Criteria for in vitro susceptibility testing of cefotetan. Correlations with clinical and bacteriologic responses.
Standardized in vitro susceptibility testing criteria and quality-control guidelines for cefotetan have been well documented in the scientific literature. Cefotetan and cefoxitin differ in their in vitro spectrums of activity and cannot be used interchangeably for in vitro tests. In vitro susceptibility information failed to correlate with clinical or bacteriologic responses of treated patients when 314 anaerobic bacteria from 145 patients were evaluated. All cefotetan-resistant anaerobic bacteria were eradicated by cefotetan therapy, and 93 percent of patients with resistant strains were clinically curved. Most members of the Bacteroides distasonis-ovatus-thetaiotaomicron group of pathogens were resistant in vitro, but only one strain persisted after cefotetan therapy for a 96.6 percent cure rate. There was better correlation when 2,336 aerobic bacteria from 1,630 infected body sites were considered. Microorganisms susceptible or moderately susceptible by in vitro tests were equally responsive to therapy (95 percent of patients clinically cured and 94 percent of isolates eradicated). However, strains that were resistant by in vitro test criteria were less likely to respond clinically. Development of resistance during therapy or superinfections (1.7 percent) were not found to be clinically important problems with cefotetan chemotherapy.


A consideration of convalescent plasma and plasma derivatives in the care of Severely-ill patients with COVID-19.
The pathogenesis and immunopathological damage of severe forms of COVID-19 resemble acute autoimmune disease sparked by SARS-CoV-2, including an early systemic overproduction of proinflammatory cytokines. Such immunopathological features provide a rationale for the use of passive immunotherapy with convalescent plasma as a source of neutralizing anti-viral antibodies and of anti-inflammatory plasma components. While convalescent plasma therapy is now being evaluated in prospective clinical trials, we further consider the therapeutic potential of human hyper immune globulins, and of heterologous, engineered and monoclonal neutralizing antibodies as anti-viral agents to treat COVID-19. Good medical practice procedures are still needed and is why we also discuss the potential use of polyclonal polyspecific immunoglobulins (IVIG), a therapeutic plasma derivative, with potent anti-inflammatory activity, in severe forms of Covid-19.


Coupled solid phase extraction and microparticle-based stability and purity-indicating immunosensor for the determination of recombinant human myelin basic protein in transgenic milk.
An optical immunosensor was developed and validated on the surface of microparticles for the determination of a biopharmaceutical protein. The recombinant human myelin basic protein (rhMBP) was produced in milk of transgenic cows as a His-tagged fusion protein. Previous work indicated exclusive association of rhMBP with milk casein micelles that hindered direct determination of the protein in milk. In this work, a solid phase extraction using a cation exchange matrix was developed in order to liberate rhMBP from casein micelles. A sandwich-type immunoassay was then used for in-process monitoring of the full-length protein in the presence of major milk proteins. The assay was successfully employed for detection of ultra-traces of rhMBP (LOD=6.04 ng mL(-1)≈0.3 n mol L(-1)) and for quantitative determination over a wide concentration range (10.00-10,000.00 ng mL(-1)). The assay was able also to detect the rhMBP in the presence of its human counterpart that lacks the His-tag. The high sensitivity along with the ability of the assay to determine the full length protein enabled monitoring of the stability of rhMBP. The testing protocol is particularly useful for intrinsically unstructured proteins that are extremely sensitive to proteolysis and lack a traceable enzymatic activity. This immunosensor provides a specific, ultrasensitive high throughput tool for in-process monitoring in biopharmaceutical industry.


Climate change exacerbates almost two-thirds of pathogenic diseases affecting humans.
A comprehensive and systematic literature review reveals that over 58% of human pathogenic diseases are aggravated by climatic hazards that are sensitive to greenhouse gas emissions.


Synthetic developmental biology: molecular tools to re-design plant shoots and roots.
Plant morphology and anatomy strongly influence agricultural yield. Crop domestication has strived for desirable growth and developmental traits, such as larger and more fruits and semi-dwarf architecture. Genetic engineering has accelerated rational, purpose-driven engineering of plant development, but it can be unpredictable. Developmental pathways are complex and riddled with environmental and hormonal inputs, as well as feedback and feedforward interactions, which occur at specific times and places in a growing multicellular organism. Rational modification of plant development would probably benefit from precision engineering based on synthetic biology approaches. This review outlines recently developed synthetic biology technologies for plant systems and highlights their potential for engineering plant growth and development. Streamlined and high-capacity genetic construction methods (Golden Gate DNA Assembly frameworks and toolkits) allow fast and variation-series cloning of multigene transgene constructs. This, together with a suite of gene regulation tools (e.g. cell type-specific promoters, logic gates, and multiplex regulation systems), is starting to enable developmental pathway engineering with predictable outcomes in model plant and crop species.


Biological consequences of hyperthermia.
Because of the potential for certain modalities of clinical ultrasound to cause tissue heating, it was deemed important to survey the literature for reports on temperatures and hyperthermia exposure durations at which biological effects occur in a wide spectrum of organisms. In general the higher the temperature or the longer the hyperthermia exposure, the greater the chance for observing a perturbation to the biological system. Special attention was given to ascertaining temperature exposure conditions below which no biological effects have been reported. The physical mechanism(s) by which heat produces biological effects is(are) not known but substantial quantities of empirically derived data have allowed for the calculation of exposure temperature-duration equivalences. It appears reasonably well established that short exposures to sharply-elevated temperatures result in a protective effect against further thermal insult; the generation of heat shock proteins by cells coincides with the onset of such "thermal protection." The information contained in this review indicates an absence of reported effects in animals below 39 degrees C.


The biology of a chronic obstructive pulmonary disease exacerbation.
Much of the morbidity and mortality in chronic obstructive pulmonary disease relates to symptomatic deteriorations in respiratory health termed exacerbations. Exacerbations also are associated with changes in lung function and both airway and systemic inflammation. The most common causes of exacerbation are micro-organisms: respiratory viruses such as rhinovirus, and various bacterial species. This article reviews and discusses current understanding of the biology of exacerbations, considering the definition, epidemiology, etiology, and the nature and evolution of the changes in symptoms, lung function, and inflammation that characterize these important events.


THERAPIST PERCEPTIONS OF INTIMATE PARTNER VIOLENCE: A REPLICATION OF HARWAY AND HANSEN2019;S STUDY AFTER MORE THAN A DECADE.
More than a decade ago, Hansen, Harway, and Cervantes (1991) and Harway and Hansen (1993) conducted a research study examining mental health providers' ability to accurately perceive violence within couples presenting for therapy and to intervene in a manner in which to reduce the risk of danger to couples. The results were alarming, with 40% of therapists sampled failing to perceive intimate partner violence (IPV) and virtually no therapists intervening to reduce the risk of lethality. Harway and colleagues questioned how well-trained and informed therapists were in assessing IPV. The present study replicates Harway and colleagues' study with the expectation that, over a decade later, therapists are better prepared to accurately identify IPV issues and intervene effectively to reduce the risk of lethality. Reproducing the two main procedures used in the original study, 111 psychologists, clinical social workers, and marriage and family therapists were asked to respond to a survey. Results show that therapists have indeed improved their ability to identify IPV issues. Twenty percent of therapists predicted an increase in conflict, compared to 4% in the original sample. However, almost no therapists accurately predicted lethality in either study. Implications concerning IPV training for therapists are discussed.


[Study on purification of 2,3,5,4'-tetrahydroxy-stilbene-2-O-beta-D-glycoside from Polygonum multiflori].
To study the conditions and parameters of purifying 2,3,5,4'-tetrahydroxy-stilbene-2-O-beta-D-glycoside from Polygonum multiflori. Absorption capacity of four resins for 2,3,5,4'-tetrahydroxy-stilbene-2-O-beta-D-glycoside was compared. With the adsorption ability as indexes, the process of absorbing and purifying 2,3,5,4'-tetrahydroxy-stilbene-2-O-beta-D-glycoside from P. multiflori with S-8 macroporous resin absorbent was selected by orthogonal design. The S-8 resin was the best of the four resins. The optimum process condition was 50% ethanol as eluting solvent, the flow rate at 1.5 mL x min(-1), pH at 7-8, and the solution concentration at 0.2 g x mL(-1). The absorption capacity by this process was 36.89 mg x g(-1). The process is simple and convenient and the regeneration of resin is easy, so this method of purification is advisable.


Partial abrogation of FXR-KNG1 signaling by carboxyl-terminal truncated HBx-C30 in hepatitis B virus-associated hepatocellular carcinoma.
Hepatitis B virus (HBV) X protein (HBx) is a key regulator of HBV-associated hepatocarcinogenesis. C-terminal-truncated HBx is frequently detected in hepatocellular carcinoma (HCC). The role of HBx, especially C-terminal-truncated HBx, in HCC pathogenesis has been controversial. To elucidate the biological role of C-terminal-truncated HBx underlying HBV-associated hepato-oncogenesis, we constructed a vector expressing HBx-C30 (deletion of 30 aa from the C terminus of HBx) and functionally analyzed its regulation on farnesoid X receptor (FXR) signaling, which is known to inhibit hepatocarcinogenesis. In the present study, we found full-length HBx and HBx C-terminal truncation coexist in HCC, and both full length HBx and HBx-C30 can activate FXR signaling. Moreover, HBx-C30 weakly coactivates FXR-KNG1 signaling compared to full-length HBx.


Analysis of monofluoroacetic acid in urine by liquid chromatography-triple quadrupole mass spectrometry and preparation of the positive sample by the bioconversion from monofluoroacetamide to monofluoroacetic acid in vitro.
Whether as a rodenticide or as a natural product, monofluoroacetic acid (FAcOH) may cause poisoning to humans or animals for its high acute toxicity. Urine is one of the most typical specimens for forensic diagnosis when poisoning case about FAcOH happens. The positive sample containing FAcOH plays a key role for the development of an accurate and reliable analytical method. The bioconversion from monofluoroacetamide (FAcNH2) to FAcOH in urine in vitro was studied for the preparation of positive urine sample containing FAcOH without standard spiking or animal experiment. The average bioconversion rates were 0%, 18.6% and 41.3% when incubated the FAcNH2 spiked urine in vitro for 21days at -20°C, room temperature (RT) and 37°C, respectively. Afterwards, a fast and sensitive analytical method was developed for determination of FAcOH in urine. Samples were diluted with water containing formic acid and cleaned with polymeric anion exchange (PAX) cartridge. The acid eluate was neutralized with ammonium hydroxide and directly measured by hydrophilic interaction liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) using basic mobile phase condition. The limit of detection and limit of quantification of FAcOH in urine were 2 and 5ngmL(-1), respectively. The linear range was 5-1000ngmL(-1) with a correlation coefficient of r=0.9993 in urine calibrated with internal standard. The recoveries at four spiking levels (5, 10, 50 and 500ngmL(-1) in urine) were 87.2%-107% with relative standard deviations ranged between 4.3%-8.8%.


