it was also explored that the plants may experience some phytotoxicity after adding chelating agents to the soil. However, due to the leaching potential of synthetic chelating agents, the use of organic chelants have been explored to be used in PTEs phytoremediation. Finally, this paper also presents comprehensive insights on the significance of using chelating agents through SWOT analysis to discuss the advantages and limitations of chelate-induced phytoremediation.


Pile-Driving Pressure and Particle Velocity at the Seabed: Quantifying Effects on Crustaceans and Groundfish.
We modeled the effects of pile driving on crustaceans, groundfish, and other animals near the seafloor. Three different waves were investigated, including the compressional wave, shear wave, and interface wave. A finite element (FE) technique was employed in and around the pile, whereas a parabolic equation (PE) code was used to predict propagation at long ranges from the pile. Pressure, particle displacement, and particle velocity are presented as a function of range at the seafloor for a shallow-water environment near Rhode Island. We discuss the potential effects on animals near the seafloor.


The effect of different hemostatic agents following dental extraction in patients under oral antithrombotic therapy: a network meta-analysis.
This network meta-analysis was done to thoroughly evaluate the available literature on the use of different hemostatic agents for dental extraction in patients under oral antithrombotic therapy, aiming to identify the agent with the best/worst performance in bleeding control. Considering that such patients have a higher risk of bleeding, choosing the right hemostatic is essential. Twenty-three randomized clinical trials articles were included after completing the literature search. Cyanoacrylate tissue adhesive showed a reduction in the odds of postoperative bleeding events compared with conventional methods (i.e., gauze/cotton pressure, sutures), with a tendency toward a statistical significance (OR 0.03, P = 0.051). Tranexamic acid was the only agent that demonstrated a significantly lower risk of developing postoperative bleeding events (OR 0.27, P = 0.007). Interestingly, chitosan dental dressing and collagen plug had the shortest time to reach hemostasis. However, they ranked last among all hemostatic agents, regarding bleeding events, revealing higher odds than conventional measures. Therefore, it is concluded that the use of cyanoacrylate tissue adhesive and tranexamic acid gives favorable results in reducing postoperative bleeding events following dental extractions. Although chitosan dental dressing and collagen exhibited a faster time to reach hemostasis, they led to a higher occurrence of bleeding events.


Can the Affective Response to Exercise Predict Future Motives and Physical Activity Behavior? A Systematic Review of Published Evidence.
Consistent with hedonic theories of behavior, the affective response to physical activity has been posited as an important determinant of future physical activity; yet, we are unaware of an overview of evidence regarding this relationship. The purpose of this study was to review the published literature regarding whether the affective response to physical activity relates to future physical activity behavior and key motivational constructs. A systematic review following PRISMA guidelines was undertaken. Twenty-four studies met the inclusion criteria. A positive change in the basic affective response during moderate intensity exercise was linked to future physical activity, but postexercise affect had a null relationship. Affective responses during and after exercise had a relatively negligible relationship with intention, mixed results for self-efficacy, and a reliable correlation with affective judgments about future physical activity. The findings support the basic premise of hedonic theory. Practical application studies with a focus on sustained behavioral interventions are warranted.


Sulfonamide-based hydroxamic acids as potent inhibitors of mouse macrophage metalloelastase.
The structural requirements of sulfonamide-based hydroxamic acid 1 for inhibition of macrophage metalloelastase (MME) were investigated. A short aliphatic group at the R2 position together with an aromatic group at the R3 position significantly improved the inhibitory activity. Compounds 32, 34, and 40 were the most potent inhibitors of MME with IC50 values between 5 and 6 nM.


A family with Dowling Degos disease showing features of Kitamura's reticulate acropigmentation.
We report a family showing a combination of features described in the two, rare genodermatoses, Dowling Degos disease and Kitamura's acropigmentatio reticularis.


Neurologic manifestations of Chagas disease.
Chagas disease is endemic in Latin America and has become an emerging problem in developed countries because of international migrations. The protozoan Trypanosoma cruzi is the etiologic agent and the disease is divided into two phases. The acute phase is mostly asymptomatic or presents with unspecific symptoms. Rarely, a severe and often fatal form occurs in immunosuppressed patients or infants, characterized by meningoencephalitis (sometimes including brain tumor-like lesions) and myocarditis. The chronic phase consists of an indeterminate, asymptomatic form followed by digestive, cardiac, or neurologic symptoms in about 30% of infected patients. Autonomous nervous system dysfunction is prominent in chagasic patients and participates in the affliction of the target organs. Stroke, mainly cardioembolic, may occur in the chronic phase, but other stroke etiologies are reported. Embolic sources and inflammation are thought to play a role in stroke mechanisms. Specific treatment for Chagas disease is scarce and preventive measures are needed.


