Effects of an outward water flow on potassium currents in a squid giant axon.
The excitation of the squid giant axon was analyzed under an outward water flow through the membrane product by an osmotic gradient. The outward water flow made an undershoot of the action potential larger by about 25 mV without decreasing its peak largely. It also made EK more negative but not ENa. The effect of the outward water flow was specific for the potassium channel. The outward current increased and its decline during a long-lasting depolarization became less prominent under the outward water flow. At the same time, inward tail currents for the potassium channel decreased extraordinarily without a large change in the time course. The potassium conductance had a marked rectification in the direction of the water flow. The undershoot of the action potential under the outward water flow was very sensitive to potassium ions in the external solution. Eight mM KCl was effective to diminish the undershoot and to restore the change in EK by about 60% but gave no effect on the reduced tail current. The outward water flow effect can be explained not only by the change in a local concentration of potassium ions at the mouths of the potassium channel due to a sieving but also by the rectification in a hydrodynamic manner.


Frame overlap Bragg edge imaging.
Neutron Bragg edge imaging enables spatially resolved studies of crystalline features through the exploitation and analysis of Bragg edges in the transmission spectra recorded in each pixel of an imaging detector. Studies with high spectral resolutions, as is required e.g. for high-resolution strain mapping, and with large wavelength ranges have been largely reserved to pulsed neutron sources. This is due to the fact, that the efficiency for high wavelength resolution measurements is significantly higher at short pulse sources. At continuous sources a large fraction of the available neutrons must be sacrificed in order to achieve high wavelength resolution for a relevant bandwidth e.g. through a chopper system. Here we introduce a pulse overlap transmission imaging technique, which is suited to increase the available flux of high wavelength resolution time-of-flight neutron Bragg edge imaging at continuous neutron sources about an order of magnitude. Proof-of-principle measurements utilizing a chopper with a fourfold repeated random slit distribution of eight slits were performed at a thermal neutron beamline. It is demonstrated, that disentanglement of the overlapping pulses is achieved with the correlation theorem for signal processing. Thus, the Bragg edge pattern can be reconstructed from the strongly overlapping Bragg edge spectra recorded and the results demonstrate the feasibility of the technique.


Initial management of the trauma patient.
Regardless of the injuries sustained or the capabilities of the treating facility, the principles described in ATLS should guide the initial assessment, resuscitation, and treatment of the multiply injured patient.3 The primary and secondary survey should be continually repeated to identify deterioration in the patient's condition and to make appropriate interventions. The use of a prioritized and systematic approach to initial management of the trauma patient ensures that optimal care is delivered and the best possible outcome is achieved.


Synthesis, characterization, molecular docking and biological evaluation of Schiff Base derivatives of cefpodoxime.
Synthesis of new Cefpodoxime derivatives via Schiff Bases mechanism and the efficiency of their antimicrobial and antiviral activities were addressed. They were analyzed for structural validation by using spectroscopic techniques using FTIR, 1HNMR, and 13CNMR. Molecular docking against IBV Virus papain-like protease (PLPro) was done with Auto dock tools against compounds having excellent IC50 values against IBV (Corona Class) virus. All derivatives showed strong zone of inhibition ranges from (55 ± 2.0 to 70 ± 0.8 mm) against E. coli. Compounds 1,2,4 and 6 derivatives showed remarkable activity against Stenotrophomonas maltophilia and Serratia marcescens. But For most the newly synthesized derivatives C 1 (64 ± 1.60), C 3 (32 ± 0.80), and C 8 (64 ± 1.60) showed potential IC50 values against two variants of Corona class viruses i.e. Avian Influenza (H9) and Avian corona (IBV) viruses. The current study revealed that newly synthesized Schiff Bases possessed strong anti-viral potential. Further studies may make a breakthrough in medical sciences to tackle latest challenges such as Corona Virus Diseases.


Context-based presets for lighting setup in residential space.
This study aims to derive context-based lighting setup presets in residential space by exploring the multilateral relationships among household activities, affects, and lighting setups. Three procedures were involved: First, sixty affective words were evaluated through which seven affect factors were extracted to facilitate the evaluation of colored illumination in the subsequent experiment. Second, in the user study, seven affect factors and thirty household activities were used to evaluate 147 lighting setups extracted from combinations of twelve hues, six illuminance levels, and three purity levels. As a result, twenty lighting setup presets were derived that were not only activity-based, but affect-based as well. Lastly, the twenty presets were prototyped as a set of testbed to further explore potentials and limitations. This study demonstrates that intuitive, context-based presets can help users explore the effects of colored illumination in creating a diverse range of user experiences.


A 23-Nucleotide Deletion in STK11 Gene Causes Peutz-Jeghers Syndrome and Malignancy in a Chinese Patient Without a Positive Family History.
Peutz-Jeghers syndrome (PJS) is an autosomal-dominant genetic disease caused by mutations in the tumor suppressor gene, STK11, which is characterized by gastrointestinal hamartomas, melanin spots on the lips and the extremities, and an increased risk of developing both gastrointestinal and extraintestinal malignancies. We treated a PJS patient without a positive family history, who possessed typical clinical manifestations including polyp canceration. In order to explore the genotype of this patient, blood samples were collected from all the available family members. The whole coding region and the flanking regions of the STK11 gene were amplified by polymerase chain reaction and analyzed by Sanger sequencing. Molecular analysis of the STK11 gene here revealed a 23-nucleotide deletion (c.426-448delCGTGCCGGAGAAGCGTTTCCCAG) in exon 3, resulting in a change of 13 codons and a truncating protein (p.S142SfsX13). This mutation was not found in normal individuals in this family including her parents or in 100 control individuals. Protein structure prediction indicated a dramatic loss of the kinase domain and complete loss of the C-terminal regulatory domain. The results presented here enlarge the spectrum of STK11 mutation both disease-causing and malignancy-causing.


Characterization of a beta-lactamase produced in Mycobacterium fortuitum D316.
A beta-lactamase from Mycobacterium fortuitum D316 was purified and some physico-chemical properties and substrate profile determined. On the basis of its N-terminal sequence and of its sensitivity to beta-iodopenicillanate inactivation, the enzyme appeared to be a class A beta-lactamase, but its substrate profile was quite unexpected, since nine cephalosporins were among the eleven best substrates. The enzyme also hydrolysed ureidopenicillins and some so-called 'beta-lactamase-stable' cephalosporins.


Hypolipidaemic effects of fenofibrate are not altered by mildronate-mediated normalization of carnitine concentration in rat liver.
The five-fold higher carnitine content in the liver of fenofibrate-treated rats addresses the question about the possible role of this enhancement in the hypolipidaemic effect of the drug and the underlying mechanisms. When fenofibrate was administered with mildronate (a gamma-butyrobetaine hydroxylase inhibitor) in suitable amount, the content in carnitine was found to be normalized in liver. However, triglyceride contents of liver and serum were then at least as low as in rats treated by fenofibrate only. When carnitine concentration was lowered by mildronate to the third of the normal value, a marked increase in triglycerides occurred both in liver and serum, while the five-fold increase in carnitine due to fenofibrate enhanced blood ketone body concentration with no effect on liver and serum triglycerides. Data suggest that the normal carnitine concentration is largely sufficient to meet the usual requirement for carnitine palmitoyltransferase I activity (CPT I). In rat liver, increase in mitochondrial CPT I activity and in peroxisomal fatty acid oxidation may constitute part of the hypolipidaemic effect of fenofibrate.


Structures of microbial communities found in anaerobic batch runs that produce methane from propionic acid--Seeded from full-scale anaerobic digesters above a certain threshold.
The volatile fatty acid propionate inhibits anaerobic digestion during organic waste treatments. To examine potential microbial interactions that accelerate propionate oxidation, anaerobic digestion systems seeded with various types of anaerobic sludge were analyzed. Seed samples were collected from 10 different full-scale anaerobic reactors in South Korea. Propionate oxidation was estimated as the methane production rate per gram of propionate used per day. Two domestic sewage sludge showed the highest methane production rate values, 109.1 ± 4.2 and 74.5 ± 8.6 mL CH4/(g propionate ∙ d). A food waste recycling wastewater source exhibited the lowest methane production rate, 33.2 ± 2.6 mL CH4/(g propionate ∙ d). To investigate how the microbial community structure affected propionate oxidation, qualitative molecular analyses were carried out using denaturing gradient gel electrophoresis. Methanosaeta concilii, an aceticlastic methanogen, was detected in most batch runs. Smithella propionica, a unique propionate oxidizer and simultaneous producer of acetate, was found in domestic sewage sludge sources showing the highest methane production rate; in contrast, Desulfobulbus rhabdoformis, a sulfate reducer coupled with the consumption of acetate to be used as a precursor of methane, was observed in food waste recycling wastewater sludge source showing the lowest methane production rate. Thus, we propose that S. propionica, a syntrophic acetate producer using propionate, might cooperate with aceticlastic methanogens for high methane production during anaerobic digestion that included propionate.


Evaluation of risk factors for bite wounds inflicted on caregivers by dogs and cats in a veterinary teaching hospital.
To identify factors associated with increased risk of being bitten by a dog or cat in a veterinary teaching hospital. Unmatched case-control study. 207 animal caregivers. Case subjects (n = 75) were any caregiver that reported being bitten by a dog or cat. Control subjects (n = 132) were randomly selected from a list of all caregivers interacting with dogs or cats. Information on the characteristics of the caregivers, characteristics of the dogs and cats, and the nature of the interaction between the dog or cat and the caregiver was obtained by use of self-administered questionnaires. Caregivers were more likely to be bitten by dogs or cats that had warning signs on their cages indicating the potential to bite or that were considered difficult to handle. Caregivers interacting with cats or with older dogs and cats were more likely to be bitten. Only 37 to 55% of dogs and cats that had characteristics traditionally associated with biting or were considered likely to bite were muzzled. Muzzling dogs and cats should be considered more frequently. Dogs and cats considered to have the propensity to bite frequently do bite, and precautions, such as muzzling, should be taken if the medical condition or conformation of the dog or cat is amenable to this type of restraint.


Formulation optimization of palm kernel oil esters nanoemulsion-loaded with chloramphenicol suitable for meningitis treatment.
Palm kernel oil esters nanoemulsion-loaded with chloramphenicol was optimized using response surface methodology (RSM), a multivariate statistical technique. Effect of independent variables (oil amount, lecithin amount and glycerol amount) toward response variables (particle size, polydispersity index, zeta potential and osmolality) were studied using central composite design (CCD). RSM analysis showed that the experimental data could be fitted into a second-order polynomial model. Chloramphenicol-loaded nanoemulsion was formulated by using high pressure homogenizer. The optimized chloramphenicol-loaded nanoemulsion response values for particle size, PDI, zeta potential and osmolality were 95.33nm, 0.238, -36.91mV, and 200mOsm/kg, respectively. The actual values of the formulated nanoemulsion were in good agreement with the predicted values obtained from RSM. The results showed that the optimized compositions have the potential to be used as a parenteral emulsion to cross blood-brain barrier (BBB) for meningitis treatment.