Standardized reporting of adverse events after microvascular decompression of cranial nerves; a population-based single-institution consecutive series.
To investigate frequencies of adverse events occurring within 30 days after microvascular decompression (MVD) surgery using a standardized report form of adverse events. We conducted a retrospective review of 98 adult patients (≥16 years) treated with MVD between 1 January 1994 and 1 June 2013. Adverse events occurring within 30 days were classified according to the Landriel Ibanez classification for neurosurgical complications: grade I represents any non-life threatening complication treated without invasive procedures; grade II is complications requiring invasive management; grade III is life-threatening adverse events requiring treatment in an intensive care unit (ICU); grade IV is death as a result of complications. We sought to compare our results with reports from the literature. Patients' median age was 61 years (range 26-83), and 64 (65 %) were females. Indications for MVD were trigeminal neuralgia (n = 77, 79 %), glossopharyngeal neuralgia (n = 4, 4 %), hemifacial spasm (n = 16, 16 %) and combined trigeminal neuralgia and hemifacial spasm (n = 1, 1 %). The overall 30-day complication rate was 20 %, with 14 % grade I complications, 5 % grade II complications and 1 % grade III complications. The comparison with the literature was hampered by the diverse and unsystematic way of reporting complications. We provide a standardized report of postoperative complications in a consecutive patient series undergoing MVD. Due to the heterogeneous and non-standardized reporting of complications in the literature, it is difficult to know if our 20 % complication rate is low or high. Standardized reporting is a necessity for meaningful and more valid comparisons across studies. The safety of MVD, a fairly standardized neurosurgical procedure, is well suited for comparisons across centers provided that complications are reported in a standardized manner.


Nicotine effects on associative learning in human non-smokers.
Tobacco smoking is the most common preventable cause of death in the US. Nicotine is considered the primary constituent responsible for tobacco addiction. Its paradoxically high abuse potential may reflect behavioral control by drug-associated stimuli, which appears to play a larger role for tobacco dependence than for other abused drugs. We tested a potential explanation, hypothesizing that nicotine enhances associative learning, the mechanism underlying the conditioning of drug-associated stimuli. Thirty-two non-smokers were exposed to transdermal nicotine (7 mg/24 h) and placebo in a double-blind cross-over study and tested with behavioral paradigms designed to isolate incidental stimulus-stimulus or stimulus-response learning. The stop signal task required speeded gender judgments of face stimuli. A tone signaled when to withhold the response. Unbeknownst to participants, some faces were always paired with stop trials. Nicotine enhanced the facilitation of stop-responses to these stimuli, and the slowing of go-responses when previously stop-associated stimuli were paired with go trials, indicating stronger associations between paired stimuli and the stop signal/stop response. Another task required feedback-based learning of associations between pairs of shape stimuli. Five pairs were made from either ten different stimuli, or from different combinations of two identical sets of five stimuli with correct associations depending on contextual information. Nicotine increased incorrect choices of stimuli that were associated in a different context, indicating stronger stimulus-stimulus associations at the expense of flexible context-adaptive behavior. The results indicate that nicotine can enhance incidental associative learning, a mechanism that may promote the formation of smoking-associated stimuli and cue-controlled drug-taking.


Incidence and severity of retinopathy of prematurity in Vietnam, a developing middle-income country.
Although retinopathy of prematurity (ROP) is a leading cause of childhood blindness, its impact in lower income countries is not well documented. The World Health Organization has proclaimed that infants at risk for ROP should have screening eye examinations and access to treatment. A prospective study was conducted from January 1 through December 31, 2001, at Tu Du Hospital in Ho Chi Minh City for premature infants who weighed 1,500 g or less at birth or were 33 gestational weeks or younger. Serial examinations were used to classify ROP, and treatment outcomes were noted. Two hundred twenty-five consecutive infants were included in the data analysis. Birth weights ranged from 900 to 2,000 g (mean, 1,512 g). Gestational ages ranged from 26 to 36 weeks (mean, 31 weeks). ROP was present in 103 (45.8%) of the 225 infants. In infants who weighed 1,250 g or less at birth, the ROP rate was 81.2% (26 of 32 infants). Threshold ROP was present in 9.3% of the 225 infants but in 25% of the 32 infants. Twenty-four eyes received treatment, whereas 16 lacked the family resources. Of the 24 treated eyes, 18 (75%) had a favorable outcome. Of the 16 untreated eyes, only 3 had a favorable outcome. ROP incidence is high in Vietnam, similar to that in the United States. However, larger, older infants are at risk in Vietnam and the rate of severe ROP seems to be higher. This necessitates an ROP screening paradigm different from that currently used in the United States.


Multidisciplinary approaches to intrahepatic cholangiocarcinoma.
After hepatocellular carcinoma, intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy. The etiology of ICC in most patients is not known, but its incidence is on the rise worldwide. There are 3 morphologic subtypes of ICC that can be characterized on cross-sectional imaging, mass forming, periductal infiltrating, and intraductal growth; and the radiographic characteristics of ICC may vary based on the subtype. Complete surgical resection remains the only potentially curative option for patients with ICC. Routine lymphadenectomy at the time of surgical resection should be strongly considered, because lymph node status provides important prognostic information. After surgery, the 5-year survival rate for ICC remains poor at only 25% to 35% in most series. Although numerous clinical trials have been conducted using a variety of chemotherapy regimens to treat ICC, systemic options for ICC remain limited. Doublet gemcitabine and cisplatin therapy is currently considered the standard-of-care first-line therapy for patients with advanced disease. Because ICC is typically confined to the liver and systemic chemotherapy traditionally has had only limited efficacy, there has been increasing interest in locoregional therapy. Although locoregional therapy may include intra-arterial therapies, stereotactic radiotherapy, hepatic artery pump therapy, or ablation, most data are limited. The purpose of this article was to provide a multidisciplinary appraisal of the current therapeutic approaches to ICC.


Validation of a clinically applicable device for fast and accurate quantification of blood volume.
Determination of blood volume (BV) using the dual-isotope (e.g., 99m Tc-labeled red blood cells [99m Tc-RBC] and 125 I-labeled human serum albumin [125 I-HSA]) injection method is limited in medicine due to the long isotope half-life. However, BV has been determined in laboratory settings for 100 years using the carbon monoxide (CO)-rebreathing-based procedure, which allows frequent BV measurements. We investigated the reliability and accuracy of a semi-automated CO-rebreathing device by comparing it against the dual-isotope methodology and its ability to detect a known blood removal. In study A, BV was determined three times in ~2 h; twice using the device with rebreathing protocols lasting 2 (CO2min ) and 10 min (CO10min ) and once with the dual-isotope technique. In study B, the accuracy of the device was assessed by its ability to detect a 2% removal of BV. A good correlation was observed between both the CO-rebreathing protocols (r2 = 0.89-0.98; p < 0.001) and the dual-isotope approach (r2 = 0.89-0.95; p < 0.001). In absolute terms BV was 425 ± 263 mL and 491 ± 388 mL lower (p < 0.001) when quantified with the dual-isotope compared to the CO-rebreathing protocols. When reducing BV by 132 ± 25 mL (2%), the device quantified a lower (p < 0.001) BV of 150 ± 45 mL. This study emphasizes that the semi-automated device accurately determines small changes (i.e., 2%) in BV and that a high correlation with the dual-isotope methodology exists. The findings are clinically relevant owing to the method's simple and fast nature (the absence of radioactive tracers and reduced time requirements, i.e., ~15 min vs. ~180 min) and the possibility for repeated measurements within a single day.


Arterial stiffness and the non-dipping pattern in type 1 diabetes males with and without erectile dysfunction.
Arterial stiffness (AS) and non-dipping pattern are early predictors of cardiovascular diseases but are not used in clinical practice. We aimed to assess if AS and the non-dipping pattern are more prevalent in the erectile dysfunction (ED) group than in the non-ED group among subjects with type 1 diabetes (T1DM). The study group consisted of adults with T1DM. Aortic pulse wave velocity (PWV Ao)-a marker of increased AS, central systolic blood pressure, and heart rate (HR) were measured with a brachial oscillometric device (Arteriograph 24). Erectile dysfunction (ED) was assessed by the International Index of Erectile Function-5. A comparison between the groups with and without ED was performed. Of 34 investigated men with T1DM, 12 (35.3%) suffered from ED. The group with ED had higher mean 24 h HR (77.7 [73.7-86.5] vs 69.9 [64.0-76.8]/min; p = 0.04, nighttime PWV Ao (8.1 [6.8-8.5] vs 6.8 [6.1-7.5] m/s; p = 0.015) and prevalence of non-dipping SBP Ao pattern (11 [91.7] vs 12 [54.5]%; p = 0.027) than individuals without ED. The presence of ED detected a central non-dipping pattern with a sensitivity of 47.8% and a specificity of 90.9%. The central non-dipping pattern was more prevalent and the nighttime PWV was higher in T1DM subjects with ED than in those without ED.


Physical Therapist-Led Ambulatory Rehabilitation for Patients Receiving CentriMag Short-Term Ventricular Assist Device Support: Retrospective Case Series.
Short-term ventricular assist device (VAD) support is used in the intensive care unit (ICU) to support individuals in end-stage heart failure prior to heart transplantation or implantation of a long-term left VAD. The literature investigating the feasibility, safety, and content of rehabilitation for this patient group is lacking. This report retrospectively describes the rehabilitation strategy, safety measures used, and nature of any adverse events and, therefore, the feasibility of this practice. Ten individuals (80% male) admitted to the ICU in critical cardiogenic shock required support via a short-term VAD. A prerehabilitation risk assessment was used to reduce the risk of cannula dislodgement. The therapeutic strategy was a stepwise progression of exercises, mobilization, and ambulation. Retrospective inspection of the case notes showed 330 rehabilitation sessions (X̅=33, SD=18.1, range=16-72) were performed and progressed to ambulation on 71 occasions (X̅=7.1, SD=7.7, range=1-27). Distance ambulated ranged from 7 to 1,200 m (X̅=157.7, SD=367.3). The Chelsea Critical Care Physical Assessment Tool (CPAx) score for 7 patients improved from a median of 0 (interquartile range=0-1) on day 1 to a median peak score of 39 (interquartile range=37-42). There were 8 episodes of minor adverse events (2.4% incidence rate), including 7 of transient low VAD flows. There were no major adverse events. Early rehabilitation and ambulation of recipients of short-term VAD support was safe and feasible. Recipients demonstrated improvements in physical function (CPAx score) while the VAD was in situ.