Analysis of Spanish vocational radiographers' education through clinical training and perceptions of core subject teachers: A survey.
This work presents a prospective analysis of the key aspects involved in the Spanish radiographer's perception of the weaknesses of the current educational curriculum in terms of teaching staff's qualifications and composition in the clinical training and core subjects. The goal is to show clinical training and professional's perception of the teaching quality and to characterise the weakness detected within the context of the European radiographer's academic system. The perception of the quality of the training received by the professionals was collected through an anonymous survey. A total of 758 valid responses were received, and were analysed to three hypotheses: the variability of the teachers' qualifications in the core subjects, the variability in terms of internships time carried out by the students, and assessment about teaching quality of the teachers. The results prove there is a huge variability and little academic affinity of the teachers' degrees with the core subjects. On the other hand, the results shows there is a scarcity of clinical training hours in Spain, especially compared to European standards. It was demonstrated that teachers with a specific radiographer degree obtained the best scores. It is mandatory to adjust the criteria for selecting clinical imaging teachers to improve the teaching quality in Spain and increase the clinical training period of the Spanish radiographers to match their European counterparts. Improving the training of Spanish radiographers will contribute to standardising the training quality of the whole European profession.


Weight loss: long-term results in an ambulatory setting.
Maintenance of weight loss is an issue of interest to the dietetic practitioner. A series of 12 weight-loss classes was conducted using the behavioral approach. Mean weight loss of 11.1 lb. in this study compared favorably with weight losses in other studies reported in the literature. Continuous evaluation and updating of the program did not result in greater weight loss nor was it cost-effective. The participants who lost weight during the program tended to maintain weight loss over time. One-third of those participants attended additional weight-loss programs.


Beneficial effect of low-dose mianserin on fluvoxamine-induced akathisia in an obsessive-compulsive patient.
Extrapyramidal side effects induced by some selective serotonin reuptake inhibitors (SSRIs), i.e. fluoxetine and sertraline, have been previously reported in patients with depression and obsessive-compulsive disorder (OCD). However, the occurrence and management of akathisia induced by fluvoxamine have not been described. In the presented case fluvoxamine-induced akathisia in an OCD patient was partially resistant to the anticholinergic agent biperiden, and was successfully treated with the 5-HT2A/5-HT2C antagonist mianserin. Mianserin (15 mg/day at 21.00 h) was discontinued and then reinstituted (off-on-off-on design). Biperiden was transiently effective in the acute akathisia, while the more persistent akathisia was alleviated by mianserin. Discontinuation of mianserin resulted in recurrence of akathisia, while full amelioration of the symptoms of akathisia was noted when mianserin was reinstituted. No aggravation of OCD symptoms was noted during mianserin administration.


The relationship between length of incubation, bacterial growth and tuberculin yield of a strain of Mycobacterium tuberculosis.
The relationship was studied between length of incubation in a liquid synthetic medium, amount of bacterial growth, pH of the culture filtrate and tuberculin yield of a single strain, DT, of Mycobacterium tuberculosis. No sinple relationship was found between the total crop of bacteria and the tuberculoprotein content of the culture filtrate. On the other hand, protein release and the pH of the culture filtrate were closely related. In each of two trials the bacterial crop increased rapidly during the early period of incubation, although maximum growth was not reached until 9 and 13 weeks respectively. The pH of the culture filtrate reached its maximum at a value of more than 9-0 after 5 weeks incubation and then fell until the 10th week; a second rise occurred until the 13th week when the pH dropped again and levelled off slightly on the alkaline side of neutrality. The rate of increase in tuberculin yield was most rapid during the first 7 weeks of incubation. After this, the rate of increase slowed down but the yield was still rising after 18 weeks. It is concluded that for the large-scale production of mammalian tuberculin by the method used in these trials, it is profitable to incubate production cultures for 14 weeks or longer.


Reaction of fluorogenic reagents with proteins I. Mass spectrometric characterization of the reaction with 3-(2-furoyl)quinoline-2-carboxaldehyde, Chromeo P465, and Chromeo P503.
3-(2-Furoyl)quinoline-2-carboxaldehyde (FQ), Chromeo P465, and Chromeo P503 are weakly fluorescent reagents that react with primary amines to produce fluorescent products. We studied the reaction of these reagents with alpha-lactalbumin by mass spectrometry. The reaction generated a set of products by the addition of one or more labels to the protein. At room temperature, the reaction was an order of magnitude faster with the Chromeo reagents than with FQ; however, the steady-state labeling efficiency was a factor of two higher for FQ compared with the Chromeo reagents. The relative abundance of the products with FQ usually followed a binomial distribution, which suggests that the labeling sites were uniformly accessible to this reagent. In contrast, the distribution of reaction products with the Chromeo reagents did not follow a binomial distribution for reactions performed in the absence of sodium dodecyl sulfate (SDS); it appears that the protein labeled with the Chromeo reagents refolded into a relatively stable secondary structure that hid some reactive sites. The reaction with the Chromeo reagent did follow the binomial distribution if the protein underwent treatment with 1% SDS at 95 degrees C for 5 min, which apparently disrupts the protein's secondary structure and allowed uniform access to all labeling sites. Chromeo 503 labeled seven of the 13 primary amines in denatured alpha-lactalbumin.