Something new under the sun: caspases promote cell survival under moderate heat stress.
Since the discovery of caspases in 1993 (Yuan et al, 1993), they have largely been regarded as essential Cys proteases in apoptosis. However, more recently, it has become evident that caspases also have non-apoptotic functions in the so-called caspase-dependent non-lethal processes (CDPs) including cell proliferation and cell differentiation (Aram et al, 2017). While most of the non-apoptotic functions were characterized under normal developmental conditions, a new study by Galasso et al took this examination a step further-to the analysis of moderate stress conditions. The authors now report that caspases have a non-apoptotic prosurvival function in Drosophila ovarian somatic cells exposed to moderate heat stress by controlling Hedgehog signaling and autophagy (Galasso et al, 2023).


Does prenatal healthcare improve child birthweight outcomes in Azerbaijan? Results of the national Demographic and Health Survey.
This paper evaluates the effectiveness of prenatal healthcare in Azerbaijan on improving child birthweight using the 2006 Azerbaijan Demographic and Health Survey, a nationally representative survey of reproductive aged women. Two measures of prenatal health utilization are used to measure healthcare input-the number of prenatal visits and the quality index of health care. Endogeneity in prenatal healthcare utilization is controlled by 2SLS regression. Selection bias of probability of child being weighed is controlled by a binomial probit regression. We found that prenatal healthcare does improve child birthweight. The results of the 2SLS suggest that an additional prenatal visit increases birthweight by about 26g, or approximately 0.8% of the raw mean of birthweight in the country. Likewise, a unit increase in quality of prenatal healthcare increases birthweight by 21g or by approximately 1.3% of the birthweight. In general, the magnitude of prenatal care impact in Azerbaijan is comparable with that in other countries.


Free nicotine patch giveaway program 12-month follow-up of participants.
To estimate the effectiveness of a free nicotine patch giveaway program offered to New York City (NYC) smokers conducted in 2003. The effectiveness of the program was assessed by contrasting the 12-month quit rate of program participants with the quit rate from a group of Quitline callers who were not offered free nicotine patches. The follow-up surveys were conducted in 2004 and the analysis in 2005. The 7-day nonsmoking prevalence rate measured at 12 months among callers who received the nicotine patches was 1.78 times higher (95% confidence interval [CI] = 1.19-2.66) than the quit rate among a comparable group of callers to the Quitline from NYC a year earlier who did not receive nicotine patches. The provision of free nicotine patches through a telephone quitline was effective in inducing a large number of smokers to make a quit attempt and stop smoking, above and beyond the efficacy of the quitline support alone.


Dendritic cell-based tumor vaccine for cervical cancer I: in vitro stimulation with recombinant protein-pulsed dendritic cells induces specific T cells to HPV16 E7 or HPV18 E7.
Human papillomavirus (HPV) type 16 and 18 are the most prevalent genotypes in cervical cancers. The viral oncoproteins E6 and E7 are considered to be tumor-specific targets for immunotherapy. HPV E7 antigen-loaded dendritic cells (DC) were evaluated as cellular tumor vaccine. Autologous monocyte-derived DCs loaded with recombinant HPV16 or HPV18 E7 oncoprotein were used to induce in vitro a specific T cell response. Specificities of activated T cells were determined. E7-specific T cells could be identified in 18/20 T cell lines from healthy blood donors. CD4(+) T cell responses (13/16) were found by proliferation assay. CD8(+) CTLs (12/18) were detectable by interferon-gamma (IFN-gamma) ELISpot analysis. Seven donors reacted in both assays and only 2/20 T cell lines did not react in any assay. Thus, specific T cells could be activated in >80% of healthy individuals. T cell lines from suitable donors were specific for HLA-A*0201-restricted epitopes. Furthermore, HPV E7 antigen-loaded DC stimulated specific responses in freshly isolated tumor infiltrating lymphocyte (TIL) populations of cervical cancer patients. Autologous dendritic cells loaded with HPV E7 protein can induce T cell responses in healthy individuals by in vitro stimulation and evoke responses in TIL from cervical cancer biopsies. Since there are no limitations with respect to specific HLA-haplotypes, these findings may be a basis for the development of a therapeutic protein-based DC tumor vaccine against cervical cancer for HPV16- and HPV18-positive patients.


Phosphate sources and their suitability for remediation of contaminated soils.
Phosphate minerals and specifically apatite show promise for environmental cleanup because they can form stable compounds with a wide range of cationic contaminants. However, phosphate minerals naturally accumulate some heavy metals that may cause additional contamination of the environment if used improperly. Nine commercially available phosphate materials were evaluated for remediation of contaminated soil based on solubility, concentration of metal/metalloid impurities, and leachability of impurity metal/metalloids. The phosphate materials consisted of three groups: processed (i.e., fertilizers), mined (rock phosphates from different formations), and biogenic (ground fish bone). Processed and mined rock phosphates contained relatively high total concentrations of As, Co, Cr, and Cu but did not exceed the RCRA toxicity characteristic leaching procedure (TCLP) limits. Biogenic apatite contained much lower metal concentrations than processed and mined rock phosphate and was appreciably more soluble. By combining biogenic and mined phosphate it is possible to obtain a wide range of phosphate release rates, permitting rapid immobilization of contaminants while providing a slow release of phosphate for continued long-term treatment.


Counter intelligence?
A hospital's bed count can have a significant effect on its Medicare payments. Determining what to count is a challenge, however, because published guidance and response to litigation often vary. Providers should: Pay particular attention to the period in which the bed count is applied. Not rely solely on the definition of available beds in the Provider Reimbursement Manual.


[An active medical intern with a painful lower leg].
A 23-year-old female athlete presented with progressive pain in her right lower leg since 3 months. Conventional radiography did not reveal a fracture. However, a CT-scan showed a proximal posteromedial tibial stress fracture, matching with the localisation of the pain.


Stabilization energies of the hydrogen-bonded and stacked structures of nucleic acid base pairs in the crystal geometries of CG, AT, and AC DNA steps and in the NMR geometry of the 5'-d(GCGAAGC)-3' hairpin: Complete basis set calculations at the MP2 and CCSD(T) levels.
Stabilization energies of the H-bonded and stacked structures of a DNA base pair were studied in the crystal structures of adenine-thymine, cytosine-guanine, and adenine-cytosine steps as well as in the 5'-d(GCGAAGC)-3' hairpin (utilizing the NMR geometry). Stabilization energies were determined as the sum of the complete basis set (CBS) limit of MP2 stabilization energies and the Delta E(CCSD(T)) - Delta E(MP2) correction term evaluated with the 6-31G*(0.25) basis set. The CBS limit was determined by a two-point extrapolation using the aug-cc-pVXZ basis sets for X = D and T. While the H-bonding energies are comparable to those of base pairs in a crystal and a vacuum, the stacking energies are considerably smaller in a crystal. Despite this, the stacking is still important and accounts for a significant part of the overall stabilization. It contributes equally to the stability of DNA as does H-bonding for AT-rich DNAs, while in the case of GC-rich DNAs it forms about one-third of the total stabilization. Interstrand stacking reaches surprisingly large values, well comparable to the intrastrand ones, and thus contributes significantly to the overall stabilization. The hairpin structure is characterized by significant stacking, and both guanine...cytosine pairs possess stacking energies larger than 11.5 kcal/mol. A high portion of stabilization in the studied hairpin comes from stacking (similar to that found for AT-rich DNAs) despite the fact that it contains two GC Watson-Crick pairs having very large H-bonding stabilization. The DFT/B3LYP/6-31G** method yields satisfactory values of interaction energies for H-bonded structures, while it fails completely for stacking.


Endocrine toxicity of immune checkpoint inhibitors: a real-world study leveraging US Food and Drug Administration adverse events reporting system.
Immune-checkpoint inhibitors (ICIs) emerged as a novel class of drugs for the treatment of a broad spectrum of malignancies. ICIs can produce durable antitumor responses but they are also associated with immune-related adverse events (irAEs). Endocrinopathies have reported as one of the most common irAEs of ICIs. This study aimed to quantify association of endocrine adverse events (AEs) and ICI therapy and also to characterize the profiles of ICI-related endocrine complications from real-world practice. Data from the first quarter of 2014 to first quarter of 2019 in FDA Adverse Event Reporting System (FAERS) database were gathered to conduct disproportionality analysis. The definition of endocrine AEs relied on the preferred terms (PTs) provided by the Medical Dictionary for Regulatory Activities (MedDRA). Two signal indices based on statistical shrinkage transformation, reporting odds ratios (ROR) and information component (IC), were used to evaluate correlations between ICIs and endocrine events. For ROR, it was defined a signal if the lower limit of the 95% confidence interval (ROR025) more than one, with at least 3 cases. For IC, lower end of the 95% confidence interval of IC (IC025) exceeding zero was deemed statistically significant. A total of 29,294,336 records were involved, among these 6260 records related to endocrine AEs after ICIs treatment were identified. In general, male had a slightly lower reporting frequencies for ICIs-related endocrinopathies compared with female but not significant (ROR = 0.98 95%CI: 0.93-1.04) and the difference varied in several common endocrine AEs. Notably, in general, ICI drugs were significantly associated with over-reporting frequencies of endocrine complications, corresponding to IC025 = 2.49 and ROR025 = 5.99. For monotherapy, three strategies (anti-PD-1, anti-PD-L1 and anti-CTLA-4) were all associated with significant increasing endocrine events. Different reporting frequencies emerged when anti-CTLA-4 therapy was compared with anti-PD-1/PD-L1 medications for endocrine toxicities, corresponding to ROR = 1.68 (95%CI 1.55-1.83), ROR = 2.54 (95%CI 2.20-2.93), respectively. Combination therapy was associated with higher risk of endocrinopathies compared with monotherapy (ROR = 2.00, 95%CI 1.89-2.11). When further analysis, the spectrum of endocrine AEs differed in immunotherapy regimens. Hypothyroidism (N = 885,14.14%), adrenal insufficiency(N = 730,11.66%), hypophysitis (N = 688,10.99%) and hyperthyroidism (N = 472,7.54%) were top 4 ranked endocrine events after ICI therapy and their reporting frequency also differed in ICI immunotherapies. Our pharmacovigilance analysis shows a high reporting frequency of endocrine AEs provoked by ICI monotherapy (especially anti-CTLA-4 therapy) and further reinforced by combination therapy. In addition, treatment with different ICI immunotherapies may result in a unique and distinct profile of endocrinopathies. Early recognition and management of ICI-related endocrine irAEs is of vital importance in clinical practice.