Identification of the initiation codons for translation of cowpea mosaic virus middle component RNA using site-directed mutagenesis of an infectious cDNA clone.
A full-length cDNA copy of CPMV M RNA has been cloned downstream of a phage lambda promoter in the plasmid pPMI. Transcripts obtained from this clone can be translated in vitro and replicated in cowpea mesophyll protoplasts in the presence of viral B RNA. We have constructed a series of site-directed mutants of this clone to investigate the mechanism of translation of CPMV M RNA. The results obtained confirm that the AUG at position 161 is used to direct the synthesis of a 105K protein in vitro and the detection of a 58K protein in infected cowpea protoplasts suggests that it is also used in vivo. The synthesis of the 95K protein can be initiated from either of the AUGs at positions 512 and 524, though synthesis of this protein does not appear to be essential for CPMV replication in protoplasts.


Fossilized leftover falls as sources of palaeoecological data: a 'pabulite' comprising a crustacean, a belemnite and a vertebrate from the Early Jurassic Posidonia Shale.
Especially in Lagerstätten with exceptionally preserved fossils, we can sometimes recognize fossilized remains of meals of animals. We suggest the term leftover fall for the event and the term pabulite for the fossilized meal when it never entered the digestive tract (difference to regurgitalites). Usually, pabulites are incomplete organismal remains and show traces of the predation. Pabulites have a great potential to inform about predation as well as anatomical detail, which is invisible otherwise. Here, we document a pabulite comprising the belemnite Passaloteuthis laevigata from the Toarcian of the Holzmaden region. Most of its soft parts are missing while the arm crown is one of the best preserved that is known. Its arms embrace an exuvia of a crustacean. We suggest that the belemnite represents the remnant of the food of a predatory fish such as the shark Hybodus.


SARS-CoV-2 spike-protein targeted serology test results and their association with subsequent COVID-19-related outcomes.
In the absence of evidence of clinical utility, the United States' Centers for Disease Control and Prevention does not currently recommend the assessment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike-protein antibody levels. Clinicians and their patients, especially immunocompromised patients, may benefit from an adjunctive objective clinical laboratory measure of risk, using SARS-CoV-2 serology. The aim of this study is to estimate the association between SARS-CoV-2 spike-protein targeted antibody levels and clinically relevant outcomes overall and among clinically relevant subgroups, such as vaccine and immunocompetency statuses. A retrospective cohort study was conducted using laboratory-based data containing SARS-CoV-2 antibody testing results, as well as medical and pharmacy claim data. SARS-CoV-2 testing was performed by two large United States-based reference clinical laboratories, Labcorp® and Quest Diagnostics, and was linked to medical insurance claims, including vaccination receipt, through the HealthVerity Marketplace. Follow-up for outcomes began after each eligible individual's first SARS-CoV-2 semiquantitative spike-protein targeted antibody test, from 16 November 2020 to 30 December 2021. Exposure is defined as having SARS-CoV-2 spike-protein targeted antibody testing. Study outcomes were SARS-CoV-2 infection and a serious composite outcome (hospitalization with an associated SARS-CoV-2 infection or all-cause death). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Propensity score matching was used for confounding covariate control. In total, 143,091 (73.2%) and 52,355 (26.8%) eligible individuals had detectable and non-detectable levels of SARS-CoV-2 spike-protein targeted antibodies, respectively. In the overall population, having detectable vs. non-detectable antibodies was associated with an estimated 44% relative reduction in SARS-CoV-2 subsequent infection risk (HR, 0.56; 95% CI 0.53-0.59) and an 80% relative reduction in the risk of serious composite outcomes (HR 0.20; 95% CI 0.15-0.26). Relative risk reductions were observed across subgroups, including among immunocompromised persons. Individuals with detectable SARS-CoV-2 spike-protein targeted antibody levels had fewer associated subsequent SARS-CoV-2 infections and serious adverse clinical outcomes. Policymakers and clinicians may find SARS-CoV-2 spike-protein targeted serology testing to be a useful adjunct in counseling patients with non-detectable antibody levels about adverse risks and reinforcing appropriate actions to mitigate such risks.


p.R270X MECP2 mutation and mortality in Rett syndrome.
Among cases in the Australian Rett Syndrome Database, the nonsense mutation p.R270X is one of the most commonly occurring single pathogenic MECP2 mutations. In two recent published reports of the MECP2 mutational spectrum the p.R270X appeared to be under represented. We hypothesised that increased mortality arising from this mutation may underlie this apparent discrepancy. We investigated our hypothesis in two independent study groups from Australia and the UK with prospective data collections (total n=524). Only females with Rett syndrome and an identified MECP2 mutation were included. Significant differences in survival were detected among Rett syndrome cases grouped for the eight most frequent mutations (log-rank chi(2) (7)=15.71, P=0.03). Moreover, survival among cases with p.R270X, when compared with survival among cases with all the other mutations was reduced (log-rank chi(2) (2)=6.94, P=0.01). Our observation of a reduced survival associated with the p.R270X mutation offers an explanation for the under representation of p.R270X in older subjects with Rett syndrome.


Changes in serum immunoglobulin levels in Jerseys and Friesians near calving.
IgG1 and IgM levels were significantly lower in bovine serum from four weeks before, until at least two months after calving, whereas IgG2 levels were elevated at this time. The shapes of the changes in Ig levels were different for first and second calving and it appeared that IgG1 levels were secreted earlier, from serum to colostrum, in heifers. Changes in management caused marked changes in Ig levels particularly after third calving when the cows were transferred from a balanced complete diet to grass or hay. IgG1 levels increased by 130 per cent and stayed high whereas the increase in IgM was transitory, and IgG2 levels largely unaffected. In Friesians the IgG2 levels increased with age as anticipated from previous studies but in Jerseys the levels appeared to decline with age. Mean IgG2 levels in Jerseys were also significantly lower than in Friesians.


Predictors of Physical Restraint Use in Hospitalized Veterans at End of Life: An Analysis of Data from the BEACON Trial.
The use of physical restraints in dying patients may be a source of suffering and loss of dignity. Little is known about the prevalence or predictors for restraint use at end of life in the hospital setting. The objective was to determine the prevalence and predictors of physical restraint use at the time of death in hospitalized adults. Secondary analysis was performed on data from the "Best Practices for End-of-Life Care for Our Nation's Veterans" (BEACON) trial conducted between 2005 and 2011. Medical record data were abstracted from six Veterans Administration Medical Centers (VAMCs). Data on processes of care in the last seven days of life were abstracted from the medical records of 5476 who died in the six VAMCs. We prospectively identified potential risk factors for restraint use at the time of death from among the variables measured in the parent trial, including location of death, medications administered, nasogastric tube, intravenous (IV) fluids, family presence, and receipt of a palliative care consultation. Physical restraint use at time of death was documented in 890 decedents (16.3%). Restraint use varied by location of death, with patients in intensive settings being at higher risk. Restraint use was significantly more likely in patients with a nasogastric tube and those receiving IV fluids, benzodiazepines, or antipsychotics. This is the first study to document that one in six hospitalized veterans were restrained at the time of death and to identify predictors of restraint use. Further research is needed to identify intervention opportunities.


Effects of recording sequence on flicker electroretinographics recorded with natural pupils corrected for pupil area.
A new handheld electroretinographic (ERG) recording system can record ERGs without mydriasis. However, this RETeval system cannot record ERGs from both eyes simultaneously. Thus, the purpose of this study was to determine whether the sequence of the ERG recordings will alter the results. We studied 30 eyes of 30 healthy subjects. The flicker ERGs were recorded with the RETeval system without mydriasis and were elicited by 8, 16 and 32 photopic Td-s. The flicker ERGs were recorded at two sessions. Session 1, the ERGs were recorded from the right eye and then the left eye, and Session 2, ERGs were recorded from the left eye then the right eye. We compared the implicit times, amplitudes and pupil diameters of the right eye between these two sessions. The implicit time of the flicker ERGs was significantly shorter (p < 0.001), and the pupil diameters were significantly smaller (p = 0.013) at Session 2 than Session 1 but only for the lower stimulus intensity of eight Td-s. There was a significant correlation of the differences in the implicit times and the differences in the pupil diameter between the two sessions (r = 0.406, p = 0.026). The results indicate that the implicit times of the fundamental components of RETeval flicker ERGs can be affected by the sequence of recordings for lower stimulus intensities. This was most likely due to the differences of the pupil diameter during the recordings. We recommend that stronger stimuli be used to record the RETeval flicker ERGs to minimize the effects of the sequence of recordings.


Arbuscular mycorrhizal fungi promote small-scale vegetation recovery in the forest understorey.
Root-associating arbuscular mycorrhizal (AM) fungi foster vegetation recovery in degraded habitats. AM fungi increase nutrient availability for host plants; therefore, their importance is expected to be higher when nutrient availability is low. However, little is known about how small-scale variation in nutrient availability influences plant and AM fungal communities in a stable ecosystem. We conducted a 2-year field study in the understorey of a boreonemoral forest where we examined plant and AM fungal communities at microsites (15 cm diameter) with intact vegetation cover and at disturbed microsites where vegetation was cleared away and soil was sterilized to remove soil biota. We manipulated soil nutrient content (increased with fertilizer, unchanged, or decreased with sucrose addition) and fungal activity (natural or suppressed by fungicide addition) at these microsites. After two vegetation seasons, manipulations with nutrient content resulted in significant, although moderate, differences in the content of soil nutrients (e.g. in soil phosphorus). Suppression of fungal activity resulted in lower richness, abundance and phylogenetic diversity of AM fungal community, independently of microsite type and soil fertility level. Plant species richness and diversity decreased when fungal activity was suppressed at disturbed but not in intact microsites. The correlation between plant and AM fungal communities was not influenced by microsite type or soil fertility. We conclude that small-scale variation in soil fertility and habitat integrity does not influence the interactions between plants and AM fungi. The richness, but not composition, of AM fungal communities recovered fast after small-scale disturbance and supported the recovery of species-rich vegetation.