Functional changes of the gustatory organ caused by local radiation exposure during radiotherapy of the head-and-neck region.
The aim of this prospective study was to investigate how often and at which dose levels gustatory disturbances appear during radiotherapy of the tongue and to which extent permanent gustatory deficiencies occur. The study included 44 patients treated by definitive irradiation for malignant head-and-neck tumors. In 22 patients the posterior two thirds of the tongue (group 1), and in the other 22 patients the entire tongue (group 2) were exposed to radiation. The control group comprised 30 patients with non-small cell lung cancer receiving definitive radiation therapy (group 3). The dose distribution in the tongue area was calculated using CT-based three-dimensional planning. Before, during and after irradiation the gustatory function was determined by means of gustometry and correlated with the corresponding results of enoral inspection and the patients' subjective statements on gustatory function. The gustatory ability of the control group was not affected, whereas patients in the locally irradiated groups in parallel with enoral mucositis suffered from loss of gustatory function after a total dose of 20 Gy with a maximum between 40 and 60 Gy. Supportive measures had little influence on acute side effects. The gustatory disturbances regressed within 8 weeks after radiotherapy in patients with partial-tongue irradiation and almost completely after 6 months in patients with entire-tongue irradiation. The severity of gustatory disturbances and the longer recovery time in patients with entire-tongue irradiation suggest an influence of the volume exposed. Therefore, reduction of the highly exposed tongue volume by intensity-modulated radiotherapy opens up possibilities for a reduction of this undesirable side effect.


Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection.
The SARS-CoV-2 pandemic had stimulated the emergence of numerous publications on the α1-proteinase inhibitor (α1-PI, α1-antitrypsin), especially when it was found that the regions of high mortality corresponded to the regions with deficient α1-PI alleles. By analogy with the data obtained in the last century, when the first cause of the genetic deficiency of α1-antitrypsin leading to elastase activation in pulmonary emphysema was proven, it can be supposed that proteolysis hyperactivation in COVID-19 may be associated with the impaired functions of α1-PI. The purpose of this review was to systematize the scientific data and critical directions for translational studies on the role of α1-PI in SARS-CoV-2-induced proteolysis hyperactivation as a diagnostic marker and a therapeutic target. This review describes the proteinase-dependent stages of viral infection: the reception and penetration of the virus into a cell and the imbalance of the plasma aldosterone-angiotensin-renin, kinin, and blood clotting systems. The role of ACE2, TMPRSS, ADAM17, furin, cathepsins, trypsin- and elastase-like serine proteinases in the virus tropism, the activation of proteolytic cascades in blood, and the COVID-19-dependent complications is considered. The scientific reports on α1-PI involvement in the SARS-CoV-2-induced inflammation, the relationship with the severity of infection and comorbidities were analyzed. Particular attention is paid to the acquired α1-PI deficiency in assessing the state of patients with proteolysis overactivation and chronic non-inflammatory diseases, which are accompanied by the risk factors for comorbidity progression and the long-term consequences of COVID-19. Essential data on the search and application of protease inhibitor drugs in the therapy for bronchopulmonary and cardiovascular pathologies were analyzed. The evidence of antiviral, anti-inflammatory, anticoagulant, and anti-apoptotic effects of α1-PI, as well as the prominent data and prospects for its application as a targeted drug in the SARS-CoV-2 acquired pneumonia and related disorders, are presented.