CMR findings in patients referred for suspected myocarditis following mRNA-based COVID vaccination compared with pre-COVID myocarditis referrals: A single-centre observational study.
Vaccination is considered the key to overcome the COVID pandemic. For the first time mRNA-based vaccinations are used in humans. Case series suggested an increased risk of myocarditis after vaccination. This study sought to describe CMR findings in patients with suspected mRNA-vaccine associated myocarditis. A total of 33 consecutive patients referred for CMR work-up of suspected myocarditis associated with mRNA-based vaccination were included. A historical cohort of 135 consecutive patients referred for suspected myocarditis in the pre-COVID era served as control group. All patients underwent multi-parametric CMR including CINE and late gadolinium enhancement (LGE) imaging as well as parametric T1/T2 mapping of the left ventricular myocardium. Patients referred for suspected vaccination-related myocarditis were more often female (55 % vs 32 %, p = 0.015) and demonstrated smaller LV dimensions as well as a better LV function compared to patients of the control group. CMR revealed a lower prevalence of non-ischemic LGE in patients with suspected vaccination-myocarditis (6 % vs 22 %, p = 0.04). However, among patients without LGE we observed a higher prevalence of an abnormal T1/T2 mapping result in patients with suspected vaccination-myocarditis compared to the control group (45 % vs 18 %, p = 0.010). In this small single-centre study, compared to myocarditis referrals in the pre-COVID era, patients currently referred for CMR work-up of suspected mRNA-vaccination-associated myocarditis demonstrated lower prevalence of LGE but higher prevalence of abnormal T1/T2 mapping. These hypothesis-generating observations may point towards a rather subtle myocardial damage and support the routine use of T1/T2 mapping in this indication.


[LDL-apheresis in patients with familial autosomal recessive hypercholesterolemia].
LDL-apheresis reduces the cardiovascular risk in patients with familial hypercholesterolemia. The addition of statin therapy in patients with autosomal recessive hypercholesterolemia may change the lipid profile to a less atherogenic pattern.


[Impacted acetabular cups].
The failure modes of impacted acetabular cups are: deterioration of the polyethylene insert, disassembly of the modular components, excessive polyethylene wear, severe peri-prosthetic osteolysis. These failures can be explained; solutions are suggested.Primary stability: Screws are pathways for polyethylene debris; impacting elastic cups increases the press-fit effect in order to provide stability without screw fixation.Polyethylene thickness: by increasing polyethylene thickness from a minimum 8 to 10 mm, the risk of insert deterioration is decreased and so too is creep of the core which can induce micromotion between the insert and its metal backing.Liner stability: Tilting of the liner is the most common mecanism of disassembly in two-piece acetabular cups. The solution we suggest is to use a liner with a cylindrical periphery.Polyethylene wear: Excess polyethylene wear in metal backed acetabular cups was reported. Conversly, other authors concluded to no excess wear in impacted cups. This may be due to differences in prosthetic components, as well as patient selection. We noticed no significant wear in our series (0.10 mm per year). Studies are contradictory and it is not obvious that excessive wear in impacted cups has to be feared.Osteointegration is mandatory for obtaining long term stability and is provided by porous coating. The osteoconductive properties of hydroxyapatite have been demonstrated by a large number of studies, including fundamental research, animal experiments and clinical applications. Within a few weeks, hydroxyapatite brings about bonding with the host bone without any intervening fibrous tissue layer. We expect hydroxyapatite-induced osteointegration to prevent particulate migration. Biodegradation of the hydroxyapatite coating occurs after 5 to 10 years. Bone ingrowth later relies on the surface roughness of the substrate.In conclusion, we suggest that the combination of impacted elastic acetabular cups with a thick polyethylene liner and bioactive coating can provide long term durability.


Role of brainstem thyrotropin-releasing hormone-triggered sympathetic overactivation in cardiovascular mortality in type 2 diabetic Goto-Kakizaki rats.
Sympathetic hyperactivity has an important role in cardiovascular mortality in patients with type 2 diabetes (T2D). Thyrotropin-releasing hormone (TRH)-containing fibers innervate autonomic motor and premotor nuclei of the brainstem and spinal cord that regulate cardiovascular functions. We compared cardiovascular responses to application of TRH-analog in the brainstem of Wistar and T2D Goto-Kakizaki (GK) rats. GK rats exhibited basal systolic hypertension (152±2 mm Hg) and had a significantly potentiated, dose-related hypertensive response to intracisternal (i.c.) injection of the TRH-analog RX77368 (10-60 ng). In GK rats only, i.c. RX77368 (30-60 ng) markedly increased heart rate (HR; +88 b.p.m.) and induced acute cardiac mortality (100%), concurrent with extreme hyperglycemia (>26 mmol l(-1)), increased plasma H(2)O(2) and 8-isoprostane, and enhanced heart expression of NADPH oxidase 4 and vascular cell adhesion molecule-1 mRNAs. GK rats also had elevated basal plasma epinephrine, higher adrenal gene expression of tyrosine hydroxylase and dopamine β-hydroxylase (DβH), and greater plasma catecholamine and adrenal DβH responses to i.c. TRH-analog, compared with Wistar rats. In GK rats, hexamethonium blocked i.c. RX77368-induced hypertensive and tachycardic responses, and reduced mortality by 86%, whereas phentolamine abolished the hypertensive response but enhanced tachycardia (+160 b.p.m.), and reduced mortality by 50%. The angiotensin II type 1 receptor antagonist irbesartan prevented i.c. RX77368-induced increases in blood pressure, HR and mortality. In conclusion, sympathetic overactivation triggered by brainstem TRH contributes to the mechanism of cardiovascular morbidity and mortality in T2D, which involves heightened cardiac inflammation and peripheral oxidative stress responses to sympathetic drive, and a mediating role of the renin-angiotensin system.


Seasonal patterns of total and energy reserve lipids of dominant zooplanktonic crustaceans from a hyper-eutrophic lake.
Seasonal patterns of lipid reserves and lipid classes of dominant zooplankton in a hyper-eutrophic lake were examined in relation to algal food resources. Triacylglycerol was the principle lipid energy reserve in all five species examined. During the height of the yearlyAphanizomenon flos-aquae bloom, lipid levels of the principle herbivores (Daphnia pulex andLeptodiaptomus sicilis) and an omnivore (Diacyclops bicuspidatus thomasi), were at their lowest concentration, suggesting that this cyanobacterium is nutritionally inadequate. As the cyanobacterial bloom began to collapse, bacterial numbers increased rapidly. The increase in bacterial numbers coincided with a large increase in areal lipid energy reserves ofDiaphanosoma leuchtenbergianum andChydorus sphaericus. Examination of seasonal patterns in the biomass of different algal species suggested thatRhodomonas minuta andCryptomonas erosa played a key role in nutrition, lipid deposition, and reproduction ofD. pulex andL. sicilis.


NNMT contributes to high metastasis of triple negative breast cancer by enhancing PP2A/MEK/ERK/c-Jun/ABCA1 pathway mediated membrane fluidity.
Elucidating the mechanism for high metastasis capacity of triple negative breast cancers (TNBC) is crucial to improve treatment outcomes of TNBC. We have recently reported that nicotinamide N-methyltransferase (NNMT) is overexpressed in breast cancer, especially in TNBC, and predicts poor survival of patients undergoing chemotherapy. Here, we aimed to determine the function and mechanism of NNMT on metastasis of TNBC. Additionally, analysis of public datasets indicated that NNMT is involved in cholesterol metabolism. In vitro, NNMT overexpression promoted migration and invasion of TNBCs by reducing cholesterol levels in the cytoplasm and cell membrane. Mechanistically, NNMT activated MEK/ERK/c-Jun/ABCA1 pathway by repressing protein phosphatase 2A (PP2A) activity leading to cholesterol efflux and membrane fluidity enhancement, thereby promoting the epithelial-mesenchymal transition (EMT) of TNBCs. In vivo, the metastasis capacity of TNBCs was weakened by targeting NNMT. Collectively, our findings suggest a new molecular mechanism involving NNMT in metastasis and poor survival of TNBC mediated by PP2A and affecting cholesterol metabolism.


A study of oil of bergamot and its importance as a phototoxic agent. II. Factors which affect the phototoxic reaction induced by bergamot oil and psoralen derivatives.
Using a standardized open photopatch test technique, the phototoxic reactions produced by bergamot oil bergapten (5-methoxypsoralen) the active component of the oil, and xanthotoxin (8-methoxypsoralen) were studied. The reaction was affected by a range of factors such as the vehicle (PMF or ethanol), the concentration of ethanol in the vehicle, the skin site, the interval between application of the psoralen and irradiation, the hydration of the skin, and the degree of natural or sun-induced pigmentation. Repeated photopatch testing at the same skin site produced an increase in sensitivity. Eye colour, natural susceptibility to suntanning, age, and sex, had no effect on the phototoxic response to psoralens.


Green in situ immobilisation of gold nanoparticles on bacterial nanocellulose membranes using Tannic acid and its detection of Fe3.
Oxidative stress is one of the factors that promote melanogenesis. Trivalent iron ions play a key role in regulating the iron-catalysed oxidative stress response. A novel SERS flexible membrane sensor based on tannic acid with good sensitivity and uniformity was prepared by green in situ reduction of gold nanoparticles on bacterial cellulose membrane(BCM)with a simple and highly selective method to detect Fe3+. Under alkaline conditions, Fe3+ is adsorbed on the BCM-TA@Au NPs flexible membrane by tannic acid (TA) through chelation, thus enabling the detection of Fe3+. Furthermore, this simple detection system has a wide linear detection range and high sensitivity to effortlessly evaluate Fe3+ at concentrations up to 10-7 M. More importantly, the proposed SERS flexible substrate performed well in determining Fe3+ concentrations in B16 melanocytes, providing new insights into the factors affecting the melanin synthesis pathway and providing a potential biomarker for melanoma treatment.


Atrial tachycardia mimicking atrioventricular nodal reentry tachycardia.
The term supraventricular tachycardia (SVT) is used to describe tachydysrhythmias that require atrial or atrioventricular nodal tissue for their initiation and maintenance. SVT can be used to describe atrioventricular nodal reentry tachycardia, atrioventricular reentry tachycardia, and atrial tachycardia (AT). AT is the least common of these SVT subtypes, accounting for only 10% of cases. Although the suggested initial management of each SVT subtype is different, they all can present with similar symptoms and electrocardiographic findings. Discuss the pathophysiology, diagnosis, and treatment of AT as compared with other types of SVT. We report a 56-year-old woman with symptoms and electrocardiographic findings consistent with SVT. Although standard treatment with intravenous adenosine failed to convert the SVT, it revealed AT as the cause of the tachydysrhythmia. The AT was successfully terminated with beta-blockade and the patient eventually underwent successful radioablation of three separate AT foci. AT frequently mimics other more common forms of SVT. AT might be recognized only when standard treatment of SVT has failed. Identification of AT in this setting is crucial to allow for more definitive therapy.