Ciprostene, a stable prostacyclin analog, produces peripheral vasodilation, platelet inhibition and increased clot dissolution in the cat.
The effect of the stable prostacyclin analog ciprostene on hemodynamic parameters, platelet aggregation and clot dissolution was examined in the sodium pentobarbital anesthetized cat. Hemodynamic and platelet aggregation effects were measured in 5 cats following infusion of 5, 10, 20, 40 and 80 micrograms/kg/min of ciprostene. Drug was dissolved in Tyrode's buffer (pH 7.4) and all doses were infused for 20 minute intervals in ascending order. The hemodynamic data were consistent with peripheral vasodilation. The total peripheral resistance and mean aortic pressure decreased with increasing dose. No change in heart rate, cardiac index, or left ventricle dP/dt (contractility) was observed. All doses infused produced inhibition of ADP induced platelet aggregation. In vivo fibrinolytic activity was assessed with an aortic thrombus positioned at the bifurcation of the aorta. Five cats were infused with vehicle and 5 cats each were infused with 8 and 20 micrograms/kg/min ciprostene respectively. All infusions were via a 4F catheter positioned in the aorta proximal to the thrombus. Infusion time was 3 hours. Infusion of 8 micrograms/kg/min did not enhance dissolution of the aortic thrombus. However, the 20 micrograms/kg/min infusion significantly reduced the thrombus weight (mean = 13.2 mg) compared to vehicle (mean = 38.7 mg) (p less than 0.03). The results suggest that ciprostene is a potent vasodilator and platelet inhibitor with clot dissolution properties.


[Study on rat nasal absorption in situ of borneol based on single pass perfusion method].
To investigate the absorption characteristic of borneol. Using single pass perfusion model, the active ingredient of borneol were detected by GC. The drug concentration, perfusion rate and pH value on the absorption of borneol were studied. Perfusion rate on the absorption rate constants (Ka) had significant effects. Drug concentration and pH value on the absorption rate constants had no significant impact. the absorption of borneol is good by nasal. The absorption rate constants of borneol have no effected by drug concentration. The absorption of borneol is via a simple diffusion.


Trends and prospects in dairy protein replacement in yogurt and cheese.
There is a growing demand for nutritional, functional, and eco-friendly dairy products, which has increased the need for research regarding alternative and sustainable protein sources. Plant-based, single-cell (SCP), and recombinant proteins are being explored as alternatives to dairy proteins. Plant-Based Proteins (PBPs) are commonly used to replace total dairy protein. However, PBPs are generally mixed with dairy proteins to improve their functional properties, which makes them dependent on animal protein sources. In contrast, single-Cell Proteins (SCPs) and recombinant dairy proteins are promising alternatives for dairy protein replacement since they provide nutritional components, essential amino acids, and high protein yield and can use industrial and agricultural waste as carbon sources. Although alternative protein sources offer numerous advantages over conventional dairy proteins, several technical and sensory challenges must be addressed to fully incorporate them into cheese and yogurt products. Future research can focus on improving the functional and sensory properties of alternative protein sources and developing new processing technologies to optimize their use in dairy products. This review highlights the current status of alternative dairy proteins in cheese and yogurt, their functional properties, and the challenges of their use in these products.


A 5-Year-Old Palestinian Bedouin Girl with Repeated Self-Induced Injuries to the Digits, a Diagnosis of Congenital Insensitivity to Pain, and Anhidrosis.
BACKGROUND Congenital insensitivity to pain with anhidrosis (CIPA), also referred to as hereditary sensory and autonomic neuropathy type IV, is a rare autosomal recessive disease caused by mutations in the NTRK1 gene. The inability to feel pain and temperature often leads to repeated severe and unintentional self-inflicted injuries; these can result in severe complications, as patients heal slowly from skin and bone injuries. This case report describes a 5-year-old Palestinian girl with self-inflicted injury to the digits, a dislocated distal inter-phalangeal joint of the left big toe, and a diagnosis of CIPA. CASE REPORT A 5-year-old girl, a daughter of related Palestinian Bedouin parents, presented with a chronic unhealed wound over the planter surface of the left foot. Painless repetitive minor traumata over the same area badly affected wound healing and this led to wound dehiscence and dislocation of the distal inter-phalangeal joint of the left big toe. Surgical fixation of the dislocated joint along with intravenous antibiotics and close follow-up resulted in eventual improvement and near complete wound healing despite the obviously slow healing process. The girl also displayed evidence of unintentional self-inflicted injury, which within the overall clinical context warranted a clinical suspicion of CIPA. This was confirmed by genetic testing for the presence of a homozygous frameshift mutation in the NTRK1 gene (c.1842_1843insT; p.Pro615Serfs*12). CONCLUSIONS This case report shows that a physician should have a low threshold of suspicion to investigate for CIPA when managing children with multiple unintentional self-inflicted injuries, anhidrosis, and pain insensitivity, mainly through genetic testing to detect mutations in the NTRK1 gene.


Karyotypic abnormality of the X chromosome is rare in mutant HPRT-lymphocyte clones.
Lymphocyte clones mutated at the hypoxanthine-guanine phosphoribosyl-transferase (HPRT) locus on the X chromosome were studied by synchronization and G banding to determine the proportion of mutant clones having visible karyotypic change. 47 spontaneously mutant clones, 17 mutant clones induced by X-irradiation and 33 wild-type clones were studied. All clones were karyotypically normal except for 1 clone induced by X-irradiation in which an interstitial deletion of the short arm of the X chromosome had been inserted into the long arm of the same chromosome between q23 and q24; this change may have been coincidental or may have resulted in a position effect mutation. It was concluded that the great majority of mutations were not associated with a visible chromosome abnormality. This conclusion complements molecular studies which suggest that gene changes at the HPRT locus in HPRT- mutants generally extend over segments of DNA too small to be resolved by karyotypic analysis.


Adenocarcinoma in tubular duplication of the sigmoid colon.
A rare case of mucus-secreting adenocarcinoma in a tubular duplication of the sigmoid colon is presented. The pertinent radiographic manifestations were: a calcium containing soft tissue mass located at the blind end of a 20 cm barium filled tubular duplication originating at the sigmoid colon.


Safety and efficacy of interventional treatment of acute limb ischemia in Germany 2021.
Interventional procedures have become a mainstay in the therapy of acute limb ischemia caused by embolism or arterial thrombosis. Treatment options include pharmacological thrombolysis (PT) and mechanical thrombectomy (MT). The aim of this study was to evaluate success and major complication rates of interventional radiological treatments of arterial embolism and thrombosis in Germany in 2021 and to compare their results with accepted international quality standards. Data for PT and MT for 2021 was obtained from the quality management system of the German interventional radiological society (DeGIR). 2431 PT and 1582 MT procedures were documented for 2021, with 459 combinations of PT and MT. Data was analysed for technical and clinical success rates, as well as major complication rates such as intracranial bleeding, major bleeding, distal embolization, aneurysm formation, organ-failure and cardiac-decompensation. PT alone had technical and clinical success rate of 90.21% and 81.08%, respectively. MT alone had technical and clinical success rates of 97.41% and 95.39%, respectively. MT&PT had technical and clinical success rates of 91.07% and 84.75%, respectively. Major complications were: distal embolization (PT:2.02%; MT:1.74%; PT&MT:2.61%), major bleeding (PT:0.94%; MT:1.14%; PT&MT:0.87%), aneurysm formation (PT:0.33%;MT: 1.14%;PT&MT: 0%), intracranial bleeding (PT:0.16%;MT:0%;PT&MT:0.22%), cardiac-decompensation (PT:0.21%;MT: 0.06%;PT&MT:0%) and organ-failure (PT:0%;MT:0.06%;PT&MT:0.22%). Technical and clinical success rates were higher, while complication rates were lower than the corresponding threshold recommended by the Society of Interventional Radiology for percutaneous management of acute lower-extremity ischemia. Treatment of arterial embolism and thrombosis performed by interventional radiologists in Germany is effective and safe with outcomes exceeding internationally accepted standards.


Seismic microzonation of a region with complex surficial geology based on different site classification approaches.
A seismic microzonation study was conducted to refine the seismic hazard model for the city of Saguenay, Canada. The Quaternary geology underlying Saguenay shows complex glacial and post-glacial stratigraphy with a number of buried valleys filled with fluvioglacial and glaciomarine sediments. High impedance contrast between rock formations and surficial sediments is prone to seismic amplification. To evaluate their applicability, advantages and limitations in capturing the geological specificity of the study area, four site classification methods were applied: the current National Building Code of Canada (NBCC) and Eurocode 8, both mainly based on the average shear-wave velocity for the surficial sediments (V S,avg ) and for the top 30 m (V S,30 ); a method based on the fundamental site period (T 0 ); and a hybrid method based on the combination of V S,30 , T 0 and V S,avg . The study specifically aimed to evaluate the importance of the site classification parameters on the resulting microzonation maps. V S,30 is capable to present the geological and geotechnical site conditions, however, the results may be further improved by considering V s,avg in shallow and T 0 in thick layers of soil sediments as secondary parameters. The T 0 method gives also satisfactory results with T 0 showing a better correlation to V s,30 than to V s,avg . The versatile hybrid method may be challenging to apply in certain cases with its nine different site categories and parameters.


Diagnosis Disclosure: Patient Preferences and the Role of the Breast Nurse Navigator.
Receiving a breast cancer diagnosis can be traumatic and anxiety-producing. The way the diagnosis is disclosed to patients can affect their experience. The aim of this article is to determine patient preferences for being informed of a breast cancer diagnosis and the breast nurse navigator (BNN) role during the diagnostic experience. A survey was mailed to 517 patients with breast cancer. Summary statistics were performed on 199 completed surveys. Patients preferred to hear their diagnosis in person. BNNs were more likely to provide the right amount of support and resources compared to other providers. Patients described the following preferences.