Molecular cloning, sequence analysis, in vitro expression, and immunoprecipitation of the major inner capsid protein of the IDIR strain of group B rotavirus (GBR).
The sixth genomic segment of the infectious diarrhea of infant rats (IDIR) strain of group B rotavirus (GBR) was cloned from double-stranded RNA purified from infected rat feces. Sequence comparison with group A rotaviruses (GAR) and the human ADRV strain of GBR indicated that IDIR gene 6 encoded the major inner capsid protein. The nucleic acid sequences of the two GBR genes were 72.9% conserved, and 83.4% of the amino acids were identical. Sequence substitutions between IDIR and ADRV were more numerous than reported for heterologous GAR strains, indicating that the two GBR strains may have diverged from one another over a longer period of time. Despite the sequence heterogeneity exhibited by the major inner capsid proteins of ADRV and IDIR, hydrophilicity plots of the two gene products were nearly indistinguishable. The GBR hydrophilicity plots displayed little similarity with those of rotavirus groups A or C, indicating substantial differences in the structures of those major inner capsid proteins. In vitro transcription and translation of IDIR gene 6 yielded a polypeptide product consistent in size with that predicted from the deduced amino acid sequence and the virion major inner capsid protein. The IDIR 6 polypeptide was immunoprecipitated by antisera directed against IDIR as well as antisera directed against ADRV and a heterologous bovine strain of GBR. No immunoprecipitation was observed with control sera or antisera directed against GAR. These results confirmed that group-specific epitopes were displayed by the major inner capsid protein encoded by IDIR gene 6. Reactivity with heterologous GBR antisera also indicated that the IDIR gene 6 product may prove useful as a standard reagent in immunoassays for the detection of GBR.


Neurophysiological markers of cognitive deficits and recovery in concussed adolescents.
The present study sought to determine: 1) whether concussed adolescents exhibited deficits in neurocognitive functioning as reflected by neurophysiological alterations; 2) if neurophysiological alterations could be linked to supplementary data such as the number of previous concussions and days since injury; and 3) if deficits in psychological health and behavioural tests increased during diagnosis duration. Twenty-six concussed adolescents were compared to twenty-eight healthy controls with no prior concussions. Self-report inventories evaluated depressive and concussive symptomatology, while behavioral tests evaluated cognitive ability qualitatively. To assess neurophysiological markers of cognitive function, two separate auditory oddball tasks were employed: 1) an active oddball task measuring executive control and attention as reflected by the N2b and P300, respectively; and 2) a passive oddball task assessing the early, automatic pre-conscious awareness processes as reflected by the MMN. Concussed adolescents displayed delayed N2b and attenuated P300 responses relative to controls; showed elevated levels of depressive and concussive symptomatology; scored average-to- low-average in behavioral tests; and exhibited N2b response latencies that correlated with number of days since injury. These findings demonstrate that concussed adolescents exhibit clear deficiencies in neurocognitive function, and that N2b response latency may be a marker of concussion recovery.


A prospective, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of SNZ TriBac, a three-strain Bacillus probiotic blend for undiagnosed gastrointestinal discomfort.
This prospective, randomized, double-blind, placebo-controlled, parallel-group study aimed to determine the efficacy and safety of a multistrain (Bacillus coagulans [SNZ 1969], Bacillus clausii [SNZ 1971], and Bacillus subtilis [SNZ 1972]) probiotic blend (SNZ TriBac) in managing symptoms of gastrointestinal (GI) discomfort in the absence of specific pathologies. Sixty adults with symptoms of GI discomfort were enrolled (mean age, 34.89 ± 9.95 years) and randomized to receive either SNZ TriBac or placebo. Changes from baseline in Severity of Dyspepsia Assessment (SODA), Gastrointestinal Symptom Rating Scale (GSRS), and Quality of Life (QoL) scales over the course of product use were determined at baseline and on days 30 and 37 as study outcomes. On day 30, significant improvement with SNZ TriBac was noted in SODA burping/belching (P = 0.025), bloating (P = 0.048), sour taste (P = 0.025), and total (P = 0.007) scores as well as pain (P = 0.003), non-pain (P = 0.04), and satisfaction (P = 0.03) subscores. Significant improvement with SNZ TriBac was also observed in SODA burping/belching (P = 0.011), sour taste (P = 0.011), and total SODA scores (P < 0.001), and in SODA pain (P = 0.005), non-pain (P = 0.06), and satisfaction (P = 0.004) subscores on day 37. No adverse events were reported. Significant improvement in final SODA scores and subscores with SNZ TriBac versus placebo indicates improvement in several symptoms of gastrointestinal discomfort. This multistrain probiotic blend was well tolerated and could be an effective option for treatment of GI discomfort. Clinical Trials Registry of India (CTRI/2018/05/014071).