Population-based incidence of complicated diverticular disease of the sigmoid colon based on gender and age.
The purpose of this study was to characterize the gender and age differences in patients with clinically symptomatic sigmoid diverticular disease requiring surgery. All surgical patients hospitalized with proven diverticular disease requiring sigmoid resection from January 1988 to January 1998 were reviewed. A total of 934 patients requiring surgical resection for diverticular disease were admitted. There were 443 men and 491 women with an average age of 64. Forty-nine patients presented with massive rectal bleeding (males, 3.6 percent; females, 1.6 percent), 329 with chronic diverticulitis (males, 15.8 percent; females, 19.3 percent), 61 with obstructive symptoms (males, 2.7 percent; females, 3.9 percent), 148 with fistulas (males, 8.0 percent; females, 7.8 percent), 170 with perforation (male, 8.7 percent; female, 9.4 percent), 79 with abscess (males, 4.0 percent; females, 4.5 percent), 59 with stricture (males, 2.2 percent; females, 4.0 percent), and 39 with acute diverticulitis (males, 2.2 percent; females, 1.9 percent). Overall, patients younger than 50 presented more often with chronic or recurrent diverticulitis. Female patients present, on average, five years later than male with complications requiring surgery. Overall, men have a higher incidence of bleeding (P = 0.015), whereas women present more often with stricture and obstruction (P = 0.02). Young males present more with fistula (P = 0.03), whereas older males present with bleeding (P = 0.001). Young females present with perforation (P = 0.002), and older females present with chronic diverticulitis (P = 0.04) and stricture (P = 0.04).


The dynamic changes of chemical components and microbiota during the natural fermentation process in Da-Jiang, a Chinese popular traditional fermented condiment.
There is limited information on the chemical components and microbiota changes involved in da-jiang, a Chinese popular traditional fermented soybean condiment. Therefore, dynamic changes both in physicochemical quality and microbial community diversity of 20 samples of naturally fermented da-jiang collected over 95 days were measured, and we classified the samples into 5 groups (each containing 4 time points) according to the results. Based on OTUs analysis, Group 2 and Group 3 might represent the shift-stage between bacteria and fungi. Also, our results demonstrated that the formation of flavour, nutrient and quality of the traditional da-jiang were actually related to all of microbial community, especially the increased bacteria, including Staphylococcus and Leuconostoc. Correspondingly, 'Membrane Transport', 'Carbohydrate Metabolism', 'Amino Acid Metabolism' and 'Replication and Repair' were the top 4 KEGG pathways based on bacterial genes. The findings are expected to be helpful for us not only to understand the formation of flavour, taste and quality of traditional fermented da-jiang, but also to improve the industrialised fermented da-jiang.


Emetine protects mice from enterovirus infection by inhibiting viral translation.
IRES-driven translation plays an essential role in picornavirus infection. However, there are seldom reports of compounds targeting this pathway with effective protection in animal models. Here, we identified emetine, an antiprotozoal drug, which inhibits EV-A71 with an EC50 value of 0.04 μM and a CC50 value of 10 μM in RD cell culture. Interestingly, emetine exhibits activities against a series of human enteroviruses, including CV-A16, CV-B1, EV-D68, Echov-6, etc., at the nanomolar level. When orally administered at 0.20 mg/kg twice a day in an EV-A71 mouse model, emetine reduced viral loads in various organs and completely prevented diseases and death. A mechanistic study demonstrated that emetine suppressed EV-A71 by inhibiting viral IRES-driven translation. Taken together, these data indicate emetine as a promising candidate to treat picornavirus infection.


Biological age and its estimation. II. Assessment of biological age of albino rats by multiple regression analysis.
Multiple regression model of biological age (BA) theoretically gives agreement with the main concept of BA. When assessment of BA is based on the model, the age being in regression center, the method provides satisfactory results, whereas BA estimates of individuals in extreme age groups are erroneous. Investigation of male and female Wistar rats of age 5-29 months showed the BA estimates calculated from 4-10 physiological indices in young (5-7 mo) animals are overestimated, and in old (24-28 mo) animals are underestimated. Coincidence of average BA in one-age group of animals with its chronological age served as a criterion for the correspondence of the estimate to "real" BA. The paper also examines the following questions: the necessary and sufficient number of physiological indices; the sample size from the intact animal population to establish normal aging standard; the relationship between BA and animal weight.


Long term risk of death and readmission after hospital admission with covid-19 among older adults: retrospective cohort study.
To characterize the long term risk of death and hospital readmission after an index admission with covid-19 among Medicare fee-for-service beneficiaries, and to compare these outcomes with historical control patients admitted to hospital with influenza. Retrospective cohort study. United States. 883 394 Medicare fee-for-service beneficiaries age ≥65 years discharged alive after an index hospital admission with covid-19 between 1 March 2020 and 31 August 2022, compared with 56 409 historical controls discharged alive after a hospital admission with influenza between 1 March 2018 and 31 August 2019. Weighting methods were used to account for differences in observed characteristics. All cause death within 180 days of discharge. Secondary outcomes included first all cause readmission and a composite of death or readmission within 180 days. The covid-19 cohort compared with the influenza cohort was younger (77.9 v 78.9 years, standardized mean difference -0.12) and had a lower proportion of women (51.7% v 57.3%, -0.11). Both groups had a similar proportion of black beneficiaries (10.3% v 8.1%, 0.07) and beneficiaries with dual Medicaid-Medicare eligibility status (20.1% v 19.2%; 0.02). The covid-19 cohort had a lower comorbidity burden, including atrial fibrillation (24.3% v 29.5%, -0.12), heart failure (43.4% v 49.9%, -0.13), and chronic obstructive pulmonary disease (39.2% v 52.9%, -0.27). After weighting, the covid-19 cohort had a higher risk (ie, cumulative incidence) of all cause death at 30 days (10.9% v 3.9%; standardized risk difference 7.0%, 95% confidence interval 6.8% to 7.2%), 90 days (15.5% v 7.1%; 8.4%, 8.2% to 8.7%), and 180 days (19.1% v 10.5%; 8.6%, 8.3% to 8.9%) compared with the influenza cohort. The covid-19 cohort also experienced a higher risk of hospital readmission at 30 days (16.0% v 11.2%; 4.9%, 4.6% to 5.1%) and 90 days (24.1% v 21.3%; 2.8%, 2.5% to 3.2%) but a similar risk at 180 days (30.6% v 30.6%;-0.1%, -0.5% to 0.3%). Over the study period, the 30 day risk of death for patients discharged after a covid-19 admission decreased from 17.9% to 7.2%. Medicare beneficiaries who were discharged alive after a covid-19 hospital admission had a higher post-discharge risk of death compared with historical influenza controls; this difference, however, was concentrated in the early post-discharge period. The risk of death for patients discharged after a covid-19 related hospital admission substantially declined over the course of the pandemic.


Designed synthesis of double-stage two-dimensional covalent organic frameworks.
Covalent organic frameworks (COFs) are an emerging class of crystalline porous polymers in which organic building blocks are covalently and topologically linked to form extended crystalline polygon structures, constituting a new platform for designing π-electronic porous materials. However, COFs are currently synthesised by a few chemical reactions, limiting the access to and exploration of new structures and properties. The development of new reaction systems that avoid such limitations to expand structural diversity is highly desired. Here we report that COFs can be synthesised via a double-stage connection that polymerises various different building blocks into crystalline polygon architectures, leading to the development of a new type of COFs with enhanced structural complexity and diversity. We show that the double-stage approach not only controls the sequence of building blocks but also allows fine engineering of pore size and shape. This strategy is widely applicable to different polymerisation systems to yield hexagonal, tetragonal and rhombus COFs with predesigned pores and π-arrays.


Rough annealing by two-step clustering, with application to neuronal signals.
To accomplish analyses on the properties of neuronal populations it is mandatory that each unit activity is identified within the overall noise background and the other unit signals merged in the same trace. The problem, addressed as a clustering one, is particularly difficult as no assumption can be made on the prior data distribution. We propose an algorithm that achieves this goal by a two-phase agglomerative hierarchical clustering. First, an inflated estimation (overly) of the number of clusters is cast down and, by a maximum entropy principle (MEP) approach, is made to collapse towards an arrangement near natural ones. In the second step consecutive partitions are created by merging, two at time previously aggregated partitions, according to similarity criteria, in order to reveal a cluster solution. The procedure makes no assumptions about data distributions and guarantees high robustness with respect to noise. An application on real data out of multiple unit recordings from spinal cord neurons of mixed gas-anaesthetized rats is presented.


Synchronized retroperfusion of coronary veins for circulatory support of jeopardized ischemic myocardium.
A retroperfusion system was developed that augments retrograde delivery of arterial blood into an acutely ischemic myocardial region during diastole and facilitates coronary venous drainage in systole. An electrocardiogram-synchronized, gas-actuated bladder pump propels retroperfusate through an autoinflatable balloon catheter whose tip is placed within the regional coronary vein that drains the ischemic myocardium. Experiments were performed in 26 closed chest dogs with 4 hour intracoronary balloon occlusion of the proximal left anterior descending coronary artery. An untreated control series consisted of 13 dogs; the remaining 13 dogs were treated with retroperfusion, which was initiated after the first hour of acute coronary occlusion. Synchronized retroperfusion resulted in a significant 37 +/- 10 per cent (mean +/- standard error of the mean) decrease in left ventricular end-diastolic pressure from 11 +/- 2 to 5 +/- 21 mm Hg, a 20 +/- 4 percent decrease in peak systolic pressure (140 +/- 7 to 110 +/- 6 mm Hg) and a 25 +/- 6 percent reduction in systemic vascular resistance (3,880 +/- 340 to 2,380 +/- 300 dynes sec cm-5). Ischemic region intracoronary S-T segment elevation decreased 40 +/- 15 percent, and potassium loss was reduced 92 +/- 22 percent. Partial pressure of oxygen measured distal to the coronary occlusion decreased 36 +/- 2 percent, suggesting oxygen delivery to and extraction by the jeopardized ischemic myocardium. Ventriculography in four dogs revealed an increase in left ventricular ejection fraction and reversal of ischemic segment dyskinesia by synchronized retroperfusion. A nitro-blue tetrazolium study of 10 excised hearts indicated that 3 hours of synchronized retroperfusion significantly reduced the size of ischemic injury to 3.3 +/- 2 percent of the left ventricle (versus 16.2 +/- 5 percent in the untreated control group). In addition, retroperfusion appeared to correct ischemic arrhythmias. The experimental data suggest that this treatment is capable of improving cardiac function and salvaging jeopardized myocardium. Clinical application is envisioned as a prompt temporary emergency support for acute and profound ischemic dysfunction not readily treatable by other interventions.