Hypercalcaemic and hypocalcaemic conditions due to calcium-sensing receptor mutations.
The extracellular calcium (Ca2+o)-sensing receptor (CaSR) enables the parathyroid glands and other CaSR-expressing cells involved in calcium homeostasis, such as the kidney and bone, to sense alterations in the level of Ca2+o and to respond with changes in function that are directed at normalizing the blood calcium concentration. Several disorders of Ca2+o sensing arise from inherited or acquired abnormalities that 'reset' the serum calcium concentration upwards or downwards. Heterozygous inactivating mutations of the CaSR produce a benign form of hypercalcaemia, termed 'familial hypocalciuric hypercalcaemia', while homozygous mutations produce a much more severe hypercalcaemic disorder resulting from marked hyperparathyroidism, called 'neonatal severe hyperparathyroidism'. Activating mutations cause a hypocalcaemic syndrome of varying severity, termed 'autosomal-dominant hypocalcaemia or hypoparathyroidism' as well as Bartter's syndrome type V. Calcimimetic CaSR activators and calcilytic CaSR antagonists have also been developed with potential for use in the treatment of these disorders.


Homosubtypic and heterosubtypic antibodies against highly pathogenic avian influenza H5N1 recombinant proteins in H5N1 survivors and non-H5N1 subjects.
Six recombinant vaccinia viruses containing HA, NA, NP, M or NS gene insert derived from a highly pathogenic avian influenza H5N1 virus, and the recombinant vaccinia virus harboring plasmid backbone as the virus control were constructed. The recombinant proteins were characterized for their expression and subcellular locations in TK(-) cells. Antibodies to the five recombinant proteins were detected in all 13 sequential serum samples collected from four H5N1 survivors during four years of follow-up; and those directed to rVac-H5 HA and rVac-NA proteins were found in higher titers than those directed to the internal proteins as revealed by indirect immunofluorescence assay. Although all 28 non-H5N1 subjects had no neutralizing antibodies against H5N1 virus, they did have cross-reactive antibodies to those five recombinant proteins. A significant increase in cross-reactive antibody titer to rVac-H5 HA and rVac-NA was found in paired blood samples from patients infected with the 2009 pandemic virus.


Continuous oxygen monitoring in subcutaneous adipose tissue using microdialysis.
A measurement system, consisting of an optochemical glass capillary oxygen sensor, an optoelectronic measuring unit and a microdialysis catheter (CMA 60) for the extraction of the biological fluid from the subcutaneous adipose tissue of critically ill patients is reported. The capillary sensor is based on the oxygen sensitive dye platinum (II) meso-tetra(pentafluorophenyl) porphyrin (Pt-TFPP) incorporated in a polystyrene matrix. The measuring system has been tested in vitro and in vivo. In particular in vitro long-term stability of the sensor has been investigated in different measurement media (elomel, 5% mannitol, Ringer, dialysed blood). The influence of different flow rates from 0.1 up to 7.0 microl min(-1) on the sensor response as well as the oxygen recovery rate are discussed. The presented measurement system allows the measurement of oxygen in biological fluid in the range from 0 to 300 mmHg, with a resolution better than 1 mmHg and high accuracy (better than +/-1 mmHg absolute). Finally, the suitability of the described measurement system for the continuous oxygen monitoring in subcutaneous adipose tissue has been proved in in vivo investigations performed on test animals.


Text Mining of Adverse Events in Clinical Trials: Deep Learning Approach.
Pharmacovigilance and safety reporting, which involve processes for monitoring the use of medicines in clinical trials, play a critical role in the identification of previously unrecognized adverse events or changes in the patterns of adverse events. This study aims to demonstrate the feasibility of automating the coding of adverse events described in the narrative section of the serious adverse event report forms to enable statistical analysis of the aforementioned patterns. We used the Unified Medical Language System (UMLS) as the coding scheme, which integrates 217 source vocabularies, thus enabling coding against other relevant terminologies such as the International Classification of Diseases-10th Revision, Medical Dictionary for Regulatory Activities, and Systematized Nomenclature of Medicine). We used MetaMap, a highly configurable dictionary lookup software, to identify the mentions of the UMLS concepts. We trained a binary classifier using Bidirectional Encoder Representations from Transformers (BERT), a transformer-based language model that captures contextual relationships, to differentiate between mentions of the UMLS concepts that represented adverse events and those that did not. The model achieved a high F1 score of 0.8080, despite the class imbalance. This is 10.15 percent points lower than human-like performance but also 17.45 percent points higher than that of the baseline approach. These results confirmed that automated coding of adverse events described in the narrative section of serious adverse event reports is feasible. Once coded, adverse events can be statistically analyzed so that any correlations with the trialed medicines can be estimated in a timely fashion.


Invariant allometric scaling of nitrogen and phosphorus in leaves, stems, and fine roots of woody plants along an altitudinal gradient.
Nitrogen (N) to phosphorus (P) allocation in plant organs is of particular interest, as both elements are important to regulate plant growth. We analyzed the scaling relationship of N and P in leaves, stems and fine roots of 224 plant species along an altitudinal transect (500-2,300 m) on the northern slope of Changbai Mountain, China. We tested whether the scaling relationships of N and P were conserved in response to environmental variations. We found that the N and P concentrations of the leaves, stems and fine roots decreased, whereas the N:P ratios increased with increasing altitude. Allometric scaling relationships of N and P were found in the leaves, stems and fine roots, with allometric exponents of 0.78, 0.71 and 0.87, respectively. An invariant allometric scaling of N and P in the leaves, stems and fine roots was detected for woody plants along the altitudinal gradient. These results may advance our understanding of plant responses to climate change, and provide a basis for practical implication of various ecological models.


Hypersensitivity to Vitamins with a Focus on Immediate-Type Reactions: Food or Drug Allergy?
Vitamins are essential substances for normal cell functions, growth, and development. However, they cannot be produced by the human organism, so intake must be through the diet. Vitamin deficiency causes the onset of different diseases, ranging from pellagra to pernicious anemia, which can be corrected by reintroducing the missing vitamin form. To supply the right amount of vitamins to the body, every vitamin naturally occurring in foodstuff has been identified, extracted and synthetically produced, thus allowing either food fortification with these compounds or their pharmaceutical production. Furthermore, the increased importance attributed nowadays to body wellness and the pursuit of a permanent status of health at all costs has greatly encouraged a high consumption of vitamin supplements in modern society, since vitamin megadoses may be responsible for adverse or toxic effects. However, excessive vitamins can induce hypervitaminosis. In the USA, a national survey confirmed that 52% of adult Americans take at least one or more supplement products, vitamins and minerals being the most popular supplements in that country. Although vitamins are widespread natural substances, they may induce immediate or delayed type hypersensitivity reactions. Such adverse events are still underestimated and poorly recognized because only single cases have been reported in the literature, and no general review has yet investigated the mechanisms underlying sensitization to each vitamin, the diagnosis, and the management strategies adopted for vitamin hypersensitivity. Although delayed-type reactions to different vitamins are described in the literature, in our review, attention has been focused mainly on immediate- type reactions. Due to the importance of vitamins, further information regarding the above aspects (pathomechanisms, diagnosis and management) would be highly desirable to focus the state of the art on this particular, underestimated form of allergy, thus increasing allergists' awareness on these elusive hypersensitivity reactions.


The Effects of Pythagorean Self-Awareness Intervention on Irritable Bowel Syndrome Patients: A Non-randomized Controlled Trial.
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that affects a considerable percentage of the global population, mainly middle-aged women. IBS causes a constellation of symptoms with repercussions on patients' physical, psychological, and social well-being. Stress seems to play an important role in the pathogenesis of the disease as well as in its management. This study evaluated the effects of a novel non-pharmacological 8-week stress management intervention, the Pythagorean Self-Awareness Intervention (PSAI), in patients with IBS. In this non-randomized controlled trial, 60 IBS patients were assigned to an intervention and a control group. Self-reported questionnaires were used for the evaluation of IBS symptoms and a variety of biopsychological characteristics, pre- and post-intervention. All IBS-related symptoms were significantly reduced in the intervention group compared to the control group with 50% of the patients in the intervention group reporting less abdominal pain. The most potent effects of the intervention were observed in anger externalization, anger control, visuospatial memory, information processing speed, verbal memory, sense of coherence, stress, anxiety, and anger internalization. No side effects in the PSAI group were noted. In conclusion, PSAI was beneficial for patients suffering from IBS. Future research should expand and validate the results of this study.


Amyand's hernia- outcome of nylon darn repairs after complicated appendix surgeries in a district hospital: case series.
Complicated appendix is a least expected sac content of inguinal hernias that always require appendix surgery and hernia repair. The current recommendations for posterior wall repairs however, continue to attract conflicting views as to which modality gives the best outcome in infected surgical wounds. New posterior wall repair methods with properties to withstand surgical site infections, minimise hernia recurrence, affordable and easy skill to acquire with a potential to be widely adopted are continuosly sort. To determine the surgical outcomes of complicated Amyand Hernias repaired using the open tissue base Nylon Darn posterior wall re-enforcement method. A retrospective review of medical records of patients who had surgery for emergency inguinal hernia with intra-operative confirmation of complicated appendix in the hernia sac from January 2015 to December 2020 at the Margaret Marquart Catholic Hospital, Kpando were included. Data on age, sex, clinical presentation, surgical procedure, intra-operative findings, post operative complications were captured and presented as descriptive statistics. Twelve out of 286(4.6%) repairs were complicated Amyand Hernias in patients aged 6weeks to 76-years{median age 54.5-years}. Most of them were adults, long-standing hernias. All diagnosis were made on-table. Surgical site infections was the most frequent complication in types III and IV AHs which resolved with antibiotic treatment. The incidence of complicated AHs is higher and should be anticipated in surgeries for long-standing complicated inguinal hernias. Even though complications were significantly associated with longer hospital stay, no second procedure or mortality was recorded.


Immunological detection of the messenger RNA cap-binding protein.
The 24-kilodalton messenger RNA cap-binding protein (CBP) was purified from the rabbit reticulocyte postribosomal supernatant fraction using an affinity resin consisting of the p-aminophenyl gamma-ester of m7GTP coupled to Sepharose. The affinity-purified CBP was used to raise a goat antiserum. Anti-CBP antibodies were purified by adsorption to CBP coupled to either Controlled-Pore Glass or diazobenzyloxymethyl paper. The affinity-purified antibodies reacted specifically with only the 24-kilodalton polypeptide in whole reticulocyte lysate and in initiation factors prepared from the same source. During a conventional (nonaffinity) purification of CBP from a high salt extract of the ribosomal pellet, immunological reactivity paralleled the ability to reverse cap analogue inhibition of translation, indicating that the 24-kilodalton polypeptide present in the postribosomal supernatant fraction is immunologically cross-reactive with the CBP purified from ribosomes. Fractionation of whole reticulocyte lysate by sucrose gradient sedimentation followed by immunoblotting revealed that CBP was present in the supernatant fraction and the region of the gradient corresponding to ribosomal subunits but not in mono- or polysomes. The CBP to ribosome ratio was found to be approximately 0.02, assuming that the m7GTP-Sepharose retains all of the protein. This is considerably lower than that of other initiation factors and suggests that CBP may be the limiting polypeptide factor involved in the initiation of protein synthesis. The antibodies also inhibited the translation of a capped messenger RNA (globin). Inhibition of the translation of an uncapped RNA (satellite tobacco necrosis virus) was also observed, but to a lesser degree than with globin mRNA.