α-amanitin induces autophagy through AMPK-mTOR-ULK1 signaling pathway in hepatocytes.
Amanitin poisoning is one of the most life-threatening mushroom poisonings. α-Amanitin plays a key role in Amanita phalloides intoxication. α-Amanitin shows toxic effects on the liver. However, the mechanism by which α-amanitin induces liver injury has not been elucidated. Autophagy plays a crucial role in maintaining cellular homeostasis and is closely related to the occurrence of a variety of diseases. Studies have shown that autophagy may play an important role in the process of α-amanitin-induced liver injury. However, the mechanism of α-amanitin-induced autophagy remains unclear. Thus, this study aimed to explore the mechanisms of α-amanitin in inducing hepatotoxicity in Sprague Dawley (SD) rats and the normal human liver cell line L02 cells. The SD rats and L02 cells exposed to α-amanitin were observed to determine whether α-amanitin could induce the autophagy of rat liver and L02 cells. The regulatory relationship between autophagy and the AMPK-mTOR-ULK pathway by exposing the autophagy agonist (rapamycin (RAPA)), autophagy inhibitor (3-methylademine (3-MA)), and AMPK inhibitor (compound C) was also explored. Autophagy-related proteins and AMPK-mTOR-ULK pathway-related proteins were detected using Western blot. The results of the study indicated that exposure to different concentrations of α-amanitin led to morphological changes in liver cells and significantly elevated levels of ALT and AST in the serum of SD rats. Additionally, the expression levels of LC3-II, Beclin-1, ATG5, ATG7, AMPK, p-AMPK, mTOR, p-mTOR, and ULK1 were significantly increased in the rat liver. And we found that L02 cells exposed to 0.5 μM α-amanitin for 6 h significantly induced autophagy and activated the AMPK-mTOR-ULK1 pathway. Pretreated with RAPA, 3-MA, and compound C for 1 h, the expression levels of autophagy-related proteins and AMPK-mTOR-ULK pathway-related proteins significantly changed. Our results indicates that autophagy and the AMPK-mTOR-ULK pathway are involved in the process of α-amanitin-induced liver injury. This study may foster the identification of actionable therapeutic targets for A. phalloides intoxication.


Lymphocytic pleural effusion in acute melioidosis.
An endemic outbreak of melioidosis developed in southern Taiwan following a flood caused by a typhoon in July 2005. A total of 27 patients were diagnosed with the acute and indigenous form of pulmonary melioidosis. Parapneumonic pleural effusions were noted on chest X-rays in six patients. Thoracentesis was done in three patients and all revealed lymphocyte predominance in differential cell count. Burkholderia pseudomallei was isolated in the pleural effusion in one of them. All three patients survived after antibiotic treatment. Lymphocytic pleural effusion is generally seen in tuberculosis or malignancy. However, our findings suggest that melioidosis should be considered in the differential diagnosis of lymphocytic pleural effusion.


A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway.
The pluripotency factor Lin28 blocks the expression of let-7 microRNAs in undifferentiated cells during development, and functions as an oncogene in a subset of cancers. Lin28 binds to let-7 precursor (pre-let-7) RNAs and recruits 3' terminal uridylyl transferases to selectively inhibit let-7 biogenesis. Uridylated pre-let-7 is refractory to processing by Dicer, and is rapidly degraded by an unknown RNase. Here we identify Dis3l2 as the 3'-5' exonuclease responsible for the decay of uridylated pre-let-7 in mouse embryonic stem cells. Biochemical reconstitution assays show that 3' oligouridylation stimulates Dis3l2 activity in vitro, and knockdown of Dis3l2 in mouse embryonic stem cells leads to the stabilization of pre-let-7. Our study establishes 3' oligouridylation as an RNA decay signal for Dis3l2, and identifies the first physiological RNA substrate of this new exonuclease, which is mutated in the Perlman syndrome of fetal overgrowth and causes a predisposition to Wilms' tumour development.


Patterns of metastatic spread following resection of extremity soft-tissue sarcomas and strategies for treatment.
This study examines recurrence patterns in 255 patients with soft-tissue sarcoma treated with preoperative chemotherapy and radiation, followed by limb-sparing surgery. Eighty-five patients developed metastatic disease: 13 had isolated local recurrence, 43 had isolated pulmonary metastases, 11 had metastases to lung and elsewhere, and 18 had metastases to multiple sites. Of the patients with isolated pulmonary metastases, 19/43 had resection of the metastases, and 9 are disease free. All 13 patients with local recurrences had resection of the recurrence, and 9 remain disease-free. Patients with multiple sites of recurrence had a 2-year survival of less than 10%. Resection of metastases is beneficial to a small number of patients who develop metastatic disease.