Lithium-sensitive production of inositol phosphates during amphibian embryonic mesoderm induction.
Mesoderm induction and body axis determination in frog (Xenopus) embryos are thought to involve growth factor-mediated cell-cell signaling, but the signal transduction pathways are unknown. Li+, which inhibits the polyphosphoinositide (PI) cycle signal transduction pathway in many cells, also disrupts axis determination and mesoderm induction. Amounts of the PI cycle-derived second messenger, inositol 1,4,5-trisphosphate, increased during mesoderm induction in normal embryos; addition of Li+ inhibited the embryonic inositol monophosphatase and reversed this increase. Embryonic PI cycle activity thus shows characteristics that indicate it may function in mesoderm induction and axis determination.


Effect of H2O2 on Na,K-ATPase.
Na,K-ATPase is a member of the P-type ATPase family, which transforms the energy of ATP to the transmembrane Na/K gradient that is used to create membrane potential, support the excitability of neurons and myocytes, control pH, and transport substances. The regulation of the Na,K-ATPase function by physiological regulators also comprises a central role in the adaptation of organisms to different conditions. H2O2 is one of the main signaling molecules in redox metabolism and plays important function in cellular physiology. H2O2 also regulates signaling pathways via the specific oxidation of proteins harboring redox-sensitive moieties, like metal centers or cysteine residues, which control their activity. The Na,K-ATPase is redox-sensitive with an "optimal redox potential range," where the reactive oxygen species (ROS), levels beyond this "optimal range" are responsible for enzyme inhibition. Thus reactive oxygen species manifest a hermetic effect, which is expressed by biphasic action; stimulation by low doses and inhibition by high doses. This study was aimed to reveal redox-sensitivity of brain synaptic membrane fractions Na,K-ATPase via H2O2 effects. Different concentrations of H2O2 change the kinetic parameters of the enzyme system for MgATP complex, Na+, and K+ differently. Moreover, H2O2 changes p-chloromercuribenzoic acids (PCMB) affinity. H2O2 targets thiols of the Na,K-ATPase - low and high concentrations of H2O2 change the oxidative state of thiolate (S-) from Cys differently, resulting in the corresponding activation or inhibition of the enzyme. Targeting thiols of the Na,K-ATPase tunes the activity of the Na,K-ATPase to the cellular demands and sustains the enzyme activity at the "optimal" level.


Camalexin accumulation in Arabis lyrata.
Inoculation of leaves of Arabis lyrata with either a bacterial pathogen Pseudomonas syringae pv. maculicola strain ES4326 or Cochliobolus carbonum, a fungal nonpathogen of A. lyrata, resulted in the accumulation of a compound with similar chromatographic and fluorescent properties to that of camalexin (I), a phytoalexin produced by Arabidopsis thaliana. A. lyrata is closely related to A. thaliana. High resolution electron impact mass spectroscopic and proton NMR analysis confirmed that the compound produced by A. lyrata is camalexin.


Invisible genomes: the genomics revolution and patenting practice.
In the mid-1990s, the company Human Genome Sciences submitted three potentially revolutionary patent applications to the US Patent and Trademark Office, each of which claimed the entire genome sequence of a microorganism. The patent examiners, however, objected to these applications, and after negotiation they were eventually re-written to resemble more traditional gene patents. In this paper, which is based on a study of the patent examination files, we examine the reasons why these patent applications were unsuccessful in their original form. We show that with respect to utility and novelty, the patent attorney's case built on an understanding of the genome as a computer-related invention. The patent examiners did not object to the patenting of complete genome sequences as computer-related inventions on moral grounds or in terms of the distinction between a discovery and an invention. Instead, their objections were based on classification, rules and procedure. Rather than patent examiners having a notion of a genome that should not be patented, the notion of a 'genome', and the ways in which it may be different from a 'gene', played no role in these debates. We discuss the consequences of our findings for patenting in the biosciences.


Neuronal correlates of a perceptual decision.
The relationship between neuronal activity and psychophysical judgement has long been of interest to students of sensory processing. Previous analyses of this problem have compared the performance of human or animal observers in detection or discrimination tasks with the signals carried by individual neurons, but have been hampered because neuronal and perceptual data were not obtained at the same time and under the same conditions. We have now measured the performance of monkeys and of visual cortical neurons while the animals performed a psychophysical task well matched to the properties of the neurons under study. Here we report that the reliability and sensitivity of most neurons on this task equalled or exceeded that of the monkeys. We therefore suggest that under our conditions, psychophysical judgements could be based on the activity of a relatively small number of neurons.


Validation of the Parama-Tech PS-501 device for office blood pressure measurement according to the international protocol.
The PS-501 device (Parama-Tech, Fukuoka, Japan), an automated device for office blood pressure measurement based on the Korotkoff method and designed for professional use in clinical settings, was validated. Consecutive outpatients with hypertension and ≥30 years old at an outpatient hypertension clinic were recruited. According to the European Society of Hypertension protocol, 33 participants were included in the validation study (phase 1, n = 15; phase 2, n = 18). The cuff deflation rate can be selected manually from 2, 3, and 4 mm Hg/beat. The validation was performed with the device deflating at a rate of 2 mm Hg/beat. All blood pressure readings were measured on the left arm. The tested device passed all criteria for both systolic and diastolic blood pressure measurements. The mean (± standard deviation) differences in systolic and diastolic blood pressure between the tested device and the mean of observer readings were -1.9 ± 4.6 and -2.5 ± 2.9 mm Hg, respectively. The PS-501 device for office blood pressure measurement passed all the validation criteria of the European Society of Hypertension and can therefore be recommended for clinical use in an adult population.


Fabrication of polyelectrolyte multilayered nano-capsules using a continuous layer-by-layer approach.
The layer-by-layer approach is a highly versatile method for the fabrication of multilayered polymeric films and capsules. It has been widely investigated in research for various polyelectrolyte pairs and core template particles. However, the fabrication of nano-sized capsules at the larger scale is difficult and time consuming, due to the necessity of washing and centrifugation steps before the deposition of each polyelectrolyte layer. This results not only in a very long fabrication time, but also in the partial loss of particles during those intermediate steps. In this study, we introduced a continuous approach for the fabrication of multilayer polyelectrolyte based nano-capsules using calcium phosphate core nanoparticles and a tubular flow type reactor with the potential for synthesizing tens of milligrams of capsules per hour. Adsorption of the polyelectrolyte layer occurred in the tubing where particles and polyelectrolyte solution of choice were mixed, creating a layer of polyelectrolyte on the particles. After this, these newly surfaced-modified particles passed into the next segment of tubing, where they were mixed with a second polyelectrolyte of opposite charge. This process can be continuously repeated until the desired number of layers is achieved. One potential problem with this method concerned the presence of any excess polyelectrolyte in the tubing, so careful control of the amount of polymer added was crucial. It was found that slightly under dosing the amount of added polyelectrolyte ensured that negligible unadsorbed polyelectrolyte remained in solution. The particles created at each deposition step were stable, as they all had a zeta potential of greater than ±25mV. Furthermore the zeta potential measurements showed that charge reversal occurred at each stage. Having achieved the necessary number of polyelectrolyte layers, the calcium phosphate cores were easily removed via dissolution in either hydrochloric or acetic acid.


Pneumococcal Disease in the Era of Pneumococcal Conjugate Vaccine.
Universal immunization of infants and toddlers with pneumococcal conjugate vaccines over the last 15 years has dramatically altered the landscape of pneumococcal disease. Decreases in invasive pneumococcal disease, all-cause pneumonia, empyema, mastoiditis, acute otitis media, and complicated otitis media have been reported from multiple countries in which universal immunization has been implemented. Children with comorbid conditions have higher rates of pneumococcal disease and increased case fatality rates compared with otherwise healthy children, and protection for the most vulnerable pediatric patients will require new strategies to address the underlying host susceptibility and the expanded spectrum of serotypes observed.


Analysis of the anatomical distribution of GAD67 mRNA encoding truncated glutamic acid decarboxylase proteins in the embryonic rat brain.
During development of the central nervous system (CNS) the gene that encodes the 67 kDa form of glutamic acid decarboxylase (GAD) undergoes alternative splicing. The alternatively spliced variants include an exon (referred to as ES, for embryonic stop) that contains a premature stop codon. The detection of mRNA containing the ES exon in embryonic rat brain has been previously reported (Proc. Natl. Acad. Sci., 87 (1990) 8771-8775). We have used in situ hybridization to identify the anatomical distribution of ES mRNA in the embryonic rat brain during two stages of development, embryonic day 17 (E17) and E20. At E17, GAD67 mRNA was expressed in several CNS regions that were destined to contain GABAergic neurons when mature. ES transcripts were predominantly localized to ventricular zones and other regions associated with populations of proliferative cells at E17 and E20. At both ages, however, the alternatively spliced variants were also detected in regions of brain associated with migratory or post-mitotic neurons. GAD67 transcripts that did not include the ES exon were localized to anatomical areas that contained post-mitotic, and often post-migratory neurons. The temporal and spatial disappearance of mRNA containing the ES exon generally followed a caudal-to-rostral gradient which paralleled neuronal terminal mitosis and differentiation.


The Relationship between KIT Copy Number Variation, Protein Expression, and Angiogenesis in Sporadic Breast Cancer.
KIT is a protooncogene that encodes for the KIT oncoprotein, which is a transmembrane tyrosine kinase growth factor receptor that holds a critical role in a variety of normal physiological and pathological processes including angiogenesis. KIT has been shown to be involved in tumorigenesis, contributing to the development of gastrointestinal carcinoma and leukemia. A link between KIT overexpression and breast cancer development has previously been reported. In the current study, we explored KIT gene expression and exonic copy number variants (CNV) and the relationship with angiogenesis (CD34) and the clinicopathological features of breast cancer. MLPA technique was used to determine the CNV in 64 breast cancer tumor samples from patients diagnosed with primary sporadic breast cancer. Results were confirmed by quantitative PCR. Expression of KIT and CD34 was determined using immunohistochemistry (IHC). Our results show that 28.1% of the tumor samples from patients with primary sporadic breast cancer had CNV in the KIT gene. Among the breast tumor samples, 54.7% showed positive KIT expression. The expression of the CD34 angiogenesis marker was reported in 43.8% of the tumor samples as low, 42.2% as moderate and 14.1% as high. A significant correlation between increased CNV of KIT exons, a high level of angiogenesis (CD34) and increased tumor grade was observed (p< 0.05). A significant correlation between the KIT CNV and the angiogenesis marker was found. Examining KIT expression and CNV has the potential to function as a biomarker for tyrosine kinase inhibitor drugs in breast cancer.