The therapeutic effect of hemodialysis on schizophrenia: comments and further possibilities.
Intermittent hemodialysis was recently found to have a therapeutic effect on schizophrenia, pointing to biochemical disturbances and possibly to renal malfunction as the cause of some forms of mental disorder. This paper points out that intermittent hemodialysis is not equally effective for the elimination of all solutes in the plasma. It can dispose of significant quantities of substances for which the normal urine/plasma concentration ratio is small, not of substances which the kidney concentrates in the urine by a large factor. It is further pointed out that for substances with a small urine/plasma concentration ratio thermogenic sweating could also constitute an effective means of disposal and its use is suggested as possible alternative to hemodialysis.


Plasma homocysteine, methylenetetrahydrofolate reductase genotypes, and age at onset of symptoms of myocardial ischemia.
Elevated fasting plasma homocysteine is a graded risk factor of coronary artery disease (CAD) and may accelerate onset of CAD. Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is commonly but inconsistently associated with hyperhomocysteinemia. In the present study we examined the possible relation between levels of fasting plasma homocysteine and age at CAD onset in different MTHFR genotypes. We studied 182 patients with CAD, 74 patients with early onset CAD (aged < or = 45 years), and 108 patients with later onset CAD (aged 46 to 65 years). Plasma homocysteine levels in 90 subjects without CAD were used for control. Fasting plasma homocysteine levels in T/T homozygotes with early onset CAD (20.2 +/-12.5 micromol/L) was markedly higher than in T/T homozygotes with later onset CAD (13.4 +/- 6.8 micromol/L) and in patients with early onset CAD who were not T/T homozygotes (11.9 +/- 3.7 micromol/L; p = 0.034 and p = 0.0001, respectively). CAD developed earlier in T/T homozygotes who were hyperhomocysteinemic (>15 micromol/L) than in the T/T homozygotes who were not (p = 0.036). Plasma homocysteine levels had no effect on age at onset of CAD in patients who were non-T/T genotypes. Homocysteine levels in control subjects and in patients who were non-T/T genotypes were comparable and were not influenced by age. The results reveal an inverse relation between the level of fasting plasma homocysteine and age at onset of CAD in T/T homozygotes as opposed to no association in patients who were non-T/T genotypes. Additionally, these results show that hyperhomocysteinemia and the T/T genotype have a stronger effect on the pathogenesis of CAD when they are combined, and that a marked increase (>15 micromol/L) in fasting plasma homocysteine in T/T homozygotes is a risk factor for early onset of CAD.


Ethyl acetate fraction of Fagara zanthoxyloides root-bark possess antidiabetic property against alloxan-induced diabetes and its complications in Wistar rat model.
Fagara zanthoxyloides Lam., an African traditional medicinal plant, is used for treatment of malaria and diabetes. To investigate the antidiabetic property of ethyl acetate fraction of F. zanthoxyloides root-bark (EAFFZRB) on alloxan-induced diabetic rats. Extraction, isolation, preliminary phytochemical analysis, and acute toxicity study of ethanol extract and fractions of F. zanthoxyloides root-bark were achieved using standard methods. Phyto-constituents in EAFFZRB were identified using HPLC technique. Forty-eight male Wistar rats (140-185 g) were randomized into 6 groups (n = 8). Groups 1 and 2 served as normal and negative controls, respectively. Diabetes was induced in test groups (2-6) using 150 mg/kg body weight (b.w) Alloxan monohydrate. Rats in groups 4-6 received of 200, 400 and 600 mg/kg b.w. EAFFZRB orally, respectively, for 21 days. Group 3 rats received 5 mg/kg b.w Glibenclamide. The effect of EAFFZRB on alterations in hematological, biochemical, and histological indices of study rats were assessed. Extraction of 3500 g ethanol extract yielded 15.71 g EAFFZRB. HPLC fingerprint of EAFFZRB indicated presence of luteolin, rutin, quercetin, apigenin, cinnamic acid and catechin. Diabetes triggered significant (p < 0.05) alterations in b.w., hematological, biochemical and histological indices of test rats relative to normal control. Treatment with EAFFZRB (LD50 = 3807.9 mg/kg b.w.) resulted in remarkable improvements in altered b.w. changes, hematological, biochemical and histological parameters of diabetic rats. The study demonstrated the antidiabetic potential of EAFFZRB, providing scientific basis for traditional use of the plant in treatment of diabetes and its complications.


Increasing fertility knowledge and awareness by tailored education: a randomized controlled trial.
Women of reproductive age have insufficient fertility knowledge and awareness. Reproductive lifespan and assisted reproduction are the primary areas in which awareness is lacking. Relatively simple interventions can be used to increase knowledge among university students; however, no intervention has been tested to date in a population with more varied education levels. The aim of this study was to evaluate which intervention most improved fertility knowledge in women attending a fertility centre for oocyte donation. A randomized controlled trial was conducted with three intervention groups: tailored, untailored and control. A questionnaire was administered on the day of the first consultation, and again at the oocyte retrieval. Two hundred and one women were enrolled and completed the pre-test, 109 started the cycle and 90 completed the post-test. The effect of the intervention was measured as the difference between the groups in their score from the pre-test to the post test. Only the tailored group showed a significant increase (+2.5; 95% CI [1.8, 3.3]; P = 0.001). Information relating to a woman's most fertile age and limits for childbearing were the most useful. Tailored oral education, therefore, increases fertility knowledge in young women, particularly in relation to their fertility lifespan.


Intrinsic instability of the concentration field in diffusion-limited growth and its effect on crystallization.
The dynamic behavior of the concentration field in crystallization is investigated by considering the coupling of the bulk concentration field and interfacial kinetics. It is shown that the concentration field may become unstable for perturbations with certain wavelength. When instability occurs, the physical environment in front of the growing interface will fluctuate and the interfacial growth mode will be affected accordingly. We suggest that our analysis can be used to interpret some spatial-temporal instabilities observed in crystallization.


Effect of serotonin on cytosolic free calcium in adrenal glomerulosa and vascular smooth muscle cells.
In view of its vasoconstricting action and of its stimulating effect on aldosterone biosynthesis, serotonin (5-hydroxytryptamine, 5-HT) could play a role in the genesis and/or maintenance of hypertension. The effects are mediated by different specific receptors whose transmembrane signaling system is not elucidated. We have used the fluorescent probe quin 2 to study the effect of 5-HT on cytosolic free calcium in enzymatically dispersed bovine adrenal glomerulosa cells and in cultured rat aortic smooth muscle cells. We also examined the effect of 5-HT on prostacyclin production by rat aortic smooth muscle cells. Serotonin did not modify the level of cytosolic free calcium in adrenal glomerulosa cells. In contrast, serotonin induced rapid, concentration-dependent (10(-8) -10(-5) M) rises of cytosolic free calcium in monolayers of cultured rat aortic smooth muscle cells, from a basal level of 153 +/- 27 nM to peak levels of about 400 nM. Ketanserin (10(-6) M), a specific 5-HT2-receptor antagonist completely blocked the free calcium rise induced by 5-HT. 5-HT induced a concentration-dependent increase in 6-keto-PGF1 alpha production in smooth muscle cells, which was suppressed by ketanserin, indomethacin or removal of calcium from the incubation medium. In contrast nifedipine (10(-6) M) did not modify the response to 5-HT while it abolished the response to vasopressin and did not modify the response to angiotensin II. We conclude that the 5-HT receptors of adrenal glomerulosa cells and vascular smooth muscle cells are linked to two distinct signalling systems which mediate the different biological responses.


Phagocyte extracellular traps formation contributes to host defense against Clostridium perfringens infection.
Clostridium perfringens (C. perfringens) is an important Gram-positive anaerobic spore-forming pathogen that provokes life-threatening gas gangrene and acute enterotoxaemia, although it colonizes as a component of the symbiotic bacteria in humans and animals. However, the mechanisms by which C. perfringens is cleared from the host remains poorly understood, thereby impeding the development of novel strategies for control this infection. Here, we uncover a beneficial effect of extracellular traps (ETs) formation on bacterial killing and clearance by phagocytes. C. perfringens strain ATCC13124, and wild-type isolates CP1 and CP3 markedly trigger ETs formation in macrophages and neutrophils. As expected, visualization of DNA decorated with histone, myeloperoxidase (MPO) and neutrophils elastase (NE) in C. perfringens-triggered classical ETs structures. Notably, the bacteria-induced ETs formation is an ERK1/2-, P38 MAPK-, store-operated calcium entry (SOCE)-, NADPH oxidase-, histone-, NE-, and MPO-dependent process, and is independent of LDH activity. Meanwhile, the defect of bactericidal activity is mediated by impairing ETs formation in phagocytes. Moreover, In vivo studies indicated that degradation of ETs by DNase I administration leads to a defect in the protection against experimental gas gangrene, with higher mortality rates, exacerbated tissue damage, and more bacterial colonization. Together, these results suggest that phagocyte ETs formation is essential for the host defense against C. perfringens infection.


Emerging roles of immunoproteasomes beyond MHC class I antigen processing.
The proteasome is a multi-catalytic protein complex whose primary function is the degradation of abnormal or foreign proteins. Upon exposure of cells to interferons (IFNs), the β1i/LMP2, β2i/MECL-1, and β5i/LMP7 subunits are induced and incorporated into newly synthesized immunoproteasomes (IP), which are thought to function solely as critical players in the optimization of the CD8(+) T-cell response. However, the observation that IP are present in several non-immune tissues under normal conditions and/or following pathological events militates against the view that its role is limited to MHC class I presentation. In support of this concept, the recent use of genetic models deficient for β1i/LMP2, β2i/MECL-1, or β5i/LMP7 has uncovered unanticipated functions for IP in innate immunity and non-immune processes. Herein, we review recent data in an attempt to clarify the role of IP beyond MHC class I epitope presentation with emphasis on its involvement in the regulation of protein homeostasis, cell proliferation, and cytokine gene expression.