Foot-and-mouth disease virus 5'-terminal S fragment is required for replication and modulation of the innate immune response in host cells.
The S fragment of the FMDV 5' UTR is predicted to fold into a long stem-loop structure and it has been implicated in virus-host protein interactions. In this study, we report the minimal S fragment sequence required for virus viability and show a direct correlation between the extent of the S fragment deletion mutations and attenuated phenotypes. Furthermore, we provide novel insight into the role of the S fragment in modulating the host innate immune response. Importantly, in an FMDV mouse model system, all animals survive the inoculation with the live A24 FMDV-S4 mutant, containing a 164 nucleotide deletion in the upper S fragment loop, at a dose 1000 higher than the one causing lethality by parental A24 FMDV, indicating that the A24 FMDV-S4 virus is highly attenuated in vivo. Additionally, mice exposed to high doses of live A24 FMDV-S4 virus are fully protected when challenged with parental A24 FMDV virus.


Blast tattoos resulting from black powder firearms.
Blast tattoos occur when fragments of gunpowder are propelled into the skin during a firearm discharge. This unusual type of injury is often associated with accidents involving replica firearms. Some of the more superficially embedded powder fragments may be removed with dermabrasion; however, deeper fragments may cause permanent tattooing. Blast injuries to the face also have the potential of causing permanent eye injury.


Distinct cellular immune profiles in lung adenocarcinoma manifesting as pure ground glass opacity versus solid nodules.
Ground glass opacity featured lung adenocarcinomas (GGO-LUAD) display more indolent biological behavior than solid nodule featured lung adenocarcinomas (SN-LUAD) and have an excellent prognosis. However, the cellular immune characteristics of GGO-LUAD remain poorly understood. Immunohistochemistry technique was performed to stain related immune markers (CD8, CD103, CD20, CD138, CD4, FOXP3, CD68, CD163, PD-1 and PD-L1) and TGF-β from 15 patients with pure GGO-LUAD and 15 patients with SN-LUAD tissue sections (Paired cohort), and then, the related markers with significant differences were verified on 10 patients (Verified cohort) with both pure GGO-LUAD and SN-LUAD. For localization analysis of CD68 + tumor-associated macrophages (TAMs) and FOXP3 + Terg cells in tumor areas, pure GGO-LUAD and SN-LUAD were also stained for simultaneous detection of pan-CK, CD68 and FOXP3 by multiplex immunofluorescence. In the Paired cohort, compared with SN-LUAD, only the infiltration of TAMs and Treg cells was significantly lower in GGO-LUAD. The infiltration of the remaining immune cells including CD8 + T cells, CD4 + T cells, CD103 + T cells, CD20 + B cells and CD138 + Plasma cells in GGO-LUAD, although relatively low, was not significantly different. Meanwhile, the expression of TGF-β was significantly higher in SN-LUAD. And the above results have also been confirmed in the Verified cohort. Moreover, there was no significantly difference in PD-L1 expression in GGO-LUAD compared to SN-LUAD both in the Paired cohort and Verified cohort. GGO-LUAD demonstrates an overall less active immune landscape as compared with SN-LUAD. TAMs and TGF-β may play an important role in the progression of GGO-LUAD. More importantly, PD-L1 expression in GGO-LUAD is comparable to that in SN-LUAD, indicating that there may be other reasons for the insensitivity of GGO-LUAD to immunotherapy.


Dietary pectin caused great changes in bile acid profiles of Pelteobagrus fulvidraco.
To reveal the impact of dietary fiber (DF) on the bile acid (BA) profiles of fish, yellow catfish (Pelteobagrus fulvidraco) were fed a diet containing 300 g kg-1 dextrin (CON diet, control) or pectin (a type of soluble DF, PEC diet) for 7 days, and then the BA profiles were analyzed by UHPLC-MS/MS. A total of 26 individuals of BAs were detected in the fish body, with 8, 10, 14, and 22 individuals of BAs detected in the liver, serum, bile, and hindgut digesta, respectively. The conjugated BAs (CBAs) of fish were dominated by taurine CBAs (TCBAs). The concentrations of free BAs (FBAs) and the value of FBAs/CBAs in the bile of fish fed the PEC diet were nearly 5 and 7 times higher, respectively than those in fish fed the CON diet. The value of glycine CBAs/TCBAs in the liver, serum and bile of fish fed the PEC diet was significantly lower, and in the hindgut digesta was higher than that of fish fed the CON diet (P < 0.05). These results suggested that dietary pectin greatly changed the BA profiles of Pelteobagrus fulvidraco, attributed to inhibition of reabsorption of BAs. Therefore, attention should be paid to the impact on BA homeostasis when replacing fishmeal with DF-rich plant ingredients in the fish diet.