A gene located at 72A in Drosophila melanogaster encodes a novel zinc-finger protein that interacts with protein kinase CK2.
Drosophila melanogaster protein kinase CK2 (DmCK2) is a Ser/Thr protein kinase composed of catalytic alpha and regulatory beta subunits associated as an alpha2beta2 heterotetramer. Using the two hybrid system, we have screened a Drosophila embryo cDNA library in order to identify proteins that interact with DmCK2alpha. One of these cDNAs encodes a novel previously undescribed zinc-finger protein, which we call ZFP47. ZFP47 interacts with DmCK2alpha but not with DmCK2beta, indicating that this interaction is specific for the catalytic subunit of CK2. In situ hybridization to polytene chromosomes indicates that the corresponding gene is located at the 72A interval of chromosome III. Sequence analysis indicates that ZFP47 contains a consensus site for phosphorylation by CK2, 4 C1H1-type zinc-fingers, and a bipartite nuclear localization signal. Consistent with the prediction of a site for phosphorylation by CK2, we demonstrate that ZFP47 is phosphorylated by CK2 purified from Drosophila embryos. These studies demonstrate that ZFP47 is a new physiological partner and substrate of CK2.


Distribution of substance P-like immunoreactivity in the lower brainstem of the human fetus: an immunohistochemical study.
The regional distribution of substance P-like immunoreactive (SPI) structures in the lower brainstem of the human fetus was investigated using the indirect immunofluorescence technique. SPI cells were found in a number of areas including the inferior colliculus, central gray matter of the midbrain, n. laterodorsalis tegmenti, midbrain and medullary reticular formation, n. vestibularis inferior, and n. prepositus hypoglossi. An extensive network of SPI fibers of varying densities were identified throughout the lower brainstem.


The Psychoanalytic Concept of Jouissance and the Kindling Hypothesis.
This article aims to define the conceptual field of jouissance in Lacanian theory, and put forth the hypothesis of a relationship between certain neurophysiological mechanisms and specific clinical phenomena where jouissance is "kindled" and outside the control of the symbolic process. First, the author briefly introduces Lacan's notion of jouissance and the way it draws on Freud's theorization, and describes the preliminary stages of this conceptual field in Lacan's work. Then, the jouissance related to two other concepts: repetition, with its Freudian and Lacanian nuances, as well as the-exclusively-Lacanian concept of the object petit a. Lacan's later conceptualization of language as jouissance (the notion of lalangue) is then discussed in relation to Freud's early ideas ("Letter 52") on the different kinds of inscriptions that help form the mental apparatus. Finally, the author tries to formulate a hypothesis regarding specific neurophysiological mechanisms, based on clinical situations where jouissance becomes "kindled" and escapes the control of the symbolic processes through the neurophysiological mechanisms of conditioning, "kindling-sensitization" and "excitotoxicity." In these cases, jouissance can have a destructive effect on the body and can affect, among others organs, the brain-a process the author has previously described heuristically as the "psychosomatic diseases of the brain." This would be a special mechanism of automatism that would be triggered under the specific conditions of the fragility of the signifying chain (foreclosure of the Name-of-the-Father or solidification of the signifying chain) in combination with biological factors, including genetic factors. In this process, signifiers are reduced to signals, which in turn may be reduced to stimuli, with a tendency toward self-perpetuation, while affects are reduced to emotions and moods. Thus, conditioning and kindling-sensitization could also be understood in terms of a "semiotic reduction." Can we therefore consider that certain phenomena of automatism and certain deficits (delusional moods, schizophrenic apathy, etc.) could be seen as psychosomatic disorders of the brain? The phenomena in question might also serve-albeit at random-as a kind of shield to mitigate excessive jouissance.


Dietary isoflavone-induced, estrogen receptor-β-mediated proliferation of Caco-2 cells is modulated by gallic acid.
Dietary isoflavones and their biotransformation products (from food fermentation) are estrogen mimics which activate estrogen receptors (ER)α and ERβ. In silico molecular modelling is used to determine theoretical binding energies of genistein, daidzein and hydroxylated biotransformation products, and to investigate structure-binding energy relationships with ERβ. Results suggest that ligand hydroxyl arrangement determines binding energy and influences binding affinity. Caco-2 cells (ERβ expressing) are used to study the proliferative effect of genistein, daidzein and their hydroxylated biotransformation products. Isoflavones/biotransformation products showed weaker enhancement of Caco-2 proliferation than 17β-estradiol. The EC50s of isoflavones/biotransformation products agreed with in silico-predicted binding affinity order. Hydroxylated biotransformation products studied showed greater Caco-2 proliferative effects than the parent isoflavones except 8-hydroxygenistein, probably due to unfavourable ERβ interactions caused by 8-hydroxygenistein's extra hydroxyl. Caco-2 pre-treatment with UDP-glucose dehydrogenase inhibitor gallic acid promoted genistein/8-hydroxygenistein-mediated proliferation. This is probably due to a reduced isoflavone glucuronidation to form low estrogenicity glucuronides. Findings are discussed in the context of dietary isoflavones/gallic acid and effects on proliferation of ERβ-expressing gut cancer cells.


Food taboos in maternal and child health: the views of traditional healers in Ile-Ife, Nigeria.
This paper reports the interviews with 82 randomly selected healers in Ile-Ife about food taboos in relation to maternal and child health. The healers were asked to list the childhood ailments they treat most often and the food proscriptions and prescriptions associated with these ailments. Of particular interest in the study was the fact that these food proscriptions and prescriptions form an integral part of traditional medical procedures in that relapses or slow rate of recovery are sometimes attributed to a break of these food norms. Moreover, these proscriptions and prescriptions reflect: (i) the healers' concept of the various childhood diseases and (ii) the healers' belief in the respect for the traditional Yoruba gods in health matters. It was further noted that although these taboos reinforce the beliefs in traditional medicine, their relevance from the point of view of the health of the clientele needs further investigation.


Differential effects of apolipoprotein E isoforms on lipolysis of very low-density lipoprotein triglycerides.
Apolipoprotein (apo) E plays a key role in lipoprotein metabolism and has been proposed to modulate triglyceride (TG) lipolysis. However, no systematic investigation on lipolysis using all 3 isoforms of apoE has been performed. To clarify the role of common human apoE isoforms in the lipolysis of very low-density lipoprotein (VLDL) TGs, we overexpressed human apoE isoforms in apoE and low-density lipoprotein receptor-deficient mice using adenoviral-mediated gene transfer and used VLDL particles obtained from these mice for in vitro lipolysis assay. Overexpression of apoE, regardless of its isoforms, increased the TG content of VLDL in mice in vivo. In vitro analysis of the effect of apoE on lipolysis revealed that irrespective of its isoforms, apoE did inhibit TG lipolysis at every concentration of apoE examined, and this inhibitory effect became more pronounced as the apoE content of VLDL increased. No difference was observed in TG lipolysis activity among isoforms at low apoE/TG ratio; however, intermediate ratios of apoE/TG, which reflect physiologic VLDL apoE/TG ratios, demonstrated a significantly greater level of lipolysis inhibition in apoE2, but less so in apoE4 compared with other isoforms. This differential effect by apoE isoforms on lipolysis was attenuated at higher apoE/TG ratios; nevertheless, apoE2 still inhibited lipolysis significantly more than did apoE4. Enrichment of VLDL with apoE decreased both the apoC contents and apoC-II/C-III ratios of VLDL, contributing, at least in part, to the inhibitory function of apoE on lipolysis. The present study clarifies the differential lipolysis-modulating effect of apoE isoforms, which would help explain the difference in pre- and postprandial TG levels among humans carrying different apoE isoforms.


Clinimetric evaluation of a new overall disability scale in immune mediated polyneuropathies.
To determine the validity, reliability, and responsiveness of a new overall disability sum score in immune mediated polyneuropathies. Three impairment measures (MRC sum score, sensory sum score, grip strength (Vigorimeter)) and three disability scales (an overall disability sum score (ODSS), Hughes' functional scale (f score), Rankin scale) were assessed in a cross sectional group of 113 clinically stable patients (83 with Guillain-Barré syndrome, 22 with chronic inflammatory demyelinating polyneuropathy (CIDP), eight with a gammopathy related polyneuropathy). The ODSS was also used serially in 20 patients with recently diagnosed Guillain-Barré syndrome (n = 7) or CIDP (n = 13) and changing clinical conditions. Multiple regression studies were performed to compare the impact of impairment disturbances (independent variables) on the various disability scales (dependent variable). Moderate to good construct validity (stable group: Spearman's rank test (absolute values), r = 0.41-0.79; longitudinal group: multiple correlation coefficient, R = 0.69-0.89; p < 0.006 for all associations) and reliability (intraclass correlation coefficient, R = 0.90-0.95; p < 0.0001) were demonstrated for the ODSS. Its SRM values were high (> 0.8), indicating good responsiveness. Impairment measures accounted for a higher variance proportion of the ODSS compared with the f score and Rankin (R = 0.64 v 0.56 and 0.45, respectively). All clinimetric requirements were met by the overall (arm and leg) disability sum score in immune mediated polyneuropathies. Its use is therefore suggested in evaluating immune mediated polyneuropathies.


Guinea pig pancreatic polypeptide: structure and pancreatic content.
Guinea pig (GP) pancreatic polypeptide (PP) has been purified from an acid-alcohol extract of 6 GP pancreata by a series of 3 HPLC steps. The sequence for GP PP as compared with that of beef and human is shown: (Sequence: see text). In a single GP pancreas weighing 2.4 g the total PP content was 1.0 nmol and the total glucagon content 61 nmol; in a single dog pancreas weighing 35 g the total PP was 385 nmol and the total glucagon 81 nmol. The relatively low content of PP in GP pancreas is consistent with the fact that the GP lacks a ventral pancreas, the region in which PP is found in highest concentration. The high glucagon content of GP pancreas is consistent with that reported in earlier studies.