A family of partial-linear single-index models for analyzing complex environmental exposures with continuous, categorical, time-to-event, and longitudinal health outcomes.
Statistical methods to study the joint effects of environmental factors are of great importance to understand the impact of correlated exposures that may act synergistically or antagonistically on health outcomes. This study proposes a family of statistical models under a unified partial-linear single-index (PLSI) modeling framework, to assess the joint effects of environmental factors for continuous, categorical, time-to-event, and longitudinal outcomes. All PLSI models consist of a linear combination of exposures into a single index for practical interpretability of relative direction and importance, and a nonparametric link function for modeling flexibility. We presented PLSI linear regression and PLSI quantile regression for continuous outcome, PLSI generalized linear regression for categorical outcome, PLSI proportional hazards model for time-to-event outcome, and PLSI mixed-effects model for longitudinal outcome. These models were demonstrated using a dataset of 800 subjects from NHANES 2003-2004 survey including 8 environmental factors. Serum triglyceride concentration was analyzed as a continuous outcome and then dichotomized as a binary outcome. Simulations were conducted to demonstrate the PLSI proportional hazards model and PLSI mixed-effects model. The performance of PLSI models was compared with their counterpart parametric models. PLSI linear, quantile, and logistic regressions showed similar results that the 8 environmental factors had both positive and negative associations with triglycerides, with a-Tocopherol having the most positive and trans-b-carotene having the most negative association. For the time-to-event and longitudinal settings, simulations showed that PLSI models could correctly identify directions and relative importance for the 8 environmental factors. Compared with parametric models, PLSI models got similar results when the link function was close to linear, but clearly outperformed in simulations with nonlinear effects. We presented a unified family of PLSI models to assess the joint effects of exposures on four commonly-used types of outcomes in environmental research, and demonstrated their modeling flexibility and effectiveness, especially for studying environmental factors with mixed directional effects and/or nonlinear effects. Our study has expanded the analytical toolbox for investigating the complex effects of environmental factors. A practical contribution also included a coherent algorithm for all proposed PLSI models with R codes available.


Comparison of mortality and feeding behavior of the false cleanerfish Aspidontus taeniatus and the lance blenny A. dussumieri regarding the effects of mimicry.
Many examples of mimicry have been reported in coral reef fishes of which the most well known is the mimicry of the bluestreak cleaner wrasse, Labroides dimidiatus by the false cleanerfish, Aspidontus taeniatus. To examine the effect of protective and aggressive mimicry of A. taeniatus, mortality and feeding behavior were compared with those of the non-mimic lance blenny, Aspidontus dussumieri, by field observations on the coral reefs of Miyako Island, Okinawa, southern Japan. Survival rate of A. taeniatus was more than twice higher than that of A. dussumieri, but the detected differences were not significant, and the effect of protective mimicry could not be determined. The benthic foods common to both species (the tubeworm, Spirobranchus giganteus, and the boring clam, Tridacna crocea) were very scarce in the study sites, and the feeding behavior of the two species was clearly different: A. dussumieri pecked at the bottom substrate, whereas A. taeniatus fed on fish fins and eggs of damselfish, regardless of body size. Our findings are the first documented evidence of the effect of aggressive mimicry on biting fish fins in relation to the availability of other foods not only in small but also in large A. taeniatus. The online version contains supplementary material available at 10.1007/s10164-022-00769-8.


A reproducible mechano-responsive luminescent system based on a discotic crown ether derivative doped with fluorophores: taking advantage of the phase transition of a matrix.
A reproducible mechano-responsive luminescent system based on a discotic crown ether derivative (1) doped with a small amount of fluorophore has been prepared. The emission intensity was enhanced when the material was subjected to mechanical shear with localized response.


Evolution of EF-hand calcium-modulated proteins. I. Relationships based on amino acid sequences.
The relationships among 153 EF-hand (calcium-modulated) proteins of known amino acid sequence were determined using the method of maximum parsimony. These proteins can be ordered into 12 distinct subfamilies--calmodulin, troponin C, essential light chain of myosin, regulatory light chain, sarcoplasmic calcium binding protein, calpain, aequorin, Stronglyocentrotus purpuratus ectodermal protein, calbindin 28 kd, parvalbumin, alpha-actinin, and S100/intestinal calcium-binding protein. Eight individual proteins--calcineurin B from Bos, troponin C from Astacus, calcium vector protein from Branchiostoma, caltractin from Chlamydomonas, cell-division-cycle 31 gene product from Saccharomyces, 10-kd calcium-binding protein from Tetrahymena, LPS1 eight-domain protein from Lytechinus, and calcium-binding protein from Streptomyces--are tentatively identified as unique; that is, each may be the sole representative of another subfamily. We present dendrograms showing the relationships among the subfamilies and uniques as well as dendrograms showing relationships within each subfamily. The EF-hand proteins have been characterized from a broad range of organismal sources, and they have an enormous range of function. This is reflected in the complexity of the dendrograms. At this time we urge caution in assigning a simple scheme of gene duplications to account for the evolution of the 600 EF-hand domains of known sequence.


Immunohistochemical localization of the angiotensin-(1-7) receptor Mas in the murine forebrain.
Apart from the well-known biologically active angiotensin II, other biologically active angiotensins have been discovered, including angiotensin IV and angiotensin-(1-7). Some years ago, we and others discovered that the Mas proto-oncogene encodes a receptor that is essential for angiotensin-(1-7) signaling. Angiotensin-(1-7) is not only expressed in the periphery but also within the brain. Based on that, we examined the distribution of Mas within the murine brain, using an antibody directed against the 3(rd) cytoplasmic loop of the receptor protein. Strongest Mas protein expression was detected in the dentate gyrus of the hippocampus and within the piriform cortex. However, Mas protein expression is not restricted to these areas, since Mas immunopositive neurons were also seen in different parts of the cortex, hippocampus, amygdala, basal ganglia, thalamus and hypothalamus. Based on the expression of Mas protein in the cortex and the limbic system, angiotensin-(1-7) signaling may play a role in synaptic plasticity, learning, memory and emotion, as has been described for angiotensin II and IV.


Nuclear magnetic resonance spectroscopic studies of the interaction of methyl methacrylate and ethylene dimethacrylate with phosphatidylcholine liposomes as a model for biomembranes.
The interaction of methyl methacrylate (MMA) and ethylene dimethacrylate (EDMA) with dipalmitoyl phosphatidylcholine (DPPC) liposomes was studied by 1H and 13C nuclear magnetic resonance spectroscopy (NMR). It was found that the changes in the 1H chemical shift of EDMA were larger than those of MMA when comparing membrane-bound state with free state and that the amount of EDMA incorporated into DPPC liposomes was approximately 74%, whilst MMA was approximately 41%. The major changes in chemical shifts of EDMA appeared to be due to its interaction with the acyl chains of DPPC liposomes.


[Study on the expression and potential effect of PD-L1mRNA and PD-L2mRNA in oral lichen planus].
To study the expression of PD-L1 and PD-L2mRNA in oral lichen planus(OLP) patients' peripheral blood and focal mucosa, and the different expression of target molecules in gene level in different clinical and pathological OLP groups. The expression of PD-L1 and PD-L2 mRNA in OLP patients, which included 35 reticular and 25 atrophic-erosive OLP patients, 38 cases without dysplasia and 22 cases with dysplasia, was examined by real-time PCR. Peripheral blood and mucosa from 10 volunteers were used as control. All the results were analysed with Wilcoxon test by SAS.6.12 software package. The expression of PD-L2mRAN, but not PD-L1, was significantly higher in oral mucosa of OLP patients (P<0.01), while decreased in OLP patients' peripheral blood (P=0.0415). The gene expression of PD-L2 differed between different clinical types, and had highly significant correlation between the OLP patients' focal mucosa and peripheral blood(r=0.6976, P<0.0001). PD-L2 may have some potential effect on the pathogenesis of OLP at systemic and local level.


Evaluation of alternatives to warfarin as probes for Sudlow site I of human serum albumin: characterization by high-performance affinity chromatography.
Warfarin is often used as a site-specific probe for examining the binding of drugs and other solutes to Sudlow site I of human serum albumin (HSA). However, warfarin has strong binding to HSA and the two chiral forms of warfarin have slightly different binding affinities for this protein. Warfarin also undergoes a slow change in structure when present in common buffers used for binding studies. This report examined the use of four related, achiral compounds (i.e., coumarin, 7-hydroxycoumarin, 7-hydroxy-4-methylcoumarin, and 4-hydroxycoumarin) as possible alternative probes for Sudlow site I in drug binding studies. High-performance affinity chromatography and immobilized HSA columns were used to compare and evaluate the binding properties of these probe candidates. Binding for each of the tested probe candidates to HSA was found to give a good fit to a two-site model. The first group of sites had moderate-to-high affinities for the probe candidates with association equilibrium constants that ranged from 6.4 x 10(3)M(-1) (coumarin) to 5.5 x 10(4)M(-1) (4-hydroxycoumarin) at pH 7.4 and 37 degrees C. The second group of weaker, and probably non-specific, binding regions, had association equilibrium constants that ranged from 3.8 x 10(1)M(-1) (7-hydroxy-4-methylcoumarin) to 7.3 x 10(2)M(-1) (coumarin). Competition experiments based on zonal elution indicated that all of these probe candidates competed with warfarin at their high affinity regions. Warfarin also showed competition with coumarin, 7-hydroxycoumarin and 7-hydroxy-4-methycoumarin for their weak affinity sites but appeared to not bind and/or compete for all of the weak sites of 4-hydroxycoumarin. It was found from this group that 4-hydroxycoumarin was the best alternative to warfarin for examining the interactions of drugs at Sudlow site I on HSA. These results also provided information on how the major structural components of warfarin contribute to the binding of this drug at Sudlow site I.