The effects of seed weight on growth and competitive ability of Rumex acetosella from two successional old-fields.
The effects of seed size on growth, biomass allocation and competitive ability of Rumex acetosella plants grown either individually or in competition were studied in two populations (6 months and 15 years old respectively) sampled from a postcultivation successional gradient. For plants grown individually there were highly significant effects of seed weight on growth after 43 days, with a higher relative growth rate (RGR) observed for plants raised from heavier seeds. However at the end of the experiment, seedlings developed from lighter seeds had a RGR 2 times greater than those from heavier seeds. Final biomass of the two types was not significantly different after 73 days of growth. When plants were grown individually, there were only slight differences between populations, but when grown in monocultures of 4 plants per pot, plants from the old population had higher root and leaf biomass per pot whereas those from the young population had a higher reproductive effort per pot. This suggests that a trade-off between allocation to sexual and vegetative reproduction occurs over successional time. In mixtures of light and heavy seeds, plants from light seeds were shorter, had fewer leaves and lower biomass than plants from heavy seeds, which were also taller and produced more dry matter than plants grown from heavy seeds in monoculture. The significant effects of seed weight and population on biomass parameters persisted unit the end of the experiment. Seedlings from heavy seeds were strong competitors: those from the young population grew better in the presence of neighbors than in monoculture and those from the late successional population suppressed the more the growth of their partners. Seedlings from light seeds were subordinate competitors. These results suggest that seedlings from seeds of different sizes benefit from contrasting ecological conditions and that selection acts on reproductive output along successional gradients.


The endocannabinoid system in vertebrate male reproduction: a comparative overview.
Prevailing studies emphasize on endocannabinoid activity in brain. However, sporadic evidences hint that endocannabinoid system controls male reproduction ranging from invertebrates to vertebrates. Although N-arachidonoylethanolamine is described in rat testis, its activity is still poorly known. Type-1 cannabinoid receptor and fatty acid amide hydrolase are particularly expressed in elongating spermatids and spermatozoa suggesting that endocannabinoids affect spermiogenesis and sperm physiology. Aim of this paper is to provide an analysis of the information available in vertebrates on male germ cell progression and sperm maturation mediated by the endocannabinoid system.


Penetration of DGAVP (Org 5667) across the blood-brain barrier in human subjects.
To assess the penetration of desglycinamide-arginine-vasopressin (DGAVP, Org 5667) to the central nervous system, levels of DGAVP were measured in the lumbar CSF after peripheral administration. DGAVP (2 mg) was administered intranasally to 37 patients and CSF samples were collected from these patients 5 to 240 minutes later. Detectable levels of DGAVP in CSF could be found 5 minutes after administration, but levels declined rapidly during the next 90 minutes. The DGAVP levels in CSF correlated with plasma levels of DGAVP (r=0.586, p less than 0.001). According to these results, DGAVP may gain access to the central nervous system and may induce central effects.


Approach to the patient with suspected radiculopathy.
Radiculopathy is a common neurologic disorder. Electrodiagnosis can provide a physiologic assessment of the localization, degree of axon loss, severity, and chronicity of the intraspinal canal lesion, and distinguish it from other neuromuscular disorders. This article reviews electrodiagnostic aspects related to evaluating patients with suspected radiculopathies.


Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction.
T cells become dysfunctional when they encounter self antigens or are exposed to chronic infection or to the tumour microenvironment1. The function of T cells is tightly regulated by a combinational co-stimulatory signal, and dominance of negative co-stimulation results in T cell dysfunction2. However, the molecular mechanisms that underlie this dysfunction remain unclear. Here, using an in vitro T cell tolerance induction system in mice, we characterize genome-wide epigenetic and gene expression features in tolerant T cells, and show that they are distinct from effector and regulatory T cells. Notably, the transcription factor NR4A1 is stably expressed at high levels in tolerant T cells. Overexpression of NR4A1 inhibits effector T cell differentiation, whereas deletion of NR4A1 overcomes T cell tolerance and exaggerates effector function, as well as enhancing immunity against tumour and chronic virus. Mechanistically, NR4A1 is preferentially recruited to binding sites of the transcription factor AP-1, where it represses effector-gene expression by inhibiting AP-1 function. NR4A1 binding also promotes acetylation of histone 3 at lysine 27 (H3K27ac), leading to activation of tolerance-related genes. This study thus identifies NR4A1 as a key general regulator in the induction of T cell dysfunction, and a potential target for tumour immunotherapy.