[Demographic development of Lymnaea (Galba) truncatula Müller in Haute-Vienne, France. About observations on 4 years (1973-1976) (author's transl)].
Notes on the influence of shallow drainage and predation by Zonitoides nitidus on Lymnaea truncatula populations in 4 types of habitats. The populations of snails are observed with large and perceptibly constant numbers by the regular maintenance of drainage. Irregular maintenance is followed by a gradual fall of numbers of snails with their rapid increase in the year following autumnal ditch-digging. Grass-mowing of swampy meadows at the beginning of summer drying distinctly restricts numbers of snails, when Zonitoides nitidus lives in the habitats.


A theoretical model for layered visual processing.
A theoretical general model of layered computation in the retina is presented. Each layer is functional in the sense that it may correspond or not to an anatomical layer. It is formed by computing elements which can perform in principle any non-linear arbitrary function on a three-dimensional input space. This space consists of 2 spatial dimensions, plus time. The function performed by each computing element of a layer is simplified for the cases of invariance, space or time linearity and for time independence. Two illustrations are also presented. The first is a model of the simple ganglion cells in cat's retina. The second, a model of the group 2 ganglion cell of the frog's retina.


Increased osteopontin in muscle and serum from patients with idiopathic inflammatory myopathies.
Osteopontin (OPN) is a non-traditional pro-inflammatory cytokine and is involved in muscle regeneration and inflammation. The aim of this study was to investigate the expression of OPN in skeletal muscle and serum of patients with IIMs. 45 patients with IIMs (27 with PM and 18 with DM) were included in the study. Patients received initial prednisone therapy (1-1.5 mg/kg/day) without other immunosuppressive agents. Muscle biopsies were taken before start of treatment and serum samples were collected from each patient before and after corticosteroid treatment. The expression of OPN in skeletal muscle was using immunofluorescence staining and western blotting. Serum OPN levels were detected by enzyme-linked immunosorbent assays (ELISA). OPN expression was increased in muscle samples from IIM patients compared to control muscle. The serum level of OPN was significantly higher in IIM patients than in controls. Moreover, the serum concentrations in the DM subgroup were significantly higher compared to the PM groups. Serum OPN levels positively correlated with creatinine kinase (CK), C-reactive protein (CRP) in PM and DM patients, respectively. After corticosteroid treatment, serum OPN levels decreased significantly in steroid responders compared to baseline, but no significant decrease was observed in steroid non-responders. OPN is increased in patients with DM and PM, both in muscle and serum. OPN may play an important role in the pathogenesis of IIMs. Moreover, serum OPN may be a potential biomarker for this illness, and changes in serum OPN may provide an index of therapeutic efficacy.


Integrating remote sensing and machine learning to detect turbidity anomalies in hydroelectric reservoirs.
Monitoring water quality in reservoirs is essential for the maintenance of aquatic ecosystems and socioeconomic services. In this scenario, the observation of abrupt elevations of physicochemical parameters, such as turbidity and other indicators, can signal anomalies associated with the occurrence of critical events, requiring operational actions and planning to mitigate negative environmental impacts on water resources. This work aims to integrate Machine Learning methods specialized in anomaly detection with data obtained from remote sensing images to identify with high turbidity events in the surface water of the Três Marias Hydroelectric Reservoir. Four distinct threshold-based scenarios were evaluated, in which the overall performance, based on F1-score, showed decreasing trends as the thresholds became more restrictive. In general, the anomaly identification maps generated through the models ratified the applicability of the methods in the diagnosis of surface water in reservoirs in distinct hydrological contexts (dry and wet), effectively identifying locations with anomalous turbidity values.


Sialolithiasis. A survey on 245 patients and a review of the literature.
245 patients with sialolithiasis, treated during a period of 20 years, were evaluated and the literature has been reviewed. The submandibular gland was involved in 231 patients, the parotid gland in 11 patients, and the sublingual gland only in 1 patient. There is some indication that patients with sialolithiasis are more prone to develop nephrolithiasis. A relationship with other systemic disorders could not be detected. Laser treatment seems to be a promising treatment modality for stone removal, even in acute phases.


Environmental Effectors on the Inactivation of Human Adenoviruses in Water.
Environmental factors are highly relevant to the global dissemination of viral pathogens. However, the specific contribution of major effectors such as temperature and sunlight on the inactivation of waterborne viruses is not well characterized. In this study, the effect of temperature (7, 20, and 37 °C), UVB and UVA radiation on viral inactivation was evaluated in phosphate buffered saline (PBS), mineral water, wastewater, 1,000-fold diluted wastewater and seawater. The stability of human adenoviruses infectivity, known as human pathogens and indicators of fecal contamination, was monitored during 24 h, both in the dark and exposed to UV radiation by immunofluorescence assays. In the dark, no Human adenovirus (HAdV) inactivation was observed in PBS and mineral water at any of the temperatures studied, whereas at 37 °C in reactors with higher microbial concentration (wastewater, diluted wastewater, and seawater), decays between 2.5 and 5 log were recorded. UVB radiation showed a dramatic effect on HAdV inactivation and 6-log were achieved in all reactors by the end of the experiments. The effect of UVA showed to be dependent on the water matrix analyzed. At 20 °C, HAdV showed a 2-log decay in all reactors radiation while at 37 °C, results in wastewater, diluted wastewater, and seawater reactors were equivalent to those observed in the dark. These results suggest UVB radiation as the major environmental factor challenging viral inactivation, followed by biotic activity indirectly associated to higher temperatures and finally, by UVA radiation.


Quinolone-resistant Neisseria gonorrhoeae: the beginning of the end? Report of quinolone-resistant isolates and surveillance in the southwestern United States, 1989 to 1997.
Fluoroquinolones are one of the most widely used treatments for gonorrhoeae. Changes in the susceptibility of Neisseria gonorrhoeae to these agents may threaten their use. To report several resistant strains (>1 mcg/ml) isolated in the western United States and to evaluate the prevalence of strains with reduced susceptibility (ofloxacin 0.25 mcg/ml, ciprofloxacin 0.06 mcg/ml). The microbiology and epidemiology of three resistant strains were characterized and 12,761 other strains were evaluated for fluoroquinolone susceptibility as part of the Gonococcal Isolate Surveillance Project of the Centers for Disease Control and Prevention. Fluoroquinolone-resistant strains may appear sporadically. The prevalence of isolates with reduced susceptibility to fluoroquinolones remains low in the Southwest region of the United States. Continued active surveillance is needed to detect and control the spread of quinolone-resistant Neisseria gonorrhoeae.


One stage reconstruction of a massive back defect with a large fasciocutaneous flap.
The use of fasciocutaneous flaps in the treatment of soft tissue defects has been widely accepted. This study presents a case in which a huge defect after surgical resection of an advanced rhabdomyosarcoma was reconstructed by an extraordinarily large vertical fasciocutaneous flap from the back.


Assessment of knowledge, skills, and attitudes of nuns with regard to breast cancer prophylaxis.
The aim of the study was to verify whether nuns are aware of the need to self-examine their breasts and whether their level of knowledge and skills is sufficient to carry out the control properly. Subject to the study were nuns from various convents from the town of Przemyśl. The sample consisted of 82 nuns. The research tool used was a self-constructed questionnaire. On the basis of the study, it has been found that the subjects' level of knowledge regarding breast cancer is unsatisfactory and, although the awareness of the need of self-control is high, it does not influence the regularity of performance thereof.


COVID-19 in patients with cancer: can baseline radiologic severity and early evolution predict clinical outcomes?
To determine whether the degree of parenchymal involvement on chest radiograph (CXR) at the time of COVID-19 diagnosis and its early radiologic evolution can predict adverse events including hospitalization, intubation, and death in patients with cancer. Retrospective study of 627 COVID-19-positive patients between March and April 2020, of which 248 had baseline CXR within 72 h of diagnosis and 64 patients had follow-up wihtin72 h. CXRs were classified as abnormal (i.e., radiologic findings suggestive of COVID-19 infection were noted), normal, or indeterminate. Baseline and follow-up severity scores were calculated based on lung regions in abnormal CXRs. Statistical analysis was performed to determine associations between abnormal CXR or severity score with adverse events. Of 248 patients (median age = 65) with a baseline CXR, 172/248 (69%) had an abnormal baseline study, which was associated with hospitalization (p < 0.001), intubation (p = 0.001), and death (p = 0.005). For patients with solid neoplasms, when adjusted for stage, it was associated with hospitalization (p = 0.0002), intubation (p = 0.019), and death (p = 0.03). The median baseline severity score was 3 (range = 1-10); the greater the score, the higher the likelihood of adverse outcome (p < 0.003 for all). A baseline severity score > 9 predicted > 50% probability of intubation and a score of ≥ 10 predicted > 50% of probability of death. The baseline severity score was not correlated with cancer-related treatment. Early radiologic progression was not correlated with hospitalization, intubation, or death. The degree of parenchymal involvement on CXR within 72 h of COVID-19 diagnosis is associated with adverse outcomes in patients with cancer. • In patients with cancer, the presence and severity of radiologic manifestation of COVID-19 on chest radiographs within 72 h of COVID-19 diagnosis are associated with hospitalization, intubation, and death. • Early radiologic progression on chest radiographs is not correlated with adverse outcomes.


Immunosuppression by mesenchymal stromal cells: from culture to clinic.
Extensive in vitro studies have shown that multipotent mesenchymal stromal cells (MSC) can exert profound immunosuppressive effects via modulation of both cellular and innate immune pathways. Their ability to be readily isolated from a number of tissues and expanded ex vivo makes them attractive candidates for systemic immunosuppressive therapy. In this article, we will review recent experimental data on the mechanisms by which MSC inhibit the alloproliferative response and the clinical relevance for their potential use in hematopoietic stem cell transplantation, solid organ transplantation, and treatment of autoimmune diseases. While in vitro data consistently demonstrate the immunosuppressive capability of MSC, current studies in animals and humans suggest that MSC are less effective in producing systemic immunosuppression. Further mechanistic studies and randomized controlled trials using standardized cell populations are needed to define the optimal conditions for the use of MSC as immunotherapy.


Cluster analysis on multiple drugs susceptibility supplements genotyping of methicillin-resistant Staphylococcus aureus.
To evaluate the typing power of cluster analysis of antimicrobial susceptibility. Results of pulsed-field gel electrophoresis in 71 strains of methicillin-resistant Staphylococcus aureus were compared with cluster analysis of the diameter of growth inhibition in 11 drugs. Subjects were a consecutive series of patients (n = 71) from the wards and outpatient units of a community teaching hospital. The cluster analysis took 2 to 3 seconds once the data were entered into a computer. The sensitivity, specificity, and accuracy of the cluster analysis were 76.3%, 58.3%, and 73.2%, respectively, using genotyping as the reference. The cluster analysis offered real-time epidemiologic data at minimal cost and labor, warranting its cost-effective role.