[Cybernetical approach to enemy-prey systems].
The interactions between one enemy and one prey population are described by the aid of cybernetic concepts, including plants as prey.By their numerical responses the populations of enemy and prey together constitute a feedback control system (Fig.1). Both of them can be interpreted either as regulator or as controlled system. The negative feedback is made possible by limitation of the enemy's searching ability. The difference between (the logarithms of) density independent fertility and mortality of both populations can be regarded as disturbance or as command variable. The encounter of both populations has the effect of a detecting element or of an correcting element (Fig. 2).To a first approximation, both populations react like integrating elements with dead time. Their interactions in the feedback control system can be described appropriately by these means. Thus there is no need for interpreting the enemies as temporarily defective regulator.If the individual prey organisms cannot be utilized by different enemies as often as they are found, there exists a competition for prey. Its intensity depends on enemy density. In the mode of a second regulator the competition reacts negatively upon the enemy population. In the information flow diagram it can be represented by an additional element (Fig. 3). Together with the prey it composes a PI-regulator of the enemy (Fig.4).The limited feeding capacity of the enemy often causes a relative decrease of the enemy's activity with increasing prey density. This decrease can be taken into account by a further element (Fig. 5), that reacts positively upon the prey population.Considering only numerial responses the enemy-prey system is composed of two integrating elements. Consequently both densities oscillate after every change of disturbance with amplitudes that increase because of the dead time in each element. The competition for prey among enemies is probably able to damp the oscillations in certain cases. On the other hand, the relative decrease of activity caused by the limited feeding capacity favours instability. If the system is not damped sufficiently by itself quenching is possible only by the proportional effects of additional regulators.By the cybernetical approach the complex system is divided into simple components. With that cybernetics provides a model of structure which, among others, facilitates insight into kind and degree of density dependence of different factors. When the effects of the single elements are characterized by mathematical functions a dynamic model will arise.On principle the cybernetical model can be extended by adding further components.


The evil circle of poverty: a qualitative study of malaria and disability.
This article discusses the link between disability and malaria in a poor rural setting. Global malaria programmes and rehabilitation programmes are organized as vertical and separate programmes, and as such they focus on prevention, cure and control, and disability respectively. When looking at specific conditions and illnesses, the impairing long-term consequences of illness incidents during childhood are not questioned. The study design was ethnographic with an open, exploratory approach. Data were collected in Mangochi District in Malawi through qualitative in-depth interviews and participant observation. Despite a local-based health service system, people living in poor rural areas are confronted with a multitude of barriers when accessing malaria prevention and treatment. Lack of skilled health personnel and equipment add to the general burden of poverty: insufficient knowledge about health care, problems connected to accessing the health facility in time, insufficient initiatives to prevent malaria attacks, and a general lack of attention to the long term disabling effects of a malaria attack. This study points to the importance of building malaria programmes, research and statistics that take into consideration the consequences of permanent impairment after a malaria attack, as well as the context of poverty in which they often occur. In order to do so, one needs to develop methods for detecting people whose disabilities are a direct result of not having received health services after a malaria episode. This may be done through qualitative approaches in local communities and should also be supplemented by suitable surveys in order to estimate the problem on a larger scale.


NeuroD1 regulation of migration accompanies the differential sensitivity of neuroendocrine carcinomas to TrkB inhibition.
The developmental transcription factor NeuroD1 is anomalously expressed in a subset of aggressive neuroendocrine tumors. Previously, we demonstrated that TrkB and neural cell adhesion molecule (NCAM) are downstream targets of NeuroD1 that contribute to the actions of neurogenic differentiation 1 (NeuroD1) in neuroendocrine lung. We found that several malignant melanoma and prostate cell lines express NeuroD1 and TrkB. Inhibition of TrkB activity decreased invasion in several neuroendocrine pigmented melanoma but not in prostate cell lines. We also found that loss of the tumor suppressor p53 increased NeuroD1 expression in normal human bronchial epithelial cells and cancer cells with neuroendocrine features. Although we found that a major mechanism of action of NeuroD1 is by the regulation of TrkB, effective targeting of TrkB to inhibit invasion may depend on the cell of origin. These findings suggest that NeuroD1 is a lineage-dependent oncogene acting through its downstream target, TrkB, across multiple cancer types, which may provide new insights into the pathogenesis of neuroendocrine cancers.


Estimation of the effects of inset heights and slit configurations in an acetabular cup on the pull-out behavior of an artificial hip joint with a structure for preventing dislocation using finite element analysis.
Joint dislocation is a critical problem of total hip replacement. We have newly proposed an artificial hip joint with a structure that prevents dislocation. The proposed joint has a simple form with a femoral head partially covered with an acetabular cup. In the present study, the effects of inset heights and slit configurations of the cup on the pull-out forces of the joint were evaluated using finite element analysis. Joint models with different inset heights and those with or without a slit in the cup were used for the analyses to estimate the pull-out forces of the joint. In the case without the slit, the maximum pull-out force of the joint with 1.0 and 1.5 mm of the inset height was approximately 12 and 40 N, respectively. In the case of 1.0-mm inset height, the maximum force of the joint with and without the slit was approximately 9 and 12 N, respectively. These results reveal that the maximum force is markedly changed by the inset height and is moderately affected by the slit. Thus, we can gain insights into a strategy to optimally design an artificial joint in which dislocation does not occur easily. Graphical abstract.


Effect of methylprednisolone sodium succinate on quality of life in preterminal cancer patients: a placebo-controlled, multicenter study. The Methylprednisolone Preterminal Cancer Study Group.
The effectiveness of an 8-week, 125 mg/day intravenous course of methylprednisolone sodium succinate (MPSS) for improving quality of life in patients with preterminal cancer was investigated in a double-blind, placebo-controlled, multicenter study. Quality of life was assessed using the Nurses' Observational Scale for Inpatient Evaluation (NOSIE), the Linear Analog Self-Assessment Scale (LASA), and the Physicians' Global Evaluation. A total of 403 patients were enrolled: 207 were treated with MPSS and 196 were treated with placebo. MPSS was significantly more effective than placebo in improving quality of life as judged by the changes from baseline in the NOSIE and LASA total scores. (P less than 0.05) and by the Physicians' Global Evaluation (P less than 0.001). The mortality rate was similar between MPSS-treated males (40.2%), placebo-treated males (35.5%), and MPSS-treated females (40.0%). However, the mortality rate of 27.7% for female placebo-treated females was significantly lower than for their MPSS-treated counterparts. The reason for lower mortality among placebo-treated females is unknown and warrants further study.


Catecholamine content and adenylate cyclase activity in corpora lutea of different ages of the PMSG-treated immature rat.
The catecholamine content and adenylate cyclase response were studied in a well-characterized corpus luteum model, where ovulation was induced by treatment of prepubertal Sprague-Dawley rats with pregnant mare's serum gonadotropin. The luteal content of noradrenaline, determined with HPLC, was constant during the first 7 days of pseudopregnancy, followed by a 3-fold increase in older corpora lutea. No detectable amounts of dopamine were found, while trace amounts of adrenaline were found in a few cases. The increase in noradrenaline content was not associated with a changed sensitivity of luteal adenylate cyclase to catecholamines. The response to adrenaline was maximal in 3-day-old corpora lutea, whereafter a decrease was seen. The significance of the increased endogenous levels of noradrenaline at the end of pseudopregnancy is at present unknown. However, the fact that the increase in noradrenaline occurs a few days before spontaneous luteolysis is of special interest, since it has been suggested that an adrenergic innervation is a prerequisite for the antigonadotropic effect of prostaglandin F2 alpha in the human corpus luteum.


Umbilical and portal vein calcification following umbilical vein catheterization.
Calcifications of the umbilical vein and intrahepatic branches of the portal vein developed in a newborn who had an umbilical vein catheter inserted for 11 days postnatally. The calcified intrahepatic portal veins can still be demonstrated sonographically at the age of three years, but these calcifications were no longer detectable radiologically.


Cryptic subtelomeric translocation t(2;16)(q37;q24) segregating in a family with unexplained stillbirths and a dysmorphic, slightly retarded child.
We here describe a submicroscopic translocation affecting the subtelomeric regions of chromosomes 2q and 16q, and segregating in a family with stillbirths, early pregnancy losses, and two dysmorphic and slightly retarded babies. FISH analysis showed a 46,XY,der(2)t(2;16)(q37.3;q24.3) in the propositus, and a balanced t(2;16) in his mother, her conceptus and maternal grandfather. FISH with YACs and BACs made it possible to map the 2q37 breakpoint precisely between the regions covered by y952E1 and y746H1, and the 16q breakpoint between the regions encompassed by bA 309g16 and bA 533d19. The contribution of 2q37.3 monosomy and 16q24.3 trisomy to the proband's phenotype is compared with that in reported patients with similar imbalances of either chromosome.


An examination of avoidance in major depression in comparison to social anxiety disorder.
The construct of avoidance has begun to receive attention in theoretical models and empirical investigations of depression. However, little is known about relative levels of avoidance across diagnostic categories or about the relationships between avoidance and other correlates of depression. The present study compared levels of avoidance across groups of depressed women without social anxiety disorder (MDD without SAD), depressed women with social anxiety disorder (MDD with SAD), women with social anxiety disorder (SAD), and nonclinical women, and investigated the relationships among avoidance, and sociotropy and autonomy, rumination, and negative and positive problem orientations within the clinically depressed group. Avoidance was found to be significantly higher in all clinical groups relative to the nonclinical group of women, and highest in the comorbid MDD with SAD group. Avoidance showed significant positive relationships with sociotropy, autonomy, rumination, and negative problem orientation, and a significant negative relationship with positive problem orientation within the overall sample of depressed women. These results suggest that avoidance should be given greater consideration in psychosocial models of depression and point to several important directions for future research.


Radiology of acute spinal trauma.
Radiologic diagnostic modalities utilized to evaluate acute spine trauma include plain films, tomography, computerized tomography (CT), myelography and CT-myelography, and magnetic resonance imaging. The initial evaluation is aimed at delineating the nature and extent of both boney and soft tissue injuries, with particular attention directed toward differentiating intrinsic cord damage from extrinsic spinal cord or nerve root compression that may respond to surgical intervention. The selection of the optimal radiologic diagnostic algorithm requires familiarization with the techniques and limitations of each diagnostic procedure.


Use of Old World monkeys for acquired immunodeficiency syndrome research.
Mangabeys, macaques, and baboons persistently infected with human immunodeficiency virus (HIV)-2 NIH-DZ demonstrated no signs of immunodeficiency disease after 6-11 months following seroconversion. Thus Old World monkeys provide an animal model to investigate the effects of passive immunization (anti-HIV-2 antibodies) on HIV infection in primates.