Application of Pb-Fe spinel-activated carbon for phenol removal from aqueous solutions: fixed-bed adsorption studies.
Fixed-bed studies for phenol uptake from water were carried out using a novel Pb-Fe spinel-activated carbon adsorbent. A characterization phase including TGA, FTIR, SEM, and BET analyses was performed for the developed active carbon. In column studies, the influence of initial phenol concentration, column bed height, and the solution flow rate was investigated at natural pH. Adsorption of phenol onto Pb-Fe spinel-activated carbon composite and pristine activated carbon was analyzed in the form of breakthrough curves. Under optimum conditions, the maximum adsorption capacities for the magnetic active carbon composite and pristine activated carbon were found to be 113.95 and 102.61 mg/g, respectively. Results indicated that the adsorption capacity of adsorbent for all examined conditions was higher than that obtained for unmodified activated carbon because the composite contains additional metal hydroxides compared with the pristine activated carbon. The Yoon and Nelson, Thomas, and instantaneous local equilibrium (ILE) models were used to explain column data collected under different operating conditions. Finally, the results of the continuous adsorption process were explained successfully using the Yoon-Nelson and Thomas models. Thus, the phenol adsorption on Pb-Fe@MAC was a feasible operation to be performed in fixed-bed mode.


The distribution of consumption model of prevention of alcohol problems. A critical assessment.
The conceptual framework and empirical basis of the distribution model are examined, and it is concluded that a more satisfactory model is required.


Tempo discrimination of musical patterns: effects due to pitch and rhythmic structure.
The purpose of this research was to investigate a set of factors that may influence the perceived rate of an auditory event. In a paired-comparison task, subjects were presented with a set of music-like patterns that differed in their relative number of contour changes and in the magnitude of pitch skips (Experiment 1) as well as in the compatibility of rhythmic accent structure with the arrangement of pitch relations (Experiment 2) Results indicated that, relative to their standard referents, comparison melodies were judged to unfold more slowly when they displayed more changes in pitch direction, greater pitch distances, and an incompatible rhythmic accent structure. These findings are suggested to stem from an imputed velocity hypothesis, in which people overgeneralize certain invariant relations that typically occur between melodic and temporal accent structure within Western music.


Occurrence of methicillin-resistant Staphylococcus aureus in surface waters near industrial hog operation spray fields.
Industrial hog operations (IHOs) have been identified as a source of antibiotic-resistant Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). However, few studies have investigated the presence of antibiotic-resistant S. aureus in the environment near IHOs, specifically surface waters proximal to spray fields where IHO liquid lagoon waste is sprayed. Surface water samples (n=179) were collected over the course of approximately one year from nine locations in southeastern North Carolina and analyzed for the presence of presumptive MRSA using CHROMagar MRSA media. Culture-based, biochemical, and molecular tests, as well as matrix-assisted laser desorption/ionization-time of flight mass spectrometry were used to confirm that isolates that grew on CHROMagar MRSA media were S. aureus. Confirmed S. aureus isolates were then tested for susceptibility to 16 antibiotics and screened for molecular markers of MRSA (mecA, mecC) and livestock adaptation (absence of scn). A total of 12 confirmed MRSA were detected in 9 distinct water samples. Nine of 12 MRSA isolates were also multidrug-resistant (MDRSA [i.e., resistant to ≥3 antibiotic classes]). All MRSA were scn-positive and most (11/12) belonged to a staphylococcal protein A (spa) type t008, which is commonly associated with humans. Additionally, 12 confirmed S. aureus that were methicillin-susceptible (MSSA) were recovered, 7 of which belonged to spa type t021 and were scn-negative (a marker of livestock-adaptation). This study demonstrated the presence of MSSA, MRSA, and MDRSA in surface waters adjacent to IHO lagoon waste spray fields in southeastern North Carolina. To our knowledge, this is the first report of waterborne S. aureus from surface waters proximal to IHOs.


An assessment of a short-term tumour chemosensitivity assay in chronic lymphocytic leukaemia.
A 4-day tumour sensitivity assay of potential use in predicting tumour response to cytotoxic drugs has been investigated in patients with chronic lymphocytic leukaemia. The method comprised isolation of white cells from peripheral blood, drug exposure and incubation for 4 days. Drug-induced tumour cell kill was assessed by differential staining of dead and live cells such that the latter could be morphologically identified, with subsequent calculation of tumour cell viability. Concentrations of drug for use in the assay were chosen for chlorambucil (2 micrograms ml-1), 4-hydroperoxy-cyclophosphamide (2 micrograms ml-1)--which was used in vitro in place of cyclophosphamide--prednisolone (0.5 microgram ml-1) and vincristine (0.1 microgram ml-1), to give a scatter of values which was in good agreement with clinical expectations. In 21 cases where the in vitro result could be compared with the in vivo response, there were 4 true positive comparisons (sensitive in vitro, sensitive in vivo), 15 true negative comparisons (resistant both in vitro and in vivo) and 2 false positive comparisons (sensitive in vitro, resistant in vivo). A result was obtained in 86% (65/76) of samples received. The assay appears to show considerable promise as a tumour chemosensitivity test and warrants wider investigation, including prospective in vivo/in vitro correlations that could be based on the results presented here.