The initiation and sequence of digital joint motion. A three-dimensional motion analysis.
We studied the initiation and sequence of digital joint motion during unrestricted flexion and extension using a 3-D motion analysis of all fingers moving simultaneously. Our results showed that motion started in a single joint in 83%, of flexion and 80%, of extension cycles. The DIP joint initiated flexion and extension in the index, middle, and ring fingers, but in the little finger, flexion started in the PIP joint, and extension in the MP joint. The two most frequent sequences of joint movement during flexion of the three radial fingers were DIP-PIP-MP and PIP-DIP-MP. The two most frequent sequences during extension of the three radial fingers were DIP-MP-PIP followed by DIP-MP/PIP. In the little finger, however, the most frequent sequences during flexion were PIP-DIP-MP followed by DIP-PIP-MP and during extension, DIP-MP/PIP followed by PIP/DIP-MP.


Regional and seasonal effects on the gastrointestinal parasitism of captive forest musk deer.
Parasite infections can cause adverse effects on health, survival and welfare of forest musk deer. However, few studies have quantified the parasite infection status and evaluated the parasite temporal dynamics and differences between breeding centers for captive forest musk deer. The purpose of this study was to assess seasonal and regional effects on the parasite prevalence, shedding capacity, diversity, aggregation and infracommunity to establish baseline data on captive forest musk deer. The McMaster technique was applied to count parasite eggs or oocysts in 990 fecal samples collected at three breeding centers located in Qinling Mountains and Tibetan Plateau during spring, summer, and winter. Five gastrointestinal parasite groups were found in musk deer, and Eimeria spp. were dominant (mean oocysts per gram=1273.7±256.3). A positive correlation between Eimeria spp. and Strongyloides spp. (r=0.336, p<0.001) based on shedding capacity data was found, as well as a negative correlation between Eimeria spp. and Moniezia spp. (r=-0.375, p=0.003). Both seasonal and regional differences in diversity, prevalence, shedding capacity, aggregation and infracommunity were observed for five parasite groups. The low level of aggregation and high shedding capacity of Eimeria spp. and Strongyloides spp. might reflect the contaminated environment, and indicate that host-parasite relationships are unstable. The high degree of aggregation of Trichuris spp., Ascaris spp., and Moniezia spp. also suggests that some individual hosts had less ability to resist pathogens and greater transmission potential than others. These conclusions suggest that a focus on disease control strategies could improve the health of forest musk deer in captivity.


CO2 Fractional Laser Combined with 5-Fluorouracil Ethosomal Gel Treatment of Hypertrophic Scar Macro-, Microscopic, and Molecular Mechanism of Action in a Rabbit Animal Model.
The treatment of hypertrophic scar (HS) has thus far been a clinical challenge. We evaluated the therapeutic effect of CO2 fractional laser combined with 5-fluorouracil ethosomal gel (5-FU EG) in rabbit HS model. HS model was established as standardized scars on the ventral surface of rabbit ears, divided into four groups: control (no intervention), EG treatment, laser treatment, and combined treatment group (laser plus 5-FU EG). Clinical macroscopic and H&E-stained microscopic observations were conducted to assess HS improvement. The mRNA levels of types I and III collagen, transforming growth factor-β1 (TGF-β1), and interleukin-6 (IL-6) were detected by real-time PCR. After 14 days, H&E staining shows that the thickness of HS in treatment groups was significantly lower compared with the control group, and the thickness in laser treatment group and combined treatment group was significantly lower compared with the EG treatment group. The mRNA levels of types I and III collagen, TGF-β1 were significantly low in all treatment groups, whereas IL-6 was highest in the laser treatment group at day 14. The macro- and microscopic effects of the combined and CO2 fractional laser treatment were better compared with 5-FU EG only. Inhibition of types I and III collagen, TGF-β1 are the possible underlying mechanism of action, whereas the function of IL-6 remains to be further studied. Our study suggests that the effect of combined 5-FU EG and laser, as well as laser-only treatment are superior to 5-FU EG monotreatment. The mechanism of HS improvement is related to reduction of collagen I/III and the inhibition of TGF-β1 expression.


Fixation of displaced femoral neck fractures in young adults: Fixed-angle devices or Pauwel screws?
We sought to compare the incidence of complications after fixation of displaced femoral neck fractures in young adults treated with fixed-angle devices versus multiple cancellous screws and a trochanteric lag screw (Pauwel screw). We conducted a retrospective cohort study at a level I trauma centre. Sixty-two skeletally mature patients (age range, 16-60 years) with displaced femoral neck fractures were included in the study. Forty-seven were treated with a fixed-angle device (sliding hip plate with screw or helical blade) and 15 with multiple cancellous screws placed in a Pauwel configuration. The main outcome measure was postoperative complication of osteonecrosis or nonunion treated with a surgical procedure. Significantly fewer failures occurred in the fixed-angle group (21%) than in the screws group (60%) (p=0.008). Osteonecrosis was rare in the fixed-angle group, occurring in 2% of cases versus 33% of cases in the screws group (p=0.002). Consistent with previous studies, good to excellent reductions were associated with a failure rate of 25% and fair to poor reductions were associated with a failure rate of 55% (p=0.07). The best-case scenario of a good to excellent reduction stabilised with a fixed-angle device yielded a success rate of 85%. In young patients with displaced high-energy femoral neck fractures, fixed-angle devices resulted in fewer treatment failures than did Pauwel screws.


A case of primary clear cell hepatocellular carcinoma comprised mostly of clear cells.
Clear cell hepatocellular carcinoma (CHCC) is defined as a tumor which contains more than 50% of clear cells. However, CHCC with more than 90% of clear cells are extremely rare. We report a case of a 65-year-old woman who was found to have a solitary mass, which was histologically diagnosed as clear cell hepatocellular carcinoma composed of 90% or more clear cells. The tumor presented rim arterial phase hyperenhancement in computed tomography, magnetic resonance imaging, and computed tomography during hepatic arteriography, and was classified as LR-M category according to The Liver Imaging Reporting and Data System version 2018(LI-RADS v2018). This tumor may mimic other tumors with similar radiographic features, such as intrahepatic cholangiocellular carcinoma and metastatic tumor.


Identifying key drivers of harmful algal blooms in a tributary of the Three Gorges Reservoir between different seasons: Causality based on data-driven methods.
Intense harmful algal blooms (HABs) can occur in the backwaters of tributaries supplying large-scale reservoirs. Due to the characteristics of process-based models and difficulties in modelling complex nonlinear processes, traditional models have difficulties disentangling the driving factors of HABs. In this study, we used data-driven methods (i.e., correlation analysis and machine-learning models) to identify the most important drivers of HABs in the Xiangxi River, a tributary of the Three Gorges Reservoir, China (2017-2018), for the dry season (from October to mid-April) and wet season (from April to September). We utilized the maximal information coefficient (MIC) combined with a time lag strategy and prior knowledge to quantitatively identify the driving variables of HABs. An extra trees regression (ETR) model was developed to assess the relative importance of causal variables driving algal blooms for the different periods. The results showed that water temperature was the most important driver for the duration of the study, followed by total nitrogen. Nitrogen had a stronger effect on algal blooms than phosphorus during both the wet and dry seasons. HABs were mainly affected by ammonia nitrogen in the wet season and by other forms of nitrogen in the dry season. In contrast, rather than the water temperature and nutrients, the operation of the Three Gorges Dam (difference between inflow and outflow discharge rate) was the most significant factor for algal blooms during the dry season, but its influence sharply declined during the wet season. This study showed that the key drivers of HABs can differ between seasons and suggests that HAB management should take seasonality into account.


The rhetoric of recovery and change.
How can we know whether people who have been treated for an illness or been helped with a problem have indeed regained their health or solved their problem? Is "health" an objective condition-something that is observable, visible, perhaps even measurable? This article discusses these questions with the help of an analysis of the account given by a patient in psychotherapy regarding her recovery from a problematic life situation. The point of departure here is that recovery from illness or from a condition of ill-health should be understood as a reorganization of cultural, social and psychological elements which together are able to convey the picture that treatment has been successful and full recovery has been achieved. What the patient presents is not a "report" on an "actual" transformation process, nor is it an accumulated description. Rather, the patient presents a narrative, shaped by and created out of her own life situation and the interview situation in which she is engaged. It is a narrative that highlights certain aspects of a course of events and which arranges the pieces of the puzzle in such a way as to convey a picture of transformation and recovery.


Changes in Cancer Screening in the US During the COVID-19 Pandemic.
Health care was disrupted in the US during the first quarter of 2020 with the emergence of the COVID-19 pandemic. Early reports in selected samples suggested that cancer screening services decreased greatly, but population-based estimates of cancer screening prevalence during 2020 have not yet been reported. To examine changes in breast cancer (BC), cervical cancer (CC), and colorectal cancer (CRC) screening prevalence with contemporary national, population-based Behavioral Risk Factor Surveillance System (BRFSS) data. This survey study included respondents from the 2014, 2016, 2018, and 2020 BRFSS surveys who were eligible for BC (women aged 50-74 years), CC (women aged 25-64 years), and CRC (women and men aged 50-75 years) screening. Data analysis was performed from September 2021 to February 2022. Calendar year. Self-reported receipt of a recent (defined as in the past year) BC, CC, and CRC screening test. Adjusted prevalence ratios (aPRs) comparing 2020 vs 2018 prevalence and 95% CIs were computed. In total, 479 248 individuals were included in the analyses of BC screening, 301 453 individuals were included in CC screening, and 854 210 individuals were included in CRC screening, In 2020, among respondents aged 50 to 75 years, 14 815 (11.4%) were Black, 12 081 (12.6%) were Hispanic, 156 198 (67.3%) were White, and 79 234 (29.9%) graduated from college (all percentages are weighted). After 4 years (2014-2018) of nearly steady prevalence, past-year BC screening decreased by 6% between 2018 and 2020 (from 61.6% in 2018 to 57.8% in 2020; aPR, 0.94; 95% CI, 0.92-0.96), and CC screening decreased by 11% (from 58.3% in 2018 to 51.9% in 2020; aPR, 0.89; 95% CI, 0.87-0.91). The magnitude of these decreases was greater in people with lower educational attainment and Hispanic persons. CRC screening prevalence remained steady; past-year stool testing increased by 7% (aPR, 1.07; 95% CI, 1.02-1.12), offsetting a 16% decrease in colonoscopy (aPR, 0.84; 95% CI, 0.82-0.88) between 2018 and 2020. In this survey study, stool testing increased and counterbalanced a decrease in colonoscopy during 2020, and BC and CC screening modestly decreased. How these findings might be associated with outcomes is not yet known, but they will be important to monitor, especially in populations with lower socioeconomic status, who experienced greater screening decreases during the COVID-19 pandemic.